Case Finding of Mild Cognitive Impairment and Dementia and Subsequent Care; Results of a Cluster RCT in Primary Care.

PubMed

van den Dungen, Pim; Moll van Charante, Eric P; van de Ven, Peter M; van Marwijk, Harm W J; van der Horst, Henriëtte E; van Hout, Hein P J

2016-01-01

Despite a call for earlier diagnosis of dementia, the diagnostic yield of case finding and its impact on the mental health of patients and relatives are unclear. This study assessed the effect of a two-component intervention of case finding and subsequent care on these outcomes. In a cluster RCT we assessed whether education of family physicians (FPs; trial stage 1) resulted in more mild cognitive impairment (MCI) and dementia diagnoses among older persons in whom FPs suspected cognitive decline and whether case finding by a practice nurse and the FP (trial stage 2) added to this number of diagnoses. In addition, we assessed mental health effects of case finding and subsequent care (trial stage 2). FPs of 15 primary care practices (PCPs = clusters) judged the cognitive status of all persons ≥ 65 years. The primary outcome, new MCI and dementia diagnoses by FPs after 12 months as indicated on a list, was assessed among all persons in whom FPs suspected cognitive impairment but without a formal diagnosis of dementia. The secondary outcome, mental health of patients and their relatives, was assessed among persons consenting to participate in trial stage 2. Trial stage 1 consisted of either intervention component 1: training FPs to diagnose MCI and dementia, or control: no training. Trial stage 2 consisted of either intervention component 2: case finding of MCI and dementia and care by a trained nurse and the FP, or control: care as usual. Seven PCPs were randomized to the intervention; eight to the control condition. MCI or dementia was diagnosed in 42.3% (138/326) of persons in the intervention, and in 30.5% (98/321) in the control group (estimated difference GEE: 10.8%, OR: 1.51, 95%-CI 0.60-3.76). Among patients and relatives who consented to stage 2 of the trial (n = 145; 25%), there were no differences in mental health between the intervention and control group. We found a non-significant increase in the number of new MCI diagnoses. As we cannot exclude a clinically relevant effect, a larger study is warranted to replicate ours. Nederlands Trial Register NTR3389.

Retinopathy of prematurity: mutations in the Norrie disease gene and the risk of progression to advanced stages.

PubMed

Haider, M Z; Devarajan, L V; Al-Essa, M; Srivastva, B S; Kumar, H; Azad, R; Rashwan, N

2001-04-01

Retinopathy of prematurity (ROP) is a retinal vascular disease that occurs in infants with short gestational age and low birth weight and may lead to retinal detachment and blindness. Missense mutations in the Norrie disease (ND) gene have been associated with the risk of progression to advanced stages in cases of ROP from the US and also in clinically similar ND and familial exudative vitreoretinopathy. We have screened two ND gene mutations, namely A105T and Val60Glu, by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific PCR methods, respectively, in 210 Kuwaiti premature newborns to replicate these findings in a different ethnic group. In the Kuwaiti premature newborn cohort, 115 of 210 babies had no eye problems and served as controls, while 95 were cases of ROP. In 71 of 95 ROP cases, the disease regressed spontaneously on or before stage 3, while in 24 of 95 ROP cases the disease progressed to advanced stages 4 and 5. In case of missense mutation (A105T), the AA genotype was detected in 96% of controls compared with 87% of ROP cases (NS); similarly no significant difference was found between spontaneously regressed ROP cases and those who progressed to advanced stages. For the Val60Glu mutation, no significant association was detected between the genotype and progression of ROP to advanced stages. Unlike data from the US, our findings from a Kuwaiti cohort of ROP cases and controls suggest a lack of association between the two ND gene mutations (A105T and Val60Glu) and ROP and the risk of progression of the disease to advanced stages.

Myospherulosis following sinus surgery: pathological curiosity or important clinical entity?

PubMed

Sindwani, Raj; Cohen, Jacob T; Pilch, Ben Z; Metson, Ralph B

2003-07-01

Myospherulosis is a foreign body reaction to lipid material used on nasal packing at the conclusion of sinus surgery. This reaction has been associated with postoperative adhesion formation. The purpose of the study was to determine whether the occurrence of myospherulosis has an adverse effect on clinical outcome following sinus surgery. Case-control study at an academic medical center. Thirty-two cases of myospherulosis were identified in 28 patients (4 with bilateral disease) who underwent sinus surgery between 1989 and 1999. Cases were staged according to histological and radiological grading systems. Clinical outcome was compared with a control group of 28 patients who had similar surgery during the same time period. Patients with myospherulosis were found to have a significantly higher likelihood of developing postoperative adhesions compared with control subjects (50% vs. 18%, respectively [P =.023]). Histological stage, based on the extent of lipid vacuoles and spherules (erythrocyte remnants) present in the surgical specimen, was found to correlate with disease severity based on preoperative sinus computed tomography staging (P =.009). Patients with myospherulosis tended to have a shorter interval between their last two surgeries than did control subjects (2.2 +/- 2.1 vs. 4.5 +/- 7.1 y, respectively [P =.086]). Patient age, sex, comorbid conditions, CT stage, and number of previous operations were not predictive for the occurrence of myospherulosis. Patients who develop myospherulosis from lipid-based packing material used during sinus surgery are more likely to form postoperative adhesions. These adhesions appear to be clinically relevant and may hasten the need for revision surgery.

[Clinical observation on acupuncture by stages combined with exercise therapy for treatment of Bell palsy at acute stage].

PubMed

Qu, Yong

2005-08-01

To find out a method for increasing clinical therapeutic effect on Bell palsy at acute stage. Ninety cases of Bell palsy were randomly divided into an observation group, a control group I and a control group II, 30 cases in each group. They were treated respectively with acupuncture plus exercise therapy, simple acupuncture therapy, and simple exercise therapy, and their therapeutic effects were observed. The cured rate was 66.7% in the observation group, 53.3% in the control group I and 46.70% in the control group II, the observation group being better than the two control groups (P<0.05). Acupuncture by stage combined with exercise therapy can increase the therapeutic effect on Bell palsy at acute stage, and it is a better therapy for Bell palsy.

SNP rs2071095 in LincRNA H19 is associated with breast cancer risk.

PubMed

Cui, Ping; Zhao, Yanrui; Chu, Xinlei; He, Na; Zheng, Hong; Han, Jiali; Song, Fengju; Chen, Kexin

2018-05-08

An increasing number of long intergenic non-coding RNAs (lincRNAs) appear to play critical roles in cancer development and progression. To assess the association between SNPs that reside in regions of lincRNAs and breast cancer risk, we performed a large case-control study in China. We carried out a two-stage case-control study including 2881 breast cancer cases and 3220 controls. In stage I, we genotyped 17 independent (r 2  < 0.5) SNPs located in 6 tumor-related lincRNAs by using the TaqMan platform. In stage II, SNPs potentially associated with breast cancer risk were replicated in an independent population. Quantitative real-time PCR was used to measure H19 levels in tissues from 228 breast cancer patients with different genotypes. We identified 2 SNPs significantly associated with breast cancer risk in stage I (P < 0.05), but not significantly replicated in stage II. We combined the data from stage I and stage II, and found that, compared with the rs2071095 CC genotype, AA and CA + AA genotypes were associated with significantly decreased risk of breast cancer (adjusted OR 0.83, 95% CI 0.69-0.99; adjusted OR 0.88, 95% CI 0.80-0.98, respectively). Stratified analyses showed that rs2071095 was associated with breast cancer risk in estrogen receptor (ER)-positive patients (P = 0.002), but not in ER-negative ones (P = 0.332). Expression levels of H19 in breast cancer cases with AA genotype were significantly lower than those with CC genotype. We identified that rs2071095 may contribute to the susceptibility of breast cancer in Chinese women via affecting H19 expression. The mechanisms underlying the association remain to be investigated.

Genome-wide association study of colorectal cancer identifies six new susceptibility loci.

PubMed

Schumacher, Fredrick R; Schmit, Stephanie L; Jiao, Shuo; Edlund, Christopher K; Wang, Hansong; Zhang, Ben; Hsu, Li; Huang, Shu-Chen; Fischer, Christopher P; Harju, John F; Idos, Gregory E; Lejbkowicz, Flavio; Manion, Frank J; McDonnell, Kevin; McNeil, Caroline E; Melas, Marilena; Rennert, Hedy S; Shi, Wei; Thomas, Duncan C; Van Den Berg, David J; Hutter, Carolyn M; Aragaki, Aaron K; Butterbach, Katja; Caan, Bette J; Carlson, Christopher S; Chanock, Stephen J; Curtis, Keith R; Fuchs, Charles S; Gala, Manish; Giovannucc, Edward L; Giocannucci, Edward L; Gogarten, Stephanie M; Hayes, Richard B; Henderson, Brian; Hunter, David J; Jackson, Rebecca D; Kolonel, Laurence N; Kooperberg, Charles; Küry, Sébastien; Kury, Sebastian; LaCroix, Andrea; Laurie, Cathy C; Laurie, Cecelia A; Lemire, Mathieu; Lemire, Mathiew; Levine, David; Ma, Jing; Makar, Karen W; Qu, Conghui; Taverna, Darin; Ulrich, Cornelia M; Wu, Kana; Kono, Suminori; West, Dee W; Berndt, Sonja I; Bezieau, Stéphane; Brenner, Hermann; Campbell, Peter T; Chan, Andrew T; Chang-Claude, Jenny; Coetzee, Gerhard A; Conti, David V; Duggan, David; Figueiredo, Jane C; Fortini, Barbara K; Gallinger, Steven J; Gauderman, W James; Giles, Graham; Green, Roger; Haile, Robert; Harrison, Tabitha A; Hoffmeister, Michael; Hopper, John L; Hudson, Thomas J; Jacobs, Eric; Iwasaki, Motoki; Jee, Sun Ha; Jenkins, Mark; Jia, Wei-Hua; Joshi, Amit; Li, Li; Lindor, Noralene M; Matsuo, Keitaro; Moreno, Victor; Mukherjee, Bhramar; Newcomb, Polly A; Potter, John D; Raskin, Leon; Rennert, Gad; Rosse, Stephanie; Severi, Gianluca; Schoen, Robert E; Seminara, Daniela; Shu, Xiao-Ou; Slattery, Martha L; Tsugane, Shoichiro; White, Emily; Xiang, Yong-Bing; Zanke, Brent W; Zheng, Wei; Le Marchand, Loic; Casey, Graham; Gruber, Stephen B; Peters, Ulrike

2015-07-07

Genetic susceptibility to colorectal cancer is caused by rare pathogenic mutations and common genetic variants that contribute to familial risk. Here we report the results of a two-stage association study with 18,299 cases of colorectal cancer and 19,656 controls, with follow-up of the most statistically significant genetic loci in 4,725 cases and 9,969 controls from two Asian consortia. We describe six new susceptibility loci reaching a genome-wide threshold of P<5.0E-08. These findings provide additional insight into the underlying biological mechanisms of colorectal cancer and demonstrate the scientific value of large consortia-based genetic epidemiology studies.

Semiparametric time varying coefficient model for matched case-crossover studies.

PubMed

Ortega-Villa, Ana Maria; Kim, Inyoung; Kim, H

2017-03-15

In matched case-crossover studies, it is generally accepted that the covariates on which a case and associated controls are matched cannot exert a confounding effect on independent predictors included in the conditional logistic regression model. This is because any stratum effect is removed by the conditioning on the fixed number of sets of the case and controls in the stratum. Hence, the conditional logistic regression model is not able to detect any effects associated with the matching covariates by stratum. However, some matching covariates such as time often play an important role as an effect modification leading to incorrect statistical estimation and prediction. Therefore, we propose three approaches to evaluate effect modification by time. The first is a parametric approach, the second is a semiparametric penalized approach, and the third is a semiparametric Bayesian approach. Our parametric approach is a two-stage method, which uses conditional logistic regression in the first stage and then estimates polynomial regression in the second stage. Our semiparametric penalized and Bayesian approaches are one-stage approaches developed by using regression splines. Our semiparametric one stage approach allows us to not only detect the parametric relationship between the predictor and binary outcomes, but also evaluate nonparametric relationships between the predictor and time. We demonstrate the advantage of our semiparametric one-stage approaches using both a simulation study and an epidemiological example of a 1-4 bi-directional case-crossover study of childhood aseptic meningitis with drinking water turbidity. We also provide statistical inference for the semiparametric Bayesian approach using Bayes Factors. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Essential fatty acids supplementation in different-stage atopic dogs fed on a controlled diet.

PubMed

Abba, C; Mussa, P P; Vercelli, A; Raviri, G

2005-01-01

The aim of this trial was to evaluate the effects of polyunsaturated fatty acid (PUFA) supplementation in different-stages atopic dogs fed on a controlled diet. Twenty-two non-seasonal atopic dogs of different breeds and ages were included in the 2-month trial. All the patients were given an essential fatty acid (EFA) supplementation [17 mg/kg eicosapentaenoic acid (EPA) + 5 mg/kg docosahexaenoic acid (DHA) + 35 mg/kg gammalinolenic acid (GLA)], the global (diet + supplementation) omega-6 to omega-3 ratio was 5.5-1. Two groups of dogs were considered: group A 'pre-immunotherapy' (15 cases) included dogs with early stages atopy, which had not been submitted to any treatment yet; group B 'post-immunotherapy' (seven cases) included dogs with chronic atopy immunotherapy non-responsive. Clinical evaluations were performed at the beginning, on day 30 and at the end of the trial. Blood serum fatty acids profile was determined at the beginning and at the end of the study. Better clinical results were obtained in group A, a great difference was found between the two groups on pruritus score. Serum arachidonic acid (AA) was significantly lower at the end of the trial in group A while GLA was significantly higher in group B. We hypothesized that different-stages atopic dogs could have different response to EFA supplementation, maybe because of a different fatty acids metabolism. Early stages cases seem to be more responsive to EFA supplementation.

Propensity score matching for selection of local areas as controls for evaluation of effects of alcohol policies in case series and quasi case-control designs.

PubMed

de Vocht, F; Campbell, R; Brennan, A; Mooney, J; Angus, C; Hickman, M

2016-03-01

Area-level public health interventions can be difficult to evaluate using natural experiments. We describe the use of propensity score matching (PSM) to select control local authority areas (LAU) to evaluate the public health impact of alcohol policies for (1) prospective evaluation of alcohol policies using area-level data, and (2) a novel two-stage quasi case-control design. Ecological. Alcohol-related indicator data (Local Alcohol Profiles for England, PHE Health Profiles and ONS data) were linked at LAU level. Six LAUs (Blackpool, Bradford, Bristol, Ipswich, Islington, and Newcastle-upon-Tyne) as sample intervention or case areas were matched to two control LAUs each using PSM. For the quasi case-control study a second stage was added aimed at obtaining maximum contrast in outcomes based on propensity scores. Matching was evaluated based on average standardized absolute mean differences (ASAM) and variable-specific P-values after matching. The six LAUs were matched to suitable control areas (with ASAM < 0.20, P-values >0.05 indicating good matching) for a prospective evaluation study that sought areas that were similar at baseline in order to assess whether a change in intervention exposure led to a change in the outcome (alcohol related harm). PSM also generated appropriate matches for a quasi case-control study--whereby the contrast in health outcomes between cases and control areas needed to be optimized in order to assess retrospectively whether differences in intervention exposure were associated with the outcome. The use of PSM for area-level alcohol policy evaluation, but also for other public health interventions, will improve the value of these evaluations by objective and quantitative selection of the most appropriate control areas. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Acupotomy and acupuncture in the treatment of avascular necrosis of femoral head at the early and middle stages:a clinical randomized controlled trial].

PubMed

Wang, Zhanyou; Zhou, Xuelong; Xie, Lishuang; Liang, Dongyue; Wang, Ying; Zhang, Hong-An; Zheng, Jinghong

2016-10-12

To compare the efficacy difference between acupotomy and acupuncture in the treatment of avascular necrosis of femoral head at the early and middle stages. The randomized controlled prospective study method was adopted. Sixty cases of avascular necrosis of femoral head at Ficat-ArletⅠto Ⅱ stages were randomized into an acupotomy group (32 cases) and an acupuncture group (28 cases) by the third part. In the acupotomy group, the acupotomy was adopted for the loose solution at the treatment sites of hip joint, once every two weeks, totally for 3 times. In the acupuncture group, ashi points around the hip joint were selected and stimulated with warm acupuncture therapy, once every day, for 6 weeks. Harris hip score was observed before and after treatment. The efficacy was evaluated in the two groups. Harris hip score was improved significantly after treatment in the two groups (both P <0.05). The result in acupotomy group was better than that in the acupuncture group ( P <0.05). The effective rate was 90.6% (29/32) in the acupotomy group, better than 75.0% (21/28) in the acupuncture group after treatment ( P <0.05). Harris hip score and the effective rate in the acupotomy group are better than those in the treatment with routine acupuncture for avascular necrosis of femoral head at the early and middle stages.

Systematic investigation of the relationship between high myopia and polymorphisms of the MMP2, TIMP2, and TIMP3 genes by a DNA pooling approach.

PubMed

Leung, Kim Hung; Yiu, Wai Chi; Yap, Maurice K H; Ng, Po Wah; Fung, Wai Yan; Sham, Pak Chung; Yip, Shea Ping

2011-06-01

This study examined the relationship between high myopia and three myopia candidate genes--matrix metalloproteinase 2 (MMP2) and tissue inhibitor of metalloproteinase-2 and -3 (TIMP2 and TIMP3)--involved in scleral remodeling. Recruited for the study were unrelated adult Han Chinese who were high myopes (spherical equivalent, ≤ -6.0 D in both eyes; cases) and emmetropes (within ±1.0 D in both eyes; controls). Sample set 1 had 300 cases and 300 controls, and sample set 2 had 356 cases and 354 controls. Forty-nine tag single-nucleotide polymorphisms (SNPs) were selected from these candidate genes. The first stage was an initial screen of six case pools and six control pools constructed from sample set 1, each pool consisting of 50 distinct subjects of the same affection status. In the second stage, positive SNPs from the first stage were confirmed by genotyping individual samples forming the DNA pools. In the third stage, positive SNPs from stage 2 were replicated, with sample set 2 genotyped individually. Of the 49 SNPs screened by DNA pooling, three passed the lenient threshold of P < 0.10 (nested ANOVA) and were followed up by individual genotyping. Of the three SNPs genotyped, two TIMP3 SNPs were found to be significantly associated with high myopia by single-marker or haplotype analysis. However, the initial positive results could not be replicated by sample set 2. MMP2, TIPM2, and TIMP3 genes were not associated with high myopia in this Chinese sample and hence are unlikely to play a major role in the genetic susceptibility to high myopia.

Two-stage revisions for culture-negative infected total knee arthroplasties: A five-year outcome in comparison with one-stage and two-stage revisions for culture-positive cases.

PubMed

Li, Heng; Ni, Ming; Li, Xiang; Zhang, Qingmeng; Li, Xin; Chen, Jiying

2017-03-01

Culture-negative periprosthetic joint infection (PJI) is very intractable when dealing with an infected total knee arthroplasty (TKA) patient. Two-stage revision has been proved to be a reliable solution for PJI patients. Whether it is still credible for culture-negative infected patients remains uncertain. Our group retrospectively reviewed all total knee revision patients from January 2003 to January 2014, 145 PJI patients were diagnosed as infection with the PJI diagnostic criteria and 129 patients were successfully followed. As different treating strategies were utilized, these patients were divided into culture-negative (18 cases, CN) group, culture-positive with one-stage revision group (CP1, 21 cases) and culture-positive with two-stage revision group (CP2, 87 cases) groups. The CN group and CP2 group underwent two-stage revision with antibiotic loaded cement spacers and intravenous antibiotics, CP1 group received one-stage revision. All the culture results and relevant medical records were thoroughly reviewed. The mean follow-up time was 59.5 ± 32.3 months (range 12-158 months). The culture-negative rate was 14.2%. The overall infection control rate was 92.12%. Infection recurrence was observed in two cases in CP1 group (9.09%), six cases in CP2 group (6.90%) and two cases in CN group (11.1%). The reinfection rate of culture-negative patients and culture-positive patients was 7.34% and 11.1% with no significant difference (p = 0.94). No statistically difference was observed between CP2 group and CN group (p = 0.90). No Spacer fracture or dislocation was observed. With combined or broad spectrum antibiotics, two-stage revision showed comparable outcome when treating culture-negative infected TKA patients at five-year follow-up. Copyright © 2016. Published by Elsevier B.V.

MicroRNA expression in benign breast tissue and risk of subsequent invasive breast cancer.

PubMed

Rohan, Thomas; Ye, Kenny; Wang, Yihong; Glass, Andrew G; Ginsberg, Mindy; Loudig, Olivier

2018-01-01

MicroRNAs are endogenous, small non-coding RNAs that control gene expression by directing their target mRNAs for degradation and/or posttranscriptional repression. Abnormal expression of microRNAs is thought to contribute to the development and progression of cancer. A history of benign breast disease (BBD) is associated with increased risk of subsequent breast cancer. However, no large-scale study has examined the association between microRNA expression in BBD tissue and risk of subsequent invasive breast cancer (IBC). We conducted discovery and validation case-control studies nested in a cohort of 15,395 women diagnosed with BBD in a large health plan between 1971 and 2006 and followed to mid-2015. Cases were women with BBD who developed subsequent IBC; controls were matched 1:1 to cases on age, age at diagnosis of BBD, and duration of plan membership. The discovery stage (316 case-control pairs) entailed use of the Illumina MicroRNA Expression Profiling Assay (in duplicate) to identify breast cancer-associated microRNAs. MicroRNAs identified at this stage were ranked by the strength of the correlation between Illumina array and quantitative PCR results for 15 case-control pairs. The top ranked 14 microRNAs entered the validation stage (165 case-control pairs) which was conducted using quantitative PCR (in triplicate). In both stages, linear regression was used to evaluate the association between the mean expression level of each microRNA (response variable) and case-control status (independent variable); paired t-tests were also used in the validation stage. None of the 14 validation stage microRNAs was associated with breast cancer risk. The results of this study suggest that microRNA expression in benign breast tissue does not influence the risk of subsequent IBC.

MicroRNA expression in benign breast tissue and risk of subsequent invasive breast cancer

PubMed Central

Ye, Kenny; Wang, Yihong; Ginsberg, Mindy; Loudig, Olivier

2018-01-01

MicroRNAs are endogenous, small non-coding RNAs that control gene expression by directing their target mRNAs for degradation and/or posttranscriptional repression. Abnormal expression of microRNAs is thought to contribute to the development and progression of cancer. A history of benign breast disease (BBD) is associated with increased risk of subsequent breast cancer. However, no large-scale study has examined the association between microRNA expression in BBD tissue and risk of subsequent invasive breast cancer (IBC). We conducted discovery and validation case-control studies nested in a cohort of 15,395 women diagnosed with BBD in a large health plan between 1971 and 2006 and followed to mid-2015. Cases were women with BBD who developed subsequent IBC; controls were matched 1:1 to cases on age, age at diagnosis of BBD, and duration of plan membership. The discovery stage (316 case-control pairs) entailed use of the Illumina MicroRNA Expression Profiling Assay (in duplicate) to identify breast cancer-associated microRNAs. MicroRNAs identified at this stage were ranked by the strength of the correlation between Illumina array and quantitative PCR results for 15 case-control pairs. The top ranked 14 microRNAs entered the validation stage (165 case-control pairs) which was conducted using quantitative PCR (in triplicate). In both stages, linear regression was used to evaluate the association between the mean expression level of each microRNA (response variable) and case-control status (independent variable); paired t-tests were also used in the validation stage. None of the 14 validation stage microRNAs was associated with breast cancer risk. The results of this study suggest that microRNA expression in benign breast tissue does not influence the risk of subsequent IBC. PMID:29432432

Novel genes identified in a high-density genome wide association study for nicotine dependence.

PubMed

Bierut, Laura Jean; Madden, Pamela A F; Breslau, Naomi; Johnson, Eric O; Hatsukami, Dorothy; Pomerleau, Ovide F; Swan, Gary E; Rutter, Joni; Bertelsen, Sarah; Fox, Louis; Fugman, Douglas; Goate, Alison M; Hinrichs, Anthony L; Konvicka, Karel; Martin, Nicholas G; Montgomery, Grant W; Saccone, Nancy L; Saccone, Scott F; Wang, Jen C; Chase, Gary A; Rice, John P; Ballinger, Dennis G

2007-01-01

Tobacco use is a leading contributor to disability and death worldwide, and genetic factors contribute in part to the development of nicotine dependence. To identify novel genes for which natural variation contributes to the development of nicotine dependence, we performed a comprehensive genome wide association study using nicotine dependent smokers as cases and non-dependent smokers as controls. To allow the efficient, rapid, and cost effective screen of the genome, the study was carried out using a two-stage design. In the first stage, genotyping of over 2.4 million single nucleotide polymorphisms (SNPs) was completed in case and control pools. In the second stage, we selected SNPs for individual genotyping based on the most significant allele frequency differences between cases and controls from the pooled results. Individual genotyping was performed in 1050 cases and 879 controls using 31 960 selected SNPs. The primary analysis, a logistic regression model with covariates of age, gender, genotype and gender by genotype interaction, identified 35 SNPs with P-values less than 10(-4) (minimum P-value 1.53 x 10(-6)). Although none of the individual findings is statistically significant after correcting for multiple tests, additional statistical analyses support the existence of true findings in this group. Our study nominates several novel genes, such as Neurexin 1 (NRXN1), in the development of nicotine dependence while also identifying a known candidate gene, the beta3 nicotinic cholinergic receptor. This work anticipates the future directions of large-scale genome wide association studies with state-of-the-art methodological approaches and sharing of data with the scientific community.

Severity of Carpal Tunnel Syndrome and Diagnostic Accuracy of Hand and Body Anthropometric Measures

PubMed Central

Mondelli, Mauro; Farioli, Andrea; Mattioli, Stefano; Aretini, Alessandro; Ginanneschi, Federica; Greco, Giuseppe; Curti, Stefania

2016-01-01

Objective To study the diagnostic properties of hand/wrist and body measures according to validated clinical and electrophysiological carpal tunnel syndrome (CTS) severity scales. Methods We performed a prospective case-control study. For each case, two controls were enrolled. Two five-stage clinical and electrophysiological scales were used to evaluate CTS severity. Anthropometric measurements were collected and obesity indicators and hand/wrist ratios were calculated. Area under the receiver operating characteristic curves (AUC), sensitivity, specificity, and likelihood ratios were calculated separately by gender. Results We consecutively enrolled 370 cases and 747 controls. The wrist-palm ratio, waist-hip-height ratio and waist-stature ratio showed the highest proportion of cases with abnormal values in the severe stages of CTS for clinical and electrophysiological severity scales in both genders. Accuracy tended to increase with CTS severity for females and males. In severe stage, most of the indexes presented moderate accuracy in both genders. Among subjects with severe CTS, the wrist-palm ratio presented the highest AUC for hand measures in the clinical and electrophysiological severity scales both in females (AUC 0.83 and 0.76, respectively) and males (AUC 0.91 and 0.82, respectively). Among subjects with severe CTS, the waist-stature ratio showed the highest AUC for body measures in the clinical and electrophysiological severity scales both in females (AUC 0.78 and 0.77, respectively) and males (AUC 0.84 and 0.76, respectively). The results of waist-hip-height ratio AUC were similar. Conclusions Wrist-palm ratio, waist-hip-height ratio and waist-stature ratio could contribute to support the diagnostic hypothesis of severe CTS that however has to be confirmed by nerve conduction study. PMID:27768728

Genome-wide association analysis of young onset stroke identifies a locus on chromosome 10q25 near HABP2

PubMed Central

Cheng, Yu-Ching; Stanne, Tara M.; Giese, Anne-Katrin; Ho, Weang Kee; Traylor, Matthew; Amouyel, Philippe; Holliday, Elizabeth G.; Malik, Rainer; Xu, Huichun; Kittner, Steven J.; Cole, John W.; O’Connell, Jeffrey R.; Danesh, John; Rasheed, Asif; Zhao, Wei; Engelter, Stefan; Grond-Ginsbach, Caspar; Kamatani, Yoichiro; Lathrop, Mark; Leys, Didier; Thijs, Vincent; Metso, Tiina M.; Tatlisumak, Turgut; Pezzini, Alessandro; Parati, Eugenio A.; Norrving, Bo; Bevan, Steve; Rothwell, Peter M; Sudlow, Cathie; Slowik, Agnieszka; Lindgren, Arne; Walters, Matthew R; Jannes, Jim; Shen, Jess; Crosslin, David; Doheny, Kimberly; Laurie, Cathy C.; Kanse, Sandip M.; Bis, Joshua C.; Fornage, Myriam; Mosley, Thomas H.; Hopewell, Jemma C.; Strauch, Konstantin; Müller-Nurasyid, Martina; Gieger, Christian; Waldenberger, Melanie; Peters, Annette; Meisinger, Christine; Ikram, M. Arfan; Longstreth, WT; Meschia, James F.; Seshadri, Sudha; Sharma, Pankaj; Worrall, Bradford; Jern, Christina; Levi, Christopher; Dichgans, Martin; Boncoraglio, Giorgio B.; Markus, Hugh S.; Debette, Stephanie; Rolfs, Arndt; Saleheen, Danish; Mitchell, Braxton D.

2015-01-01

Background and Purpose Although a genetic contribution to ischemic stroke is well recognized, only a handful of stroke loci have been identified by large-scale genetic association studies to date. Hypothesizing that genetic effects might be stronger for early- versus late-onset stroke, we conducted a two-stage meta-analysis of genome-wide association studies (GWAS), focusing on stroke cases with an age of onset < 60 years old. Methods The Discovery stage of our GWAS included 4,505 cases and 21,968 controls of European, South-Asian and African ancestry, drawn from 6 studies. In Stage 2, we selected the lead genetic variants at loci with association P<5×10−6 and performed in silico association analyses in an independent sample of up to 1,003 cases and 7,745 controls. Results One stroke susceptibility locus at 10q25 reached genome-wide significance in the combined analysis of all samples from the Discovery and Follow-up Stages (rs11196288, OR=1.41, P=9.5×10−9). The associated locus is in an intergenic region between TCF7L2 and HABP2. In a further analysis in an independent sample, we found that two SNPs in high linkage disequilibrium with rs11196288 were significantly associated with total plasma factor VII-activating protease levels, a product of HABP2. Conclusions HABP2, which encodes an extracellular serine protease involved in coagulation, fibrinolysis, and inflammatory pathways, may be a genetic susceptibility locus for early-onset stroke. PMID:26732560

Medical and Non-Medical Factors Influencing Utilization of Delayed Pushing in the Second Stage

PubMed Central

FREY, Heather A.; TUULI, Methodius G.; CORTEZ, Sarah; ODIBO, Anthony O.; ROEHL, Kimberly A.; SHANKS, Anthony L.; MACONES, George A.; CAHILL, Alison G.

2014-01-01

Objective To evaluate factors impacting selection to delayed pushing in the second stage of labor. Study design This case-control study was a secondary analysis of a large retrospective cohort study. Cases included women who delayed pushing for 60 minutes or more in the second stage of labor. Controls began pushing prior to 60 minutes from the time of diagnosis of complete dilation. Demographic, labor, and nonmedical factors were compared among cases and controls. Logistic regression modelling was used to identify factors independently associated with delayed pushing. Results We identified 471 women who delayed pushing and 4,819 controls. Nulliparity, maternal body mass index > 25, high fetal station at complete dilation, regional anesthesia use, and start of second stage during staffing shift change were independent factors associated with increased use of delayed pushing. On the other hand, black race and second stage management during night shift were associated with lower odds of employing delayed pushing. Delayed pushing was more commonly employed in nulliparous women, but 38.9% of multiparous women also delayed pushing. Conclusion We identified multiple factors associated with use of delayed pushing. This study helps to define current patterns of second stage labor management. PMID:23208765

Long-term outcome of cochlear implant in patients with chronic otitis media: one-stage surgery is equivalent to two-stage surgery.

PubMed

Jang, Jeong Hun; Park, Min-Hyun; Song, Jae-Jin; Lee, Jun Ho; Oh, Seung Ha; Kim, Chong-Sun; Chang, Sun O

2015-01-01

This study compared long-term speech performance after cochlear implantation (CI) between surgical strategies in patients with chronic otitis media (COM). Thirty patients with available open-set sentence scores measured more than 2 yr postoperatively were included: 17 who received one-stage surgeries (One-stage group), and the other 13 underwent two-stage surgeries (Two-stage group). Preoperative inflammatory status, intraoperative procedures, postoperative outcomes were compared. Among 17 patients in One-stage group, 12 underwent CI accompanied with the eradication of inflammation; CI without eradicating inflammation was performed on 3 patients; 2 underwent CIs via the transcanal approach. Thirteen patients in Two-stage group received the complete eradication of inflammation as first-stage surgery, and CI was performed as second-stage surgery after a mean interval of 8.2 months. Additional control of inflammation was performed in 2 patients at second-stage surgery for cavity problem and cholesteatoma, respectively. There were 2 cases of electrode exposure as postoperative complication in the two-stage group; new electrode arrays were inserted and covered by local flaps. The open-set sentence scores of Two-stage group were not significantly higher than those of One-stage group at 1, 2, 3, and 5 yr postoperatively. Postoperative long-term speech performance is equivalent when either of two surgical strategies is used to treat appropriately selected candidates.

Two-stage graft urethroplasty for proximal and complicated hypospadias in children: A retrospective study.

PubMed

Faure, Alice; Bouty, Aurore; Nyo, Yoke Lin; O'Brien, Mike; Heloury, Yves

2016-10-01

Although two-stage graft urethroplasty is widely used, the literature regarding the complication rates and functional characteristics of reconstructed neourethra is relatively modest. The aim was to analyze the complication rates and uroflow data of boys who have previously undergone a two-stage graft urethroplasty procedure for proximal and complicated hypospadias. We retrospectively reviewed the clinical outcomes of 52 boys with proximal (n = 44) and complicated (n = 8) hypospadias who underwent two-stage graft urethroplasty repair (median age of 15 months and 3 years respectively) between 2004 and 2015. Fifteen toilet-trained boys without fistulas underwent uroflowmetry. The uroflow data were plotted on age-volume-dependent normograms with normal controls. The median follow-up was 34 months (8 months-8 years). Complications were identified in three patients (6%) after the first stage (i.e. contracture of the graft) and in 20 patients (38.4%) after the second stage, including meatal stenosis (n = 8, 15.3%), urethral stricture (n = 4, 7.6%), urethrocutaneous fistula (n = 8, 15.3%), glandular dehiscence (n = 1, 1.9%), and diverticulum (n = 1, 1.9%). The patients with failed hypospadias experienced fewer complications than those who underwent the two-stage procedure for primary repair (25% and 45%, respectively). The reoperation rate was 36.8%. Eleven of the 15 toilet-trained boys were asymptomatic but exhibited flow rates below the normal range (median Q max  = 7 mL/s, range 3.5-16.7). Only one of the boys with a low flow rate was confirmed to have urethral stenosis under general anesthesia. In our study, primary hypospadias repair requiring urethral plate transection elicited worse outcomes than those observed in the prior failed hypospadias cases. However, because of our study's retrospective design, we were unable to accurately assess the initial position of the meatus in the redo hypospadias cases. Our data also demonstrated that the majority of cases without any voiding symptoms exhibited flow rates that were below the normal range despite no urethral stricture under general anesthesia. These findings indicate that urethras reconstructed via two-stage graft urethroplasty repair are not functionally equivalent to normal urethras, at least prior to puberty. Two-stage graft urethroplasty repair was successful in 62% of cases after the second-stage procedure, but one-third of the boys required a reoperation after the two-stage planned repair. We demonstrated that although we used a urethral tissue substitute, the urine flow patterns of the patients without strictures were abnormal. Copyright © 2016 Journal of Pediatric Urology Company. All rights reserved.

Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis

PubMed Central

Whitcomb, David C.; LaRusch, Jessica; Krasinskas, Alyssa M.; Klei, Lambertus; Smith, Jill P.; Brand, Randall E.; Neoptolemos, John P.; Lerch, Markus M.; Tector, Matt; Sandhu, Bimaljit S.; Guda, Nalini M.; Orlichenko, Lidiya; Alkaade, Samer; Amann, Stephen T.; Anderson, Michelle A.; Baillie, John; Banks, Peter A.; Conwell, Darwin; Coté, Gregory A.; Cotton, Peter B.; DiSario, James; Farrer, Lindsay A.; Forsmark, Chris E.; Johnstone, Marianne; Gardner, Timothy B.; Gelrud, Andres; Greenhalf, William; Haines, Jonathan L.; Hartman, Douglas J.; Hawes, Robert A.; Lawrence, Christopher; Lewis, Michele; Mayerle, Julia; Mayeux, Richard; Melhem, Nadine M.; Money, Mary E.; Muniraj, Thiruvengadam; Papachristou, Georgios I.; Pericak-Vance, Margaret A.; Romagnuolo, Joseph; Schellenberg, Gerard D.; Sherman, Stuart; Simon, Peter; Singh, Vijay K.; Slivka, Adam; Stolz, Donna; Sutton, Robert; Weiss, Frank Ulrich; Wilcox, C. Mel; Zarnescu, Narcis Octavian; Wisniewski, Stephen R.; O'Connell, Michael R.; Kienholz, Michelle L.; Roeder, Kathryn; Barmada, M. Michael; Yadav, Dhiraj; Devlin, Bernie; Albert, Marilyn S.; Albin, Roger L.; Apostolova, Liana G.; Arnold, Steven E.; Baldwin, Clinton T.; Barber, Robert; Barnes, Lisa L.; Beach, Thomas G.; Beecham, Gary W.; Beekly, Duane; Bennett, David A.; Bigio, Eileen H.; Bird, Thomas D.; Blacker, Deborah; Boxer, Adam; Burke, James R.; Buxbaum, Joseph D.; Cairns, Nigel J.; Cantwell, Laura B.; Cao, Chuanhai; Carney, Regina M.; Carroll, Steven L.; Chui, Helena C.; Clark, David G.; Cribbs, David H.; Crocco, Elizabeth A.; Cruchaga, Carlos; DeCarli, Charles; Demirci, F. Yesim; Dick, Malcolm; Dickson, Dennis W.; Duara, Ranjan; Ertekin-Taner, Nilufer; Faber, Kelley M.; Fallon, Kenneth B.; Farlow, Martin R.; Ferris, Steven; Foroud, Tatiana M.; Frosch, Matthew P.; Galasko, Douglas R.; Ganguli, Mary; Gearing, Marla; Geschwind, Daniel H.; Ghetti, Bernardino; Gilbert, John R.; Gilman, Sid; Glass, Jonathan D.; Goate, Alison M.; Graff-Radford, Neill R.; Green, Robert C.; Growdon, John H.; Hakonarson, Hakon; Hamilton-Nelson, Kara L.; Hamilton, Ronald L.; Harrell, Lindy E.; Head, Elizabeth; Honig, Lawrence S.; Hulette, Christine M.; Hyman, Bradley T.; Jicha, Gregory A.; Jin, Lee-Way; Jun, Gyungah; Kamboh, M. Ilyas; Karydas, Anna; Kaye, Jeffrey A.; Kim, Ronald; Koo, Edward H.; Kowall, Neil W.; Kramer, Joel H.; Kramer, Patricia; Kukull, Walter A.; LaFerla, Frank M.; Lah, James J.; Leverenz, James B.; Levey, Allan I.; Li, Ge; Lin, Chiao-Feng; Lieberman, Andrew P.; Lopez, Oscar L.; Lunetta, Kathryn L.; Lyketsos, Constantine G.; Mack, Wendy J.; Marson, Daniel C.; Martin, Eden R.; Martiniuk, Frank; Mash, Deborah C.; Masliah, Eliezer; McKee, Ann C.; Mesulam, Marsel; Miller, Bruce L.; Miller, Carol A.; Miller, Joshua W.; Montine, Thomas J.; Morris, John C.; Murrell, Jill R.; Naj, Adam C.; Olichney, John M.; Parisi, Joseph E.; Peskind, Elaine; Petersen, Ronald C.; Pierce, Aimee; Poon, Wayne W.; Potter, Huntington; Quinn, Joseph F.; Raj, Ashok; Raskind, Murray; Reiman, Eric M.; Reisberg, Barry; Reitz, Christiane; Ringman, John M.; Roberson, Erik D.; Rosen, Howard J.; Rosenberg, Roger N.; Sano, Mary; Saykin, Andrew J.; Schneider, Julie A.; Schneider, Lon S.; Seeley, William W.; Smith, Amanda G.; Sonnen, Joshua A.; Spina, Salvatore; Stern, Robert A.; Tanzi, Rudolph E.; Trojanowski, John Q.; Troncoso, Juan C.; Tsuang, Debby W.; Valladares, Otto; Van Deerlin, Vivianna M.; Van Eldik, Linda J.; Vardarajan, Badri N.; Vinters, Harry V.; Vonsattel, Jean Paul; Wang, Li-San; Weintraub, Sandra; Welsh-Bohmer, Kathleen A.; Williamson, Jennifer; Woltjer, Randall L.; Wright, Clinton B.; Younkin, Steven G.; Yu, Chang-En; Yu, Lei

2012-01-01

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR, and SPINK1 variants were associated with pancreatitis risk. We now report two significant genome-wide associations identified and replicated at PRSS1-PRSS2 (1×10-12) and x-linked CLDN2 (p < 1×10-21) through a two-stage genome-wide study (Stage 1, 676 cases and 4507 controls; Stage 2, 910 cases and 4170 controls). The PRSS1 variant affects susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous male) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men – male hemizygous frequency is 0.26, female homozygote is 0.07. PMID:23143602

EPIBLASTER-fast exhaustive two-locus epistasis detection strategy using graphical processing units

PubMed Central

Kam-Thong, Tony; Czamara, Darina; Tsuda, Koji; Borgwardt, Karsten; Lewis, Cathryn M; Erhardt-Lehmann, Angelika; Hemmer, Bernhard; Rieckmann, Peter; Daake, Markus; Weber, Frank; Wolf, Christiane; Ziegler, Andreas; Pütz, Benno; Holsboer, Florian; Schölkopf, Bernhard; Müller-Myhsok, Bertram

2011-01-01

Detection of epistatic interaction between loci has been postulated to provide a more in-depth understanding of the complex biological and biochemical pathways underlying human diseases. Studying the interaction between two loci is the natural progression following traditional and well-established single locus analysis. However, the added costs and time duration required for the computation involved have thus far deterred researchers from pursuing a genome-wide analysis of epistasis. In this paper, we propose a method allowing such analysis to be conducted very rapidly. The method, dubbed EPIBLASTER, is applicable to case–control studies and consists of a two-step process in which the difference in Pearson's correlation coefficients is computed between controls and cases across all possible SNP pairs as an indication of significant interaction warranting further analysis. For the subset of interactions deemed potentially significant, a second-stage analysis is performed using the likelihood ratio test from the logistic regression to obtain the P-value for the estimated coefficients of the individual effects and the interaction term. The algorithm is implemented using the parallel computational capability of commercially available graphical processing units to greatly reduce the computation time involved. In the current setup and example data sets (211 cases, 222 controls, 299468 SNPs; and 601 cases, 825 controls, 291095 SNPs), this coefficient evaluation stage can be completed in roughly 1 day. Our method allows for exhaustive and rapid detection of significant SNP pair interactions without imposing significant marginal effects of the single loci involved in the pair. PMID:21150885

Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk: A genome-wide interaction study

PubMed Central

Rudolph, Anja; Hein, Rebecca; Lindström, Sara; Beckmann, Lars; Behrens, Sabine; Liu, Jianjun; Aschard, Hugues; Bolla, Manjeet K.; Wang, Jean; Truong, Thérèse; Cordina-Duverger, Emilie; Menegaux, Florence; Brüning, Thomas; Harth, Volker; Severi, Gianluca; Baglietto, Laura; Southey, Melissa; Chanock, Stephen J.; Lissowska, Jolanta; Figueroa, Jonine D.; Eriksson, Mikael; Humpreys, Keith; Darabi, Hatef; Olson, Janet E.; Stevens, Kristen N.; Vachon, Celine M.; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Ashworth, Alan; Orr, Nicholas; Schoemaker, Minouk; Webb, Penny M.; Guénel, Pascal; Brauch, Hiltrud; Giles, Graham; García-Closas, Montserrat; Czene, Kamila; Chenevix-Trench, Georgia; Couch, Fergus J.; Andrulis, Irene L.; Swerdlow, Anthony; Hunter, David J.; Flesch-Janys, Dieter; Easton, Douglas F.; Hall, Per; Nevanlinna, Heli; Kraft, Peter; Chang-Claude, Jenny

2013-01-01

Women using menopausal hormone therapy (MHT) are at increased risk to develop breast cancer (BC). To detect genetic modifiers of the association between current use of MHT and BC risk, we conducted a meta-analysis of four genome-wide case-only studies followed by replication in eleven case-control studies. We used a case-only design to assess interactions between single nucleotide polymorphisms (SNPs) and current MHT use on risk of overall and lobular BC. The discovery stage included 2,920 cases (541 lobular) from four genome-wide association studies. The top 1,391 SNPs showing P-values for interaction (Pint) <3.0×10−03 were selected for replication using pooled case-control data from eleven studies of the Breast Cancer Association Consortium, including 7,689 cases (676 lobular) and 9,266 controls. Fixed effects meta-analysis was used to derive combined Pint. No SNP reached genome-wide significance in either the discovery or combined stage. We observed effect modification of current MHT use on overall BC risk by two SNPs on chr13 near POMP (combined Pint≤8.9×10−06), two SNPs in SLC25A21 (combined Pint≤4.8×10−05), and three SNPs in PLCG2 (combined Pint≤4.5×10−05). The association between lobular BC risk was potentially modified by one SNP in TMEFF2 (combined Pint≤2.7×10−05), one SNP in CD80 (combined Pint≤8.2×10−06), three SNPs on chr17 near TMEM132E (combined Pint≤2.2×10−06), and two SNPs on chr18 near SLC25A52 (combined Pint≤4.6×10−05). In conclusion, polymorphisms in genes related to solute transportation in mitochondria, transmembrane signaling and immune cell activation are potentially modifying BC risk associated with current use of MHT. These findings warrant replication in independent studies. PMID:24080446

Genetic variation in the peroxisome proliferator-activated receptor (PPAR) and peroxisome proliferator-activated receptor gamma co-activator 1 (PGC1) gene families and type 2 diabetes

PubMed Central

Villegas, Raquel; Williams, Scott M.; Gao, Yu-Tang; Long, Jirong; Shi, Jiajun; Cai, Hui; Li, Honglan; Chen, Ching-Chu; Tai, E. Shyong; Hu, Frank; Cai, Qiuyin; Zheng, Wei; Shu, Xiao-Ou

2014-01-01

Summary We used a two-stage study design to evaluate whether variations in the peroxisome proliferator-activated receptors (PPAR) and the peroxisome proliferator-activated receptor gamma co-activator 1 (PGC1) gene families (PPARA, PPARG, PPARD, PPARGC1A, and PPARGC1B) are associated with T2D risk. Stage I used data from a genome-wide association study (GWAS) from Shanghai, China (1,019 T2D cases and 1,709 controls) and from a meta-analysis of data from the Asian Genetic Epidemiology Network for T2D (AGEN-T2D). Criteria for selection of SNPs for stage II were: 1) P<0.05 in single marker analysis in Shanghai GWAS and P<0.05 in the meta-analysis or 2) P<10−3 in the meta-analysis alone and 3) minor allele frequency ≥0.10. Nine SNPs from the PGC1 family were assessed in stage II (an independent set of middle-aged men and women from Shanghai with 1,700 T2D cases and 1,647 controls). One SNP in PPARGC1B, rs251464, was replicated in stage II (OR=0.87; 95% CI: 0.77–0.99). Gene-body mass index (BMI) and gene-exercise interactions and T2D risk were evaluated in a combined dataset (Shanghai GWAS and stage II data: 2,719 cases and 3,356 controls). One SNP in PPARGC1A, rs12640088, had a significant interaction with BMI. No interactions between the PPARGC1B gene and BMI or exercise were observed. PMID:24359475

Medical and nonmedical factors influencing utilization of delayed pushing in the second stage.

PubMed

Frey, Heather A; Tuuli, Methodius G; Cortez, Sarah; Odibo, Anthony O; Roehl, Kimberly A; Shanks, Anthony L; Macones, George A; Cahill, Alison G

2013-08-01

To evaluate factors impacting selection to delayed pushing in the second stage of labor. This case-control study was a secondary analysis of a large retrospective cohort study. Cases included women who delayed pushing for 60 minutes or more in the second stage of labor. Controls began pushing prior to 60 minutes from the time of diagnosis of complete dilation. Demographic, labor, and nonmedical factors were compared among cases and controls. Logistic regression modeling was used to identify factors independently associated with delayed pushing. We identified 471 women who delayed pushing and 4819 controls. Nulliparity, maternal body mass index > 25, high fetal station at complete dilation, regional anesthesia use, and start of second stage during staffing shift change were independent factors associated with increased use of delayed pushing. On the other hand, black race and second-stage management during night shift were associated with lower odds of employing delayed pushing. Delayed pushing was more commonly employed in nulliparous women, but 38.9% of multiparous women also delayed pushing. We identified multiple factors associated with use of delayed pushing. This study helps to define current patterns of second-stage labor management. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Lung cancer in renal transplant recipients: A case-control study.

PubMed

Rousseau-Gazaniol, Claire; Fraboulet, Séverine; Couderc, Louis-Jean; Kreis, Henri; Borie, Raphaël; Tricot, Leila; Anglicheau, Dany; Martinez, Frank; Doubre, Hélène; Bonnette, Pierre; Mellot, François; Massiani, Marie-Ange; Pelle, Gaëlle; Sage, Edouard; Moisson, Patricia; Delahousse, Michel; Zemoura, Leila; Chapelier, Alain; Hamid, Abdul Monem; Puyo, Philippe; Longchampt, Elisabeth; Legendre, Christophe; Friard, Sylvie; Catherinot, Emilie

2017-09-01

Solid organ transplant patients are at heightened risk of several cancers compared to the general population. Secondary to a higher number of procedures and better survival after transplantation, cancer is a rising health concern in this situation. Limited data exist for lung cancer (LC) after renal transplantation. We report here the most important series of renal transplant recipients with lung cancer. Retrospective study of all cases of LC diagnosed in three French Renal Transplant Units from 2003 to 2012. A control group consisted of non-transplant patients with LC matched with the cases for age (<30; 30-50; 50-65; >65 years), gender and diagnosis date. We recruited two controls for each case. Thirty patients (median age 60 years; range 29-85; male/female ratio 80/20%) with LC were analysed. LC incidence was 1.89/1000 person-years over the period 2008-2012. All patients were former or active smokers (median 30 pack-years). Transplanted patients had significantly more comorbidities, mainly cardiovascular disease. The median interval of time from kidney transplantation (KT) to diagnosis of LC was 7 years (range 0.5-47 years). LC was incidentally diagnosed in 40%. Most patients (70%) had advanced LC (stage III or IV) disease. Stage of LC at diagnosis was similar in cases and controls. Surgery and chemotherapy were proposed to the same proportion of patients. In cases, mortality was cancer related in 87% and median survival time after diagnosis was 24 months. Survival was not significantly different between the 2 groups. Despite frequent medical and radiological examinations, diagnosis of LC is usually made at an advanced stage and the overall prognosis remains poor. Copyright © 2017 Elsevier B.V. All rights reserved.

Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-β1b (MIRACLE trial): study protocol for a randomized controlled trial.

PubMed

Arabi, Yaseen M; Alothman, Adel; Balkhy, Hanan H; Al-Dawood, Abdulaziz; AlJohani, Sameera; Al Harbi, Shmeylan; Kojan, Suleiman; Al Jeraisy, Majed; Deeb, Ahmad M; Assiri, Abdullah M; Al-Hameed, Fahad; AlSaedi, Asim; Mandourah, Yasser; Almekhlafi, Ghaleb A; Sherbeeni, Nisreen Murad; Elzein, Fatehi Elnour; Memon, Javed; Taha, Yusri; Almotairi, Abdullah; Maghrabi, Khalid A; Qushmaq, Ismael; Al Bshabshe, Ali; Kharaba, Ayman; Shalhoub, Sarah; Jose, Jesna; Fowler, Robert A; Hayden, Frederick G; Hussein, Mohamed A

2018-01-30

It had been more than 5 years since the first case of Middle East Respiratory Syndrome coronavirus infection (MERS-CoV) was recorded, but no specific treatment has been investigated in randomized clinical trials. Results from in vitro and animal studies suggest that a combination of lopinavir/ritonavir and interferon-β1b (IFN-β1b) may be effective against MERS-CoV. The aim of this study is to investigate the efficacy of treatment with a combination of lopinavir/ritonavir and recombinant IFN-β1b provided with standard supportive care, compared to treatment with placebo provided with standard supportive care in patients with laboratory-confirmed MERS requiring hospital admission. The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. Hospitalized adult patients with laboratory-confirmed MERS will be enrolled in this recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The trial is initially designed to include 2 two-stage components. The first two-stage component is designed to adjust sample size and determine futility stopping, but not efficacy stopping. The second two-stage component is designed to determine efficacy stopping and possibly readjustment of sample size. The primary outcome is 90-day mortality. This will be the first randomized controlled trial of a potential treatment for MERS. The study is sponsored by King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. Enrollment for this study began in November 2016, and has enrolled thirteen patients as of Jan 24-2018. ClinicalTrials.gov, ID: NCT02845843 . Registered on 27 July 2016.

Comprehensive Pathway-Based Association Study of DNA Repair Gene Variants and the Risk of Nasopharyngeal Carcinoma

PubMed Central

Qin, Hai-De; Shugart, Yin Yao; Bei, Jin-Xin; Pan, Qing-Hua; Chen, Lina; Feng, Qi-Sheng; Chen, Li-Zhen; Huang, Wei; Liu, Jian Jun; Jorgensen, Timothy J.; Zeng, Yi-Xin; Jia, Wei-Hua

2011-01-01

DNA repair plays a central role in protecting against environmental carcinogenesis, and genetic variants of DNA repair genes have been reported to be associated with several human malignancies. To assess whether DNA gene variants were associated with nasopharyngeal carcinoma (NPC) risk, a candidate gene association study was conducted among the Cantonese population within the Guangdong Province, China --the ethnic group with the highest risk for NPC. A two-stage study design was utilized. In the discovery stage, 676 tagging SNPs covering 88 DNA repair genes were genotyped in a matched case-control study (cases/controls = 755/755). Eleven SNPs with Ptrend <0.01 were identified. Seven of these SNPs were located within three genes, RAD51L1, BRCA2 and TP53BP1. In the validation stage, these 11 SNPs were genotyped in a separate Cantonese population (cases/controls = 1,568/1,297). Two of the SNPs (rs927220 and rs11158728) – both in RAD51L1 – remained strongly associated with NPC. The SNP rs927220 had a significant Pcombined of 5.55 × 10−5, with OR = 1.20 (95%CI = 1.10 to 1.30), Bonferroni corrected P = 0.0381. The other SNP (rs11158728), which is in strong LD with rs927220 (r2 = 0.7), had a significant Pcombined of 2.0 × 10−4, Bonferroni corrected P = 0.1372. Gene-environment interaction analysis suggested that the exposures of salted-fish consumption and cigarette smoking had potential interactions with DNA repair gene variations, but need to be further investigated. Our findings support the notion that DNA repair genes, in particular RAD51L1, play a role in NPC etiology and development. PMID:21368091

Genome-wide interaction study of smoking behavior and non-small cell lung cancer risk in Caucasian population.

PubMed

Li, Yafang; Xiao, Xiangjun; Han, Younghun; Gorlova, Olga; Qian, David; Leighl, Natasha; Johansen, Jakob S; Barnett, Matt; Chen, Chu; Goodman, Gary; Cox, Angela; Taylor, Fiona; Woll, Penella; Wichmann, H-Erich; Manz, Judith; Muley, Thomas; Risch, Angela; Rosenberger, Albert; Arnold, Susanne M; Haura, Eric B; Bolca, Ciprian; Holcatova, Ivana; Janout, Vladimir; Kontic, Milica; Lissowska, Jolanta; Mukeria, Anush; Ognjanovic, Simona; Orlowski, Tadeusz M; Scelo, Ghislaine; Swiatkowska, Beata; Zaridze, David; Bakke, Per; Skaug, Vidar; Zienolddiny, Shanbeh; Duell, Eric J; Butler, Lesley M; Houlston, Richard; Soler Artigas, María; Grankvist, Kjell; Johansson, Mikael; Shepherd, Frances A; Marcus, Michael W; Brunnström, Hans; Manjer, Jonas; Melander, Olle; Muller, David C; Overvad, Kim; Trichopoulou, Antonia; Tumino, Rosario; Liu, Geoffrey; Bojesen, Stig E; Wu, Xifeng; Marchand, Loic Le; Albanes, Demetrios; Bickeböller, Heike; Aldrich, Melinda C; Bush, William S; Tardon, Adonina; Rennert, Gad; Teare, M Dawn; Field, John K; Kiemeney, Lambertus A; Lazarus, Philip; Haugen, Aage; Lam, Stephen; Schabath, Matthew B; Andrew, Angeline S; Bertazzi, Pier Alberto; Pesatori, Angela C; Christiani, David C; Caporaso, Neil; Johansson, Mattias; McKay, James D; Brennan, Paul; Hung, Rayjean J; Amos, Christopher I

2018-03-08

Non-small cell lung cancer is the most common type of lung cancer. Both environmental and genetic risk factors contribute to lung carcinogenesis. We conducted a genome-wide interaction analysis between single nucleotide polymorphisms (SNPs) and smoking status (never- versus ever-smokers) in a European-descent population. We adopted a two-step analysis strategy in the discovery stage: we first conducted a case-only interaction analysis to assess the relationship between SNPs and smoking behavior using 13336 non-small cell lung cancer cases. Candidate SNPs with P-value <0.001 were further analyzed using a standard case-control interaction analysis including 13970 controls. The significant SNPs with P-value <3.5 × 10-5 (correcting for multiple tests) from the case-control analysis in the discovery stage were further validated using an independent replication dataset comprising 5377 controls and 3054 non-small cell lung cancer cases. We further stratified the analysis by histological subtypes. Two novel SNPs, rs6441286 and rs17723637, were identified for overall lung cancer risk. The interaction odds ratio and meta-analysis P-value for these two SNPs were 1.24 with 6.96 × 10-7 and 1.37 with 3.49 × 10-7, respectively. In addition, interaction of smoking with rs4751674 was identified in squamous cell lung carcinoma with an odds ratio of 0.58 and P-value of 8.12 × 10-7. This study is by far the largest genome-wide SNP-smoking interaction analysis reported for lung cancer. The three identified novel SNPs provide potential candidate biomarkers for lung cancer risk screening and intervention. The results from our study reinforce that gene-smoking interactions play important roles in the etiology of lung cancer and account for part of the missing heritability of this disease.

Dihydrotestosterone and testosterone levels in men screened for prostate cancer: a study of a randomized population.

PubMed

Gustafsson, O; Norming, U; Gustafsson, S; Eneroth, P; Aström, G; Nyman, C R

1996-03-01

To investigate the possible relationship between serum levels of prostate specific antigen (PSA), dihydrotestosterone (DHT), testosterone, sexual-hormone binding globulin (SHBG) and tumour stage, grade and ploidy in 65 cases of prostate cancer diagnosed in a screening study compared to 130 controls from the same population. From a population of 26,602 men between the ages of 55 and 70 years, 2400 were selected randomly and invited to undergo screening for prostate cancer using a digital rectal examination, transrectal ultrasonography and PSA analysis. Among the 1782 attendees, 65 cases of prostate cancer were diagnosed. Each case was matched with two control subjects of similar age and prostate volume from the screening population. Frozen serum samples were analysed for PSA, DHT, testosterone and SHBG, and compared to the diagnosis and tumour stage, grade and ploidy. Comparisons between these variables, and multivariate and regression analyses were performed. There were significant differences in PSA level with all variables except tumour ploidy. DHT levels were slightly lower in patients with prostate cancer but the difference was not statistically significant. There was a trend towards lower DHT values in more advanced tumours and the difference for T-stages was close to statistical significance (P = 0.059). Testosterone levels were lower in patients with cancer than in the control group, but the differences were not significant. There was no correlation between testosterone levels, tumour stage and ploidy, but the differences in testosterone level in tumours of a low grade of differentiation compared to those with intermediate and high grade was nearly significant (P = 0.058). The testosterone/DHT ratio tended to be higher in patients with more advanced tumours. SHBG levels were lower in patients with cancer than in controls but the differences were not statistically significant. There were no systematic variations of tumour stage, grade and ploidy. Multivariate analysis showed that if the PSA level was known, then DHT, testosterone or SHBG added no further information concerning diagnosis, stage, grade or ploidy. Regression analysis on T-stage, PSA level and DHT showed an inverse linear relationship between PSA and DHT for stage T-3 (P = 0.035), but there was no relationship between PSA and testosterone. PSA was of value in discriminating between cases and controls and between various tumour stages and grades, but no statistically significant correlation was found for ploidy. If PSA level was known, no other variable added information in individual cases. Within a group, DHT levels tended to be lower among cases and in those with more advanced tumours. There was an inverse relationship between tumour volume, as defined by PSA level, and 5 alpha-reductase activity, as defined by DHT level, and the testosterone/DHT ratio. This trend was most obvious with T-stage. No systematic variation were found in the levels of testosterone or SHBG.

[Two-stage revision of infected total knee arthroplasty using antibiotic-impregnated articulating cement spacer].

PubMed

Cai, Pengde; Hu, Yihe; Xie, Lie; Wang, Long

2012-10-01

To investigate the effectiveness of two-stage revision of infected total knee arthroplasty (TKA) using an antibiotic-impregnated articulating cement spacer. The clinical data were analyzed from 23 patients (23 knees) undergoing two-stage revision for late infection after primary TKA between January 2007 and December 2009. There were 15 males and 8 females, aged from 43 to 75 years (mean, 65.2 years). Infection occurred at 13-52 months (mean, 17.3 months) after TKA. The time interval between infection and admission ranged from 15 days to 7 months (mean, 2.1 months). One-stage operation included surgical debridement and removal of all knee prosthesis and cement, then an antibiotic-impregnated articulating cement spacer was implanted. The re-implantation of prosthesis was performed after 8-10 weeks when infections were controlled. The American Hospital for Special Surgery (HSS) score and Knee Society Score (KSS) were used to compare the function of the knee between pre- and post-revision. The rate of infection control and complication were analyzed. All incisions healed primarily. Re-infection occurred in 2 cases after two-stage revision, and infection was controlled in the other 21 cases, with an infection control rate of 91.3%. The patients were followed up 2-5 years (mean, 3.6 years). The HSS score was increased from 60.6 +/- 9.8 at pre-revision to 82.3 +/- 7.4 at last follow-up, the KSS score was increased from 110.7 +/- 9.6 at pre-revision to 134.0 +/- 10.5 at last follow-up, all showing significant differences (P < 0.01). Radiographs showed that prosthesis had good position with no loosening, fracture, or periprosthetic radiolucent. Two-stage revision using an antibiotic-impregnated articulating cement spacer is an effective method to control infected TKA and to restore the function of affected knee.

A two-stage genome-wide association study of sporadic amyotrophic lateral sclerosis.

PubMed

Chiò, Adriano; Schymick, Jennifer C; Restagno, Gabriella; Scholz, Sonja W; Lombardo, Federica; Lai, Shiao-Lin; Mora, Gabriele; Fung, Hon-Chung; Britton, Angela; Arepalli, Sampath; Gibbs, J Raphael; Nalls, Michael; Berger, Stephen; Kwee, Lydia Coulter; Oddone, Eugene Z; Ding, Jinhui; Crews, Cynthia; Rafferty, Ian; Washecka, Nicole; Hernandez, Dena; Ferrucci, Luigi; Bandinelli, Stefania; Guralnik, Jack; Macciardi, Fabio; Torri, Federica; Lupoli, Sara; Chanock, Stephen J; Thomas, Gilles; Hunter, David J; Gieger, Christian; Wichmann, H Erich; Calvo, Andrea; Mutani, Roberto; Battistini, Stefania; Giannini, Fabio; Caponnetto, Claudia; Mancardi, Giovanni Luigi; La Bella, Vincenzo; Valentino, Francesca; Monsurrò, Maria Rosaria; Tedeschi, Gioacchino; Marinou, Kalliopi; Sabatelli, Mario; Conte, Amelia; Mandrioli, Jessica; Sola, Patrizia; Salvi, Fabrizio; Bartolomei, Ilaria; Siciliano, Gabriele; Carlesi, Cecilia; Orrell, Richard W; Talbot, Kevin; Simmons, Zachary; Connor, James; Pioro, Erik P; Dunkley, Travis; Stephan, Dietrich A; Kasperaviciute, Dalia; Fisher, Elizabeth M; Jabonka, Sibylle; Sendtner, Michael; Beck, Marcus; Bruijn, Lucie; Rothstein, Jeffrey; Schmidt, Silke; Singleton, Andrew; Hardy, John; Traynor, Bryan J

2009-04-15

The cause of sporadic amyotrophic lateral sclerosis (ALS) is largely unknown, but genetic factors are thought to play a significant role in determining susceptibility to motor neuron degeneration. To identify genetic variants altering risk of ALS, we undertook a two-stage genome-wide association study (GWAS): we followed our initial GWAS of 545 066 SNPs in 553 individuals with ALS and 2338 controls by testing the 7600 most associated SNPs from the first stage in three independent cohorts consisting of 2160 cases and 3008 controls. None of the SNPs selected for replication exceeded the Bonferroni threshold for significance. The two most significantly associated SNPs, rs2708909 and rs2708851 [odds ratio (OR) = 1.17 and 1.18, and P-values = 6.98 x 10(-7) and 1.16 x 10(-6)], were located on chromosome 7p13.3 within a 175 kb linkage disequilibrium block containing the SUNC1, HUS1 and C7orf57 genes. These associations did not achieve genome-wide significance in the original cohort and failed to replicate in an additional independent cohort of 989 US cases and 327 controls (OR = 1.18 and 1.19, P-values = 0.08 and 0.06, respectively). Thus, we chose to cautiously interpret our data as hypothesis-generating requiring additional confirmation, especially as all previously reported loci for ALS have failed to replicate successfully. Indeed, the three loci (FGGY, ITPR2 and DPP6) identified in previous GWAS of sporadic ALS were not significantly associated with disease in our study. Our findings suggest that ALS is more genetically and clinically heterogeneous than previously recognized. Genotype data from our study have been made available online to facilitate such future endeavors.

A two-stage genome-wide association study of sporadic amyotrophic lateral sclerosis

PubMed Central

Chiò, Adriano; Schymick, Jennifer C.; Restagno, Gabriella; Scholz, Sonja W.; Lombardo, Federica; Lai, Shiao-Lin; Mora, Gabriele; Fung, Hon-Chung; Britton, Angela; Arepalli, Sampath; Gibbs, J. Raphael; Nalls, Michael; Berger, Stephen; Kwee, Lydia Coulter; Oddone, Eugene Z.; Ding, Jinhui; Crews, Cynthia; Rafferty, Ian; Washecka, Nicole; Hernandez, Dena; Ferrucci, Luigi; Bandinelli, Stefania; Guralnik, Jack; Macciardi, Fabio; Torri, Federica; Lupoli, Sara; Chanock, Stephen J.; Thomas, Gilles; Hunter, David J.; Gieger, Christian; Wichmann, H. Erich; Calvo, Andrea; Mutani, Roberto; Battistini, Stefania; Giannini, Fabio; Caponnetto, Claudia; Mancardi, Giovanni Luigi; La Bella, Vincenzo; Valentino, Francesca; Monsurrò, Maria Rosaria; Tedeschi, Gioacchino; Marinou, Kalliopi; Sabatelli, Mario; Conte, Amelia; Mandrioli, Jessica; Sola, Patrizia; Salvi, Fabrizio; Bartolomei, Ilaria; Siciliano, Gabriele; Carlesi, Cecilia; Orrell, Richard W.; Talbot, Kevin; Simmons, Zachary; Connor, James; Pioro, Erik P.; Dunkley, Travis; Stephan, Dietrich A.; Kasperaviciute, Dalia; Fisher, Elizabeth M.; Jabonka, Sibylle; Sendtner, Michael; Beck, Marcus; Bruijn, Lucie; Rothstein, Jeffrey; Schmidt, Silke; Singleton, Andrew; Hardy, John; Traynor, Bryan J.

2009-01-01

The cause of sporadic amyotrophic lateral sclerosis (ALS) is largely unknown, but genetic factors are thought to play a significant role in determining susceptibility to motor neuron degeneration. To identify genetic variants altering risk of ALS, we undertook a two-stage genome-wide association study (GWAS): we followed our initial GWAS of 545 066 SNPs in 553 individuals with ALS and 2338 controls by testing the 7600 most associated SNPs from the first stage in three independent cohorts consisting of 2160 cases and 3008 controls. None of the SNPs selected for replication exceeded the Bonferroni threshold for significance. The two most significantly associated SNPs, rs2708909 and rs2708851 [odds ratio (OR) = 1.17 and 1.18, and P-values = 6.98 × 10−7 and 1.16 × 10−6], were located on chromosome 7p13.3 within a 175 kb linkage disequilibrium block containing the SUNC1, HUS1 and C7orf57 genes. These associations did not achieve genome-wide significance in the original cohort and failed to replicate in an additional independent cohort of 989 US cases and 327 controls (OR = 1.18 and 1.19, P-values = 0.08 and 0.06, respectively). Thus, we chose to cautiously interpret our data as hypothesis-generating requiring additional confirmation, especially as all previously reported loci for ALS have failed to replicate successfully. Indeed, the three loci (FGGY, ITPR2 and DPP6) identified in previous GWAS of sporadic ALS were not significantly associated with disease in our study. Our findings suggest that ALS is more genetically and clinically heterogeneous than previously recognized. Genotype data from our study have been made available online to facilitate such future endeavors. PMID:19193627

Identification of common variants influencing risk of the tauopathy Progressive Supranuclear Palsy

PubMed Central

Höglinger, Günter U.; Melhem, Nadine M.; Dickson, Dennis W.; Sleiman, Patrick M.A.; Wang, Li-San; Klei, Lambertus; Rademakers, Rosa; de Silva, Rohan; Litvan, Irene; Riley, David E.; van Swieten, John C.; Heutink, Peter; Wszolek, Zbigniew K.; Uitti, Ryan J.; Vandrovcova, Jana; Hurtig, Howard I.; Gross, Rachel G.; Maetzler, Walter; Goldwurm, Stefano; Tolosa, Eduardo; Borroni, Barbara; Pastor, Pau; Cantwell, Laura B.; Han, Mi Ryung; Dillman, Allissa; van der Brug, Marcel P.; Gibbs, J Raphael; Cookson, Mark R.; Hernandez, Dena G.; Singleton, Andrew B.; Farrer, Matthew J.; Yu, Chang-En; Golbe, Lawrence I.; Revesz, Tamas; Hardy, John; Lees, Andrew J.; Devlin, Bernie; Hakonarson, Hakon; Müller, Ulrich; Schellenberg, Gerard D.

2011-01-01

Progressive supranuclear palsy (PSP) is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common being Alzheimer’s disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 PSP cases and 3,247 controls (Stage 1) followed up by a second stage where 1,051 cases and 3,560 controls were genotyped for Stage 1 SNPs that yielded P ≤ 10−3. We found significant novel signals (P < 5 × 10−8) associated with PSP risk at STX6, EIF2AK3, and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response, and for a myelin structural component. PMID:21685912

Malaria situation and anopheline mosquitoes in qom province, central iran.

PubMed

Farzinnia, B; Saghafipour, A; Abai, Mr

2010-01-01

The aims of this study was to analysis the current situation of malaria and to find the distribution of anopheline mosquitoes, as probable vectors of the disease, in Qom Province, central Iran. This study was carried out in two parts. First stage was data collection about malaria cases using recorded documents of patients in the Province health center, during 2001-2008. The second stage was entomological survey conducted by mosquito larval collection method in 4 villages with different geographical positions in 2008. Data were analyzed using Excel software. Of 4456 blood slides, 10.9% out were positive. Most of cases were imported from other countries (90.4%), mainly from Afghanistan (56.5%) and Pakistan (16.3%). Slide positive rate showed a maximum of 16.9% and a minimum of 2.9% in 2008 and 2007, respectively. Plasmodium vivax was causative agent of 93.75% of cases, followed by P. falciparum (6.25%). More than 15 years old age group contained the most malaria reported cases (66.7%). Two Anopheles species, An. superpictus and An. claviger were collected and identified. This is the first report of Anopheles claviger in Qom Province. Malaria is in the control stage in Qom Province. The rate of local transmission is very low (only 1 case), shows Anopheles superpictus, as the main malaria vector of central part of Iran, can play its role in malaria transmission in the area.

Frictional processes of bimaterial interfaces at seismic slip rates.

NASA Astrophysics Data System (ADS)

Passelegue, F. X.; Fabbri, O.; Leclère, H.; Spagnuolo, E.; Di Toro, G.

2017-12-01

Large subduction earthquakes ruptures propagate from crustal rock toward the sea floor along frictional interfaces of different lythologies. Up to now, frictional processes of rocks were mainly investigated along single material experimental faults. Here, we present the results of high velocity friction experiments coupled with high frequency acoustic monitoring system on biomaterial interfaces including gabbro, pyroxenite and serpentinized peridotite (>95%), following a recent field investigation highlighting bimaterial contacts in the Corsica ophiolitic nappe. We first studied the frictional processes of single materials which result in a mechanical behaviour comparable to previous studies. Both gabbro and pyroxenite exhibit two weakening stages. The first one corresponds to flash heating and the second stage occurs concomitantly with complete melting of the interface. In the case of serpentinite, only one weakening stage is observed, after a weakening slip distance of only few centimeters. We then conducted bimaterial experiments. The two couples tested were gabbro/pyroxenite and gabbro/serpentinite, as observed along natural fault zones (Corsica, France). In the case of gabbro/serpentinite, we observe that frictional processes are controlled by serpentinite. Mechanical curves replicate the behaviour of single serpentinite friction experiments. We observe that few melting occurs, and that the product of experiments consists in fine grained cataclasite, as observed in the field. The case of gabbro/pyroxenite is more complicated. The first weakening is controlled by the lithology of the sample installed on the static part of the rotary apparatus. However, the second weakening is controlled by the gabbro and mechanical curves are identical than those obtained in the case of single gabbro experiments. Supported by microstructural analysis and acoustic activity, our results suggest that frictional processes of bimaterial interfaces are controlled by the material presenting the lower weakening temperature. Finally, we show that bimaterial interfaces are expected to affect locally the rate of the stress transfer during large earthquakes, and induce accelerations or decelerations of the rupture front, explaining local emissions of high frequencies recorded during large ruptures.

Concerns About Lung Cancer Among Prisoners.

PubMed

Renault, Luc; Perrot, Emmanuel; Pradat, Eric; Bartoli, Christophe; Greillier, Laurent; Remacle-Bonnet, Anne; Telmon, Norbert; Mazières, Julien; Molinier, Laurent; Couraud, Sébastien

2018-02-01

Few studies have looked at lung cancer in prisoners, despite this population is possibly at increased risk of malignancy. In a previous study, we found an early onset of lung cancer in prisoners. Thus, the present CARCAN study was aimed at assessing the epidemiological characteristics, management, prognosis, and incidence of lung cancer in prisoners compared to a sample of non-prisoner patients. We performed a multi-center observational case-control study. Cases were prisoners diagnosed with lung cancer from 2005 to 2013. Controls were non-prisoner lung cancer patients selected from hospital databases and randomly matched to cases (targeted case-control ratio: 1:3). Incidence rates in both groups were calculated using national statistics. Seventy-two cases and 170 controls met inclusion criteria. Cases were mainly men (99%). Mean age at diagnosis was 52.9 (± 11.0) in cases and 64.3 (± 10.1) in controls (p < 0.0001). More case patients were current smokers compared to control patients (83% vs 53%; p < 0.0001). We found no significant differences between the two groups as concerns histologic types, TNM stages at diagnosis, initially-employed treatments, times to management or survival. Incidence rates (2008-2012) in male prisoners were higher than those in the general population in all concerned age groups. There is a shift of lung cancer toward young people in prisons. However, the presentation, management, and prognosis of lung cancer are similar between prisoners and non-prisoners. These finding could justify a specific screening policy for the incarcerated populations.

Methods to control for unmeasured confounding in pharmacoepidemiology: an overview.

PubMed

Uddin, Md Jamal; Groenwold, Rolf H H; Ali, Mohammed Sanni; de Boer, Anthonius; Roes, Kit C B; Chowdhury, Muhammad A B; Klungel, Olaf H

2016-06-01

Background Unmeasured confounding is one of the principal problems in pharmacoepidemiologic studies. Several methods have been proposed to detect or control for unmeasured confounding either at the study design phase or the data analysis phase. Aim of the Review To provide an overview of commonly used methods to detect or control for unmeasured confounding and to provide recommendations for proper application in pharmacoepidemiology. Methods/Results Methods to control for unmeasured confounding in the design phase of a study are case only designs (e.g., case-crossover, case-time control, self-controlled case series) and the prior event rate ratio adjustment method. Methods that can be applied in the data analysis phase include, negative control method, perturbation variable method, instrumental variable methods, sensitivity analysis, and ecological analysis. A separate group of methods are those in which additional information on confounders is collected from a substudy. The latter group includes external adjustment, propensity score calibration, two-stage sampling, and multiple imputation. Conclusion As the performance and application of the methods to handle unmeasured confounding may differ across studies and across databases, we stress the importance of using both statistical evidence and substantial clinical knowledge for interpretation of the study results.

Single-Session Personalized Cognitive Counseling to Change HIV Risk Behavior among HIV-Negative Men Who Have Sex with Men: A Two-Part Case Study

ERIC Educational Resources Information Center

McPhee, Brian; Skinta, Matthew D.; Paul, Jay; Dilley, James W.

2012-01-01

Two previous randomized controlled clinical trials have shown the effectiveness of a single-session cognitive intervention, personalized cognitive counseling (PCC), in decreasing HIV risk among men who have sex with men (MSM; Dilley et al., 2002; Dilley et al., 2007). PCC is a counseling technique based on social cognitive theory and the stages of…

The Efficacy of Propranolol in Retinopathy of Prematurity and its Correlation with the Platelet Mass Index.

PubMed

Korkmaz, Levent; Baştuğ, Osman; Ozdemir, Ahmet; Korkut, Sabriye; Karaca, Cagatay; Akin, Mustafa Ali; Gunes, Tamer; Kurtoglu, Selim; Ozturk, Mehmet Adnan

2017-01-01

Retinopathy of Prematurity (ROP) is a proliferative vitreoretinopathy which is one of the most frequent causes of blindness in children. In an attempt to find a solution to this important problem in preterm children, the search for new, effective treatment modalities with fewer side effects is underway. In our study, which was planned for this reason, we aimed to investigate the effects of propranolol treatment applied to cases of ROP in various stages during the second phase (known as the neovascularization-hypoxia phase) and to determine the correlation of these effects with the platelet mass index (PMI). A total of 171 preterm infants at risk of ROP were selected randomly for inclusion in the study. All of the patients were classified according to their stage of ROP and were divided into control and treatment groups. While the cases in the control group were administered physiological saline solution, those in the treatment group were administered propranolol in the period that corresponded to the second stage of the disease. The thrombocyte and PMI values in the first and second stages of each study group were recorded. A significant difference was found between the control and treatment groups of the stage 2 ROP study subjects. In the stage 2 ROP study group, no significant difference was detected between the control and treatment cases in terms of platelet counts in phase 1 or in the PMI values and the thrombolytic counts in phase 2. On the other hand, in phase 2 of the stage 2 ROP study subjects significant differences were detected between the control and treatment group in terms of PMI values. In the study, it was found in the stage 2 ROP study group that propranolol reduced the need for laser photocoagulation significantly. Also, in parallel to the efficacy of propranolol in this study group, a decrease was observed in PMI values.

Genome-wide association study identifies novel breast cancer susceptibility loci

PubMed Central

Easton, Douglas F.; Pooley, Karen A.; Dunning, Alison M.; Pharoah, Paul D. P.; Thompson, Deborah; Ballinger, Dennis G.; Struewing, Jeffery P.; Morrison, Jonathan; Field, Helen; Luben, Robert; Wareham, Nicholas; Ahmed, Shahana; Healey, Catherine S.; Bowman, Richard; Meyer, Kerstin B.; Haiman, Christopher A.; Kolonel, Laurence K.; Henderson, Brian E.; Marchand, Loic Le; Brennan, Paul; Sangrajrang, Suleeporn; Gaborieau, Valerie; Odefrey, Fabrice; Shen, Chen-Yang; Wu, Pei-Ei; Wang, Hui-Chun; Eccles, Diana; Evans, D. Gareth; Peto, Julian; Fletcher, Olivia; Johnson, Nichola; Seal, Sheila; Stratton, Michael R.; Rahman, Nazneen; Chenevix-Trench, Georgia; Bojesen, Stig E.; Nordestgaard, Børge G.; Axelsson, Christen K.; Garcia-Closas, Montserrat; Brinton, Louise; Chanock, Stephen; Lissowska, Jolanta; Peplonska, Beata; Nevanlinna, Heli; Fagerholm, Rainer; Eerola, Hannaleena; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Ahn, Sei-Hyun; Hunter, David J.; Hankinson, Susan E.; Cox, David G.; Hall, Per; Wedren, Sara; Liu, Jianjun; Low, Yen-Ling; Bogdanova, Natalia; Schürmann, Peter; Dörk, Thilo; Tollenaar, Rob A. E. M.; Jacobi, Catharina E.; Devilee, Peter; Klijn, Jan G. M.; Sigurdson, Alice J.; Doody, Michele M.; Alexander, Bruce H.; Zhang, Jinghui; Cox, Angela; Brock, Ian W.; MacPherson, Gordon; Reed, Malcolm W. R.; Couch, Fergus J.; Goode, Ellen L.; Olson, Janet E.; Meijers-Heijboer, Hanne; van den Ouweland, Ans; Uitterlinden, André; Rivadeneira, Fernando; Milne, Roger L.; Ribas, Gloria; Gonzalez-Neira, Anna; Benitez, Javier; Hopper, John L.; McCredie, Margaret; Southey, Melissa; Giles, Graham G.; Schroen, Chris; Justenhoven, Christina; Brauch, Hiltrud; Hamann, Ute; Ko, Yon-Dschun; Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Mannermaa, Arto; Kosma, Veli-Matti; Kataja, Vesa; Hartikainen, Jaana; Day, Nicholas E.; Cox, David R.; Ponder, Bruce A. J.; Luccarini, Craig; Conroy, Don; Shah, Mitul; Munday, Hannah; Jordan, Clare; Perkins, Barbara; West, Judy; Redman, Karen; Driver, Kristy; Aghmesheh, Morteza; Amor, David; Andrews, Lesley; Antill, Yoland; Armes, Jane; Armitage, Shane; Arnold, Leanne; Balleine, Rosemary; Begley, Glenn; Beilby, John; Bennett, Ian; Bennett, Barbara; Berry, Geoffrey; Blackburn, Anneke; Brennan, Meagan; Brown, Melissa; Buckley, Michael; Burke, Jo; Butow, Phyllis; Byron, Keith; Callen, David; Campbell, Ian; Chenevix-Trench, Georgia; Clarke, Christine; Colley, Alison; Cotton, Dick; Cui, Jisheng; Culling, Bronwyn; Cummings, Margaret; Dawson, Sarah-Jane; Dixon, Joanne; Dobrovic, Alexander; Dudding, Tracy; Edkins, Ted; Eisenbruch, Maurice; Farshid, Gelareh; Fawcett, Susan; Field, Michael; Firgaira, Frank; Fleming, Jean; Forbes, John; Friedlander, Michael; Gaff, Clara; Gardner, Mac; Gattas, Mike; George, Peter; Giles, Graham; Gill, Grantley; Goldblatt, Jack; Greening, Sian; Grist, Scott; Haan, Eric; Harris, Marion; Hart, Stewart; Hayward, Nick; Hopper, John; Humphrey, Evelyn; Jenkins, Mark; Jones, Alison; Kefford, Rick; Kirk, Judy; Kollias, James; Kovalenko, Sergey; Lakhani, Sunil; Leary, Jennifer; Lim, Jacqueline; Lindeman, Geoff; Lipton, Lara; Lobb, Liz; Maclurcan, Mariette; Mann, Graham; Marsh, Deborah; McCredie, Margaret; McKay, Michael; McLachlan, Sue Anne; Meiser, Bettina; Milne, Roger; Mitchell, Gillian; Newman, Beth; O'Loughlin, Imelda; Osborne, Richard; Peters, Lester; Phillips, Kelly; Price, Melanie; Reeve, Jeanne; Reeve, Tony; Richards, Robert; Rinehart, Gina; Robinson, Bridget; Rudzki, Barney; Salisbury, Elizabeth; Sambrook, Joe; Saunders, Christobel; Scott, Clare; Scott, Elizabeth; Scott, Rodney; Seshadri, Ram; Shelling, Andrew; Southey, Melissa; Spurdle, Amanda; Suthers, Graeme; Taylor, Donna; Tennant, Christopher; Thorne, Heather; Townshend, Sharron; Tucker, Kathy; Tyler, Janet; Venter, Deon; Visvader, Jane; Walpole, Ian; Ward, Robin; Waring, Paul; Warner, Bev; Warren, Graham; Watson, Elizabeth; Williams, Rachael; Wilson, Judy; Winship, Ingrid; Young, Mary Ann; Bowtell, David; Green, Adele; deFazio, Anna; Chenevix-Trench, Georgia; Gertig, Dorota; Webb, Penny

2009-01-01

Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860 cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were estimated to correlate with 77% of known common SNPs in Europeans at r2>0.5. SNPs in five novel independent loci exhibited strong and consistent evidence of association with breast cancer (P<10−7). Four of these contain plausible causative genes (FGFR2, TNRC9, MAP3K1 and LSP1). At the second stage, 1,792 SNPs were significant at the P<0.05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach. PMID:17529967

Convergent Genetic and Expression Datasets Highlight TREM2 in Parkinson's Disease Susceptibility.

PubMed

Liu, Guiyou; Liu, Yongquan; Jiang, Qinghua; Jiang, Yongshuai; Feng, Rennan; Zhang, Liangcai; Chen, Zugen; Li, Keshen; Liu, Jiafeng

2016-09-01

A rare TREM2 missense mutation (rs75932628-T) was reported to confer a significant Alzheimer's disease (AD) risk. A recent study indicated no evidence of the involvement of this variant in Parkinson's disease (PD). Here, we used the genetic and expression data to reinvestigate the potential association between TREM2 and PD susceptibility. In stage 1, using 10 independent studies (N = 89,157; 8787 cases and 80,370 controls), we conducted a subgroup meta-analysis. We identified a significant association between rs75932628 and PD (P = 3.10E-03, odds ratio (OR) = 3.88, 95 % confidence interval (CI) 1.58-9.54) in No-Northern Europe subgroup, and significantly increased PD risks (P = 0.01 for Mann-Whitney test) in No-Northern Europe subgroup than in Northern Europe subgroup. In stage 2, we used the summary results from a large-scale PD genome-wide association study (GWAS; N = 108,990; 13,708 cases and 95,282 controls) to search for other TREM2 variants contributing to PD susceptibility. We identified 14 single-nucleotide polymorphisms (SNPs) associated with PD within 50-kb upstream and downstream range of TREM2. In stage 3, using two brain expression GWAS datasets (N = 773), we identified 6 of the 14 SNPs regulating increased expression of TREM2. In stage 4, using the whole human genome microarray data (N = 50), we further identified significantly increased expression of TREM2 in PD cases compared with controls in human prefrontal cortex. In summary, convergent genetic and expression datasets demonstrate that TREM2 is a potent risk factor for PD and may be a therapeutic target in PD and other neurodegenerative diseases.

Does cemented or cementless single-stage exchange arthroplasty of chronic periprosthetic hip infections provide similar infection rates to a two-stage? A systematic review.

PubMed

George, D A; Logoluso, N; Castellini, G; Gianola, S; Scarponi, S; Haddad, F S; Drago, L; Romano, C L

2016-10-10

The best surgical modality for treating chronic periprosthetic hip infections remains controversial, with a lack of randomised controlled studies. The aim of this systematic review is to compare the infection recurrence rate after a single-stage versus a two-stage exchange arthroplasty, and the rate of cemented versus cementless single-stage exchange arthroplasty for chronic periprosthetic hip infections. We searched for eligible studies published up to December 2015. Full text or abstract in English were reviewed. We included studies reporting the infection recurrence rate as the outcome of interest following single- or two-stage exchange arthroplasty, or both, with a minimum follow-up of 12 months. Two reviewers independently abstracted data and appraised quality assessment. After study selection, 90 observational studies were included. The majority of studies were focused on a two-stage hip exchange arthroplasty (65 %), 18 % on a single-stage exchange, and only a 17 % were comparative studies. There was no statistically significant difference between a single-stage versus a two-stage exchange in terms of recurrence of infection in controlled studies (pooled odds ratio of 1.37 [95 % CI = 0.68-2.74, I 2  = 45.5 %]). Similarly, the recurrence infection rate in cementless versus cemented single-stage hip exchanges failed to demonstrate a significant difference, due to the substantial heterogeneity among the studies. Despite the methodological limitations and the heterogeneity between single cohorts studies, if we considered only the available controlled studies no superiority was demonstrated between a single- and two-stage exchange at a minimum of 12 months follow-up. The overalapping of confidence intervals related to single-stage cementless and cemented hip exchanges, showed no superiority of either technique.

Surgical management and clinical prognosis of adrenocortical carcinoma.

PubMed

Dong, Dexin; Li, Hanzhong; Yan, Weigang; Ji, Zhigang; Mao, Quanzong

2012-01-01

To study the relationship between surgical management and prognosis of adrenocortical carcinoma (ACC) in order to guide the surgical management of ACC. Clinical data of 45 cases of ACC treated in our hospital were retrospectively analyzed. The 45 cases included 3 cases in stage I, 12 cases in stage II, 7 cases in stage III, and 23 cases in stage IV. 17 cases underwent complete excision, 14 cases underwent palliative excision, 8 cases had non-operative treatment and 6 cases gave up treatment. All patients were followed up from 2 to 141 months. The average survival time of 31 patients with surgery was 32.46 months, and the average survival time of 14 patients without surgery was 4.75 months. There were statistically significant differences between the two groups (p < 0.01). There were no statistically significant differences between the two groups in survival time in stage III and stage IV (p > 0.05). Surgery is considered to be the only method to cure ACC. For ACC in stage I and II, tumor resection is the most effective treatment, and second surgical operation is recommended for local recurrence. For ACC in stage III, extensive surgical operation is recommended, and for ACC in stage IV, surgical operation has no effect on the prognosis. Copyright © 2012 S. Karger AG, Basel.

CA27.29: a valuable marker for breast cancer management. A confirmatory multicentric study on 603 cases.

PubMed

Gion, M; Mione, R; Leon, A E; Lüftner, D; Molina, R; Possinger, K; Robertson, J F

2001-02-01

Recently, a fully automated method has become commercially available to measure the MUC-1-associated antigen CA27.29. The present investigation was performed in order to compare CA27.29 and CA15.3 in a wide series of patients affected with breast cancer. Overall, 603 cases with breast cancer and 194 healthy controls were investigated. Patients were enrolled in 4 institutions, while assays were performed in one laboratory. CA27.29 was measured by the ACS:180 BR assay (Bayer Diagnostics) and CA15.3 by the AxSYM (Abbott Laboratories). An excellent correlation was found between the results obtained by the two methods. The two markers showed comparable results in healthy controls, with higher levels in post-menopausal than in pre-menopausal subjects. The markers were significantly higher in primary breast cancer than in controls. The areas under the receiver operating characteristics (ROC) curves of the two tests were comparable, but CA27.29 showed better sensitivity in cases with low antigen concentrations (below the cut-off point). Accordingly, when comparing each test in different stage categories, significance levels of the differences were higher for CA27.29 than for CA15.3 for all T categories versus healthy controls, for pT1 versus pT2, for all N categories versus healthy controls and for node-negative versus N1-3 patients. From the results of the present study, that has been performed on samples taken at diagnosis and prior to any treatment from the widest series of patients with primary breast cancer reported so far, we can draw the following conclusions: CA27.29 provides comparable results to CA15.3; CA27.29 seems more sensitive than CA15.3 to limited variations of tumour extension; however, it cannot help clinicians in distinguishing stage I patients from stage II patients. However, from the point of view of clinical decision making, CA27.29 provides comparable results to CA15.3. CA27.29 is therefore suitable for routine use in the management of patients with breast cancer.

Genome-wide Analysis of Genetic Loci Associated with Alzheimer’s Disease

PubMed Central

Seshadri, Sudha; Fitzpatrick, Annette L.; Arfan Ikram, M; DeStefano, Anita L.; Gudnason, Vilmundur; Boada, Merce; Bis, Joshua C.; Smith, Albert V.; Carassquillo, Minerva M.; Charles Lambert, Jean; Harold, Denise; Schrijvers, Elisabeth M. C.; Ramirez-Lorca, Reposo; Debette, Stephanie; Longstreth, W.T.; Janssens, A. Cecile J.W.; Shane Pankratz, V.; Dartigues, Jean François; Hollingworth, Paul; Aspelund, Thor; Hernandez, Isabel; Beiser, Alexa; Kuller, Lewis H.; Koudstaal, Peter J.; Dickson, Dennis W.; Tzourio, Christophe; Abraham, Richard; Antunez, Carmen; Du, Yangchun; Rotter, Jerome I.; Aulchenko, Yurii S.; Harris, Tamara B.; Petersen, Ronald C.; Berr, Claudine; Owen, Michael J.; Lopez-Arrieta, Jesus; Varadarajan, Badri N.; Becker, James T.; Rivadeneira, Fernando; Nalls, Michael A.; Graff-Radford, Neill R.; Campion, Dominique; Auerbach, Sanford; Rice, Kenneth; Hofman, Albert; Jonsson, Palmi V.; Schmidt, Helena; Lathrop, Mark; Mosley, Thomas H.; Au, Rhoda; Psaty, Bruce M.; Uitterlinden, Andre G.; Farrer, Lindsay A.; Lumley, Thomas; Ruiz, Agustin; Williams, Julie; Amouyel, Philippe; Younkin, Steve G.; Wolf, Philip A.; Launer, Lenore J.; Lopez, Oscar L.; van Duijn, Cornelia M.; Breteler, Monique M. B.

2010-01-01

Context Genome wide association studies (GWAS) have recently identified CLU, PICALM and CR1 as novel genes for late-onset Alzheimer’s disease (AD). Objective In a three-stage analysis of new and previously published GWAS on over 35000 persons (8371 AD cases), we sought to identify and strengthen additional loci associated with AD and confirm these in an independent sample. We also examined the contribution of recently identified genes to AD risk prediction. Design, Setting, and Participants We identified strong genetic associations (p<10−3) in a Stage 1 sample of 3006 AD cases and 14642 controls by combining new data from the population-based Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium (1367 AD cases (973 incident)) with previously reported results from the Translational Genomics Research Institute (TGEN) and Mayo AD GWAS. We identified 2708 single nucleotide polymorphisms (SNPs) with p-values<10−3, and in Stage 2 pooled results for these SNPs with the European AD Initiative (2032 cases, 5328 controls) to identify ten loci with p-values<10−5. In Stage 3, we combined data for these ten loci with data from the Genetic and Environmental Risk in AD consortium (3333 cases, 6995 controls) to identify four SNPs with a p-value<1.7×10−8. These four SNPs were replicated in an independent Spanish sample (1140 AD cases and 1209 controls). Main outcome measure Alzheimer’s Disease. Results We showed genome-wide significance for two new loci: rs744373 near BIN1 (OR:1.13; 95%CI:1.06–1.21 per copy of the minor allele; p=1.6×10−11) and rs597668 near EXOC3L2/BLOC1S3/MARK4 (OR:1.18; 95%CI1.07–1.29; p=6.5×10−9). Associations of CLU, PICALM, BIN1 and EXOC3L2 with AD were confirmed in the Spanish sample (p<0.05). However, CLU and PICALM did not improve incident AD prediction beyond age, sex, and APOE (improvement in area under receiver-operating-characteristic curve <0.003). Conclusions Two novel genetic loci for AD are reported that for the first time reach genome-wide statistical significance; these findings were replicated in an independent population. Two recently reported associations were also confirmed, but these loci did not improve AD risk prediction, although they implicate biological pathways that may be useful targets for potential interventions. PMID:20460622

Feeling connected to younger versus older selves: the asymmetric impact of life stage orientation.

PubMed

O'Brien, Ed

2015-01-01

The concept of life-stage orientation is proposed. Youth is a period of time characterised by strong feelings and emotions, but weak reasoning and cognitive skill. Conversely, adulthood is characterised by strong rationality, but weak emotionality. Two studies revealed that merely bringing these concepts to mind changes real-time feelings and behaviour. Participants who were instructed to act like their "adult" selves exhibited greater self-control in a cold pressor test than control participants and those who acted like their "youth" selves (Experiment 1). However, being induced to feel connected to youth enhanced enjoyment for fun videos (Experiment 2). Hence, the extent to which people are oriented towards youth versus adulthood has asymmetric costs and benefits for the present. Connecting to youth boosts experiential capacities (in this case, enjoying oneself) at the cost of agency, whereas connecting to adulthood boosts agentic capacities (in this case, exerting will-power) at the cost of experience.

Detection of fetal sex chromosome aneuploidy by massively parallel sequencing of maternal plasma DNA: initial experience in a Chinese hospital.

PubMed

Yao, H; Jiang, F; Hu, H; Gao, Y; Zhu, Z; Zhang, H; Wang, Y; Guo, Y; Liu, L; Yuan, Y; Zhou, L; Wang, J; Du, B; Qu, N; Zhang, R; Dong, Y; Xu, H; Chen, F; Jiang, H; Liu, Y; Zhang, L; Tian, Z; Liu, Q; Zhang, C; Pan, X; Yang, S; Zhao, L; Wang, W; Liang, Z

2014-07-01

To evaluate the performance of a massively parallel sequencing (MPS)-based test in detecting fetal sex chromosome aneuploidy (SCA) and to present a comprehensive clinical counseling protocol for SCA-positive patients. This was a retrospective study in a large patient cohort of 5950 singleton pregnancies which underwent MPS-based testing as a prenatal screening test for trisomies 21, 18 and 13, with X and Y chromosomes as secondary findings, in Southwest Hospital in China. MPS-based SCA-positive women were offered the choice of knowing whether their SCA results were positive and those who did commenced a two-stage post-test clinical counseling protocol. In Stage 1, general information about SCA was given, and women were given the option of invasive testing for confirmation of findings; in Stage 2, those who had chosen to undergo invasive testing were informed about the specific SCA affecting their fetus and their management options. Thirty-three cases were classified as SCA-positive by MPS-based testing. After Stage 1 of the two-stage post-test clinical counseling session, 33 (100%) of these pregnant women chose to know the screening test results, and 25 (75.76%) underwent an invasive diagnostic procedure and karyotype analysis, in one of whom karyotyping failed. In thirteen cases, karyotyping confirmed the MPS-based test results (two X0 cases, seven XXX cases, three XXY cases and one XYY case), giving a positive predictive value of 54.17% (13/24 cases confirmed by karyotyping). After post-test clinical counseling session Stage 2, seven women chose to terminate the pregnancy: one X0 case, two XXX cases, the three XXY cases and the single XYY case. Six women decided to continue with pregnancy: one X0 case and five XXX cases. Our study showed the feasibility of clinical application of the MPS-based test in the non-invasive detection of fetal SCA. Together with a two-stage post-test clinical counseling protocol, it leads to a well-informed decision-making procedure. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Malaria Situation and Anopheline Mosquitoes in Qom Province, Central Iran

PubMed Central

Farzinnia, B; Saghafipour, A; Abai, MR

2010-01-01

Background: The aims of this study was to analysis the current situation of malaria and to find the distribution of anopheline mosquitoes, as probable vectors of the disease, in Qom Province, central Iran. Methods: This study was carried out in two parts. First stage was data collection about malaria cases using recorded documents of patients in the Province health center, during 2001–2008. The second stage was entomological survey conducted by mosquito larval collection method in 4 villages with different geographical positions in 2008. Data were analyzed using Excel software. Results: Of 4456 blood slides, 10.9% out were positive. Most of cases were imported from other countries (90.4%), mainly from Afghanistan (56.5%) and Pakistan (16.3%). Slide positive rate showed a maximum of 16.9% and a minimum of 2.9% in 2008 and 2007, respectively. Plasmodium vivax was causative agent of 93.75% of cases, followed by P. falciparum (6.25%). More than 15 years old age group contained the most malaria reported cases (66.7%). Two Anopheles species, An. superpictus and An. claviger were collected and identified. This is the first report of Anopheles claviger in Qom Province. Conclusion: Malaria is in the control stage in Qom Province. The rate of local transmission is very low (only 1 case), shows Anopheles superpictus, as the main malaria vector of central part of Iran, can play its role in malaria transmission in the area. PMID:22808402

Sleep architecture and obstructive sleep apnea in obese children with and without metabolic syndrome: a case control study.

PubMed

Jalilolghadr, Shabnam; Yazdi, Zohreh; Mahram, Manoochehr; Babaei, Farkhondeh; Esmailzadehha, Neda; Nozari, Hoormehr; Saffari, Fatemeh

2016-05-01

Obesity and biochemical parameters of metabolic disorders are both closely related to obstructive sleep apnea (OSA). The aim of this study was to compare sleep architecture and OSA in obese children with and without metabolic syndrome. Forty-two children with metabolic syndrome were selected as case group and 38 children without metabolic syndrome were matched for age, sex, and BMI as control group. The standardized Persian version of bedtime problems, excessive daytime sleepiness, awakenings during the night, regularity and duration of sleep, snoring (BEARS) and Children's Sleep Habits Questionnaires were completed, and polysomnography (PSG) was performed for all study subjects. Scoring was performed using the manual of American Academy of Sleep Medicine for children. Data were analyzed using chi-square test, T test, Mann-Whitney U test, and logistic regression analysis. Non-rapid eye movement (NREM) sleep and N1 stage in the case group were significantly longer than the control group, while REM sleep was significantly shorter. Waking after sleep onset (WASO) was significantly different between two groups. Severe OSA was more frequent in the control group. Multivariate logistic regression analysis showed that severe OSA (OR 21.478, 95 % CI 2.160-213.600; P = 0.009) and REM sleep (OR 0.856, 95 % CI 0.737-0.994; P = 0.041) had independent association with metabolic syndrome. Obese children with metabolic syndrome had increased WASO, N1 sleep stage, and severe OSA. But the results regarding sleep architecture are most likely a direct result of OSA severity. More longitudinal studies are needed to confirm the association of metabolic syndrome and OSA.

Effect of Breathing Technique of Blowing on the Extent of Damage to the Perineum at the Moment of Delivery: A Randomized Clinical Trial

PubMed Central

Ahmadi, Zohre; Torkzahrani, Shahnaz; Roosta, Firouze; Shakeri, Nezhat; Mhmoodi, Zohre

2017-01-01

Introduction: One of the important tasks in managing labor is the protection of perineum. An important variable affecting this outcome is maternal pushing during the second stage of labor. This study was done to investigate the effect of breathing technique on perineal damage extention in laboring Iranian women. Materials and Methods: This randomized clinical trial was performed on 166 nulliparous pregnant women who had reached full-term pregnancy, had low risk pregnancy, and were candidates for vaginal delivery in two following groups: using breathing techniques (case group) and valsalva maneuver (control group). In the control group, pushing was done with holding the breath. In the case group, the women were asked to take 2 deep abdominal breaths at the onset of pain, then take another deep breath, and push 4–5 seconds with the open mouth while controlling exhalation. From the crowning stage onward, the women were directed to control their pushing, and do the blowing technique. Results: According to the results, intact perineum was more observed in the case group (P = 0.002). Posterior tears (Grade 1, 2, and 3) was considerably higher in the control group (P = 0.003). Anterior tears (labias) and episiotomy were not significantly different in the two groups. Conclusions: It was concluded that breathing technique of blowing can be a good alternative to Valsalva maneuver in order to reduce perineal damage in laboring women. PMID:28382061

Individual socioeconomic status and breast cancer diagnostic stages: a French case-control study.

PubMed

Orsini, Mattea; Trétarre, Brigitte; Daurès, Jean-Pierre; Bessaoud, Faiza

2016-06-01

Health inequalities have increased over the last 30 years. Our goal was to investigate the relationship between low individual socioeconomic status and poor breast cancer prognosis. Our hypothesis was: low socioeconomic status patients have a higher risk of being diagnosed with late stage breast cancer than high socioeconomic status ones due to delayed diagnosis. We conducted a matched case-control study on 619 women with breast cancer, living in the Hérault, a French administrative area. Both Cases and Controls were recruited among invasive cases diagnosed in 2011 and 2012 and treated in Hérault care centers. Cases were defined as patients with advanced stages. Controls were composed of early stage patients. Individual socioeconomic status was assessed using a validated individual score adapted to the French population and health care system. We observed that low socioeconomic status patients have a 2-fold risk of having late stage breast cancer regardless of cancer characteristics and detection mode (screening vs. clinical signs). One reason explaining those results could be that low socioeconomic status patients have less regular follow-up which can lead to later and poorer diagnosis. Follow-up is improved for women with a better awareness of breast cancer. Health policy makers could reduce health inequalities by reducing the delay in breast cancer diagnosis for low socioeconomic status women. © The Author 2016. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

A genome-wide association study of breast cancer in women of African ancestry

PubMed Central

Chen, Fang; Chen, Gary K.; Stram, Daniel O.; Millikan, Robert C.; Ambrosone, Christine B.; John, Esther M.; Bernstein, Leslie; Zheng, Wei; Palmer, Julie R.; Hu, Jennifer J.; Rebbeck, Tim R.; Ziegler, Regina G.; Nyante, Sarah; Bandera, Elisa V.; Ingles, Sue A.; Press, Michael F.; Ruiz-Narvaez, Edward A.; Deming, Sandra L.; Rodriguez-Gil, Jorge L.; DeMichele, Angela; Chanock, Stephen J.; Blot, William; Signorello, Lisa; Cai, Qiuyin; Li, Guoliang; Long, Jirong; Huo, Dezheng; Zheng, Yonglan; Cox, Nancy J.; Olopade, Olufunmilayo I.; Ogundiran, Temidayo O.; Adebamowo, Clement; Nathanson, Katherine L.; Domchek, Susan M.; Simon, Michael S.; Hennis, Anselm; Nemesure, Barbara; Wu, Suh-Yuh; Leske, M. Cristina; Ambs, Stefan; Hutter, Carolyn M.; Young, Alicia; Kooperberg, Charles; Peters, Ulrike; Rhie, Suhn K.; Wan, Peggy; Sheng, Xin; Pooler, Loreall C.; Van Den Berg, David J.; Le Marchand, Loic; Kolonel, Laurence N.; Henderson, Brian E.; Haiman, Christopher A.

2013-01-01

Genome-wide association studies (GWAS) in diverse populations are needed to reveal variants that are more common and/or limited to defined populations. We conducted a GWAS of breast cancer in women of African ancestry, with genotyping of > 1,000,000 SNPs in 3,153 African American cases and 2,831 controls, and replication testing of the top 66 associations in an additional 3,607 breast cancer cases and 11,330 controls of African ancestry. Two of the 66 SNPs replicated (p < 0.05) in stage 2, which reached statistical significance levels of 10−6 and 10−5 in the stage 1 and 2 combined analysis (rs4322600 at chromosome 14q31: OR = 1.18, p = 4.3×10−6; rs10510333 at chromosome 3p26: OR = 1.15, p = 1.5×10−5). These suggestive risk loci have not been identified in previous GWAS in other populations and will need to be examined in additional samples. Identification of novel risk variants for breast cancer in women of African ancestry will demand testing of a substantially larger set of markers from stage 1 in a larger replication sample. PMID:22923054

Energy efficient engine high pressure turbine test hardware detailed design report

NASA Technical Reports Server (NTRS)

Halila, E. E.; Lenahan, D. T.; Thomas, T. T.

1982-01-01

The high pressure turbine configuration for the Energy Efficient Engine is built around a two-stage design system. Moderate aerodynamic loading for both stages is used to achieve the high level of turbine efficiency. Flowpath components are designed for 18,000 hours of life, while the static and rotating structures are designed for 36,000 hours of engine operation. Both stages of turbine blades and vanes are air-cooled incorporating advanced state of the art in cooling technology. Direct solidification (DS) alloys are used for blades and one stage of vanes, and an oxide dispersion system (ODS) alloy is used for the Stage 1 nozzle airfoils. Ceramic shrouds are used as the material composition for the Stage 1 shroud. An active clearance control (ACC) system is used to control the blade tip to shroud clearances for both stages. Fan air is used to impinge on the shroud casing support rings, thereby controlling the growth rate of the shroud. This procedure allows close clearance control while minimizing blade tip to shroud rubs.

Knee movement patterns of injured and uninjured adolescent basketball players when landing from a jump: A case-control study

PubMed Central

Louw, Quinette; Grimmer, Karen; Vaughan, Christopher

2006-01-01

Background A common knee injury mechanism sustained during basketball is landing badly from a jump. Landing is a complex task and requires good coordination, dynamic muscle control and flexibility. For adolescents whose coordination and motor control has not fully matured, landing badly from a jump can present a significant risk for injury. There is currently limited biomechanical information regarding the lower limb kinetics of adolescents when jumping, specifically regarding jump kinematics comparing injured with uninjured adolescents. This study reports on an investigation of biomechanical differences in landing patterns of uninjured and injured adolescent basketball players. Methods A matched case-control study design was employed. Twenty-two basketball players aged 14–16 years participated in the study: eleven previously knee-injured and eleven uninjured players matched with cases for age, gender, weight, height and years of play, and playing for the same club. Six high-speed, three-dimensional Vicon 370 cameras (120 Hz), Vicon biomechanical software and SAS Version 8 software were employed to analyse landing patterns when subjects performed a "jump shot". Linear correlations determined functional relationships between the biomechanical performance of lower limb joints, and paired t-tests determined differences between the normalised peak biomechanical parameters. Results The average peak vertical ground reaction forces between the cases and controls were similar. The average peak ground reaction forces between the cases and controls were moderately correlated (r = -0.47). The control (uninjured) players had significantly greater hip and knee flexion angles and significantly greater eccentric activity on landing than the uninjured cases (p < 0.01). Conclusion The findings of the study indicate that players with a history of knee injuries had biomechanically compromised landing techniques when compared with uninjured players matched for gender, age and club. Descriptions (norms) of expected levels of knee control, proprioceptive acuity and eccentric strength relative to landing from a jump, at different ages and physical developmental stages, would assist clinicians and coaches to identify players with inappropriate knee performance comparable to their age or developmental stage. PMID:16522210

[Role of creative discussion in the learning of critical reading of scientific articles].

PubMed

Cobos-Aguilar, Héctor; Viniegra-Velázquez, Leonardo; Pérez-Cortés, Patricia

2011-01-01

To compare two active educational strategies on critical reading (two and three stages) for research learning in medical students. Four groups were conformed in a quasi-experimental design. The medical student group, related to three stages (critical reading guide resolution, creative discussion, group discussion) g1, n = 9 with school marks > 90 and g2, n = 19 with a < 90, respectively. The two-stage groups (guide resolution and group discussion) were conformed by pre-graduate interns, g3, n = 17 and g4, n = 12, who attended social security general hospitals. A validated and consistent survey with 144 items was applied to the four groups before and after educational strategies. Critical reading with its subcomponents: interpretation, judgment and proposal were evaluated with 47, 49 and 48 items, respectively. The case control studies, cohort studies, diagnostic test and clinical trial designs were evaluated. Nonparametric significance tests were performed to compare the groups and their results. A bias calculation was performed for each group. The highest median was obtained by the three-stage groups (g1 and g2) and so were the medians in interpretation, judgment and proposal. The several research design results were higher in the same groups. An active educational strategy with three stages is superior to another with two stages in medical students. It is advisable to perform these activities in goal of better learning in our students.

Severe motor and vocal tics controlled with Sativex®.

PubMed

Trainor, David; Evans, Lois; Bird, Rupert

2016-12-01

A single case report on cannabinoid treatment for treatment-resistant Tourette syndrome (TS). Our subject received 10.8 mg Tetrahydocannabinol and 10 mg cannabidiol daily, in the form of two oro-mucosal sprays of 'Sativex ® ', twice daily. Assessment was pre-treatment and at week one, two, and four during treatment. He completed the Yale Global Tic Severity Scale as a subjective measure, and was videoed at each stage. The videos were objectively rated by two assessors, blind to the stage of treatment, using the Original Rush Videotape Rating Scale. Both subjective and objective measures demonstrated marked improvement in the frequency and severity of motor and vocal tics post-treatment. There was good interrater reliability of results. Our results support previous research suggesting that cannabinoids are a safe and effective treatment for TS and should be considered in treatment-resistant cases. Further studies are needed to substantiate our findings. © The Royal Australian and New Zealand College of Psychiatrists 2016.

Identification of a novel susceptibility locus at 13q34 and refinement of the 20p12.2 region as a multi-signal locus associated with bladder cancer risk in individuals of European ancestry

PubMed Central

Figueroa, Jonine D.; Middlebrooks, Candace D.; Banday, A. Rouf; Ye, Yuanqing; Garcia-Closas, Montserrat; Chatterjee, Nilanjan; Koutros, Stella; Kiemeney, Lambertus A.; Rafnar, Thorunn; Bishop, Timothy; Furberg, Helena; Matullo, Giuseppe; Golka, Klaus; Gago-Dominguez, Manuela; Taylor, Jack A.; Fletcher, Tony; Siddiq, Afshan; Cortessis, Victoria K.; Kooperberg, Charles; Cussenot, Olivier; Benhamou, Simone; Prescott, Jennifer; Porru, Stefano; Dinney, Colin P.; Malats, Núria; Baris, Dalsu; Purdue, Mark P.; Jacobs, Eric J.; Albanes, Demetrius; Wang, Zhaoming; Chung, Charles C.; Vermeulen, Sita H.; Aben, Katja K.; Galesloot, Tessel E.; Thorleifsson, Gudmar; Sulem, Patrick; Stefansson, Kari; Kiltie, Anne E.; Harland, Mark; Teo, Mark; Offit, Kenneth; Vijai, Joseph; Bajorin, Dean; Kopp, Ryan; Fiorito, Giovanni; Guarrera, Simonetta; Sacerdote, Carlotta; Selinski, Silvia; Hengstler, Jan G.; Gerullis, Holger; Ovsiannikov, Daniel; Blaszkewicz, Meinolf; Castelao, Jose Esteban; Calaza, Manuel; Martinez, Maria Elena; Cordeiro, Patricia; Xu, Zongli; Panduri, Vijayalakshmi; Kumar, Rajiv; Gurzau, Eugene; Koppova, Kvetoslava; Bueno-De-Mesquita, H. Bas; Ljungberg, Börje; Clavel-Chapelon, Françoise; Weiderpass, Elisabete; Krogh, Vittorio; Dorronsoro, Miren; Travis, Ruth C.; Tjønneland, Anne; Brennan, Paul; Chang-Claude, Jenny; Riboli, Elio; Conti, David; Stern, Marianna C.; Pike, Malcolm C.; Van Den Berg, David; Yuan, Jian-Min; Hohensee, Chancellor; Jeppson, Rebecca P.; Cancel-Tassin, Geraldine; Roupret, Morgan; Comperat, Eva; Turman, Constance; De Vivo, Immaculata; Giovannucci, Edward; Hunter, David J.; Kraft, Peter; Lindstrom, Sara; Carta, Angela; Pavanello, Sofia; Arici, Cecilia; Mastrangelo, Giuseppe; Kamat, Ashish M.; Zhang, Liren; Gong, Yilei; Pu, Xia; Hutchinson, Amy; Burdett, Laurie; Wheeler, William A.; Karagas, Margaret R.; Johnson, Alison; Schned, Alan; Monawar Hosain, G. M.; Schwenn, Molly; Kogevinas, Manolis; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; García-Closas, Reina; Lloreta, Josep; Andriole, Gerald; Grubb, Robert; Black, Amanda; Diver, W. Ryan; Gapstur, Susan M.; Weinstein, Stephanie; Virtamo, Jarmo; Haiman, Christopher A.; Landi, Maria Teresa; Caporaso, Neil E.; Fraumeni, Joseph F.; Vineis, Paolo; Wu, Xifeng; Chanock, Stephen J.; Silverman, Debra T.; Prokunina-Olsson, Ludmila; Rothman, Nathaniel

2016-01-01

Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P < 1 × 10−6), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 × 10−11) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 × 10−10). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region—the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r2 = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case–case P ≤ 0.02 for both rs62185668 and rs6108803). Functional analyses are needed to explore the biological mechanisms underlying these novel genetic associations with risk for bladder cancer. PMID:26732427

Choline and betaine intake is inversely associated with breast cancer risk: a two-stage case-control study in China.

PubMed

Zhang, Cai-Xia; Pan, Mei-Xia; Li, Bin; Wang, Lian; Mo, Xiong-Fei; Chen, Yu-Ming; Lin, Fang-Yu; Ho, Suzanne C

2013-02-01

Few epidemiological studies have evaluated the association of choline and betaine intake with breast cancer risk and the results remain inconsistent. This study aimed to assess the relationship between dietary intake of choline and betaine and the risk of breast cancer among Chinese women. A two-stage case-control study was conducted, with 807 cases and 807 age- (5-year interval) and residence (rural/urban)-matched controls. A validated food frequency questionnaire was used to assess dietary intake by face-to-face interview. An unconditional logistic regression model was used to calculate multivariate-adjusted odds ratios (OR) and 95% confidence intervals (CI). A significant inverse association was found between dietary choline and betaine consumption and breast cancer risk. The adjusted OR for the highest quartile of intake compared with the lowest were 0.40 (95% CI = 0.28-0.57, P(trend) < 0.001) for total choline intake, 0.58 (95% CI = 0.42-0.80, P(trend) < 0.001) for betaine intake and 0.38 (0.27-0.53, P(trend) < 0.001) for choline plus betaine intake, respectively. Intakes of individual choline compouds, choline from glycerophosphocholine, phosphocholine, phosphatidylcholine, sphingomyelin and free choline were also negatively associated with breast cancer risk. The inverse association between choline intake and breast cancer risk was primarily confined to participants with low folate level (<242 g/day), with an OR (95% CI) of 0.46 (0.23-0.91) comparing the fourth quartile with the first quartile of choline intake (P(trend) = 0.005). The present study suggests that consumption of choline and betaine is inversely associated with the risk of breast cancer. The association of choline intake with breast cancer risk is probably modified by folate intake. © 2012 Japanese Cancer Association.

The IASLC Lung Cancer Staging Project: A Renewed Call to Participation.

PubMed

Giroux, Dorothy J; Van Schil, Paul; Asamura, Hisao; Rami-Porta, Ramón; Chansky, Kari; Crowley, John J; Rusch, Valerie W; Kernstine, Kemp

2018-06-01

Over the past two decades, the International Association for the Study of Lung Cancer (IASLC) Staging Project has been a steady source of evidence-based recommendations for the TNM classification for lung cancer published by the Union for International Cancer Control and the American Joint Committee on Cancer. The Staging and Prognostic Factors Committee of the IASLC is now issuing a call for participation in the next phase of the project, which is designed to inform the ninth edition of the TNM classification for lung cancer. Following the case recruitment model for the eighth edition database, volunteer site participants are asked to submit data on patients whose lung cancer was diagnosed between January 1, 2011, and December 31, 2019, to the project by means of a secure, electronic data capture system provided by Cancer Research And Biostatistics in Seattle, Washington. Alternatively, participants may transfer existing data sets. The continued success of the IASLC Staging Project in achieving its objectives will depend on the extent of international participation, the degree to which cases are entered directly into the electronic data capture system, and how closely externally submitted cases conform to the data elements for the project. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Expert Elicitation Provides a Rapid Alternative to Formal Case-Control Study of an H7N9 Avian Influenza Outbreak in the United States.

PubMed

Gustafson, L; Jones, R; Dufour-Zavala, L; Jensen, E; Malinak, C; McCarter, S; Opengart, K; Quinn, J; Slater, T; Delgado, A; Talbert, M; Garber, L; Remmenga, M; Smeltzer, M

2018-06-01

An expert elicitation was staged to rapidly decipher plausible routes and risks of pathogen transmission in the 2017 H7N9 avian influenza (AI) outbreak in the four-state region of Tennessee, Alabama, Georgia, and Kentucky. The process included the identification of risk factors found in a preponderance of commercial broiler breeder case farms over matched controls and an opinion-based weighting of risks and mitigations perceived influential to this outbreak. Although the two highly pathogenic AI case farms had general location and company ownership in common, obvious connections were lacking for the remainder of H7N9-infected (all low pathogenicity) commercial farms. Expert elicitation of differences between known cases and controls suggested a key role for environmental rather than lateral (business network) pathways in the distribution of low pathogenicity AI across commercial broiler breeder operations. Factors with greatest strength as predictors of disease, whether or not they were causal, included mesopredator or rodent incursions, enclosure defects, and habitat disturbance that might attract wildlife to the farm (e.g., feed spills and vacating of neighboring properties). Business affiliations that may have facilitated farm-to-farm transfer, in contrast, were limited. Biosecurity standards varied across this study group but were no more or less stringent among cases over controls. However, results from a parallel hypothetical scenario staged to address field data gaps suggest that uniformity and consistency in the implementation of biosecurity practices may impact risk of disease introduction. Importantly, this study was conducted within a few weeks and with little disruption to emergency response activities. As such, the approach offers an alternative model for interim field investigation of new or emerging high-consequence diseases with immediate decision support needs.

Extending Vulnerability Assessment to Include Life Stages Considerations

PubMed Central

Hodgson, Emma E.; Essington, Timothy E.; Kaplan, Isaac C.

2016-01-01

Species are experiencing a suite of novel stressors from anthropogenic activities that have impacts at multiple scales. Vulnerability assessment is one tool to evaluate the likely impacts that these stressors pose to species so that high-vulnerability cases can be identified and prioritized for monitoring, protection, or mitigation. Commonly used semi-quantitative methods lack a framework to explicitly account for differences in exposure to stressors and organism responses across life stages. Here we propose a modification to commonly used spatial vulnerability assessment methods that includes such an approach, using ocean acidification in the California Current as an illustrative case study. Life stage considerations were included by assessing vulnerability of each life stage to ocean acidification and were used to estimate population vulnerability in two ways. We set population vulnerability equal to: (1) the maximum stage vulnerability and (2) a weighted mean across all stages, with weights calculated using Lefkovitch matrix models. Vulnerability was found to vary across life stages for the six species explored in this case study: two krill–Euphausia pacifica and Thysanoessa spinifera, pteropod–Limacina helicina, pink shrimp–Pandalus jordani, Dungeness crab–Metacarcinus magister and Pacific hake–Merluccius productus. The maximum vulnerability estimates ranged from larval to subadult and adult stages with no consistent stage having maximum vulnerability across species. Similarly, integrated vulnerability metrics varied greatly across species. A comparison showed that some species had vulnerabilities that were similar between the two metrics, while other species’ vulnerabilities varied substantially between the two metrics. These differences primarily resulted from cases where the most vulnerable stage had a low relative weight. We compare these methods and explore circumstances where each method may be appropriate. PMID:27416031

Extending Vulnerability Assessment to Include Life Stages Considerations.

PubMed

Hodgson, Emma E; Essington, Timothy E; Kaplan, Isaac C

2016-01-01

Species are experiencing a suite of novel stressors from anthropogenic activities that have impacts at multiple scales. Vulnerability assessment is one tool to evaluate the likely impacts that these stressors pose to species so that high-vulnerability cases can be identified and prioritized for monitoring, protection, or mitigation. Commonly used semi-quantitative methods lack a framework to explicitly account for differences in exposure to stressors and organism responses across life stages. Here we propose a modification to commonly used spatial vulnerability assessment methods that includes such an approach, using ocean acidification in the California Current as an illustrative case study. Life stage considerations were included by assessing vulnerability of each life stage to ocean acidification and were used to estimate population vulnerability in two ways. We set population vulnerability equal to: (1) the maximum stage vulnerability and (2) a weighted mean across all stages, with weights calculated using Lefkovitch matrix models. Vulnerability was found to vary across life stages for the six species explored in this case study: two krill-Euphausia pacifica and Thysanoessa spinifera, pteropod-Limacina helicina, pink shrimp-Pandalus jordani, Dungeness crab-Metacarcinus magister and Pacific hake-Merluccius productus. The maximum vulnerability estimates ranged from larval to subadult and adult stages with no consistent stage having maximum vulnerability across species. Similarly, integrated vulnerability metrics varied greatly across species. A comparison showed that some species had vulnerabilities that were similar between the two metrics, while other species' vulnerabilities varied substantially between the two metrics. These differences primarily resulted from cases where the most vulnerable stage had a low relative weight. We compare these methods and explore circumstances where each method may be appropriate.

Case Study 4: Using Game-Based Learning for Induction

ERIC Educational Resources Information Center

Javaid, Osman

2017-01-01

This case study tracks the development of a digital induction resource implementing game elements that focuses on the first two stages of Gilly Salmon's Five Stage Model, namely "access and motivation" and "online socialisation" (Salmon, 2011). In the summer of 2016, a prototype was developed and presented at the Playful…

Identification of seven new prostate cancer susceptibility loci through a genome-wide association study.

PubMed

Eeles, Rosalind A; Kote-Jarai, Zsofia; Al Olama, Ali Amin; Giles, Graham G; Guy, Michelle; Severi, Gianluca; Muir, Kenneth; Hopper, John L; Henderson, Brian E; Haiman, Christopher A; Schleutker, Johanna; Hamdy, Freddie C; Neal, David E; Donovan, Jenny L; Stanford, Janet L; Ostrander, Elaine A; Ingles, Sue A; John, Esther M; Thibodeau, Stephen N; Schaid, Daniel; Park, Jong Y; Spurdle, Amanda; Clements, Judith; Dickinson, Joanne L; Maier, Christiane; Vogel, Walther; Dörk, Thilo; Rebbeck, Timothy R; Cooney, Kathleen A; Cannon-Albright, Lisa; Chappuis, Pierre O; Hutter, Pierre; Zeegers, Maurice; Kaneva, Radka; Zhang, Hong-Wei; Lu, Yong-Jie; Foulkes, William D; English, Dallas R; Leongamornlert, Daniel A; Tymrakiewicz, Malgorzata; Morrison, Jonathan; Ardern-Jones, Audrey T; Hall, Amanda L; O'Brien, Lynne T; Wilkinson, Rosemary A; Saunders, Edward J; Page, Elizabeth C; Sawyer, Emma J; Edwards, Stephen M; Dearnaley, David P; Horwich, Alan; Huddart, Robert A; Khoo, Vincent S; Parker, Christopher C; Van As, Nicholas; Woodhouse, Christopher J; Thompson, Alan; Christmas, Tim; Ogden, Chris; Cooper, Colin S; Southey, Melissa C; Lophatananon, Artitaya; Liu, Jo-Fen; Kolonel, Laurence N; Le Marchand, Loic; Wahlfors, Tiina; Tammela, Teuvo L; Auvinen, Anssi; Lewis, Sarah J; Cox, Angela; FitzGerald, Liesel M; Koopmeiners, Joseph S; Karyadi, Danielle M; Kwon, Erika M; Stern, Mariana C; Corral, Roman; Joshi, Amit D; Shahabi, Ahva; McDonnell, Shannon K; Sellers, Thomas A; Pow-Sang, Julio; Chambers, Suzanne; Aitken, Joanne; Gardiner, R A Frank; Batra, Jyotsna; Kedda, Mary Anne; Lose, Felicity; Polanowski, Andrea; Patterson, Briony; Serth, Jürgen; Meyer, Andreas; Luedeke, Manuel; Stefflova, Klara; Ray, Anna M; Lange, Ethan M; Farnham, Jim; Khan, Humera; Slavov, Chavdar; Mitkova, Atanaska; Cao, Guangwen; Easton, Douglas F

2009-10-01

Prostate cancer (PrCa) is the most frequently diagnosed cancer in males in developed countries. To identify common PrCa susceptibility alleles, we previously conducted a genome-wide association study in which 541,129 SNPs were genotyped in 1,854 PrCa cases with clinically detected disease and in 1,894 controls. We have now extended the study to evaluate promising associations in a second stage in which we genotyped 43,671 SNPs in 3,650 PrCa cases and 3,940 controls and in a third stage involving an additional 16,229 cases and 14,821 controls from 21 studies. In addition to replicating previous associations, we identified seven new prostate cancer susceptibility loci on chromosomes 2, 4, 8, 11 and 22 (with P = 1.6 x 10(-8) to P = 2.7 x 10(-33)).

Frequency analysis of a two-stage planetary gearbox using two different methodologies

NASA Astrophysics Data System (ADS)

Feki, Nabih; Karray, Maha; Khabou, Mohamed Tawfik; Chaari, Fakher; Haddar, Mohamed

2017-12-01

This paper is focused on the characterization of the frequency content of vibration signals issued from a two-stage planetary gearbox. To achieve this goal, two different methodologies are adopted: the lumped-parameter modeling approach and the phenomenological modeling approach. The two methodologies aim to describe the complex vibrations generated by a two-stage planetary gearbox. The phenomenological model describes directly the vibrations as measured by a sensor fixed outside the fixed ring gear with respect to an inertial reference frame, while results from a lumped-parameter model are referenced with respect to a rotating frame and then transferred into an inertial reference frame. Two different case studies of the two-stage planetary gear are adopted to describe the vibration and the corresponding spectra using both models. Each case presents a specific geometry and a specific spectral structure.

Contribution to reconstruction of third degree rectovestibular lacerations in mares

PubMed Central

Elkasapy, A.H.; Ibrahim, I.M.

2015-01-01

The study was conducted on ten mares suffering from third degree rectovestibular laceration. Four uterine washes were performed in all cases by using diluted betadine (mixing 5ml of betadine antiseptic solution in 1 liter of sterile saline) to control vaginal and uterine infections before surgery. Surgical repair of third degree rectovestibular laceration was done by one-stage Goetz technique after four to six weeks of initial injury, with the lateral dissection continued extensively until the two flaps were created and brought to the midline without any tension. Primary healing occurred in all cases without significant complications. The obtained results indicate that mares with third degree rectovestibular lacerations are candidates for uterine wash and one-stage Goetz technique with excessive lateral continuation of the flap. PMID:26623358

[Risk factors and clinical prediction of shoulder dystocia in non-macrosomia].

PubMed

Li, Na; Li, Qiuling; Chang, Liang; Liu, Caixia

2015-01-01

To investigate the risk factors, clinical prediction and intrapartum management of shoulder dystocia in non-macrosomia. Totally 7 811 cases of vaginal delivery were retrospectively reviewed from Juanary 2009 to December 2013 in Shengjing Hospital. Shoulder dystocia was found in 11 cases (0.14% , 11/7 811), including 1 case of macrosomia and 10 cases of non-macrosomia (shoulder dystocia group). Each non-macrosomia shoulder dystocia case was matched with 10 cases of normal delivery in the same week, which were selected randomly as the control group. The tendency and risk factors of shoulder dystocia in macrosomia and non-macrosomia were analyzed, and the following data between the two groups were compared, including the height of uterus fundus, abdominal circumference of the pregnant woman, the increasing of body mass index (BMI), fetal biparietal diameter (BPD), fetal femur length (FL), duration of every stage of labor, birth weight of the newborn, head circumference and chest circumference of the newborn, Apgar score. (1) There were 213 macrosomias among the 7 811 vaginal deliveries, with the incidence of 2.73% (213/7 811). Only 1 shoulder dystocia was macrosomia (0.46%, 1/213); while the other 10 cases were non-macrosomia ( 0.13%, 10/7 598). (2) From 2009 to 2013, the macrosomia happened by 24 cases (2.32%, 24/1 034), 42 cases (3.61%, 42/1 164), 46 cases (2.60%, 46/1 772), 62 cases (3.01%, 62/2 060), 39 cases (2.19%, 39/1781), respectively. The incidence of macrosomia had no significant difference among these 5 years (P > 0.05). The shoulder dystosia occurrence without macrosia in these 5 years were 1 case ( 0.10% , 1/1 034), 3 cases (0.26%, 3/1 164), 2 cases ( 0.11%, 2/1 172), 2 cases (0.10%, 2/2 060), 2 cases ( 0.11%, 1/1 781), respectively. The incidence of shoulder dystocia without macrosomia had no significant difference among these 5 years (P > 0.05). (3) In the should dystocia group, 5 cases were complicated with premature rupture of membrane (5/10), 4 cases were mother≥ 35 years old (4/10), 3 cases were multipara(3/10), 3 cases had gestational diabetes mellitus(3/10), 3 cases were occiput posterior during the first stage of labor (3/10), 3 cases had prolonged second stage of labor (3/10) and 6 cases had routine lateral incision (6/10). In the control group, 3 cases were complicated with premature rupture of membrane(3/10); 1 case was mother≥35 years old (1/10); 2 cases were multipara(2/10), 3 cases had gestational diabetes mellitus (3/10), 1 case had prolonged second stage (1/10) and 7 cases had routine lateral incision (7/10). (4) There were no significant difference in the height of uterus fundus, BMI, BPD, FL, and duration of the first stage of labor between the shoulder dystocia group and the control group (P > 0.05). Compared with the control group, the increasing of BMI [(6.8±3.1) vs (4.8±1.4) kg/m(2)], the time of the second stage of labor[(86±65) vs (38±28) minutes ] and abdominal circumference[(108±8) vs (101±7) cm] were significantly higher in the shoulder dystosia group (P < 0.05). (5) There were significant difference in the chest circumference of the newborn [(34.0±1.6) vs (32.2±1.9) cm ] and the ratio of chest circumference to head circumference of the newborn [(0.99±0.03) vs (0.97±0.03) ] between the two groups (P < 0.05). The 1-minute Apgar score of the newborn (7.4±2.8) was significantly lower than the control group (10.0±0.0) (P < 0.01). Clavicular fracture occurred in 3 newborns and brachial plexus injury occurred in 4 newborns in the shoulder dystosia group. It is difficult to predict shoulder dystocia in non-macrosomia. Shoulder dystocia of non-macrosomia could be predicted by measurement of the head circumference, chest circumference, the ratio of chest circumference to head circumference by using prenatal ultrasound. The risk factors may complicated with premature rupture of membrane, abnormal occiput position during the first stage of labor and prolonged second stage of labor.

A case-control study of the relationship between a passive second stage of labor and obstetric anal sphincter injuries.

PubMed

Gossett, Dana R; Deibel, Philip; Lewicky-Gaupp, Christina

2016-02-01

To estimate the relationship between a passive second stage of labor and obstetric anal sphincter injuries (OASIS). A retrospective, case-control study was undertaken of women who delivered at a tertiary-care center in Chicago, IL, USA, between November 2005 and December 2012. Cases had sustained OASIS and were matched on the basis of parity with controls who had no OASIS. Data were obtained from an electronic repository and chart review. Participants with a passive second stage of labor lasting 60 minutes or more were deemed to have "labored down." A logistic regression model to predict OASIS was created. Overall, 1629 cases were compared with 1312 controls. OASIS were recorded among 1452 (57.8%) of 2510 women who did not labor down compared with 169 (40.0%) of 423 women who labored down (P<0.001). However, in binary logistic regression, the addition of laboring down to the model only increased the predictive accuracy from 80.1% to 80.7%. When known risk factors for OASIS are accounted for, the effect of laboring down on perineal outcome is negligible. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Cerebral Amyloid Burden and Hoehn and Yahr Stage 3 Scoring in Parkinson Disease.

PubMed

Kotagal, Vikas; Bohnen, Nicolaas I; Müller, Martijn L T M; Frey, Kirk A; Albin, Roger L

2017-01-01

Progression to Hoehn and Yahr (HY) stage 3 marks the transition to advanced disease staging and disability in Parkinson disease (PD). We conducted a case-control study of 36 PD subjects at HY stage 2.5 or 3, with groups matched for gender, age, and disease duration. Positron Emission tomography (PET) imaging included dihydrotetrabenazine [11C]DTBZ and Pittsburgh Compound B [11C]PiB. Subjects with HY 2.5 differed from HY 3.0 in mean cortical PiB distribution volume ratio (1.14 vs. 1.23; Wilcoxon two-sample Z = 2.36, p = 0.024) but not striatal DTBZ PET. Cortical amyloid burden differentiates subjects below and at HY stage 3. These results suggest that cortical amyloid accumulation influences the transition from HY2.5 to HY3 and that cortical amyloidopathy may be a therapeutic target in PD.

Pediatric thymomas: report of two cases and comprehensive review of the literature.

PubMed

Fonseca, Annabelle L; Ozgediz, Doruk E; Christison-Lagay, Emily R; Detterbeck, Frank C; Caty, Michael G

2014-03-01

Thymomas are rare pediatric malignancies with indolent behavior. There are fewer than 50 reported cases and no comprehensive review. We sought to evaluate our recent experience with pediatric thymomas, and comprehensively review the extant literature. A systematic search of the PubMed database was performed using keywords: "thymoma", "pediatric", "juvenile", "childhood", and "child". Additional studies were identified by a manual search of the reference list. We report two patients with thymomas. We identified 22 case reports or series that described 48 patients; 62 % were male, 15 % presented with myasthenia gravis. Fifty percent were Masaoka Stage I, 15 % were Stage II, 13 % were Stage III, and 23 % were Stage IV. Four patients with early stage (I or II) disease were treated with adjuvant therapies in addition to surgical excision, while five patients with late stage (III or IV) disease treated with surgical excision alone. Of studies reporting at least 2-year follow-up, survival was 71 %. Pediatric thymomas are rare tumors with a slight male predominance. Wide variations were observed in the treatment of thymomas across all stages. Our review indicates a need for large database and multi-institutional studies to clearly elucidate clinical course, prognostic factors and outcome.

Combination of preoperative NLR, PLR and CEA could increase the diagnostic efficacy for I-III stage CRC.

PubMed

Peng, Hong-Xin; Yang, Lin; He, Bang-Shun; Pan, Yu-Qin; Ying, Hou-Qun; Sun, Hui-Ling; Lin, Kang; Hu, Xiu-Xiu; Xu, Tao; Wang, Shu-Kui

2017-09-01

Inflammation plays an important role in the development and progression of CRC. The members of inflammatory biomarkers, preoperative NLR and PLR, have been proved by numerous studies to be promising prognostic biomarkers for CRC. However, the diagnostic value of the two biomarkers in CRC remains unknown, and no study reported the combined diagnostic efficacy of NLR, PLR and CEA. Five hundred and fifty-nine patients with I-III stage CRC undergoing surgical resection and 559 gender- and age-matched healthy controls were enrolled in this retrospective study. NLR and PLR were calculated from preoperative peripheral blood cell count detected using white blood cell five classification by Sysmex XT-1800i Automated Hematology System and serum CEA were measured by electrochemiluminescence by ELECSYS 2010. The diagnostic performance of NLR, PLR and CEA for CRC was evaluated by ROC curve. Levels of NLR and PLR in the cases were significantly higher than them in the healthy controls. ROC curves comparison analyses showed that the diagnostic efficacy of NLR (AUC=.755, 95%CI=.728-.780) alone for CRC was significantly higher than PLR (AUC=.723, 95%CI=.696-.749, P=.037) and CEA (AUC=.690, 95%CI=.662-.717, P=.002) alone. In addition, the diagnostic efficacy of the combination of NLR, PLR and CEA(AUC=.831, 95%CI=.807-.852)for CRC was not only significantly higher than NLR alone but also higher than any combinations of the two of these three biomarkers (P<.05). Moreover, the NLR and PLR in the patients with TNM stage I/II was higher than that in the healthy controls, and patients with stage III had a higher NLR and PLR than those with stage I/II, but no significant difference was observed. Our study indicated that preoperative NLR could be a CRC diagnostic biomarker, even for early stage CRC, and the combination of NLR, PLR and CEA could significantly improve the diagnostic efficacy. © 2016 Wiley Periodicals, Inc.

Identification of seven new prostate cancer susceptibility loci through a genome-wide association study

PubMed Central

Eeles, Rosalind A.; Kote-Jarai, Zsofia; Olama, Ali Amin Al; Giles, Graham G.; Guy, Michelle; Severi, Gianluca; Muir, Kenneth; Hopper, John L.; Henderson, Brian E.; Haiman, Christopher A.; Schleutker, Johanna; Hamdy, Freddie C.; Neal, David E.; Donovan, Jenny L.; Stanford, Janet L.; Ostrander, Elaine A.; Ingles, Sue A.; John, Esther M.; Thibodeau, Stephen N.; Schaid, Daniel; Park, Jong Y.; Spurdle, Amanda; Clements, Judith; Dickinson, Joanne L.; Maier, Christiane; Vogel, Walther; Dörk, Thilo; Rebbeck, Timothy R.; Cooney, Kathleen A.; Cannon-Albright, Lisa; Chappuis, Pierre O.; Hutter, Pierre; Zeegers, Maurice; Kaneva, Radka; Zhang, Hong-Wei; Lu, Yong-Jie; Foulkes, William D.; English, Dallas R.; Leongamornlert, Daniel A.; Tymrakiewicz, Malgorzata; Morrison, Jonathan; Ardern-Jones, Audrey T.; Hall, Amanda L.; O’Brien, Lynne T.; Wilkinson, Rosemary A.; Saunders, Edward J.; Page, Elizabeth C.; Sawyer, Emma J.; Edwards, Stephen M.; Dearnaley, David P.; Horwich, Alan; Huddart, Robert A.; Khoo, Vincent S.; Parker, Christopher C.; Van As, Nicholas; Woodhouse, Christopher J.; Thompson, Alan; Christmas, Tim; Ogden, Chris; Cooper, Colin S.; Southey, Melissa C.; Lophatananon, Artitaya; Liu, Jo-Fen; Kolonel, Laurence N.; Le Marchand, Loic; Wahlfors, Tiina; Tammela, Teuvo L.; Auvinen, Anssi; Lewis, Sarah J.; Cox, Angela; FitzGerald, Liesel M.; Koopmeiners, Joseph S.; Karyadi, Danielle M.; Kwon, Erika M.; Stern, Mariana C.; Corral, Roman; Joshi, Amit D.; Shahabi, Ahva; McDonnell, Shannon K.; Sellers, Thomas A; Pow-Sang, Julio; Chambers, Suzanne; Aitken, Joanne; Gardiner, R.A. (Frank); Batra, Jyotsna; Kedda, Mary Anne; Lose, Felicity; Polanowski, Andrea; Patterson, Briony; Serth, Jürgen; Meyer, Andreas; Luedeke, Manuel; Stefflova, Klara; Ray, Anna M.; Lange, Ethan M.; Farnham, Jim; Khan, Humera; Slavov, Chavdar; Mitkova, Atanaska; Cao, Guangwen; Easton, Douglas F.

2010-01-01

Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. To identify common PrCa susceptibility alleles, we have previously conducted a genome-wide association study in which 541, 129 SNPs were genotyped in 1,854 PrCa cases with clinically detected disease and 1,894 controls. We have now evaluated promising associations in a second stage, in which we genotyped 43,671 SNPs in 3,650 PrCa cases and 3,940 controls, and a third stage, involving an additional 16,229 cases and 14,821 controls from 21 studies. In addition to previously identified loci, we identified a further seven new prostate cancer susceptibility loci on chromosomes 2, 4, 8, 11, and 22 (P=1.6×10−8 to P=2.7×10−33). PMID:19767753

Quantitative safety assessment of air traffic control systems through system control capacity

NASA Astrophysics Data System (ADS)

Guo, Jingjing

Quantitative Safety Assessments (QSA) are essential to safety benefit verification and regulations of developmental changes in safety critical systems like the Air Traffic Control (ATC) systems. Effectiveness of the assessments is particularly desirable today in the safe implementations of revolutionary ATC overhauls like NextGen and SESAR. QSA of ATC systems are however challenged by system complexity and lack of accident data. Extending from the idea "safety is a control problem" in the literature, this research proposes to assess system safety from the control perspective, through quantifying a system's "control capacity". A system's safety performance correlates to this "control capacity" in the control of "safety critical processes". To examine this idea in QSA of the ATC systems, a Control-capacity Based Safety Assessment Framework (CBSAF) is developed which includes two control capacity metrics and a procedural method. The two metrics are Probabilistic System Control-capacity (PSC) and Temporal System Control-capacity (TSC); each addresses an aspect of a system's control capacity. And the procedural method consists three general stages: I) identification of safety critical processes, II) development of system control models and III) evaluation of system control capacity. The CBSAF was tested in two case studies. The first one assesses an en-route collision avoidance scenario and compares three hypothetical configurations. The CBSAF was able to capture the uncoordinated behavior between two means of control, as was observed in a historic midair collision accident. The second case study compares CBSAF with an existing risk based QSA method in assessing the safety benefits of introducing a runway incursion alert system. Similar conclusions are reached between the two methods, while the CBSAF has the advantage of simplicity and provides a new control-based perspective and interpretation to the assessments. The case studies are intended to investigate the potential and demonstrate the utilities of CBSAF and are not intended for thorough studies of collision avoidance and runway incursions safety, which are extremely challenging problems. Further development and thorough validations are required to allow CBSAF to reach implementation phases, e.g. addressing the issues of limited scalability and subjectivity.

Case control study of neuroblastoma in west-Germany after the Chernobyl accident.

PubMed

Michaelis, J; Haaf, H G; Zöllner, J; Kaatsch, P; Krummenauer, F; Berthold, F

1996-01-01

To explore possible causes of a 1988 incidence peak of infant neuroblastoma in west German regions which were contaminated with more than 6000 Bq/m2 Cs137 from the Chernobyl accident. The primary working hypothesis was that parents of the diseased children had been contaminated by an excessive intake of locally produced food, especially mushrooms or deer. Case control study with 1:2 (cases:controls) matching. Data were collected from the children's parents by questionnaires and telephone interviews. Nation-wide study (former FRG) based on the German Childhood Cancer Registry. Cases born in 1988 and reported with a neuroblastoma to the registry until March 1992. Population-based healthy controls, matched for age, sex and residence at time of diagnosis. The working hypothesis could not be confirmed by the study, because the parents of cases tended to eat less locally grown food than the parents of controls (RR = 0.63, 95% CI:0.20-1.97). Possible influence factors which previously have been described to be associated with neuroblastoma incidence could not be confirmed by the study. Parental exposure to herbicides and pesticides was associated with the occurrence of neuroblastoma (RR = 4.2, 95% CI:1.4-12.9). Neuroblastoma stage distribution in the contaminated regions was shifted towards lower stages as compared to the less contaminated regions and previous age cohorts. The study does not show additional evidence that the observed increase in neuroblastoma incidence might have been caused by exposure to fallout from the Chernobyl accident. The observed shift towards lower clinical stages may rather indicate increased diagnostic awareness. The association between neuroblastoma and parental exposure with herbicides and pesticides resulted from an extensive exploratory data analysis and needs to be confirmed in further studies.

Radiotherapy is associated with significant improvement in local and regional control in Merkel cell carcinoma

PubMed Central

2012-01-01

Introduction Merkel cell carcinoma (MCC) is a rare tumour of skin. This study is a retrospective audit of patients with MCC from St Vincent’s and Mater Hospital, Sydney, Australia. The aim of this study was to investigate the influence of radiotherapy (RT) on the local and regional control of MCC lesions and survival of patients with MCC. Method The data bases in anatomical pathology, RT and surgery. We searched for patients having a diagnosis of MCC between 1996 and 2007. Patient, tumour and treatment characteristics were collected and analysed. Univariate survival analysis of categorical variables was conducted with the Kaplan-Meier method together with the Log-Rank test for statistical significance. Continuous variables were assessed using the Cox regression method. Multivariate analysis was performed for significant univariate results. Results Sixty seven patients were found. Sixty two who were stage I-III and were treated with radical intent were analysed. 68% were male. The median age was 74 years. Forty-two cases (68%) were stage I or II, and 20 cases (32%) were stage III. For the subset of 42 stage I and II patients, those that had RT to their primary site had a 2-year local recurrence free survival of 89% compared with 36% for patients not receiving RT (p<0.001). The cumulative 2-year regional recurrence free survival for patients having adjuvant regional RT was 84% compared with 43% for patients not receiving this treatment (p<0.001). Immune status at initial surgery was a significant predictor for OS and MCCSS. In a multivariate analysis combining macroscopic size (mm) and immune status at initial surgery, only immune status remained a significant predictor of overall survival (HR=2.096, 95% CI: 1.002-4.385, p=0.049). Conclusions RT is associated with significant improvement in local and regional control in Merkel cell carcinoma. Immunosuppression is an important factor in overall survival. PMID:23075308

Head and neck adenoid cystic carcinoma: A prospective multicenter REFCOR study of 95 cases.

PubMed

Meyers, M; Granger, B; Herman, P; Janot, F; Garrel, R; Fakhry, N; Poissonnet, G; Baujat, B

2016-02-01

To describe the clinical, histological and therapeutic characteristics of a prospective multicenter series of 95 head and neck adenoid cystic carcinoma patients, and to determine any prognostic factors for disease-free survival. Ninety-five patients with adenoid cystic carcinoma were included in the Réseau d'Expertise Français Des Cancers ORL Rares (REFCOR, French Rare Head and Neck Cancer Expert Network) database between 2009 and 2012. The primary site was the salivary glands in 39 cases, sinus cavities (including hard palate) in 36 cases, pharynx-larynx-trachea in 14 cases, and lips and oral cavity in 4 cases. The tumor was stage I in 15% of cases, stage II in 23%, stage III in 26% and stage IV in 36%. Nine patients had cervical lymph node involvement and 5 had metastases at diagnosis. Fifty-six percent of patients were managed by surgery with postoperative radiation therapy. During follow-up, 3 patients died, 9 developed metastases and 12 showed recurrence or local progression. Mean follow-up was 18 months. On univariate analysis, disease-free survival correlated with T stage (P=0.05), N stage (P=0.003), resection margins (P=0.04), lymph node involvement on histology (P=0.01), and absence of chemotherapy (P=0.03). On multivariate analysis, disease-free survival correlated with T stage (P=0.01), N stage (P=0.09) and surgery (P=0.005). The essential issue in adenoid cystic carcinoma is long-term control. The present results confirm that the reference attitude is radical surgical resection for optimal local control. Adjuvant radiation therapy did not emerge as a prognostic factor. This study also provides a starting-point for translational studies in pathology and genetics. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Outcomes in Patients with Persistent Ventricular Dysfunction After Stage I Palliation for Hypoplastic Left Heart Syndrome.

PubMed

Jean-St-Michel, Emilie; Chetan, Devin; Schwartz, Steven M; Van Arsdell, Glen S; Floh, Alejandro A; Honjo, Osami; Conway, Jennifer

2016-02-01

We sought to describe the clinical course for patients with hypoplastic left heart syndrome and persistent ventricular dysfunction and identify risk factors for death or transplantation before stage II palliation. 138 children undergoing stage I palliation from 2004 to 2011 were reviewed. Twenty-two (16 %) patients (seven Hybrid, 15 Norwood) with two consecutive echocardiograms reporting at least moderate dysfunction were included and compared to case-matched controls. Eleven of the 22 patients with dysfunction (50 %) underwent stage II, seven (32 %) were transplanted, and four (18 %) died prior to stage II. Of the patients who survived to hospital discharge (n = 17) following stage 1, 14 (82 %) required readmission for heart failure (HF) compared to only two (10 %) for controls (p < 0.001). Among patients with ventricular dysfunction, there was an increased use of ACE inhibitors or beta-blockers (82 vs. 25 %; p = 0.001), inotropes (71 vs. 15 %; p = 0.001), ventilation (58 vs. 10 %; p = 0.001), and ECMO (29 vs. 0 %; p = 0.014) for HF management post-discharge when compared to controls. There was a lower heart transplant-free survival at 7 months in patients with dysfunction compared to controls (50.6 vs. 90.9 %; p = 0.040). ECMO support (p = 0.001) and duration of inotropic support (p = 0.04) were significantly associated with death or transplantation before stage II palliation. Patients with ventricular dysfunction received more HF management and related admissions. Longer inotropic support should prompt discussion regarding alternative treatment strategies given its association with death or transplant.

Asymmetrical booster guidance and control system design study. Volume 3: Space shuttle vehicle SRB actuator failure study. [space shuttle development

NASA Technical Reports Server (NTRS)

Williams, F. E.; Lemon, R. S.

1974-01-01

The investigation of single actuator failures on the space shuttle solid rocket booster required the analysis of both square pattern and diamond pattern actuator configurations. It was determined that for failures occuring near or prior to the region of maximum dynamic pressure, control gain adjustments can be used to achieve virtually nominal mid-boost vehicle behavior. A distinct worst case failure condition was established near staging that could significantly delay staging. It is recommended that the square pattern be retained as a viable alternative to the baseline diamond pattern because the staging transient is better controlled resulting in earlier staging.

Single-stage autologous ear reconstruction for microtia.

PubMed

Kasrai, Leila; Snyder-Warwick, Alison K; Fisher, David M

2014-03-01

The authors have been using the Nagata technique since 2002. In this review of 100 consecutive ear reconstructions, the authors present technique modifications that have evolved over this period that have contributed to improved auricular contour and that now allow for auricular reconstruction in a single stage. This study is a retrospective review of a prospectively acquired database. The series is restricted to primary reconstructions performed for congenital microtia. Photographs of 10 consecutive patients are presented to demonstrate the results of the technique. Surgical complication rates are discussed. One hundred ear reconstructions were performed in 96 patients. There were 75 primary cases of congenital microtia. Twenty-four ears underwent a two-stage reconstruction, and 51 ears were reconstructed with a Nagata stage I procedure or a single-stage reconstruction. There was a gradual shift in technique, with a trend to perform fewer Nagata stage II outsetting procedures and more single-stage reconstructions. In patients who underwent an ear reconstruction in two stages, the surgical complication rate was 22 percent. In the last 40 consecutive ear reconstructions since abandoning the two-stage approach, the surgical complication rate is now 15 percent. A modification of Nagata's technique of autologous ear reconstruction for microtia is described. Modifications of the three-dimensional framework address the contour of the inferior crus and control tragal projection and position. Inclusion of a projection block and recruitment of retroauricular skin allow for symmetric projection of the ear in a single stage. Therapeutic, IV.

Treatment and prognosis of primary thymic carcinoma.

PubMed

Yano, T; Hara, N; Ichinose, Y; Asoh, H; Yokoyama, H; Ohta, M

1993-04-01

From 1972 to 1990, we treated eight cases of thymic carcinoma (6 squamous cell and 2 small cell carcinomas). According to the classification by Masaoka et al., they consisted of one stage I, four stage III, one stage IVa, and two stage IVb. A complete resection of the primary tumour could be done in only three patients; the others had diagnostic biopsy and then radiation treatment. Four of five patients had a prolonged regression of the primary tumors after irradiation at 40-61.2 Gy. Six patients suffered from extrathoracic metastases. All patients received systemic chemotherapy with different regimens to counter either metastatic or locally recurrent lesions. Only two patients (with a regimen including cyclophosphamide, doxorubicin, and vincristine) obtained a partial response. The median survival of the eight patients was 70 months after surgical operation. The identification of an effective drug combination may thus improve the long-term prognosis of thymic carcinoma since radiotherapy is able to control primary lesions, even in the case of unresectable advanced disease.

A Multiphase Design Strategy for Dealing with Participation Bias

PubMed Central

Haneuse, S.; Chen, J.

2012-01-01

Summary A recently funded study of the impact of oral contraceptive use on the risk of bone fracture employed the randomized recruitment scheme of Weinberg and Wacholder (1990, Biometrics 46, 963–975). One potential complication in the bone fracture study is the potential for differential response rates between cases and controls; participation rates in previous, related studies have been around 70%. Although data from randomized recruitment schemes may be analyzed within the two-phase study framework, ignoring potential differential participation may lead to biased estimates of association. To overcome this, we build on the two-phase framework and propose an extension by introducing an additional stage of data collection aimed specifically at addressing potential differential participation. Four estimators that correct for both sampling and participation bias are proposed; two are general purpose and two are for the special case where covariates underlying the participation mechanism are discrete. Because the fracture study is ongoing, we illustrate the methods using infant mortality data from North Carolina. PMID:20377576

Methodological proposal for the remediation of a site affected by phosphogypsum deposits

NASA Astrophysics Data System (ADS)

Martínez-Sanchez, M. J.; Perez-Sirvent, C.; Bolivar, J. P.; Garcia-Tenorio, R.

2012-04-01

The accumulation of phosphogysum (PY) produces a well known environmental problems. The proposals for the remediation of these sites require multidisciplinary and very specific studies. Since they cover large areas a sampling design specifically outlined for each case is necessary in order the contaminants, transfer pathways and particular processes can be correctly identified. In addition to a suitable sampling of the soil, aquatic medium and biota, appropriate studies of the space-temporal variations by means of control samples are required. Two different stages should be considered: 1.- Diagnostic stage This stage includes preliminary studies, identification of possible sources of radiosotopes, design of the appropriate sampling plan, hydrogeological study, characterization and study of the space-temporal variability of radioisotopes and other contaminants, as well as the risk assessement for health and ecosystems, that depends on the future use of the site. 2.- Remediation proposal stage It comprises the evaluation and comparison of the different procedures for the decontamination/remediation, including models experiments at the laboratory. To this respect, the preparation and detailed study of a small scale pilot project is a task of particular relevance. In this way the suitability of the remediating technology can be checked, and its performance optimized. These two stages allow a technically well-founded proposal to be presented to the Organisms or Institutions in charge of the problem and facilitate decision-making. It both stages be included in a social communication campaign in order the final proposal be accepted by stakeholders.

Mechatronic system design course for undergraduate programmes

NASA Astrophysics Data System (ADS)

Saleem, A.; Tutunji, T.; Al-Sharif, L.

2011-08-01

Technology advancement and human needs have led to integration among many engineering disciplines. Mechatronics engineering is an integrated discipline that focuses on the design and analysis of complete engineering systems. These systems include mechanical, electrical, computer and control subsystems. In this paper, the importance of teaching mechatronic system design to undergraduate engineering students is emphasised. The paper offers the collaborative experience in preparing and delivering the course material for two universities in Jordan. A detailed description of such a course is provided and a case study is presented. The case study used is a final year project, where students applied a six-stage design procedure that is described in the paper.

Social support networks and depression of women suffering from early-stage breast cancer: a case control study.

PubMed

Gagliardi, Cristina; Vespa, Anna; Papa, Roberta; Mariotti, Carlo; Cascinu, Stefano; Rossini, Simonetta

2009-01-01

The aim of this study was to investigate the areas of depression, anxiety, and social support using the structural model of the social network. By comparing the networks of two samples of breast cancer sufferers and healthy control participants, it was possible to identify differences in their relationships, in the shape of the networks themselves, and in the levels of depression and anxiety. Women with breast cancer described smaller and denser networks, including mainly kins whereas the healthy women included more friends, coworkers, and leisure companions. The levels of anxiety and depression were higher in women with breast cancer. Social network and social support measure correlated differently with depression and anxiety in the two groups.

Polymorphisms in inflammation pathway genes and endometrial cancer risk

PubMed Central

Delahanty, Ryan J.; Xiang, Yong-Bing; Spurdle, Amanda; Beeghly-Fadiel, Alicia; Long, Jirong; Thompson, Deborah; Tomlinson, Ian; Yu, Herbert; Lambrechts, Diether; Dörk, Thilo; Goodman, Marc T.; Zheng, Ying; Salvesen, Helga B.; Bao, Ping-Ping; Amant, Frederic; Beckmann, Matthias W.; Coenegrachts, Lieve; Coosemans, An; Dubrowinskaja, Natalia; Dunning, Alison; Runnebaum, Ingo B.; Easton, Douglas; Ekici, Arif B.; Fasching, Peter A.; Halle, Mari K.; Hein, Alexander; Howarth, Kimberly; Gorman, Maggie; Kaydarova, Dylyara; Krakstad, Camilla; Lose, Felicity; Lu, Lingeng; Lurie, Galina; O’Mara, Tracy; Matsuno, Rayna K.; Pharoah, Paul; Risch, Harvey; Corssen, Madeleine; Trovik, Jone; Turmanov, Nurzhan; Wen, Wanqing; Lu, Wei; Cai, Qiuyin; Zheng, Wei; Shu, Xiao-Ou

2013-01-01

Background Experimental and epidemiological evidence have suggested that chronic inflammation may play a critical role in endometrial carcinogenesis. Methods To investigate this hypothesis, a two-stage study was carried out to evaluate single nucleotide polymorphisms (SNPs) in inflammatory pathway genes in association with endometrial cancer risk. In stage 1, 64 candidate pathway genes were identified and 4,542 directly genotyped or imputed SNPs were analyzed among 832 endometrial cancer cases and 2,049 controls, using data from the Shanghai Endometrial Cancer Genetics Study. Linkage disequilibrium of stage 1 SNPs significantly associated with endometrial cancer (P<0.05) indicated that the majority of associations could be linked to one of 24 distinct loci. One SNP from each of the 24 loci was then selected for follow-up genotyping. Of these, 21 SNPs were successfully designed and genotyped in stage 2, which consisted of ten additional studies including 6,604 endometrial cancer cases and 8,511 controls. Results Five of the 21 SNPs had significant allelic odds ratios and 95% confidence intervals as follows: FABP1, 0.92 (0.85-0.99); CXCL3, 1.16 (1.05-1.29); IL6, 1.08 (1.00-1.17); MSR1, 0.90 (0.82-0.98); and MMP9, 0.91 (0.87-0.97). Two of these polymorphisms were independently significant in the replication sample (rs352038 in CXCL3 and rs3918249 in MMP9). The association for the MMP9 polymorphism remained significant after Bonferroni correction and showed a significant association with endometrial cancer in both Asian- and European-ancestry samples. Conclusions These findings lend support to the hypothesis that genetic polymorphisms in genes involved in the inflammatory pathway may contribute to genetic susceptibility to endometrial cancer. Impact Statement This study adds to the growing evidence that inflammation plays an important role in endometrial carcinogenesis. PMID:23221126

Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma

PubMed Central

Fogarty, Rhys; Sharma, Shiwani; Hewitt, Alex W.; Martin, Sarah; Law, Matthew H.; Cremin, Katie; Bailey, Jessica N. Cooke; Loomis, Stephanie J.; Pasquale, Louis R.; Haines, Jonathan L.; Hauser, Michael A.; Viswanathan, Ananth C.; McGuffin, Peter; Topouzis, Fotis; Foster, Paul J.; Graham, Stuart L; Casson, Robert J; Chehade, Mark; White, Andrew J; Zhou, Tiger; Souzeau, Emmanuelle; Landers, John; Fitzgerald, Jude T; Klebe, Sonja; Ruddle, Jonathan B; Goldberg, Ivan; Healey, Paul R; Mills, Richard A.; Wang, Jie Jin; Montgomery, Grant W.; Martin, Nicholas G.; Radford-Smith, Graham; Whiteman, David C.; Brown, Matthew A.; Wiggs, Janey L.; Mackey, David A; Mitchell, Paul; MacGregor, Stuart; Craig, Jamie E.

2014-01-01

Primary open-angle glaucoma (POAG) is a major cause of irreversible blindness worldwide. We performed a genome-wide association study in an Australian discovery cohort comprising 1,155 advanced POAG cases and 1,992 controls. Association of the top SNPs from the discovery stage was investigated in two Australian replication cohorts (total 932 cases, 6,862 controls) and two US replication cohorts (total 2,616 cases, 2,634 controls). Meta-analysis of all cohorts revealed three novel loci associated with development of POAG. These loci are located upstream of ABCA1 (rs2472493 [G] OR=1.31, P= 2.1 × 10−19), within AFAP1 (rs4619890 [G] OR=1.20, P= 7.0 × 10−10) and within GMDS (rs11969985 [G] OR=1.31, and P= 7.7 × 10−10). Using RT-PCR and immunolabelling, we also showed that these genes are expressed within human retina, optic nerve and trabecular meshwork and that ABCA1 and AFAP1 are also expressed in retinal ganglion cells. PMID:25173105

Phase 1b randomized trial and follow-up study in Uganda of the blood-stage malaria vaccine candidate BK-SE36.

PubMed

Palacpac, Nirianne Marie Q; Ntege, Edward; Yeka, Adoke; Balikagala, Betty; Suzuki, Nahoko; Shirai, Hiroki; Yagi, Masanori; Ito, Kazuya; Fukushima, Wakaba; Hirota, Yoshio; Nsereko, Christopher; Okada, Takuya; Kanoi, Bernard N; Tetsutani, Kohhei; Arisue, Nobuko; Itagaki, Sawako; Tougan, Takahiro; Ishii, Ken J; Ueda, Shigeharu; Egwang, Thomas G; Horii, Toshihiro

2013-01-01

Up to now a malaria vaccine remains elusive. The Plasmodium falciparum serine repeat antigen-5 formulated with aluminum hydroxyl gel (BK-SE36) is a blood-stage malaria vaccine candidate that has undergone phase 1a trial in malaria-naive Japanese adults. We have now assessed the safety and immunogenicity of BK-SE36 in a malaria endemic area in Northern Uganda. We performed a two-stage, randomized, single-blinded, placebo-controlled phase 1b trial (Current Controlled trials ISRCTN71619711). A computer-generated sequence randomized healthy subjects for 2 subcutaneous injections at 21-day intervals in Stage1 (21-40 year-olds) to 1-mL BK-SE36 (BKSE1.0) (n = 36) or saline (n = 20) and in Stage2 (6-20 year-olds) to BKSE1.0 (n = 33), 0.5-mL BK-SE36 (BKSE0.5) (n = 33), or saline (n = 18). Subjects and laboratory personnel were blinded. Safety and antibody responses 21-days post-second vaccination (Day42) were assessed. Post-trial, to compare the risk of malaria episodes 130-365 days post-second vaccination, Stage2 subjects were age-matched to 50 control individuals. Nearly all subjects who received BK-SE36 had induration (Stage1, n = 33, 92%; Stage2, n = 63, 96%) as a local adverse event. No serious adverse event related to BK-SE36 was reported. Pre-existing anti-SE36 antibody titers negatively correlated with vaccination-induced antibody response. At Day42, change in antibody titers was significant for seronegative adults (1.95-fold higher than baseline [95% CI, 1.56-2.43], p = 0.004) and 6-10 year-olds (5.71-fold [95% CI, 2.38-13.72], p = 0.002) vaccinated with BKSE1.0. Immunogenicity response to BKSE0.5 was low and not significant (1.55-fold [95% CI, 1.24-1.94], p = 0.75). In the ancillary analysis, cumulative incidence of first malaria episodes with ≥5000 parasites/µL was 7 cases/33 subjects in BKSE1.0 and 10 cases/33 subjects in BKSE0.5 vs. 29 cases/66 subjects in the control group. Risk ratio for BKSE1.0 was 0.48 (95% CI, 0.24-0.98; p = 0.04). BK-SE36 is safe and immunogenic. The promising potential of BK-SE36, observed in the follow-up study, warrants a double-blind phase 1/2b trial in children under 5 years. Controlled-Trials.com ISRCTN71619711.

A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11.

PubMed

Siddiq, Afshan; Couch, Fergus J; Chen, Gary K; Lindström, Sara; Eccles, Diana; Millikan, Robert C; Michailidou, Kyriaki; Stram, Daniel O; Beckmann, Lars; Rhie, Suhn Kyong; Ambrosone, Christine B; Aittomäki, Kristiina; Amiano, Pilar; Apicella, Carmel; Baglietto, Laura; Bandera, Elisa V; Beckmann, Matthias W; Berg, Christine D; Bernstein, Leslie; Blomqvist, Carl; Brauch, Hiltrud; Brinton, Louise; Bui, Quang M; Buring, Julie E; Buys, Saundra S; Campa, Daniele; Carpenter, Jane E; Chasman, Daniel I; Chang-Claude, Jenny; Chen, Constance; Clavel-Chapelon, Françoise; Cox, Angela; Cross, Simon S; Czene, Kamila; Deming, Sandra L; Diasio, Robert B; Diver, W Ryan; Dunning, Alison M; Durcan, Lorraine; Ekici, Arif B; Fasching, Peter A; Feigelson, Heather Spencer; Fejerman, Laura; Figueroa, Jonine D; Fletcher, Olivia; Flesch-Janys, Dieter; Gaudet, Mia M; Gerty, Susan M; Rodriguez-Gil, Jorge L; Giles, Graham G; van Gils, Carla H; Godwin, Andrew K; Graham, Nikki; Greco, Dario; Hall, Per; Hankinson, Susan E; Hartmann, Arndt; Hein, Rebecca; Heinz, Judith; Hoover, Robert N; Hopper, John L; Hu, Jennifer J; Huntsman, Scott; Ingles, Sue A; Irwanto, Astrid; Isaacs, Claudine; Jacobs, Kevin B; John, Esther M; Justenhoven, Christina; Kaaks, Rudolf; Kolonel, Laurence N; Coetzee, Gerhard A; Lathrop, Mark; Le Marchand, Loic; Lee, Adam M; Lee, I-Min; Lesnick, Timothy; Lichtner, Peter; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Martin, Nicholas G; McLean, Catriona A; Meijers-Heijboer, Hanne; Meindl, Alfons; Miron, Penelope; Monroe, Kristine R; Montgomery, Grant W; Müller-Myhsok, Bertram; Nickels, Stefan; Nyante, Sarah J; Olswold, Curtis; Overvad, Kim; Palli, Domenico; Park, Daniel J; Palmer, Julie R; Pathak, Harsh; Peto, Julian; Pharoah, Paul; Rahman, Nazneen; Rivadeneira, Fernando; Schmidt, Daniel F; Schmutzler, Rita K; Slager, Susan; Southey, Melissa C; Stevens, Kristen N; Sinn, Hans-Peter; Press, Michael F; Ross, Eric; Riboli, Elio; Ridker, Paul M; Schumacher, Fredrick R; Severi, Gianluca; Dos Santos Silva, Isabel; Stone, Jennifer; Sund, Malin; Tapper, William J; Thun, Michael J; Travis, Ruth C; Turnbull, Clare; Uitterlinden, Andre G; Waisfisz, Quinten; Wang, Xianshu; Wang, Zhaoming; Weaver, Joellen; Schulz-Wendtland, Rüdiger; Wilkens, Lynne R; Van Den Berg, David; Zheng, Wei; Ziegler, Regina G; Ziv, Elad; Nevanlinna, Heli; Easton, Douglas F; Hunter, David J; Henderson, Brian E; Chanock, Stephen J; Garcia-Closas, Montserrat; Kraft, Peter; Haiman, Christopher A; Vachon, Celine M

2012-12-15

Genome-wide association studies (GWAS) of breast cancer defined by hormone receptor status have revealed loci contributing to susceptibility of estrogen receptor (ER)-negative subtypes. To identify additional genetic variants for ER-negative breast cancer, we conducted the largest meta-analysis of ER-negative disease to date, comprising 4754 ER-negative cases and 31 663 controls from three GWAS: NCI Breast and Prostate Cancer Cohort Consortium (BPC3) (2188 ER-negative cases; 25 519 controls of European ancestry), Triple Negative Breast Cancer Consortium (TNBCC) (1562 triple negative cases; 3399 controls of European ancestry) and African American Breast Cancer Consortium (AABC) (1004 ER-negative cases; 2745 controls). We performed in silico replication of 86 SNPs at P ≤ 1 × 10(-5) in an additional 11 209 breast cancer cases (946 with ER-negative disease) and 16 057 controls of Japanese, Latino and European ancestry. We identified two novel loci for breast cancer at 20q11 and 6q14. SNP rs2284378 at 20q11 was associated with ER-negative breast cancer (combined two-stage OR = 1.16; P = 1.1 × 10(-8)) but showed a weaker association with overall breast cancer (OR = 1.08, P = 1.3 × 10(-6)) based on 17 869 cases and 43 745 controls and no association with ER-positive disease (OR = 1.01, P = 0.67) based on 9965 cases and 22 902 controls. Similarly, rs17530068 at 6q14 was associated with breast cancer (OR = 1.12; P = 1.1 × 10(-9)), and with both ER-positive (OR = 1.09; P = 1.5 × 10(-5)) and ER-negative (OR = 1.16, P = 2.5 × 10(-7)) disease. We also confirmed three known loci associated with ER-negative (19p13) and both ER-negative and ER-positive breast cancer (6q25 and 12p11). Our results highlight the value of large-scale collaborative studies to identify novel breast cancer risk loci.

A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11

PubMed Central

Siddiq, Afshan; Couch, Fergus J.; Chen, Gary K.; Lindström, Sara; Eccles, Diana; Millikan, Robert C.; Michailidou, Kyriaki; Stram, Daniel O.; Beckmann, Lars; Rhie, Suhn Kyong; Ambrosone, Christine B.; Aittomäki, Kristiina; Amiano, Pilar; Apicella, Carmel; Baglietto, Laura; Bandera, Elisa V.; Beckmann, Matthias W.; Berg, Christine D.; Bernstein, Leslie; Blomqvist, Carl; Brauch, Hiltrud; Brinton, Louise; Bui, Quang M.; Buring, Julie E.; Buys, Saundra S.; Campa, Daniele; Carpenter, Jane E.; Chasman, Daniel I.; Chang-Claude, Jenny; Chen, Constance; Clavel-Chapelon, Françoise; Cox, Angela; Cross, Simon S.; Czene, Kamila; Deming, Sandra L.; Diasio, Robert B.; Diver, W. Ryan; Dunning, Alison M.; Durcan, Lorraine; Ekici, Arif B.; Fasching, Peter A.; Feigelson, Heather Spencer; Fejerman, Laura; Figueroa, Jonine D.; Fletcher, Olivia; Flesch-Janys, Dieter; Gaudet, Mia M.; Gerty, Susan M.; Rodriguez-Gil, Jorge L.; Giles, Graham G.; van Gils, Carla H.; Godwin, Andrew K.; Graham, Nikki; Greco, Dario; Hall, Per; Hankinson, Susan E.; Hartmann, Arndt; Hein, Rebecca; Heinz, Judith; Hoover, Robert N.; Hopper, John L.; Hu, Jennifer J.; Huntsman, Scott; Ingles, Sue A.; Irwanto, Astrid; Isaacs, Claudine; Jacobs, Kevin B.; John, Esther M.; Justenhoven, Christina; Kaaks, Rudolf; Kolonel, Laurence N.; Coetzee, Gerhard A.; Lathrop, Mark; Le Marchand, Loic; Lee, Adam M.; Lee, I-Min; Lesnick, Timothy; Lichtner, Peter; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Martin, Nicholas G.; McLean, Catriona A.; Meijers-Heijboer, Hanne; Meindl, Alfons; Miron, Penelope; Monroe, Kristine R.; Montgomery, Grant W.; Müller-Myhsok, Bertram; Nickels, Stefan; Nyante, Sarah J.; Olswold, Curtis; Overvad, Kim; Palli, Domenico; Park, Daniel J.; Palmer, Julie R.; Pathak, Harsh; Peto, Julian; Pharoah, Paul; Rahman, Nazneen; Rivadeneira, Fernando; Schmidt, Daniel F.; Schmutzler, Rita K.; Slager, Susan; Southey, Melissa C.; Stevens, Kristen N.; Sinn, Hans-Peter; Press, Michael F.; Ross, Eric; Riboli, Elio; Ridker, Paul M.; Schumacher, Fredrick R.; Severi, Gianluca; dos Santos Silva, Isabel; Stone, Jennifer; Sund, Malin; Tapper, William J.; Thun, Michael J.; Travis, Ruth C.; Turnbull, Clare; Uitterlinden, Andre G.; Waisfisz, Quinten; Wang, Xianshu; Wang, Zhaoming; Weaver, JoEllen; Schulz-Wendtland, Rüdiger; Wilkens, Lynne R.; Van Den Berg, David; Zheng, Wei; Ziegler, Regina G.; Ziv, Elad; Nevanlinna, Heli; Easton, Douglas F.; Hunter, David J.; Henderson, Brian E.; Chanock, Stephen J.; Garcia-Closas, Montserrat; Kraft, Peter; Haiman, Christopher A.; Vachon, Celine M.

2012-01-01

Genome-wide association studies (GWAS) of breast cancer defined by hormone receptor status have revealed loci contributing to susceptibility of estrogen receptor (ER)-negative subtypes. To identify additional genetic variants for ER-negative breast cancer, we conducted the largest meta-analysis of ER-negative disease to date, comprising 4754 ER-negative cases and 31 663 controls from three GWAS: NCI Breast and Prostate Cancer Cohort Consortium (BPC3) (2188 ER-negative cases; 25 519 controls of European ancestry), Triple Negative Breast Cancer Consortium (TNBCC) (1562 triple negative cases; 3399 controls of European ancestry) and African American Breast Cancer Consortium (AABC) (1004 ER-negative cases; 2745 controls). We performed in silico replication of 86 SNPs at P ≤ 1 × 10-5 in an additional 11 209 breast cancer cases (946 with ER-negative disease) and 16 057 controls of Japanese, Latino and European ancestry. We identified two novel loci for breast cancer at 20q11 and 6q14. SNP rs2284378 at 20q11 was associated with ER-negative breast cancer (combined two-stage OR = 1.16; P = 1.1 × 10−8) but showed a weaker association with overall breast cancer (OR = 1.08, P = 1.3 × 10–6) based on 17 869 cases and 43 745 controls and no association with ER-positive disease (OR = 1.01, P = 0.67) based on 9965 cases and 22 902 controls. Similarly, rs17530068 at 6q14 was associated with breast cancer (OR = 1.12; P = 1.1 × 10−9), and with both ER-positive (OR = 1.09; P = 1.5 × 10−5) and ER-negative (OR = 1.16, P = 2.5 × 10−7) disease. We also confirmed three known loci associated with ER-negative (19p13) and both ER-negative and ER-positive breast cancer (6q25 and 12p11). Our results highlight the value of large-scale collaborative studies to identify novel breast cancer risk loci. PMID:22976474

Validation of Serum Markers for the Early Detection of Hepatocellular Carcinoma — EDRN Public Portal

Cancer.gov

Using the guidelines for cancer biomarker validation suggested by Pepe et al. (23), we propose to perform a Phase 2 study of DCP for the detection of early stage HCC. In this proposal, we plan to perform a larger case-control study to compare the sensitivity and specificity of DCP and AFP alone and in combination in differentiating patients with all stages of HCC and more importantly those with early HCC from patients with cirrhosis. We plan to enroll consecutive patients with HCC seen at 7 centers in the United States. Controls are frequency matched to cases (all center combined) using the following criteria: age (±10 years), gender (+10%) and etiology of liver disease (viral vs non-viral (+5%). Within each participating institution, there will be an equal number (+20%) of cases and controls.

Rocket nozzle expansion ratio analysis for dual-fuel earth-to-orbit vehicles

NASA Technical Reports Server (NTRS)

Martin, James A.

1989-01-01

Results are reported from a recent study of the effects of Space Shuttle Main Engine expansion ratio modifications, in the cases of both single-stage and two-stage systems. Two-position nozzles were employed; after varying the lower expansion ratio while the higher was held constant at 120, the lower expansion ratio was held constant at 40 or 60 while the higher expansion ratio was varied. The expansion ratios for minimum vehicle dry mass are different for single-stage and two-stage systems. For two-stage systems, a single expansion ratio of 77.5 provides a lower dry mass than any two-position nozzle.

Evaluating genetic risk for prostate cancer among Japanese and Latinos

PubMed Central

Cheng, Iona; Chen, Gary K.; Nakagawa, Hidewaki; He, Jing; Wan, Peggy; Laurie, Cathy; Shen, Jess; Sheng, Xin; Pooler, Loreall C.; Crenshaw, Andrew T.; Mirel, Daniel B.; Takahashi, Atsushi; Kubo, Michiaki; Nakamura, Yusuke; Al Olama, Ali Amin; Benlloch, Sara; Donovan, Jenny L.; Guy, Michelle; Hamdy, Freddie C.; Kote-Jarai, Zsofia; Neal, David E.; Wilkens, Lynne R.; Monroe, Kristine R.; Stram, Daniel O.; Muir, Kenneth; Eeles, Rosalind A.; Easton, Douglas F.; Kolonel, Laurence N.; Henderson, Brian E.; Le Marchand, Loïc; Haiman, Christopher A.

2012-01-01

Background There have been few genome-wide association studies (GWAS) of prostate cancer among diverse populations. To search for novel prostate cancer risk variants, we conducted GWAS of prostate cancer in Japanese and Latinos. In addition, we tested prostate cancer risk variants and developed genetic risk models of prostate cancer for Japanese and Latinos. Methods Our first stage GWAS of prostate cancer included Japanese (cases/controls=1,033/1,042) and Latino (cases/controls=1,043/1,057) from the Multiethnic Cohort. Significant associations from stage 1 (P < 1.0×10−4) were examined in silico in GWAS of prostate cancer (stage 2) in Japanese (cases/controls=1,583/3,386) and Europeans (cases/controls=1,854/1,894). Results No novel stage 1 SNPs outside of known risk regions reached genome-wide significance. For Japanese, in stage 1, the most notable putative novel association was seen with 10 SNPs (P<8.0. x10−6) at chromosome 2q33; however, this was not replicated in stage 2. For Latinos, the most significant association was observed with rs17023900 at the known 3p12 risk locus (stage 1: OR=1.45; P=7.01×10−5 and stage 2: OR=1.58; P =3.05×10−7). The majority of the established risk variants for prostate cancer, 79% and 88%, were positively associated with prostate cancer in Japanese and Latinos (stage I), respectively. The cumulative effects of these variants significantly influence prostate cancer risk (OR per allele=1.10; P = 2.71×10−25 and OR=1.07; P = 1.02×10−16 for Japanese and Latinos, respectively). Conclusion and Impact Our GWAS of prostate cancer did not identify novel genome-wide significant variants. However, our findings demonstrate that established risk variants for prostate cancer significantly contribute to risk among Japanese and Latinos. PMID:22923026

Evaluating genetic risk for prostate cancer among Japanese and Latinos.

PubMed

Cheng, Iona; Chen, Gary K; Nakagawa, Hidewaki; He, Jing; Wan, Peggy; Laurie, Cathy C; Shen, Jess; Sheng, Xin; Pooler, Loreall C; Crenshaw, Andrew T; Mirel, Daniel B; Takahashi, Atsushi; Kubo, Michiaki; Nakamura, Yusuke; Al Olama, Ali Amin; Benlloch, Sara; Donovan, Jenny L; Guy, Michelle; Hamdy, Freddie C; Kote-Jarai, Zsofia; Neal, David E; Wilkens, Lynne R; Monroe, Kristine R; Stram, Daniel O; Muir, Kenneth; Eeles, Rosalind A; Easton, Douglas F; Kolonel, Laurence N; Henderson, Brian E; Le Marchand, Loïc; Haiman, Christopher A

2012-11-01

There have been few genome-wide association studies (GWAS) of prostate cancer among diverse populations. To search for novel prostate cancer risk variants, we conducted GWAS of prostate cancer in Japanese and Latinos. In addition, we tested prostate cancer risk variants and developed genetic risk models of prostate cancer for Japanese and Latinos. Our first-stage GWAS of prostate cancer included Japanese (cases/controls = 1,033/1,042) and Latino (cases/controls = 1,043/1,057) from the Multiethnic Cohort (MEC). Significant associations from stage I (P < 1.0 × 10(-4)) were examined in silico in GWAS of prostate cancer (stage II) in Japanese (cases/controls = 1,583/3,386) and Europeans (cases/controls = 1,854/1,894). No novel stage I single-nucleotide polymorphism (SNP) outside of known risk regions reached genome-wide significance. For Japanese, in stage I, the most notable putative novel association was seen with 10 SNPs (P ≤ 8.0 × 10(-6)) at chromosome 2q33; however, this was not replicated in stage II. For Latinos, the most significant association was observed with rs17023900 at the known 3p12 risk locus (stage I: OR = 1.45; P = 7.01 × 10(-5) and stage II: OR = 1.58; P = 3.05 × 10(-7)). The majority of the established risk variants for prostate cancer, 79% and 88%, were positively associated with prostate cancer in Japanese and Latinos (stage I), respectively. The cumulative effects of these variants significantly influence prostate cancer risk (OR per allele = 1.10; P = 2.71 × 10(-25) and OR = 1.07; P = 1.02 × 10(-16) for Japanese and Latinos, respectively). Our GWAS of prostate cancer did not identify novel genome-wide significant variants. However, our findings show that established risk variants for prostate cancer significantly contribute to risk among Japanese and Latinos. ©2012 AACR.

Stationary Treatment Compared with Individualized Chinese Medicine for Type 2 Diabetes Patients with Microvascular Complications: Study Protocol for a Randomized Controlled Trial.

PubMed

Huo, Jian; Liu, Li-Sha; Jian, Wen-Yuan; Zeng, Jie-Ping; Duan, Jun-Guo; Lu, Xue-Jing; Yin, Shuo

2018-06-18

Microvascular complications in type 2 diabetes (T2DM), including diabatic retinopathy (DR), diabetic kidney disease (DKD), diabetic peripheral neuropathy (DPN) are the leading causes of visual loss, end-stage renal disease or amputation, while the current therapies are still unsatisfactory. Chinese medicine (CM) has been widely used for treating diabetic mellitus. However, most of the previous studies focused on the single complication. The role of CM treatment in T2DM patients with 2 or multiple microvascular complications is not clear. To appraise the curative effect of CM in T2DM patients with 2 or multiple microvascular complications, and to compare the effects of stationary treatment and individualized treatment in T2DM patients with microvascular complications. This trial will be an 8-center, randomized, controlled study with 8 parallel groups. A total of 432 patients will be randomized to 8 groups: DR study group (32 cases) and a corresponding control group (32 cases), DR+DKD study group (64 cases) and a corresponding control group (64 cases), DR+DPN study group (64 cases) and a corresponding control group (64 cases), DR+DKD+DPN study group (56 cases) and a corresponding control group (56 cases). The control group will receive stationary treatment, and the study group will receive individualized treatment based on CM syndrome differentiation in addition to stationary treatment. The study duration will be 50 weeks, comprising a 2-week run-in period, 24 weeks of intervention, and 24 weeks of follow-up. The outcomes will assess efficacy of treatment, improvement in CM symptoms, safety assessments, adherence to the treatment, and adverse events. This study will provide evidence of evidence-based medicine for CM treatment in two or multiple microvascular complications caused by T2DM. (Registration No. ChiCTR-IPR-15007072).

Comparative evaluation of the diagnosis, reporting and investigation of malaria cases in China, 2005-2014: transition from control to elimination for the national malaria programme.

PubMed

Sun, Jun-Ling; Zhou, Sheng; Geng, Qi-Bin; Zhang, Qian; Zhang, Zi-Ke; Zheng, Can-Jun; Hu, Wen-Biao; Clements, Archie C A; Lai, Sheng-Jie; Li, Zhong-Jie

2016-06-27

The elimination of malaria requires high-quality surveillance data to enable rapid detection and response to individual cases. Evaluation of the performance of a national malaria surveillance system could identify shortcomings which, if addressed, will improve the surveillance program for malaria elimination. Case-level data for the period 2005-2014 were extracted from the China National Notifiable Infectious Disease Reporting Information System and Malaria Enhanced Surveillance Information System. The occurrence of cases, accuracy and timeliness of case diagnosis, reporting and investigation, were assessed and compared between the malaria control stage (2005-2010) and elimination stage (2011-2014) in mainland China. A total of 210 730 malaria cases were reported in mainland China in 2005-2014. The average annual incidence declined dramatically from 2.5 per 100 000 people at the control stage to 0.2 per 100 000 at the elimination stage, but the proportion of migrant cases increased from 9.8 % to 41.0 %. Since the initiation of the National Malaria Elimination Programme in 2010, the overall proportion of cases diagnosed by laboratory testing consistently improved, with the highest of 99.0 % in 2014. However, this proportion was significantly lower in non-endemic provinces (79.0 %) than that in endemic provinces (91.4 %) during 2011-2014. The median interval from illness onset to diagnosis was 3 days at the elimination stage, with one day earlier than that at the control stage. Since 2011, more than 99 % cases were reported within 1 day after being diagnosed, while the proportion of cases that were reported within one day after diagnosis was lowest in Tibet (37.5 %). The predominant source of cases reporting shifted from town-level hospitals at the control stage (67.9 % cases) to city-level hospitals and public health institutes at the eliminate stage (69.4 % cases). The proportion of investigation within 3 days after case reporting has improved, from 74.6 % in 2010 to 98.5 % in 2014. The individual case-based malaria surveillance system in China operated well during the malaria elimination stage. This ensured that malaria cases could be diagnosed, reported and timely investigated at local level. However, domestic migrants and overseas populations, as well as cases in the historically malarial non-endemic areas and hard-to-reach area are new challenges in the surveillance for malaria elimination.

Characteristics and outcomes of patients with multiple myeloma aged 21-40 years versus 41-60 years: a multi-institutional case-control study.

PubMed

Jurczyszyn, Artur; Nahi, Hareth; Avivi, Irit; Gozzetti, Alessandro; Niesvizky, Ruben; Yadlapati, Sujitha; Jayabalan, David S; Robak, Paweł; Pika, Tomas; Andersen, Kristian T; Rasche, Leo; Mądry, Krzysztof; Woszczyk, Dariusz; Raźny, Małgorzata; Usnarska-Zubkiewicz, Lidia; Knopińska-Posłuszny, Wanda; Wojciechowska, Małgorzata; Guzicka-Kazimierczak, Renata; Joks, Monika; Grosicki, Sebastian; Ciepłuch, Hanna; Rymko, Marcin; Vesole, David H; Castillo, Jorge J

2016-12-01

We compared the outcomes of multiple myeloma (MM) patients aged 21-40 and 41-60 years in the novel agent era. This case-control study included 1089 patients between 2000 and 2015. Cases and controls were matched for sex, International Staging System (ISS) stage and institution. There were 173 patients in the younger group and 916 patients in the older group. Younger patients presented with a higher incidence of lytic lesions (82% vs. 72%; P = 0·04) and high-risk cytogenetic abnormalities (83% vs. 68%; P = 0·007), but lower rate of elevated lactate dehydrogenase (21% vs. 44%; P < 0·001). Five- and 10-year overall survival (OS) in younger versus older patients was 83% vs. 67% and 56% vs. 39%, respectively (P < 0·001). Similar results were seen when studying the subset of 780 patients who underwent autologous transplantation. Younger patients with ISS stage 1 had a better OS than older patients (P < 0·001). There was no survival difference between younger and older patients with ISS stage 2 or 3. Younger MM patients, aged 21-40 years, treated in the era of novel agents have a better OS than their counterparts aged 41-60 years, but the survival advantage observed in younger patients was lost in more advanced stages of MM. © 2016 John Wiley & Sons Ltd.

Linear Parameter Varying Control Synthesis for Actuator Failure, Based on Estimated Parameter

NASA Technical Reports Server (NTRS)

Shin, Jong-Yeob; Wu, N. Eva; Belcastro, Christine

2002-01-01

The design of a linear parameter varying (LPV) controller for an aircraft at actuator failure cases is presented. The controller synthesis for actuator failure cases is formulated into linear matrix inequality (LMI) optimizations based on an estimated failure parameter with pre-defined estimation error bounds. The inherent conservatism of an LPV control synthesis methodology is reduced using a scaling factor on the uncertainty block which represents estimated parameter uncertainties. The fault parameter is estimated using the two-stage Kalman filter. The simulation results of the designed LPV controller for a HiMXT (Highly Maneuverable Aircraft Technology) vehicle with the on-line estimator show that the desired performance and robustness objectives are achieved for actuator failure cases.

Immunohistochemical expression of galectin-3 is significantly associated with grade, stage and differentiation of endometrial carcinomas.

PubMed

Al-Maghrabi, Jaudah; Abdelrahman, Amer Shafie; Ghabrah, Tawfik; Butt, Nadeem Shafique; Al-Maghrabi, Basim; Khabaz, Mohamad Nidal

2017-04-01

This study describes galectin-3 immunohistochemical phenotype and its association with clinicopathological factors in the carcinoma of endometrium. Seventy one cases of endometrial carcinoma and 30 cases of benign and normal endometrium were employed for the detection of galectin-3 protein using tissue microarrays and immunohistochemistry staining. Thirty nine (55%) cases, including 54.2% of endometrioid adenocarcinomas and 55.5% serous carcinomas, were positively stained for galectin-3. Brown granular expression of this glycoprotein was detected in transformed epithelial cells of 36 cases including 28 cases with membranous and cytoplasmic staining and 8 cases with only cytoplasmic staining; nuclear expression was present in stromal cells of the remaining 3 cases. Twenty-four (80%) control cases showed granular cytoplasmic and membranous expression, and six control cases were negative. Tumor grade, stage and differentiation were significantly associated with galectin-3 immunoreactivity (p-values are 0.043, 0.016, and 0.044 respectively), cases with membranous and cytoplasmic staining is significantly associated with grade I and stage II, while cases with loss of staining are more frequent in grade II, III and poorly differentiated tumors. No significant association of galectin-3 staining was observed with age, diagnosis, recurrence and alive status. The current study supports the tumor suppression role of galectin-3 in endometrial carcinoma. Greater galectin-3 immunostaining has been found in control endometrial tissues compared to endometrial tumors. Loss or decreased galectin-3 immunoexpression gives a sign for poor prognoses in endometrial carcinoma patients. Copyright © 2017 Elsevier GmbH. All rights reserved.

Surgical Resection for Hepatoblastoma-Updated Survival Outcomes.

PubMed

Sunil, Bhanu Jayanand; Palaniappan, Ravisankar; Venkitaraman, Balasubramanian; Ranganathan, Rama

2017-09-30

Hepatoblastoma is the most common liver malignancy in the pediatric age group. The management of hepatoblastoma involves multidisciplinary approach. Patients with hepatoblastoma who underwent liver resection between 2000 and 2013 were analyzed and survival outcomes were studied. The crude incidence rate of hepatoblastoma at the Madras Metropolitan Tumor Registry (MMTR) is 0.4/1,00,000 population per year. Twelve patients underwent liver resection for hepatoblastoma during the study period; this included eight males and four females. The median age at presentation was 1.75 years (Range 5 months to 3 years). The median serum AFP in the study population was 20,000 ng/ml (Range 4.5 to 1,40,000 ng/ml). Three patients had stage I, one patient had stage II, and eight patients had stage III disease as per the PRETEXT staging system. Two patients were categorized as high risk and ten patients were categorized as standard risk. Seven of these patients received two to four cycles of neoadjuvant chemotherapy (PLADO regimen), and one patient received neoadjuvant radiation up to 84 Gy. Major liver resection was performed in nine patients. Nine patients received adjuvant chemotherapy. The most common histological subtype was embryonal type. Microscopic margin was positive in three cases. One patient recurred 7 months after surgery and the site of failure was the lung. The 5-year overall survival of the case series was 91%. The median survival was 120 months. Liver resections can be safely performed in pediatric populations after neoadjuvant treatment. Patients undergoing surgery had good disease control and long-term survival.

Abnormal plasma DNA profiles in early ovarian cancer using a non-invasive prenatal testing platform: implications for cancer screening.

PubMed

Cohen, Paul A; Flowers, Nicola; Tong, Stephen; Hannan, Natalie; Pertile, Mark D; Hui, Lisa

2016-08-24

Non-invasive prenatal testing (NIPT) identifies fetal aneuploidy by sequencing cell-free DNA in the maternal plasma. Pre-symptomatic maternal malignancies have been incidentally detected during NIPT based on abnormal genomic profiles. This low coverage sequencing approach could have potential for ovarian cancer screening in the non-pregnant population. Our objective was to investigate whether plasma DNA sequencing with a clinical whole genome NIPT platform can detect early- and late-stage high-grade serous ovarian carcinomas (HGSOC). This is a case control study of prospectively-collected biobank samples comprising preoperative plasma from 32 women with HGSOC (16 'early cancer' (FIGO I-II) and 16 'advanced cancer' (FIGO III-IV)) and 32 benign controls. Plasma DNA from cases and controls were sequenced using a commercial NIPT platform and chromosome dosage measured. Sequencing data were blindly analyzed with two methods: (1) Subchromosomal changes were called using an open source algorithm WISECONDOR (WIthin-SamplE COpy Number aberration DetectOR). Genomic gains or losses ≥ 15 Mb were prespecified as "screen positive" calls, and mapped to recurrent copy number variations reported in an ovarian cancer genome atlas. (2) Selected whole chromosome gains or losses were reported using the routine NIPT pipeline for fetal aneuploidy. We detected 13/32 cancer cases using the subchromosomal analysis (sensitivity 40.6 %, 95 % CI, 23.7-59.4 %), including 6/16 early and 7/16 advanced HGSOC cases. Two of 32 benign controls had subchromosomal gains ≥ 15 Mb (specificity 93.8 %, 95 % CI, 79.2-99.2 %). Twelve of the 13 true positive cancer cases exhibited specific recurrent changes reported in HGSOC tumors. The NIPT pipeline resulted in one "monosomy 18" call from the cancer group, and two "monosomy X" calls in the controls. Low coverage plasma DNA sequencing used for prenatal testing detected 40.6 % of all HGSOC, including 38 % of early stage cases. Our findings demonstrate the potential of a high throughput sequencing platform to screen for early HGSOC in plasma based on characteristic multiple segmental chromosome gains and losses. The performance of this approach may be further improved by refining bioinformatics algorithms and targeting selected cancer copy number variations.

Initial Results of Hypofractionated Carbon Ion Radiotherapy for Cholangiocarcinoma.

PubMed

Abe, Takanori; Shibuya, Kei; Koyama, Yoshinori; Okamoto, Masahiko; Kiyohara, Hiroki; Katoh, Hiroyuki; Shimada, Hirohumi; Kuwano, Hiroyuki; Ohno, Tatsuya; Nakano, Takashi

2016-06-01

To report initial results of hypofractionated carbon ion radiotherapy (C-ion RT) for cholangiocarcinoma. Data regarding seven patients with cholangiocarcinoma treated by C-ion RT were analyzed. Prescribed doses were 52.8 Gy [relative biological effectiveness (RBE)] or 60.0 Gy (RBE) in four fractions for intrahepatic cases and 12 fractions for hilar hepatic/close to gastro-intestinal tract cases. Local control and overall survival were evaluated and toxicity was graded using Common Terminology Criteria for Adverse Events, version 4.0. The median follow-up period was 16 months. There were two patients with stage I cancer, one with stage II, one with stage III, and three with stage IVA. Local control was achieved in five out of seven patients (71%) and survival was maintained in six out of seven patients (86%). There were no occurrences of acute or late toxicity of grade 3 or higher. Initial results show that hypofractionated C-ion RT appears to be tolerated and effective for cholangiocarcinoma. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Effects of pushing techniques during the second stage of labor: A randomized controlled trial.

PubMed

Koyucu, Refika Genç; Demirci, Nurdan

2017-10-01

Spontaneous pushing is a method that is used in the management of the second stage of labor and suggested to be more physiological for the mother and infant. The present study aims to evaluate the effects of pushing techniques on the mother and newborn. This randomized prospective study was performed between June 2013-March 2014 in a tertiary maternity clinic in Istanbul. 80 low risk, nulliparous cases were randomized to pushing groups. Valsalva pushing group was told to hold their breath while pushing. No visual-verbal instructions were given to spontaneous pushing group and they were encouraged to push without preventing respiration. Demographic data, second stage period, perineal laceration rates, fetal heart rate patterns, presence of meconium stained amniotic liquid, newborn APGAR scores, POP-Q examination and Q-tip test results were evaluated in these cases. The second stage of labor was significantly longer with spontaneous pushing. Decrease in Hb levels in valsalva pushing group was determined to be higher than spontaneous pushing group. An increased urethral mobility was observed in valsalva pushing group. Although the duration of the second stage of labor was longer compared to valsalva pushing technique, women were able to give birth without requiring any verbal or visual instruction, without exceeding the limit value of two hours and without affecting fetal wellness and neonatal results. Copyright © 2017. Published by Elsevier B.V.

A Two-Stage Meta-Analysis Identifies Several New Loci for Parkinson's Disease

PubMed Central

2011-01-01

A previous genome-wide association (GWA) meta-analysis of 12,386 PD cases and 21,026 controls conducted by the International Parkinson's Disease Genomics Consortium (IPDGC) discovered or confirmed 11 Parkinson's disease (PD) loci. This first analysis of the two-stage IPDGC study focused on the set of loci that passed genome-wide significance in the first stage GWA scan. However, the second stage genotyping array, the ImmunoChip, included a larger set of 1,920 SNPs selected on the basis of the GWA analysis. Here, we analyzed this set of 1,920 SNPs, and we identified five additional PD risk loci (combined p<5×10−10, PARK16/1q32, STX1B/16p11, FGF20/8p22, STBD1/4q21, and GPNMB/7p15). Two of these five loci have been suggested by previous association studies (PARK16/1q32, FGF20/8p22), and this study provides further support for these findings. Using a dataset of post-mortem brain samples assayed for gene expression (n = 399) and methylation (n = 292), we identified methylation and expression changes associated with PD risk variants in PARK16/1q32, GPNMB/7p15, and STX1B/16p11 loci, hence suggesting potential molecular mechanisms and candidate genes at these risk loci. PMID:21738488

Just Do It: Flipped Lecture, Determinants and Debate

ERIC Educational Resources Information Center

Kensington-Miller, Barbara; Novak, Julia; Evans, Tanya

2016-01-01

This paper describes a case study of two pure mathematicians who flipped their lecture to teach matrix determinants in two large mathematics service courses (one at Stage I and the other at Stage II). The purpose of the study was to transform the passive lecture into an active learning opportunity and to introduce valuable mathematical skills,…

MiR-608, pre-miR-124-1 and pre-miR26a-1 polymorphisms modify susceptibility and recurrence-free survival in surgically resected CRC individuals.

PubMed

Ying, Hou-Qun; Peng, Hong-Xin; He, Bang-Shun; Pan, Yu-Qin; Wang, Feng; Sun, Hui-Ling; Liu, Xian; Chen, Jie; Lin, Kang; Wang, Shu-Kui

2016-11-15

Genetic variation within microRNA (miRNA) may result in its abnormal folding or aberrant expression, contributing to colorectal turmorigenesis and metastasis. However, the association of six polymorphisms (miR-608 rs4919510, miR-499a rs3746444, miR-146a rs2910164, pre-miR-143 rs41291957, pre-miR-124-1 rs531564 and pre-miR-26a-1 rs7372209) with colorectal cancer (CRC) risk, therapeutic response and survival remains unclear. A retrospective study was carried out to investigate the association in 1358 0-III stage resected CRC patients and 1079 healthy controls using Sequenom's MassARRAY platform. The results showed that rs4919510 was significantly associated with a decreased susceptibility to CRC in co-dominant, allele and recessive genetic models, and the protective role of rs4919510 allele G and genotype GG was more pronounced among stage 0-II cases; significant association between rs531564 and poor RFS was observed in cases undergoing adjuvant chemo-radiotherapy in co-dominant, allele and dominant models; moreover, there was a positive association between rs7372209 and recurrence-free survival in stage II cases in co-dominant and over-dominant models; additionally, a cumulative effect of rs531564 and rs7372209 at-risk genotypes with hazard ratio at 1.30 and 1.95 for one and two at-risk genotypes was examined in stage II cases, respectively. Our findings indicated that rs4919510 allele G and genotype GG were protective factors for 0-II stage CRC, rs7372209 and rs531564 could decrease RFS in II stage individuals and resected CRC patients receiving adjuvant chemo-radiology.

Densification kinetics of nanocrystalline zirconia powder using microwave and spark plasma sintering--a comparative study.

PubMed

Vasylkiv, Oleg; Demirskyi, Dmytro; Sakka, Yoshio; Ragulya, Andrey; Borodianska, Hanna

2012-06-01

Two-stage densification process of nanosized 3 mol% yttria-stabilized zirconia (3Y-SZ) polycrystalline compacts during consolidation via microwave and spark-plasma sintering have been observed. The values of activation energies obtained for microwave and spark-plasma sintering 260-275 kJ x mol(-1) are quite similar to that of conventional sintering of zirconia, suggesting that densification during initial stage is controlled by the grain-boundary diffusion mechanism. The sintering behavior during microwave sintering was significantly affected by preliminary pressing conditions, as the surface diffusion mechanism (230 kJ x mol(-1)) is active in case of cold-isostatic pressing procedure was applied.

History of chickenpox in glioma risk: a report from the glioma international case-control study (GICC).

PubMed

Amirian, E Susan; Scheurer, Michael E; Zhou, Renke; Wrensch, Margaret R; Armstrong, Georgina N; Lachance, Daniel; Olson, Sara H; Lau, Ching C; Claus, Elizabeth B; Barnholtz-Sloan, Jill S; Il'yasova, Dora; Schildkraut, Joellen; Ali-Osman, Francis; Sadetzki, Siegal; Jenkins, Robert B; Bernstein, Jonine L; Merrell, Ryan T; Davis, Faith G; Lai, Rose; Shete, Sanjay; Amos, Christopher I; Melin, Beatrice S; Bondy, Melissa L

2016-06-01

Varicella zoster virus (VZV) is a neurotropic α-herpesvirus that causes chickenpox and establishes life-long latency in the cranial nerve and dorsal root ganglia of the host. To date, VZV is the only virus consistently reported to have an inverse association with glioma. The Glioma International Case-Control Study (GICC) is a large, multisite consortium with data on 4533 cases and 4171 controls collected across five countries. Here, we utilized the GICC data to confirm the previously reported associations between history of chickenpox and glioma risk in one of the largest studies to date on this topic. Using two-stage random-effects restricted maximum likelihood modeling, we found that a positive history of chickenpox was associated with a 21% lower glioma risk, adjusting for age and sex (95% confidence intervals (CI): 0.65-0.96). Furthermore, the protective effect of chickenpox was stronger for high-grade gliomas. Our study provides additional evidence that the observed protective effect of chickenpox against glioma is unlikely to be coincidental. Future studies, including meta-analyses of the literature and investigations of the potential biological mechanism, are warranted. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Fetal heart rate monitoring category 3 during the 2nd stage of labor is an independent predictor of fetal acidosis.

PubMed

Silberstein, Tali; Sheiner, Eyal; Salem, Shimrit Yaniv; Hamou, Batel; Aricha, Barak; Baumfeld, Yael; Yohay, Zehava; Elharar, Debora; Idan, Inbal; Yohay, David

2017-02-01

To determine whether fetal heart rate (FHR) monitoring categories during the 1st and 2nd stage of labor can predict arterial cord pH <7.2. A case control study was conducted including 653 consecutive term deliveries (37 weeks gestation and above) that were divided according to fetal pH ≤ 7.2 (n = 315) and fetal pH > 7.2 (n = 338). Deliveries occurred during the year 2013 in tertiary medical center, where arterial cord pH is routinely taken after birth. Intrapartum FHR monitoring categorization was defined according to the ACOG committee guidelines by two obstetricians. Multivariable models were constructed to control for confounders. Variable decelerations, late decelerations and bradycardia during the 1st and 2nd stages of labor were significantly higher in group of deliveries ended in cord pH < 7.2 compared with group of deliveries ended in cord pH > 7.2. A significant association was observed between category 2 and 3 during the 1st stage of labor and pH ≤ 7.2. However, while controlling for FHR category 3 at the 2nd stage of labor, 1st stage categorization lost its association with pH <7.2, and only category 3 during the 2nd stage were noted as an independent risk factor for acidosis. FHR monitoring category 3 during the 2nd stage of labor is an independent predictor of fetal acidosis as expressed by arterial cord pH < 7.2.

New use of low-dose aspirin and risk of colorectal cancer by stage at diagnosis: a nested case-control study in UK general practice.

PubMed

García Rodríguez, Luis A; Soriano-Gabarró, Montse; Bromley, Susan; Lanas, Angel; Cea Soriano, Lucía

2017-09-07

Evidence from clinical trial populations suggests low-dose aspirin reduces the risk of colorectal cancer (CRC). Part of this reduction in risk might be due to protection against metastatic disease. We investigated the risk of CRC among new-users of low-dose aspirin (75-300 mg), including risk by stage at diagnosis. Using The Health Improvement Network, we conducted a cohort study with nested case-control analysis. Two cohorts (N = 170,336 each) aged 40-89 years from 2000 to 2009 and free of cancer were identified: i) new-users of low-dose aspirin, ii) non-users of low-dose aspirin, at start of follow-up, matched by age, sex and previous primary care practitioner visits. Patients were followed for up to 12 years to identify incident CRC. 10,000 frequency-matched controls were selected by incidence density sampling where the odds ratio is an unbiased estimator of the incidence rate ratio (RR). RRs with 95% confidence intervals were calculated. Low-dose aspirin use was classified 'as-treated' independent from baseline exposure status to account for changes in exposure during follow-up. Current users of low-dose aspirin (use on the index date or in the previous 90 days) had a significantly reduced risk of CRC, RR 0.66 (95% CI 0.60-0.74). The reduction in risk was apparent across all age groups, and was unrelated to dose, indication, gender, CRC location or case-fatality status. Reduced risks occurred throughout treatment duration and with all low-dose aspirin doses. RRs by aspirin indication were 0.71 (0·63-0·79) and 0.60 (0.53-0.68) for primary and secondary cardiovascular protection, respectively. Among cases with staging information (n = 1421), RRs for current use of low-dose aspirin were 0.94 (0.66-1.33) for Dukes Stage A CRC, 0.54 (0.42-0.68) for Dukes B, 0.71 (0.56-0.91) for Dukes C, and 0.60 (0.48-0.74) for Dukes D. After 5 years' therapy, the RR for Dukes Stage A CRC was 0.53 (0.24-1.19). Patients starting low-dose aspirin therapy have a reduced risk of Stages B-D CRC, suggesting a role for low-dose aspirin in the progression of established CRC; a substantial reduction in the risk of Dukes A CRC may occur after 5 years' therapy.

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease.

PubMed

Sims, Rebecca; van der Lee, Sven J; Naj, Adam C; Bellenguez, Céline; Badarinarayan, Nandini; Jakobsdottir, Johanna; Kunkle, Brian W; Boland, Anne; Raybould, Rachel; Bis, Joshua C; Martin, Eden R; Grenier-Boley, Benjamin; Heilmann-Heimbach, Stefanie; Chouraki, Vincent; Kuzma, Amanda B; Sleegers, Kristel; Vronskaya, Maria; Ruiz, Agustin; Graham, Robert R; Olaso, Robert; Hoffmann, Per; Grove, Megan L; Vardarajan, Badri N; Hiltunen, Mikko; Nöthen, Markus M; White, Charles C; Hamilton-Nelson, Kara L; Epelbaum, Jacques; Maier, Wolfgang; Choi, Seung-Hoan; Beecham, Gary W; Dulary, Cécile; Herms, Stefan; Smith, Albert V; Funk, Cory C; Derbois, Céline; Forstner, Andreas J; Ahmad, Shahzad; Li, Hongdong; Bacq, Delphine; Harold, Denise; Satizabal, Claudia L; Valladares, Otto; Squassina, Alessio; Thomas, Rhodri; Brody, Jennifer A; Qu, Liming; Sánchez-Juan, Pascual; Morgan, Taniesha; Wolters, Frank J; Zhao, Yi; Garcia, Florentino Sanchez; Denning, Nicola; Fornage, Myriam; Malamon, John; Naranjo, Maria Candida Deniz; Majounie, Elisa; Mosley, Thomas H; Dombroski, Beth; Wallon, David; Lupton, Michelle K; Dupuis, Josée; Whitehead, Patrice; Fratiglioni, Laura; Medway, Christopher; Jian, Xueqiu; Mukherjee, Shubhabrata; Keller, Lina; Brown, Kristelle; Lin, Honghuang; Cantwell, Laura B; Panza, Francesco; McGuinness, Bernadette; Moreno-Grau, Sonia; Burgess, Jeremy D; Solfrizzi, Vincenzo; Proitsi, Petra; Adams, Hieab H; Allen, Mariet; Seripa, Davide; Pastor, Pau; Cupples, L Adrienne; Price, Nathan D; Hannequin, Didier; Frank-García, Ana; Levy, Daniel; Chakrabarty, Paramita; Caffarra, Paolo; Giegling, Ina; Beiser, Alexa S; Giedraitis, Vilmantas; Hampel, Harald; Garcia, Melissa E; Wang, Xue; Lannfelt, Lars; Mecocci, Patrizia; Eiriksdottir, Gudny; Crane, Paul K; Pasquier, Florence; Boccardi, Virginia; Henández, Isabel; Barber, Robert C; Scherer, Martin; Tarraga, Lluis; Adams, Perrie M; Leber, Markus; Chen, Yuning; Albert, Marilyn S; Riedel-Heller, Steffi; Emilsson, Valur; Beekly, Duane; Braae, Anne; Schmidt, Reinhold; Blacker, Deborah; Masullo, Carlo; Schmidt, Helena; Doody, Rachelle S; Spalletta, Gianfranco; Longstreth, W T; Fairchild, Thomas J; Bossù, Paola; Lopez, Oscar L; Frosch, Matthew P; Sacchinelli, Eleonora; Ghetti, Bernardino; Yang, Qiong; Huebinger, Ryan M; Jessen, Frank; Li, Shuo; Kamboh, M Ilyas; Morris, John; Sotolongo-Grau, Oscar; Katz, Mindy J; Corcoran, Chris; Dunstan, Melanie; Braddel, Amy; Thomas, Charlene; Meggy, Alun; Marshall, Rachel; Gerrish, Amy; Chapman, Jade; Aguilar, Miquel; Taylor, Sarah; Hill, Matt; Fairén, Mònica Díez; Hodges, Angela; Vellas, Bruno; Soininen, Hilkka; Kloszewska, Iwona; Daniilidou, Makrina; Uphill, James; Patel, Yogen; Hughes, Joseph T; Lord, Jenny; Turton, James; Hartmann, Annette M; Cecchetti, Roberta; Fenoglio, Chiara; Serpente, Maria; Arcaro, Marina; Caltagirone, Carlo; Orfei, Maria Donata; Ciaramella, Antonio; Pichler, Sabrina; Mayhaus, Manuel; Gu, Wei; Lleó, Alberto; Fortea, Juan; Blesa, Rafael; Barber, Imelda S; Brookes, Keeley; Cupidi, Chiara; Maletta, Raffaele Giovanni; Carrell, David; Sorbi, Sandro; Moebus, Susanne; Urbano, Maria; Pilotto, Alberto; Kornhuber, Johannes; Bosco, Paolo; Todd, Stephen; Craig, David; Johnston, Janet; Gill, Michael; Lawlor, Brian; Lynch, Aoibhinn; Fox, Nick C; Hardy, John; Albin, Roger L; Apostolova, Liana G; Arnold, Steven E; Asthana, Sanjay; Atwood, Craig S; Baldwin, Clinton T; Barnes, Lisa L; Barral, Sandra; Beach, Thomas G; Becker, James T; Bigio, Eileen H; Bird, Thomas D; Boeve, Bradley F; Bowen, James D; Boxer, Adam; Burke, James R; Burns, Jeffrey M; Buxbaum, Joseph D; Cairns, Nigel J; Cao, Chuanhai; Carlson, Chris S; Carlsson, Cynthia M; Carney, Regina M; Carrasquillo, Minerva M; Carroll, Steven L; Diaz, Carolina Ceballos; Chui, Helena C; Clark, David G; Cribbs, David H; Crocco, Elizabeth A; DeCarli, Charles; Dick, Malcolm; Duara, Ranjan; Evans, Denis A; Faber, Kelley M; Fallon, Kenneth B; Fardo, David W; Farlow, Martin R; Ferris, Steven; Foroud, Tatiana M; Galasko, Douglas R; Gearing, Marla; Geschwind, Daniel H; Gilbert, John R; Graff-Radford, Neill R; Green, Robert C; Growdon, John H; Hamilton, Ronald L; Harrell, Lindy E; Honig, Lawrence S; Huentelman, Matthew J; Hulette, Christine M; Hyman, Bradley T; Jarvik, Gail P; Abner, Erin; Jin, Lee-Way; Jun, Gyungah; Karydas, Anna; Kaye, Jeffrey A; Kim, Ronald; Kowall, Neil W; Kramer, Joel H; LaFerla, Frank M; Lah, James J; Leverenz, James B; Levey, Allan I; Li, Ge; Lieberman, Andrew P; Lunetta, Kathryn L; Lyketsos, Constantine G; Marson, Daniel C; Martiniuk, Frank; Mash, Deborah C; Masliah, Eliezer; McCormick, Wayne C; McCurry, Susan M; McDavid, Andrew N; McKee, Ann C; Mesulam, Marsel; Miller, Bruce L; Miller, Carol A; Miller, Joshua W; Morris, John C; Murrell, Jill R; Myers, Amanda J; O'Bryant, Sid; Olichney, John M; Pankratz, Vernon S; Parisi, Joseph E; Paulson, Henry L; Perry, William; Peskind, Elaine; Pierce, Aimee; Poon, Wayne W; Potter, Huntington; Quinn, Joseph F; Raj, Ashok; Raskind, Murray; Reisberg, Barry; Reitz, Christiane; Ringman, John M; Roberson, Erik D; Rogaeva, Ekaterina; Rosen, Howard J; Rosenberg, Roger N; Sager, Mark A; Saykin, Andrew J; Schneider, Julie A; Schneider, Lon S; Seeley, William W; Smith, Amanda G; Sonnen, Joshua A; Spina, Salvatore; Stern, Robert A; Swerdlow, Russell H; Tanzi, Rudolph E; Thornton-Wells, Tricia A; Trojanowski, John Q; Troncoso, Juan C; Van Deerlin, Vivianna M; Van Eldik, Linda J; Vinters, Harry V; Vonsattel, Jean Paul; Weintraub, Sandra; Welsh-Bohmer, Kathleen A; Wilhelmsen, Kirk C; Williamson, Jennifer; Wingo, Thomas S; Woltjer, Randall L; Wright, Clinton B; Yu, Chang-En; Yu, Lei; Garzia, Fabienne; Golamaully, Feroze; Septier, Gislain; Engelborghs, Sebastien; Vandenberghe, Rik; De Deyn, Peter P; Fernadez, Carmen Muñoz; Benito, Yoland Aladro; Thonberg, Hakan; Forsell, Charlotte; Lilius, Lena; Kinhult-Stählbom, Anne; Kilander, Lena; Brundin, RoseMarie; Concari, Letizia; Helisalmi, Seppo; Koivisto, Anne Maria; Haapasalo, Annakaisa; Dermecourt, Vincent; Fievet, Nathalie; Hanon, Olivier; Dufouil, Carole; Brice, Alexis; Ritchie, Karen; Dubois, Bruno; Himali, Jayanadra J; Keene, C Dirk; Tschanz, JoAnn; Fitzpatrick, Annette L; Kukull, Walter A; Norton, Maria; Aspelund, Thor; Larson, Eric B; Munger, Ron; Rotter, Jerome I; Lipton, Richard B; Bullido, María J; Hofman, Albert; Montine, Thomas J; Coto, Eliecer; Boerwinkle, Eric; Petersen, Ronald C; Alvarez, Victoria; Rivadeneira, Fernando; Reiman, Eric M; Gallo, Maura; O'Donnell, Christopher J; Reisch, Joan S; Bruni, Amalia Cecilia; Royall, Donald R; Dichgans, Martin; Sano, Mary; Galimberti, Daniela; St George-Hyslop, Peter; Scarpini, Elio; Tsuang, Debby W; Mancuso, Michelangelo; Bonuccelli, Ubaldo; Winslow, Ashley R; Daniele, Antonio; Wu, Chuang-Kuo; Peters, Oliver; Nacmias, Benedetta; Riemenschneider, Matthias; Heun, Reinhard; Brayne, Carol; Rubinsztein, David C; Bras, Jose; Guerreiro, Rita; Al-Chalabi, Ammar; Shaw, Christopher E; Collinge, John; Mann, David; Tsolaki, Magda; Clarimón, Jordi; Sussams, Rebecca; Lovestone, Simon; O'Donovan, Michael C; Owen, Michael J; Behrens, Timothy W; Mead, Simon; Goate, Alison M; Uitterlinden, Andre G; Holmes, Clive; Cruchaga, Carlos; Ingelsson, Martin; Bennett, David A; Powell, John; Golde, Todd E; Graff, Caroline; De Jager, Philip L; Morgan, Kevin; Ertekin-Taner, Nilufer; Combarros, Onofre; Psaty, Bruce M; Passmore, Peter; Younkin, Steven G; Berr, Claudine; Gudnason, Vilmundur; Rujescu, Dan; Dickson, Dennis W; Dartigues, Jean-François; DeStefano, Anita L; Ortega-Cubero, Sara; Hakonarson, Hakon; Campion, Dominique; Boada, Merce; Kauwe, John Keoni; Farrer, Lindsay A; Van Broeckhoven, Christine; Ikram, M Arfan; Jones, Lesley; Haines, Jonathan L; Tzourio, Christophe; Launer, Lenore J; Escott-Price, Valentina; Mayeux, Richard; Deleuze, Jean-François; Amin, Najaf; Holmans, Peter A; Pericak-Vance, Margaret A; Amouyel, Philippe; van Duijn, Cornelia M; Ramirez, Alfredo; Wang, Li-San; Lambert, Jean-Charles; Seshadri, Sudha; Williams, Julie; Schellenberg, Gerard D

2017-09-01

We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10 -4 ) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10 -8 ) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10 -10 , odds ratio (OR) = 0.68, minor allele frequency (MAF) cases = 0.0059, MAF controls = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10 -10 , OR = 1.43, MAF cases = 0.011, MAF controls = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10 -14 , OR = 1.67, MAF cases = 0.0143, MAF controls = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.

Association of CASP9, CASP10 gene polymorphisms and tea drinking with colorectal cancer risk in the Han Chinese population.

PubMed

Liu, He; Jiang, Xia; Zhang, Ming-wu; Pan, Yi-feng; Yu, Yun-xian; Zhang, Shan-chun; Ma, Xin-yuan; Li, Qi-long; Chen, Kun

2013-01-01

The initiators caspase-9 (CASP9) and caspase-10 (CASP10) are two key controllers of apoptosis and play important roles in carcinogenesis. This study aims to explore the association between CASPs gene polymorphisms and colorectal cancer (CRC) susceptibility in a population-based study. A two-stage designed population-based case-control study was carried out, including a testing set with 300 cases and 296 controls and a validation set with 206 cases and 845 controls. A total of eight tag selected single nucleotide polymorphisms (SNPs) in CASP9 and CASP10 were chosen based on HapMap and the National Center of Biotechnology Information (NCBI) datasets and genotyped by restriction fragment length polymorphism (RFLP) assay. Multivariate logistic regression models were applied to evaluate the association of SNPs with CRC risk. In the first stage, from eight tag SNPs, three polymorphisms rs4646077 (odds ratio (OR)(AA+AG): 0.654, 95% confidence interval (CI): 0.406-1.055; P=0.082), rs4233532 (OR(CC): 1.667, 95% CI: 0.967-2.876; OR(CT): 1.435, 95% CI: 0.998-2.063; P=0.077), and rs2881930 (OR(CC): 0.263, 95% CI: 0.095-0.728, P=0.036) showed possible association with CRC risk. However, none of the three SNPs, rs4646077 (OR(AA+AG): 1.233, 95% CI: 0.903-1.683), rs4233532 (OR(CC): 0.892, 95% CI: 0.640-1.243; OR(CT): 1.134, 95% CI: 0.897-1.433), and rs2881930 (OR(CC): 1.096, 95% CI: 0.620-1.938; OR(CT): 1.009, 95% CI: 0.801-1.271), remained significant with CRC risk in the validation set, even after stratification for different tumor locations (colon or rectum). In addition, never tea drinking was associated with a significantly increased risk of CRC in testing set together with validation set (OR: 1.755, 95% CI: 1.319-2.334). Our results found that polymorphisms of CASP9 and CASP10 genes may not contribute to CRC risk in Chinese population and thereby the large-scale case-control studies might be in consideration. In addition, tea drinking was a protective factor for CRC.

Association of CASP9, CASP10 gene polymorphisms and tea drinking with colorectal cancer risk in the Han Chinese population*

PubMed Central

Liu, He; Jiang, Xia; Zhang, Ming-wu; Pan, Yi-feng; Yu, Yun-xian; Zhang, Shan-chun; Ma, Xin-yuan; Li, Qi-long; Chen, Kun

2013-01-01

The initiators caspase-9 (CASP9) and caspase-10 (CASP10) are two key controllers of apoptosis and play important roles in carcinogenesis. This study aims to explore the association between CASPs gene polymorphisms and colorectal cancer (CRC) susceptibility in a population-based study. A two-stage designed population-based case-control study was carried out, including a testing set with 300 cases and 296 controls and a validation set with 206 cases and 845 controls. A total of eight tag selected single nucleotide polymorphisms (SNPs) in CASP9 and CASP10 were chosen based on HapMap and the National Center of Biotechnology Information (NCBI) datasets and genotyped by restriction fragment length polymorphism (RFLP) assay. Multivariate logistic regression models were applied to evaluate the association of SNPs with CRC risk. In the first stage, from eight tag SNPs, three polymorphisms rs4646077 (odds ratio (OR)AA+AG: 0.654, 95% confidence interval (CI): 0.406–1.055; P=0.082), rs4233532 (ORCC: 1.667, 95% CI: 0.967–2.876; ORCT: 1.435, 95% CI: 0.998–2.063; P=0.077), and rs2881930 (ORCC: 0.263, 95% CI: 0.095–0.728, P=0.036) showed possible association with CRC risk. However, none of the three SNPs, rs4646077 (ORAA+AG: 1.233, 95% CI: 0.903–1.683), rs4233532 (ORCC: 0.892, 95% CI: 0.640–1.243; ORCT: 1.134, 95% CI: 0.897–1.433), and rs2881930 (ORCC: 1.096, 95% CI: 0.620–1.938; ORCT: 1.009, 95% CI: 0.801–1.271), remained significant with CRC risk in the validation set, even after stratification for different tumor locations (colon or rectum). In addition, never tea drinking was associated with a significantly increased risk of CRC in testing set together with validation set (OR: 1.755, 95% CI: 1.319–2.334). Our results found that polymorphisms of CASP9 and CASP10 genes may not contribute to CRC risk in Chinese population and thereby the large-scale case-control studies might be in consideration. In addition, tea drinking was a protective factor for CRC. PMID:23303631

Breast Cancer Screening in Patients With Newly Diagnosed Lung and Colorectal Cancer: A Population-Based Study of Utilization

PubMed Central

Sadigh, Gelareh; Carlos, Ruth C.; Ward, Kevin C.; Switchenko, Jeffrey M.; Jiang, Renjian; Applegate, Kimberly E.; Duszak, Richard

2017-01-01

Purpose To assess breast cancer screening utilization in Medicare beneficiaries with colorectal and lung cancer versus cancer-free controls. Methods Female fee-for-service Medicare beneficiaries who were ≥67 years old and diagnosed with lung or colorectal cancer between 2000 and 2011 and who reported to a Surveillance, Epidemiology, and End Results (SEER) registry (case group) were followed for 2 years after their diagnoses, unless death, a diagnosis of breast cancer, or the end of 2013 came first. A similar number of cancer-free controls were individually matched to cases by age, race, registry region, and follow-up time. Screening utilization was defined as the percentage of women with ≥1 screening mammogram during follow-up. Results Overall, 104,164 cases (48% colorectal, 52% lung; 30% advanced cancer) and 104,164 controls were included. Among women with lung or colorectal cancer, 22% underwent ≥1 screening mammogram versus 26% of controls (odds ratio [OR] 0.80; 95% confidence interval [CI] 0.78–0.82). Stratified by cancer type, 28% of colorectal cancer cases versus 29% of controls (OR 0.98; 95% CI 0.95–1.01) and 17% of lung cancer cases versus 23% of controls (OR 0.63; 95% CI 0.60–0.65) received ≥1 mammogram. When stratified by stage, 8% with advanced cancer versus 18% of controls (OR 0.33; 95% CI 0.31–0.35) and 30% with early-stage cancer versus 30% of controls (OR 1; 95% CI 0.97–1.02) underwent ≥1 mammogram. Conclusion Screening mammography utilization rates are similar between Medicare beneficiaries with early-stage cancer versus controls. Although the majority of patients with advanced-stage cancer appropriately do not pursue screening mammography, a small number (8%) continue with screening. PMID:28325489

Breast Cancer Screening in Patients With Newly Diagnosed Lung and Colorectal Cancer: A Population-Based Study of Utilization.

PubMed

Sadigh, Gelareh; Carlos, Ruth C; Ward, Kevin C; Switchenko, Jeffrey M; Jiang, Renjian; Applegate, Kimberly E; Duszak, Richard

2017-07-01

To assess breast cancer screening utilization in Medicare beneficiaries with colorectal and lung cancer versus cancer-free controls. Female fee-for-service Medicare beneficiaries who were ≥67 years old and diagnosed with lung or colorectal cancer between 2000 and 2011 and who reported to a Surveillance, Epidemiology, and End Results (SEER) registry (case group) were followed for 2 years after their diagnoses, unless death, a diagnosis of breast cancer, or the end of 2013 came first. A similar number of cancer-free controls were individually matched to cases by age, race, registry region, and follow-up time. Screening utilization was defined as the percentage of women with ≥1 screening mammogram during follow-up. Overall, 104,164 cases (48% colorectal, 52% lung; 30% advanced cancer) and 104,164 controls were included. Among women with lung or colorectal cancer, 22% underwent ≥1 screening mammogram versus 26% of controls (odds ratio [OR] 0.80; 95% confidence interval [CI] 0.78-0.82). Stratified by cancer type, 28% of colorectal cancer cases versus 29% of controls (OR 0.98; 95% CI 0.95-1.01) and 17% of lung cancer cases versus 23% of controls (OR 0.63; 95% CI 0.60-0.65) received ≥1 mammogram. When stratified by stage, 8% with advanced cancer versus 18% of controls (OR 0.33; 95% CI 0.31-0.35) and 30% with early-stage cancer versus 30% of controls (OR 1; 95% CI 0.97-1.02) underwent ≥1 mammogram. Screening mammography utilization rates are similar between Medicare beneficiaries with early-stage cancer versus controls. Although the majority of patients with advanced-stage cancer appropriately do not pursue screening mammography, a small number (8%) continue with screening. Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Sleep-wake patterns, non-rapid eye movement, and rapid eye movement sleep cycles in teenage narcolepsy.

PubMed

Xu, Xing; Wu, Huijuan; Zhuang, Jianhua; Chen, Kun; Huang, Bei; Zhao, Zhengqing; Zhao, Zhongxin

2017-05-01

To further characterize sleep disorders associated with narcolepsy, we assessed the sleep-wake patterns, rapid eye movement (REM), and non-REM (NREM) sleep cycles in Chinese teenagers with narcolepsy. A total of 14 Chinese type 1 narcoleptic patients (13.4 ± 2.6 years of age) and 14 healthy age- and sex-matched control subjects (13.6 ± 1.8 years of age) were recruited. Ambulatory 24-h polysomnography was recorded for two days, with test subjects adapting to the instruments on day one and the study data collection performed on day two. Compared with the controls, the narcoleptic patients showed a 1.5-fold increase in total sleep time over 24 h, characterized by enhanced slow-wave sleep and REM sleep. Frequent sleep-wake transitions were identified in nocturnal sleep with all sleep stages switching to wakefulness, with more awakenings and time spent in wakefulness after sleep onset. Despite eight cases of narcolepsy with sleep onset REM periods at night, the mean duration of NREM-REM sleep cycle episode and the ratio of REM/NREM sleep between patients and controls were not significantly different. Our study identified hypersomnia in teenage narcolepsy despite excessive daytime sleepiness. Sleep fragmentation extended to all sleep stages, indicating impaired sleep-wake cycles and instability of sleep stages. The limited effects on NREM-REM sleep cycles suggest the relative conservation of ultradian regulation of sleep. Copyright © 2016 Elsevier B.V. All rights reserved.

Genetic variants underlying risk of endometriosis: insights from meta-analysis of eight genome-wide association and replication datasets

PubMed Central

Rahmioglu, Nilufer; Nyholt, Dale R.; Morris, Andrew P.; Missmer, Stacey A.; Montgomery, Grant W.; Zondervan, Krina T.

2014-01-01

BACKGROUND Endometriosis is a heritable common gynaecological condition influenced by multiple genetic and environmental factors. Genome-wide association studies (GWASs) have proved successful in identifying common genetic variants of moderate effects for various complex diseases. To date, eight GWAS and replication studies from multiple populations have been published on endometriosis. In this review, we investigate the consistency and heterogeneity of the results across all the studies and their implications for an improved understanding of the aetiology of the condition. METHODS Meta-analyses were conducted on four GWASs and four replication studies including a total of 11 506 cases and 32 678 controls, and on the subset of studies that investigated associations for revised American Fertility Society (rAFS) Stage III/IV including 2859 cases. The datasets included 9039 cases and 27 343 controls of European (Australia, Belgium, Italy, UK, USA) and 2467 cases and 5335 controls of Japanese ancestry. Fixed and Han and Elkin random-effects models, and heterogeneity statistics (Cochran's Q test), were used to investigate the evidence of the nine reported genome-wide significant loci across datasets and populations. RESULTS Meta-analysis showed that seven out of nine loci had consistent directions of effect across studies and populations, and six out of nine remained genome-wide significant (P < 5 × 10−8), including rs12700667 on 7p15.2 (P = 1.6 × 10−9), rs7521902 near WNT4 (P = 1.8 × 10−15), rs10859871 near VEZT (P = 4.7 × 10−15), rs1537377 near CDKN2B-AS1 (P = 1.5 × 10−8), rs7739264 near ID4 (P = 6.2 × 10−10) and rs13394619 in GREB1 (P = 4.5 × 10−8). In addition to the six loci, two showed borderline genome-wide significant associations with Stage III/IV endometriosis, including rs1250248 in FN1 (P = 8 × 10−8) and rs4141819 on 2p14 (P = 9.2 × 10−8). Two independent inter-genic loci, rs4141819 and rs6734792 on chromosome 2, showed significant evidence of heterogeneity across datasets (P < 0.005). Eight of the nine loci had stronger effect sizes among Stage III/IV cases, implying that they are likely to be implicated in the development of moderate to severe, or ovarian, disease. While three out of nine loci were inter-genic, the remaining were in or near genes with known functions of biological relevance to endometriosis, varying from roles in developmental pathways to cellular growth/carcinogenesis. CONCLUSIONS Our meta-analysis shows remarkable consistency in endometriosis GWAS results across studies, with little evidence of population-based heterogeneity. They also show that the phenotypic classifications used in GWAS to date have been limited. Stronger associations with Stage III/IV disease observed for most loci emphasize the importance for future studies to include detailed sub-phenotype information. Functional studies in relevant tissues are needed to understand the effect of the variants on downstream biological pathways. PMID:24676469

Integrating genome-wide association studies and gene expression data highlights dysregulated multiple sclerosis risk pathways.

PubMed

Liu, Guiyou; Zhang, Fang; Jiang, Yongshuai; Hu, Yang; Gong, Zhongying; Liu, Shoufeng; Chen, Xiuju; Jiang, Qinghua; Hao, Junwei

2017-02-01

Much effort has been expended on identifying the genetic determinants of multiple sclerosis (MS). Existing large-scale genome-wide association study (GWAS) datasets provide strong support for using pathway and network-based analysis methods to investigate the mechanisms underlying MS. However, no shared genetic pathways have been identified to date. We hypothesize that shared genetic pathways may indeed exist in different MS-GWAS datasets. Here, we report results from a three-stage analysis of GWAS and expression datasets. In stage 1, we conducted multiple pathway analyses of two MS-GWAS datasets. In stage 2, we performed a candidate pathway analysis of the large-scale MS-GWAS dataset. In stage 3, we performed a pathway analysis using the dysregulated MS gene list from seven human MS case-control expression datasets. In stage 1, we identified 15 shared pathways. In stage 2, we successfully replicated 14 of these 15 significant pathways. In stage 3, we found that dysregulated MS genes were significantly enriched in 10 of 15 MS risk pathways identified in stages 1 and 2. We report shared genetic pathways in different MS-GWAS datasets and highlight some new MS risk pathways. Our findings provide new insights on the genetic determinants of MS.

Genome-wide association study of perioperative myocardial infarction after coronary artery bypass surgery.

PubMed

Kertai, Miklos D; Li, Yi-Ju; Li, Yen-Wei; Ji, Yunqi; Alexander, John; Newman, Mark F; Smith, Peter K; Joseph, Diane; Mathew, Joseph P; Podgoreanu, Mihai V

2015-05-06

Identification of patient subpopulations susceptible to develop myocardial infarction (MI) or, conversely, those displaying either intrinsic cardioprotective phenotypes or highly responsive to protective interventions remain high-priority knowledge gaps. We sought to identify novel common genetic variants associated with perioperative MI in patients undergoing coronary artery bypass grafting using genome-wide association methodology. 107 secondary and tertiary cardiac surgery centres across the USA. We conducted a stage I genome-wide association study (GWAS) in 1433 ethnically diverse patients of both genders (112 cases/1321 controls) from the Genetics of Myocardial Adverse Outcomes and Graft Failure (GeneMAGIC) study, and a stage II analysis in an expanded population of 2055 patients (225 cases/1830 controls) combined from the GeneMAGIC and Duke Perioperative Genetics and Safety Outcomes (PEGASUS) studies. Patients undergoing primary non-emergent coronary bypass grafting were included. The primary outcome variable was perioperative MI, defined as creatine kinase MB isoenzyme (CK-MB) values ≥10× upper limit of normal during the first postoperative day, and not attributable to preoperative MI. Secondary outcomes included postoperative CK-MB as a quantitative trait, or a dichotomised phenotype based on extreme quartiles of the CK-MB distribution. Following quality control and adjustment for clinical covariates, we identified 521 single nucleotide polymorphisms in the stage I GWAS analysis. Among these, 8 common variants in 3 genes or intergenic regions met p<10(-5) in stage II. A secondary analysis using CK-MB as a quantitative trait (minimum p=1.26×10(-3) for rs609418), or a dichotomised phenotype based on extreme CK-MB values (minimum p=7.72×10(-6) for rs4834703) supported these findings. Pathway analysis revealed that genes harbouring top-scoring variants cluster in pathways of biological relevance to extracellular matrix remodelling, endoplasmic reticulum-to-Golgi transport and inflammation. Using a two-stage GWAS and pathway analysis, we identified and prioritised several potential susceptibility loci for perioperative MI. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Autoantibodies to MUC1 glycopeptides cannot be used as a screening assay for early detection of breast, ovarian, lung or pancreatic cancer

PubMed Central

Burford, B; Gentry-Maharaj, A; Graham, R; Allen, D; Pedersen, J W; Nudelman, A S; Blixt, O; Fourkala, E O; Bueti, D; Dawnay, A; Ford, J; Desai, R; David, L; Trinder, P; Acres, B; Schwientek, T; Gammerman, A; Reis, C A; Silva, L; Osório, H; Hallett, R; Wandall, H H; Mandel, U; Hollingsworth, M A; Jacobs, I; Fentiman, I; Clausen, H; Taylor-Papadimitriou, J; Menon, U; Burchell, J M

2013-01-01

Background: Autoantibodies have been detected in sera before diagnosis of cancer leading to interest in their potential as screening/early detection biomarkers. As we have found autoantibodies to MUC1 glycopeptides to be elevated in early-stage breast cancer patients, in this study we analysed these autoantibodies in large population cohorts of sera taken before cancer diagnosis. Methods: Serum samples from women who subsequently developed breast cancer, and aged-matched controls, were identified from UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and Guernsey serum banks to formed discovery and validation sets. These were screened on a microarray platform of 60mer MUC1 glycopeptides and recombinant MUC1 containing 16 tandem repeats. Additional case–control sets comprised of women who subsequently developed ovarian, pancreatic and lung cancer were also screened on the arrays. Results: In the discovery (273 cases, 273 controls) and the two validation sets (UKCTOCS 426 cases, 426 controls; Guernsey 303 cases and 606 controls), no differences were found in autoantibody reactivity to MUC1 tandem repeat peptide or glycoforms between cases and controls. Furthermore, no differences were observed between ovarian, pancreatic and lung cancer cases and controls. Conclusion: This robust, validated study shows autoantibodies to MUC1 peptide or glycopeptides cannot be used for breast, ovarian, lung or pancreatic cancer screening. This has significant implications for research on the use of MUC1 in cancer detection. PMID:23652307

Age is not a prognostic factor in children with Wilms tumor beyond stage I in Africa.

PubMed

Aronson, D C; Hadley, G P

2014-06-01

Patients under age 4 with stage I favorable histology (FH) Wilms tumor have a reported survival advantage. Among children above 10 years, a poorer prognosis has been associated with a higher prevalence of diffuse anaplasia. To determine if, in our practice, patients with Wilms tumors >8 years of age (stage II-V) have a poorer prognosis than those aged <8 years or <4 years. Case-control study of 19 patients >8 years with Wilms tumor stages II-V who were identified from a cohort of 192 new patients (2002-2012). For each patient two controls were chosen matched for stage and histology, one 0-3 years and one 4-7 years. Neo-adjuvant chemotherapy was offered to all, combined with intensive supportive care. Postoperative treatment was determined by local stage and histology. OS and EFS at 5 years for the different age groups were compared. Each age group contained 19 patients, of whom 6 had stage II tumors, 3 stage III, 8 stage IV, and 2 stage V. Histology was intermediate risk (IR) in 17 and high risk (HR) in 2. OS at 5 years was 80.8% and EFS was 79.2% for the whole group. No significant difference in outcome could be shown between age groups. Loss to follow up was 6/57 (11%). The survival advantage of young age (<4 years) associated with stage I FH could not be demonstrated in higher stages. Age had no significant impact on prognosis although a trend to better outcome was seen in children <4 years. © 2014 Wiley Periodicals, Inc.

A C597-->A polymorphism in the Norrie disease gene is associated with advanced retinopathy of prematurity in premature Kuwaiti infants.

PubMed

Haider, M Z; Devarajan, L V; Al-Essa, M; Kumar, H

2002-01-01

Retinopathy of prematurity (ROP) is a retinal vascular disease which occurs in infants with a short gestational age and low birth weight and may lead to retinal detachment and blindness. In some premature infants, ROP progresses to advanced stages despite rigorous intervention, but in the majority, it spontaneously regresses before the threshold stage. Genetic factors, e.g. mutations in the Norrie disease (ND) gene, have been implicated in determining the progression of ROP to advanced stages. We have identified a novel C597A polymorphism of the ND gene; we screened this and another mutation in the ND gene, C110G, in 210 premature Kuwaiti infants using PCR-RFLP, DNA sequence analysis and DNA enzyme immunoassay hybridization to investigate their association with advanced-stage ROP. In this cohort of premature Kuwaiti newborns, 115 of 210 babies had no eye problems and served as controls, while 95 were found to have ROP. In 71 of the 95 ROP cases, the disease spontaneously regressed at or before stage 3, while in 24 of 95 ROP cases, the disease progressed to advanced stages 4 or 5. The incidence of the AA genotype of the C597A polymorphism was considerably higher in advanced-stage ROP cases (83.3%) compared to spontaneously regressing ROP cases (0%) and the normal controls (10.4%) (p < 0.0001). For the other genotypes, no significant difference was detected between the controls and ROP cases. In the case of the C110G mutation in the ND gene, no significant differences were detected between the controls and ROP cases, and the majority of subjects had a CC genotype in all three groups. Copyright 2002 National Science Council, ROC and S. Karger AG, Basel

SPORE/EDRN/PRE-PLCO Ovarian Phase II Validation Study — EDRN Public Portal

Cancer.gov

Create a new set of phase II specimens (160 cases with pre-operative bloods representing major histologic types and including 80 early-staged and 80 late-staged cases, 160 controls with benign disease, 480 general population controls, and a small set of serial Samples collected either at least 3 months apart, but not more than 6 months apart OR between 10 months apart and no more than 14 months apart in 40 healthy controls) will be used to evaluate markers identified in preliminary work. The top 5-10 markers, plus an expanded panel of Luminex markers, will comprise a “working consensus panel” for subsequent analysis in PLCO specimens.

Urine and plasma metabolites predict the development of diabetic nephropathy in individuals with Type 2 diabetes mellitus.

PubMed

Pena, M J; Lambers Heerspink, H J; Hellemons, M E; Friedrich, T; Dallmann, G; Lajer, M; Bakker, S J L; Gansevoort, R T; Rossing, P; de Zeeuw, D; Roscioni, S S

2014-09-01

Early detection of individuals with Type 2 diabetes mellitus or hypertension at risk for micro- or macroalbuminuria may facilitate prevention and treatment of renal disease. We aimed to discover plasma and urine metabolites that predict the development of micro- or macroalbuminuria. Patients with Type 2 diabetes (n = 90) and hypertension (n = 150) were selected from the community-cohort 'Prevention of REnal and Vascular End-stage Disease' (PREVEND) and the Steno Diabetes Center for this case-control study. Cases transitioned in albuminuria stage (from normo- to microalbuminuria or micro- to macroalbuminuria). Controls, matched for age, gender, and baseline albuminuria stage, remained in normo- or microalbuminuria stage during follow-up. Median follow-up was 2.9 years. Metabolomics were performed on plasma and urine. The predictive performance of a metabolite for albuminuria transition was assessed by the integrated discrimination index. In patients with Type 2 diabetes with normoalbuminuria, no metabolites discriminated cases from controls. In patients with Type 2 diabetes with microalbuminuria, plasma histidine was lower (fold change = 0.87, P = 0.02) and butenoylcarnitine was higher (fold change = 1.17, P = 0.007) in cases vs. controls. In urine, hexose, glutamine and tyrosine were lower in cases vs. controls (fold change = 0.20, P < 0.001; 0.32, P < 0.001; 0.51, P = 0.006, respectively). Adding the metabolites to a model of baseline albuminuria and estimated glomerular filtration rate metabolites improved risk prediction for macroalbuminuria transition (plasma integrated discrimination index = 0.28, P < 0.001; urine integrated discrimination index = 0.43, P < 0.001). These metabolites did not differ between hypertensive cases and controls without Type 2 diabetes. Type 2 diabetes-specific plasma and urine metabolites were discovered that predict the development of macroalbuminuria beyond established renal risk markers. These results should be confirmed in a large, prospective cohort. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

Evaluation of Transtheoretical Model-Based Family Education Among Females of Zahedan (Southeast of Iran)

PubMed Central

Kamalikhah, Tahereh; Rakhshani, Fatemeh; Rahmati Najarkolaei, Fatemeh; Gholian Avval, Mehdi

2015-01-01

Background: It cannot be denied that many improvements in female and child health have been achieved worldwide through international family planning programs. More than half of the females (57%) with unintended pregnancy admitted that they had not used birth control the month before conception. Objectives: The aim of this study was to promote family planning practice among females of Zahedan (southeast of Iran) through the transtheoretical model (TTM). Patients and Methods: The current quasi-experimental study was conducted on 96 eligible females, who were allocated either to the case or the control group and were selected from homes in the border of Zahedan city (southeast of Iran) during 2010. Convenience sampling by door-to-door visits was used for finding eligible cases. A TTM-based self-administrated family planning questionnaire was used for data collection. Participants in the intervention group received education in two groups, based on their stage of change: precontemplation, contemplation, preparation, action, maintenance, and all groups were followed for three months. Results: The result of the chi-square test did not show any significant difference in the stage of change: precontemplation, contemplation, preparation, action, maintenance before education between the control and intervention groups (P = 0.55). After education, subjects in the intervention group moved forward through stage of change and got at least one step closer to the family planning behavior., with this change being significant (P < 0.001), while the movement of participants through stage of change not being significant in control group (P = 1). The results of statistical tests illustrated that the mean knowledge of the intervention group was 7.5 ± 7.1 versus 0.5 ± 4 for the control group (P < 0.001), mean of attitude of the intervention group was 5.5 ± 5.41 versus 0.09 ± 2.04 for the control group (P < 0.001), and practicing family planning methods (P < 0.007) in the intervention group was higher than the control group after education based on TTM. Conclusions: According to this study, the educational plan based on TTM was effective in changing knowledge, attitude, and practice and directing females towards taking action. Moreover, self-efficacy, perceived barriers and benefits are factors that affect the use of family planning methods. PMID:26568846

Sensitive Detection of Colorectal Cancer in Peripheral Blood by Septin 9 DNA Methylation Assay

PubMed Central

Grützmann, Robert; Molnar, Bela; Pilarsky, Christian; Habermann, Jens K.; Schlag, Peter M.; Saeger, Hans D.; Miehlke, Stephan; Stolz, Thomas; Model, Fabian; Roblick, Uwe J.; Bruch, Hans-Peter; Koch, Rainer; Liebenberg, Volker; deVos, Theo; Song, Xiaoling; Day, Robert H.; Sledziewski, Andrew Z.; Lofton-Day, Catherine

2008-01-01

Background Colorectal cancer (CRC) is the second leading cause of cancer deaths despite the fact that detection of this cancer in early stages results in over 90% survival rate. Currently less than 45% of at-risk individuals in the US are screened regularly, exposing a need for better screening tests. We performed two case-control studies to validate a blood-based test that identifies methylated DNA in plasma from all stages of CRC. Methodology/Principal Findings Using a PCR assay for analysis of Septin 9 (SEPT9) hypermethylation in DNA extracted from plasma, clinical performance was optimized on 354 samples (252 CRC, 102 controls) and validated in a blinded, independent study of 309 samples (126 CRC, 183 controls). 168 polyps and 411 additional disease controls were also evaluated. Based on the training study SEPT9-based classification detected 120/252 CRCs (48%) and 7/102 controls (7%). In the test study 73/126 CRCs (58%) and 18/183 control samples (10%) were positive for SEPT9 validating the training set results. Inclusion of an additional measurement replicate increased the sensitivity of the assay in the testing set to 72% (90/125 CRCs detected) while maintaining 90% specificity (19/183 for controls). Positive rates for plasmas from the other cancers (11/96) and non-cancerous conditions (41/315) were low. The rate of polyp detection (>1 cm) was ∼20%. Conclusions/Significance Analysis of SEPT9 DNA methylation in plasma represents a straightforward, minimally invasive method to detect all stages of CRC with potential to satisfy unmet needs for increased compliance in the screening population. Further clinical testing is warranted. PMID:19018278

Two-stage approach for risk estimation of fetal trisomy 21 and other aneuploidies using computational intelligence systems.

PubMed

Neocleous, A C; Syngelaki, A; Nicolaides, K H; Schizas, C N

2018-04-01

To estimate the risk of fetal trisomy 21 (T21) and other chromosomal abnormalities (OCA) at 11-13 weeks' gestation using computational intelligence classification methods. As a first step, a training dataset consisting of 72 054 euploid pregnancies, 295 cases of T21 and 305 cases of OCA was used to train an artificial neural network. Then, a two-stage approach was used for stratification of risk and diagnosis of cases of aneuploidy in the blind set. In Stage 1, using four markers, pregnancies in the blind set were classified into no risk and risk. No-risk pregnancies were not examined further, whereas the risk pregnancies were forwarded to Stage 2 for further examination. In Stage 2, using seven markers, pregnancies were classified into three types of risk, namely no risk, moderate risk and high risk. Of 36 328 unknown to the system pregnancies (blind set), 17 512 euploid, two T21 and 18 OCA were classified as no risk in Stage 1. The remaining 18 796 cases were forwarded to Stage 2, of which 7895 euploid, two T21 and two OCA cases were classified as no risk, 10 464 euploid, 83 T21 and 61 OCA as moderate risk and 187 euploid, 50 T21 and 52 OCA as high risk. The sensitivity and the specificity for T21 in Stage 2 were 97.1% and 99.5%, respectively, and the false-positive rate from Stage 1 to Stage 2 was reduced from 51.4% to ∼1%, assuming that the cell-free DNA test could identify all euploid and aneuploid cases. We propose a method for early diagnosis of chromosomal abnormalities that ensures that most T21 cases are classified as high risk at any stage. At the same time, the number of euploid cases subjected to invasive or cell-free DNA examinations was minimized through a routine procedure offered in two stages. Our method is minimally invasive and of relatively low cost, highly effective at T21 identification and it performs better than do other existing statistical methods. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Refining and validating a two-stage and web-based cancer risk assessment tool for village doctors in China.

PubMed

Shen, Xing-Rong; Chai, Jing; Feng, Rui; Liu, Tong-Zhu; Tong, Gui-Xian; Cheng, Jing; Li, Kai-Chun; Xie, Shao-Yu; Shi, Yong; Wang, De-Bin

2014-01-01

The big gap between efficacy of population level prevention and expectations due to heterogeneity and complexity of cancer etiologic factors calls for selective yet personalized interventions based on effective risk assessment. This paper documents our research protocol aimed at refining and validating a two-stage and web- based cancer risk assessment tool, from a tentative one in use by an ongoing project, capable of identifying individuals at elevated risk for one or more types of the 80% leading cancers in rural China with adequate sensitivity and specificity and featuring low cost, easy application and cultural and technical sensitivity for farmers and village doctors. The protocol adopted a modified population-based case control design using 72, 000 non-patients as controls, 2, 200 cancer patients as cases, and another 600 patients as cases for external validation. Factors taken into account comprised 8 domains including diet and nutrition, risk behaviors, family history, precancerous diseases, related medical procedures, exposure to environment hazards, mood and feelings, physical activities and anthropologic and biologic factors. Modeling stresses explored various methodologies like empirical analysis, logistic regression, neuro-network analysis, decision theory and both internal and external validation using concordance statistics, predictive values, etc..

Expression and clinical significance of CD147 in renal cell carcinoma: a meta-analysis

PubMed Central

Shi, Shupeng; Xu, Yadong; Wei, Ling; Liu, Jing; Liu, Yanting

2017-01-01

Objective To assess clinical significance of CD147 in renal cell carcinoma. Methods Collect case-control studies which focus on CD147's expression in renal cell carcinoma. Trails were retrieved from CBM, CNKI, Wan-fang database, PubMed, Cochrane Library and Embase. According to the inclusion and exclusion criteria, data extraction and quality assessment were done by two researchers independently, and outcomes were pooled with Revman5.3 and STATA14.0. Results A total of 11 studies were confirmed, among which renal cell carcinoma 887 cases, non-cancer 505cases. As for the positive rate of CD147, there are statistical differences among survival, renal cell carcinoma tissue vs. non-cancer tissues [OR= 8.19, P= 0.0002], with vs. without lymph node metastases [OR= 6.52, P= 0.001], clinical stage III~IV vs. II~I [OR= 4.07, P< 0.00001], histopathological stage III~IV vs. II [OR= 3.01, P= 0.002], histopathological stage III~IV vs. I [OR= 7.50, P< 0.00001], tumor size [OR= 5.01, P= 0.0007]. No significant difference was tested among different age, gender, histological types and Position of cancer. Conclusion As shown in our results, CD 147 may participate the whole course of carcinogenesis of renal cell carcinoma, which might be valuable for the diagnosis, treatment and prognosis. PMID:28881651

The balance effect of acupuncture therapy among stroke patients.

PubMed

Huang, Shih-Wei; Wang, Wei-Te; Yang, Tsung-Hsien; Liou, Tsan-Hon; Chen, Guan-Yu; Lin, Li-Fong

2014-08-01

To analyze how acupuncture therapy affects balance in patients experiencing their first stroke and to identify the stroke group with greatest improvement in balance after acupuncture intervention. Retrospective case-control study. Ward of a medical university hospital. A total of 629 stroke patients were enrolled initially; 345 patients met the study criteria and 132 were analyzed (66 each in the study and control groups). The study group received physiotherapy combined with acupuncture and the control group received only physiotherapy. The Postural Assessment Scale for Stroke patients (PASS) was used to evaluate balance. This balance scale system can be subdivided into static balance (PASS-MP, maintain posture) and dynamic balance (PASS-CP, change posture). This study revealed no statistically significant improvement of balance in the study group (t test). When patients with high Brunnstrom stage (Br stage) and low Br stage were analyzed separately, once again no statistical difference was detected between the study and control groups of those with high Br stage. However, among low-Br stage patients, the study group showed significant improvement in static balance (mean PASS-MP score±standard deviation: 4.7±3.7) compared with the control group (PASS-MP score: 2.8±2.7) (p<0.05). In first-ever stroke patients with a low Br stage, acupuncture therapy can improve static balance during rehabilitation. However, the effect on balance was limited among high-Br stage patients. This study provides information valuable to patients with hemiplegic stroke because it suggests that acupuncture can be used to improve balance. A prospective double-blind, randomized, controlled study design is recommended for future studies in patients with hemiplegic stroke.

Recommendations for choosing an analysis method that controls Type I error for unbalanced cluster sample designs with Gaussian outcomes.

PubMed

Johnson, Jacqueline L; Kreidler, Sarah M; Catellier, Diane J; Murray, David M; Muller, Keith E; Glueck, Deborah H

2015-11-30

We used theoretical and simulation-based approaches to study Type I error rates for one-stage and two-stage analytic methods for cluster-randomized designs. The one-stage approach uses the observed data as outcomes and accounts for within-cluster correlation using a general linear mixed model. The two-stage model uses the cluster specific means as the outcomes in a general linear univariate model. We demonstrate analytically that both one-stage and two-stage models achieve exact Type I error rates when cluster sizes are equal. With unbalanced data, an exact size α test does not exist, and Type I error inflation may occur. Via simulation, we compare the Type I error rates for four one-stage and six two-stage hypothesis testing approaches for unbalanced data. With unbalanced data, the two-stage model, weighted by the inverse of the estimated theoretical variance of the cluster means, and with variance constrained to be positive, provided the best Type I error control for studies having at least six clusters per arm. The one-stage model with Kenward-Roger degrees of freedom and unconstrained variance performed well for studies having at least 14 clusters per arm. The popular analytic method of using a one-stage model with denominator degrees of freedom appropriate for balanced data performed poorly for small sample sizes and low intracluster correlation. Because small sample sizes and low intracluster correlation are common features of cluster-randomized trials, the Kenward-Roger method is the preferred one-stage approach. Copyright © 2015 John Wiley & Sons, Ltd.

Revision of Infected Total Knee Arthroplasty: Two-Stage Reimplantation Using an Antibiotic-Impregnated Static Spacer

PubMed Central

Almeida, Fernando; Renovell, Pablo; Morante, Elena; López, Raúl

2013-01-01

Background A two-stage revision remains as the "gold standard" treatment for chronically infected total knee arthroplasties. Methods Forty-five septic knee prostheses were revised with a minimum follow-up of 5 years. Static antibiotic-impregnated cement spacers were used in all cases. Intravenous antibiotics according to sensitivity test of the culture were applied during patients' hospital stay. Oral antibiotics were given for another 5 weeks. Second-stage surgery was undertaken after control of infection with normal erythrocyte sedimentation rate and C-reactive protein values. Extensile techniques were used if needed and metallic augments were employed for bone loss in 32 femoral and 29 tibial revisions. Results The average interval between the first-stage resection and reimplantation was 4.4 months. Significant improvement was obtained with respect to visual analog scale pain and clinical and functional scores, and infection was eradicated in 95.6% of cases following a two-stage revision total knee arthroplasty. Radiographic evaluation showed suitable alignment without signs of mechanical loosening. Conclusions This technique is a reasonable procedure to eradicate chronic infection in knee arthroplasty and provides proper functional and clinical results. However, it sometimes requires extensile surgical approaches that could imply arduous surgeries. Metallic augments with cementless stems available in most of the knee revision systems are a suitable alternative to handle bone deficiencies, avoiding the use of bone allografts with its complications. PMID:24009903

Revision of infected total knee arthroplasty: two-stage reimplantation using an antibiotic-impregnated static spacer.

PubMed

Silvestre, Antonio; Almeida, Fernando; Renovell, Pablo; Morante, Elena; López, Raúl

2013-09-01

A two-stage revision remains as the "gold standard" treatment for chronically infected total knee arthroplasties. Forty-five septic knee prostheses were revised with a minimum follow-up of 5 years. Static antibiotic-impregnated cement spacers were used in all cases. Intravenous antibiotics according to sensitivity test of the culture were applied during patients' hospital stay. Oral antibiotics were given for another 5 weeks. Second-stage surgery was undertaken after control of infection with normal erythrocyte sedimentation rate and C-reactive protein values. Extensile techniques were used if needed and metallic augments were employed for bone loss in 32 femoral and 29 tibial revisions. The average interval between the first-stage resection and reimplantation was 4.4 months. Significant improvement was obtained with respect to visual analog scale pain and clinical and functional scores, and infection was eradicated in 95.6% of cases following a two-stage revision total knee arthroplasty. Radiographic evaluation showed suitable alignment without signs of mechanical loosening. This technique is a reasonable procedure to eradicate chronic infection in knee arthroplasty and provides proper functional and clinical results. However, it sometimes requires extensile surgical approaches that could imply arduous surgeries. Metallic augments with cementless stems available in most of the knee revision systems are a suitable alternative to handle bone deficiencies, avoiding the use of bone allografts with its complications.

Survival outcome of women with stage IV uterine carcinosarcoma who received neoadjuvant chemotherapy followed by surgery.

PubMed

Matsuo, Koji; Johnson, Marian S; Im, Dwight D; Ross, Malcolm S; Bush, Stephen H; Yunokawa, Mayu; Blake, Erin A; Takano, Tadao; Klobocista, Merieme M; Hasegawa, Kosei; Ueda, Yutaka; Shida, Masako; Baba, Tsukasa; Satoh, Shinya; Yokoyama, Takuhei; Machida, Hiroko; Ikeda, Yuji; Adachi, Sosuke; Miyake, Takahito M; Iwasaki, Keita; Yanai, Shiori; Takeuchi, Satoshi; Nishimura, Masato; Nagano, Tadayoshi; Takekuma, Munetaka; Shahzad, Mian M K; Pejovic, Tanja; Omatsu, Kohei; Kelley, Joseph L; Ueland, Frederick R; Roman, Lynda D

2018-03-01

To examine survival of women with stage IV uterine carcinosarcoma (UCS) who received neoadjuvant chemotherapy followed by hysterectomy. This is a nested case-control study within a retrospective cohort of 1192 UCS cases. Women who received neoadjuvant chemotherapy followed by hysterectomy based-surgery for stage IV UCS (n = 26) were compared to those who had primary hysterectomy-based surgery without neoadjuvant chemotherapy for stage IV UCS (n = 120). Progression-free survival (PFS) and cause-specific survival (CSS) were examined. The most common regimen for neoadjuvant chemotherapy was carboplatin/paclitaxel (53.8%). Median number of neoadjuvant chemotherapy cycles was 4. PFS was similar between the neoadjuvant chemotherapy group and the primary surgery group (unadjusted-hazard ratio [HR] 1.19, 95% confidence interval [CI] 0.75-1.89, P = 0.45). Similarly, CSS was comparable between the two groups (unadjusted-HR 1.13, 95%CI 0.68-1.90, P = 0.64). When the types of neoadjuvant chemotherapy regimens were compared, women who received a carboplatin/paclitaxel regimen had better survival outcomes compared to those who received other regimens: PFS, unadjusted-HR 0.38, 95%CI 0.15-0.93, P = 0.027; and CSS, unadjusted-HR 0.21, 95%CI 0.07-0.61, P = 0.002. Our study found that there is no statistically significant difference in survival between women with stage IV UCS who are tolerated neoadjuvant chemotherapy and those who undergo primary surgery. © 2017 Wiley Periodicals, Inc.

Application of fundamental principles to mineral scale reduction : case studies

Treesearch

Peter W. Hart; Alan W. Rudie

2005-01-01

This paper will present several successful case studies where scale has been eliminated in mills including calcium carbonate scale in a white liquor strainer, calcium oxalate scale in the D0 stage, enzymatic treatment of brown stock to eliminate oxalate scale, and control of barium sulfate scale.

[Modified two-stage surgery for total auriculoplasty with autogenous rib cartilage].

PubMed

Zhang, Zheng-wen; Kang, Shen-song; Xie, Feng; Ma, Teng-xiao; Li, Lei; Zhai, Hong-feng; Chou, Hai-yan; Li, Hao; Zhong, Ai-mei; Zhang, Dong-yi

2011-09-01

To introduce a modified surgery for total auriculoplasty and the experience in one hundred and forty-six cases (155 ears). The procedure was a two-stage operation. The first stage involved fabrication and grafting of a costal cartilage framework. A U-shaped skin incision was made on the posterior edge of the lobule and the remnant ear cartilage was removed completely. The area for the insertion of the cartilage framework was undermined. Skin flaps were sutured after insertion of the cartilage framework. The second-stage surgery was usually performed six months after the first-stage operation. The reconstructed auricle was elevated, and a costal cartilage block was fixed to the posterior part of the auricle. A temporoparietal fascia flap was then used to cover the costal cartilage block. Finally, the posterior aspect of the projected auricle was covered with a spit-thickness skin graft. The incisions healed in one hundred and forty-one patients (150 ears) after the first stage operation. Partial necrosis of the postauricular flap was observed in five cases (5 ears) after the first stage operation, but no exposure or absorption of the cartilage took place. The skin grafts survived in one hundred and thirty-nine cases (147 ears) after the second-stage surgery. Partial necrosis of the skin graft was observed in seven cases (8 ears), but healed after one-week of dressing changes. Ninety-four cases (97 ears) were followed up, but fifty-two cases (58 ears) were lost to follow up. The follow-up at six months to two years showed satisfactory contour and projection of the constructed ears. This two-stage surgery is simple and ideal for auricloplasty with few complications.

Completeness of T, N, M and stage grouping for all cancers in the Mallorca Cancer Registry.

PubMed

Ramos, M; Franch, P; Zaforteza, M; Artero, J; Durán, M

2015-11-04

TNM staging of cancer is used to establish the treatment and prognosis for cancer patients, and also allows the assessment of screening programmes and hospital performance. Collection of staging data is becoming a cornerstone for cancer registries. The objective of the study was to assess the completeness of T, N, M and stage grouping registration for all cancers in the Mallorca Cancer Registry in 2006-2008 and to explore differences in T, N, M and stage grouping completeness by site, gender, age and type of hospital. All invasive cancer cases during the period 2006-2008 were selected. DCO, as well as children's cancers, CNS, unknown primary tumours and some haematological cases were excluded. T, N, M and stage grouping were collected separately and followed UICC (International Union Against Cancer) 7th edition guidelines. For T and N, we registered whether they were pathological or clinical. Ten thousand two hundred fifty-seven cases were registered. After exclusions, the study was performed with 9283 cases; 39.4 % of whom were women and 60.6 % were men. T was obtained in 48.6 % cases, N in 36.5 %, M in 40 % and stage in 37.9 %. T and N were pathological in 71 % of cases. Stage completeness exceeded 50 % in lung, colon, ovary and oesophagus, although T also exceeded 50 % at other sites, including rectum, larynx, colon, breast, bladder and melanoma. No differences were found in TNM or stage completeness by gender. Completeness was lower in younger and older patients, and in cases diagnosed in private clinics. T, N, M and stage grouping data collection in population-based cancer registries is feasible and desirable.

Dynamic Modeling and Control Studies of a Two-Stage Bubbling Fluidized Bed Adsorber-Reactor for Solid-Sorbent CO{sub 2} Capture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Modekurti, Srinivasarao; Bhattacharyya, Debangsu; Zitney, Stephen E.

2013-07-31

A one-dimensional, non-isothermal, pressure-driven dynamic model has been developed for a two-stage bubbling fluidized bed (BFB) adsorber-reactor for solid-sorbent carbon dioxide (CO{sub 2}) capture using Aspen Custom Modeler® (ACM). The BFB model for the flow of gas through a continuous phase of downward moving solids considers three regions: emulsion, bubble, and cloud-wake. Both the upper and lower reactor stages are of overflow-type configuration, i.e., the solids leave from the top of each stage. In addition, dynamic models have been developed for the downcomer that transfers solids between the stages and the exit hopper that removes solids from the bottom ofmore » the bed. The models of all auxiliary equipment such as valves and gas distributor have been integrated with the main model of the two-stage adsorber reactor. Using the developed dynamic model, the transient responses of various process variables such as CO{sub 2} capture rate and flue gas outlet temperatures have been studied by simulating typical disturbances such as change in the temperature, flowrate, and composition of the incoming flue gas from pulverized coal-fired power plants. In control studies, the performance of a proportional-integral-derivative (PID) controller, feedback-augmented feedforward controller, and linear model predictive controller (LMPC) are evaluated for maintaining the overall CO{sub 2} capture rate at a desired level in the face of typical disturbances.« less

One-stage vs. two-stage BAHA implantation in a pediatric population.

PubMed

Saliba, Issam; Froehlich, Patrick; Bouhabel, Sarah

2012-12-01

BAHA implantation surgery in a pediatric population is usually done in two-stage surgeries. This study aims to evaluate the safety and possible superiority of the one-stage over the two-stage BAHA implantation and which one would be the best standard of care for our pediatric patients. A retrospective chart review of 55 patients operated in our tertiary care institutions between 2005 and 2010 was conducted. The actual tendency in our institutions, applied at the time of the study, is to perform a one-stage surgery for all operated patients (pediatric and adult), except for patients undergoing translabyrinthine surgeries for cerebellopontine tumor excision. These patients indeed had a two-stage insertion. 26 patients underwent one-stage surgery (group I) while 29 patients had a two-stage (group II) BAHA insertion. A period of 4 months was allowed for osseointegration before BAHA processor fitting. As for the safety assessment of the one-stage surgery, we compared both groups regarding the incidence and severity (minor, moderate and major) of encountered complications, as well as the operating time and follow-up. The operating time of the two-stage surgery includes the time of the first and of the second stage. The mean age at surgery was 8.5 years old for the group I and 50 years old for the group II patients. There was no difference in the incidence of minor (p=0.12), moderate (p=0.41) nor severe (p=0.68) complications between groups I and II. Two cases of traumatic extrusion were noted in the group I. Furthermore, the one-stage BAHA implantation requests a significantly lower operating time (mean: 54 [32-100] min) than the two-stage surgery (mean: 79 [63-148] min) (p=0.012). All pediatric cases of BAHA insertion were performed in a one day surgery. The mean postoperative follow-up was 114 and 96 weeks for groups I and II respectively (p=0.058). One-stage BAHA insertion surgery in the pediatric population is a reliable, safe and efficient therapeutic option that allows a good result in a significantly lower operating time compared to the two-stage insertion and is achieved in a one day surgery. It could therefore be considered as a standard of care for pediatric patients. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Genome-wide meta-analysis identifies five new susceptibility loci for cutaneous malignant melanoma

PubMed Central

Law, Matthew H.; Bishop, D. Timothy; Martin, Nicholas G.; Moses, Eric K.; Song, Fengju; Barrett, Jennifer H.; Kumar, Rajiv; Easton, Douglas F.; Pharoah, Paul D. P.; Swerdlow, Anthony J.; Kypreou, Katerina P.; Taylor, John C.; Harland, Mark; Randerson-Moor, Juliette; Akslen, Lars A.; Andresen, Per A.; Avril, Marie-Françoise; Azizi, Esther; Scarrà, Giovanna Bianchi; Brown, Kevin M.; Dębniak, Tadeusz; Duffy, David L.; Elder, David E.; Fang, Shenying; Friedman, Eitan; Galan, Pilar; Ghiorzo, Paola; Gillanders, Elizabeth M.; Goldstein, Alisa M.; Gruis, Nelleke A.; Hansson, Johan; Helsing, Per; Hočevar, Marko; Höiom, Veronica; Ingvar, Christian; Kanetsky, Peter A.; Chen, Wei V.; Landi, Maria Teresa; Lang, Julie; Lathrop, G. Mark; Lubiński, Jan; Mackie, Rona M.; Mann, Graham J.; Molven, Anders; Montgomery, Grant W.; Novaković, Srdjan; Olsson, Håkan; Puig, Susana; Puig-Butille, Joan Anton; Qureshi, Abrar A.; Radford-Smith, Graham L.; van der Stoep, Nienke; van Doorn, Remco; Whiteman, David C.; Craig, Jamie E.; Schadendorf, Dirk; Simms, Lisa A.; Burdon, Kathryn P.; Nyholt, Dale R.; Pooley, Karen A.; Orr, Nick; Stratigos, Alexander J.; Cust, Anne E.; Ward, Sarah V.; Hayward, Nicholas K.; Han, Jiali; Schulze, Hans-Joachim; Dunning, Alison M.; Bishop, Julia A. Newton; MacGregor, Stuart; Iles, Mark M.

2015-01-01

Thirteen common susceptibility loci have been reproducibly associated with cutaneous malignant melanoma (CMM). We report the results of an international 2-stage meta-analysis of CMM genome-wide association studies (GWAS). This meta-analysis combines 11 GWAS (5 previously unpublished) and a further three stage 2 data sets, totaling 15,990 CMM cases and 26,409 controls. Five loci not previously associated with CMM risk reached genome-wide significance (P < 5×10–8), as did two previously-reported but un-replicated loci and all thirteen established loci. Novel SNPs fall within putative melanocyte regulatory elements, and bioinformatic and expression quantitative trait locus (eQTL) data highlight candidate genes including one involved in telomere biology. PMID:26237428

Surgical protocol and outcome for sigmoidovesical fistula secondary to diverticular disease of the left colon: A retrospective cohort study.

PubMed

El-Haddad, Hany M; Kassem, Mohamed I; Sabry, Ahmed A; Abouelfotouh, Ahmed

2018-06-11

Diverticular disease of sigmoid colon can rarely be complicated by a connective track to urinary bladder. Pneumaturia and fecaluria are the pathognomonic symptoms. Resection surgery is the preferred treatment to overcome the renal sequellae of the disease. The purpose of this study is to propose a guiding classification to help general surgeons during surgical management of diverticular disease complicated by sigmoidovesical fistula (SVF). The data of 40 cases with colovesical fistula due to diverticular disease of sigmoid colon were retrospectively analyzed. Clinicopathological variables, imaging reports, types of treatment and patient outcome were evaluated. There were 36 men (90%) and four women (10%) in which the ages ranged from 32 to 79 with a mean of 58.1 years. Pneumaturia was the most common presenting symptom in 38 cases (95%) followed by urinary symptoms in 35 cases (87.5%) then fecaluria in 33 cases (82.5%). 37 patients underwent surgical resection while three patients were in poor general condition to withstand major resection. 16 patients underwent one stage resection and anastomosis, 16 patients were managed by two stage procedure and the remaining 5 patients were treated by three stages operation. Adequately performed CT followed by colonoscopy is the mainstay for diagnosis. Type 1 SVF should be treated in a single stage by complete resection and immediate anastomosis without a stoma. Type 2 cases are best managed in two stages while those with type 3 SVF are emergently managed by three stage procedure. Treatment of type 4 should be individualized. Copyright © 2018. Published by Elsevier Ltd.

Evidence of MRSE on a gentamicin and vancomycin impregnated polymethyl-methacrylate (PMMA) bone cement spacer after two-stage exchange arthroplasty due to periprosthetic joint infection of the knee

PubMed Central

2014-01-01

Background Periprosthetic joint infections (PJI) are often treated by two stage exchange with the use of an antibiotic impregnated spacer. Most of the two-stage exchange algorithms recommend the implantation of an antibiotic-impregnated spacer during the first stage for a period of 2–24 weeks before reimplantation of the new prosthesis. For the spacer to have a therapeutic effect, the local antibiotic concentration must be greater than the minimal inhibition concentration (MIC) against the pathogens causing the PJI. It must remain so for the entire spacer period, otherwise recurrence of infection or resistances might occur. The question as to whether a sufficient concentration of antibiotics in vivo is reached for the entire spacer period has not been answered satisfactorily. Case presentation We here present a case of a histologically confirmed chronic PJI 20 month after primary arthroplasty. The primary knee arthroplasty was performed due to osteoarthritis of the joint. Initial assessment did not detect a causative pathogen, and two stage exchange with a vancomycin-gentamycin impregnated spacer was performed. At the time of reimplantation, sonication of the explanted spacer revealed a multi-resistant strain of staphylococcus epidermidis on the device and in the joint. Adaption of the therapy and prolonged treatment successfully eradicated the infection. Conclusion According to the authors’ knowledge, the case presented here confirms for the first time the surface contamination (proven through sonication) of a vancomycin-/gentamicin- impregnated Vancogenx®-spacer with a MRSE after ten weeks of implantation. This case study demonstrates the difficulties still associated with the diagnostics of PJI and the published different two stage treatment regimes with the use of antibiotic impregnated spacers. PMID:24641471

[Endoscopic transnasal approach for nasopharyngeal angiofibroma without arterial embolism].

PubMed

Yang, Donghui; Qiu, Qianhui; Liang, Minzhi; Tan, Xianggao; Xia, Guangsheng

2014-01-01

To explore the feasibility of endoscopic resection without arterial embolism for nasopharyngeal angiofibroma and the strategy of decreasing the bleeding during the operation. The clinical data of twenty-five cases of nasopharyngeal angiofibroma were retrospective analyzed, including 3 cases of Radowski stageIIa, 5 cases of stageIIb, 4 cases of stageIIc and with 13 cases of stage IIIa. All cases did not receive the arterial embolism, and controlled hypotension were adopted under endoscopic transnasal approach during the tumor resection. Two cases were added the labiogingival incision. During the operation, under the opening vision, cutting out the outside of the infratemporal fossa, and the pterygoid process to adequate exposure the pterygopalatine fossa and infratemporal fossa.Early recognition of anatomical landmarks and establish the safety plane, along the periphery of the tumor to proceed with micro-separation, early blocking tumor nutrient vessels, en bloc resection of the tumor and some other ways to reduce bleeding and tumor resection. Amount of bleeding during operation was 600-1500 ml, none of them had internal carotid artery injury and intracranial injury or some other complication.Follow-up 2-3 years was available in all patients, except 1 case with residual of tumor surrounding the optic nerve, the other 24 cases had no residual tumor and relapses. The preoperative occlusion and artery ligation may not be needed.Surgical technique is the key to reduce blood loss, and it is feasible to have endoscopic resection of nasopharyngeal angiofibroma with proper operating technique.

Association of prostate cancer risk variants with clinicopathologic characteristics of the disease

PubMed Central

Xu, Jianfeng; Isaacs, Sarah D.; Sun, Jielin; Li, Ge; Wiley, Kathleen E.; Zhu, Yi; Hsu, Fang-Chi; Wiklund, Fredrik; Turner, Aubrey R.; Adams, Tamara S.; Liu, Wennuan; Trock, Bruce J.; Partin, Alan W.; Chang, Baoli; Walsh, Patrick C.; Grönberg, Henrik; Isaacs, William; Zheng, Siqun

2009-01-01

Purpose Fifteen independent genetic variants have been implicated in prostate cancer risk by recent genome-wide association studies. However, their association with clinicopathologic features of prostate cancer is uncertain. Experimental Design We systematically evaluated these 15 variants in 1,563 prostate cancer patients undergoing radical prostatectomy, taking advantage of the uniform tumor stage and grade information available for each of these cases. Associations of these variants with aggressiveness, pathologic Gleason scores, pathologic stage, age at diagnosis, or serum PSA levels were tested. Results After adjusting for multiple testing, none of the SNPs was individually or cumulatively associated with aggressiveness or individual clinicopathologic variables of prostate cancer such as Gleason scores, pathologic stage, or age at diagnosis of prostate cancer. The reported risk allele (G) for SNP rs2735839 in the KLK3 gene at 19q13 was more frequent in less aggressive prostate cancer patients (0.89) than in more aggressive prostate cancer patients (0.86), nominal P = 0.03, or in controls (0.86), nominal P = 0.04. Considering that this allele was also significantly associated with higher serum PSA levels among controls (nominal P = 0.003), the observed trend of higher frequency of this risk allele between less and more aggressive prostate cancer, or between less aggressive and controls may be due to detection bias of PSA screening. Conclusions Prostate cancer risk variants recently discovered from genome-wide case-control association studies are not associated with clinicopathologic variables in this population. Case-case studies are urgently needed in order to discover genetic variants that predict tumor aggressiveness. PMID:18794092

Epidemiologic and molecular characteristics of borderline and malignant epithelial ovarian tumors

NASA Astrophysics Data System (ADS)

Bastos, Eugenia Maria Chaves De Moraes

Data from the Cancer and Steroid Hormone Study, a multicenter, population-based, case-control study were used to identify risk factors for epithelial ovarian cancer according to tumor behavior, histologic types, as well as p53 expression. Cases were women between 20 to 54 years old diagnosed with epithelial ovarian cancer from 1980 to 1982. Controls were women selected by random digit dialing. Tumor samples were analyzed for p53 overexpression using immunohistochemistry. Case-case and case-control conditional logistic regression models matched on age and diagnosing centers were used to calculate odds ratios (OR's) and 95% confidence intervals (CI's) for borderline, malignant, mucinous, and nonmucinous tumors, and p53 positive and p53 negative cases. The OR's for high number of lifetime ovulatory cycles (376-533 compared with less than 234) were 3.1 (95% CI 1.6-6.1) for malignant and 1.4 (95% CI 0.5-3.7) for borderline cases. The high number of ovulatory cycles was also a strong risk factor among nonmucinous cases. OR's for current and recent ex-smokers compared with never smokers were 2.8 (95% CI 1.7-4.8) for mucinous and 0.9 (95% CI 0.7-1.1) for nonmucinous types. Infertility showed a positive association with borderline ovarian cancer. Family history of ovarian or breast cancer was positively associated with malignant and nonmucinous cases. Parity had an inverse association with malignant ovarian cancer cases. When cases were subdivided by p53 results, the OR for tobacco smoking and p53 positive ovarian cancer was elevated for mucinous (OR = 3.9; 95% CI 0.8-18) at localized stage. Alcohol use showed a positive association with p53 positive malignant cases at advanced stage (OR = 2.0; 95% CI 1.2-3.2) and with p53 positive nonmucinous cases at advanced stage (OR = 2.1; 95% CI 1.2-3.4). A positive association between high number of ovulatory cycles and p53 positive malignant cases was observed in cases with localized stage (OR = 6.6; 95% CI 1.0-45) and advanced stage (OR = 7.0; 95% CI 1.6-30). Our findings suggest that ovarian tumors defined according to borderline versus malignant tumor behavior and mucinous versus nonmucinous histology, and p53 status show different associations for some risk factors, suggesting that cases defined by these subsets could have different etiologic pathways. However, the interpretation of results from subgroup analysis should consider the possibility of findings due to chance or artifact. Future studies should consider borderline, malignant, mucinous and other histologic types as separate endpoints.

Design and Construction Process of Two LEED Certified University Buildings: A Collective Case Study

ERIC Educational Resources Information Center

Rich, Kim

2011-01-01

This study was conducted at the early stages of integrating LEED into the design process in which a clearer understanding of what sustainable and ecological design was about became evident through the duration of designing and building of two academic buildings on a university campus. In this case study, due to utilizing a grounded theory…

[Case-control study on comprehensive traditional Chinese medicine therapy for preventing postsurgery stiffness after operation for terrible triad of the elbow].

PubMed

Lin, Guang-Mao; Liu, Liang-Le; Ye, Li-Jie; Li, Qi; Liu, Mei-Fen

2014-11-01

To study therapeutic effects of comprehensive traditional Chinese medicine therapy for preventing postsurgery stiffness after operation for terrible triad of the elbow. From December 2008 to December 2013,32 patients with elbow triad were randomly divided into two groups: therapy group and control group. There were 17 patients in control group including 12 males and 5 females with a mean age of (41.0 ± 7.1) years old. The patients in control group were received the past procedure therapy. There were 15 patients in therapy group, including 10 males and 5 females with a mean age of (41.3 ± 7.6) years old. The patients in therapy group were received comprehensive traditional Chinese medicine therapy, including passive exercise training at early stage (0 to 2 weeks after operation), transition from passive to active exercise training at middle stage (3 to 4 weeks after operation), and active exercise training at late stage (5 to 12 weeks after operation). Other treatment methods, such as orally taking or externally use of Chinese herbal medicine, manipulation and physiotherapy, were used at all stages. The Mayo Elbow Performance Score, patient satisfaction and complications were evaluated and analyzed. All the patients were followed up, and the mean duration was 7.5 months. There were no complications such as internal fixation loosing, obvious displacement fracture and heterotopic ossification occurred. The Mayo score and patient satisfaction in therapy group were higher than those in control group (t = 12.78, P = 0.00; χ2 = 8.719, P = 0.003). Seven patients needed reoperation in control group, compared with 1 patient in therapy group (χ2 = 4.626, P = 0.032). The comprehensive traditional Chinese medicine therapy is effective to prevent postoperative stiffness after operation for terrible triad of the elbow by using different methods at different stages, which is worthy of spread and application.

Expression of nestin in embryonic tissues and its effects on clinicopathological characteristics of patients with placenta previa.

PubMed

Qiao, Yan-Yan; Chu, Ping

2018-02-01

In this study, we examined expression of nestin in the spinal cord, lung, kidney, stomach, colon, and intestine tissues at different stages of embryos in patients with placenta previa. Fetuses of 75 patients with placenta previa were assigned to case group and 80 fetuses from healthy pregnant women with normal placenta who voluntarily terminated pregnancy to control group. Clinical data of pregnant women were collected at the time of admission. Blood from elbow vein was collected to determine expression of serum nestin. Tissues from spinal cord, lung, kidney, stomach, colon, and intestine in 3-7 months fetuses of the two groups were extracted. Expression of nestin in tissues was detected by immunohistochemistry, Western blotting and RT-qPCR. The mRNA expression of nestin in the case group was increased. Nestin expression was correlated with the gestational age, age of foetus, and type of placenta previa in patients with placenta previa. Positive nestin expression was detected in the spinal cord, lung, kidney, stomach, intestine, and colon tissues in normal and placenta previa embryo at Stage I. The positive cell density and nestin expression decreased at Stage II, and further decreased at Stage III. The case group had higher nestin mRNA and protein levels throughout human fetal development. Findings of this study suggested that, nestin, as a specific marker of neural precursor cells, was expressed in various tissues of the embryo in patients with placenta previa and nestin expression was lower with increased maturation of the embryo. © 2017 Wiley Periodicals, Inc.

Meta-analysis identifies a MECOM gene as a novel predisposing factor of osteoporotic fracture

PubMed Central

Hwang, Joo-Yeon; Lee, Seung Hun; Go, Min Jin; Kim, Beom-Jun; Kou, Ikuyo; Ikegawa, Shiro; Guo, Yan; Deng, Hong-Wen; Raychaudhuri, Soumya; Kim, Young Jin; Oh, Ji Hee; Kim, Youngdoe; Moon, Sanghoon; Kim, Dong-Joon; Koo, Heejo; Cha, My-Jung; Lee, Min Hye; Yun, Ji Young; Yoo, Hye-Sook; Kang, Young-Ah; Cho, Eun-Hee; Kim, Sang-Wook; Oh, Ki Won; Kang, Moo II; Son, Ho Young; Kim, Shin-Yoon; Kim, Ghi Su; Han, Bok-Ghee; Cho, Yoon Shin; Cho, Myeong-Chan; Lee, Jong-Young; Koh, Jung-Min

2014-01-01

Background Osteoporotic fracture (OF) as a clinical endpoint is a major complication of osteoporosis. To screen for OF susceptibility genes, we performed a genome-wide association study and carried out de novo replication analysis of an East Asian population. Methods Association was tested using a logistic regression analysis. A meta-analysis was performed on the combined results using effect size and standard errors estimated for each study. Results In a combined meta-analysis of a discovery cohort (288 cases and 1139 controls), three hospital based sets in replication stage I (462 cases and 1745 controls), and an independent ethnic group in replication stage II (369 cases and 560 for controls), we identified a new locus associated with OF (rs784288 in the MECOM gene) that showed genome-wide significance (p=3.59×10−8; OR 1.39). RNA interference revealed that a MECOM knockdown suppresses osteoclastogenesis. Conclusions Our findings provide new insights into the genetic architecture underlying OF in East Asians. PMID:23349225

[Clinical research of analgesic for labor with acupoint injection and electroacupuncture].

PubMed

Liu, Xiaohui; Wu, Lingling; Yi, Wei

2015-11-01

To explore a safe and effective scheme of analgesic for labor. Eighty-four primiparas without contraindication of vaginal delivery were divided into an observation group and a control group, 42 cases in each one. In the observation group, the acupoint injection was given at Zusanli (ST 36) combined with electroacupuncture (EA) at Hegu (LI 4) and Sanyinjiao (SP 6) till the cervical opening at the end of first stage labor. In the control group, the routine respiratory instruction was applied. In 5 min, 10 min and 60 min of acupuncture (the same time points in the control group) as well as at the end of the first and second stage labor, the analgesic effect was assessed for the primiparas of the two groups. The labor stages, adverse reactions, postpartum hemorrhage, postpartum urine retention, newborn asphyxia rate and usage rate of oxytocin were compared between the two groups. In the observation group, in 5 min, 10 min and 60 min of acupuncture as well as at the end of the first and second stages, the visual analogue scale (VAS) was lower apparently as compared with the control group at the corresponding time points (all P < 0.05). The differences in the time limit in the active period, the second and third stages were not significant between the two groups (all P > 0.05). The incidence of adverse reactions and the usage rate of oxytocin were lower than those in the control group [2.4% (1/42) vs 31.0% (13/42); 2.4% (1/42) vs 23.8% (10/42), both P < 0.05]. The differences in postpartum hemorrhage, postpartum urine retention and newborn asphyxia rate were not significant between the two groups (all P > 0.05). The combination of acupoint injection and EA is the effective analgesic scheme for labor. This scheme effectively alleviates labor pain and has no maternal and child complications.

Seismicity Controlled by a Frictional Afterslip During a Small-Magnitude Seismic Sequence (ML < 5) on the Chihshang Fault, Taiwan

NASA Astrophysics Data System (ADS)

Canitano, Alexandre; Godano, Maxime; Hsu, Ya-Ju; Lee, Hsin-Ming; Linde, Alan T.; Sacks, Selwyn

2018-02-01

We report evidence for frictional afterslip at shallow depths (about 5 to 7 km) during a small-magnitude seismic sequence (with ML<5) along the Chihshang Fault, a main active structure of the Longitudinal Valley, in southeast Taiwan. The afterslip, which was recorded by a nearby borehole dilatometer, lasted about a month with a cumulative geodetic moment magnitude of 4.8 ± 0.2. The afterslip comprised two stages and controlled the aftershock sequence. The first postseismic stage, which followed a ML 4.6 earthquake, lasted about 6 h and mostly controlled the ruptures of neighboring asperities (e.g., multiplets) near the hypocenter. Then, a 4 week duration large afterslip event following a ML 4.9 earthquake controlled the rate of aftershocks during its first 2 days through brittle creep. The study presents a rare case of simultaneous seismological and geodetic observations for afterslip following earthquakes with magnitude lower than 5. Furthermore, the geodetic moment of the postseismic phase is at least equivalent to the coseismic moment of the sequence.

Dual-stage periodic event-triggered output-feedback control for linear systems.

PubMed

Ruan, Zhen; Chen, Wu-Hua; Lu, Xiaomei

2018-05-01

This paper proposes an event-triggered control framework, called dual-stage periodic event-triggered control (DSPETC), which unifies periodic event-triggered control (PETC) and switching event-triggered control (SETC). Specifically, two period parameters h 1 and h 2 are introduced to characterize the new event-triggering rule, where h 1 denotes the sampling period, while h 2 denotes the monitoring period. By choosing some specified values of h 2 , the proposed control scheme can reduce to PETC or SETC scheme. In the DSPETC framework, the controlled system is represented as a switched system model and its stability is analyzed via a switching-time-dependent Lyapunov functional. Both the cases with/without network-induced delays are investigated. Simulation and experimental results show that the DSPETC scheme is superior to the PETC scheme and the SETC scheme. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

Is Single-stage Revision Safe Following Infected Total Knee Arthroplasty? A Critical Review.

PubMed

Vaishya, Raju; Agarwal, Amit Kumar; Rawat, Sudheer K; Singh, Harsh; Vijay, Vipul

2017-08-30

With the improvement in outcomes and modern prosthesis design, total knee arthroplasty (TKA) has now become a commonly performed surgery. It is postulated that a total of 2-5% of the primary and revision TKA becomes infected every year, requiring a revision procedure which to date is the conventional two-stage revision. The diagnosis and treatment of these periprosthetic infections is a major and challenging task, as it requires precise identification of the pathogen, meticulous debridement, and postoperative rehabilitation. To date, there have been very few studies in existing literature comparing the outcomes of single-stage versus two-stage procedure in infected TKA. The aim of the review was to provide the clinicians an insight into the outcome of the single-stage procedure compared to two-stage procedures and to suggest ways to improve the results further. In the following critical review, a total of 669 cases that underwent either a single or two-stage revision for infected TKA were studied. The postoperative functional scores were comparable in most studies during the early postoperative period. Our data supports the use of a single-stage revision surgery in infected TKA as an alternative to a conventional two-stage procedure. However, larger prospective and multicentric trials are required to validate our findings.

Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder

PubMed Central

Hou, Liping; Bergen, Sarah E.; Akula, Nirmala; Song, Jie; Hultman, Christina M.; Landén, Mikael; Adli, Mazda; Alda, Martin; Ardau, Raffaella; Arias, Bárbara; Aubry, Jean-Michel; Backlund, Lena; Badner, Judith A.; Barrett, Thomas B.; Bauer, Michael; Baune, Bernhard T.; Bellivier, Frank; Benabarre, Antonio; Bengesser, Susanne; Berrettini, Wade H.; Bhattacharjee, Abesh Kumar; Biernacka, Joanna M.; Birner, Armin; Bloss, Cinnamon S.; Brichant-Petitjean, Clara; Bui, Elise T.; Byerley, William; Cervantes, Pablo; Chillotti, Caterina; Cichon, Sven; Colom, Francesc; Coryell, William; Craig, David W.; Cruceanu, Cristiana; Czerski, Piotr M.; Davis, Tony; Dayer, Alexandre; Degenhardt, Franziska; Del Zompo, Maria; DePaulo, J. Raymond; Edenberg, Howard J.; Étain, Bruno; Falkai, Peter; Foroud, Tatiana; Forstner, Andreas J.; Frisén, Louise; Frye, Mark A.; Fullerton, Janice M.; Gard, Sébastien; Garnham, Julie S.; Gershon, Elliot S.; Goes, Fernando S.; Greenwood, Tiffany A.; Grigoroiu-Serbanescu, Maria; Hauser, Joanna; Heilbronner, Urs; Heilmann-Heimbach, Stefanie; Herms, Stefan; Hipolito, Maria; Hitturlingappa, Shashi; Hoffmann, Per; Hofmann, Andrea; Jamain, Stephane; Jiménez, Esther; Kahn, Jean-Pierre; Kassem, Layla; Kelsoe, John R.; Kittel-Schneider, Sarah; Kliwicki, Sebastian; Koller, Daniel L.; König, Barbara; Lackner, Nina; Laje, Gonzalo; Lang, Maren; Lavebratt, Catharina; Lawson, William B.; Leboyer, Marion; Leckband, Susan G.; Liu, Chunyu; Maaser, Anna; Mahon, Pamela B.; Maier, Wolfgang; Maj, Mario; Manchia, Mirko; Martinsson, Lina; McCarthy, Michael J.; McElroy, Susan L.; McInnis, Melvin G.; McKinney, Rebecca; Mitchell, Philip B.; Mitjans, Marina; Mondimore, Francis M.; Monteleone, Palmiero; Mühleisen, Thomas W.; Nievergelt, Caroline M.; Nöthen, Markus M.; Novák, Tomas; Nurnberger, John I.; Nwulia, Evaristus A.; Ösby, Urban; Pfennig, Andrea; Potash, James B.; Propping, Peter; Reif, Andreas; Reininghaus, Eva; Rice, John; Rietschel, Marcella; Rouleau, Guy A.; Rybakowski, Janusz K.; Schalling, Martin; Scheftner, William A.; Schofield, Peter R.; Schork, Nicholas J.; Schulze, Thomas G.; Schumacher, Johannes; Schweizer, Barbara W.; Severino, Giovanni; Shekhtman, Tatyana; Shilling, Paul D.; Simhandl, Christian; Slaney, Claire M.; Smith, Erin N.; Squassina, Alessio; Stamm, Thomas; Stopkova, Pavla; Streit, Fabian; Strohmaier, Jana; Szelinger, Szabolcs; Tighe, Sarah K.; Tortorella, Alfonso; Turecki, Gustavo; Vieta, Eduard; Volkert, Julia; Witt, Stephanie H.; Wright, Adam; Zandi, Peter P.; Zhang, Peng; Zollner, Sebastian; McMahon, Francis J.

2016-01-01

Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behaviour. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, P =  5.87 × 10 − 9; odds ratio (OR) = 1.12) and markers within ERBB2 (rs2517959, P =  4.53 × 10 − 9; OR = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS. PMID:27329760

Economic and Clinical Outcomes Resulting From the Stage 4 Chronic Kidney Disease Case Management Quality Improvement Initiative

PubMed Central

Everett, Beverly; McGinnis, Matthew; Beresky, Amy; Cane, Rudolph C.; Cooper, Tasha; Davda, Rajesh K.; Farmer, Donna; John, Stella M.; Sollars, Denise L.; Rausch, John F.

2017-01-01

Purpose of Study: Chronic kidney disease (CKD) is a costly and burdensome public health concern. The goal of this study was to evaluate the impact on outcomes and utilization of a pilot program to identify and engage beneficiaries with CKD at risk for progression from Stage 4 to Stage 5. Primary Practice Settings: A quality improvement initiative was conducted to assess the impact of case management on costs and outcomes among 7,720 Cigna commercial medical beneficiaries with Stage 4 CKD enrolled in the United States between January 2012 and October 2012. Methodology and Sample: Claims data were analyzed to compare 3,861 beneficiaries randomized to receive condition-focused case management with 3,859 controls, with follow-up through July 2013. After using an algorithm to identify beneficiaries at highest risk of progression, a case management team implemented, among those assigned to the intervention, an evidence-based assessment tool, provided education and follow-up, engaged nephrologists and other providers, and conducted weekly rounds. Primary outcome measures were hospital admissions, emergency department visits, nephrologist visits, dialysis, arteriovenous (AV) fistula creation, and total medical costs. Analysis of variance techniques were used to test group differences. Results: As compared with controls, intervention beneficiaries were 12% more likely to have fistula creation (p = .004). Intervention beneficiaries were observed to have savings of $199 per member per month (PMPM), F = 23.05, p = .04. This difference equated to 6% lower total medical costs in the intervention group. Savings observed were derived half from improved in-network utilization and half from reduced hospital costs. Implications for Case Management Practice: The observed 12% increased rate of creation of AV fistulas and $199 (6%) decrease in PMPM cost between the intervention and control groups corresponded to a savings of more than $18 million in 2015 U.S. dollars (USD). On the basis of observation of substantial improvements in outcomes and cost savings, health plan administrators could better serve those at highest risk of progression by implementing focused case management. Our findings support the value of care coordination between nephrologists, providers, and health plan case managers in improving outcomes and reducing total medical costs among beneficiaries at risk for CKD progression from Stage 4 to Stage 5. PMID:28902768

Coupled simulation of CFD-flight-mechanics with a two-species-gas-model for the hot rocket staging

NASA Astrophysics Data System (ADS)

Li, Yi; Reimann, Bodo; Eggers, Thino

2016-11-01

The hot rocket staging is to separate the lowest stage by directly ignite the continuing-stage-motor. During the hot staging, the rocket stages move in a harsh dynamic environment. In this work, the hot staging dynamics of a multistage rocket is studied using the coupled simulation of Computational Fluid Dynamics and Flight Mechanics. Plume modeling is crucial for a coupled simulation with high fidelity. A 2-species-gas model is proposed to simulate the flow system of the rocket during the staging: the free-stream is modeled as "cold air" and the exhausted plume from the continuing-stage-motor is modeled with an equivalent calorically-perfect-gas that approximates the properties of the plume at the nozzle exit. This gas model can well comprise between the computation accuracy and efficiency. In the coupled simulations, the Navier-Stokes equations are time-accurately solved in moving system, with which the Flight Mechanics equations can be fully coupled. The Chimera mesh technique is utilized to deal with the relative motions of the separated stages. A few representative staging cases with different initial flight conditions of the rocket are studied with the coupled simulation. The torque led by the plume-induced-flow-separation at the aft-wall of the continuing-stage is captured during the staging, which can assist the design of the controller of the rocket. With the increasing of the initial angle-of-attack of the rocket, the staging quality becomes evidently poorer, but the separated stages are generally stable when the initial angle-of-attack of the rocket is small.

[Study on the distribution of Chinese medical constitutions of hypertension complicated diabetes patients].

PubMed

Han, Shu-Hui; Li, Kang-Zeng; Zheng, Jian-Ming; Zheng, Zhi-Xiong; Lin, Miao-Chun; Xu, Ming-Yuan; Yue, Zeng-Chang

2013-02-01

To investigate the distribution features of Chinese medical constitutions in hypertension complicated diabetes patients. Recruited were 251 primary hypertension inpatients at the Department of Neurology and the Department of Cardiology, Mindong Hospital of Ningde City from October 2010 to March 2011. They were assigned to two groups according to whether they were complicated with diabetes, i.e., the primary hypertension complicated diabetes (as the case group, 78 cases) and the primary hypertension without complicated diabetes (as the control group, 173 cases). The constitution types were investigated by questionnaire. The constitution type distribution was compared between the two groups. The data including gender, age, and the distribution of the constitution type were compared between the two groups. The levels of TG, TC, LDL-C, Hb, FPG, and ALB were detected on the 2nd day after admission. The levels of TG, TC, LDL-C, Hb, and ALB were compared be- tween the two groups in patients of yin deficiency constitution, phlegm dampness constitution, and qi deficiency constitution. There was no statistical difference in the hypertension grading, the disease course, and chronic disease complications between the two groups (P > 0.05). The main constitution types were yin deficiency (accounting for 26.0%), phlegm dampness (accounting for 19.1%), and qi deficiency (accounting for 19.1%) in the control group. The main constitution types were yin deficiency (accounting for 32.1%), phlegm dampness (accounting for 30.8%), and qi deficiency (accounting for 17.9%) in the case group. The ratio of phlegm dampness type in the case group was higher than that in the control group with statistical difference (P = 0.041). There was no statistical difference in the constitution distribution in the same gender between the two groups (P > 0.05). There was no statistical difference in the constitution distribution in those younger than 80 years between the two groups (P > 0.05). Compared with those older than 80 years in the control group, the ratio of phlegm dampness was higher, and the ratios of yang deficiency, yin deficiency, qi deficiency, and dampness heat were lower in the case group with statistical difference (P = 0.020). There was no statistical difference in the constitution distribution among different age stages in the case group (P > 0. 05). But there was statistical difference in the constitution distribution among different age stages in the control group (P < 0.05). The yin deficiency and qi deficiency constitutions were dominated in thinner patients of the control group, while yin deficiency constitution was dominated in thinner patients of the case group, showing no statistical difference between the two groups (P > 0.05). There was no statistical difference in the distribution of constitution type in overweight patients between the two groups (P = 0.458). Compared with those of gentle type constitution in the same group, the levels of TC and LDL-C increased in those of phlegm dampness constitution in the two groups (P < 0.05). The level of TC increased in those of qi deficiency constitution in the case group. The level of Hb decreased in those of qi deficiency constitution in the control group (P < 0.05). Compared with those of qi deficiency constitution in the same group, the levels of TC and Hb obviously increased in those of phlegm dampness constitution in the control group (P < 0.05). The level of ALB increased in those of yin deficiency constitution in the case group (P < 0. 05). Compared with the control group, the level of FPG of those of each constitution increased in the case group (P < 0.05) ,.and the level of TC increased in those of qi deficiency constitution (P = 0.007). The main constitution types of hypertension complicated diabetes patients were yin deficiency, phlegm dampness, and qi deficiency. The ratio of phlegm dampness was higher in hypertension complicated diabetes patients than hypertension without complicated diabetes patients. The levels of TC and LDL-C were higher in those of phlegm dampness constitution type. The level of TC was higher in hypertension complicated diabetes patients of qi deficiency constitution.

Counter-intuitive plasma vitamin D and zinc status in HIV-1-infected adults with persistent low-level viraemia after treatment initiation: a pilot case-control study.

PubMed

Melliez, H; Duhamel, A; Robineau, O; Bocket, L; Kim, I; Sauser, E; Loiseleur, F; Viget, N; Pasquet, A; Senneville, E; Seguy, D

2017-11-01

Determinants of persistent low-level viraemia [PLLV, a viral load (VL) of between 50 and 500 copies/mL] have not been elucidated. In a case-control study, we evaluated the influence of micronutrients on PLLV in a population of 454 HIV-1 adults having initiated antiretroviral therapy (ART) between January 2007 and December 2011. Plasma levels of retinol (vitamin A), 25-OH vitamin D 2  + D 3 , vitamin E and zinc were measured at ART initiation in cases (PLLV after 6 months of ART) and in controls (VL <50 copies/mL after 6 months). Cases and controls were matched for the CD4 cell count (±50/mm 3 ) and ethnic origin. Intergroup differences in demographic, biological and treatment parameters and sunshine intensity at ART initiation were adjusted using a propensity score. A receiver operating characteristic (ROC) curve was used to assess intergroup differences in plasma micronutrient levels. Thirty-three of the 454 patients (7.3%) displayed PLLV (median VL: 92 copies/mL). Patients were predominantly male (89%), Caucasian (64%) and CDC stage C (25%). The median age was 38 years, the median initial VL was 5.2 log 10 copies/mL and the median CD4 count was 74/mm 3 . The 22 cases and matched controls were balanced in these respects, and had similar vitamin A/E levels. Two cases (9%) and 9 controls (41%) had a vitamin D level <10.3 ng/mL (p = 0.0015), and 2 cases (9%) and 10 controls (48%) had a zinc level <74.6 μg/dL (p = 0.04). Our results support in vitro studies suggesting that vitamin D favours HIV-1 replication and that HIV-1 is zinc-dependent. Wide-scale, prospective studies are required.

Organizational influence on the occurrence of work accidents involving exposure to biological material.

PubMed

Marziale, Maria Helena Palucci; Rocha, Fernanda Ludmilla Rossi; Robazzi, Maria Lúcia do Carmo Cruz; Cenzi, Camila Maria; dos Santos, Heloisa Ehmke Cardoso; Trovó, Marli Elisa Mendes

2013-01-01

to analyze work accidents involving exposure to biological materials which took place among personnel working in nursing and to evaluate the influence of the organizational culture on the occurrence of these accidents. a retrospective, analytical study, carried out in two stages in a hospital that was part of the Network for the Prevention of Work Accidents. The first stage involved the analysis of the characteristics of the work accidents involving exposure to biological materials as recorded over a seven-year period by the nursing staff in the hospital studied, and registered in the Network databank. The second stage involved the analysis of 122 nursing staff members' perception of the institutional culture, who were allocated to the control group (workers who had not had an accident) and the case group (workers who had had an accident). 386 accidents had been recorded: percutaneous lesions occurred in 79% of the cases, needles were the materials involved in 69.7% of the accidents, and in 81.9% of the accident there was contact with blood. Regarding the influence of the organizational culture on the occurrence of accidents, the results obtained through the analysis of the two groups did not demonstrate significant differences between the average scores attributed by the workers in each organizational value or practice category. It is concluded that accidents involving exposure to biological material need to be avoided, however, it was not possible to confirm the influence of organizational values or practices on workers' behavior concerning the occurrence of these accidents.

A simple two-stage design for quantitative responses with application to a study in diabetic neuropathic pain.

PubMed

Whitehead, John; Valdés-Márquez, Elsa; Lissmats, Agneta

2009-01-01

Two-stage designs offer substantial advantages for early phase II studies. The interim analysis following the first stage allows the study to be stopped for futility, or more positively, it might lead to early progression to the trials needed for late phase II and phase III. If the study is to continue to its second stage, then there is an opportunity for a revision of the total sample size. Two-stage designs have been implemented widely in oncology studies in which there is a single treatment arm and patient responses are binary. In this paper the case of two-arm comparative studies in which responses are quantitative is considered. This setting is common in therapeutic areas other than oncology. It will be assumed that observations are normally distributed, but that there is some doubt concerning their standard deviation, motivating the need for sample size review. The work reported has been motivated by a study in diabetic neuropathic pain, and the development of the design for that trial is described in detail. Copyright 2008 John Wiley & Sons, Ltd.

Relative Quantification and Higher-Order Modeling of the Plasma Glycan Cancer Burden Ratio in Ovarian Cancer Case-Control Samples

PubMed Central

Hecht, Elizabeth S.; Scholl, Elizabeth H.; Walker, S. Hunter; Taylor, Amber D.; Cliby, William A.; Motsinger-Reif, Alison A.; Muddiman, David C.

2016-01-01

An early-stage, population-wide biomarker for ovarian cancer (OVC) is essential to reverse its high mortality rate. Aberrant glycosylation by OVC has been reported, but studies have yet to identify an N-glycan with sufficiently high specificity. We curated a human biorepository of 82 case-control plasma samples, with 27%, 12%, 46%, and 15% falling across stages I–IV, respectively. For relatve quantitation, glycans were analyzed by the individuality normalization when labeling with glycan hydrazide tags (INLIGHT) strategy for enhanced electrospray ionization, MS/MS analysis. Sixty-three glycan cancer burden ratios (GBRs), defined as the log10 ratio of the case-control extracted ion chromatogram abundances, were calculated above the limit of detection. The final GBR models, built using stepwise forward regression, included three significant terms: OVC stage, normalized mean GBR, and tag chemical purity; glycan class, fucosylation, or sialylation were not significant variables. After Bonferroni correction, seven N-glycans were identified as significant (p < 0.05), and after false discovery rate correction, an additional four glycans were determined to be significant (p < 0.05), with one borderline (p = 0.05). For all N-glycans, the vectors of the effects from stages II–IV were sequentially reversed, suggesting potential biological changes in OVC morphology or in host response. PMID:26347193

A methodology for identification and control of electro-mechanical actuators

PubMed Central

Tutunji, Tarek A.; Saleem, Ashraf

2015-01-01

Mechatronic systems are fully-integrated engineering systems that are composed of mechanical, electronic, and computer control sub-systems. These integrated systems use electro-mechanical actuators to cause the required motion. Therefore, the design of appropriate controllers for these actuators are an essential step in mechatronic system design. In this paper, a three-stage methodology for real-time identification and control of electro-mechanical actuator plants is presented, tested, and validated. First, identification models are constructed from experimental data to approximate the plants’ response. Second, the identified model is used in a simulation environment for the purpose of designing a suitable controller. Finally, the designed controller is applied and tested on the real plant through Hardware-in-the-Loop (HIL) environment. The described three-stage methodology provides the following practical contributions: • Establishes an easy-to-follow methodology for controller design of electro-mechanical actuators. • Combines off-line and on-line controller design for practical performance. • Modifies the HIL concept by using physical plants with computer control (rather than virtual plants with physical controllers). Simulated and experimental results for two case studies, induction motor and vehicle drive system, are presented in order to validate the proposed methodology. These results showed that electromechanical actuators can be identified and controlled using an easy-to-duplicate and flexible procedure. PMID:26150992

A methodology for identification and control of electro-mechanical actuators.

PubMed

Tutunji, Tarek A; Saleem, Ashraf

2015-01-01

Mechatronic systems are fully-integrated engineering systems that are composed of mechanical, electronic, and computer control sub-systems. These integrated systems use electro-mechanical actuators to cause the required motion. Therefore, the design of appropriate controllers for these actuators are an essential step in mechatronic system design. In this paper, a three-stage methodology for real-time identification and control of electro-mechanical actuator plants is presented, tested, and validated. First, identification models are constructed from experimental data to approximate the plants' response. Second, the identified model is used in a simulation environment for the purpose of designing a suitable controller. Finally, the designed controller is applied and tested on the real plant through Hardware-in-the-Loop (HIL) environment. The described three-stage methodology provides the following practical contributions: •Establishes an easy-to-follow methodology for controller design of electro-mechanical actuators.•Combines off-line and on-line controller design for practical performance.•Modifies the HIL concept by using physical plants with computer control (rather than virtual plants with physical controllers). Simulated and experimental results for two case studies, induction motor and vehicle drive system, are presented in order to validate the proposed methodology. These results showed that electromechanical actuators can be identified and controlled using an easy-to-duplicate and flexible procedure.

Edmonton obesity staging system among pediatric patients: a validation and obesogenic risk factor analysis.

PubMed

Grammatikopoulou, M G; Chourdakis, M; Gkiouras, K; Roumeli, P; Poulimeneas, D; Apostolidou, E; Chountalas, I; Tirodimos, I; Filippou, O; Papadakou-Lagogianni, S; Dardavessis, T

2018-01-08

The Edmonton Obesity Staging System for Pediatrics (EOSS-P) is a useful tool, delineating different obesity severity tiers associated with distinct treatment barriers. The aim of the study was to apply the EOSS-P on a Greek pediatric cohort and assess risk factors associated with each stage, compared to normal weight controls. A total of 361 children (2-14 years old), outpatients of an Athenian hospital, participated in this case-control study by forming two groups: the obese (n = 203) and the normoweight controls (n = 158). Anthropometry, blood pressure, blood and biochemical markers, comorbidities and obesogenic lifestyle parameters were recorded and the EOSS-P was applied. Validation of EOSS-P stages was conducted by juxtaposing them with IOTF-defined weight status. Obesogenic risk factors' analysis was conducted by constructing gender-and-age-adjusted (GA) and multivariate logistic models. The majority of obese children were stratified at stage 1 (46.0%), 17.0% were on stage 0, and 37.0% on stage 2. The validation analysis revealed that EOSS-P stages greater than 0 were associated with diastolic blood pressure and levels of glucose, cholesterol, LDL and ALT. Reduced obesity odds were observed among children playing outdoors and increased odds for every screen time hour, both in the GA and in the multivariate analyses (all P < 0.05). Although participation in sports > 2 times/week was associated with reduced obesity odds in the GA analysis (OR = 0.57, 95% CI = 0.33-0.98, P linear = 0.047), it lost its significance in the multivariate analysis (P linear = 0.145). Analogous results were recorded in the analyses of the abovementioned physical activity risk factors for the EOSS-P stages. Linear relationships were observed for fast-food consumption and IOTF-defined obesity and higher than 0 EOSS-P stages. Parental obesity status was associated with all EOSS-P stages and IOTF-defined obesity status. Few outpatients were healthy obese (stage 0), while the majority exhibited several comorbidities. Since each obesity tier entails different impacts to disease management, the study herein highlights modifiable factors facilitating descend to lower stages, and provides insight for designing tailored approaches tackling the high national pediatric obesity rates.

Solar Photovoltaic (PV) Distributed Generation Systems - Control and Protection

NASA Astrophysics Data System (ADS)

Yi, Zhehan

This dissertation proposes a comprehensive control, power management, and fault detection strategy for solar photovoltaic (PV) distribution generations. Battery storages are typically employed in PV systems to mitigate the power fluctuation caused by unstable solar irradiance. With AC and DC loads, a PV-battery system can be treated as a hybrid microgrid which contains both DC and AC power resources and buses. In this thesis, a control power and management system (CAPMS) for PV-battery hybrid microgrid is proposed, which provides 1) the DC and AC bus voltage and AC frequency regulating scheme and controllers designed to track set points; 2) a power flow management strategy in the hybrid microgrid to achieve system generation and demand balance in both grid-connected and islanded modes; 3) smooth transition control during grid reconnection by frequency and phase synchronization control between the main grid and microgrid. Due to the increasing demands for PV power, scales of PV systems are getting larger and fault detection in PV arrays becomes challenging. High-impedance faults, low-mismatch faults, and faults occurred in low irradiance conditions tend to be hidden due to low fault currents, particularly, when a PV maximum power point tracking (MPPT) algorithm is in-service. If remain undetected, these faults can considerably lower the output energy of solar systems, damage the panels, and potentially cause fire hazards. In this dissertation, fault detection challenges in PV arrays are analyzed in depth, considering the crossing relations among the characteristics of PV, interactions with MPPT algorithms, and the nature of solar irradiance. Two fault detection schemes are then designed as attempts to address these technical issues, which detect faults inside PV arrays accurately even under challenging circumstances, e.g., faults in low irradiance conditions or high-impedance faults. Taking advantage of multi-resolution signal decomposition (MSD), a powerful signal processing technique based on discrete wavelet transformation (DWT), the first attempt is devised, which extracts the features of both line-to-line (L-L) and line-to-ground (L-G) faults and employs a fuzzy inference system (FIS) for the decision-making stage of fault detection. This scheme is then improved as the second attempt by further studying the system's behaviors during L-L faults, extracting more efficient fault features, and devising a more advanced decision-making stage: the two-stage support vector machine (SVM). For the first time, the two-stage SVM method is proposed in this dissertation to detect L-L faults in PV system with satisfactory accuracies. Numerous simulation and experimental case studies are carried out to verify the proposed control and protection strategies. Simulation environment is set up using the PSCAD/EMTDC and Matlab/Simulink software packages. Experimental case studies are conducted in a PV-battery hybrid microgrid using the dSPACE real-time controller to demonstrate the ease of hardware implementation and the controller performance. Another small-scale grid-connected PV system is set up to verify both fault detection algorithms which demonstrate promising performances and fault detecting accuracies.

Informed genome-wide association analysis with family history as a secondary phenotype identifies novel loci of lung cancer.

PubMed

Poirier, Julia G; Brennan, Paul; McKay, James D; Spitz, Margaret R; Bickeböller, Heike; Risch, Angela; Liu, Geoffrey; Le Marchand, Loic; Tworoger, Shelley; McLaughlin, John; Rosenberger, Albert; Heinrich, Joachim; Brüske, Irene; Muley, Thomas; Henderson, Brian E; Wilkens, Lynne R; Zong, Xuchen; Li, Yafang; Hao, Ke; Timens, Wim; Bossé, Yohan; Sin, Don D; Obeidat, Ma'en; Amos, Christopher I; Hung, Rayjean J

2015-03-01

Lung cancer is the leading cause of cancer death worldwide. Although several genetic variants associated with lung cancer have been identified in the past, stringent selection criteria of genome-wide association studies (GWAS) can lead to missed variants. The objective of this study was to uncover missed variants by using the known association between lung cancer and first-degree family history of lung cancer to enrich the variant prioritization for lung cancer susceptibility regions. In this two-stage GWAS study, we first selected a list of variants associated with both lung cancer and family history of lung cancer in four GWAS (3,953 cases, 4,730 controls), then replicated our findings for 30 variants in a meta-analysis of four additional studies (7,510 cases, 7,476 controls). The top ranked genetic variant rs12415204 in chr10q23.33 encoding FFAR4 in the Discovery set was validated in the Replication set with an overall OR of 1.09 (95% CI=1.04, 1.14, P=1.63×10(-4)). When combining the two stages of the study, the strongest association was found in rs1158970 at Ch4p15.2 encoding KCNIP4 with an OR of 0.89 (95% CI=0.85, 0.94, P=9.64×10(-6)). We performed a stratified analysis of rs12415204 and rs1158970 across all eight studies by age, gender, smoking status, and histology, and found consistent results across strata. Four of the 30 replicated variants act as expression quantitative trait loci (eQTL) sites in 1,111 nontumor lung tissues and meet the genome-wide 10% FDR threshold. © 2015 Wiley Periodicals, Inc.

Prognosis of women with stage I endometrioid endometrial cancer and synchronous stage I endometrioid ovarian cancer.

PubMed

Matsuo, Koji; Machida, Hiroko; Frimer, Marina; Marcus, Jenna Z; Pejovic, Tanja; Roman, Lynda D; Wright, Jason D

2017-12-01

Synchronous endometrial and ovarian cancer with endometrioid histology at two cancer sites typically presents with early-stage disease and is thought to have a good prognosis. We examined the survival of women with early-stage endometrioid endometrial cancer who had synchronous early-stage endometrioid ovarian cancer. This is a retrospective case-control study examining the Surveillance, Epidemiology, and End Result Program between 1973 and 2013. Survival of women with stage I endometrioid endometrial cancer with stage I endometrioid ovarian cancer (n=839) were compared to women with stage I endometrioid endometrial cancer without synchronous ovarian cancer (n=123,692) after propensity score matching. Women with synchronous stage I endometrioid ovarian cancer were more likely to be diagnosed recently, be younger, have stage IA disease, grade 1 tumors, to have undergone lymphadenectomy, and were less likely to receive radiotherapy compared to those without synchronous ovarian cancer (all, P<0.001). In a propensity score matched model, the presence of synchronous ovarian cancer was not associated with endometrial cancer-specific survival (10-year rates 96.0% versus 95.3%, P=0.97) or overall survival (85.6% versus 87.2%, P=0.10). Among tumors with concordant grades at the two cancer sites, survival was similar regardless of presence of synchronous ovarian tumors (grade 1 tumors, 10-year rate for overall survival, 88.2% versus 89.1%, P=0.40; and grade 2 tumors, 84.0% versus 85.8%, P=0.78). Women with stage I endometrioid endometrial cancer with synchronous stage I endometrioid ovarian cancer have a survival outcome similar to those with stage I endometrioid endometrial cancer without synchronous ovarian cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Serous Tubal Carcinogenesis: The Recent Concept of Origin of Ovarian, Primary Peritoneal and Fallopian Tube High-Grade Serous Carcinoma.

PubMed

Kar, Tushar; Kar, Asaranti; Dhal, Ipsita; Panda, Sasmita; Biswal, Priyadarshini; Nayak, Bhagyalaxmi; Rout, Niranjan; Samantray, Sagarika

2017-12-01

Pelvic (non-uterine) high-grade serous carcinomas (PHGSC) including ovarian, tubal and primary peritoneal serous carcinomas have increased death: incidence ratio due to presentation at advanced stage, rapid progression, poor prognosis and high morbidity. Ambiguity regarding their pathogenesis and lack of a proper screening method is the cause of their late detection and high fatality rate. This study was undertaken to assess the fallopian tube for the presence of precursor lesions in pelvic serous carcinoma. This was a prospective case-control study carried out in a tertiary care center. Consecutive specimens of 55 cases of pelvic high-grade serous carcinoma and 41 controls inclusive of 21 low-grade serous carcinoma, 10 benign adnexal masses and 10 normal adnexa were included in the study. Both side fallopian tubes in each case were subjected to histopathological examination and p53, Ki67 immunohistochemistry. There were 55 cases of PHGSC comprising of 50 cases of ovarian HGSC, two cases of primary peritoneal carcinoma (PPC) and three cases of tubal carcinoma. Serous tubal intraepithelial carcinoma (STIC) was detected in 14 cases (28%), p53 signature in 13 cases (26%) and tubal intraepithelial lesion in transition in 10 cases (20%) of ovarian HGSC. One case (50%) of PPC and one (33%) case of tubal carcinoma revealed the presence of STIC. None of the controls exhibited any precursor lesion except ovarian low-grade serous carcinoma where p53 was detected in 20% of cases. This revelation concludes that fallopian tubes are the sites of precursors of PHGSC to a large extent. In the absence of a proper screening method of HGSC, prophylactic bilateral salpingectomy at hysterectomy for benign diseases can achieve ultimate goal of reduction in incidence of PHGSC.

Five-minute Apgar score ≤ 5 and Molar Incisor Hypomineralisation (MIH) - a case control study.

PubMed

Sidaly, Rivan; Schmalfuss, Andreas; Skaare, Anne B; Sehic, Amer; Stiris, Tom; Espelid, Ivar

2016-07-22

The aetiology of molar incisor hypomineralisation (MIH) is unclear. The asymmetric distribution of MIH in the dentition may indicate that an insult of short duration that affects ameloblasts at a vulnerable stage could be a causative factor. Apgar ≤ 5 at 5 min may indicate asphyxia (hypoxic-ischemic insult) during birth. It was hypnotised that low Apgar score during birth may cause MIH. The present study aimed to examine a possible association between Apgar ≤ 5 at 5 min and the occurrence of MIH. Two study groups were selected for examination. The cases comprised 67 children aged 8-10 years born with Apgar score equal to or below 5 after 5 min. The control group comprised 157 age-matched healthy children. First permanent molars, second primary molars and all permanent incisors were examined in all children. Clinical examination was undertaken by two calibrated examiners and intraoral close-up photographs of the teeth were later evaluated by three calibrated and blinded clinicians. Demarcated opacities, post-eruptive breakdown, atypical restorations and extractions due to MIH, according to the criteria of the European Association of Paediatric Dentistry, were assessed. The prevalence of MIH did not differ between the two groups. A chi-square test failed to confirm any statistically significant relationship between 5-min Apgar scores and MIH occurrence. In addition, there was no statistically significant relationship between the number of affected first permanent molars in cases and controls. There was no association between Apgar ≤ 5 at 5 min and the occurrence of MIH.

Nasal symptoms and clinical findings in adult patients treated for unilateral cleft lip and palate.

PubMed

Morén, Staffan; Mani, Maria; Lundberg, Kristina; Holmström, Mats

2013-10-01

The aim of the study was to investigate self-experienced nasal symptoms among adults treated for UCLP and the association to clinical findings, and to evaluate whether palate closure in one-stage or two-stages affected the symptoms or clinical findings. All people with UCLP born between 1960-1987, treated at Uppsala University Hospital, were considered for participation in this cross-sectional population study with long-term follow-up. Eighty-three patients (76% participation rate) participated, a mean of 37 years after the first operation. Fifty-two patients were treated with one-stage palate closure and 31 with two-stage palate closure. An age-matched group of 67 non-cleft controls completed the same study protocol, which included a questionnaire regarding nasal symptoms, nasal inspection, anterior rhinoscopy, and nasal endoscopy. Patients reported a higher frequency of nasal symptoms compared with the control group, e.g., nasal obstruction (81% compared with 60%) and mouth breathing (20% compared with 5%). Patients also rated their nasal symptoms as having a more negative impact on their daily life and physical activities than controls. Nasal examination revealed higher frequencies of nasal deformities among patients. No positive correlation was found between nasal symptoms and severity of findings at nasal examination. No differences were identified between patients treated with one-stage and two-stage palate closure regarding symptoms or nasal findings. Adult patients treated for UCLP suffer from more nasal symptoms than controls. However, symptoms are not associated with findings at clinical nasal examination or method of palate closure.

Association between floods and infectious diarrhea and their effect modifiers in Hunan province, China: A two-stage model.

PubMed

Liu, Zhidong; Zhang, Feifei; Zhang, Ying; Li, Jing; Liu, Xuena; Ding, Guoyong; Zhang, Caixia; Liu, Qiyong; Jiang, Baofa

2018-06-01

Understanding the potential links between floods and infectious diarrhea is important under the context of climate change. However, little is known about the risk of infectious diarrhea after floods and what factors could modify these effects in China. This study aims to quantitatively examine the relationship between floods and infectious diarrhea and their effect modifiers. Weekly number of infectious diarrhea cases from 2004 to 2011 during flood season in Hunan province were supplied by the National Notifiable Disease Surveillance System. Flood and meteorological data over the same period were obtained. A two-stage model was used to estimate a provincial average association and their effect modifiers between floods and infectious diarrhea, accounting for other confounders. A total of 134,571 cases of infectious diarrhea were notified from 2004 to 2011. After controlling for seasonality, long-term trends, and meteorological factors, floods were significantly associated with infectious diarrhea in the provincial level with a cumulative RR of 1.22 (95% CI: 1.05, 1.43) with a lagged effect of 0-1 week. Geographic locations and economic levels were identified as effect modifiers, with a higher impact of floods on infectious diarrhea in the western and regions with a low economic level of Hunan. Our study provides strong evidence of a positive association between floods and infectious diarrhea in the study area. Local control strategies for public health should be taken in time to prevent and reduce the risk of infectious diarrhea after floods, especially for the vulnerable regions identified. Copyright © 2018 Elsevier B.V. All rights reserved.

Spiritual Diversity and Living with Early-Stage Dementia.

PubMed

McGee, Jocelyn Shealy; Zhao, Holly Carlson; Myers, Dennis R; Seela Eaton, Hannah

2018-01-01

Attention to spiritual diversity is necessary for the provision of culturally informed clinical care for people with early-stage dementia and their family members. In this article, an evidence-based theoretical framework for conceptualizing spiritual diversity is described in detail (Pargament, 2011). The framework is then applied to two clinical case studies of people living with early-stage dementia to elucidate the multilayered components of spiritual diversity in this population. The case studies were selected from a larger mixed-methods study on spirituality, positive psychological factors, health, and well-being in people living with early-stage dementia and their family members. To our knowledge this is the first systematic attempt to apply a theoretical framework for understanding spiritual diversity in this population. Implications for clinical practice are provided.

Labor Dystocia and the Risk of Uterine Rupture in Women with Prior Cesarean.

PubMed

Vachon-Marceau, Chantale; Demers, Suzanne; Goyet, Martine; Gauthier, Robert; Roberge, Stéphanie; Chaillet, Nils; Laroche, Jasmin; Bujold, Emmanuel

2016-05-01

Objective The objective of this study was to evaluate the association between labor dystocia and uterine rupture. Methods We performed a secondary analysis of a multicenter case-control study that included women with single, prior, low-transverse cesarean section who experienced complete uterine rupture during a trial of labor (TOL). For each case, three women who underwent a TOL without uterine rupture were selected as controls. Data were collected on cervical dilatations from admission to delivery. We evaluated the relationship between uterine rupture and labor dystocia according to several criteria, including the World Health Organization's (WHO's) partogram. Results Data were available for 90 cases and 260 controls. Compared with the controls, uterine rupture was associated with less cervical dilatation on admission, slower cervical dilatation in the first stage of labor and longer second stage of labor (all with p < 0.05). Performing cesarean when the labor curve crossed the ACTION line of WHO's partogram or when the second stage was greater than 2 hours could have (1) prevented up to 56% of uterine rupture and (2) reduced the duration of labor in 57% of women with failed TOL. Conclusion Labor dystocia is a significant risk factor for uterine rupture. Labor progression should be assessed regularly in women with prior cesarean. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Interleukin 12B (IL12B) Genetic Variation and Pulmonary Tuberculosis: A Study of Cohorts from The Gambia, Guinea-Bissau, United States and Argentina

PubMed Central

Hill, Philip C.; Wejse, Christian; Bisseye, Cyrille; Olesen, Rikke; Edwards, Todd L.; Gilbert, John R.; Myers, Jamie L.; Stryjewski, Martin E.; Abbate, Eduardo; Estevan, Rosa; Hamilton, Carol D.; Tacconelli, Alessandra; Novelli, Giuseppe; Brunetti, Ercole; Aaby, Peter; Sodemann, Morten; Østergaard, Lars; Adegbola, Richard; Williams, Scott M.; Scott, William K.; Sirugo, Giorgio

2011-01-01

We examined whether polymorphisms in interleukin-12B (IL12B) associate with susceptibility to pulmonary tuberculosis (PTB) in two West African populations (from The Gambia and Guinea-Bissau) and in two independent populations from North and South America. Nine polymorphisms (seven SNPs, one insertion/deletion, one microsatellite) were analyzed in 321 PTB cases and 346 controls from Guinea-Bissau and 280 PTB cases and 286 controls from The Gambia. For replication we studied 281 case and 179 control African-American samples and 221 cases and 144 controls of European ancestry from the US and Argentina. First-stage single locus analyses revealed signals of association at IL12B 3′ UTR SNP rs3212227 (unadjusted allelic p = 0.04; additive genotypic p = 0.05, OR = 0.78, 95% CI [0.61–0.99]) in Guinea-Bissau and rs11574790 (unadjusted allelic p = 0.05; additive genotypic p = 0.05, OR = 0.76, 95% CI [0.58–1.00]) in The Gambia. Association of rs3212227 was then replicated in African-Americans (rs3212227 allelic p = 0.002; additive genotypic p = 0.05, OR = 0.78, 95% CI [0.61–1.00]); most importantly, in the African-American cohort, multiple significant signals of association (seven of the nine polymorphisms tested) were detected throughout the gene. These data suggest that genetic variation in IL12B, a highly relevant candidate gene, is a risk factor for PTB in populations of African ancestry, although further studies will be required to confirm this association and identify the precise mechanism underlying it. PMID:21339808

Two-stage fan. 3: Data and performance with rotor tip casing treatment, uniform and distorted inlet flows

NASA Technical Reports Server (NTRS)

Burger, G. D.; Hodges, T. R.; Keenan, M. J.

1975-01-01

A two stage fan with a 1st-stage rotor design tip speed of 1450 ft/sec, a design pressure ratio of 2.8, and corrected flow of 184.2 lbm/sec was tested with axial skewed slots in the casings over the tips of both rotors. The variable stagger stators were set in the nominal positions. Casing treatment improved stall margin by nine percentage points at 70 percent speed but decreased stall margin, efficiency, and flow by small amounts at design speed. Treatment improved first stage performance at low speed only and decreased second stage performance at all operating conditions. Casing treatment did not affect the stall line with tip radially distorted flow but improved stall margin with circumferentially distorted flow. Casing treatment increased the attenuation for both types of inlet flow distortion.

Identification of a three-miRNA signature as a blood-borne diagnostic marker for early diagnosis of lung adenocarcinoma

PubMed Central

Gao, Xujie; Wei, Feng; Zhang, Xinwei; Su, Yanjun; Wang, Changli; Li, Hui; Ren, Xiubao

2016-01-01

Background The subtypes of NSCLC have unique characteristics of pathogenic mechanism and responses to targeted therapies. Thus, non-invasive markers for diagnosis of different subtypes of NSCLC at early stage are needed. Results Based on the results from the screening and validation process, 3 miRNAs (miR-532, miR-628-3p and miR-425-3p) were found to display significantly different expression levels in early-stage lung adenocarcinoma, as compared to those in healthy controls. ROC analysis showed that the miRNA–based biomarker could distinguish lung adenocarcinoma from healthy controls with high AUC (0.974), sensitivity (91.5%), and specificity (97.8%). Importantly, these three miRNAs could also distinguish lung adenocarcinoma from lung benigh diseases and other subtypes of lung cancer. Methods Two hundreds and one early-stage lung adenocarcinoma cases and one hundreds seventy eight age- and sex-matched healthy controls were recruited to this study. We screened the differentially expressed plasma miRNAs using TaqMan Low Density Arrays (TLDA) followed by three-phase qRT-PCR validation. A risk score model was established to evaluate the diagnostic value of the plasma miRNA profiling system. Conclusions Taken together, these findings suggest that the 3 miRNA–based biomarker might serve as a novel non-invasive approach for diagnosis of early-stage lung adenocarcinoma. PMID:27036025

Evaluation of a proposed expert system development methodology: Two case studies

NASA Technical Reports Server (NTRS)

Gilstrap, Lewey

1990-01-01

Two expert system development projects were studied to evaluate a proposed Expert Systems Development Methodology (ESDM). The ESDM was developed to provide guidance to managers and technical personnel and serve as a standard in the development of expert systems. It was agreed that the proposed ESDM must be evaluated before it could be adopted; therefore a study was planned for its evaluation. This detailed study is now underway. Before the study began, however, two ongoing projects were selected for a retrospective evaluation. They were the Ranging Equipment Diagnostic Expert System (REDEX) and the Backup Control Mode Analysis and Utility System (BCAUS). Both projects were approximately 1 year into development. Interviews of project personnel were conducted, and the resulting data was used to prepare the retrospective evaluation. Decision models of the two projects were constructed and used to evaluate the completeness and accuracy of key provisions of ESDM. A major conclusion reached from these case studies is that suitability and risk analysis should be required for all AI projects, large and small. Further, the objectives of each stage of development during a project should be selected to reduce the next largest area of risk or uncertainty on the project.

Prevalence of pulmonary artery hypertension in patients of chronic obstructive pulmonary disease and its correlation with stages of chronic obstructive pulmonary disease, exercising capacity, and quality of life.

PubMed

Gupta, Kamlesh Kumar; Roy, Bidyut; Chaudhary, Shyam Chand; Mishra, Arvind; Patel, M L; Singh, Jitendra; Kumar, Vivek

2018-01-01

Pulmonary arterial hypertension (PAH) is a complication of chronic obstructive pulmonary disease (COPD) in advance stages, and its presence indicates poor prognosis. The present study was design to know the prevalence of PAH in patients with COPD and its correlation with stages of COPD, exercising capacity, and quality of life. It is a cross-sectional prevalence study over a period of 1 year from August 2015 to July 2016. The study included 109 COPD patients, diagnosed by spirometry, and severity was determined according Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification criteria. Screening two-dimensional echocardiography was done to determine pulmonary arterial hypertension and exercising capacity assessed by 6 min walk test (6MWT) while the quality of life was assessed by St George respiratory Questionnaire for COPD (SGRQ-C) Questionnaires. Out of 109 patients, PAH was present in 68 (62.4%) cases consisting of mild grade 41 (37.6%), moderate grade 11 (10.1%), and severe grade 16 (14.7%). In GOLD A stage, there were 20 cases of mild PAH and Stage B included 18 cases of mild and 3 cases of moderate PAH. Stage C had 3 cases of mild and 8 cases of moderate PAH while Stage D had 16 cases of severe PAH. In 6MWT, patients with severe grade PAH fail to perform the test while patients with mild to moderate PAH walked short distance. In SGRQ-C Questionnaires symptom, activity, impact, and total score were high with the severity of PAH. The prevalence of PAH in COPD was significant. Therefore, every COPD patient should be evaluated for PAH.

Prevalence of pulmonary artery hypertension in patients of chronic obstructive pulmonary disease and its correlation with stages of chronic obstructive pulmonary disease, exercising capacity, and quality of life

PubMed Central

Gupta, Kamlesh Kumar; Roy, Bidyut; Chaudhary, Shyam Chand; Mishra, Arvind; Patel, M. L.; Singh, Jitendra; Kumar, Vivek

2018-01-01

Background: Pulmonary arterial hypertension (PAH) is a complication of chronic obstructive pulmonary disease (COPD) in advance stages, and its presence indicates poor prognosis. Aims and Objective: The present study was design to know the prevalence of PAH in patients with COPD and its correlation with stages of COPD, exercising capacity, and quality of life. Materials and Methods: It is a cross-sectional prevalence study over a period of 1 year from August 2015 to July 2016. The study included 109 COPD patients, diagnosed by spirometry, and severity was determined according Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification criteria. Screening two-dimensional echocardiography was done to determine pulmonary arterial hypertension and exercising capacity assessed by 6 min walk test (6MWT) while the quality of life was assessed by St George respiratory Questionnaire for COPD (SGRQ-C) Questionnaires. Results: Out of 109 patients, PAH was present in 68 (62.4%) cases consisting of mild grade 41 (37.6%), moderate grade 11 (10.1%), and severe grade 16 (14.7%). In GOLD A stage, there were 20 cases of mild PAH and Stage B included 18 cases of mild and 3 cases of moderate PAH. Stage C had 3 cases of mild and 8 cases of moderate PAH while Stage D had 16 cases of severe PAH. In 6MWT, patients with severe grade PAH fail to perform the test while patients with mild to moderate PAH walked short distance. In SGRQ-C Questionnaires symptom, activity, impact, and total score were high with the severity of PAH. Conclusion: The prevalence of PAH in COPD was significant. Therefore, every COPD patient should be evaluated for PAH. PMID:29915733

The Misconception of Case-Control Studies in the Plastic Surgery Literature: A Literature Audit.

PubMed

Hatchell, Alexandra C; Farrokhyar, Forough; Choi, Matthew

2017-06-01

Case-control study designs are commonly used. However, many published case-control studies are not true case-controls and are in fact mislabeled. The purpose of this study was to identify all case-control studies published in the top three plastic surgery journals over the past 10 years, assess which were truly case-control studies, clarify the actual design of the articles, and address common misconceptions. MEDLINE, Embase, and Web of Science databases were searched for case-control studies in the three highest-impact factor plastic surgery journals (2005 to 2015). Two independent reviewers screened the resulting titles, abstracts, and methods, if applicable, to identify articles labeled as case-control studies. These articles were appraised and classified as true case-control studies or non-case-control studies. The authors found 28 articles labeled as case-control studies. However, only six of these articles (21 percent) were truly case-control designs. Of the 22 incorrectly labeled studies, one (5 percent) was a randomized controlled trial, three (14 percent) were nonrandomized trials, two (9 percent) were prospective comparative cohort designs, 14 (64 percent) were retrospective comparative cohort designs, and two (9 percent) were cross-sectional designs. The mislabeling was worse in recent years, despite increases in evidence-based medicine awareness. The majority of published case-control studies are not in fact case-control studies. This misunderstanding is worsening with time. Most of these studies are actually comparative cohort designs. However, some studies are truly clinical trials and thus a higher level of evidence than originally proposed.

Effects of a psychosocial intervention on survival among patients with stage I breast and prostate cancer: a matched case-control study.

PubMed

Shrock, D; Palmer, R F; Taylor, B

1999-05-01

Psychosocial factors have been linked to the development and progression of cancer and shown to be relevant in cancer care. However, the evidence that psychosocial interventions affect cancer survival is less conclusive. Few methodologically sound studies have addressed this issue. To investigate the effects of a 6-week psychosocial intervention on survival among patients with stage I breast and prostate cancer. Matched case-control. 3 rural hospitals or cancer centers in central Pennsylvania. 21 breast and 29 prostate stage I cancer patients (treatment group) matched with 74 breast and 65 prostate stage I cancer patients from the same hospitals who did not receive the intervention (control group). Six 2-hour health psychology classes conducted by a licensed staff psychologist. Survival time was compared between the 2 groups and with national norms. The intervention group lived significantly longer than did matched controls. At 4- to 7-year follow-up (median = 4.2 years), none of the breast cancer patients in the intervention group died, whereas 12% of those in the control group died. Twice as many matched-control prostate cancer patients died compared with those in the intervention group (28% vs 14%). Control group survival was similar to national norms. These results are consistent with prior clinical trials and suggest that short-term psychosocial interventions that encourage the expression of emotions, provide social support, and teach coping skills can influence survival among cancer patients. However, self-selection bias cannot be ruled out as an alternative explanation for the results. These interventions merit further consideration and research.

[Asthenia in advanced cancer and the use of psychostimulants].

PubMed

Portela Tejedor, M A; Sanz Rubiales, A; Martínez, M; Centeno Cortés, C

2011-01-01

Asthenia is the most frequent symptom in patients with advanced cancer and is probably what most affects the quality of life of oncology patients since it interferes in their physical and social activity. Treatment in the majority of cases is symptomatic. There is growing interest in the use of psychostimulants for treating asthenia. Methylphenidate and modafinil are two psychostimulants that have already been tested in controlled studies on asthenia of the patient with advanced cancer; they have proved to be efficient, particularly in patients in very advanced stages who are very tired.

Two case studies in river naturalization: planform migration and bank erosion control

NASA Astrophysics Data System (ADS)

Abad, J. D.; Guneralp, I.; Rhoads, B. L.; Garcia, M. H.

2005-05-01

A sound understanding of river planform evolution and bank erosion control, along with integration of expertise from several disciplines is required for the development of predictive models for river naturalization. Over the last few years, several methodologies have been presented for naturalization projects, from purely heuristic to more advanced methods. Since the time and space scales of concern in naturalization vary widely, there is a need for appropriate tools at a variety of time and space scales. This study presents two case studies at different scales. The first case study describes the prediction of river planform evolution for a remeandering project based on a simplified two-dimensional hydrodynamic model. The second case study describes the applicability of a Computational Fluid Dynamics (CFD) model for evaluating the effectiveness of bank-erosion control structures in individual meander bends. Understanding the hydrodynamic influence of control structures on flow through bends allows accurate prediction of depositional and erosional distribution patterns, resulting in better assessment on river planform stability, especially for the case of natural complex systems. The first case study introduces a mathematical model for evolution of meandering rivers that can be used in remeandering projects. In United States in particular, several rivers have been channelized in the past causing environmental and ecological problems. Following Newton's third law, "for every action, there is a reaction", naturalization techniques evolve as natural reactive solutions to channelization. This model (herein referred as RVR Meander) can be used as a stand-alone Windows application or as module in a Geographic Information System. The model was applied to the Poplar Creek re-meanderization project and used to evaluate re-meandering alternatives for an approximately 800-meter long reach of Poplar Creek that was straightened in 1938. The second case study describes a streambank protection project using bendway weirs. In the State of Illinois, bendway weirs constructed of rock have been installed at hundreds of sites, especially on small streams, to control streambank erosion. Bendway weirs are low hard structures installed in the concave bank of a meander bend. Design criteria for these weirs are approximate and have not been rigorously evaluated for overall effectiveness at low-, medium- and high flows. This initial step of the study attempted to describe the hydrodynamics around the weirs and the influence of the hydrodynamic patterns on sediment transport (near-field and far-field). To do that, a state-of-the-art three-dimensional CFD model was used to simulate flow through meander bends where 3D velocity measurements have been obtained to validate model predictions at low stages. Results indicate that the weirs produce highly complex patterns of flow around the weirs, which in some cases may actually increase erosional potential near the outer bank. These two case studies represent components of an emerging initiative to develop predictive tools for naturalization over a range of spatial and temporal scales

Age- or stage-appropriate? Recreation and the relevance of Piaget's theory in dementia care.

PubMed

Mahoney, Alison E J

2003-01-01

In this study, the immediate effects (within 10 minutes) of age- and stage-appropriate activities and two control activities were observed in 56 dementia sufferers. Compared with the control activities, the two experimental treatment conditions elicited greater reductions in agitation and negative emotion and increases in positive emotion and duration of activity. Stage-appropriate activity was superior to age-appropriate activity in increasing positive emotion and had about the same effect in reducing negative emotion and agitation. The study also addressed the idea that people with Alzheimer's disease may regress through Piaget's stages of cognitive development and thus display the play interests associated with each stage. There was a significant relationship between cognitive level and type of Piagetian play observed; however, Piaget's descriptions of play were not entirely appropriate for persons with with Alzheimer's disease.

May one-stage exchange for Candida albicans peri-prosthetic infection be successful?

PubMed

Jenny, J-Y; Goukodadja, O; Boeri, C; Gaudias, J

2016-02-01

Fungal infection of a total joint arthroplasty has a low incidence but is generally considered as more difficult to cure than bacterial infection. As for bacterial infection, two-stage exchange is considered as the gold standard of treatment. We report two cases of one-stage total joint exchange for fungal peri-prosthetic infection with Candida albicans, where the responsible pathogens was only identified on intraoperative samples. This situation can be considered as a one-stage exchange for fungal peri-prosthetic infection without preoperative identification of the responsible organism, which is considered as having a poor prognosis. Both cases were free of infection after two years. One-stage revision has several potential advantages over two-stage revision, including shorter hospital stay and rehabilitation, no interim period with significant functional impairment, shorter antibiotic treatment, better functional outcome and probably lower costs. We suggest that one-stage revision for C. albicans peri-prosthetic infection may be successful even without preoperative fungal identification. Level IV-Historical cases. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Adverse obstetric outcomes in women with previous cesarean for dystocia in second stage of labor.

PubMed

Jastrow, Nicole; Demers, Suzanne; Gauthier, Robert J; Chaillet, Nils; Brassard, Normand; Bujold, Emmanuel

2013-03-01

To evaluate obstetric outcomes in women undergoing a trial of labor (TOL) after a previous cesarean for dystocia in second stage of labor. A retrospective cohort study of women with one previous low transverse cesarean undergoing a first TOL was performed. Women with previous cesarean for dystocia in first stage and those with previous dystocia in second stage were compared with those with previous cesarean for nonrecurrent reasons (controls). Multivariable regressions analyses were performed. Of 1655 women, those with previous dystocia in second stage of labor (n = 204) had greater risks than controls (n = 880) to have an operative delivery [odds ratio (OR): 1.5; 95% confidence intervals (CI) 1.1 to 2.2], shoulder dystocia (OR: 2.9; 95% CI 1.1 to 8.0), and uterine rupture in the second stage of labor (OR: 4.9; 95% CI 1.1 to 23), and especially in case of fetal macrosomia (OR: 29.6; 95% CI 4.4 to 202). The median second stage of labor duration before uterine rupture was 2.5 hours (interquartile range: 1.5 to 3.2 hours) in these women. Previous cesarean for dystocia in the second stage of labor is associated with second-stage uterine rupture at next delivery, especially in cases of suspected fetal macrosomia and prolonged second stage of labor. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Rectosigmoidian Involvement in Advanced-stage Ovarian Cancer – Intraoperative Decisions

PubMed Central

BACALBASA, NICOLAE; BALESCU, IRINA; DIMA, SIMONA

2017-01-01

Background/Aim: Ovarian cancer remains one of the most commonly encountered malignancies affecting women worldwide, that is unfortunately commonly diagnosed in advanced stages of the disease. In these stages, the tumoral process usually involves the surrounding viscera throughout contiguity or induces the apparition of distant metastases via peritoneal, lymphatic or hematogenous spread, multiple resections being needed in order to achieve a good control of the disease. Patients and Methods: In the present study, we present a case series of 12 patients in whom various surgical procedures on the rectosigmoidian loop were performed in order to achieve debulking surgery to no residual disease. Results: Digestive tract resections consisted of rectosigmoidian resection with left colostomy in three cases, low rectosigmoidian resections with anastomosis in eight cases and a stripping procedure of the peritoneal layer in one case. Conclusion: Due to the close proximity of the digestive and gynecological tract, advanced-stage ovarian tumors frequently involve the rectosigmoidian loop, imposing association of digestive tract surgical procedures. PMID:28882968

Rectosigmoidian Involvement in Advanced-stage Ovarian Cancer - Intraoperative Decisions.

PubMed

Bacalbasa, Nicolae; Balescu, Irina; Dima, Simona

2017-01-01

Ovarian cancer remains one of the most commonly encountered malignancies affecting women worldwide, that is unfortunately commonly diagnosed in advanced stages of the disease. In these stages, the tumoral process usually involves the surrounding viscera throughout contiguity or induces the apparition of distant metastases via peritoneal, lymphatic or hematogenous spread, multiple resections being needed in order to achieve a good control of the disease. In the present study, we present a case series of 12 patients in whom various surgical procedures on the rectosigmoidian loop were performed in order to achieve debulking surgery to no residual disease. Digestive tract resections consisted of rectosigmoidian resection with left colostomy in three cases, low rectosigmoidian resections with anastomosis in eight cases and a stripping procedure of the peritoneal layer in one case. Due to the close proximity of the digestive and gynecological tract, advanced-stage ovarian tumors frequently involve the rectosigmoidian loop, imposing association of digestive tract surgical procedures. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Use of a surgical specimen-collection kit to improve mediastinal lymph-node examination of resectable lung cancer.

PubMed

Osarogiagbon, Raymond U; Miller, Laura E; Ramirez, Robert A; Wang, Christopher G; O'Brien, Thomas F; Yu, Xinhua; Khandekar, Alim; Schoettle, Glenn P; Robbins, Samuel G; Robbins, Edward T; Gibson, Jeffrey B

2012-08-01

Pathologic examination of mediastinal lymph nodes (MLNs) after resection of non-small-cell lung cancer is critical in the determination of prognosis and postoperative management. Although systematic nodal dissection is recommended, the quality of pathologic lymph-node staging often falls short of recommendations in practice. We tested the feasibility of improving pathologic lymph-node staging of resectable non-small-cell lung cancer by using a prelabeled specimen-collection kit. Case-control study with comparison of 51 resections, using a special lymph-node collection kit, with 51 controls matched for surgeon, extent of resection, pathologist, and T category. Appropriate statistical methods were used for all comparisons. The median number of MLNs examined increased from one in the control group, to six in the case group (p < 0.001). The percentage of resections attaining the National Comprehensive Cancer Network-recommended quality of MLN examination, and the proportion that would have been eligible for recent landmark postresection adjuvant therapy trials increased significantly (p < 0.001). The duration of surgery and postoperative complication rates were similar between cases and controls. Eighteen percent of kit cases had positive MLN, compared with 8% of controls. The use of a specialized specimen-collection kit for MLN examination was feasible, markedly improved MLN staging, and showed a trend toward increased detection of patients with MLN metastasis, with only a modest increase in duration of surgery, and no increase in perioperative morbidity, mortality, or hospital length of stay.

Clusterin immunoexpression is associated with early stage endometrial carcinomas.

PubMed

Al-Maghrabi, Jaudah Ahmed; Butt, Nadeem Shafique; Anfinan, Nisrin; Sait, Khalid; Sait, Hesham; Bajouh, Osama; Khabaz, Mohamad Nidal

2016-05-01

Clusterin has anti-apoptotic, regeneration and migration stimulating effects on tumor cells. This study investigates the relation between clusterin expression and the clinicopathological parameters in endometrial carcinomas. Seventy one cases of previously diagnosed endometrial carcinoma (including 59 endometrioid adenocarcinoma, 9 serous adenocarcinoma, 1 clear cell adenocarcinoma, and 2 malignant mixed Mullerian tumor) and 30 tissue samples of non-cancerous endometrium (including 16 proliferative endometrium, 10 secretory endometrium and 4 endometrial polyps) were employed for clusterin detection using tissue microarrays and immunostaining. A total number of 23 (32.4%) cases were positive for clusterin immunostaining. Brown granular cytoplasmic expression of clusterin was detected in 33.9% of endometrioid adenocarcinomas, 22.2% papillary serous endometrial carcinomas. Three (10%) control cases showed granular cytoplasmic expression. Positive clusterin immunostaining was found more frequent in well differentiated and stage I endometrial carcinomas, showing significant statistical association (p-value=0.036 and p-value=0.002 respectively). Significant difference in clusterin expression was observed between tumor cases and control group (P-Value=0.019), i.e., endometrial carcinoma cases are more than four times likely to show positive clusterin immunostaining (odds ratio 4.313 with 95% confidence interval 1.184-15.701). This study did not find relation between clusterin expression and disease recurrence, survival or any of the other clinicopathological parameters in endometrial tumors. The results of our study confirms the diagnostic values of clusterin in supporting the diagnosis of endometrioid carcinoma. When clusterin is expressed in endometrial tumors, it is associated with lower stage. The correlation of clusterin with tumor stage suggests involvement of this molecule in endometrial tumor progression. Copyright © 2016 Elsevier GmbH. All rights reserved.

A Prospective Study of Infectious Mononucleosis in College Students.

PubMed

Jason, Leonard A; Katz, Ben; Gleason, Kristen; McManimen, Stephanie; Sunnquist, Madison; Thorpe, Taylor

2017-01-01

The present study aims to prospectively investigate possible biological and psychological factors present in college students who will go on to develop chronic fatigue syndrome (CFS) following Infectious Mononucleosis (IM). Identification of risk factors predisposing patients towards developing CFS may help to understand the underlying mechanisms and ultimately prevent its occurrence. Our study is enrolling healthy college students over the age of 18. Enrollment began in March of 2013 and is ongoing. Biological and psychological data are collected when students are well (Stage 1), when they develop IM (Stage 2), and approximately 6 months after IM diagnosis (Stage 3). Two case studies demonstrate the progression of student symptomology across all three stages. The Case Studies presented illustrate the usefulness of a prospective research design that tracks healthy students, following their trajectory of IM illness to either a) full recovery or b) diagnosis with CFS.

A Prospective Study of Infectious Mononucleosis in College Students

PubMed Central

Jason, Leonard A.; Katz, Ben; Gleason, Kristen; McManimen, Stephanie; Sunnquist, Madison; Thorpe, Taylor

2017-01-01

Background The present study aims to prospectively investigate possible biological and psychological factors present in college students who will go on to develop chronic fatigue syndrome (CFS) following Infectious Mononucleosis (IM). Identification of risk factors predisposing patients towards developing CFS may help to understand the underlying mechanisms and ultimately prevent its occurrence. Our study is enrolling healthy college students over the age of 18. Enrollment began in March of 2013 and is ongoing. Methods Biological and psychological data are collected when students are well (Stage 1), when they develop IM (Stage 2), and approximately 6 months after IM diagnosis (Stage 3). Results Two case studies demonstrate the progression of student symptomology across all three stages. Conclusion The Case Studies presented illustrate the usefulness of a prospective research design that tracks healthy students, following their trajectory of IM illness to either a) full recovery or b) diagnosis with CFS. PMID:28717787

Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study

PubMed Central

Guerreiro, Rita; Ross, Owen A; Kun-Rodrigues, Celia; Hernandez, Dena G; Orme, Tatiana; Eicher, John D; Shepherd, Claire E; Parkkinen, Laura; Darwent, Lee; Heckman, Michael G; Scholz, Sonja W; Troncoso, Juan C; Pletnikova, Olga; Ansorge, Olaf; Clarimon, Jordi; Lleo, Alberto; Morenas-Rodriguez, Estrella; Clark, Lorraine; Honig, Lawrence S; Marder, Karen; Lemstra, Afina; Rogaeva, Ekaterina; St George-Hyslop, Peter; Londos, Elisabet; Zetterberg, Henrik; Barber, Imelda; Braae, Anne; Brown, Kristelle; Morgan, Kevin; Troakes, Claire; Al-Sarraj, Safa; Lashley, Tammaryn; Holton, Janice; Compta, Yaroslau; Van Deerlin, Vivianna; Serrano, Geidy E; Beach, Thomas G; Lesage, Suzanne; Galasko, Douglas; Masliah, Eliezer; Santana, Isabel; Pastor, Pau; Diez-Fairen, Monica; Aguilar, Miquel; Tienari, Pentti J; Myllykangas, Liisa; Oinas, Minna; Revesz, Tamas; Lees, Andrew; Boeve, Brad F; Petersen, Ronald C; Ferman, Tanis J; Escott-Price, Valentina; Graff-Radford, Neill; Cairns, Nigel J; Morris, John C; Pickering-Brown, Stuart; Mann, David; Halliday, Glenda M; Hardy, John; Trojanowski, John Q; Dickson, Dennis W; Singleton, Andrew; Stone, David J; Bras, Jose

2018-01-01

Summary Background Dementia with Lewy bodies is the second most common form of dementia in elderly people but has been overshadowed in the research field, partly because of similarities between dementia with Lewy bodies, Parkinson’s disease, and Alzheimer’s disease. So far, to our knowledge, no large-scale genetic study of dementia with Lewy bodies has been done. To better understand the genetic basis of dementia with Lewy bodies, we have done a genome-wide association study with the aim of identifying genetic risk factors for this disorder. Methods In this two-stage genome-wide association study, we collected samples from white participants of European ancestry who had been diagnosed with dementia with Lewy bodies according to established clinical or pathological criteria. In the discovery stage (with the case cohort recruited from 22 centres in ten countries and the controls derived from two publicly available database of Genotypes and Phenotypes studies [phs000404.v1.p1 and phs000982.v1.p1] in the USA), we performed genotyping and exploited the recently established Haplotype Reference Consortium panel as the basis for imputation. Pathological samples were ascertained following autopsy in each individual brain bank, whereas clinical samples were collected after participant examination. There was no specific timeframe for collection of samples. We did association analyses in all participants with dementia with Lewy bodies, and also only in participants with pathological diagnosis. In the replication stage, we performed genotyping of significant and suggestive results from the discovery stage. Lastly, we did a meta-analysis of both stages under a fixed-effects model and used logistic regression to test for association in each stage. Findings This study included 1743 patients with dementia with Lewy bodies (1324 with pathological diagnosis) and 4454 controls (1216 patients with dementia with Lewy bodies vs 3791 controls in the discovery stage; 527 vs 663 in the replication stage). Results confirm previously reported associations: APOE (rs429358; odds ratio [OR] 2·40, 95% CI 2·14–2·70; p=1·05 × 10−48), SNCA (rs7681440; OR 0·73, 0·66–0·81; p=6·39 × 10−10), and GBA (rs35749011; OR 2·55, 1·88–3·46; p=1·78 × 10−9). They also provide some evidence for a novel candidate locus, namely CNTN1 (rs7314908; OR 1·51, 1·27–1·79; p=2·32 × 10−6); further replication will be important. Additionally, we estimate the heritable component of dementia with Lewy bodies to be about 36%. Interpretation Despite the small sample size for a genome-wide association study, and acknowledging the potential biases from ascertaining samples from multiple locations, we present the most comprehensive and well powered genetic study in dementia with Lewy bodies so far. These data show that common genetic variability has a role in the disease. PMID:29263008

“End-Stage” Neurofibrillary Tangle Pathology in Preclinical Alzheimer's Disease: Fact or Fiction?

PubMed Central

Abner, Erin L.; Kryscio, Richard J.; Schmitt, Frederick A.; SantaCruz, Karen S.; Jicha, Gregory A.; Lin, Yushun; Neltner, Janna M.; Smith, Charles D.; Van Eldik, Linda J.; Nelson, Peter T.

2011-01-01

Among individuals who were cognitively intact before death, autopsies may reveal some Alzheimer's disease-type pathology. The presence of end-stage pathology in cognitively intact persons would support the hypothesis that pathological markers are epiphenomena. We assessed advanced neurofibrillary (Braak stages V and VI) pathology focusing on nondemented individuals. Data from the National Alzheimer's Coordinating Center database (n = 4,690 included initially) and from the Nun Study (n = 526 included initially) were analyzed, with antemortem information about global cognition and careful postmortem studies available from each case. Global cognition (final Mini-Mental State Examination scores [MMSE] and clinical ‘dementia’ status) was correlated with neuropathology, including the severity of neurofibrillary pathology (Braak stages and neurofibrillary tangle counts in cerebral neocortex). Analyses support three major findings: 1. Braak stage V cases and Braak VI cases are significantly different from each other in terms of associated antemortem cognition; 2. There is an appreciable range of pathology within the category of Braak stage VI based on tangle counts such that brains with the most neurofibrillary tangles in neocortex always had profound antemortem cognitive impairment; and 3. There was no nondemented case with final MMSE score of 30 within a year of life and Braak stage VI pathology. It may be inappropriate to combine Braak stages V and VI cases, particularly in patients with early cognitive dysfunction, since the two pathological stages appear to differ dramatically in terms of both pathological severity and antemortem cognitive status. There is no documented example of truly end-stage neurofibrillary pathology coexisting with intact cognition. PMID:21471646

[Therapeutic effect observation of chronic knee joint pain assisted with the central-square needling technique of the thumb-tack needles].

PubMed

Yang, Yang; Qi, Si; Liu, Mengyue; Zhao, Yu; Li, Ning

2017-10-12

To compare the differences in the clinical therapeutic effects on chronic knee joint pain between the combination of the central-square needling technique of thumb-tack needles with the routine therapy of acupuncture, moxibustion and tuina and the routine therapy of acupuncture, moxibustion and tuina . One hundred and twenty patients of chronic knee joint pain were randomized into an observation group and a control group, 60 cases in each one. In the control group, the routine therapy of acupuncture, moxibustion and tuina was adopted. In the observation group, at the end of treatment with the routine therapy of acupuncture, moxibustion and tuina , the subcutaneous embedding therapy was followed with four thumb-tack needles at the sites 1 to 1.5 cm above, below and bilateral to the main point ( ashi point) separately, and the needles were retained for 24 h to 48 h. The treatment was given once every two days, three times a week, totally 6 times in two weeks; and the follow-up visit was done for 3 months in patients of the two groups. The visual analogue scale (VAS) score before and after each treatment, Lequesne index score before treatment and at the end of follow-up and the case numbers of proactive use of painkillers or receiving acupuncture treatment in the follow-up stage were compared and observed in the patients of the two groups. The VAS score was reduced gradually after treatment in the patients of the two groups. The differences were significant statistically after the second treatment as compared with those before the treatment in the two groups (all P <0.05), in which, the improvements in VAS scores after the third treatment in the observation group were more obvious than those in the control group (all P <0.05). At the end of follow-up visit, Lequesne index scores were all improved as compared with those before treatment in the two groups (both P <0.05) and the improvements were similar between the two groups ( P >0.05). In the follow-up stage, there were 0 case in the observation group and 9 cases in the control group in terms of proactive use of painkillers ( P <0.05). There were 5 cases in the observation group and 1 case in the control group receiving acupuncture treatment again ( P >0.05). The acupuncture scheme in assistance with the central-square needling technique of thumb-tack needles obviously relieves chronic knee joint pain, much better sustains the analgesic effects of acupuncture and improves patient compliance.

Nasopharyngeal carcinoma with headaches as the main symptom: A potential diagnostic pitfall.

PubMed

Wu, Zhou-Xue; Xiang, Li; Rong, Jin-Feng; He, Huai-Lin; Li, Dan

2016-01-01

The aim of this study was to investigate medical-related reasons for misdiagnosis of nasopharyngeal carcinoma. (NPC) patients presenting with headaches alone or accompanied by other symptoms. Two-hundred and nineteen NPC cases describing headaches as one of the initial symptoms during primary treatment were selected for this prospective study. Medical records were carefully collected and all data were summarized for final analyses. Distributions of NPC stage in the patients were: Stage II, 1.4%; stage III, 46.6%; stage IVA, 36.1%; stage IVB, 7.7%; and stage IVC, 8.2%. The ratio of men to women was 2.42:1 (155/64 cases). The total misdiagnosis rate was 43.4%. Patients that only complained of headaches had the highest misdiagnosis rate of 86.4% (19/22 cases). The lowest misdiagnosis rate of 10.9% (5/46 cases) was observed in patients with both headaches and epistaxis. The misdiagnosis rate in rural hospitals was more than two times that in provincial hospitals. Neurosurgery departments had a 100% misdiagnosis rate. Frequently, headaches are the only prominent symptom of NPC. Due to the various clinical manifestations, NPC patients encounter a high misdiagnosis rate, which leads to unsatisfactory treatment outcomes. Improved awareness of the various nonspecific symptoms of NPC by nonspecialist physicians will be a pivotal step in decreasing the misdiagnosis rate. Mini Abstract: The misdiagnosis rate of nasopharyngeal carcinoma (NPC) patients with headaches was 43.4%. Improved awareness of the various nonspecific symptoms of NPC is a pivotal step in decreasing the misdiagnosis rate.

Description of the early stage of pandemic (H1N1) 2009 in Germany, 27 April-16 June 2009.

PubMed

2009-08-06

We report characteristics of the early stage of the pandemic (H1N1) 2009 in Germany. Until 16 June 2009, 198 confirmed cases were notified. Almost half of the cases (47%) were imported, mostly from Mexico and the United States. About two third of indigenous cases were outbreak-related (with two large school-associated outbreaks, n=74). According to our results Germany is still in the early stage of the pandemic with limited domestic transmission.

Exclusive radiotherapy for stage T1-T2N0M0 lanryngeal cancer: retrospective study of 59 patients at CFB and CHU de Caen.

PubMed

Cuny, F; Géry, B; Florescu, C; Clarisse, B; Blanchard, D; Rame, J-P; Babin, E; De Raucourt, D

2013-11-01

Study of patients with stage T1N0M0 or T2N0M0 glottic cancer treated by exclusive radiotherapy and comparison of the survival and functional results of this series with those of the literature. Retrospective study of stage T1N0M0 or T2N0M0 glottic cancers diagnosed between 1st January 2000 and 31st December 2010 and treated by exclusive radiotherapy. Evaluation of survival, recurrence and larynx preservation rates. CLCC François-Baclesse and CHU de Caen. Fifty-nine patients (53 men and sixwomen) treated for glottic cancer (57 squamous cell carcinomas, two verrucous carcinomas) comprising 51 T1N0M0 and eight T2N0M0 tumours. Treatment with exclusive radiotherapy (mean dose of 70 Grays limited to the thyroid cartilage for 57 patients, with lymph node irradiation for two patients). In this series, five (9.8%) patients with stage T1N0M0 glottic cancer and three patients (37.5%) with stage T2N0M0 glottic cancer relapsed, corresponding to a global recurrence rate of 13.6%. Three of the eight recurrences involved lymph nodes exclusively (N), two patients relapsed exclusively at the primary tumour site (T) and three patients presented local and lymph node recurrence (T and N). Treatment consisted of salvage total laryngectomy with bilateral cervical lymph node dissection in three cases, bilateral cervical lymph node dissection and sensitized radiotherapy in two cases, exclusive chemotherapy in one case, cervical lymph node dissection and cervical radiotherapy in one case. The last patient with recurrence died prior to salvage therapy. The larynx preservation rate was 94.9%. In comparison with the literature, treatment of stage T1-T2N0M0 glottic cancer by exclusive radiotherapy gives very good results, with a larynx preservation rate of 95%. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Preliminary investigation into application of problem-based learning in the practical teaching of diagnostics

PubMed Central

Rui, Zeng; Rong-Zheng, Yue; Hong-Yu, Qiu; Jing, Zeng; Xue-Hong, Wan; Chuan, Zuo

2015-01-01

Background Problem-based learning (PBL) is a pedagogical approach based on problems. Specifically, it is a student-centered, problem-oriented teaching method that is conducted through group discussions. The aim of our study is to explore the effects of PBL in diagnostic teaching for Chinese medical students. Methods A prospective, randomized controlled trial was conducted. Eighty junior clinical medical students were randomly divided into two groups. Forty students were allocated to a PBL group and another 40 students were allocated to a control group using the traditional teaching method. Their scores in the practice skills examination, ability to write and analyze medical records, and results on the stage test and behavior observation scale were compared. A questionnaire was administered in the PBL group after class. Results There were no significant differences in scores for writing medical records, content of interviewing, physical examination skills, and stage test between the two groups. However, compared with the control group, the PBL group had significantly higher scores on case analysis, interviewing skills, and behavioral observation scales. Conclusion The questionnaire survey revealed that PBL could improve interest in learning, cultivate an ability to study independently, improve communication and analytical skills, and good team cooperation spirit. However, there were some shortcomings in systematization of imparting knowledge. PBL has an obvious advantage in teaching with regard to diagnostic practice. PMID:25848334

Common Genetic Variants and Modification of Penetrance of BRCA2-Associated Breast Cancer

PubMed Central

Guiducci, Candace; Segrè, Ayellet V.; McGee, Kate; McGuffog, Lesley; Kartsonaki, Christiana; Morrison, Jonathan; Healey, Sue; Sinilnikova, Olga M.; Stoppa-Lyonnet, Dominique; Mazoyer, Sylvie; Gauthier-Villars, Marion; Sobol, Hagay; Longy, Michel; Frenay, Marc; GEMO Study Collaborators; Hogervorst, Frans B. L.; Rookus, Matti A.; Collée, J. Margriet; Hoogerbrugge, Nicoline; van Roozendaal, Kees E. P.; Piedmonte, Marion; Rubinstein, Wendy; Nerenstone, Stacy; Van Le, Linda; Blank, Stephanie V.; Caldés, Trinidad; de la Hoya, Miguel; Nevanlinna, Heli; Aittomäki, Kristiina; Lazaro, Conxi; Blanco, Ignacio; Arason, Adalgeir; Johannsson, Oskar T.; Barkardottir, Rosa B.; Devilee, Peter; Olopade, Olofunmilayo I.; Neuhausen, Susan L.; Wang, Xianshu; Fredericksen, Zachary S.; Peterlongo, Paolo; Manoukian, Siranoush; Barile, Monica; Viel, Alessandra; Radice, Paolo; Phelan, Catherine M.; Narod, Steven; Rennert, Gad; Lejbkowicz, Flavio; Flugelman, Anath; Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi; Toland, Amanda E.; Montagna, Marco; D'Andrea, Emma; Friedman, Eitan; Laitman, Yael; Borg, Ake; Beattie, Mary; Ramus, Susan J.; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Tim; Spurdle, Amanda B.; Chen, Xiaoqing; Holland, Helene; John, Esther M.; Hopper, John L.; Buys, Saundra S.; Daly, Mary B.; Southey, Melissa C.; Terry, Mary Beth; Tung, Nadine; Overeem Hansen, Thomas V.; Nielsen, Finn C.; Greene, Mark I.; Mai, Phuong L.; Osorio, Ana; Durán, Mercedes; Andres, Raquel; Benítez, Javier; Weitzel, Jeffrey N.; Garber, Judy; Hamann, Ute; Peock, Susan; Cook, Margaret; Oliver, Clare; Frost, Debra; Platte, Radka; Evans, D. Gareth; Lalloo, Fiona; Eeles, Ros; Izatt, Louise; Walker, Lisa; Eason, Jacqueline; Barwell, Julian; Godwin, Andrew K.; Schmutzler, Rita K.; Wappenschmidt, Barbara; Engert, Stefanie; Arnold, Norbert; Gadzicki, Dorothea; Dean, Michael; Gold, Bert; Klein, Robert J.; Couch, Fergus J.; Chenevix-Trench, Georgia; Easton, Douglas F.; Daly, Mark J.; Antoniou, Antonis C.; Altshuler, David M.; Offit, Kenneth

2010-01-01

The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (<40 years) affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (λ) was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values<10−5 and 39 SNPs had p-values<10−4. These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499) and chromosome 10 (rs16917302). The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR) and 95% confidence intervals (CI) for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66–0.86, ) and for rs311499 was 0.72 (95% CI 0.61–0.85, ). FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18–1.39, ). These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer. PMID:21060860

Antibiotic cements in articular prostheses: current orthopaedic concepts.

PubMed

Langlais, F; Belot, N; Ropars, M; Thomazeau, H; Lambotte, J C; Cathelineau, G

2006-08-01

The possibilities and limits of antibiotic cements (ACs) have been assessed by many researchers. ACs are now approved by many drug agencies, including the US Food and Drug Administration (approval in 2003), with widespread use in prophylaxis and curative treatments. Laboratory experiments have achieved satisfactory antibiotic delivery without impairing the mechanical properties of ACs. Implantation in large animals (e.g. sheep) showed an antibiotic concentration in the bone cortex four times the minimal inhibitory concentration (MIC) 6 months after implantation. Human pharmacokinetics during total hip replacement (THR) show antibiotic concentrations 20 times the MIC in drainage fluids. No toxic concentrations have been detected in blood or urine, and no allergies, toxic effects, mechanical failures or selection of resistant microorganisms have been observed. Antibioprophylaxis has been assessed in prospective studies in over 1600 cases. In data from the Scandinavian arthroplasty registers, with an exhaustive follow-up of more than 240000 THRs, infection rate was reduced by ca. 50% (0.9% compared with 1.9%). In prostheses with severe infection, use of AC increases the infection control rate from 86% to 93% when using two-stage prosthetic exchanges. In moderate infection, a similar infection control rate (86%) was achieved either by two-stage exchange without local antibiotic or by one-stage exchange with AC; however, one-stage exchange achieved better functional results at lower cost and with reduced pain and hospital stay. Therefore, AC prophylaxis is widely used in countries with prostheses registers (Northern Europe), and use of ACs as treatment for infected prostheses is often considered as the gold standard in the EU and North America. However, AC is only an adjuvant treatment, and excision of infected and devascularized tissues as well as systemic antibiotic treatment managed by a multidisciplinary team remain the main factors of infection control.

Bellini's duct carcinoma: A report of two cases and a review of the literature

PubMed Central

LI, YIFAN; JIN, LU; LIU, JIAJU; CHEN, DUQUN; SU, ZHENGMING; ZHOU, LIQUN; SHI, BENTAO; LAI, YONGQING

2016-01-01

Bellini's duct carcinoma (BDC) is a rare and aggressive variant of renal cell carcinoma that possesses an extremely poor prognosis. The greater the grade or stage of disease, the poorer the prognosis tends to be. This study presents two cases of BDC; one case of low grade BDC and one case of high grade BDC in a 47-year-old male and 74-year-old female, respectively. The 47-year-old male patient presented with painless gross hematuria, which had lasted for 3 weeks and subsequently underwent purely laparoscopic nephroureterectomy. After 4-years of follow-up, the patient remained disease-free. By contrast, a right renal tumor was identified in the 74-year-old female patient during a routine examination. Radical right nephrectomy and lymph node dissection were performed, however, 10 months after surgery the patient succumbed due to wide-spread metastasis. The two cases reported in the present study not only represent excellent examples of the disease spectrum, but also act as a reminder of the possibility of detecting BDC in an early stage of disease. Therefore, the epidemiology of BDC has been discussed, and the aggressive growth pattern of BDC has been presented in terms of signs, symptoms and imaging examinations, including ultrasonography, computed tomography (CT), angiography and single photon emission CT, in the early stage of disease. PMID:27313704

Bellini's duct carcinoma: A report of two cases and a review of the literature.

PubMed

Li, Yifan; Jin, L U; Liu, Jiaju; Chen, Duqun; Su, Zhengming; Zhou, Liqun; Shi, Bentao; Lai, Yongqing

2016-06-01

Bellini's duct carcinoma (BDC) is a rare and aggressive variant of renal cell carcinoma that possesses an extremely poor prognosis. The greater the grade or stage of disease, the poorer the prognosis tends to be. This study presents two cases of BDC; one case of low grade BDC and one case of high grade BDC in a 47-year-old male and 74-year-old female, respectively. The 47-year-old male patient presented with painless gross hematuria, which had lasted for 3 weeks and subsequently underwent purely laparoscopic nephroureterectomy. After 4-years of follow-up, the patient remained disease-free. By contrast, a right renal tumor was identified in the 74-year-old female patient during a routine examination. Radical right nephrectomy and lymph node dissection were performed, however, 10 months after surgery the patient succumbed due to wide-spread metastasis. The two cases reported in the present study not only represent excellent examples of the disease spectrum, but also act as a reminder of the possibility of detecting BDC in an early stage of disease. Therefore, the epidemiology of BDC has been discussed, and the aggressive growth pattern of BDC has been presented in terms of signs, symptoms and imaging examinations, including ultrasonography, computed tomography (CT), angiography and single photon emission CT, in the early stage of disease.

Two-Stage Thoracoscopic Repair of Long-Gap Esophageal Atresia Using Internal Traction Is Safe and Feasible.

PubMed

Tainaka, Takahisa; Uchida, Hiroo; Tanano, Akihide; Shirota, Chiyoe; Hinoki, Akinari; Murase, Naruhiko; Yokota, Kazuki; Oshima, Kazuo; Shirotsuki, Ryo; Chiba, Kosuke; Amano, Hizuru; Kawashima, Hiroshi; Tanaka, Yujiro

2017-01-01

The treatment of long-gap esophageal atresia remains an issue for pediatric surgeons. Many techniques for treating long-gap esophageal atresia have been proposed, but the optimal method has not been established. The thoracoscopic esophageal elongation technique has recently been developed. We previously reported a case in which two-stage thoracoscopic repair was performed using internal esophageal traction without esophageal tearing, and we retrospectively reviewed the outcomes of this procedure in this study. Five patients underwent thoracoscopic treatment involving internal esophageal traction for esophageal atresia involving a long gap or vascular ring over a 5-year period. Between November 2010 and November 2015, 5 patients were treated with thoracoscopic traction. All of these patients successfully underwent thoracoscopic-delayed primary anastomosis. Conversion to open thoracotomy was not required in any case. The postoperative complications experienced by the patients included minor anastomotic leakage in 2 cases, anastomotic stenosis in 1 case, gastroesophageal reflux (GER) in 4 cases, and a hiatal hernia in 1 case. None of the patients died. Two-stage thoracoscopic repair for esophageal atresia involving a long gap or vascular ring is a safe and feasible procedure; however, we must develop methods for treating minor anastomotic complications and GER due to esophageal traction in future.

[Post-operative peritoneal washing cytology in cases of stage IIIa endometrial carcinoma with positive peritoneal cytology].

PubMed

Kato, T; Hirai, Y; Hasumi, K

1995-07-01

According to the new FIGO staging of corpus cancer, the cases with positive peritoneal cytology alone belong in stage IIIa. The authors previously reported, however, good prognosis of IIIa cases with only positive peritoneal cytology. In order to assess the potential of malignant cells in the peritoneal cavity to metastasize, post-operative peritoneal washing cytology was undertaken. This study was conducted on a total of 115 consecutive patients with endometrial carcinoma who underwent primary surgical therapy at the Cancer Institute Hospital during the 25-month period from December, 1991 to December, 1993. Fifteen cases were included in stage IIIa with positive intraoperative peritoneal cytology alone. In 12 cases with endometrioid adenocarcinoma, a Silascon tube was indwelt in the abdominal cavity before closure of the abdomen. The peritoneal cavity was washed with 500 ml of physiological saline through the indwelt tube 14 days after the operation. The cytology of recovered washings was negative in all cases. Only two cases received postoperative chemotherapy owing to other prognostic factors. These 12 cases are alive with no evidence of disease after 12 to 36 months. The present study demonstrated that malignant cells in the peritoneal cavity appear to have a very low potential for implantation into the peritoneum.

Jointly determining significance levels of primary and replication studies by controlling the false discovery rate in two-stage genome-wide association studies.

PubMed

Jiang, Wei; Yu, Weichuan

2017-01-01

In genome-wide association studies, we normally discover associations between genetic variants and diseases/traits in primary studies, and validate the findings in replication studies. We consider the associations identified in both primary and replication studies as true findings. An important question under this two-stage setting is how to determine significance levels in both studies. In traditional methods, significance levels of the primary and replication studies are determined separately. We argue that the separate determination strategy reduces the power in the overall two-stage study. Therefore, we propose a novel method to determine significance levels jointly. Our method is a reanalysis method that needs summary statistics from both studies. We find the most powerful significance levels when controlling the false discovery rate in the two-stage study. To enjoy the power improvement from the joint determination method, we need to select single nucleotide polymorphisms for replication at a less stringent significance level. This is a common practice in studies designed for discovery purpose. We suggest this practice is also suitable in studies with validation purpose in order to identify more true findings. Simulation experiments show that our method can provide more power than traditional methods and that the false discovery rate is well-controlled. Empirical experiments on datasets of five diseases/traits demonstrate that our method can help identify more associations. The R-package is available at: http://bioinformatics.ust.hk/RFdr.html .

Quality analysis of population-based information on cancer stage at diagnosis across Europe, with presentation of stage-specific cancer survival estimates: A EUROCARE-5 study.

PubMed

Minicozzi, Pamela; Innos, Kaire; Sánchez, Maria-José; Trama, Annalisa; Walsh, Paul M; Marcos-Gragera, Rafael; Dimitrova, Nadya; Botta, Laura; Visser, Otto; Rossi, Silvia; Tavilla, Andrea; Sant, Milena

2017-10-01

Cancer registries (CRs) are fundamental for estimating cancer burden, evaluating screening and monitoring health service performance. Stage at diagnosis-an essential information item collected by CRs-has been made available, for the first time, by CRs participating in EUROCARE-5. We analysed the quality of this information and estimated stage-specific survival across Europe for CRs with good data quality. Sixty-two CRs sent stage (as TNM, condensed TNM or extent of disease) for 15 cancers diagnosed in 2000-2007. We assessed the quality, partly by comparing stage according to the three systems. We also developed procedures to reconstruct stage (categories: local, regional, metastatic and unknown) using information from all three systems, thus minimising the amount of missing information. Moderate-to-excellent stage concordance was found for practically all 24 CRs, for which it was possible to compare at least two staging systems. However, since stage was often incorrectly assigned, and information on the presence/absence of metastases was often lacking, data on only 7/15 cancers from 34/62 CRs (15 countries) were of sufficient quality for further analysis. Cases diagnosed ≥70 years had more advanced (or lacking) stage- and worse stage-specific survival than those <70 years. Many European CRs collect and record reasonably accurate stage information. Others have difficulties. Both the completeness of primary data and the accuracy of stage coding need to be improved in order for CRs to fulfil their expanding roles in cancer control. We propose our stage reconstruction/checking procedures as a means of fully exploiting the stage information provided by EUROCARE CRs. More advanced (or lacking) stage at diagnosis plus poorer stage-specific survival in the elderly are worrying. Copyright © 2017 Elsevier Ltd. All rights reserved.

Proteomic Approach for Diagnostic Applications in Head and Neck Cancer — EDRN Public Portal

Cancer.gov

To evaluate the test characteristics of a panel of biomarkers for identifying patients with early stage head and neck squamous cell carcinoma (HNSCC). The primary endpoints are sensitivity, specificity and accuracy of the marker panel. This study of the test characteristics of a modeling strategy for diagnosing HNSCC uses a case-control design, with several types of cases and several types of controls.

Association of calcium sensing receptor polymorphisms at rs1801725 with circulating calcium in breast cancer patients.

PubMed

Wang, Li; Widatalla, Sarrah E; Whalen, Diva S; Ochieng, Josiah; Sakwe, Amos M

2017-08-02

Breast cancer (BC) patients with late-stage and/or rapidly growing tumors are prone to develop high serum calcium levels which have been shown to be associated with larger and aggressive breast tumors in post and premenopausal women respectively. Given the pivotal role of the calcium sensing receptor (CaSR) in calcium homeostasis, we evaluated whether polymorphisms of the CASR gene at rs1801725 and rs1801726 SNPs in exon 7, are associated with circulating calcium levels in African American and Caucasian control subjects and BC cases. In this retrospective case-control study, we assessed the mean circulating calcium levels, the distribution of two inactivating CaSR SNPs at rs1801725 and rs1801726 in 199 cases and 384 age-matched controls, and used multivariable regression analysis to determine whether these SNPs are associated with circulating calcium in control subjects and BC cases. We found that the mean circulating calcium levels in African American subjects were higher than those in Caucasian subjects (p < 0.001). As expected, the mean calcium levels were higher in BC cases compared to control subjects (p < 0.001), but the calcium levels in BC patients were independent of race. We also show that in BC cases and control subjects, the major alleles at rs1801725 (G/T, A986S) and at rs1801726 (C/G, Q1011E) were common among Caucasians and African Americans respectively. Compared to the wild type alleles, polymorphisms at the rs1801725 SNP were associated with higher calcium levels (p = 0.006) while those at rs1801726 were not. Using multivariable linear mixed-effects models and adjusting for age and race, we show that circulating calcium levels in BC cases were associated with tumor grade (p = 0.009), clinical stage (p = 0.003) and more importantly, with inactivating mutations of the CASR at the rs1801725 SNP (p = 0.038). These data suggest that decreased sensitivity of the CaSR to calcium due to inactivating polymorphisms at rs1801725, may predispose up to 20% of BC cases to high circulating calcium-associated larger and/or aggressive breast tumors.

[Clinicopathological characteristics of hereditary ovarian cancer syndrome].

PubMed

Zhong, Yan; Sheng, Xiu-gui; Ma, Zhi-fang; Ma, Yue-bing; Liu, Nai-fu; Chen, Yue-ting; Gao, Rong; Wang, Ying-ying; Sun, Li

2009-09-01

To explore the clinicopathological characteristics of hereditary ovarian cancer syndrome (HOCS). From Jan. 2000 to Jan. 2007, among 580 cases of primary ovarian cancer, 42 cases (hereditary group), who had a positive family history of ovarian cancer and met the diagnostic criteria of HOCS, were analyzed retrospectively. One hundred cases without a family history of ovarian cancer were enrolled randomizely as control group (sporadic group). The incidence of HOCS was 7.2% (42/580). Forty-two cases associated tumors affected at least 2 successive generations in 31 families and affected 1 generation in 8 families. Eighty-seven percent (27/31) was from maternal lineage, while 13% (4/31) from paternal lineage. Earlier age of onset was significantly difference between two groups [(49 +/- 10) years vs. (55 +/- 10) years, P < 0.05]. There were 90% belong to serous adenocarcinoma in the hereditary group, while 84% in the sporadic group. There was statistical difference in the proportion of mucinous adenocarcinoma (0 vs. 11%, P < 0.05). The most common clinical manifestations were abdominal distention and anorexia (64% vs. 70%, P > 0.05), International Federational of Gynecology Obstetrics (FIGO) stage III (62% vs. 63%, P > 0.05) between two groups. Fourteen cases (33%,14/42) were previously untreated in the hereditary group, while 40 cases (40%, 40/100) in the sporadic group. There were 15 cases (36%, 15/42) underwent secondary surgery and 15 cases (36%, 15/42) underwent third surgery or more in hereditary group, while 50 cases (50%,50/100) and 27 cases (27%, 27/100) in the sporadic group. The mean number of chemotherapy cycles received in two groups was 13.3 and 11.8 (P > 0.05). The 3-year and 5-year survival rate in hereditary group were 73.6% and 54.9% respectively, compared with 47.4% and 21.2% (P < 0.05) in sporadic group. Hereditary ovarian cancer mostly from maternal lineage are featuring in early age of onset, serous adenocarcinoma, advanced stage (stage III), and better prognosis after the comprehensive treated by cytoreductive surgery plus with chemotherapy.

Do hospital treatments represent a 'teachable moment' for quitting smoking? A study from a stage-theoretical perspective.

PubMed

Dohnke, B; Ziemann, C; Will, K E; Weiss-Gerlach, E; Spies, C D

2012-01-01

Hospital treatments are assumed to be a 'teachable moment'. This phenomenon, however, is only poorly conceptualised and untested. A stage-theoretical perspective implies that a cueing event such as hospital treatments is a teachable moment if a stage progression, change of cognitions, or both occur. This concept is examined in a cross-sectional study by comparing smokers in two treatment settings, an emergency department (ED) and inpatient treatment after elective surgery, with smokers in a control setting. Setting differences were hypothesised in stage distribution, and levels of and stage differences in social-cognitive factors under control for possible confounders. Stage, social-cognitive factors and possible confounders were assessed in 185 ED smokers, 193 inpatient smokers and 290 control smokers. Compared to control smokers, ED and inpatient smokers were in higher stages; they perceived fewer risks and cons; inpatient smokers reported more concrete plans. Stage differences in self-efficacy among ED and inpatient smokers differed from those among control smokers, but the former corresponded more strongly to the theoretical stage assumptions. The results suggest that hospital treatments lead to a stage progression and change of corresponding cognitions, and thus represent a 'teachable moment'. Stage-matched interventions should be provided but consider differences in cognitions to be effective.

CD147 overexpression may serve as a promising diagnostic and prognostic marker for gastric cancer: evidence from original research and literature.

PubMed

Hu, Chenghao; Dong, Xiaoxia; Wu, Junbo; Xiao, Feifan; Shang, Jun; Liu, Liang; Yang, Yuan; Luo, Dongmei; Li, Qiuting; Song, Qian; Yang, Jingcheng; Zhang, Chengdong; Shen, Li; Luo, Zhiguo

2017-05-09

Gastric cancer (GC) is one of the most common malignancies worldwide. The expression of CD147 protein is associated with GC. However, the clinical role of CD147 in GC has not been investigated extensively. Hence, we focused on studying the association between the expression of CD147 and clinicopathological features of GC patients in this study. Firstly, sixteen publications (1752 cases and 391 controls) and one from our own original research (143 cases) were included in the meta-analysis to obtain a more precise estimation of the diagnostic value of CD147. The results showed that expression rate of CD147 in the GC group is higher than that in control group. Moreover, gender, TNM stage, lymph node metastasis, and depth of invasion are all associated with CD147. Further, sections of gastric tissue from 143 cases underwent immunohistochemical staining for evaluation of CD147 protein expression. Our retrospective analysis demonstrated CD147 protein expression was significantly associated with clinical N stage, and tumor stage. Meanwhile, it can also serve as an independent prognosis biomarker. In conclusion, our results support the role of CD147 as a good indicator of diagnosis and prognosis.

Common variants on 2p16.1, 6p22.1 and 10q24.32 are associated with schizophrenia in Han Chinese population.

PubMed

Yu, H; Yan, H; Li, J; Li, Z; Zhang, X; Ma, Y; Mei, L; Liu, C; Cai, L; Wang, Q; Zhang, F; Iwata, N; Ikeda, M; Wang, L; Lu, T; Li, M; Xu, H; Wu, X; Liu, B; Yang, J; Li, K; Lv, L; Ma, X; Wang, C; Li, L; Yang, F; Jiang, T; Shi, Y; Li, T; Zhang, D; Yue, W

2017-07-01

Many schizophrenia susceptibility loci have been identified through genome-wide association studies (GWASs) in European populations. However, until recently, schizophrenia GWASs in non-European populations were limited to small sample sizes and have yielded few loci associated with schizophrenia. To identify genetic risk variations for schizophrenia in the Han Chinese population, we performed a two-stage GWAS of schizophrenia comprising 4384 cases and 5770 controls, followed by independent replications of 13 single-nucleotide polymorphisms in an additional 4339 schizophrenia cases and 7043 controls of Han Chinese ancestry. Furthermore, we conducted additional analyses based on the results in the discovery stage. The combined analysis confirmed evidence of genome-wide significant associations in the Han Chinese population for three loci, at 2p16.1 (rs1051061, in an exon of VRK2, P=1.14 × 10 -12 , odds ratio (OR)=1.17), 6p22.1 (rs115070292 in an intron of GABBR1, P=4.96 × 10 -10 , OR=0.77) and 10q24.32 (rs10883795 in an intron of AS3MT, P=7.94 × 10 -10 , OR=0.87; rs10883765 at an intron of ARL3, P=3.06 × 10 -9 , OR=0.87). The polygenic risk score based on Psychiatric Genomics Consortium schizophrenia GWAS data modestly predicted case-control status in the Chinese population (Nagelkerke R 2 : 1.7% ~5.7%). Our pathway analysis suggested that neurological biological pathways such as GABAergic signaling, dopaminergic signaling, cell adhesion molecules and myelination pathways are involved in schizophrenia. These findings provide new insights into the pathogenesis of schizophrenia in the Han Chinese population. Further studies are needed to establish the biological context and potential clinical utility of these findings.

Arthrodesis after failed knee arthroplasty. A nationwide multicenter investigation of 91 cases.

PubMed

Knutson, K; Hovelius, L; Lindstrand, A; Lidgren, L

1984-12-01

Ninety-one patients with attempted arthrodesis after failed knee arthroplasty were identified in a prospective nationwide study of knee arthroplasties performed from October 1975 through January 1982 in Sweden. The study included 43 hinged or stabilized, 34 bi- or tricompartment, and 14 unicompartment endoprostheses. Three-fourths of the failures were caused by infections. At follow-up evaluation, two patients had expired from infection and four patients had amputations. Fusion was achieved in only 50% of 108 attempts in 91 knees. Patients with unstable joints had limited function. The fusion rate was relatively high after unicompartment endoprostheses, in cases with sustained rigid fixation, or in cases where infection was brought under control at arthrodesis. Rigid fixation was best achieved with an external double frame or an intramedullary nail. Repeated attempts were worthwhile. Removal of all foreign material, eradication of the infectious lesion, and an arthrodesis performed in a one- or two-stage procedure with insertion of gentamicin beads seemed to be the best way to combat infection. The treatment of prosthetic failures should be referred to centers with special interest in knee arthroplasty.

Treatment of field cases of East Coast fever with halofuginone lactate.

PubMed

Njau, B C; Mkonyi, P A; Mleche, W C; Kitaly, J I; Maiseli, N C

1985-11-01

In a series of field trials 48 (55%) of 88 field cases of East Coast fever treated with halofuginone lactate recovered and survived and 40 (45%) died while 31 (86%) of 36 untreated control animals died of East Coast fever and five (14%) recovered. For cases diagnosed and treated early a 100% recovery rate was achieved. A single dose at 1.2 mg/kg body weight per os was adequate. Recovery rate was only 36% for cases diagnosed and treated at an advanced stage. Such cases required two doses at 1.2 mg/kg or a combination of 1.2 and 2.4 mg/kg body weight given at about two days interval. The temperature dropped to normal levels within 48 h of treatment and schizonts started degenerating as early as 24 h after treatment and had disappeared by 48 to 72 h. Piroplasms were not affected by the drug. Recovered animals remained free of East Coast fever for periods up to 12 months of observation despite continuous tick challenge. It was concluded that, with early detection and treatment augmented with proper tick control, outbreaks of East Coast fever can be effectively controlled with halofuginone lactate.

Core compressor exit stage study. Volume 4: Data and performance report for the best stage configuration

NASA Technical Reports Server (NTRS)

Wisler, D. C.

1981-01-01

The core compressor exit stage study program develops rear stage blading designs that have lower losses in their endwall boundary layer regions. The test data and performance results for the best stage configuration consisting of Rotor-B running with Stator-B are described. The technical approach in this efficiency improvement program utilizes a low speed research compressor. Tests were conducted in two ways: (1) to use four identical stages of blading to obtain test data in a true multistage environment and (2) to use a single stage of blading to compare with the multistage test results. The effects of increased rotor tip clearances and circumferential groove casing treatment are evaluated.

Binding of bile acids by pastry products containing bioactive substances during in vitro digestion.

PubMed

Dziedzic, Krzysztof; Górecka, Danuta; Szwengiel, Artur; Smoczyńska, Paulina; Czaczyk, Katarzyna; Komolka, Patrycja

2015-03-01

The modern day consumer tends to choose products with health enhancing properties, enriched in bioactive substances. One such bioactive food component is dietary fibre, which shows a number of physiological properties including the binding of bile acids. Dietary fibre should be contained in everyday, easily accessible food products. Therefore, the aim of this study was to determine sorption capacities of primary bile acid (cholic acid - CA) and secondary bile acids (deoxycholic - DCA and lithocholic acids - LCA) by muffins (BM) and cookies (BC) with bioactive substances and control muffins (CM) and cookies (CC) in two sections of the in vitro gastrointestinal tract. Variations in gut flora were also analysed in the process of in vitro digestion of pastry products in a bioreactor. Enzymes: pepsin, pancreatin and bile salts: cholic acid, deoxycholic acid and lithocholic acid were added to the culture. Faecal bacteria, isolated from human large intestine, were added in the section of large intestine. The influence of dietary fibre content in cookies and concentration of bile acids in two stages of digestion were analysed. Generally, pastry goods with bioactive substances were characterized by a higher content of total fibre compared with the control samples. These products also differ in the profile of dietary fibre fractions. Principal Component Analysis (PCA) showed that the bile acid profile after two stages of digestion depends on the quality and quantity of fibre. The bile acid profile after digestion of BM and BC forms one cluster, and with the CM and CC forms a separate cluster. High concentration of H (hemicellulose) is positively correlated with LCA (low binding effect) and negatively correlated with CA and DCA contents. The relative content of bile acids in the second stage of digestion was in some cases above the content in the control sample, particularly LCA. This means that the bacteria introduced in the 2nd stage of digestion synthesize the LCA.

Successful Leadership in Three High-Poverty Urban Elementary Schools

ERIC Educational Resources Information Center

Jacobson, Stephen L.; Brooks, Sharon; Giles, Corrie; Johnson, Lauri; Ylimaki, Rose

2007-01-01

This study examined the beliefs and practices of three principals during whose tenure their high-poverty urban elementary schools experienced improved student achievement. A two-stage, multiple case-study methodology was employed. First, New York State Education Department (NYSED) school report card data were analyzed to identify case-study sites.…

Screening Methodologies to Support Risk and Technology Reviews (RTR): A Case Study Analysis

EPA Science Inventory

The Clean Air Act establishes a two-stage regulatory process for addressing emissions of hazardous air pollutants (HAPs) from stationary sources. In the first stage, the Act requires the EPA to develop technology-based standards for categories of industrial sources. We have lar...

A two-stage epidemiological study of eating disorders and muscle dysmorphia in male university students in Buenos Aires.

PubMed

Compte, Emilio J; Sepulveda, Ana R; Torrente, Fernando

2015-12-01

Studies using traditional screening instruments tend to report a lower prevalence of eating disorders (EDs) in men than is observed in women. It is therefore unclear whether such instruments are valid for the assessment of ED in males. Lack of a formal diagnostic definition of muscle dysmorphia syndrome (MD) makes it difficult to identify men at risk. The study aimed to assess the prevalence of ED and MD in male university students of Buenos Aires. A cross-sectional, two-stage, representative survey was of 472 male students from six different schools in Buenos Aires, mostly aged between 18 and 28 years. The first stage involved administration of self-report questionnaires (Eating Attitude Test-26; scores ≥15 indicate "at risk" status). In Stage 2 students at risk of developing EDs were evaluated with a clinical interview, the Eating Disorder Examination (EDE; 12th edition). Two control students were interviewed for every at risk student. The prevalence of EDs among university male students was 1.9% (n = 9). All participants with an ED presented with illness classified as eating disorder not otherwise specified (EDNOS). Using the Drive for Muscularity Scale (DMS) with a 52-point threshold we identified possible MD in 6.99% (n = 33) of the sample. The prevalence of ED detected in this study is comparable with previous findings in male populations, and below that observed in female populations. However, the prevalence of possible cases of MD resembles the total rate of EDs in women. Characteristics associated with EDs and MD in men are also discussed. © 2015 Wiley Periodicals, Inc.

The Effect of Two-Staged Warm Compress on the Pain Duration of First and Second Labor Stages and Apgar Score in Prim Gravida Women: a Randomized Clinical Trial

PubMed Central

Akbarzadeh, Marzieh; Nematollahi, Azar; Farahmand, Mahnaz; Amooee, Sedigheh

2018-01-01

Introduction: The aim of this study was to assess the effect of two-stage warm compress technique on the pain duration of the first and second labor stages and neonatal outcomes. Methods: The clinical trial was done on 150 women (75 subjects in each groups) in Shiraz-affiliated hospitals in 2012 A two-staged warm compress was done for 15-20 minutes in the first and second labor phase (cervical dilatation of 7 and 10 cm with zero status) while the control group received hospital routine care. The duration of labor and Apgar score were evaluated. Results: According to t-test, the average of labor duration was lower in the intervention group compared to the control group at the second stage. However, there was no significant difference for labor duration at the first stage and the first and fifth minute Apgar score. Conclusion: According to the result, this intervention seems a good method for decreasing labor duration at the second stage of parturition. PMID:29637053

A Study of a Two Stage Maximum Power Point Tracking Control of a Photovoltaic System under Partially Shaded Insolation Conditions

NASA Astrophysics Data System (ADS)

Kobayashi, Kenji; Takano, Ichiro; Sawada, Yoshio

A photovoltaic array shows relatively low output power density, and has a greatly drooping Current-Voltage (I-V) characteristic. Therefore, Maximum Power Point Tracking (MPPT) control is used to maximize the output power of the array. Many papers have been reported in relation to MPPT. However, the Current-Power (I-P) curve sometimes shows multi-local maximum points mode under non-uniform insolation conditions. The operating point of the PV system tends to converge to a local maximum output point which is not the real maximal output point on the I-P curve. Some papers have been also reported, trying to avoid this difficulty. However most of those control systems become rather complicated. Then, the two stage MPPT control method is proposed in this paper to realize a relatively simple control system which can track the real maximum power point even under non-uniform insolation conditions. The feasibility of this control concept is confirmed for steady insolation as well as for rapidly changing insolation by simulation study using software PSIM and LabVIEW. In addition, simulated experiment confirms fundament al operation of the two stage MPPT control.

[HOMA-IR in patients with chronic hepatitis C].

PubMed

Botshorishvili, T; Vashakidze, E

2012-02-01

The aim of investigation was to study the frequency of IR in type of viral hepatitis C, correlation with the degree of hepatic lesion and liver cirrhosis. 130 patients were investigated: 20 with acute hepatitis C; 38 with chronic hepatitis C; 72 with cirrhosis: among them 10 with Stage A, 14 with Stage B and 48 with Stage C. Also we used 30 healthy people as the controls. The study demonstrates significant changes of insulin, glucose, HOMA-IR type of viral hepatitis C, correlation with the degree of hepatic lesion and liver cirrhosis. In patients with liver cirrhosis levels of HOMA-IR is higher than in patients with chronic hepatitis C. In patients with acute hepatitis C levels of HOMA-IR was normal as in the control group. The results showed that various types of chronic viral hepatitis C and stages of cirrhosis set to increase HOMA-IR versus the controls., which were the most prominent in cases of severe hepatic lesion, which indicates that insulin resistance is a frequent companion of CHC.

Satisfactory surgical outcome of T2 gastric cancer after modified D2 lymphadenectomy.

PubMed

Zhang, Shupeng; Wu, Liangliang; Wang, Xiaona; Ding, Xuewei; Liang, Han

2017-04-01

Though D2 lymphadenectomy has been increasingly regarded as standard surgical procedure for advanced gastric cancer (GC), the modified D2 (D1 + 7, 8a and 9) lymphadenectomy may be more suitable than D2 dissection for T2 stage GC. The purpose of this study is to elucidate whether the surgical outcome of modified D2 lymphadenectomy was comparable to that of standard D2 dissection in T2 stage GC patients. A retrospective cohort study with 77 cases and 77 controls matched for baseline characteristics was conducted. Patients were categorized into two groups according to the extent of lymphadenectomy: the modified D2 group (mD2) and the standard D2 group (D2). Surgical outcome and recurrence date were compared between the two groups. The 5-year overall survival (OS) rate was 71.4% for patients accepted mD2 lymphadenectomy and 70.1% for those accepted standard D2, respectively, and the difference was not statistically significant. Multivariate survival analysis revealed that curability, tumor size, TNM stage and postoperative complications were independently prognostic factors for T2 stage GC patients. Patients in the mD2 group tended to have less intraoperative blood loss (P=0.001) and shorter operation time (P<0.001) than those in the D2 group. While there were no significant differences in recurrence rate and types, especially lymph node recurrence, between the two groups. The surgical outcome of mD2 lymphadenectomy was equal to that of standard D2, and the use of mD2 instead of standard D2 can be a better option for T2 stage GC.

Critical period of weed control in winter canola (Brassica napus L.) in a semi-arid region.

PubMed

Aghaalikhani, M; Yaghoobi, S R

2008-03-01

In order to determine the critical period of weed control in winter canola (Brassica napus L. cv. Okapi) an experiment was carried out at research field of Tarbiat Modarres University, Tehran, Iran on 2004-2005 growing season. Fourteen experimental treatments which divided into two sets were arranged in Randomized complete blocks design with four replications. In the first set, the crop was kept weed-free from emergence time to two-leaf stage (V2), four-leaf stage (V4), six-leaf stage (V6), eight-leaf stage (V8), early flowering (IF), 50% of silique set (50% SS) and final harvest (H). In the second set, weeds where permitted to grow with the crop until above mentioned stages. In this study critical period of weed control was determined according to evaluate seed bank emerged weed biomass effect on canola grain yield loss using Gompertz and logistic equations. Result showed a critical time of weed control about 25 days after emergence (between four to six-leaf stages) with 5% accepted yield loss. Therefore, weed control in this time could provide the best result and avoid yield loss and damage to agroecosystem.

Diagnosis Of Persistent Infection In Prosthetic Two-Stage Exchange: PCR analysis of Sonication fluid From Bone Cement Spacers.

PubMed

Mariaux, Sandrine; Tafin, Ulrika Furustrand; Borens, Olivier

2017-01-01

Introduction: When treating periprosthetic joint infections with a two-stage procedure, antibiotic-impregnated spacers are used in the interval between removal of prosthesis and reimplantation. According to our experience, cultures of sonicated spacers are most often negative. The objective of our study was to investigate whether PCR analysis would improve the detection of bacteria in the spacer sonication fluid. Methods: A prospective monocentric study was performed from September 2014 to January 2016. Inclusion criteria were two-stage procedure for prosthetic infection and agreement of the patient to participate in the study. Beside tissues samples and sonication, broad range bacterial PCRs, specific S. aureus PCRs and Unyvero-multiplex PCRs were performed on the sonicated spacer fluid. Results: 30 patients were identified (15 hip, 14 knee and 1 ankle replacements). At reimplantation, cultures of tissue samples and spacer sonication fluid were all negative. Broad range PCRs were all negative. Specific S. aureus PCRs were positive in 5 cases. We had two persistent infections and four cases of infection recurrence were observed, with bacteria different than for the initial infection in three cases. Conclusion: The three different types of PCRs did not detect any bacteria in spacer sonication fluid that was culture-negative. In our study, PCR did not improve the bacterial detection and did not help to predict whether the patient will present a persistent or recurrent infection. Prosthetic 2-stage exchange with short interval and antibiotic-impregnated spacer is an efficient treatment to eradicate infection as both culture- and molecular-based methods were unable to detect bacteria in spacer sonication fluid after reimplantation.

Loci associated with ischaemic stroke and its subtypes (SiGN): a genome-wide association study.

PubMed

2016-02-01

The discovery of disease-associated loci through genome-wide association studies (GWAS) is the leading genetic approach to the identification of novel biological pathways underlying diseases in humans. Until recently, GWAS in ischaemic stroke have been limited by small sample sizes and have yielded few loci associated with ischaemic stroke. We did a large-scale GWAS to identify additional susceptibility genes for stroke and its subtypes. To identify genetic loci associated with ischaemic stroke, we did a two-stage GWAS. In the first stage, we included 16 851 cases with state-of-the-art phenotyping data and 32 473 stroke-free controls. Cases were aged 16 to 104 years, recruited between 1989 and 2012, and subtypes of ischaemic stroke were recorded by centrally trained and certified investigators who used the web-based protocol, Causative Classification of Stroke (CCS). We constructed case-control strata by identifying samples that were genotyped on nearly identical arrays and were of similar genetic ancestral background. We cleaned and imputed data by use of dense imputation reference panels generated from whole-genome sequence data. We did genome-wide testing to identify stroke-associated loci within each stratum for each available phenotype, and we combined summary-level results using inverse variance-weighted fixed-effects meta-analysis. In the second stage, we did in-silico lookups of 1372 single nucleotide polymorphisms identified from the first stage GWAS in 20 941 cases and 364 736 unique stroke-free controls. The ischaemic stroke subtypes of these cases had previously been established with the Trial of Org 10 172 in Acute Stroke Treatment (TOAST) classification system, in accordance with local standards. Results from the two stages were then jointly analysed in a final meta-analysis. We identified a novel locus (G allele at rs12122341) at 1p13.2 near TSPAN2 that was associated with large artery atherosclerosis-related stroke (first stage odds ratio [OR] 1·21, 95% CI 1·13-1·30, p=4·50 × 10 -8 ; joint OR 1·19, 1·12-1·26, p=1·30 × 10 -9 ). Our results also supported robust associations with ischaemic stroke for four other loci that have been reported in previous studies, including PITX2 (first stage OR 1·39, 1·29-1·49, p=3·26 × 10 -19 ; joint OR 1·37, 1·30-1·45, p=2·79 × 10 -32 ) and ZFHX3 (first stage OR 1·19, 1·11-1·27, p=2·93 × 10 -7 ; joint OR 1·17, 1·11-1·23, p=2·29 × 10 -10 ) for cardioembolic stroke, and HDAC9 (first stage OR 1·29, 1·18-1·42, p=3·50 × 10 -8 ; joint OR 1·24, 1·15-1·33, p=4·52 × 10 -9 ) for large artery atherosclerosis stroke. The 12q24 locus near ALDH2, which has previously been associated with all ischaemic stroke but not with any specific subtype, exceeded genome-wide significance in the meta-analysis of small artery stroke (first stage OR 1·20, 1·12-1·28, p=6·82 × 10 -8 ; joint OR 1·17, 1·11-1·23, p=2·92 × 10 -9 ). Other loci associated with stroke in previous studies, including NINJ2, were not confirmed. Our results suggest that all ischaemic stroke-related loci previously implicated by GWAS are subtype specific. We identified a novel gene associated with large artery atherosclerosis stroke susceptibility. Follow-up studies will be necessary to establish whether the locus near TSPAN2 can be a target for a novel therapeutic approach to stroke prevention. In view of the subtype-specificity of the associations detected, the rich phenotyping data available in the Stroke Genetics Network (SiGN) are likely to be crucial for further genetic discoveries related to ischaemic stroke. US National Institute of Neurological Disorders and Stroke, National Institutes of Health. Copyright © 2016 Elsevier Ltd. All rights reserved.

Development of time-trend model for analysing and predicting case pattern of dog bite injury induced rabies-like-illness in Liberia, 2014-2017.

PubMed

Jomah, N D; Ojo, J F; Odigie, E A; Olugasa, B O

2014-12-01

The post-civil war records of dog bite injuries (DBI) and rabies-like-illness (RLI) among humans in Liberia is a vital epidemiological resource for developing a predictive model to guide the allocation of resources towards human rabies control. Whereas DBI and RLI are high, they are largely under-reported. The objective of this study was to develop a time model of the case-pattern and apply it to derive predictors of time-trend point distribution of DBI-RLI cases. A retrospective 6 years data of DBI distribution among humans countrywide were converted to quarterly series using a transformation technique of Minimizing Squared First Difference statistic. The generated dataset was used to train a time-trend model of the DBI-RLI syndrome in Liberia. An additive detenninistic time-trend model was selected due to its performance compared to multiplication model of trend and seasonal movement. Parameter predictors were run on least square method to predict DBI cases for a prospective 4 years period, covering 2014-2017. The two-stage predictive model of DBI case-pattern between 2014 and 2017 was characterised by a uniform upward trend within Liberia's coastal and hinterland Counties over the forecast period. This paper describes a translational application of the time-trend distribution pattern of DBI epidemics, 2008-2013 reported in Liberia, on which a predictive model was developed. A computationally feasible two-stage time-trend permutation approach is proposed to estimate the time-trend parameters and conduct predictive inference on DBI-RLI in Liberia.

Exploring the Contribution of Professional Staff to Student Outcomes: A Comparative Study of Australian and UK Case Studies

ERIC Educational Resources Information Center

Graham, Carroll; Regan, Julie-Anne

2016-01-01

This paper reports on the second stage of a comparative study between two higher education institutions: one in Australia and the other in the United Kingdom, which explored the contributions of professional staff to student outcomes. The first stage acted as a scoping exercise to ascertain how the contributions of professional staff to student…

Two-stage laparoscopic approaches for high anorectal malformation: transumbilical colostomy and anorectoplasty.

PubMed

Yang, Li; Tang, Shao-Tao; Li, Shuai; Aubdoollah, T H; Cao, Guo-Qing; Lei, Hai-Yan; Wang, Xin-Xing

2014-11-01

Trans-umbilical colostomy (TUC) has been previously created in patients with Hirschsprung's disease and intermediate anorectal malformation (ARM), but not in patients with high-ARM. The purposes of this study were to assess the feasibility, safety, complications and cosmetic results of TUC in a divided fashion, and subsequently stoma closure and laparoscopic assisted anorectoplasty (LAARP) were simultaneously completed by using the colostomy site for a laparoscopic port in high-ARM patients. Twenty male patients with high-ARMs were chosen for this two-stage procedure. The first-stage consisted of creating the TUC in double-barreled fashion colostomy with a high chimney at the umbilicus, and the loop was divided at the same time, in such a way that the two diverting ends were located at the umbilical incision with the distal end half closed and slightly higher than proximal end. In the second-stage, 3 to 7 months later, the stoma was closed through a peristomal skin incision followed by end-to-end anastomosis and simultaneously LAARP was performed by placing a laparoscopic port at the umbilicus, which was previously the colonostomy site. Umbilical wound closure was performed in a semi-opened fashion to create a deep umbilicus. TUC and LAARP were successfully performed in 20 patients. Four cases with bladder neck fistulas and 16 cases with prostatic urethra fistulas were found. Postoperative complications were rectal mucosal prolapsed in three cases, anal stricture in two cases and wound dehiscence in one case. Neither umbilical ring narrowing, parastomal hernia nor obstructive symptoms was observed. Neither umbilical nor perineal wound infection was observed. Stoma care was easily carried-out by attaching stoma bag. Healing of umbilical wounds after the second-stage was excellent. Early functional stooling outcome were satisfactory. The umbilicus may be an alternative stoma site for double-barreled colostomy in high-ARM patients. The two-stage laparoscopic approaches for high-ARM, TUC and stoma closure with simultaneously LAARP are both technically feasible and safe with excellent cosmetic result. Copyright © 2014 Elsevier Inc. All rights reserved.

Associations of adiponectin and leptin with stage and grade of PSA-detected prostate cancer: the ProtecT study.

PubMed

Burton, Anya; Martin, Richard M; Holly, Jeff; Lane, J Athene; Donovan, Jenny L; Hamdy, Freddie C; Neal, David E; Tilling, Kate

2013-02-01

Obesity has been associated with an increased risk of advanced and fatal prostate cancer; adipokines may mediate this association. We examined associations of the adipokines leptin and adiponectin with the stage and grade of PSA-detected prostate cancer. We conducted a nested case-control study comparing 311 men with mainly locally advanced (≥T3, N1, or M1 cases) vs. 413 men with localized (T ≤2 & NX-0 & M0 controls) PSA-detected prostate cancer, recruited 2001-2009 from 9 UK regions to the ProtecT study. Associations of body mass index and adipokine levels with prostate cancer stage were determined by conditional logistic regression and with grade (Gleason score ≥7 vs. ≤6) by unconditional logistic regression. Adiponectin was inversely associated with prostate cancer stage in overweight and obese men (OR 0.62; 95 % CI 0.42-0.90; p = 0.01), but not in normal weight men (OR 1.48; 0.77-2.82; p = 0.24) (p for interaction 0.007), or all men (OR 0.86; 0.66-1.11; p = 0.24). There was no compelling evidence of associations between leptin or leptin to adiponectin ratio and prostate cancer stage. No strong associations of adiponectin, leptin, or leptin:adiponectin ratio with grade were seen. This study provides some evidence that adiponectin levels may be associated with prostate cancer stage, dependent on the degree of adiposity of the man. Our results are consistent with adiponectin countering the adverse effects of obesity on prostate cancer progression.

Timing of neck dissection in patients undergoing transoral robotic surgery for head and neck cancer.

PubMed

Möckelmann, N; Busch, C-J; Münscher, A; Knecht, R; Lörincz, B B

2015-06-01

Oncologic transoral robotic surgery (TORS) requires in most cases the concurrent or staged surgical treatment of the regional lymph nodes in the neck as well. The purpose of this study was to determine whether the timing of the regional lymphadenectomy (neck dissection) has an impact on the surgical outcomes and on the complication rates. Single-institution, prospective case series with internal control group. Twenty-one patients underwent TORS and appropriate neck dissection concurrently (control group), while 20 patients underwent neck dissection in a timely staged fashion, 8.4 days (median; range, 3-28 days) following their TORS procedure (experimental group). Outcome measures included nodal yield, intraoperative pharyngocervical fistula formation, postoperative fistula formation, postoperative bleeding from the primary and from the neck dissection site, haematoma, seroma, and infection. Nodal yield values, as the oncologic quality indicator of a neck dissection, were comparable in the experimental and in the control group. Complication rates did not differ between the groups: intraoperative and postoperative fistula formation, postoperative bleeding, haematoma and seroma rates were similarly low in the two groups. There was no infection in either group. In the present cohort of 41 TORS-patients, the timing of neck dissection did not make a significant difference in the outcomes. We suggest therefore that aspiring and established TORS-teams do not restrict their appropriate indications due to robotic slot and theatre time constraints, but perform each indicated TORS-case as soon as possible within their given systems, even if the neck dissections cannot be done on the same day. Copyright © 2015 Elsevier Ltd. All rights reserved.

Determining Relationships between Young Children's Cognitive Stage of Development and Art Stage of Development as They Relate to Literacy.

ERIC Educational Resources Information Center

Hale, Judy A.

The primary purpose of this study was to investigate how children's responses to literature can help develop literacy. The subjects were 15 first-grade students at Overstreet Elementary School in Starkville (Mississippi). Two school observations were carried out prior to the collection of data on individual students. Case studies were conducted…

Effect of Topical Estrogen in the Mangement of Traumatic Facial Wounds

PubMed Central

Ghazizadeh Hashemi, Seyed Amirhosein; Barati, Behrooz; Mohammadi, Hosein; Saeidi, Masumeh; Bahreini, Abbas; Kiani, Mohammad Ali

2016-01-01

Introduction: Acute skin wound healing is a complicated process comprising various phases. Recent animal studies have shown that steroid sex hormones such as estrogen maybe helpful in the regulation of several pathophysiologic stages that are involved in wound healing. In this study we examined the effects of topical estrogen in the treatment of traumatic facial wounds. Materials and Methods: Patients referred to Luqman Hospital, Tehran with traumatic wounds were enrolled in this case-control study into two groups of equal size. From the second week of the study, topical estrogen (0.625 mg conjugated topical estrogen ointment) was administered in the case group, while the control group received a Eucerin dressing only. The two groups were then compared in terms of wound healing rate on Day 7,14, and 30. Results: Thirty patients with mean age of 16.02+36.23 years were compared in the control and estrogen-treated groups. After treatment, no scars or keloids were observed in either group. The wound area in the estrogen group was lower than that in the control group on Day 14 and 30, but the difference was not significant (P>0.05). Healing rates in the control group on Day 14 (7.1+42.3 vs.50.3+4.9 mm2) and Day 30 (1.9+93.5 vs. + 97.3+0.6 mm2) (were lower than those in the estrogen group, but the differences were not significant (P>0.05). Findings show that the required time for wound healing in the estrogen-treated group was lower than that in the control group, but the difference was not significant (P>0.05). Conclusion: Based on this study, topical estrogen has no effect on the rate of wound healing or the rate of wound area. PMID:26878003

Effect of Topical Estrogen in the Mangement of Traumatic Facial Wounds.

PubMed

Ghazizadeh Hashemi, Seyed Amirhosein; Barati, Behrooz; Mohammadi, Hosein; Saeidi, Masumeh; Bahreini, Abbas; Kiani, Mohammad Ali

2016-01-01

Acute skin wound healing is a complicated process comprising various phases. Recent animal studies have shown that steroid sex hormones such as estrogen maybe helpful in the regulation of several pathophysiologic stages that are involved in wound healing. In this study we examined the effects of topical estrogen in the treatment of traumatic facial wounds. Patients referred to Luqman Hospital, Tehran with traumatic wounds were enrolled in this case-control study into two groups of equal size. From the second week of the study, topical estrogen (0.625 mg conjugated topical estrogen ointment) was administered in the case group, while the control group received a Eucerin dressing only. The two groups were then compared in terms of wound healing rate on Day 7,14, and 30. Thirty patients with mean age of 16.02+36.23 years were compared in the control and estrogen-treated groups. After treatment, no scars or keloids were observed in either group. The wound area in the estrogen group was lower than that in the control group on Day 14 and 30, but the difference was not significant (P>0.05). Healing rates in the control group on Day 14 (7.1+42.3 vs.50.3+4.9 mm2) and Day 30 (1.9+93.5 vs. + 97.3+0.6 mm2) (were lower than those in the estrogen group, but the differences were not significant (P>0.05). Findings show that the required time for wound healing in the estrogen-treated group was lower than that in the control group, but the difference was not significant (P>0.05). Based on this study, topical estrogen has no effect on the rate of wound healing or the rate of wound area.

The writing process: A powerful approach for the language-disabled student.

PubMed

Moulton, J R; Bader, M S

1985-01-01

Our understanding of the writing process can be a powerful tool for teaching language-disabled students the "how" of writing. Direct, explicit instruction in writing process helps these students learn to explore their ideas and to manage the multiple demands of writing. A case study of one student, Jeff, demonstrates how we structure the stages of writing: prewriting, planning, drafting, revising, and proofreading. When these stages are clearly defined and involve specific skills, language-disabled students can reach beyond their limitations and strengthen their expression. The case study of Jeff reveals the development of his sense of control and his regard for himself as a writer.

Accelerated Monte Carlo Simulation on the Chemical Stage in Water Radiolysis using GPU

PubMed Central

Tian, Zhen; Jiang, Steve B.; Jia, Xun

2018-01-01

The accurate simulation of water radiolysis is an important step to understand the mechanisms of radiobiology and quantitatively test some hypotheses regarding radiobiological effects. However, the simulation of water radiolysis is highly time consuming, taking hours or even days to be completed by a conventional CPU processor. This time limitation hinders cell-level simulations for a number of research studies. We recently initiated efforts to develop gMicroMC, a GPU-based fast microscopic MC simulation package for water radiolysis. The first step of this project focused on accelerating the simulation of the chemical stage, the most time consuming stage in the entire water radiolysis process. A GPU-friendly parallelization strategy was designed to address the highly correlated many-body simulation problem caused by the mutual competitive chemical reactions between the radiolytic molecules. Two cases were tested, using a 750 keV electron and a 5 MeV proton incident in pure water, respectively. The time-dependent yields of all the radiolytic species during the chemical stage were used to evaluate the accuracy of the simulation. The relative differences between our simulation and the Geant4-DNA simulation were on average 5.3% and 4.4% for the two cases. Our package, executed on an Nvidia Titan black GPU card, successfully completed the chemical stage simulation of the two cases within 599.2 s and 489.0 s. As compared with Geant4-DNA that was executed on an Intel i7-5500U CPU processor and needed 28.6 h and 26.8 h for the two cases using a single CPU core, our package achieved a speed-up factor of 171.1-197.2. PMID:28323637

Accelerated Monte Carlo simulation on the chemical stage in water radiolysis using GPU

NASA Astrophysics Data System (ADS)

Tian, Zhen; Jiang, Steve B.; Jia, Xun

2017-04-01

The accurate simulation of water radiolysis is an important step to understand the mechanisms of radiobiology and quantitatively test some hypotheses regarding radiobiological effects. However, the simulation of water radiolysis is highly time consuming, taking hours or even days to be completed by a conventional CPU processor. This time limitation hinders cell-level simulations for a number of research studies. We recently initiated efforts to develop gMicroMC, a GPU-based fast microscopic MC simulation package for water radiolysis. The first step of this project focused on accelerating the simulation of the chemical stage, the most time consuming stage in the entire water radiolysis process. A GPU-friendly parallelization strategy was designed to address the highly correlated many-body simulation problem caused by the mutual competitive chemical reactions between the radiolytic molecules. Two cases were tested, using a 750 keV electron and a 5 MeV proton incident in pure water, respectively. The time-dependent yields of all the radiolytic species during the chemical stage were used to evaluate the accuracy of the simulation. The relative differences between our simulation and the Geant4-DNA simulation were on average 5.3% and 4.4% for the two cases. Our package, executed on an Nvidia Titan black GPU card, successfully completed the chemical stage simulation of the two cases within 599.2 s and 489.0 s. As compared with Geant4-DNA that was executed on an Intel i7-5500U CPU processor and needed 28.6 h and 26.8 h for the two cases using a single CPU core, our package achieved a speed-up factor of 171.1-197.2.

Accelerated Monte Carlo simulation on the chemical stage in water radiolysis using GPU.

PubMed

Tian, Zhen; Jiang, Steve B; Jia, Xun

2017-04-21

The accurate simulation of water radiolysis is an important step to understand the mechanisms of radiobiology and quantitatively test some hypotheses regarding radiobiological effects. However, the simulation of water radiolysis is highly time consuming, taking hours or even days to be completed by a conventional CPU processor. This time limitation hinders cell-level simulations for a number of research studies. We recently initiated efforts to develop gMicroMC, a GPU-based fast microscopic MC simulation package for water radiolysis. The first step of this project focused on accelerating the simulation of the chemical stage, the most time consuming stage in the entire water radiolysis process. A GPU-friendly parallelization strategy was designed to address the highly correlated many-body simulation problem caused by the mutual competitive chemical reactions between the radiolytic molecules. Two cases were tested, using a 750 keV electron and a 5 MeV proton incident in pure water, respectively. The time-dependent yields of all the radiolytic species during the chemical stage were used to evaluate the accuracy of the simulation. The relative differences between our simulation and the Geant4-DNA simulation were on average 5.3% and 4.4% for the two cases. Our package, executed on an Nvidia Titan black GPU card, successfully completed the chemical stage simulation of the two cases within 599.2 s and 489.0 s. As compared with Geant4-DNA that was executed on an Intel i7-5500U CPU processor and needed 28.6 h and 26.8 h for the two cases using a single CPU core, our package achieved a speed-up factor of 171.1-197.2.

The role of Leptospira spp. in horses affected with recurrent uveitis in the UK.

PubMed

Malalana, F; Blundell, R J; Pinchbeck, G L; Mcgowan, C M

2017-11-01

Equine recurrent uveitis (ERU) is a common cause of ocular pain and blindness in horses. Leptospira spp. have been commonly implicated in the pathophysiology of ERU in mainland Europe and the USA. No recent studies have been carried out in the UK, but Leptospira is reported not to be a major factor in the aetiology of ERU in the UK. To establish the prevalence of Leptospira-associated ERU in the UK and to identify the serovars involved in these cases; to compare serum vs. aqueous humour antibody levels in cases and controls in order to confirm the diagnosis of Leptospira-associated ERU, and to assess the usefulness of serology alone as a confirmatory test for Leptospira-associated ERU in the UK. Case-control study. Eyes enucleated for clinical reasons in ERU-affected horses were collected. Blood and aqueous humour were obtained to determine antibody levels against a variety of Leptospira serovars and C-values (aqueous humour value/serum value) were calculated. In addition, eyes, blood and aqueous humour were obtained from control cases for comparison. Histopathology was performed in all eyes to confirm uveitis in each case. Differences in seroprevalences between ERU and control cases and between Leptospira- and non-Leptospira-associated ERU cases were calculated. A total of 30 ERU and 43 control eyes were analysed. Of the ERU eyes, only two had a C-value of >4 (prevalence of Leptospira-associated uveitis: 6.7%). Serovars hardjo and javanica were detected. There was no difference in seroprevalence between horses with uveitis and control cases (65.5% and 41.9%, respectively; P = 0.11) or between Leptospira- and non-Leptospira-associated uveitis cases (100% and 63.0%, respectively; P = 0.52). The study was limited by low case numbers. Eyes were presented at different stages of disease. The only test used to detect Leptospira was the microscopic agglutination test. Leptospira-associated ERU is uncommon in the UK. Serology alone may not help to definitively diagnose Leptospira-associated uveitis in this country. © 2017 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.

Preliminary study on the treatment of vitiligo with carbon dioxide fractional laser together with tacrolimus.

PubMed

Chen, Wei; Zhou, Yuan; Huang, Fei-Ran; Luo, Dan; Wang, Da-Guang

2018-04-10

Tacrolimus is a conventional medication for the treatment of vitiligo, but the effect of a single medication is limited. This paper aims at observing the effects, adverse responses, and repigmentation results of the joint treatment of vitiligo by Carbon dioxide (CO 2 ) fractional laser together with tacrolimus. Forty-five patients with vitiligo were randomly divided into two groups: treatment (T) group and control (C) group, and each group was further divided into three subgroups (face, torso and limbs, and hand and foot) according to the location of the skin defect. Both groups used topical 0.1% tacrolimus cream, but the T group was given one CO 2 fractional laser treatment each month. We observed the clinical efficacy, adverse responses, and repigmentation results after 6 months. Compared to the C group, the T group showed better improvement in both objective and subjective assessments. When the treatment time was increased, the efficacy was also improved, and the repigmentation in the T group occured in three ways: perifollicular repigmentation, marginal repigmentation and diffuse repigmentation. There were three cases of isomorphic responses (2 cases in the rapid progression stage, one case in the progression stage), and 1 case formed scarring on the neck in the T group. The treatment of vitiligo by CO 2 fractional laser together with tacrolimus is significantly effective and is most suitable for patients in the progression stage. Patients in the rapid progression stage should use this approach with caution, and its efficacy was limited for patients in the stable stage. An extended course of treatment is helpful for the repigmentation of white patches. All three forms of repigmentation can occur in the joint treatment of vitiligo by CO 2 fractional laser together with tacrolimus. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Stage-oriented comprehensive acupuncture treatment plus rehabilitation training for apoplectic hemiplegia.

PubMed

Mao, Min; Chen, Xin; Chen, Yuefeng; Rao, Ping; Liu, Jian

2008-06-01

To study the effect of stage-oriented comprehensive acupuncture treatment plus rehabilitation training for the recovery of apoplectic hemiplegia. The 60 cases of acute apoplectic hemiplegia were divided randomly into the treatment and control groups with 30 in each. Based on the routine medication, acupuncture combined with modern rehabilitation techniques was applied for the treatment group, while only rehabilitation treatment for the control group. Before and three months after treatment, the evaluation was done on the motor function and daily life ability for both groups respectively with simplified Fugl-Meyer Evaluation and modified Barthel index. The therapeutic effect of treatment group was significantly superior to that of the control group (P < 0.05). Based on Brunnstrom's theory of six-stage in the recovery of hemiplegia, the effect of stage-oriented comprehensive acupuncture therapy combined with rehabilitation training is very good, helpful in raising the daily life ability of patients.

Genome-Wide Association Analysis of Young-Onset Stroke Identifies a Locus on Chromosome 10q25 Near HABP2.

PubMed

Cheng, Yu-Ching; Stanne, Tara M; Giese, Anne-Katrin; Ho, Weang Kee; Traylor, Matthew; Amouyel, Philippe; Holliday, Elizabeth G; Malik, Rainer; Xu, Huichun; Kittner, Steven J; Cole, John W; O'Connell, Jeffrey R; Danesh, John; Rasheed, Asif; Zhao, Wei; Engelter, Stefan; Grond-Ginsbach, Caspar; Kamatani, Yoichiro; Lathrop, Mark; Leys, Didier; Thijs, Vincent; Metso, Tiina M; Tatlisumak, Turgut; Pezzini, Alessandro; Parati, Eugenio A; Norrving, Bo; Bevan, Steve; Rothwell, Peter M; Sudlow, Cathie; Slowik, Agnieszka; Lindgren, Arne; Walters, Matthew R; Jannes, Jim; Shen, Jess; Crosslin, David; Doheny, Kimberly; Laurie, Cathy C; Kanse, Sandip M; Bis, Joshua C; Fornage, Myriam; Mosley, Thomas H; Hopewell, Jemma C; Strauch, Konstantin; Müller-Nurasyid, Martina; Gieger, Christian; Waldenberger, Melanie; Peters, Annette; Meisinger, Christine; Ikram, M Arfan; Longstreth, W T; Meschia, James F; Seshadri, Sudha; Sharma, Pankaj; Worrall, Bradford; Jern, Christina; Levi, Christopher; Dichgans, Martin; Boncoraglio, Giorgio B; Markus, Hugh S; Debette, Stephanie; Rolfs, Arndt; Saleheen, Danish; Mitchell, Braxton D

2016-02-01

Although a genetic contribution to ischemic stroke is well recognized, only a handful of stroke loci have been identified by large-scale genetic association studies to date. Hypothesizing that genetic effects might be stronger for early- versus late-onset stroke, we conducted a 2-stage meta-analysis of genome-wide association studies, focusing on stroke cases with an age of onset <60 years. The discovery stage of our genome-wide association studies included 4505 cases and 21 968 controls of European, South-Asian, and African ancestry, drawn from 6 studies. In Stage 2, we selected the lead genetic variants at loci with association P<5×10(-6) and performed in silico association analyses in an independent sample of ≤1003 cases and 7745 controls. One stroke susceptibility locus at 10q25 reached genome-wide significance in the combined analysis of all samples from the discovery and follow-up stages (rs11196288; odds ratio =1.41; P=9.5×10(-9)). The associated locus is in an intergenic region between TCF7L2 and HABP2. In a further analysis in an independent sample, we found that 2 single nucleotide polymorphisms in high linkage disequilibrium with rs11196288 were significantly associated with total plasma factor VII-activating protease levels, a product of HABP2. HABP2, which encodes an extracellular serine protease involved in coagulation, fibrinolysis, and inflammatory pathways, may be a genetic susceptibility locus for early-onset stroke. © 2016 American Heart Association, Inc.

Acrylamide exposure measured by food frequency questionnaire and hemoglobin adduct levels and prostate cancer risk in the Cancer of the Prostate in Sweden Study

PubMed Central

Wilson, Kathryn M.; Bälter, Katarina; Adami, Hans-Olov; Grönberg, Henrik; Vikström, Anna C.; Paulsson, Birgit; Törnqvist, Margareta; Mucci, Lorelei A.

2010-01-01

Acrylamide, a probable human carcinogen, is formed during the cooking of many commonly consumed foods. Data are scant on whether dietary acrylamide represents an important cancer risk in humans. We studied the association between acrylamide and prostate cancer risk using two measures of acrylamide exposure: intake from a food frequency questionnaire (FFQ) and acrylamide adducts to hemoglobin. We also studied the correlation between these two exposure measures. We used data from the population-based case-control study Cancer of the Prostate in Sweden (CAPS). Dietary data was available for 1499 cases and 1118 controls. Hemoglobin adducts of acrylamide were measured in blood samples from a subset of 170 cases and 161 controls. We calculated odds ratios (ORs) for the risk of prostate cancer in high versus low quantiles of acrylamide exposure using logistic regression. The correlation between FFQ acrylamide intake and acrylamide adducts in non-smokers was 0.25 (95% confidence interval: 0.14–0.35), adjusted for age, region, energy intake, and laboratory batch. Among controls the correlation was 0.35 (95% CI: 0.21–0.48); among cases it was 0.15 (95% CI: 0.00–0.30). The OR of prostate cancer for the highest versus lowest quartile of acrylamide adducts was 0.93 (95% CI: 0.47–1.85, p-value for trend=0.98). For FFQ acrylamide, the OR of prostate cancer for the highest versus lowest quintile was 0.97 (95% CI: 0.75–1.27, p trend=0.67). No significant associations were found between acrylamide exposure and risk of prostate cancer by stage, grade, or PSA level. Acrylamide adducts to hemoglobin and FFQ-measured acrylamide intake were moderately correlated. Neither measure of acrylamide exposure – hemoglobin adducts or FFQ – was associated with risk of prostate cancer. PMID:19142870

Influence of the Size of Cohorts in Adaptive Design for Nonlinear Mixed Effects Models: An Evaluation by Simulation for a Pharmacokinetic and Pharmacodynamic Model for a Biomarker in Oncology

PubMed Central

Lestini, Giulia; Dumont, Cyrielle; Mentré, France

2015-01-01

Purpose In this study we aimed to evaluate adaptive designs (ADs) by clinical trial simulation for a pharmacokinetic-pharmacodynamic model in oncology and to compare them with one-stage designs, i.e. when no adaptation is performed, using wrong prior parameters. Methods We evaluated two one-stage designs, ξ0 and ξ*, optimised for prior and true population parameters, Ψ0 and Ψ*, and several ADs (two-, three- and five-stage). All designs had 50 patients. For ADs, the first cohort design was ξ0. The next cohort design was optimised using prior information updated from the previous cohort. Optimal design was based on the determinant of the Fisher information matrix using PFIM. Design evaluation was performed by clinical trial simulations using data simulated from Ψ*. Results Estimation results of two-stage ADs and ξ* were close and much better than those obtained with ξ0. The balanced two-stage AD performed better than two-stage ADs with different cohort sizes. Three-and five-stage ADs were better than two-stage with small first cohort, but not better than the balanced two-stage design. Conclusions Two-stage ADs are useful when prior parameters are unreliable. In case of small first cohort, more adaptations are needed but these designs are complex to implement. PMID:26123680

Influence of the Size of Cohorts in Adaptive Design for Nonlinear Mixed Effects Models: An Evaluation by Simulation for a Pharmacokinetic and Pharmacodynamic Model for a Biomarker in Oncology.

PubMed

Lestini, Giulia; Dumont, Cyrielle; Mentré, France

2015-10-01

In this study we aimed to evaluate adaptive designs (ADs) by clinical trial simulation for a pharmacokinetic-pharmacodynamic model in oncology and to compare them with one-stage designs, i.e., when no adaptation is performed, using wrong prior parameters. We evaluated two one-stage designs, ξ0 and ξ*, optimised for prior and true population parameters, Ψ0 and Ψ*, and several ADs (two-, three- and five-stage). All designs had 50 patients. For ADs, the first cohort design was ξ0. The next cohort design was optimised using prior information updated from the previous cohort. Optimal design was based on the determinant of the Fisher information matrix using PFIM. Design evaluation was performed by clinical trial simulations using data simulated from Ψ*. Estimation results of two-stage ADs and ξ * were close and much better than those obtained with ξ 0. The balanced two-stage AD performed better than two-stage ADs with different cohort sizes. Three- and five-stage ADs were better than two-stage with small first cohort, but not better than the balanced two-stage design. Two-stage ADs are useful when prior parameters are unreliable. In case of small first cohort, more adaptations are needed but these designs are complex to implement.

Metacarpal lengthening in children: comparison of three different techniques in 15 consecutive cases.

PubMed

Dana, C; Aurégan, J-C; Salon, A; Guéro, S; Glorion, C; Pannier, S

2016-09-22

Metacarpal lengthening is a useful procedure to address hand deficiencies in children. In this study, we aimed to compare the results of three different techniques from one consecutive clinical series of hand deficiencies. A total of 15 metacarpal lengthenings have been performed in 12 children aged from 9 to 14 years. The callotasis technique was used in seven cases, the two-stage distraction-graft technique in four cases and the single-stage lengthening in four cases. All the metacarpals healed with bone. The lengthening obtained was a mean of 13 mm (range 8-21 mm), a mean of 22 mm (range 13-32 mm) and a mean of 12 mm (range 9-15 mm), respectively, in the three different techniques. The healing index was longer for callotasis (81 days/cm) compared with the other techniques (41 days/cm and 46 days/cm, respectively). We observed one case of fracture after callotasis and one after distraction-graft. One patient underwent tenolysis of the extensor mechanism after single-stage lengthening. In conclusion, distraction graft and single-stage lengthening may be valuable alternatives to callotasis. IV; therapeutic study; multi-case series. © The Author(s) 2016.

Oocyte competence in in vitro fertilization and intracytoplasmic sperm injection patients suffering from endometriosis and its possible association with subsequent treatment outcome: a matched case-control study.

PubMed

Shebl, Omar; Sifferlinger, Ida; Habelsberger, Alwin; Oppelt, Peter; Mayer, Richard B; Petek, Erwin; Ebner, Thomas

2017-06-01

Endometriosis affects up to 15% of women of reproductive age. There is an obvious lack of studies dealing with morphological parameters of oocyte morphology in endometriosis patients in assisted reproduction. One aim of the study is to describe oocyte morphology in patients undergoing intracytoplasmic sperm injection suffering from endometriosis. In addition, the impact of endometriosis on in vitro fertilization results is analyzed. Both in vitro fertilization and intracytoplasmic sperm injection patients are then matched with an endometriosis-free control group for highlighting the possible association of endometriosis with pregnancy outcome. Oocyte morphology of endometriosis patients was assessed in two groups. Both study group and control group consisted of 129 in vitro fertilization/intracytoplasmic sperm injection cycles each. Patients were matched according to anti-Müllerian hormone, female age, previous treatment cycles, and method of fertilization. Endometriosis was graded according to the revised American Society for Reproductive Medicine guidelines of 1997. Patients with endometriosis had a significantly lower rate of mature oocytes (p < 0.03) and morphologically normal oocytes (p < 0.001). In particular, brownish oocytes (p < 0.009; stage I-IV) and the presence of refractile bodies (p < 0.001; stage IV) were found to be increased. Endometriosis stage IV was associated with significantly worse-quality oocytes than stages I-III (p < 0.01). Fertilization was significantly reduced in conventional in vitro fertilization but not in intracytoplasmic sperm injection (p < 0.03). This was due to lower fertilization rates in stage III-IV endometriosis compared with stage I-II (p < 0.04). No difference was observed with respect to rates of implantation, clinical pregnancy, miscarriage, live birth, and malformation. Endometriosis patients, in particular those with severe endometriosis, present lower-quality oocytes. Once fertilized, no impairment of further preimplantation embryo development and pregnancy outcome right up to healthy live birth rate has to be expected. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

New application of 18F-fluoride PET for the detection of bone remodeling in early-stage osteoarthritis of the hip.

PubMed

Kobayashi, Naomi; Inaba, Yutaka; Tateishi, Ukihide; Yukizawa, Yohei; Ike, Hiroyuki; Inoue, Tomio; Saito, Tomoyuki

2013-10-01

Recent studies have reported the acceleration of subchondral bone remodeling during the development of osteoarthritis (OA). However, it is not possible to evaluate such molecular abnormalities using conventional radiographic techniques. We have applied 18F-fluoride PET to the analysis of painful or dysplastic hips at various stages of OA and then compared this with radiographic findings and clinical findings. A consecutive series of 65 joints from 48 patients (average age, 40 years; range, 19-72 years) with a hip joint complaint or radiographic dysplastic hip were enrolled in this study. Twenty-five contralateral joints without any evidence of OA or clinical symptoms were assigned as a normal control group. Radiographic evaluations were performed on the basis of Kellgren and Lawrence grade and the minimum joint space. Clinical evaluations were performed using the grading scale for pain severity and the SUVmax was measured for each joint. The association between SUVmax and the radiographic or clinical findings was evaluated. 18F-fluoride PET shows a significantly higher uptake value for progressive-stage OA cases than for early-stage cases and also shows a significantly higher uptake value in cases with severe pain. Even in early-OA-stage patients who do not show joint space narrowing on a plain x-ray, cases with severe pain show a significantly higher uptake value. 18F-fluoride PET has great potential as an imaging method for diagnosing early-stage OA without any marked radiographic changes.

Robust Frequency-Domain Constrained Feedback Design via a Two-Stage Heuristic Approach.

PubMed

Li, Xianwei; Gao, Huijun

2015-10-01

Based on a two-stage heuristic method, this paper is concerned with the design of robust feedback controllers with restricted frequency-domain specifications (RFDSs) for uncertain linear discrete-time systems. Polytopic uncertainties are assumed to enter all the system matrices, while RFDSs are motivated by the fact that practical design specifications are often described in restricted finite frequency ranges. Dilated multipliers are first introduced to relax the generalized Kalman-Yakubovich-Popov lemma for output feedback controller synthesis and robust performance analysis. Then a two-stage approach to output feedback controller synthesis is proposed: at the first stage, a robust full-information (FI) controller is designed, which is used to construct a required output feedback controller at the second stage. To improve the solvability of the synthesis method, heuristic iterative algorithms are further formulated for exploring the feedback gain and optimizing the initial FI controller at the individual stage. The effectiveness of the proposed design method is finally demonstrated by the application to active control of suspension systems.

Genome-wide association studies suggest that APOL1-environment interactions more likely trigger kidney disease in African Americans with nondiabetic nephropathy than strong APOL1-second gene interactions.

PubMed

Langefeld, Carl D; Comeau, Mary E; Ng, Maggie C Y; Guan, Meijian; Dimitrov, Latchezar; Mudgal, Poorva; Spainhour, Mitzie H; Julian, Bruce A; Edberg, Jeffrey C; Croker, Jennifer A; Divers, Jasmin; Hicks, Pamela J; Bowden, Donald W; Chan, Gary C; Ma, Lijun; Palmer, Nicholette D; Kimberly, Robert P; Freedman, Barry I

2018-06-06

African Americans carrying two apolipoprotein L1 gene (APOL1) renal risk variants have a high risk for nephropathy. However, only a minority develops end-stage renal disease (ESRD). Hence, modifying factors likely contribute to initiation of kidney disease such as endogenous (HIV infection) or exogenous (interferon treatment) environmental modifiers. In this report, genome-wide association studies and a meta-analysis were performed to identify novel loci for nondiabetic ESRD in African Americans and to detect genetic modifiers in APOL1-associated nephropathy. Two African American cohorts were analyzed, 1749 nondiabetic ESRD cases and 1136 controls from Wake Forest and 901 lupus nephritis (LN)-ESRD cases and 520 controls with systemic lupus erythematosus but lacking nephropathy from the LN-ESRD Consortium. Association analyses adjusting for APOL1 G1/G2 renal-risk variants were completed and stratified by APOL1 risk genotype status. Individual genome-wide association studies and meta-analysis results of all 2650 ESRD cases and 1656 controls did not detect significant genome-wide associations with ESRD beyond APOL1. Similarly, no single nucleotide polymorphism showed significant genome-wide evidence of an interaction with APOL1 risk variants. Thus, although variants with small individual effects cannot be ruled out and are likely to exist, our results suggest that APOL1-environment interactions may be of greater clinical importance in triggering nephropathy in African Americans than APOL1 interactions with other single nucleotide polymorphisms. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

[Two Cases of Laparoscopic Resection of Colon Cancer Manifested by Liver Abscess].

PubMed

Ohashi, Motonari; Iwama, Masahiro; Ikenaga, Shojirokazunori; Yokoyama, Makoto

2017-11-01

We report 2 cases of laparoscopic surgery for patients who had liver abscess as the initial manifestation of underlying colon cancer. The first case was in an 80-year-old woman who presented to our hospital with a diagnosis ofliver abscess. Percutaneous transhepatic abscess drainage(PTAD)was performed as initial treatment. Subsequent colonoscopy revealed a type 1 tumor in the cecum, and biopsy results ofthe mass indicated adenocarcinoma. The patient underwent laparoscopic right hemicolectomy as curative treatment. The pathological findings were as follows: tub1, T2, N0, M0 and Stage I . Two years later, she remains disease free. The second case was in a 59-year-old man with liver abscess. Colonoscopy also revealed a type 2 tumor in the sigmoid colon. After treatment of the liver abscess with PTAD, laparoscopic sigmoidectomy was performed with a preoperative diagnosis of sigmoid colon cancer. The pathological findings were as follows: tub2, T3, N0, M0 and Stage II . Lung metastases appeared 10 months after surgery, and systemic chemotherapy was administered. In conclusion, liver abscess is occasionally caused by malignancy, and complete gastrointestinal evaluation should be conducted. Laparoscopic radical surgery can be safely performed in cases in which the liver abscesses are controlled.

Comparisons of serum miRNA expression profiles in patients with diabetic retinopathy and type 2 diabetes mellitus.

PubMed

Ma, Jianping; Wang, Jufang; Liu, Yanfen; Wang, Changyi; Duan, Donghui; Lu, Nanjia; Wang, Kaiyue; Zhang, Lu; Gu, Kaibo; Chen, Sihan; Zhang, Tao; You, Dingyun; Han, Liyuan

2017-02-01

The aim of this study was to compare the expression levels of serum miRNAs in diabetic retinopathy and type 2 diabetes mellitus. Serum miRNA expression profiles from diabetic retinopathy cases (type 2 diabetes mellitus patients with diabetic retinopathy) and type 2 diabetes mellitus controls (type 2 diabetes mellitus patients without diabetic retinopathy) were examined by miRNA-specific microarray analysis. Quantitative real-time polymerase chain reaction was used to validate the significantly differentially expressed serum miRNAs from the microarray analysis of 45 diabetic retinopathy cases and 45 age-, sex-, body mass index- and duration-of-diabetes-matched type 2 diabetes mellitus controls. The relative changes in serum miRNA expression levels were analyzed using the 2-ΔΔCt method. A total of 5 diabetic retinopathy cases and 5 type 2 diabetes mellitus controls were included in the miRNA-specific microarray analysis. The serum levels of miR-3939 and miR-1910-3p differed significantly between the two groups in the screening stage; however, quantitative real-time polymerase chain reaction did not reveal significant differences in miRNA expression for 45 diabetic retinopathy cases and their matched type 2 diabetes mellitus controls. Our findings indicate that miR-3939 and miR-1910-3p may not play important roles in the development of diabetic retinopathy; however, studies with a larger sample size are needed to confirm our findings.

Percutaneously drilling through femoral head and neck fenestration combining with compacted autograft for early femoral head necrosis: A retrospective study.

PubMed

Li, Donghai; Xie, Xiaowei; Kang, Pengde; Shen, Bin; Pei, Fuxing; Wang, Changde

2017-11-01

The purpose of this study was to evaluate the clinical results, survivorship and quick rehabilitation effects of modified surgery of percutaneously drilling and decompression through femoral head and neck fenestration combined with compacted autograft for early femoral head necrosis. We conducted a retrospective cohort study with 83 hips performed percutaneous decompression through femoral head and neck fenestration (Modified group) combined with autogenous bone grafting for early ONFH. For comparison, another 90 hips treated with conventional core decompression with bone grafting (Control group). Median follow-up was 36 months (32-44 months). The length of incision, blood loss in operation, incision drainage, operation time and hospital stays in Modified group had better results than those in control group (P < 0.001). There were four cases in Modified group and five cases in control group had complications (P = 0.9). The VAS score and range of hip motion were better in Modified group during hospital stays summarily (P < 0.05). The average Harris score in modified group was higher than the control group at the first month (P = 0.005), while at other time of follow-up the two groups were with similar Harris scores (P > 0.05). There were 22 hips progressed to stage III in Modified group, while 23 hips progressed to stage III in control group (P = 0.89). The clinical success rate in Modified group were 86.7%, compared with that in control group (87.8%) ( P= 0.84). Percutaneous drilling and decompression through femoral head and neck fenestration combined with compacted autograft we reported showed an good surgical effect with a quick rehabilitation and had similar short-term effects compared with the conventional core decompression in treatment of early ONFH. Copyright © 2017 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

Systems Thinking Tools for Improving Evidence-Based Practice: A Cross-Case Analysis of Two High School Leadership Teams

ERIC Educational Resources Information Center

Kensler, Lisa A. W.; Reames, Ellen; Murray, John; Patrick, Lynne

2012-01-01

Teachers and administrators have access to large volumes of data but research suggests that they lack the skills to use data effectively for continuous school improvement. This study involved a cross-case analysis of two high school leadership teams' early stages of evidence-based practice development; differing forms of external support were…

The effects of EGF and IGF-1 on FSH-mediated in vitro maturation of domestic cat oocytes derived from follicular and luteal stages.

PubMed

Yıldırım, Koray; Vural, M Rıfat; Küplülü, Sükrü; Ozcan, Ziya; Polat, I Mert

2014-04-01

The objective of this study was to evaluate the influence of epidermal growth factor (EGF) and insulin like growth factor-I (IGF-1) on the in vitro maturation of cat oocytes recovered from follicular and luteal stage ovaries. Oocytes from follicular (n=580) and luteal (n=209) stages were harvested and divided into four groups, which were cultured in FSH-mediated maturation medium supplemented with: (1) EGF alone (25ng/mL); (2) IGF-1 alone (100ng/mL); (3) EGF+IGF-1 (25ng/mL EGF+100ng/mL IGF-I); or (4) no growth factor (control). The proportion of follicular stage oocytes reaching the metaphase II stage was significantly higher than that of oocytes obtained at the luteal stage in both control and study groups (p<0.001). The percentages of oocytes reaching the metaphase II stage during the follicular period were 62.6% in control; 70.9% in EGF; 72.8% in IGF-1, and 78.1% in EGF+IGF-1 groups, whereas the respective values for gametes collected from luteal stage ovaries were 12.5%, 17.5%, 12.5%, and 16.9%. Additionally, the differences between the study and control groups were significant in the case of follicular stage oocytes. Finally, supplementing the maturation medium with EGF and/or IGF-1 significantly enhanced the meiotic maturation of oocytes recovered from follicular stage ovaries. The present study also demonstrated that the combination of EGF and IGF-I provides an additional or synergic effect on meiotic maturation of oocytes recovered from the follicular stage. Copyright © 2014 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Attention and Working Memory-Related EEG Markers of Subtle Cognitive Deterioration in Healthy Elderly Individuals.

PubMed

Deiber, Marie-Pierre; Meziane, Hadj Boumediene; Hasler, Roland; Rodriguez, Cristelle; Toma, Simona; Ackermann, Marine; Herrmann, François; Giannakopoulos, Panteleimon

2015-01-01

Future treatments of Alzheimer's disease need the identification of cases at high risk at the preclinical stage of the disease before the development of irreversible structural damage. We investigated here whether subtle cognitive deterioration in a population of healthy elderly individuals could be predicted by EEG signals at baseline under cognitive activation. Continuous EEG was recorded in 97 elderly control subjects and 45 age-matched mild cognitive impairment (MCI) cases during a simple attentional and a 2-back working memory task. Upon 18-month neuropsychological follow-up, the final sample included 55 stable (sCON) and 42 deteriorated (dCON) controls. We examined the P1, N1, P3, and PNwm event-related components as well as the oscillatory activities in the theta (4-7 Hz), alpha (8-13 Hz), and beta (14-25 Hz) frequency ranges (ERD/ERS: event-related desynchronization/synchronization, and ITC: inter-trial coherence). Behavioral performance, P1, and N1 components were comparable in all groups. The P3, PNwm, and all oscillatory activity indices were altered in MCI cases compared to controls. Only three EEG indices distinguished the two control groups: alpha and beta ERD (dCON >  sCON) and beta ITC (dCON <  sCON). These findings show that subtle cognitive deterioration has no impact on EEG indices associated with perception, discrimination, and working memory processes but mostly affects attention, resulting in an enhanced recruitment of attentional resources. In addition, cognitive decline alters neural firing synchronization at high frequencies (14-25 Hz) at early stages, and possibly affects lower frequencies (4-13 Hz) only at more severe stages.

Two-Stage Revision for Infected Total Knee Arthroplasty: Based on Autoclaving the Recycled Femoral Component and Intraoperative Molding Using Antibiotic-Impregnated Cement on the Tibial Side.

PubMed

Lee, Byoung-Joo; Kyung, Hee-Soo; Yoon, Seong-Dae

2015-09-01

The purpose of this study was to determine the degree of infection control and postoperative function for new articulating metal-on-cement spacer. A retrospective study of 19 patients (20 cases), who underwent a two-stage revision arthroplasty using mobile cement prosthesis, were followed for a minimum of 2 years. This series consisted of 16 women and 3 men, having an overall mean age of 71 years. During the first stage of revision, the femoral implant and all the adherent cement was removed, after which it was autoclaved before replacement. The tibial component was removed and a doughy state, antibiotic-impregnated cement was inserted on the tibial side. To achieve joint congruency, intraoperative molding was performed by flexing and extending the knee joint. Each patient was evaluated clinically and radiologically. The clinical assessments included range of motion, and the patients were scored as per the Hospital for Special Surgery (HSS) and Knee Society (KS) criteria. The mean range of knee joint motion was 70° prior to the first stage operation and 72° prior to the second stage revision arthroplasty; following revision arthroplasty, it was 113° at the final follow-up. The mean HSS score and KS knee and function scores were 86, 82, and 54, respectively, at the final follow-up. The success rate in terms of infection eradication was 95% (19/20 knees). No patient experienced soft tissue contracture requiring a quadriceps snip. This novel technique provides excellent radiological and clinical outcomes. It offers a high surface area of antibiotic-impregnated cement, a good range of motion between first and second stage revision surgery for the treatment of chronic infection after total knee arthroplasty, and is of a reasonable cost.

Two-stage repair for severe proximal hypospadias using oral mucosal grafts: combination of a modified Bracka method and a modified Byars flap method.

PubMed

Mitsukawa, Nobuyuki; Saiga, Atsuomi; Akita, Shinsuke; Kubota, Yoshitaka; Kuriyama, Motone; Satoh, Kaneshige

2015-02-01

One-stage repair is a conventional treatment of hypospadias. If hypospadias is severe as in the scrotal type and perineal type, penile curvature sometimes cannot be corrected by dorsal midline plication alone. In addition to resection of the urethral plate, ventral grafting becomes necessary for insufficient skin and subcutaneous tissue. In recent years, there has been renewed interest in 2-stage repair for such severe cases and salvage of failed cases with scarring. In the present study, novel 2-stage urethroplasty was performed in 6 cases to repair severe proximal hypospadias which required resection of the urethral plate. This novel method consisted of a combination of a modified Bracka method using oral mucosal grafts and a modified Byars flap of the dorsal foreskin. Good results were obtained using this novel method.

Influence of different palate repair protocols on facial growth in unilateral complete cleft lip and palate.

PubMed

Xu, Xue; Kwon, Hyuk-Jae; Shi, Bing; Zheng, Qian; Yin, Heng; Li, Chenghao

2015-01-01

To address the question of whether one- or two-stage palatal treatment protocol has fewer detrimental effects on craniofacial growth in patients aged 5 years with unilateral complete cleft lip and palate. Forty patients with non-syndromic unilateral complete cleft lip and palate (UCCLPs) who had received primary cleft lip repair at age 6-12 months and cleft palate repair at age 18-30 months were selected in this study. Eighteen UCCLP patients who received two-stage palate repair were selected as group 1, and 22 UCCLP patients who received one-stage palate repair were selected as group 2. The control group consisted of 20 patients with unilateral incomplete cleft lip (UICL patients) whose age and gender matched with UCCLP patients. A one-sample Kolmogorov-Smirnov test was used to analyze the nature of data distribution. Bonferroni test and Kruskal-Wallis H tests were used for multiple comparisons. Both case groups showed reduced maxillary sagittal length (ANS-PMP, A-PM, p < 0.05) and retrusion of the maxilla (S-Ptm, p < 0.05), A point and ANS point (Ba-N-A, Ba-N-ANS, p < 0.05). Patients treated with two-stage palate repair had a reduced posterior maxillary vertical height (R-PMP, p < 0.05). Our results indicated that maxillary sagittal length and position could be perturbed by both one- and two-stage palate repair. Vomer flap repair inhibited maxilla vertical growth. Delayed hard palate repair showed less detrimental effects on maxillary growth compared to early hard palate repair in UCCLP patients aged 5 years. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Birth preparedness, complication readiness and other determinants of place of delivery among mothers in Goba District, Bale Zone, South East Ethiopia.

PubMed

Belda, Semere Sileshi; Gebremariam, Mulugeta Betre

2016-04-06

Ethiopia is one of the countries with the highest maternal mortality ratio 676/100,000 LB and the lowest skilled delivery at birth (10%) in 2011. Skilled delivery care and provision of emergency obstetric care prevents many of these deaths. Despite implementation of birth preparedness and complication readiness packages to antenatal care users since 2007 in the study area, yet an overwhelming proportion of births take place at home. The effect of birth preparedness and complication readiness on place of delivery is not well known and studied in this context. A community based case control study preceded by initial census was conducted on a total of 358 sampled respondents (119 cases and 239 controls) who were selected using stratified two stage sampling technique. A pre-tested and standardized questionnaire with a face-to-face interview was used to collect the data, and then data was cleaned, coded and entered in to SPSS version-21 for analysis. Binary logistic regression models were run to identify predictors of place of delivery and Odds ratio with 95% CI was used to assess presence of associations at a 0.05 level of significance. The mean (± Standard Deviation) age of respondents was; 27.41(±5.8) and 28.84(±5.7) years for the cases and the controls respectively. Two third (67.1%) of the childbirths took place in the respondents house while only (32.9%) gave birth in health facilities. Great proportion (79.7%) of the cases and two third (34.0%) of the controls were well-prepared for birth and complication. Maternal education, religion, distance from health facility, knowledge of availability of ambulance transport and history of obstetric complication were significantly associated with place of delivery (P-value <0.01). Birth preparedness and complication readiness practice had an independent effect on place of delivery (AOR =2.55, 95% CI: 1.12, 5.84). The study identified better institutional delivery service utilization by mothers who were well-prepared for birth and complication. Strategies that increase the preparedness of mothers for birth and complication ahead of childbirth are recommended to improve institutional delivery service utilization.

Cross-cancer genome-wide analysis of lung, ovary, breast, prostate and colorectal cancer reveals novel pleiotropic associations

PubMed Central

Fehringer, Gordon; Kraft, Peter; Pharoah, Paul D.; Eeles, Rosalind A.; Chatterjee, Nilanjan; Schumacher, Fred; Schildkraut, Joellen; Lindström, Sara; Brennan, Paul; Bickeböller, Heike; Houlston, Richard S.; Landi, Maria Teresa; Caporaso, Neil; Risch, Angela; Olama, Ali Amin Al; Berndt, Sonja I; Giovannucci, Edward; Grönberg, Henrik; Kote-Jarai, Zsofia; Ma, Jing; Muir, Kenneth; Stampfer, Meir; Stevens, Victoria L.; Wiklund, Fredrik; Willett, Walter; Goode, Ellen L.; Permuth, Jennifer; Risch, Harvey A.; Reid, Brett M.; Bezieau, Stephane; Brenner, Hermann; Chan, Andrew T.; Chang-Claude, Jenny; Hudson, Thomas J.; Kocarnik, Jonathan K.; Newcomb, Polly A.; Schoen, Robert E.; Slattery, Martha L.; White, Emily; Adank, Muriel A.; Ahsan, Habibul; Aittomäki, Kristiina; Baglietto, Laura; Blomquist, Carl; Canzian, Federico; Czene, Kamila; dos-Santos-Silva, Isabel; Eliassen, A. Heather; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Garcia-Closas, Montserrat; Gaudet, Mia M.; Johnson, Nichola; Hall, Per; Hazra, Aditi; Hein, Rebecca; Hofman, Albert; Hopper, John L.; Irwanto, Astrid; Johansson, Mattias; Kaaks, Rudolf; Kibriya, Muhammad G.; Lichtner, Peter; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Meindl, Alfons; Müller-Myhsok, Bertram; Muranen, Taru A.; Nevanlinna, Heli; Peeters, Petra H.; Peto, Julian; Prentice, Ross L.; Rahman, Nazneen; Sanchez, Maria Jose; Schmidt, Daniel F.; Schmutzler, Rita K.; Southey, Melissa C.; Tamimi, Rulla; Travis, Ruth C.; Turnbull, Clare; Uitterlinden, Andre G.; Wang, Zhaoming; Whittemore, Alice S.; Yang, Xiaohong R.; Zheng, Wei; Rafnar, Thorunn; Gudmundsson, Julius; Stacey, Simon N.; Stefansson, Kari; Sulem, Patrick; Chen, Y. Ann; Tyrer, Jonathan P.; Christiani, David C.; Wei, Yongyue; Shen, Hongbing; Hu, Zhibin; Shu, Xiao-Ou; Shiraishi, Kouya; Takahashi, Atsushi; Bossé, Yohan; Obeidat, Ma’en; Nickle, David; Timens, Wim; Freedman, Matthew L.; Li, Qiyuan; Seminara, Daniela; Chanock, Stephen J.; Gong, Jian; Peters, Ulrike; Gruber, Stephen B.; Amos, Christopher I.; Sellers, Thomas A.; Easton, Douglas F.; Hunter, David J.; Haiman, Christopher A.; Henderson, Brian E.; Hung, Rayjean J.

2016-01-01

Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-staged approach to conduct genome-wide association studies for lung, ovary, breast, prostate and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. PMID:27197191

Reproductive isolation in hybrid mice due to spermatogenesis defects at three meiotic stages.

PubMed

Oka, Ayako; Mita, Akihiko; Takada, Yuki; Koseki, Haruhiko; Shiroishi, Toshihiko

2010-09-01

Early in the process of speciation, reproductive failures occur in hybrid animals between genetically diverged populations. The sterile hybrid animals are often males in mammals and they exhibit spermatogenic disruptions, resulting in decreased number and/or malformation of mature sperms. Despite the generality of this phenomenon, comparative study of phenotypes in hybrid males from various crosses has not been done, and therefore the comprehensive genetic basis of the disruption is still elusive. In this study, we characterized the spermatogenic phenotype especially during meiosis in four different cases of reproductive isolation: B6-ChrX(MSM), PGN-ChrX(MSM), (B6 × Mus musculus musculus-NJL/Ms) F(1), and (B6 × Mus spretus) F(1). The first two are consomic strains, both bearing the X chromosome of M. m. molossinus; in B6-ChrX(MSM), the genetic background is the laboratory strain C57BL/6J (predominantly M. m. domesticus), while in PGN-ChrX(MSM) the background is the PGN2/Ms strain purely derived from wild M. m. domesticus. The last two cases are F(1) hybrids between mouse subspecies or species. Each of the hybrid males exhibited cell-cycle arrest and/or apoptosis at either one or two of three distinct meiotic stages: premeiotic stage, zygotene-to-pachytene stage of prophase I, and metaphase I. This study shows that the sterility in hybrid males is caused by spermatogenic disruptions at multiple stages, suggesting that the responsible genes function in different cellular processes. Furthermore, the stages with disruptions are not correlated with the genetic distance between the respective parental strains.

A two-stage design for multiple testing in large-scale association studies.

PubMed

Wen, Shu-Hui; Tzeng, Jung-Ying; Kao, Jau-Tsuen; Hsiao, Chuhsing Kate

2006-01-01

Modern association studies often involve a large number of markers and hence may encounter the problem of testing multiple hypotheses. Traditional procedures are usually over-conservative and with low power to detect mild genetic effects. From the design perspective, we propose a two-stage selection procedure to address this concern. Our main principle is to reduce the total number of tests by removing clearly unassociated markers in the first-stage test. Next, conditional on the findings of the first stage, which uses a less stringent nominal level, a more conservative test is conducted in the second stage using the augmented data and the data from the first stage. Previous studies have suggested using independent samples to avoid inflated errors. However, we found that, after accounting for the dependence between these two samples, the true discovery rate increases substantially. In addition, the cost of genotyping can be greatly reduced via this approach. Results from a study of hypertriglyceridemia and simulations suggest the two-stage method has a higher overall true positive rate (TPR) with a controlled overall false positive rate (FPR) when compared with single-stage approaches. We also report the analytical form of its overall FPR, which may be useful in guiding study design to achieve a high TPR while retaining the desired FPR.

Performance of two-stage fan having low-aspect-ratio first-stage rotor blading

NASA Technical Reports Server (NTRS)

Urasek, D. C.; Gorrell, W. T.; Cunnan, W. S.

1979-01-01

The NASA two stage fan was tested with a low aspect ratio first stage rotor having no midspan dampers. At design speed the fan achieved an adiabatic design efficiency of 0.846, and peak efficiencies for the first stage and rotor of 0.870 and 0.906, respectively. Peak efficiency occurred very close to the stall line. In an attempt to improve stall margin, the fan was retested with circumferentially grooved casing treatment and with a series of stator blade resets. Results showed no improvement in stall margin with casing treatment but increased to 8 percent with stator blade reset.

Nonlinear control of rotating stall and surge with axisymmetric bleed and air injection on axial flow compressors

NASA Astrophysics Data System (ADS)

Yeung, Chung-Hei (Simon)

The study of compressor instabilities in gas turbine engines has received much attention in recent years. In particular, rotating stall and surge are major causes of problems ranging from component stress and lifespan reduction to engine explosion. In this thesis, modeling and control of rotating stall and surge using bleed valve and air injection is studied and validated on a low speed, single stage, axial compressor at Caltech. Bleed valve control of stall is achieved only when the compressor characteristic is actuated, due to the fast growth rate of the stall cell compared to the rate limit of the valve. Furthermore, experimental results show that the actuator rate requirement for stall control is reduced by a factor of fourteen via compressor characteristic actuation. Analytical expressions based on low order models (2--3 states) and a high fidelity simulation (37 states) tool are developed to estimate the minimum rate requirement of a bleed valve for control of stall. A comparison of the tools to experiments show a good qualitative agreement, with increasing quantitative accuracy as the complexity of the underlying model increases. Air injection control of stall and surge is also investigated. Simultaneous control of stall and surge is achieved using axisymmetric air injection. Three cases with different injector back pressure are studied. Surge control via binary air injection is achieved in all three cases. Simultaneous stall and surge control is achieved for two of the cases, but is not achieved for the lowest authority case. This is consistent with previous results for control of stall with axisymmetric air injection without a plenum attached. Non-axisymmetric air injection control of stall and surge is also studied. Three existing control algorithms found in literature are modeled and analyzed. A three-state model is obtained for each algorithm. For two cases, conditions for linear stability and bifurcation criticality on control of rotating stall are derived and expressed in terms of implementation-oriented variables such as number of injectors. For the third case, bifurcation criticality conditions are not obtained due to complexity, though linear stability property is derived. A theoretical comparison between the three algorithms is made, via the use of low-order models, to investigate pros and cons of the algorithms in the context of operability. The effects of static distortion on the compressor facility at Caltech is characterized experimentally. Results consistent with literature are obtained. Simulations via a high fidelity model (34 states) are also performed and show good qualitative as well as quantitative agreement to experiments. A non-axisymmetric pulsed air injection controller for stall is shown to be robust to static distortion.

[Value of surgery for stage IIIa non-small cell lung cancer].

PubMed

Liu, Huihui; Wang, Mengzhao; Hu, Ke; Xu, Yan; Ma, Manjiao; Zhong, Wei; Zhao, Jing; Li, Longyun; Wang, Huazhu

2013-12-01

Nowadays, comprehensive treatment, including surgery, chemotherapy and radiotherapy is advocated for stage III non-small cell lung cancer (NSCLC). However, many researchers have questioned the effectiveness of surgery. The aim of this study is to evaluate the effect of surgery for stage III NSCLC. Between March 2002 and October 2012, 310 cases that have completed followed-up data with stage III NSCLC were received in the Peking Union Medical College Hospital. They were divided into surgical and non-surgical groups according to whether received surgery when diagnosed. In TNM staging, stage III NSCLC includes stage IIIa and IIIb, and stage IIIa NSCLC can be grouped into stage T4N0/T3-4N1M0 and T1-3N2M0 according to different N stages. Analyzed the enumeration data by Chi-Square test. Kaplan-Meier survival method was used to calculate the overall survival (OS) and progression-free survival (PFS), and to draw the survival curves. A P value less than 0.05 was evaluated as statistically significant. Three hundred and ten stage III NSCLC patients include surgical group 189 cases and non-surgical group 121 cases. One hundred and eighty-eight stage IIIa NSCLC patients include surgical group 152 cases and non-surgical group 36 cases. In stage IIIa, stage T4N0/T3-4N1M0 had 57 patients with 44 surgical and 13 non-surgical patients, and stage T1-3N2M0 had 131 patients with 108 surgical and 23 non-surgical patients. Thirty-seven out of 121 stage IIIb NSCLC patients received surgery. They had 22 stage T4N2M0 cases and 15 stage T1-4N3M0 cases. The patient whose performance status was 0 and staging was stage IIIa was more inclined to undergo surgery. For stage IIIa NSCLC patients, the median OS of surgical and non-surgical groups were 38.9 and 21.8 months, and the median PFS of them were 19.2 and 11.9 months respectively. The difference of OS between the two groups was significant (P=0.041), but the PFS of them had no significant difference (P=0.209). For stage T4N0/T3-4N1M0 which belongs to stage IIIa, the median OS of surgical and non-surgical groups were 48.7 and 20.1 months, and the median PFS of them were 14.6 and 10.5 months respectively. There were no significant differences of OS and PFS between the two groups (P>0.05). For stage T1-3N2M0 which also belongs to stage IIIa, the median OS of surgical and non-surgical groups were 38.9 and 30.8 months, and the median PFS of them were 19.8 and 12.7 months respectively. There were also no significant differences of OS and PFS between the two groups (P>0.05). The maximum diameter of tumor and auxillary chemotherapy had significant influences on OS and PFS of stage IIIa-N2 NSCLC patients, while the histology of tumor only influenced the OS of them (P<0.05). The patient whose performance status is 0 and staging is stage IIIa is more inclined to undergo surgery. Surgery can prolong OS of patients with stage IIIa, especially for stage T4N0/T3-4N1M0. However, it has no benefit on PFS. The maximum diameter of tumor and auxillary chemotherapy have significant influences on OS and PFS of stage IIIa-N2 NSCLC patients, while the histology of tumor only influence the OS of them.

The effect of initial flow nonuniformity on second-stage fuel injection and combustion in a supersonic duct. [supersonic combustion ramjet engine

NASA Technical Reports Server (NTRS)

Russin, W. R.

1975-01-01

The effects of flow nonuniformity on second-stage hydrogen fuel injection and combustion in supersonic flow were evaluated. The first case, second-stage fuel injection into a uniform duct flow, produced data indicating that fuel mixing is considerably slower than estimates based on an empirical mixing correlation. The second-case, two-stage fuel injection (or second-stage fuel injection into a nonuniform duct flow), produced a large interaction between stages with extensive flow separation. For this case the measured wall pressure, heat transfer, and amount of reaction at the duct exit were significantly greater than estimates based on the mixing correlation. Substantially more second-stage fuel burned in the second case than in the first case. Overall effects of unmixedness/chemical kinetics were found not to be significant at the exit for stoichiometric fuel injection.

Risk factors for first trimester miscarriage--results from a UK-population-based case-control study.

PubMed

Maconochie, N; Doyle, P; Prior, S; Simmons, R

2007-02-01

The aim of this study was to examine the association between biological, behavioural and lifestyle risk factors and risk of miscarriage. Population-based case-control study. Case-control study nested within a population-based, two-stage postal survey of reproductive histories of women randomly sampled from the UK electoral register. Six hundred and three women aged 18-55 years whose most recent pregnancy had ended in first trimester miscarriage (<13 weeks of gestation; cases) and 6116 women aged 18-55 years whose most recent pregnancy had progressed beyond 12 weeks (controls). Women were questioned about socio-demographic, behavioural and other factors in their most recent pregnancy. First trimester miscarriage. After adjustment for confounding, the following were independently associated with increased risk: high maternal age; previous miscarriage, termination and infertility; assisted conception; low pre-pregnancy body mass index; regular or high alcohol consumption; feeling stressed (including trend with number of stressful or traumatic events); high paternal age and changing partner. Previous live birth, nausea, vitamin supplementation and eating fresh fruits and vegetables daily were associated with reduced risk, as were feeling well enough to fly or to have sex. After adjustment for nausea, we did not confirm an association with caffeine consumption, smoking or moderate or occasional alcohol consumption; nor did we find an association with educational level, socio-economic circumstances or working during pregnancy. The results confirm that advice to encourage a healthy diet, reduce stress and promote emotional wellbeing might help women in early pregnancy (or planning a pregnancy) reduce their risk of miscarriage. Findings of increased risk associated with previous termination, stress, change of partner and low pre-pregnancy weight are noteworthy, and we recommend further work to confirm these findings in other study populations.

Automatic staging of bladder cancer on CT urography

NASA Astrophysics Data System (ADS)

Garapati, Sankeerth S.; Hadjiiski, Lubomir M.; Cha, Kenny H.; Chan, Heang-Ping; Caoili, Elaine M.; Cohan, Richard H.; Weizer, Alon; Alva, Ajjai; Paramagul, Chintana; Wei, Jun; Zhou, Chuan

2016-03-01

Correct staging of bladder cancer is crucial for the decision of neoadjuvant chemotherapy treatment and minimizing the risk of under- or over-treatment. Subjectivity and variability of clinicians in utilizing available diagnostic information may lead to inaccuracy in staging bladder cancer. An objective decision support system that merges the information in a predictive model based on statistical outcomes of previous cases and machine learning may assist clinicians in making more accurate and consistent staging assessments. In this study, we developed a preliminary method to stage bladder cancer. With IRB approval, 42 bladder cancer cases with CTU scans were collected from patient files. The cases were classified into two classes based on pathological stage T2, which is the decision threshold for neoadjuvant chemotherapy treatment (i.e. for stage >=T2) clinically. There were 21 cancers below stage T2 and 21 cancers at stage T2 or above. All 42 lesions were automatically segmented using our auto-initialized cascaded level sets (AI-CALS) method. Morphological features were extracted, which were selected and merged by linear discriminant analysis (LDA) classifier. A leave-one-case-out resampling scheme was used to train and test the classifier using the 42 lesions. The classification accuracy was quantified using the area under the ROC curve (Az). The average training Az was 0.97 and the test Az was 0.85. The classifier consistently selected the lesion volume, a gray level feature and a contrast feature. This predictive model shows promise for assisting in assessing the bladder cancer stage.

Use of real time gas production data for more accurate comparison of continuous single-stage and two-stage fermentation.

PubMed

Massanet-Nicolau, Jaime; Dinsdale, Richard; Guwy, Alan; Shipley, Gary

2013-02-01

Changes in fermenter gas composition within a given 24h period can cause severe bias in calculations of biogas or energy yields based on just one or two measurements of gas composition per day, as is common in other studies of two-stage fermentation. To overcome this bias, real time recording of gas composition and production were used to undertake a detailed and controlled comparison of single-stage and two-stage fermentation using a real world substrate (wheat feed pellets). When a two-stage fermentation system was used, methane yields increased from 261 L kg(-1)VS using a 20 day HRT, single-stage fermentation, to 359 L kg(-1) VS using a two-stage fermentation with the same overall retention time--an increase of 37%. Additionally a hydrogen yield of 7 L kg(-1) VS was obtained when two-stage fermentation was used. The two-stage system could also be operated at a shorter, 12 day HRT and still produce higher methane yields (306 L kg(-1) VS). Both two-stage fermentation systems evaluated exhibited methane yields in excess of that predicted by a biological methane potential test (BMP) performed using the same feedstock (260 L kg(-1)VS). Copyright © 2012 Elsevier Ltd. All rights reserved.

Cancer Stage at Diagnosis in HIV-infected People and Transplant Recipients

PubMed Central

Shiels, Meredith S.; Copeland, Glenn; Goodman, Marc T.; Harrell, Janna; Lynch, Charles F.; Pawlish, Karen; Pfeiffer, Ruth M.; Engels, Eric A.

2015-01-01

Background It is unknown whether immunosuppression results in more aggressive, advanced stage cancers. As cancer stage is influenced both by tumor biology and medical surveillance, we assessed cancer stage in HIV-infected individuals and solid organ transplant recipients, two immunosuppressed groups with differences in healthcare utilization. Methods We used data on all cases of 15 cancer types, diagnosed during 1996–2010 in two studies that linked U.S. cancer registries to HIV and transplant registries. Odds ratios (ORs) for advanced (vs. local) disease were estimated comparing HIV and transplant populations to immunocompetent people in polytomous logistic regression models, adjusted for age, sex, race, registry and year. Results A total of 8,411 of 4.5 million cancer cases occurred in HIV-infected people, and 7,322 of 6.4 million cancer cases occurred in transplant recipients. Compared to immunocompetent people with cancer, HIV-infected people were more likely to be diagnosed with distant stage lung (OR=1.13), female breast (OR=1.99), and prostate cancers (OR=1.57), while transplant recipients had fewer distant stage lung (OR=0.54), female breast (OR=0.75) and prostate cancers (OR=0.72). Both immunosuppressed populations had a shift toward advanced stage melanoma (ORs: HIV=1.97; transplant=1.82) and bladder cancer (ORs: HIV=1.42; transplant=1.54). Conclusions Bladder cancer and melanoma were more likely to be diagnosed at non-local stage in both HIV-infected people and transplant recipients, suggesting a role of immunosuppression in their progression. Additionally, we observed a shift for some common cancers toward later stages in HIV-infected individuals and toward earlier stages in transplant recipients, consistent with differential access to medical care or surveillance. PMID:25739496

Occupational factors and pancreatic cancer.

PubMed Central

Norell, S; Ahlbom, A; Olin, R; Erwald, R; Jacobson, G; Lindberg-Navier, I; Wiechel, K L

1986-01-01

The relation between occupational factors and pancreatic cancer has been studied by two different approaches: a population based case-control study with two series of controls and a retrospective cohort study based on register data. With both approaches, some support was found for an association with occupational exposure to petroleum products. Associations were also indicated with exposure to paint thinner (case-control study) and work in painting and in paint and varnish factories (cohort study), for exposure to detergents, floor cleaning agents, or polish (case-control study) and with floor polishing or window cleaning (cohort study), and for exposure to refuse (case-control study) and work in refuse disposal plants (cohort study). PMID:3790458

Patients With Failed Prior Two-Stage Exchange Have Poor Outcomes After Further Surgical Intervention.

PubMed

Kheir, Michael M; Tan, Timothy L; Gomez, Miguel M; Chen, Antonia F; Parvizi, Javad

2017-04-01

Failure of 2-stage exchange arthroplasty for the management of periprosthetic joint infection (PJI) poses a major clinical challenge. There is a paucity of information regarding the outcomes of further surgical intervention in these patients. Thus, we aim to report the clinical outcomes of subsequent surgery for a failed prior 2-stage exchange arthroplasty. Our institutional database was used to identify 60 patients (42 knees and 18 hips), with a failed prior 2-stage exchange, who underwent further surgical intervention between 1998 and 2012, and had a minimum 2-year follow-up. A retrospective review was performed to extract relevant clinical information, including mortality, microbiology, and subsequent surgeries. Musculoskeletal Infection Society criteria were used to define PJI, and treatment success was defined using Delphi criteria. Irrigation and debridement (I&D) was performed after a failed 2-stage exchange in 61.7% of patients; 56.8% subsequently failed. Forty patients underwent an intended second 2-stage exchange; 6 cases required a spacer exchange. Reimplantation occurred only in 65% of cases, and 61.6% had infection controlled. The 14 cases that were not reimplanted resulted in 6 retained spacers, 5 amputations, 2 PJI-related mortalities, and 1 arthrodesis. Further surgical intervention after a failed prior 2-stage exchange arthroplasty has poor outcomes. Although I&D has a high failure rate, many patients who are deemed candidates for a second 2-stage exchange either do not undergo reimplantation or fail after reimplantation. The management of PJI clearly remains imperfect, and there is a dire need for further innovations that may improve the care of these patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Approaching a Scientific Consensus on the Association between Allergies and Glioma Risk: A Report from the Glioma International Case-Control Study.

PubMed

Amirian, E Susan; Zhou, Renke; Wrensch, Margaret R; Olson, Sara H; Scheurer, Michael E; Il'yasova, Dora; Lachance, Daniel; Armstrong, Georgina N; McCoy, Lucie S; Lau, Ching C; Claus, Elizabeth B; Barnholtz-Sloan, Jill S; Schildkraut, Joellen; Ali-Osman, Francis; Sadetzki, Siegal; Johansen, Christoffer; Houlston, Richard S; Jenkins, Robert B; Bernstein, Jonine L; Merrell, Ryan T; Davis, Faith G; Lai, Rose; Shete, Sanjay; Amos, Christopher I; Melin, Beatrice S; Bondy, Melissa L

2016-02-01

Several previous studies have found inverse associations between glioma susceptibility and a history of allergies or other atopic conditions. Some evidence indicates that respiratory allergies are likely to be particularly relevant with regard to glioma risk. Using data from the Glioma International Case-Control Study (GICC), we examined the effects of respiratory allergies and other atopic conditions on glioma risk. The GICC contains detailed information on history of atopic conditions for 4,533 cases and 4,171 controls, recruited from 14 study sites across five countries. Using two-stage random-effects restricted maximum likelihood modeling to calculate meta-analysis ORs, we examined the associations between glioma and allergy status, respiratory allergy status, asthma, and eczema. Having a history of respiratory allergies was associated with an approximately 30% lower glioma risk, compared with not having respiratory allergies (mOR, 0.72; 95% confidence interval, 0.58-0.90). This association was similar when restricting to high-grade glioma cases. Asthma and eczema were also significantly protective against glioma. A substantial amount of data on the inverse association between atopic conditions and glioma has accumulated, and findings from the GICC study further strengthen the existing evidence that the relationship between atopy and glioma is unlikely to be coincidental. As the literature approaches a consensus on the impact of allergies in glioma risk, future research can begin to shift focus to what the underlying biologic mechanism behind this association may be, which could, in turn, yield new opportunities for immunotherapy or cancer prevention. ©2016 American Association for Cancer Research.

Approaching a Scientific Consensus on the Association between Allergies and Glioma Risk: A Report from the Glioma International Case-Control Study

PubMed Central

Amirian, E. Susan; Zhou, Renke; Wrensch, Margaret R.; Olson, Sara H.; Scheurer, Michael E.; Il’yasova, Dora; Lachance, Daniel; Armstrong, Georgina N.; McCoy, Lucie S.; Lau, Ching C.; Claus, Elizabeth B.; Barnholtz-Sloan, Jill S.; Schildkraut, Joellen; Ali-Osman, Francis; Sadetzki, Siegal; Johansen, Christoffer; Houlston, Richard S.; Jenkins, Robert B.; Bernstein, Jonine L.; Merrell, Ryan T.; Davis, Faith G.; Lai, Rose; Shete, Sanjay; Amos, Christopher I.; Melin, Beatrice S.; Bondy, Melissa L.

2015-01-01

Background Several previous studies have found inverse associations between glioma susceptibility and a history of allergies or other atopic conditions. Some evidence indicates that respiratory allergies are likely to be particularly relevant with regard to glioma risk. Using data from the Glioma International Case-Control Study (GICC), we examined the effects of respiratory allergies and other atopic conditions on glioma risk. Methods The GICC contains detailed information on history of atopic conditions for 4533 cases and 4171 controls, recruited from 14 study sites across five countries. Using two-stage random-effects restricted maximum likelihood modeling to calculate meta-analysis odds ratios, we examined the associations between glioma and allergy status, respiratory allergy status, asthma, and eczema. Results Having a history of respiratory allergies was associated with an approximately 30% lower glioma risk, compared to not having respiratory allergies (mOR: 0.72, 95% CI: 0.58–0.90). This association was similar when restricting to high-grade glioma cases. Asthma and eczema were also significantly protective against glioma. Conclusions A substantial amount of data on the inverse association between atopic conditions and glioma has accumulated, and findings from the GICC study further strengthen the existing evidence that the relationship between atopy and glioma is unlikely to be coincidental. Impact As the literature approaches a consensus on the impact of allergies in glioma risk, future research can begin to shift focus to what the underlying biological mechanism behind this association may be, which could, in turn, yield new opportunities for immunotherapy or cancer prevention. PMID:26908595

The dynamic changes of vaginal microecosystem in patients with recurrent vulvovaginal candidiasis: a retrospective study of 800 patients.

PubMed

Yue, Xin-Ai; Chen, Ping; Tang, Yuanting; Wu, Xiuli; Hu, Zhengqiang

2015-12-01

Vaginal microecological environment is an important factor of recurrent vulvovaginal candidiasis (RVVC). This study was undertaken to investigate dynamic changes of vaginal microecosystem in patients with RVVC. Four hundred patients with VVC and 400 healthy women of reproductive age who admitted to the hospital from January 2012 to December 2013 were evaluated retrospectively. Vaginal microecological factors were evaluated before and after treatment until no recurrence, including vaginal cleanliness, white blood cells, Lactobacillus, Lactobacillus classification, bacteria density, flora diversity, Nugent scores, etc. The grouping was done according to the recurrence of the disease. Every time after treatment, the relapsing patients were defined as case group and the cured patients without recurrence were defined as control group. The differences in the results between the case and the control groups were analyzed by t test. With the development of RVVC, the ages of all case groups were lower than the corresponding control groups. In different stages of the disease, the bacteria density of the case groups and their corresponding control groups had no significant difference (P > 0.05). Most of the microecological indicators of the first occurring group were significantly different (P < 0.05) from that of the control group. In the recurrence groups, only a few indicators were significantly different from the control groups. The values of all vaginal microecological indicators (except Lactobacillus) of all case groups were higher than that of the control groups. The values of Lactobacillus of all RVVC case groups were lower than that of the RVVC control groups. There were vaginal microecological imbalances in all developing stages of RVVC. As for vaginal flora, diverse sorts changed to normal Lactobacillus dominantly with the development of RVVC. In the first occurrence of RVVC, after antifungal treatment, Lactobacillus is suggested to be timely supplemented to restore vaginal microecological balance.

Positive Culture During Reimplantation Increases the Risk of Subsequent Failure in Two-Stage Exchange Arthroplasty.

PubMed

Tan, Timothy L; Gomez, Miguel M; Manrique, Jorge; Parvizi, Javad; Chen, Antonia F

2016-08-03

It is strongly recommended that tissue and synovial fluid culture samples be obtained during reimplantation performed as part of a 2-stage exchange arthroplasty. The rate of positive cultures during reimplantation and the influence of positive cultures on subsequent outcomes, to our knowledge, are unknown. This study was designed to determine the rate of positive cultures during reimplantation and to investigate the association between positive cultures at reimplantation and subsequent outcomes. We retrospectively reviewed the data of 259 patients who met the Musculoskeletal Infection Society criteria for periprosthetic joint infection (PJI) and who underwent both stages of 2-stage exchange arthroplasty at our institution from 1999 to 2013. Among these patients were 267 PJIs (186 knees and 81 hips); 33 (12.4%) had ≥1 positive culture result at reimplantation. Treatment failure was assessed according to the Delphi-based consensus definition. Logistic regression analysis was performed to assess the predictors of positive culture and risk factors for failure of 2-stage exchange arthroplasty. Of the 33 cases with PJI, 15 (45.5%) had a subsequent failure of the 2-stage exchange arthroplasty compared with 49 (20.9%) of the cases that were culture-negative at reimplantation. When controlling for other variables using multivariate analyses, the risk of treatment failure was higher (odds ratio = 2.53; 95% confidence interval [CI] = 1.13 to 5.64) and reinfection occurred earlier (hazard ratio = 2.00; 95% CI = 1.05 to 3.82) for the cases with a positive culture during reimplantation. The treatment failure rate did not differ (p = 0.73) between cases with ≥2 positive cultures (36.4%) and 1 positive culture (50%). Positive intraoperative culture at the time of reimplantation, regardless of the number of positive samples, was independently associated with >2 times the risk of subsequent treatment failure and earlier reinfection. Surgeons should be aware that a positive culture at the time of reimplantation independently increases the risk of subsequent failure. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence. Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated.

Ischemic Stroke Is Associated with the ABO Locus: The EuroCLOT Study

PubMed Central

Williams, Frances M K; Carter, Angela M; Hysi, Pirro G; Surdulescu, Gabriela; Hodgkiss, Dylan; Soranzo, Nicole; Traylor, Matthew; Bevan, Steve; Dichgans, Martin; Rothwell, Peter M W; Sudlow, Cathie; Farrall, Martin; Silander, Kaisa; Kaunisto, Mari; Wagner, Peter; Saarela, Olli; Kuulasmaa, Kari; Virtamo, Jarmo; Salomaa, Veikko; Amouyel, Philippe; Arveiler, Dominique; Ferrieres, Jean; Wiklund, Per-Gunnar; Arfan Ikram, M; Hofman, Albert; Boncoraglio, Giorgio B; Parati, Eugenio A; Helgadottir, Anna; Gretarsdottir, Solveig; Thorsteinsdottir, Unnur; Thorleifsson, Gudmar; Stefansson, Kari; Seshadri, Sudha; DeStefano, Anita; Gschwendtner, Andreas; Psaty, Bruce; Longstreth, Will; Mitchell, Braxton D; Cheng, Yu-Ching; Clarke, Robert; Ferrario, Marco; Bis, Joshua C; Levi, Christopher; Attia, John; Holliday, Elizabeth G; Scott, Rodney J; Fornage, Myriam; Sharma, Pankaj; Furie, Karen L; Rosand, Jonathan; Nalls, Mike; Meschia, James; Mosely, Thomas H; Evans, Alun; Palotie, Aarno; Markus, Hugh S; Grant, Peter J; Spector, Tim D

2013-01-01

Objective End-stage coagulation and the structure/function of fibrin are implicated in the pathogenesis of ischemic stroke. We explored whether genetic variants associated with end-stage coagulation in healthy REFVIDunteers account for the genetic predisposition to ischemic stroke and examined their influence on stroke subtype. Methods Common genetic variants identified through genome-wide association studies of coagulation factors and fibrin structure/function in healthy twins (n = 2,100, Stage 1) were examined in ischemic stroke (n = 4,200 cases) using 2 independent samples of European ancestry (Stage 2). A third clinical collection having stroke subtyping (total 8,900 cases, 55,000 controls) was used for replication (Stage 3). Results Stage 1 identified 524 single nucleotide polymorphisms (SNPs) from 23 linkage disequilibrium blocks having significant association (p < 5 × 10–8) with 1 or more coagulation/fibrin phenotypes. The most striking associations included SNP rs5985 with factor XIII activity (p = 2.6 × 10–186), rs10665 with FVII (p = 2.4 × 10–47), and rs505922 in the ABO gene with both von Willebrand factor (p = 4.7 × 10–57) and factor VIII (p = 1.2 × 10–36). In Stage 2, the 23 independent SNPs were examined in stroke cases/noncases using MOnica Risk, Genetics, Archiving and Monograph (MORGAM) and Wellcome Trust Case Control Consortium 2 collections. SNP rs505922 was nominally associated with ischemic stroke (odds ratio = 0.94, 95% confidence interval = 0.88–0.99, p = 0.023). Independent replication in Meta-Stroke confirmed the rs505922 association with stroke, beta (standard error, SE) = 0.066 (0.02), p = 0.001, a finding specific to large-vessel and cardioembolic stroke (p = 0.001 and p = < 0.001, respectively) but not seen with small-vessel stroke (p = 0.811). Interpretation ABO gene variants are associated with large-vessel and cardioembolic stroke but not small-vessel disease. This work sheds light on the different pathogenic mechanisms underpinning stroke subtype. Ann Neurol 2013 PMID:23381943

Associations of tea and coffee consumption with prostate cancer risk

PubMed Central

Geybels, Milan S.; Neuhouser, Marian L.; Stanford, Janet L.

2013-01-01

Purpose: Tea and coffee contain bioactive compounds and both beverages have recently been associated with a reduced risk of prostate cancer (PCa). Methods: We studied associations of tea and coffee consumption with PCa risk in a population-based case-control study from King County, Washington, US. Prostate cancer cases were diagnosed in 2002-2005 and matched to controls by five-year age groups. Logistic regression was used to generate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Among controls, 19% and 58% consumed at least one cup per day of tea and coffee, respectively. The analysis of tea included 892 cases and 863 controls and tea consumption was associated with a reduced overall PCa risk with an adjusted OR of 0.63 (95% CI: 0.45, 0.90; P for trend = 0.02) for men in the highest compared to lowest category of tea intake (≥2 cups/day versus ≤1 cup/week). Risk estimates did not vary substantially by Gleason grade or disease stage. Coffee consumption was not associated with risk of overall PCa or PCa in subgroups defined by tumor grade or stage. Conclusions: Our results contribute further evidence that tea consumption may be a modifiable exposure that reduces PCa risk. PMID:23412806

Stochastic Robust Mathematical Programming Model for Power System Optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Cong; Changhyeok, Lee; Haoyong, Chen

2016-01-01

This paper presents a stochastic robust framework for two-stage power system optimization problems with uncertainty. The model optimizes the probabilistic expectation of different worst-case scenarios with ifferent uncertainty sets. A case study of unit commitment shows the effectiveness of the proposed model and algorithms.

Genome-wide search followed by replication reveals genetic interaction of CD80 and ALOX5AP associated with systemic lupus erythematosus in Asian populations.

PubMed

Zhang, Yan; Yang, Jing; Zhang, Jing; Sun, Liangdan; Hirankarn, Nattiya; Pan, Hai-Feng; Lau, Chak Sing; Chan, Tak Mao; Lee, Tsz Leung; Leung, Alexander Moon Ho; Mok, Chi Chiu; Zhang, Lu; Wang, Yongfei; Shen, Jiangshan Jane; Wong, Sik Nin; Lee, Ka Wing; Ho, Marco Hok Kung; Lee, Pamela Pui Wah; Chung, Brian Hon-Yin; Chong, Chun Yin; Wong, Raymond Woon Sing; Mok, Mo Yin; Wong, Wilfred Hing Sang; Tong, Kwok Lung; Tse, Niko Kei Chiu; Li, Xiang-Pei; Avihingsanon, Yingyos; Rianthavorn, Pornpimol; Deekajorndej, Thavatchai; Suphapeetiporn, Kanya; Shotelersuk, Vorasuk; Ying, Shirley King Yee; Fung, Samuel Ka Shun; Lai, Wai Ming; Wong, Chun-Ming; Ng, Irene Oi Lin; Garcia-Barcelo, Maria-Merce; Cherny, Stacey S; Cui, Yong; Sham, Pak Chung; Yang, Sen; Ye, Dong-Qing; Zhang, Xue-Jun; Lau, Yu Lung; Yang, Wanling

2016-05-01

Genetic interaction has been considered as a hallmark of the genetic architecture of systemic lupus erythematosus (SLE). Based on two independent genome-wide association studies (GWAS) on Chinese populations, we performed a genome-wide search for genetic interactions contributing to SLE susceptibility. The study involved a total of 1 659 cases and 3 398 controls in the discovery stage and 2 612 cases and 3 441 controls in three cohorts for replication. Logistic regression and multifactor dimensionality reduction were used to search for genetic interaction. Interaction of CD80 (rs2222631) and ALOX5AP (rs12876893) was found to be significantly associated with SLE (OR_int=1.16, P_int_all=7.7E-04 at false discovery rate<0.05). Single nuclear polymorphism rs2222631 was found associated with SLE with genome-wide significance (P_all=4.5E-08, OR=0.86) and is independent of rs6804441 in CD80, whose association was reported previously. Significant correlation was observed between expression of these two genes in healthy controls and SLE cases, together with differential expression of these genes between cases and controls, observed from individuals from the Hong Kong cohort. Genetic interactions between BLK (rs13277113) and DDX6 (rs4639966), and between TNFSF4 (rs844648) and PXK (rs6445975) were also observed in both GWAS data sets. Our study represents the first genome-wide evaluation of epistasis interactions on SLE and the findings suggest interactions and independent variants may help partially explain missing heritability for complex diseases. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Optimality, sample size, and power calculations for the sequential parallel comparison design.

PubMed

Ivanova, Anastasia; Qaqish, Bahjat; Schoenfeld, David A

2011-10-15

The sequential parallel comparison design (SPCD) has been proposed to increase the likelihood of success of clinical trials in therapeutic areas where high-placebo response is a concern. The trial is run in two stages, and subjects are randomized into three groups: (i) placebo in both stages; (ii) placebo in the first stage and drug in the second stage; and (iii) drug in both stages. We consider the case of binary response data (response/no response). In the SPCD, all first-stage and second-stage data from placebo subjects who failed to respond in the first stage of the trial are utilized in the efficacy analysis. We develop 1 and 2 degree of freedom score tests for treatment effect in the SPCD. We give formulae for asymptotic power and for sample size computations and evaluate their accuracy via simulation studies. We compute the optimal allocation ratio between drug and placebo in stage 1 for the SPCD to determine from a theoretical viewpoint whether a single-stage design, a two-stage design with placebo only in the first stage, or a two-stage design is the best design for a given set of response rates. As response rates are not known before the trial, a two-stage approach with allocation to active drug in both stages is a robust design choice. Copyright © 2011 John Wiley & Sons, Ltd.

The SNP rs6500843 in 16p13.3 is associated with survival specifically among chemotherapy-treated breast cancer patients.

PubMed

Fagerholm, Rainer; Schmidt, Marjanka K; Khan, Sofia; Rafiq, Sajjad; Tapper, William; Aittomäki, Kristiina; Greco, Dario; Heikkinen, Tuomas; Muranen, Taru A; Fasching, Peter A; Janni, Wolfgang; Weinshilboum, Richard; Loehberg, Christian R; Hopper, John L; Southey, Melissa C; Keeman, Renske; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Chenevix-Trench, Georgia; Lambrechts, Diether; Wildiers, Hans; Chang-Claude, Jenny; Seibold, Petra; Couch, Fergus J; Olson, Janet E; Andrulis, Irene L; Knight, Julia A; García-Closas, Montserrat; Figueroa, Jonine; Hooning, Maartje J; Jager, Agnes; Shah, Mitul; Perkins, Barbara J; Luben, Robert; Hamann, Ute; Kabisch, Maria; Czene, Kamila; Hall, Per; Easton, Douglas F; Pharoah, Paul D P; Liu, Jianjun; Eccles, Diana; Blomqvist, Carl; Nevanlinna, Heli

2015-04-10

We have utilized a two-stage study design to search for SNPs associated with the survival of breast cancer patients treated with adjuvant chemotherapy. Our initial GWS data set consisted of 805 Finnish breast cancer cases (360 treated with adjuvant chemotherapy). The top 39 SNPs from this stage were analyzed in three independent data sets: iCOGS (n=6720 chemotherapy-treated cases), SUCCESS-A (n=3596), and POSH (n=518). Two SNPs were successfully validated: rs6500843 (any chemotherapy; per-allele HR 1.16, 95% C.I. 1.08-1.26, p=0.0001, p(adjusted)=0.0091), and rs11155012 (anthracycline therapy; per-allele HR 1.21, 95% C.I. 1.08-1.35, p=0.0010, p(adjusted)=0.0270). The SNP rs6500843 was found to specifically interact with adjuvant chemotherapy, independently of standard prognostic markers (p(interaction)=0.0009), with the rs6500843-GG genotype corresponding to the highest hazard among chemotherapy-treated cases (HR 1.47, 95% C.I. 1.20-1.80). Upon trans-eQTL analysis of public microarray data, the rs6500843 locus was found to associate with the expression of a group of genes involved in cell cycle control, notably AURKA, the expression of which also exhibited differential prognostic value between chemotherapy-treated and untreated cases in our analysis of microarray data. Based on previously published information, we propose that the eQTL genes may be connected to the rs6500843 locus via a RBFOX1-FOXM1 -mediated regulatory pathway.

LIVER TRANSPLANTATION AFTER SEVERE HEPATIC TRAUMA: CURRENT INDICATIONS AND RESULTS

PubMed Central

RIBEIRO-JR, Marcelo Augusto Fontenelle; MEDRADO, Melina Botelho; ROSA, Otto Mauro; SILVA, Ana Júlia de Deus; FONTANA, Mariana Prado; CRUVINEL-NETO, José; FONSECA, Alexandre Zanchenko

2015-01-01

Background : The liver is the most injured organ in abdominal trauma. Currently, the treatment in most cases is non-operative, but surgery may be necessary in severe abdominal trauma with blunt liver damage, especially those that cause uncontrollable bleeding. Despite the damage control approaches in order to achieve hemodynamic stability, many patients develop hypovolemic shock, acute liver failure, multiple organ failure and death. In this context, liver transplantation appears as the lifesaving last resource Aim : Analyze the use of liver transplantation as a treatment option for severe liver trauma. Methods : Were reviewed 14 articles in the PubMed, Medline and Lilacs databases, selected between 2008-2014 and 10 for this study. Results : Were identified 46 cases undergoing liver transplant after liver trauma; the main trauma mechanism was closed/blunt abdominal trauma in 83%, and severe trauma (>grade IV) in 81 %. The transplant can be done, in this context, performing one-stage procedure (damaged organ removed with immediate transplantation), used in 72% of cases. When the two-stage approach is performed, end-to-side temporary portacaval shunt is provided, until new organ becomes available to be transplanted. If two different periods are considered - from 1980 to 2000 and from 2000 to 2014 - the survival rate increased significantly, from 48% to 76%, while the mortality decreased from 52% to 24%. Conclusion : Despite with quite restricted indications, liver transplantation in hepatic injury is a therapeutic modality viable and feasible today, and can be used in cases when other therapeutic modalities in short and long term, do not provide the patient survival chances. PMID:26734803

SF3A1 and pancreatic cancer: new evidence for the association of the spliceosome and cancer.

PubMed

Tian, Jing; Liu, Yaping; Zhu, Beibei; Tian, Yao; Zhong, Rong; Chen, Wei; Lu, Xinghua; Zou, Li; Shen, Na; Qian, Jiaming; Li, Hui; Miao, Xiaoping; Wang, Li

2015-11-10

A two-stage case-control study was conducted to examine the association between six candidate U2-depedent spliceosome genes (SRSF1, SRSF2, SF3A1, SF3B1, SF1 and PRPF40B) and pancreatic cancer (PC). Subjects with one or two T alleles at rs2074733 in SF3A1 had a lower risk of PC compared to those with two C alleles in combined two populations (OR: 0.59, 95% confidence interval: 0.48-0.73, False discovery rate (FDR)-P = 1.5E-05). Moreover, the presence of the higher-risk genotype at rs2074733 plus smoking or drinking had synergic effects on PC risk. These findings illustrate that RNA splicing-related genes appear to be associated with the occurrence of PC, and show synergic interactions with smoking and drinking in the additive model. In the future, our novel findings should be further confirmed by functional studies and independent large-scale population studies.

Picture agnosia as a characteristic of posterior cortical atrophy.

PubMed

Sugimoto, Azusa; Midorikawa, Akira; Koyama, Shinichi; Futamura, Akinori; Hieda, Sotaro; Kawamura, Mitsuru

2012-01-01

Posterior cortical atrophy (PCA) is a degenerative disease characterized by progressive visual agnosia with posterior cerebral atrophy. We examine the role of the picture naming test and make a number of suggestions with regard to diagnosing PCA as atypical dementia. We investigated 3 cases of early-stage PCA with 7 control cases of Alzheimer disease (AD). The patients and controls underwent a naming test with real objects and colored photographs of familiar objects. We then compared rates of correct answers. Patients with early-stage PCA showed significant inability to recognize photographs compared to real objects (F = 196.284, p = 0.0000) as measured by analysis of variants. This difficulty was also significant to AD controls (F = 58.717, p = 0.0000). Picture agnosia is a characteristic symptom of early-stage PCA, and the picture naming test is useful for the diagnosis of PCA as atypical dementia at an early stage. Copyright © 2012 S. Karger AG, Basel.

Can Good Infection Control Be Obtained in One-stage Exchange of the Infected TKA to a Rotating Hinge Design? 10-year Results.

PubMed

Zahar, Akos; Kendoff, Daniel O; Klatte, Till O; Gehrke, Thorsten A

2016-01-01

Prosthetic joint infection (PJI) occurs in 1% to 2% of total knee arthroplasties (TKAs). Although two-stage exchange is the preferred management method of patients with chronic PJI in TKA in North America, one-stage exchange is an alternative treatment method, but long-term studies of this approach have not been conducted. We reviewed our minimum 9-year results of 70 patients who underwent one-stage exchange arthroplasty with a rotating hinge design to determine: (1) What was the proportion of patients free of infection? (2) What was the patient rate of survival free of any reoperation? (3) What were the clinical outcomes as measured by Hospital for Special Surgery scores? (4) What proportion of patients developed radiographic evidence of loosening? All one-stage revision TKAs for infection between January 1 and December 31, 2002, with a minimum 9-year followup (mean, 10 years; range, 9-11 years), in which patients had been seen within the last 1 year, were included in this retrospective review. During that period, 11 patients with infected TKAs were treated with other approaches (including two-stage approaches in eight); the general indication for one-stage revision was the diagnosis of PJI with a known causative organism. Exclusion criteria were culture-negative preoperative aspiration, known allergy to local antibiotics or bone cement, or cases in which radical débridement was impossible as a result of the involvement of important anatomical structures. Eighty-one patients with PJI were seen during this period; 70 underwent one-stage exchange using our strict protocol and were reimplanted with a rotating hinge TKA. Eleven patients (15.7%) were lost to followup. Hospital for Special Surgery scores were recorded and all radiographs were evaluated for prosthetic loosening. Failure was defined as revision surgery for infection or any other cause. Our 10-year infection-free survival was 93% (mean, 4.1; 95% confidence interval [CI], 89%-96%; p < 0.007); and the patient 10-year survival rate free of revision for other causes was 91% (mean, 5.2; 95% CI, 86%-95%; p < 0.002). Mean Hospital for Special Surgery knee score at last followup was 69.6 (± 22.5 SD; range, 22-100) and the mean improvement in Hospital for Special Surgery knee score from preoperative to most recent followup was 35 (± 24.2 SD; range, 13-99). Evidence of radiographic loosening was seen in 11 patients at last followup, whereby in six patients, there was need for revision surgery. Our study results showed an overall infection control rate of 93% and good clinical results using our one-stage approach, which combines aggressive débridement of the collateral ligaments and posterior capsule with a rotating hinge implant. These results are comparable with two-stage techniques at a followup of 10 years; further research into one-stage exchange techniques for PJI in TKA appears warranted. Level IV, therapeutic study.

Optimal land use management for soil erosion control by using an interval-parameter fuzzy two-stage stochastic programming approach.

PubMed

Han, Jing-Cheng; Huang, Guo-He; Zhang, Hua; Li, Zhong

2013-09-01

Soil erosion is one of the most serious environmental and public health problems, and such land degradation can be effectively mitigated through performing land use transitions across a watershed. Optimal land use management can thus provide a way to reduce soil erosion while achieving the maximum net benefit. However, optimized land use allocation schemes are not always successful since uncertainties pertaining to soil erosion control are not well presented. This study applied an interval-parameter fuzzy two-stage stochastic programming approach to generate optimal land use planning strategies for soil erosion control based on an inexact optimization framework, in which various uncertainties were reflected. The modeling approach can incorporate predefined soil erosion control policies, and address inherent system uncertainties expressed as discrete intervals, fuzzy sets, and probability distributions. The developed model was demonstrated through a case study in the Xiangxi River watershed, China's Three Gorges Reservoir region. Land use transformations were employed as decision variables, and based on these, the land use change dynamics were yielded for a 15-year planning horizon. Finally, the maximum net economic benefit with an interval value of [1.197, 6.311] × 10(9) $ was obtained as well as corresponding land use allocations in the three planning periods. Also, the resulting soil erosion amount was found to be decreased and controlled at a tolerable level over the watershed. Thus, results confirm that the developed model is a useful tool for implementing land use management as not only does it allow local decision makers to optimize land use allocation, but can also help to answer how to accomplish land use changes.

Optimal Land Use Management for Soil Erosion Control by Using an Interval-Parameter Fuzzy Two-Stage Stochastic Programming Approach

NASA Astrophysics Data System (ADS)

Han, Jing-Cheng; Huang, Guo-He; Zhang, Hua; Li, Zhong

2013-09-01

Soil erosion is one of the most serious environmental and public health problems, and such land degradation can be effectively mitigated through performing land use transitions across a watershed. Optimal land use management can thus provide a way to reduce soil erosion while achieving the maximum net benefit. However, optimized land use allocation schemes are not always successful since uncertainties pertaining to soil erosion control are not well presented. This study applied an interval-parameter fuzzy two-stage stochastic programming approach to generate optimal land use planning strategies for soil erosion control based on an inexact optimization framework, in which various uncertainties were reflected. The modeling approach can incorporate predefined soil erosion control policies, and address inherent system uncertainties expressed as discrete intervals, fuzzy sets, and probability distributions. The developed model was demonstrated through a case study in the Xiangxi River watershed, China's Three Gorges Reservoir region. Land use transformations were employed as decision variables, and based on these, the land use change dynamics were yielded for a 15-year planning horizon. Finally, the maximum net economic benefit with an interval value of [1.197, 6.311] × 109 was obtained as well as corresponding land use allocations in the three planning periods. Also, the resulting soil erosion amount was found to be decreased and controlled at a tolerable level over the watershed. Thus, results confirm that the developed model is a useful tool for implementing land use management as not only does it allow local decision makers to optimize land use allocation, but can also help to answer how to accomplish land use changes.

Speech in Adults Treated for Unilateral Cleft Lip and Palate: Long-Term Follow-Up After One- or Two-Stage Palate Repair.

PubMed

Morén, Staffan; Mani, Maria; Lilian, Stålhammar; Lindestad, Per Åke; Holmström, Mats

2017-11-01

  To evaluate speech in adults treated for unilateral cleft lip and palate with one-stage or two-stage palate closure and compare the speech of the patients with that of a noncleft control group.   Cross-sectional study with long-term follow-up.   All unilateral cleft lip and palate patients born from 1960 to 1987 and treated at Uppsala University Hospital, Sweden, were invited (n = 109). Participation rate was 67% (n = 73) at a mean of 35 years after primary surgery. Forty-seven had been treated according to one-stage palate closure and 26 according to two-stage palate closure. Pharyngeal flap surgery had been performed in 11 of the 73 patients (15%). The noncleft control group consisted of 63 age-matched volunteers.   Speech-language pathologists rated perceptual speech characteristics from blinded audio recordings.   Among patients, seven (10%) presented with hypernasality, 12 (16%) had audible nasal emission and/or nasal turbulence, five (7%) had consonant production errors, one (2%) had glottal reinforcements/substitutions, and one (2%) had reduced intelligibility. Controls had no audible signs of velopharyngeal insufficiency and no quantifiable problems with the other speech production variables. No significant differences were identified between patients treated with one-stage and two-stage palate closure for any of the variables.   The prevalence of speech outcome indicative of velopharyngeal insufficiency among adult patients treated for unilateral cleft lip and palate was low but higher compared with individuals without cleft. Whether palatal closure is performed in one or two stages does not seem to affect the speech outcome at a mean age of 35 years.

Extraction of liver volumetry based on blood vessel from the portal phase CT dataset

NASA Astrophysics Data System (ADS)

Maklad, Ahmed S.; Matsuhiro, Mikio; Suzuki, Hidenobu; Kawata, Yoshiki; Niki, Noboru; Utsunomiya, Tohru; Shimada, Mitsuo

2012-02-01

At liver surgery planning stage, the liver volumetry would be essential for surgeons. Main problem at liver extraction is the wide variability of livers in shapes and sizes. Since, hepatic blood vessels structure varies from a person to another and covers liver region, the present method uses that information for extraction of liver in two stages. The first stage is to extract abdominal blood vessels in the form of hepatic and nonhepatic blood vessels. At the second stage, extracted vessels are used to control extraction of liver region automatically. Contrast enhanced CT datasets at only the portal phase of 50 cases is used. Those data include 30 abnormal livers. A reference for all cases is done through a comparison of two experts labeling results and correction of their inter-reader variability. Results of the proposed method agree with the reference at an average rate of 97.8%. Through application of different metrics mentioned at MICCAI workshop for liver segmentation, it is found that: volume overlap error is 4.4%, volume difference is 0.3%, average symmetric distance is 0.7 mm, Root mean square symmetric distance is 0.8 mm, and maximum distance is 15.8 mm. These results represent the average of overall data and show an improved accuracy compared to current liver segmentation methods. It seems to be a promising method for extraction of liver volumetry of various shapes and sizes.

One-stage or two-stage revision surgery for prosthetic hip joint infection--the INFORM trial: a study protocol for a randomised controlled trial.

PubMed

Strange, Simon; Whitehouse, Michael R; Beswick, Andrew D; Board, Tim; Burston, Amanda; Burston, Ben; Carroll, Fran E; Dieppe, Paul; Garfield, Kirsty; Gooberman-Hill, Rachael; Jones, Stephen; Kunutsor, Setor; Lane, Athene; Lenguerrand, Erik; MacGowan, Alasdair; Moore, Andrew; Noble, Sian; Simon, Joanne; Stockley, Ian; Taylor, Adrian H; Toms, Andrew; Webb, Jason; Whittaker, John-Paul; Wilson, Matthew; Wylde, Vikki; Blom, Ashley W

2016-02-17

Periprosthetic joint infection (PJI) affects approximately 1% of patients following total hip replacement (THR) and often results in severe physical and emotional suffering. Current surgical treatment options are debridement, antibiotics and implant retention; revision THR; excision of the joint and amputation. Revision surgery can be done as either a one-stage or two-stage operation. Both types of surgery are well-established practice in the NHS and result in similar rates of re-infection, but little is known about the impact of these treatments from the patient's perspective. The main aim of this randomised controlled trial is to determine whether there is a difference in patient-reported outcome measures 18 months after randomisation for one-stage or two-stage revision surgery. INFORM (INFection ORthopaedic Management) is an open, two-arm, multi-centre, randomised, superiority trial. We aim to randomise 148 patients with eligible PJI of the hip from approximately seven secondary care NHS orthopaedic units from across England and Wales. Patients will be randomised via a web-based system to receive either a one-stage revision or a two-stage revision THR. Blinding is not possible due to the nature of the intervention. All patients will be followed up for 18 months. The primary outcome is the WOMAC Index, which assesses hip pain, function and stiffness, collected by questionnaire at 18 months. Secondary outcomes include the following: cost-effectiveness, complications, re-infection rates, objective hip function assessment and quality of life. A nested qualitative study will explore patients' and surgeons' experiences, including their views about trial participation and randomisation. INFORM is the first ever randomised trial to compare two widely accepted surgical interventions for the treatment of PJI: one-stage and two-stage revision THR. The results of the trial will benefit patients in the future as the main focus is on patient-reported outcomes: pain, function and wellbeing in the long term. Patients state that these outcomes are more important than those that are clinically derived (such as re-infection) and have been commonly used in previous non-randomised studies. Results from the INFORM trial will also benefit clinicians and NHS managers by enabling the comparison of these key interventions in terms of patients' complication rates, health and social resource use and their overall cost-effectiveness. Current controlled trials ISRCTN10956306 (registered on 29 January 2015); UKCRN ID 18159.

A modified varying-stage adaptive phase II/III clinical trial design.

PubMed

Dong, Gaohong; Vandemeulebroecke, Marc

2016-07-01

Conventionally, adaptive phase II/III clinical trials are carried out with a strict two-stage design. Recently, a varying-stage adaptive phase II/III clinical trial design has been developed. In this design, following the first stage, an intermediate stage can be adaptively added to obtain more data, so that a more informative decision can be made. Therefore, the number of further investigational stages is determined based upon data accumulated to the interim analysis. This design considers two plausible study endpoints, with one of them initially designated as the primary endpoint. Based on interim results, another endpoint can be switched as the primary endpoint. However, in many therapeutic areas, the primary study endpoint is well established. Therefore, we modify this design to consider one study endpoint only so that it may be more readily applicable in real clinical trial designs. Our simulations show that, the same as the original design, this modified design controls the Type I error rate, and the design parameters such as the threshold probability for the two-stage setting and the alpha allocation ratio in the two-stage setting versus the three-stage setting have a great impact on the design characteristics. However, this modified design requires a larger sample size for the initial stage, and the probability of futility becomes much higher when the threshold probability for the two-stage setting gets smaller. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Corticobasal degeneration initially developing motor versus non-motor symptoms: a comparative clinicopathological study.

PubMed

Ikeda, Chikako; Yokota, Osamu; Nagao, Shigeto; Ishizu, Hideki; Morisada, Yumi; Terada, Seishi; Nakashima, Yoshihiko; Akiyama, Haruhiko; Uchitomi, Yosuke

2014-09-01

Clinical presentations of pathologically confirmed corticobasal degeneration (CBD) vary, and the heterogeneity makes its clinical diagnosis difficult, especially when a patient lacks any motor disturbance in the early stage. We compared clinical and pathological features of four pathologically confirmed CBD cases that initially developed non-motor symptoms, including behavioural and psychiatric symptoms but without motor disturbance (CBD-NM), and five CBD cases that initially developed parkinsonism and/or falls (CBD-M). The age range at death for the CBD-NM and CBD-M subjects (58-85 years vs 45-67 years) and the range of disease duration (2-18 years vs 2-6 years) did not significantly differ between the groups. Prominent symptoms in the early stage of CBD-NM cases included self-centred behaviours such as frontotemporal dementia (n = 1), apathy with and without auditory hallucination (n = 2), and aggressive behaviours with delusion and visual hallucination (n = 1). Among the four CBD-NM cases, only one developed asymmetric motor disturbance, and two could walk without support throughout the course. Final clinical diagnoses of the CBD-NM cases were frontotemporal dementia (n = 2), senile psychosis with delirium (n = 1), and schizophrenia (n = 1). Neuronal loss was significantly less severe in the subthalamic nucleus and substantia nigra in the CBD-NM cases than in the CBD-M cases. The severity of tau pathology in all regions examined was comparable in the two groups. CBD cases that initially develop psychiatric and behavioural changes without motor symptoms may have less severe degenerative changes in the subthalamic nucleus and substantia nigra, and some CBD cases can lack motor disturbance not only in the early stage but also in the last stage of the course. © 2014 The Authors. Psychogeriatrics © 2014 Japanese Psychogeriatric Society.

[Helicobacter pylori gastritis: assessment of OLGA and OLGIM staging systems].

PubMed

Ben Slama, Sana; Ben Ghachem, Dorra; Dhaoui, Amen; Jomni, Mohamed Taieb; Dougui, Mohamed Hédi; Bellil, Khadija

2016-01-01

Helicobacter pylori (H pylori) gastritis presents a risk of cancer related to atrophy and intestinal metaplasia. Two recent classifications OLGA (Operative Link on Gastritis Assessment) and OLGIM (Operative Link on Gastritic Intestinal Metaplasia assessment) have been proposed to identify high-risk forms (stages III and IV). The aim of this study is to evaluate the OLGA and OLGIM staging systems in H pylori gastritis. A descriptive study of 100 cases of chronic H pylori gastritis was performed. The revaluation of Sydney System parameters of atrophy and intestinal metaplasia, of gastric antrum and corpus, allowed identifying respectively the stages of OLGA and OLGIM systems. The progressive risk of our H pylori gastritis was 6% according to OLGA staging and 7% according to OLGIM staging. Significant correlation was revealed between age and OLGA staging. High-risk gastritis according to OLGIM staging was significantly associated with moderate to severe atrophy. High-risk forms according to OLGA staging were associated in 80% of the cases to intestinal metaplasia. OLGA and OLGIM systems showed a highly significant positive correlation between them with a mismatch at 5% for H pylori gastritis. The OLGA and OLGIM staging systems in addition to Sydney System, allow selection of high risk forms of chronic gastritis requiring accurate observation.

North American Multicenter Volumetric CT Study for Clinical Staging of Malignant Pleural Mesothelioma: Feasibility and Logistics of Setting Up a Quantitative Imaging Study.

PubMed

Gill, Ritu R; Naidich, David P; Mitchell, Alan; Ginsberg, Michelle; Erasmus, Jeremy; Armato, Samuel G; Straus, Christopher; Katz, Sharyn; Patios, Demetrois; Richards, William G; Rusch, Valerie W

2016-08-01

Clinical tumor (T), node, and metastasis staging is based on a qualitative assessment of features defining T descriptors and has been found to be suboptimal for predicting the prognosis of patients with malignant pleural mesothelioma (MPM). Previous work suggests that volumetric computed tomography (VolCT) is prognostic and, if found practical and reproducible, could improve clinical MPM classification. Six North American institutions electronically submitted clinical, pathologic, and imaging data on patients with stages I to IV MPM to an established multicenter database and biostatistical center. Two reference radiologists blinded to clinical data independently reviewed the scans; calculated clinical T, node, and metastasis stage by standard criteria; performed semiautomated tumor volume calculations using commercially available software; and submitted the findings to the biostatistical center. Study end points included the feasibility of a multi-institutional VolCT network, concordance of independent VolCT assessments, and association of VolCT with pathological T classification. Of 164 submitted cases, 129 were evaluated by both reference radiologists. Discordant clinical staging of most cases confirmed the inadequacy of current criteria. The overall correlation between VolCT estimates was good (Spearman correlation 0.822), but some were significantly discordant. Root cause analysis of the most discordant estimates identified four common sources of variability. Despite these limitations, median tumor volume estimates were similar within subgroups of cases representing each pathological T descriptor and increased monotonically for each reference radiologist with increasing pathological T status. The good correlation between VolCT estimates obtained for most cases reviewed by two independent radiologists and qualitative association of VolCT with pathological T status combine to encourage further study. The identified sources of user error will inform design of a follow-up prospective trial to more formally assess interobserver variability of VolCT and its potential contribution to clinical MPM staging. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

The Complex Pre-Execution Stage of Auditory Cognitive Control: ERPs Evidence from Stroop Tasks

PubMed Central

Yu, Bo; Wang, Xunda; Ma, Lin; Li, Liang; Li, Haifeng

2015-01-01

Cognitive control has been extensively studied from Event-Related Potential (ERP) point of view in visual modality using Stroop paradigms. Little work has been done in auditory Stroop paradigms, and inconsistent conclusions have been reported, especially on the conflict detection stage of cognitive control. This study investigated the early ERP components in an auditory Stroop paradigm, during which participants were asked to identify the volume of spoken words and ignore the word meanings. A series of significant ERP components were revealed that distinguished incongruent and congruent trials: two declined negative polarity waves (the N1 and the N2) and three declined positive polarity wave (the P1, the P2 and the P3) over the fronto-central area for the incongruent trials. These early ERP components imply that both a perceptual stage and an identification stage exist in the auditory Stroop effect. A 3-stage cognitive control model was thus proposed for a more detailed description of the human cognitive control mechanism in the auditory Stroop tasks. PMID:26368570

Is interleukin-17 a proatherogenic biomarker?

PubMed

Cătană, Cristina-Sorina; Cristea, Victor; Miron, Nicolae; Neagoe, Ioana Berindan

2011-01-01

The importance of chronic inflammation in atherogenesis and cytokine involvement in all stages of atherosclerotic plaque development is now obvious. Our approach of the significant cytokines involved in atherogenesis or cardiovascular diseases is based on a correlation between clinical research and experiments on animal models. The contribution of IL-17 in atherogenesis remains controversial. In this study we investigated the role of IL-17 in cardiovascular diseases and in atherosclerosis associated with pathological aging. We performed a case-control study, enrolling subjects aged over 65 years in both groups. We included 40 patients with cardiovascular disorders and 10 healthy volunteers. IL-17 levels were measured in the serum of patients and healthy controls, along with serum total cholesterol and triglycerides. Significantly higher levels of IL-17 were obtained in patients compared to healthy controls (p<0.001). The level of this biomarker correlated significantly with two biochemical parameters - serum total cholesterol and triglycerides (the Pearson coefficient showed statistical significance, p=0.033, respectively p=0.043). We did not find any correlation between IL-17 and these two parameters in the control group. Our study is useful in understanding the physiopathological implications of IL-17 in the atherogenesis process. This could represent a starting point for future studies, including research regarding the therapeutic potential of IL-17 in pathological aging.

Title IV Quality Control Project, Stage II. Management Option II: Delivery System Quality Improvements.

ERIC Educational Resources Information Center

Advanced Technology, Inc., Reston, VA.

Stage Two of the Title IV Quality Control Project is an integrated study of quality in five related Federal financial aid programs for postsecondary students. Section 1 of the paper establishes a framework for defining quality improvements, in order to identify the types of changes that would tend to improve quality across all facets of the…

A prospective evaluation of early detection biomarkers for ovarian cancer in the European EPIC cohort

PubMed Central

Terry, Kathryn L.; Schock, Helena; Fortner, Renée T.; Hüsing, Anika; Fichorova, Raina N.; Yamamoto, Hidemi S.; Vitonis, Allison F.; Johnson, Theron; Overvad, Kim; Tjønneland, Anne; Boutron-Ruault, Marie-Christine; Mesrine, Sylvie; Severi, Gianluca; Dossus, Laure; Rinaldi, Sabina; Boeing, Heiner; Benetou, Vassiliki; Lagiou, Pagona; Trichopoulou, Antonia; Krogh, Vittorio; Kuhn, Elisabetta; Panico, Salvatore; Bueno-de-Mesquita, H. Bas; Onland-Moret, N. Charlotte; Peeters, Petra H.; Gram, Inger Torhild; Weiderpass, Elisabete; Duell, Eric J.; Sanchez, Maria-Jose; Ardanaz, Eva; Etxezarreta, Nerea; Navarro, Carmen; Idahl, Annika; Lundin, Eva; Jirström, Karin; Manjer, Jonas; Wareham, Nicholas J.; Khaw, Kay-Tee; Byrne, Karl Smith; Travis, Ruth C.; Gunter, Marc J.; Merritt, Melissa A.; Riboli, Elio; Cramer, Daniel W.; Kaaks, Rudolf

2016-01-01

Purpose About 60% of ovarian cancers are diagnosed at late stage, when 5-year survival is less than 30% in contrast to 90% for local disease. This has prompted search for early detection biomarkers. For initial testing, specimens taken months or years before ovarian cancer diagnosis are the best source of information to evaluate early detection biomarkers. Here we evaluate the most promising ovarian cancer screening biomarkers in prospectively collected samples from the European Prospective Investigation into Cancer and Nutrition study. Experimental Design We measured CA125, HE4, CA72.4 and CA15.3 in 810 invasive epithelial ovarian cancer cases and 1,939 controls. We calculated the sensitivity at 95% and 98% specificity as well as Area under the Receiver Operator Curve (C-statistic) for each marker individually and in combination. Additionally, we evaluated marker performance by stage at diagnosis and time between blood draw and diagnosis. Results We observed the best discrimination between cases and controls within six months of diagnosis for CA125 (C-statistic=0.92), then HE4 (0.84), CA72.4 (0.77), and CA15.3 (0.73). Marker performance declined with longer time between blood draw and diagnosis and for earlier staged disease. However, assessment of discriminatory ability at early stage was limited by small numbers. Combinations of markers performed modestly, but significantly better than any single marker. Conclusions CA125 remains the single best marker for the early detection of invasive epithelial ovarian cancer, but can be slightly improved by combining with other markers. Identifying novel markers for ovarian cancer will require studies including larger numbers of early stage cases. PMID:27060155

A Prospective Evaluation of Early Detection Biomarkers for Ovarian Cancer in the European EPIC Cohort.

PubMed

Terry, Kathryn L; Schock, Helena; Fortner, Renée T; Hüsing, Anika; Fichorova, Raina N; Yamamoto, Hidemi S; Vitonis, Allison F; Johnson, Theron; Overvad, Kim; Tjønneland, Anne; Boutron-Ruault, Marie-Christine; Mesrine, Sylvie; Severi, Gianluca; Dossus, Laure; Rinaldi, Sabina; Boeing, Heiner; Benetou, Vassiliki; Lagiou, Pagona; Trichopoulou, Antonia; Krogh, Vittorio; Kuhn, Elisabetta; Panico, Salvatore; Bueno-de-Mesquita, H Bas; Onland-Moret, N Charlotte; Peeters, Petra H; Gram, Inger Torhild; Weiderpass, Elisabete; Duell, Eric J; Sanchez, Maria-Jose; Ardanaz, Eva; Etxezarreta, Nerea; Navarro, Carmen; Idahl, Annika; Lundin, Eva; Jirström, Karin; Manjer, Jonas; Wareham, Nicholas J; Khaw, Kay-Tee; Byrne, Karl Smith; Travis, Ruth C; Gunter, Marc J; Merritt, Melissa A; Riboli, Elio; Cramer, Daniel W; Kaaks, Rudolf

2016-09-15

About 60% of ovarian cancers are diagnosed at late stage, when 5-year survival is less than 30% in contrast to 90% for local disease. This has prompted search for early detection biomarkers. For initial testing, specimens taken months or years before ovarian cancer diagnosis are the best source of information to evaluate early detection biomarkers. Here we evaluate the most promising ovarian cancer screening biomarkers in prospectively collected samples from the European Prospective Investigation into Cancer and Nutrition study. We measured CA125, HE4, CA72.4, and CA15.3 in 810 invasive epithelial ovarian cancer cases and 1,939 controls. We calculated the sensitivity at 95% and 98% specificity as well as area under the receiver operator curve (C-statistic) for each marker individually and in combination. In addition, we evaluated marker performance by stage at diagnosis and time between blood draw and diagnosis. We observed the best discrimination between cases and controls within 6 months of diagnosis for CA125 (C-statistic = 0.92), then HE4 (0.84), CA72.4 (0.77), and CA15.3 (0.73). Marker performance declined with longer time between blood draw and diagnosis and for earlier staged disease. However, assessment of discriminatory ability at early stage was limited by small numbers. Combinations of markers performed modestly, but significantly better than any single marker. CA125 remains the single best marker for the early detection of invasive epithelial ovarian cancer, but can be slightly improved by combining with other markers. Identifying novel markers for ovarian cancer will require studies including larger numbers of early-stage cases. Clin Cancer Res; 22(18); 4664-75. ©2016 AACRSee related commentary by Skates, p. 4542. ©2016 American Association for Cancer Research.

DNA pooling: a comprehensive, multi-stage association analysis of ACSL6 and SIRT5 polymorphisms in schizophrenia.

PubMed

Chowdari, K V; Northup, A; Pless, L; Wood, J; Joo, Y H; Mirnics, K; Lewis, D A; Levitt, P R; Bacanu, S-A; Nimgaonkar, V L

2007-04-01

Many candidate gene association studies have evaluated incomplete, unrepresentative sets of single nucleotide polymorphisms (SNPs), producing non-significant results that are difficult to interpret. Using a rapid, efficient strategy designed to investigate all common SNPs, we tested associations between schizophrenia and two positional candidate genes: ACSL6 (Acyl-Coenzyme A synthetase long-chain family member 6) and SIRT5 (silent mating type information regulation 2 homologue 5). We initially evaluated the utility of DNA sequencing traces to estimate SNP allele frequencies in pooled DNA samples. The mean variances for the DNA sequencing estimates were acceptable and were comparable to other published methods (mean variance: 0.0008, range 0-0.0119). Using pooled DNA samples from cases with schizophrenia/schizoaffective disorder (Diagnostic and Statistical Manual of Mental Disorders edition IV criteria) and controls (n=200, each group), we next sequenced all exons, introns and flanking upstream/downstream sequences for ACSL6 and SIRT5. Among 69 identified SNPs, case-control allele frequency comparisons revealed nine suggestive associations (P<0.2). Each of these SNPs was next genotyped in the individual samples composing the pools. A suggestive association with rs 11743803 at ACSL6 remained (allele-wise P=0.02), with diminished evidence in an extended sample (448 cases, 554 controls, P=0.062). In conclusion, we propose a multi-stage method for comprehensive, rapid, efficient and economical genetic association analysis that enables simultaneous SNP detection and allele frequency estimation in large samples. This strategy may be particularly useful for research groups lacking access to high throughput genotyping facilities. Our analyses did not yield convincing evidence for associations of schizophrenia with ACSL6 or SIRT5.

Genetic variants in long non-coding RNA MIAT contribute to risk of paranoid schizophrenia in a Chinese Han population.

PubMed

Rao, Shu-Quan; Hu, Hui-Ling; Ye, Ning; Shen, Yan; Xu, Qi

2015-08-01

The heritability of schizophrenia has been reported to be as high as ~80%, but the contribution of genetic variants identified to this heritability remains to be estimated. Long non-coding RNAs (LncRNAs) are involved in multiple processes critical to normal cellular function and dysfunction of lncRNA MIAT may contribute to the pathophysiology of schizophrenia. However, the genetic evidence of lncRNAs involved in schizophrenia has not been documented. Here, we conducted a two-stage association analysis on 8 tag SNPs that cover the whole MIAT locus in two independent Han Chinese schizophrenia case-control cohorts (discovery sample from Shanxi Province: 1093 patients with paranoid schizophrenia and 1180 control subjects; replication cohort from Jilin Province: 1255 cases and 1209 healthy controls). In discovery stage, significant genetic association with paranoid schizophrenia was observed for rs1894720 (χ(2)=74.20, P=7.1E-18), of which minor allele (T) had an OR of 1.70 (95% CI=1.50-1.91). This association was confirmed in the replication cohort (χ(2)=22.66, P=1.9E-06, OR=1.32, 95%CI 1.18-1.49). Besides, a weak genotypic association was detected for rs4274 (χ(2)=4.96, df=2, P=0.03); the AA carriers showed increased disease risk (OR=1.30, 95%CI=1.03-1.64). No significant association was found between any haplotype and paranoid schizophrenia. The present studies showed that lncRNA MIAT was a novel susceptibility gene for paranoid schizophrenia in the Chinese Han population. Considering that most lncRNAs locate in non-coding regions, our result may explain why most susceptibility loci for schizophrenia identified by genome wide association studies were out of coding regions. Copyright © 2015 Elsevier B.V. All rights reserved.

A quantitative comparison of plaque types in Alzheimer's disease and senile dementia of the Lewy body type.

PubMed

McKenzie, J E; Edwards, R J; Gentleman, S M; Ince, P G; Perry, R H; Royston, M C; Roberts, G W

1996-01-01

In a previous study we reported no difference in the overall beta-amyloid protein (beta AP) load between Alzheimer's disease (AD) and senile dementia of the Lewy body type (SDLT). However, it is possible that differences in the morphology of beta AP plaque types exist, analogous to the differences in cytoskeletal pathology found in these two disorders. We have carried out a quantitative image analysis of plaque subtypes in the temporal lobe of AD (n = 8), SDLT (n = 9) and control (n = 11) cases. Measurements of beta AP load and plaque density were consistently higher in AD and SDLT than in controls. When AD and SDLT cases were compared no differences were seen in either the density or relative proportions of classic and diffuse plaques. Based on these results we suggest that the variation in the clinical course of these diseases reflects differences in the cytoskeletal pathology, whereas the final stages of profound dementia common to both disorders is associated with the deposition of beta AP.

Necrotizing enterocolitis as a prognostic factor for the neurodevelopmental outcome of preterm infants - match control study after 2years.

PubMed

Allendorf, Antje; Dewitz, Ruth; Weber, Joy; Bakthiar, Shahrzad; Schloesser, Rolf; Rolle, Udo

2018-01-31

Necrotizing enterocolitis (NEC) in very low birth weight infants is a risk factor for developmental delay. To our knowledge, there are no studies published investigating the neurodevelopmental outcome of patients with NEC comparing surgically treated and conservatively treated patients versus match paired controls. The aim of this retrospective case control study was to measure the neurodevelopmental outcome of patients with NEC who were treated surgically or conservatively METHODS: All patients were identified, who have been diagnosed with NEC (ICD-10 code, P77) born between 2006 and 2013. Patients with NEC received antibiotic therapy, nasogastric decompression and fasting. Surgical treatment was indicated for patients with Bell stages IIIb. We excluded patients suffering from other relevant diseases with a possible impact on their neurodevelopmental outcome (e.g., intraventricular hemorrhage, associated malformations, asphyxia, focal intestinal perforation, short bowel syndrome). Patients were tested at the corrected gestational age of 24months according to the Bayley Scales of Infant Development II. Each participant was compared to a child of the same sex, gestational age at birth (+/-two days), birth weight (+/-10%), and age at neurodevelopmental testing (IRB approval, No. 14/2014). The outcome measures were the psychomotor index (PDI) and the mental developmental index (MDI). We included 13 conservatively and 24 surgically treated patients. The patients in group A (without surgery) achieved a mean PDI of 106, and those in group B (with surgery) a mean PDI of 90. These values were significantly higher in the conservative group A. The mean MDIs were 99 in the patient group A and 85 in patient group B. This difference was also significant. We found significantly lower MDIs and PDIs in children with surgical treatment of NEC. Further systematic prospective research on the prevention of NEC and systematic follow-ups at later stages in the patients' development are necessary in order to implement early intervention. case control study. III. Copyright © 2018. Published by Elsevier Inc.

Evaluation of effect of self-examination and physical examination on breast cancer.

PubMed

Hassan, Lotfi Mohammad; Mahmoud, Noori; Miller, Anthony B; Iraj, Harrirchi; Mohsen, Mirzaei; Majid, Jafarizadea; Reza, Sadeghian Mohammad; Mojgan, Minosepehr

2015-08-01

Breast cancer is the number one cancer of women in the world. More than 90% of breast cancers can be cured with early diagnosis followed by effective multimodality treatment. The efficacy of screening by breast self-examination (BSE) and breast physical examination (BPx) is best evaluated using randomized screening trials. A total of 12,660 women aged 35-64 years, 6330 in the intervention group and 6330 in the control group, were randomly selected from four areas of Yazd city, I.R. of Iran. The number of detected cancers along with kind of cancer, staging of cancer, the route of detected cancer and the number of deaths during the first 5 years of the study were collected and analyzed. No significance difference between the two groups was seen in respect to socio-demographic and socio-economic variables (P > 0.05). Subjects in the intervention group had a response rate of 83.5% for attending the health center and 80.2% for visiting the assigned surgeon. A total of 31 and 13 new cases of breast cancer were identified in the intervention and control groups, respectively, of which 48.5% of cases in the intervention group were <50 yr of age. A significant difference between the cumulative incidence of breast cancer in the two groups with a ratio of 2.4 was observed. BSE & BPx have a significant effect in detecting breast cancers at early stages (<3) suggesting they are effective screening tests with high availability and low costs that can be applied at the community level. Copyright © 2015 Elsevier Ltd. All rights reserved.

Genetics of schizophrenia and smoking: an approach to studying their comorbidity based on epidemiological findings

PubMed Central

de Leon, Jose; Diaz, Francisco J.

2012-01-01

The association between schizophrenia and tobacco smoking has been described in more than 1,000 articles, many with inadequate methodology. The studies on this association can focus on: (1) current smoking, ever smoking or smoking cessation; (2) non-psychiatric controls or controls with severe mental illness (e.g., bipolar disorder); and (3) higher smoking frequency or greater usage in smokers. The association with the most potential for genetic studies is that between ever daily smoking and schizophrenia; it may reflect a shared genetic vulnerability. To reduce the number of false-positive genes, we propose a three-stage approach derived from epidemiological knowledge. In the first stage, only genetic variations associated with ever daily smoking that are simultaneously significant within the non-psychiatric controls, the bipolar disorder controls and the schizophrenia cases will be selected. Only those genetic variations that are simultaneously significant in the three hypothesis tests will be tested in the second stage, where the prevalence of the genes must be significantly higher in schizophrenia than in bipolar disorder, and significantly higher in bipolar disorder than in controls. The genes simultaneously significant in the second stage will be included in a third stage where the gene variations must be significantly more frequent in schizophrenia patients who did not start smoking daily until their 20s (late start) versus those who had an early start. Any genetic approach to psychiatric disorders may fail if attention is not given to comorbidity and epidemiological studies that suggest which comorbidities are likely to be explained by genetics and which are not. Our approach, which examines the results of epidemiological studies on comorbidities and then looks for genes that simultaneously satisfy epidemiologically suggested sets of hypotheses, may also apply to the study of other major illnesses. PMID:22190153

Impact of the 2009 AJCC staging guidelines for melanoma on the number of mitotic figures reported by dermatopathologists at one institution.

PubMed

Larson, Allison R; Rothschild, Brian; Walls, Andrew C; Granter, Scott R; Qureshi, Abrar A; Murphy, George F; Laga, Alvaro C

2015-08-01

In 2009 the revised seventh staging system for melanoma recommended the use of mitotic count to separate stage T1a from T1b. However, careful scrutiny of cases may lead to an inadvertent selection effect, with consequent increased reporting of mitotic counts. We investigated whether there is a significant increase in mitotic counts reported since 2009 for melanomas with a Breslow thickness of 1.0 mm or less. We conducted a retrospective, case-controlled study examining invasive melanoma cases at a large academic center. Mitotic counts were compared between pathology reports before 2009 (n = 61) and after 2009 (n = 125), with a subset of slides re-examined in a blinded fashion. Before the 2009 staging guidelines, 51% of cases had one or more mitosis reported compared to 38% after 2009 (p = 0.113). Blinded re-counting did not yield a significant difference when compared with the original pathology reports in either group. There was not a significant difference in the number of mitoses reported after the implementation of the new guidelines. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Single-stage-to-orbit versus two-stage-two-orbit: A cost perspective

NASA Astrophysics Data System (ADS)

Hamaker, Joseph W.

1996-03-01

This paper considers the possible life-cycle costs of single-stage-to-orbit (SSTO) and two-stage-to-orbit (TSTO) reusable launch vehicles (RLV's). The analysis parametrically addresses the issue such that the preferred economic choice comes down to the relative complexity of the TSTO compared to the SSTO. The analysis defines the boundary complexity conditions at which the two configurations have equal life-cycle costs, and finally, makes a case for the economic preference of SSTO over TSTO.

Tendon 'turnover lengthening' technique.

PubMed

Cerovac, S; Miranda, B H

2013-11-01

Tendon defect reconstruction is amongst the most technically challenging areas in hand surgery. Tendon substance deficiency reconstruction techniques include lengthening, grafting, two-stage reconstruction and tendon transfers, however each is associated with unique challenges over and above direct repair. We describe a novel 'turnover lengthening' technique for hand tendons that has successfully been applied to the repair of several cases, including a case of attritional flexor and traumatic extensor tendon rupture in two presented patients where primary tenorrhaphy was not possible. In both cases a good post-operative outcome was achieved, as the patients were happy having returned back to normal activities of daily living such that they were discharged 12 weeks post-operatively. Our technique avoids the additional morbidity and complications associated with grafting, transfers and two stage reconstructions. It is quick, simple and reproducible for defects not exceeding 3-4 cm, provides a means of immediate one stage reconstruction, no secondary donor site morbidity and does not compromise salvage by tendon transfer and/or two-stage reconstruction in cases of failure. To our knowledge no such technique has been previously been described to reconstruct such hand tendon defects. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

The versican gene and the risk of intracranial aneurysms.

PubMed

Ruigrok, Ynte M; Rinkel, Gabriël J E; Wijmenga, Cisca

2006-09-01

The proteoglycan versican is an excellent candidate gene for intracranial aneurysms (IAs) because it plays an important role in extracellular matrix assembly and is localized in a previously implicated locus for IAs on chromosome 5q. We analyzed all the common variations using 16-tag single nucleotide polymorphisms (SNPs) and haplotypes in the versican gene using a 2-stage genotyping approach. For stage 1, 16 SNPs were genotyped in 307 cases and 639 controls. For stage 2, the two SNPs yielding the most significant associations (P<0.01) were genotyped in a second independent cohort of 310 cases for confirmation of the associations. In stage 1, we found several SNPs in strong linkage disequilibrium and haplotypes constituting these SNPs associated with IAs in the Dutch population (strongest SNP association for rs173686 with odds ratio=1.34, 95% CI=1.09 to 1.65, P=0.004). In stage 2, we confirmed association for the 2 SNPs with the most significant associations (strongest SNP association for rs173686 with odds ratio=1.36, 95% CI=1.11 to 1.67, P=0.003). SNPs in strong linkage disequilibrium and haplotypes constituting these SNPs in the versican gene are associated with IAs suggesting that variation in or near the versican gene plays a role in susceptibility to IAs.

Two stage algorithm vs commonly used approaches for the suspect screening of complex environmental samples analyzed via liquid chromatography high resolution time of flight mass spectroscopy: A test study.

PubMed

Samanipour, Saer; Baz-Lomba, Jose A; Alygizakis, Nikiforos A; Reid, Malcolm J; Thomaidis, Nikolaos S; Thomas, Kevin V

2017-06-09

LC-HR-QTOF-MS recently has become a commonly used approach for the analysis of complex samples. However, identification of small organic molecules in complex samples with the highest level of confidence is a challenging task. Here we report on the implementation of a two stage algorithm for LC-HR-QTOF-MS datasets. We compared the performances of the two stage algorithm, implemented via NIVA_MZ_Analyzer™, with two commonly used approaches (i.e. feature detection and XIC peak picking, implemented via UNIFI by Waters and TASQ by Bruker, respectively) for the suspect analysis of four influent wastewater samples. We first evaluated the cross platform compatibility of LC-HR-QTOF-MS datasets generated via instruments from two different manufacturers (i.e. Waters and Bruker). Our data showed that with an appropriate spectral weighting function the spectra recorded by the two tested instruments are comparable for our analytes. As a consequence, we were able to perform full spectral comparison between the data generated via the two studied instruments. Four extracts of wastewater influent were analyzed for 89 analytes, thus 356 detection cases. The analytes were divided into 158 detection cases of artificial suspect analytes (i.e. verified by target analysis) and 198 true suspects. The two stage algorithm resulted in a zero rate of false positive detection, based on the artificial suspect analytes while producing a rate of false negative detection of 0.12. For the conventional approaches, the rates of false positive detection varied between 0.06 for UNIFI and 0.15 for TASQ. The rates of false negative detection for these methods ranged between 0.07 for TASQ and 0.09 for UNIFI. The effect of background signal complexity on the two stage algorithm was evaluated through the generation of a synthetic signal. We further discuss the boundaries of applicability of the two stage algorithm. The importance of background knowledge and experience in evaluating the reliability of results during the suspect screening was evaluated. Copyright © 2017 Elsevier B.V. All rights reserved.

The effect of hydroxyzine on treating bruxism of 2- to 14-year-old children admitted to the clinic of Bandar Abbas Children Hospital in 2013-2014.

PubMed

Rahmati, M; Moayedi, A; Zakery Shahvari, S; Golmirzaei, J; Zahirinea, M; Abbasi, B

2015-01-01

Introduction. Bruxism is to press or grind teeth against each other in non-physiologic cases, when an individual does not swallow or chew. If not treated, teeth problems, stress, mental disorders, frequent night waking, and headache is expected. This research aimed to study the effect of hydroxyzine on treating bruxism of 2- to 14-year-old children admitted to the clinic of Bandar Abbas Children Hospital. Methodology. In this clinical trial, 143 children with the ages between 4-12 years were admitted to the Children Hospital and were divided randomly into test and control groups. The test group consisted of 88 hydroxyzine-treated children and the control group consisted of 55 children who used hot towels. Both groups were examined in some stages including the pre-test stages or the stage before starting treatments at two, four, and six weeks and four months after stopping the treatment. The effects of each treatment on reducing bruxism symptoms were assessed by a questionnaire. The data were analyzed by using SPSS in descriptive statistics, t-test, and ANOVA. Results. As far as bruxism severity was concerned, the results showed a significant difference between the test group members who received hydroxyzine and the control group members who received no medication. T-test results showed a statistically significant difference between the test and the control groups in the second post-test (four weeks later) (p. value ≤ 0.05). Mean of the scores of bruxism severity in the test group has changed significantly in the post-test (at two weeks, four weeks, and six weeks later) as compared to the pre-test. Whereas, as far as the response to the treatment, no significant difference was recorded between the control group and the test group 4 weeks after the treatment. Discussion. The results showed that prescribing hydroxyzine for 4 weeks had a considerable effect in diminishing bruxism severity between the test groups.

Exposure to ACEI/ARB and β-Blockers Is Associated with Improved Survival and Decreased Tumor Progression and Hospitalizations in Patients with Advanced Colon Cancer1

PubMed Central

Engineer, Diana R; Burney, Basil O; Hayes, Teresa G; Garcia, Jose M

2013-01-01

BACKGROUND: Advanced colon cancer is associated with weight loss and decreased survival. Studies suggest that angiotensin and β-adrenergic blockade decrease colon cancer progression and ameliorate weight loss. This study aims to determine whether exposure to β-adrenoceptor blockers (BBs), angiotensin-converting enzyme inhibitors (ACEIs), or angiotensin receptor blockers (ARBs) is associated with decreased mortality, tumor progression, number of hospitalizations, or weight loss in colorectal cancer. METHODS: Retrospective chart review included patients with advanced colorectal cancer. Survival, stage, hospitalization, cancer progression, cancer treatment, and body weight history were collected. RESULTS: Two hundred sixty-two of 425 new stage III to IV colorectal cancer cases reviewed met the study criteria. Those exposed to ACEI/ARB, BB, or both were more likely to have diabetes, hypertension, and stage III colorectal cancer. Adjusting for age, presence of hypertension and diabetes, and stage, ACEI/ARB + BB exposure was associated with decreased mortality compared to unexposed individuals [hazard ratio (HR) = 0.5, confidence interval (CI) = 0.29–0.85; Cox regression, P = .01]. Fewer total and cancer-related hospitalizations and decreased cancer progression in the ACEI/ARB + BB group versus the unexposed group (HR = 0.59, CI = 0.36–0.99, P = .047) were seen. Exposure did not affect weight changes; furthermore, body weight changes from both prediagnosis and at diagnosis to 6, 12, 18, and 24 months postdiagnosis predicted survival. CONCLUSIONS: We have observed an association between exposure to a combination of ACEI/ARB + BB and increased survival, decreased hospitalizations, and decreased tumor progression in advanced colorectal cancer. Future studies will be needed to replicate these results and generalize them to broader populations. Determination of causality will require a randomized controlled trial. PMID:24151534

Relationship of associated secondary hyperparathyroidism to serum fibroblast growth factor-23 in end stage renal disease: A case-control study

PubMed Central

Sliem, Hamdy; Tawfik, Gamal; Moustafa, Fadia; Zaki, Heba

2011-01-01

Introduction: Secondary hyperparathyroidism (SHPT) is an insidious disease that develops early in the course of chronic kidney disease (CKD) and increases in severity as the glomerular filtration rate deteriorates. Recent studies have identified fibroblast growth factor-23 (FGF23) as a new protein with phosphaturic activity. It is mainly secreted by osteoblasts and is now considered the most important factor for regulation of phosphorus homeostasis. It is not yet proven if there is any direct relation between parathyroid hormone (PTH) and FGF23. The present study aims to evaluate the relation between serum FGF23, phosphorus, and PTH in end-stage renal disease in patients with SHPT on regular hemodialysis. Materials and Methods: Forty-six consecutive CKD adult patients (case group) and 20 healthy adults (control group) were included in the study. All patients had SHPT and were on regular hemodialysis. Both groups were subjected to full medical history, clinical examination and biochemical studies. Serum phosphorus, calcium, ferritin, hemoglobin level, blood urea, creatinine, PTH, and FGF23 were analyzed. Results: Levels of FGF23 were significantly higher in the case group in comparison with those in the control group, viz., 4-fold, and positively correlated with PTH. Phosphorus levels in the case group were significantly high in spite of the increasing levels of FGF23. Both PTH and FGF23 were positively correlated with phosphorus and negatively with hemoglobin levels. Conclusion: SHPT and FGF23 may have a partial role in the development of anemia in patients with CKD. FGF23 could be a central factor in the pathogenesis of SHPT. Its role in controlling hyperphosphatemia in CKD is vague. PMID:21731867

Incidental Prophylactic Nodal Irradiation and Patterns of Nodal Relapse in Inoperable Early Stage NSCLC Patients Treated With SBRT: A Case-Matched Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lao, Louis; Department of Radiation Oncology, Auckland City Hospital, Auckland; Hope, Andrew J.

2014-09-01

Purpose: Reported rates of non-small cell lung cancer (NSCLC) nodal failure following stereotactic body radiation therapy (SBRT) are lower than those reported in the surgical series when matched for stage. We hypothesized that this effect was due to incidental prophylactic nodal irradiation. Methods and Materials: A prospectively collected group of medically inoperable early stage NSCLC patients from 2004 to 2010 was used to identify cases with nodal relapses. Controls were matched to cases, 2:1, controlling for tumor volume (ie, same or greater) and tumor location (ie, same lobe). Reference (normalized to equivalent dose for 2-Gy fractions [EQD2]) point doses atmore » the ipsilateral hilum and carina, demographic data, and clinical outcomes were extracted from the medical records. Univariate conditional logistical regression analyses were performed with variables of interest. Results: Cases and controls were well matched except for size. The controls, as expected, had larger gross tumor volumes (P=.02). The mean ipsilateral hilar doses were 9.6 Gy and 22.4 Gy for cases and controls, respectively (P=.014). The mean carinal doses were 7.0 Gy and 9.2 Gy, respectively (P=.13). Mediastinal nodal relapses, with and without ipsilateral hilar relapse, were associated with mean ipsilateral hilar doses of 3.6 Gy and 19.8 Gy, respectively (P=.01). The conditional density plot appears to demonstrate an inverse dose-effect relationship between ipsilateral hilar normalized total dose and risk of ipsilateral hilar relapse. Conclusions: Incidental hilar dose greater than 20 Gy is significantly associated with fewer ipsilateral hilar relapses in inoperable early stage NSCLC patients treated with SBRT.« less

A Role of Base Plate Jerk Feedback Scheme for Suppression of the Self Vibration in a Pneumatic Positioning Stage

NASA Astrophysics Data System (ADS)

Wali, Mohebullah; Nakamura, Yukinori; Wakui, Shinji

In this study, a positioning stage is considered, which is actuated by four pneumatic cylinders and vertically supported by four coil-type spring isolators. Previously, we realized the base plate jerk feedback (BPJFB) to be analogues to a Master-Slave system which can synchronize the motion of the stage as a Slave to the motion of the base plate as a Master. However, in the case of real positioning, the stage had slightly self oscillation with higher frequency due to the higher gains set to the outer feedback loop controller besides its oscillation due to the natural vibration of the base plate. The self oscillation of stage was misunderstood to be the natural vibration of base plate due to the reaction force. However, according to the experimental results, the BPJFB scheme was able to control both of the mentioned vibrations. Suppression of the self vibration of stage is an interesting phenomenon, which should be experimentally investigated. Therefore, the current study focuses on the suppression of the self vibration of stage by using the BPJFB scheme. The experimental results show that besides operating as a Master-Slave synchronizing system, the PBJFB scheme is able to increase the damping ratio and stiffness of stage against its self vibration. This newly recognized phenomenon contributes to further increase the proportional gain of the outer feedback loop controller. As a result, the positioning speed and stability can be improved.

Family clustering of secondary chronic kidney disease with hypertension or diabetes mellitus. A case-control study.

PubMed

de Almeida, Fernando Antonio; Ciambelli, Giuliano Serafino; Bertoco, André Luz; Jurado, Marcelo Mai; Siqueira, Guilherme Vasconcelos; Bernardo, Eder Augusto; Pavan, Maria Valeria; Gianini, Reinaldo José

2015-02-01

In Brazil hypertension and type 2 diabetes mellitus are responsible for 60% of cases of end-stage renal disease in renal replacement therapy. In the United States studies have identified family clustering of chronic kidney disease, predominantly in African-Americans. A single Brazilian study observed family clustering among patients with chronic kidney disease when compared with hospitalized patients with normal renal function. This article aims to assess whether there is family clustering of chronic kidney disease in relatives of individuals in renal replacement therapy caused by hypertension and/or diabetes mellitus. A case-control study with 336 patients in renal replacement therapy with diabetes mellitus or hypertension for at least 5 years (cases) and a control matched sample group of individuals with hypertension or diabetes mellitus and normal renal function (n = 389). Individuals in renal replacement therapy (cases) had a ratio of 2.35 (95% CI 1.42-3.89, p < 0.001) versus the control group in having relatives with chronic renal disease, irrespective of race or causative illness. There is family clustering of chronic kidney disease in the sample studied, and this predisposition is irrespective of race and underlying disease (hypertension or diabetes mellitus).

Pulmonary Hypertension Among End-Stage Renal Failure Patients Following Hemodialysis Access Thrombectomy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harp, Richard J.; Stavropoulos, S. William; Wasserstein, Alan G.

Purpose: Percutaneous hemodialysis thrombectomy causes subclinical pulmonary emboli without short-term clinical consequence; the long-term effects on the pulmonary arterial vasculature are unknown. We compared the prevalence of pulmonary hypertension between patients who underwent one or more hemodialysis access thrombectomy procedures with controls without prior thrombectomy.Methods: A retrospective case-control study was performed. Cases (n = 88) had undergone one or more hemodialysis graft thrombectomy procedures, with subsequent echocardiography during routine investigation of comorbid cardiovascular disease. Cases were compared with controls without end-stage renal disease (ESRD) (n = 100, group 1), and controls with ESRD but no prior thrombectomy procedures (n =more » 117, group 2). The presence and velocity of tricuspid regurgitation on echocardiography was used to determine the prevalence and grade of pulmonary hypertension; these were compared between cases and controls using the chi-square test and logistic regression.Results: The prevalence of pulmonary hypertension among cases was 52% (46/88), consisting of mild, moderate and severe in 26% (n = 23), 10% (n = 9) and 16% (n = 14), respectively. Prevalence of pulmonary hypertension among group 1 controls was 26% (26/100), consisting of mild, moderate and severe pulmonary hypertension in 14%, 5% and 7%, respectively. Cases had 2.7 times greater odds of having pulmonary hypertension than group 1 controls (p = 0.002). The prevalence of pulmonary hypertension among group 2 controls was 42% (49/117), consisting of mild, moderate and severe pulmonary arterial hypertension in 25% (n = 49), 10% (n = 12) and 4% (n = 5), respectively. Cases were slightly more likely to have pulmonary hypertension than group 2 controls (OR = 1.5), although this failed to reach statistical significance (p = 0.14).Conclusion: Prior hemodialysis access thrombectomy does not appear to be a risk factor for pulmonary arterial hypertension. Patients with ESRD are more likely to have pulmonary hypertension.« less

Unconditional or Conditional Logistic Regression Model for Age-Matched Case-Control Data?

PubMed

Kuo, Chia-Ling; Duan, Yinghui; Grady, James

2018-01-01

Matching on demographic variables is commonly used in case-control studies to adjust for confounding at the design stage. There is a presumption that matched data need to be analyzed by matched methods. Conditional logistic regression has become a standard for matched case-control data to tackle the sparse data problem. The sparse data problem, however, may not be a concern for loose-matching data when the matching between cases and controls is not unique, and one case can be matched to other controls without substantially changing the association. Data matched on a few demographic variables are clearly loose-matching data, and we hypothesize that unconditional logistic regression is a proper method to perform. To address the hypothesis, we compare unconditional and conditional logistic regression models by precision in estimates and hypothesis testing using simulated matched case-control data. Our results support our hypothesis; however, the unconditional model is not as robust as the conditional model to the matching distortion that the matching process not only makes cases and controls similar for matching variables but also for the exposure status. When the study design involves other complex features or the computational burden is high, matching in loose-matching data can be ignored for negligible loss in testing and estimation if the distributions of matching variables are not extremely different between cases and controls.

Prognosis for advanced-stage primary peritoneal serous papillary carcinoma and serous ovarian cancer in Taiwan.

PubMed

Chao, Kuan-Chong; Chen, Yi-Jen; Juang, Chi-Mou; Lau, Hei-Yu; Wen, Kuo-Chang; Sung, Pi-Lin; Fang, Feng-Ying; Twu, Nae-Fang; Yen, Ming-Shyen

2013-03-01

To compare the prognosis of patients with advanced-stage primary peritoneal serous papillary carcinoma (PSPC) or papillary serous ovarian cancer (PSOC). This was a retrospective case-control study and included two study groups: one with stage III/IV PSPC (n = 38) patients and the other with PSOC (n = 53) patients. Patients were matched for histologic subtype (serous tumor), tumor stage, tumor grade, residual disease at the end of debulking surgery (primary or interval), and age (±5 years). Mean age was significantly greater for patients with PSPC (63.03 ± 11.88 years) than for patients with PSOC (55.92 ± 12.56 years, p = 0.008). Optimal debulking surgery was performed initially in 71.9% of PSPC patients and 66.0% of PSOC patients. In addition, 93.9% of PSPC patients and 92.3% of PSOC patients were treated with platinum-paclitaxel chemotherapy. The frequency of high-grade tumors was significantly higher in the PSPC (100%) than in the PSOC group (68.3%; p < 0.001). Progression-free survival (PFS) was similar in the PSPC [median 12 months, 95% confidence interval (CI) 7.3-16.7] and PSOC groups (median 16.7 months, 95% CI 12.9-20.4; p = 0.470). Overall survival was shorter in the PSPC (median 62 months, 95% CI 19.6-104.4) than in the PSOC group (median 77.5 months, 95% CI 69.7-85.2; p = 0.006, log-rank statistic). PFS was similar for advanced-stage PSPC and PSOC patients. Since the PSPC patients tended to be older and have more high-grade tumors, OS was shorter for PSPC than for POSC patients. Thus, management of the two types of cancer should not differ. Copyright © 2013. Published by Elsevier B.V.

Correlates of comorbid depression, anxiety and helplessness with obsessive-compulsive disorder in Chinese adolescents.

PubMed

Sun, Jing; Li, Zhanjiang; Buys, Nicholas; Storch, Eric A

2015-03-15

Youth with obsessive-compulsive disorder (OCD) are at risk of experiencing comorbid psychiatric conditions, such as depression and anxiety. Studies of Chinese adolescents with OCD are limited. The aim of this study was to investigate the association of depression, anxiety, and helplessness with the occurrence of OCD in Chinese adolescents. This study consisted of two stages. The first stage used a cross-sectional design involving a stratified clustered non-clinical sample of 3174 secondary school students. A clinical interview procedure was then employed to diagnose OCD in students who had a Leyton 'yes' score of 15 or above. The second phase used a case-control study design to examine the relationship of OCD to depression, anxiety and helplessness in a matched sample of 288 adolescents with clinically diagnosed OCD and 246 students without OCD. Helplessness, depression and anxiety scores were directly associated with the probability of OCD caseness. Canonical correlation analysis indicated that the OCD correlated significantly with depression, anxiety, and helplessness. Cluster analysis further indicated that the degree of the OCD is also associated with severity of depression and anxiety, and the level of helplessness. These findings suggest that depression, anxiety and helplessness are important correlates of OCD in Chinese adolescents. Future studies using longitudinal and prospective designs are required to confirm these relationships as causal. Copyright © 2014 Elsevier B.V. All rights reserved.

Risk of lung cancer associated with six types of chlorinated solvents: results from two case-control studies in Montreal, Canada

EPA Science Inventory

Methods: Two case-control studies of occupation and lung cancer were conducted in Montreal, including 2,016 cases and 2,001 population controls. Occupational exposure to a host of agents was evaluated using a combination of subject-reported job history and expert assessment. We e...

Empirical study of classification process for two-stage turbo air classifier in series

NASA Astrophysics Data System (ADS)

Yu, Yuan; Liu, Jiaxiang; Li, Gang

2013-05-01

The suitable process parameters for a two-stage turbo air classifier are important for obtaining the ultrafine powder that has a narrow particle-size distribution, however little has been published internationally on the classification process for the two-stage turbo air classifier in series. The influence of the process parameters of a two-stage turbo air classifier in series on classification performance is empirically studied by using aluminum oxide powders as the experimental material. The experimental results show the following: 1) When the rotor cage rotary speed of the first-stage classifier is increased from 2 300 r/min to 2 500 r/min with a constant rotor cage rotary speed of the second-stage classifier, classification precision is increased from 0.64 to 0.67. However, in this case, the final ultrafine powder yield is decreased from 79% to 74%, which means the classification precision and the final ultrafine powder yield can be regulated through adjusting the rotor cage rotary speed of the first-stage classifier. 2) When the rotor cage rotary speed of the second-stage classifier is increased from 2 500 r/min to 3 100 r/min with a constant rotor cage rotary speed of the first-stage classifier, the cut size is decreased from 13.16 μm to 8.76 μm, which means the cut size of the ultrafine powder can be regulated through adjusting the rotor cage rotary speed of the second-stage classifier. 3) When the feeding speed is increased from 35 kg/h to 50 kg/h, the "fish-hook" effect is strengthened, which makes the ultrafine powder yield decrease. 4) To weaken the "fish-hook" effect, the equalization of the two-stage wind speeds or the combination of a high first-stage wind speed with a low second-stage wind speed should be selected. This empirical study provides a criterion of process parameter configurations for a two-stage or multi-stage classifier in series, which offers a theoretical basis for practical production.

Validation of a TFE3 break-apart FISH assay for Xp11.2 translocation renal cell carcinomas.

PubMed

Mosquera, Juan-Miguel; Dal Cin, Paola; Mertz, Kirsten D; Perner, Sven; Davis, Ian J; Fisher, David E; Rubin, Mark A; Hirsch, Michelle S

2011-09-01

Renal cell carcinomas (RCCs) with an Xp11.2 translocation predominantly affect young patients, and can present at an advanced stage. However, more cases in older patients and incidentally detected cancers at earlier stages are also being identified. As the histology of Xp11.2 RCCs overlaps with clear cell and papillary RCCs, it is not infrequent that Xp11.2 RCCs are overlooked and misdiagnosed. The objective of this study was to validate the use of fluorescence in-situ hybridization (FISH) for identifying Xp11.2 RCCs. One hundred fifty-eight consecutive, unselected renal tumors were evaluated in tissue microarrays, including 109 clear cell RCCs, 20 papillary RCCs, 3 RCCs with mixed papillary and clear cell features, 1 Xp11.2 translocation RCC, 8 chromophobe RCCs, 10 oncocytomas, and 7 angiomyolipomas. FISH evaluation was performed blinded to karyotype data, available in about two-thirds of cases. Furthermore, conventional sections of 4 Xp11.2 RCCs, 4 RCCs with mixed papillary and clear cell features, and 4 cases of alveolar soft part sarcoma (the latter for control purposes) were also assessed by FISH. Break-apart signals were homogeneously identified throughout tumor cells in 2 cases from the tissue microarrays including 1 known Xp11.2 RCC and 1 misdiagnosed Xp11.2 RCC. All conventional sections from the Xp11.2 RCC and alveolar soft part sarcoma cases were positive for the TFE3 rearrangement by FISH. All remaining cases were negative. Our study shows the clinical application of FISH in formalin-fixed, paraffin-embedded tissue for detection of Xp11.2 translocation RCCs and other tumors with this genetic aberration.

Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes.

PubMed

Albrechtsen, A; Grarup, N; Li, Y; Sparsø, T; Tian, G; Cao, H; Jiang, T; Kim, S Y; Korneliussen, T; Li, Q; Nie, C; Wu, R; Skotte, L; Morris, A P; Ladenvall, C; Cauchi, S; Stančáková, A; Andersen, G; Astrup, A; Banasik, K; Bennett, A J; Bolund, L; Charpentier, G; Chen, Y; Dekker, J M; Doney, A S F; Dorkhan, M; Forsen, T; Frayling, T M; Groves, C J; Gui, Y; Hallmans, G; Hattersley, A T; He, K; Hitman, G A; Holmkvist, J; Huang, S; Jiang, H; Jin, X; Justesen, J M; Kristiansen, K; Kuusisto, J; Lajer, M; Lantieri, O; Li, W; Liang, H; Liao, Q; Liu, X; Ma, T; Ma, X; Manijak, M P; Marre, M; Mokrosiński, J; Morris, A D; Mu, B; Nielsen, A A; Nijpels, G; Nilsson, P; Palmer, C N A; Rayner, N W; Renström, F; Ribel-Madsen, R; Robertson, N; Rolandsson, O; Rossing, P; Schwartz, T W; Slagboom, P E; Sterner, M; Tang, M; Tarnow, L; Tuomi, T; van't Riet, E; van Leeuwen, N; Varga, T V; Vestmar, M A; Walker, M; Wang, B; Wang, Y; Wu, H; Xi, F; Yengo, L; Yu, C; Zhang, X; Zhang, J; Zhang, Q; Zhang, W; Zheng, H; Zhou, Y; Altshuler, D; 't Hart, L M; Franks, P W; Balkau, B; Froguel, P; McCarthy, M I; Laakso, M; Groop, L; Christensen, C; Brandslund, I; Lauritzen, T; Witte, D R; Linneberg, A; Jørgensen, T; Hansen, T; Wang, J; Nielsen, R; Pedersen, O

2013-02-01

Human complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) >1% with common metabolic phenotypes. The study comprised three stages. We performed medium-depth (8×) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI >27.5 kg/m(2) and hypertension and in 1,000 controls (stage 1). We selected 16,192 polymorphisms nominally associated (p < 0.05) with case-control status, from four selected annotation categories or from loci reported to associate with metabolic traits. These variants were genotyped in 15,989 Danes to search for association with 12 metabolic phenotypes (stage 2). In stage 3, polymorphisms showing potential associations were genotyped in a further 63,896 Europeans. Exome sequencing identified 70,182 polymorphisms with MAF >1%. In stage 2 we identified 51 potential associations with one or more of eight metabolic phenotypes covered by 45 unique polymorphisms. In meta-analyses of stage 2 and stage 3 results, we demonstrated robust associations for coding polymorphisms in CD300LG (fasting HDL-cholesterol: MAF 3.5%, p = 8.5 × 10(-14)), COBLL1 (type 2 diabetes: MAF 12.5%, OR 0.88, p = 1.2 × 10(-11)) and MACF1 (type 2 diabetes: MAF 23.4%, OR 1.10, p = 8.2 × 10(-10)). We applied exome sequencing as a basis for finding genetic determinants of metabolic traits and show the existence of low-frequency and common coding polymorphisms with impact on common metabolic traits. Based on our study, coding polymorphisms with MAF above 1% do not seem to have particularly high effect sizes on the measured metabolic traits.

Two-stage thyroidectomy in the era of intraoperative neuromonitoring

PubMed Central

Papandrikos, Ioannis; Polyzois, Georgios; Roukounakis, Nikolaos; Dionigi, Gianlorenzo; Vamvakidis, Kyriakos

2017-01-01

Background The use of intraoperative neuromonitoring (IONM) provides surgeons with real time information about recurrent laryngeal nerves (RLN) functional integrity. Hence, allowing them to modify the initially scheduled bilateral procedure, to a two-stage thyroidectomy in cases of loss of signal (LOS) on the first side of resection resulting in minimization of bilateral RLN injury. The purpose of our study was to present our results since the implementation of the above mentioned process in both malignant and benign thyroid disease. Methods We conducted a retrospective, observational cohort study of prospectively collected data from all patients who underwent a scheduled total thyroidectomy with or without neck dissection in our Department over the last 4 years [2013–2016]. From the 1,138 patients who received surgical treatment during that period, 284 were excluded since they did not meet the criteria. Exclusion criteria involved previous neck operation, parathyroid surgery, pre-existing vocal cord palsy (VCP) and unilateral surgery. A total of 854 patients were eligible for our study. All patients were subjected to pre- and postoperative indirect laryngoscopy by the same experienced ENT specialist team and all the surgeries were performed by the same experienced team. The whole procedure followed the International Neural Monitoring Study Group’s (INMSG) Guideline Statement. Results We experienced 70 cases (70/854, 8.2%) with postoperative VCP. Two of them (0.23%) had permanent VCP and the rest of those patients (7.97%) experienced transient VCP. Twenty-three (2.7%) patients were candidates for staged thyroidectomy after LOS on the first side of resection, including ten patients with papillary or medullary thyroid carcinoma and one with toxic multinodular goiter (MNG). Of those patients, 22 incidents of VCP (95.7%) have recovered within two months and one of them persisted for more than six months (permanent VCP). We did not experience any permanent bilateral RLN palsy after the implementation of the staged procedure. Conclusions Staged thyroidectomy seems a very attractive and promising procedure for both patient and surgeon, since it nearly eliminates one of the most fearful complications in thyroid surgery. We suggest staged thyroidectomy in all cases with first side of resection signal loss, even in malignancies, since the benefits are much more than the disabilities in a patient’s morbidity and quality of life. PMID:29142834

Prevalence of Hyperkalemia in Diabetic and Non-Diabetic Patients with Chronic Kidney Disease: A Nested Case-Control Study.

PubMed

Loutradis, Charalampos; Tolika, Panagiota; Skodra, Alexandra; Avdelidou, Afroditi; Sarafidis, Pantelis A

2015-01-01

Hyperkalemia is a potentially life-threatening disorder, usually complicating chronic kidney disease (CKD). Factors superimposed to reduced renal function are further elevating hyperkalemia risk, but their contribution is not fully elucidated. This study aimed to compare the prevalence of hyperkalemia in diabetic and non-diabetic patients with CKD. This is a nested case-control study of 180 type-2 diabetic and 180 non-diabetic patients with CKD followed in a Nephrology outpatient clinic, matched for gender, age and estimated glomerular filtration rate. Type-1 diabetes or end-stage renal disease patients were excluded. Prevalence of hyperkalemia was defined as potassium >5 mEq/l or use of sodium polystyrene sulfonate, and further by potassium >5, ≥5.2 and ≥5.5 mEq/l. It was calculated in both groups in whole and CKD stages separately. Univariate and multivariate logistic regression analysis were conducted to identify factors associated with hyperkalemia. The prevalence of hyperkalemia was higher in diabetic CKD patients (27.2 vs. 20%, p = 0.107) and remained around 30% higher with all secondary definitions used, but never reached statistical significance. In Stage 2, no difference was noted (8.7 vs. 17.4%, p = 0.665); in Stage 3, it was significantly higher in diabetics (28.6 vs. 17.5%, p = 0.036); and in Stage 4, it was equally high in both groups (35.5 vs. 32.3%, p = 0.788). In multivariate analysis, Stage 4 CKD (OR 4.535, 95% CI 1.561-13.173), use of angiotensin-converting enzyme inhibitors (ACEIs; OR 2.228, 95% CI 1.254-3.958) and smoking (OR 2.254, 95% CI 1.218-4.171) were independently associated with hyperkalemia. Diabetes mellitus was found to elevate the prevalence of hyperkalemia only in CKD Stage 3 patients (moderately impaired renal function). Advanced CKD at Stage 4 and ACEIs are major determinants of hyperkalemia occurrence. © 2015 S. Karger AG, Basel.

The Effects of Teachers' In-Class Motivational Intervention on Learners' EFL Achievement

ERIC Educational Resources Information Center

Alrabai, Fakieh

2016-01-01

This article reports the findings of a controlled quasi-experimental study investigating the effects of motivational strategies on learner motivation and achievement in English language classes in Saudi Arabia. The study was conducted in two stages. In the first stage, the most important motivational strategies were identified. In the second…

Grammar Is Differentially Impaired in Subgroups of Autism Spectrum Disorders: Evidence from an Investigation of Tense Marking and Morphosyntax

PubMed Central

Modyanova, Nadezhda; Perovic, Alexandra; Wexler, Ken

2017-01-01

Deficits in the production of verbal inflection (tense marking, or finiteness) are part of the Optional Infinitive (OI) stage of typical grammatical development. They are also a hallmark of language impairment: they have been used as biomarkers in guiding genetic studies of Specific Language Impairment (SLI), and have also been observed in autism spectrum disorders (ASD). To determine the detailed nature of finiteness abilities in subgroups of ASD [autism with impaired language (ALI) vs. autism with normal language (ALN)], we compared tense marking abilities in 46 children with ALI and 37 children with ALN with that of two groups of nonverbal mental age (MA) and verbal MA-matched typically developing (TD) controls, the first such study described in the literature. Our participants' performance on two elicited production tasks, probing third-person-singular -s and past tense -ed, from the Rice/Wexler Test of Early Grammatical Impairment (TEGI, Rice and Wexler, 2001), revealed extensive deficits in the ALI group: their ability to correctly mark tense was significantly worse than their much younger TD controls', and significantly worse than that of the ALN group. In contrast, the ALN group performed similarly to their TD controls. We found good knowledge of the meaning of tense, and of case and agreement, in both ASD groups. Similarly, both ASD groups showed distributions of null or overt subjects with nonfinite and finite verbs in line with those found in young TD children. A key difference, however, was that the ALI group used (rather than simply omitted) the wrong tense in some sentences, a feature not reported in the OI stage for TD or SLI children. Our results confirm a clear distinction in the morphosyntactic abilities of the two subgroups of children with ASD: the language system responsible for finiteness in the ALN group seems to be functioning comparably to that of the TD children, whereas the ALI group, despite showing knowledge of case and agreement, seems to experience an extensive grammatical deficit with respect to finiteness which does not seem to improve with age. Crucially, our ALI group seems to have worse grammatical abilities even than those reported for SLI. PMID:28400738

Analysis of molecular subtypes for the increased HER2 equivocal cases caused by application of the updated 2013 ASCO/CAP HER2 testing guidelines in breast cancer.

PubMed

Guo, Lei; Yuan, Pei; Zhang, Jing; Ling, Yun; Li, Wenbin; Zhao, Bohui; Ying, Jianming; Xuan, Lixue

2017-11-01

Accurate testing of the status of human epidermal growth factor receptor type 2 (HER2) is a prerequisite for HER2-directed therapy. The American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) published joint guideline recommendations for HER2 testing in breast cancer in 2007 and it was updated in 2013. We compared the HER2 gene amplification status based on these two guidelines and analyzed the molecular characteristics of the equivocal cases. A total of 1894 patient samples were analyzed for both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). HER2 FISH amplification was examined and re-assessed using 2013 guidelines. According to the 2013 ASCO/CAP recommendations, 763 (40.3%) cases were classified as HER2 positive compared with 729 (38.5%) cases defined by 2007 guidelines. There was a significant increase of 6.1% in the proportion of HER2 FISH equivocal cases that were interpreted using ASCO/CAP 2013 (7.3%) compared with 2007 (1.2%) guidelines (P < 0.001). Of 138 FISH equivocal cases defined by 2013 guidelines, 125 cases were IHC2+ and 13 cases were IHC1+. These 125 cases included 4 double equivocal cases which were defined as equivocal by both 2007 and 2013 guidelines and 121 cases whose status was changed from negative defined by 2007 guidelines to equivocal defined by 2013 guidelines. Compared with luminal A type and luminal B type respectively, these 121 equivocal cases demonstrated no significant difference with luminal B type in T stage and N stage (P = 0.192, P = 0.421). When we divided the luminal B type into two parts that included HER2 negative cases and HER2 positive cases, the equivocal cases also showed no significant difference with these two subtypes in T stage and N stage. Our study suggested that implementation of the revised ASCO/CAP 2013 guidelines resulted in an increase of 1.7% in overall HER2 positivity rate and of 6.1% in equivocal cases. Pathological analysis revealed that these equivocal cases exhibit similar biological behavior with luminal B type tumors. Clinical utility data on targeted therapy in equivocal patients should be further investigated.

Long-term outcomes in primary spinal osteochondroma: a multicenter study of 27 patients

PubMed Central

Sciubba, Daniel M.; Macki, Mohamed; Bydon, Mohamad; Germscheid, Niccole M.; Wolinsky, Jean-Paul; Boriani, Stefano; Bettegowda, Chetan; Chou, Dean; Luzzati, Alessandro; Reynolds, Jeremy J.; Szövérfi, Zsolt; Zadnik, Patti; Rhines, Laurence D.; Gokaslan, Ziya L.; Fisher, Charles G.; Varga, Peter Paul

2016-01-01

OBJECT Clinical outcomes in patients with primary spinal osteochondromas are limited to small series and sporadic case reports. The authors present data on the first long-term investigation of spinal osteochondroma cases. METHODS An international, multicenter ambispective study on primary spinal osteochondroma was performed. Patients were included if they were diagnosed with an osteochondroma of the spine and received surgical treatment between October 1996 and June 2012 with at least 1 follow-up. Perioperative prognostic variables, including patient age, tumor size, spinal level, and resection, were analyzed in reference to long-term local recurrence and survival. Tumor resections were compared using Enneking appropriate (EA) or Enneking inappropriate surgical margins. RESULTS Osteochondromas were diagnosed in 27 patients at an average age of 37 years. Twenty-two lesions were found in the mobile spine (cervical, thoracic, or lumbar) and 5 in the fixed spine (sacrum). Twenty-three cases (88%) were benign tumors (Enneking tumor Stages 1–3), whereas 3 (12%) exhibited malignant changes (Enneking tumor Stages IA–IIB). Sixteen patients (62%) underwent en bloc treatment—that is, wide or marginal resection—and 10 (38%) underwent intralesional resection. Twenty-four operations (92%) followed EA margins. No one received adjuvant therapy. Two patients (8%) experienced recurrences: one in the fixed spine and one in the mobile spine. Both recurrences occurred in latent Stage 1 tumors following en bloc resection. No osteochondroma-related deaths were observed. CONCLUSIONS In the present study, most patients underwent en bloc resection and were treated as EA cases. Both recurrences occurred in the Stage 1 tumor cohort. Therefore, although benign in character, osteochondromas still require careful management and thorough follow-up. PMID:25793467

Quality of Life Over Time in Women Diagnosed with Ductal Carcinoma In situ, Early-Stage Invasive Breast Cancer, and Age-Matched Controls

PubMed Central

Jeffe, DB; Pérez, M; Liu, Y; Collins, KK; Aft, RL; Schootman, M

2012-01-01

Little is known about quality-of-life (QOL) differences over time between incident ductal carcinoma in situ (DCIS) and early-stage invasive breast cancer (EIBC) cases as compared with same-aged women without breast cancer (controls). We prospectively recruited and interviewed 1096 women (16.8% DCIS, 33.3% EIBC [25.7% Stage I, 7.6% Stage IIA], 49.9% controls; mean age 58; 23.7% non-white) a mean 6.7 weeks (T1), and 6.2 (T2), 12.3 (T3), and 24.4 months (T4) after surgery (patients) or screening mammogram (controls). We tested two hypotheses: (1) DCIS patients would report lower levels of QOL compared with controls but would report similar QOL compared with EIBC patients at baseline; and (2) DCIS patients’ QOL would improve during 2-year follow-up and approach levels similar to that of controls faster than EIBC patients. We tested Hypothesis 1 using separate general linear regression models for each of the eight subscales on the RAND 36-item Health Survey, controlling for variables associated with at least one subscale at T1. Both DCIS and EIBC patients reported lower QOL at T1 than controls on all subscales (each p < .05). We tested Hypothesis 2 using generalized estimating equations to examine change in each QOL subscale over time across the three diagnostic groups adjusting for covariates. By T3, physical functioning, role limitations due to physical problems, energy/fatigue, and general health each differed significantly by diagnostic group at P < 0.05, due to larger differences between EIBC patients and controls; but DCIS patients no longer differed significantly from controls on any of the QOL subscales. At T4, EIBC patients still reported worse physical functioning (P = 0.0001) and general health (P = 0.0017) than controls, possibly due to lingering treatment effects. DCIS patients’ QOL was similar to that of controls two years after diagnosis, but some aspects of EIBC patients’ QOL remained lower. PMID:22484800

Bone marrow in pediatric patients with Hodgkin's disease.

PubMed

Khan, Fauzia Shafi; Hasan, Rabiya Fayyaz

2012-01-01

Hodgkin's disease is a malignant process of lymphoreticular system that constitutes 6% of childhood cancers Accurate staging of lymphoma is the basis for rational therapeutic planning and assessment of the presence or absence of marrow involvement is a basic part of the staging evaluation. The objective of this study was to determine the incidence of marrow infiltration in paediatric patients with Hodgkin's disease and to ascertain its morphological spectrum in the marrow. The study included 85 paediatric patients with diagnosed Hodgkin's disease seen at The Children's Hospital/Institute of Child Health, Lahore, from January 2010 to December 2011, referred to haematology department for bone marrow biopsies. Ages ranged between two years to fourteen years with an average age of seven years, the male female ratio being 13:1. Mixed cellularity was the commonest histological type present in 66 (78%) cases. The presenting feature common in all cases was superficial lymphadenopathy followed by hepatomegaly in 17 (20%) cases and splenomegaly in 16 (19%). All the marrow aspirates were negative for infiltration. Trephine biopsies revealed marrow infiltration in 9 (10.5%). Five (56%) cases had bilateral while 4 (44%) had unilateral involvement. Pattern of infiltration was diffuse in 8 (89%) and focal in one (11%) trephines. Increased marrow fibrosis was present in eight (89%) cases. Diagnostic Reed Sternberg cells were identified in only one case and the mononuclear variants were present in six cases and atypical cells were present in two cases in these immunohistochemistry for CD15 and CD30 was performed which was positive. Granulomas in one and lymphoid aggregates were present in two trephine biopsies otherwise negative for Hodgkin's infiltration. Bone marrow infiltration was present in 10.5% cases, immunohistochemistry was used to confirm infiltration in two cases, the pattern of infiltration being diffuse in majority (89%).

The cost-effectiveness of an eradication programme in the end game: Evidence from guinea worm disease

PubMed Central

Sankara, Dieudonné P.; Agua, Junerlyn Farah; Jonnalagedda, Lakshmi; Rumi, Filippo; Weiss, Adam; Braden, Matthew; Ruiz-Tiben, Ernesto; Kruse, Nicole; Braband, Kate; Biswas, Gautam

2017-01-01

Background Of the three diseases targeted for eradication by WHO, two are so-called Neglected Tropical Diseases (NTDs)–guinea worm disease (GWD) and yaws. The Guinea Worm Eradication Programme (GWEP) is in its final stages, with only 25 reported in 2016. However, global eradication still requires certification by WHO of the absence of transmission in all countries. We analyze the cost-effectiveness of the GWEP in the end game, when the number of cases is lower and the cost per case is higher than at any other time. Ours is the first economic evaluation of the GWEP since a World Bank study in 1997. Methods Using data from the GWEP, we estimate the cost of the implementation, pre-certification and certification stages. We model cost-effectiveness in the period 1986–2030. We compare the GWEP to two alternative scenarios: doing nothing (no intervention since 1986) and control (only surveillance and outbreak response during 2016–2030). We report the cost per case averted, cost per disability adjusted life year (DALY) averted and cost per at-risk life year averted. We assess cost-effectiveness against a threshold of about one half GDP per capita (less than US$ 500 in low income countries). All costs are expressed in US$ of 2015. Results The GWEP cost an estimated US$ 11 (95% uncertainty interval, 4.70–12.49) per case averted in the period 1986–2030. The pre-certification and certification phases can cost as much as US$ 0.0041 and US$ 0.0015 per capita per year. The cost per DALY averted by the GWEP relative to doing nothing is estimated at US$ 222 (118–372) in 1986–2030. The GWEP is probably more cost-effective than control by the year 2030. The GWEP is certainly more cost-effective than control if willingness to pay for one year of life lived without the risk of GWD exceeds US$ 0.10. Discussion Even if economic costs are two times as high as the financial costs estimated for the period to 2020, the GWEP will still be cost-effective relative to doing nothing. Whether the GWEP turns out to be the most cost-effective alternative in the period beyond 2015 depends on the time horizon. When framed in terms of the number of years of life lived without the risk of GWD, a case can be made more easily for finishing the end game, including certification of the absence of transmission. PMID:28981510

The cost-effectiveness of an eradication programme in the end game: Evidence from guinea worm disease.

PubMed

Fitzpatrick, Christopher; Sankara, Dieudonné P; Agua, Junerlyn Farah; Jonnalagedda, Lakshmi; Rumi, Filippo; Weiss, Adam; Braden, Matthew; Ruiz-Tiben, Ernesto; Kruse, Nicole; Braband, Kate; Biswas, Gautam

2017-10-01

Of the three diseases targeted for eradication by WHO, two are so-called Neglected Tropical Diseases (NTDs)-guinea worm disease (GWD) and yaws. The Guinea Worm Eradication Programme (GWEP) is in its final stages, with only 25 reported in 2016. However, global eradication still requires certification by WHO of the absence of transmission in all countries. We analyze the cost-effectiveness of the GWEP in the end game, when the number of cases is lower and the cost per case is higher than at any other time. Ours is the first economic evaluation of the GWEP since a World Bank study in 1997. Using data from the GWEP, we estimate the cost of the implementation, pre-certification and certification stages. We model cost-effectiveness in the period 1986-2030. We compare the GWEP to two alternative scenarios: doing nothing (no intervention since 1986) and control (only surveillance and outbreak response during 2016-2030). We report the cost per case averted, cost per disability adjusted life year (DALY) averted and cost per at-risk life year averted. We assess cost-effectiveness against a threshold of about one half GDP per capita (less than US$ 500 in low income countries). All costs are expressed in US$ of 2015. The GWEP cost an estimated US$ 11 (95% uncertainty interval, 4.70-12.49) per case averted in the period 1986-2030. The pre-certification and certification phases can cost as much as US$ 0.0041 and US$ 0.0015 per capita per year. The cost per DALY averted by the GWEP relative to doing nothing is estimated at US$ 222 (118-372) in 1986-2030. The GWEP is probably more cost-effective than control by the year 2030. The GWEP is certainly more cost-effective than control if willingness to pay for one year of life lived without the risk of GWD exceeds US$ 0.10. Even if economic costs are two times as high as the financial costs estimated for the period to 2020, the GWEP will still be cost-effective relative to doing nothing. Whether the GWEP turns out to be the most cost-effective alternative in the period beyond 2015 depends on the time horizon. When framed in terms of the number of years of life lived without the risk of GWD, a case can be made more easily for finishing the end game, including certification of the absence of transmission.

[Effectiveness of two-stage operation of auricular reconstruction in treatment of lobule-type microtia].

PubMed

Wang, Meishui; Wang, Biao; Zheng, Houbing; Wu, Shanying; Shan, Xiuying; Zhuang, Fulian

2011-12-01

To investigate the method and effectiveness of two-stage operation of auricular reconstruction in treating lobule-type microtia. Between March 2007 and April 2010, 19 patients (19 ears) of lobule-type microtia were treated. There were 13 males and 6 females, aged 5 to 27 years (mean, 12.6 years). Of 19 patients, 11 were less than or equal to 14 years old. The locations were left ear in 9 cases and right ear in 10 cases. Two-stage operation for auricular reconstruction of lobule-type microtia included fabrication and grafting of the costal cartilage framework at the first-stage operation and the ear elevation operation at the second-stage operation. Pseudomonas aeruginosa infection occurred in 1 patient after the first-stage operation, who was not given the second-stage operation. Skin necrosis occurred in 1 patient 8 days after the second-stage operation and healed after symptomatic treatment. Eighteen patients were followed up 6 months to 2 years (mean, 14 months). Retraction of cranioauricular angle and thoracic deformity occurred in 1 patient. The surgical results were satisfactory in the other 17 patients whose reconstructive ear had verisimilar shape and suitable cranioauricular angle. Two-stage operation of auricular reconstruction is considered to be an ideal method for lobule-type microtia.

The CAG repeat polymorphism in the Androgen receptor gene modifies the risk for hypospadias in Caucasians

PubMed Central

2012-01-01

Background Hypospadias is a birth defect of the urethra in males, and a milder form of 46,XY disorder of sexual development (DSD). The disease is characterized by a ventrally placed urinary opening due to a premature fetal arrest of the urethra development. Moreover, the Androgen receptor (AR) gene has an essential role in the hormone-dependent stage of sexual development. In addition, longer AR polyglutamine repeat lengths encoded by CAG repeats are associated with lower transcriptional activity in vitro. In the present study, we aimed at investigating the role of the CAG repeat length in the AR gene in hypospadias cases as compared to the controls. Our study included 211 hypospadias and 208 controls of Caucasian origin. Methods We amplified the CAG repeat region with PCR, and calculated the difference in the mean CAG repeat length between the hypospadias and control group using the T-test for independent groups. Results We detected a significant increase of the CAG repeat length in the hypospadias cases when compared to the controls (contrast estimate: 2.29, 95% Confidence Interval (1.73-2.84); p-value: 0.001). In addition, the odds ratios between the hypospadias and controls revealed that the hypospadias cases are two to 3 times as likely to have longer CAG repeats than a shorter length for each repeat length investigated. Conclusions We have investigated the largest number of hypospadias cases with regards to the CAG repeat length, and we provide evidence that a higher number of the CAG repeat sequence in the AR gene have a clear effect on the risk of hypospadias in Caucasians. PMID:23167717

Posttraumatic severe infection of the ankle joint - long term results of the treatment with resection arthrodesis in 133 cases

PubMed Central

2010-01-01

Although there is a clear trend toward internal fixation for ankle arthrodesis, there is general consensus that external fixation is required for cases of posttraumatic infection. We retrospectively evaluated the technique and clinical long term results of external fixation in a triangular frame for cases of posttraumatic infection of the ankle. From 1993 to 2006 a consecutive series of 155 patients with an infection of the ankle was included in our study. 133 cases of the advanced "Gächter" stage III and IV were treated with arthrodesis. We treated the patients with a two step treatment plan. After radical debridement and sequestrectomy the malleoli and the joint surfaces were resected. An AO fixator was applied with two Steinmann-nails inserted in the tibia and in the calcaneus and the gap was temporary filled with gentamicin beads as the first step. In the second step we performed an autologous bone graft after a period of four weeks. The case notes were evaluated regarding trauma history, medical complaints, further injuries and illnesses, walking and pain status and occupational issues. Mean age at the index procedure was 49.7 years (18-82), 104 patients were male (67,1%). Follow up examination after mean 4.5 years included a standardised questionnaire and a clinical examination including the criteria of the AO-FAS-Score and radiographs. 92,7% of the cases lead to a stable arthrodesis. In 5 patients the arthrodesis was found partly-stable. In six patients (4,5%) the infection was not controllable during the treatment process. These patients had to be treated with a below knee amputation. The mean AOFAS score at follow up was 63,7 (53-92). Overall there is a high degree of remaining disability. The complication rate and the reduced patient comfort reserve this method mainly for infection. Joint salvage is possible in the majority of cases with an earlier stage I and II infection. PMID:20452884

Posttraumatic severe infection of the ankle joint - long term results of the treatment with resection arthrodesis in 133 cases.

PubMed

Kienast, Benjamin; Kiene, J; Gille, J; Thietje, R; Gerlach, U; Schulz, A P

2010-02-26

Although there is a clear trend toward internal fixation for ankle arthrodesis, there is general consensus that external fixation is required for cases of posttraumatic infection. We retrospectively evaluated the technique and clinical long term results of external fixation in a triangular frame for cases of posttraumatic infection of the ankle. From 1993 to 2006 a consecutive series of 155 patients with an infection of the ankle was included in our study. 133 cases of the advanced "Gächter" stage III and IV were treated with arthrodesis. We treated the patients with a two step treatment plan. After radical debridement and sequestrectomy the malleoli and the joint surfaces were resected. An AO fixator was applied with two Steinmann-nails inserted in the tibia and in the calcaneus and the gap was temporary filled with gentamicin beads as the first step. In the second step we performed an autologous bone graft after a period of four weeks. The case notes were evaluated regarding trauma history, medical complaints, further injuries and illnesses, walking and pain status and occupational issues. Mean age at the index procedure was 49.7 years (18-82), 104 patients were male (67.1%). Follow up examination after mean 4.5 years included a standardised questionnaire and a clinical examination including the criteria of the AOFAS-Score and radiographs. 92.7% of the cases lead to a stable arthrodesis. In 5 patients the arthrodesis was found partly-stable. In six patients (4,5%) the infection was not controllable during the treatment process. These patients had to be treated with a below knee amputation. The mean AOFAS score at follow up was 63.7 (53-92). Overall there is a high degree of remaining disability. The complication rate and the reduced patient comfort reserve this method mainly for infection. Joint salvage is possible in the majority of cases with an earlier stage I and II infection.

Drug resistance patterns in Mycobacterium leprae isolates from relapsed leprosy patients attending The Leprosy Mission (TLM) Hospitals in India.

PubMed

Lavania, Mallika; Jadhav, Rupendra S; Chaitanya, Vedithi Sundeep; Turankar, Ravindra; Selvasekhar, Abraham; Das, Loretta; Darlong, Famkima; Hambroom, Ujjwal K; Kumar, Sandip; Sengupta, Utpal

2014-09-01

Implementation of multidrug therapy (MDT) in leprosy control programmes has significantly reduced the global prevalence of the disease in the last two decades. After many years of use of MDT, it is expected that drug resistance in Mycobacterium leprae may emerge. This is a major concern, especially during the stage of elimination. In the present study, slit-skin smears were collected from 140 leprosy relapse cases from different Leprosy Mission hospitals across India. DNA extracted from 111 (79%) of these samples was analysed for the genes associated with drug resistance in M. leprae. More than 90% of the patients relapsed as multibacillary (MB) cases. In our study, four (3.6%) of the DNA samples analysed showed mutations associated with rifampicin resistance. We also observed that mutations associated with resistance to dapsone and ofloxacin were observed in 9 (8.1%) of the DNA samples each; two samples had both dapsone and ofloxacin resistance. Further surveillance and appropriate interventions are needed to ensure the continued success of chemotherapy for leprosy.

Preoperative Magnetic Resonance Imaging in Patients With Stage I Invasive Ductal Breast Cancer: A Prospective Randomized Study.

PubMed

Brück, N; Koskivuo, I; Boström, P; Saunavaara, J; Aaltonen, R; Parkkola, R

2018-03-01

Preoperative magnetic resonance imaging has become an important complementary imaging technique in patients with breast cancer, providing additional information for preoperative local staging. Magnetic resonance imaging is recommended selectively in lobular breast cancer and in patients with dense breast tissue in the case when mammography and ultrasound fail to fully evaluate the lesion, but the routine use of magnetic resonance imaging in all patients with invasive ductal carcinoma is controversial. The purpose of this randomized study was to investigate the diagnostic value of preoperative magnetic resonance imaging and its impact on short-term surgical outcome in newly diagnosed unifocal stage I invasive ductal carcinoma. A total of 100 patients were randomized to either receive preoperative breast magnetic resonance imaging or to be scheduled directly to operation without magnetic resonance imaging on a 1:1 basis. There were 50 patients in both study arms. In 14 patients (28%), breast magnetic resonance imaging detected an additional finding and seven of them were found to be malignant. Six additional cancer foci were found in the ipsilateral breast and one in the contralateral breast. Magnetic resonance imaging findings caused a change in planned surgical management in 10 patients (20%). Mastectomy was performed in six patients (12%) in the magnetic resonance imaging group and in two patients (4%) in the control group ( p = 0.140). The breast reoperation rate was 14% in the magnetic resonance imaging group and 24% in the control group ( p = 0.202). The mean interval between referral and first surgical procedure was 34 days in the magnetic resonance imaging group and 21 days in the control group ( p < 0.001). Preoperative magnetic resonance imaging may be beneficial for some patients with early-stage invasive ductal carcinoma, but its routine use is not recommended without specific indications.

Alterations in the antioxidant defense system in prepubertal children with a history of extrauterine growth restriction.

PubMed

Ortiz-Espejo, M; Gil-Campos, M; Mesa, M D; García-Rodríguez, C E; Muñoz-Villanueva, M C; Pérez-Navero, J L

2014-01-01

The role of oxidative stress is well known in the pathogenesis of acquired malnutrition. Intrauterine growth restriction has been associated with an imbalance in oxidative stress/antioxidant system. Therefore, early postnatal environment and, consequently, extrauterine growth restriction might be associated with alterations in the antioxidant defense system, even in the prepubertal stage. This is a descriptive, analytical, and observational case-control study. The study included two groups; 38 Caucasian prepubertal children born prematurely and with a history of extrauterine growth restriction as the case group, and 123 gender- and age-matched controls. Plasma exogenous antioxidant (retinol, β-carotene, and α-tocopherol) concentrations were measured by HPLC; antioxidant enzyme activities of catalase, glutathione reductase, glutathione peroxidase, and superoxide dismutase were determined in lysed erythrocytes by spectrophotometric techniques. Catalase and glutathione peroxidase concentrations were significantly lower in extrauterine growth restriction children than in controls (P < 0.001). Lower plasma retinol concentrations were found in the case group (P = 0.029), while concentrations of β-carotene and α-tocopherol were higher (P < 0.001) in extrauterine growth restriction prepubertal children as compared with controls. After correction by gestational age, birth weight, and length, statistically significant differences were also found, except for retinol. Prepubertal children with a history of extrauterine growth restriction present alterations in their antioxidant defense system. Knowing these alterations may be important in establishing pharmacological and nutritional treatments as this situation might be associated with higher metabolic disorders in adulthood.

Local search heuristic for the discrete leader-follower problem with multiple follower objectives

NASA Astrophysics Data System (ADS)

Kochetov, Yury; Alekseeva, Ekaterina; Mezmaz, Mohand

2016-10-01

We study a discrete bilevel problem, called as well as leader-follower problem, with multiple objectives at the lower level. It is assumed that constraints at the upper level can include variables of both levels. For such ill-posed problem we define feasible and optimal solutions for pessimistic case. A central point of this work is a two stage method to get a feasible solution under the pessimistic case, given a leader decision. The target of the first stage is a follower solution that violates the leader constraints. The target of the second stage is a pessimistic feasible solution. Each stage calls a heuristic and a solver for a series of particular mixed integer programs. The method is integrated inside a local search based heuristic that is designed to find near-optimal leader solutions.

Molasses supplementation of grazing dairy cows: summary of case study, continuous culture fermenter trials, and controlled research farm study

USDA-ARS?s Scientific Manuscript database

This fact sheet summarizes the results of a three-tiered research approach (case study, two continuous culture fermenter studies, and a controlled research farm study) to evaluate molasses as an alternative supplement source for grazing dairy cows. A two-year case study of a New York organic dairy f...

Three-Stage Decision-Making Model under Restricted Conditions for Emergency Response to Ships Not under Control.

PubMed

Wu, Bing; Yan, Xinping; Wang, Yang; Zhang, Di; Guedes Soares, C

2017-12-01

A ship that is not under control (NUC) is a typical incident that poses serious problems when in confined waters close to shore. The emergency response to NUC ships is to select the best risk control options, which is a challenge in restricted conditions (e.g., time limitation, resource constraint, and information asymmetry), particularly in inland waterway transportation. To enable a quick and effective response, this article develops a three-stage decision-making framework for NUC ship handling. The core of this method is (1) to propose feasible options for each involved entity (e.g., maritime safety administration, NUC ship, and ships passing by) under resource constraint in the first stage, (2) to select the most feasible options by comparing the similarity of the new case and existing cases in the second stage, and (3) to make decisions considering the cooperation between the involved organizations by using a developed Bayesian network in the third stage. Consequently, this work provides a useful tool to achieve well-organized management of NUC ships. © 2017 Society for Risk Analysis.

Blood RNA biomarker panel detects both left- and right-sided colorectal neoplasms: a case-control study.

PubMed

Chao, Samuel; Ying, Jay; Liew, Gailina; Marshall, Wayne; Liew, Choong-Chin; Burakoff, Robert

2013-07-23

Colonoscopy is widely regarded to be the gold standard for colorectal cancer (CRC) detection. Recent studies, however, suggest that the effectiveness of colonoscopy is mostly confined to tumors on the left side of the colon (descending, sigmoid, rectum), and that the technology has poor tumor detection for right-sided (cecum, ascending, transverse) lesions. A minimally invasive test that can detect both left-sided and right-sided lesions could increase the effectiveness of screening colonoscopy by revealing the potential presence of neoplasms in the right-sided "blind spot". We previously reported on a seven-gene, blood-based biomarker panel that effectively stratifies a patient's risk of having CRC. For the current study, we assessed the effectiveness of the seven-gene panel for the detection of left- and right-sided CRC lesions. Results were evaluated for 314 patients with CRC (left-sided: TNM I, 65; TNM II, 57; TNM III, 60; TNM IV, 17; unknown, 9. right-sided: TNM I, 28; TNM II, 29; TNM III, 38; TNM IV, 12; unknown, 1 and including two samples with both left and right lesions) and 328 control samples. Blood samples were obtained prior to clinical staging and therapy. Most CRC subjects had localized disease (stages I and II, 58%); regional (stage III) and systemic (stage IV) disease represented 32% and 9%, respectively, of the study population. The panel detected left-sided (74%, 154/208) and right-sided (85%, 92/108) lesions with an overall sensitivity of 78% (215/316) at a specificity of 66% (215/328). Treatable cancer (stages I to III) was detected with left-sided lesion sensitivity of 76% (138/182) and right-sided sensitivity of 84% (80/95). This seven-gene biomarker panel detected right-sided CRC lesions across all cancer stages with a sensitivity that is at least equal to that for left-sided lesions. This study supports the use of this panel as the basis for a patient-friendly, blood-based test that can be easily incorporated into a routine physical examination in advance of colonoscopy to provide a convenient companion diagnostic and a pre-screening alert, ultimately leading to enhanced CRC screening effectiveness.

Modeling Multibody Stage Separation Dynamics Using Constraint Force Equation Methodology

NASA Technical Reports Server (NTRS)

Tartabini, Paul V.; Roithmayr, Carlos M.; Toniolo, Matthew D.; Karlgaard, Christopher D.; Pamadi, Bandu N.

2011-01-01

This paper discusses the application of the constraint force equation methodology and its implementation for multibody separation problems using three specially designed test cases. The first test case involves two rigid bodies connected by a fixed joint, the second case involves two rigid bodies connected with a universal joint, and the third test case is that of Mach 7 separation of the X-43A vehicle. For the first two cases, the solutions obtained using the constraint force equation method compare well with those obtained using industry- standard benchmark codes. For the X-43A case, the constraint force equation solutions show reasonable agreement with the flight-test data. Use of the constraint force equation method facilitates the analysis of stage separation in end-to-end simulations of launch vehicle trajectories

Nearshore hydrodynamics at pocket beaches with contrasting wave exposure in southern Portugal

NASA Astrophysics Data System (ADS)

Horta, João; Oliveira, Sónia; Moura, Delminda; Ferreira, Óscar

2018-05-01

Pocket beaches on rocky coasts with headlands that control hydro-sedimentary processes are considered to be constrained sedimentary systems, generally with limited sediment inputs. Pocket beaches face severe changes over time. Under worst-case scenarios, these changes can result in the loss of the beach, causing waves to directly attack adjacent cliffs. Studies of nearshore hydrodynamics can help to understand such changes and optimise sediment nourishment procedures. The present work contributes to the knowledge of hydrodynamic forcing mechanisms at pocket beaches by providing a comprehensive description of the nearshore circulation at two beaches with contrasting wave exposures. Two pocket beaches in southern Portugal were studied by combining field measurements of waves and currents with numerical models (STWAVE and BOUSS-2D). The aim of this analysis was to evaluate nearshore hydrodynamics under different wave exposure forcing conditions (e.g. variable wave heights/directions and different tidal levels). The results show that the beach circulation can rapidly shift from longshore-to rip-dominated depending on changes in both the offshore wave direction and tidal levels. Waves with higher obliquity (for both low and moderate wave energy conditions) tend to generate longshore circulation in all considered tidal stages, while waves with lower obliquity tend to produce rip flow with higher-velocity rip currents during low to intermediate tidal stages. The results indicate that the location and intensity of rip currents strongly depend on geomorphological constraints, that is, the control exerted by shore platforms. A larger morphological control is observed at mean sea level because most platforms are submerged/exposed during high/low tide and therefore exert less control on nearshore circulation.

Association of Krouse Classification for Sinonasal Inverted Papilloma With Recurrence: A Systematic Review and Meta-analysis.

PubMed

Lisan, Quentin; Moya-Plana, Antoine; Bonfils, Pierre

2017-11-01

The risk factors for the recurrence of sinonasal inverted papilloma are still unclear. To investigate the potential association between the Krouse classification and the recurrence rates of sinonasal inverted papilloma. The EMBASE and MEDLINE databases were searched for the period January 1, 1964, through September 30, 2016, using the following search strategy: (paranasal sinuses [Medical Subject Headings (MeSH) terms] OR sinonasal [all fields]) AND (inverted papilloma [MeSH terms] OR (inverted [all fields] AND papilloma [all fields]). The inclusion criteria were (1) studies including sinonasal inverted papilloma only and no other forms of papillomas, such as oncocytic papilloma; (2) minimum follow-up of 1 year after the surgery; and (3) clear report of cases (recurrence) and controls according to the Krouse classification system or deducible from the full-text article. Literature search was performed by 2 reviewers. Of the 625 articles retrieved in the literature, 97 full-text articles were reviewed. Observational cohort studies or randomized controlled trials were included, and the following variables were extracted from full-text articles: authors of the study, publication year, follow-up data, and number of cases (recurrence) and controls (no recurrence) in each of the 4 stages of the Krouse classification system. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed. Odds ratios (ORs) and 95% CIs were estimated, and data of included studies were pooled using a random-effects model. The main outcome was recurrence after surgical removal of sinonasal inverted papilloma according to each stage of the Krouse classification system. Thirteen studies comprising 1787 patients were analyzed. A significant increased risk of recurrence (51%) was highlighted for Krouse stage T3 disease when compared with stage T2 (pooled OR, 1.51; 95% CI, 1.09-2.09). No significant difference in risk of recurrence was found between Krouse stages T1 and T2 disease (pooled OR, 1.14; 95% CI, 0.63-2.04) or between stages T3 and T4 (pooled OR, 1.27; 95% CI, 0.72-2.26). Inverted papillomas classified as stage T3 according to the Krouse classification system presented a 51% higher likelihood of recurrence. Head and neck surgeons must be aware of this higher likelihood of recurrence when planning and performing surgery for sinonasal inverted papilloma.

Autoignition of hydrogen in shear flows

NASA Astrophysics Data System (ADS)

Kalbhor, Abhijit; Chaudhuri, Swetaprovo; Chitilappilly, Lazar

2018-05-01

In this paper, we compare the autoignition characteristics of laminar, nitrogen-diluted hydrogen jets in two different oxidizer flow configurations: (a) co-flowing heated air and (b) wake of heated air, using two-dimensional numerical simulations coupled with detailed chemical kinetics. In both cases, autoignition is observed to initiate at locations with low scalar dissipation rates and high HO2 depletion rates. It is found that the induction stage prior to autoignition is primarily dominated by chemical kinetics and diffusion while the improved scalar mixing imparted by the large-scale flow structures controls the ignition progress in later stages. We further investigate the ignition transience and its connection with mixing by varying the initial wake conditions and fuel jet to oxidizer velocity ratios. These studies reveal that the autoignition delay times are independent of initial wake flow conditions. However, with increased jet velocity ratios, the later stages of ignition are accelerated, mainly due to enhanced mixing facilitated by the higher scalar dissipation rates. Furthermore, the sensitivity studies for the jet in wake configuration show a significant reduction in ignition delay even for about 0.14% (by volume) hydrogen dilution in the oxidizer. In addition, the detailed autoignition chemistry and the relative roles of certain radical species in the initiation of the autoignition process in these non-premixed jets are investigated by tracking the evolution of important chain reactions using a Lagrangian particle tracking approach. The reaction H2 + O2 ↔ HO2 + H is recognized to be the dominant chain initiation reaction that provides H radicals essential for the progress of subsequent elementary reactions during the pre-ignition stage.

An Analysis of STEM/STEAM Teacher Education in Korea with a Case Study of Two Schools from a Community of Practice Perspective

ERIC Educational Resources Information Center

Jho, Hunkoog; Hong, Oksu; Song, Jinwoong

2016-01-01

The aim of this study was to investigate STEAM (Science, Technology, Engineering, Arts, and Mathematics) teacher education and to examine the successful conditions for its implementation. This study observed two leading schools that have actively participated in STEAM education since the initial stage of STEAM education in Korea. Through…

Reduced Boil-Off System Sizing

NASA Technical Reports Server (NTRS)

Guzik, Monica C.; Plachta, David W.; Feller, Jeffrey R.

2015-01-01

NASA is currently developing cryogenic propellant storage and transfer systems for future space exploration and scientific discovery missions by addressing the need to raise the technology readiness level of cryogenic fluid management technologies. Cryogenic propellants are baselined in many propulsion systems due to their inherently high specific impulse; however, their low boiling points can cause substantial boil-off losses over time. Recent efforts such as the Reduced Boil-off Testing and the Active Thermal Control Scaling Study provide important information on the benefit of an active cooling system applied to LH2 propellant storage. Findings show that zero-boil off technologies can reduce overall mass in LH2 storage systems when low Earth orbit loiter periods extend beyond two months. A significant part of this mass reduction is realized by integrating two stages of cooling: a 20 K stage to intercept heat at the tank surface, and a 90 K stage to reduce the heat entering the less efficient 20 K stage. A missing element in previous studies, which is addressed in this paper, is the development of a direct method for sizing the 90 K cooling stage. Such a method requires calculation of the heat entering both the 90 K and 20 K stages as compared to the overall system masses, and is reliant upon the temperature distribution, performance, and unique design characteristics of the system in question. By utilizing the known conductance of a system without active thermal control, the heat being intercepted by a 90 K stage can be calculated to find the resultant lift and mass of each active thermal control stage. Integral to this is the thermal conductance of the cooling straps and the broad area cooling shield, key parts of the 90 K stage. Additionally, a trade study is performed to show the ability of the 90 K cooling stage to reduce the lift on the 20 K cryocooler stage, which is considerably less developed and efficient than 90 K cryocoolers.

High-Throughput Chemical Screening Identifies Compounds that Inhibit Different Stages of the Phytophthora agathidicida and Phytophthora cinnamomi Life Cycles.

PubMed

Lawrence, Scott A; Armstrong, Charlotte B; Patrick, Wayne M; Gerth, Monica L

2017-01-01

Oomycetes in the genus Phytophthora are among the most damaging plant pathogens worldwide. Two important species are Phytophthora cinnamomi , which causes root rot in thousands of native and agricultural plants, and Phytophthora agathidicida , which causes kauri dieback disease in New Zealand. As is the case for other Phytophthora species, management options for these two pathogens are limited. Here, we have screened over 100 compounds for their anti-oomycete activity, as a potential first step toward identifying new control strategies. Our screening identified eight compounds that showed activity against both Phytophthora species. These included five antibiotics, two copper compounds and a quaternary ammonium cation. These compounds were tested for their inhibitory action against three stages of the Phytophthora life cycle: mycelial growth, zoospore germination, and zoospore motility. The inhibitory effects of the compounds were broadly similar between the two Phytophthora species, but their effectiveness varied widely among life cycle stages. Mycelial growth was most successfully inhibited by the antibiotics chlortetracycline and paromomycin, and the quaternary ammonium salt benzethonium chloride. Copper chloride and copper sulfate were most effective at inhibiting zoospore germination and motility, whereas the five antibiotics showed relatively poor zoospore inhibition. Benzethonium chloride was identified as a promising antimicrobial, as it is effective across all three life cycle stages. While further testing is required to determine their efficacy and potential phytotoxicity in planta , we have provided new data on those agents that are, and those that are not, effective against P. agathidicida and P. cinnamomi . Additionally, we present here the first published protocol for producing zoospores from P. agathidicida , which will aid in the further study of this emerging pathogen.

Establishment of a New School and an Innovative School: Lessons from Two Israeli Case Studies

ERIC Educational Resources Information Center

Tubin, Dorit

2008-01-01

Purpose: The paper aims to explore the stages involved in the school establishment phase and detect differences between new and innovative schools startup. Design/methodology/approach: The exploratory study was conducted on the creation phase of two Israeli elementary schools: one new and one innovative. The data were collected through interviews…

Improvement of Eustachian Tube Function by Tissue-Engineered Regeneration of Mastoid Air Cells

PubMed Central

Kanemaru, Shin-ichi; Umeda, Hiroo; Yamashita, Masaru; Hiraumi, Harukazu; Hirano, Shigeru; Nakamura, Tatsuo; Ito, Juichi

2013-01-01

Objectives/Hypothesis Most cases of chronic otitis media (OMC) are associated with poor development of the mastoid air cells (MACs) and poor Eustachian tube (ET) function. We have previously reported that MAC regeneration can effectively eliminate intractable OMC. In this study, we assessed the ability of regenerated MACs to restore normal gas exchange function and contribute to improved ET function. Study Design Clinical trial with control. Setting General hospitals. Materials and Methods Seventy-six patients with OMC, including cholesteatoma and adhesive otitis media, received tympanoplasty and MAC regeneration therapy. At the first-stage of tympanoplasty, artificial pneumatic bones and/or autologous bone fragments were implanted into the opened mastoid cavity. At the 2nd-stage operation, a nitrous oxide (N2O) gas study was performed in 10 patients to measure middle ear pressure (MEP). For the control group, MEP was measured in five patients with good MAC development during cochlear implantation or facial nerve decompression. ET function was measured twice in each patient, once before the 1st operation and 6 months after the second operation. Results At the 2nd-stage operation, in all cases with regenerated MACs and in the normal control group, MEP changed after administration of N2O. In contrast, no change in MEP was observed in cases with unregenerated MACs. In 70% (n = 37/53) of the regenerated MAC group, ET function was improved, whereas improvement of ET function was observed in only 13% (n = 3/23) of the unregenerated MAC group. Conclusions Tissue-engineered regeneration of MACs improves ET function and gas exchange in the middle ear. Laryngoscope, 2012 Level of Evidence 3b PMID:23086494

Measures to assess the performance of an Australian non-government charitable non-acute health service: A Delphi Survey of Organisational Stakeholders.

PubMed

Colbran, Richard; Ramsden, Robyn; Stagnitti, Karen; Adams, Samantha

2018-02-01

Organisation performance measurement is relevant for non-profit charitable organisations as they strive for security in an increasingly competitive funding environment. This study aimed to identify the priority measures and indicators of organisational performance of an Australian non-government charitable organisation that delivers non-acute health services. Seventy-seven and 59 participants across nine stakeholder groups responded to a two-staged Delphi technique study of a case study organisation. The stage one questionnaire was developed using information garnered through a detailed review of literature. Data from the first round were aggregated and analysed for the stage two survey. The final data represented a group consensus. Quality of care was ranked the most important of six organisational performance measures. Service user satisfaction was ranked second followed by financial performance, internal processes, employee learning and growth and community engagement. Thirteen priority indicators were determined across the six measures. Consensus was reached on the priority organisational performance measures and indicators. Stakeholders of the case study organisation value evidence-based practice, technical strength of services and service user satisfaction over more commercially orientated indicators.

Factorial versus multi-arm multi-stage designs for clinical trials with multiple treatments.

PubMed

Jaki, Thomas; Vasileiou, Despina

2017-02-20

When several treatments are available for evaluation in a clinical trial, different design options are available. We compare multi-arm multi-stage with factorial designs, and in particular, we will consider a 2 × 2 factorial design, where groups of patients will either take treatments A, B, both or neither. We investigate the performance and characteristics of both types of designs under different scenarios and compare them using both theory and simulations. For the factorial designs, we construct appropriate test statistics to test the hypothesis of no treatment effect against the control group with overall control of the type I error. We study the effect of the choice of the allocation ratios on the critical value and sample size requirements for a target power. We also study how the possibility of an interaction between the two treatments A and B affects type I and type II errors when testing for significance of each of the treatment effects. We present both simulation results and a case study on an osteoarthritis clinical trial. We discover that in an optimal factorial design in terms of minimising the associated critical value, the corresponding allocation ratios differ substantially to those of a balanced design. We also find evidence of potentially big losses in power in factorial designs for moderate deviations from the study design assumptions and little gain compared with multi-arm multi-stage designs when the assumptions hold. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Optimized strategy for the control and prevention of newly emerging influenza revealed by the spread dynamics model.

PubMed

Zhang, Wen-Dou; Zu, Zheng-Hu; Xu, Qing; Xu, Zhi-Jing; Liu, Jin-Jie; Zheng, Tao

2014-01-01

No matching vaccine is immediately available when a novel influenza strain breaks out. Several nonvaccine-related strategies must be employed to control an influenza epidemic, including antiviral treatment, patient isolation, and immigration detection. This paper presents the development and application of two regional dynamic models of influenza with Pontryagin's Maximum Principle to determine the optimal control strategies for an epidemic and the corresponding minimum antiviral stockpiles. Antiviral treatment was found to be the most effective measure to control new influenza outbreaks. In the case of inadequate antiviral resources, the preferred approach was the centralized use of antiviral resources in the early stage of the epidemic. Immigration detection was the least cost-effective; however, when used in combination with the other measures, it may play a larger role. The reasonable mix of the three control measures could reduce the number of clinical cases substantially, to achieve the optimal control of new influenza.

Optimized Strategy for the Control and Prevention of Newly Emerging Influenza Revealed by the Spread Dynamics Model

PubMed Central

Zhang, Wen-Dou; Zu, Zheng-Hu; Xu, Qing; Xu, Zhi-Jing; Liu, Jin-Jie; Zheng, Tao

2014-01-01

No matching vaccine is immediately available when a novel influenza strain breaks out. Several nonvaccine-related strategies must be employed to control an influenza epidemic, including antiviral treatment, patient isolation, and immigration detection. This paper presents the development and application of two regional dynamic models of influenza with Pontryagin’s Maximum Principle to determine the optimal control strategies for an epidemic and the corresponding minimum antiviral stockpiles. Antiviral treatment was found to be the most effective measure to control new influenza outbreaks. In the case of inadequate antiviral resources, the preferred approach was the centralized use of antiviral resources in the early stage of the epidemic. Immigration detection was the least cost-effective; however, when used in combination with the other measures, it may play a larger role. The reasonable mix of the three control measures could reduce the number of clinical cases substantially, to achieve the optimal control of new influenza. PMID:24392151

[Quality of life and sexual function of cervical cancer patients following radical hysterectomy and vaginal extension].

PubMed

Ye, Shuang; Yang, Jiaxin; Cao, Dongyan; Zhu, Lan; Lang, Jinghe; Shen, Keng

2014-08-01

To investigate the quality of life and sexual function of cervical cancer patients following radical hysterectomy (RH) and vaginal extension. Case-control and questionnaire- based method was employed in this study. Thirty-one patients of early-stage (I b1-I b2) cervical cancer who had undergone vaginal extension following classic RH in Peking Union Medical College Hospital from December 2008 to September 2012 were included in study group, while 28 patients with matching factors and RH only during the same period were allocated to control group. There was no significant difference between two groups in terms of clinical and demographic variables including age at diagnosis, tumor stage and follow-up time (P > 0.05). Patients were assessed retrospectively by validated self-reported questionnaires the European Organization for Research and Treatment of Cancer Cervix Cancer Module Questionnaire (EORTC QLQ-CX24) mainly for quality of life and sexual function for cervical cancer patients; the Sexual Function and Vaginal Changes Questionnaire (SVQ) further investigates sexual function and vaginal changes of patients with gynecologic malignancy at least 6 months after treatment. Vaginal length acquired by pelvic examination by gynecologic oncologists during follow-up visits was (10.0 ± 1.3) cm and (5.9 ± 1.0)cm in study group and control group respectively (P = 0.000). Sixty-eight percent (21/31) of cases in study group and 64% (18/28) of cases in control group had resumed sexual activity at the time of interview, and the time interval between treatment and regular sexual activity was mean 6 months (range 3-20 months) and mean 5 months (range 1-12 months) in study and control group respectively, in which there was not statistical significance (P > 0.05). No difference was observed regarding pelvic floor symptoms (P > 0.05) while difficulty emptying bladder, incomplete emptying and constipation were most commonly reported. Both group presented with hypoactive sexual desire disorder [88% (52/59)], orgasm dysfunction [72% (28/39)] and low enjoyment or relaxation after sex [51% (20/39)], which was not statistically significant (P > 0.05). Reduced vagina size and shorter vagina was more prominent in control group (12/18) than that in study group [19% (4/21)] with statistical significance (P < 0.05), while no difference in sexual desire, vaginal lubrication, dyspareunia and sexual enjoyment (P > 0.05). Patients with peritoneovaginoplasty following RH had much longer vagina and less self-perceived short vagina. Vaginal extension following RH does not worsen the pelvic floor symptoms.

Evaluation of the implantation site morphology in spontaneous abortion.

PubMed

Manolea, Maria Magdalena; Dijmărescu, Anda Lorena; Popescu, Florina Carmen; Novac, Marius Bogdan; DiŢescu, Damian

2015-01-01

The aim of this study was the characterization of the implantation site through histological and immunohistochemical exams and the evaluation of the changes that appear in the pregnancies ended by spontaneous abortion compared to normal pregnancies ended by requested abortion. One hundred eight patients were divided in two groups: the study group that included 58 patients with spontaneous abortion and the control group that included 50 patients with requested abortion. There has been made uterine curettage in all the cases after a complete preoperative evaluation and the obtained product was sent for histopathological evaluation and immunohistochemical study using a VEGF antibody. Studying the histological sections, we noticed the vasculogenesis stages chronology and then according to the histological aspects of normal pregnancy we noticed the histological changes that occurred at the site of implantation in the cases with pathological pregnancies ended by miscarriage. Our results from this study seem to indicate a correlation between decidual vascular changes and the appearance of miscarriage. In pregnancies ended by miscarriage, we found delays in the trophoblast development according to the gestational age at which the event abortifacient happened. The study emphases the temporal differentiation of utero-placental angiogenesis comparing to villous vasculogenesis and angiogenesis in the first trimester miscarriage and normal pregnancy. At the control group, VEGF expression was positive in 88% of cases, while in the study group, pregnancies ended by spontaneous abortion, positive expression of VEGF was present in only 31% of cases. Our data suggest vascular disorders and are in concordance with other histological and ultrasound studies postulating the idea of a link between miscarriage and placental vascular bed pattern changes.

Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations.

PubMed

Fehringer, Gordon; Kraft, Peter; Pharoah, Paul D; Eeles, Rosalind A; Chatterjee, Nilanjan; Schumacher, Fredrick R; Schildkraut, Joellen M; Lindström, Sara; Brennan, Paul; Bickeböller, Heike; Houlston, Richard S; Landi, Maria Teresa; Caporaso, Neil; Risch, Angela; Amin Al Olama, Ali; Berndt, Sonja I; Giovannucci, Edward L; Grönberg, Henrik; Kote-Jarai, Zsofia; Ma, Jing; Muir, Kenneth; Stampfer, Meir J; Stevens, Victoria L; Wiklund, Fredrik; Willett, Walter C; Goode, Ellen L; Permuth, Jennifer B; Risch, Harvey A; Reid, Brett M; Bezieau, Stephane; Brenner, Hermann; Chan, Andrew T; Chang-Claude, Jenny; Hudson, Thomas J; Kocarnik, Jonathan K; Newcomb, Polly A; Schoen, Robert E; Slattery, Martha L; White, Emily; Adank, Muriel A; Ahsan, Habibul; Aittomäki, Kristiina; Baglietto, Laura; Blomquist, Carl; Canzian, Federico; Czene, Kamila; Dos-Santos-Silva, Isabel; Eliassen, A Heather; Figueroa, Jonine D; Flesch-Janys, Dieter; Fletcher, Olivia; Garcia-Closas, Montserrat; Gaudet, Mia M; Johnson, Nichola; Hall, Per; Hazra, Aditi; Hein, Rebecca; Hofman, Albert; Hopper, John L; Irwanto, Astrid; Johansson, Mattias; Kaaks, Rudolf; Kibriya, Muhammad G; Lichtner, Peter; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Meindl, Alfons; Müller-Myhsok, Bertram; Muranen, Taru A; Nevanlinna, Heli; Peeters, Petra H; Peto, Julian; Prentice, Ross L; Rahman, Nazneen; Sanchez, Maria Jose; Schmidt, Daniel F; Schmutzler, Rita K; Southey, Melissa C; Tamimi, Rulla; Travis, Ruth C; Turnbull, Clare; Uitterlinden, Andre G; Wang, Zhaoming; Whittemore, Alice S; Yang, Xiaohong R; Zheng, Wei; Buchanan, Daniel D; Casey, Graham; Conti, David V; Edlund, Christopher K; Gallinger, Steven; Haile, Robert W; Jenkins, Mark; Le Marchand, Loïc; Li, Li; Lindor, Noralene M; Schmit, Stephanie L; Thibodeau, Stephen N; Woods, Michael O; Rafnar, Thorunn; Gudmundsson, Julius; Stacey, Simon N; Stefansson, Kari; Sulem, Patrick; Chen, Y Ann; Tyrer, Jonathan P; Christiani, David C; Wei, Yongyue; Shen, Hongbing; Hu, Zhibin; Shu, Xiao-Ou; Shiraishi, Kouya; Takahashi, Atsushi; Bossé, Yohan; Obeidat, Ma'en; Nickle, David; Timens, Wim; Freedman, Matthew L; Li, Qiyuan; Seminara, Daniela; Chanock, Stephen J; Gong, Jian; Peters, Ulrike; Gruber, Stephen B; Amos, Christopher I; Sellers, Thomas A; Easton, Douglas F; Hunter, David J; Haiman, Christopher A; Henderson, Brian E; Hung, Rayjean J

2016-09-01

Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer, and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. Cancer Res; 76(17); 5103-14. ©2016 AACR. ©2016 American Association for Cancer Research.

Obesity is associated with increased risk of invasive penile cancer.

PubMed

Barnes, Kerri T; McDowell, Bradley D; Button, Anna; Smith, Brian J; Lynch, Charles F; Gupta, Amit

2016-07-13

To validate the association between obesity and penile cancer at a population level, we conducted a matched case-control study linking the Iowa Department of Motor Vehicles Drivers' License Database (DLD) with cancer surveillance data collected by the State Health Registry of Iowa (SHRI). All men diagnosed with invasive penile squamous cell carcinoma from 1985 to 2010 were identified by SHRI. Two hundred sixty-six cancer cases and 816 cancer-free male controls, selected from the Iowa DLD, were matched within 5-year age and calendar year strata. Body mass index (BMI) was calculated using self-reported height and weight from the DLD. Conditional logistic regression was used to evaluate the association between BMI and the risk of developing invasive penile cancer. Obesity was significantly associated with an increased risk of developing penile cancer. For every five-unit increase in BMI the risk of invasive penile cancer increased by 53 % (OR 1.53, 95 % CI 1.29-1.81, p < 0.0001). We previously reported an association between obesity and higher risk of invasive penile cancer and advanced cancer stage at diagnosis in a hospital-based retrospective study. This population-based study confirms an association between obesity and invasive penile cancer.

The Role of Intuition in the Process of Objectification of Mathematical Phenomena from a Husserlian Perspective: A Case Study

ERIC Educational Resources Information Center

Zagorianakos, Andonis; Shvarts, Anna

2015-01-01

The research is a study of the Husserlian approach to intuition, informed by Merleau-Ponty's theory of perception, in the case of a prospective teacher of mathematics. It explores the two major stages-categories of intuition, the essential relations between them, and their vital role in the emergence of empirical and abstract mathematical…

Whiplash in individuals with known pre-accident, clinical neck status.

PubMed

Sjaastad, Ottar; Fredriksen, Torbjörn A; Båtnes, Jan; Petersen, Hans C; Bakketeig, Leiv S

2006-02-01

In whiplash studies, there may be interpretation difficulties: are post-whiplash findings, when present, a consequence of the whiplash trauma, or did they exist prior to trauma? In the Vågå headache epidemiology study (1995-1997), there was a headache history and detailed physical/neurological findings from the face/head/neck in 1838 18-65-year-old parishioners. In September 2001, four years after the Vågå study, a search through the Health Centre files divulged six cases with whiplash trauma in the intervening period. These parishioners could thus be their own controls. Two females did not develop new complaints. In the four parishioners with apparently new, subjective complaints, i.e., headache, neck pain, and a feeling of stiffness in the neck, there were corresponding findings as regards various parameters: shoulder area skin-roll test, changes in two, possible changes in two; range of motion, neck, changes in two, borderline changes in one; "features indicative of cervical abnormality" ("CF"), changes in all four; the mean, post-whiplash stage value was: 3.6+, against 1.6+ prior to accident (Vågå: only 0.93%, "CF" exceeding 3+). In the two without new complaints, the mean "CF" value was 1.0+. The number of cases is small, but the similarity of the symptoms--and signs--following whiplash injury may suggest an element of organic origin in the whiplash syndrome.

Influence of ROBO1 and RORA on risk of age-related macular degeneration reveals genetically distinct phenotypes in disease pathophysiology.

PubMed

Jun, Gyungah; Nicolaou, Michael; Morrison, Margaux A; Buros, Jacqueline; Morgan, Denise J; Radeke, Monte J; Yonekawa, Yoshihiro; Tsironi, Evangelia E; Kotoula, Maria G; Zacharaki, Fani; Mollema, Nissa; Yuan, Yang; Miller, Joan W; Haider, Neena B; Hageman, Gregory S; Kim, Ivana K; Schaumberg, Debra A; Farrer, Lindsay A; DeAngelis, Margaret M

2011-01-01

ROBO1 is a strong candidate gene for age-related macular degeneration (AMD) based upon its location under a linkage peak on chromosome 3p12, its expression pattern, and its purported function in a pathway that includes RORA, a gene previously associated with risk for neovascular AMD. Previously, we observed that expression of ROBO1 and RORA is down-regulated among wet AMD cases, as compared to their unaffected siblings. Thus, we hypothesized that contribution of association signals in ROBO1, and interaction between these two genes may be important for both wet and dry AMD. We evaluated association of 19 single nucleotide polymorphisms (SNPs) in ROBO1 with wet and dry stages of AMD in a sibling cohort and a Greek case-control cohort containing 491 wet AMD cases, 174 dry AMD cases and 411 controls. Association signals and interaction results were replicated in an independent prospective cohort (1070 controls, 164 wet AMD cases, 293 dry AMD cases). The most significantly associated ROBO1 SNPs were rs1387665 under an additive model (meta P = 0.028) for wet AMD and rs9309833 under a recessive model (meta P = 6 × 10(-4)) for dry AMD. Further analyses revealed interaction between ROBO1 rs9309833 and RORA rs8034864 for both wet and dry AMD (interaction P<0.05). These studies were further supported by whole transcriptome expression profile studies from 66 human donor eyes and chromatin immunoprecipitation assays from mouse retinas. These findings suggest that distinct ROBO1 variants may influence the risk of wet and dry AMD, and the effects of ROBO1 on AMD risk may be modulated by RORA variants.

Stage of change and motivation to healthier lifestyle in non-alcoholic fatty liver disease.

PubMed

Centis, Elena; Moscatiello, Simona; Bugianesi, Elisabetta; Bellentani, Stefano; Fracanzani, Anna Ludovica; Calugi, Simona; Petta, Salvatore; Dalle Grave, Riccardo; Marchesini, Giulio

2013-04-01

Healthy diet and physical activity are the treatment cornerstones of non-alcoholic fatty liver disease (NAFLD); their effectiveness is however limited by difficulties in implementing lifestyle changes. We aimed at determining the stage of change and associated psychological factors as a prerequisite to refine strategies to implement behavior changes. We studied 138 consecutive NAFLD patients (73% male, age 19-73 years). The diagnosis was confirmed by liver biopsy in 64 cases (steatohepatitis, 47%). All cases completed the validated EMME-3 questionnaire, consisting of two parallel sets of instruments (for diet and physical activity, respectively) and providing stages of change according to transtheoretical model. Logistic regression analysis was used to identify factors associated with stages making behavioral changes more demanding. The individual profiles were variable; for diet, no cases had precontemplation as prevalent stage of change (highest score in individual profiles); 36% had contemplation. For physical activity, 50% were classified in either precontemplation or contemplation. Minor differences were recorded in relation to associated metabolic complications or steatohepatitis. Logistic regression identified male sex (odds ratio, 4.51; 95% confidence interval, 1.69-12.08) and age (1.70; 1.20-2.43 per decade) as the independent parameters predicting precontemplation or contemplation for diet. No predictors were identified for physical activity. NAFLD cases have scarce readiness to lifestyle changes, particularly with regard to physical activity. Defining stages of change and motivation offers the opportunity to improve clinical care of NAFLD people through individual programs exploiting the powerful potential of behavioral counseling, an issue to be tested in longitudinal studies. Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Dynamic characteristics of a variable-mass flexible missile: Dynamics of a two-stage variable-mass flexible rocket

NASA Technical Reports Server (NTRS)

Meirovitch, L.; Bankovskis, J.

1969-01-01

The dynamic characteristics of two-stage slender elastic body were investigated. The first stage, containing a solid-fuel rocket, possesses variable mass while the second stage, envisioned as a flexible case, contains packaged instruments of constant mass. The mathematical formulation was in terms of vector equations of motion transformed by a variational principle into sets of scalar differential equations in terms of generalized coordinates. Solutions to the complete equations were obtained numerically by means of finite difference techniques. The problem has been programmed in the FORTRAN 4 language and solved on an IBM 360/50 computer. Results for limited cases are presented showing the nature of the solutions.

[Vascularloops in reconstructive microsurgery: A review of the literature].

PubMed

Shipkov, H; Traikova, N; Voinov, P; Boucher, F; Braye, F; Mojallal, A

2014-02-01

The success of free tissue transfer depends on the quality of vascular micro-anastomosis and recipient vessels. Adequate recipient vessels are sometimes not available near the recipient site for they can be either destroyed or of poor quality (radiotherapy, traumatism). In such cases, good quality recipient vessels are at a distance from the reconstructed site. If this distance is important flap pedicle lengthening implies - for the artery, for the vein or for both flap artery and vein. This lengthening can be carried out in two manners - by interpositional vein grafts (VG) or by a vascular loop (VL) in one or two stages. The aim of this study was to review the utilisation of VL and their type since their introduction in the clinical practice of reconstructive microsurgery. Two main types of VL are used - BV by VG and VL "in situ". Both of them can be carried out in one or two stages. Each of these techniques has its advantages and disadvantages. The overall data from the literature shows that VL are indicated in cases where both artery and vein are damaged or destroyed. There is not enough evidence concerning the VL in one or two stages but there are some tendencies in favour of the VL in one stage. The technique of VL seems to be more avantageous over the interpositional VG but with a smaller success rate compared to free-flaps with direct anastomosis to recipient vessels. Further studies are necessary to investigate these controversial questions. Copyright © 2013. Published by Elsevier SAS.

Gracilis tendon transfer associated with distal alignment for patella alta with recurrent dislocations: an original surgical technique.

PubMed

Marteau, E; Burdin, P; Brilhault, J-M

2011-06-01

Many surgical techniques for the medial patellofemoral ligament have recently been suggested, all of which included problems identifying the femoral anchorage point and determining the proper extent of knee flexion for the transplant. P. Burdin proposed a different and original approach consisting in performing a gracilis muscle transfer to the medial edge of the patella, thus obtaining progressive tension of the transfer during knee flexion by means of the myotatic reflex. We report the results herein. We retrospectively assessed 17 knees treated for patellofemoral instability using this technique. Two cases presented subjective patellofemoral instability and 15 presented objective patellofemoral instability. The patients' mean age was 17.4 years (range, 8-47 years) during the first episode of dislocation. Two cases of instability were secondary to advanced neuromuscular disease. Two knees had already undergone two stabilization attempts. Fifteen knees presented trochlear dysplasia (four stage A, eight stage B, and three stage C). The mean age at surgery was 28.2 years (range, 16-47 years). In 15 cases, the gracilis transfer was associated with lowering the anterior tibial tuberosity (mean, 10mm). No patellar fracture occurred. A persistent sensory deficit of the anterior branch of the internal saphenous nerve was observed in 15 cases. One knee remained painful and retained subjective instability; total knee arthroplasty was performed 3 years after the intervention. The mean follow-up at revision was 5.5 years (range, 1.5-16.5 years). No recurrence of dislocation was reported. Eight cases retained subjective instability. The SF-36 and IKDC scores were good or excellent in 12 cases and the KOOS was good or excellent in 13 cases. Radiologically, patellar tilt persisted in six cases out of 14, translation persisted in two cases out of 14, and secondary patella baja was observed in one. Medial patellofemoral osteoarthritis was observed in five cases: one case IWANO stage I and four cases IWANO stage II. These satisfactory results seem stable over time and were acquired using a simple procedure with reduced morbidity, making it possible to avoid significant displacement of the anterior tibial tuberosity and stabilize the extensor apparatus. It can also be hoped that the onset of secondary patellofemoral osteoarthritis, undoubtedly inevitable, has been delayed. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Stages and levels of automation in support of space teleoperations.

PubMed

Li, Huiyang; Wickens, Christopher D; Sarter, Nadine; Sebok, Angelia

2014-09-01

This study examined the impact of stage of automation on the performance and perceived workload during simulated robotic arm control tasks in routine and off-nominal scenarios. Automation varies with respect to the stage of information processing it supports and its assigned level of automation. Making appropriate choices in terms of stages and levels of automation is critical to ensure robust joint system performance. To date, this issue has been empirically studied in domains such as aviation and medicine but not extensively in the context of space operations. A total of 36 participants played the role of a payload specialist and controlled a simulated robotic arm. Participants performed fly-to tasks with two types of automation (camera recommendation and trajectory control automation) of varying stage. Tasks were performed during routine scenarios and in scenarios in which either the trajectory control automation or a hazard avoidance automation failed. Increasing the stage of automation progressively improved performance and lowered workload when the automation was reliable, but incurred severe performance costs when the system failed. The results from this study support concerns about automation-induced complacency and automation bias when later stages of automation are introduced. The benefits of such automation are offset by the risk of catastrophic outcomes when system failures go unnoticed or become difficult to recover from. A medium stage of automation seems preferable as it provides sufficient support during routine operations and helps avoid potentially catastrophic outcomes in circumstances when the automation fails.

[Major tricuspid insufficiency and absence of systolic valvular coaptation. Echocardiographic study. Apropos of 6 cases].

PubMed

Roudaut, R; Héraudeau, A; Gosse, P; Aouizerate, E; Dequecker, J L; Dallocchio, M

1986-09-01

In a retrospective series of 960 cases of tricuspid regurgitation studied by two-dimensional echocardiography 6 patients presented a systolic defect of valvular coaptation. The origin of this defect varied: one case was due to carcinoid, two to rheumatic cardiopathy, two to papyraceous right ventricle and one to sclerodermia associated with pulmonary arterial hypertension. The mechanism of the lacking coaptation varies according to the etiology: valvular retraction in carcinoid cardiopathy, right-ventricle dilatation, dilatation of the tricuspid ring and altered kinetics of the right ventricle in the other cases. Changed contractility of the right ventricle is the only element allowing to distinguish tricuspid regurgitation with and without a coaptation defect. Clinically this abnormality always points to an advanced stage of severe tricuspid regurgitation.

Vision-based stabilization of nonholonomic mobile robots by integrating sliding-mode control and adaptive approach

NASA Astrophysics Data System (ADS)

Cao, Zhengcai; Yin, Longjie; Fu, Yili

2013-01-01

Vision-based pose stabilization of nonholonomic mobile robots has received extensive attention. At present, most of the solutions of the problem do not take the robot dynamics into account in the controller design, so that these controllers are difficult to realize satisfactory control in practical application. Besides, many of the approaches suffer from the initial speed and torque jump which are not practical in the real world. Considering the kinematics and dynamics, a two-stage visual controller for solving the stabilization problem of a mobile robot is presented, applying the integration of adaptive control, sliding-mode control, and neural dynamics. In the first stage, an adaptive kinematic stabilization controller utilized to generate the command of velocity is developed based on Lyapunov theory. In the second stage, adopting the sliding-mode control approach, a dynamic controller with a variable speed function used to reduce the chattering is designed, which is utilized to generate the command of torque to make the actual velocity of the mobile robot asymptotically reach the desired velocity. Furthermore, to handle the speed and torque jump problems, the neural dynamics model is integrated into the above mentioned controllers. The stability of the proposed control system is analyzed by using Lyapunov theory. Finally, the simulation of the control law is implemented in perturbed case, and the results show that the control scheme can solve the stabilization problem effectively. The proposed control law can solve the speed and torque jump problems, overcome external disturbances, and provide a new solution for the vision-based stabilization of the mobile robot.

Breast-conserving therapy for early-stage breast cancer in Chinese women: a meta-analysis of case-control studies.

PubMed

Cai, Xiaopeng; Liu, Xu; Yu, Haitao; Li, Jiguang; Zheng, Xinyu

2012-01-01

Breast cancer has a high incidence worldwide, while Chinese patients have some special characteristics compared to Western patients. A meta-analysis was carried out to determine the effectiveness of breast-conserving therapy (BCT) or mastectomy therapy (MT) for early-stage breast cancers in Chinese women. A fully recursive literature search was conducted in the Chinese Biomedical Literature Database. Case-control trials were considered for inclusion. Analyses were carried out using the Review Manager software (RevMan, version 5.0). The meta-analysis showed that the 3-year or 5-year overall survival, the locoregional recurrence rate, and the metastasis rate were not statistically different between the BCT group and the MT group, but the complication recurrence rate increased in the MT group. Subgroup analysis indicated that no significant differences were observed in the affected limb swelling recurrence rate between the BCT group and the MT group. BCT was the better choice than MT for Chinese women with early-stage breast cancer. Copyright © 2012 S. Karger AG, Basel.

Higher Prevalence of Endometrial Polyps in Infertile Patients with Endometriosis.

PubMed

Zhang, Ya-Nan; Zhang, You-Sheng; Yu, Qian; Guo, Zi-Zhen; Ma, Jin-Long; Yan, Lei

2018-06-07

To study whether infertile patients with endometriosis have a higher prevalence of endometrial polyps, and to clarify the characteristics of the pathology of combined polyps. Infertile patients who had undergone both hysteroscopy and laparoscopy in Reproductive Hospital Affiliated with Shandong University from January 2014 to May 2017 were enrolled. Patients with and without endometriosis, diagnosed by laparoscopy, were staged and included in the study group and control group, respectively, and the prevalence of polyps was compared. The pathological types of endometrial polyps were analyzed. A total of 414 cases were enrolled in the study group and 3,048 cases in the control group; polyps were diagnosed, with endoscopy, in 1,107 patients. Endometrial polyps were detected by hysteroscopy in 47.83% of the endometriosis group and 29.82% of the control group. The prevalence of endometrial polyps was significantly higher in the endometriosis group than in the control group (p < 0.001) but not significantly different between stages of endometriosis (p = 0.580). The pathological diagnosis included 899 endometrial polyps and 208 polypoid hyperplasia; 66.5% of endometrial polyps were combined with simple hyperplasia. The infertile patients with endometriosis had a higher prevalence of endometrial polyps, and those polyps are often combined with simple hyperplasia. © 2018 S. Karger AG, Basel.

Effect of cerclage on labor course and obstetric outcome: a case-control study.

PubMed

Shin, Jae Eun; Shin, Jong Chul; Kim, Sa Jin; Lee, Young

2012-09-01

The purpose of this study was to evaluate the effects of cervical cerclage on labor course and obstetric outcome. In a retrospective case-control study, we compared labor course, total labor duration, and obstetric complications in 127 women who received cervical cerclage with 254 controls. There was no significant difference in the duration of the first stage of labor (477 ± 576 vs. 373 ± 437 min, p = 0.075) or the second stage of labor (18 ± 17 vs. 20 ± 19 min, p = 0.287) between the 2 groups. In the multivariate analysis, women in the cerclage group were found to be significantly more likely to have a prolonged latent phase (odds ratio [OR], 2.802; 95% confidence interval [CI], 1.103-7.120; p = 0.030), cervical laceration (OR, 15.984; 95% CI, 3.169-80.624; p = 0.001), and treatment with tocolytics (OR, 2.580; 95% CI, 1.217-5.468; p = 0.013) than the control group. No significant difference was noted in cesarean delivery rate. Cervical cerclage is more likely to be associated with a prolonged latent phase and minor obstetric complications, but not with a difference in the total duration of labor or increased cesarean delivery rate.

Process simulation and dynamic control for marine oily wastewater treatment using UV irradiation.

PubMed

Jing, Liang; Chen, Bing; Zhang, Baiyu; Li, Pu

2015-09-15

UV irradiation and advanced oxidation processes have been recently regarded as promising solutions in removing polycyclic aromatic hydrocarbons (PAHs) from marine oily wastewater. However, such treatment methods are generally not sufficiently understood in terms of reaction mechanisms, process simulation and process control. These deficiencies can drastically hinder their application in shipping and offshore petroleum industries which produce bilge/ballast water and produced water as the main streams of marine oily wastewater. In this study, the factorial design of experiment was carried out to investigate the degradation mechanism of a typical PAH, namely naphthalene, under UV irradiation in seawater. Based on the experimental results, a three-layer feed-forward artificial neural network simulation model was developed to simulate the treatment process and to forecast the removal performance. A simulation-based dynamic mixed integer nonlinear programming (SDMINP) approach was then proposed to intelligently control the treatment process by integrating the developed simulation model, genetic algorithm and multi-stage programming. The applicability and effectiveness of the developed approach were further tested though a case study. The experimental results showed that the influences of fluence rate and temperature on the removal of naphthalene were greater than those of salinity and initial concentration. The developed simulation model could well predict the UV-induced removal process under varying conditions. The case study suggested that the SDMINP approach, with the aid of the multi-stage control strategy, was able to significantly reduce treatment cost when comparing to the traditional single-stage process optimization. The developed approach and its concept/framework have high potential of applicability in other environmental fields where a treatment process is involved and experimentation and modeling are used for process simulation and control. Copyright © 2015 Elsevier Ltd. All rights reserved.

Visual assessment of the cervical vertebral maturation stages: A study of diagnostic accuracy and repeatability.

PubMed

Perinetti, Giuseppe; Caprioglio, Alberto; Contardo, Luca

2014-11-01

To evaluate the diagnostic accuracy and repeatability of the visual assessment of the cervical vertebral maturation (CVM) stages. Ten operators underwent training sessions in visual assessment of CVM staging. Subsequently, they were asked to stage 72 cases equally divided into the six stages. Such assessment was repeated twice in two sessions (T1 and T2) 4 weeks apart. A reference standard for each case was created according to a cephalometric analysis of both the concavities and shapes of the cervical vertebrae. The overall agreement with the reference standard was about 68% for both sessions and 76.9% for intrarater repeatability. The overall kappa coefficients with the reference standard were up to 0.86 for both sessions, and 0.88 for intrarater repeatability. Overall, disagreements one stage and twp stage apart were 23.5% (T1) and 5.1% (T2), respectively. Sensitivity ranged from 53.3% for CS5 (T1) to 99.9% for CS1 (T2), positive predictive values ranged from 52.4% for CS5 (T2) to 94.3% for CS6 (T1), and accuracy ranged from 83.6% for CS4 (T2) to 94.9% for CS1 (T1). Visual assessment of the CVM stages is accurate and repeatable to a satisfactory level. About one in three cases remain misclassified; disagreement is generally limited to one stage and is mostly seen in stages 4 and 5.

Tumor Stage-Related Role of Radiotherapy in Patients with an External Auditory Canal and Middle Ear Carcinoma.

PubMed

Choi, Jinhyun; Kim, Se-Heon; Koh, Yoon Woo; Choi, Eun Chang; Lee, Chang Geol; Keum, Ki Chang

2017-01-01

The purpose of this study was to evaluate the clinical outcomes of patients treated with radiotherapy (RT) for a carcinoma of the external auditory canal (EAC) and middle ear. The records of 32 patients who received RT from 1990 to 2013 were reviewed retrospectively. The Pittsburgh classification was used to stage all the cancers (early stage, T1/T2 [n=12]; advanced stage, T3/T4 or N positive [n=20]). Twenty-one patients (65.6%) were treated with postoperative RT and 11 patients (34.4%) were treated with definitive RT. The median radiation doses for postoperative and definitive RT were 60 Gy and 64.8 Gy, respectively. Chemotherapy was administered to seven patients (21.9%). The 5-year overall survival and disease-free survival rates for all patients were 57% and 52%, respectively. The disease control rates for the patients with early stage versus advanced stage carcinomawere 55.6% (5/9) and 50% (6/12) in the postoperative RT group and 66.7% (2/3) and 37.5% (3/8) in the definitive RT group, respectively. Overall, 15 cases (14 patients, 46.7%) experienced treatment failure; these failures were classified as local in four cases, regional in one case, and distant in 10 cases. The median follow-up period after RT was 51 months (range, 7 to 286 months). Patients with early stage carcinoma achieved better outcomes when definitive RT was used. Advanced stage carcinoma patients experienced better outcomes with postoperative RT. The high rate of distant failure after RT, with or without surgery, reflected the lack of a consensus regarding the best therapeutic approach for treating carcinoma of the EAC and middle ear.

Inversion Method for Early Detection of ARES-1 Case Breach Failure

NASA Technical Reports Server (NTRS)

Mackey, Ryan M.; Kulikov, Igor K.; Bajwa, Anupa; Berg, Peter; Smelyanskiy, Vadim

2010-01-01

A document describes research into the problem of detecting a case breach formation at an early stage of a rocket flight. An inversion algorithm for case breach allocation is proposed and analyzed. It is shown how the case breach can be allocated at an early stage of its development by using the rocket sensor data and the output data from the control block of the rocket navigation system. The results are simulated with MATLAB/Simulink software. The efficiency of an inversion algorithm for a case breach location is discussed. The research was devoted to the analysis of the ARES-l flight during the first 120 seconds after the launch and early prediction of case breach failure. During this time, the rocket is propelled by its first-stage Solid Rocket Booster (SRB). If a breach appears in SRB case, the gases escaping through it will produce the (side) thrust directed perpendicular to the rocket axis. The side thrust creates torque influencing the rocket attitude. The ARES-l control system will compensate for the side thrust until it reaches some critical value, after which the flight will be uncontrollable. The objective of this work was to obtain the start time of case breach development and its location using the rocket inertial navigation sensors and GNC data. The algorithm was effective for the detection and location of a breach in an SRB field joint at an early stage of its development.

TMPRSS2-ERG gene fusions are infrequent in prostatic ductal adenocarcinomas.

PubMed

Lotan, Tamara L; Toubaji, Antoun; Albadine, Roula; Latour, Mathieu; Herawi, Mehsati; Meeker, Alan K; DeMarzo, Angelo M; Platz, Elizabeth A; Epstein, Jonathan I; Netto, George J

2009-03-01

Ductal adenocarcinoma of the prostate is an unusual subtype that may be associated with a more aggressive clinical course, and is less responsive to conventional therapies than the more common prostatic acinar adenocarcinoma. However, given its frequent association with an acinar component at prostatectomy, some have challenged the concept of prostatic ductal adenocarcinoma as a distinct clinicopathologic entity. We studied the occurrence of the TMPRSS2-ERG gene fusion, in 40 surgically resected ductal adenocarcinoma cases, and in their associated acinar component using fluorescence in situ hybridization. A group of 38 'pure' acinar adenocarcinoma cases matched with the ductal adenocarcinoma group for pathological grade and stage was studied as a control. Compared with the matched acinar adenocarcinoma cases, the TMPRSS2-ERG gene fusion was significantly less frequently observed in ductal adenocarcinoma (45 vs 11% of cases, P=0.002, Fisher's exact test). Here, of the ductal adenocarcinoma cases with the gene fusion, 75% were fused through deletion, and the remaining case was fused through translocation. The TMPRSS2-ERG gene fusion was also rare in the acinar component of mixed ductal-acinar tumors when compared with the pure acinar adenocarcinoma controls (5 vs 45%, P=0.001, Fisher's exact test). In 95% of the ductal adenocarcinoma cases in which a concurrent acinar component was analyzed, there was concordance for presence/absence of the TMPRSS2-ERG gene fusion between the different histologic subtypes. In the control group of pure acinar adenocarcinoma cases, 59% were fused through deletion and 41% were fused through translocation. The presence of the TMPRSS2-ERG gene fusion in some cases of prostatic ductal adenocarcinoma supports the concept that ductal adenocarcinoma and acinar adenocarcinoma may be related genetically. However, the significantly lower rate of the gene fusion in pure ductal adenocarcinoma cases underscores the fact that genetic and biologic differences exist between these two tumors that may be important for future therapeutic strategies.

Sinonasal mucosal melanoma: retrospective survival study of 25 patients.

PubMed

Vandenhende, C; Leroy, X; Chevalier, D; Mortuaire, G

2012-02-01

To determine potential prognostic factors for survival in patients with mucosal malignant melanoma of the sinonasal tract. Patients managed between 1991 and 2008 were assessed retrospectively. The seventh edition Union for International Cancer Control (7th UICC) tumour-node-metastasis classification was used for tumour staging. Kaplan-Meier and log rank tests were used for survival analysis. Twenty-five patients were studied (six were tumour stage three, eight tumour stage four(a) and 11 tumour stage four(b)). Surgery was performed on 23 patients (92 per cent). Fifteen received post-operative radiotherapy. Mean follow up was 31.3 months (range, two to 99 months). Three-year disease-free survival was improved in patients with stage four tumour arising from the nasal fossa, versus other sites, and in those with stage four tumour treated with surgery plus adjuvant radiotherapy, versus other treatments. Patients with melanoma of the nasal cavity have very poor survival rates. Treatment is still based on adequate surgical resection with safe margins. In this study, post-operative radiotherapy improved local control only for stage four tumours.

Effectiveness of a community-based program for suicide prevention among elders with early-stage dementia: A controlled observational study.

PubMed

Kim, Jong-Pill; Yang, Jinhyang

The purpose of this study was to develop a small-group-focused suicide prevention program for elders with early-stage dementia and to assess its effects. This was a quasi-experimental study with a control group pretest-posttest design. A total of 62 elders diagnosed with early-stage dementia who were receiving care services at nine daycare centers in J City Korea participated in this study. The experimental group participated in the suicide prevention program twice a week for 5 weeks with a pretest and two posttests The developed suicide prevention program had a significant effect on the perceived health status, social support, depression, and suicidal ideation of elders with early-stage dementia. Nurses should integrate risk factors such as depression and protective factors such as health status and social support into a suicide prevention program. This community-based program in geriatric nursing practice can be effective in preventing suicide among elders with early-stage dementia. Copyright © 2016 Elsevier Inc. All rights reserved.

Acquired resistance L747S mutation in an epidermal growth factor receptor-tyrosine kinase inhibitor-naïve patient: A report of three cases.

PubMed

Yamaguchi, Fumihiro; Fukuchi, Kunihiko; Yamazaki, Yohei; Takayasu, Hiromi; Tazawa, Sakiko; Tateno, Hidetsugu; Kato, Eisuke; Wakabayashi, Aya; Fujimori, Mami; Iwasaki, Takuya; Hayashi, Makoto; Tsuchiya, Yutaka; Yamashita, Jun; Takeda, Norikazu; Kokubu, Fumio

2014-02-01

The purpose of the present study was to report cases of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-naïve patients carrying a mutation associated with acquired resistance to the drug. Gene alterations in 77 lung carcinoma patients were analyzed by collecting and studying curette lavage fluid at the time of diagnosis. PCRs were performed to amplify mutation hotspot regions in EGFR genes. The PCR products were direct-sequenced and the mutations confirmed by resequencing using different primers. Case 1 was a 78-year-old Japanese male diagnosed with stage IB lung adenocarcinoma who was found to have two EGFR mutations, G719S and L747S. Case 2 was a 73-year-old Japanese male diagnosed with stage IV squamous cell lung carcinoma and bone metastasis who had the EGFR mutation, L747S. Case 3 was an 82-year-old Japanese male diagnosed with hyponatremia due to inappropriate secretion of antidiuretic hormone and stage IIIB small cell lung carcinoma (SCLC) who had the EGFR mutation, L747S. Thus, the EGFR mutation L747S associated with acquired EGFR-TKI resistance was detected in two non-small cell lung carcinoma (NSCLC) patients and one SCLC patient, none of whom had ever received EGFR-TKI. The patients were current smokers with stages at diagnosis ranging from IB to IV, and their initial tumors contained resistant clones carrying L747S. L747S may be associated with primary resistance. To the best of our knowledge, this study is the first report of an EGFR mutation associated with resistance to EGFR-TKI in SCLC patients. The early detection of EGFR-TKI resistance mutations may be beneficial in making treatment decisions for lung carcinoma patients, including those with SCLC.

Long-term survival of patients with mismatch repair protein-deficient, high-stage ovarian clear cell carcinoma.

PubMed

Stewart, Colin J R; Bowtell, David D L; Doherty, Dorota A; Leung, Yee C

2017-01-01

Gynaecological cancer patients with germline mutations appear to have a better prognosis than those with sporadic malignancies. Following the observation of long-term survival in a patient with stage III ovarian clear cell carcinoma (CCC) and possible Lynch syndrome (LS), DNA mismatch repair (MMR) protein immunohistochemistry was performed in a series of high-stage CCC and correlated with patient outcomes. Thirty-two consecutive cases of stage III/IV ovarian CCCs accessioned between 1992 and 2015 were examined. The tumours from two patients (6%), including the index case, showed loss of MSH2/MSH6 expression while MLH1/PMS2 staining was retained. The index patient subsequently developed colonic and rectal carcinomas that were also MSH2/MSH6-deficient, while the second patient had a genetically confirmed germline MSH2 mutation. All other tumours showed retained expression of the four MMR proteins. The two patients with MMR protein-deficient tumours were alive 160 months and 124 months following surgery, whereas the median survival of patients with MMR protein-intact CCCs was 11.8 months (75th and 25th percentiles of 8.1 months and 39.3 months, respectively), with 21 patients deceased due to tumour. Larger studies are required but high-stage, MMR protein-deficient CCCs may have a relatively favourable prognosis. © 2016 John Wiley & Sons Ltd.

Study on Reduction Kinetics of Briquettes of Hematite Fines with Boiler Grade Coal and Coke Dust in Two Different Forms: Intermixing and Multilayered

NASA Astrophysics Data System (ADS)

Roy, Gopal Ghosh; Sarkar, Bitan Kumar; Chaudhuri, Mahua Ghosh; Mitra, Manoj Kumar; Dey, Rajib

2017-10-01

An attempt has been made to utilise hematite ore fines in the form of briquettes with two different form of mixing i.e. intermixing and multilayered by means of carbothermal reduction along with boiler grade coal and coke dust. The influence of reduction temperature (1323, 1373 and 1423 K) and reduction time (10, 20, 30, 45 and 60 min) has been investigated in detail and the reduced briquettes are characterised by XRD, SEM analyses. The reducibility of intermixing briquettes is found to be higher for multilayered briquettes. In addition, isothermal kinetic study has also been carried out for both intermixing and multilayered briquettes. The activation energy for intermixing briquettes are evaluated to be 125.88 kJ/mol for the initial stage of reaction (CG3 controlled mechanism) and 113.11 kJ/mol for the later part of reaction (D3 controlled mechanism), respectively. In case of multilayered briquettes, the corresponding activation energy is found to be 235.59 kJ/mol for reaction (CG3 controlled mechanism). These results corroborate the observed better reducibility of the intermixing briquettes over multilayered briquettes.

Optimal control in adaptive optics modeling of nonlinear systems

NASA Astrophysics Data System (ADS)

Herrmann, J.

The problem of using an adaptive optics system to correct for nonlinear effects like thermal blooming is addressed using a model containing nonlinear lenses through which Gaussian beams are propagated. The best correction of this nonlinear system can be formulated as a deterministic open loop optimal control problem. This treatment gives a limit for the best possible correction. Aspects of adaptive control and servo systems are not included at this stage. An attempt is made to determine that control in the transmitter plane which minimizes the time averaged area or maximizes the fluence in the target plane. The standard minimization procedure leads to a two-point-boundary-value problem, which is ill-conditioned in the case. The optimal control problem was solved using an iterative gradient technique. An instantaneous correction is introduced and compared with the optimal correction. The results of the calculations show that for short times or weak nonlinearities the instantaneous correction is close to the optimal correction, but that for long times and strong nonlinearities a large difference develops between the two types of correction. For these cases the steady state correction becomes better than the instantaneous correction and approaches the optimum correction.

Failure of the first step of two-stage revision due to polymicrobial prosthetic joint infection of the hip.

PubMed

Bozhkova, Svetlana; Tikhilov, Rashid; Labutin, Dmitry; Denisov, Alexey; Shubnyakov, Igor; Razorenov, Vadim; Artyukh, Vasilii; Rukina, Anna

2016-12-01

The unsuccessful treatment of prosthetic joint infection (PJI) with two-stage revision leads to infection recurrence. The objectives of the study were to assess the clinical and demographic characteristics of patients with polymicrobial PJI, and to evaluate the role of the microbial profile involved in PJI in the risk of infection recurrence after the first step of two-stage revision surgery. A retrospective analysis of 189 cases of culture-positive PJI following total hip replacement over a 5-year period was performed. The demographic characteristics of patients, clinical symptoms, microbiology cultures of intraoperative biopsies, laboratory values of C-reactive protein (CRP), white blood cell count and erythrocyte sedimentation rate were analyzed. Patients were divided into two groups-135 with monomicrobial and 54 with polymicrobial infection. Of all patients, 68.9 % in the monomicrobial and 83.3 % in the polymicrobial group had a body mass index >25 kg/m 2 (p = 0.05). The median CRP values were 5.7 mg/L (IQR 4.0-10.0 mg/L) in the monomicrobial compared to 8.8 mg/L (IQR 5.0-27 mg/L) in the polymicrobial group (p = 0.01). The percentage of successful outcomes was 27.8 % in patients with microbial associations (p < 0.0001). Gram-negative pathogens caused polymicrobial PJI in 61.5 % of cases with infection recurrence (OR 4.4; 95 % CI 1.18-16.37; p = 0.03). Overweight and obese patients or those with elevated CRP had a greater risk of polymicrobial PJI. They were predisposed to recurrence of infection after the first step of two-stage revision. An unsuccessful outcome was more likely in cases with polymicrobial infection compared to those with monomicrobial infection. In addition, the presence of multidrug-resistant strains of Gram-negative bacteria substantially increased the risk of PJI treatment being unsuccessful. Level III, therapeutic study.

[Prognostic factors in neoplasms of the upper 2/3 of the stomach compared to the lower 1/3. Our experience].

PubMed

De Leo, S; Carlini, G F; Covarelli, P; Borgognoni, F; Lepri, P; Murgolo, V; Dominici, C

1990-10-15

The choice of the type of surgical treatment used in gastric cancer, in cases where it is possible to operate in relation to the extent of cancer, raises the question of whether the surgeon should perform a total exeresis of the organ, even in cases where the tumour is located in the 3rd distal of the stomach. A retrospective study was carried out on patients admitted to the Surgical Department of the University of Perugia between January 1963 and December 1988. Having rejected 123 cases because of incomplete data or insufficient follow-up, 1.140 cases were selected from a total of 1.263 patients. The sites of neoplasia were as follows: terminal esophagus: 1.76% of cases; cardia: 6.67%; fornix of the stomach: 9.37%; the body of the stomach and lesser curvature: 23.65%; body of the stomach (other portions): 10.07%; angulus: 3.63%; gastric antrum: 37.82%, pylorus: 4.45%; the remaining 2.58% showed a diffuse form involving two or more the above parts. The subdivision of the cases into stages, using the TNM classification, revealed the following groupings: 7.04% of patients were first observed at stage I, 20.70% at stage II, 42.04% at stage III and 30.20% at stage IV. From the above figures it is evident that radical surgical was indicated only in some of the patients observed. The prognostic factors examined in the comparative study of different tumour sites were: age, sex, macroscopic and histological tumour type, size, infiltration of neoplasia through gastric wall coat, lymph node and/or systemic diffusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Study on casing treatment and stator matching on multistage fan

NASA Astrophysics Data System (ADS)

Wu, Chuangliang; Yuan, Wei; Deng, Zhe

2017-10-01

Casing treatments are required for expanding the stall margin of multi-stage high-load turbofans designed with high blade-tip Mach numbers and high leakage flow. In the case of a low mass flow, the casing treatment effectively reduces the blockages caused by the leakage flow and enlarges the stall margin. However, in the case of a high mass flow, the casing treatment affects the overall flow capacity of the fan, the thrust when operating at the high speeds usually required by design-point specifications. Herein, we study a two-stage high-load fan with three-dimensional numerical simulations. We use the simulation results to propose a scheme that enlarges the stall margin of multistage high-load fans without sacrificing the flow capacity when operating with a large mass flow. Furthermore, a circumferential groove casing treatment is used and adjustments are made to the upstream stator angle to match the casing treatment. The stall margin is thus increased to 16.3%, with no reduction in the maximum mass flow rate or the design thrust performance.

Laparoscopic surgery for colorectal cancer is safe and has survival outcomes similar to those of open surgery in elderly patients with a poor performance status: subanalysis of a large multicenter case-control study in Japan.

PubMed

Niitsu, Hiroaki; Hinoi, Takao; Kawaguchi, Yasuo; Ohdan, Hideki; Hasegawa, Hirotoshi; Suzuka, Ichio; Fukunaga, Yosuke; Yamaguchi, Takashi; Endo, Shungo; Tagami, Soichi; Idani, Hitoshi; Ichihara, Takao; Watanabe, Kazuteru; Watanabe, Masahiko

2016-01-01

It remains controversial whether open or laparoscopic surgery should be indicated for elderly patients with colorectal cancer and a poor performance status. In those patients aged 80 years or older with Eastern Cooperative Oncology Group performance status score of 2 or greater who received elective surgery for stage 0 to stage III colorectal adenocarcinoma and had no concomitant malignancies and who were enrolled in a multicenter case-control study entitled "Retrospective study of laparoscopic colorectal surgery for elderly patients" that was conducted in Japan between 2003 and 2007, background characteristics and short-term and long-term outcomes for open surgery and laparoscopic surgery were compared. Of the 398 patients included, 295 underwent open surgery and 103 underwent laparoscopic surgery. There were no significant differences in the baseline characteristics between open surgery and laparoscopic surgery patients, except for previous abdominal surgery and TNM stage. The median operation duration was shorter with open surgery (open surgery, 153 min; laparoscopic surgery, 202 min; P < 0.001), and less blood loss occurred with laparoscopic surgery (median open surgery, 109 g; median laparoscopic surgery, 30 g; P < 0.001). An operation duration of 180 min or more (odds ratio, 1.97; 95 % confidence interval, 1.17-3.37; P = 0.011) and selection of laparoscopic surgery (odds ratio, 0.41; 95 % confidence interval, 0.22-0.75; P = 0.003) were statistically significant in the multivariate analysis for postoperative morbidity. Moreover, laparoscopic surgery did not result in an inferior overall survival rate compared with open surgery (log-rank test P = 0.289, 0.278, 0.346, 0.199, for all-stage, stage 0-I, stage II, and stage III disease, respectively). Laparoscopic surgery in elderly colorectal cancer patients with a poor performance status is safe and not inferior to open surgery in terms of overall survival.

Is VEGF under-expressed in Indian children with Perthes disease?

PubMed

Tiwari, V; Poudel, R R; Khan, S A; Mehra, S; Chauhan, S S; Raje, A

2018-04-01

The role of vascular endothelial growth factor (VEGF) after ischaemic necrosis of the femoral head in Legg-Calve-Perthes disease (LCPD) has not been adequately studied in humans, especially in Indian population. Therefore, we aimed to evaluate the serum levels of VEGF-A in Indian children with various stages of LCPD and compare them with those of an age- and sex-matched control group of healthy children. In this case-control study, we enrolled 42 children (below 14 years age) suffering from LCPD and 21 age- and sex-matched healthy controls. Patients were classified radiographically according to Waldenstrom's classification. Serum VEGF-A was estimated by sandwich enzyme-linked immunosorbent assay technique. The serum values were compared between the patient group and the control group, as well as between the Waldenstrom subgroups. Results were expressed as means with ranges or median with interquartile range. The mean age in the patient as well as the control group was 9 years (range 4-13 years). The median value (interquartile range) of serum VEGF-A was 162.5 pg/ml (673.75 pg/ml) in the patient group and 652 pg/ml (190.5 pg/ml) in the control group (p = 0.013). When compared between lower Waldenstrom stages (initial stage + stage of fragmentation) and higher Waldenstrom stages (re-ossification stage + stage of healing), the mean values of serum VEGF-A were 464.7 pg/ml (range 0-2211 pg/ml) and 301.1 pg/ml (range 0-1910 pg/ml), respectively (p = 0.305). VEGF is under-expressed in Indian children suffering from LCPD. As VEGF acts as a key regulator of endochondral ossification, our finding may open new therapeutic approaches to the disease. Also, serum VEGF may act as a valuable marker for the follow-up of the disease. Our study also provides baseline data about serum VEGF-A levels in Indian cohort of LCPD patients. Future multi-centre studies are warranted with a larger sample size to fully appreciate the patho-physiological changes in VEGF occurring in LCPD.

MicroRNA-21 in laryngeal squamous cell carcinoma: Diagnostic and prognostic features.

PubMed

Erkul, Evren; Yilmaz, Ismail; Gungor, Atila; Kurt, Onuralp; Babayigit, Mustafa A

2017-02-01

We aimed to determine the microRNA-21 expression in laryngeal squamous cell carcinoma and assess the association between the disease and clinical characteristics of patients. Retrospective case-control study. A retrospective study was conducted from January 2005 to May 2011, in a tertiary hospital following tumor resection in 72 patients with laryngeal squamous cell carcinoma. We used formalin-fixed paraffin-embedded tissue samples of laryngeal squamous cell carcinomas (study group) and adjacent nontumor tissues (control group) for microRNA-21 expressions, and we successfully extracted microRNAs detectable by real-time polymerase chain reaction. All patients were evaluated separately, and the study and control groups were compared. The study group was assessed in terms of localization, smoking, alcohol consumption, lymph node staging, tumor stage, overall survival, disease-free survival, perineural, and vascular invasion. All patients were male, and the average age of patients was 64.2 ± 10.3 years. MicroRNA-21 was upregulated in laryngeal squamous cell carcinomas compared to adjacent nontumor tissues (P = .005). However, the microRNA-21 did not differ significantly according to any clinicopathological features (P > .05). MicroRNA-21 has been found to be expressed at lower levels in early stage (stages 1 and 2) compared with advanced stage (stages 3 and 4), but this was not statistically significant (P = .455). We conclude that the microRNA-21 level may play an important role in diagnosis and serve as a potential biomarker; such measurement thus has clinical applications. However, any possible prognostic associations with microRNA-21 levels should be re-evaluated in future studies on laryngeal squamous cell carcinoma samples amenable to retrospective analysis. NA Laryngoscope, 2016 127:E62-E66, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Language Mapping in Awake Surgery: Report of Two Cases with Review of Language Networks.

PubMed

Lim, Liang Hooi; Idris, Zamzuri; Reza, Faruque; Wan Hassan, Wan Mohd Nazaruddin; Mukmin, Laila Abd; Abdullah, Jafri Malin

2018-01-01

The role of language in communication plays a crucial role in human development and function. In patients who have a surgical lesion at the functional language areas, surgery should be intricately planned to avoid incurring further morbidity. This normally requires extensive functional and anatomical mappings of the brain to identify regions that are involved in language processing and production. In our case report, regions of the brain that are important for language functions were studied before surgery by employing (a) extraoperative methods such as functional magnetic resonance imaging, transmagnetic stimulation, and magnetoencephalography; (b) during the surgery by utilizing intraoperative awake surgical methods such as an intraoperative electrical stimulation; and (c) a two-stage surgery, in which electrical stimulation and first mapping are made thoroughly in the ward before second remapping during surgery. The extraoperative methods before surgery can guide the neurosurgeon to localize the functional language regions and tracts preoperatively. This will be confirmed using single-stage intraoperative electrical brain stimulation during surgery or a two-stage electrical brain stimulation before and during surgery. Here, we describe two cases in whom one has a superficial lesion and another a deep-seated lesion at language-related regions, in which language mapping was done to preserve its function. Additional review on the neuroanatomy of language regions, language network, and its impairment was also described.

150 000 Years of Loess Deposition in Interior Alaska as Told by Magnetic Susceptibility

NASA Astrophysics Data System (ADS)

Jensen, B. J. L.; Evans, M. E.; Froese, D. G.; Kravchinsky, V. A.

2015-12-01

The Halfway House loess deposit in interior Alaska contains a well-studied and complex paleomagnetic and paleoenvironmental record. Unfortunately, a lack of chronologic control has made it difficult to interpret the results of these studies. Detailed reexamination of stratigraphy, paleomagnetics and tephrostratigraphy reveals a relatively complete marine isotope stage (MIS) 6 to Holocene record constrained by the Old Crow (124 ± 10 ka), VT (106 ± 10 ka), Sheep Creek-Klondike (ca. 80 ka), Dominion Creek (77 ± 8 ka) and Dawson (ca. 30.2 cal ka BP) tephras. Two well-developed paleosols are shown to have formed during Marine Isotope Stages (MIS) 5e and 5a, while MIS 5c and 5b are either poorly represented or absent. A magnetic excursion is identified as the post-Blake excursion (94.1 ± 7.8 ka) and provides independent age control while adding to an increasing body of evidence that Alaskan loess is a detailed recorder of variations of the Earth's magnetic field over time. High-resolution magnetic susceptibility profiles placed into this new chronostratigraphic framework help refine loess deposition models for the interior of Alaska, while providing a means to correlate to previous magnetic studies at this site. The profiles support the hypothesis that wind-intensity is the main variable controlling fluctuations in susceptibility, with the highest susceptibility during peak glacial times and the lowest values in paleosols representing interglacials. However, the correlation of the susceptibility record to global marine d18O records is complicated by highly variable accumulation rates. We find the lowest rates of accumulation during peak warm and cold stages, while abrupt increases are associated with periods of transition between marine isotope stages, represented by intermediate susceptibility values. Previous accumulation models for Alaska have emphasized the role of surface roughness as an important variable controlling loess accumulation. However our results suggest that while this may be the case during transitions and peak cold periods, the negligible accumulation during the peak warmth of MIS 5e and 5a suggests loess production was exceedingly low, negating the role of surface roughness.

Cohort Profile: the National Prostate Cancer Register of Sweden and Prostate Cancer data Base Sweden 2.0.

PubMed

Van Hemelrijck, Mieke; Wigertz, Annette; Sandin, Fredrik; Garmo, Hans; Hellström, Karin; Fransson, Per; Widmark, Anders; Lambe, Mats; Adolfsson, Jan; Varenhorst, Eberhard; Johansson, Jan-Erik; Stattin, Pär

2013-08-01

In 1987, the first Regional Prostate Cancer Register was set up in the South-East health-care region of Sweden. Other health-care regions joined and since 1998 virtually all prostate cancer (PCa) cases are registered in the National Prostate Cancer Register (NPCR) of Sweden to provide data for quality assurance, bench marking and clinical research. NPCR includes data on tumour stage, Gleason score, serum level of prostate-specific antigen (PSA) and primary treatment. In 2008, the NPCR was linked to a number of other population-based registers by use of the personal identity number. This database named Prostate Cancer data Base Sweden (PCBaSe) has now been extended with more cases, longer follow-up and a selection of two control series of men free of PCa at the time of sampling, as well as information on brothers of men diagnosed with PCa, resulting in PCBaSe 2.0. This extension allows for studies with case-control, cohort or longitudinal case-only design on aetiological factors, pharmaceutical prescriptions and assessment of long-term outcomes. The NPCR covers >96% of all incident PCa cases registered by the Swedish Cancer Register, which has an underreporting of <3.7%. The NPCR is used to assess trends in incidence, treatment and outcome of men with PCa. Since the national registers linked to PCBaSe are complete, studies from PCBaSe 2.0 are truly population based.

Identification of Immune-Relevant Factors Conferring Sarcoidosis Genetic Risk

PubMed Central

Fischer, Annegret; Ellinghaus, David; Nutsua, Marcel; Hofmann, Sylvia; Montgomery, Courtney G.; Iannuzzi, Michael C.; Rybicki, Benjamin A.; Petrek, Martin; Mrazek, Frantisek; Pabst, Stefan; Grohé, Christian; Grunewald, Johan; Ronninger, Marcus; Eklund, Anders; Padyukov, Leonid; Mihailovic-Vucinic, Violeta; Jovanovic, Dragana; Sterclova, Martina; Homolka, Jiri; Nöthen, Markus M.; Herms, Stefan; Gieger, Christian; Strauch, Konstantin; Winkelmann, Juliane; Boehm, Bernhard O.; Brand, Stephan; Büning, Carsten; Schürmann, Manfred; Ellinghaus, Eva; Baurecht, Hansjörg; Lieb, Wolfgang; Nebel, Almut; Müller-Quernheim, Joachim; Franke, Andre

2015-01-01

Rationale: Genetic variation plays a significant role in the etiology of sarcoidosis. However, only a small fraction of its heritability has been explained so far. Objectives: To define further genetic risk loci for sarcoidosis, we used the Immunochip for a candidate gene association study of immune-associated loci. Methods: Altogether the study population comprised over 19,000 individuals. In a two-stage design, 1,726 German sarcoidosis cases and 5,482 control subjects were genotyped for 128,705 single-nucleotide polymorphisms using the Illumina Immunochip for the screening step. The remaining 3,955 cases, 7,514 control subjects, and 684 parents of affected offspring were used for validation and replication of 44 candidate and two established risk single-nucleotide polymorphisms. Measurements and Main Results: Four novel susceptibility loci were identified with genome-wide significance in the European case-control populations, located on chromosomes 12q24.12 (rs653178; ATXN2/SH2B3), 5q33.3 (rs4921492; IL12B), 4q24 (rs223498; MANBA/NFKB1), and 2q33.2 (rs6748088; FAM117B). We further defined three independent association signals in the HLA region with genome-wide significance, peaking in the BTNL2 promoter region (rs5007259), at HLA-B (rs4143332/HLA-B*0801) and at HLA-DPB1 (rs9277542), and found another novel independent signal near IL23R (rs12069782) on chromosome 1p31.3. Conclusions: Functional predictions and protein network analyses suggest a prominent role of the drug-targetable IL23/Th17 signaling pathway in the genetic etiology of sarcoidosis. Our findings reveal a substantial genetic overlap of sarcoidosis with diverse immune-mediated inflammatory disorders, which could be of relevance for the clinical application of modern therapeutics PMID:26051272

Determinants of stage at diagnosis of breast cancer in Nigerian women: sociodemographic, breast cancer awareness, health care access and clinical factors.

PubMed

Jedy-Agba, Elima; McCormack, Valerie; Olaomi, Oluwole; Badejo, Wunmi; Yilkudi, Monday; Yawe, Terna; Ezeome, Emmanuel; Salu, Iliya; Miner, Elijah; Anosike, Ikechukwu; Adebamowo, Sally N; Achusi, Benjamin; Dos-Santos-Silva, Isabel; Adebamowo, Clement

2017-07-01

Advanced stage at diagnosis is a common feature of breast cancer in Sub-Saharan Africa (SSA), contributing to poor survival rates. Understanding its determinants is key to preventing deaths from this cancer in SSA. Within the Nigerian Integrative Epidemiology of Breast Cancer Study, a multicentred case-control study on breast cancer, we studied factors affecting stage at diagnosis of cases, i.e. women diagnosed with histologically confirmed invasive breast cancer between January 2014 and July 2016 at six secondary and tertiary hospitals in Nigeria. Stage was assessed using clinical and imaging methods. Ordinal logistic regression was used to examine associations of sociodemographic, breast cancer awareness, health care access and clinical factors with odds of later stage (I, II, III or IV) at diagnosis. A total of 316 women were included, with a mean age (SD) of 45.4 (11.4) years. Of these, 94.9% had stage information: 5 (1.7%), 92 (30.7%), 157 (52.4%) and 46 (15.3%) were diagnosed at stages I, II, III and IV, respectively. In multivariate analyses, lower educational level (odds ratio (OR) 2.35, 95% confidence interval: 1.04, 5.29), not believing in a cure for breast cancer (1.81: 1.09, 3.01), and living in a rural area (2.18: 1.05, 4.51) were strongly associated with later stage, whilst age at diagnosis, tumour grade and oestrogen receptor status were not. Being Muslim (vs. Christian) was associated with lower odds of later stage disease (0.46: 0.22, 0.94). Our findings suggest that factors that are amenable to intervention concerning breast cancer awareness and health care access, rather than intrinsic tumour characteristics, are the strongest determinants of stage at diagnosis in Nigerian women.

Preservation Effect of Two-Stage Cinnamon Bark (Cinnamomum Burmanii) Oleoresin Microcapsules On Vacuum-Packed Ground Beef During Refrigerated Storage

NASA Astrophysics Data System (ADS)

Irfiana, D.; Utami, R.; Khasanah, L. U.; Manuhara, G. J.

2017-04-01

The purpose of this study was to determine the effect of two stage cinnamon bark oleoresin microcapsules (0%, 0.5% and 1%) on the TPC (Total Plate Count), TBA (thiobarbituric acid), pH, and RGB color (Red, Green, and Blue) of vacuum-packed ground beef during refrigerated storage (at 0, 4, 8, 12, and 16 days). This study showed that the addition of two stage cinnamon bark oleoresin microcapsules affected the quality of vacuum-packed ground beef during 16 days of refrigerated storage. The results showed that the TPC value of the vacuum-packed ground beef sample with the addition 0.5% and 1% microcapsules was lower than the value of control sample. The TPC value of the control sample, sample with additional 0.5% and 1% microcapsules were 5.94; 5.46; and 5.16 log CFU/g respectively. The TBA value of vacuum-packed ground beef were 0.055; 0.041; and 0.044 mg malonaldehyde/kg, resepectively on the 16th day of storage. The addition of two-stage cinnamon bark oleoresin microcapsules could inhibit the growth of microbia and decrease the oxidation process of vacuum-packed ground beef. Moreover, the change of vacuum-packed ground beef pH and RGB color with the addition 0.5% and 1% microcapsules were less than those of the control sample. The addition of 1% microcapsules showed the best effect in preserving the vacuum-packed ground beef.

Retrospective histopathological analysis of various neoplasms of the female reproductive system (FRS) seen at the Kathmandu University Teaching Hospital, (KUTH) Dhulikhel, Nepal.

PubMed

Mohammad, A; Makaju, R

2006-01-01

To find out the spectrum of various histopathological types of primary neoplasms of different parts/organs of the female reproductive system seen at the Kathmandu University Teaching Hospital (KUTH) as there exists a worldwide wide variation in the distribution of various neoplasms, which appears largely due to exogenous factors rather than due to inherent differences between populations. This was a retrospective study. It was carried out at KUTH. All neoplasms of the female reproductive system seen at the KUTH during the period of 20 months from 1st January 2004 to 31st August 2005 were included in this study and examined by light microscope (LM). A total number of 60 cases of neoplasms of the female reproductive system were seen. Out of these, 1 (1.7%) was of the vagina (squamous cell carcinoma, papillary variant); 16 (26.7%) were of the cervix of the uterus (all squamous cell carcinoma in advanced stage); none were of the endometrium; 20 (33.3%) were of the body of the uterus/uterine muscle (all liomyomas); 16 (26.7%) were of the ovary, (11 benign, consisting of nine mature cystic tertoma, also known as dermoid cyst, one serous papillary cystdenoma and one mucinous cystadenoma; and, five malignant, consisting of two serous cystadenocarcinoma, two mucinous cystadenocarcinoma and one mixed mucinous and serous cystadenocarcinoma); and, 7 (11.6%) were of the breast (two benign, consisting of fibroadenoma and five malignant, all consisting of infiltrating ductal carcinoma in advanced stage). There were relatively a large number of cases of advanced stage of cancer of uterine cervix. All breast cancers seen were also in advanced stage. Endometrial carcinoma was conspicuously absent in our this small series of cases.

Analysis of Parallel Burn, No-Crossfeed TSTO RLV Architectures and Comparison to Parallel Burn with Crossfeed and Series Burn Architectures

NASA Technical Reports Server (NTRS)

Smith, Garrett; Philips, Alan

2003-01-01

Three dominant Two Stage To Orbit (TSTO) class architectures were studied: Series Burn (SB), Parallel Bum with crossfeed (PBw/cf), and Parallel Burn, no-crossfeed (PBncf). The study goal was to determine what factors uniquely affect PBncf architectures, how each of these factors interact, and to determine from a performance perspective whether a PBncf vehicle could be competitive with a PBw/cf or a SB vehicle using equivalent technology and assumptions. In all cases, performance was evaluated on a relative basis for a fixed payload and mission by comparing gross and dry vehicle masses of a closed vehicle. Propellant combinations studied were LOX: LH2 propelled booster and orbiter (HH) and LOX: Kerosene booster with LOX: LH2 orbiter (KH). The study observations were: 1) A PBncf orbiter should be throttled as deeply as possible after launch until the staging point. 2) A PBncf TSTO architecture is feasible for systems that stage at mach 7. 2a) HH architectures can achieve a mass growth relative to PBw/cf of <20%. 2b) KH architectures can achieve a mass growth relative to Series Burn of <20%. 3) Center of gravity (CG) control will be a major issue for a PBncf vehicle, due to the low orbiter specific thrust to weight ratio and to the position of the orbiter required to align the nozzle heights at liftoff. 4) Thrust to weight ratios of 1.3 at liftoff and between 1.0 and 0.9 when staging at mach 7 appear to be close to ideal for PBncf vehicles. 5) Performance for HH vehicles was better when staged at mach 7 instead of mach 5. The study suggests possible methods to maximize performance of PBncf vehicle architectures in order to meet mission design requirements.

Radiation management of carcinoma of the cervical stump. [Complications following external and internal radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prempree, T.; Patanaphan, V.; Scott, R.M.

1979-04-01

In spite of a low incidence of carcinoma of the cervical stump at the present time, the management of this interesting disease deserves special attention because of the success which can be obtained with proper treatment. Of 107 cases treated, only 100 cases were true cases of carcinoma of the stump and were eligible for this study. 7 cases were excluded from the study because they were probably coincidental carcinomas and were treated soon after subtotal hysterectomy. The lesions were staged according to the FIGO system. 93 cases were invasive squamous cell carcinoma, 6 cases adenocarcinoma and 1 case transitionalmore » cell carcinoma. Of 100 cases with a minimum 5 year follow-up, the absolute 5-year cure rate for various clinical stages is as follows: State I 83.3% (20/24); Stage IIA 75.0% (9/12); Stage IIB 62.5% (20/32); Stage IIIA 50% (1/2); Stage IIIB 48% (12/25); Stage IV 20% (1/5). The overall absolute 5-year cure rate for all stages combined is 63%. A better result in Stage IIIB as compared to several previous reports is thought to be due to extensive and aggressive interstitial radium therapy properly combined with external supervoltage irradiation. Techniques of treatment stage by stage including computerized dosimetry are discussed along with complications and failures.« less

A 5-year retrospective case series evaluating Brånemark Integration BioHelix (™) dental implants placed in a private practice by a specialist.

PubMed

Thomsson, Mats; Larsson Wexell, Cecilia

2013-09-01

To evaluate, in a case series, survival rate and complications of Brånemark Integration BioHelix(™) dental implants, placed according to conventional procedures in patients treated consecutively in a Swedish specialist private practice after 5 years. Eighty-three consecutively-treated patients received 89 final fixed prostheses supported by 310 implants placed according to 'conventional' procedure, i.e. no implants shorter than 10 mm, no immediate post-extraction implants and no bone-grafting procedures. In 70 patients, implants were left to heal submerged, whereas 13 patients were treated according to the one-stage protocol. All implants were incorporated in a prosthetic restoration. Probing was only performed when clinical signs of inflammation were present and this was then evaluated further with intra-oral radiographic examination. Outcome measures were implant survival and prosthetic complications. Five years after implant placement, two fixtures were removed because of loosening. One fixture was lost after 12 months in the lower jaw in one patient and one fixture was lost in the upper jaw in another patient after 3 years, both inserted using the two-stage technique. No other prosthetic complications occurred, giving a 99.3% cumulative survival rate. Brånemark Integration BioHelix(™) dental implants placed according to one- or two-stage procedures in patients in a private practice produced excellent 5-year results. Randomized clinical trials with suitable controls are suggested to confirm these results.

Inclusion of persons with disabilities in systems of social protection: a population-based survey and case-control study in Peru.

PubMed

Bernabe-Ortiz, Antonio; Diez-Canseco, Francisco; Vasquez, Alberto; Kuper, Hannah; Walsham, Matthew; Blanchet, Karl

2016-08-26

This study aims to assess the needs of people with disabilities and their level of inclusion in social protection programmes. Population based-survey with a nested case-control study. Morropon, a semiurban district located in Piura, northern Peru. For the population survey, a two-stage sampling method was undertaken using data from the most updated census available and information of each household member aged ≥5 years was collected. In the nested case-control study, only one participant, case or control, per household was included in the study. Disability was screened using the Washington Group short questionnaire. A case, defined as an individual aged ≥5 years with disabilities, was matched with one control without disabilities by sex and age (±5 years). Information was collected on socioeconomic status, education, health and rehabilitation and social protection participation. The survey included 3684 participants, 1848 (50.1%) females, mean age: 36.4 (SD: 21.7). A total of 290 participants (7.9%; 95% CI 7.0% to 8.7%) were classified as having disability. Adults with disabilities were more likely to be single (OR=3.40; 95% CI 1.54 to 7.51) and not to be working (OR=4.36; 95% CI 2.26 to 8.40), while those who did work were less likely to receive the national minimum wage (ie, 750 PEN or about US$265; p=0.007). People with disabilities were more likely to experience health problems. There was no difference between those enrolled in any social protection programme among participants with and without disabilities. People with disabilities were found to have higher needs for social protection, but were not more likely to be enrolled in social protection programmes. The Peruvian social protection system should consider adding disability status to selection criteria in their cash transfer programmes as well as implementing disability-specific interventions. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

A Bayesian Semiparametric Approach for Incorporating Longitudinal Information on Exposure History for Inference in Case-Control Studies

PubMed Central

Bhadra, Dhiman; Daniels, Michael J.; Kim, Sungduk; Ghosh, Malay; Mukherjee, Bhramar

2014-01-01

In a typical case-control study, exposure information is collected at a single time-point for the cases and controls. However, case-control studies are often embedded in existing cohort studies containing a wealth of longitudinal exposure history on the participants. Recent medical studies have indicated that incorporating past exposure history, or a constructed summary measure of cumulative exposure derived from the past exposure history, when available, may lead to more precise and clinically meaningful estimates of the disease risk. In this paper, we propose a flexible Bayesian semiparametric approach to model the longitudinal exposure profiles of the cases and controls and then use measures of cumulative exposure based on a weighted integral of this trajectory in the final disease risk model. The estimation is done via a joint likelihood. In the construction of the cumulative exposure summary, we introduce an influence function, a smooth function of time to characterize the association pattern of the exposure profile on the disease status with different time windows potentially having differential influence/weights. This enables us to analyze how the present disease status of a subject is influenced by his/her past exposure history conditional on the current ones. The joint likelihood formulation allows us to properly account for uncertainties associated with both stages of the estimation process in an integrated manner. Analysis is carried out in a hierarchical Bayesian framework using Reversible jump Markov chain Monte Carlo (RJMCMC) algorithms. The proposed methodology is motivated by, and applied to a case-control study of prostate cancer where longitudinal biomarker information is available for the cases and controls. PMID:22313248

OPTIMIZED REAL-TIME CONTROL OF COMBINED SEWERAGE SYSTEMS: TWO CASE STUDIES

EPA Science Inventory

The paper presents results of two case studies of Real-Time Control (RTC) alternatives evaluations that were conducted on portions of sewerage systems near Paris, France and in Quebec City, Canada, respectively. The studies were performed at real-scale demonstration sites. RTC ...

Ultraprecision XY stage using a hybrid bolt-clamped Langevin-type ultrasonic linear motor for continuous motion.

PubMed

Lee, Dong-Jin; Lee, Sun-Kyu

2015-01-01

This paper presents a design and control system for an XY stage driven by an ultrasonic linear motor. In this study, a hybrid bolt-clamped Langevin-type ultrasonic linear motor was manufactured and then operated at the resonance frequency of the third longitudinal and the sixth lateral modes. These two modes were matched through the preload adjustment and precisely tuned by the frequency matching method based on the impedance matching method with consideration of the different moving weights. The XY stage was evaluated in terms of position and circular motion. To achieve both fine and stable motion, the controller consisted of a nominal characteristics trajectory following (NCTF) control for continuous motion, dead zone compensation, and a switching controller based on the different NCTFs for the macro- and micro-dynamics regimes. The experimental results showed that the developed stage enables positioning and continuous motion with nanometer-level accuracy.

Knee arthrodesis with the Vari-Wall nail for treatment of infected total knee arthroplasty.

PubMed

Garcia-Lopez, Ignacio; Aguayo, Miguel Anguel; Cuevas, Antonio; Navarro, Pablo; Prieto, Cristobal; Carpintero, Pedro

2008-12-01

We reviewed 20 patients who had undergone one-stage (7 cases) or two-stage (13 cases) knee arthrodesis using the Vari-Wall intramedullary nail, as a salvage operation following infection of a total knee arthroplasty. The procedure was followed by systemic antibiotic administration and early rehabilitation. Intraoperative microbiological cultures were taken. The average period of follow-up was 20 months. Solid union was achieved in 80%; mean time to fusion was 9 months. There was no recurrence of infection. The average limb length discrepancy was 2.45 cm. A walking aid was needed by 95% of the patients. The complication rate was 30% including 4 pseudarthroses, one intraoperative fracture and one peroneal nerve palsy. The Vari-Wall intramedullary nail is a good option when an arthrodesis is indicated for salvage of an infected total knee arthroplasty. It can be performed in one or two stages depending on several factors such as microbiologic culture results. It achieved good pain relief and acceptable functional results in this study.

Role of the cerebellum in high stages of motor planning hierarchy

PubMed Central

Federici, Alessandra; Cesareo, Ambra; Biffi, Emilia; Valtorta, Giulia; Molteni, Massimo; Ronconi, Luca; Borgatti, Renato

2017-01-01

Motor planning is not a monolithic process, and distinct stages of motor planning are responsible for encoding different levels of abstractness. However, how these distinct components are mapped into different neural substrates remains an open question. We studied one of these high-level motor planning components, defined as second-order motor planning, in a patient (R.G.) with an extremely rare case of cerebellar agenesis but without any other cortical malformations. Second-order motor planning dictates that when two acts must be performed sequentially, planning of the second act can influence execution of the first. We used an optoelectronic system for kinematic analysis to compare R.G.’s performance with age-matched controls in a second-order motor planning task. The first act was to reach for an object, and the second was to place it into a small or large container. Our results showed that despite the expected difficulties in fine-motor skills, second-order motor planning (i.e., the ability to modulate the first act as a function of the nature of the second act) was preserved even in the patient with congenital absence of the cerebellum. These results open new intriguing speculations about the role of the cerebellum in motor planning abilities. Although prudence is imperative when suggesting conclusions made on the basis of single-case findings, this evidence suggests fascinating hypotheses about the neural circuits that support distinct stages of the motor planning hierarchy, and regarding the functional role of second-order motor planning in motor cognition and its potential dysfunction in autism. NEW & NOTEWORTHY Traditionally, the cerebellum was considered essential for motor planning. By studying an extremely rare patient with cerebellar agenesis and a group of neurotypical controls, we found that high stages of the motor planning hierarchy can be preserved even in this patient with congenital absence of the cerebellum. Our results provide interesting insights that shed light on the neural circuits supporting distinct levels of motor planning. Furthermore, the results are intriguing because of their potential clinical implications in autism. PMID:28077667

The Identification of Hail Storms in the Early Stage Using Time Series Analysis

NASA Astrophysics Data System (ADS)

Wang, Ping; Shi, Jinyu; Hou, Jinyi; Hu, Yan

2018-01-01

This study investigates the characteristics of hail storms and cumulonimbus storms in China from 2005 to 2016. Ten features are proposed to identify storm cells that can produce hail, especially in the early stage of hail formation. These features describe hail storms based on three factors: the height and thickness of the cell core, the radar echo intensity, and the overhang structure and the horizontal reflectivity gradient. The 10 features are transformed into two-dimensional comprehensive features by principal component analysis (PCA). The two comprehensive features are named the volume measurement comprehensive feature (VMCF) and the height-gradient comprehensive feature (HGCF). Through an analysis of 49 hail cases and 35 heavy rainfall cases with S-band radar data, the time series exhibit a distinct increase in VMCF or HGCF values in the early stage of a hail storm. However, the VMCF and HGCF values of heavy rainfall events remain relatively stable throughout the storm life cycle. An experiment involving real-storm events, including 31 hail cases and 33 heavy rainfall cases, indicated that the probability of detection of hail storms was 93.33% and the false alarm ratio was 15.66%. In the cases that could be successfully identified as hail storms, 80.00% were detected within 18 min of reaching a hail storm reflectivity of 40 dBZ.

Validity of the Greek Eating Disorder Examination Questionnaire 6.0 (EDE-Q-6.0) among Greek adolescents.

PubMed

Pliatskidou, S; Samakouri, M; Kalamara, E; Papageorgiou, E; Koutrouvi, K; Goulemtzakis, C; Nikolaou, E; Livaditis, M

2015-01-01

The aim of this study is to examine the validity of the Greek version of the Eating Disorder Examination Questionnaire 6.0 (EDE-Q-6.0) in a sample of adolescent pupils. EDE-Q is a self- report instrument that assesses attitudes and behaviors related to Eating Disorders (EDs). A two-stage identification protocol has been applied to the 16 schools that agreed to participate in the present study. Initially, 2058 adolescents, in class under the supervision of one research assistant and one teacher, completed a Questionnaire on socio-demographic data, the Greek EDE-Q-6.0 and the Greek Eating Attitudes Test (EAT-26) while their weight and height were measured. Six-hundred and twenty six participants, who had scores on EAT-26≥20 and/or were underweight or overweight, were considered as "possible-cases" while the remaining 1432 pupils of the sample were thought as "non-possible cases". At the second stage, parents of 66 of the participants identified as possible-cases as well as parents of 72 participants from 358 controls randomly selected from the sample of "non-possible cases" agreed that their children would be examined by means of Best Estimate Diagnostic Procedure. Participants meeting DSM-IV-TR Eating Disorders criteria were identified. Receiver Operating Characteristics (ROC) analysis was applied to reveal EDE-Q's criterion validity. The kappa statistic test was used as measure of agreement between categorical variables at EDE-Q and at interview (the presence of objective binge eating episode, of self-induced vomiting, the use of laxatives and of excessive exercise). The Discriminant and Convergent validity were assessed using the non-parametric Mann-Whitney U test and by means of the Spearman's correlation coefficient, respectively. Nineteen cases of EDs were identified [one case of Anorexia Nervosa (AN), 13 cases of Eating Disorder Not Otherwise Specified (EDNOS), 5 cases of Binge Eating Disorder (BED)]. At the cut off point of 2.6125 on the EDE-Q's global scale the instrument screens with a sensitivity (Se) of 89.5% and a specificity (Sp) of 73.1%, a Positive Predictive Value (PPV) of 34.7% and a Negative Predictive Value (NPV) of 97.8% The same analyses for both sexes revealed a cut-off point of 2.612 for females and of 3.125 for males on the global EDE-Q-6.0 score (Se=84.62%, Sp=73.33% for females and Se=83.33%, Sp= 84.09% for males), yielding a PPV and a NPV of 35.5% and of 96.5% for females and 41.7% and 97.4% for males, respectively. A very low agreement level, between EDE-Q and interview, was observed regarding the presence of objective bulimic episodes (OBEs) [k=0.191 (SE=0.057)] and the unhealthy weight control behaviors [k=0.295 (SE=0.073)]. Positive correlations were found between EAT-26 and EDE-Q-6.0 for both global scale and subscales (rho=0.50-0.57). The results suggest that EDE-Q-6.0, when using its global score, appears to be a proper screening tool for assessing the core psychopathology of eating disorders in community samples in two-stage screening studies since it distinguishes very well the cases from the non-cases. However, the assessment of the presence and frequency of pathological behaviours which characterize EDs appears to be problematic since adolescents, especially the younger ones, misunderstood terms like large amount of food and loss of control or misinterpret the motivation for excessive exercise. Therefore, marked discrepancies were observed between pathological behaviors self-reported at questionnaire and those detected at interview. We may assume that giving participants more information regarding the definition of these concepts may increase the accuracy with which the participants report these behaviors.

Intake of key micronutrients and food groups in patients with late-stage age-related macular degeneration compared with age-sex-matched controls.

PubMed

Gopinath, Bamini; Liew, Gerald; Russell, Joanna; Cosatto, Victoria; Burlutsky, George; Mitchell, Paul

2017-08-01

Knowledge of the risk factor profile of patients presenting with late-stage age-related macular degeneration (AMD) could help identify the most frequent modifiable AMD precursors among people who are referred for treatment. We aimed to assess dietary behaviours by comparing adjusted mean intakes of micronutrients and major food groups (fruits, vegetables, fish) among patients with AMD and a sample of age-sex-matched controls. Cross-sectional analysis of 480 late AMD cases and 518 population-based age-sex-matched controls with no AMD signs. AMD cases (aged 60+ years) were those presenting for treatment to a hospital eye clinic in Sydney, Australia, during 2012-2015. The comparator group were obtained from a cohort study (Blue Mountains Eye Study; Sydney, Australia) during 2002-2009. Dietary intake was assessed using a semiquantitative food-frequency questionnaire. AMD lesions were assessed from retinal photographs. After multivariable adjustment, patients with late-stage AMD compared with controls had significantly lower intakes of vitamin E (7.4 vs 9.8 mg/day; p<0.0001), beta-carotene (6232 vs 7738 μg/day; p<0.0001), vitamin C (161 vs 184 mg/day; p=0.0002) and folate (498.3 vs 602 μg/day; p<0.0001); but had higher intakes of zinc (13.0 vs 11.9 mg/day; p<0.0001). A significantly lower proportion of patients with late AMD met the recommended intake of vegetables than controls: 52.9% versus 64.5%; p=0.0002. This study showed significant differences in intakes of vitamins C and E, beta-carotene, folate and vegetables between patients with late-stage AMD and healthy controls, and thus has provided a better understanding of the nutritional intake of patients presenting with advanced AMD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Exploration of the utility of ancestry informative markers for genetic association studies of African Americans with type 2 diabetes and end stage renal disease.

PubMed

Keene, Keith L; Mychaleckyj, Josyf C; Leak, Tennille S; Smith, Shelly G; Perlegas, Peter S; Divers, Jasmin; Langefeld, Carl D; Freedman, Barry I; Bowden, Donald W; Sale, Michèle M

2008-09-01

Admixture and population stratification are major concerns in genetic association studies. We wished to evaluate the impact of admixture using empirically derived data from genetic association studies of African Americans (AA) with type 2 diabetes (T2DM) and end-stage renal disease (ESRD). Seventy ancestry informative markers (AIMs) were genotyped in 577 AA with T2DM-ESRD, 596 AA controls, 44 Yoruba Nigerian (YRI) and 39 European American (EA) controls. Genotypic data and association results for eight T2DM candidate gene studies in our AA population were included. Ancestral estimates were calculated using FRAPPE, ADMIXMAP and STRUCTURE for all AA samples, using varying numbers of AIMs (25, 50, and 70). Ancestry estimates varied significantly across all three programs with the highest estimates obtained using STRUCTURE, followed by ADMIXMAP; while FRAPPE estimates were the lowest. FRAPPE estimates were similar using varying numbers of AIMs, while STRUCTURE estimates using 25 AIMs differed from estimates using 50 and 70 AIMs. Female T2DM-ESRD cases showed higher mean African proportions as compared to female controls, male cases, and male controls. Age showed a weak but significant correlation with individual ancestral estimates in AA cases (r2 = 0.101; P = 0.019) and in the combined set (r2 = 0.131; P = 3.57 x 10(-5)). The absolute difference between frequencies in parental populations, absolute delta, was correlated with admixture impact for dominant, additive, and recessive genotypic models of association. This study presents exploratory analyses of the impact of admixture on studies of AA with T2DM-ESRD and supports the use of ancestral proportions as a means of reducing confounding effects due to admixture.

Exploration of the utility of ancestry informative markers for genetic association studies of African Americans with type 2 diabetes and end stage renal disease

PubMed Central

Keene, Keith L.; Mychaleckyj, Josyf C.; Leak, Tennille S.; Smith, Shelly G.; Perlegas, Peter S.; Divers, Jasmin; Langefeld, Carl D.; Freedman, Barry I.; Bowden, Donald W.; Sale, Michèle M.

2009-01-01

Admixture and population stratification are major concerns in genetic association studies. We wished to evaluate the impact of admixture using empirically derived data from genetic association studies of African Americans (AA) with type 2 diabetes (T2DM) and end-stage renal disease (ESRD). Seventy ancestry informative markers (AIMs) were genotyped in 577 AA with T2DM-ESRD, 596 AA controls, 44 Yoruba Nigerian (YRI) and 39 European American (EA) controls. Genotypic data and association results for eight T2DM candidate gene studies in our AA population were included. Ancestral estimates were calculated using FRAPPE, ADMIXMAP and STRUCTURE for all AA samples, using varying numbers of AIMs (25, 50, and 70). Ancestry estimates varied significantly across all three programs with the highest estimates obtained using STRUCTURE, followed by ADMIXMAP; while FRAPPE estimates were the lowest. FRAPPE estimates were similar using varying numbers of AIMs, while STRUCTURE estimates using 25 AIMs differed from estimates using 50 and 70 AIMs. Female T2DM-ESRD cases showed higher mean African proportions as compared to female controls, male cases, and male controls. Age showed a weak but significant correlation with individual ancestral estimates in AA cases (r2=0.101; P=0.019) and in the combined set (r2=0.131; P=3.57×10−5). The absolute difference between frequencies in parental populations, absolute δ, was correlated with admixture impact for dominant, additive, and recessive genotypic models of association. This study presents exploratory analyses of the impact of admixture on studies of AA with T2DM-ESRD and supports the use of ancestral proportions as a means of reducing confounding effects due to admixture. PMID:18654799

The Effectiveness of Keyword-Based Instruction in Enhancing English Vocabulary Achievement and Retention of Intermediate Stage Pupils with Different Working Memory Capacities

ERIC Educational Resources Information Center

Al-Zahrani, Mona Abdullah Bakheet

2011-01-01

The current study aimed at investigating the effectiveness of keyword-based instruction in enhancing English vocabulary achievement and retention of intermediate stage pupils with different working memory capacities. The study adopted a quasi experimental design employing two groups (experimental and control). The design included an independent…

Effects of delivery on maternal & neonatal irisin levels in normal and preeclamptic pregnant women.

PubMed

Foda, Ashraf A; Foda, Engy A

2017-10-01

The aim of this work was to measure the irisin levels in maternal and umbilical cord serums at cesarean section and vaginal delivery. This is a case-control study conducted at the Obstetric Department of the Mansoura University Hospital, Mansoura University, Egypt. The 150 nulliparous cases were divided into three groups. Serum irisin concentrations were assayed by enzyme-linked immunosorbent assay (ELISA) method. Unpaired t-test and correlation were done by using the Statistical Package for Social Scientists (SPSS). The maternal irisin levels in cases with mild preeclampsia were found to be significantly lower than that of the normal cases. In cases with mild preeclampsia, the maternal irisin levels early in labor for vaginal deliveries were significantly higher than that during cesarean section. The maternal irisin levels after vaginal deliveries were significantly higher than the levels early in labor. The maternal serum irisin was a significantly correlated with the duration of the first stage. The umbilical cord serum irisin levels were significantly correlated with the neonatal weight and with the duration of the first stage of labor. Labor is a strong stimulus to the release of irisin into the maternal and fetal circulations. Neonatal serum irisin levels are positively correlated with the birth weight and with the duration of the first stage. The neonatal birth weight and the duration of the first stage of labor are positively correlated with the umbilical cord serum irisin levels. Copyright © 2017 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Small Foci of Serous Component as a Predictor of Recurrence and Prognosis for Stage IA Endometrial Carcinomas.

PubMed

Miyamoto, Morikazu; Takano, Masashi; Tsuda, Hitoshi; Soyama, Hiroaki; Aoyama, Tadashi; Ishibashi, Hiroki; Kato, Kento; Iwahashi, Hideki; Matuura, Hiroko; Yoshikawa, Tomoyuki; Suzuki, Ayako; Hirata, Junko; Furuya, Kenichi

2017-01-01

Most of the endometrial carcinomas are detected in early stages and have a better prognosis; however, predictive factors for recurrence have not been determined. Patients with grade 1 endometrioid carcinoma (EG1) according to the 2014 WHO criteria at FIGO 2009 stage IA that were identified through scanning medical charts were included, and we assessed whether the presence of uterine serous carcinoma (SC) component which comprised less than 5% of the total volume using the ovarian two-tiered grading system could be a recurrent risk factor in these patients. Among 126 cases which met inclusion criteria, 12 cases had SC. SC tumors were divided into 2 groups: SC resembling high-grade serous carcinoma (HGSC) and SC resembling low-grade serous carcinoma (LGSC). Five (3.9%) cases had HGSC and 7 (5.6%) cases had LGSC. Recurrence was observed in 3 of all cases (2.3%): 2 cases with HGSC, and 1 case with LGSC. Regarding several clinicopathological factors, only the presence of SC was associated with recurrence. The sensitivity and specificity to predict recurrence using this system were 100 and 93%, respectively. The identification of SC using the ovarian two-tiered grading system could be an accurate predictor of recurrence in stage IA EG1. © 2017 S. Karger AG, Basel.

Colon cancer: personality factors predictive of onset and stage of presentation.

PubMed

Kavan, M G; Engdahl, B E; Kay, S

1995-11-01

This study examined premorbid personality correlates of colon cancer and stage of presentation of colon cancer to health care providers. Sixty-one male veterans who completed the MMPI between 1947 and 1975 and were then diagnosed with colon cancer between 1977 and 1988 were matched with control patients. A 21-factor solution of the MMPI [1] was used to seek potential personality differences between colon cancer cases and their controls in terms of presence of colon cancer and stage of presentation for this disease. A stepwise conditional regression analysis found significant differences between the colon cancer and control groups on the Aggressive Hostility variable (p < 0.018). A multivariate analysis of variance conducted across the stages of colon cancer presentation found that patients who presented later on for colon cancer had higher Phobia scores (p < 0.05). Religious Fundamentalism was also related to presentation (p < 0.05), but in a nonlinear manner. Discussion is related to previous findings regarding the relationship between personality and development of cancer, as well as to implications for patient screening.

Two-Stage Mucogingival Surgery with Free Gingival Autograft and Biomend Membrane and Coronally Advanced Flap in Treatment of Class III Millers Recession

PubMed Central

Paul, Renny

2016-01-01

Introduction. Gingival recession is an apical shift of the gingival margin with exposure of the root surface. This migration of the marginal tissue leads to esthetic concerns, dentin hypersensitivity, root caries, and cervical wear. It is, paradoxically, a common finding in patients with a high standard of oral hygiene, as well as in periodontally untreated populations with poor oral hygiene. Changing the topography of the marginal soft tissue in order to facilitate plaque control is a common indication for root coverage procedures and forms a major aspect of periodontal plastic surgeries. The regeneration of a new connective tissue attachment to denuded root surface is by allowing the selective coronal regrowth of periodontal ligament cells while excluding the gingival tissues from the root during wound healing by means of a barrier membrane. Case Presentation. This case reports a two-stage surgical technique for treatment of Miller's class III defect using free gingival autograft and type I absorbable collagen membrane (BioMend®, Zimmer Dental, USA)§. Conclusions. The 6-month follow-up of the case showed a significant increase in attached gingiva suggesting it as a predictable alternative in the treatment of Millers class III defects. PMID:27525131

Comparison of two control groups for estimation of oral cholera vaccine effectiveness using a case-control study design.

PubMed

Franke, Molly F; Jerome, J Gregory; Matias, Wilfredo R; Ternier, Ralph; Hilaire, Isabelle J; Harris, Jason B; Ivers, Louise C

2017-10-13

Case-control studies to quantify oral cholera vaccine effectiveness (VE) often rely on neighbors without diarrhea as community controls. Test-negative controls can be easily recruited and may minimize bias due to differential health-seeking behavior and recall. We compared VE estimates derived from community and test-negative controls and conducted bias-indicator analyses to assess potential bias with community controls. From October 2012 through November 2016, patients with acute watery diarrhea were recruited from cholera treatment centers in rural Haiti. Cholera cases had a positive stool culture. Non-cholera diarrhea cases (test-negative controls and non-cholera diarrhea cases for bias-indicator analyses) had a negative culture and rapid test. Up to four community controls were matched to diarrhea cases by age group, time, and neighborhood. Primary analyses included 181 cholera cases, 157 non-cholera diarrhea cases, 716 VE community controls and 625 bias-indicator community controls. VE for self-reported vaccination with two doses was consistent across the two control groups, with statistically significant VE estimates ranging from 72 to 74%. Sensitivity analyses revealed similar, though somewhat attenuated estimates for self-reported two dose VE. Bias-indicator estimates were consistently less than one, with VE estimates ranging from 19 to 43%, some of which were statistically significant. OCV estimates from case-control analyses using community and test-negative controls were similar. While bias-indicator analyses suggested possible over-estimation of VE estimates using community controls, test-negative analyses suggested this bias, if present, was minimal. Test-negative controls can be a valid low-cost and time-efficient alternative to community controls for OCV effectiveness estimation and may be especially relevant in emergency situations. Copyright © 2017. Published by Elsevier Ltd.

Performance of centralized versus decentralized tuberculosis treatment services in Southern Brazil, 2006-2015.

PubMed

Scheffer, Mara Cristina; Prim, Rodrigo Ivan; Wildner, Leticia Muraro; Medeiros, Taiane Freitas; Maurici, Rosemeri; Kupek, Emil; Bazzo, Maria Luiza

2018-04-25

Tuberculosis (TB) control programs face the challenges of decreasing incidence, mortality rates, and drug resistance while increasing treatment adherence. The Brazilian TB control program recommended the decentralization of patient care as a strategy for combating the disease. This study evaluated the performance of this policy in an area with high default rates, comparing epidemiological and operational indicators between two similar municipalities. This study analyzed epidemiological and operational indicators on new cases of pulmonary tuberculosis reported in the Brazilian Notifiable Diseases Information System between 2006 and 2015. In addition, to characterize differences between the populations of the two studied municipalities, a prospective cohort study was conducted between 2014 and 2015, in which patients with new cases of culture-confirmed pulmonary tuberculosis were interviewed and monitored until the disease outcome. A descriptive analysis, the chi-square test, and a Poisson regression model were employed to compare TB treatment outcomes and health care indicators between the municipalities. Two thousand three hundred nine cases were evaluated, of which 207 patients were interviewed. Over the 2006-2015 period, TB incidence per 100,000 population in the municipality with decentralized care was significantly higher (39%, 95% CI 27-49%) in comparison to that of the municipality with centralized care. TB treatment default rate (45%, 95% CI 12-90%) was also higher in the municipality with decentralized care. During the two-year follow-up, significant differences were found between patients in centralized care and those in decentralized care regarding treatment success (84.5 vs. 66.1%), treatment default (10.7 vs. 25.8%), illicit drug use (27.7 vs. 45.9%), and homelessness (3.6 vs. 12.9%). The operational indicators revealed that the proportion of control smear tests, medical imaging, and HIV tests were all significantly higher in the centralized care. However, a significantly higher proportion of patients started treatment in the early stages of the disease in the municipality with decentralized care. These data showed a low success rate in TB treatment in both municipalities. Decentralization of TB care, alone, did not improve the main epidemiological and operational indicators related to disease control when compared to centralized care. Full implementation of strategies already recommended is needed to improve TB treatment success rates.

Design and control of a decoupled two degree of freedom translational parallel micro-positioning stage.

PubMed

Lai, Lei-Jie; Gu, Guo-Ying; Zhu, Li-Min

2012-04-01

This paper presents a novel decoupled two degrees of freedom (2-DOF) translational parallel micro-positioning stage. The stage consists of a monolithic compliant mechanism driven by two piezoelectric actuators. The end-effector of the stage is connected to the base by four independent kinematic limbs. Two types of compound flexure module are serially connected to provide 2-DOF for each limb. The compound flexure modules and mirror symmetric distribution of the four limbs significantly reduce the input and output cross couplings and the parasitic motions. Based on the stiffness matrix method, static and dynamic models are constructed and optimal design is performed under certain constraints. The finite element analysis results are then given to validate the design model and a prototype of the XY stage is fabricated for performance tests. Open-loop tests show that maximum static and dynamic cross couplings between the two linear motions are below 0.5% and -45 dB, which are low enough to utilize the single-input-single-out control strategies. Finally, according to the identified dynamic model, an inversion-based feedforward controller in conjunction with a proportional-integral-derivative controller is applied to compensate for the nonlinearities and uncertainties. The experimental results show that good positioning and tracking performances are achieved, which verifies the effectiveness of the proposed mechanism and controller design. The resonant frequencies of the loaded stage at 2 kg and 5 kg are 105 Hz and 68 Hz, respectively. Therefore, the performance of the stage is reasonably good in term of a 200 N load capacity. © 2012 American Institute of Physics

Management of anorectal melanoma: report of 17 cases and literature review.

PubMed

Belbaraka, Rhizlane; Elharroudi, Tijani; Ismaili, Nabil; Fetohi, Mohammed; Tijami, Fouad; Jalil, Abdelouahed; Errihani, Hassan

2012-03-01

Primary anorectal melanoma is a rare and aggressive disease. It accounts for 0.5% of all rectal tumors. They are very agressive tumors with poor prognosis. The aim of this study is to report the clinical and evolutionary profile and therapeutical approach of these tumors. A retrospective study of 17 patients with anorectal melanoma diagnosed between January 1998 and December 2007 was performed. The signs and symptoms, diagnostic study, and surgical and medical treatments were analyzed. The average age was 58 years. Sex ratio was 12 men per five women. Patients had symptoms present for an average of 6 months. The most common symptom was rectal bleeding. According to Slingluff classification, five patients had stage I (localized tumor), four cases had stage II (regional nodes metastasis), and eight cases had stage III (distant metastasis). Seven patients have radical surgery. Only two patients received adjuvant immunotherapy. Eight patients received palliative chemotherapy based on dacarbazine or cisplatinum. The median survival was 8 months. Prognosis of anorectal melanoma is still very poor. However, some patients when treated by radical resection may experience long-term survival. The use of adjuvant immunotherapy needs large collaborative studies in view of the rarity of the tumor.

What is the evidence base to guide surgical treatment of infected hip prostheses? systematic review of longitudinal studies in unselected patients

PubMed Central

2012-01-01

Background Prosthetic joint infection is an uncommon but serious complication of hip replacement. There are two main surgical treatment options, with the choice largely based on the preference of the surgeon. Evidence is required regarding the comparative effectiveness of one-stage and two-stage revision to prevent reinfection after prosthetic joint infection. Methods We conducted a systematic review to identify randomised controlled trials, systematic reviews and longitudinal studies in unselected patients with infection treated exclusively by one- or two-stage methods or by any method. The Embase, MEDLINE and Cochrane databases were searched up to March 2011. Reference lists were checked, and citations of key articles were identified by using the ISI Web of Science portal. Classification of studies and data extraction were performed independently by two reviewers. The outcome measure studied was reinfection within 2 years. Data were combined to produce pooled random-effects estimates using the Freeman-Tukey arc-sine transformation. Results We identified 62 relevant studies comprising 4,197 patients. Regardless of treatment, the overall rate of reinfection after any treatment was 10.1% (95% CI = 8.2 to 12.0). In 11 studies comprising 1,225 patients with infected hip prostheses who underwent exclusively one-stage revision, the rate of reinfection was 8.6% (95% CI = 4.5 to 13.9). After two-stage revision exclusively in 28 studies comprising 1,188 patients, the rate of reinfection was 10.2% (95% CI = 7.7 to 12.9). Conclusion Evidence of the relative effectiveness of one- and two-stage revision in preventing reinfection of hip prostheses is largely based on interpretation of longitudinal studies. There is no suggestion in the published studies that one- or two stage methods have different reinfection outcomes. Randomised trials are needed to establish optimum management strategies. PMID:22340795

[Clinical observation on the principle of "single usage of acupoints of Shaoyang meridian" for treatment of facial paralysis in acute stage].

PubMed

Shen, Te-Li; Zhang, Wei; Li, Yan

2010-06-01

To compare different therapeutic effects between single usage of acupoints of Shaoyang meridian and the routine ones for treatment of Bell palsy in acute stage. One hundred and twenty cases with Bell palsy during the first three days were random divided into an observation group and a control group, 60 cases in each group. In observation group, acupoints of Shaoyang meridians were used from the 3rd day till the 14th day, Fengchi (GB 20), Yifeng (TE 17), Wangu (GB 12) at the affected side etc. were selected, after the 15th day, the routine acupoints were applied, Hegu (LI 4) on both sides, Fengchi (GB 20), Quchi (LI 11), Yangbai (GB 14) at the affected side etc. were selected; the control group were treated with the same acupoints as the routine ones in observation group since the 3rd day. And both two groups were treated with oral administration of Prednisone. House-Brackmann (H-B) functional grading of facial nerve on the 3rd day with the one of the 60th day as well as electroneurography (ENoG) on the 3rd day with the one of the 14th day were compared respectively. The H-B grading improvement and cured rate were 95.0% (57/60) in observation group, which were suprior to 83.3% (50/60) in control group; the cured time in observation group was (34.21 +/- 8.026) days, significantly shorter than (42.78 +/- 9.029) days in control group (P < 0.05). On the basis of oral administration of Prednisone, single usage of acupoints of Shaoyang meridian in acute stage can make great improvement for recovery of Bell palsy, better than routine point selection.

Heuristic for Critical Machine Based a Lot Streaming for Two-Stage Hybrid Production Environment

NASA Astrophysics Data System (ADS)

Vivek, P.; Saravanan, R.; Chandrasekaran, M.; Pugazhenthi, R.

2017-03-01

Lot streaming in Hybrid flowshop [HFS] is encountered in many real world problems. This paper deals with a heuristic approach for Lot streaming based on critical machine consideration for a two stage Hybrid Flowshop. The first stage has two identical parallel machines and the second stage has only one machine. In the second stage machine is considered as a critical by valid reasons these kind of problems is known as NP hard. A mathematical model developed for the selected problem. The simulation modelling and analysis were carried out in Extend V6 software. The heuristic developed for obtaining optimal lot streaming schedule. The eleven cases of lot streaming were considered. The proposed heuristic was verified and validated by real time simulation experiments. All possible lot streaming strategies and possible sequence under each lot streaming strategy were simulated and examined. The heuristic consistently yielded optimal schedule consistently in all eleven cases. The identification procedure for select best lot streaming strategy was suggested.

Who gets a second chance? An investigation of Ohio's blended juvenile sentence.

PubMed

Cheesman, Fred L; Waters, Nicole L; Hurst, Hunter

2010-01-01

Factors differentiating blended sentencing cases (Serious Youthful Offenders or SYOs) from conventional juvenile cases and cases transferred to the adult criminal court in Ohio were investigated using a two-stage probit. Conventional juvenile cases differed from cases selected for non-conventional processing (i.e., SYO or transfer) according to offense seriousness, number of prior Ohio Department of Youth Services placements, age and gender. Controlling for probability of selection for nonconventional processing, transfers differed from SYOs according to age, gender, and race. Minorities were significantly more likely than Whites to be transfers rather than SYOs, suggesting possible bias in the decision-making process. Objective risk and needs assessments should be used to identify the most suitable candidates for blended sentences and adult transfer and enhanced services should be provided to juvenile offenders given blended sentences.

Use of Two-Way Interactive Television in Education. Training and Development Research Center. Project Number Eighteen.

ERIC Educational Resources Information Center

McClelland, Jerry

Four case studies in varying stages of completion are currently being conducted in the Department of Vocational and Technical Education at the University of Minnesota using live, two-way television to link multiple sites for interactive television classes. Two of the four classes, which are offered via closed-circuit television, are a vocational…

Dynamics of a Stochastic Predator-Prey Model with Stage Structure for Predator and Holling Type II Functional Response

NASA Astrophysics Data System (ADS)

Liu, Qun; Jiang, Daqing; Hayat, Tasawar; Alsaedi, Ahmed

2018-01-01

In this paper, we develop and study a stochastic predator-prey model with stage structure for predator and Holling type II functional response. First of all, by constructing a suitable stochastic Lyapunov function, we establish sufficient conditions for the existence and uniqueness of an ergodic stationary distribution of the positive solutions to the model. Then, we obtain sufficient conditions for extinction of the predator populations in two cases, that is, the first case is that the prey population survival and the predator populations extinction; the second case is that all the prey and predator populations extinction. The existence of a stationary distribution implies stochastic weak stability. Numerical simulations are carried out to demonstrate the analytical results.

Dynamics of a Stochastic Predator-Prey Model with Stage Structure for Predator and Holling Type II Functional Response

NASA Astrophysics Data System (ADS)

Liu, Qun; Jiang, Daqing; Hayat, Tasawar; Alsaedi, Ahmed

2018-06-01

In this paper, we develop and study a stochastic predator-prey model with stage structure for predator and Holling type II functional response. First of all, by constructing a suitable stochastic Lyapunov function, we establish sufficient conditions for the existence and uniqueness of an ergodic stationary distribution of the positive solutions to the model. Then, we obtain sufficient conditions for extinction of the predator populations in two cases, that is, the first case is that the prey population survival and the predator populations extinction; the second case is that all the prey and predator populations extinction. The existence of a stationary distribution implies stochastic weak stability. Numerical simulations are carried out to demonstrate the analytical results.

Neuropathological diagnostic criteria for Alzheimer's disease.

PubMed

Murayama, Shigeo; Saito, Yuko

2004-09-01

Neuropathological diagnostic criteria for Alzheimer's disease (AD) are based on tau-related pathology: NFT or neuritic plaques (NP). The Consortium to Establish a Registry for Alzheimer's disease (CERAD) criterion evaluates the highest density of neocortical NP from 0 (none) to C (abundant). Clinical documentation of dementia and NP stage A in younger cases, B in young old cases and C in older cases fulfils the criterion of AD. The CERAD criterion is most frequently used in clinical outcome studies because of its inclusion of clinical information. Braak and Braak's criterion evaluates the density and distribution of NFT and classifies them into: I/II, entorhinal; III/IV, limbic; and V/VI, neocortical stage. These three stages correspond to normal cognition, cognitive impairment and dementia, respectively. As Braak's criterion is based on morphological evaluation of the brain alone, this criterion is usually adopted in the research setting. The National Institute for Aging and Ronald and Nancy Reagan Institute of the Alzheimer's Association criterion combines these two criteria and categorizes cases into NFT V/VI and NP C, NFT III/IV and NP B, and NFT I/II and NP A, corresponding to high, middle and low probability of AD, respectively. As most AD cases in the aged population are categorized into Braak tangle stage IV and CERAD stage C, the usefulness of this criterion has not yet been determined. The combination of Braak's NFT stage equal to or above IV and Braak's senile plaque Stage C provides, arguably, the highest sensitivity and specificity. In future, the criteria should include in vivo dynamic neuropathological data, including 3D MRI, PET scan and CSF biomarkers, as well as more sensitive and specific immunohistochemical and immunochemical grading of AD.

Diagnosis of Persistent Infection in Prosthetic Two-Stage Exchange: Evaluation of the Effect of Sonication on Antibiotic Release from Bone Cement Spacers.

PubMed

Mariaux, Sandrine; Furustrand Tafin, Ulrika; Borens, Olivier

2018-01-01

Introduction : When treating periprosthetic joint infection with a two-stage procedure, antibiotic-impregnated spacers can be used in the interval between prosthetic removal and reimplantation. In our experience, cultures of sonicated spacers are most often negative. The objective of the study was to assess whether that sonication causes an elution of antibiotics, leading to elevated antibiotic concentrations in the sonication fluid inhibiting bacterial growth and thus causing false-negative cultures. Methods : A prospective monocentric study was performed from September 2014 to March 2016. Inclusion criteria were a two-stage procedure for prosthetic infection and agreement of the patient to participate in the study. Spacers were made of gentamicin-containing cement to which tobramycin and vancomycin were added. Antibiotic concentrations in the sonication fluid were determined by mass-spectometry (LC-MS). Results : 30 patients were identified (15 hip and 14 knee and 1 ankle arthroplasties). No cases of culture positive sonicated spacer fluid were observed in our serie. In the sonication fluid median concentrations of 13.2µg/ml, 392 µg/ml and 16.6 µg/ml were detected for vancomycin, tobramycin and gentamicin, respectively. According to the European Committee on antimicrobial susceptibility testing (EUCAST), these concentrations released from cement spacer during sonication are higher than the minimal inhibitory concentrations (MICs) for most bacteria relevant in prosthetic joint infections. Conclusion: Spacer sonication cultures remained sterile in all of our cases. Elevated concentrations of antibiotics released during sonication could explain partly negative-cultured sonicated spacers. Indeed, the absence of antibiotic free interval during the two-stages can also contribute to false-negative spacers sonicated cultures.

A conflict model for the international hazardous waste disposal dispute.

PubMed

Hu, Kaixian; Hipel, Keith W; Fang, Liping

2009-12-15

A multi-stage conflict model is developed to analyze international hazardous waste disposal disputes. More specifically, the ongoing toxic waste conflicts are divided into two stages consisting of the dumping prevention and dispute resolution stages. The modeling and analyses, based on the methodology of graph model for conflict resolution (GMCR), are used in both stages in order to grasp the structure and implications of a given conflict from a strategic viewpoint. Furthermore, a specific case study is investigated for the Ivory Coast hazardous waste conflict. In addition to the stability analysis, sensitivity and attitude analyses are conducted to capture various strategic features of this type of complicated dispute.

[Decompensated valvular disease and coarctation. One-stage repair using a median approach with an ascending aorta-abdominal aorta shunt].

PubMed

Baille, Y; Sigwalt, M; Vaillant, A; Sicard Desnuelle, M P; Varnet, B

1981-11-01

The tactical decision in patients with decompensated valvular disease associated with a severe stenosis of the aortic isthmus is always difficult. One stage surgical repair using two separate approaches is a long and high risk procedure. It would seem more logical and safer to treat the lesions in two stages a few weeks apart, the severest lesion being managed first. In the two cases reported. The isthmic stenoses and valvular lesions were of the same severity and made both classical techniques impracticable. Therefore the patients underwent a single stage procedure by a median approach associating valve replacement under cardiopulmonary bypass (mitral and tricuspid in one and aortic in the other case) and an ascending aorta-abdominal aorta dacron conduit. The present postoperative survival periods are 30 and 9 months. The functional result was good (Class 1 and 0) and postoperative angiography has shown the montage to be working satisfactorily. This technique is exceptional but may be useful in borderline cases with decompensated valvular disease and severe isthmic stenosis.

Cross-sectional study of the association of abomasal displacement or volvulus with serum electrolyte and mineral concentrations in dairy cows.

PubMed Central

Delgado-Lecaroz, R; Warnick, L D; Guard, C L; Smith, M C; Barry, D A

2000-01-01

The objective of this study was to evaluate serum mineral and electrolyte concentrations at the time of on-farm diagnosis of left displaced abomasum, right displaced abomasum, or abomasal volvulus in dairy cows. Data were collected from 104 affected cows and 96 control cows matched with cases, based on herd, parity, and stage of lactation. Cows with abomasal displacement or volvulus had significantly lower calcium, phosphorous, magnesium, potassium, and chloride concentrations and increased anion gap at the time of diagnosis compared with control cows from the same herds. The percentages of cases and controls with total serum calcium concentrations below the lower limit of the laboratory reference range (2.08 mmol/L [8.3 mg/dL]) were 70% and 23%, respectively. Based on the large percentage of cases with hypocalcemia, administering calcium salts at the time of treatment of field cases of abomasal displacement or volvulus may be beneficial. PMID:10769767

A two-stage storage routing model for green roof runoff detention.

PubMed

Vesuviano, Gianni; Sonnenwald, Fred; Stovin, Virginia

2014-01-01

Green roofs have been adopted in urban drainage systems to control the total quantity and volumetric flow rate of runoff. Modern green roof designs are multi-layered, their main components being vegetation, substrate and, in almost all cases, a separate drainage layer. Most current hydrological models of green roofs combine the modelling of the separate layers into a single process; these models have limited predictive capability for roofs not sharing the same design. An adaptable, generic, two-stage model for a system consisting of a granular substrate over a hard plastic 'egg box'-style drainage layer and fibrous protection mat is presented. The substrate and drainage layer/protection mat are modelled separately by previously verified sub-models. Controlled storm events are applied to a green roof system in a rainfall simulator. The time-series modelled runoff is compared to the monitored runoff for each storm event. The modelled runoff profiles are accurate (mean Rt(2) = 0.971), but further characterization of the substrate component is required for the model to be generically applicable to other roof configurations with different substrate.

Transverse maxillary deficit and its influence on the cervical vertebrae maturation index.

PubMed

Cossellu, G; Farronato, G; Nicotera, O; Biagi, R

2016-06-01

The aim of this study is to evaluate whether a transverse maxillary deficit can cause an alteration of vertebral development and therefore of the skeletal maturation comparing the cervical maturation stages index with the hand-wrist index. For the study were selected 200 patients aged 7-14 years, equally distributed by gender and divided into 100 study subjects with maxillary deficit and 100 controls without maxillary deficit. The skeletal maturation index (SM according to Fishman) was evaluated and compared with the hand-wrist x-rays and the cervical vertebrae maturation (CVM according to Hassel and Farmann). Forty-one per cent of the subjects in the test group show a discrepancy between CVM and SM. Among these 73% (30 subjects) present an advanced stage of CVM compared with the corresponding SM. Only 16% of the subjects in the control group show a discrepancy between CVM and SM. Among these 69% (11 subjects) appear in an advanced CVM stage. The analysis of the CVM stage in subjects with transverse maxillary deficit appears to be altered compared with the SM identified through a hand-wrist x-ray. In the case of individuals with transverse maxillary deficit it is advisable to use also a hand-wrist x-ray, thus not relying only on CVM for the evaluation of the skeletal growth stages.

Verification of a Constraint Force Equation Methodology for Modeling Multi-Body Stage Separation

NASA Technical Reports Server (NTRS)

Tartabini, Paul V.; Roithmayr, Carlos; Toniolo, Matthew D.; Karlgaard, Christopher; Pamadi, Bandu N.

2008-01-01

This paper discusses the verification of the Constraint Force Equation (CFE) methodology and its implementation in the Program to Optimize Simulated Trajectories II (POST2) for multibody separation problems using three specially designed test cases. The first test case involves two rigid bodies connected by a fixed joint; the second case involves two rigid bodies connected with a universal joint; and the third test case is that of Mach 7 separation of the Hyper-X vehicle. For the first two cases, the POST2/CFE solutions compared well with those obtained using industry standard benchmark codes, namely AUTOLEV and ADAMS. For the Hyper-X case, the POST2/CFE solutions were in reasonable agreement with the flight test data. The CFE implementation in POST2 facilitates the analysis and simulation of stage separation as an integral part of POST2 for seamless end-to-end simulations of launch vehicle trajectories.

Family-based treatment of a 17-year-old twin presenting with emerging anorexia nervosa: a case study using the "Maudsley method".

PubMed

Loeb, Katharine L; Hirsch, Alicia M; Greif, Rebecca; Hildebrandt, Thomas B

2009-01-01

This article describes the successful application of family-based treatment (FBT) for a 17-year-old identical twin presenting with a 4-month history of clinically significant symptoms of anorexia nervosa (AN). FBT is a manualized treatment that has been studied in randomized controlled trials for adolescents with AN. This case study illustrates the administration of this evidence-based intervention in a clinical setting, highlighting how the best available research was used to make clinical decisions at each stage of treatment delivery.

A genome wide association study of pulmonary tuberculosis susceptibility in Indonesians.

PubMed

Png, Eileen; Alisjahbana, Bachti; Sahiratmadja, Edhyana; Marzuki, Sangkot; Nelwan, Ron; Balabanova, Yanina; Nikolayevskyy, Vladyslav; Drobniewski, Francis; Nejentsev, Sergey; Adnan, Iskandar; van de Vosse, Esther; Hibberd, Martin L; van Crevel, Reinout; Ottenhoff, Tom H M; Seielstad, Mark

2012-01-13

There is reason to expect strong genetic influences on the risk of developing active pulmonary tuberculosis (TB) among latently infected individuals. Many of the genome wide linkage and association studies (GWAS) to date have been conducted on African populations. In order to identify additional targets in genetically dissimilar populations, and to enhance our understanding of this disease, we performed a multi-stage GWAS in a Southeast Asian cohort from Indonesia. In stage 1, we used the Affymetrix 100 K SNP GeneChip marker set to genotype 259 Indonesian samples. After quality control filtering, 108 cases and 115 controls were analyzed for association of 95,207 SNPs. In stage 2, we attempted validation of 2,453 SNPs with promising associations from the first stage, in 1,189 individuals from the same Indonesian cohort, and finally in stage 3 we selected 251 SNPs from this stage to test TB association in an independent Caucasian cohort (n = 3,760) from Russia. Our study suggests evidence of association (P = 0.0004-0.0067) for 8 independent loci (nominal significance P < 0.05), which are located within or near the following genes involved in immune signaling: JAG1, DYNLRB2, EBF1, TMEFF2, CCL17, HAUS6, PENK and TXNDC4. Mechanisms of immune defense suggested by some of the identified genes exhibit biological plausibility and may suggest novel pathways involved in the host containment of infection with TB.

Key considerations for the experimental training and evaluation of cancer odour detection dogs: lessons learnt from a double-blind, controlled trial of prostate cancer detection

PubMed Central

2014-01-01

Background Cancer detection using sniffer dogs is a potential technology for clinical use and research. Our study sought to determine whether dogs could be trained to discriminate the odour of urine from men with prostate cancer from controls, using rigorous testing procedures and well-defined samples from a major research hospital. Methods We attempted to train ten dogs by initially rewarding them for finding and indicating individual prostate cancer urine samples (Stage 1). If dogs were successful in Stage 1, we then attempted to train them to discriminate prostate cancer samples from controls (Stage 2). The number of samples used to train each dog varied depending on their individual progress. Overall, 50 unique prostate cancer and 67 controls were collected and used during training. Dogs that passed Stage 2 were tested for their ability to discriminate 15 (Test 1) or 16 (Tests 2 and 3) unfamiliar prostate cancer samples from 45 (Test 1) or 48 (Tests 2 and 3) unfamiliar controls under double-blind conditions. Results Three dogs reached training Stage 2 and two of these learnt to discriminate potentially familiar prostate cancer samples from controls. However, during double-blind tests using new samples the two dogs did not indicate prostate cancer samples more frequently than expected by chance (Dog A sensitivity 0.13, specificity 0.71, Dog B sensitivity 0.25, specificity 0.75). The other dogs did not progress past Stage 1 as they did not have optimal temperaments for the sensitive odour discrimination training. Conclusions Although two dogs appeared to have learnt to select prostate cancer samples during training, they did not generalise on a prostate cancer odour during robust double-blind tests involving new samples. Our study illustrates that these rigorous tests are vital to avoid drawing misleading conclusions about the abilities of dogs to indicate certain odours. Dogs may memorise the individual odours of large numbers of training samples rather than generalise on a common odour. The results do not exclude the possibility that dogs could be trained to detect prostate cancer. We recommend that canine olfactory memory is carefully considered in all future studies and rigorous double-blind methods used to avoid confounding effects. PMID:24575737

Genetic variation at MECOM, TERT, JAK2 and HBS1L-MYB predisposes to myeloproliferative neoplasms

PubMed Central

Tapper, William; Jones, Amy V.; Kralovics, Robert; Harutyunyan, Ashot S.; Zoi, Katerina; Leung, William; Godfrey, Anna L.; Guglielmelli, Paola; Callaway, Alison; Ward, Daniel; Aranaz, Paula; White, Helen E.; Waghorn, Katherine; Lin, Feng; Chase, Andrew; Joanna Baxter, E.; Maclean, Cathy; Nangalia, Jyoti; Chen, Edwin; Evans, Paul; Short, Michael; Jack, Andrew; Wallis, Louise; Oscier, David; Duncombe, Andrew S.; Schuh, Anna; Mead, Adam J.; Griffiths, Michael; Ewing, Joanne; Gale, Rosemary E.; Schnittger, Susanne; Haferlach, Torsten; Stegelmann, Frank; Döhner, Konstanze; Grallert, Harald; Strauch, Konstantin; Tanaka, Toshiko; Bandinelli, Stefania; Giannopoulos, Andreas; Pieri, Lisa; Mannarelli, Carmela; Gisslinger, Heinz; Barosi, Giovanni; Cazzola, Mario; Reiter, Andreas; Harrison, Claire; Campbell, Peter; Green, Anthony R.; Vannucchi, Alessandro; Cross, Nicholas C.P.

2015-01-01

Clonal proliferation in myeloproliferative neoplasms (MPN) is driven by somatic mutations in JAK2, CALR or MPL, but the contribution of inherited factors is poorly characterized. Using a three-stage genome-wide association study of 3,437 MPN cases and 10,083 controls, we identify two SNPs with genome-wide significance in JAK2V617F-negative MPN: rs12339666 (JAK2; meta-analysis P=1.27 × 10−10) and rs2201862 (MECOM; meta-analysis P=1.96 × 10−9). Two additional SNPs, rs2736100 (TERT) and rs9376092 (HBS1L/MYB), achieve genome-wide significance when including JAK2V617F-positive cases. rs9376092 has a stronger effect in JAK2V617F-negative cases with CALR and/or MPL mutations (Breslow–Day P=4.5 × 10−7), whereas in JAK2V617F-positive cases rs9376092 associates with essential thrombocythemia (ET) rather than polycythemia vera (allelic χ2 P=7.3 × 10−7). Reduced MYB expression, previously linked to development of an ET-like disease in model systems, associates with rs9376092 in normal myeloid cells. These findings demonstrate that multiple germline variants predispose to MPN and link constitutional differences in MYB expression to disease phenotype. PMID:25849990

Nephrogenic systemic fibrosis is associated with hypophosphataemia: a case-control study.

PubMed

Bernstein, Elana J; Isakova, Tamara; Sullivan, Mary E; Chibnik, Lori B; Wolf, Myles; Kay, Jonathan

2014-09-01

Nephrogenic systemic fibrosis (NSF) is an iatrogenic fibrosing disorder that primarily affects individuals with chronic kidney disease (CKD) following exposure to gadolinium-based contrast agents (GBCAs). Derangements of calcium and phosphorus have been reported in patients with NSF. The aim of this study was to investigate potential factors in addition to GBCA exposure that may be involved in the pathogenesis of NSF. We hypothesized that patients with stage 5 CKD and NSF would manifest greater alterations in calcium, phosphorus and fibroblast growth factor 23 (FGF23) levels than those who do not have NSF. Levels of phosphorus, calcium, FGF23 and 25-hydroxy-vitamin D were measured in 10 patients with stage 5 CKD and biopsy-proven NSF and in 19 patients with stage 5 CKD without NSF. Statistical analyses were performed using Fisher's exact test for categorical variables and the Kruskal-Wallis test for continuous variables. Patients with NSF had significantly lower phosphorus levels compared with controls (P = 0.01). There were no significant differences between NSF patients and controls in calcium, 25-hydroxy-vitamin D, intact parathyroid hormone or FGF23 levels. Differences in phosphorus metabolism may exist between patients with stage 5 CKD and NSF compared with patients with stage 5 CKD without NSF. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The effectiveness of wet cupping vs. venesection on arterial O2 saturation level of cigarette smokers: A randomized controlled clinical trial

PubMed Central

D, Hekmatpou; L, Moeini; S, Haji-Nadali

2013-01-01

Objective: Wet cupping is a traditional bloodletting method recommended for controlling of respiratory disease complications. This study aimed to compare the efficacy of wet cupping vs. venesection on arterial O2 saturation level of smokers. Methods: This is a randomized controlled clinical trial which started with simple sampling of smokers. After administering spirometery, participants (N = 110 male smokers) with positive pulmonary function test (PFT), who manifested Chronic Obstructive Pulmonary Disease (COPD), were randomly assigned to intervention and control groups. The two groups were assessed in terms of demographic data, rate of hemoglobin (Hb), hematocrit (Hct), and arterial O2 saturation. Then, the intervention participants underwent wet cupping whereas venesection was performed on the control participants. At four stages after the two treatments, pulse oximetery was performed. Data was analyzed using SPSS (Version 17). Results: Result shows that mean arterial O2 sat level increased at three stages, namely before, immediately after, and 6 and 12 hrs after these two treatments (p ≤ 0.001). This indicates that wet cupping and venesection alike were effective on O2 sat level in the two groups, but the increasing pattern was maintained 12 hrs afterward only in those participants who had received wet cupping (p ≤ 0.001). Moreover, the results of repeated measure ANOVA between the two groups at the four stages showed that there were significant differences between the means of O2 saturation level at the 6- and 12-hrs stages (F = 66.92, p ≤ 0.001). Conclusion: Wet cupping caused a continued O2 saturation in the intervention group even up to 12 hrs afterward. Participants expressed liveliness and improved respiration after wet cupping. Therefore, wet cupping is recommended for promoting the health of cigarette smokers. PMID:24550951

Priorities for the elimination of sleeping sickness.

PubMed

Welburn, Susan C; Maudlin, Ian

2012-01-01

Sleeping sickness describes two diseases, both fatal if left untreated: (i) Gambian sleeping sickness caused by Trypanosoma brucei gambiense, a chronic disease with average infection lasting around 3 years, and (ii) Rhodesian sleeping sickness caused by T. b. rhodesiense, an acute disease with death occurring within weeks of infection. Control of Gambian sleeping sickness is based on case detection and treatment involving serological screening, followed by diagnostic confirmation and staging. In stage I, patients can remain asymptomatic as trypanosomes multiply in tissues and body fluids; in stage II, trypanosomes cross the blood-brain barrier, enter the central nervous system and, if left untreated, death follows. Staging is crucial as it defines the treatment that is prescribed; for both forms of disease, stage II involves the use of the highly toxic drug melarsoprol or, in the case of Gambian sleeping sickness, the use of complex and very expensive drug regimes. Case detection of T. b. gambiense sleeping sickness is known to be inefficient but could be improved by the identification of parasites using molecular tools that are, as yet, rarely used in the field. Diagnostics are not such a problem in relation to T. b. rhodesiense sleeping sickness, but the high level of under-reporting of this disease suggests that current strategies, reliant on self-reporting, are inefficient. Sleeping sickness is one of the 'neglected tropical diseases' that attracts little attention from donors or policymakers. Proper quantification of the burden of sleeping sickness matters, as the primary reason for its 'neglect' is that the true impact of the disease is unknown, largely as a result of under-reporting. Certainly, elimination will not be achieved without vast improvements in field diagnostics for both forms of sleeping sickness especially if there is a hidden reservoir of 'chronic carriers'. Mass screening would be a desirable aim for Gambian sleeping sickness and could be handled on a national scale in the endemic countries - perhaps by piggybacking on programmes committed to other diseases. As well as improved diagnostics, the search for non-toxic drugs for stage II treatment should remain a research priority. There is good evidence that thorough active case finding is sufficient to control T. b. gambiense sleeping sickness, as there is no significant animal reservoir. Trypanosoma brucei rhodesiense sleeping sickness is a zoonosis and control involves interrupting the fly-animal-human cycle, so some form of tsetse control and chemotherapy of the animal reservoir must be involved. The restricted application of insecticide to cattle is the most promising, affordable and sustainable technique to have emerged for tsetse control. Animal health providers can aid disease control by treating cattle and, when allied with innovative methods of funding (e.g. public-private partnerships) not reliant on the public purse, this approach may prove more sustainable. Sleeping sickness incidence for the 36 endemic countries has shown a steady decline in recent years and we should take advantage of the apparent lull in incidence and aim for elimination. This is feasible in some sleeping sickness foci but must be planned and paid for increasingly by the endemic countries themselves. The control and elimination of T. b. gambiense sleeping sickness may be seen as a public good, as appropriate strategies depend on local health services for surveillance and treatment, but public-private funding mechanisms should not be excluded. It is timely to take up the tools available and invest in new tools - including novel financial instruments - to eliminate this disease from Africa. Copyright © 2012 Elsevier Ltd. All rights reserved.

Treatment of bilateral inguinal hernia -- minimally invasive versus open surgery procedure.

PubMed

Timişescu, L; Turcu, F; Munteanu, R; Gîdea, C; Drăghici, L; Ginghină, O; Iordache, N

2013-01-01

The aim of this study is to evaluate and compare the treatment outcomes of the bilateral inguinal hernia repair in one stage using minimally invasive technique (totally extraperitoneal) and conventional surgery (Lichtenstein). Records from all hospitalized cases in our institution between 2006 and 2011 that underwent surgery having the diagnosis of bilateral inguinal hernia were analysed. The study consists of two groups selected by means of the used procedure: the study arm which is laparoscopic (234 cases) and the control arm that consists of Lichtenstein procedure (91 cases). One conversion was recorded due to difficult dissection (0.4% of cases). There were complications reported in 2.5% cases in the laparoscopic group and 27.4% complications noted in the conventional group (p less then 0.01). Reinterventions were logged in 1.7% cases in the laparoscopic group and 2.1% reinterventions in the open group (p less then 0.01). The postoperative hospital stay was 2.1 days in the laparoscopic group and 4.7 days for the open procedure. Mortality was not recorded. In our department the procedure of choice for bilateral inguinal repair is the laparoscopic approach (TEP) which has a 10 fold decrease in complications rate than Lichtenstein operation and also a shortening by half of the hospital stay. Hernia recurrence is the same for both procedures. Celsius.

Osteo-Odonto-Keratoprosthesis in Severe Thermal and Chemical Injuries.

PubMed

Vasquez-Perez, Alfonso; Zarei-Ghanavati, Mehran; Avadhanam, Venkata; Liu, Christopher

2018-05-16

To report the results of osteo-odonto-keratoprosthesis (OOKP) surgery in patients who sustained severe chemical and thermal injuries. This is a noncomparative retrospective case series of 14 patients who underwent OOKP surgery between 2001 and 2016 at the Sussex Eye Hospital, Brighton, UK, because of severe chemical and thermal injuries RESULTS:: OOKP surgery was performed in 14 eyes of 14 patients. Eight patients (57%) sustained thermal injuries and 6 patients (43%) chemical injuries. Every eye had previously undergone adnexal or ocular surgery, including 2 cases that underwent synthetic keratoprosthesis implantation. One case had choroidal hemorrhage during stage 2. Laminar retention was observed in 11 cases (85%) at the end of the study. The Kaplan-Meier curve showed a probability of 81% of laminar retention at 5 years and a decrease at 15 years to 61%. Functional visual success was observed in only 7 patients (50%) because of end-stage glaucomatous optic neuropathy in 4 cases and macular scar in 1 case. Two cases developed endophthalmitis. Two cases required removal of laminae, one because of endophthalmitis, bone resorption and aqueous leak and the other because of development of a retroprosthetic membrane. Glaucoma was the most frequent complication (79%) and required surgical intervention with tube shunts in 5 cases. Six cases (43%) required buccal mucosal repair, which included two cases that developed endophthalmitis. Anatomic success was achieved in 11 of 13 cases in this series of OOKP surgery after severe chemical and thermal trauma; 8 of these cases had at least 5 years of follow-up and thus qualified as long-term.

Seroreactivity against Merkel cell polyomavirus and other polyomaviruses in chronic lymphocytic leukaemia, the MCC-Spain study.

PubMed

Robles, Claudia; Casabonne, Delphine; Benavente, Yolanda; Costas, Laura; Gonzalez-Barca, Eva; Aymerich, Marta; Campo, Elias; Tardon, Adonina; Jiménez-Moleón, José J; Castaño-Vinyals, Gemma; Dierssen-Sotos, Trinidad; Michel, Angelika; Kranz, Lena; Aragonés, Nuria; Pollan, Marina; Kogevinas, Manolis; Pawlita, Michael; de Sanjose, Silvia

2015-08-01

Merkel cell polyomavirus (MCPyV) has been suspected to cause chronic lymphocytic leukaemia (CLL) but previous data are inconsistent. We measured seroreactivities of nine polyomaviruses (MCPyV, BKPyV, JCPyV, LPyV, KIPyV, WUPyV, HPyV-6, HPyV-7 and TSPyV) in 359 CLL cases and 370 controls using bead-based multiplex serology technology. We additionally tested two herpesviruses (HSV-1 and CMV). Associations between disease and viral seroreactivities were assessed using logistic regression. All human viruses showed high seroprevalences (69-99%) against structural proteins in controls but significantly lower viral seroprevalences in cases (58-94%; OR range = 0.21-0.70, P value < 0.05), except for MCPyV (OR = 0.79, 95% CI = 0.54-1.16). Lower seroreactivity levels were observed among CLL subjects, with significant differences already observed at early stages of disease, unrelated to treatment status. Seroreactivities against polyomavirus related oncoproteins were almost null. Our data suggest no association for MCPyV polyomavirus with CLL development and an unlikely association for other polyomaviruses tested.

Optimized Real-Time Control of Combined Sewerage Systems: Two Case Studies (Proceedings Paper)

EPA Science Inventory

The paper presents results of two case studies of Real-Time Control (RTC) alternatives evaluations that were conducted on portions of sewerage systems near Paris, France and in Quebec City, Canada, respectively. The studies were performed at real-scale demonstration sites. RTC al...

Outcome of a ceftriaxone/cefotaxime interchange programme in a major teaching hospital.

PubMed

Gutensohn, A; Bunz, D; Frighetto, L; Jewesson, P

1991-01-01

A two-stage intervention programme was performed to enable the effective substitution of ceftriaxone for cefotaxime in a teaching hospital with large numbers of transient prescribers. One hundred and sixteen patients with a variety of bacterial infections were randomized to an open, historical control comparative study to determine if ceftriaxone was an acceptable replacement for cefotaxime. For 6 months prior to the intervention, both cephalosporins were available on formulary. Following an initial informational stage, a therapeutic interchange programme was implemented to convert prescriptions for cefotaxime to ceftriaxone. Ceftriaxone and cefotaxime were equivalent in terms of microbiological and clinical efficacy and patient tolerance in 77 evaluable patients. No changes in prescriber service occurred after the changeover. Post-intervention treatment courses required a ceftriaxone/cefotaxime interchange in 28% of the cases. Ceftriaxone appeared to be a suitable and cost-effective alternative to cefotaxime in this hospital. The intervention programme successfully invoked the formulary change with minimal expense and prescriber opposition.

Three-Stage Production Cost Modeling Approach for Evaluating the Benefits of Intra-Hour Scheduling Between Balancing Authorities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Samaan, Nader; Milligan, Michael; Hunsaker, Matt

This paper introduces a production cost modeling approach for evaluating the benefits of intra-hour scheduling among Balancing Authorities (BAs). System operation is modeled in a three-stage sequential manner: day ahead (DA)-hour ahead (HA) real time (RT). In addition to contingency reserve, each BA will need to carry out 'up' and 'down' load following and regulation reserve capacity requirements in the DA and HA time frames. In the RT simulation, only contingency and regulation reserves are carried out as load following is deployed. To model current RT operation with hourly schedules, a new constraint was introduced to force each BA netmore » exchange schedule deviation from HA schedules to be within North American Electric Reliability Corporation (NERC) area control error (ACE) limits. Case studies that investigate the benefits of moving from hourly exchange schedules between Western Electricity Coordinating Council (WECC) BAs into 10-minute exchange schedules under two different levels of wind and solar penetration (11% and 33%) are presented.« less

Statistical Analysis of Individual Participant Data Meta-Analyses: A Comparison of Methods and Recommendations for Practice

PubMed Central

Stewart, Gavin B.; Altman, Douglas G.; Askie, Lisa M.; Duley, Lelia; Simmonds, Mark C.; Stewart, Lesley A.

2012-01-01

Background Individual participant data (IPD) meta-analyses that obtain “raw” data from studies rather than summary data typically adopt a “two-stage” approach to analysis whereby IPD within trials generate summary measures, which are combined using standard meta-analytical methods. Recently, a range of “one-stage” approaches which combine all individual participant data in a single meta-analysis have been suggested as providing a more powerful and flexible approach. However, they are more complex to implement and require statistical support. This study uses a dataset to compare “two-stage” and “one-stage” models of varying complexity, to ascertain whether results obtained from the approaches differ in a clinically meaningful way. Methods and Findings We included data from 24 randomised controlled trials, evaluating antiplatelet agents, for the prevention of pre-eclampsia in pregnancy. We performed two-stage and one-stage IPD meta-analyses to estimate overall treatment effect and to explore potential treatment interactions whereby particular types of women and their babies might benefit differentially from receiving antiplatelets. Two-stage and one-stage approaches gave similar results, showing a benefit of using anti-platelets (Relative risk 0.90, 95% CI 0.84 to 0.97). Neither approach suggested that any particular type of women benefited more or less from antiplatelets. There were no material differences in results between different types of one-stage model. Conclusions For these data, two-stage and one-stage approaches to analysis produce similar results. Although one-stage models offer a flexible environment for exploring model structure and are useful where across study patterns relating to types of participant, intervention and outcome mask similar relationships within trials, the additional insights provided by their usage may not outweigh the costs of statistical support for routine application in syntheses of randomised controlled trials. Researchers considering undertaking an IPD meta-analysis should not necessarily be deterred by a perceived need for sophisticated statistical methods when combining information from large randomised trials. PMID:23056232

Superiority of fluorescent in situ hybridization over immunohistochemistry in detection of HER2 gene in carcinoma of the urinary bladder associated with and without schistosomiasis.

PubMed

Hammam, Olfat; Wishahi, Mohamed; Hindawi, All; Mosaad, Maha; Akl, Maha; Khalil, Heba; Al Ganzoury, Hossam; Badawy, Mohamed; Elesaily, Khaled

2014-12-01

HER2 is an oncogene encoding a type 1 tyrosine kinase growth factor receptor and the role of HER2 in the development of numerous types of human cancer is still understood and correlates with clinical outcome, poor prognosis, it is a predictor factor for poor response to chemotherapy. HER2 overexpression is associated with reduced disease free and overall survival. Patients who have HER2 negative expression have a poor prognosis. The aim of the present study is to explore the accuracy of detection of expression of HER2 protein by two different techniques of immunohistochemistry (IHC) and gene amplification by fluorescent in situ hybridization (FISH). The two techniques were applied to sixty two patients that included different cell types of carcinoma of the bladder, benign bilharzial lesions and control. Characteristics of the 62 patients are: 10 chronic cystitis, 19 squamous cell carcinoma (SCC) with schistosomiasis, 33 urothelial carcinoma (UC) schistosomal and non-schistosomal, ten healthy individuals without schistosomiasis served as controls. Gene amplification of HER2 was done using FISH and protein expression of HER2 by IHC. The study was applied on archival data of formalin-fixed paraffin embedded tissues and patient clinical data and follow up for 5 years. Overexpression of HER2 protein was found in 30/52 (57.7%). Fourteen cases had score of 2+, and sixteen cases had score of 3+. Using FISH technique it showed more accurate detection of HER2 gene as those fourteen cases who had score of 2+ had been found to be 5 out of 14 were positive for gene over expression, the other sixteen who had score of 3+ all were positive for gene amplification. HER2 protein and gene was found to be significantly overexpressed in carcinoma of the bladder in both cell types SCC and UC with or without schistosomiasis compared to the benign lesions and control groups (P <0.01) by both techniques. There is significant increase in expression of HER2 protein and gene in SCC compared to UC (P< 0.01). In UC overexpression of HER2 protein and gene was evident in all stages Ta, T1, T2-4. HER2 protein and gene overexpressed in different grades of UC. In SCC HER2 protein and gene had overexpression in different stages and grades.

Stochastic modeling of wetland-groundwater systems

NASA Astrophysics Data System (ADS)

Bertassello, Leonardo Enrico; Rao, P. Suresh C.; Park, Jeryang; Jawitz, James W.; Botter, Gianluca

2018-02-01

Modeling and data analyses were used in this study to examine the temporal hydrological variability in geographically isolated wetlands (GIWs), as influenced by hydrologic connectivity to shallow groundwater, wetland bathymetry, and subject to stochastic hydro-climatic forcing. We examined the general case of GIWs coupled to shallow groundwater through exfiltration or infiltration across wetland bottom. We also examined limiting case with the wetland stage as the local expression of the shallow groundwater. We derive analytical expressions for the steady-state probability density functions (pdfs) for wetland water storage and stage using few, scaled, physically-based parameters. In addition, we analyze the hydrologic crossing time properties of wetland stage, and the dependence of the mean hydroperiod on climatic and wetland morphologic attributes. Our analyses show that it is crucial to account for shallow groundwater connectivity to fully understand the hydrologic dynamics in wetlands. The application of the model to two different case studies in Florida, jointly with a detailed sensitivity analysis, allowed us to identify the main drivers of hydrologic dynamics in GIWs under different climate and morphologic conditions.

Predictors of clinical-pathologic stage discrepancy in oral cavity squamous cell carcinoma: A National Cancer Database study.

PubMed

Kılıç, Sarah S; Kılıç, Suat; Crippen, Meghan M; Varughese, Denny; Eloy, Jean Anderson; Baredes, Soly; Mahmoud, Omar M; Park, Richard Chan Woo

2018-04-01

Few studies have examined the frequency and survival implications of clinicopathologic stage discrepancy in oral cavity squamous cell carcinoma (SCC). Oral cavity SCC cases with full pathologic staging information were identified in the National Cancer Database (NCDB). Clinical and pathologic stages were compared. Multivariate logistic regressions were performed to identify factors associated with stage discrepancy. There were 9110 cases identified, of which 67.3% of the cases were stage concordant, 19.9% were upstaged, and 12.8% were downstaged. The N classification discordance (28.5%) was more common than T classification discordance (27.6%). In cases of T classification discordance, downstaging is more common than upstaging (15.4% vs 12.1% of cases), but in cases of N classification discordance, the reverse is true; upstaging is much more common than downstaging (20.1 vs 8.4% of cases). Clinicopathologic stage discrepancy in oral cavity SCC is a common phenomenon that is associated with a number of clinical factors and has survival implications. © 2018 Wiley Periodicals, Inc.

Evaluation of cycloate followed by two-leaf stage phenmedipham application in fresh market spinach

USDA-ARS?s Scientific Manuscript database

Fresh market spinach has one primary herbicide, cycloate, which does not control all weeds. Previous studies demonstrated that cycloate PRE followed by (fb) phenmedipham at the four-leaf spinach stage is a safe and effective treatment. However, this treatment is not useful for the main growing seaso...

Demographic analysis, a comparison of the jackknife and bootstrap methods, and predation projection: a case study of Chrysopa pallens (Neuroptera: Chrysopidae).

PubMed

Yu, Ling-Yuan; Chen, Zhen-Zhen; Zheng, Fang-Qiang; Shi, Ai-Ju; Guo, Ting-Ting; Yeh, Bao-Hua; Chi, Hsin; Xu, Yong-Yu

2013-02-01

The life table of the green lacewing, Chrysopa pallens (Rambur), was studied at 22 degrees C, a photoperiod of 15:9 (L:D) h, and 80% relative humidity in the laboratory. The raw data were analyzed using the age-stage, two-sex life table. The intrinsic rate of increase (r), the finite rate of increase (lambda), the net reproduction rate (R0), and the mean generation time (T) of Ch. pallens were 0.1258 d(-1), 1.1340 d(-1), 241.4 offspring and 43.6 d, respectively. For the estimation of the means, variances, and SEs of the population parameters, we compared the jackknife and bootstrap techniques. Although similar values of the means and SEs were obtained with both techniques, significant differences were observed in the frequency distribution and variances of all parameters. The jackknife technique will result in a zero net reproductive rate upon the omission of a male, an immature death, or a nonreproductive female. This result represents, however, a contradiction because an intrinsic rate of increase exists in this situation. Therefore, we suggest that the jackknife technique should not be used for the estimation of population parameters. In predator-prey interactions, the nonpredatory egg and pupal stages of the predator are time refuges for the prey, and the pest population can grow during these times. In this study, a population projection based on the age-stage, two-sex life table is used to determine the optimal interval between releases to fill the predation gaps and maintain the predatory capacity of the control agent.

Interactions between household air pollution and GWAS-identified lung cancer susceptibility markers in the Female Lung Cancer Consortium in Asia (FLCCA).

PubMed

Hosgood, H Dean; Song, Minsun; Hsiung, Chao Agnes; Yin, Zhihua; Shu, Xiao-Ou; Wang, Zhaoming; Chatterjee, Nilanjan; Zheng, Wei; Caporaso, Neil; Burdette, Laurie; Yeager, Meredith; Berndt, Sonja I; Landi, Maria Teresa; Chen, Chien-Jen; Chang, Gee-Chen; Hsiao, Chin-Fu; Tsai, Ying-Huang; Chien, Li-Hsin; Chen, Kuan-Yu; Huang, Ming-Shyan; Su, Wu-Chou; Chen, Yuh-Min; Chen, Chung-Hsing; Yang, Tsung-Ying; Wang, Chih-Liang; Hung, Jen-Yu; Lin, Chien-Chung; Perng, Reury-Perng; Chen, Chih-Yi; Chen, Kun-Chieh; Li, Yao-Jen; Yu, Chong-Jen; Chen, Yi-Song; Chen, Ying-Hsiang; Tsai, Fang-Yu; Kim, Christopher; Seow, Wei Jie; Bassig, Bryan A; Wu, Wei; Guan, Peng; He, Qincheng; Gao, Yu-Tang; Cai, Qiuyin; Chow, Wong-Ho; Xiang, Yong-Bing; Lin, Dongxin; Wu, Chen; Wu, Yi-Long; Shin, Min-Ho; Hong, Yun-Chul; Matsuo, Keitaro; Chen, Kexin; Wong, Maria Pik; Lu, Dara; Jin, Li; Wang, Jiu-Cun; Seow, Adeline; Wu, Tangchun; Shen, Hongbing; Fraumeni, Joseph F; Yang, Pan-Chyr; Chang, I-Shou; Zhou, Baosen; Chanock, Stephen J; Rothman, Nathaniel; Lan, Qing

2015-03-01

We previously carried out a multi-stage genome-wide association study (GWAS) on lung cancer among never smokers in the Female Lung Cancer Consortium in Asia (FLCCA) (6,609 cases, 7,457 controls) that identified novel susceptibility loci at 10q25.2, 6q22.2, and 6p21.32, and confirmed two previously identified loci at 5p15.33 and 3q28. Household air pollution (HAP) attributed to solid fuel burning for heating and cooking, is the leading cause of the overall disease burden in Southeast Asia, and is known to contain lung carcinogens. To evaluate the gene-HAP interactions associated with lung cancer in loci independent of smoking, we analyzed data from studies participating in FLCCA with fuel use information available (n = 3; 1,731 cases; 1,349 controls). Coal use was associated with a 30% increased risk of lung cancer (OR 1.3, 95% CI 1.0-1.6). Among the five a priori SNPs identified by our GWAS, two showed a significant interaction with coal use (HLA Class II rs2395185, p = 0.02; TP63 rs4488809 (rs4600802), p = 0.04). The risk of lung cancer associated with coal exposure varied with the respective alleles for these two SNPs. Our observations provide evidence that genetic variation in HLA Class II and TP63 may modify the association between HAP and lung cancer risk. The roles played in the cell cycle and inflammation pathways by the proteins encoded by these two genes provide biological plausibility for these interactions; however, additional replication studies are needed in other non-smoking populations.

ABCC9 gene polymorphism is associated with hippocampal sclerosis of aging pathology

PubMed Central

Estus, Steven; Abner, Erin L.; Parikh, Ishita; Malik, Manasi; Neltner, Janna H.; Ighodaro, Eseosa; Wang, Wang-Xia; Wilfred, Bernard R.; Wang, Li-San; Kukull, Walter A.; Nandakumar, Kannabiran; Farman, Mark L.; Poon, Wayne W.; Corrada, Maria M.; Kawas, Claudia H.; Cribbs, David H.; Bennett, David A.; Schneider, Julie A.; Larson, Eric B.; Crane, Paul K.; Valladares, Otto; Schmitt, Frederick A.; Kryscio, Richard J.; Jicha, Gregory A.; Smith, Charles D.; Scheff, Stephen W.; Sonnen, Joshua A.; Haines, Jonathan L.; Pericak-Vance, Margaret A.; Mayeux, Richard; Farrer, Lindsay A.; Van Eldik, Linda J.; Horbinski, Craig; Green, Robert C.; Gearing, Marla; Poon, Leonard W.; Kramer, Patricia L.; Woltjer, Randall L.; Montine, Thomas J.; Partch, Amanda B.; Rajic, Alexander J.; Richmire, KatieRose; Monsell, Sarah E.; Schellenberg, Gerard D.

2014-01-01

Hippocampal sclerosis of aging (HS-Aging) is a high-morbidity brain disease in the elderly but risk factors are largely unknown. We report the first genome-wide association study (GWAS) with HS-Aging pathology as an endophenotype. In collaboration with the Alzheimer’s Disease Genetics Consortium, data were analyzed from large autopsy cohorts: (#1) National Alzheimer’s Coordinating Center (NACC); (#2) Rush University Religious Orders Study and Memory and Aging Project; (#3) Group Health Research Institute Adult Changes in Thought study; (#4) University of California at Irvine 90+ Study; and (#5) University of Kentucky Alzheimer’s Disease Center. Altogether, 363 HS-Aging cases and 2,303 controls, all pathologically confirmed, provided statistical power to test for risk alleles with large effect size. A two-tier study design included GWAS from cohorts #1–3 (Stage I) to identify promising SNP candidates, followed by focused evaluation of particular SNPs in cohorts #4–5 (Stage II). Polymorphism in the ATP-binding cassette, sub-family C member 9 (ABCC9) gene, also known as sulfonylurea receptor 2, was associated with HS-Aging pathology. In the meta-analyzed Stage I GWAS, ABCC9 polymorphisms yielded the lowest p values, and factoring in the Stage II results, the meta-analyzed risk SNP (rs704178:G) attained genome-wide statistical significance (p = 1.4 × 10−9), with odds ratio (OR) of 2.13 (recessive mode of inheritance). For SNPs previously linked to hippocampal sclerosis, meta-analyses of Stage I results show OR = 1.16 for rs5848 (GRN) and OR = 1.22 rs1990622 (TMEM106B), with the risk alleles as previously described. Sulfonylureas, a widely prescribed drug class used to treat diabetes, also modify human ABCC9 protein function. A subsample of patients from the NACC database (n = 624) were identified who were older than age 85 at death with known drug history. Controlling for important confounders such as diabetes itself, exposure to a sulfonylurea drug was associated with risk for HS-Aging pathology (p = 0.03). Thus, we describe a novel and targetable dementia risk factor. PMID:24770881

Aerosciences, Aero-Propulsion and Flight Mechanics Technology Development for NASA's Next Generation Launch Technology Program

NASA Technical Reports Server (NTRS)

Cockrell, Charles E., Jr.

2003-01-01

The Next Generation Launch Technology (NGLT) program, Vehicle Systems Research and Technology (VSR&T) project is pursuing technology advancements in aerothermodynamics, aeropropulsion and flight mechanics to enable development of future reusable launch vehicle (RLV) systems. The current design trade space includes rocket-propelled, hypersonic airbreathing and hybrid systems in two-stage and single-stage configurations. Aerothermodynamics technologies include experimental and computational databases to evaluate stage separation of two-stage vehicles as well as computational and trajectory simulation tools for this problem. Additionally, advancements in high-fidelity computational tools and measurement techniques are being pursued along with the study of flow physics phenomena, such as boundary-layer transition. Aero-propulsion technology development includes scramjet flowpath development and integration, with a current emphasis on hypervelocity (Mach 10 and above) operation, as well as the study of aero-propulsive interactions and the impact on overall vehicle performance. Flight mechanics technology development is focused on advanced guidance, navigation and control (GN&C) algorithms and adaptive flight control systems for both rocket-propelled and airbreathing vehicles.

Evaluation of the utility of 99m Tc-MDP bone scintigraphy versus MIBG scintigraphy and cross-sectional imaging for staging patients with neuroblastoma.

PubMed

Gauguet, Jean-Marc; Pace-Emerson, Tamara; Grant, Frederick D; Shusterman, Suzanne; DuBois, Steven G; Frazier, A Lindsay; Voss, Stephan D

2017-11-01

Accurate staging of neuroblastoma requires multiple imaging examinations. The purpose of this study was to determine the relative contribution of 99m Tc-methylene diphosphonate (MDP) bone scintigraphy (bone scan) versus metaiodobenzylguanidine scintigraphy (MIBG scan) for accurate staging of neuroblastoma. A medical record search by the identified patients with neuroblastoma from 1993 to 2012 who underwent both MIBG and bone scan for disease staging. Cross-sectional imaging was used to corroborate the scintigraphy results. Clinical records were used to correlate imaging findings with clinical staging and patient management. One hundred thirty-two patients underwent both MIBG and bone scan for diagnosis. All stage 1 (n = 12), 2 (n = 8), and 4S (n = 4) patients had a normal bone scan with no skeletal MIBG uptake. Six of 30 stage 3 patients had false (+) bone scans. In the 78 stage 4 patients, 58/78 (74%) were both skeletal MIBG(+)/bone scan (+). In 56 of the 58 cases, skeletal involvement detected with MIBG was equal to or greater than that detected by bone scan. Only 3/78 had (-) skeletal MIBG uptake and (+) bone scans; all 3 had other sites of metastatic disease. Five of 78 had (+) skeletal MIBG with a (-) bone scan, while 12/78 had no skeletal involvement by either MIBG or bone scan. In no case did a positive bone scan alone determine a stage 4 designation. In the staging of neuroblastoma, 99m Tc-MDP bone scintigraphy does not identify unique sites of disease that affect disease stage or clinical management, and in the majority of cases bone scans can be omitted from the routine neuroblastoma staging algorithm. © 2017 Wiley Periodicals, Inc.

Bayesian analysis of stage-fall-discharge rating curves and their uncertainties

NASA Astrophysics Data System (ADS)

Mansanarez, V.; Le Coz, J.; Renard, B.; Lang, M.; Pierrefeu, G.; Vauchel, P.

2016-09-01

Stage-fall-discharge (SFD) rating curves are traditionally used to compute streamflow records at sites where the energy slope of the flow is variable due to variable backwater effects. We introduce a model with hydraulically interpretable parameters for estimating SFD rating curves and their uncertainties. Conventional power functions for channel and section controls are used. The transition to a backwater-affected channel control is computed based on a continuity condition, solved either analytically or numerically. The practical use of the method is demonstrated with two real twin-gauge stations, the Rhône River at Valence, France, and the Guthusbekken stream at station 0003ṡ0033, Norway. Those stations are typical of a channel control and a section control, respectively, when backwater-unaffected conditions apply. The performance of the method is investigated through sensitivity analysis to prior information on controls and to observations (i.e., available gaugings) for the station of Valence. These analyses suggest that precisely identifying SFD rating curves requires adapted gauging strategy and/or informative priors. The Madeira River, one of the largest tributaries of the Amazon, provides a challenging case typical of large, flat, tropical river networks where bed roughness can also be variable in addition to slope. In this case, the difference in staff gauge reference levels must be estimated as another uncertain parameter of the SFD model. The proposed Bayesian method is a valuable alternative solution to the graphical and empirical techniques still proposed in hydrometry guidance and standards.

Is uniportal thoracoscopic surgery a feasible approach for advanced stages of non-small cell lung cancer?

PubMed Central

Fieira, Eva; Delgado, Maria; Mendez, Lucía; Fernandez, Ricardo; de la Torre, Mercedes

2014-01-01

Objectives Conventional video-assisted thoracoscopic (VATS) lobectomy for advanced lung cancer is a feasible and safe surgery in experienced centers. The aim of this study is to assess the feasibility of uniportal VATS approach in the treatment of advanced non-small cell lung cancer (NSCLC) and compare the perioperative outcomes and survival with those in early-stage tumors operated through the uniportal approach. Methods From June 2010 to December 2012, we performed 163 uniportal VATS major pulmonary resections. Only NSCLC cases were included in this study (130 cases). Patients were divided into two groups: (A) early stage and (B) advanced cases (>5 cm, T3 or T4, or tumors requiring neoadjuvant treatment). A descriptive and retrospective study was performed, comparing perioperative outcomes and survival obtained in both groups. A survival analysis was performed with Kaplan-Meier curves and the log-rank test was used to compare survival between patients with early and advanced stages. Results A total of 130 cases were included in the study: 87 (A) vs. 43 (B) patients (conversion rate 1.1 vs. 6.5%, P=0.119). Mean global age was 64.9 years and 73.8% were men. The patient demographic data was similar in both groups. Upper lobectomies (A, 52 vs. B, 21 patients) and anatomic segmentectomies (A, 4 vs. B, 0) were more frequent in group A while pneumonectomy was more frequent in B (A, 1 vs. B, 6 patients). Surgical time was longer (144.9±41.3 vs. 183.2±48.9, P<0.001), and median number of lymph nodes (14 vs. 16, P=0.004) were statistically higher in advanced cases. Median number of nodal stations (5 vs. 5, P=0.165), days of chest tube (2 vs. 2, P=0.098), HOS (3 vs. 3, P=0.072), and rate of complications (17.2% vs. 14%, P=0.075) were similar in both groups. One patient died on the 58th postoperative day. The 30-month survival rate was 90% for the early stage group and 74% for advanced cases Conclusions Uniportal VATS lobectomy for advanced cases of NSCLC is a safe and reliable procedure that provides perioperative outcomes similar to those obtained in early stage tumours operated through this same technique. Further long term survival analyses are ongoing on a large number of patients. PMID:24976985

[Long-term Efficacy of Radiofrequency Ablation Combined with Chemotherapy 
in the Treatment of Patients with Advanced Non-small Cell Lung Cancer
--A Retrospective Study].

PubMed

Du, Shuhui; Qin, Da; Pang, Ruiqi; Zhang, Yeqing; Zhao, Siqi; Hu, Mu; Zhi, Xiuyi

2017-10-20

Radiofrequency ablation (RFA) combined with chemotherapy has a certain short-term therapeutic effect for the treatment of advanced non-small cell lung cancer (NSCLC), but whether it can improve the long-term survival rate of patients is still controversy. This study retrospectively analyzed the difference of long-term efficacy between RFA combined with chemotherapy and chemotherapy alone in the treatment of patients with advanced NSCLC. A total of 77 patients with stage IIIb and stage IV NSCLC who underwent radiofrequency ablation and chemotherapy in the Department of Thoracic Surgery, Xuanwu Hospital, Capital University of Medical Sciences from September 2009 to December 2015 were enrolled as the treatment group. Chemotherapy with no radiofrequency ablation was performed in 56 patients with stage IIIb and stage IV NSCLC as the control group. Two groups of patients were followed up by telephone about their living conditions. "Survival" package of R software version 3.4.1 was used for statistical analysis. Two sets of data baseline levels were tested by chi-square test. The bias was processed by Cox regression model and the survival curve was plotted using covariate mean substitution method. The first-year survival rate of the treatment group was 70.74%, the two-year survival rate was 39.31% and the median survival time was 22.1 months. The one-year survival rate was 54.54% in the control group, the two-year survival rate was 19.49%, the median survival for 18.1 months. The long-term survival rate of the treatment group was better than that of the control group (P<0.05, OR=0.571). Radiofrequency ablation of lung cancer combined with chemotherapy can significantly improve the 2-year survival rate of patients with stage IIIb and stage IV NSCLC.

Romantic Love Is Associated with Enhanced Inhibitory Control in an Emotional Stop-Signal Task

PubMed Central

Song, Sensen; Zou, Zhiling; Song, Hongwen; Wang, Yongming; d’Oleire Uquillas, Federico; Wang, Huijun; Chen, Hong

2016-01-01

Purpose: This study explored whether romantic lovers differ in emotion-related inhibitory control capacity from those who are single. Methods: 88 healthy undergraduate college students participated in the study. Half were currently in love and in a romantic relationship (love group, LG), and half were single and had never been in a romantic relationship (single group, SG). Based on duration of romantic relationship (i.e., love duration), the LG were further divided into two subgroups: “early stage love” and “longer periods of love”. All participants completed an emotional Stop Signal Task, consisting of a variety of human face stimuli displaying either sad or neutral affect. Results: Results found that relative to SG, lovers showed greater inhibitory control [shorter stop-signal reaction time (SSRT)] during negative emotion condition trials. Furthermore, in early stages of love, SSRT for negative emotion condition trials was significantly shorter compared to that in “longer periods of love” or SG individuals, with no significant differences between the two latter groups. Conclusion: Compared with individuals who were single, early stage lovers showed greater capacity for inhibiting action during presentation of negative emotional stimuli. Within a greater social context, greater inhibitory control capacity during early stages of love may be related to the successful formation of romantic relationships, particularly to the ability to persevere in goal-directed action despite negative emotional contexts such as that of sadness. PMID:27826260

Can the DSM-5 differentiate between nonpathological possession and dissociative identity disorder? A case study from an Afro-Brazilian religion.

PubMed

Delmonte, Romara; Lucchetti, Giancarlo; Moreira-Almeida, Alexander; Farias, Miguel

2016-01-01

The aim of this article is to examine whether the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), are able to differentiate between nonpathological religious possession and dissociative identity disorder (DID). We use the case study of an individual who leads an Afro-Brazilian religious group (Umbanda), focusing on her personal development and possession experiences from early childhood to the present, spanning a period of more than 40 years, and examine these data following DSM-5 criteria for DID (300.14). Her experiences of possession can be broken into 2 distinct stages. In the 1st stage (childhood and early adulthood), she displayed intrusive thoughts and a lack of control over possession states, which were associated with a heightened state of anxiety, loneliness, amnesia, and family conflict (meeting all 5 criteria for DID). In the 2nd stage (late 20s up to the present), she regularly experienced possession states but felt in control of their onset and found them religiously meaningful. In this 2nd stage, she only fulfilled 3 criteria for DID. We question the accuracy of diagnosing this individual with DID in her earlier life and suggest that the DSM-5 criteria fail to address the ambiguity of affect surrounding possession experiences (positive at the individual level, negative at the interpersonal level) and lack a clearer acknowledgment of the prevalence of possession and other unusual experiences in general populations.

Polymorphisms of genes coding for ghrelin and its receptor in relation to colorectal cancer risk: a two-step gene-wide case-control study

PubMed Central

2010-01-01

Background Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHSR), has two major functions: the stimulation of the growth hormone production and the stimulation of food intake. Accumulating evidence also indicates a role of ghrelin in cancer development. Methods We conducted a case-control study to examine the association of common genetic variants in the genes coding for ghrelin (GHRL) and its receptor (GHSR) with colorectal cancer risk. Pairwise tagging was used to select the 11 polymorphisms included in the study. The selected polymorphisms were genotyped in 680 cases and 593 controls from the Czech Republic. Results We found two SNPs associated with lower risk of colorectal cancer, namely SNPs rs27647 and rs35683. We replicated the two hits, in additional 569 cases and 726 controls from Germany. Conclusion A joint analysis of the two populations indicated that the T allele of rs27647 SNP exerted a protective borderline effect (Ptrend = 0.004). PMID:20920174

Polymorphisms of genes coding for ghrelin and its receptor in relation to colorectal cancer risk: a two-step gene-wide case-control study.

PubMed

Campa, Daniele; Pardini, Barbara; Naccarati, Alessio; Vodickova, Ludmila; Novotny, Jan; Steinke, Verena; Rahner, Nils; Holinski-Feder, Elke; Morak, Monika; Schackert, Hans K; Görgens, Heike; Kötting, Judith; Betz, Beate; Kloor, Matthias; Engel, Christoph; Büttner, Reinhard; Propping, Peter; Försti, Asta; Hemminki, Kari; Barale, Roberto; Vodicka, Pavel; Canzian, Federico

2010-09-28

Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHSR), has two major functions: the stimulation of the growth hormone production and the stimulation of food intake. Accumulating evidence also indicates a role of ghrelin in cancer development. We conducted a case-control study to examine the association of common genetic variants in the genes coding for ghrelin (GHRL) and its receptor (GHSR) with colorectal cancer risk. Pairwise tagging was used to select the 11 polymorphisms included in the study. The selected polymorphisms were genotyped in 680 cases and 593 controls from the Czech Republic. We found two SNPs associated with lower risk of colorectal cancer, namely SNPs rs27647 and rs35683. We replicated the two hits, in additional 569 cases and 726 controls from Germany. A joint analysis of the two populations indicated that the T allele of rs27647 SNP exerted a protective borderline effect (Ptrend = 0.004).

Sentinel lymph node mapping reduces practice pattern variations in surgical staging for endometrial adenocarcinoma: A before and after study.

PubMed

Liu, Christina Y; Elias, Kevin M; Howitt, Brooke E; Lee, Larissa J; Feltmate, Colleen M

2017-05-01

To examine the effects of universal sentinel lymph node mapping on the use of nodal staging in endometrial adenocarcinoma. Two approaches to laparoscopic staging for endometrial adenocarcinoma were compared using a before and after study design. The before cohort underwent selective lymphadenectomy from January 1, 2014-October 1, 2015 while the after cohort underwent universal sentinel lymph node (SLN) mapping from October 2, 2015-September 29, 2016. The before cohort comprised 215 patients and the after cohort 166 patients. In women undergoing SLN mapping, a sentinel node was identified at least unilaterally in 146/153 cases (95.4%), and bilaterally in 114/153 (74.5%) of cases. Pelvic nodes were removed in 35.8% of the before cohort versus 92.2% of the after cohort (p<0.0001) with more nodal evaluation among both low risk (9.6% vs. 91%, p<0.0001) and high risk cases (66% vs. 94%, p<0.0001). While the proportion of low risk cases diagnosed with nodal involvement did not significantly change (0.9% to 3.1%, p=0.32), there was a trend toward more diagnoses of nodal involvement in high risk cases (5% to 13.2%, p=0.06). Mean number of pelvic lymph nodes removed (15 vs. 4, p<0.0001), mean operative time (181min vs. 137min, p<0.0001), estimated blood loss (80ml vs. 56ml, p=0.004), and rate of post-operative complications (13% vs. 5.2%, p=0.04) all decreased after the adoption of SLN dissection. Universal sentinel lymph node dissection for laparoscopic endometrial cancer staging reduces heterogeneity in surgeon staging practice, increases nodal detection, and lowers post-operative complications. Copyright © 2017 Elsevier Inc. All rights reserved.

Compact cold stage for micro-computerized tomography imaging of chilled or frozen samples

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hullar, Ted; Anastasio, Cort, E-mail: canastasio@ucdavis.edu; Paige, David F.

2014-04-15

High resolution X-ray microCT (computerized tomography) can be used to image a variety of objects, including temperature-sensitive materials. In cases where the sample must be chilled or frozen to maintain sample integrity, either the microCT machine itself must be placed in a refrigerated chamber, or a relatively expensive commercial cold stage must be purchased. We describe here the design and construction of a low-cost custom cold stage suitable for use in a microCT imaging system. Our device uses a boron nitride sample holder, two-stage Peltier cooler, fan-cooled heat sink, and electronic controller to maintain sample temperatures as low as −25 °Cmore » ± 0.2 °C for the duration of a tomography acquisition. The design does not require modification to the microCT machine, and is easily installed and removed. Our custom cold stage represents a cost-effective solution for refrigerating CT samples for imaging, and is especially useful for shared equipment or machines unsuitable for cold room use.« less

Studies of Cost Effective Structures Design for Future Space Systems - Summary

DTIC Science & Technology

1968-06-01

low-cost steels , such as HY-150, in high-pressure tankage for lower stages of launch vehicles. Specific implications are: 1) A new, two-stage Earth...relationships for each of these types obviously differ from one to another. In some cases, structures and mechanisms show similar behaviors . The way...necessary before reuse. Research efforts should also be directed at the configuration and pack- aging of expensive launch vehicle components so that

A comparison of direct and two-stage transportation of patients to hospital in Poland.

PubMed

Rosiek, Anna; Rosiek-Kryszewska, Aleksandra; Leksowski, Łukasz; Leksowski, Krzysztof

2015-04-24

The rapid international expansion of telemedicine reflects the growth of technological innovations. This technological advancement is transforming the way in which patients can receive health care. The study was conducted in Poland, at the Department of Cardiology of the Regional Hospital of Louis Rydygier in Torun. The researchers analyzed the delay in the treatment of patients with acute coronary syndrome. The study was conducted as a survey and examined 67 consecutively admitted patients treated invasively in a two-stage transport system. Data were analyzed statistically. Two-stage transportation does not meet the timeframe guidelines for the treatment of patients with acute myocardial infarction. Intervals for the analyzed group of patients were statistically significant (p < 0.0001). Direct transportation of the patient to a reference center with interventional cardiology laboratory has a significant impact on reducing in-hospital delay in case of patients with acute coronary syndrome. This article presents the results of two-stage transportation of the patient with acute coronary syndrome. This measure could help clinicians who seek to assess time needed for intervention. It also shows how time from the beginning of pain in chest is important and may contribute to patient disability, death or well-being.

Second primary malignancies after treatment for malignant lymphoma

PubMed Central

Okines, A; Thomson, C S; Radstone, C R; Horsman, J M; Hancock, B W

2005-01-01

To determine the incidence and possible causes of second primary malignancies after treatment for Hodgkin's and Non-Hodgkin's lymphoma (HL and NHL). A cohort of 3764 consecutive patients diagnosed with HL or NHL between January 1970 and July 2001 was identified using the Sheffield Lymphoma Group database. A search was undertaken for all patients diagnosed with a subsequent primary malignancy. Two matched controls were identified for each case. Odds ratios were calculated to detect and quantify any risk factors in the cases compared to their matched controls. Mean follow-up for the cohort was 5.2 years. A total of 68 patients who developed second cancers at least 6 months after their primary diagnosis were identified, giving a crude incidence of 1.89% overall: 3.21% among the patients treated for HL, 1.32% in those treated for NHL. Most common were bronchial, breast, colorectal and haematological malignancies. High stage at diagnosis almost reached statistical significance in the analysis of just the NHL patients (odds ratio=3.48; P=0.068) after adjustment for other factors. Treatment modality was not statistically significant in any analysis. High stage at diagnosis of NHL may be a risk factor for developing a second primary cancer. PMID:16106249

Erosion controls transpressional wedge kinematics

NASA Astrophysics Data System (ADS)

Leever, K. A.; Oncken, O.

2012-04-01

High resolution digital image analysis of analogue tectonic models reveals that erosion strongly influences the kinematics of brittle transpressional wedges. In the basally-driven experimental setup with low-angle transpression (convergence angle of 20 degrees) and a homogeneous brittle rheology, a doubly vergent wedge develops above the linear basal velocity discontinuity. In the erosive case, the experiment is interrupted and the wedge topography fully removed at displacement increments of ~3/4 the model thickness. The experiments are observed by a stereo pair of high resolution CCD cameras and the incremental displacement field calculated by Digital Particle Image Velocimetry (DPIV). From this dataset, fault slip on individual fault segments - magnitude and angle on the horizontal plane relative to the fault trace - is extracted using the method of Leever et al. (2011). In the non-erosive case, after an initial stage of strain localization, the wedge experiences two transient stages of (1) oblique slip and (2) localized strain partitioning. In the second stage, the fault slip angle on the pro-shear(s) rotates by some 30 degrees from oblique to near-orthogonal. Kinematic steady state is attained in the third stage when a through-going central strike-slip zone develops above the basal velocity discontinuity. In this stage, strain is localized on two main faults (or fault zones) and fully partitioned between plate boundary-parallel displacement on the central strike-slip zone and near-orthogonal reverse faulting at the front (pro-side) of the wedge. The fault slip angle on newly formed pro-shears in this stage is stable at 60-65 degrees (see also Leever et al., 2011). In contrast, in the erosive case, slip remains more oblique on the pro-shears throughout the experiment and a separate central strike-slip zone does not form, i.e. strain partitioning does not fully develop. In addition, more faults are active simultaneously. Definition of stages is based on slip on the retro-side of the wedge. In the first stage, the slip angle on the retro-shear is 27 +/- 12 degrees. In a subsequent stage, slip on the retro-side is partitioned between strike-slip and oblique (~35 degrees) faulting. In the third stage, the slip angle on the retro side stabilizes at ~10 degrees. The pro-shears are characterized by very different kinematics. Two pro-shears tend to be active simultaneously, the extinction of the older fault shortly followed by the initiation of a new one in a forelandward breaking sequence. Throughout the experiment, the fault slip on the pro-shears is 40-60 degrees at their initiation, gradually decreasing to nearly strike-slip at the moment of fault extinction. This is a rotation of similar magnitude but in the reverse direction compared to the non-erosive case. The fault planes themselves do not rotate. Leever, K. A., R. H. Gabrielsen, D. Sokoutis, and E. Willingshofer (2011), The effect of convergence angle on the kinematic evolution of strain partitioning in transpressional brittle wedges: Insight from analog modeling and high-resolution digital image analysis, Tectonics, 30(2), TC2013.

Prevalence of food sensitization and probable food allergy among adults in India: the EuroPrevall INCO study.

PubMed

Mahesh, P A; Wong, Gary W K; Ogorodova, L; Potts, J; Leung, T F; Fedorova, O; Holla, Amrutha D; Fernandez-Rivas, M; Clare Mills, E N; Kummeling, I; Versteeg, S A; van Ree, R; Yazdanbakhsh, M; Burney, P

2016-07-01

Data are lacking regarding the prevalence of food sensitization and probable food allergy among general population in India. We report the prevalence of sensitization and probable food allergy to 24 common foods among adults from general population in Karnataka, South India. The study was conducted in two stages: a screening study and a case-control study. A total of 11 791 adults in age group 20-54 were randomly sampled from general population in South India and answered a screening questionnaire. A total of 588 subjects (236 cases and 352 controls) participated in the case-control study involving a detailed questionnaire and specific IgE estimation for 24 common foods. A high level of sensitization (26.5%) was observed for most of the foods in the general population, higher than that observed among adults in Europe, except for those foods that cross-react with birch pollen. Most of the sensitization was observed in subjects who had total IgE above the median IgE level. A high level of cross-reactivity was observed among different pollens and foods and among foods. The prevalence of probable food allergy (self-reports of adverse symptoms after the consumption of food and specific IgE to the same food) was 1.2%, which was mainly accounted for cow's milk (0.5%) and apple (0.5%). Very high levels of sensitization were observed for most foods, including those not commonly consumed in the general population. For the levels of sensitization, the prevalence of probable food allergy was low. This disassociation needs to be further explored in future studies. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Analysis of Parallel Burn Without Crossfeed TSTO RLV Architectures and Comparison to Parallel Burn With Crossfeed and Series Burn Architectures

NASA Technical Reports Server (NTRS)

Smith, Garrett; Phillips, Alan

2002-01-01

There are currently three dominant TSTO class architectures. These are Series Burn (SB), Parallel Burn with crossfeed (PBw/cf), and Parallel Burn without crossfeed (PBncf). The goal of this study was to determine what factors uniquely affect PBncf architectures, how each of these factors interact, and to determine from a performance perspective whether a PBncf vehicle could be competitive with a PBw/cf or SB vehicle using equivalent technology and assumptions. In all cases, performance was evaluated on a relative basis for a fixed payload and mission by comparing gross and dry vehicle masses of a closed vehicle. Propellant combinations studied were LOX: LH2 propelled orbiter and booster (HH) and LOX: Kerosene booster with LOX: LH2 orbiter (KH). The study conclusions were: 1) a PBncf orbiter should be throttled as deeply as possible after launch until the staging point. 2) a detailed structural model is essential to accurate architecture analysis and evaluation. 3) a PBncf TSTO architecture is feasible for systems that stage at mach 7. 3a) HH architectures can achieve a mass growth relative to PBw/cf of < 20%. 3b) KH architectures can achieve a mass growth relative to Series Burn of < 20%. 4) center of gravity (CG) control will be a major issue for a PBncf vehicle, due to the low orbiter specific thrust to weight ratio and to the position of the orbiter required to align the nozzle heights at liftoff. 5 ) thrust to weight ratios of 1.3 at liftoff and between 1.0 and 0.9 when staging at mach 7 appear to be close to ideal for PBncf vehicles. 6) performance for all vehicles studied is better when staged at mach 7 instead of mach 5. The study showed that a Series Burn architecture has the lowest gross mass for HH cases, and has the lowest dry mass for KH cases. The potential disadvantages of SB are the required use of an air-start for the orbiter engines and potential CG control issues. A Parallel Burn with crossfeed architecture solves both these problems, but the mechanics of a large bipropellant crossfeed system pose significant technical difficulties. Parallel Burn without crossfeed vehicles start both booster and orbiter engines on the ground and thus avoid both the risk of orbiter air-start and the complexity of a crossfeed system. The drawback is that the orbiter must use 20% to 35% of its propellant before reaching the staging point. This induces a weight penalty in the orbiter in order to carry additional propellant, which causes a further weight penalty in the booster to achieve the same staging point. One way to reduce the orbiter propellant consumption during the first stage is to throttle down the orbiter engines as much as possible. Another possibility is to use smaller or fewer engines. Throttling the orbiter engines soon after liftoff minimizes CG control problems due to a low orbiter liftoff thrust, but may result in an unnecessarily high orbiter thrust after staging. Reducing the number or size of engines size may cause CG control problems and drift at launch. The study suggested possible methods to maximize performance of PBncf vehicle architectures in order to meet mission design requirements.

Genome-wide genetic analyses highlight mitogen-activated protein kinase (MAPK) signaling in the pathogenesis of endometriosis

PubMed Central

Uimari, Outi; Rahmioglu, Nilufer; Nyholt, Dale R.; Vincent, Katy; Missmer, Stacey A.; Becker, Christian; Morris, Andrew P.; Montgomery, Grant W.

2017-01-01

Abstract STUDY QUESTION Do genome-wide association study (GWAS) data for endometriosis provide insight into novel biological pathways associated with its pathogenesis? SUMMARY ANSWER GWAS analysis uncovered multiple pathways that are statistically enriched for genetic association signals, analysis of Stage A disease highlighted a novel variant in MAP3K4, while top pathways significantly associated with all endometriosis and Stage A disease included several mitogen-activated protein kinase (MAPK)-related pathways. WHAT IS KNOWN ALREADY Endometriosis is a complex disease with an estimated heritability of 50%. To date, GWAS revealed 10 genomic regions associated with endometriosis, explaining <4% of heritability, while half of the heritability is estimated to be due to common risk variants. Pathway analyses combine the evidence of single variants into gene-based measures, leveraging the aggregate effect of variants in genes and uncovering biological pathways involved in disease pathogenesis. STUDY DESIGN, SIZE, DURATION Pathway analysis was conducted utilizing the International Endogene Consortium GWAS data, comprising 3194 surgically confirmed endometriosis cases and 7060 controls of European ancestry with genotype data imputed up to 1000 Genomes Phase three reference panel. GWAS was performed for all endometriosis cases and for Stage A (revised American Fertility Society (rAFS) I/II, n = 1686) and B (rAFS III/IV, n = 1364) cases separately. The identified significant pathways were compared with pathways previously investigated in the literature through candidate association studies. PARTICIPANTS/MATERIALS, SETTING, METHODS The most comprehensive biological pathway databases, MSigDB (including BioCarta, KEGG, PID, SA, SIG, ST and GO) and PANTHER were utilized to test for enrichment of genetic variants associated with endometriosis. Statistical enrichment analysis was performed using the MAGENTA (Meta-Analysis Gene-set Enrichment of variaNT Associations) software. MAIN RESULTS AND THE ROLE OF CHANCE The first genome-wide association analysis for Stage A endometriosis revealed a novel locus, rs144240142 (P = 6.45 × 10−8, OR = 1.71, 95% CI = 1.23–2.37), an intronic single-nucleotide polymorphism (SNP) within MAP3K4. This SNP was not associated with Stage B disease (P = 0.086). MAP3K4 was also shown to be differentially expressed in eutopic endometrium between Stage A endometriosis cases and controls (P = 3.8 × 10−4), but not with Stage B disease (P = 0.26). A total of 14 pathways enriched with genetic endometriosis associations were identified (false discovery rate (FDR)-P < 0.05). The pathways associated with any endometriosis were Grb2-Sos provides linkage to MAPK signaling for integrins pathway (P = 2.8 × 10−5, FDR-P = 3.0 × 10−3), Wnt signaling (P = 0.026, FDR-P = 0.026) and p130Cas linkage to MAPK signaling for integrins pathway (P = 6.0 × 10−4, FDR-P = 0.029); with Stage A endometriosis: extracellular signal-regulated kinase (ERK)1 ERK2 MAPK (P = 5.0 × 10−4, FDR-P = 5.0 × 10−4) and with Stage B endometriosis: two overlapping pathways that related to extracellular matrix biology—Core matrisome (P = 1.4 × 10−3, FDR-P = 0.013) and ECM glycoproteins (P = 1.8 × 10−3, FDR-P = 7.1 × 10−3). Genes arising from endometriosis candidate gene studies performed to date were enriched for Interleukin signaling pathway (P = 2.3 × 10−12), Apoptosis signaling pathway (P = 9.7 × 10−9) and Gonadotropin releasing hormone receptor pathway (P = 1.2 × 10−6); however, these pathways did not feature in the results based on GWAS data. LARGE SCALE DATA Not applicable. LIMITATIONS, REASONS FOR CAUTION The analysis is restricted to (i) variants in/near genes that can be assigned to pathways, excluding intergenic variants; (ii) the gene-based pathway definition as registered in the databases; (iii) women of European ancestry. WIDER IMPLICATIONS OF THE FINDINGS The top ranked pathways associated with overall and Stage A endometriosis in particular involve integrin-mediated MAPK activation and intracellular ERK/MAPK acting downstream in the MAPK cascade, both acting in the control of cell division, gene expression, cell movement and survival. Other top enriched pathways in Stage B disease include ECM glycoprotein pathways important for extracellular structure and biochemical support. The results highlight the need for increased efforts to understand the functional role of these pathways in endometriosis pathogenesis, including the investigation of the biological effects of the genetic variants on downstream molecular processes in tissue relevant to endometriosis. Additionally, our results offer further support for the hypothesis of at least partially distinct causal pathophysiology for minimal/mild (rAFS I/II) vs. moderate/severe (rAFS III/IV) endometriosis. STUDY FUNDING/COMPETING INTEREST(S) The genome-wide association data and Wellcome Trust Case Control Consortium (WTCCC) were generated through funding from the Wellcome Trust (WT084766/Z/08/Z, 076113 and 085475) and the National Health and Medical Research Council (NHMRC) of Australia (241944, 339462, 389927, 389875, 389891, 389892, 389938, 443036, 442915, 442981, 496610, 496739, 552485 and 552498). N.R. was funded by a grant from the Medical Research Council UK (MR/K011480/1). A.P.M. is a Wellcome Trust Senior Fellow in Basic Biomedical Science (grant WT098017). All authors declare there are no conflicts of interest. PMID:28333195

Quadriceps muscle injury in trans-femoral amputees.

PubMed

Alsindi, Z; Datta, D

1998-12-01

Two male trans-femoral amputees using modular trans-femoral prostheses lost control and fell to the ground when their prosthetic knees gave way. The semi-automatic knee lock malfunctioned in the first case while the free knee stabilising mechanics gave way in the second case. This resulted in a high tensile force acting on the contralateral quadriceps muscle causing it to rupture. As there are a significant number of patients with both kinds of prostheses it is important to be aware of this possibility so that necessary actions can be taken to minimise its occurrence. Even with the currently available weight activated stance phase control, the prosthetic knee will give way if the knee is flexed more than 20 degrees on weight bearing. Good power and control of hip extensors on the amputation side is needed to control the prosthetic knee joint, especially in the early stage of the walking cycle, i.e., from heel strike to mid-stance. Quadriceps muscle injury in amputees, as far as the authors are aware, has not been reported previously.