Prevalence, awareness, treatment, and control rate of hypertension in HIV-infected patients: the HIV-HY study.

PubMed

De Socio, Giuseppe Vittorio; Ricci, Elena; Maggi, Paolo; Parruti, Giustino; Pucci, Giacomo; Di Biagio, Antonio; Calza, Leonardo; Orofino, Giancarlo; Carenzi, Laura; Cecchini, Enisia; Madeddu, Giordano; Quirino, Tiziana; Schillaci, Giuseppe

2014-02-01

We aimed to assess the prevalence of hypertension in an unselected human immunodeficiency virus (HIV)-infected population and to identify factors associated with hypertension prevalence, treatment, and control. We used a multicenter, cross-sectional, nationwide study that sampled 1,182 unselected, consecutive, HIV-infected patients. Office blood pressure was accurately measured with standard procedures. Patients were 71% men and 92% white, with a median age of 47 years (range = 18-78); 6% were antiretroviral treatment naive. The overall prevalence of hypertension was 29.3%; high-normal pressure accounted for an additional 12.3%. Among hypertensive subjects, 64.9% were aware of their hypertensive condition, 52.9% were treated, and 33.0% were controlled (blood pressure < 140/90 mm Hg). Blood pressure-lowering medications were used in monotherapy in 54.3% of the subjects. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers were the most frequently used drugs (76.1%: monotherapy = 39.1%, combination treatment = 37.0%). In multivariable regression models, hypertension was independently predicted by traditional risk factors, including age ≥50 years, male sex, family history of cardiovascular disease, body mass index ≥25 kg/m2, previous cardiovascular events, diabetes, central obesity, and metabolic syndrome, as well as by duration of HIV infection, duration of antiretroviral therapy, and nadir CD4+ T-cell count <200/μl. The choice of protease inhibitors vs. nonnucleoside reverse transcriptase inhibitors as a third antiretroviral drug was irrelevant. Hypertension affects nearly 30% of HIV adult outpatients in Italy. More than one-third of the hypertensive subjects are unaware of their condition, and more than two-thirds are uncontrolled. A higher level of attention to the diagnosis and treatment of hypertension is mandatory in this setting.

Vitamin D status of psychiatric inpatients in New Zealand's Waikato region.

PubMed

Menkes, David B; Lancaster, Kaye; Grant, Michael; Marsh, Reginald W; Dean, Peter; du Toit, Stephen A

2012-06-26

Vitamin D deficiency is widespread in New Zealand, confers multiple health risks, and may be particularly common among people with psychiatric illness. We studied vitamin D status in an unselected sample of adult psychiatric inpatients in Hamilton (latitude 37.5 S) during late winter. We recruited 102 consenting subjects and measured 25-hydroxy vitamin D3 levels in venous blood using a competitive electrochemiluminescence immunoassay. In addition to descriptive statistics, we used one-sample t-tests to determine the extent to which ethnic and diagnostic subgroups fell below the vitamin D deficiency threshold of 50 nM. 75 subjects (74%) had vitamin D levels <50 nM and thus had at least mild deficiency, while 19 (19%) were severely deficient with levels <25 nM. Rates of deficiency were comparable for men and women; only the former showed a correlation of vitamin D levels with age (r = 0.45, p < 0.01). Maori participants constituted half the sample (n = 51) and were more likely to be deficient than their European counterparts (p = 0.04). Vitamin D also varied by diagnosis, with schizophrenia associated with markedly lower levels than mania and depression (p < 0.001). Vitamin D deficiency is prevalent in the psychiatric inpatient setting in New Zealand and may be relevant to poor physical health outcomes, notably among Maori and those with schizophrenia. These findings support proposals to provide vitamin D supplementation, particularly during the winter months.

Prevalence of gastroesophageal reflux symptoms in a large unselected general population in Japan

PubMed Central

Yamagishi, Hatsushi; Koike, Tomoyuki; Ohara, Shuichi; Kobayashi, Shigeyuki; Ariizumi, Ken; Abe, Yasuhiko; Iijima, Katsunori; Imatani, Akira; Inomata, Yoshifumi; Kato, Katsuaki; Shibuya, Daisuke; Aida, Shigemitsu; Shimosegawa, Tooru

2008-01-01

AIM: To examine the prevalence of gastroesophageal reflux disease (GERD) symptoms in a large unselected general population in Japan. METHODS: In Japan, mature adults are offered regular check-ups for the prevention of gastric cancer. A notice was sent by mail to all inhabitants aged > 40 years. A total of 160 983 Japanese (60 774 male, 100 209 female; mean age 61.9 years) who underwent a stomach check up were enrolled in this study. In addition, from these 160 983 subjects, we randomly selected a total of 82 894 (34 275 male, 48 619 female; mean age 62.4 years) to evaluate the prevalence of abdominal pain. The respective subjects were prospectively asked to complete questionnaires concerning the symptoms of heartburn, dysphagia, and abdominal pain for a 1 mo period. RESULTS: The respective prevalences of the symptoms in males and females were: heartburn, 15.8% vs 20.7%; dysphagia, 5.4% vs 7.8%; and abdominal pain, 6.6% vs 9.6%. Among these symptoms, heartburn was significantly high compared with the other symptoms, and the prevalence of heartburn was significantly more frequent in females than in males in the 60-89-year age group. Dysphagia was also significantly more frequent in female patients. CONCLUSION: The prevalence of typical GERD symptoms (heartburn) was high, at about 20% of the Japan population, and the frequency was especially high in females in the 60-89 year age group. PMID:18322948

Randomized Selection Design Trial Evaluating CD8+-Enriched Versus Unselected Tumor-Infiltrating Lymphocytes for Adoptive Cell Therapy for Patients With Melanoma

PubMed Central

Dudley, Mark E.; Gross, Colin A.; Somerville, Robert P.T.; Hong, Young; Schaub, Nicholas P.; Rosati, Shannon F.; White, Donald E.; Nathan, Debbie; Restifo, Nicholas P.; Steinberg, Seth M.; Wunderlich, John R.; Kammula, Udai S.; Sherry, Richard M.; Yang, James C.; Phan, Giao Q.; Hughes, Marybeth S.; Laurencot, Carolyn M.; Rosenberg, Steven A.

2013-01-01

Purpose Adoptive cell therapy (ACT) with autologous tumor-infiltrating lymphocytes (TILs) and high-dose interleukin-2 (IL-2) administered to lymphodepleted patients with melanoma can cause durable tumor regressions. The optimal TIL product for ACT is unknown. Patients and Methods Patients with metastatic melanoma were prospectively assigned to receive unselected young TILs versus CD8+-enriched TILs. All patients received lymphodepleting chemotherapy and high-dose IL-2 therapy and were assessed for response, toxicity, survival, and immunologic end points. Results Thirty-four patients received unselected young TILs with a median of 8.0% CD4+ lymphocytes, and 35 patients received CD8+-enriched TILs with a median of 0.3% CD4+ lymphocytes. One month after TIL infusion, patients who received CD8+-enriched TILs had significantly fewer CD4+ peripheral blood lymphocytes (P = .01). Twelve patients responded to therapy with unselected young TILs (according to Response Evaluation Criteria in Solid Tumors [RECIST]), and seven patients responded to CD8+-enriched TILs (35% v 20%; not significant). Retrospective studies showed a significant association between response to treatment and interferon gamma secretion by the infused TILs in response to autologous tumor (P = .04), and in the subgroup of patients who received TILs from subcutaneous tumors, eight of 15 patients receiving unselected young TILs responded but none of eight patients receiving CD8+-enriched TILs responded. Conclusion A randomized selection design trial was feasible for improving individualized TIL therapy. Since the evidence indicates that CD8+-enriched TILs are not more potent therapeutically and they are more laborious to prepare, future studies should focus on unselected young TILs. PMID:23650429

The effects of armodafinil on objective sleepiness and performance in a shift work disorder sample unselected for objective sleepiness.

PubMed

Howard, Ryan; Roth, Thomas; Drake, Christopher L

2014-06-01

Armodafinil is a medication used to treat excessive sleepiness in individuals with shift work disorder (SWD). In the present study, we investigate whether armodafinil can normalize nocturnal sleepiness in a group of typical SWD patients. Participants were 12 night workers (aged 33.8 ± 8.57 years, 7 female subjects) with excessive sleepiness (≥10 on the Epworth Sleepiness Scale; mean, 14.8 ± 3.16), meeting the International Classification of Sleep Disorders, Second Edition criteria for SWD, with no other sleep or medical disorders verified by polysomnogram. The multiple sleep latency test (MSLT) was not used as an entry criteria. Armodafinil was administered at 10:30 pm in a randomized, double-blind, placebo-controlled, crossover design with experimental nights separated by 1 week. Primary end point was the MSLT, with naps at 1:30, 3:30, 5:30, and 7:30 am. Other study measures included a sleepiness-alertness visual analog scale administered before each nap, and 2 computer-based performance tests evaluating attention and memory. Subjects with SWD had a mean MSLT of 5.3 ± 3.25 minutes, indicating a mean level of pathological sleepiness. Armodafinil significantly improved MSLT score to 11.1 ± 4.79 minutes (P = 0.006). Subjective levels of alertness on the visual analog scale also improved (P = 0.008). For performance, reaction time to central (P = 0.006) and peripheral (P = 0.003) stimuli and free recall memory (P = 0.05) were also improved. Armodafinil 150 mg administered at the beginning of a night shift normalizes nocturnal sleepiness in individuals with SWD unselected for objective sleepiness. Subjective measures of sleepiness and cognitive performance are also improved. This suggests that armodafinil can improve levels of nocturnal alertness to within normal daytime levels in the majority of patients with SWD.

Model of inter-cell interference phenomenon in 10 nm magnetic tunnel junction with perpendicular anisotropy array due to oscillatory stray field from neighboring cells

NASA Astrophysics Data System (ADS)

Ohuchida, Satoshi; Endoh, Tetsuo

2018-06-01

In this paper, we propose a new model of inter-cell interference phenomenon in a 10 nm magnetic tunnel junction with perpendicular anisotropy (p-MTJ) array and investigated the interference effect between a program cell and unselected cells due to the oscillatory stray field from neighboring cells by Landau–Lifshitz–Gilbert micromagnetic simulation. We found that interference brings about a switching delay in a program cell and excitation of magnetization precession in unselected cells even when no programing current passes through. The origin of interference is ferromagnetic resonance between neighboring cells. During the interference period, the precession frequency of the program cell is 20.8 GHz, which synchronizes with that of the theoretical precession frequency f = γH eff in unselected cells. The disturbance strength of unselected cells decreased to be inversely proportional to the cube of the distance from the program cell, which is in good agreement with the dependence of stray field on the distance from the program cell calculated by the dipole approximation method.

Clinical relevance of radiologic examination of the skeleton and bone density measurements in osteoporosis of old age

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

Kuester, W.; Seidl, G.; Linkesch, W.

1981-10-01

For the diagnosis of primary osteoporosis, various semiquantitative radiologic methods were compared in 149 unselected patients, aged over 50 years. Crush fracture syndrome (CFS), lumbar spine index (LSI), and Singh Index (SI) were assessed by three radiologists and after reevaluation, the intra- and interobserver errors were calculated. The reliability of the subjective grading was improved by joint and repeated reading of the radiographs. Additionally, the peripheral trabecular bone content was measured by photon absorption densitometry (PAD). To test the value of the various semiquantitative methods. LSI, Si, and PAD have been compared with sex-matching before and after separation into agemore » in decades in CFS-positive and CFS-negative patients. In an attempt to differentiate osteoporotics and non-osteoporotics by CFS, our results indicate that CFS-positive and CFS-negative males cannot be separated by LSI, Si, and PAD, whereas in females these methods can discriminate irrespective of the age in decades. However, in age related groups, only SI can discriminate significantly between CFS-positive and CFS-negative females. Correlation of the semiquantitative methods, regardless of the diagnosis of a CFS, revealed a significant correlation-between SI and PAD, but no correlation between LSI and SI, and LSI and PAD, respectively.« less

Feasibility of outpatient total hip and knee arthroplasty in unselected patients

PubMed Central

Gromov, Kirill; Kjærsgaard-Andersen, Per; Revald, Peter; Kehlet, Henrik; Husted, Henrik

2017-01-01

Background and purpose The number of patients who are suitable for outpatient total hip and knee arthroplasty (THA and TKA) in an unselected patient population remains unknown. The purpose of this prospective 2-center study was to identify the number of patients suitable for outpatient THA and TKA in an unselected patient population, to investigate the proportion of patients who were discharged on the day of surgery (DOS), and to identify reasons for not being discharged on the DOS. Patients and methods All consecutive, unselected patients who were referred to 2 participating centers and who were scheduled for primary THA and TKA were screened for eligibility for outpatient surgery with discharge to home on DOS. If patients did not fulfill the discharge criteria, the reasons preventing discharge were noted. Odds factors with relative risk intervals for not being discharged on DOS were identified while adjusting for age, sex, ASA score, BMI and distance to home. Results Of the 557 patients who were referred to the participating surgeons during the study period, 54% were potentially eligible for outpatient surgery. Actual DOS discharge occurred in 13–15% of the 557 patients. Female sex and surgery late in the day increased the odds of not being discharged on the DOS. Interpretation This study shows that even in unselected THA and TKA patients, same-day discharge is feasible in about 15% of patients. Future studies should evaluate safety aspects and economic benefits. PMID:28426262

Multidimensional QoE of Multiview Video and Selectable Audio IP Transmission

PubMed Central

Nunome, Toshiro; Ishida, Takuya

2015-01-01

We evaluate QoE of multiview video and selectable audio (MVV-SA), in which users can switch not only video but also audio according to a viewpoint change request, transmitted over IP networks by a subjective experiment. The evaluation is performed by the semantic differential (SD) method with 13 adjective pairs. In the subjective experiment, we ask assessors to evaluate 40 stimuli which consist of two kinds of UDP load traffic, two kinds of fixed additional delay, five kinds of playout buffering time, and selectable or unselectable audio (i.e., MVV-SA or the previous MVV-A). As a result, MVV-SA gives higher presence to the user than MVV-A and then enhances QoE. In addition, we employ factor analysis for subjective assessment results to clarify the component factors of QoE. We then find that three major factors affect QoE in MVV-SA. PMID:26106640

Prevalence of pathogenic germline variants detected by multigene sequencing in unselected Japanese patients with ovarian cancer

PubMed Central

Hirasawa, Akira; Imoto, Issei; Naruto, Takuya; Akahane, Tomoko; Yamagami, Wataru; Nomura, Hiroyuki; Masuda, Kiyoshi; Susumu, Nobuyuki; Tsuda, Hitoshi; Aoki, Daisuke

2017-01-01

Pathogenic germline BRCA1, BRCA2 (BRCA1/2), and several other gene variants predispose women to primary ovarian, fallopian tube, and peritoneal carcinoma (OC), although variant frequency and relevance information is scarce in Japanese women with OC. Using targeted panel sequencing, we screened 230 unselected Japanese women with OC from our hospital-based cohort for pathogenic germline variants in 75 or 79 OC-associated genes. Pathogenic variants of 11 genes were identified in 41 (17.8%) women: 19 (8.3%; BRCA1), 8 (3.5%; BRCA2), 6 (2.6%; mismatch repair genes), 3 (1.3%; RAD51D), 2 (0.9%; ATM), 1 (0.4%; MRE11A), 1 (FANCC), and 1 (GABRA6). Carriers of BRCA1/2 or any other tested gene pathogenic variants were more likely to be diagnosed younger, have first or second-degree relatives with OC, and have OC classified as high-grade serous carcinoma (HGSC). After adjustment for these variables, all 3 features were independent predictive factors for pathogenic variants in any tested genes whereas only the latter two remained for variants in BRCA1/2. Our data indicate similar variant prevalence in Japanese patients with OC and other ethnic groups and suggest that HGSC and OC family history may facilitate genetic predisposition prediction in Japanese patients with OC and referring high-risk patients for genetic counseling and testing. PMID:29348823

Prevalence of pathogenic germline variants detected by multigene sequencing in unselected Japanese patients with ovarian cancer.

PubMed

Hirasawa, Akira; Imoto, Issei; Naruto, Takuya; Akahane, Tomoko; Yamagami, Wataru; Nomura, Hiroyuki; Masuda, Kiyoshi; Susumu, Nobuyuki; Tsuda, Hitoshi; Aoki, Daisuke

2017-12-22

Pathogenic germline BRCA1 , BRCA2 ( BRCA1/2 ), and several other gene variants predispose women to primary ovarian, fallopian tube, and peritoneal carcinoma (OC), although variant frequency and relevance information is scarce in Japanese women with OC. Using targeted panel sequencing, we screened 230 unselected Japanese women with OC from our hospital-based cohort for pathogenic germline variants in 75 or 79 OC-associated genes. Pathogenic variants of 11 genes were identified in 41 (17.8%) women: 19 (8.3%; BRCA1 ), 8 (3.5%; BRCA2 ), 6 (2.6%; mismatch repair genes), 3 (1.3%; RAD51D ), 2 (0.9%; ATM ), 1 (0.4%; MRE11A ), 1 ( FANCC ), and 1 ( GABRA6 ). Carriers of BRCA1/2 or any other tested gene pathogenic variants were more likely to be diagnosed younger, have first or second-degree relatives with OC, and have OC classified as high-grade serous carcinoma (HGSC). After adjustment for these variables, all 3 features were independent predictive factors for pathogenic variants in any tested genes whereas only the latter two remained for variants in BRCA1/2 . Our data indicate similar variant prevalence in Japanese patients with OC and other ethnic groups and suggest that HGSC and OC family history may facilitate genetic predisposition prediction in Japanese patients with OC and referring high-risk patients for genetic counseling and testing.

Genomic Footprints in Selected and Unselected Beef Cattle Breeds in Korea.

PubMed

Lim, Dajeong; Strucken, Eva M; Choi, Bong Hwan; Chai, Han Ha; Cho, Yong Min; Jang, Gul Won; Kim, Tae-Hun; Gondro, Cedric; Lee, Seung Hwan

2016-01-01

Korean Hanwoo cattle have been subjected to intensive artificial selection over the past four decades to improve meat production traits. Another three cattle varieties very closely related to Hanwoo reside in Korea (Jeju Black and Brindle) and in China (Yanbian). These breeds have not been part of a breeding scheme to improve production traits. Here, we compare the selected Hanwoo against these similar but presumed to be unselected populations to identify genomic regions that have been under recent selection pressure due to the breeding program. Rsb statistics were used to contrast the genomes of Hanwoo versus a pooled sample of the three unselected population (UN). We identified 37 significant SNPs (FDR corrected) in the HW/UN comparison and 21 known protein coding genes were within 1 MB to the identified SNPs. These genes were previously reported to affect traits important for meat production (14 genes), reproduction including mammary gland development (3 genes), coat color (2 genes), and genes affecting behavioral traits in a broader sense (2 genes). We subsequently sequenced (Illumina HiSeq 2000 platform) 10 individuals of the brown Hanwoo and the Chinese Yanbian to identify SNPs within the candidate genomic regions. Based on allele frequency differences, haplotype structures, and literature research, we singled out one non-synonymous SNP in the APP gene (APP: c.569C>T, Ala199Val) and predicted the mutational effect on the protein structure. We found that protein-protein interactions might be impaired due to increased exposed hydrophobic surfaces of the mutated protein. The APP gene has also been reported to affect meat tenderness in pigs and obesity in humans. Meat tenderness has been linked to intramuscular fat content, which is one of the main breeding goals for brown Hanwoo, potentially supporting a causal influence of the herein described nsSNP in the APP gene.

[Use of the EvalObs® adherence scale in an unselected French population of treated subjects with antihypertensive, hypolipemiants or oral antidiabetics medications: The FLAHS 2017 adherence survey].

PubMed

Girerd, X; Hanon, O; Vaïsse, B

2018-06-01

A Visual Analog Scale (VAS) is useful for diagnosing medication nonadherence and its validity has been evaluated using electronic pillbox as the gold standard. We have developed the EvaLobs ® scale for use on paper or on smartphone and the aim of the study was to administrate the scale among FLAHS 2017 participants treated for an hypertension, a dyslipidemia or diabetes. In subjects treated with antihypertensive medications, participants completed the 6-item Girerd Scale and EvaLobs ® . The French League Against Hypertension Survey (FLAHS) are carried out by self-questionnaire sent by mail to individuals from the French Kantar Health sampling frame (representative panel of the population living in metropolitan France). In 2017, FLAHS was conducted in 4783 subjects aged 35 and over. The EvaLobs ® has a scale from 0 to 15 and the use instruction is "how many days have you taken the drug in the past 15 days". A score>12 indicates a "good compliance". The 6-item Girerd scale was also completed. "Good adherence" was determined for a score of 0 to 2 and "nonadherence" for a score of 3 or more. The agreement between EvaLobs ® and the 6-item Girerd scale was evaluated in treated hypertensives. The survey included 4783 subjects with 1308 treated hypertensives, 942 subjects treated with lipid-lowering drugs and 405 subjects treated with anti-diabetics. EVALOBS ® indicates "Good adherence" in 96% of subjects and the 6 questions questionnaire indicates "good adherence" in 95% of subjects. An excellent agreement is noted in 93.8%. An EvaLobs ® score indicating nonadherence or an absence of response to EvaLobs ® is observed in 3.6% [CI 95, 2.5-4.7] of hypertensives, in 6.0% [CI 95, 3.9-8.1] of diabetics and in 8.2% [CI 95, 6.5-9.9] of dyslipidemic patients. In the population living in France and in unselected patients treated for metabolic disease or hypertension, non-adherence is lowest for antihypertensive medications and highest for statins. EvaLobs ® , which shows good agreement with an adherence questionnaire, is a quick and simple tool for assessing adherence. The smartphone app EvaLobs ® is available for free on Google play and the Apple store. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

[Comparative follow-up study of unselected male population with congenital defective color vision from inland and Mediterranean areas of Croatia].

PubMed

Rogosić, Veljko; Bojić, Lovro; Karaman, Ksenija; Rogosić, Lucija Vanjaka; Titlić, Marina; Poljak, Nikola Kolja; Plestina-Borjan, Ivna; Smerdelj, Andro; Duplancić, Darko; Alpeza-Dunato, Zvjezdana

2011-03-01

The aim of this ten-year study (from the end of 1998 to the end of 2008) was to assess the prevalence of congenital dyschromatopsia in unselected healthy male population aged 15-45 from two Croatian regions, i.e. inland and Mediterranean parts of Croatia. Results collected in these two regions were compared and respective conclusions drawn. The results primarily referred to the prevalence of color vision disturbances and their differences according to the main color groups (dichromacy and anomalous trichromacy) and subgroups (protanopia, deuteranopia, protanomaly, deuteranomaly, and others). To our knowledge, no such a long-term study in a large population sample has been carried out in southeast Europe to date. Color vision was examined after complete ophthalmologic examination in all subjects presenting for examination required for amateur driver license. Color vision examination was performed by use of pseudoisochromatic Ishihara tables, Nagel II anomaloscope and Panel D-15 color test at industrial medicine offices and ophthalmology departments in the two regions. There were 12,974 and 9,974 subjects in inland and Mediterranean Croatia, respectively. The results confirmed the hypothesis and clinical perception of a lower prevalence of color vision disturbances in southern parts, i.e. in Mediterranean Croatia (8.50%) as compared with inland Croatia (8.90%). The rate of dichromacy was higher in Mediterranean Croatia (2.40%), while the rate of anomalous trichromacy was greater in inland Croatia (6.93%). The results of this study provide better insight in the status of color vision disturbances and possible differences between the relatively close areas of north (inland) and south (Mediterranean) Croatia.

Management of advanced ovarian cancer in South West Wales - a comparison between primary debulking surgery and primary chemotherapy treatment strategies in an unselected, consecutive patient cohort.

PubMed

Drews, F; Bertelli, G; Lutchman-Singh, K

2017-08-01

This study represents the first reported outcomes for patients with advanced ovarian cancer (AOC) in South-West Wales undergoing treatment with primary debulking surgery or primary chemotherapy respectively. This is a retrospective study of consecutive, unselected patients with advanced ovarian, fallopian tube or primary peritoneal cancer (FIGO III/IV) presenting to a regional cancer centre between October 2007 and October 2014. Patients were identified from Welsh Cancer Services records and relevant data was extracted from electronic National Health Service (NHS) databases. Main outcome measures were median overall survival (OS), progression free survival (PFS) and perioperative adverse events. Hazard ratio estimation was carried out with Cox Regression analysis and survival determined by Kaplan-Meier plots. Of 220 women with AOC, 32.3% underwent primary debulking surgery (PDS) and 67.7% primary chemotherapy and interval debulking (PCT-IDS). Patients were often elderly (median age 67 years) with a poor performance status (26.5% PS >1). Complete cytoreduction (0cm residual) was achieved in 32.4% of patients in the PDS group and in 50.0% of patients undergoing IDS. Median OS for all patients was 21.9 months (PDS: 27.0 and PCT-IDS: 19.2 months; p >0.05) and median PFS was 13.1 months (PDS: 14.3 months and PCT-IDS: 13.0 months; p >0.05). Median overall and progression free survival for patients achieving complete cytoreduction were 48.0 and 23.2 months respectively in the PDS group and 35.4 months and 18.6 months in the IDS group (p >0.05). This retrospective study of an unselected, consecutive cohort of women with AOC in South West Wales shows comparable survival outcomes with recently published trials, despite the relatively advanced age and poor performance status of our patient cohort. Over the seven-year study period, our data also demonstrated a non-significant trend towards improved survival following primary surgery in patients who achieved maximal cytoreduction. Our future aim therefore is to examine and develop the role of extended surgery in these patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

The consequences of balanced harvesting of fish communities

PubMed Central

Jacobsen, Nis S.; Gislason, Henrik; Andersen, Ken H.

2014-01-01

Balanced harvesting, where species or individuals are exploited in accordance with their productivity, has been proposed as a way to minimize the effects of fishing on marine fish communities and ecosystems. This calls for a thorough examination of the consequences balanced harvesting has on fish community structure and yield. We use a size- and trait-based model that resolves individual interactions through competition and predation to compare balanced harvesting with traditional selective harvesting, which protects juvenile fish from fishing. Four different exploitation patterns, generated by combining selective or unselective harvesting with balanced or unbalanced fishing, are compared. We find that unselective balanced fishing, where individuals are exploited in proportion to their productivity, produces a slightly larger total maximum sustainable yield than the other exploitation patterns and, for a given yield, the least change in the relative biomass composition of the fish community. Because fishing reduces competition, predation and cannibalism within the community, the total maximum sustainable yield is achieved at high exploitation rates. The yield from unselective balanced fishing is dominated by small individuals, whereas selective fishing produces a much higher proportion of large individuals in the yield. Although unselective balanced fishing is predicted to produce the highest total maximum sustainable yield and the lowest impact on trophic structure, it is effectively a fishery predominantly targeting small forage fish. PMID:24307676

Prevalence of chronic atrophic gastritis in different parts of the world.

PubMed

Weck, Melanie Nicole; Brenner, Hermann

2006-06-01

Chronic atrophic gastritis (CAG) is a well-established precursor of intestinal gastric cancer, but epidemiologic data about its occurrence are sparse. We provide an overview on studies that examined the prevalence of CAG in different parts of the world. Articles containing data about the prevalence of chronic atrophic gastritis in unselected population samples and published until November 2005 were identified by searching the MEDLINE database. Furthermore, the references in the identified publications were screened for additional suitable studies. Studies comprising at least 50 subjects were included. Forty-one studies providing data on the prevalence of CAG in unselected population samples could be identified. CAG was determined by gastroscopy in 15 studies and by pepsinogen serum levels in 26 studies. Although results are difficult to compare due to the various definitions of CAG used, a strong increase with age, the lack of major gender differences, and strong variations between populations and population groups (in particular, relatively high rates in certain Asian populations) could be observed quite consistently. We conclude that CAG is relatively common among older adults in different parts of the world, but large variations exist. Large-scale international comparative studies with standardized methodology to determine CAG are needed to provide a coherent picture of the epidemiology of CAG in various populations. Noninvasive measurements of CAG by pepsinogen levels may be particularly suited for that purpose.

Elevated carboxyhemoglobin: sources of carbon monoxide exposure.

PubMed

Buchelli Ramirez, Herminia; Fernández Alvarez, Ramón; Rubinos Cuadrado, Gemma; Martinez Gonzalez, Cristina; Rodriguez Jerez, Francisco; Casan Clara, Pere

2014-11-01

Inhalation of carbon monoxide (CO) can result in poisoning, with symptoms ranging from mild and nonspecific to severe, or even death. CO poisoning is often underdiagnosed because exposure to low concentrations goes unnoticed, and threshold values for normal carboxyhemoglobin vary according to different authors. The aim of our study was to analyze carboxyhemoglobin (COHb) levels in an unselected population and detect sources of CO exposure In a cross-sectional descriptive study, we analyzed consecutive arterial blood gas levels processed in our laboratory. We selected those with COHb≥2.5% in nonsmokers and ≥5% in smokers. In these cases a structured telephone interview was conducted. Elevated levels of COHb were found in 64 (20%) of 306 initial determinations. Of these, data from 51 subjects aged 65±12 years, 31 (60%) of which were men, were obtained. Mean COHb was 4.0%. Forty patients (78%) were non-smokers with mean COHb of 3.2%, and 11 were smokers with COHb of 6.7%. In 45 patients (88.2%) we detected exposure to at least one source of ambient CO other than cigarette smoke. A significant proportion of individuals from an unselected sample had elevated levels of COHb. The main sources of CO exposure were probably the home, so this possibility should be explored. The population should be warned about the risks and encouraged to take preventive measures. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

How do medical students engaging in elective courses on acupuncture and homeopathy differ from unselected students? A survey.

PubMed

Jocham, Alexandra; Kriston, Levente; Berberat, Pascal O; Schneider, Antonius; Linde, Klaus

2017-03-09

We aimed to investigate whether students at German medical schools participating in elective courses on acupuncture and homeopathy differ from an unselected group of students regarding attitudes and personality traits. Elective courses on acupuncture and homeopathy in the academic half-year 2013/14 all over Germany were identified and participants invited to fill in a questionnaire including nineteen questions on attitudes towards Complementary and Alternative Medicine (CAM), orientation towards science, care and status orientation, and a short validated instrument (Big-Five-Inventory-10) to measure personality traits (extraversion, neuroticism, openness, conscientiousness, and agreeableness). Participants of a mandatory family medicine course at one university served as unselected control group. Two hundred twenty and 113 students from elective courses on acupuncture and homeopathy, respectively, and 315 control students participated (response rate 93%). Students participating in elective courses had much more positive attitudes towards CAM, somewhat lower science and status orientation, and somewhat higher care orientation than control group students (all p-values for three-group comparisons < 0.001). There were no differences between the three groups regarding personality traits with the exception of lower values for agreeableness in controls (p = 0.009). The findings of this study show that attitudes of students participating in elective courses on acupuncture or homeopathy at German medical schools differ to a considerable degree from the attitudes of unselected students.

Studies on strain sensitivity of Trichomonas vaginalis to metronidazole.

PubMed Central

Meingassner, J G; Havelec, L; Mieth, H

1978-01-01

Ninety-four strains of Trichomonas vaginalis isolated from unselected patients in Vienna during the period from November 1975 to November 1975 were subjected to sensitivity tests against metronidazole in vitro and in vivo. Nearly 90% of the isolates examined showed in vitro growth inhibition at concentrations of 0.4 to 1.6 microgram metronidazole/ml and only about 10% at concentrations of less than 0.4 microgram/ml. All isolates showed some inhibition of growth after incubation for 48 hours with 3.2 microgram metroidazole/ml. Tests on treatment carried out on experimentally infected mice revealed that all strains of T. vaginalis examined were sensitive to metronidazole (MDE: less than 3 x 35 mg/kg peroral). PMID:305807

Frontal hemisphere lateralization and depressive personality traits.

PubMed

Biondi, M; Parise, P; Venturi, P; Riccio, L; Brunetti, G; Pancheri, P

1993-12-01

To assess the relationship between hemispheric differences in information processing and interhemispheric asymmetries in terms of brain bioelectrical activity, we correlated scores on the MMPI Depression scale with interhemispheric asymmetry, measured as peak amplitude and latency of the P3 component of somatosensory evoked potentials (SEPs) at the frontocortical region of 14 healthy unselected volunteers (8 men and 6 women) who were about to start a course in autogenic training. The sample was subdivided into two groups on the basis of the median score on the MMPI Depression scale. Subjects scoring above the median showed a right lateralization at the frontocentral region and a significantly shorter P3 latency at the right hemisphere compared to the left.

Propranolol reduces the anxiety associated with day case surgery.

PubMed

Mealy, K; Ngeh, N; Gillen, P; Fitzpatrick, G; Keane, F B; Tanner, A

1996-01-01

To find out if propranolol, a non-cardioselective beta-blocker, can reduce the anxiety associated with day case surgery. Prospective randomized double blind trial. University hospital, Ireland. An unselected group of 53 patients undergoing day case surgery. Subjects randomised to receive either propranolol (10 mg) or placebo on the morning of operation. Blood pressure; pulse, anxiety, pain score and patient satisfaction. Mean (SD) Hospital Anxiety and Depression score was significantly lower in the propranolol group than in the control group (2.5 (0.7) compared with 4.6 (0.7), p < 0.0001) before discharge. A low dose of propranolol given on the morning of day case surgery significantly reduced patients' anxiety.

A new pretest probability score for diagnosis of lower limb deep vein thrombosis in unselected population of outpatients and inpatients.

PubMed

Sermsathanasawadi, Nuttawut; Chaivanit, Trakarn; Suparatchatpun, Pinyo; Chinsakchai, Khamin; Wongwanit, Chumpol; Ruangsetakit, Chanean; Mutirangura, Pramook

2017-03-01

Objective To develop a new pretest probability score for deep vein thrombosis (DVT) in unselected population of outpatients and inpatients. Methods The new score was developed using independent factors from 500 patients clinically suspected of leg DVT. The new score was validated in a second group of 315 patients. Results The score consists of four components: unilateral leg pain, confinement to bed, calf enlargement >3 cm compared with the other side, and previous venous thromboembolism. A score ≥2 indicated a high probability while a score <2 indicated low probability. The sensitivity and specificity of the new score were 71.60% and 79.49%, respectively. The area under the receiver operating characteristic curve for the new score was 0.79. The combination of a new score <2 and D-dimer level <500 µg/L had a negative predictive value of 96.43%. Conclusions Our new score was valid in an unselected population of outpatients and inpatients.

BRCA1 and BRCA2 mutations in Japanese patients with ovarian, fallopian tube, and primary peritoneal cancer.

PubMed

Sakamoto, Ikuko; Hirotsu, Yosuke; Nakagomi, Hiroshi; Ouchi, Hidetaka; Ikegami, Atsushi; Teramoto, Katsuhiro; Amemiya, Kenji; Mochizuki, Hitoshi; Omata, Masao

2016-01-01

The contribution of BRCA1 and BRCA2 to ovarian cancer in Japanese patients is still unclear. This study investigated the frequency of germline mutations in BRCA1/2 in Japanese patients with ovarian, peritoneal, or fallopian tube cancer, regardless of their family histories, which were suggestive of hereditary breast and ovarian cancer. Ninety-five unselected women with ovarian cancer who were seen from 2013 to 2015 at Yamanashi Prefectural Central Hospital were enrolled. Analyses of BRCA1/2 gene mutations were performed with next-generation sequencing. Twelve of the 95 patients (12.6%), including 5 in the BRCA1 (5.3%) and 7 in the BRCA2 (7.4%), had deleterious mutations. Among the 36 cases with a family history, 6 (16.7%) were found to carry mutations in BRCA1 and BRCA2. Notably, 6 of the 59 cases (10.2%) without a family history also had BRCA1/2 germline mutations. There was no statistical difference between the 2 groups (P = .36). The presence of mutations and their clinical relevance were studied. Mutation carriers were diagnosed at advanced stages (100% of positive cases among stage III or IV cases) and had poor prognostic histological subtypes (100% of positive cases had high-grade serous adenocarcinomas). In this unselected Japanese population, approximately 13% of the cases with ovarian cancer appeared to be associated with an inherited risk, regardless of a family history. This finding indicates that BRCA1/2 genetic testing should be performed for all patients with ovarian cancers. © 2015 American Cancer Society.

Transbulbar B-Mode Sonography in Multiple Sclerosis: Clinical and Biological Relevance.

PubMed

De Masi, Roberto; Orlando, Stefania; Conte, Aldo; Pasca, Sergio; Scarpello, Rocco; Spagnolo, Pantaleo; Muscella, Antonella; De Donno, Antonella

2016-12-01

Optic nerve sheath diameter quantification by transbulbar B-mode sonography is a recently validated technique, but its clinical relevance in relapse-free multiple sclerosis patients remains unexplored. In an open-label, comparative, cross-sectional study, we aimed to assess possible differences between patients and healthy controls in terms of optic nerve sheath diameter and its correlation with clinical/paraclinical parameters in this disease. Sixty unselected relapse-free patients and 35 matched healthy controls underwent transbulbar B-mode sonography. Patients underwent routine neurologic examination, brain magnetic resonance imaging and visual evoked potential tests. The mean optic nerve sheath diameter 3 and 5 mm from the eyeball was 22-25% lower in patients than controls and correlated with the Expanded Disability Status Scale (r = -0.34, p = 0.048, and r = -0.32, p = 0.042, respectively). We suggest that optic nerve sheath diameter quantified by transbulbar B-mode sonography should be included in routine assessment of the disease as an extension of the neurologic examination. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Non-smoking worksites in the residential construction sector: using an online forum to study perspectives and practices.

PubMed

Bondy, Susan J; Bercovitz, Kim L

2011-05-01

Blue-collar workers are a recognised priority for tobacco control. Construction workers have very high smoking rates and are difficult to study and reach with interventions promoting smoke-free workplaces and cessation. The objectives of this study were to explore the smoking-related social climate in the North American residential construction sector and to identify potential barriers and facilitators to creating smoke-free worksites. The data source used was a popular internet forum on home building. Participants included a broad and unselected population of employers, employees and freelance tradespersons working in residential construction. The forum archive contained 10 years of discourse on the subjects of smoking, workplace secondhand smoke and smoking restrictions on construction sites. Qualitative data analysis methods were used to describe major and minor discussion themes relevant to workplace smoking culture and policies in this sector. Participants described considerable tension between smoking and non-smoking tradespersons, but there was also much interpersonal support for cessation and support for non-smokers' rights. Employers and employees described efforts to make construction sites smoke free, and a movement towards preferential hiring of non-smoking tradespersons was discussed. Board participants wanted detailed scientific evidence on secondhand smoke exposure levels and risk thresholds, particularly in open-air workplaces. Experience with success of smoking bans in other challenging workplaces can be applied to the construction sector. Potential movement of smokers out of the workforce represents a challenge for public health systems to ensure equitable access to cessation supports and services.

Test--retest variability of Randot stereoacuity measures gathered in an unselected sample of UK primary school children.

PubMed

Adler, Paul; Scally, Andrew J; Barrett, Brendan T

2012-05-01

To determine the test-retest reliability of the Randot stereoacuity test when used as part of vision screening in schools. Randot stereoacuity (graded-circles) and logMAR visual acuity measures were gathered in an unselected sample of 139 children (aged 4-12, mean 8.1±2.1 years) in two schools. Randot testing was repeated on two occasions (average interval between successive tests 8 days, range: 1-21 days). Three Randot scores were obtained in 97.8% of children. Randot stereoacuity improved by an average of one plate (ie, one test level) on repeat testing but was little changed when tested on the third occasion. Within-subject variability was up to three test levels on repeat testing. When stereoacuity was categorised as 'fine', 'intermediate' or 'coarse', the greatest variability was found among younger children who exhibited 'intermediate' or 'coarse'/nil stereopsis on initial testing. Whereas 90.8% of children with 'fine' stereopsis (≤50 arc-seconds) on the first test exhibited 'fine' stereopsis on both subsequent tests, only ∼16% of children with 'intermediate' (>50 but ≤140 arc-seconds) or 'coarse'/nil (≥200 arc-seconds) stereoacuity on initial testing exhibited stable test results on repeat testing. Children exhibiting abnormal stereoacuity on initial testing are very likely to exhibit a normal result when retested. The value of a single, abnormal Randot graded-circles stereoacuity measure from school screening is therefore questionable.

Dissociation between the Prevalence of Atopy and Allergic Disease in Rural China among Children and Adults

PubMed Central

Kim, Jennifer S; Ouyang, Fengxiu; Pongracic, Jacqueline A; Fang, Yaping; Wang, Binyan; Liu, Xue; Xing, Houxun; Caruso, Deanna; Liu, Xin; Zhang, Shanchun; Xu, Xiping; Wang, Xiaobin

2009-01-01

Background The prevalence of allergic diseases is increasing worldwide, but the reasons are not well understood. Previous studies suggest that this trend may be associated with lifestyle and urbanization. Objective To describe patterns of sensitization and allergic disease in an unselected agricultural Chinese population. Methods The data was derived from a community-based twin study in Anqing, China. Skin prick testing was performed to foods and aeroallergens. Atopy was defined as sensitization to ≥1 allergen. Allergic disease was ascertained by self-report. The analysis was stratified by sex and age (children [11-17 years] and adults [≥18 years]) and included 1059 same-sex twin pairs. Results Of 2118 subjects, 57.6% were male (n=1220). Ages ranged from 11-71 years; 43.3% were children (n=918). Atopy was observed in 47.2% (n=999) of participants. The most common sensitizing foods were shellfish (16.7%) and peanut (12.3%). The most common sensitizing aeroallergens were dust mite (30.6%) and cockroach (25.2%). Birth order and zygosity had no effect on sensitization rates. Multivariate logistic regression models revealed risk factors for sensitization include age for foods and sex for aeroallergens. The rates of food allergy and asthma were estimated to be <1%. Conclusions Atopic sensitization was common in this rural farming Chinese population, particularly to shellfish, peanut, dust mite, and cockroach. The prevalence of allergic disease, in contrast, was quite low. Clinical Implications Allergen sensitization was far more common than the rate of self-reported allergic disease in this community. Evidence of sensitization is an inadequate marker of allergic disease and better correlates with clinical disease are needed. Capsule summary Among this large unselected Chinese rural farming community, atopy was observed in nearly half of the study subjects, but the rate of allergic disease was comparatively very low. PMID:18805578

Glaucoma incidence in an unselected cohort of diabetic patients: is diabetes mellitus a risk factor for glaucoma? DARTS/MEMO collaboration. Diabetes Audit and Research in Tayside Study. Medicines Monitoring Unit.

PubMed

Ellis, J D; Evans, J M; Ruta, D A; Baines, P S; Leese, G; MacDonald, T M; Morris, A D

2000-11-01

To evaluate whether diabetes mellitus is a risk factor for the development of primary open angle glaucoma or ocular hypertension (OHT). A historical cohort study of an unselected population comprising all residents of the Tayside region of Scotland was performed using record linkage techniques followed by case note review. Ascertainment of prevalent diabetes was achieved using the Diabetes Audit and Research in Tayside Study (DARTS) validated regional diabetes register. Glaucoma and treated OHT were defined by encashment of community prescriptions and the statutory surgical procedure coding database. The study population comprised 6631 diabetic subjects and 166 144 non-diabetic subjects aged >40 years without glaucoma or OHT at study entry. 65 patients with diabetes and 958 without diabetes were identified as new cases of glaucoma or treated OHT during the 24 month study period, yielding a standardised morbidity ratio of 127 (95% CI, 96-158). Case note review demonstrated non-differential misclassification of prevalent glaucoma and OHT as incident disease (diabetic cohort 20%, non-diabetic cohort 24%; p=0.56) primarily as a result of non-compliance in medically treated disease. Removing misclassified cases and adjusting for age yielded an incidence of primary open angle glaucoma in diabetes of 1.1/1000 patient years (95% CI, 0.89-1. 31) compared to 0.7/1000 patient years (95% CI, 0.54-0.86) in the non-diabetic cohort; RR 1.57 (95% CI, 0.99-2.48). This study failed to confirm an association between diabetes mellitus and primary open angle glaucoma and ocular hypertension. A non-significant increase in diagnosed and treated disease in the diabetic population was observed, but evidence was also found that detection bias contributes to this association.

A phase 2, open-label, multi-center study of amuvatinib in combination with platinum etoposide chemotherapy in platinum-refractory small cell lung cancer patients

PubMed Central

Byers, Lauren Averett; Horn, Leora; Ghandi, Jitendra; Kloecker, Goetz; Owonikoko, Taofeek; Waqar, Saiama Naheed; Krzakowski, Maciej; Cardnell, Robert J.; Fujimoto, Junya; Taverna, Pietro; Azab, Mohammad; Camidge, David Ross

2017-01-01

Background Amuvatinib (MP-470) is a multi-targeted kinase inhibitor with potent activity against c-Kit, synergistic with DNA-damaging agents. We evaluated amuvatinib in combination with platinum-etoposide (EP) chemotherapy by objective response rate, survival, and tolerability in platinum-refractory small cell lung cancer (SCLC) patients. Methods This study used a Simon 2-stage design requiring ≥3 centrally confirmed responses in the first 21 subjects. Subjects received EP with 300 mg amuvatinib orally three times daily in cycles of 21 days. A three-day amuvatinib run-in period before EP occurred in Cycle 1. Subjects received the same EP chemotherapy regimen given prior to progression/relapse. Results Among 23 subjects treated, we observed four PRs (17.4%) per RECIST 1.1, only two of which were centrally confirmed (8.7%, response duration 119, 151 days). Three subjects (13%) had confirmed stable disease. c-Kit H-score was ≥100 in two subjects whose respective durations of disease control were 151 and 256 days. Conclusions The addition of amuvatinib to EP chemotherapy in unselected, platinum-refractory SCLC did not meet the primary endpoint of ≥3 confirmed responses in stage 1. However, high c-Kit expression in two subjects with durable disease control suggests the potential for further study of amuvatinib in SCLC patients with high c-Kit expression. PMID:29113403

A phase 2, open-label, multi-center study of amuvatinib in combination with platinum etoposide chemotherapy in platinum-refractory small cell lung cancer patients.

PubMed

Byers, Lauren Averett; Horn, Leora; Ghandi, Jitendra; Kloecker, Goetz; Owonikoko, Taofeek; Waqar, Saiama Naheed; Krzakowski, Maciej; Cardnell, Robert J; Fujimoto, Junya; Taverna, Pietro; Azab, Mohammad; Camidge, David Ross

2017-10-06

Amuvatinib (MP-470) is a multi-targeted kinase inhibitor with potent activity against c-Kit, synergistic with DNA-damaging agents. We evaluated amuvatinib in combination with platinum-etoposide (EP) chemotherapy by objective response rate, survival, and tolerability in platinum-refractory small cell lung cancer (SCLC) patients. This study used a Simon 2-stage design requiring ≥3 centrally confirmed responses in the first 21 subjects. Subjects received EP with 300 mg amuvatinib orally three times daily in cycles of 21 days. A three-day amuvatinib run-in period before EP occurred in Cycle 1. Subjects received the same EP chemotherapy regimen given prior to progression/relapse. Among 23 subjects treated, we observed four PRs (17.4%) per RECIST 1.1, only two of which were centrally confirmed (8.7%, response duration 119, 151 days). Three subjects (13%) had confirmed stable disease. c-Kit H-score was ≥100 in two subjects whose respective durations of disease control were 151 and 256 days. The addition of amuvatinib to EP chemotherapy in unselected, platinum-refractory SCLC did not meet the primary endpoint of ≥3 confirmed responses in stage 1. However, high c-Kit expression in two subjects with durable disease control suggests the potential for further study of amuvatinib in SCLC patients with high c-Kit expression.

Positive view and increased likely uptake of follow-up testing with analysis of cell-free fetal DNA as alternative to invasive testing among Danish pregnant women.

PubMed

Miltoft, Caroline B; Rode, Line; Tabor, Ann

2018-05-01

The aim of this study was to investigate the attitude (view, likely uptake and preferred strategy) towards cell-free fetal DNA (cfDNA) testing among pregnant women before a first-trimester risk assessment for trisomy 21 (unselected women) and after obtaining a high risk. Unselected and high-risk women attending first-trimester screening (Rigshospitalet, Copenhagen University Hospital) were invited to fill out the questionnaire Antenatal testing for Down syndrome as an online survey. The survey included 203 unselected and 50 high-risk women (response rates of 74.8% and 84.7%, respectively). Nearly all considered cfDNA testing a positive development in antenatal care, and 97.2% would like it to be offered. Offering cfDNA testing as an alternative to invasive testing would increase the uptake of follow-up testing compared with invasive testing alone (98.8% vs. 90.7%, p < 0.001). Women who would only accept follow up by cfDNA testing were more likely to continue an affected pregnancy (30.0% vs. 3.6%, p < 0.001) or have doubts about termination (50.0% vs. 32.1%, p < 0.001). Offering cfDNA testing would likely increase the uptake of follow-up testing without a corresponding rise in the termination rate of affected fetuses as some women test for information only. However, both unselected and high-risk women had overwhelmingly positive views underlining attention to avoid routinization. © 2018 Nordic Federation of Societies of Obstetrics and Gynecology.

NT-ProBNP Levels in Saliva and Its Clinical Relevance to Heart Failure

PubMed Central

Foo, Jared Yong Yang; Wan, Yunxia; Kostner, Karam; Arivalagan, Alicia; Atherton, John; Cooper-White, Justin; Dimeski, Goce; Punyadeera, Chamindie

2012-01-01

Background Current blood based diagnostic assays to detect heart failure (HF) have large intra-individual and inter-individual variations which have made it difficult to determine whether the changes in the analyte levels reflect an actual change in disease activity. Human saliva mirrors the body’s health and well being and ∼20% of proteins that are present in blood are also found in saliva. Saliva has numerous advantages over blood as a diagnostic fluid which allows for a non-invasive, simple, and safe sample collection. The aim of our study was to develop an immunoassay to detect NT-proBNP in saliva and to determine if there is a correlation with blood levels. Methods Saliva samples were collected from healthy volunteers (n = 40) who had no underlying heart conditions and HF patients (n = 45) at rest. Samples were stored at −80°C until analysis. A customised homogeneous sandwich AlphaLISA(R) immunoassay was used to quantify NT-proBNP levels in saliva. Results Our NT-proBNP immunoassay was validated against a commercial Roche assay on plasma samples collected from HF patients (n = 37) and the correlation was r2 = 0.78 (p<0.01, y = 1.705× +1910.8). The median salivary NT-proBNP levels in the healthy and HF participants were <16 pg/mL and 76.8 pg/mL, respectively. The salivary NT-proBNP immunoassay showed a clinical sensitivity of 82.2% and specificity of 100%, positive predictive value of 100% and negative predictive value of 83.3%, with an overall diagnostic accuracy of 90.6%. Conclusion We have firstly demonstrated that NT-proBNP can be detected in saliva and that the levels were higher in heart failure patients compared with healthy control subjects. Further studies will be needed to demonstrate the clinical relevance of salivary NT-proBNP in unselected, previously undiagnosed populations. PMID:23119023

The horizontal computerized rotational impulse test.

PubMed

Furman, Joseph M; Shirey, Ian; Roxberg, Jillyn; Kiderman, Alexander

2016-01-01

Whole-body impulsive rotations were used to overcome several limitations associated with manual head impulse testing. A computer-controlled rotational chair delivered brief, whole-body, earth-vertical axis yaw impulsive rotations while eye movements were measured using video-oculography. Results from an unselected group of 20 patients with dizziness and a group of 22 control subjects indicated that the horizontal computerized rotational head impulse test (crHIT) is well-tolerated and provides an estimate of unidirectional vestibulo-ocular reflex gain comparable to results from caloric testing. This study demonstrates that the horizontal crHIT is a new assessment tool that overcomes many of the limitations of manual head impulse testing and provides a reliable laboratory-based measure of unilateral horizontal semicircular canal function.

How Long Should Routine EEG Be Recorded to Get Relevant Information?

PubMed

Doudoux, Hannah; Skaare, Kristina; Geay, Thomas; Kahane, Philippe; Bosson, Jean L; Sabourdy, Cécile; Vercueil, Laurent

2017-03-01

The optimal duration of routine EEG (rEEG) has not been determined on a clinical basis. This study aims to determine the time required to obtain relevant information during rEEG with respect to the clinical request. All rEEGs performed over 3 months in unselected patients older than 14 years in an academic hospital were analyzed retrospectively. The latency required to obtain relevant information was determined for each rEEG by 2 independent readers blinded to the clinical data. EEG final diagnoses and latencies were analyzed with respect to the main clinical requests: subacute cognitive impairment, spells, transient focal neurologic manifestation or patients referred by epileptologists. From 430 rEEGs performed in the targeted period, 364 were analyzed: 92% of the pathological rEEGs were provided within the first 10 minutes of recording. Slowing background activity was diagnosed from the beginning, whereas interictal epileptiform discharges were recorded over time. Moreover, the time elapsed to demonstrate a pattern differed significantly in the clinical groups: in patients with subacute cognitive impairment, EEG abnormalities appeared within the first 10 minutes, whereas in the other groups, data could be provided over time. Patients with subacute cognitive impairment differed from those in the other groups significantly in the elapsed time required to obtain relevant information during rEEG, suggesting that 10-minute EEG recordings could be sufficient, arguing in favor of individualized rEEG. However, this conclusion does not apply to intensive care unit patients.

An inherited NBN mutation is associated with poor prognosis prostate cancer

PubMed Central

Cybulski, C; Wokołorczyk, D; Kluźniak, W; Jakubowska, A; Górski, B; Gronwald, J; Huzarski, T; Kashyap, A; Byrski, T; Dębniak, T; Gołąb, A; Gliniewicz, B; Sikorski, A; Świtała, J; Borkowski, T; Borkowski, A; Antczak, A; Wojnar, Ł; Przybyła, J; Sosnowski, M; Małkiewicz, B; Zdrojowy, R; Sikorska-Radek, P; Matych, J; Wilkosz, J; Różański, W; Kiś, J; Bar, K; Bryniarski, P; Paradysz, A; Jersak, K; Niemirowicz, J; Słupski, P; Jarzemski, P; Skrzypczyk, M; Dobruch, J; Domagała, P; Narod, S A; Lubiński, J

2013-01-01

Background: To establish the contribution of eight founder alleles in three DNA damage repair genes (BRCA1, CHEK2 and NBS1) to prostate cancer in Poland, and to measure the impact of these variants on survival among patients. Methods: Three thousand seven hundred fifty men with prostate cancer and 3956 cancer-free controls were genotyped for three founder alleles in BRCA1 (5382insC, 4153delA, C61G), four alleles in CHEK2 (1100delC, IVS2+1G>A, del5395, I157T), and one allele in NBS1 (657del5). Results: The NBS1 mutation was detected in 53 of 3750 unselected cases compared with 23 of 3956 (0.6%) controls (odds ratio (OR)=2.5; P=0.0003). A CHEK2 mutation was seen in 383 (10.2%) unselected cases and in 228 (5.8%) controls (OR=1.9; P<0.0001). Mutation of BRCA1 (three mutations combined) was not associated with the risk of prostate cancer (OR=0.9; P=0.8). In a subgroup analysis, the 4153delA mutation was associated with early-onset (age ⩽60 years) prostate cancer (OR=20.3, P=0.004). The mean follow-up was 54 months. Mortality was significantly worse for carriers of a NBS1 mutation than for non-carriers (HR=1.85; P=0.008). The 5-year survival for men with an NBS1 mutation was 49%, compared with 72% for mutation-negative cases. Conclusion: A mutation in NBS1 predisposes to aggressive prostate cancer. These data are relevant to the prospect of adapting personalised medicine to prostate cancer prevention and treatment. PMID:23149842

Behavioral effects of bidirectional selection for behavior towards human in virgin and lactate Norway rats.

PubMed

Konoshenko, Maria Yu; Plyusnina, Irina Z

2012-06-01

Although numerous studies have demonstrated strong differences in behavioral, hormonal and neurobiological characteristics between male rats selected for elimination (tame) and enhancement (aggressive) of aggressiveness towards humans, few studies have examined changes in female behavior under this selection. The objective of the current work was to evaluate the effects of bidirectional selection for aggressiveness towards humans on behavioral profiles of virgin and lactating rats compared with the behavior in tame, aggressive and unselected (wild-type) females. The behavior of virgin females was studied using the light-dark box, the startle response test and the modified glove test. Tame females were less anxious and more tolerant towards humans than unselected and aggressive rats. Principal component analysis of all behavioral parameters produced three independent factors, explaining 66.37% of the total variability. The measures of behavior towards humans and the measures of anxiety mainly loaded on PC1 (first principal component) which separated the tame females from the unselected and aggressive ones. These data suggest the genetic correlation between the selected behavior towards humans and anxiety-related behavior in virgin rats. No significant effect of line was found for PC2 scores, associated with risk assessment behavior. Measurements of freezing behavior mainly loaded on PC3, and this component separated rats of different genetic groups from each other. The behavior of lactating rats was studied in maternal defense and pup retrieval tests. Females of selected lines did not significantly differ in behavioral measurements of these tests and were characterized by higher maternal motivation than unselected rats. It is suggested that long-term breeding of tame and aggressive rats in captivity has reduced the threshold for maternal behavior. Copyright © 2012 Elsevier B.V. All rights reserved.

Utility of the CPS+EG staging system in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer treated with neoadjuvant chemotherapy.

PubMed

Marmé, Frederik; Lederer, Bianca; Blohmer, Jens-Uwe; Costa, Serban Dan; Denkert, Carsten; Eidtmann, Holger; Gerber, Bernd; Hanusch, Claus; Hilfrich, Jörn; Huober, Jens; Jackisch, Christian; Kümmel, Sherko; Loibl, Sibylle; Paepke, Stefan; Untch, Michael; von Minckwitz, Gunter; Schneeweiss, Andreas

2016-01-01

Pathologic complete response after neoadjuvant chemotherapy (NACT) correlates with overall survival (OS) in primary breast cancer. A recently described staging system based on pre-treatment clinical stage (CS), final pathological stage (PS), estrogen receptor (ER) status and nuclear grade (NG) leads to a refined estimation of prognosis in unselected patients. Its performance in luminal type breast cancers has not been determined. This study investigates the clinical utility of this CPS+EG score when restricted to hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) patients and compares the results to a cohort of unselected patients. The CPS+EG score was calculated for 6637 unselected patients and 2454 patients with HR+/HER2- tumours who received anthracycline/taxane-based NACT within 8 prospective German trials. Five-year disease-free survival (DFS) and OS were 75.6% and 84.1% for the unselected cohort and 80.6% and 87.8% for the HR+/HER2- subgroup, respectively. The CPS+EG system distinguished different prognostic groups with 5-year DFS ranging from 0% to 91%. The CPS+EG system leads to an improved categorisation of patients by outcome compared to CS, PS, ER or NG alone. When applying the CPS+EG score to the HR+/HER2- subgroup, a shift to lower scores was observed compared to the overall population, but 5-year DFS and OS for the individual scores were identical to that observed in the overall population. In HR+/HER2- patients, the CPS+EG staging system retains its ability to facilitate a refined stratification of patients according to outcome. It can help to select candidates for post-neoadjuvant clinical trials in luminal breast cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluation of the Revised International Staging System in an independent cohort of unselected patients with multiple myeloma

PubMed Central

Kastritis, Efstathios; Terpos, Evangelos; Roussou, Maria; Gavriatopoulou, Maria; Migkou, Magdalini; Eleutherakis-Papaiakovou, Evangelos; Fotiou, Despoina; Ziogas, Dimitrios; Panagiotidis, Ioannis; Kafantari, Eftychia; Giannouli, Stavroula; Zomas, Athanasios; Konstantopoulos, Konstantinos; Dimopoulos, Meletios A.

2017-01-01

The Revised International Staging System (R-ISS) was recently introduced in order to improve risk stratification over that provided by the widely used standard International Staging System. In addition to the parameters of the standard system, the R-ISS incorporates the presence of chromosomal abnormalities detected by interphase fluorescence in situ hybridization [t(4;14), t(14;16) and del17p] and elevated serum lactate dehydrogenase. The R-ISS was formulated on the basis of a large dataset of selected patients who had participated in clinical trials and has not been validated in an independent cohort of unselected patients. Thus, we evaluated the R-ISS in 475 consecutive, unselected patients, treated in a single center. Our patients were older and more often had severe renal dysfunction than those in the original publication on the R-ISS. As regards distribution by group, 18% had R-ISS-1, 64.5% R-ISS-2 and 18% R-ISS-3. According to R-ISS group, the 5-year survival rate was 77%, 53% and 19% for R-ISS-1, -2 and -3, respectively (P<0.001). The R-ISS could identify three groups with distinct outcomes among patients treated with or without autologous stem cell transplantation, among those treated with either bortezomib-based or immunomodulatory drug-based primary therapy and in patients ≤65, 66–75 or >75 years. However, in patients with severe renal dysfunction the distinction between groups was less clear. In conclusion, our data in consecutive, unselected patients, with differences in the characteristics and treatment approaches compared to the original International Myeloma Working Group cohort, verified that R-ISS is a robust tool for risk stratification of newly diagnosed patients with symptomatic myeloma. PMID:27789676

Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer.

PubMed

Couch, Fergus J; Hart, Steven N; Sharma, Priyanka; Toland, Amanda Ewart; Wang, Xianshu; Miron, Penelope; Olson, Janet E; Godwin, Andrew K; Pankratz, V Shane; Olswold, Curtis; Slettedahl, Seth; Hallberg, Emily; Guidugli, Lucia; Davila, Jaime I; Beckmann, Matthias W; Janni, Wolfgang; Rack, Brigitte; Ekici, Arif B; Slamon, Dennis J; Konstantopoulou, Irene; Fostira, Florentia; Vratimos, Athanassios; Fountzilas, George; Pelttari, Liisa M; Tapper, William J; Durcan, Lorraine; Cross, Simon S; Pilarski, Robert; Shapiro, Charles L; Klemp, Jennifer; Yao, Song; Garber, Judy; Cox, Angela; Brauch, Hiltrud; Ambrosone, Christine; Nevanlinna, Heli; Yannoukakos, Drakoulis; Slager, Susan L; Vachon, Celine M; Eccles, Diana M; Fasching, Peter A

2015-02-01

Recent advances in DNA sequencing have led to the development of breast cancer susceptibility gene panels for germline genetic testing of patients. We assessed the frequency of mutations in 17 predisposition genes, including BRCA1 and BRCA2, in a large cohort of patients with triple-negative breast cancer (TNBC) unselected for family history of breast or ovarian cancer to determine the utility of germline genetic testing for those with TNBC. Patients with TNBC (N = 1,824) unselected for family history of breast or ovarian cancer were recruited through 12 studies, and germline DNA was sequenced to identify mutations. Deleterious mutations were identified in 14.6% of all patients. Of these, 11.2% had mutations in the BRCA1 (8.5%) and BRCA2 (2.7%) genes. Deleterious mutations in 15 other predisposition genes were detected in 3.7% of patients, with the majority observed in genes involved in homologous recombination, including PALB2 (1.2%) and BARD1, RAD51D, RAD51C, and BRIP1 (0.3% to 0.5%). Patients with TNBC with mutations were diagnosed at an earlier age (P < .001) and had higher-grade tumors (P = .01) than those without mutations. Deleterious mutations in predisposition genes are present at high frequency in patients with TNBC unselected for family history of cancer. Mutation prevalence estimates suggest that patients with TNBC, regardless of age at diagnosis or family history of cancer, should be considered for germline genetic testing of BRCA1 and BRCA2. Although mutations in other predisposition genes are observed among patients with TNBC, better cancer risk estimates are needed before these mutations are used for clinical risk assessment in relatives. © 2014 by American Society of Clinical Oncology.

Inherited Mutations in 17 Breast Cancer Susceptibility Genes Among a Large Triple-Negative Breast Cancer Cohort Unselected for Family History of Breast Cancer

PubMed Central

Couch, Fergus J.; Hart, Steven N.; Sharma, Priyanka; Toland, Amanda Ewart; Wang, Xianshu; Miron, Penelope; Olson, Janet E.; Godwin, Andrew K.; Pankratz, V. Shane; Olswold, Curtis; Slettedahl, Seth; Hallberg, Emily; Guidugli, Lucia; Davila, Jaime I.; Beckmann, Matthias W.; Janni, Wolfgang; Rack, Brigitte; Ekici, Arif B.; Slamon, Dennis J.; Konstantopoulou, Irene; Fostira, Florentia; Vratimos, Athanassios; Fountzilas, George; Pelttari, Liisa M.; Tapper, William J.; Durcan, Lorraine; Cross, Simon S.; Pilarski, Robert; Shapiro, Charles L.; Klemp, Jennifer; Yao, Song; Garber, Judy; Cox, Angela; Brauch, Hiltrud; Ambrosone, Christine; Nevanlinna, Heli; Yannoukakos, Drakoulis; Slager, Susan L.; Vachon, Celine M.; Eccles, Diana M.; Fasching, Peter A.

2015-01-01

Purpose Recent advances in DNA sequencing have led to the development of breast cancer susceptibility gene panels for germline genetic testing of patients. We assessed the frequency of mutations in 17 predisposition genes, including BRCA1 and BRCA2, in a large cohort of patients with triple-negative breast cancer (TNBC) unselected for family history of breast or ovarian cancer to determine the utility of germline genetic testing for those with TNBC. Patients and Methods Patients with TNBC (N = 1,824) unselected for family history of breast or ovarian cancer were recruited through 12 studies, and germline DNA was sequenced to identify mutations. Results Deleterious mutations were identified in 14.6% of all patients. Of these, 11.2% had mutations in the BRCA1 (8.5%) and BRCA2 (2.7%) genes. Deleterious mutations in 15 other predisposition genes were detected in 3.7% of patients, with the majority observed in genes involved in homologous recombination, including PALB2 (1.2%) and BARD1, RAD51D, RAD51C, and BRIP1 (0.3% to 0.5%). Patients with TNBC with mutations were diagnosed at an earlier age (P < .001) and had higher-grade tumors (P = .01) than those without mutations. Conclusion Deleterious mutations in predisposition genes are present at high frequency in patients with TNBC unselected for family history of cancer. Mutation prevalence estimates suggest that patients with TNBC, regardless of age at diagnosis or family history of cancer, should be considered for germline genetic testing of BRCA1 and BRCA2. Although mutations in other predisposition genes are observed among patients with TNBC, better cancer risk estimates are needed before these mutations are used for clinical risk assessment in relatives. PMID:25452441

New paradigms for BRCA1/BRCA2 testing in women with ovarian cancer: results of the Genetic Testing in Epithelial Ovarian Cancer (GTEOC) study

PubMed Central

Plaskocinska, Inga; Shipman, Hannah; Drummond, James; Thompson, Edward; Buchanan, Vanessa; Newcombe, Barbara; Hodgkin, Charlotte; Barter, Elisa; Ridley, Paul; Ng, Rita; Miller, Suzanne; Dann, Adela; Licence, Victoria; Webb, Hayley; Tan, Li Tee; Daly, Margaret; Ayers, Sarah; Rufford, Barnaby; Earl, Helena; Parkinson, Christine; Duncan, Timothy; Jimenez-Linan, Mercedes; Sagoo, Gurdeep S; Abbs, Stephen; Hulbert-Williams, Nicholas; Pharoah, Paul; Crawford, Robin; Brenton, James D; Tischkowitz, Marc

2016-01-01

Background Over recent years genetic testing for germline mutations in BRCA1/BRCA2 has become more readily available because of technological advances and reducing costs. Objective To explore the feasibility and acceptability of offering genetic testing to all women recently diagnosed with epithelial ovarian cancer (EOC). Methods Between 1 July 2013 and 30 June 2015 women newly diagnosed with EOC were recruited through six sites in East Anglia, UK into the Genetic Testing in Epithelial Ovarian Cancer (GTEOC) study. Eligibility was irrespective of patient age and family history of cancer. The psychosocial arm of the study used self-report, psychometrically validated questionnaires (Depression Anxiety and Stress Scale (DASS-21); Impact of Event Scale (IES)) and cost analysis was performed. Results 232 women were recruited and 18 mutations were detected (12 in BRCA1, 6 in BRCA2), giving a mutation yield of 8%, which increased to 12% in unselected women aged <70 years (17/146) but was only 1% in unselected women aged ≥70 years (1/86). IES and DASS-21 scores in response to genetic testing were significantly lower than equivalent scores in response to cancer diagnosis (p<0.001). Correlation tests indicated that although older age is a protective factor against any traumatic impacts of genetic testing, no significant correlation exists between age and distress outcomes. Conclusions The mutation yield in unselected women diagnosed with EOC from a heterogeneous population with no founder mutations was 8% in all ages and 12% in women under 70. Unselected genetic testing in women with EOC was acceptable to patients and is potentially less resource-intensive than current standard practice. PMID:27208206

Population Response Profiles in Early Visual Cortex Are Biased in Favor of More Valuable Stimuli

PubMed Central

Saproo, Sameer

2010-01-01

Voluntary and stimulus-driven shifts of attention can modulate the representation of behaviorally relevant stimuli in early areas of visual cortex. In turn, attended items are processed faster and more accurately, facilitating the selection of appropriate behavioral responses. Information processing is also strongly influenced by past experience and recent studies indicate that the learned value of a stimulus can influence relatively late stages of decision making such as the process of selecting a motor response. However, the learned value of a stimulus can also influence the magnitude of cortical responses in early sensory areas such as V1 and S1. These early effects of stimulus value are presumed to improve the quality of sensory representations; however, the nature of these modulations is not clear. They could reflect nonspecific changes in response amplitude associated with changes in general arousal or they could reflect a bias in population responses so that high-value features are represented more robustly. To examine this issue, subjects performed a two-alternative forced choice paradigm with a variable-interval payoff schedule to dynamically manipulate the relative value of two stimuli defined by their orientation (one was rotated clockwise from vertical, the other counterclockwise). Activation levels in visual cortex were monitored using functional MRI and feature-selective voxel tuning functions while subjects performed the behavioral task. The results suggest that value not only modulates the relative amplitude of responses in early areas of human visual cortex, but also sharpens the response profile across the populations of feature-selective neurons that encode the critical stimulus feature (orientation). Moreover, changes in space- or feature-based attention cannot easily explain the results because representations of both the selected and the unselected stimuli underwent a similar feature-selective modulation. This sharpening in the population response profile could theoretically improve the probability of correctly discriminating high-value stimuli from low-value alternatives. PMID:20410360

Enhanced broadband absorption in nanowire arrays with integrated Bragg reflectors

NASA Astrophysics Data System (ADS)

Aghaeipour, Mahtab; Pettersson, Håkan

2018-05-01

A near-unity unselective absorption spectrum is desirable for high-performance photovoltaics. Nanowire (NW) arrays are promising candidates for efficient solar cells due to nanophotonic absorption resonances in the solar spectrum. The absorption spectra, however, display undesired dips between the resonance peaks. To achieve improved unselective broadband absorption, we propose to enclose distributed Bragg reflectors (DBRs) in the bottom and top parts of indium phosphide (InP) NWs, respectively. We theoretically show that by enclosing only two periods of In0.56Ga0.44As/InP DBRs, an unselective 78% absorption efficiency (72% for NWs without DBRs) is obtained at normal incidence in the spectral range from 300 nm to 920 nm. Under oblique light incidence, the absorption efficiency is enhanced up to about 85% at an incidence angle of 50°. By increasing the number of DBR periods from two to five, the absorption efficiency is further enhanced up to 95% at normal incidence. In this work, we calculated optical spectra for InP NWs, but the results are expected to be valid for other direct band gap III-V semiconductor materials. We believe that our proposed idea of integrating DBRs in NWs offers great potential for high-performance photovoltaic applications.

Inductive learning of thyroid functional states using the ID3 algorithm. The effect of poor examples on the learning result.

PubMed

Forsström, J

1992-01-01

The ID3 algorithm for inductive learning was tested using preclassified material for patients suspected to have a thyroid illness. Classification followed a rule-based expert system for the diagnosis of thyroid function. Thus, the knowledge to be learned was limited to the rules existing in the knowledge base of that expert system. The learning capability of the ID3 algorithm was tested with an unselected learning material (with some inherent missing data) and with a selected learning material (no missing data). The selected learning material was a subgroup which formed a part of the unselected learning material. When the number of learning cases was increased, the accuracy of the program improved. When the learning material was large enough, an increase in the learning material did not improve the results further. A better learning result was achieved with the selected learning material not including missing data as compared to unselected learning material. With this material we demonstrate a weakness in the ID3 algorithm: it can not find available information from good example cases if we add poor examples to the data.

Ex-vivo expansion of CFU-GM and BFU-E in unselected PBMC cultures with Flt3L is enhanced by autologous plasma.

PubMed

Guo, M; Miller, W M; Papoutsakis, E T; Patel, S; James, C; Goolsby, C; Winter, J N

1999-01-01

Previous ex-vivo expansion studies in our laboratory, comparing unselected and CD34(+)-selected PBMC, have shown no advantage for CD34(+) cell selection, in terms of the expansion achieved. Our goal was to develop procedures for consistent generation of large numbers of hematopoietic progenitor and post-progenitor cells from unselected PBMC. Unselected PBMC, collected from cancer patients undergoing apheresis prior to high-dose chemotherapy and autologous stem cell rescue, were expanded ex vivo in static cultures, without a stromal layer, in the presence of Flt3 ligand (Flt3L), a recombinant GM-CSF/IL-3 fusion protein (PIXY321), G-CSF and GM-CSF for 10 days. The addition of 2% autologous plasma to this cytokine combination enhanced expansion of total cell numbers (3.2 fold versus 1.9 fold; p < 0.01), colony-forming units granulocyte-macrophage (CFU-GM) (22.0 fold versus 8.1 fold, p < 0.01) and burst-forming units erythroid (BFU-E) (17.6 fold versus 7.0 fold, 0.01 < p < 0.02). The optimal seeding density for a given specimen was inversely related to the frequency of CD34(+) cells in the sample. CFU-GM expansion with the Flt3L-containing cytokine cocktail was equivalent to that obtained with IL-3, IL-6, G-CSF and SCF, whether or not the cultures were supplemented with autologous plasma. In plasma-free cultures, BFU-E expansion was significantly higher with IL-3, IL-6, G-CSF and SCF than with Flt3L, PIXY321, G-CSF and GM-CSF. In the presence of autologous plasma, however BFU-E expansion was higher in the Flt3L-containing media. In comparison studies, autologous plasma suppressed BFU-E expansion in SCF-containing cultures. Consistent with our colony assay results, dual-parameter flow cytometric analysis of the expanded cell population revealed that supplementation with autologous plasma yielded a significant increase in the numbers of myeloid progenitors in Flt3L-containing cultures. Unselected PBMC from cancer patients can be effectively expanded ex vivo in Flt3L, PIXY321, G-CSF and GM-CSF, supplemented with autologous plasma, yielding high numbers of myeloid and erythroid progenitors.

Intelligence: shared genetic basis between Mendelian disorders and a polygenic trait.

PubMed

Franić, Sanja; Groen-Blokhuis, Maria M; Dolan, Conor V; Kattenberg, Mathijs V; Pool, René; Xiao, Xiangjun; Scheet, Paul A; Ehli, Erik A; Davies, Gareth E; van der Sluis, Sophie; Abdellaoui, Abdel; Hansell, Narelle K; Martin, Nicholas G; Hudziak, James J; van Beijsterveldt, Catherina E M; Swagerman, Suzanne C; Hulshoff Pol, Hilleke E; de Geus, Eco J C; Bartels, Meike; Ropers, H Hilger; Hottenga, Jouke-Jan; Boomsma, Dorret I

2015-10-01

Multiple inquiries into the genetic etiology of human traits indicated an overlap between genes underlying monogenic disorders (eg, skeletal growth defects) and those affecting continuous variability of related quantitative traits (eg, height). Extending the idea of a shared genetic basis between a Mendelian disorder and a classic polygenic trait, we performed an association study to examine the effect of 43 genes implicated in autosomal recessive cognitive disorders on intelligence in an unselected Dutch population (N=1316). Using both single-nucleotide polymorphism (SNP)- and gene-based association testing, we detected an association between intelligence and the genes of interest, with genes ELP2, TMEM135, PRMT10, and RGS7 showing the strongest associations. This is a demonstration of the relevance of genes implicated in monogenic disorders of intelligence to normal-range intelligence, and a corroboration of the utility of employing knowledge on monogenic disorders in identifying the genetic variability underlying complex traits.

Minor head injury: pathophysiological or iatrogenic sequelae?

PubMed Central

Newcombe, F; Rabbitt, P; Briggs, M

1994-01-01

This study addresses the possibility that cognitive sequelae--albeit of a transient or minor character--can be associated with mild head injury. Twenty men (aged 16-30 years of age), whose post-traumatic amnesia did not exceed eight hours, were examined within 48 hours of their accident and again one month later. This unselected sample had no previous history of head injury. A control group of 20 men of similar socioeconomic background, was selected from medical wards (where they had been admitted for orthopaedic treatment or a minor operation). They were also retested one month after the first examination. Neuropsychological tests were selected to measure abilities often compromised after significant head injury, namely memory and attention. The experimental component consisted of the fractionation of a complex skill (paced addition) to probe for deficits at different stages of information processing: perception and input into storage; search for and retrieval of information from working memory; and paced and unpaced addition. In general, no significant difference was found between the experimental and control groups, with the possible exception of an initial decrement on two working memory tasks: probe digits and a keeping track task (where the subject has to keep in mind and update a number of variables at the same time). The keeping track paradigm, ostensibly of ecological relevance, may well be worth further exploration in memory research, and in studies of more severely head-injured patients. It is further suggested that the appropriate management and counselling of mildly head-injured patients may help to avert symptoms that are of psychological rather than pathophysiological origin. PMID:8006652

Non-smoking worksites in the residential construction sector: using an online forum to study perspectives and practices

PubMed Central

Bercovitz, Kim L

2010-01-01

Objectives Blue-collar workers are a recognised priority for tobacco control. Construction workers have very high smoking rates and are difficult to study and reach with interventions promoting smoke-free workplaces and cessation. The objectives of this study were to explore the smoking-related social climate in the North American residential construction sector and to identify potential barriers and facilitators to creating smokefree worksites. Methods The data source used was a popular internet forum on home building. Participants included a broad and unselected population of employers, employees and freelance tradespersons working in residential construction. The forum archive contained 10 years of discourse on the subjects of smoking, workplace secondhand smoke and smoking restrictions on construction sites. Qualitative data analysis methods were used to describe major and minor discussion themes relevant to workplace smoking culture and policies in this sector. Results Participants described considerable tension between smoking and non-smoking tradespersons, but there was also much interpersonal support for cessation and support for non-smokers' rights. Employers and employees described efforts to make construction sites smoke free, and a movement towards preferential hiring of non-smoking tradespersons was discussed. Board participants wanted detailed scientific evidence on secondhand smoke exposure levels and risk thresholds, particularly in open-air workplaces. Conclusions Experience with success of smoking bans in other challenging workplaces can be applied to the construction sector. Potential movement of smokers out of the workforce represents a challenge for public health systems to ensure equitable access to cessation supports and services. PMID:21118847

Sexually transmitted conditions among women college students.

PubMed

McCormack, W M; Evrard, J R; Laughlin, C F; Rosner, B; Alpert, S; Crockett, V A; McComb, D; Zinner, S H

1981-01-15

We studied 500 unselected young women who consulted a gynecologist in a student health service. Most participants were symptom-free and had normal physical examinations. Few sexually transmitted infections were encountered. Neisseria gonorrhoeae was recovered from two and Trichomonas vaginalis was obtained from 14 of 500 women. Chlamydia trachomatis was recovered from 20 (4.6%) of 439 participants. Genital warts, genital herpes, and molluscum contagiosum, respectively, were noted in seven, four, and one of the 500 participants. There was no cases of syphilis, scabies, or pediculosis pubis. Mycoplasma hominis and Ureaplasma urealyticum, respectively, were recovered from 17.6 and 56.8% of the subjects. Prevalent vaginal bacteria included lactobacilli, streptococci, Staphylococcus epidermidis, and diphtheroids. Gardnerella vaginalis was isolated from the vaginal specimens of about one third of the participants.

Surgical restoration of vas continuity after vasectomy: further clinical evaluation of a new operation technique.

PubMed

Pardanani, D S; Kothari, M L; Pradhan, S A; Mahendrakar, M N

1974-04-01

20 unselected former vasectomy patients were subjected to scrotal exploration and vas recanalization operation. Anastomosis was carried out using a large diameter silicone rubber splint; the splint was removed 7 days postoperatively. No complications or side effects were encountered, and there were no patient complaints of discomfort or pain. 92.3% of the men considered satisfactory candidates for recanalization had successful results, and 30.8% of their wives became pregnant. The low fertility rate following successful vas recanalization is not understood. The 2 conditions which were found to be unfavorable for vas recanalization were a vasectomy where a long segment of the vas had been excised or where the vas section had been made very low and involved its convoluted segment.

New Issues for New Methods: Ethical and Editorial Challenges for an Experimental Philosophy.

PubMed

Polonioli, Andrea

2017-08-01

This paper examines a constellation of ethical and editorial issues that have arisen since philosophers started to conduct, submit and publish empirical research. These issues encompass concerns over responsible authorship, fair treatment of human subjects, ethicality of experimental procedures, availability of data, unselective reporting and publishability of research findings. This study aims to assess whether the philosophical community has as yet successfully addressed such issues. To do so, the instructions for authors, submission process and published research papers of 29 main journals in philosophy have been considered and analyzed. In light of the evidence reported here, it is argued that the philosophical community has as yet failed to properly tackle such issues. The paper also delivers some recommendations for authors, reviewers and editors in the field.

Sodium and potassium intake and risk of cardiovascular events and all-cause mortality: the Rotterdam Study

PubMed Central

Witteman, Jacqueline C. M.; Stijnen, Theo; Kloos, Margot W.; Hofman, Albert; Grobbee, Diederick E.

2007-01-01

Background Dietary electrolytes influence blood pressure, but their effect on clinical outcomes remains to be established. We examined sodium and potassium intake in relation to cardiovascular disease (CVD) and mortality in an unselected older population. Methods A case–cohort analysis was performed in the Rotterdam Study among subjects aged 55 years and over, who were followed for 5 years. Baseline urinary samples were analyzed for sodium and potassium in 795 subjects who died, 206 with an incident myocardial infarction and 181 subjects with an incident stroke, and in 1,448 randomly selected subjects. For potassium, dietary data were additionally obtained by food-frequency questionnaire for 78% of the cohort. Results There was no consistent association of urinary sodium, potassium, or sodium/potassium ratio with CVD and all-cause mortality over the range of intakes observed in this population. Dietary potassium estimated by food frequency questionnaire, however, was associated with a lower risk of all-cause mortality in subjects initially free of CVD and hypertension (RR = 0.71 per standard deviation increase; 95% confidence interval: 0.51–1.00). We observed a significant positive association between urinary sodium/potassium ratio and all-cause mortality, but only in overweight subjects who were initially free of CVD and hypertension (RR = 1.19 (1.02–1.39) per unit). Conclusion The effect of sodium and potassium intake on CVD morbidity and mortality in Western societies remains to be established. PMID:17902026

Potential source of cerebral embolism in migraine with aura: a transcranial Doppler study.

PubMed

Anzola, G P; Magoni, M; Guindani, M; Rozzini, L; Dalla Volta, G

1999-05-12

The recently found association between patent foramen ovale (PFO) and transient global amnesia (TGA) has suggested that paradoxical microembolization in the terminal vertebrobasilar territory might underlie at least some TGA cases. Migraine with visual aura is another paroxysmal disturbance in which a sudden dysfunction of cortical areas fed by the terminal branches of the basilar artery is believed to trigger the attack. Therefore we investigated the prevalence of PFO in a consecutive unselected cohort of migraine patients. To investigate the prevalence of PFO in a consecutive unselected cohort of migraine patients to search for a possible mechanism for the reported association of migraine with stroke. A total of 113 patients, consecutively referred by the Headache Outpatient Clinic for migraine with aura (MA+, mean age 34+/-12 years) were compared with 53 patients with migraine without aura (MA-, mean age 36+/-13 years) and with 25 age-matched nonmigraine subjects (mean age 31+/-10 years) selected from the hospital staff. PFO was assessed with transcranial Doppler sonography with IV injection of agitated saline, a technique that is 90% sensitive and 100% specific. The prevalence of PFO was 48% (54/113) in MA+ patients, 23% (12/53) in MA- patients, and 20% (5/25) in control subjects. The difference between MA+ and MA- patients was significant (odds ratio [OR] = 3.13, 95% confidence interval [CI] = 1.41 to 7.04, chi2 = 9.52,p = 0.002) as was the difference between MA+ patients and controls (OR = 3.66, 95% CI = 1.21 to 13.25, chi2 = 6.46, p = 0.01), whereas MA- patients did not differ from controls (OR = 1.17, 95% CI = 0.32 to 4.45, chi2 = 0.07). MRI was negative in 22 MA+ and 8 MA- patients. Patency of the foramen ovale is associated with migraine with aura but not with migraine without aura. The increased risk of stroke found in epidemiologic studies in patients with migraine with aura may be explained by an increased propensity to paradoxical cerebral embolism.

A recurrent CHEK2 p.H371Y mutation is associated with breast cancer risk in Chinese women.

PubMed

Liu, Yin; Liao, Ji; Xu, Ye; Chen, Weiqiu; Liu, Dongyun; Ouyang, Tao; Li, Jinfeng; Wang, Tianfeng; Fan, Zhaoqing; Fan, Tie; Lin, Benyao; Xu, Xingzhi; Xie, Yuntao

2011-09-01

The association between the CHEK2 and breast cancer risk in Chinese women is unknown. Here, we screened the full CHEK2 coding sequence in 118 Chinese familial breast cancer cases who are negative for mutations in BRCA1 and BRCA2, one recurrent mutation, CHEK2 c.1111C>T (p.H371Y), was identified in five index cases in this cohort. Functional analysis suggested that CHEK2 p.H371Y was a pathogenic mutation that resulted in decreased kinase activity. We further screened the CHEK2 p.H371Y mutation in 909 unselected breast cancer cases and 1,228 healthy individuals. The frequencies of the CHEK2 p.H371Y in familial and unselected breast cancer cases and controls were 4.24% (5/118), 1.76% (16/909), and 0.73% (9/1228), respectively. The p.H371Y mutation was significantly associated with increased breast cancer risk in unselected breast cancer (odds ratio [OR] 2.43, 95% confidence interval [CI] 1.07-5.52, P = 0.034). Our results indicate that the recurrent mutation, p.H371Y, confers a moderate risk of breast cancer in Chinese women. © 2011 Wiley-Liss, Inc.

Bone breaking strength and apparent metabolisability of calcium and phosphorus in selected and unselected broiler chicken genotypes.

PubMed

McDevitt, R M; McEntee, G M; Rance, K A

2006-10-01

1. The present study examined the bone strength and apparent mineral metabolisability of a selected broiler chicken compared with those of a relatively unselected genotype. 2. Selected (SB) and unselected genotypes (UB) were reared under standard conditions and were fed on either a high quality (HQ) or a low quality (LQ) diet. Tibiotarsi samples were collected at 42 d from SB and compared to tibiotarsi from UB of the same age and the same body mass (BM). 3. Bones were assessed for: bone breaking strength (BBS), morphology (weight and length), and both organic (OM) and inorganic content (ASH). Apparent dry matter digestibility and the coefficient of apparent metabolisability of calcium and phosphorus were determined at the same BM. 4. The BBS of SB (214 +/- 9 N) was greater than that of same-age UB (119 +/- 8 N) but the same as that of same-BM UB (218 +/- 10 N). At the same age, the SB had stronger, heavier bones with more ash and organic matter per unit length of tibiotarsus than UB. At the same BM, the tibiotarsi of the SB were shorter and lighter, with a higher ash and a similar organic content than the bones of the UB. At the same BM, BBS was about 15% lower in both genotypes fed on the LQ compared to the HQ diet. 5. The coefficients of apparent metabolisability of calcium and phosphorus were the same in both genotypes when fed on the HQ diet, but were lower in the SB than in the UB genotype when the birds were given the LQ diet. 6. The tibiotarsi of the selected broilers were stronger, or at least as strong, as those of the unselected broiler genotype, which may be due to similar levels of apparent calcium metabolisability of the selected chickens.

New paradigms for BRCA1/BRCA2 testing in women with ovarian cancer: results of the Genetic Testing in Epithelial Ovarian Cancer (GTEOC) study.

PubMed

Plaskocinska, Inga; Shipman, Hannah; Drummond, James; Thompson, Edward; Buchanan, Vanessa; Newcombe, Barbara; Hodgkin, Charlotte; Barter, Elisa; Ridley, Paul; Ng, Rita; Miller, Suzanne; Dann, Adela; Licence, Victoria; Webb, Hayley; Tan, Li Tee; Daly, Margaret; Ayers, Sarah; Rufford, Barnaby; Earl, Helena; Parkinson, Christine; Duncan, Timothy; Jimenez-Linan, Mercedes; Sagoo, Gurdeep S; Abbs, Stephen; Hulbert-Williams, Nicholas; Pharoah, Paul; Crawford, Robin; Brenton, James D; Tischkowitz, Marc

2016-10-01

Over recent years genetic testing for germline mutations in BRCA1/BRCA2 has become more readily available because of technological advances and reducing costs. To explore the feasibility and acceptability of offering genetic testing to all women recently diagnosed with epithelial ovarian cancer (EOC). Between 1 July 2013 and 30 June 2015 women newly diagnosed with EOC were recruited through six sites in East Anglia, UK into the Genetic Testing in Epithelial Ovarian Cancer (GTEOC) study. Eligibility was irrespective of patient age and family history of cancer. The psychosocial arm of the study used self-report, psychometrically validated questionnaires (Depression Anxiety and Stress Scale (DASS-21); Impact of Event Scale (IES)) and cost analysis was performed. 232 women were recruited and 18 mutations were detected (12 in BRCA1, 6 in BRCA2), giving a mutation yield of 8%, which increased to 12% in unselected women aged <70 years (17/146) but was only 1% in unselected women aged ≥70 years (1/86). IES and DASS-21 scores in response to genetic testing were significantly lower than equivalent scores in response to cancer diagnosis (p<0.001). Correlation tests indicated that although older age is a protective factor against any traumatic impacts of genetic testing, no significant correlation exists between age and distress outcomes. The mutation yield in unselected women diagnosed with EOC from a heterogeneous population with no founder mutations was 8% in all ages and 12% in women under 70. Unselected genetic testing in women with EOC was acceptable to patients and is potentially less resource-intensive than current standard practice. 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/

Influence of Honey Bee Genotype and Wintering Method on Wintering Performance of Varroa destructor (Parasitiformes: Varroidae)-Infected Honey Bee (Hymenoptera: Apidae) Colonies in a Northern Climate.

PubMed

Bahreini, Rassol; Currie, Robert W

2015-08-01

The objective of this study was to assess the effectiveness of a cooperative breeding program designed to enhance winter survival of honey bees (Apis mellifera L.) when exposed to high levels of varroa (Varroa destructor Anderson and Trueman) in outdoor-wintered and indoor-wintered colonies. Half of the colonies from selected and unselected stocks were randomly assigned to be treated with late autumn oxalic acid treatment or to be left untreated. Colonies were then randomly assigned to be wintered either indoors (n = 37) or outdoors (n = 40). Late autumn treatment with oxalic acid did not improve wintering performance. However, genotype of bees affected colony survival and the proportion of commercially viable colonies in spring, as indicated by greater rates of colony survival and commercially viable colonies for selected stock (43% survived and 33% were viable) in comparison to unselected stock (19% survived and 9% were viable) across all treatment groups. Indoor wintering improved spring bee population score, proportion of colonies surviving, and proportion of commercially viable colonies relative to outdoor wintering (73% of selected stock and 41% of unselected stock survived during indoor wintering). Selected stock showed better "tolerance" to varroa as the selected stock also maintained higher bee populations relative to unselected stock. However, there was no evidence of "resistance" in selected colonies (reduced mite densities). Collectively, this experiment showed that breeding can improve tolerance to varroa and this can help minimize colony loss through winter and improve colony wintering performance. Overall, colony wintering success of both genotypes of bees was better when colonies were wintered indoors than when colonies were wintered outdoors. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Significant prevalence of sickle cell disease in Southwest Germany: results from a birth cohort study indicate the necessity for newborn screening.

PubMed

Kunz, Joachim B; Awad, Saida; Happich, Margit; Muckenthaler, Lena; Lindner, Martin; Gramer, Gwendolyn; Okun, Jürgen G; Hoffmann, Georg F; Bruckner, Thomas; Muckenthaler, Martina U; Kulozik, Andreas E

2016-02-01

Children with sickle cell disease (SCD) benefit from newborn screening, because life-threatening complications can be prevented by pre-symptomatic diagnosis. In Germany, the immigration of people from endemic countries is steadily growing. Comprehensive data about the epidemiology and prevalence of SCD in Germany are however lacking, and SCD is not included in the national newborn screening program. We provide data on the prevalence of SCD in a population from both urban and rural areas in Southwest Germany. Anonymized dried blood spots from 37,838 unselected newborns were analyzed by allele-specific PCR for the HbS mutation. Samples tested positive were subjected to Sanger sequencing of the entire β-globin coding sequence firstly to validate the screening and secondly to identify compound heterozygous SCD patients with other mutations of the β-globin gene. We identified 83 carriers of the sickle cell trait, three compound heterozygous SCD patients (two with sickle cell-β-thalassemia, one with sickle cell-Hb Tianshui) but no homozygous SCD patients. The novel molecular method and strategy for newborn screening for SCD presented here compares favorably in terms of sensitivity (1.0 for homozygous HbS, 0.996 for heterozygous HbS), specificity (0.996), practicability, and costs with conventional biochemical screening. Our results demonstrate a significant prevalence of SCD of approximately 1:12,000 in an unselected urban and rural population in Southwest Germany. Together with previously published even higher results from exclusively urban populations in Berlin and Hamburg, our data provide the basis for the decision on a newborn screening program for SCD in Germany.

Deficit in automatic sound-change detection may underlie some music perception deficits after acute hemispheric stroke.

PubMed

Kohlmetz, C; Altenmüller, E; Schuppert, M; Wieringa, B M; Münte, T F

2001-01-01

Music perception deficits following acute neurological damage are thought to be rare. By a newly devised test battery of music-perception skills, however, we were able to identify among a group of 12 patients with acute hemispheric stroke six patients with music perception deficits (amusia) while six others had no such deficits. In addition we recorded event-related brain potentials (ERPs) in a passive listening task with frequent standard and infrequent pitch deviants designed to elicit the mismatch negativity (MMN). The MMN in the patients with amusia was grossly reduced, while the non-amusic patients and control subjects had MMNs of equal size. These data show that amusia is quite common in unselected stroke patients. The MMN reduction suggests that amusia is related to unspecific automatic stimulus classification deficits in these patients.

Mathematics anxiety among talented students.

PubMed

Lupkowski, A E; Schumacker, R E

1991-12-01

In order to test the assumption that mathematically talented students show little mathematics anxiety, students participating in an early entrance to college program for talented students were asked to complete the Mathematics Anxiety Rating Scale. Results indicated that these talented students were less math anxious than most unselected college students. However, they were more math anxious than a group of college students majoring in physics. Females in the study showed a tendency to be more math anxious than males (d=-.32), although this finding was not significant. No relationship between level of mathematics anxiety and grades or math anxiety and Scholastic Aptitude Test - Mathematics scores was found for the group of subjects. However, when those relationships were examined for males alone, higher verbal scores and higher grades were associated with lower levels of mathematics anxiety. These relationships were not evident for females.

Temporal trends in sperm count: a systematic review and meta-regression analysis.

PubMed

Levine, Hagai; Jørgensen, Niels; Martino-Andrade, Anderson; Mendiola, Jaime; Weksler-Derri, Dan; Mindlis, Irina; Pinotti, Rachel; Swan, Shanna H

2017-11-01

Reported declines in sperm counts remain controversial today and recent trends are unknown. A definitive meta-analysis is critical given the predictive value of sperm count for fertility, morbidity and mortality. To provide a systematic review and meta-regression analysis of recent trends in sperm counts as measured by sperm concentration (SC) and total sperm count (TSC), and their modification by fertility and geographic group. PubMed/MEDLINE and EMBASE were searched for English language studies of human SC published in 1981-2013. Following a predefined protocol 7518 abstracts were screened and 2510 full articles reporting primary data on SC were reviewed. A total of 244 estimates of SC and TSC from 185 studies of 42 935 men who provided semen samples in 1973-2011 were extracted for meta-regression analysis, as well as information on years of sample collection and covariates [fertility group ('Unselected by fertility' versus 'Fertile'), geographic group ('Western', including North America, Europe Australia and New Zealand versus 'Other', including South America, Asia and Africa), age, ejaculation abstinence time, semen collection method, method of measuring SC and semen volume, exclusion criteria and indicators of completeness of covariate data]. The slopes of SC and TSC were estimated as functions of sample collection year using both simple linear regression and weighted meta-regression models and the latter were adjusted for pre-determined covariates and modification by fertility and geographic group. Assumptions were examined using multiple sensitivity analyses and nonlinear models. SC declined significantly between 1973 and 2011 (slope in unadjusted simple regression models -0.70 million/ml/year; 95% CI: -0.72 to -0.69; P < 0.001; slope in adjusted meta-regression models = -0.64; -1.06 to -0.22; P = 0.003). The slopes in the meta-regression model were modified by fertility (P for interaction = 0.064) and geographic group (P for interaction = 0.027). There was a significant decline in SC between 1973 and 2011 among Unselected Western (-1.38; -2.02 to -0.74; P < 0.001) and among Fertile Western (-0.68; -1.31 to -0.05; P = 0.033), while no significant trends were seen among Unselected Other and Fertile Other. Among Unselected Western studies, the mean SC declined, on average, 1.4% per year with an overall decline of 52.4% between 1973 and 2011. Trends for TSC and SC were similar, with a steep decline among Unselected Western (-5.33 million/year, -7.56 to -3.11; P < 0.001), corresponding to an average decline in mean TSC of 1.6% per year and overall decline of 59.3%. Results changed minimally in multiple sensitivity analyses, and there was no statistical support for the use of a nonlinear model. In a model restricted to data post-1995, the slope both for SC and TSC among Unselected Western was similar to that for the entire period (-2.06 million/ml, -3.38 to -0.74; P = 0.004 and -8.12 million, -13.73 to -2.51, P = 0.006, respectively). This comprehensive meta-regression analysis reports a significant decline in sperm counts (as measured by SC and TSC) between 1973 and 2011, driven by a 50-60% decline among men unselected by fertility from North America, Europe, Australia and New Zealand. Because of the significant public health implications of these results, research on the causes of this continuing decline is urgently needed. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Item Selection, Evaluation, and Simple Structure in Personality Data

PubMed Central

Pettersson, Erik; Turkheimer, Eric

2010-01-01

We report an investigation of the genesis and interpretation of simple structure in personality data using two very different self-reported data sets. The first consists of a set of relatively unselected lexical descriptors, whereas the second is based on responses to a carefully constructed instrument. In both data sets, we explore the degree of simple structure by comparing factor solutions to solutions from simulated data constructed to have either strong or weak simple structure. The analysis demonstrates that there is little evidence of simple structure in the unselected items, and a moderate degree among the selected items. In both instruments, however, much of the simple structure that could be observed originated in a strong dimension of positive vs. negative evaluation. PMID:20694168

Spatial working memory function in twins with schizophrenia and bipolar disorder.

PubMed

Pirkola, Tiia; Tuulio-Henriksson, Annamari; Glahn, David; Kieseppä, Tuula; Haukka, Jari; Kaprio, Jaakko; Lönnqvist, Jouko; Cannon, Tyrone D

2005-12-15

Family studies are in conflict as to whether schizophrenia and bipolar disorder have independent genetic etiologies. Given the relatively low prevalence (approximately 1%) of these disorders, the use of quantitative endophenotypic markers of genetic liability might provide a more sensitive strategy for evaluating their genetic overlap. We have previously demonstrated that spatial working memory deficits increase in a dose-dependent fashion with increasing genetic proximity to a proband among the unaffected co-twins of schizophrenic patients. Here, we evaluated whether such deficits might also mark genetic susceptibility to bipolar disorder. The Wechsler Memory Scale-Revised Visual Memory Span and Digit Span subtests were administered to 46 schizophrenic patients, 32 of their unaffected co-twins, 22 bipolar patients, 16 of their unaffected co-twins, and 100 control twins, representing unselectively nationwide twin samples. Schizophrenic patients and their unaffected co-twins performed significantly worse than control subjects on the spatial working memory task, whereas only the schizophrenic patients performed significantly below the control subjects on the verbal working memory task. Neither bipolar patients nor their unaffected co-twins differed from control subjects on these measures. Our findings support the hypothesis that impairment in spatial working memory might effectively reflect an expression of genetic liability to schizophrenia but less clearly to bipolar disorder.

The long-term outcome of delinquent children: a 30-year follow-up study.

PubMed

Remschmidt, Helmut; Walter, Reinhard

2010-05-01

This study reports the results of a longitudinal study of unselected samples of German delinquent children, stratified by frequency of offences recorded before and after the age of criminal responsibility (14 years). A total of 256 young adults (mean age, 22 years), juvenile offenders and control non-offenders, were assessed using the following: a standardized interview regarding family, child development and life history; a multidimensional personality inventory (the Freiburg Personality Inventory, FPI); a version of the Wechsler Adult Intelligence Scale; a self-report questionnaire on the delinquency for which the subject was not apprehended during childhood; and a questionnaire concerning parental child-rearing style. The subsequent criminal records of subjects were followed over the next 20 years. It was possible to define three outcome groups (non-offenders, persisters and desisters), which differed in many respects. The outcome was significantly predicted by several variables. Psychosocial risk variables were the most effective predictors, followed by personality variables and childhood delinquency for which the subject had not been apprehended. The distinction between early-onset and late-onset delinquency as a predictor of adult criminality proved valid only if non-apprehended childhood offending was taken into account. The implications of the study for preventive intervention are discussed.

Mortality of subjects with mood disorders in the Lundby community cohort: a follow-up over 50 years.

PubMed

Mattisson, C; Bogren, M; Brådvik, L; Horstmann, V

2015-06-01

To compare causes of death and mortality among subjects with and without mood disorder in the Lundby Cohort and to analyse additional mental disorders as risk factors for mortality in subjects with mood disorders. The Lundby study is a longitudinal study that investigated mental health in an unselected population. The study commenced in 1947; the population was further investigated in 1957, 1972, and 1997. Experienced psychiatrists performed semi-structured diagnostic interviews, and best estimate consensus diagnoses of mental disorders were assessed at each field investigation. Subjects with mood disorder (n=508, 195 males, 313 females) were identified until 1997. Causes and dates of death between 1947 and 2011 were obtained from the Swedish cause of death register and were compared between subjects diagnosed with mood disorder and other participants. Mortality was compared between those with mood disorders and the remaining cohort with Cox regression analyses. Other mental disorders were considered as risk factors for death for subjects with mood disorders. The hazard ratio for mortality in mood disorders was HR=1.18. However, the mortality was elevated only for males, HR=1.5. Comorbid anxiety disorders, organic disorders, dementia and psychotic disorders were significant risk factors for death. A total of 6.3% of the participants with mood disorder and 1.2% of the remaining participants committed suicide. As expected, the suicide rate was higher among participants with mood disorders. Only males with mood disorders had elevated mortality. The impact on mortality from other mental disorders seems to vary between the genders. Copyright © 2015 Elsevier B.V. All rights reserved.

Hyperventilation syndrome in adolescents with and without asthma.

PubMed

D'Alba, Irene; Carloni, Ines; Ferrante, Anna Lisa; Gesuita, Rosaria; Palazzi, Maria Laura; de Benedictis, Fernando Maria

2015-12-01

Data on the prevalence of hyperventilation syndrome (HVS) in adolescents are scanty. To determine the prevalence of HVS in a population of adolescents with and without asthma, and to verify whether HVS was related to asthma activity. A population of adolescents was asked to self-complete a questionnaire, including the Nijmegen questionnaire to assess HVS, and a standardized asthma questionnaire. Seven hundred and sixty questionnaires were suitable for analysis. One hundred and twenty subjects (15.8%) were classified as asthmatic. Forty-seven subjects (6.2%) had a Nijmegen score ≥ 23, which was suggestive of HVS. Symptoms indicative of HVS were ten times more common in subjects with asthma (25%) than in those without asthma (2.5%). Nijmegen score was significantly higher in subjects with lifetime asthma (P < 0.001), current episodic asthma (P < 0.05) and current active asthma (P < 0.001) than in those with no asthma. In the whole population, girls presented HVS more frequently than boys (P < 0.001). There was a significant effect of gender (females, OR 3.2) and status of asthma (lifetime asthma, OR 11.2; current episodic asthma, OR 8.9; current active asthma, OR 41.5) on the probability of suffering from HVS. The prevalence of symptoms indicative of HVS in an unselected population of adolescents was relatively high. Symptoms were more common in girls and in subjects with asthma, and there was a significant effect of asthma activity on the probability of suffering from HVS. Further studies need to be performed in order to validate a screening tool for HVS in both adolescents and asthmatic subjects. © 2014 Wiley Periodicals, Inc.

MLH1 Promoter Methylation Frequency in Colorectal Cancer Patients and Related Clinicopathological and Molecular Features

PubMed Central

Li, Xia; Yao, Xiaoping; Wang, Yibaina; Hu, Fulan; Wang, Fan; Jiang, Liying; Liu, Yupeng; Wang, Da; Sun, Guizhi; Zhao, Yashuang

2013-01-01

Purpose To describe the frequency of MLH1 promoter methylation in colorectal cancer (CRC); to explore the associations between MLH1 promoter methylation and clinicopathological and molecular factors using a systematic review and meta-analysis. Methods A literature search of the PubMed and Embase databases was conducted to identify relevant articles published up to September 7, 2012 that described the frequency of MLH1 promoter methylation or its associations with clinicopathological and molecular factors in CRC. The pooled frequency, odds ratio (OR) and 95% confidence intervals (95% CI) were calculated. Results The pooled frequency of MLH1 promoter methylation in unselected CRC was 20.3% (95% CI: 16.8–24.1%). They were 18.7% (95% CI: 14.7–23.6%) and 16.4% (95% CI: 11.9–22.0%) in sporadic and Lynch syndrome (LS) CRC, respectively. Significant associations were observed between MLH1 promoter methylation and gender (pooled OR = 1.641, 95% CI: 1.215–2.215; P = 0.001), tumor location (pooled OR = 3.804, 95% CI: 2.715–5.329; P<0.001), tumor differentiation (pooled OR = 2.131, 95% CI: 1.464–3.102; P<0.001), MSI (OR: 27.096, 95% CI: 13.717–53.526; P<0.001). Significant associations were also observed between MLH1 promoter methylation and MLH1 protein expression, BRAF mutation (OR = 14.919 (95% CI: 6.427–34.631; P<0.001) and 9.419 (95% CI: 2.613–33.953; P = 0.001), respectively). Conclusion The frequency of MLH1 promoter methylation in unselected CRC was 20.3%. They were 18.7% in sporadic CRC and 16.4% in LS CRC, respectively. MLH1 promoter methylation may be significantly associated with gender, tumor location, tumor differentiation, MSI, MLH1 protein expression, and BRAF mutation. PMID:23555617

Anti-tumour activity of platinum compounds in advanced prostate cancer-a systematic literature review.

PubMed

Hager, S; Ackermann, C J; Joerger, M; Gillessen, S; Omlin, A

2016-06-01

For men with advanced castration-resistant prostate cancer (CRPC), several treatment options are available, including androgen receptor (AR) pathway inhibitors (abiraterone acetate, enzalutamide), taxanes (docetaxel, cabazitaxel) and the radionuclide (radium-223). However, cross-resistance is a clinically relevant problem. Platinum compounds have been tested in a number of clinical trials in molecularly unselected prostate cancer patients. Advances in CRPC molecular profiling have shown that a significant proportion of patients harbour DNA repair defects, which may serve as predictive markers for sensitivity to platinum agents. To systematically identify and analyse clinical trials that have evaluated platinum agents in advanced prostate cancer patients. PubMed was searched to identify published clinical trials of platinum agents in advanced prostate cancer. The PRIMSA statement was followed for the systematic review process. Identified trials are analysed for study design, statistical plan, assessments of anti-tumour activity and the potential value of predictive biomarkers. A total of 163 references were identified by the literature search and 72 publications that met the selection criteria were included in this review; of these 33 used carboplatin, 27 cisplatin, 6 satraplatin, 4 oxaliplatin and 2 other platinum compounds. Overall, anti-tumour activity varies in the range of 10%-40% for objective response and 20%-70% for PSA decline ≥50%. Response seemed highest for the combinations of carboplatin with taxanes or oxaliplatin with gemcitabine. The interpretation of the clinical data is limited by differences in response criteria used and patient populations studied. Platinum compounds have moderate anti-tumour activity in molecularly unselected patients with advanced prostate cancer. Translational evidence of DNA repair deficiency should be leveraged in future studies to select prostate cancer patients most likely to benefit from platinum-based therapy. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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

Lentiviral-mediated genetic correction of hematopoietic and mesenchymal progenitor cells from Fanconi anemia patients.

PubMed

Jacome, Ariana; Navarro, Susana; Río, Paula; Yañez, Rosa M; González-Murillo, Africa; Lozano, M Luz; Lamana, Maria Luisa; Sevilla, Julian; Olive, Teresa; Diaz-Heredia, Cristina; Badell, Isabel; Estella, Jesus; Madero, Luis; Guenechea, Guillermo; Casado, José; Segovia, Jose C; Bueren, Juan A

2009-06-01

Previous clinical trials based on the genetic correction of purified CD34(+) cells with gamma-retroviral vectors have demonstrated clinical efficacy in different monogenic diseases, including X-linked severe combined immunodeficiency, adenosine deaminase deficient severe combined immunodeficiency and chronic granulomatous disease. Similar protocols, however, failed to engraft Fanconi anemia (FA) patients with genetically corrected cells. In this study, we first aimed to correlate the hematological status of 27 FA patients with CD34(+) cell values determined in their bone marrow (BM). Strikingly, no correlation between these parameters was observed, although good correlations were obtained when numbers of colony-forming cells (CFCs) were considered. Based on these results, and because purified FA CD34(+) cells might have suboptimal repopulating properties, we investigated the possibility of genetically correcting unselected BM samples from FA patients. Our data show that the lentiviral transduction of unselected FA BM cells mediates an efficient phenotypic correction of hematopoietic progenitor cells and also of CD34(-) mesenchymal stromal cells (MSCs), with a reported role in hematopoietic engraftment. Our results suggest that gene therapy protocols appropriate for the treatment of different monogenic diseases may not be adequate for stem cell diseases like FA. We propose a new approach for the gene therapy of FA based on the rapid transduction of unselected hematopoietic grafts with lentiviral vectors (LVs).

Lentiviral-mediated Genetic Correction of Hematopoietic and Mesenchymal Progenitor Cells From Fanconi Anemia Patients

PubMed Central

Jacome, Ariana; Navarro, Susana; Río, Paula; Yañez, Rosa M; González-Murillo, Africa; Luz Lozano, M; Lamana, Maria Luisa; Sevilla, Julian; Olive, Teresa; Diaz-Heredia, Cristina; Badell, Isabel; Estella, Jesus; Madero, Luis; Guenechea, Guillermo; Casado, José; Segovia, Jose C; Bueren, Juan A

2009-01-01

Previous clinical trials based on the genetic correction of purified CD34+ cells with γ-retroviral vectors have demonstrated clinical efficacy in different monogenic diseases, including X-linked severe combined immunodeficiency, adenosine deaminase deficient severe combined immunodeficiency and chronic granulomatous disease. Similar protocols, however, failed to engraft Fanconi anemia (FA) patients with genetically corrected cells. In this study, we first aimed to correlate the hematological status of 27 FA patients with CD34+ cell values determined in their bone marrow (BM). Strikingly, no correlation between these parameters was observed, although good correlations were obtained when numbers of colony-forming cells (CFCs) were considered. Based on these results, and because purified FA CD34+ cells might have suboptimal repopulating properties, we investigated the possibility of genetically correcting unselected BM samples from FA patients. Our data show that the lentiviral transduction of unselected FA BM cells mediates an efficient phenotypic correction of hematopoietic progenitor cells and also of CD34− mesenchymal stromal cells (MSCs), with a reported role in hematopoietic engraftment. Our results suggest that gene therapy protocols appropriate for the treatment of different monogenic diseases may not be adequate for stem cell diseases like FA. We propose a new approach for the gene therapy of FA based on the rapid transduction of unselected hematopoietic grafts with lentiviral vectors (LVs). PMID:19277017

Enhanced treatment of secondary municipal wastewater effluent: comparing (biological) filtration and ozonation in view of micropollutant removal, unselective effluent toxicity, and the potential for real-time control.

PubMed

Chys, Michael; Demeestere, Kristof; Ingabire, Ange Sabine; Dries, Jan; Van Langenhove, Herman; Van Hulle, Stijn W H

2017-07-01

Ozonation and three (biological) filtration techniques (trickling filtration (TF), slow sand filtration (SSF) and biological activated carbon (BAC) filtration) have been evaluated in different combinations as tertiary treatment for municipal wastewater effluent. The removal of 18 multi-class pharmaceuticals, as model trace organic contaminants (TrOCs), has been studied. (Biological) activated carbon filtration could reduce the amount of TrOCs significantly (>99%) but is cost-intensive for full-scale applications. Filtration techniques mainly depending on biodegradation mechanisms (TF and SSF) are found to be inefficient for TrOCs removal as a stand alone technique. Ozonation resulted in 90% removal of the total amount of quantified TrOCs, but a post-ozonation step is needed to cope with an increased unselective toxicity. SSF following ozonation showed to be the only technique able to reduce the unselective toxicity to the same level as before ozonation. In view of process control, innovative correlation models developed for the monitoring and control of TrOC removal during ozonation, are verified for their applicability during ozonation in combination with TF, SSF or BAC. Particularly for the poorly ozone reactive TrOCs, statistically significant models were obtained that correlate TrOC removal and reduction in UVA 254 as an online measured surrogate parameter.

Online attentional bias modification training targeting anxiety and depression in unselected adolescents: Short- and long-term effects of a randomized controlled trial.

PubMed

de Voogd, E L; Wiers, R W; Prins, P J M; de Jong, P J; Boendermaker, W J; Zwitser, R J; Salemink, E

2016-12-01

Based on information processing models of anxiety and depression, we investigated the efficacy of multiple sessions of online attentional bias modification training to reduce attentional bias and symptoms of anxiety and depression, and to increase emotional resilience in youth. Unselected adolescents (N = 340, age: 11-18 years) were randomly allocated to eight sessions of a dot-probe, or a visual search-based attentional training, or one of two corresponding placebo control conditions. Cognitive and emotional measures were assessed pre- and post-training; emotional outcome measures also at three, six and twelve months follow-up. Only visual search training enhanced attention for positive information, and this effect was stronger for participants who completed more training sessions. Symptoms of anxiety and depression reduced, whereas emotional resilience improved. However, these effects were not especially pronounced in the active conditions. Thus, this large-scale randomized controlled study provided no support for the efficacy of the current online attentional bias modification training as a preventive intervention to reduce symptoms of anxiety or depression or to increase emotional resilience in unselected adolescents. However, the absence of biased attention related to symptomatology at baseline, and the large drop-out rates at follow-up preclude strong conclusions. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Overexpression of epithelial cell adhesion molecule protein is associated with favorable prognosis in an unselected cohort of ovarian cancer patients.

PubMed

Battista, Marco Johannes; Cotarelo, Cristina; Jakobi, Sina; Steetskamp, Joscha; Makris, Georgios; Sicking, Isabel; Weyer, Veronika; Schmidt, Marcus

2014-07-01

The aim of this study was to evaluate the prognostic influence of epithelial cell adhesion molecule (EpCAM) in an unselected cohort of ovarian cancer (OC) patients. Expression of EpCAM was determined by immunohistochemistry in an unselected cohort of 117 patients with OC. Univariable and multivariable Cox regression analyses adjusted for age, tumor stage, histological grading, histological subtype, postoperative tumor burden and completeness of chemotherapy were performed in order to determine the prognostic influence of EpCAM. The Kaplan-Meier method is used to estimate survival rates. Univariable Cox regression analysis showed that overexpression of EpCAM is associated with favorable prognosis in terms of progression-free survival (PFS) (p = 0.011) and disease-specific survival (DSS) (p = 0.003). In multivariable Cox regression analysis, overexpression of EpCAM retains its significance independent of established prognostic factors for longer PFS [hazard ratios (HR) 0.408, 95 % confidence interval (CI) 0.197-0.846, p = 0.003] but not for PFS (HR 0.666, 95 % CI 0.366-1.212, p = 0.183). Kaplan-Meier plots demonstrate an influence on 5-year PFS rates (0 vs. 27.6 %, p = 0.048) and DSS rates (11.8 vs. 54.0 %, p = 0.018). These findings support the hypothesis that the expression of EpCAM is associated with favorable prognosis in OC.

Overall survival with crizotinib and next-generation ALK inhibitors in ALK-positive non-small-cell lung cancer (IFCT-1302 CLINALK): a French nationwide cohort retrospective study.

PubMed

Duruisseaux, Michaël; Besse, Benjamin; Cadranel, Jacques; Pérol, Maurice; Mennecier, Bertrand; Bigay-Game, Laurence; Descourt, Renaud; Dansin, Eric; Audigier-Valette, Clarisse; Moreau, Lionel; Hureaux, José; Veillon, Remi; Otto, Josiane; Madroszyk-Flandin, Anne; Cortot, Alexis; Guichard, François; Boudou-Rouquette, Pascaline; Langlais, Alexandra; Missy, Pascale; Morin, Franck; Moro-Sibilot, Denis

2017-03-28

Overall survival (OS) with the anaplastic lymphoma kinase (ALK) inhibitor (ALKi) crizotinib in a large population of unselected patients with ALK-positive non-small-cell lung cancer (NSCLC) is not documented. We sought to assess OS with crizotinib in unselected ALK-positive NSCLC patients and whether post-progression systemic treatments affect survival outcomes.ALK-positive NSCLC patients receiving crizotinib in French expanded access programs or as approved drug were enrolled. We collected clinical and survival data, RECIST-defined progressive disease (PD) and post-PD systemic treatment efficacy. We performed multivariable analysis of OS from crizotinib initiation and PD under crizotinib.At time of analysis, 209 (65.7%) of the 318 included patients had died. Median OS with crizotinib was 16.6 months. The line of crizotinib therapy did not impact survival outcomes. Of the 263 patients with PD, 105 received best supportive care, 74 subsequent drugs other than next-generation ALKi and 84 next-generation ALKi. Next-generation ALKi treatment correlated with better survival outcomes in multivariate analysis. These patients had a median post-PD survival of 25.0 months and median OS from metastatic disease diagnosis of 89.6 months.Unselected ALK-positive NSCLC patients achieve good survival outcomes with crizotinib therapy. Next-generation ALKi may provide survival improvement after PD under crizotinib.

Behavioral and Brain Measures of Phasic Alerting Effects on Visual Attention.

PubMed

Wiegand, Iris; Petersen, Anders; Finke, Kathrin; Bundesen, Claus; Lansner, Jon; Habekost, Thomas

2017-01-01

In the present study, we investigated effects of phasic alerting on visual attention in a partial report task, in which half of the displays were preceded by an auditory warning cue. Based on the computational Theory of Visual Attention (TVA), we estimated parameters of spatial and non-spatial aspects of visual attention and measured event-related lateralizations (ERLs) over visual processing areas. We found that the TVA parameter sensory effectiveness a , which is thought to reflect visual processing capacity, significantly increased with phasic alerting. By contrast, the distribution of visual processing resources according to task relevance and spatial position, as quantified in parameters top-down control α and spatial bias w index , was not modulated by phasic alerting. On the electrophysiological level, the latencies of ERLs in response to the task displays were reduced following the warning cue. These results suggest that phasic alerting facilitates visual processing in a general, unselective manner and that this effect originates in early stages of visual information processing.

The Wiley Protocol: an analysis of ethical issues.

PubMed

Rosenthal, M Sara

2008-01-01

: This review explores the ethical issues surrounding an unregulated protocol that is advertised to women through consumer books, the popular press, and the Internet, known as the Wiley Protocol. : A content analysis of relevant documents was conducted, followed by telephone interviews with investigators and former participants to verify facts. : The Wiley Protocol is an example of unregulated research involving potentially unsafe doses of bioidentical hormones applied to an unselected population of women. This protocol fails to use research ethics guidelines such as informed consent, investigator expertise, sound methodology, standardized data collection, and data safety monitoring. : Clinical ethics breaches include lack of full disclosure of risks, coercive influences, as well as misinformation about the study goals and safety. Breaches of professional ethics include conflicts of interest with respect to financial incentives, patient accrual, and inadequate standards of awareness and proficiency among participating investigators. It appears evident that the failure to regulate nutriceuticals and products of compounding pharmacy has provided the opportunity for these ethical violations.

Maximum unbiased validation (MUV) data sets for virtual screening based on PubChem bioactivity data.

PubMed

Rohrer, Sebastian G; Baumann, Knut

2009-02-01

Refined nearest neighbor analysis was recently introduced for the analysis of virtual screening benchmark data sets. It constitutes a technique from the field of spatial statistics and provides a mathematical framework for the nonparametric analysis of mapped point patterns. Here, refined nearest neighbor analysis is used to design benchmark data sets for virtual screening based on PubChem bioactivity data. A workflow is devised that purges data sets of compounds active against pharmaceutically relevant targets from unselective hits. Topological optimization using experimental design strategies monitored by refined nearest neighbor analysis functions is applied to generate corresponding data sets of actives and decoys that are unbiased with regard to analogue bias and artificial enrichment. These data sets provide a tool for Maximum Unbiased Validation (MUV) of virtual screening methods. The data sets and a software package implementing the MUV design workflow are freely available at http://www.pharmchem.tu-bs.de/lehre/baumann/MUV.html.

Immunophenotypic analysis of adult patients with T-cell lymphoblastic lymphoma treated with hyper-CVAD.

PubMed

Kato, Harumi; Yamamoto, Kazuhito; Kodaira, Takeshi; Higuchi, Yusuke; Yamamoto, Hideyuki; Saito, Toko; Taji, Hirofumi; Yatabe, Yasushi; Nakamura, Shigeo; Kinoshita, Tomohiro

2018-03-01

Immunophenotype is an important prognostic factor for childhood and adult T-cell acute lymphoblastic leukemia. However, immunophenotypic data from adult patients with T-cell lymphoblastic lymphoma (T-LBL) are scarcely available. Subjects were unselected adult patients with T-LBL who were treated with intensive chemotherapy. Immunophenotyping of tumor cells was performed according to standard techniques. A total of eight patients with a median age of 31 years were analyzed who received hyper-CVAD treatment for LBL. Immunophenotypic analysis showed that the most common tumor type was cortical T-cell type [early T (n = 2), cortical T (n = 4), and medullary T (n = 2)]. Two patients diagnosed with early T-cell type had early disease progression. Assessment of T-cell differentiation stages in malignant T lymphoblasts would be important in choosing treatment strategies for adult patients with T-LBL.

Association of Arrhythmia-Related Genetic Variants With Phenotypes Documented in Electronic Medical Records.

PubMed

Van Driest, Sara L; Wells, Quinn S; Stallings, Sarah; Bush, William S; Gordon, Adam; Nickerson, Deborah A; Kim, Jerry H; Crosslin, David R; Jarvik, Gail P; Carrell, David S; Ralston, James D; Larson, Eric B; Bielinski, Suzette J; Olson, Janet E; Ye, Zi; Kullo, Iftikhar J; Abul-Husn, Noura S; Scott, Stuart A; Bottinger, Erwin; Almoguera, Berta; Connolly, John; Chiavacci, Rosetta; Hakonarson, Hakon; Rasmussen-Torvik, Laura J; Pan, Vivian; Persell, Stephen D; Smith, Maureen; Chisholm, Rex L; Kitchner, Terrie E; He, Max M; Brilliant, Murray H; Wallace, John R; Doheny, Kimberly F; Shoemaker, M Benjamin; Li, Rongling; Manolio, Teri A; Callis, Thomas E; Macaya, Daniela; Williams, Marc S; Carey, David; Kapplinger, Jamie D; Ackerman, Michael J; Ritchie, Marylyn D; Denny, Joshua C; Roden, Dan M

2016-01-05

Large-scale DNA sequencing identifies incidental rare variants in established Mendelian disease genes, but the frequency of related clinical phenotypes in unselected patient populations is not well established. Phenotype data from electronic medical records (EMRs) may provide a resource to assess the clinical relevance of rare variants. To determine the clinical phenotypes from EMRs for individuals with variants designated as pathogenic by expert review in arrhythmia susceptibility genes. This prospective cohort study included 2022 individuals recruited for nonantiarrhythmic drug exposure phenotypes from October 5, 2012, to September 30, 2013, for the Electronic Medical Records and Genomics Network Pharmacogenomics project from 7 US academic medical centers. Variants in SCN5A and KCNH2, disease genes for long QT and Brugada syndromes, were assessed for potential pathogenicity by 3 laboratories with ion channel expertise and by comparison with the ClinVar database. Relevant phenotypes were determined from EMRs, with data available from 2002 (or earlier for some sites) through September 10, 2014. One or more variants designated as pathogenic in SCN5A or KCNH2. Arrhythmia or electrocardiographic (ECG) phenotypes defined by International Classification of Diseases, Ninth Revision (ICD-9) codes, ECG data, and manual EMR review. Among 2022 study participants (median age, 61 years [interquartile range, 56-65 years]; 1118 [55%] female; 1491 [74%] white), a total of 122 rare (minor allele frequency <0.5%) nonsynonymous and splice-site variants in 2 arrhythmia susceptibility genes were identified in 223 individuals (11% of the study cohort). Forty-two variants in 63 participants were designated potentially pathogenic by at least 1 laboratory or ClinVar, with low concordance across laboratories (Cohen κ = 0.26). An ICD-9 code for arrhythmia was found in 11 of 63 (17%) variant carriers vs 264 of 1959 (13%) of those without variants (difference, +4%; 95% CI, -5% to +13%; P = .35). In the 1270 (63%) with ECGs, corrected QT intervals were not different in variant carriers vs those without (median, 429 vs 439 milliseconds; difference, -10 milliseconds; 95% CI, -16 to +3 milliseconds; P = .17). After manual review, 22 of 63 participants (35%) with designated variants had any ECG or arrhythmia phenotype, and only 2 had corrected QT interval longer than 500 milliseconds. Among laboratories experienced in genetic testing for cardiac arrhythmia disorders, there was low concordance in designating SCN5A and KCNH2 variants as pathogenic. In an unselected population, the putatively pathogenic genetic variants were not associated with an abnormal phenotype. These findings raise questions about the implications of notifying patients of incidental genetic findings.

The influence of social environment in early life on the behavior, stress response, and reproductive system of adult male Norway rats selected for different attitudes to humans.

PubMed

Gulevich, R G; Shikhevich, S G; Konoshenko, M Yu; Kozhemyakina, R V; Herbeck, Yu E; Prasolova, L A; Oskina, I N; Plyusnina, I Z

2015-05-15

The influence of social disturbance in early life on behavior, response of blood corticosterone level to restraint stress, and endocrine and morphometric indices of the testes was studied in 2-month Norway rat males from three populations: not selected for behavior (unselected), selected for against aggression to humans (tame), and selected for increased aggression to humans (aggressive). The experimental social disturbance included early weaning, daily replacement of cagemates from days 19 to 25, and subsequent housing in twos till the age of 2months. The social disturbance increased the latent period of aggressive behavior in the social interaction test in unselected males and reduced relative testis weights in comparison to the corresponding control groups. In addition, experimental unselected rats had smaller diameters of seminiferous tubules and lower blood testosterone levels. In the experimental group, tame rats had lower basal corticosterone levels, and aggressive animals had lower hormone levels after restraint stress in comparison to the control. The results suggest that the selection in two directions for attitude to humans modifies the response of male rats to social disturbance in early life. In this regard, the selected rat populations may be viewed as a model for investigation of (1) neuroendocrinal mechanisms responsible for the manifestation of aggression and (2) interaction of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal systems in stress. Copyright © 2015 Elsevier Inc. All rights reserved.

Retrospective study evaluating the performance of a first-trimester combined screening for trisomy 21 in an Italian unselected population

PubMed Central

Padula, Francesco; Cignini, Pietro; Giannarelli, Diana; Brizzi, Cristiana; Coco, Claudio; D’Emidio, Laura; Giorgio, Elsa; Giorlandino, Maurizio; Mangiafico, Lucia; Mastrandrea, Marialuisa; Milite, Vincenzo; Mobili, Luisa; Nanni, Cinzia; Raffio, Raffaella; Taramanni, Cinzia; Vigna, Roberto; Mesoraca, Alvaro; Bizzoco, Domenico; Gabrielli, Ivan; Di Giacomo, Gianluca; Barone, Maria Antonietta; Cima, Antonella; Giorlandino, Francesca Romana; Emili, Sabrina; Cupellaro, Marina; Giorlandino, Claudio

2014-01-01

Objectives to assess the performance of a combined first-trimester screening for trisomy 21 in an unselected Italian population referred to a specialized private center for prenatal medicine. Methods a retrospective validation of first-trimester screening algorithms [risk calculation based on maternal age and nuchal translucency (NT) alone, maternal age and serum parameters (free β-hCG and PAPP-A) alone and a combination of both] for fetal aneuploidies evaluated in an unselected Italian population at Artemisia Fetal-Maternal Medical Centre in Rome. All measurements were performed between 11+0 and 13+6 weeks of gestation, between April 2007 and December 2008. Results of 3,610 single fetuses included in the study, we had a complete follow-up on 2,984. Fourteen of 17 cases of trisomy 21 were detected when a cut-off of 1:300 was applied [detection rate (DR) 82.4%, 95% confidence interval (CI) 64.2–100; false-positive rate (FPR) 4.7%, 95% CI 3.9–5.4; false-negative rate (FNR) 17.6%, 95% CI 0–35.8%]. Conclusion in our study population the detection rate for trisomy 21, using the combined risk calculation based on maternal age, fetal NT, maternal PAPP-A and free β-hCG levels, was superior to the application of either parameter alone. The algorithm has been validated for first trimester screening in the Italian population. PMID:26266002

Early cancer diagnoses through BRCA1/2 screening of unselected adult biobank participants

PubMed Central

Buchanan, Adam H; Manickam, Kandamurugu; Meyer, Michelle N; Wagner, Jennifer K; Hallquist, Miranda L G; Williams, Janet L; Rahm, Alanna Kulchak; Williams, Marc S; Chen, Zong-Ming E; Shah, Chaitali K; Garg, Tullika K; Lazzeri, Amanda L; Schwartz, Marci L B; Lindbuchler, D'Andra M; Fan, Audrey L; Leeming, Rosemary; Servano, Pedro O; Smith, Ashlee L; Vogel, Victor G; Abul-Husn, Noura S; Dewey, Frederick E; Lebo, Matthew S; Mason-Suares, Heather M; Ritchie, Marylyn D; Davis, F Daniel; Carey, David J; Feinberg, David T; Faucett, W Andrew; Ledbetter, David H; Murray, Michael F

2018-01-01

Purpose The clinical utility of screening unselected individuals for pathogenic BRCA1/2 variants has not been established. Data on cancer risk management behaviors and diagnoses of BRCA1/2-associated cancers can help inform assessments of clinical utility. Methods Whole-exome sequences of participants in the MyCode Community Health Initiative were reviewed for pathogenic/likely pathogenic BRCA1/2 variants. Clinically confirmed variants were disclosed to patient–participants and their clinicians. We queried patient–participants’ electronic health records for BRCA1/2-associated cancer diagnoses and risk management that occurred within 12 months after results disclosure, and calculated the percentage of patient–participants of eligible age who had begun risk management. Results Thirty-seven MyCode patient–participants were unaware of their pathogenic/likely pathogenic BRCA1/2 variant, had not had a BRCA1/2-associated cancer, and had 12 months of follow-up. Of the 33 who were of an age to begin BRCA1/2-associated risk management, 26 (79%) had performed at least one such procedure. Three were diagnosed with an early-stage, BRCA1/2-associated cancer—including a stage 1C fallopian tube cancer—via these procedures. Conclusion Screening for pathogenic BRCA1/2 variants among unselected individuals can lead to occult cancer detection shortly after disclosure. Comprehensive outcomes data generated within our learning healthcare system will aid in determining whether population-wide BRCA1/2 genomic screening programs offer clinical utility. PMID:29261187

Effect of Artificial Selection on Runs of Homozygosity in U.S. Holstein Cattle

PubMed Central

Kim, Eui-Soo; Cole, John B.; Huson, Heather; Wiggans, George R.; Van Tassell, Curtis P.; Crooker, Brian A.; Liu, George; Da, Yang; Sonstegard, Tad S.

2013-01-01

The intensive selection programs for milk made possible by mass artificial insemination increased the similarity among the genomes of North American (NA) Holsteins tremendously since the 1960s. This migration of elite alleles has caused certain regions of the genome to have runs of homozygosity (ROH) occasionally spanning millions of continuous base pairs at a specific locus. In this study, genome signatures of artificial selection in NA Holsteins born between 1953 and 2008 were identified by comparing changes in ROH between three distinct groups under different selective pressure for milk production. The ROH regions were also used to estimate the inbreeding coefficients. The comparisons of genomic autozygosity between groups selected or unselected since 1964 for milk production revealed significant differences with respect to overall ROH frequency and distribution. These results indicate selection has increased overall autozygosity across the genome, whereas the autozygosity in an unselected line has not changed significantly across most of the chromosomes. In addition, ROH distribution was more variable across the genomes of selected animals in comparison to a more even ROH distribution for unselected animals. Further analysis of genome-wide autozygosity changes and the association between traits and haplotypes identified more than 40 genomic regions under selection on several chromosomes (Chr) including Chr 2, 7, 16 and 20. Many of these selection signatures corresponded to quantitative trait loci for milk, fat, and protein yield previously found in contemporary Holsteins. PMID:24348915

Individual differences in circadian waveform of Siberian hamsters under multiple lighting conditions

PubMed Central

Evans, Jennifer A.; Elliott, Jeffrey A.; Gorman, Michael R.

2013-01-01

Because the circadian clock in the mammalian brain derives from a network of interacting cellular oscillators, characterizing the nature and bases of circadian coupling is fundamental to understanding how the pacemaker operates. Various phenomena involving plasticity in circadian waveform have been theorized to reflect changes in oscillator coupling; however, it remains unclear whether these different behavioral paradigms reference a unitary underlying process. To test if disparate coupling assays index a common mechanism, we examined whether there is co-variation among behavioral responses to various lighting conditions that produce changes in circadian waveform. Siberian hamsters, Phodopus sungorus, were transferred from long to short photoperiods to distinguish short photoperiod responders (SP-R) from non-responders (SP-NR). Short photoperiod chronotyped hamsters were subsequently transferred, along with unselected controls, to 24 h light:dark:light:dark cycles (LDLD) with dim nighttime illumination, a procedure that induces bifurcated entrainment. Under LDLD, SP-R hamsters were more likely to bifurcate their rhythms than SP-NR hamsters or unselected controls. After transfer from LDLD to constant dim light, SP-R hamsters were also more likely to become arrhythmic compared to SP-NR hamsters and unselected controls. In contrast, short photoperiod chronotype did not influence more transient changes in circadian waveform. The present data reveal a clear relationship in the plasticity of circadian waveform across three distinct lighting conditions, suggesting a common mechanism wherein individual differences reflect variation in circadian coupling. PMID:23010663

Humans identify negative (but not positive) arousal in silver fox vocalizations: implications for the adaptive value of interspecific eavesdropping.

PubMed

Filippi, Piera; Gogoleva, Svetlana S; Volodina, Elena V; Volodin, Ilya A; de Boer, Bart

2017-08-01

The ability to identify emotional arousal in heterospecific vocalizations may facilitate behaviors that increase survival opportunities. Crucially, this ability may orient inter-species interactions, particularly between humans and other species. Research shows that humans identify emotional arousal in vocalizations across multiple species, such as cats, dogs, and piglets. However, no previous study has addressed humans' ability to identify emotional arousal in silver foxes. Here, we adopted low- and high-arousal calls emitted by three strains of silver fox-Tame, Aggressive, and Unselected-in response to human approach. Tame and Aggressive foxes are genetically selected for friendly and attacking behaviors toward humans, respectively. Unselected foxes show aggressive and fearful behaviors toward humans. These three strains show similar levels of emotional arousal, but different levels of emotional valence in relation to humans. This emotional information is reflected in the acoustic features of the calls. Our data suggest that humans can identify high-arousal calls of Aggressive and Unselected foxes, but not of Tame foxes. Further analyses revealed that, although within each strain different acoustic parameters affect human accuracy in identifying high-arousal calls, spectral center of gravity, harmonic-to-noise ratio, and F0 best predict humans' ability to discriminate high-arousal calls across all strains. Furthermore, we identified in spectral center of gravity and F0 the best predictors for humans' absolute ratings of arousal in each call. Implications for research on the adaptive value of inter-specific eavesdropping are discussed.

Clinicomanometric factors associated with clinically relevant esophagogastric junction outflow obstruction from the Sandhill high-resolution manometry system.

PubMed

Song, B G; Min, Y W; Lee, H; Min, B-H; Lee, J H; Rhee, P-L; Kim, J J

2018-03-01

Integrated relaxation pressure (IRP) is a key metric for diagnosing esophagogastric junction outflow obstruction (EGJOO). However, its normal value might be different according to the manufacturer of high-resolution manometry (HRM). This study aimed to investigate optimal value of IRP for diagnosing EGJOO in Sandhill HRM and to find clinicomanometric variables to segregate clinically relevant EGJOO. We analyzed 262 consecutive subjects who underwent HRM between June 2011 and December 2016 showing elevated median IRP (> 15 mm Hg) but did not satisfy criteria for achalasia. Clinically relevant subjects were defined as follows: (i) subsequent HRM met achalasia criteria during follow-up (early achalasia); (ii) Eckardt score was decreased at least two points without exceeding a score of 3 after pneumatic dilatation (variant achalasia); and (iii) significant passage disturbance on esophagogram without structural abnormality (possible achalasia). Seven subjects were clinically relevant, including two subjects with early achalasia, four subjects with variant achalasia, and one subject with possible achalasia. All clinically relevant subjects had IRP 20 mm Hg or above. Among subjects (n = 122) with IRP 20 mm Hg or more, clinically relevant group (n = 7) had significantly higher rate of dysphagia (100% vs 24.3%, P < .001) and compartmentalized pressurization (85.7% vs 21.7%, P = .001) compared to clinically non-relevant group (n = 115). Our results suggest that IRP of 20 mm Hg or higher could segregate clinically relevant subjects showing EGJOO in Sandhill HRM. Additionally, if subjects have both dysphagia and compartmentalized pressurization, careful follow-up is essential. © 2017 John Wiley & Sons Ltd.

Heart rate variability and turbulence in hyperthyroidism before, during, and after treatment.

PubMed

Osman, Faizel; Franklyn, Jayne A; Daykin, Jacqueline; Chowdhary, Saqib; Holder, Roger L; Sheppard, Michael C; Gammage, Michael D

2004-08-15

Patients with subclinical and treated overt hyperthyroidism have an excess vascular mortality rate. Several symptoms and signs in overt hyperthyroidism suggest abnormality of cardiac autonomic function that may account in part for this excess mortality rate, but few studies have examined cardiac autonomic function in untreated and treated hyperthyroidism. We assessed heart rate turbulence (HRT) and time-domain parameters of heart rate variability in a large, unselected cohort of patients with overt hyperthyroidism referred to our thyroid clinic (n = 259) and compared findings with a group of normal subjects with euthyroidism (n = 440). These measures were also evaluated during antithyroid therapy (when serum-free thyroxine and triiodothyronine concentrations returned to normal but thyrotropin remained suppressed (i.e., subclinical hyperthyroidism, n = 110) and when subjects were rendered clinically and biochemically euthyroid (normal serum thyrotropin, free thyroxine and triiodothyronine concentrations, n = 219). We found that overall measures of heart rate variability and those specific for cardiac vagal modulation were attenuated in patients with overt hyperthyroidism compared with normal subjects; measurements of overall heart rate variability remained low in those with low levels of serum thyrotropin but returned to normal in patients with biochemical euthyroidism. Measurements of HRT (onset and slope) were also decreased in patients with overt hyperthyroidism, but HRT slope returned to normal values with antithyroid treatment. This study is the first to evaluate HRT in overt and treated hyperthyroidism.

Body dysmorphic concerns, social adaptation, and motivation for psychotherapeutic support in dermatological outpatients.

PubMed

Ritter, Viktoria; Fluhr, Joachim W; Schliemann-Willers, Sibylle; Elsner, Peter; Strauß, Bernhard; Stangier, Ulrich

2016-09-01

Dermatologists are increasingly confronted with patients affected by body dysmorphic disorder (BDD). BDD is characterized by excessive preoccupation with one or more perceived defect(s) or flaw(s) in physical appearance which are not observable or appear slight to others. So far, there have been only few studies examining the prevalence of BDD in dermatological outpatients. In addition, the need for psychotherapeutic support in dermatological outpatients with body dysmorphic concerns has not yet been systematically examined. The objective of the present study was therefore to investigate the frequency of body dysmorphic concerns as well as social adaptation and the need for psychotherapeutic support in the aforementioned patient group. A total of 252 dermatological outpatients seen at a German university hospital were consecutively enrolled, and examined using the Dysmorphic Concerns Questionnaire, the Social Adaptation Self-Evaluation Scale, and the German version of the University of Rhode Island Change Assessment Scale. 7.9 % of all outpatients (unselected sample) showed positive test results, suggesting clinically relevant body dysmorphic concerns. Patients with clinically relevant body dysmorphic concerns exhibited poor social adaptation. Contrary to expectations, these patients revealed a high motivation for change, indicating the necessity for psychotherapeutic support. Our findings confirm previous prevalence rates of BDD in dermatological outpatients, and highlight the need for providing psychotherapeutic support to dermatological patients. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

The role of KRAS rs61764370 in invasive epithelial ovarian cancer: implications for clinical testing

PubMed Central

Pharoah, Paul D. P.; Palmieri, Rachel T.; Ramus, Susan J.; Gayther, Simon A.; Andrulis, Irene L.; Anton-Culver, Hoda; Antonenkova, Natalia; Antoniou, Antonis C.; Beattie, Mary S.; Beckmann, Matthias W.; Birrer, Michael J.; Bogdanova, Natalia; Bolton, Kelly L.; Brewster, Wendy; Brooks-Wilson, Angela; Brown, Robert; Butzow, Ralf; Caldes, Trinidad; Caligo, Maria Adelaide; Campbell, Ian; Chang-Claude, Jenny; Chen, Y. Ann; Chenevix-Trench, Georgia; Cook, Linda S.; Couch, Fergus J.; Cramer, Daniel W.; Cunningham, Julie M.; Despierre, Evelyn; Doherty, Jennifer A.; Dörk, Thilo; Dürst, Matthias; Eccles, Diana M.; Ekici, Arif B.; Fasching, Peter A.; de Fazio, Anna; Fenstermacher, David A.; Flanagan, James M.; Fridley, Brooke L.; Friedman, Eitan; Gao, Bo; Gentry-Maharaj, Aleksandra; Godwin, Andrew K.; Goode, Ellen L.; Goodman, Marc T.; Gross, Jenny; Hansen, Thomas V. O.; Harnett, Paul; Heikkinen, Tuomas; Hein, Rebecca; Høgdall, Claus; Høgdall, Estrid; Iversen, Edwin S.; Jakubowska, Anna; Johnatty, Sharon E.; Karlan, Beth Y.; Kauff, Noah D.; Kaye, Stanley B.; Kelemen, Linda E.; Kiemeney, Lambertus A.; Kjaer, Susanne Krüger; Lambrechts, Diether; LaPolla, James P.; Lázaro, Conxi; Le, Nhu D.; Leminen, Arto; Leunen, Karin; Levine, Douglas A.; Lu, Yi; Lundvall, Lene; Macgregor, Stuart; Marees, Tamara; Massuger, Leon F.; McLaughlin, John R.; Menon, Usha; Montagna, Marco; Moysich, Kirsten B.; Narod, Steven A.; Nathanson, Katherine L.; Nedergaard, Lotte; Ness, Roberta B.; Nevanlinna, Heli; Nickels, Stefan; Osorio, Ana; Paul, Jim; Pearce, Celeste Leigh; Phelan, Catherine M.; Pike, Malcolm C.; Radice, Paolo; Rossing, Mary Anne; Schildkraut, Joellen M.; Sellers, Thomas A.; Singer, Christian F.; Song, Honglin; Stram, Daniel O.; Sutphen, Rebecca; Terry, Kathryn L.; Tsai, Ya-Yu; van Altena, Anne M.; Vergote, Ignace; Vierkant, Robert A.; Vitonis, Allison F.; Walsh, Christine; Wang-Gohrke, Shan; Wappenschmidt, Barbara; Wu, Anna H.; Ziogas, Argyrios; Berchuck, Andrew; Risch, Harvey A.

2011-01-01

Purpose An assay for the single nucleotide polymorphism (SNP) rs61764370 has recently been commercially marketed as a clinical test to aid ovarian cancer risk evaluation in women with family histories of the disease. rs67164370 is in a 3′UTR miRNA binding site of the KRAS oncogene, and is a candidate for epithelial ovarian cancer (EOC) susceptibility. However, only one published paper, analyzing fewer than 1,000 subjects in total, has examined this association. Experimental Design Risk association was evaluated in 8,669 cases of invasive EOC and 10,012 controls from nineteen studies participating in the Ovarian Cancer Association Consortium, and in 683 cases and 2,044 controls carrying BRCA1 mutations from studies in the Consortium of Investigators of Modifiers of BRCA1/2. Prognosis association was also examined in a subset of five studies with progression-free survival data and eighteen studies with all-cause mortality data. Results No evidence of association was observed between genotype and risk of unselected EOC (odds ratio (OR)=1.02, 95% confidence interval (CI)=0.95-1.10), serous EOC (OR=1.08, 95%CI=0.98-1.18), familial EOC (OR=1.09, 95%CI=0.78-1.54), or among women carrying deleterious mutations in BRCA1 (OR=1.09, 95%CI=0.88-1.36). There was little evidence for association with survival time among unselected cases (hazard ratio (HR)=1.10, 95%CI=0.99-1.22), among serous cases (HR=1.12, 95%CI=0.99-1.28), or with progression-free survival in 540 cases treated with carboplatin and paclitaxel (HR=1.18, 95%CI=0.93-1.52). Conclusions These data exclude the possibility of an association between rs61764370 and a clinically significant risk of ovarian cancer or of familial ovarian cancer. Use of this SNP for ovarian cancer clinical risk prediction therefore appears unwarranted. PMID:21385923

The effect of queen pheromone status on Varroa mite removal from honey bee colonies with different grooming ability.

PubMed

Bahreini, Rassol; Currie, Robert W

2015-07-01

The objective of this study was to assess the effects of honey bees (Apis mellifera L.) with different grooming ability and queen pheromone status on mortality rates of Varroa mites (Varroa destructor Anderson and Trueman), mite damage, and mortality rates of honey bees. Twenty-four small queenless colonies containing either stock selected for high rates of mite removal (n = 12) or unselected stock (n = 12) were maintained under constant darkness at 5 °C. Colonies were randomly assigned to be treated with one of three queen pheromone status treatments: (1) caged, mated queen, (2) a synthetic queen mandibular pheromone lure (QMP), or (3) queenless with no queen substitute. The results showed overall mite mortality rate was greater in stock selected for grooming than in unselected stock. There was a short term transitory increase in bee mortality rates in selected stock when compared to unselected stock. The presence of queen pheromone from either caged, mated queens or QMP enhanced mite removal from clusters of bees relative to queenless colonies over short periods of time and increased the variation in mite mortality over time relative to colonies without queen pheromone, but did not affect the proportion of damaged mites. The effects of source of bees on mite damage varied with time but damage to mites was not reliably related to mite mortality. In conclusion, this study showed differential mite removal of different stocks was possible under low temperature. Queen status should be considered when designing experiments using bioassays for grooming response.

Strengths and weaknesses of 'real-world' studies involving non-vitamin K antagonist oral anticoagulants.

PubMed

Camm, A John; Fox, Keith A A

2018-01-01

Randomised controlled trials (RCTs) provide the reference standard for comparing the efficacy of one therapy or intervention with another. However, RCTs have restrictive inclusion and exclusion criteria; thus, they are not fully representative of an unselected real-world population. Real-world evidence (RWE) studies encompass a wide range of research methodologies and data sources and can be broadly categorised as non-interventional studies, patient registries, claims database studies, patient surveys and electronic health record studies. If appropriately designed, RWE studies include a patient population that is far more representative of unselected patient populations than those of RCTs, but they do not provide a robust basis for comparing treatment strategies. RWE studies can have very large sample sizes, can provide information on treatments in patient groups that are usually excluded from RCTs, are generally less expensive and quicker than RCTs, and can assess a broad range of outcomes. Limitations of RWE studies can include low internal validity, lack of quality control surrounding data collection and susceptibility to multiple sources of bias for comparing outcomes. RWE studies can complement the findings from RCTs by providing valuable information on treatment practices and patient characteristics among unselected patients. This information is necessary to guide treatment decisions and for reimbursement and payment decisions. RWE studies have been extensively applied in the postmarketing approval assessment of non-vitamin K antagonist oral anticoagulants since 2010. However, the benefits, costs, limitations and methodological challenges associated with the different types of RWE must be considered carefully when interpreting the findings.

Strengths and weaknesses of ‘real-world’ studies involving non-vitamin K antagonist oral anticoagulants

PubMed Central

Camm, A John; Fox, Keith A A

2018-01-01

Randomised controlled trials (RCTs) provide the reference standard for comparing the efficacy of one therapy or intervention with another. However, RCTs have restrictive inclusion and exclusion criteria; thus, they are not fully representative of an unselected real-world population. Real-world evidence (RWE) studies encompass a wide range of research methodologies and data sources and can be broadly categorised as non-interventional studies, patient registries, claims database studies, patient surveys and electronic health record studies. If appropriately designed, RWE studies include a patient population that is far more representative of unselected patient populations than those of RCTs, but they do not provide a robust basis for comparing treatment strategies. RWE studies can have very large sample sizes, can provide information on treatments in patient groups that are usually excluded from RCTs, are generally less expensive and quicker than RCTs, and can assess a broad range of outcomes. Limitations of RWE studies can include low internal validity, lack of quality control surrounding data collection and susceptibility to multiple sources of bias for comparing outcomes. RWE studies can complement the findings from RCTs by providing valuable information on treatment practices and patient characteristics among unselected patients. This information is necessary to guide treatment decisions and for reimbursement and payment decisions. RWE studies have been extensively applied in the postmarketing approval assessment of non-vitamin K antagonist oral anticoagulants since 2010. However, the benefits, costs, limitations and methodological challenges associated with the different types of RWE must be considered carefully when interpreting the findings. PMID:29713485

Ultrasonographically detected gallbladder polyps: A reason for concern? A seven-year follow-up study

PubMed Central

Kratzer, Wolfgang; Haenle, Mark M; Voegtle, Andrea; Mason, Richard A; Akinli, Atilla S; Hirschbuehl, Klaus; Schuler, Andreas; Kaechele, Volker

2008-01-01

Background The management of coincidental detected gallbladder polyps (GP) is still nebulous. There are few published data regarding their long-term growth. Objective of the present study was to investigate the prevalence and growth of gallbladder polyps in a survey of unselected subjects from the general population of a complete rural community. Methods A total of 2,415 subjects (1,261 women; 1,154 men) underwent ultrasound examination of the gallbladder, in November 1996 as part of a prospective study. Subjects in whom GP were detected at the initial survey underwent follow-up ultrasound examinations after 30 and 84 months. Results At the initial survey gallbladder polyps were detected in 34 subjects (1.4%; females: 1.1%, range 14 to 74 years; males: 1.7%, range 19 to 63 years). Median diameter was 5 ± 2.1 mm (range 2 to10 mm) at the initial survey, 5 mm ± 2.8 mm (range 2 to 12 mm) at 30 months and 4 ± 2.3 mm (range 2 to 9 mm) at 84 months. At the time of first follow-up no change in diameter was found in 81.0% (n = 17), reduction in diameter in 4.8% (n = 1) and increase in diameter in 14.3% (n = 3). At the time of second follow-up no increase in polyp diameter was found in 76.9% (n = 10) and reduction in diameter in 7.7% (n = 1). No evidence of malignant disease of the gallbladder was found. Conclusion Over a period of seven years little change was measured in the diameter of gallbladder polyps. There was no evidence of malignant disease of the gallbladder in any subject. PMID:18793401

Ultrasonographically detected gallbladder polyps: a reason for concern? A seven-year follow-up study.

PubMed

Kratzer, Wolfgang; Haenle, Mark M; Voegtle, Andrea; Mason, Richard A; Akinli, Atilla S; Hirschbuehl, Klaus; Schuler, Andreas; Kaechele, Volker

2008-09-15

The management of coincidental detected gallbladder polyps (GP) is still nebulous. There are few published data regarding their long-term growth. Objective of the present study was to investigate the prevalence and growth of gallbladder polyps in a survey of unselected subjects from the general population of a complete rural community. A total of 2,415 subjects (1,261 women; 1,154 men) underwent ultrasound examination of the gallbladder, in November 1996 as part of a prospective study. Subjects in whom GP were detected at the initial survey underwent follow-up ultrasound examinations after 30 and 84 months. At the initial survey gallbladder polyps were detected in 34 subjects (1.4%; females: 1.1%, range 14 to 74 years; males: 1.7%, range 19 to 63 years). Median diameter was 5 +/- 2.1 mm (range 2 to 10 mm) at the initial survey, 5 mm +/- 2.8 mm (range 2 to 12 mm) at 30 months and 4 +/- 2.3 mm (range 2 to 9 mm) at 84 months. At the time of first follow-up no change in diameter was found in 81.0% (n = 17), reduction in diameter in 4.8% (n = 1) and increase in diameter in 14.3% (n = 3). At the time of second follow-up no increase in polyp diameter was found in 76.9% (n = 10) and reduction in diameter in 7.7% (n = 1). No evidence of malignant disease of the gallbladder was found. Over a period of seven years little change was measured in the diameter of gallbladder polyps. There was no evidence of malignant disease of the gallbladder in any subject.

Specific IgG4 antibodies to cow's milk proteins in pediatric patients with eosinophilic esophagitis.

PubMed

Schuyler, Alexander J; Wilson, Jeffrey M; Tripathi, Anubha; Commins, Scott P; Ogbogu, Princess U; Kruzsewski, Patrice G; Barnes, Barrett H; McGowan, Emily C; Workman, Lisa J; Lidholm, Jonas; Rifas-Shiman, Sheryl L; Oken, Emily; Gold, Diane R; Platts-Mills, Thomas A E; Erwin, Elizabeth A

2018-04-18

Allergen-specific IgG 4 (sIgG 4 ) antibodies are often associated with tolerance, but sIgG 4 antibodies to causally relevant foods have been reported recently in adults with eosinophilic esophagitis (EoE). Prevalence and levels of food sIgG 4 are not well established in the general pediatric population. We sought to investigate serum food sIgG 4 with component diagnostics in children with EoE and children from an unselected birth cohort and to explore the effects of sex, age, and milk consumption on sIgG 4 levels. Sera from 71 pediatric patients with EoE and 210 early adolescent children from an unselected birth cohort (Project Viva) were assayed for sIgG 4 and specific IgE (sIgE) to major cow's milk (CM) proteins (α-lactalbumin, β-lactoglobulin, and caseins) and to wheat, soy, egg, and peanut proteins. In the EoE cohort high-titer sIgG 4 (≥10 μg/mL) to CM proteins was more common than in control sera and achieved odds ratios for EoE ranging from 5.5 to 8.4. sIgE levels to CM proteins were mostly 4 IU/mL or less in patients with EoE, such that sIgG 4 /sIgE ratios were often 10,000 or greater. When adjusted for age and milk consumption, high-titer sIgG 4 to CM proteins was strongly associated with EoE, with an odds ratio of greater than 20 to all 3 CM proteins in boys. sIgG 4 to CM proteins are common and high titer in children with EoE. Although it is not clear that this response is pathogenic, sIgG 4 levels imply that these antibodies are an important feature of the local immune response that gives rise to EoE. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Automated point-of-care testing for ABO agglutination test: proof of concept and validation.

PubMed

El Kenz, H; Corazza, F

2015-07-01

ABO-incompatible red blood cell transfusions still represent an important hazard in transfusion medicine. Therefore, some countries have introduced a systematic bedside ABO agglutination test checking that the right blood is given to the right patient. However, this strategy requires an extremely time-consuming learning programme and relies on a subjective interpretation of ABO test cards agglutination. We developed a prototype of a fully automated device performing the bedside agglutination test that could be completed by reading of a barcoded wristband. This POCT checks the ABO compatibility between the patient and the blood bag. Proof of concept and analytical validation of the prototype has been completed on 451 blood samples: 238 donor packed red blood cells, 137 consecutive unselected patients for whom a blood group determination had been ordered and on 76 patient samples selected with pathology that could possibly interfere with or impair performances of the assay. We observed 100% concordance for ABO blood groups between the POCT and the laboratory instrument. These preliminary results demonstrate the feasibility of ABO determination with a simple POCT device eliminating manipulation and subjective interpretation responsible for transfusion errors. This device should be linked to the blood bank system allowing all cross-check of the results. © 2015 International Society of Blood Transfusion.

Recovery after uncomplicated laparoscopic cholecystectomy.

PubMed

Bisgaard, Thue; Klarskov, Birthe; Kehlet, Henrik; Rosenberg, Jacob

2002-11-01

After laparoscopic cholecystectomy, the duration of convalescence is 2 to 3 weeks with an unclear pathogenesis. This study was undertaken to analyze postoperative recovery after uncomplicated elective laparoscopic cholecystectomy. Twenty-four consecutive unselected employed patients were followed up prospectively from 1 week before to 1 week after outpatient laparoscopic cholecystectomy. Daily computerized monitoring of physical motor activity and sleep duration and night sleep fragmentation (actigraphy), subjective sleep quality, pulmonary function, pain, and fatigue were registered. Treadmill exercise performance (preoperatively and at postoperative days 2 and 8) and nocturnal pulse oximetry at the patients' homes (preoperatively and postoperative nights 1-3) were completed. Median age was 41 years (range, 21-56). Compared with preoperatively, levels of physical motor activity, fatigue, and pain scores were normalized 2 days after operation. Subjective sleep quality was significantly worsened on the first postoperative night, and sleep duration was significantly increased on the first 2 postoperative nights. There were no significant perioperative changes in actigraphy night sleep fragmentation, incidence of self-reported awakenings or nightmares/distressing dreams, exercise performance, or nocturnal oxygenation. Pulmonary peak flow measurements were normalized the day after operation. After uncomplicated outpatient laparoscopic cholecystectomy, there is no pathophysiologic basis for recommending a postoperative convalescence of more than 2 to 3 days in otherwise healthy younger patients.

Exclusion Performance in Dwarf Goats (Capra aegagrus hircus) and Sheep (Ovis orientalis aries)

PubMed Central

Nawroth, Christian; von Borell, Eberhard; Langbein, Jan

2014-01-01

Using a comparative approach, we investigated the ability of dwarf goats and sheep to use direct and indirect information about the location of a food reward in an object-choice task. Subjects had to choose between two cups with only one covering a reward. Before making a choice, subjects received information about the baited (direct information) or non-baited cup (indirect information). Both goats and sheep were able to use direct information (presence of food) in the object choice task. After controlling for local enhancement, we found that goats rather than sheep were able to use indirect information (i.e., the absence of food) to find a reward. The actual test setup could not clarify whether individual goats were able to inferentially reason about the content of the baited cup when only shown the content of the non-baited cup or if they simply avoided the empty cup in that situation. As browsing species, feral and wild goats exhibit highly selective feeding behaviour compared to the rather unselective grazing sheep. The potential influence of this species-specific foraging flexibility of goats and sheep for using direct and indirect information to find a food reward is discussed in relation to a higher aversion to losses in food acquisition in goats compared to sheep. PMID:24695781

Reduced size of the amygdala in individuals with 47,XXY and 47,XXX karyotypes.

PubMed

Patwardhan, Anil J; Brown, Wendy E; Bender, Bruce G; Linden, Mary G; Eliez, Stephan; Reiss, Allan L

2002-01-08

The excess of 47,XXX and 47,XXY karyotypes found in cytogenetic screening studies of individuals with schizophrenia has given support for an increased risk of psychiatric illness among men and women with sex chromosomal aneuploidy (SCA). Mesial temporal lobe structures, including the amygdala and hippocampus, are thought to be associated with abnormalities of mood and behavior in humans and in the neurobiology of schizophrenia. This study focuses on variations in volumes of mesial temporal lobe structures in men and women with SCA. Utilizing an unselected birth cohort of subjects with SCA and high-resolution magnetic resonance imaging (MRI), we investigated the neuroanatomical consequences of a supernumerary X chromosome on the morphology of the amygdala and hippocampus. Regional and total brain volumes were measured in 10 subjects with 47,XXY, 10 subjects with 47,XXX, and 20 euploid controls. Amygdala volumes were significantly reduced in men with 47,XXY, compared to control men, while the decrease in women with 47,XXX was not as pronounced. Hippocampus volumes were preserved in both groups, compared to same-gender controls. Longitudinal studies of SCA individuals have shown an increased incidence of mild psychopathology and behavioral dysfunction in men with 47,XXY and more overt psychiatric illness in women with 47,XXX, compared to control populations. The alteration in amygdala volumes in individuals with a supernumerary X chromosome may provide a neuroanatomic basis for these findings. Copyright 2001 Wiley-Liss, Inc.

Low diagnostic and predictive value of anti-dsDNA antibodies in unselected patients with recent onset of rheumatic symptoms: results from a long-term follow-up Scandinavian multicentre study.

PubMed

Compagno, M; Jacobsen, S; Rekvig, O P; Truedsson, L; Heegaard, N H; Nossent, J; Jönsen, A; Jacobsen, R S; Eilertsen, G Ø; Sturfelt, G; Bengtsson, A A

2013-01-01

To verify the diagnostic accuracy of anti-double-stranded DNA (anti-dsDNA) antibodies detected by the Crithidia luciliae immunofluorescence test (CLIFT) in a cohort of unselected patients, referred to a rheumatologist due to recent onset of rheumatic symptoms. A total of 1073 consecutive patients were screened for anti-nuclear antibodies (ANAs). Serum samples from 292 ANA-positive and 292 matching ANA-negative patients were tested three times for anti-dsDNA antibodies, using two different CLIFT kits (ImmunoConcepts(®) and Euroimmun(®)). An initial clinical diagnosis was made by rheumatologists unaware of the results. The diagnoses were updated after a median follow-up of 4.8 years. CLIFT was positive at least once in 60 patients but only 23 patients were CLIFT positive in all of the assays. Diagnosis of systemic lupus erythematosus (SLE) was made initially in 65 patients, of whom 24 (37%) were CLIFT positive. Many other diagnoses were observed among the CLIFT-positive patients. Overall, 16 (5.5%) ANA-negative patients were CLIFT positive. After approximately 5 years, the diagnosis of SLE remained unchanged in 63 patients (23 CLIFT positive) and altered in only two (one CLIFT positive). Among the 36 CLIFT-positive patients who were not diagnosed with SLE at study entry, only one developed SLE during the follow-up period. CLIFT was not reliable as a diagnostic tool in unselected patients with rheumatic symptoms. ANAs were of little value as a screening test before the CLIFT analysis. CLIFT had surprisingly low positive predictive value (PPV) for the diagnosis of SLE despite its high specificity. For non-SLE patients, being CLIFT positive poses little risk of developing SLE within 5 years.

Evidence for naive T-cell repopulation despite thymus irradiation after autologous transplantation in adults with multiple myeloma: role of ex vivo CD34+ selection and age.

PubMed

Malphettes, Marion; Carcelain, Guislaine; Saint-Mezard, Pierre; Leblond, Véronique; Altes, Hester Korthals; Marolleau, Jean-Pierre; Debré, Patrice; Brouet, Jean-Claude; Fermand, Jean-Paul; Autran, Brigitte

2003-03-01

Immunodeficiency following autologous CD34+-purified peripheral blood stem cell (PBSC) transplantation could be related to T-cell depletion of the graft or impaired T-cell reconstitution due to thymus irradiation. Aiming to assess the role of irradiated thymus in T-cell repopulation, we studied 32 adults with multiple myeloma, randomly assigned to receive high-dose therapy including total body irradiation (TBI) followed by autologous transplantation with either unselected or CD34+-selected PBSCs. The median number of reinfused CD3+ cells was lower in the selected group (0.03 versus 14 x 10(6)/kg; P =.002). Lymphocyte subset counts were evaluated from month 3 to 24 after grafting. Naive CD4+ T cells were characterized both by phenotype and by quantification of T-cell receptor rearrangement excision circles (TRECs). The reconstitution of CD3+ and CD4+ T cells was significantly delayed in the CD34+-selected group, but eventually led to counts similar to those found in the unselected group after month 12. Mechanism of reconstitution differed, however, between both groups. Indeed, a marked increase in the naive CD62L+CD45RA+CD4+ subset was observed in the selected group, but not in the unselected group in which half of the CD45RA+CD4+ T cells appear to be CD62L-. Age was identified as an independent adverse factor for CD4+ and CD62L+CD45RA+CD4+ T-cell reconstitution. Our results provide evidence that infusing PBSCs depleted of T cells after TBI in adults delays T-cell reconstitution but accelerates thymic regeneration.

Estimated home ranges can misrepresent habitat relationships on patchy landscapes

USGS Publications Warehouse

Mitchell, M.S.; Powell, R.A.

2008-01-01

Home ranges of animals are generally structured by the selective use of resource-bearing patches that comprise habitat. Based on this concept, home ranges of animals estimated from location data are commonly used to infer habitat relationships. Because home ranges estimated from animal locations are largely continuous in space, the resource-bearing patches selected by an animal from a fragmented distribution of patches would be difficult to discern; unselected patches included in the home range estimate would bias an understanding of important habitat relationships. To evaluate potential for this bias, we generated simulated home ranges based on optimal selection of resource-bearing patches across a series of simulated resource distributions that varied in the spatial continuity of resources. For simulated home ranges where selected patches were spatially disjunct, we included interstitial, unselected cells most likely to be traveled by an animal moving among selected patches. We compared characteristics of the simulated home ranges with and without interstitial patches to evaluate how insights derived from field estimates can differ from actual characteristics of home ranges, depending on patchiness of landscapes. Our results showed that contiguous home range estimates could lead to misleading insights on the quality, size, resource content, and efficiency of home ranges, proportional to the spatial discontinuity of resource-bearing patches. We conclude the potential bias of including unselected, largely irrelevant patches in the field estimates of home ranges of animals can be high, particularly for home range estimators that assume uniform use of space within home range boundaries. Thus, inferences about the habitat relationships that ultimately define an animal's home range can be misleading where animals occupy landscapes with patchily distributed resources.

Epstein-Barr Virus, Human Papillomavirus and Mouse Mammary Tumour Virus as Multiple Viruses in Breast Cancer

PubMed Central

Glenn, Wendy K.; Heng, Benjamin; Delprado, Warick; Iacopetta, Barry; Whitaker, Noel J.; Lawson, James S.

2012-01-01

Background The purpose of this investigation is to determine if Epstein Barr virus (EBV), high risk human papillomavirus (HPV), and mouse mammary tumour viruses (MMTV) co-exist in some breast cancers. Materials and Methods All the specimens were from women residing in Australia. For investigations based on standard PCR, we used fresh frozen DNA extracts from 50 unselected invasive breast cancers. For normal breast specimens, we used DNA extracts from epithelial cells from milk donated by 40 lactating women. For investigations based on in situ PCR we used 27 unselected archival formalin fixed breast cancer specimens and 18 unselected archival formalin fixed normal breast specimens from women who had breast reduction surgery. Thirteen of these fixed breast cancer specimens were ductal carcinoma in situ (dcis) and 14 were predominantly invasive ductal carcinomas (idc). Results EBV sequences were identified in 68%, high risk HPV sequences in 50%, and MMTV sequences in 78% of DNA extracted from 50 invasive breast cancer specimens. These same viruses were identified in selected normal and breast cancer specimens by in situ PCR. Sequences from more than one viral type were identified in 72% of the same breast cancer specimens. Normal controls showed these viruses were also present in epithelial cells in human milk – EBV (35%), HPV, 20%) and MMTV (32%) of 40 milk samples from normal lactating women, with multiple viruses being identified in 13% of the same milk samples. Conclusions We conclude that (i) EBV, HPV and MMTV gene sequences are present and co-exist in many human breast cancers, (ii) the presence of these viruses in breast cancer is associated with young age of diagnosis and possibly an increased grade of breast cancer. PMID:23183846

Epstein-Barr virus, human papillomavirus and mouse mammary tumour virus as multiple viruses in breast cancer.

PubMed

Glenn, Wendy K; Heng, Benjamin; Delprado, Warick; Iacopetta, Barry; Whitaker, Noel J; Lawson, James S

2012-01-01

The purpose of this investigation is to determine if Epstein Barr virus (EBV), high risk human papillomavirus (HPV), and mouse mammary tumour viruses (MMTV) co-exist in some breast cancers. All the specimens were from women residing in Australia. For investigations based on standard PCR, we used fresh frozen DNA extracts from 50 unselected invasive breast cancers. For normal breast specimens, we used DNA extracts from epithelial cells from milk donated by 40 lactating women. For investigations based on in situ PCR we used 27 unselected archival formalin fixed breast cancer specimens and 18 unselected archival formalin fixed normal breast specimens from women who had breast reduction surgery. Thirteen of these fixed breast cancer specimens were ductal carcinoma in situ (dcis) and 14 were predominantly invasive ductal carcinomas (idc). EBV sequences were identified in 68%, high risk HPV sequences in 50%, and MMTV sequences in 78% of DNA extracted from 50 invasive breast cancer specimens. These same viruses were identified in selected normal and breast cancer specimens by in situ PCR. Sequences from more than one viral type were identified in 72% of the same breast cancer specimens. Normal controls showed these viruses were also present in epithelial cells in human milk - EBV (35%), HPV, 20%) and MMTV (32%) of 40 milk samples from normal lactating women, with multiple viruses being identified in 13% of the same milk samples. We conclude that (i) EBV, HPV and MMTV gene sequences are present and co-exist in many human breast cancers, (ii) the presence of these viruses in breast cancer is associated with young age of diagnosis and possibly an increased grade of breast cancer.

Absence of Bacteria on Coronary Angioplasty Balloons from Unselected Patients: Results with Use of a High Sensitivity Polymerase Chain Reaction Assay

PubMed Central

Hansen, Gorm Mørk; Nilsson, Martin; Nielsen, Claus Henrik; Holmstrup, Palle; Helqvist, Steffen; Tolker-Nielsen, Tim; Givskov, Michael; Hansen, Peter Riis

2015-01-01

Periodontitis is a chronic, bacterially-induced inflammatory disease of the tooth-supporting tissues, which may result in transient bacteremia and a systemic inflammatory response. Periodontitis is associated with coronary artery disease independently of established cardiovascular risk factors, and translocation of bacteria from the oral cavity to the coronary arteries may play a role in the development of coronary artery disease. Very few studies have used angioplasty balloons for in vivo sampling from diseased coronary arteries, and with varying results. Therefore, the aim of this study was to assess if bacterial DNA from primarily oral bacteria could be detected on coronary angioplasty balloons by use of an optimized sampling process combined with an internally validated sensitive polymerase chain reaction (PCR) assay. Coronary angioplasty balloons and control samples from a total of 45 unselected patients with stable angina, unstable angina/non-ST elevation myocardial infarction, and ST-elevation myocardial infarction (n = 15 in each group) were collected and analyzed using a PCR assay with high sensitivity and specificity for 16S rRNA genes of the oral microbiome. Despite elimination of extraction and purification steps, and demonstration of sensitivity levels of 25–125 colony forming units (CFU), we did not detect bacterial DNA from any of the coronary angioplasty balloons. A subsequent questionnaire indicated that the prevalence of periodontitis in the study cohort was at least 39.5%. Although coronary angioplasty balloons are unlikely to be useful for detection of bacteria with current PCR techniques in unselected patients with coronary artery disease, more studies are warranted to determine the extent to which bacteria contribute to atherosclerosis and its clinical manifestations and whether the presence of bacteria in the arteries is a transient phenomenon. PMID:26695491

NOR-SASS (Norwegian Sonothrombolysis in Acute Stroke Study): Randomized Controlled Contrast-Enhanced Sonothrombolysis in an Unselected Acute Ischemic Stroke Population.

PubMed

Nacu, Aliona; Kvistad, Christopher E; Naess, Halvor; Øygarden, Halvor; Logallo, Nicola; Assmus, Jörg; Waje-Andreassen, Ulrike; Kurz, Kathinka D; Neckelmann, Gesche; Thomassen, Lars

2017-02-01

The NOR-SASS (Norwegian Sonothrombolysis in Acute Stroke Study) aimed to assess effect and safety of contrast-enhanced ultrasound treatment in an unselected acute ischemic stroke population. Patients treated with intravenous thrombolysis within 4.5 hours after symptom onset were randomized 1:1 to either contrast-enhanced sonothrombolysis (CEST) or sham CEST. A visible arterial occlusion on baseline computed tomography angiography was not a prerequisite for inclusion. Pulse-wave 2 MHz ultrasound was given for 1 hour and contrast (SonoVue) as an infusion for ≈30 minutes. Magnetic resonance imaging and angiography were performed after 24 to 36 hours. Primary study end points were neurological improvement at 24 hours defined as National Institutes of Health Stroke Scale score 0 or reduction of ≥4 National Institutes of Health Stroke Scale points compared with baseline National Institutes of Health Stroke Scale and favorable functional outcome at 90 days defined as modified Rankin scale score 0 to 1. A total of 183 patients were randomly assigned to either CEST (93 patient) or sham CEST (90 patients). The rates of symptomatic intracerebral hemorrhage, asymptomatic intracerebral hemorrhage, or mortality were not increased in the CEST group. Neurological improvement at 24 hours and functional outcome at 90 days was similar in the 2 groups both in the intention-to-treat analysis and in the per-protocol analysis. CEST is safe among unselected ischemic stroke patients with or without a visible occlusion on computed tomography angiography and with varying grades of clinical severity. There was, however, statistically no significant clinical effect of sonothrombolysis in this prematurely stopped trial. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01949961. © 2016 The Authors.

Automatic management of atrial and ventricular stimulation in a contemporary unselected population of pacemaker recipients: the ESSENTIAL Registry.

PubMed

Biffi, Mauro; Bertini, Matteo; Saporito, Davide; Belotti, Giuseppina; Quartieri, Fabio; Piancastelli, Maurizio; Pucci, Angelo; Boggian, Giulio; Mazzocca, Gian Franco; Giorgi, Davide; Diotallevi, Paolo; Diemberger, Igor; Martignani, Cristian; Pancaldi, Stefano; Ziacchi, Matteo; Marcantoni, Lina; Toselli, Tiziano; Attala, Simone; Iori, Matteo; Bottoni, Nicola; Argnani, Selina; Tomasi, Corrado; Sassone, Biagio; Boriani, Giuseppe

2016-10-01

We investigated the applicability of the Ventricular Capture Control (VCC) and Atrial Capture Control (ACC) algorithms for automatic management of cardiac stimulation featured by Biotronik pacemakers in a broad, unselected population of pacemaker recipients. Ventricular Capture Control and Atrial Capture Control were programmed to work at a maximum adapted output voltage as 4.8 V in consecutive recipients of Biotronik pacemakers. Ambulatory threshold measurements were made 1 and 12 months after pacemaker implant/replacement in all possible pacing/sensing configurations, and were compared with manual measurements. Among 542 patients aged 80 (73-85) years, 382 had a pacemaker implant and 160 a pacemaker replacement. Ventricular Capture Control could work at long term in 97% of patients irrespectively of pacing indication, lead type, and lead service life, performance being superior with discordant pacing/sensing configurations. Atrial Capture Control could work in 93% of patients at 4.8 V maximum adapted voltage and at any pulse width, regardless of pacing indication, lead type, and service life. At 12-month follow-up, a ventricular threshold increase ≥1.5 V had occurred in 4.4% of patients uneventfully owing to VCC functioning. Projected pacemaker longevity at 1 month was strongly correlated with the 12-month estimate, and exceeded 13 years in >60% of patients. These algorithms for automatic management of pacing output ensure patient safety in the event of a huge increase of pacing threshold, while enabling maximization of battery longevity. Their applicability is quite broad in an unselected pacemaker population irrespectively of lead choice and service of life. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Two-year safety and effectiveness of sirolimus-eluting stents (from a prospective registry).

PubMed

Claessen, Bimmer E; Mehran, Roxana; Leon, Martin B; Heller, Eric A; Weisz, Giora; Syros, George; Mintz, Gary S; Franklin-Bond, Theresa; Apostolidou, Irene; Henriques, Jose P S; Stone, Gregg W; Moses, Jeffrey W; Dangas, George D

2011-02-15

Uncertainty exists about the long-term safety and efficacy outcomes of sirolimus-eluting stents (SESs) in unselected patients. The present study was performed to evaluate the safety and efficacy of the SES in treatment of patients with coronary artery disease in an unselected population. Over a 2-year period, 1,504 consecutive patients undergoing percutaneous coronary intervention with ≥1 SES were enrolled. The primary end point was the occurrence of target vessel failure (TVF; a composite of cardiac death, myocardial infarction, or clinically driven target vessel revascularization). An independent clinical event committee adjudicated all adverse events up to 2-year follow-up. Dual antiplatelet therapy was recommended for ≥1 year throughout the study period. Mean age was 65 ± 11 years; 75% were men, and 34% were diabetics. SESs were implanted for off-label indications in 86% of cases. TVF rates were 3.3%, 6.9%, 11.5%, and 15.5% at 30-day, 6-month, 1-year, and 2-year follow-ups, respectively. The 2-year cumulative rate of definite/probable stent thrombosis was 0.9%; 0.2% was very late thrombosis, occurring from 1 year to 2 years. Patients off dual antiplatelet therapy at 6 months had a significantly increased rate of subsequent death from noncardiac causes. Patients off dual antiplatelet therapy at 1 year had a significantly decreased rate of subsequent clinically driven target lesion revascularization. In conclusion, use of SESs in unselected patients with coronary artery disease was associated with a low TVF rate at 2 years with an acceptable incidence of stent thrombosis. Copyright © 2011 Elsevier Inc. All rights reserved.

Procalcitonin as a marker of micro-inflammation in hemodialysis.

PubMed

Conti, Giovanni; Amore, Alessandro; Chiesa, Monica; Mancuso, Domenico; Cirina, Paola; Mengozzi, Giulio; Santoro, Antonio; Coppo, Rosanna

2005-01-01

In searching for a rapid and sensitive test to detect micro-inflammation in patients on hemodialysis (HD), we measured serum procalcitonin (PCT) levels and made a comparison with other traditional markers such as C-reactive protein (CRP), serum amyloid (SAA) and homocysteine, considered related to vascular damage. We investigated 51 HD patients, without signs of infection, in basal conditions (during standard bicarbonate dialysis and unselected filters: X) and after 4 months of possibly more biocompatible treatments (on-line hemofiltration (HF) or HD with ultra-pure dialysate and biocompatible membranes: Y). Serum PCT (measured by immunoluminometric assay), CRP and SAA (nephelometric assay) and plasma homocysteine (measured by high performance liquid chromatography) concentrations were assessed at the beginning of dialysis (T0) and after 4 hr (T4). Patients on unselected dialysis displayed mean PCT values significantly increased after 4 hr of dialysis in comparison to those at the start of the sessions (XT4 1.56 +/- 3.93 vs. XT0 0.4 +/- 0.34 ng/mL; p < 0.05). The PCT levels detected after 4 hr of biocompatible treatments were significantly lower than those detected after 4 hr of unselected treatments (YT4 0.78 +/- 0.34 ng/mL; p < 0.05), even though the percentage of patients with positive PCT values (> 0.5 ng/mL) remained almost unchanged. No significant modification in mean levels or in the frequency of positive values was observed for CRP, SAA and homocysteine. After 4 months of highly biocompatible treatments, a reduction in intradialytic enhancements of all inflammation markers was detected. Our data support the conclusion that PCT is a more precise marker than other traditional tests to evaluate micro-inflammation and biocompatibility in HD.

Maternal use of probiotics during pregnancy and effects on their offspring's health in an unselected population.

PubMed

Rutten, Nicole; Van der Gugten, Anne; Uiterwaal, Cuno; Vlieger, Arine; Rijkers, Ger; Van der Ent, Kors

2016-02-01

Probiotics are used by women in the perinatal period and may improve balance of microbiota, with possible health benefits for both mother and baby. Characteristics and (health) behaviour patterns of mothers using probiotics during pregnancy, and health effects on their offspring, were investigated. Differences between mothers using probiotics during pregnancy and those who did not, were assessed. In total, 341 out of 2491 (13.7%) mothers reported use of probiotics during pregnancy. There were no significant differences in maternal features (gestation, age, ethnicity, education) between users and non-users. Logistic regression analyses showed that consumption of probiotics was significantly associated with use of homeopathic products [odds ratio (OR) 1.65, 95% confidence interval (CI) 1.17-2.33, p = 0.005], maternal history of smoking (OR 1.72, 95% CI 1.25-2.37, p = 0.001) and paternal history of smoking (OR 1.39, 95% CI 1.01-1.89, p = 0.05). Common disease symptoms during the first year of life in the offspring did not differ between both groups. The use of probiotics or other health-related products without doctor's prescription during pregnancy might point to compensation for types of less favourable behaviour. Probiotic use during pregnancy does not seem to induce positive health effects in the offspring in an unselected population. Aberrant microbiota compositions have been detected during critical periods when early programming occurs including pregnancy and early neonatal life. Probiotics modulate intestinal microbiota composition and are associated with positive health effects. The use of probiotics or other health-related products without doctor's prescription during pregnancy is associated with and might point to compensation for types of less favourable behaviour. Probiotic use during pregnancy does not induce positive health effects in the offspring in this unselected population.

Prevalence of Lynch syndrome in unselected patients with endometrial or ovarian cancer.

PubMed

Kast, Karin; Dobberschütz, Catharina; Sadowski, Carolin Eva; Pistorius, Steffen; Wimberger, Pauline

2016-11-01

Lynch syndrome is known by healthcare providers mainly for patients with colorectal cancer. Awareness of other associated tumors, such as endometrial or ovarian cancer, is low. This study aimed to analyze the prevalence of Lynch syndrome in unselected patients with endometrial or ovarian cancer. In addition, the willingness of patients and family members to undergo germline mutation testing was investigated. The medical records of all patients diagnosed with endometrial or ovarian cancer at the Department of Gynecology and Obsterics, University Hospital Dresden, between 1998 and 2012, were screened for a family history of HNPCC-associated cancer. Telephone interviews were used to screen, inform, and enroll patients in this genetic analysis study. Molecular analysis was performed by prescreening of tumor tissue, followed by germline mutation analysis. Two hundred and eighty-three patients were diagnosed with endometrial cancer, 291 with ovarian cancer, and 14 with both. A positive family history for tumors associated with Lynch syndrome was documented for 61 patients. Two pathogenic mutations in the genes MLH1 and MSH2 in nine genetic analyses had already been detected before. After genetic counseling, only 10 of 31 index patients (32.3 %) consented for mutation analysis. However, no additional pathogenic heterozygous mutations were found. In this retrospective cohort study in unselected patients with endometrial or ovarian cancer, only a small number of patients with suspected Lynch syndrome could be identified. Of those, acceptance of germline analyses was moderate, only. As a result, the rate of identified pathogenic germline mutations was lower than expected. Therefore, we are convinced that more information on cancer risks, options for predictive molecular testing and preventive procedures, needs to be provided to patients and gynecologists.

[Corifollitropin alfa in women stimulated for the first time in in vitro fertilization programme].

PubMed

Vraná-Mardešićová, N; Vobořil, J; Melicharová, L; Jelínková, L; Vilímová, Š; Mardešić, T

2017-01-01

To compare results after stimulation with corifollitropin alfa (Elonva) in unselected group of women entering for the first time in in vitro fertilization programme (IVF) with results from Phase III randomized trials with selected groups of women. Prospective study. Sanatorium Pronatal, Praha. 40 unselected women with adequat ovarian reserve entering for the first time in IVF programme were stimulated with corifollitropin alfa and GnRH antagonists. Avarage age in the study group was 32,8 years (29-42 years), women younger then 36 and less then 60 kg received Elonva 100 µg , all others (age > 36 let, weight > 60 kg) Elonva 150 µg. Five days after egg retrieval one blastocyst was transferred (single embryo transfer - eSET). Our results were compared with the resuls in higly selected groups of women from Phase III randomized trials. After stimulation with corifollitropin alfa and GnRH antagonists on average 10,6 (9,2 ± 4,2) eggs could be retrieved, among them 7,3 (6,6 ± 3,9) were M II oocytes (68,9%) and fertilisation rate was 84,6%. After first embryo transfer ("fresh" embryos and embryos from "freeze all" cycles) 14 pregnancies were achieved (37,8%), three pregnancies were achieved later from transfer of frozen-thawed embryos (cumulative pregnancy rate 45,9%). There were three abortions. No severe hyperstimulation syndrom occured. Our results in unselected group of women stimulated for the first in an IVF programme with corifollitropin alfa are fully comparable with results published in randomized trials with selected group of patiens. Corifollitropin alfa in combination with daily GnRH antagonist can be successfully used in normal-responder patients stimulated for the first time in an IVF programmeKeywords: corifollitropin alfa, GnRH antagonists, ovarian stimulation, pregnancy.

RNA sequencing for global gene expression associated with muscle growth in a single male modern broiler line compared to a foundational Barred Plymouth Rock chicken line.

PubMed

Kong, Byung-Whi; Hudson, Nicholas; Seo, Dongwon; Lee, Seok; Khatri, Bhuwan; Lassiter, Kentu; Cook, Devin; Piekarski, Alissa; Dridi, Sami; Anthony, Nicholas; Bottje, Walter

2017-01-13

Modern broiler chickens exhibit very rapid growth and high feed efficiency compared to unselected chicken breeds. The improved production efficiency in modern broiler chickens was achieved by the intensive genetic selection for meat production. This study was designed to investigate the genetic alterations accumulated in modern broiler breeder lines during selective breeding conducted over several decades. To identify genes important in determining muscle growth and feed efficiency in broilers, RNA sequencing (RNAseq) was conducted with breast muscle in modern pedigree male (PeM) broilers (n = 6 per group), and with an unselected foundation broiler line (Barred Plymouth Rock; BPR). The RNAseq analysis was carried out using Ilumina Hiseq (2 x 100 bp paired end read) and raw reads were assembled with the galgal4 reference chicken genome. With normalized RPM values, genes showing >10 average read counts were chosen and genes showing <0.05 p-value and >1.3 fold change were considered as differentially expressed (DE) between PeM and BPR. DE genes were subjected to Ingenuity Pathway Analysis (IPA) for bioinformatic functional interpretation. The results indicate that 2,464 DE genes were identified in the comparison between PeM and BPR. Interestingly, the expression of genes encoding mitochondrial proteins in chicken are significantly biased towards the BPR group, suggesting a lowered mitochondrial content in PeM chicken muscles compared to BPR chicken. This result is inconsistent with more slow muscle fibers bearing a lower mitochondrial content in the PeM. The molecular, cellular and physiological functions of DE genes in the comparison between PeM and BPR include organismal injury, carbohydrate metabolism, cell growth/proliferation, and skeletal muscle system development, indicating that cellular mechanisms in modern broiler lines are tightly associated with rapid growth and differential muscle fiber contents compared to the unselected BPR line. Particularly, PDGF (platelet derived growth factor) signaling and NFE2L2 (nuclear factor, erythroid 2-like 2; also known as NRF2) mediated oxidative stress response pathways appear to be activated in modern broiler compared to the foundational BPR line. Upstream and network analyses revealed that the MSTN (myostatin) -FST (follistatin) interactions and inhibition of AR (androgen receptor) were predicted to be effective regulatory factors for DE genes in modern broiler line. PRKAG3 (protein kinase, AMP-activated, gamma 3 non-catalytic subunit) and LIPE (lipase E) are predicted as core regulatory factors for myogenic development, nutrient and lipid metabolism. The highly upregulated genes in PeM may represent phenotypes of subclinical myopathy commonly observed in the commercial broiler breast tissue, that can lead to muscle hardening, named as woody breast. By investigating global gene expression in a highly selected pedigree broiler line and a foundational breed (Barred Plymouth Rock), the results provide insight into cellular mechanisms that regulate muscle growth, fiber composition and feed efficiency.

Study designs for identification of rare disease variants in complex diseases: the utility of family-based designs.

PubMed

Ionita-Laza, Iuliana; Ottman, Ruth

2011-11-01

The recent progress in sequencing technologies makes possible large-scale medical sequencing efforts to assess the importance of rare variants in complex diseases. The results of such efforts depend heavily on the use of efficient study designs and analytical methods. We introduce here a unified framework for association testing of rare variants in family-based designs or designs based on unselected affected individuals. This framework allows us to quantify the enrichment in rare disease variants in families containing multiple affected individuals and to investigate the optimal design of studies aiming to identify rare disease variants in complex traits. We show that for many complex diseases with small values for the overall sibling recurrence risk ratio, such as Alzheimer's disease and most cancers, sequencing affected individuals with a positive family history of the disease can be extremely advantageous for identifying rare disease variants. In contrast, for complex diseases with large values of the sibling recurrence risk ratio, sequencing unselected affected individuals may be preferable.

A Membrane-Free Neutral pH Formate Fuel Cell Enabled by a Selective Nickel Sulfide Oxygen Reduction Catalyst.

PubMed

Yan, Bing; Concannon, Nolan M; Milshtein, Jarrod D; Brushett, Fikile R; Surendranath, Yogesh

2017-06-19

Polymer electrolyte membranes employed in contemporary fuel cells severely limit device design and restrict catalyst choice, but are essential for preventing short-circuiting reactions at unselective anode and cathode catalysts. Herein, we report that nickel sulfide Ni 3 S 2 is a highly selective catalyst for the oxygen reduction reaction in the presence of 1.0 m formate. We combine this selective cathode with a carbon-supported palladium (Pd/C) anode to establish a membrane-free, room-temperature formate fuel cell that operates under benign neutral pH conditions. Proof-of-concept cells display open circuit voltages of approximately 0.7 V and peak power values greater than 1 mW cm -2 , significantly outperforming the identical device employing an unselective platinum (Pt) cathode. The work establishes the power of selective catalysis to enable versatile membrane-free fuel cells. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Heterogeneous Photocatalysis and Photoelectrocatalysis: From Unselective Abatement of Noxious Species to Selective Production of High-Value Chemicals.

PubMed

Augugliaro, Vincenzo; Camera-Roda, Giovanni; Loddo, Vittorio; Palmisano, Giovanni; Palmisano, Leonardo; Soria, Javier; Yurdakal, Sedat

2015-05-21

Heterogeneous photocatalysis and photoelectrocatalysis have been considered as oxidation technologies to abate unselectively noxious species. This article focuses instead on the utilization of these methods for selective syntheses of organic molecules. Some promising reactions have been reported in the presence of various TiO2 samples and the important role played by the amorphous phase has been discussed. The low solubility of most of the organic compounds in water limits the utilization of photocatalysis. Dimethyl carbonate has been proposed as an alternative green organic solvent. The recovery of the products by coupling photocatalysis with pervaporation membrane technology seems to be a solution for future industrial applications. As far as photoelectrocatalysis is concerned, a decrease in recombination of the photogenerated pairs occurs, enhancing the rate of the oxidation reactions and the quantum yield. Another benefit is to avoid reaction(s) between the intermediates and the substrate, as anodic and cathodic reactions take place in different places.

Sleep assessment in a population-based study of chronic fatigue syndrome

PubMed Central

Unger, Elizabeth R; Nisenbaum, Rosane; Moldofsky, Harvey; Cesta, Angela; Sammut, Christopher; Reyes, Michele; Reeves, William C

2004-01-01

Background Chronic fatigue syndrome (CFS) is a disabling condition that affects approximately 800,000 adult Americans. The pathophysiology remains unknown and there are no diagnostic markers or characteristic physical signs or laboratory abnormalities. Most CFS patients complain of unrefreshing sleep and many of the postulated etiologies of CFS affect sleep. Conversely, many sleep disorders present similarly to CFS. Few studies characterizing sleep in unselected CFS subjects have been published and none have been performed in cases identified from population-based studies. Methods The study included 339 subjects (mean age 45.8 years, 77% female, 94.1% white) identified through telephone screen in a previously described population-based study of CFS in Wichita, Kansas. They completed questionnaires to assess fatigue and wellness and 2 self-administered sleep questionnaires. Scores for five of the six sleep factors (insomnia/hypersomnia, non-restorative sleep, excessive daytime somnolence, sleep apnea, and restlessness) in the Centre for Sleep and Chronobiology's Sleep Assessment Questionnaire© (SAQ©) were dichotomized based on threshold. The Epworth Sleepiness Scale score was used as a continuous variable. Results 81.4% of subjects had an abnormality in at least one SAQ© sleep factor. Subjects with sleep factor abnormalities had significantly lower wellness scores but statistically unchanged fatigue severity scores compared to those without SAQ© abnormality. CFS subjects had significantly increased risk of abnormal scores in the non-restorative (adjusted odds ratio [OR] = 28.1; 95% confidence interval [CI]= 7.4–107.0) and restlessness (OR = 16.0; 95% CI = 4.2–61.6) SAQ© factors compared to non-fatigued, but not for factors of sleep apnea or excessive daytime somnolence. This is consistent with studies finding that, while fatigued, CFS subjects are not sleepy. A strong correlation (0.78) of Epworth score was found only for the excessive daytime somnolence factor. Conclusions SAQ© factors describe sleep abnormalities associated with CFS and provide more information than the Epworth score. Validation of these promising results will require formal polysomnographic sleep studies. PMID:15096280

Left atrial enlargement increases the risk of major adverse cardiac events independent of coronary vasodilator capacity.

PubMed

Koh, Angela S; Murthy, Venkatesh L; Sitek, Arkadiusz; Gayed, Peter; Bruyere, John; Wu, Justina; Di Carli, Marcelo F; Dorbala, Sharmila

2015-09-01

Longstanding uncontrolled atherogenic risk factors may contribute to left atrial (LA) hypertension, LA enlargement (LAE) and coronary vascular dysfunction. Together they may better identify risk of major adverse cardiac events (MACE). The aim of this study was to test the hypothesis that chronic LA hypertension as assessed by LAE modifies the relationship between coronary vascular function and MACE. In 508 unselected subjects with a normal clinical (82)Rb PET/CT, ejection fraction ≥40 %, no prior coronary artery disease, valve disease or atrial fibrillation, LAE was determined based on LA volumes estimated from the hybrid perfusion and CT transmission scan images and indexed to body surface area. Absolute myocardial blood flow and global coronary flow reserve (CFR) were calculated. Subjects were systematically followed-up for the primary end-point - MACE - a composite of all-cause death, myocardial infarction, hospitalization for heart failure, stroke, coronary artery disease progression or revascularization. During a median follow-up of 862 days, 65 of the subjects experienced a composite event. Compared with subjects with normal LA size, subjects with LAE showed significantly lower CFR (2.25 ± 0.83 vs. 1.95 ± 0.80, p = 0.01). LAE independently and incrementally predicted MACE even after accounting for clinical risk factors, medication use, stress left ventricular ejection fraction, stress left ventricular end-diastolic volume index and CFR (chi-squared statistic increased from 30.9 to 48.3; p = 0.001). Among subjects with normal CFR, those with LAE had significantly worse event-free survival (risk adjusted HR 5.4, 95 % CI 2.3 - 12.8, p < 0.0001). LAE and reduced CFR are related but distinct cardiovascular adaptations to atherogenic risk factors. LAE is a risk marker for MACE independent of clinical factors and left ventricular volumes; individuals with LAE may be at risk of MACE despite normal coronary vascular function.

Characteristics of compensated hypogonadism in patients with sexual dysfunction.

PubMed

Corona, Giovanni; Maseroli, Elisa; Rastrelli, Giulia; Sforza, Alessandra; Forti, Gianni; Mannucci, Edoardo; Maggi, Mario

2014-07-01

In the last few years, a view that subclinical endocrine disorders represent milder forms of the clinically overt disease has emerged. Accordingly, it has been proposed that compensated hypogonadism represents a genuine clinical subset of late-onset hypogonadism. The aim of the present study is to investigate the associations of compensated hypogonadism with particular clinical and psychological characteristics of male subjects complaining of sexual dysfunction. After excluding documented genetic causes of hypogonadism, an unselected consecutive series of 4,173 patients consulting our unit for sexual dysfunction was studied. Compensated hypogonadism was identified according to the European Male Ageing study criteria: total testosterone ≥10.5 nmol/L and luteinizing hormone >9.4 U/L. Several hormonal, biochemical, and instrumental (penile Doppler ultrasound) parameters were studied, along with results of the Structured Interview on Erectile Dysfunction (SIEDY) and ANDROTEST. One hundred seventy (4.1%) subjects had compensated hypogonadism, whereas 827 (19.8%) had overt hypogonadism. After adjustment for confounding factors, no specific sexual symptoms were associated with compensated hypogonadism. However, compensated hypogonadism individuals more often reported psychiatric symptoms, as detected by Middlesex Hospital Questionnaire score, when compared with both eugonadal and overt hypogonadal subjects (adjusted odds ratios = 1.018 [1.005;1.031] and 1.014 [1.001;1.028], respectively; both P < 0.005). In addition, subjects with compensated or overt hypogonadism had an increased predicted risk of cardiovascular events (as assessed by Progetto Cuore risk algorithm) when compared with eugonadal individuals. Accordingly, mortality related to major adverse cardiovascular events (MACEs), but not MACE incidence, was significantly higher in subjects with both compensated and overt hypogonadism when compared with eugonadal subjects. The present data do not support the concept that compensated (subclinical) hypogonadism represents a new clinical entity. The possibility that subclinical hypogonadism could be a normal response of the hypothalamus-pituitary-testis axis to somatic illness should be considered. Further studies are urgently needed to clarify this latter point. © 2014 International Society for Sexual Medicine.

Classification of non-demented patients attending a memory clinic using the new diagnostic criteria for Alzheimer's disease with disease-related biomarkers.

PubMed

Ivanoiu, Adrian; Dricot, Laurence; Gilis, Nathalie; Grandin, Cécile; Lhommel, Renaud; Quenon, Lisa; Hanseeuw, Bernard

2015-01-01

New diagnostic criteria for predemential Alzheimer's disease (AD) advocate the use of biomarkers. However, the benefit of using biomarkers has not been clearly demonstrated in clinical practice. To investigate whether a combination of biomarkers may be helpful in classifying a population of non-demented patients attending a Memory Clinic. Sixty non-demented patients were compared with 31 healthy elderly subjects. All subjects underwent a neuropsychological examination, brain 3T magnetic resonance imaging, [F18]-fluorodeoxyglucose and [F18]-flutemetamol positron emission tomography. According to their performance on memory, language, executive, and visuo-spatial domains, the patients were classified as mild cognitive impairment (amnestic, non-amnestic, single, or multiple domain) or subjective cognitive impairment. Patients were then classified according to the National Institute on Aging-Alzheimer's Association (NIA-AA) criteria, using the normalized mean hippocampal volume (Freesurfer), [F18]-FDG PALZAD, and [F18]-flutemetamol standard uptake value ratio (SUVr) (cut-off at the 10th percentile of controls). The standard of truth was the clinical status at study entry (patient versus control). The sensitivity/specificity of the clinical classification was 65/84%. The NIA-AA criteria were applicable in 85% of patients and 87% of controls. For biomarkers the best sensitivity (72%) at a fixed specificity of 84% was achieved by a combination of the three biomarkers. The clinical diagnosis was reconsidered in more than one third of the patients (42%) as a result of including the biomarker results. Application of the new NIA-AA AD diagnostic criteria based on biomarkers in an unselected sample of non-demented patients attending a Memory Clinic was useful in allowing for a better classification of the subjects.

Treatment of Sleep Disorders after Traumatic Brain Injury

PubMed Central

Castriotta, Richard J.; Atanasov, Strahil; Wilde, Mark C.; Masel, Brent E.; Lai, Jenny M.; Kuna, Samuel T.

2009-01-01

Study Objectives: Determine whether treatment of sleep disorders identified in brain injured adults would result in resolution of those sleep disorders and improvement of symptoms and daytime function. Methods: Prospective evaluation of unselected traumatic brain injury patients with nocturnal polysomnography (NPSG), multiple sleep latency test (MSLT), Epworth Sleepiness Scale (ESS), and neuropsychological testing including Psychomotor Vigilance Test (PVT), Profile of Mood States (POMS), and Functional Outcome of Sleep Questionnaire (FOSQ) before and after treatment with continuous positive airway pressure (CPAP) for obstructive sleep apnea (OSA), modafinil (200 mg) for narcolepsy and posttraumatic hypersomnia (PTH), or pramipexole (0.375 mg) for periodic limb movements in sleep (PLMS). Setting: Three academic medical centers. Participants: Fifty-seven (57) adults ≥ 3 months post traumatic brain injury (TBI). Measurements And Results: Abnormal sleep studies were found in 22 subjects (39%), of whom 13 (23%) had OSA, 2 (3%) had PTH, 3 (5%) had narcolepsy, 4 (7%) had PLMS, and 12 had objective excessive daytime sleepiness with MSLT score < 10 minutes. Apneas, hypopneas, and snoring were eliminated by CPAP in OSA subjects, but there was no significant change in MSLT scores. Periodic limb movements were eliminated with pramipexole. One of 3 narcolepsy subjects and 1 of 2 PTH subjects had resolution of hypersomnia with modafinil. There was no significant change in FOSQ, POMS, or PVT results after treatment. Conclusions: Treatment of sleep disorders after TBI may result in polysomnographic resolution without change in sleepiness or neuropsychological function. Citation: Castriotta RJ; Atanasov S; Wilde MC; Masel BE; Lai JM; Kuna ST. Treatment of sleep disorders after traumatic brain injury. J Clin Sleep Med 2009;5(2):137-144. PMID:19968047

Sexual Orientation in Adolescents Who Commit Suicide.

ERIC Educational Resources Information Center

Shaffer, David; And Others

1995-01-01

Examined relationship between suicidal behavior and homosexuality in adolescence in an unselected, matched sample. Found no evidence that suicide is a common characteristic of gay youth, or that when suicide does occur among gay teenagers, that it is a direct consequence of stigmatization or lack of support. (JBJ)

An Evaluation of the Navy’s Health Promotion Videotapes

DTIC Science & Technology

1990-04-30

1263. Fisher, L., Rowley, P. T., & Lipkin. M. (1981). Genetic counseling for beta- thalassemia trait following health screening in a health maintenence...counseling for x, ta- thalassemia trait in a population unselected for interest: Effects on knowledge and m ,ood. American Journal of Human Genetics

Repeatability of measurements of removal of mite-infested brood to assess Varroa Sensitive Hygiene

USDA-ARS?s Scientific Manuscript database

Varroa Sensitive Hygiene is a useful resistance trait that bee breeders could increase in different populations with cost-effective and reliable tests. We investigated the reliability of a one-week test estimating the changes in infestation of brood introduced into highly selected and unselected co...

Selection signature analysis in Holstein cattle identified genes known to affect reproduction

USDA-ARS?s Scientific Manuscript database

Using direct comparison of 45,878 SNPs between a group of Holstein cattle unselected since 1964 and contemporary Holsteins that on average take 30 days longer for successful conception than the 1964 Holsteins, we conducted selection signature analyses to identify genomic regions associated with dair...

Mitochondrial FAD-glycerophosphate dehydrogenase and G-protein-coupled inwardly rectifying K+ channel: No evidence for linkage in maturity-onset diabetes of the young or NIDDM.

PubMed

Warren-Perry, M G; Stoffel, M; Saker, P J; Zhang, Y; Brown, L J; MacDonald, M J; Turner, R C

1996-05-01

Two genes that have potentially important regulatory roles in insulin secretion are both located on chromosome 2q24.1. G-protein-coupled muscarinic potassium channel (GIRK1) is an inwardly rectifying K+ channel that helps to maintain the resting potential and excitability of cells. Mitochondrial FAD-linked glycerophosphate dehydrogenase (m-GDH) catalyzes a rate-limiting step of the glycerol phosphate shuttle in pancreatic islets. Reduced m-GDH activity has been demonstrated in islets isolated from diabetic subjects compared with islets from nondiabetic control subjects and from the diabetic GK rat. To study the relationship between these candidate genes and NIDDM, we have examined a simple tandem-repeat polymorphism (STRP) close to both the KCN J3 (GIRK1) locus and the m-GDH locus. In a linkage study of three maturity-onset diabetes of the young (MODY) pedigrees, not linked to MODY1, MODY2, or MODY3, a cumulative score of - 9.6 at a recombination fraction of theta = 0 excluded linkage. In a population-association study, no linkage disequilibrium for the STRP was found between 190 unselected NIDDM patients and 60 geographically and age-matched white nondiabetic subjects (chi2 = 1.51 on 3 df, P = 0.68). Thus, mutations involving the genes for GIRK1 or FAD-glycerophosphate dehydrogenase are unlikely to cause MODY, and a common mutation in either gene is unlikely to contribute to NIDDM in whites. These data do not exclude mutations in some families or other ethnic groups.

Prevalence of organic disease at colonoscopy in patients with symptoms compatible with irritable bowel syndrome: cross-sectional survey.

PubMed

Patel, Purav; Bercik, Premysl; Morgan, David G; Bolino, Carolina; Pintos-Sanchez, Maria Ines; Moayyedi, Paul; Ford, Alexander C

2015-07-01

Guidelines for the management of irritable bowel syndrome (IBS) encourage a positive diagnosis, but some evidence suggests organic disease may be missed unless investigations are performed. We examined yield of colonoscopy in a cohort of secondary care patients meeting criteria for IBS. Demographic data, symptoms and findings at colonoscopy were recorded prospectively in consecutive, unselected adults with gastrointestinal (GI) symptoms compatible with IBS according to the Rome III criteria. Prevalence of organic GI disease was compared between those meeting criteria for IBS, according to the presence or absence of co-existent alarm features, and by IBS subtype. A total of 559 patients met Rome III criteria for IBS, of whom 423 reported ≥1 alarm feature and 136 none. There was a significantly higher prevalence of organic GI disease among those reporting alarm features (117 [27.7%]), compared with those without (21 [15.4%]) (p = 0.002). In the latter group of 136 patients, Crohn's disease was the commonest finding (10 [7.4%] subjects), followed by coeliac disease (4 [2.9%] subjects), and microscopic colitis (3 [2.2%] subjects). Regardless of presence or absence of alarm features, patients with constipation-predominant IBS were less likely to exhibit organic GI disease than those with diarrhea-predominant or mixed IBS (12.7% vs. 32.1% and 23.8%, p = 0.006). One in six patients with symptoms compatible with IBS without alarm features in this selected group exhibited organic GI disease following investigation. Assessment of alarm features in a comprehensive history is vital to reduce diagnostic uncertainty that can surround IBS.

Pharmacy students' perceptions of natural science and mathematics subjects.

PubMed

Prescott, Julie; Wilson, Sarah Ellen; Wan, Kai-Wai

2014-08-15

To determine the level of importance pharmacy students placed on science and mathematics subjects for pursuing a career in pharmacy. Two hundred fifty-four students completed a survey instrument developed to investigate students' perceptions of the relevance of science and mathematics subjects to a career in pharmacy. Pharmacy students in all 4 years of a master of pharmacy (MPharm) degree program were invited to complete the survey instrument. Students viewed chemistry-based and biology-based subjects as relevant to a pharmacy career, whereas mathematics subjects such as physics, logarithms, statistics, and algebra were not viewed important to a career in pharmacy. Students' experience in pharmacy and year of study influenced their perceptions of subjects relevant to a pharmacy career. Pharmacy educators need to consider how they can help students recognize the importance of scientific knowledge earlier in the pharmacy curriculum.

Local hyperthermia benefits natural and experimental common colds.

PubMed Central

Tyrrell, D.; Barrow, I.; Arthur, J.

1989-01-01

OBJECTIVE--To determine whether inhaling fully humidified air at 43 degrees C gave more benefit to cold sufferers than inhaling air at 30 degrees C. DESIGN--Randomised double blind trial. Setting--General practice and the common cold research unit. SUBJECTS--87 Unselected patients with typical acute nasal and upper respiratory symptoms (general practice study), and 84 volunteers aged 18-50 without a history of chronic or allergic diseases. INTERVENTIONS--Subjects breathed from apparatus delivering 40 litres of room air heated to 43 degrees C or 30 degrees C and fully humidified (relative humidity 100%) per minute. End point--Reduction in severity of disease. MEASUREMENTS and main results--Patients recorded their symptoms (general practice study) and observers recorded symptoms and signs, weight of nasal secretions, isolation of virus, and antibody responses in volunteers. Patients treated for 20 minutes at 43 degrees C had in the succeeding days roughly half the score for symptoms of those treated at 30 degrees C. Volunteers treated for 30 minutes on three occasions when they were starting a cold showed an 18% [corrected] reduction in symptoms. Treatment of volunteers for 20 minutes at the onset of the cold and for 10 minutes on succeeding days showed no difference between 43 degrees C and 30 degrees C. CONCLUSIONS--Nasal hyperthermia can improve the course of a common cold and also give immediate relief of symptoms. PMID:2500196

Serum TSH reference interval in healthy Finnish adults using the Abbott Architect 2000i Analyzer.

PubMed

Schalin-Jäntti, Camilla; Tanner, Pirjo; Välimäki, Matti J; Hämäläinen, Esa

2011-07-01

Current serum TSH reference intervals have been criticized as they were established from unselected background populations. A special concern is that the upper limit, which defines subclinical hypothyroidism, is too high. The objective was to redefine the TSH reference interval in the adult Finnish population. The current reference interval for the widely used Abbott Architect method in Finland is 0.4-4.0 mU/L. Serum TSH and free T4 concentrations were derived from 606 healthy, non-pregnant, 18-91-year-old Finns from the Nordic Reference Interval Project (NORIP) and the possible effects of age, sex and thyroid peroxidase antibody (TPOAb) status were evaluated. After excluding TPOAb-positive subjects and outliers, a reference population of 511 subjects was obtained. In the reference population, no statistically significant gender- or age-specific differences in mean TSH (1.55 ± 3.30 mU/L) or TSH reference intervals were observed. The new reference interval was 0.5-3.6 mU/L (2.5th-97.5th percentiles). The current upper TSH reference limit is 10% too high. A TSH > 3.6 mU/L, confirmed with a repeat TSH sampling, may indicate subclinical hypothyroidism. Differences in ethnicity, regional iodine-intake and analytical methods underline the need for redefining the TSH reference interval in central laboratories in different countries.

Headache and musculoskeletal complaints among subjects with self reported whiplash injury. The HUNT-2 study

PubMed Central

2011-01-01

Background To evaluate the life-time prevalence of self reported whiplash injury and the relationship to chronic musculoskeletal complaints (MSCs) and headache in a large unselected adult population. Methods Between 1995 and 1997, all inhabitants 20 years and older in Nord-Trondelag county in Norway were invited to a comprehensive health survey. Out of 92,936 eligible for participation, a total of 59,104 individuals (63.6%) answered the question about whiplash injury (whiplash). Among these, 46,895 (79.3%) responded to the questions of musculoskeletal complaints and headache. Results The total life-time prevalence of self reported whiplash injury was 2.9%, for women 2.7% and for men 3.0%. There was a significant association between self reported whiplash injury and headache (OR = 2.1; 95% CI 1.8-2.4), and chronic MSCs (OR = 3.3; 95% CI 2.8-3.8), evident for all ten anatomical sites investigated. The association was most pronounced for those with a combination of headache and chronic MSC for both men (OR = 4.8; 95% CI 3.6-6.2) and women (OR = 5.2; 95% CI 3.7-7.1). Conclusions Subjects with self reported whiplash injury had significantly more headache and musculoskeletal complaints than those without, and may in part be due to selective reporting. The causal mechanism remains unclear and cannot be addressed in the present study design. PMID:21651816

High prevalence of Anisakis simplex hypersensitivity and allergy in Sicily, Italy.

PubMed

Heffler, Enrico; Sberna, Maria Eva; Sichili, Stefania; Intravaia, Rossella; Nicolosi, Giuliana; Porto, Morena; Liuzzo, Maria Teresa; Picardi, Giuseppe; Fichera, Silvia; Crimi, Nunzio

2016-02-01

Anisakis simplex can elicit allergic reactions when ingested in raw or marinated fish. The prevalence of A simplex hypersensitivity and allergy in Sicily (Italy), an area where the consumption of raw or marinated fish is very common, has not been investigated thus far. To investigate the prevalence of A simplex sensitization and its clinical relevance in a large group of unselected patients. All consecutive patients referred to the authors' allergy clinic during a 22 month-period were included in the study, evaluated for sensitization to A simplex and other allergens depending on their clinical history, and investigated for allergic symptoms after the ingestion of raw or marinated fish. Of 3,419 patients screened, 527 (15.4%) were sensitized to A simplex and 29 of these (5.5% of sensitized patients) had a history of A simplex allergy. Approximately 30% of patients had mono-sensitization to A simplex. Co-sensitization to house dust mites or molds yielded an odds ratio of 1.98 or 3.18, respectively, for allergy to A simplex. A high prevalence of A simplex sensitization in a large proportion of patients with mono-sensitization was found, confirming that eating habits influence sensitization to this nematode. Allergic symptoms from A simplex ingestion in raw or marinated fish were quite frequent, with symptoms ranging from oral allergy syndrome to anaphylaxis. Patients sensitized to A simplex were more prone to have allergic symptoms when they had co-sensitization to house dust mites or molds, suggesting possible cross-reactive but clinically relevant allergens between these allergenic sources. Copyright © 2016. Published by Elsevier Inc.

Sex-Ratio and Gender Differences in Depression in an Unselected Adult Population.

ERIC Educational Resources Information Center

Baumgart, E. P.; Oliver, J. M.

1981-01-01

Neither sex-ratio nor gender differences in depression were found in adult sample, similar to pattern found among university students. No demographic variable was correlated significantly with depression. Suggests results may be due to the elimination of face-to-face interviews, which expose males to greater negative repercussions for exhibiting…

High-Frequency Oscillations and Seizure Generation in Neocortical Epilepsy

ERIC Educational Resources Information Center

Worrell, Greg A.; Parish, Landi; Cranstoun, Stephen D.; Jonas, Rachel; Baltuch, Gordon; Litt, Brian

2004-01-01

Neocortical seizures are often poorly localized, explosive and widespread at onset, making them poorly amenable to epilepsy surgery in the absence of associated focal brain lesions. We describe, for the first time in an unselected group of patients with neocortical epilepsy, the finding that high-frequency (60--100 Hz) epileptiform oscillations…

Autism Spectrum Disorders (ASD) in Blind Children: Very High Prevalence, Potentially Better Outlook

ERIC Educational Resources Information Center

Jure, Rubin; Pogonza, Ramón; Rapin, Isabelle

2016-01-01

Autism spectrum disorders affected 19 of 38 unselected children at a school for the blind in Cordoba, Argentina. Autism was linked to total congenital blindness, not blindness' etiology, acquired or incomplete blindness, sex, overt brain damage, or socioeconomic status. Autism "recovery," had occurred in 4 verbal children. Congenital…

Comparing Two Methods for Reducing Variability in Voice Quality Measurements

ERIC Educational Resources Information Center

Kreiman, Jody; Gerratt, Bruce R.

2011-01-01

Purpose: Interrater disagreements in ratings of quality plague the study of voice. This study compared 2 methods for handling this variability. Method: Listeners provided multiple breathiness ratings for 2 sets of pathological voices, one including 20 male and 20 female voices unselected for quality and one including 20 breathy female voices.…

Genome changes due to forty years of artificial selection associated with divergent dairy production and reproduction

USDA-ARS?s Scientific Manuscript database

Artificial selection in dairy cattle since 1964 has achieved steady increase in milk production that was accompanied by unintended declines in fertility. Direct comparison of 45,878 SNPs between a group of Holstein cattle unselected since 1964 and the contemporary Holsteins was conducted to identify...

Intensive Training in Youth Sport: An Example of Unequal Opportunity.

ERIC Educational Resources Information Center

Rowley, Stephen R. W.; Graham, Philip J.

1999-01-01

Examined the social composition of an unselected sample of 282 English 8- to 16-year olds involved in intensive training in football, swimming, tennis, and gymnastics. Found that working-class children and those from single-parent families were underrepresented in all sports. Concluded that financial considerations and difficulties in accessing…

Prevalence of BRCA1 and BRCA2 mutations in unselected breast cancer patients from Peru.

PubMed

Abugattas, J; Llacuachaqui, M; Allende, Y Sullcahuaman; Velásquez, A Arias; Velarde, R; Cotrina, J; Garcés, M; León, M; Calderón, G; de la Cruz, M; Mora, P; Royer, R; Herzog, J; Weitzel, J N; Narod, S A

2015-10-01

The prevalence of BRCA1 and BRCA2 mutations among breast cancer patients in Peru has not yet been explored. We enrolled 266 women with breast cancer from a National cancer hospital in Lima, Peru, unselected for age or family history. DNA was screened with a panel of 114 recurrent Hispanic BRCA mutations (HISPANEL). Among the 266 cases, 13 deleterious mutations were identified (11 in BRCA1 and 2 in BRCA2), representing 5% of the total. The average age of breast cancer in the mutation-positive cases was 44 years. BRCA1 185delAG represented 7 of 11 mutations in BRCA1. Other mutations detected in BRCA1 included: two 2080delA, one 943ins10, and one 3878delTA. The BRCA2 3036del4 mutation was seen in two patients. Given the relatively low cost of the HISPANEL test, one should consider offering this test to all Peruvian women with breast or ovarian cancer. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Survival and immune response of drones of a Nosemosis tolerant honey bee strain towards N. ceranae infections.

PubMed

Huang, Qiang; Kryger, Per; Le Conte, Yves; Moritz, Robin F A

2012-03-01

Honey bee colonies (Apis mellifera) have been selected for low level of Nosema in Denmark over decades and Nosema is now rarely found in bee colonies from these breeding lines. We compared the immune response of a selected and an unselected honey bee lineage, taking advantage of the haploid males to study its potential impact on the tolerance toward Nosema ceranae, a novel introduced microsporidian pathogen. After artificial infections of the N. ceranae spores, the lineage selected for Nosema tolerance showed a higher N. ceranae spore load, a lower mortality and an up-regulated immune response. The differences in the response of the innate immune system between the selected and unselected lineage were strongest at day six post infection. In particular genes of the Toll pathway were up-regulated in the selected strain, probably is the main immune pathway involved in N. ceranae infection response. After decades of selective breeding for Nosema tolerance in the Danish strain, it appears these bees are tolerant to N. ceranae infections. Copyright © 2012 Elsevier Inc. All rights reserved.

CHEK2 1100delC and male breast cancer in the Netherlands.

PubMed

Wasielewski, Marijke; den Bakker, Michael A; van den Ouweland, Ans; Meijer-van Gelder, Marion E; Portengen, Henk; Klijn, Jan G M; Meijers-Heijboer, Hanne; Foekens, John A; Schutte, Mieke

2009-07-01

Mutations in the breast cancer susceptibility genes BRCA1, BRCA2, and CHEK2 are known risk factors for female breast cancer. Mutations in BRCA1 and BRCA2 also are associated with male breast cancer (MBC). Similarly, it had been suggested in the original CHEK2 identification report that the CHEK2 1100delC mutation confers an increased risk for MBC. Here, we have evaluated the risk of CHEK2 1100delC for MBC by genotyping CHEK2 1100delC in 23 familial and 71 unselected Dutch MBC cases. None of the 23 familial MBC cases carried the CHEK2 1100delC mutation. In contrast, CHEK2 1100delC was present in 3 of the 71 (4.2%) unselected MBC cases, which was significantly more prevalent than the 1.1% Dutch population frequency assessed in 1,692 individuals (P = 0.05, OR = 4.1, 95% CI 1.2-14.3). Our data suggest that, in the Netherlands, CHEK2 1100delC is associated with an increased risk for MBC.

Reporting Severe Hypoglycemia in Type 1 Diabetes: Facts and Pitfalls.

PubMed

Pedersen-Bjergaard, Ulrik; Thorsteinsson, Birger

2017-10-28

To describe potential factors influencing reporting of severe hypoglycemia in adult patients with type 1 diabetes and to analyze their effect on reported rates of severe hypoglycemia. Reported rates of severe hypoglycemia defined as need for third party assistance vary between 0.3-3.0 events per patient-year in unselected cohorts, corresponding to a yearly prevalence range of 10-53%. When defined as need for parenteral therapy with glucose or glucagon or need for admission to an emergency unit or hospitalization, incidence and prevalence rates of severe hypoglycemia are 0.02-0.5 events per patient-year and 1-29%, respectively. When subjects with recurrent severe hypoglycemia in the past or suffering from impaired hypoglycemia awareness are excluded from participation in studies, lower rates are reported. Studies applying anonymous reporting or reporting by partners report higher rates of severe hypoglycemia. There is a large variation between studies reporting incidence and prevalence of severe hypoglycemia in patients with type 1 diabetes, mainly explained by definition of severity, methods of reporting, and patient selection. These findings call for consensus about hypoglycemia definition and reporting in future research.

Brain Gut Microbiome Interactions and Functional Bowel Disorders

PubMed Central

Mayer, Emeran A.; Savidge, Tor; Shulman, Robert J.

2014-01-01

Alterations in the bidirectional interactions between the gut and the nervous system play an important role in IBS pathophysiology and symptom generation. A body of largely preclinical evidence suggests that the gut microbiota can modulate these interactions. Characterizations of alterations of gut microbiota in unselected IBS patients, and assessment of changes in subjective symptoms associated with manipulations of the gut microbiota with prebiotics, probiotics and antibiotics support a small, but poorly defined role of dybiosis in overall IBS symptoms. It remains to be determined if the observed abnormalities are a consequence of altered top down signaling from the brain to the gut and microbiota, if they are secondary to a primary perturbation of the microbiota, and if they play a role in the development of altered brain gut interactions early in life. Different mechanisms may play role in subsets of patients. Characterization of gut microbiome alterations in large cohorts of well phenotyped patients as well as evidence correlating gut metabolites with specific abnormalities in the gut brain axis are required to answer these questions. PMID:24583088

How many rumbles are there? Acoustic variation and individual identity in the rumble vocalizations of African elephants (Loxodonta africana)

NASA Astrophysics Data System (ADS)

Soltis, Joseph M.; Savage, Anne; Leong, Kirsten M.

2004-05-01

The most commonly occurring elephant vocalization is the rumble, a frequency-modulated call with infrasonic components. Upwards of ten distinct rumble subtypes have been proposed, but little quantitative work on the acoustic properties of rumbles has been conducted. Rumble vocalizations (N=269) from six females housed at Disney's Animal Kingdom were analyzed. Vocalizations were recorded from microphones in collars around subject necks, and rumbles were digitized and measured using SIGNAL software. Sixteen acoustic variables were measured for each call, extracting both source and filter features. Multidimensional scaling analysis indicates that there are no acoustically distinct rumble subtypes, but that there is quantitative variation across rumbles. Discriminant function analysis showed that the acoustic characteristics of rumbles differ across females. A classification success rate of 65% was achieved when assigning unselected rumbles to one of the six females (test set =64 calls) according to the functions derived from the originally selected calls (training set =205 calls). The rumble is best viewed as a single call type with graded variation, but information regarding individual identity is encoded in female rumbles.

The role of methylenetetrahydrofolate reductase in acute lymphoblastic leukemia in a Brazilian mixed population.

PubMed

Zanrosso, Crisiane Wais; Hatagima, Ana; Emerenciano, Mariana; Ramos, Flávio; Figueiredo, Alexandre; Félix, Têmis Maria; Segal, Sandra L; Giugliani, Roberto; Guigliani, Roberto; Muniz, Maria Tereza Cartaxo; Pombo-de-Oliveira, Maria S

2006-04-01

The polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene are associated with leukemogenesis. In order to investigate the influence of two polymorphisms in the MTHFR gene, 677C>T and 1298A>C, on the risk of acute lymphoblastic leukemia (ALL) we performed a case-control study in children from different Brazilians' regions. Genotyping of 176 ALL and 199 unselected healthy subjects was performed using PCR-RFLP assay. There was no association between the 677C>T or 1298A>C and risk of ALL in total case-control sample. However, 677T allele was linked to a decrease risk of ALL [odds ratio (OR), 0.43; 95% confidence interval (CI), 0.22-0.86], whereas the 1298A>C polymorphism presents an elevated risk factor [OR, 2.01; 95% CI, 1.01-3.99] in non-White children. Our investigation provides interesting data concerning the opposite effect of A1298C polymorphisms, particularly in the light of relatively scarce data regarding the MTHFR role in leukemia susceptibility in different populations.

Cerebellar damage impairs the self-rating of regret feeling in a gambling task

PubMed Central

Clausi, Silvia; Coricelli, Giorgio; Pisotta, Iolanda; Pavone, Enea Francesco; Lauriola, Marco; Molinari, Marco; Leggio, Maria

2015-01-01

Anatomical, clinical, and neuroimaging evidence implicates the cerebellum in processing emotions and feelings. Moreover recent studies showed a cerebellar involvement in pathologies such as autism, schizophrenia and alexithymia, in which emotional processing have been found altered. However, cerebellar function in the modulation of emotional responses remains debated. In this study, emotions that are involved directly in decision-making were examined in 15 patients (six males; age range 17–60 years) affected by cerebellar damage and 15 well matched healthy controls. We used a gambling task, in which subjects’ choices and evaluation of outcomes with regard to their anticipated and actual emotional impact were analyzed. Emotions, such as regret and relief, were elicited, based on the outcome of the unselected gamble. Interestingly, despite their ability to avoid regret in subsequent choices, patients affected by cerebellar lesions were significantly impaired in evaluating the feeling of regret subjectively. These results demonstrate that the cerebellum is involved in conscious recognizing of negative feelings caused by the sense of self-responsibility for an incorrect decision. PMID:25999829

Pharmacy Students’ Perceptions of Natural Science and Mathematics Subjects

PubMed Central

Wilson, Sarah Ellen; Wan, Kai-Wai

2014-01-01

Objective. To determine the level of importance pharmacy students placed on science and mathematics subjects for pursuing a career in pharmacy. Method. Two hundred fifty-four students completed a survey instrument developed to investigate students’ perceptions of the relevance of science and mathematics subjects to a career in pharmacy. Pharmacy students in all 4 years of a master of pharmacy (MPharm) degree program were invited to complete the survey instrument. Results. Students viewed chemistry-based and biology-based subjects as relevant to a pharmacy career, whereas mathematics subjects such as physics, logarithms, statistics, and algebra were not viewed important to a career in pharmacy. Conclusion. Students’ experience in pharmacy and year of study influenced their perceptions of subjects relevant to a pharmacy career. Pharmacy educators need to consider how they can help students recognize the importance of scientific knowledge earlier in the pharmacy curriculum. PMID:25147390

Changes in plasma levels of B-type natriuretic peptide with acute exacerbations of chronic obstructive pulmonary disease.

PubMed

Nishimura, Koichi; Nishimura, Takashi; Onishi, Katsuya; Oga, Toru; Hasegawa, Yoshinori; Jones, Paul W

2014-01-01

Elevated plasma B-type natriuretic peptide (BNP) levels and their association with heart failure have been reported in subjects with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). To examine and compare plasma BNP levels and diastolic and systolic dysfunction in subjects with AECOPD and stable chronic obstructive pulmonary disease (COPD). In all, 87 unselected consecutive hospitalizations due to AECOPD in 61 subjects and a total of 190 consecutive subjects with stable COPD were recruited. Plasma BNP levels were compared cross-sectionally and longitudinally. Transthoracic echocardiographic examinations were also performed in the hospitalized subjects. In the hospitalized subjects, the median plasma BNP level (interquartile range) was 55.4 (26.9-129.3) pg/mL and was higher than that of patients with stable COPD: 18.3 (10.0-45.3) for Global Initiative for Chronic Obstructive Lung Disease grade I; 25.8 (11.0-53.7) for grade II; 22.1 (9.1-52.6) for grade III; and 17.2 (9.6-22.9) pg/mL for grade I V, all P<0.001. In 15 subjects studied prospectively, the median plasma BNP level was 19.4 (9.8-32.2) pg/mL before AECOPD, 72.7 (27.7-146.3) pg/mL during AECOPD, and 14.6 (12.9-39.0) pg/mL after AECOPD (P<0.0033 and P<0.0013, respectively). Median plasma BNP levels during AECOPD were significantly higher in ten unsuccessfully discharged subjects 260.5 (59.4-555.0) than in 48 successfully discharged subjects 48.5 (24.2-104.0) pg/mL (P=0.0066). Only 5.6% of AECOPD subjects were associated with systolic dysfunction defined as a left ventricular ejection fraction (LVEF) <50%; a further 7.4% were considered to have impaired relaxation defined as an E/A wave velocity ratio <0.8 and a deceleration time of E >240 ms. BNP levels were weakly correlated with the E/peak early diastolic velocity of the mitral annulus (Ea) ratio (Spearman's rank correlation coefficient =0.353, P=0.018), but they were not correlated with the LVEF (Spearman's rank correlation coefficient =-0.221, P=0.108). A modest elevation of plasma BNP is observed during AECOPD. It appears that AECOPD may have an impact on plasma BNP levels that is not attributable to heart failure.

Impact of intra-aortic balloon pump on long-term mortality of unselected patients with ST-segment elevation myocardial infarction complicated by cardiogenic shock

PubMed Central

Dziewierz, Artur; Siudak, Zbigniew; Rakowski, Tomasz; Kleczyński, Paweł; Zasada, Wojciech

2014-01-01

Introduction A large, randomised trial (IABP-SHOCK II) confirmed no benefit of intra-aortic balloon pump (IABP) on clinical outcomes of patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock. However, the ‘sickest’ patients are often excluded from randomised clinical trials, so it is difficult to generalise expected outcomes from randomized clinical trials to the real life setting. Aim We sought to evaluate the impact of IABP on 1-year mortality of unselected patients with STEMI presenting in cardiogenic shock. Material and methods Data were gathered for 1,650 consecutive patients with STEMI transferred for primary angioplasty from hospital networks in 7 countries in Europe from November 2005 to January 2007 (the EUROTRANSFER registry population). Of them, 51 patients with cardiogenic shock on admission were identified and stratified based on the use of IABP. Outcome results were adjusted for age and sex, to control possible selection bias. Results At the discretion of the operators, IABP was applied in 30 patients (58.8%, IABP group). The remaining 21 patients were treated without IABP (no-IABP group). The use of IABP was more frequent among males, younger patients, and patients with STEMI of the anterior wall. There was no difference in 30-day mortality in patients with and without IABP (no-IABP vs. IABP: 38.1% vs. 33.3%; adjusted OR 1.79 (95% CI 0.43–7.52); p = 0.43). Similarly, IABP had no impact on 1-year mortality (42.9% vs. 33.3%; adjusted OR 1.27 (95% CI 0.32–5.09); p = 0.74). One-year mortality was comparable among patients who survived hospitalisation (14.3% vs. 13%; p = 0.64). Conclusions We observed no benefit of IABP on short – and long-term mortality of unselected patients with STEMI complicated by cardiogenic shock. PMID:25489303

Evidence that the adenosine A3 receptor may mediate the protection afforded by preconditioning in the isolated rabbit heart.

PubMed

Liu, G S; Richards, S C; Olsson, R A; Mullane, K; Walsh, R S; Downey, J M

1994-07-01

Agonists selective for the A1 adenosine receptor mimic the protective effect of ischaemic preconditioning against infarction in the rabbit heart. Unselective adenosine antagonists block this protection but, paradoxically, the A1 adenosine receptor selective antagonist 8-cyclopentyl- 1,3-dipropylxanthine (DPCPX) does not. The aim of this study was to test the hypothesis that the newly described A3 adenosine receptor, which has an agonist profile similar to the A1 receptor but is insensitive to DPCPX, might mediate preconditioning. Isolated rabbit hearts perfused with Krebs buffer experienced 30 min of regional ischaemia followed by 120 min of reperfusion. Infarct size was measured by tetrazolium staining. In control hearts infarction was 32.2(SEM 1.5)% of the risk zone. Preconditioning by 5 min ischaemia and 10 min reperfusion reduced infarct size to 8.8(2.3)%. Replacing the regional ischaemia with 5 min perfusion with 10 microM adenosine or 65 nM N6-[2-(4-aminophenyl)ethyl]adenosine (APNEA), an adenosine A3 receptor agonist, was equally protective. The unselective antagonist 8-p-sulphophenyl theophylline at 100 microM abolished protection by preconditioning, adenosine, and APNEA, but 200 nM DPCPX did not block protection by any of the interventions. Likewise the potent but unselective A3 receptor antagonist 8-(4-carboxyethenylphenyl)-1,3-dipropylxanthine (BW A1433) completely blocked protection from ischaemic preconditioning. Because protection against infarction afforded by ischaemic preconditioning, adenosine, or the A3 receptor agonist APNEA could not be blocked by DPCPX and because the potent A3 receptor antagonist BW A1433 blocked protection from ischaemic preconditioning, these data indicate that the protection of preconditioning is not exclusively mediated by the adenosine A1 receptor in rabbit heart and could involve the A3 receptor.

Germline BRCA mutation evaluation in a prospective triple-negative breast cancer registry: implications for hereditary breast and/or ovarian cancer syndrome testing

PubMed Central

Klemp, Jennifer R.; Kimler, Bruce F.; Mahnken, Jonathan D.; Geier, Larry J.; Khan, Qamar J.; Elia, Manana; Connor, Carol S.; McGinness, Marilee K.; Mammen, Joshua M. W.; Wagner, Jamie L.; Ward, Claire; Ranallo, Lori; Knight, Catherine J.; Stecklein, Shane R.; Jensen, Roy A.; Fabian, Carol J.; Godwin, Andrew K.

2014-01-01

NCCN guidelines recommend genetic testing for all triple-negative breast cancer (TNBC) patients aged ≤60 years. However, due to the lack of prospective information in unselected patients, these guidelines are not uniformly adopted by clinicians and insurance carriers. The aim of this study was to determine the prevalence of BRCA mutations and evaluate the utility of NCCN guidelines in unselected TNBC population. Stage I–IV TNBC patients were enrolled on a prospective registry at academic and community practices. All patients underwent BRCA1/2 testing. Significant family history (SFH) was defined >1 relative with breast cancer at age ≤50 or ≥1 relative with ovarian cancer. Mutation prevalence in the entire cohort and subgroups was calculated. 207 TNBC patients were enrolled between 2011 and 2013. Racial/ethnic distribution: Caucasian (80 %), African–American (14 %), Ashkenazi (1 %). Deleterious BRCA1/2 mutations were identified in 15.4 % (32/207) of patients (BRCA1:11.1 %, BRCA2:4.3 %). SFH reported by 36 % of patients. Mutation prevalence in patients with and without SFH was 31.6 and 6.1 %, respectively. When assessed by age at TNBC diagnosis, the mutation prevalences were 27.6 % (≤50 years), 11.4 % (51–60 years), and 4.9 % (≥61 years). Using SFH or age ≤50 as criteria, 25 and 34 % of mutations, respectively, were missed. Mutation prevalence in patients meeting NCCN guidelines was 18.3 % (32/175) and 0 % (0/32) in patients who did not meet guidelines (p = .0059). In this unselected academic and community population with negligible Ashkenazi representation, we observed an overall BRCA mutation prevalence rate of 15.4 %. BRCA testing based on NCCN guidelines identified all carriers supporting its routine application in clinical practice for TNBC. PMID:24807107

Determining Clinically Relevant Changes in Community Walking Metrics to Be Tracked by the VA as Part of Routine Care in Lower Limb Amputee Veterans

DTIC Science & Technology

2016-10-01

total of 52 subjects have enrolled in the study: Veteran subjects n=34 and University of Utah subjects n= 18 . Preliminary analysis indicates that daily...relevant change 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18 . NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a. REPORT

Stable Genetic Influence on Anxiety-Related Behaviours across Middle Childhood

ERIC Educational Resources Information Center

Trzaskowski, Maciej; Zavos, Helena M. S.; Haworth, Claire M. A.; Plomin, Robert; Eley, Thalia C.

2012-01-01

We examined the aetiology of anxiety symptoms in an unselected population at ages 7 and 9, a period during which anxiety disorders first begin to develop (mean age at onset is 11 years). Specifically, the aim of the study was to investigate genetic and environmental continuity and change in components of anxiety in middle childhood. Parents of…

Scan for allele frequency differences from pooled samples in lines of pigs selected for components of litter size

USDA-ARS?s Scientific Manuscript database

Direct single trait selection within two seasonal replicates for 11 generations resulted in a 1.6 pig advantage for uterine capacity (UC) and a 3.0 advantage for ovulation rate (OR) compared to an unselected control (CO) population. Our objective was to gain insight and identify genetic loci impacte...

Unselective Overimitators: The Evolutionary Implications of Children's Indiscriminate Copying of Successful and Prestigious Models

ERIC Educational Resources Information Center

Chudek, Maciej; Baron, Andrew S.; Birch, Susan

2016-01-01

Children are both shrewd about whom to copy--they selectively learn from certain adults--and overimitators--they copy adults' obviously superfluous actions. Is overimitation also selective? Does selectivity change with age? In two experiments, 161 two- to seven-year-old children saw videos of one adult receiving better payoffs or more bystander…

WISC-R Verbal and Performance IQ Discrepancy in an Unselected Cohort: Clinical Significance and Longitudinal Stability.

ERIC Educational Resources Information Center

Moffitt, Terrie E.; Silva, P. A.

1987-01-01

Examined children whose Wechsler Intelligence Scale for Children-Revised (WISC-R) verbal and performance Intelligence Quotient discrepancies placed them beyond the 90th percentile. Longitudinal study showed 23 percent of the discrepant cases to be discrepant at two or more ages. Studied frequency of perinatal difficulties, early childhood…

Parents' Views on Changing Communication after Cochlear Implantation

ERIC Educational Resources Information Center

Watson, Linda M.; Hardie, Tim; Archbold, Sue M.; Wheeler, Alexandra

2008-01-01

We sent questionnaires to families of all 288 children who had received cochlear implants at one center in the United Kingdom at least 5 years previously. Thus, it was a large, unselected group. We received 142 replies and 119 indicated that the child and family had changed their communication approach following cochlear implantation. In 113 cases…

The Hierarchical Factor Model of ADHD: Invariant across Age and National Groupings?

ERIC Educational Resources Information Center

Toplak, Maggie E.; Sorge, Geoff B.; Flora, David B.; Chen, Wai; Banaschewski, Tobias; Buitelaar, Jan; Ebstein, Richard; Eisenberg, Jacques; Franke, Barbara; Gill, Michael; Miranda, Ana; Oades, Robert D.; Roeyers, Herbert; Rothenberger, Aribert; Sergeant, Joseph; Sonuga-Barke, Edmund; Steinhausen, Hans-Christoph; Thompson, Margaret; Tannock, Rosemary; Asherson, Philip; Faraone, Stephen V.

2012-01-01

Objective: To examine the factor structure of attention-deficit/hyperactivity disorder (ADHD) in a clinical sample of 1,373 children and adolescents with ADHD and their 1,772 unselected siblings recruited from different countries across a large age range. Hierarchical and correlated factor analytic models were compared separately in the ADHD and…

Genetic Variance for Autism Screening Items in an Unselected Sample of Toddler-Age Twins

ERIC Educational Resources Information Center

Stilp, Rebecca L. H.; Gernsbacher, Morton Ann; Schweigert, Emily K.; Arneson, Carrie L.; Goldsmith, H. Hill

2010-01-01

Objective: Twin and family studies of autistic traits and of cases diagnosed with autism suggest high heritability; however, the heritability of autistic traits in toddlers has not been investigated. Therefore, this study's goals were (1) to screen a statewide twin population using items similar to the six critical social and communication items…

Extreme antagonistic pleiotropy effects of DGAT1 on fat, milk and protein yields

USDA-ARS?s Scientific Manuscript database

A large-scale analysis using 294,079 first lactation Holstein cows, as well as a group of contemporary Holsteins and a Holstein line unselected since 1964, were used to study the genetic architecture associated with a mutation in the DGAT1 gene that has large effects on milk production. The ‘G’ alle...

Review: The Development of Coping across Childhood and Adolescence--An Integrative Review and Critique of Research

ERIC Educational Resources Information Center

Zimmer-Gembeck, Melanie J.; Skinner, Ellen A.

2011-01-01

Despite consensus that development shapes every aspect of coping, studies of age differences in coping have proven difficult to integrate, primarily because they examine largely unselected age groups, and utilize overlapping coping categories. A developmental framework was used to organize 58 studies of coping involving over 250 age comparisons or…

Prevalence of osteoporosis in men aged 65-75 in a primary care setting. A practice audit after application of the Canadian 2010 guidelines for osteoporosis screening.

PubMed

Ferrari, Robert

2015-03-01

Current Canadian osteoporosis guidelines recommend routine bone density screening of men at age 65. The purpose of this study is to determine the prevalence of osteoporosis in men aged 65-75 in after application of screening guidelines. All males aged 65-75 years who attended a large primary care clinic were advised of the 2010 Canadian osteoporosis guidelines and advised to obtain a bone density scan at or after their 65th birthday. Those who did not have a bone density scan since their 65th birthday were advised to obtain a scan, unless there was obvious reason not to do so (i.e. known osteoporosis). A record of the results for each patient were kept and tallied to determine the prevalence of osteoporosis. Osteoporosis was defined as a T-score of ≤ -2.5 in either the hip or lumbar spine. Of 574 male subjects in this clinic, between the ages of 65-75, 557 had a bone density scan, either already having done so at the time of being informed of the guidelines or obtaining a scan in the subsequent year after being informed of the guidelines. The prevalence of osteoporosis was 1.6% (9/557, 95% confidence interval 0.8-3.1%) in this sample. The average age of subjects with osteoporosis was 70.5 ± 1.4 years (range 68-75). None of the subjects under 68 years of age were found to have osteoporosis. The prevalence of osteoporosis in unselected male cohorts aged 65 may be too low to justify the routine bone density screening recommended in the 2010 Canadian osteoporosis guidelines.

Responding to a Relevance Imperative in School Science and Mathematics: Humanising the Curriculum Through Story

NASA Astrophysics Data System (ADS)

Darby-Hobbs, Linda

2013-02-01

There has been a recent push to reframe curriculum and pedagogy in ways that make school more meaningful and relevant to students' lives and perceived needs. This `relevance imperative' is evident in contemporary rhetoric surrounding quality education, and particularly in relation to the junior secondary years where student disengagement with schooling continues to abate. This paper explores how teachers translate this imperative into their mathematics and science teaching. Interview data and critical incidents from classroom practice are used to explore how six teachers attempted to make the subject matter meaningful for their students. Four `Categories of Meaning Making' emerged, highlighting key differences in how the nature of science and mathematics content constrained or enabled linkages between content and students' lifeworlds. While the teachers demonstrated a commitment to humanising the subject at some level, this analysis has shown that expecting teachers to make the curriculum relevant is not unproblematic because the meaning of relevance as a construct is complex, subject-specific, and embedded in understanding the human dimensions of learning, using, and identifying with, content. Through an examination of the construct of relevance and a humanistic turn in mathematics and science literature I argue for an expanded notion of relevance.

Augmentation in the treatment of restless legs syndrome with transdermal rotigotine.

PubMed

Beneš, Heike; García-Borreguero, Diego; Ferini-Strambi, Luigi; Schollmayer, Erwin; Fichtner, Andreas; Kohnen, Ralf

2012-06-01

To assess the risk of augmentation under treatment with the transdermally delivered dopamine agonist rotigotine for restless legs syndrome (RLS). Experts in RLS augmentation retrospectively reviewed data from two double-blind, placebo-controlled 6-month trials (745 rotigotine and 214 placebo subjects, NCT00136045 and NCT00135993) and from two open-label 1-year trials (620 rotigotine subjects, NCT00498108 and NCT00263068). All study visits were systematically evaluated applying the Max Planck Institute (MPI) criteria for the diagnosis of both augmentation and clinically relevant augmentation. MPI criteria for augmentation were met on at least one visit by 8.2% of all subjects in the double-blind trials with 12 subjects meeting the criteria for clinically relevant augmentation: 11 under rotigotine (1.5%) and one under placebo treatment. In the open-label trials, 9.7% of all subjects met the MPI criteria for augmentation and 2.9% met the criteria for clinically relevant augmentation. None of the patients treated with rotigotine for up to 1.5 years (double-blind plus open-label trial) discontinued prematurely owing to augmentation. Neither could dose-dependency or a time pattern for clinically relevant augmentation episodes be detected. Our analyses suggest that the risk for clinically relevant augmentation for the duration of up to 18 months of rotigotine treatment is low. Copyright © 2012 Elsevier B.V. All rights reserved.

Computer-Adaptive Testing: Implications for Students' Achievement, Motivation, Engagement, and Subjective Test Experience

ERIC Educational Resources Information Center

Martin, Andrew J.; Lazendic, Goran

2018-01-01

The present study investigated the implications of computer-adaptive testing (operationalized by way of multistage adaptive testing; MAT) and "conventional" fixed order computer testing for various test-relevant outcomes in numeracy, including achievement, test-relevant motivation and engagement, and subjective test experience. It did so…

When people matter more than money: an ERPs study.

PubMed

Rigoni, Davide; Polezzi, David; Rumiati, Rino; Guarino, Ramona; Sartori, Giuseppe

2010-03-16

In the present study, we showed that, in a social gambling task, individuals are influenced more by the type of social interaction than by the pattern of gains and losses. More precisely, the neural responses, as well as the level of pleasantness/unpleasantness following gains and losses, are modulated by social interaction factors. Here we present an Event-Related Potentials (ERPs) study in which three groups of participants were compared. Subjects were engaged in gambling tasks differing with regard to social factors: in a first condition, there was no social context; in a second condition, participants compared their outcomes with those of another individual; in a third condition, participants competed for a limited amount of money with another contender. In all conditions, all participants were revealed the outcome of an unselected alternative (non-obtained outcome) prior to the payoff associated with their selected option (obtained outcome). In addition, affective ratings were measured after the outcomes were presented. In the group without social context, ERPs results replicated previous findings. Interestingly, the P200 was modulated by varying social contexts, suggesting that attentive resources allocated to payoffs in comparison and competitive situations are decreased presumably in favor of social cues. Furthermore, Feedback Related Negativity (FRN) was predictive of the subjective feeling of pleasantness/unpleasantness following monetary outcomes. The present data provide information about neural and cognitive processing underlying economic decision-making when other individuals are involved. Copyright 2009 Elsevier Inc. All rights reserved.

Effect of bovine genotype on heifer response to repeated lipopolysaccharide (LPS) administration

USDA-ARS?s Scientific Manuscript database

Heifers (n = 4/genotype) from unselected (stable milk yield since 1964, UH) and contemporary (CH) Holsteins that differed in milk yield (6,200 and 11,100 kg milk/305 d) or from Red Angus cows (RA) were fed the same diet ad lib and housed together for 47 d before being challenged with 0.5 microgram L...

Stability of Infant-Mother Attachment and Its Relationship to Changing Life Circumstances in an Unselected Middle-Class Sample.

ERIC Educational Resources Information Center

Thompson, Ross A.; And Others

1982-01-01

Forty-three infants and mothers were observed in the Strange Situation when infants were 12.5 and 19.5 months old. Following each assessment, mothers completed a questionnaire concerning changes in family and care-giving circumstances. Results indicate that security of attachment reflects the current status of infant-mother interaction and that…

A Follow-Up Study of Mortality, Health Conditions and Associated Disabilities of People with Intellectual Disabilities in a Swedish County

ERIC Educational Resources Information Center

Gustavson, K.-H.; Umb-Carlsson, O.; Sonnander, K.

2005-01-01

Background: In the planning of services and health care for individuals with intellectual disability (ID), information is needed on the special requirements for habilitation and medical service and associated disabilities. Material and Methods: An unselected consecutive series of 82 adult persons with ID was studied. The medical examination…

Autism Spectrum Disorder in an Unselected Cohort of Children with Neurofibromatosis Type 1 (NF1)

ERIC Educational Resources Information Center

Eijk, S.; Mous, S. E.; Dieleman, G. C.; Dierckx, B.; Rietman, A. B.; de Nijs, P. F. A.; ten Hoopen, L. W.; van Minkelen, R.; Elgersma, Y.; Catsman-Berrevoets, C. E.; Oostenbrink, R.; Legerstee, J. S.

2018-01-01

In a non-selected sample of children with Neurofibromatosis type 1 (NF1) the prevalence rate of autism spectrum disorder (ASD) and predictive value of an observational (ADOS)--and questionnaire-based screening instrument were assessed. Complete data was available for 128 children. The prevalence rate for clinical ASD was 10.9%, which is clearly…

Children's Interracial Fiction: An Unselective Bibliography. Curricular Viewpoint Series.

ERIC Educational Resources Information Center

Glancy, Barbara Jean

This bibliography of children's books with black characters is annotated so that the reader may decide which books would be of interest to him or to her. The bibliography attempts to record as complete a listing as possible due to the reported paucity of literature in this area. In this listing of 328 books many portray biracial friendships. Each…

Effect of milk yield genotype on response to repeated lipopolysaccharide (LPS) administration to lactating Holstein cows

USDA-ARS?s Scientific Manuscript database

Cows (n = 12/genotype) from unselected (stable milk yield since 1964, UH) and contemporary (CH) Holsteins that differed by more than 4,500 kg milk/305 d were fed the same diet ad lib and housed together for more than 4 months before being blocked (2/genotype) by DIM and randomly assigned within geno...

Phase II trial of everolimus in patients with previously treated recurrent or metastatic head and neck squamous cell carcinoma.

PubMed

Geiger, Jessica L; Bauman, Julie E; Gibson, Michael K; Gooding, William E; Varadarajan, Prakash; Kotsakis, Athanasios; Martin, Daniel; Gutkind, Jorge Silvio; Hedberg, Matthew L; Grandis, Jennifer R; Argiris, Athanassios

2016-12-01

Patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) demonstrate aberrant activation of the phosphotidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. We examined the efficacy of everolimus, an mTOR inhibitor, in patients with recurrent or metastatic HNSCC. This single-arm phase II study enrolled biomarker-unselected patients with recurrent or metastatic HNSCC who failed at least 1 prior therapy. Everolimus was administered until progressive disease or unacceptable toxicity. Primary endpoint was clinical benefit rate (CBR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and evaluation of tissue and serum biomarkers related to the PIK3CA pathway. Seven of 9 patients treated in the first stage were evaluable. No objective responses were seen; CBR was 28%. Three patients discontinued everolimus because of toxicity. Median PFS and OS were 1.5 and 4.5 months, respectively. No activating PI3K mutations were identified in available tumor tissue. Everolimus was not active as monotherapy in unselected patients with recurrent/metastatic HNSCC. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1759-1764, 2016. © 2016 Wiley Periodicals, Inc.

Reduced length of hospital stay after the introduction of a rapid recovery protocol for primary THA procedures.

PubMed

den Hartog, Yvon M; Mathijssen, Nina M C; Vehmeijer, Stephan B W

2013-10-01

Rapid recovery protocols after total hip arthroplasty (THA) have been introduced worldwide in the last few years and they have reduced the length of hospital stay. We show the results of the introduction of a rapid recovery protocol for primary THA for unselected patients in our large teaching hospital. In a retrospective cohort study, we included all 1,180 patients who underwent a primary THA between July 1, 2008 and June 30, 2012. These patients were divided into 3 groups: patients operated before, during, and after the introduction of the rapid recovery protocol. There were no exclusion criteria. All complications, re-admissions, and reoperations were registered and analyzed. The mean length of hospital stay decreased from 4.6 to 2.9 nights after the introduction of the rapid recovery protocol. There were no statistically significant differences in the rate of complications, re-admissions, or reoperations between the 3 groups. In a large teaching hospital, the length of hospital stay decreased after introduction of our protocol for rapid recovery after THA in unselected patients, without any increase in complications, re-admissions, or reoperation rate.

A survey on features of allergic rhinitis in children.

PubMed

Zicari, A M; Indinnimeo, L; De Castro, G; Incorvaia, C; Frati, F; Dell'Albani, I; Puccinelli, P; Scolari, M; Duse, M

2013-05-01

A number of epidemiologic studies evaluated the prevalence of allergic rhinitis (AR), but few data are available on its different clinical presentations. We addressed this survey to assess the features of AR in children and adolescents. Thirty-five centers in Italy included 2623 pediatric patients with rhinitis, of whom 2319 suffered from AR, while 304 had other kinds of rhinitis. For each patient a standardized questionnaire was filled in, including ARIA classification, the duration of symptoms, the allergen identified as clinically relevant, the co-morbidities, the kind of treatment, the response to treatment, the satisfaction with the treatment, and the feasibility of allergen immunotherapy (AIT). Of the 2319 patients, 597 (25.7%) had mild intermittent, 701 (30.2%) mild persistent, 174 (7.5%) moderate-severe intermittent, and 773 (33.3%) moderate-severe persistent AR. The allergens most relevant were grass pollen and dust mites. The most frequently used drugs were oral antihistamines (83.1%) and topical corticosteroids (63.5%). The response to treatment was judged as excellent in 13.5%, good in 45.1%, fair in 30.8%, poor in 10%, and very bad in 0.6% of cases. The satisfaction with treatment was judged as very satisfactory in 15.2%, satisfactory in 61.8%, unsatisfactory in 22.4%, and very unsatisfactory in 0.5% of cases. AIT was considered indicated in 53.1% of patients with mild intermittent, 79.2% of moderate-severe intermittent, 72.6% of mild persistent, and 82.7% of moderate-severe persistent AR. The limitation of this study is that the population was not unselected and this prevents epidemiological significance. These results offer confirmation of the adequacy of ARIA guidelines in classifying patients with AR and of the association of severe phenotype with lack of success of drug treatment.

Clinical impact of tumour biology in the management of gastroesophageal cancer.

PubMed

Lordick, Florian; Janjigian, Yelena Y

2016-06-01

The characterization of oesophageal and gastric cancer into subtypes based on genotype has evolved in the past decade. Insights into the molecular landscapes of gastroesophageal cancer provide a roadmap to assist the development of new drugs and their use in combinations, for patient stratification, and for trials of targeted therapies. Trastuzumab is the only approved treatment for gastroesophageal cancers that overexpress HER2. Acquired resistance usually limits the duration of response to this treatment, although a number of new agents directed against HER2 have the potential to overcome or prolong the time until resistance occurs. Beyond that, anti-VEGFR2 therapy with ramucirumab was the first biological treatment strategy to produce a survival benefit in an unselected population of patients with chemotherapy-refractory gastroesophageal cancer. Large initiatives are starting to address the role of biomarker-driven targeted therapy in the metastatic and in the perioperative setting for patients with this disease. Immunotherapy also holds promise, and our understanding of subsets of gastroesophageal cancer based on patterns of immune response continues to evolve. Efforts are underway to identify more relevant genomic subsets through genomic screening, functional studies, and molecular characterization. Herein, we provide an overview of the key developments in the treatment of gastroesophageal cancer, and discuss potential strategies to further optimize therapy by targeting disease subtypes.

Analysis of polymorphic patterns in candidate genes in Israeli patients with prostate cancer.

PubMed

Figer, Arie; Friedman, Tal; Manguoglu, Ayse Esra; Flex, Dov; Vazina, Amnon; Novikov, Ilia; Shtrieker, Avi; Sidi, A Ami; Tichler, Thomas; Sapir, Einat Even; Baniel, Jack; Friedman, Eitan

2003-10-01

The precise genes involved in conferring prostate cancer risk in sporadic and familial cases are not fully known. To evaluate the genetic profile within several candidate genes of unselected prostate cancer cases and to correlate this profile with disease parameters. Jewish Israeli prostate cancer patients (n = 224) were genotyped for polymorphisms within candidate genes: p53, ER, VDR, GSTT1, CYP1A1, GSTP1, GSTM1, EPHX and HPC2/ELAC2, followed by analysis of the genotype with relevant clinical and pathologic parameters. The EPHX gene His113 allele was detected in 21.4% (33/154) of patients in whom disease was diagnosed above 61 years, compared with 5.7% (4/70) in earlier onset disease (P < 0.001). Within the group of late-onset disease, the same allele was noted in 5.5% (2/36) with grade I tumors compared with 18% (34/188) with grade II and up (P = 0.004). All other tested polymorphisms were not associated with a distinct clinical or pathologic feature in a statistically significant manner. In Israeli prostate cancer patients, the EPHX His113 allele is seemingly associated with a more advanced, late-onset disease. These preliminary data need to be confirmed by a larger and more ethnically diverse study.

Fifty-three years' experience with randomized clinical trials of emergency portacaval shunt for bleeding esophageal varices in Cirrhosis: 1958-2011.

PubMed

Orloff, Marshall J

2014-02-01

Emergency treatment of bleeding esophageal varices (BEV) consists mainly of endoscopic and pharmacologic measures, with transjugular intrahepatic portal-systemic shunt (TIPS) performed when bleeding is not controlled. Surgical shunt has been relegated to salvage. At the University of California, San Diego, Medical Center, our group has conducted 10 studies of emergency portacaval shunt (EPCS) during 46 years. To describe 2 randomized clinical trials (RCTs) conducted from 1988 to 2011 in unselected consecutive patients who received emergency treatment for BEV. In RCT No. 1, a total of 211 unselected consecutive patients with cirrhosis and acute BEV were randomized to emergency endoscopic sclerotherapy (EEST) (n=106) or EPCS (n=105). In RCT No. 2, a total of 154 unselected consecutive patients with cirrhosis and acute BEV were randomized to TIPS (n=78) or EPCS (n=76). Diagnostic workup was completed within 6 hours of initial contact, and primary treatment was initiated within 8 to 12 hours. Regular follow-up for up to 10 years was accomplished in 100% of the patients. In RCT No. 1, EEST or EPCS; in RCT No. 2, TIPS or EPCS. The 2 groups were compared with regard to survival, control of bleeding, portal-systemic encephalopathy, and direct cost of care. RESULTS Distribution in Child risk classes was almost identical. One-third of patients were in Child class C. Permanent control of bleeding was achieved by EEST in only 20% of the patients and by TIPS in only 22%. In contrast, EPCS permanently controlled bleeding in 97% and 100% of the patients in RCT No. 2 and RCT No. 1, respectively (P<.001). Survival was significantly greater following EPCS than after EEST and TIPS (P<.001). Median survival was more than 10 years following EPCS compared with 1.99 years after TIPS. Occlusion of TIPS was demonstrated in 84% of the patients, 63% of whom underwent TIPS revision, which failed in 80% of the cases. Recurrent portal-systemic encephalopathy developed in 35% of the patients who underwent EEST and 61% of those who received TIPS. In contrast, portal-systemic encephalopathy occurred in 15% of the patients who received EPCS in RCT No. 1 and 21% of those in RCT No. 2. Direct costs of care were 5 to 7 times greater in the EEST ($168100) and TIPS ($264800) groups than in the EPCS ($39000) group (P<.001). Emergency portacaval shunt permanently stopped variceal bleeding, almost never became occluded, accomplished 5 times the long-term survival than EEST or TIPS, and was much less costly than EEST or TIPS. The widespread practice of using EPCS mainly as salvage for failure of endoscopic therapy or TIPS is not supported by the definitive results of these long-term RCTs in unselected patients with cirrhosis. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00690027 and NCT00734227.

The Potential of Bee-Generated Carbon Dioxide for Control of Varroa Mite (Mesostigmata: Varroidae) in Indoor Overwintering Honey bee (Hymenoptera: Apidae) Colonies.

PubMed

Bahreini, Rassol; Currie, Robert W

2015-10-01

The objective of this study was to manipulate ventilation rate to characterize interactions between stocks of honey bees (Apis mellifera L.) and ventilation setting on varroa mite (Varroa destructor Anderson and Trueman) mortality in honey bee colonies kept indoors over winter. The first experiment used colonies established from stock selected locally for wintering performance under exposure to varroa (n = 6) and unselected bees (n = 6) to assess mite and bee mortality and levels of carbon dioxide (CO2) and oxygen (O2) in the bee cluster when kept under a simulated winter condition at 5°C. The second experiment, used colonies from selected bees (n = 10) and unselected bees (n = 12) that were exposed to either standard ventilation (14.4 liter/min per hive) or restricted ventilation (0.24 liter/min per hive, in a Plexiglas ventilation chamber) during a 16-d treatment period to assess the influence of restricted air flow on winter mortality rates of varroa mites and honey bees. Experiment 2 was repeated in early, mid-, and late winter. The first experiment showed that under unrestricted ventilation with CO2 concentrations averaging <2% there was no correlation between CO2 and varroa mite mortality when colonies were placed under low temperature. CO2 was negatively correlated with O2 in the bee cluster in both experiments. When ventilation was restricted, mean CO2 level (3.82 ± 0.31%, range 0.43-8.44%) increased by 200% relative to standard ventilation (1.29 ± 0.31%; range 0.09-5.26%) within the 16-d treatment period. The overall mite mortality rates and the reduction in mean abundance of varroa mite over time was greater under restricted ventilation (37 ± 4.2%) than under standard ventilation (23 ± 4.2%) but not affected by stock of bees during the treatment period. Selected bees showed overall greater mite mortality relative to unselected bees in both experiments. Restricting ventilation increased mite mortality, but did not affect worker bee mortality relative to that for colonies under standard ventilation. Restricted ventilation did not affect the overall level of Nosema compared with the control. However, there was an interaction between stock, season, and time of the trial. Unselected stock showed an increase in Nosema over time in the late winter trial that did not occur in the selected stock. In conclusion, these findings suggested that restricted ventilation has potential to suppress varroa mite in overwintering honey bee colonies via a low-cost and environmentally friendly measure. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Culturally Relevant Human Subjects Protection Training: A Case Study in Community-Engaged Research in the United States.

PubMed

Kue, Jennifer; Szalacha, Laura A; Happ, Mary Beth; Crisp, Abigail L; Menon, Usha

2018-02-01

Non-academic members of research teams, such as community members, can perceive traditional human subjects protection training as lacking in cultural relevance. We present a case exemplar of the development of a human subjects protection training for research staff with limited English proficiency and/or no or limited research experience. Seven modules were adapted for language, cultural examples, etc., from the standard Collaborative Institutional Training Initiative (CITI) human subjects protection training. Non-academic research staff completed a day-long training in human subjects protection (six modules) and our research protocol (one module). We assessed comprehension of content with PowerPoint slides and module quizzes. All participants successfully passed each module quiz with ≥ 80% correct. Questions answered incorrectly were discussed before proceeding to the next module. To meet the increasing demand for collaborative community-engaged research with underserved minority populations, human subjects protection training protocols can be adapted successfully to reflect real-world situations and provide culturally relevant materials to help non-academic research staff better understand the importance and necessity of research ethics.

The Fabric of Meaning and Subjective Effects in LSD-Induced States Depend on Serotonin 2A Receptor Activation.

PubMed

Preller, Katrin H; Herdener, Marcus; Pokorny, Thomas; Planzer, Amanda; Kraehenmann, Rainer; Stämpfli, Philipp; Liechti, Matthias E; Seifritz, Erich; Vollenweider, Franz X

2017-02-06

A core aspect of the human self is the attribution of personal relevance to everyday stimuli enabling us to experience our environment as meaningful [1]. However, abnormalities in the attribution of personal relevance to sensory experiences are also critical features of many psychiatric disorders [2, 3]. Despite their clinical relevance, the neurochemical and anatomical substrates enabling meaningful experiences are largely unknown. Therefore, we investigated the neuropharmacology of personal relevance processing in humans by combining fMRI and the administration of the mixed serotonin (5-HT) and dopamine receptor (R) agonist lysergic acid diethylamide (LSD), well known to alter the subjective meaning of percepts, with and without pretreatment with the 5-HT 2A R antagonist ketanserin. General subjective LSD effects were fully blocked by ketanserin. In addition, ketanserin inhibited the LSD-induced attribution of personal relevance to previously meaningless stimuli and modulated the processing of meaningful stimuli in cortical midline structures. These findings point to the crucial role of the 5-HT 2A R subtype and cortical midline regions in the generation and attribution of personal relevance. Our results thus increase our mechanistic understanding of personal relevance processing and reveal potential targets for the treatment of psychiatric illnesses characterized by alterations in personal relevance attribution. Copyright © 2017 Elsevier Ltd. All rights reserved.

C145 as a short-latency electrophysiological index of cognitive compensation in Alzheimer's disease

PubMed Central

Chapman, Robert M.; Porsteinsson, Anton P.; Gardner, Margaret N.; Mapstone, Mark; McCrary, John W.; Sandoval, Tiffany C.; Guillily, Maria D.; DeGrush, Elizabeth; Reilly, Lindsey A.

2012-01-01

Brain plasticity and cognitive compensation in the elderly are of increasing interest, and Alzheimer's disease (AD) offers an opportunity to elucidate how the brain may overcome damage. We provide neurophysiological evidence of a short-latency ERP component (C145) linked to stimulus relevancy that may reflect cognitive compensation in early-stage Alzheimer's disease (AD). Thirty-six subjects with early-stage, mild AD and 36 like-aged normal elderly (Controls) had their EEG recorded while performing our Number-Letter task, a cognitive/perceptual paradigm that manipulates stimulus relevancies. ERP components, including C145, were extracted from ERPs using Principal Components Analysis. C145 amplitudes and spatial distributions were compared among Controls, AD subjects with high performance on the Number-Letter task, and AD subjects with low performance. Compared to AD subjects, Control subjects showed enhanced C145 processing of visual stimuli in the occipital region where differential processing of relevant stimuli occurred. AD high performers recruited central brain areas in processing task relevancy. Controls and AD low performers did not show a significant task relevancy effect in these areas. We conclude that short-latency ERP components can detect electrophysiological differences in early-stage AD that reflect altered cognition. Differences in C145 amplitudes between AD and normal elderly groups regarding brain locations and types of task effects suggest compensatory mechanisms can occur in the AD brain to overcome loss of normal functionality, and this early compensation may have a profound effect on the cognitive efficiency of AD individuals. PMID:22886016

Use of Diuretics is not associated with mortality in patients admitted to the emergency department: results from a cross-sectional study.

PubMed

Haider, Dominik G; Lindner, Gregor; Wolzt, Michael; Leichtle, Alexander Benedikt; Fiedler, Georg-Martin; Sauter, Thomas C; Fuhrmann, Valentin; Exadaktylos, Aristomenis K

2016-02-01

Patients with diuretic therapy are at risk for drug-induced adverse reactions. It is unknown if presence of diuretic therapy at hospital emergency room admission is associated with mortality. In this cross sectional analysis, all emergency room patients 2010 and 2011 at the Inselspital Bern, Switzerland were included. A multivariable logistic regression model was performed to assess the association between pre-existing diuretic medication and 28 day mortality. Twenty-two thousand two hundred thirty-nine subjects were included in the analysis. A total of 8.5%, 2.5%, and 0.4% of patients used one, two, or three or more diuretics. In univariate analysis spironolactone, torasemide and chlortalidone use were associated with 28 day mortality (all p < 0.05). In a multivariate cox regression model no association with mortality was detectable (p > 0.05). No difference existed between patients with or without diuretic therapy (P > 0.05). Age and creatinine were independent risk factors for mortaliy (both p < 0.05). Use of diuretics is not associated with mortality in an unselected cohort of patients presenting in an emergency room.

Gastro-oesophageal reflux in patients with chronic rhino-sinusitis investigated with multichannel impedance - pH monitoring.

PubMed

Katle, E J; Hatlebakk, J G; Grimstad, T; Kvaløy, J T; Steinsvåg, S K

2017-03-01

The pathophysiology of chronic rhinosinusitis (CRS) is unclear. It has been discussed for decades whether gastro-oesophageal reflux (GOR) may be a contributing factor for some patients. The aim of the present study was to evaluate the level of GOR in an unselected group of patients with CRS using multichannel impedance-pH monitoring. Consecutive patients with CRS diagnosed using the EPOS2012 criteria, completed questionnaires on GOR symptoms and were offered 24-h multichannel intraluminal impedance (MII)-pH monitoring. The results were compared with a group of healthy controls. Forty-six patients completed MII-pH-monitoring and were compared with 45 control subjects, with comparable age and gender distributions. The median number of reflux episodes in the patients was 56.5 compared with 33 in controls, while, the numbers of proximal reflux episodes was 27.5 versus 3, respectively. Thirty nine patients had abnormal pH-impedance recordings compared with five controls. The CRS patients had significantly higher incidences of gastro-oesophageal reflux compared with asymptomatic controls. The results of this study suggest that GOR may be a causative or contributing factor of CRS.

Elevated total plasma homocysteine and 667C{r_arrow}T mutation of the 5,10-methylenetetrahydrofolate reductase gene in thrombotic vascular disease

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

De Franchis, R.; Sebastio, G.; Andria, G.

1996-07-01

Moderate elevation of total plasma homocysteine (tHcy) has been reported as an independent risk factor for thrombotic vascular disease, a well-known multifactorial disorder. Possible genetic causes of elevated tHcy include defects of the sulfur-containing amino acids metabolism due to deficiencies of cystathionine {Beta}-synthase, of 5,10-methylenetetrahydrofolate reductase (MTHFR), and of the enzymes of cobalamin metabolism. An impaired activity of MTHFR due to a thermolabile form of the enzyme has been observed in {le}28% of hyperhomocysteinemic patients with premature vascular disease. More recently, the molecular basis of such enzymatic thermolability has been related to a common mutation of the MTHFR gene, causingmore » a C-to-T substitution at nt 677 (677C{r_arrow}T). This mutation was found in 38% of unselected chromosomes from 57 French Canadian individuals. The homozygous state for the mutation was present in 12% of these subjects and correlated with significantly elevated tHcy. Preliminary evidence indicates that the frequency of homozygotes for the 677C{r_arrow}T mutation may vary significantly in populations from different geographic areas. 5 refs., 2 tabs.« less

The Relationship between Autistic Traits and Social Anxiety, Worry, Obsessive-Compulsive, and Depressive Symptoms: Specific and Non-Specific Mediators in a Student Sample

ERIC Educational Resources Information Center

Liew, Shi Min; Thevaraja, Nishta; Hong, Ryan Y.; Magiati, Iliana

2015-01-01

The high prevalence of anxiety symptoms in individuals with autism spectrum disorders has now been well documented. There is also a positive relationship between autistic traits and anxiety symptoms in unselected samples and individuals with anxiety disorders have more autistic traits compared to those without. Less is known, however, regarding…

Population growth of Varroa destructor (Acari: Varroidae) in colonies of Russian and unselected honey bee (Hymenoptera: Apidae) stock as related to numbers of foragers with mites

USDA-ARS?s Scientific Manuscript database

Varroa mites are an external parasite of honey bees and a leading cause of colony losses worldwide. Varroa populations can be controlled with miticides, but mite resistant stocks such as the Russian honey bee (RHB) also are available. RHB and other mite resistant stock limit Varroa population growth...

Examination of the Properties of the Modified Checklist for Autism in Toddlers (M-CHAT) in a Population Sample

ERIC Educational Resources Information Center

Yama, Brie; Freeman, Tom; Graves, Erin; Yuan, Su; Campbell, M. Karen

2012-01-01

This study examines the following properties of the Modified Checklist for Autism in Toddlers (M-CHAT) in an unselected low-risk sample: (a) the maximum age for screen administration; (b) the positive screen rate in the absence of follow-up telephone interviews and; (c) the distributional properties of positive screens. Data came from a…

The Effects and Costs of a Group-Based Education Programme for Self-Management of Patients with Type 2 Diabetes. A Community-Based Study

ERIC Educational Resources Information Center

Molsted, Stig; Tribler, Jane; Poulsen, Peter B.; Snorgaard, Ole

2012-01-01

The worldwide epidemic of Type 2 diabetes necessitates evidence-based self-management education programmes. The purpose of this study was to investigate the effects and costs of an empowerment-based structured diabetes self-management education programme in an unselected group of patients with Type 2 diabetes. Seven hundred and two patients…

Perceptual Decisions in the Presence of Relevant and Irrelevant Sensory Evidence

PubMed Central

Anders, Ursula M.; McLean, Charlotte S.; Ouyang, Bowen; Ditterich, Jochen

2017-01-01

Perceptual decisions in the presence of decision-irrelevant sensory information require a selection of decision-relevant sensory evidence. To characterize the mechanism that is responsible for separating decision-relevant from irrelevant sensory information we asked human subjects to make judgments about one of two simultaneously present motion components in a random dot stimulus. Subjects were able to ignore the decision-irrelevant component to a large degree, but their decisions were still influenced by the irrelevant sensory information. Computational modeling revealed that this influence was not simply the consequence of subjects forgetting at times which stimulus component they had been instructed to base their decision on. Instead, residual irrelevant information always seems to be leaking through, and the decision process is captured by a net sensory evidence signal being accumulated to a decision threshold. This net sensory evidence is a linear combination of decision-relevant and irrelevant sensory information. The selection process is therefore well-described by a strong linear gain modulation, which, in our experiment, resulted in the relevant sensory evidence having at least 10 times more impact on the decision than the irrelevant evidence. PMID:29176941

Perceptual Decisions in the Presence of Relevant and Irrelevant Sensory Evidence.

PubMed

Anders, Ursula M; McLean, Charlotte S; Ouyang, Bowen; Ditterich, Jochen

2017-01-01

Perceptual decisions in the presence of decision-irrelevant sensory information require a selection of decision-relevant sensory evidence. To characterize the mechanism that is responsible for separating decision-relevant from irrelevant sensory information we asked human subjects to make judgments about one of two simultaneously present motion components in a random dot stimulus. Subjects were able to ignore the decision-irrelevant component to a large degree, but their decisions were still influenced by the irrelevant sensory information. Computational modeling revealed that this influence was not simply the consequence of subjects forgetting at times which stimulus component they had been instructed to base their decision on. Instead, residual irrelevant information always seems to be leaking through, and the decision process is captured by a net sensory evidence signal being accumulated to a decision threshold. This net sensory evidence is a linear combination of decision-relevant and irrelevant sensory information. The selection process is therefore well-described by a strong linear gain modulation, which, in our experiment, resulted in the relevant sensory evidence having at least 10 times more impact on the decision than the irrelevant evidence.

Rapid microbiological screening for tuberculosis in HIV-positive patients on the first day of acute hospital admission by systematic testing of urine samples using Xpert MTB/RIF: a prospective cohort in South Africa.

PubMed

Lawn, Stephen D; Kerkhoff, Andrew D; Burton, Rosie; Schutz, Charlotte; van Wyk, Gavin; Vogt, Monica; Pahlana, Pearl; Nicol, Mark P; Meintjes, Graeme

2015-08-14

Autopsy studies of HIV/AIDS-related hospital deaths in sub-Saharan Africa reveal frequent failure of pre-mortem diagnosis of tuberculosis (TB), which is found in 34-64 % of adult cadavers. We determined the overall prevalence and predictors of TB among consecutive unselected HIV-positive adults requiring acute hospital admission and the comparative diagnostic yield obtained by screening urine and sputum samples obtained on day 1 of admission with Xpert MTB/RIF (Xpert). To determine overall TB prevalence accurately, comprehensive clinical sampling (sputum, urine, blood plus other relevant samples) was done and TB was defined by detection of Mycobacterium tuberculosis in any sample using Xpert and/or mycobacterial liquid culture. To evaluate a rapid screening strategy, we compared the diagnostic yield of Xpert testing sputum samples and urine samples obtained with assistance from a respiratory study nurse in the first 24 h of admission. Unselected HIV-positive acute adult new medical admissions (n = 427) who were not receiving TB treatment were enrolled irrespective of clinical presentation or symptom profile. From 2,391 cultures and Xpert tests done (mean, 5.6 tests/patient) on 1,745 samples (mean, 4.1 samples/patient), TB was diagnosed in 139 patients (median CD4 cell count, 80 cells/μL). TB prevalence was very high (32.6 %; 95 % CI, 28.1-37.2 %; 139/427). However, patient symptoms and risk factors were poorly predictive for TB. Overall, ≥1 non-respiratory sample(s) tested positive in 115/139 (83 %) of all TB cases, including positive blood cultures in 41/139 (29.5 %) of TB cases. In the first 24 h of admission, sputum (spot and/or induced samples) and urine were obtainable from 37.0 % and 99.5 % of patients, respectively (P <0.001). From these, the proportions of total TB cases (n = 139) that were diagnosed by Xpert testing sputum, urine or both sputum and urine combined within the first 24 h were 39/139 (28.1 %), 89/139 (64.0 %) and 108/139 (77.7 %) cases, respectively (P <0.001). The very high prevalence of active TB and its non-specific presentation strongly suggest the need for routine microbiological screening for TB in all HIV-positive medical admissions in high-burden settings. The incremental diagnostic yield from Xpert testing urine was very high and this strategy might be used to rapidly screen new admissions, especially if sputum is difficult to obtain.

Goal-driven selective attention in patients with right hemisphere lesions: how intact is the ipsilesional field?

PubMed

Snow, Jacqueline C; Mattingley, Jason B

2006-01-01

Patients with right hemisphere (RH) lesions often display a spatial bias in attention towards the ipsilesional hemifield. The behavioural manifestations of this spatial bias are typically interpreted as reflecting increased or enhanced attention for stimuli within the 'intact' ipsilesional field, and impaired attentional functioning within the contralesional field. In the healthy brain, goal-driven and stimulus-driven attentional processes interact to determine which stimuli should be prioritized for selection. Although unilateral brain damage increases the relative attentional salience of stimuli within the ipsilesional field, it might also cause problems in filtering or attenuating task-irrelevant information. We examined whether goal-driven attention modulates the processing of ipsilesional and contralesional information in 6 patients with unilateral brain damage following RH stroke (5 male, 1 female; mean age 60.8 years) and a group of age and sex-matched controls. We used a flanker task in which participants made speeded judgements on a central target item (a coloured letter). On each trial the target was flanked by a coloured letter in the left and right hemifields. In separate blocks, participants were instructed to judge either the identity or the colour of the central target and to ignore the flankers. The flanker on one side could be congruent, incongruent or neutral with respect to the target, on either the letter or the colour dimension, whereas the flanker on the other side was always neutral on both dimensions. Healthy controls showed significant interference from incongruent flankers on either side. Crucially, however, this effect only occurred for the task-relevant dimension [F(2,10) = 24.60; P < 0.001]. For patients, however, both the task-relevant and task-irrelevant dimensions of ipsilesional flankers interfered with response times [task-relevant: F(2,10) = 7.50, P < 0.05; task-irrelevant: F(1,5) = 6.20, P < 0.05]. Conversely, contralesional flankers influenced response times only when the target and distractor were incongruent on the task-relevant dimension [F(2,10) = 4.85; P < 0.05]. Our findings demonstrate that following RH damage, goal-driven biases cannot constrain the processing of task-irrelevant features of ipsilesional stimuli. We speculate that a lateralized bias in spatial attention leads to unselective prioritization of all feature-based attributes of stimuli appearing within the ipsilesional hemifield, whether or not they are relevant to performance. Attentional selection for ipsilesional stimuli in disorders such as spatial neglect and extinction may not therefore be entirely normal, as previously assumed.

An Examination of Culturally Relevant Stressors, Coping, Ethnic Identity, and Subjective Well-Being in Urban, Ethnic Minority Adolescents

ERIC Educational Resources Information Center

Vera, Elizabeth M.; Vacek, Kimberly; Coyle, Laura D.; Stinson, Jennifer; Mull, Megan; Doud, Katherine; Buchheit, Christine; Gorman, Catherine; Hewitt, Amber; Keene, Chesleigh; Blackmon, Sha'kema; Langrehr, Kimberly J.

2011-01-01

This study explored relations between culturally relevant stressors (i.e., urban hassles, perceived discrimination) and subjective well-being (SWB; i.e., positive/ negative affect, life satisfaction) to examine whether ethnic identity and/or coping strategies would serve as moderators of the relations between stress and SWB for 157 urban, ethnic…

"Biosphere Reserve"--The Actual Research Subject of the Sustainable Development Process"

ERIC Educational Resources Information Center

Khasaev, Gabibulla R.; Sadovenko, Marina Yu.; Isaev, Roman O.

2016-01-01

The relevance of the analyzed issue is caused by the growing slippage of research funds of sustainable development in its practice. The purpose of the article is the theoretical basis of the biosphere reserve as a scientific research subject that is relevant to rules of the scientific activity. The leading approach to the study of this issue is…

Using Relevance Prompts: An Exploratory Study to Promote Eighth Graders' Comprehension and Retelling of Narrative Text

ERIC Educational Resources Information Center

Fogarty, Melissa S.; Davis, John L.; Anderson, Leah L.; Myint, Ahmarlay

2017-01-01

This exploratory study investigated the effects of modifying eighth grade students' purposes for reading through a prompt designed to increase engagement with the text. The current study was conducted using a randomized between-subjects design, with a relevance prompt as the between-subjects factor and reader proficiency as a covariate. A sample…

Predictors of methamphetamine psychosis: history of ADHD-relevant childhood behaviors and drug exposure.

PubMed

Salo, Ruth; Fassbender, Catherine; Iosif, Ana-Maria; Ursu, Stefan; Leamon, Martin H; Carter, Cameron

2013-12-15

The goal of this study was to extend our previous research that reported a significant association between Attention Deficit Hyperactivity Disorder (ADHD)-relevant childhood behaviors and the frequency of methamphetamine (MA)-induced psychotic symptoms in an expanded sample. 190 participants who met DSM-IV criteria for MA dependence were administered the Methamphetamine Experience Questionnaire that assessed MA-induced psychosis. Data related to MA exposure, comorbid drug use, education, familial psychiatric history and assessments of ADHD-relevant childhood behaviors as measured by the Wender Utah Rating Scale (WURS) were collected. Although WURS scores did not differ between 145 MAP+ and 45 MAP- subjects, MAP+ subjects with higher WURS scores were significantly more likely to report more frequent psychosis. Although mean daily MA dosage did not differ between the MAP+ and MAP- subjects, MAP+ subjects who consumed larger doses of MA were significantly more likely to experience frequent psychosis. These data suggest that ADHD-relevant childhood behaviors may interact with MA exposure to reflect a neurobiological vulnerability related to the emergence of frequent MA-induced psychotic symptoms. These results may elucidate factors that contribute to the psychiatric sequelae of MA abuse. © 2013 Elsevier Ireland Ltd. All rights reserved.

A hybrid model of mathematics support for science students emphasizing basic skills and discipline relevance

NASA Astrophysics Data System (ADS)

Jackson, Deborah C.; Johnson, Elizabeth D.

2013-09-01

The problem of students entering university lacking basic mathematical skills is a critical issue in the Australian higher-education sector and relevant globally. The Maths Skills programme at La Trobe University has been developed to address under preparation in the first-year science cohort in the absence of an institutional mathematics support centre. The programme was delivered through first-year science and statistics subjects with large enrolments and focused on basic mathematical skills relevant to each science discipline. The programme offered a new approach to the traditional mathematical support centre or class. It was designed through close collaboration between science subject coordinators and the project leader, a mathematician, and includes resources relevant to science and mathematics questions written in context. Evaluation of the programme showed it improved the confidence of the participating students who found it helpful and relevant. The programme was delivered through three learning modes to allow students to select activities most suitable for them, which was appreciated by students. Mathematics skills appeared to increase following completion of the programme and student participation in the programme correlated positively and highly with academic grades in their relevant science subjects. This programme offers an alternative model for mathematics support tailored to science disciplines.

Epidermal growth factor receptor in non-small cell lung cancer

PubMed Central

2015-01-01

Following the identification of a group of patients in the initial tyrosine kinase inhibitor (TKI) trials for lung cancer, there has been detailed focus on which patients may benefit from inhibitor therapy. This article reviews the background, genetics and prevalence of epidermal growth factor mutations in non-small cell lung cancer (NSCLC). Additionally, the prevalence in unselected patients is compared against various other reviews. PMID:25870793

Biological feedstock development as part of the domestication and commercialization of Taraxacum kok-saghyz, a potential domestic source of natural rubber and inulin: progress and outlook

USDA-ARS?s Scientific Manuscript database

Wild-collected F0 seed was found to contain a mixture Taraxacum species (i.e., highly variable seedling phenotypes), a likely drag on TKS germplasm enhancement. Also, roots of unselected, wild-collected Taraxacum genotypes were found to contain, on average, 1.4 and 56.4 percent rubber and inulin, re...

External validity of the ARISTOTLE trial in real-life atrial fibrillation patients.

PubMed

Hägg, Lovisa; Johansson, Cecilia; Jansson, Jan-Håkan; Johansson, Lars

2014-10-01

Our primary objective was to determine the proportion of patients with atrial fibrillation (AF) eligible for enrollment in a randomized controlled trial for a novel oral anticoagulant, the ARISTOTLE trial. A secondary objective was to describe the reasons for trial ineligibility. We performed a cross-sectional study of an unselected population including 2274 patients in Skellefteå, Sweden with at least one verified episode of AF on or before December 31, 2010. Patients were classified as suitable or unsuitable for anticoagulant treatment according to current guidelines. The enrollment criteria from the ARISTOTLE trial were extracted from the original publication and applied to the population. Among all patients with AF, 1579 were classified as suitable for anticoagulant treatment. Of these, only 658 patients (42%) were eligible for participation in the ARISTOTLE trial. Among the 921 patients ineligible for participation, 498 did not meet the ECG criteria, 272 had psychosocial problems, and in addition, 78 patients were excluded due to both of these criteria. Our study shows that a majority of the patients in an unselected population with AF suitable for anticoagulant treatment were ineligible for participation in the ARISTOTLE trial. The applicability of the ARISTOTLE trial is therefore unknown for a considerable proportion of patients with AF in real life. © 2014 John Wiley & Sons Ltd.

Written pretest information and germline BRCA1/2 pathogenic variant testing in unselected breast cancer patients: predictors of testing uptake.

PubMed

Nilsson, Martin P; Nilsson, Erik D; Silfverberg, Barbro; Borg, Åke; Loman, Niklas

2018-06-06

This study aimed to evaluate predictors of testing uptake among unselected breast cancer patients who were offered germline BRCA1/2 testing in a prospective study. Pretest information was provided by a standardized invitation letter instead of in-person counseling. Data was abstracted from medical records. Using multivariate logistic regressions, predictors of testing uptake were analyzed. The overall uptake of testing was 67% (539 of 805 patients). Low uptake rates were found for patients aged ≥80 years (33%), and patients born outside of Europe (37%). In adjusted analysis, age ≥80 years (odds ratio [OR] 0.10; P = 0.002), psychiatric disorders (OR 0.46; P = 0.006), occupation requiring at least 3 years of university or college education (OR 2.03; P = 0.003), and breast cancer or ovarian cancer in first-degree or second-degree relatives (OR 1.66; P = 0.02) were independently associated with uptake of BRCA1/2 testing. Somatic comorbidity in patients aged <70 years was associated with lower testing uptake. Testing uptake varies across different subgroups according to patient-related factors that are readily available in the medical records. Knowledge about these factors enables health care professionals to identify patients who are less likely to pursue genetic testing.

Injection related anxiety in insulin-treated diabetes.

PubMed

Zambanini, A; Newson, R B; Maisey, M; Feher, M D

1999-12-01

The presence of injection related anxiety and phobia may influence compliance, glycaemic control and quality of life in patients with insulin-treated diabetes. Unselected consecutive, insulin-treated patients attending a diabetes clinic for follow-up, completed a standardised questionnaire providing an injection anxiety score (IAS) and general anxiety score (GAS). A total of 115 insulin-treated (80 Type 1 and 35 Type 2) diabetic patients completed the questionnaire. Injections had been avoided secondary to anxiety in 14% of cases and 42% expressed concern at having to inject more frequently. An IAS > or = 3 was seen in 28% of patients and of these, 66% injected insulin one to two times/day, 45% had avoided injections, and 70% would be bothered by more frequent injections. A significant correlation between IAS and GAS was seen (Kendall's tau-a 0.30, 95% CI 0.19-0.41, P < 0.001). GAS was significantly associated with both previous injection avoidance and expressed concern at increased injection frequency. No significant correlation was seen with HbA1c and injection or general anxiety scores. Symptoms relating to insulin injection anxiety and phobia have a high prevalence in an unselected group of diabetic patients requiring insulin injections and are associated with higher levels of general anxiety.

Estimating Fast Neural Input Using Anatomical and Functional Connectivity

PubMed Central

Eriksson, David

2016-01-01

In the last 20 years there has been an increased interest in estimating signals that are sent between neurons and brain areas. During this time many new methods have appeared for measuring those signals. Here we review a wide range of methods for which connected neurons can be identified anatomically, by tracing axons that run between the cells, or functionally, by detecting if the activity of two neurons are correlated with a short lag. The signals that are sent between the neurons are represented by the activity in the neurons that are connected to the target population or by the activity at the corresponding synapses. The different methods not only differ in the accuracy of the signal measurement but they also differ in the type of signal being measured. For example, unselective recording of all neurons in the source population encompasses more indirect pathways to the target population than if one selectively record from the neurons that project to the target population. Infact, this degree of selectivity is similar to that of optogenetic perturbations; one can perturb selectively or unselectively. Thus it becomes possible to match a given signal measurement method with a signal perturbation method, something that allows for an exact input control to any neuronal population. PMID:28066189

Processing and memory of information presented in narrative or expository texts.

PubMed

Wolfe, Michael B W; Woodwyk, Joshua M

2010-09-01

Previous research suggests that narrative and expository texts differ in the extent to which they prompt students to integrate to-be-learned content with relevant prior knowledge during comprehension. We expand on previous research by examining on-line processing and representation in memory of to-be-learned content that is embedded in narrative or expository texts. We are particularly interested in how differences in the use of relevant prior knowledge leads to differences in terms of levels of discourse representation (textbase vs. situation model). A total of 61 university undergraduates in Expt 1, and 160 in Expt 2. In Expt 1, subjects thought out loud while comprehending circulatory system content embedded in a narrative or expository text, followed by free recall of text content. In Expt 2, subjects read silently and completed a sentence recognition task to assess memory. In Expt 1, subjects made more associations to prior knowledge while reading the expository text, and recalled more content. Content recall was also correlated with amount of relevant prior knowledge for subjects who read the expository text but not the narrative text. In Expt 2, subjects reading the expository text (compared to the narrative text) had a weaker textbase representation of the to-be-learned content, but a marginally stronger situation model. Results suggest that in terms of to-be-learned content, expository texts trigger students to utilize relevant prior knowledge more than narrative texts.

Clinical Significance of Epsilon Waves in Arrhythmogenic Cardiomyopathy.

PubMed

Protonotarios, Alexandros; Anastasakis, Aris; Tsatsopoulou, Adalena; Antoniades, Loizos; Prappa, Efstathia; Syrris, Petros; Tousoulis, Dimitrios; McKENNA, William J; Protonotarios, Nikos

2015-07-16

Epsilon waves are hallmark features of arrhythmogenic cardiomyopathy (ACM) but information about their clinical significance is variable. We evaluated epsilon wave prevalence, characteristics, and their clinical significance in an ACM population. Eighty-six unselected patients fulfilling the 2010 Task Force criteria were enrolled. Seventy-six of them were carriers of desmosomal mutations. All subjects were serially evaluated with standard 12-lead ECG and 2-dimensional echocardiography. Epsilon waves were evaluated in all precordial and inferior leads. Novel parameters assessed included their duration and precordial/inferior lead extension. Twenty-five subjects (29%) had epsilon waves that were present in lead V3 and beyond in 9, and in the inferior leads in 7. Epsilon waves were associated with right ventricular outflow tract (RVOT) (P = 0.001) but not RV posterior wall (P = 0.21), RV apex (P = 0.30), or left ventricular (P = 0.94) wall motion abnormalities. Patients with epsilon waves had increased RVOT diameter (P < 0.0001). Extension of epsilon waves in lead V3 and beyond was associated with increased epsilon wave duration (P = 0.002) and RVOT diameter (P = 0.04). The duration of epsilon waves was positively correlated with RVOT diameter (r = 0.70, P = 0.0001). Epsilon waves were also associated with episodes of sustained ventricular tachycardia (P = 0.004) but not with heart failure (P = 0.41) or sudden cardiac death (P = 0.31). Detection of epsilon waves on 12-lead ECG reflects significant RVOT involvement, which was associated with episodes of sustained ventricular tachycardia but not sudden cardiac death. © 2015 Wiley Periodicals, Inc.

Evaluation of an internet-based e-learning module to introduce nuclear medicine to medical students: a feasibility study.

PubMed

Diessl, Stefanie; Verburg, Frederik A; Hoernlein, Alexander; Schumann, Martin; Luster, Markus; Reiners, Christoph

2010-12-01

The advent of electronic learning, the so-called e-learning, offers new possibilities for instruction in addition to the traditional face-to-face teaching in the education of medical students. To evaluate the additional educational value of a voluntary e-learning module in a nuclear medicine course for third-year medical students. Twenty exemplary nuclear medicine patient cases from our department were developed for e-learning purposes and presented on the internet using the web-based training program ‘CaseTrain’. Subsequently, three selected test cases were handled and evaluated by an unselected population of third-year medical students. One hundred and twenty-eight students studied the three patient cases and filled out the evaluation questionnaire completely. The most important result is that both the interest in and the subjective feeling of the knowledge level regarding the specialized field of nuclear medicine had increased significantly after working through the three e-learning cases. Ninety-seven percent of the evaluating students considered the use of computer-based learning useful. The subjective grading of the content of the cases and the handling of the software were graded with high marks by the participants, 1.9 and 2.0, respectively, on a linear scale with 1 being the best and 6 being the worst. The addition of e-learning to face-to-face teaching as a form of ‘blended learning’ is highly appreciated by medical students, and will provide an effective medium for bringing better understanding of nuclear medicine to future colleagues.

Critical Dysphagia is Common in Parkinson Disease and Occurs Even in Early Stages: A Prospective Cohort Study.

PubMed

Pflug, Christina; Bihler, Moritz; Emich, Katharina; Niessen, Almut; Nienstedt, Julie Cläre; Flügel, Till; Koseki, Jana-Christiane; Plaetke, Rosemarie; Hidding, Ute; Gerloff, Christian; Buhmann, Carsten

2018-02-01

To assess the prevalence of dysphagia and its typical findings in unselected "real-world" Parkinson patients using an objective gold-standard method. This was a prospective, controlled, cross-sectional study conducted in 119 consecutive Parkinson patients of all stages independent of subjective dysphagia. Patients and 32 controls were clinically and endoscopically examined by flexible endoscopic evaluation of swallowing (FEES) to evaluate the deglutition with regard to three consistencies (water, biscuit, and bread). Typical findings of dysphagia like penetration and aspiration, residues, and leakage were assessed. Dysphagia was common in Parkinson patients and occurred in all, even early, disease stages. Only 5% (6/119) of patients showed a completely unremarkable deglutition. Aspiration was seen in 25% (30/119) of patients and always related to water. Residues occurred in 93% (111/119), most commonly for bread. Leakage was much less frequent and was found in only 3-18%, depending on consistency. In a significant fraction of patients, objective dysphagia was not subjectively perceived. A total of 16% of asymptomatic patients suffered from critical aspiration. Significant swallowing deficiencies already occurred in early disease. Aspiration was found in 4 of 20 (20%) patients with disease duration of less than 2 years. Seven of 57 patients (12%) with Hoehn and Yahr stage 2 suffered from severe aspiration. Given the high frequency of critical aspiration in Parkinson disease, these patients should be evaluated early for dysphagia to avoid complications and recommend an adequate therapy. FEES is a simple, cost efficient, minimally invasive method that is ideally suited for this purpose.

Childhood chronic physical condition, self-reported health, and life satisfaction in adolescence.

PubMed

Määttä, Heidi; Hurtig, Tuula; Taanila, Anja; Honkanen, Meri; Ebeling, Hanna; Koivumaa-Honkanen, Heli

2013-09-01

The present study investigates the prevalence and type of chronic conditions at 7 years of age-with special reference to atopic conditions-and their longitudinal associations with self-reported health and life satisfaction in adolescence. The data were obtained from Northern Finland Birth Cohort 1986 (NFBC 1986), which is a longitudinal 1-year birth cohort from an unselected, regionally defined population (n = 9,432). The present study investigated a sample of 8,036 children with data of chronic conditions at 7 years of age and a sample of 6,680 children with data of chronic conditions at 16 years of age. According to parents' report the prevalence of CC at 7 years of age was 14.8 % among boys and 13.2 % among girls, these figures being at 16 years of age 20.7 and 19.4 %, respectively. Atopic conditions were the most common chronic conditions at 7 years of age (12.7 % vs. other chronic conditions 4.7 %). Childhood chronic condition was associated with subsequent self-reported health in adolescence, but not with subsequent self-reported life satisfaction. Chronic condition at 7 years of age increased the risk of reporting health as "poor" even if the chronic condition was no longer prevalent at 16 years of age. Atopic conditions seemed to be linked with self-reported poor/moderate health more often than other chronic conditions among girls. Conclusion Childhood chronic conditions seem to affect adolescent's subjective health, but fortunately, they do not affect adolescents' subjective well-being to such an extent that it could lower their life satisfaction.

Patent foramen ovale is not associated with an increased risk of stroke recurrence.

PubMed

Feurer, R; Sadikovic, S; Sepp, D; Esposito, L; Schleef, M; Bockelbrink, A; Schwarze, J; Hemmer, B; Sander, D; Poppert, H

2010-11-01

Despite numerous studies suggesting a relationship between paradoxical embolism from a patent foramen ovale (PFO) and stroke, the role of PFO as a risk factor for cerebral ischaemia remains controversial. We therefore sought to determine the association between a RLS detected by contrast-enhanced transcranial Doppler ultrasonography (c-TCD) and recurrent stroke in an unselected population sample. We analyzed the records of 763 patients with diagnosis of cerebral ischaemia at our institution. All patients had undergone TCD-based detection of RLS. Embolic signals have been measured both under resting conditions and after performing a Valsalva maneuver. For follow-up, all patients were contacted by mail, which included a standardized questionnaire. Endpoints of follow-up were defined as recurrence of cerebral ischaemia, occurrence of myocardial infarction or death from any cause. Follow-up data were available in 639 patients (83.7%). At baseline, a RLS was detected in 140 (28%) men and in 114 (42%) women. Ten shunt-carriers (1.6%) and 32 patients (5.0%) without RLS had suffered a recurrent stroke. After adjustment for age, sex, and atrial fibrillation, the hazard ratio of RLS for stroke recurrence was 0.86 (95% CI 0.41-1.79). The condition of RLS at rest adjusted for age, sex, stroke subtype, and cardiovascular risk factors was not found to increase the risk of stroke substantially (HR 1.16 [95% CI 0.41-3.29]) Our data suggest that the risk of recurrent stroke in subjects with PFO is not significantly increased in comparison with subject without it. © 2010 The Author(s). Journal compilation © 2010 EFNS.

Simulated Patient Studies: An Ethical Analysis

PubMed Central

Rhodes, Karin V; Miller, Franklin G

2012-01-01

Context In connection with health care reform, the U.S. Department of Health and Human Services commissioned a “mystery shopper,” or simulated patient study, to measure access to primary care. But the study was shelved because of public controversy over “government spying” on doctors. Opponents of the study also raised ethical concerns about the use of deception with human subjects without soliciting their informed consent. Methods We undertook an ethical analysis of the use of simulated patient techniques in health services research, with a particular focus on research measuring access to care. Using a case study, we explored relevant methodological considerations and ethical principles relating to deceptive research without informed consent, as well as U.S. federal regulations permitting exceptions to consent. Findings Several relevant considerations both favor and oppose soliciting consent for simulated patient studies. Making research participation conditional on informed consent protects the autonomy of research subjects and shields them from unreasonable exposure to research risks. However, scientific validity is also an important ethical principle of human subjects research, as the net risks to subjects must be justified by the value to society of the knowledge to be gained. The use of simulated patients to monitor access is a naturalistic and scientifically sound experimental design that can answer important policy-relevant questions, with minimal risks to human subjects. As interaction between researchers and subjects increases, however, so does the need for consent. Conclusions As long as adequate protections of confidentiality of research data are in place, minimally intrusive simulated patient research that gathers policy-relevant data on the health system without the consent of individuals working in that system can be ethically justified when the risks and burdens to research subjects are minimal and the research has the potential to generate socially valuable knowledge. PMID:23216428

Examining the Effects of Perceived Relevance and Work-Related Subjective Well-Being on Individual Performance for Co-Op Students

ERIC Educational Resources Information Center

Drewery, Dave; Pretti, T. Judene; Barclay, Sage

2016-01-01

The purpose of this study was to examine the relationships between co-op students' perceived relevance of their work term, work-related subjective well-being (SWB), and individual performance at work. Data were collected using a survey of co-op students (n = 1,989) upon completion of a work term. Results of regression analyses testing a…

Self-efficacy and relevance of bioscience for nursing, midwifery and healthcare students.

PubMed

Andrew, Sharon; McVicar, Andrew; Zanganeh, Mandana; Henderson, Nigel

2015-10-01

To examine nursing, midwifery and allied healthcare students' self-efficacy for science, perceived relevance of bioscience to their studies and expectations for academic success and the changes that occur after completing first-year introductory bioscience subjects. Bioscience is a foundation subject that underpins nursing, midwifery and other allied health courses. Bioscience subjects continue to be source of anxiety for students in those courses. Raising students' self-efficacy and perceptions of the importance and utility of bioscience to practice may be a way of ameliorating students' expectations and confidence in this subject area. A prospective correlational survey design. Students were surveyed in the first semester of first year and the commencement of the second year. Students were drawn from nursing, midwifery, public health and allied health courses. The surveys contained scales for self-efficacy for science, perceived relevance of bioscience to their course and personal expectations for success in their bioscience subject. Ninety-seven and 82 students completed survey 1 and 2 respectively. Twenty-six surveys could be matched. Self-efficacy increased from survey 1 to survey 2, but expectations for academic success and task value, a measure for relevance, were lower. This was statistically significant for the matched pair sample. Using a mean split, students with high self-efficacy valued science more and had higher expectations for success in their bioscience courses than those with low self-efficacy. Academic success in bioscience, confidence undertaking science tasks and perceiving bioscience as relevant to their course are interwoven concepts that are important for nursing, midwifery and applied healthcare students and ultimately for their professional practice. Literature indicates practitioners may not feel confident in their bioscience knowledge. Assisting undergraduate students to develop confidence in and perceive the relevance of bioscience to their discipline may ultimately impact on clinical practice. © 2015 John Wiley & Sons Ltd.

Neoliberal ideology, global capitalism, and science education: engaging the question of subjectivity

NASA Astrophysics Data System (ADS)

Bazzul, Jesse

2012-12-01

This paper attempts to add to the multifaceted discussion concerning neoliberalism and globalization out of two Cultural Studies of Science Education journal issues along with the recent Journal of Research in Science Teaching devoted to these topics. However, confronting the phenomena of globalization and neoliberalism will demand greater engagement with relevant sociopolitical thought in fields typically outside the purview of science education. Drawing from thinkers Michel Foucault, Jean Baudrillard, Judith Butler, and Louis Althusser this paper attempts to extend some key ideas coming from Ken Tobin, Larry Bencze, and Lyn Carter and advocates science educators taking up notions of ideology, discourse, and subjectivity to engage globalization and neoliberalism. Subjectivity (and its constitution in science education) is considered alongside two relevant textbook examples and also in terms of its importance in formulating political and culturally relevant questions in science education.

Clinical relevance vs. statistical significance: Using neck outcomes in patients with temporomandibular disorders as an example.

PubMed

Armijo-Olivo, Susan; Warren, Sharon; Fuentes, Jorge; Magee, David J

2011-12-01

Statistical significance has been used extensively to evaluate the results of research studies. Nevertheless, it offers only limited information to clinicians. The assessment of clinical relevance can facilitate the interpretation of the research results into clinical practice. The objective of this study was to explore different methods to evaluate the clinical relevance of the results using a cross-sectional study as an example comparing different neck outcomes between subjects with temporomandibular disorders and healthy controls. Subjects were compared for head and cervical posture, maximal cervical muscle strength, endurance of the cervical flexor and extensor muscles, and electromyographic activity of the cervical flexor muscles during the CranioCervical Flexion Test (CCFT). The evaluation of clinical relevance of the results was performed based on the effect size (ES), minimal important difference (MID), and clinical judgement. The results of this study show that it is possible to have statistical significance without having clinical relevance, to have both statistical significance and clinical relevance, to have clinical relevance without having statistical significance, or to have neither statistical significance nor clinical relevance. The evaluation of clinical relevance in clinical research is crucial to simplify the transfer of knowledge from research into practice. Clinical researchers should present the clinical relevance of their results. Copyright © 2011 Elsevier Ltd. All rights reserved.

A Brain Network Processing the Age of Faces

PubMed Central

Homola, György A.; Jbabdi, Saad; Beckmann, Christian F.; Bartsch, Andreas J.

2012-01-01

Age is one of the most salient aspects in faces and of fundamental cognitive and social relevance. Although face processing has been studied extensively, brain regions responsive to age have yet to be localized. Using evocative face morphs and fMRI, we segregate two areas extending beyond the previously established face-sensitive core network, centered on the inferior temporal sulci and angular gyri bilaterally, both of which process changes of facial age. By means of probabilistic tractography, we compare their patterns of functional activation and structural connectivity. The ventral portion of Wernicke's understudied perpendicular association fasciculus is shown to interconnect the two areas, and activation within these clusters is related to the probability of fiber connectivity between them. In addition, post-hoc age-rating competence is found to be associated with high response magnitudes in the left angular gyrus. Our results provide the first evidence that facial age has a distinct representation pattern in the posterior human brain. We propose that particular face-sensitive nodes interact with additional object-unselective quantification modules to obtain individual estimates of facial age. This brain network processing the age of faces differs from the cortical areas that have previously been linked to less developmental but instantly changeable face aspects. Our probabilistic method of associating activations with connectivity patterns reveals an exemplary link that can be used to further study, assess and quantify structure-function relationships. PMID:23185334

Origin and implications of bovine spongiform encephalopathy.

PubMed

Narang, H

1996-04-01

All spongiform encephalopathies in animals, including humans, are slow developing infectious diseases. The current working theory links the origin of bovine spongiform encephalopathy (BSE) to the feeding of cattle with meat and bone meal prepared from scrapie-infected sheep remains. Recycling of cattle meat and bones (MBM) essentially resulted in the selection of a single strain from the "wild type", a mixture of 20 strains. The BSE agent is easily transmitted through ingestion, with some evidence of vertical transmission. Paradoxically, cattle have selected a major new strain which appears to be more virulent than an unselected strain found in scrapie sheep. The same strain of BSE agent is implicated in the occurrence of spongiform encephalopathy in domestic cats, tiger, and some exotic species of ruminants in zoos. The properties of BSE and its spread into cattle are still disputed. Since our understanding of the disease and its transmissibility in humans must await observations that will be made over some years to come, it is important to keep a reasonable perspective and ensure that any speculative comment is consistent with fact. In risk assessment in such circumstances, it is tempting give too much credence to persuasive parallels when direct relevant information is not available. On the other hand, it would also not be wise to assume that the disease will die by itself and will have no effect on humans.

An Exploration of Cognitive Agility as Quantified by Attention Allocation in a Complex Environment

DTIC Science & Technology

2017-03-01

quantified by eye-tracking data collected while subjects played a military-relevant cognitive agility computer game (Make Goal), to determine whether...subjects played a military-relevant cognitive agility computer game (Make Goal), to determine whether certain patterns are associated with effective...Group and Control Group on Eye Tracking and Game Performance .....................36 3. Comparison between High and Low Performers on Eye tracking and

Single-Subject Evaluation: A Tool for Quality Assurance.

ERIC Educational Resources Information Center

Nuehring, Elane M.; Pascone, Anne B.

1986-01-01

The use of single-subject designs in peer review, in utilization review, and in other quality-assurance audits is encouraged. Presents an overview of the methodologies of single-subject designs and quality assurance, and provides examples of cases in which single-subject techniques furnished relevant quality assurance documentation. (Author/ABB)

Quality of Life Outcomes after Transcatheter Aortic Valve Replacement in an Unselected Population. A Report from the STS/ACC TVT Registry™

PubMed Central

Arnold, Suzanne V.; Spertus, John A.; Vemulapalli, Sreekanth; Li, Zhuokai; Matsouaka, Roland A.; Baron, Suzanne J.; Vora, Amit N.; Mack, Michael J.; Reynolds, Matthew R.; Rumsfeld, John S.; Cohen, David J.

2017-01-01

Importance In clinical trials, transcatheter aortic valve replacement (TAVR) has been shown to improve symptoms and quality of life. As this technology moves into general clinical practice, it is critical to evaluate the health status outcomes among unselected patients treated with TAVR. Design/Participants Observational study of patients with severe aortic stenosis treated with TAVR in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (TVT) Registry. Main Outcomes Disease-specific health status was assessed at baseline and at 30 days (n=31,636) and 1 year after TAVR (n=7,014) with the Kansas City Cardiomyopathy Questionnaire-overall summary score (KCCQ-OS; range 0–100 points). We examined factors associated with health status at 1 year after TAVR using multivariable linear regression, with adjustment for baseline health status and accounting for clustering of patients within sites. Results Mean baseline KCCQ-OS was 42.3±23.7, indicating substantial health status impairment. Surviving patients had, on average, large improvements in health status at 30 days that persisted to 1 year, with a mean improvement in the KCCQ-OS of 27.6 points at 30 days and 31.9 points at 1 year. Worse baseline health status, older age, higher ejection fraction, lung disease, home oxygen, lower mean aortic valve gradient, prior stroke, diabetes, pacemaker, atrial fibrillation, slower gait speed, and non-femoral access were associated with worse health status at 1 year. Overall, 62.3% of patients had a favorable outcome at 1 year (alive with reasonable quality of life [KCCQ-OS ≥60] and no significant decline [≥10 points] from baseline) with the lowest rates seen among patients with severe lung disease (51.4%), on dialysis (47.7%), or with very poor baseline health status (49.2%). Conclusion In a national, contemporary clinical practice cohort of unselected patients, we found that improvement in health status following TAVR was similar to that seen in the pivotal clinical trials. While the health status results were favorable for the majority of patients, ~1 in 3 patients still had a poor outcome 1 year after TAVR. Continued efforts are needed to improve patient selection and procedural/post-procedural care in order to maximize health status outcomes of this evolving therapy. PMID:28146260

Nine-Months Clinical Outcome of Biodegradable Polymer Coated Sirolimus-eluting Stent System: A Multi-Centre "Real-World" Experience.

PubMed

Sarma, Raghava; Prajapati, Jayesh; Raheem, Asif; Thakkar, Kamlesh; Kothari, Shivani; Thakkar, Ashok

2015-08-01

The main culprit in first-generation drug eluting stents is 'durable' polymer, whose continuous presence may impair arterial healing and ultimately have a negative impact on late outcomes. The main enigma behind the biodegradable polymer usage is its degradation after elution of drug. This reduces adverse events in unselected patients with complex coronary artery lesions treated with biodegradable polymer coated sirolimus-eluting stents. The aim of the INDOLIMUS-G Registry was to evaluate safety and efficacy of the Indolimus (Sahajanand Medical Technologies Pvt. Ltd., Surat, India) sirolimus-eluting stents in large cohorts of unselected patients with complex coronary artery lesions. It is a multi-centre, non-randomized retrospective registry with a clear aim of evaluating safety and efficacy of the Indolimus sirolimus-eluting stents in consecutive patients enrolled between April 2012 and May 2014. The primary end-point of the study was major adverse cardiac events (MACE), which is a composite of cardiac death, myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR) and stent thrombosis (ST) at the end of follow-up. Clinical follow-up were scheduled at the end of 30-days, 6-months, and 9-months period. The mean age of enrolled patients was 52.6 ± 11.0 years. A total of 1137 lesions were intervened successfully with 1242 stents (1.09 ± 0.30 stent per lesion). The average stent length and diameter was 27.42 ± 9.01 mm and 3.12 ± 0.36 mm respectively. There were 740 (73.40%) male patients, indicating their high prevalence. Diabetes, hypertension and totally occluded lesions were found in 372 (36.90%), 408 (40.47%) and 170 (16.86%) patients, respectively. This showed that study also included high risk complex lesions and not ideal recruited lesions. The incidence of MACE at 30-days, 6-months and 9-months were 3 (0.30%), 18 (1.80%) and 22 (2.20%) respectively. At 9-months, TLR was found in 6 (0.50%) patients. There were 2 (0.20%) cases of ST, 10 (1.0%) cases of MI and 4 (0.40%) cases of cardiac death at 9-month follow-up. The lower incidence of MACE, TLR and ST at 9-month follow-up clearly delineates safety and efficacy of Indolimus SES in large cohorts of unselected patients with complex coronary lesions.

N-terminal pro-B-type natriuretic peptide is an independent predictor of outcome in an unselected cohort of critically ill patients.

PubMed

Meyer, Brigitte; Huelsmann, Martin; Wexberg, Paul; Delle Karth, Georg; Berger, Rudolf; Moertl, Deddo; Szekeres, Thomas; Pacher, Richard; Heinz, Gottfried

2007-10-01

Natriuretic peptides emerged during recent years as potent prognostic markers in patients with heart failure and acute myocardial infarction. In addition, natriuretic peptides show strong predictive value in patients with pulmonary embolism, sepsis, renal failure, and shock. The present study tests the prognostic information of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) in an unselected cohort of critically ill patients. Prospective, observational study. A tertiary intensive care unit in a university hospital. A total of 289 consecutive patients admitted to the intensive care unit during a 16-month period with the following data: age 64 +/- 14 yrs, male n = 191, Simplified Acute Physiology Score II of 52 +/- 24, mechanical ventilation n = 180 (62%), vasopressors n = 179 (62%), renal failure n = 24 (8%). None. Plasma NT-pro-BNP samples (Roche Diagnostics) were obtained on intensive care unit admission. Data are given as median [range]. Intensive care unit survivors had significantly lower NT-pro-BNP values compared with intensive care unit nonsurvivors (3394 [24-35,000] vs. 6776 [303-35,000] pg/mL, survivors vs. nonsurvivors, respectively, p = .001). Hospital survivors were characterized by significantly lower NT-pro-BNP values (2656 [24-35,000] vs. 8390 [303-35,000] pg/mL, survivors vs. nonsurvivors, respectively, p = .001). NT-pro-BNP levels were not significantly different in patients with primary cardiac diagnosis compared with those with a noncardiac admission diagnosis (4794 [26-35,000], n = 202 vs. 3349 [24-35,000], n = 87, cardiac vs. noncardiac, respectively, p = .28). In a logistic regression model, Simplified Acute Physiology Score II and NT-pro-BNP were independently associated with hospital survival (chi = 35.6, p = .0001 and chi = 11.3, p = .0008, Simplified Acute Physiology Score II and NT-pro-BNP, respectively). Areas under the receiver operating characteristic curves of NT-pro-BNP and Simplified Acute Physiology Score II were not statistically significant different regarding the prediction of outcome. NT-pro-BNP on admission is an independent prognostic marker of outcome in an unselected cohort of critically ill patients. A single measurement of NT-pro-BNP might facilitate triage of emergency and intensive care unit patients.

Impact of iso-osmolar versus low-osmolar contrast agents on contrast-induced nephropathy and tissue reperfusion in unselected patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (from the Contrast Media and Nephrotoxicity Following Primary Angioplasty for Acute Myocardial Infarction [CONTRAST-AMI] Trial).

PubMed

Bolognese, Leonardo; Falsini, Giovanni; Schwenke, Carsten; Grotti, Simone; Limbruno, Ugo; Liistro, Francesco; Carrera, Arcangelo; Angioli, Paolo; Picchi, Andrea; Ducci, Kenneth; Pierli, Carlo

2012-01-01

Conflicting data have been reported on the effects of low-osmolar and iso-osmolar contrast media on contrast-induced acute kidney injury (CI-AKI). In particular, no clinical trial has yet focused on the effect of contemporary contrast media on CI-AKI, epicardial flow, and microcirculatory function in patients with ST-segment elevation acute myocardial infarction who undergo primary percutaneous coronary intervention. The Contrast Media and Nephrotoxicity Following Coronary Revascularization by Angioplasty for Acute Myocardial Infarction (CONTRAST-AMI) trial is a prospective, randomized, single-blind, parallel-group, noninferiority study aiming to evaluate the effects of the low-osmolar contrast medium iopromide compared to the iso-osmolar agent iodixanol on CI-AKI and tissue-level perfusion in patients with ST-segment elevation acute myocardial infarction. Four hundred seventy-five consecutive, unselected patients who underwent primary percutaneous coronary intervention were randomized to iopromide (n = 239) or iodixanol (n = 236). All patients received high-dose N-acetylcysteine and hydration. The primary end point was the proportion of patients with serum creatinine (sCr) increases ≥25% from baseline to 72 hours. Secondary end points were Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grade, increase in sCr ≥50%, increase in sCr ≥0.5 or ≥1 mg/dl, and 1-month major adverse cardiac events. The primary end point occurred in 10% of the iopromide group and in 13% of the iodixanol group (95% confidence interval -9% to 3%, p for noninferiority = 0.0002). A TIMI myocardial perfusion grade of 0 or 1 was present in 14% of patients in the 2 groups. No differences between the 2 groups were found in any of the secondary analyses of sCr increase. No significant difference in 1-month major adverse cardiac events was found (8% vs 6%, p = 0.37). In conclusion, in a population of unselected patients with ST-segment elevation acute myocardial infarction who underwent primary percutaneous coronary intervention, iopromide was not inferior to iodixanol in the occurrence of CI-AKI; no significant differences were found in terms of tissue-level reperfusion and major adverse cardiac events between the 2 contrast agents. Copyright © 2012 Elsevier Inc. All rights reserved.

Relevance today and tomorrow in medical education. A forum with a purpose.

PubMed

Cullen, S C; Taylor, C E; Brayton, D F

1970-04-01

Students of today question the relevance of much of their formal education. In medical schools the concern is particularly with the relevance of the educational experience to the professional commitment in modern society. To engender discussion of the subject, California Medicine in its January issue printed eight essays by authors known to have keen interest in the subject. Readers in California and elsewhere are invited to take part in a continuation of the forum in succeeding issues. The following are contributions selected from those received to date. Others will be published in the months ahead. At an appropriate time the material will be collated and, if feasible, the distillate will be prepared in the form of a statement. If you have thoughts on the subject, just address them to the editors of California Medicine, 693 Sutter Street, San Francisco, California, 94102. Keep your essays short, please.

A novel visualization model for web search results.

PubMed

Nguyen, Tien N; Zhang, Jin

2006-01-01

This paper presents an interactive visualization system, named WebSearchViz, for visualizing the Web search results and acilitating users' navigation and exploration. The metaphor in our model is the solar system with its planets and asteroids revolving around the sun. Location, color, movement, and spatial distance of objects in the visual space are used to represent the semantic relationships between a query and relevant Web pages. Especially, the movement of objects and their speeds add a new dimension to the visual space, illustrating the degree of relevance among a query and Web search results in the context of users' subjects of interest. By interacting with the visual space, users are able to observe the semantic relevance between a query and a resulting Web page with respect to their subjects of interest, context information, or concern. Users' subjects of interest can be dynamically changed, redefined, added, or deleted from the visual space.

Patent foramen ovale and migraine: a cross-sectional study from the Northern Manhattan Study (NOMAS).

PubMed

Rundek, Tatjana; Elkind, Mitchell S V; Di Tullio, Marco R; Carrera, Emmanuel; Jin, Zhezhen; Sacco, Ralph L; Homma, Shunichi

2008-09-30

A causal relationship between patent foramen ovale (PFO) and migraine has been hypothesized, and improvement of migraine frequency and severity after percutaneous PFO closure has been reported. Population-based data on the relationship between PFO and migraine are sparse, however. The objective of this study was to examine the association between PFO and migraine among stroke-free individuals in an urban, population-based, multiethnic cohort. As a part of the ongoing Northern Manhattan Study (NOMAS), 1101 stroke-free subjects were assessed for self-reported history of migraine. The presence of PFO was assessed by transthoracic echocardiography. The mean age of the group was 69+/-10 years; 58% were women. Forty-eight percent were Caribbean Hispanic, 24% were white, 26% were black, and 2% were another race/ethnicity. The prevalence of self-reported migraine was 16% (13% migraine with aura). The prevalence of PFO was 15%. Migraine was significantly more frequent among younger subjects, women, and Hispanics. The prevalence of PFO was not significantly different between subjects who had migraine (26/178, or 14.6%) and those who did not (138/923, or 15.0%; P=0.9). In an adjusted multivariate logistic regression model, the presence of PFO was not associated with increased prevalence of migraine (odds ratio 1.01, 95% confidence interval 0.63 to 1.61). Increasing age was associated with lower prevalence of migraine in both subjects with a PFO (odds ratio 0.94, 95% confidence interval 0.90 to 0.99 per year) and those without PFO (odds ratio 0.97, 95% confidence interval 0.95 to 0.99 per year). The observed lack of association between PFO and migraine (with or without aura) was not modified by diabetes mellitus, hypertension, cigarette smoking, or dyslipidemia. In this multiethnic, elderly, population-based cohort, PFO detected with transthoracic echocardiography and agitated saline was not associated with self-reported migraine. The causal relationship between PFO and migraine remains uncertain, and the role of PFO closure among unselected patients with migraine remains questionable.

Patent Foramen Ovale and Migraine: A Cross-Sectional Study from the Northern Manhattan Study (NOMAS)

PubMed Central

Rundek, Tatjana; Elkind, Mitchell SV; Di Tullio, Marco R.; Carrera, Emmanuel; Jin, Zhezhen; Sacco, Ralph L.; Homma, Shunichi

2009-01-01

Background A causal relationship between patent foramen ovale (PFO) and migraine has been hypothesized, and improvement of migraine frequency and severity after percutaneous PFO closure has been reported. Population-based data on the relationship between PFO and migraine are however sparse. The objective of this study was to examine the association between PFO and migraine among stroke-free individuals in an urban, population-based multiethnic cohort. Methods and Results As a part of the ongoing Northern Manhattan study (NOMAS), 1,101 stroke-free subjects were assessed for self-reported history of migraine. The presence of PFO was assessed by transthoracic echocardiography. The mean age of the group was 69±10 years; 58% were women; 48% Caribbean Hispanic, 24% white, 26% black, and 2% other race-ethnicity. The prevalence of self-reported migraine was 16% (13% migraine with aura). The prevalence of PFO was 15%. Migraine was significantly more frequent among younger subjects, women, and Hispanics. The prevalence of PFO was not significantly different between subjects who had migraine (26/178, or 14.6%) and those who did not (138/923, or 15.0%; p=0.9). In an adjusted multivariate logistic regression model, the presence of PFO was not associated with increased prevalence of migraine (odds ratio, OR 1.01; 95% Confidence Interval, CI 0.63–1.61). Increasing age was associated with lower prevalence of migraine in both subjects with a PFO (OR 0.94, 95% CI 0.90–0.99 per year) and without PFO (OR 0.97, 95% CI 0.95–0.99 per year). The observed lack of association between PFO and migraine (with or without aura) was not modified by diabetes, hypertension, cigarette smoking, and dyslipidemia. Conclusion In this multiethnic elderly population-based cohort, PFO detected with TTE and agitated saline was not associated with self-reported migraine. The causal relationship between PFO and migraine remains uncertain, and the role of PFO closure among unselected patients with migraine remains questionable. PMID:18794393

Hip pain onset in relation to cumulative workplace and leisure time mechanical load: a population based case-control study.

PubMed

Pope, D P; Hunt, I M; Birrell, F N; Silman, A J; Macfarlane, G J

2003-04-01

In an unselected community sample of adults, to assess the role and importance of exposure to mechanical factors both at work and leisure in the aetiology of hip pain. A population based prevalence case-control study. Cases and controls were identified from a population survey of 3847 subjects registered with two general practices in Cheshire, United Kingdom. All subjects received a postal questionnaire which inquired about hip pain during the past month. An occupational history was obtained, including exposure to each of seven physical demands. Information was also obtained on history of participation in eight common sporting activities. 88% of those invited to participate returned a completed questionnaire. The 352 subjects with hip pain were designated as cases, and the remaining 3002 subjects as controls. In people ever employed, hip pain was significantly associated with high cumulative workplace exposure (before onset) of walking long distances over rough ground, lifting/moving heavy weights, sitting for prolonged periods, walking long distances, frequent jumping between different levels, and standing for prolonged periods. Odds ratios (ORs) in the higher exposure categories ranged from 1.46 to 2.65. Cumulative exposure to three sporting activities was significantly associated with hip pain: track and field sports, jogging, and walking, with odds ratios varying between 1.57 to 1.94. On multivariate analysis three factors were independent predictors of hip pain onset: cumulative exposure of sitting for prolonged periods (higher exposure v not exposed: OR=1.82, 95% confidence interval (CI) 1.13 to 2.92), lifting weights >50 lb (23 kg) (OR=1.74, 95% CI 1.06 to 2.86) (both relating to the workplace), and walking as a leisure activity (OR=1.97, 95% CI 1.32 to 2.94). The population attributable risk associated with each of these activities was 21%, 13%, and 16%, respectively Cumulative exposure to some workplace and sporting "mechanical" risk factors for hip osteoarthritis (OA) appear to be related to hip pain in general-some (but not all) have previously been related to hip OA. Because these are common workplace or leisure time activities their attributable risk is high.

Effect of early oral feeding on length of hospital stay following gastrectomy for gastric cancer: a Japanese multicenter, randomized controlled trial.

PubMed

Shimizu, Nobuyuki; Oki, Eiji; Tanizawa, Yutaka; Suzuki, Yutaka; Aikou, Susumu; Kunisaki, Chikara; Tsuchiya, Takashi; Fukushima, Ryoji; Doki, Yuichiro; Natsugoe, Shoji; Nishida, Yasunori; Morita, Masaru; Hirabayashi, Naoki; Hatao, Fumihiko; Takahashi, Ikuo; Choda, Yasuhiro; Iwasaki, Yoshiaki; Seto, Yasuyuki

2018-05-02

This multicenter, randomized controlled study evaluates the safety of early oral feeding following gastrectomy, and its effect on the length of postoperative hospital stay. The subjects of this study were patients who underwent distal gastrectomy (DG) or total gastrectomy (TG) for gastric cancer between January 2014 and December 2015. Patients were randomly assigned to the early oral feeding group (intervention group) or the conventional postoperative management group (control group) for each procedure. We evaluated the length of postoperative hospital stay and the incidence of postoperative complications in each group. No significant differences in length of postoperative stay were found between the intervention and control groups of the patients who underwent DG. The incidence of postoperative complications was significantly greater in the DG intervention group. In contrast, the length of postoperative stay was significantly shorter in the TG intervention group, although the TG group did not attain the established target sample size. Early oral feeding did not shorten the postoperative hospital stay after DG. The higher incidence of postoperative complications precluded the unselected adoption of early oral feeding for DG patients. Further confirmative studies are required to definitively establish the potential benefits of early oral feeding for TG patients.

First-trimester nasal bone length in a normal Latin American population.

PubMed

Casasbuenas, Alexandra; Wong, Amy E; Sepulveda, Waldo

2009-02-01

To report normative data of nasal bone length (NBL) in first-trimester singleton fetuses in a normal cohort of Latin American women. NBL was measured during routine first-trimester sonographic examination in 1040 singleton fetuses from an unselected population. NBL increased linearly with advancing gestational age (GA) [NBL (mm) = - 1.10 + 0.03 x GA (days), R(2) = 0.21; p < 0.001]. Similarly, there was a linear relationship between the NBL and crown-lump length (CRL) [NBL (mm) = 0.41 + 0.02 x CRL (mm), R(2) = 0.27; p < 0.001]. The NBLs at the 50th percentile in our population were 1.5, 1.7, and 1.9 mm at 11, 12, and 13 weeks of gestation, respectively. Whereas categorizing a nasal bone as absent or present can be subjective because of variations in echogenicity due to technique and equipment, measurement of NBL is a more objective approach to nasal bone assessment in screening for aneuploidy. Measurement of NBL in the first trimester is feasible and can be easily obtained at the time of nuchal translucency assessment. The normative data we report can provide a reference for defining nasal bone hypoplasia in the first trimester in the Latin American population. Copyright (c) 2008 John Wiley & Sons, Ltd.

Survey of Bibliographies and Reference Works on Asia, Africa, Latin America, and Russia and East Europe and Compilation of Bibliographies on East Asia, South Asia, and Africa South of the Sahara for Undergraduate Libraries. Final Report.

ERIC Educational Resources Information Center

Morehouse, Ward

The project was concerned with developing three up-to-date, accurate bibliographies on Asia and Africa as resource guides and book selection tools for undergraduate libraries. Existing bibliographies and information on newer books favorably received in journals were entered on a computer system. A preliminary, unedited, unselected bibliography was…

Measurement of urinary metanephrines to screen for pheochromocytoma in an unselected hospital referral population.

PubMed

Brain, Keith L; Kay, Jonathan; Shine, Brian

2006-11-01

Despite the rarity of pheochromocytoma, diagnosis is important because of the dangers of uncontrolled severe hypertension and the availability of very effective surgical treatment. Urinary or plasma catecholamines or catecholamine derivatives are commonly used to screen for pheochromocytomas before imaging, but data from 24-h urinary metanephrine results, patient age, and sex may better predict tumors in populations with a low pretest probability. We retrospectively studied outcomes of an unselected population (1819 patients) referred to a tertiary hospital laboratory for urinary metanephrine testing and investigated the usefulness of some simple derivative measures for detecting pheochromocytoma. We normalized values for urinary 24-h excretion of metanephrine, normetanephrine, and 3-methoxytyramine by dividing by an age- and sex-specific reference range. We then compared pheochromocytoma prediction by the use of products of these normalized measures with the gold standard of biopsy-confirmed tumor. The product of the excretion of normalized metanephrine (nMAD) and normalized normetanephrine (nNMT) (nMAD.nNMT) was a highly sensitive (100%) and specific (99.1%) measure, yielding a positive predictive value of 82%. ROC curves were not improved by including the normalized 3-methoxytyramine concentrations in the product. The test for nMAD.nNMT gave higher sensitivity and specificity than the tests for either substance alone. The test for nMAD.nNMT is a useful measure for identifying pheochromocytoma in a population with a low pretest probability.

Genetic diversity of European cattle breeds highlights the conservation value of traditional unselected breeds with high effective population size.

PubMed

Medugorac, Ivica; Medugorac, Ana; Russ, Ingolf; Veit-Kensch, Claudia E; Taberlet, Pierre; Luntz, Bernhard; Mix, Henry M; Förster, Martin

2009-08-01

In times of rapid global and unforeseeable environmental changes, there is an urgent need for a sustainable cattle breeding policy, based on a global view. Most of the indigenous breeds are specialized in a particular habitat or production system but are rapidly disappearing. Thus, they represent an important resource to meet present and future breeding objectives. Based on 105 microsatellites, we obtained thorough information on genetic diversity and population structure of 16 cattle breeds that cover a geographical area from the domestication centre near Anatolia, through the Balkan and alpine regions, to the North-West of Europe. Breeds under strict artificial selection and indigenous breeds under traditional breeding schemes were included. The overall results showed that the genetic diversity is widespread in Busa breeds in the Anatolian and Balkan areas, when compared with the alpine and north-western European breeds. Our results reflect long-term evolutionary and short-term breeding events very well. The regular pattern of allele frequency distribution in the entire cattle population studied clearly suggests conservation of rare alleles by conservation of preferably unselected traditional breeds with large effective population sizes. From a global and long-term conservation genetics point of view, the native and highly variable breeds closer to the domestication centre could serve as valuable sources of genes for future needs, not only for cattle but also for other farm animals.

Attentional bias to threat in the general population is contingent on target competition, not on attentional control settings.

PubMed

Wirth, Benedikt Emanuel; Wentura, Dirk

2018-04-01

Dot-probe studies usually find an attentional bias towards threatening stimuli only in anxious participants. Here, we investigated under what conditions such a bias occurs in unselected samples. According to contingent-capture theory, an irrelevant cue only captures attention if it matches an attentional control setting. Therefore, we first tested the hypothesis that an attentional control setting tuned to threat must be activated in (non-anxious) individuals. In Experiment 1, we used a dot-probe task with a manipulation of attentional control settings ('threat' - set vs. control set). Surprisingly, we found an (anxiety-independent) attentional bias to angry faces that was not moderated by attentional control settings. Since we presented two stimuli (i.e., a target and a distractor) on the target screen in Experiment 1 (a necessity to realise the test of contingent capture), but most dot-probe studies only employ a single target, we conducted Experiment 2 to test the hypothesis that attentional bias in the general population is contingent on target competition. Participants performed a dot-probe task, involving presentation of a stand-alone target or a target competing with a distractor. We found an (anxiety-independent) attentional bias towards angry faces in the latter but not the former condition. This suggests that attentional bias towards angry faces in unselected samples is not contingent on attentional control settings but on target competition.

Mutation Analysis of IDH1/2 Genes in Unselected De novo Acute Myeloid Leukaemia Patients in India - Identification of A Novel IDH2 Mutation.

PubMed

Raveendran, Sureshkumar; Sarojam, Santhi; Vijay, Sangeetha; Geetha, Aswathy Chandran; Sreedharan, Jayadevan; Narayanan, Geetha; Sreedharan, Hariharan

2015-01-01

IDH1/2 mutations which result in alternation in DNA methylation pattern are one of the most common methylation associated mutations in Acute myeloid leukaemia. IDH1/2 mutations frequently associated with higher platelet level, normal cytogentics and NPM1 mutations. Here we analyzed IDH1/2 mutations in 200 newly diagnosed unselected Indian adult AML patients and investigated their correlation with clinical, cytogenetic parameters along with cooperating NPM1 mutation. We detected 5.5% and 4% mutations in IDH1/2 genes, respectively. Except IDH2 c.515_516GG>AA mutation, all the other identified mutations were reported mutations. Similar to reported c.515G>A mutation, the novel c.515_516GG>AA mutation replaces 172nd arginine to lysine in the active site of the enzyme. Even though there was a preponderance of IDH1/2 mutations in NK-AML, cytogenetically abnormal patients also harboured IDH1/2 mutations. IDH1 mutations showed significant higher platelet count and NPM1 mutations. IDH2 mutated patients displayed infrequent NPM1 mutations and lower WBC count. All the NPM1 mutations in the IDH1/2 mutated cases showed type A mutation. The present data suggest that IDH1/2 mutations are associated with normal cytogenetics and type A NPM1 mutations in adult Indian AML patients.

The London field trial for hoarding disorder.

PubMed

Mataix-Cols, D; Billotti, D; Fernández de la Cruz, L; Nordsletten, A E

2013-04-01

A new diagnostic category, hoarding disorder (HD), has been proposed for inclusion in DSM-5. This study field-tested the validity, reliability and perceived acceptability of the proposed diagnostic criteria for HD. Method Fifty unselected individuals with prominent hoarding behavior and 20 unselected, self-defined 'collectors' participated in thorough psychiatric assessments, involving home visits whenever possible. A semi-structured interview based on the proposed diagnostic criteria for HD was administered and scored by two independent raters. 'True' diagnoses were made by consensus according to the best-estimate diagnosis procedure. The percentage of true positive HD cases (sensitivity) and true negative HD cases (specificity) was calculated, along with inter-rater reliability for the diagnosis and each criterion. Participants were asked about their perceptions of the acceptability, utility and stigma associated with the new diagnosis. Twenty-nine (58%) of the hoarding individuals and none of the collectors fulfilled diagnostic criteria for HD. The sensitivity, specificity and inter-rater reliability of the diagnosis, and of each individual criterion and the specifiers, were excellent. Most participants with HD (96%) felt that creating a new disorder would be very or somewhat acceptable, useful (96%) and not too stigmatizing (59%). The proposed HD criteria are valid, reliable and perceived as acceptable and useful by the sufferers. Crucially, they seem to be sufficiently conservative and unlikely to overpathologize normative behavior. Minor changes in the wording of the criteria are suggested.

Tissue Factor promotes breast cancer stem cell activity in vitro.

PubMed

Shaker, Hudhaifah; Harrison, Hannah; Clarke, Robert; Landberg, Goran; Bundred, Nigel J; Versteeg, Henri H; Kirwan, Cliona C

2017-04-18

Cancer stem cells (CSCs) are a subpopulation of cells that can self-renew and initiate tumours. The clotting-initiating protein Tissue Factor (TF) promotes metastasis and may be overexpressed in cancer cells with increased CSC activity. We sought to determine whether TF promotes breast CSC activity in vitro using human breast cancer cell lines. TF expression was compared in anoikis-resistant (CSC-enriched) and unselected cells. In cells sorted into of TF-expressing and TF-negative (FACS), and in cells transfected to knockdown TF (siRNA) and overexpress TF (cDNA), CSC activity was compared by (i) mammosphere forming efficiency (MFE) (ii) holoclone colony formation (Hc) and (iii) ALDH1 activity. TF expression was increased in anoikis-resistant and high ALDH1-activity T47D cells compared to unselected cells. FACS sorted TF-expressing T47Ds and TF-overexpressing MCF7s had increased CSC activity compared to TF-low cells. TF siRNA cells (MDAMB231,T47D) had reduced CSC activity compared to control cells. FVIIa increased MFE and ALDH1 in a dose-dependent manner (MDAMB231, T47D). The effects of FVIIa on MFE were abrogated by TF siRNA (T47D). Breast CSCs (in vitro) demonstrate increased activity when selected for high TF expression, when induced to overexpress TF, and when stimulated (with FVIIa). Targeting the TF pathway in vivo may abrogate CSC activity.

Cognitive Processing and the Functional Matching Effect in Persuasion: The Mediating Role of Subjective Perceptions of Message Quality

PubMed

Lavine; Snyder

1996-11-01

In two experiments, we examined the hypothesis that subjective perceptions of message quality mediate the functional matching effect in persuasion. In Experiment 1, participants whose attitudes and behaviors serve primarily a value-expressive function (i.e., low self-monitors) or a social-adjustive function (i.e., high self-monitors) were exposed to persuasive messages that contained value-expressive, social-adjustive, or both types of arguments in favor of voting. Functionally-relevant messages (i.e., the social-adjustive message for high self-monitors and the value-expressive message for low self-monitors) produced enhanced perceptions of message quality and persuasiveness, more positive attitudes, and more message-related behavior than functionally nonrelevant messages. Functionally mixed messages were generally more effective than messages containing only functionally nonrelevant arguments, but less effective than messages containing only functionally relevant arguments. Path analyses indicated that the influence of functional relevance on attitudes and behavior was significantly mediated by subjective perceptions of the quality of the message. In Experiment 2, we exposed participants to a functionally relevant or nonrelevant voting appeal five days before a presidential election. Results replicated those of Experiment 1; functionally relevant messages produced more favorable attitudes, and this effect was mediated by enhanced perceptions of message quality. Finally, postmessage attitudes exerted a significant influence on whether participants voted in the election, and this effect was mediated by voting intentions. Discussion focuses on the subjective nature of message evaluation and on the cognitive processes underlying the functional matching effect in persuasion.

Preparation of Chemical Samples On Relevant Surfaces Using Inkjet Technology

DTIC Science & Technology

2013-04-01

PREPARATION OF CHEMICAL SAMPLES ON RELEVANT SURFACES USING INKJET TECHNOLOGY...2012 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Preparation of Chemical Samples on Relevant Surfaces Using Inkjet Technology 5b. GRANT NUMBER...SUBJECT TERMS Surface detection Inkjet Simulant deposition 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF

Translating a "Relevance Imperative" into Junior Secondary Mathematics and Science Pedagogy

ERIC Educational Resources Information Center

Darby, Linda

2009-01-01

Inquiries into the state of mathematics and science education in Australia express the need to make curriculum and teaching practices more relevant and meaningful to students' lives. This vision requires that teachers understand how relevance can enter the classroom in meaningful, appropriate, and subject-specific ways. In this paper I use…

Effects of local and widespread muscle fatigue on movement timing.

PubMed

Cowley, Jeffrey C; Dingwell, Jonathan B; Gates, Deanna H

2014-12-01

Repetitive movements can cause muscle fatigue, leading to motor reorganization, performance deficits, and/or possible injury. The effects of fatigue may depend on the type of fatigue task employed, however. The purpose of this study was to determine how local fatigue of a specific muscle group versus widespread fatigue of various muscle groups affected the control of movement timing. Twenty healthy subjects performed an upper extremity low-load work task similar to sawing for 5 continuous minutes both before and after completing a protocol that either fatigued all the muscles used in the task (widespread fatigue) or a protocol that selectively fatigued the primary muscles used to execute the pushing stroke of the sawing task (localized fatigue). Subjects were instructed to time their movements with a metronome. Timing error, movement distance, and speed were calculated for each movement. Data were then analyzed using a goal-equivalent manifold approach to quantify changes in goal-relevant and non-goal-relevant variability. We applied detrended fluctuation analysis to each time series to quantify changes in fluctuation dynamics that reflected changes in the control strategies used. After localized fatigue, subjects made shorter, slower movements and exerted greater control over non-goal-relevant variability. After widespread fatigue, subjects exerted less control over non-goal-relevant variability and did not change movement patterns. Thus, localized and widespread muscle fatigue affected movement differently. Local fatigue may reduce the available motor solutions and therefore cause greater movement reorganization than widespread muscle fatigue. Subjects altered their control strategies but continued to achieve the timing goal after both fatigue tasks.

Identifying unmet clinical need in hypertrophic cardiomyopathy using national electronic health records.

PubMed

Pujades-Rodriguez, Mar; Guttmann, Oliver P; Gonzalez-Izquierdo, Arturo; Duyx, Bram; O'Mahony, Constantinos; Elliott, Perry; Hemingway, Harry

2018-01-01

To evaluate unmet clinical need in unselected hypertrophic cardiomyopathy (HCM) patients to determine the risk of a wide range of subsequent cardiovascular disease endpoints and safety endpoints relevant for trial design. Population based cohort (CALIBER, linked primary care, hospital and mortality records in England, period 1997-2010), all people diagnosed with HCM were identified and matched by age, sex and general practice with ten randomly selected people without HCM. Random-effects Poisson models were used to assess the associations between HCM and cardiovascular diseases and bleeding. Among 3,290,455 eligible people a diagnosis of hypertrophic cardiomyopathy was found in 4 per 10,000. Forty-one percent of the 1,160 individuals with hypertrophic cardiomyopathy were women and the median age was 57 years. The median follow-up was 4.0 years. Compared to general population controls, people with HCM had higher risk of ventricular arrhythmia (incidence rate ratio = 23.53, [95% confidence interval 12.67-43.72]), cardiac arrest or sudden cardiac death (6.33 [3.69-10.85]), heart failure (4.31, [3.30-5.62]), and atrial fibrillation (3.80 [3.04-4.75]). HCM was also associated with a higher incidence of myocardial infarction ([MI] 1.90 [1.27-2.84]) and coronary revascularisation (2.32 [1.46-3.69]).The absolute Kaplan-Meier risks at 3 years were 8.8% for the composite endpoint of cardiovascular death or heart failure, 8.4% for the composite of cardiovascular death, stroke or myocardial infarction, and 1.5% for major bleeding. Our study identified major unmet need in HCM and highlighted the importance of implementing improved cardiovascular prevention strategies to increase life-expectancy of the contemporary HCM population. They also show that national electronic health records provide an effective method for identifying outcomes and clinically relevant estimates of composite efficacy and safety endpoints essential for trial design in rare diseases.

Early PTSD Symptom Trajectories: Persistence, Recovery, and Response to Treatment: Results from the Jerusalem Trauma Outreach and Prevention Study (J-TOPS)

PubMed Central

Galatzer-Levy, Isaac R.; Ankri, Yael; Freedman, Sara; Israeli-Shalev, Yossi; Roitman, Pablo; Gilad, Moran; Shalev, Arieh Y.

2013-01-01

Context Uncovering heterogeneities in the progression of early PTSD symptoms can improve our understanding of the disorder's pathogenesis and prophylaxis. Objectives To describe discrete symptom trajectories and examine their relevance for preventive interventions. Design Latent Growth Mixture Modeling (LGMM) of data from a randomized controlled study of early treatment. LGMM identifies latent longitudinal trajectories by exploring discrete mixture distributions underlying observable data. Setting Hadassah Hospital unselectively receives trauma survivors from Jerusalem and vicinity. Participants Adult survivors of potentially traumatic events consecutively admitted to the hospital's emergency department (ED) were assessed ten days and one-, five-, nine- and fifteen months after ED admission. Participants with data at ten days and at least two additional assessments (n = 957) were included; 125 received cognitive behavioral therapy (CBT) between one and nine months. Approach We used LGMM to identify latent parameters of symptom progression and tested the effect of CBT on these parameters. CBT consisted of 12 weekly sessions of either cognitive therapy (n = 41) or prolonged exposure (PE, n = 49), starting 29.8±5.7 days after ED admission, or delayed PE (n = 35) starting at 151.8±42.4 days. CBT effectively reduced PTSD symptoms in the entire sample. Main Outcome Measure Latent trajectories of PTSD symptoms; effects of CBT on these trajectories. Results Three trajectories were identified: Rapid Remitting (rapid decrease in symptoms from 1- to 5-months; 56% of the sample), Slow Remitting (progressive decrease in symptoms over 15 months; 27%) and Non-Remitting (persistently elevated symptoms; 17%). CBT accelerated the recovery of the Slow Remitting class but did not affect the other classes. Conclusions The early course of PTSD symptoms is characterized by distinct and diverging response patterns that are centrally relevant to understanding the disorder and preventing its occurrence. Studies of the pathogenesis of PTSD may benefit from using clustered symptom trajectories as their dependent variables. PMID:23990895

The effectiveness of resources created by students as partners in explaining the relevance of mathematics in engineering education

NASA Astrophysics Data System (ADS)

Dunn, Michelle; Loch, Birgit; Scott, Wendy

2018-01-01

First-year engineering students often struggle to see the relevance of theoretical mathematical concepts for their future studies and professional careers. This is an issue, as students who do not see relevance in fundamental parts of their studies may disengage from these parts and focus their efforts on other subjects they think will be more useful to them. In this study, we surveyed engineering students enrolled in a first-year mathematics subject on their perceptions of the relevance of the individual mathematical topics taught. Surveys were administered at the start of semester when some of these topics were unknown to them, and again at the end of semester when students had not only studied all these topics but also watched a set of animated videos. These videos had been produced by higher-year students to explain where they had seen applications of the mathematical concepts presented in the first year. We notice differences between the perceived relevance of topics for future study and for professional careers, with relevance to study rated higher than relevance to careers. We also find that the animations are seen as helpful in understanding the relevance of first-year mathematics. The majority of students indicated that lecturers with students as partners should work collaboratively to produce future videos.

Poor Reliability of Wrist Blood Pressure Self-Measurement at Home: A Population-Based Study.

PubMed

Casiglia, Edoardo; Tikhonoff, Valérie; Albertini, Federica; Palatini, Paolo

2016-10-01

The reliability of blood pressure measurement with wrist devices, which has not previously been assessed under real-life circumstances in general population, is dependent on correct positioning of the wrist device at heart level. We determined whether an error was present when blood pressure was self-measured at the wrist in 721 unselected subjects from the general population. After training, blood pressure was measured in the office and self-measured at home with an upper-arm device (the UA-767 Plus) and a wrist device (the UB-542, not provided with a position sensor). The upper-arm-wrist blood pressure difference detected in the office was used as the reference measurement. The discrepancy between office and home differences was the home measurement error. In the office, systolic blood pressure was 2.5% lower at wrist than at arm (P=0.002), whereas at home, systolic and diastolic blood pressures were higher at wrist than at arm (+5.6% and +5.4%, respectively; P<0.0001 for both); 621 subjects had home measurement error of at least ±5 mm Hg and 455 of at least ±10 mm Hg (bad measurers). In multivariable linear regression, a lower cognitive pattern independently determined both the systolic and the diastolic home measurement error and a longer forearm the systolic error only. This was confirmed by logistic regression having bad measurers as dependent variable. The use of wrist devices for home self-measurement, therefore, leads to frequent detection of falsely elevated blood pressure values likely because of a poor memory and rendition of the instructions, leading to the wrong position of the wrist. © 2016 American Heart Association, Inc.

Doppler indexes of left ventricular systolic and diastolic flow and central pulse pressure in relation to renal resistive index.

PubMed

Kuznetsova, Tatiana; Cauwenberghs, Nicholas; Knez, Judita; Thijs, Lutgarde; Liu, Yan-Ping; Gu, Yu-Mei; Staessen, Jan A

2015-04-01

The cardio-renal interaction occurs via hemodynamic and humoral factors. Noninvasive assessment of renal hemodynamics is currently possible by assessment of renal resistive index (RRI) derived from intrarenal Doppler arterial waveforms as ((peak systolic velocity - end-diastolic velocity)/peak systolic velocity). Limited information is available regarding the relationship between RRI and cardiac hemodynamics. We investigated these associations in randomly recruited subjects from a general population. In 171 participants (48.5% women; mean age, 52.2 years), using pulsed wave Doppler, we measured RRI (mean, 0.60) and left ventricular outflow tract (LVOT) and transmitral (E and A) blood flow peak velocities and its velocity time integrals (VTI). Using carotid applanation tonometry, we measured central pulse pressure and arterial stiffness indexes such as augmentation pressure and carotid-femoral pulse wave velocity. In stepwise regression analysis, RRI independently and significantly increased with female sex, age, body weight, brachial pulse pressure, and use of β-blockers, whereas it decreased with body height and mean arterial pressure. In multivariable-adjusted models with central pulse pressure and arterial stiffness indexes as the explanatory variables, we observed a significant and positive correlation of RRI only with central pulse pressure (P < 0.0001). Among the Doppler indexes of left ventricular blood flow, RRI was significantly and positively associated with LVOT and E peak velocities (P ≤ 0.012) and VTIs (P ≤ 0.010). We demonstrated that in unselected subjects RRI was significantly associated with central pulse pressure and left ventricular systolic and diastolic Doppler blood flow indexes. Our findings imply that in addition to the anthropometric characteristics, cardiac hemodynamic factors influence the intrarenal arterial Doppler waveform patterns. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effectiveness of eHealth interventions for reducing mental health conditions in employees: A systematic review and meta-analysis

PubMed Central

Lampit, Amit; Choi, Isabella; Calvo, Rafael A.; Harvey, Samuel B.; Glozier, Nicholas

2017-01-01

Background Many organisations promote eHealth applications as a feasible, low-cost method of addressing mental ill-health and stress amongst their employees. However, there are good reasons why the efficacy identified in clinical or other samples may not generalize to employees, and many Apps are being developed specifically for this group. The aim of this paper is to conduct the first comprehensive systematic review and meta-analysis evaluating the evidence for the effectiveness and examine the relative efficacy of different types of eHealth interventions for employees. Methods Systematic searches were conducted for relevant articles published from 1975 until November 17, 2016, of trials of eHealth mental health interventions (App or web-based) focused on the mental health of employees. The quality and bias of all identified studies was assessed. We extracted means and standard deviations from published reports, comparing the difference in effect sizes (Hedge’s g) in standardized mental health outcomes. We meta-analysed these using a random effects model, stratified by length of follow up, intervention type, and whether the intervention was universal (unselected) or targeted to selected groups e.g. “stressed”. Results 23 controlled trials of eHealth interventions were identified which overall suggested a small positive effect at both post intervention (g = 0.24, 95% CI 0.13 to 0.35) and follow up (g = 0.23, 95% CI 0.03 to 0.42). There were differential short term effects seen between the intervention types whereby Mindfulness based interventions (g = 0.60, 95% CI 0.34 to 0.85, n = 6) showed larger effects than the Cognitive Behaviour Therapy (CBT) based (g = 0.15, 95% CI 0.02 to 0.29, n = 11) and Stress Management based (g = 0.17, 95%CI -0.01 to 0.34, n = 6) interventions. The Stress Management interventions however differed by whether delivered to universal or targeted groups with a moderately large effect size at both post-intervention (g = 0.64, 95% CI 0.54 to 0.85) and follow-up (g = 0.69, 95% CI 0.06 to 1.33) in targeted groups, but no effect in unselected groups. Interpretation There is reasonable evidence that eHealth interventions delivered to employees may reduce mental health and stress symptoms post intervention and still have a benefit, although reduced at follow-up. Despite the enthusiasm in the corporate world for such approaches, employers and other organisations should be aware not all such interventions are equal, many lack evidence, and achieving the best outcomes depends upon providing the right type of intervention to the correct population. PMID:29267334

Predictors of methamphetamine psychosis: History of ADHD-relevant childhood behaviors and drug exposure

PubMed Central

Salo, Ruth; Fassbender, Catherine; Iosif, Ana- Maria; Ursu, Stefan; Leamon, Martin H; Cameron, Carter

2013-01-01

The goal of this study was to extend our previous research that reported a significant association between Attention Deficit Hyperactivity Disorder (ADHD)-relevant childhood behaviors and the frequency of methamphetamine (MA)-induced psychotic symptoms in an expanded sample. 190 participants who met DSM-IV criteria for MA dependence were administered the Methamphetamine Experience Questionnaire that assessed MA-induced psychosis. Data related to MA exposure, comorbid drug use, education, familial psychiatric history and assessments of ADHD-relevant childhood behaviors as measured by the Wender Utah Rating Scale (WURS) were collected. Although WURS scores did not differ between 145 MAP+ and 45 MAP-subjects, MAP+ subjects with higher WURS scores were significantly more likely to report more frequent psychosis. Although mean daily MA dosage did not differ between the MAP+ and MAP- subjects, MAP+ who consumed larger doses of MA were significantly more likely to experience frequent psychosis. These data suggest that ADHD-relevant childhood behaviors may interact with MA exposure to reflect a neurobiological vulnerability related to the emergence of frequent MA-induced psychotic symptoms. These results may elucidate factors that contribute to the psychiatric sequelae of MA abuse. PMID:23896355

Detection and Interpretation of Low-Level and High-Level Surprising and Important Events in Large-Scale Data Streams

DTIC Science & Technology

2016-06-28

Likewise, we have developed a new general theory of relevance that quanti - fies how new data observations may or not affect an observer’s beliefs about how...which suggests that relevance is not an inherent attribute but rather is dependent on the knowledge or beliefs of the subject evaluating the...subjects. This allowed us to evaluate the accuracy of each person as the number of image pairs for which they selected the majority image. The average

Myxomatosis. The effect of age upon survival of wild and domestic rabbits (Oryctolagus cuniculus) with a degree of genetic resistance and unselected domestic rabbits infected with myxoma virus.

PubMed

Sobey, W R; Conolly, D; Haycockp; Edmonds, J W

1970-03-01

The response of wild and domestic rabbits with a degree of genetic resistance to myxomatosis has been shown to be markedly affected by the age at which they were infected with a virulent strain of the virus. The response, in terms of mean survival time and percentage survival, fell with increasing age from 10 to 30 weeks with little change thereafter.

Myxomatosis. The effect of age upon survival of wild and domestic rabbits (Oryctolagus cuniculus) with a degree of genetic resistance and unselected domestic rabbits infected with myxoma virus

PubMed Central

Sobey, W. R.; Conolly, Dorothy; Haycock, P.; Edmonds, J. W.

1970-01-01

The response of wild and domestic rabbits with a degree of genetic resistance to myxomatosis has been shown to be markedly affected by the age at which they were infected with a virulent strain of the virus. The response, in terms of mean survival time and percentage survival, fell with increasing age from 10 to 30 weeks with little change thereafter. PMID:5267123

Identification of a Human Airway Epithelial Cell Subpopulation with Altered Biophysical, Molecular, and Metastatic Properties. | Office of Cancer Genomics

Cancer.gov

Lung cancers are documented to have remarkable intratumoral genetic heterogeneity. However, little is known about the heterogeneity of biophysical properties, such as cell motility, and its relationship to early disease pathogenesis and micrometastatic dissemination. In this study, we identified and selected a subpopulation of highly migratory premalignant airway epithelial cells that were observed to migrate through microscale constrictions at up to 100-fold the rate of the unselected immortalized epithelial cell lines.

Prototype of a Graphical CONOPS (Concept of Operations) Development Environment for Agile Systems Engineering

DTIC Science & Technology

2012-03-23

orthogonal dimensions of cognition : things, places, paths, actions, and causes suggested as key by cognitive linguists. The goal of this research task... stylistic treatment across the system? O O O 1.3 Is a single, selected icon clearly visible when surrounded by unselected icons? O O O 1.4...1.21 Complex tasks: 8-12 seconds O O O 1.22 Are response times appropriate to the user’s cognitive processing? O O O 1.23 Continuity of thinking

Artery balloon angioplasty and depression symptoms.

PubMed

Slovacek, Ladislav; Slovackova, Birgita

2011-06-01

Peripheral arterial occlusive disease (PAOD) as a chronic disease is associated with physical, psychological and social distress for elderly patients and their families. The study has three main aims: 1. to evaluate the occurrence and the relevance of depression symptoms in patients with PAOD, 2. to evaluate the effect of age and Fontaine stage of PAOD on relevance of depression in patients with PAOD, and 3. to evaluate the effect of artery balloon angioplasty (ABA) on occurence and relevance of depression symptoms. The study was prospective and longitudinal. Dates were obtained during year 2006. The total number of subjects with PAOD was 42 (28 males, 14 females). Thirty subjects with PAOD (20 male, 10 female) treated by ABA filled in Zung's scale 3-6 months after ABA (61%). The mean age of all subjects was 65.4 years (aged 45-79). The evaluation of occurrence and relevance of depression was performed with Czech version of Zung self-rating depression scale (ZSRS). The mean Zung self-rating depression score (ZSRDS) certifies the presence of signs of minimum or mildly depression in patients with PAOD. The results proved statistically significant dependence of depression on age and on Fontaine stage of PAOD. Also, the results proved that artery balloon angioplasty has a highly positive effect on occurrence and relevance of depression symptoms. The results had shown the existence of the association between PAOD, depression and ABA.

40 CFR 26.1701 - To what does this subpart apply?

Code of Federal Regulations, 2010 CFR

2010-07-01

... HUMAN SUBJECTS Ethical Standards for Assessing Whether To Rely on the Results of Human Research in EPA... valid and relevant data from research involving intentional exposure of human subjects. ...

40 CFR 26.1701 - To what does this subpart apply?

Code of Federal Regulations, 2011 CFR

2011-07-01

... HUMAN SUBJECTS Ethical Standards for Assessing Whether To Rely on the Results of Human Research in EPA... valid and relevant data from research involving intentional exposure of human subjects. ...

40 CFR 26.1701 - To what does this subpart apply?

Code of Federal Regulations, 2012 CFR

2012-07-01

... HUMAN SUBJECTS Ethical Standards for Assessing Whether To Rely on the Results of Human Research in EPA... valid and relevant data from research involving intentional exposure of human subjects. ...

Making Interdisciplinary Subjects Relevant to Students: An Interdisciplinary Approach

ERIC Educational Resources Information Center

Yang, Min

2009-01-01

This paper examines issues relating to the design/redesign of the pedagogy of interdisciplinary undergraduate subjects. Examples include: (a) law subjects for students in Business Management or Building and Surveying; (b) "English Communication for Business" for students in English; and (c) "Information technology in Business" for students in…

Students' perceptions of the relevance of mathematics in engineering

NASA Astrophysics Data System (ADS)

Flegg, Jennifer; Mallet, Dann; Lupton, Mandy

2012-09-01

In this article, we report on the findings of an exploratory study into the experience of students as they learn first year engineering mathematics. Here we define engineering as the application of mathematics and sciences to the building and design of projects for the use of society [M. Kirschenman and B. Brenner, Education for Civil Engineering: A Profession of Practice, Leader. Manag. Eng. 10 (2010), p. 54]. Qualitative and quantitative data on students' views of the relevance of their mathematics study to their engineering studies and future careers in engineering was collected. The students described using a range of mathematics techniques (mathematics skills developed, mathematics concepts applied to engineering and skills developed relevant for engineering) for various usages (as a subject of study, a tool for other subjects or a tool for real world problems). We found a number of themes relating to the design of engineering mathematics curriculum emerged from the data. These included the relevance of mathematics within different engineering majors, the relevance of mathematics to future studies, the relevance of learning mathematical rigour and the effectiveness of problem-solving tasks in conveying the relevance of mathematics more effectively than other forms of assessment. We make recommendations for the design of engineering mathematics curriculum based on our findings.

D-dimer as marker for microcirculatory failure: correlation with LOD and APACHE II scores.

PubMed

Angstwurm, Matthias W A; Reininger, Armin J; Spannagl, Michael

2004-01-01

The relevance of plasma d-dimer levels as marker for morbidity and organ dysfunction in severely ill patients is largely unknown. In a prospective study we determined d-dimer plasma levels of 800 unselected patients at admission to our intensive care unit. In 91% of the patients' samples d-dimer levels were elevated, in some patients up to several hundredfold as compared to normal values. The highest mean d-dimer values were present in the patient group with thromboembolic diseases, and particularly in non-survivors of pulmonary embolism. In patients with circulatory impairment (r=0.794) and in patients with infections (r=0.487) a statistically significant correlation was present between d-dimer levels and the APACHE II score (P<0.001). The logistic organ dysfunction score (LOD, P<0.001) correlated with d-dimer levels only in patients with circulatory impairment (r=0.474). On the contrary, patients without circulatory impairment demonstrated no correlation of d-dimer levels to the APACHE II or LOD score. Taking all patients together, no correlations of d-dimer levels with single organ failure or with indicators of infection could be detected. In conclusion, d-dimer plasma levels strongly correlated with the severity of the disease and organ dysfunction in patients with circulatory impairment or infections suggesting that elevated d-dimer levels may reflect the extent of microcirculatory failure. Thus, a therapeutic strategy to improve the microcirculation in such patients may be monitored using d-dimer plasma levels.

Genetic screening in adolescents with steroid-resistant nephrotic syndrome.

PubMed

Lipska, Beata S; Iatropoulos, Paraskevas; Maranta, Ramona; Caridi, Gianluca; Ozaltin, Fatih; Anarat, Ali; Balat, Ayse; Gellermann, Jutta; Trautmann, Agnes; Erdogan, Ozlem; Saeed, Bassam; Emre, Sevinc; Bogdanovic, Radovan; Azocar, Marta; Balasz-Chmielewska, Irena; Benetti, Elisa; Caliskan, Salim; Mir, Sevgi; Melk, Anette; Ertan, Pelin; Baskin, Esra; Jardim, Helena; Davitaia, Tinatin; Wasilewska, Anna; Drozdz, Dorota; Szczepanska, Maria; Jankauskiene, Augustina; Higuita, Lina Maria Serna; Ardissino, Gianluigi; Ozkaya, Ozan; Kuzma-Mroczkowska, Elzbieta; Soylemezoglu, Oguz; Ranchin, Bruno; Medynska, Anna; Tkaczyk, Marcin; Peco-Antic, Amira; Akil, Ipek; Jarmolinski, Tomasz; Firszt-Adamczyk, Agnieszka; Dusek, Jiri; Simonetti, Giacomo D; Gok, Faysal; Gheissari, Alaleh; Emma, Francesco; Krmar, Rafael T; Fischbach, Michel; Printza, Nikoleta; Simkova, Eva; Mele, Caterina; Ghiggeri, Gian Marco; Schaefer, Franz

2013-07-01

Genetic screening paradigms for congenital and infantile nephrotic syndrome are well established; however, screening in adolescents has received only minor attention. To help rectify this, we analyzed an unselected adolescent cohort of the international PodoNet registry to develop a rational screening approach based on 227 patients with nonsyndromic steroid-resistant nephrotic syndrome aged 10-20 years. Of these, 21% had a positive family history. Autosomal dominant cases were screened for WT1, TRPC6, ACTN4, and INF2 mutations. All other patients had the NPHS2 gene screened, and WT1 was tested in sporadic cases. In addition, 40 sporadic cases had the entire coding region of INF2 tested. Of the autosomal recessive and the sporadic cases, 13 and 6%, respectively, were found to have podocin-associated nephrotic syndrome, and 56% of them were compound heterozygous for the nonneutral p.R229Q polymorphism. Four percent of the sporadic and 10% of the autosomal dominant cases had a mutation in WT1. Pathogenic INF2 mutations were found in 20% of the dominant but none of the sporadic cases. In a large cohort of adolescents including both familial and sporadic disease, NPHS2 mutations explained about 7% and WT1 4% of cases, whereas INF2 proved relevant only in autosomal dominant familial disease. Thus, screening of the entire coding sequence of NPHS2 and exons 8-9 of WT1 appears to be the most rational and cost-effective screening approach in sporadic juvenile steroid-resistant nephrotic syndrome.

How should a district general hospital immunology service screen for anti-nuclear antibodies? An ‘in-the-field’ audit

PubMed Central

Hira-Kazal, R; Shea-Simonds, P; Peacock, J L; Maher, J

2015-01-01

Anti-nuclear antibody (ANA) testing assists in the diagnosis of several immune-mediated disorders. The gold standard method for detection of these antibodies is by indirect immunofluorescence testing on human epidermoid laryngeal carcinoma (HEp-2) cells. However, many laboratories test for these antibodies using solid-phase assays such as enzyme-linked immunosorbent assay (ELISA), which allows for higher throughput testing at reduced cost. In this study, we have audited the performance of a previously established ELISA assay to screen for ANA, making comparison with the gold standard HEp-2 immunofluorescence test. A prospective and unselected sample of 89 consecutive ANA test requests by consultant rheumatologists were evaluated in parallel over a period of 10 months using both tests. ELISA and HEp-2 screening assays yielded 40 (45%) and 72 (81%) positive test results, respectively, demonstrating lack of concordance between test methods. Using standard and clinical samples, it was demonstrated that the ELISA method did not detect several ANA with nucleolar, homogeneous and speckled immunofluorescence patterns. None of these ELISANEG HEp-2POS ANA were reactive with a panel of six extractable nuclear antigens or with double-stranded DNA. Nonetheless, 13 of these samples (15%) originated from patients with recognized ANA-associated disease (n = 7) or Raynaud's phenomenon (n = 6). We conclude that ELISA screening may fail to detect clinically relevant ANA that lack defined specificity for antigen. PMID:25412573

Automation of the consensus guidelines in diabetes care: potential impact on clinical inertia.

PubMed

Albisser, A Michael; Inhaber, Francine

2010-01-01

To propose that automation of the consensus guidelines and mandated targets (CG&MT) in glycemia, hemoglobin A1c, and body weight will facilitate optimal clinical management of patients with diabetes. (1) A simplified method for capturing diabetes outcomes at home was devised, (2) relevant portions of the CG&MT were translated into computer code and automated, and (3) algorithms were applied to transform data from self-monitoring of blood glucose into circadian profiles and hemoglobin A1c levels. (4) The resulting procedures were integrated into a USB memory drive for use by health-care providers at the point of care. For input from patients, a simple form is used to capture data on diabetes outcomes, including blood glucose measurements before and after meals and at bedtime, medication, and lifestyle events in a structured fashion. At each encounter with a health-care provider, the patient's data are transferred into the device and become available to assist in identifying deviations from mandated targets, potential risks of hypoglycemia, and necessary prescription changes. Preliminary observations during a 2 1/2-year period from a community support group dedicated to glycemic control on 20 unselected patients (10 with and 10 without use of the device) are summarized. With use of the automated information, the health professional is supported at the point of care to achieve better, safer outcomes and practice evidence-based medicine entirely in lockstep with the CG&MT. This automation helps to overcome clinical inertia.

Surface-Chemistry-Mediated Control of Individual Magnetic Helical Microswimmers in a Swarm.

PubMed

Wang, Xiaopu; Hu, Chengzhi; Schurz, Lukas; De Marco, Carmela; Chen, Xiangzhong; Pané, Salvador; Nelson, Bradley J

2018-05-31

Magnetic helical microswimmers, also known as artificial bacterial flagella (ABFs), perform 3D navigation in various liquids under low-strength rotating magnetic fields by converting rotational motion to translational motion. ABFs have been widely studied as carriers for targeted delivery and release of drugs and cells. For in vivo/ in vitro therapeutic applications, control over individual groups of swimmers within a swarm is necessary for several biomedical applications such as drug delivery or small-scale surgery. In this work, we present the selective control of individual swimmers in a swarm of geometrically and magnetically identical ABFs by modifying their surface chemistry. We confirm experimentally and analytically that the forward/rotational velocity ratio of ABFs is independent of their surface coatings when the swimmers are operated below their step-out frequency (the frequency requiring the entire available magnetic torque to maintain synchronous rotation). We also show that ABFs with hydrophobic surfaces exhibit larger step-out frequencies and higher maximum forward velocities compared to their hydrophilic counterparts. Thus, selective control of a group of swimmers within a swarm of ABFs can be achieved by operating the selected ABFs at a frequency that is below their step-out frequencies but higher than the step-out frequencies of unselected ABFs. The feasibility of this method is investigated in water and in biologically relevant solutions. Selective control is also demonstrated inside a Y-shaped microfluidic channel. Our results present a systematic approach for realizing selective control within a swarm of magnetic helical microswimmers.

Measurement of urinary metanephrines to screen for pheochromocytoma in an unselected hospital referral population

PubMed Central

Brain, Keith L.; Kay, Jonathan; Shine, Brian

2009-01-01

Background Despite the rarity of pheochromocytoma, the dangers of uncontrolled severe hypertension and the very effective surgical treatment of this condition mean that diagnosis is important. Urinary or plasma catecholamines or catecholamine-derivatives are commonly used to screen for pheochromocytomas prior to imaging. This study investigates whether derived measures obtained from 24-hour urinary metanephrine results, patient age and sex can better predict tumors in populations with a low pre-test probability. Methods This study takes a pragmatic approach by retrospectively studying the outcomes of an unselected population referred for urinary metanephrine testing (1819 patients) to a tertiary hospital laboratory, and investigates the usefulness of some simple derivative measures for detecting pheochromocytoma. Urinary 24-hour excretion of metanephrine, normetanephrine and 3-methoxytyramine were normalized by dividing by an age- and sex- specific reference range. The ability of products of these normalized measures to predict pheochromocytomas was assessed, compared to a gold standard of biopsy-confirmed tumor. Results The normalized product of urinary metanephrine and normetanephrine excretion (nMAD.nNMT) proved to be a highly sensitive (100%) and specific (99.1%) measure yielding a positive predictive value 82%. Receiver-operator characteristic curves were not improved by including the normalized 3-methoxytyramine concentrations in the product. nMAD.nNMT gave higher sensitivity and specificity than either test alone. Conclusion We suggest that nMAD.nNMT is a useful measure for identifying pheochromocytoma in a population with a low pre-test probability. PMID:16990424

Veress needle insertion into the left hypochondrium for creation of pneumoperitoneum: diagnostic value of tests to determine the position of the needle in unselected patients.

PubMed

Becker, Otávio Monteiro; Azevedo, João Luiz Moreira Coutinho; de Azevedo, Otávio Cansanção; Hypólito, Octávio Henrique Mendes; Miyahira, Susana Abe; Miguel, Gustavo Peixoto Soares; Machado, Afonso Cesar Cabral Guedes

2011-01-01

To assess the effectiveness of the Veress needle puncture in the left hypochondrium and the accuracy of the tests described for the intraperitoneal correct positioning of the tip of the Veress needle in an unselected population. Ninetyone patients consecutively scheduled for Videolaparoscopy had the abdominal wall punctured in the left hypochondrium. There were no exclusion criteria. The patients received general anesthesia and mechanical ventilation according to the protocol. After puncturing five tests were used to confirm the positioning of the needle tip within the peritoneal cavity: aspiration test--AT; resistance to infusion--Pres; recovery of the infused fluid--Prec, dripping test--DT, and test of initial intraperitoneal pressure--IIPP. The test results were compared with results from literature for groups with defined exclusion criteria. The results were used for calculating sensitivity (S) specificity (E), positive predictive value (PPV) and negative predictive value (NPV). Inferential statistical methods were used to analyze the findings. There were 13 failures. AT had E = 100% and NPV 100%. Pres had S = 100%, E = 0; PPV = 85.71%; NPV does not apply. Prec: S = 100%, E = 53.84%, PPV = 92.85%, NPV = 100%. DT: S = 100%, E = 61.53%, PPV = 93.97% NPV 100%. In IIPP, S, E, PPV and NPV were 100%. The puncture in the left hypochondrium is effective and the performed tests guide the surgeon regardless of sex, BMI, or previous laparotomy.

Transfusions and blood loss in total hip and knee arthroplasty: a prospective observational study.

PubMed

Carling, Malin S; Jeppsson, Anders; Eriksson, Bengt I; Brisby, Helena

2015-03-28

There is a high prevalence of blood product transfusions in orthopedic surgery. The reported prevalence of red blood cell transfusions in unselected patients undergoing hip or knee replacement varies between 21% and 70%. We determined current blood loss and transfusion prevalence in total hip and knee arthroplasty when tranexamic acid was used as a routine prophylaxis, and further investigated potential predictors for excessive blood loss and transfusion requirement. In total, 193 consecutive patients undergoing unilateral hip (n = 114) or knee arthroplasty (n = 79) were included in a prospective observational study. Estimated perioperative blood loss was calculated and transfusions of allogeneic blood products registered and related to patient characteristics and perioperative variables. Overall transfusion rate was 16% (18% in hip patients and 11% in knee patients, p = 0.19). Median estimated blood loss was significantly higher in hip patients (984 vs 789 mL, p < 0.001). Preoperative hemoglobin concentration was the only independent predictor of red blood cell transfusion in hip patients while low hemoglobin concentration, body mass index, and operation time were independent predictors for red blood cell transfusion in knee patients. The prevalence of red blood cell transfusion was lower than previously reported in unselected total hip or knee arthroplasty patients. Routine use of tranexamic acid may have contributed. Low preoperative hemoglobin levels, low body mass index, and long operation increase the risk for red blood cell transfusion.

Novel BRCA1 mutations and more frequent intron-20 alteration found among 236 women from Western Poland.

PubMed

Sobczak, K; Kozłowski, P; Napierała, M; Czarny, J; Woźniak, M; Kapuścińska, M; Lośko, M; Koziczak, M; Jasińska, A; Powierska, J; Braczkowski, R; Breborowicz, J; Godlewski, D; Mackiewicz, A; Krzyzosiak, W

1997-10-09

Three different novel BRCA1 mutations, five independent cases of the same 12 bp insertion-duplication in intron-20 and two novel rare BRCA1 sequence variants were identified among 122 Polish women with positive, in most cases moderate family history of breast and/or ovarian cancer, 80 controls and 34 unselected breast cancer tissue specimens. All mutations and variants were germline. The 4153 delA frameshift mutation, the Tyr105Cys missense mutation and two cases of the alteration in intron-20 were found in the group of healthy women with positive family history. Two other cases of the intronic insertion were found in unselected controls. Their carriers had no family history of breast or ovarian cancer but other cancers occurred in their families. The 1782 Trp/STOP nonsense mutation and one case of the insertion in intron-20 were first found in tissue specimens of breast cancer patient and breast/ovarian cancer patient, respectively. Their carriers also had no family history of breast or ovarian cancer. The distribution of the insertion in intron-20 in analysed groups and results of RT-PCR experiments suggest a less prominent role for this variant considered earlier a splicing mutation. This study shows also, that more population-oriented research is needed, involving women with less profound or even no family history of breast and ovarian cancer, to better understand the role and significance of different BRCA1 variants and mutations.

Tolerance of negative emotion moderates the amplification of mental contamination following an evoking task: A randomized experimental study.

PubMed

Fergus, Thomas A

2018-06-01

Contamination is a near universal feeling, with mental contamination representing a contamination feeling in the absence of direct physical contact with a source. Extant research indicates that tolerance of negative emotion is important for understanding emotional reactions to images, thoughts, and memories, all of which are common sources of mental contamination. Extending research linking distress tolerance to mental contamination, this study examined if individual differences in the tolerance of negative emotion moderates the amplification of mental contamination following an evoking task. Unselected participants completed a self-report measure of tolerance of negative emotion during an online session. They later attended an in-person session and were randomized to an experimental scenario group: betrayal (n = 49) or control (n = 49). Participants imagined themselves in a scenario, with the betrayal scenario designed to evoke mental contamination. Mental contamination was assessed by self-report before and after the scenario. The betrayal, but not control, scenario caused an increase in mental contamination. Tolerance for negative emotion moderated the effect of group on mental contamination. Group differences in mental contamination evidenced at low, but not high, distress tolerance. A novel experimental manipulation and an unselected sample were used. Future research could assess tolerance of negative emotion using a behavioral task. These results indicate that tolerance of negative emotion may be important for understanding when individuals experience mental contamination. Copyright © 2017 Elsevier Ltd. All rights reserved.

Urine output on ICU entry is associated with hospital mortality in unselected critically ill patients.

PubMed

Zhang, Zhongheng; Xu, Xiao; Ni, Hongying; Deng, Hongsheng

2014-02-01

Urine output (UO) is routinely measured in the intensive care unit (ICU) but its prognostic value remains debated. The study aimed to investigate the association between day 1 UO and hospital mortality. Clinical data were abstracted from the Multiparameter Intelligent Monitoring in Intensive Care II (version 2.6) database. UO was recorded for the first 24 h after ICU entry, and was classified into three categories: UO >0.5, 0.3-0.5 and ≤0.3 ml/kg per hour. The primary endpoint was the hospital mortality. Four models were built to adjust for the hazards ratio of mortality. A total of 21,207 unselected ICU patients including 2,401 non-survivors and 18,806 survivors were included (mortality rate 11.3 %). Mortality rate increased progressively across UO categories: >0.5 (7.67 %), 0.3-0.5 (11.27 %) and ≤0.3 ml/kg/h (18.29 %), and this relationship remained statistically significant after rigorous control of confounding factors with the Cox proportional hazards regression model. With UO >0.5 as the referent group, the hazards ratios for UO 0.3-0.5 and UO ≤0.3 were 1.41 (95 % CI 1.29-1.54) and 1.52 (95 % CI 1.38-1.67), respectively. UO obtained on ICU entry is an independent predictor of mortality irrespective of diuretic use. It would be interesting to examine whether strategies to increase UO would improve clinical outcome.

Genomic Profiling on an Unselected Solid Tumor Population Reveals a Highly Mutated Wnt/β-Catenin Pathway Associated with Oncogenic EGFR Mutations.

PubMed

Jiang, Jingrui; Protopopov, Alexei; Sun, Ruobai; Lyle, Stephen; Russell, Meaghan

2018-04-09

Oncogenic epidermal growth factor receptors (EGFRs) can recruit key effectors in diverse cellular processes to propagate oncogenic signals. Targeted and combinational therapeutic strategies have been successfully applied for treating EGFR-driven cancers. However, a main challenge in EGFR therapies is drug resistance due to mutations, oncogenic shift, alternative signaling, and other potential mechanisms. To further understand the genetic alterations associated with oncogenic EGFRs and to provide further insight into optimal and personalized therapeutic strategies, we applied a proprietary comprehensive next-generation sequencing (NGS)-based assay of 435 genes to systematically study the genomic profiles of 1565 unselected solid cancer patient samples. We found that activating EGFR mutations were predominantly detected in lung cancer, particularly in non-small cell lung cancer (NSCLC). The mutational landscape of EGFR-driven tumors covered most key signaling pathways and biological processes. Strikingly, the Wnt/β-catenin pathway was highly mutated (48 variants detected in 46% of the EGFR-driven tumors), and its variant number topped that in the TP53/apoptosis and PI3K-AKT-mTOR pathways. Furthermore, an analysis of mutation distribution revealed a differential association pattern of gene mutations between EGFR exon 19del and EGFR L858R. Our results confirm the aggressive nature of the oncogenic EGFR-driven tumors and reassure that a combinational strategy should have advantages over an EGFR-targeted monotherapy and holds great promise for overcoming drug resistance.

Unexpected severe calcification after transplantation of bone marrow cells in acute myocardial infarction.

PubMed

Yoon, Young-Sup; Park, Jong-Seon; Tkebuchava, Tengiz; Luedeman, Corinne; Losordo, Douglas W

2004-06-29

There has been a rapid increase in the number of clinical trials using unselected bone marrow (BM) cells or the mononuclear fraction of BM cells for treating ischemic heart diseases. Thus far, no significant deleterious effects or complications have been reported in any studies using BM-derived cells for treatment of various cardiac diseases. Seven-week-old female Fisher-344 rats underwent surgery to induce acute myocardial infarction and were randomized into 3 groups of 16 rats, each receiving intramyocardial injection of either 7x10(5) DiI-labeled total BM cells (TBMCs), the same number of DiI-labeled, clonally expanded BM multipotent stem cells, or the same volume of phosphate-buffered saline in the peri-infarct area. Echocardiography 2 weeks after cell transplantation indicated intramyocardial calcification in 4 of 14 surviving rats (28.5%) in the TBMC group. Histological examination with hematoxylin and eosin staining and von Kossa staining confirmed the presence of extensive intramyocardial calcification. Alkaline phosphatase staining revealed strong positivity surrounding the calcified area suggestive of ongoing osteogenic activity. Fluorescent microscopic examination revealed that acellular calcific areas were surrounded by DiI-labeled TBMCs, suggesting the direct involvement of transplanted TBMCs in myocardial calcification. In contrast, in hearts receiving equal volumes of saline or BM multipotent stem cells delivered in the same manner, there was no evidence of calcification. These results demonstrate that direct transplantation of unselected BM cells into the acutely infarcted myocardium may induce significant intramyocardial calcification.

Consumption Patterns of Nightlife Attendees in Munich: A Latent-Class Analysis.

PubMed

Hannemann, Tessa-Virginia; Kraus, Ludwig; Piontek, Daniela

2017-09-19

The affinity for substance use among patrons of nightclubs has been well established. With novel psychoactive substances (NPS) quickly emerging on the European drug market, trends, and patterns of use are potentially changing. (1) The detection of subgroups of consumers in the electronic dance music scene of a major German metropolitan city, (2) describing the consumption patterns of these subgroups, (3) exploring the prevalence and type of NPS consumption in this population at nightlife events in Munich. A total of 1571 patrons answered questions regarding their own substance use and the emergence of NPS as well as their experience with these substances. A latent class analysis was employed to detect consumption patterns within the sample. A four class model was determined reflecting different consumption patterns: the conservative class (34.9%) whose substance was limited to cannabis; the traditional class (36.6%) which especially consumed traditional club drugs; the psychedelic class (17.5%) which, in addition to traditional club drugs also consumed psychedelic drugs; and an unselective class (10.9%) which displayed the greatest likelihood of consumption of all assessed drugs. "Smoking mixtures" and methylone were the new substances mentioned most often, the number of substances mentioned differed between latent classes. Specific strategies are needed to reduce harm in those displaying the riskiest substance use. Although NPS use is still a fringe phenomenon its prevalence is greater in this subpopulation than in the general population, especially among users in the high-risk unselective class.

Detection of atrial fibrillation after ischemic stroke or transient ischemic attack: a systematic review and meta-analysis.

PubMed

Kishore, Amit; Vail, Andy; Majid, Arshad; Dawson, Jesse; Lees, Kennedy R; Tyrrell, Pippa J; Smith, Craig J

2014-02-01

Atrial fibrillation (AF) confers a high risk of recurrent stroke, although detection methods and definitions of paroxysmal AF during screening vary. We therefore undertook a systematic review and meta-analysis to determine the frequency of newly detected AF using noninvasive or invasive cardiac monitoring after ischemic stroke or transient ischemic attack. Prospective observational studies or randomized controlled trials of patients with ischemic stroke, transient ischemic attack, or both, who underwent any cardiac monitoring for a minimum of 12 hours, were included after electronic searches of multiple databases. The primary outcome was detection of any new AF during the monitoring period. We prespecified subgroup analysis of selected (prescreened or cryptogenic) versus unselected patients and according to duration of monitoring. A total of 32 studies were analyzed. The overall detection rate of any AF was 11.5% (95% confidence interval, 8.9%-14.3%), although the timing, duration, method of monitoring, and reporting of diagnostic criteria used for paroxysmal AF varied. Detection rates were higher in selected (13.4%; 95% confidence interval, 9.0%-18.4%) than in unselected patients (6.2%; 95% confidence interval, 4.4%-8.3%). There was substantial heterogeneity even within specified subgroups. Detection of AF was highly variable, and the review was limited by small sample sizes and marked heterogeneity. Further studies are required to inform patient selection, optimal timing, methods, and duration of monitoring for detection of AF/paroxysmal AF.

Phonological skills and their role in learning to read: a meta-analytic review.

PubMed

Melby-Lervåg, Monica; Lyster, Solveig-Alma Halaas; Hulme, Charles

2012-03-01

The authors report a systematic meta-analytic review of the relationships among 3 of the most widely studied measures of children's phonological skills (phonemic awareness, rime awareness, and verbal short-term memory) and children's word reading skills. The review included both extreme group studies and correlational studies with unselected samples (235 studies were included, and 995 effect sizes were calculated). Results from extreme group comparisons indicated that children with dyslexia show a large deficit on phonemic awareness in relation to typically developing children of the same age (pooled effect size estimate: -1.37) and children matched on reading level (pooled effect size estimate: -0.57). There were significantly smaller group deficits on both rime awareness and verbal short-term memory (pooled effect size estimates: rime skills in relation to age-matched controls, -0.93, and reading-level controls, -0.37; verbal short-term memory skills in relation to age-matched controls, -0.71, and reading-level controls, -0.09). Analyses of studies of unselected samples showed that phonemic awareness was the strongest correlate of individual differences in word reading ability and that this effect remained reliable after controlling for variations in both verbal short-term memory and rime awareness. These findings support the pivotal role of phonemic awareness as a predictor of individual differences in reading development. We discuss whether such a relationship is a causal one and the implications of research in this area for current approaches to the teaching of reading and interventions for children with reading difficulties.

Second Trimester Maternal Serum Screening for Fetal Down Syndrome: as a Screening Test for Hemoglobin Bart's Disease: A Prospective Population-based Study.

PubMed

Wanapirak, Chanane; Piyamomgkol, Wirawit; Sirichotiyakul, Supatra; Tongprasert, Fuanglada; Srisupundit, Kasemsri; Luewan, Suchaya; Traisrisilp, Kuntharee; Jatavan, Phudit; Tongsong, Theera

2018-06-21

To determine the effectiveness of second-trimester maternal serum screening (MSS) for Down syndrome as a screening test for fetal hemoglobin (Hb) Bart's disease among an unselected population. A secondary analysis of a large prospective database (20,254 pregnancies) was conducted to compare the levels of MSS, alpha-fetoprotein (AFP), free beta-human chorionic gonadotropin (hCG) and unconjugated estriol (uE3) between pregnancies with Hb Bart's disease and unaffected pregnancies. The median AFP levels were much higher among affected fetuses, (1.96 vs. 1.12 multiple of the median (MoM); p<0.001), yielding a sensitivity of 81.6% and specificity of 86.4%. Thus, AFP measurement is effective in predicting fetal Hb Bart's disease among an unselected population when using a cut-off value of 1.5 MoM. The serum free b-hCG levels were slightly, but significantly, higher in the affected pregnancies, while the serum uE3 levels were minimally, but significantly, lower among the affected pregnancies. Second trimester maternal serum AFP levels were significantly elevated in cases of fetal Hb Bart's disease. Pregnancies with unexplained elevated serum AFP levels in areas of high prevalence of Hb Bart's disease should always undergo a detailed ultrasound examination to detect any early signs of fetal anemia before development of hydrops fetalis. This article is protected by copyright. All rights reserved.

The risk of gastric cancer in carriers of CHEK2 mutations.

PubMed

Teodorczyk, Urszula; Cybulski, Cezary; Wokołorczyk, Dominika; Jakubowska, Anna; Starzyńska, Teresa; Lawniczak, Małgorzata; Domagała, Paweł; Ferenc, Katarzyna; Marlicz, Krzysztof; Banaszkiewicz, Zbigniew; Wiśniowski, Rafał; Narod, Steven A; Lubiński, Jan

2013-09-01

CHEK2 is a tumor suppressor gene whose functions are central to the induction of cell cycle arrest and apoptosis following DNA damage. Mutations in CHEK2 have been associated with cancers at many sites, including breast and prostate cancers, but the relationship between CHEK2 and gastric cancer has not been extensively studied. In Poland, there are four known founder alleles of CHEK2; three alleles are protein truncating (1100delC, IVS2G>A, del5395) and the other is a missense variant (I157T). We examined the frequencies of four Polish founder mutations in the CHEK2 gene in 658 unselected gastric cancer patients, in 154 familial gastric cancer patients and in 8,302 controls. A CHEK2 mutation was seen in 57 of 658 (8.7 %) unselected patients with gastric cancer compared to 480 of 8,302 (5.8 %) controls (OR 1.6, p = 0.004). A CHEK2 mutation was present in 19 of 154 (12.3 %) familial cases (OR = 2.3, p = 0.001). The odds ratio for early onset (<50 years) gastric cancer was higher (2.1, p = 0.01), than for cases diagnosed at age of 50 or above (OR 1.4, p = 0.05). Truncating mutations of CHEK2 were associated with higher risk (OR = 2.1, p = 0.02) than the missense mutation I157T (OR = 1.4, p = 0.04). CHEK2 mutations predispose to gastric cancer, in particular to young-onset cases.

Event-related brain potentials and affective responses to threat in spider/snake-phobic and non-phobic subjects.

PubMed

Miltner, Wolfgang H R; Trippe, Ralf H; Krieschel, Silke; Gutberlet, Ingmar; Hecht, Holger; Weiss, Thomas

2005-07-01

We investigated cortical responses and valence/arousal ratings of spider phobic, snake phobic, and healthy subjects while they were processing feared, fear-relevant, emotional neutral, and pleasant stimuli. Results revealed significantly larger amplitudes of late ERP components (P3 and late positive complex, LPC) but not of early components (N1, P2, N2) in phobics when subjects were processing feared stimuli. This fear-associated increase of amplitudes of late ERP components in phobic subjects was maximal at centro-parietal and occipital brain sites. Furthermore, phobics but not controls rated feared stimuli to be more negative and arousing than fear-relevant, emotional neutral, and pleasant stimuli. Since late ERP components and valence/arousal ratings were only significantly increased when phobic subjects but not when healthy controls were processing feared stimuli, the present data suggest that P3 and LPC amplitudes represent useful neural correlates of the emotional significance and meaning of stimuli.

Libraries and the Ethics of Censorship

ERIC Educational Resources Information Center

Duthie, Fiona

2010-01-01

This paper reviews a selection of literature pertaining to the subject of censorship in modern libraries. It interrogates the literature in terms of the ethical debates informing much of the contemporary academic writing on this subject. A multi-pronged approach to the subject is adopted. The review includes evaluations of the relevant aspects of…

Screening EEG in Aircrew Selection: Clinical Aerospace Neurology Perspective

NASA Technical Reports Server (NTRS)

Clark, Jonathan B.; Riley, Terrence

2001-01-01

As clinical aerospace neurologists we do not favor using screening EEG in pilot selection on unselected and otherwise asymptomatic individuals. The role of EEG in aviation screening should be as an adjunct to diagnosis, and the decision to disqualify a pilot should never be based solely on the EEG. Although a policy of using a screening EEG in an unselected population might detect an individual with a potentially increased relative risk, it would needlessly exclude many applicants who would probably never have a seizure. A diagnostic test performed on an asymptomatic individual without clinical indications, in a population with a low prevalence of disease (seizure) may be of limited or possibly detrimental value. We feel that rather than do EEGs on all candidates, a better approach would be to perform an EEG for a specific indication, such as family history of seizure, single convulsion (seizure) , history of unexplained loss of consciousness or head injury. Routine screening EEGs in unselected aviation applications are not done without clinical indication in the U.S. Air Force, Navy, or NASA. The USAF discontinued routine screening EEGs for selection in 1978, the U.S. Navy discontinued it in 1981 , and NASA discontinued it in 1995. EEG as an aeromedical screening tool in the US Navy dates back to 1939. The US Navy routinely used EEGs to screen all aeromedical personnel from 1961 to 1981. The incidence of epileptiform activity on EEG in asymptomatic flight candidates ranges from 0.11 to 2.5%. In 3 studies of asymptomatic flight candidates with epileptiform activity on EEG followed for 2 to 15 years, 1 of 31 (3.2%), 1 of 30 (3.3%), and 0 of 14 (0%) developed a seizure, for a cumulative risk of an individual with an epileptiform EEG developing a seizure of 2.67% (2 in 75). Of 28,658 student naval aviation personnel screened 31 had spikes and/or slow waves on EEG, and only 1 later developed a seizure. Of the 28,627 who had a normal EEG, 4 later developed seizures, or .0139% (4/28627). After review of the value of the EEG as a screening tool, the US Navy now uses EEG only for certain clinical indications (head injury, unexplained loss of consciousness, family history of epilepsy, and abnormal neurological exam). Currently the US Navy does not use EEG for screening for any flight applicant without a neurologic indication. In the US Navy, an electroencephalographic pattern is determined to be epileptiform by a neurologist.

Should Sponsors and DSMBs Share Interim Results Across Trials?

PubMed Central

Shah, Seema K.; Dawson, Liza; Dixon, Dennis O.; Lie, Reidar K.

2011-01-01

Increasing numbers of multinational clinical trials have generated new ethical obligations of research sponsors and their DSMBs. Although sponsors and DSMBs clearly have ethical obligations to protect subjects in their trials, future patients, and the integrity of their trial, the obligations they have to protect subjects in other trials have been overlooked. When interim results from clinical trials can significantly affect the conduct of other trials and the welfare of the subjects in those trials, sponsors and DSMBs may have obligations to disclose results to the relevant parties. We propose that sponsors and DSMBs routinely work together in advance to develop a plan for disclosing relevant information in cases where it is necessary to protect the welfare of subjects in other trials. Channels of communication between sponsors, DSMBs, IRBs, and others involved in similar and concurrent trials will better protect both research participants and the integrity of the research enterprise. PMID:21937922

Local versus Global Information Relevance in Website Use: A Case Study with the Information Literacy Portal AlfinEEES

ERIC Educational Resources Information Center

Marco, Francisco Javier Garcia; Pinto, Maria

2010-01-01

Introduction: A model to explore the relations among local and global relevance-based information behaviour is proposed that is based on objective and subjective measures of the relevance of the Website contents. Method: Global interest for the Website was researched using data on visits, while local use was explored with two surveys on the…

42 CFR 423.578 - Exceptions process.

Code of Federal Regulations, 2011 CFR

2011-10-01

... and medical and scientific evidence and the known relevant physical or mental characteristics of the... evidence and medical and scientific evidence and the known relevant physical or mental characteristics of... reasonable and complete exceptions procedures subject to CMS' approval for this type of coverage...

42 CFR 423.578 - Exceptions process.

Code of Federal Regulations, 2013 CFR

2013-10-01

... and medical and scientific evidence and the known relevant physical or mental characteristics of the... evidence and medical and scientific evidence and the known relevant physical or mental characteristics of... maintain reasonable and complete exceptions procedures subject to CMS' approval for this type of coverage...

A Markov Chain Model for Changes in Users' Assessment of Search Results.

PubMed

Zhitomirsky-Geffet, Maayan; Bar-Ilan, Judit; Levene, Mark

2016-01-01

Previous research shows that users tend to change their assessment of search results over time. This is a first study that investigates the factors and reasons for these changes, and describes a stochastic model of user behaviour that may explain these changes. In particular, we hypothesise that most of the changes are local, i.e. between results with similar or close relevance to the query, and thus belong to the same"coarse" relevance category. According to the theory of coarse beliefs and categorical thinking, humans tend to divide the range of values under consideration into coarse categories, and are thus able to distinguish only between cross-category values but not within them. To test this hypothesis we conducted five experiments with about 120 subjects divided into 3 groups. Each student in every group was asked to rank and assign relevance scores to the same set of search results over two or three rounds, with a period of three to nine weeks between each round. The subjects of the last three-round experiment were then exposed to the differences in their judgements and were asked to explain them. We make use of a Markov chain model to measure change in users' judgments between the different rounds. The Markov chain demonstrates that the changes converge, and that a majority of the changes are local to a neighbouring relevance category. We found that most of the subjects were satisfied with their changes, and did not perceive them as mistakes but rather as a legitimate phenomenon, since they believe that time has influenced their relevance assessment. Both our quantitative analysis and user comments support the hypothesis of the existence of coarse relevance categories resulting from categorical thinking in the context of user evaluation of search results.

A Markov Chain Model for Changes in Users’ Assessment of Search Results

PubMed Central

Zhitomirsky-Geffet, Maayan; Bar-Ilan, Judit; Levene, Mark

2016-01-01

Previous research shows that users tend to change their assessment of search results over time. This is a first study that investigates the factors and reasons for these changes, and describes a stochastic model of user behaviour that may explain these changes. In particular, we hypothesise that most of the changes are local, i.e. between results with similar or close relevance to the query, and thus belong to the same”coarse” relevance category. According to the theory of coarse beliefs and categorical thinking, humans tend to divide the range of values under consideration into coarse categories, and are thus able to distinguish only between cross-category values but not within them. To test this hypothesis we conducted five experiments with about 120 subjects divided into 3 groups. Each student in every group was asked to rank and assign relevance scores to the same set of search results over two or three rounds, with a period of three to nine weeks between each round. The subjects of the last three-round experiment were then exposed to the differences in their judgements and were asked to explain them. We make use of a Markov chain model to measure change in users’ judgments between the different rounds. The Markov chain demonstrates that the changes converge, and that a majority of the changes are local to a neighbouring relevance category. We found that most of the subjects were satisfied with their changes, and did not perceive them as mistakes but rather as a legitimate phenomenon, since they believe that time has influenced their relevance assessment. Both our quantitative analysis and user comments support the hypothesis of the existence of coarse relevance categories resulting from categorical thinking in the context of user evaluation of search results. PMID:27171426

Effect of heat stress on the fertility of male mice in vivo and in vitro.

PubMed

Yaeram, J; Setchell, B P; Maddocks, S

2006-01-01

A study was conducted to determine whether following exposure of male mice to high temperatures, the ability of their spermatozoa to fertilise ova was reduced, especially during the period before the males became completely infertile. Male mice placed in a microclimate chamber at 36 degrees C for two periods, each of 12 h on successive days, were less able to fertilise control females in vivo when mated and, even in those females that became pregnant, litter size was reduced. However, these effects were associated with falls in testis weight and numbers of spermatozoa in the testis and epididymis. To determine whether the effect on fertility was a result of the decreased spermatozoa numbers, spermatozoa were collected from the epididymides of heated and control males. Equal numbers of motile spermatozoa from an unselected sample or those subjected to a swim-up procedure to separate those that were motile from the immotile ones in the sample were then mixed in vitro with oocytes from superovulated normal females. Similar numbers of spermatozoa from both control and heated males bound to the zona pellucida but smaller percentages of the oocytes were fertilised by spermatozoa from the heated males and fewer of these spermatozoa penetrated the ova. The effects were first seen 7 days after the heat exposure and became more obvious after 10 or 14 days.

APOC3 -482C>T polymorphism, circulating apolipoprotein C-III and smoking: interrelation and roles in predicting type-2 diabetes and coronary disease.

PubMed

Onat, Altan; Erginel-Unaltuna, Nihan; Coban, Neslihan; Ciçek, Gökhan; Yüksel, Hüsniye

2011-04-01

We determined the relationship of smoking status on APOC3 -482C>T polymorphism and apolipoprotein C-III (apoC-III) concentrations and the latter two parameters' influence on risk of diabetes and coronary heart disease (CHD). Prediction of incident cases was assessed at 5.5years' follow-up in unselected 519 individuals of a general population genotyped for -482C>T polymorphism. Female sex and current smoking were significantly associated with low circulating apoC-III in subjects without (p≤0.033) than with abdominal obesity (p=0.053) or than insulin resistant -482TT homozygotes (p=0.034) who had 20-30% higher serum apoC-III. Multi-adjusted serum apoC-III was log-linearly associated with fasting triglycerides. ApoC-III levels determined the development of diabetes [RR 1.56 (95%CI 1.21; 2.01)] and CHD [RR 1.38 (1.10; 1.72) for an increment of 14%], after adjustment for confounders. APOC3 -482TT genotype is associated with high apoC-III concentrations only in the presence of abdominal obesity or insulin resistance, but not in current smokers who remain lean or insulin-sensitive. Rather than APOC3 -482C>T polymorphism, circulating apoC-III determines cardiometabolic risk. Copyright © 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Refined 4-group classification of left ventricular hypertrophy based on ventricular concentricity and volume dilatation outlines distinct noninvasive hemodynamic profiles in a large contemporary echocardiographic population.

PubMed

Barbieri, Andrea; Rossi, Andrea; Gaibazzi, Nicola; Erlicher, Andrea; Mureddu, Gian Francesco; Frattini, Silvia; Faden, Giacomo; Manicardi, Marcella; Beraldi, Monica; Agostini, Francesco; Lazzarini, Valentina; Moreo, Antonella; Temporelli, Pier Luigi; Faggiano, Pompilio

2018-05-23

Left ventricular hypertrophy (LVH) may reflect a wide variety of physiologic and pathologic conditions. Thus, it can be misleading to consider all LVH to be homogenous or similar. Refined 4-group classification of LVH based on ventricular concentricity and dilatation may be identified. To determine whether the 4-group classification of LVH identified distinct phenotypes, we compared their association with various noninvasive markers of cardiac stress. Cohort of unselected adult outpatients referred to a seven tertiary care echocardiographic laboratory for any indication in a 2-week period. We evaluated the LV geometric patterns using validated echocardiographic indexation methods and partition values. Standard echocardiography was performed in 1137 consecutive subjects, and LVH was found in 42%. The newly proposed 4-group classification of LVH was applicable in 88% of patients. The most common pattern resulted in concentric LVH (19%). The worst functional and hemodynamic profile was associated with eccentric LVH and those with mixed LVH had a higher prevalence of reduced EF than those with concentric LVH (P < .001 for all). The new 4-group classification of LVH system showed distinct differences in cardiac function and noninvasive hemodynamics allowing clinicians to distinguish different LV hemodynamic stress adaptations in patients with LVH. © 2018 Wiley Periodicals, Inc.

A new method for automated high-dimensional lesion segmentation evaluated in vascular injury and applied to the human occipital lobe.

PubMed

Mah, Yee-Haur; Jager, Rolf; Kennard, Christopher; Husain, Masud; Nachev, Parashkev

2014-07-01

Making robust inferences about the functional neuroanatomy of the brain is critically dependent on experimental techniques that examine the consequences of focal loss of brain function. Unfortunately, the use of the most comprehensive such technique-lesion-function mapping-is complicated by the need for time-consuming and subjective manual delineation of the lesions, greatly limiting the practicability of the approach. Here we exploit a recently-described general measure of statistical anomaly, zeta, to devise a fully-automated, high-dimensional algorithm for identifying the parameters of lesions within a brain image given a reference set of normal brain images. We proceed to evaluate such an algorithm in the context of diffusion-weighted imaging of the commonest type of lesion used in neuroanatomical research: ischaemic damage. Summary performance metrics exceed those previously published for diffusion-weighted imaging and approach the current gold standard-manual segmentation-sufficiently closely for fully-automated lesion-mapping studies to become a possibility. We apply the new method to 435 unselected images of patients with ischaemic stroke to derive a probabilistic map of the pattern of damage in lesions involving the occipital lobe, demonstrating the variation of anatomical resolvability of occipital areas so as to guide future lesion-function studies of the region. Copyright © 2012 Elsevier Ltd. All rights reserved.

Heritability of metabolic syndrome traits in a large population-based sample[S

PubMed Central

van Dongen, Jenny; Willemsen, Gonneke; Chen, Wei-Min; de Geus, Eco J. C.; Boomsma, Dorret I.

2013-01-01

Heritability estimates of metabolic syndrome traits vary widely across studies. Some studies have suggested that the contribution of genes may vary with age or sex. We estimated the heritability of 11 metabolic syndrome-related traits and height as a function of age and sex in a large population-based sample of twin families (N = 2,792–27,021, for different traits). A moderate-to-high heritability was found for all traits [from H2 = 0.47 (insulin) to H2 = 0.78 (BMI)]. The broad-sense heritability (H2) showed little variation between age groups in women; it differed somewhat more in men (e.g., for glucose, H2 = 0.61 in young females, H2 = 0.56 in older females, H2 = 0.64 in young males, and H2= 0.27 in older males). While nonadditive genetic effects explained little variation in the younger subjects, nonadditive genetic effects became more important at a greater age. Our findings show that in an unselected sample (age range, ∼18–98 years), the genetic contribution to individual differences in metabolic syndrome traits is moderate to large in both sexes and across age. Although the prevalence of the metabolic syndrome has greatly increased in the past decades due to lifestyle changes, our study indicates that most of the variation in metabolic syndrome traits between individuals is due to genetic differences. PMID:23918046

Summary of Existing Legislation Affecting People with Disabilities. [Revised.

ERIC Educational Resources Information Center

National Association of State Mental Retardation Program Directors, Alexandria, VA.

This publication provides a summary of relevant federal laws concerning the legal rights and benefits available to persons with disabilities. Relevant laws are divided into general subject areas, including education, employment, health, housing, income maintenance, nutrition, civil rights, social services, transportation, and vocational…

ECOLOGICALLY-RELEVANT QUANTIFICATION OF STREAMFLOW REGIMES IN WESTERN STREAMS

EPA Science Inventory

This report describes the rationale for and application of a protocol for estimation of ecologically-relevant streamflow metrics that quantify streamflow regime for ungaged sites subject to a range of human impact. The analysis presented here is focused on sites sampled by the U....

Towards brain-activity-controlled information retrieval: Decoding image relevance from MEG signals.

PubMed

Kauppi, Jukka-Pekka; Kandemir, Melih; Saarinen, Veli-Matti; Hirvenkari, Lotta; Parkkonen, Lauri; Klami, Arto; Hari, Riitta; Kaski, Samuel

2015-05-15

We hypothesize that brain activity can be used to control future information retrieval systems. To this end, we conducted a feasibility study on predicting the relevance of visual objects from brain activity. We analyze both magnetoencephalographic (MEG) and gaze signals from nine subjects who were viewing image collages, a subset of which was relevant to a predetermined task. We report three findings: i) the relevance of an image a subject looks at can be decoded from MEG signals with performance significantly better than chance, ii) fusion of gaze-based and MEG-based classifiers significantly improves the prediction performance compared to using either signal alone, and iii) non-linear classification of the MEG signals using Gaussian process classifiers outperforms linear classification. These findings break new ground for building brain-activity-based interactive image retrieval systems, as well as for systems utilizing feedback both from brain activity and eye movements. Copyright © 2015 Elsevier Inc. All rights reserved.

Diagnostics of Pupils' Meta-Subject Competence during Lessons on Mathematics in Secondary Schools

ERIC Educational Resources Information Center

Khuziakhmetova, Anvar N.; Naumova, Marina V.

2016-01-01

The relevance of diagnostic meta-subject competence measures in secondary schools is caused by the fact that the importance of a meta-subject competence formation was officially defined in educational standards, but there are still no qualitative and informative diagnostic tools for this competence development. The purpose of the article is to…

Pedagogical Conditions of School Students' Subjectivity Formation in the Educational Process

ERIC Educational Resources Information Center

Khairutdinova, Rezeda R.; Selivanova, Olga G.; Abildina, Saltanat K.

2016-01-01

The relevance of the research problem of the modern school student's subjectivity is caused by the necessity to develop in a growing person the integrity of innovative features such as productive independence, being active and initiative in any case. The aim of this article is to describe pedagogical conditions of students' subjectivity formation…

Improving Middle School Students' Subjective Well-Being: Efficacy of a Multicomponent Positive Psychology Intervention Targeting Small Groups of Youth

ERIC Educational Resources Information Center

Roth, Rachel A.; Suldo, Shannon M.; Ferron, John M.

2017-01-01

Most interventions intended to improve subjective well-being, termed "positive psychology interventions" (PPIs), have neglected to include relevant stakeholders in youth's lives and have not included booster sessions intended to maintain gains in subjective well-being. The current study investigated the impact of a multitarget,…

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

Bolotnikov, A. E., E-mail: bolotnik@bnl.gov; Camarda, G. S.; Cui, Y.

We investigated the feasibility of long-drift-time CdZnTe (CZT) gamma-ray detectors, fabricated from CZT material produced by Redlen Technologies. CZT crystals with cross-section areas of 5 × 5 mm{sup 2} and 6 × 6 mm{sup 2} and thicknesses of 20-, 30-, 40-, and 50-mm were configured as 3D position-sensitive drift detectors and were read out using a front-end ASIC. By correcting the electron charge losses caused by defects in the crystals, we demonstrated high performance for relatively thick detectors fabricated from unselected CZT material.

Engineering information on an Analog Signal to Discrete Time Interval Converter (ASDT-IC)

NASA Technical Reports Server (NTRS)

Schwarz, F. C.

1974-01-01

An electronic control system for nondissipative dc power converters is presented which improves (1) the routinely attainable static output voltage accuracy to the order of + or - 1% for ambient temperatures from -55 to 100 C and (2) the dynamic stability by utilizing approximately one tenth of the feedback gain needed otherwise. Performance is due to a functional philosophy of deterministic pulse modulation based on pulse area control and to an autocompensated signal processing principle. The system can be implemented with commercially available unselected components.

High-speed atomic force microscopy coming of age

NASA Astrophysics Data System (ADS)

Ando, Toshio

2012-02-01

High-speed atomic force microscopy (HS-AFM) is now materialized. It allows direct visualization of dynamic structural changes and dynamic processes of functioning biological molecules in physiological solutions, at high spatiotemporal resolution. Dynamic molecular events unselectively appear in detail in an AFM movie, facilitating our understanding of how biological molecules operate to function. This review describes a historical overview of technical development towards HS-AFM, summarizes elementary devices and techniques used in the current HS-AFM, and then highlights recent imaging studies. Finally, future challenges of HS-AFM studies are briefly discussed.

Relevant Information and Informed Consent in Research: In Defense of the Subjective Standard of Disclosure.

PubMed

Dranseika, Vilius; Piasecki, Jan; Waligora, Marcin

2017-02-01

In this article, we seek to contribute to the debate on the requirement of disclosure in the context of informed consent for research. We defend the subjective standard of disclosure and describe ways to implement this standard in research practice. We claim that the researcher should make an effort to find out what kinds of information are likely to be relevant for those consenting to research. This invites researchers to take empirical survey information seriously, attempt to understand the cultural context, talk to patients to be better able to understand what can be potentially different concerns and interests prevalent in the target population. The subjective standard of disclosure should be seen as a moral ideal that perhaps can never be perfectly implemented but still can and should be used as a normative ideal guiding research practice. In the light of these discussions, we call for more empirical research on what considerations are likely to be perceived as relevant by potential research participants recruited from different socio-economic and cultural groups.

Varying irrelevant phonetic features hinders learning of the feature being trained.

PubMed

Antoniou, Mark; Wong, Patrick C M

2016-01-01

Learning to distinguish nonnative words that differ in a critical phonetic feature can be difficult. Speech training studies typically employ methods that explicitly direct the learner's attention to the relevant nonnative feature to be learned. However, studies on vision have demonstrated that perceptual learning may occur implicitly, by exposing learners to stimulus features, even if they are irrelevant to the task, and it has recently been suggested that this task-irrelevant perceptual learning framework also applies to speech. In this study, subjects took part in a seven-day training regimen to learn to distinguish one of two nonnative features, namely, voice onset time or lexical tone, using explicit training methods consistent with most speech training studies. Critically, half of the subjects were exposed to stimuli that varied not only in the relevant feature, but in the irrelevant feature as well. The results showed that subjects who were trained with stimuli that varied in the relevant feature and held the irrelevant feature constant achieved the best learning outcomes. Varying both features hindered learning and generalization to new stimuli.

Coherent Structures in Plasmas Relevant to Electric Propulsion

DTIC Science & Technology

2016-06-24

AFRL-AFOSR-VA-TR-2016-0229 Coherent Structures in Plasmas Relevant to Electric Propulsion Mark Cappelli LELAND STANFORD JUNIOR UNIV CA Final Report...TITLE AND SUBTITLE Coherent Structures in Plasmas Relevant to Electric Propulsion 5a. CONTRACT NUMBER N/A 5b. GRANT NUMBER FA9550-14-1-0017 5c...to propulsion devices through experimental, theoretical, and numerical studies. 15. SUBJECT TERMS Plasma instabilities in magnetized discharges

Relationship Factors in Desensitization: A Persistent Trend

ERIC Educational Resources Information Center

Nawas, M. Mike; Pucel, John C.

1971-01-01

The aim of the study was to explore the relevance to the outcome of desensitization of same-sex and opposite-sex pairings of subjects and experimenters. It was concluded that desensitization is independent of the sex pairing of subject and experimenter. (Author)

Gorillas (Gorilla gorilla) and orangutans (Pongo pygmaeus) encode relevant problem features in a tool-using task.

PubMed

Mulcahy, Nicholas J; Call, Josep; Dunbar, Robin I M

2005-02-01

Two important elements in problem solving are the abilities to encode relevant task features and to combine multiple actions to achieve the goal. The authors investigated these 2 elements in a task in which gorillas (Gorilla gorilla) and orangutans (Pongo pygmaeus) had to use a tool to retrieve an out-of-reach reward. Subjects were able to select tools of an appropriate length to reach the reward even when the position of the reward and tools were not simultaneously visible. When presented with tools that were too short to retrieve the reward, subjects were more likely to refuse to use them than when tools were the appropriate length. Subjects were proficient at using tools in sequence to retrieve the reward.

[A retrospective study of expert opinions of a psychosomatic-psychotherapeutic university hospital for public and private customers over a period of 12 years].

PubMed

Uhlenbrock, Judith; Hinrichs, Jens; Heuft, Gereon

2017-09-01

A retrospective study of expert opinions of a psychosomatic-psychotherapeutic university hospital for public and private customers over a period of 12 years Objectives: Both the public and the legislative have developed an increasingly critical awareness for the fact that expert witnesses need to be independent. In contrast, to date there have been few studies concerning the quantity and the results of psychosomatic-psychotherapeutic expert opinions for public and private clients. In a retrospective study design, 285 expert opinions of a psychosomatic-psychotherapeutic university hospital stemming from consecutive, unselected random sampling over a 12-year time period (1990-2011) were analyzed using a predefined list of criteria. Besides client data, the study also noted the type and the objectives of the expertise, the sociodemographic data of the subjects, the biographic data of the subjects, the size of records, the particular psychopathological findings including conflict and structural diagnostics via the Operationalized Psychodynamic Diagnostics (OPD-2, Research Group 2006), syndromic diagnostics according to ICD-10 (WHO) including the related Impairment Scale Score (ISS, Schepank 1995), and the Global Assessment of Functioning-Scale (GAF, Heuft 2016). 54% of the subjects were men. All subjects were 46 years old at the time of examination; on average symptomatology had existed for 7 years, which made assessment of causality difficult. Most assignments referred to the effects of diseases or accidents in private contexts, followed by pension reports. Among the expert opinions related to possible implications of acts of violence, 95% were women. In 43.2% (n = 123) of the cases, the assessment had occurred in the context of legal action. In 65 cases at least one party had requested a supplemental written report during further procedure. In 17.8% (n = 22) of the cases sought by the courts, the expert witness was requested by at least one party to present the assessment verbally. It should be emphasized that OPD conflict and structural diagnostics appear indispensable also for assessing mental health prior to an external event (accident or assault). The use of the two severity ratings (ISS, GAF) is discussed. It is proposed that expert witnesses be requested to name all their clients fromthe last 5 years at the beginning or end of the expert opinion, so that their independence from possible conflicts of interest can be established.

VHL c.505 T>C mutation confers a high age related penetrance but no increased overall mortality

PubMed Central

Bender, B.; Eng, C.; Olschewski, M.; Berger, D.; Laubenberger, J.; Altehofer, C.; Kirste, G.; Orszagh, M.; van Velthoven, V.; Miosczka, H.; Schmidt, D.; Neumann, H.

2001-01-01

BACKGROUND—Germline mutations of the VHL gene cause von Hippel-Lindau syndrome (VHL). In southern Germany, a specific mutation in this gene, c.505 T>C, is one of the most frequent alterations owing to a founder effect.
METHODS—This study was conducted to evaluate morbidity, specific clinical risk profile, and mortality among a series of VHL c.505 T/C mutation carriers. A total of 125 eligible subjects carrying VHL c.505 T/C underwent ophthalmoscopy and gadolinium enhanced magnetic resonance imaging of the brain, the spinal cord, and the abdomen. Age related penetrance, morbidity, and mortality were assessed.
RESULTS—Frequently observed lesions were phaeochromocytoma (47%), retinal angiomas (36%), haemangioblastoma of the spine (36%), and haemangioblastoma of the brain (16%). Four patients developed renal cell carcinoma. VHL was symptomatic in 47% of subjects; 30% were asymptomatic despite the presence of at least one VHL related tumour and 23% of the carriers had no detectable VHL lesion. Of the 19 patients who had died (15%), 10 died of symptomatic VHL lesions. Overall penetrance by cumulative incidence functions is estimated at 48% by 35 years and 88% by 70 years. In contrast to the only existing published report based on patients with presumably unselected VHL germline mutations, the mortality rate for c.505 T/C mutation carriers is comparable to that of the general population of Germany.
CONCLUSIONS—Our results are an important example that a specific genotype, at least in the case of VHL c.505 T/C, can favourably impact on mortality despite a high age related penetrance. Our study also indirectly provides objective data which might be useful to the life and health insurance industry; it would appear that c.505 T>C mutation positive subjects have similar disease specific mortality to that of the general population owing to a combination of phenotype and timely detection of mutation carrier status followed by aggressive clinical screening and, if necessary, treatment.


Keywords: VHL gene; c.505 T/C germline mutation; VHL morbidity; VHL mortality PMID:11483638

[Prevalence of renal involvement in a population of type Ii diabetics followed up in primary care].

PubMed

Marín, R; Coca, A; Tranche, S; Rodríguez Mañas, L; Abellán, J; Moyá, A

2002-01-01

Patients with type 2 diabetes use to be managed in their primary care settings during the early stages of the disease. The main objective of the study was to determine renal impairment prevalence, and to assess its significance, within type 2 diabetics controlled by their family physicians. Transverse observation of patients with type 2 diabetes who were the first 20 unselected cases seen by 183 family physicians from 16 of the 17 Autonomic Communities of our country. The following variables were determined: serum creatinine, glucose, and HbA1c concentrations, proteinuria (dipstick test in a first-voided morning urine sample), blood pressure levels, and associated cardiovascular disease. Data from 3,583 type 2 diabetic subjects were evaluated. Mean age was 64 +/- 10 years and 45% were male. A serum creatinine > or = 1.2 mg/dl was observed in 523 (15.5%) patients. Proteinuria was present in 794 (23.5%) cases, being > or = 2 + in 215 (6.5%) subjects. Patients with a serum creatinine > or = 1.2 mg/dl were older, shower higher blood pressure levels, and suffered from more cardiovascular disease (32.0 vs 19.5%) than those with a serum creatinine < 1.2 mg/dl. In a multivariate analysis, this difference continued to be significant (OR 1.47; 95% CI 1.14 to 1.90; p = 0.002. Patients with proteinuria showed a higher prevalence of cardiovascular disease (OR 1.83; 95% CI 1.47 to 2.27; p < 0.0001) than those without proteinuria. This association was continuous through no proteinuria to the > or = 2 + proteinuria (p < 0.001). Blood pressure level was > or = 140/90 mmHg in 69% of the cases, being < 130/85 mmHg in only 8% of the subjects. There is a high prevalence of renal impairment, approximately of 25% within type 2 diabetic patients seen at the primary care level. Optimal blood pressure level seems to be extremely infrequent bearing in mind the diagnosis of diabetes and the associated cardiovascular disease.

Regional heterogeneity for the intracranial self-administration of ethanol within the ventral tegmental area of female Wistar rats.

PubMed

Rodd-Henricks, Z A; McKinzie, D L; Crile, R S; Murphy, J M; McBride, W J

2000-04-01

Because current findings indicate that the selectively bred alcohol-preferring P line of rats self-administers 50-200 mg% ethanol (EtOH) directly into the ventral tegmental area (VTA), whereas the alcohol-nonpreferring NP line does not, it is important to determine whether unselected, common stock rats would self-administer EtOH directly into the VTA. In addition, because neuroanatomical and self-administration studies indicate that the VTA may be functionally heterogeneous, the present study was designed to determine whether there were subregional differences within the VTA for the intracranial self-administration (ICSA) of EtOH. The objective of this study was to employ the ICSA technique to determine whether adult female Wistar rats would self-administer EtOH directly into the VTA, and whether regional heterogeneity existed for EtOH self-infusion within the VTA. Following surgery to implant guide cannulae aimed at either the posterior or anterior VTA, subjects were placed in standard experimental chambers equipped with an 'active lever' [fixed ratio (FR)1 schedule of reinforcement], which caused the delivery of the infusate, and an 'inactive lever', which had no programmed consequence. Subjects were assigned to groups that self-administered either artificial cerebrospinal fluid (aCSF) throughout, or 100-400 mg% EtOH for the first four sessions (acquisition), aCSF in sessions 5 and 6 (extinction), and EtOH again during session 7 (reinstatement). During the four acquisition sessions, rats with posterior VTA placements readily self-administered 200 mg% and 250 mg% EtOH and discriminated between the active and inactive levers. These subjects also demonstrated extinction, when aCSF was substituted for EtOH, and reinstatement when EtOH was reintroduced. Rats with posterior VTA placements self-infused 300 mg% and 400 mg% EtOH, and demonstrated lever discrimination only during the initial acquisition sessions. In contrast, rats with anterior VTA placements did not self-administer EtOH. The findings suggest that EtOH is reinforcing within the posterior VTA of Wistar rats, and the VTA is a functionally heterogeneous structure with regard to EtOH reinforcement.

Reviewing the curriculum for physics and technology in postgraduate sonography courses.

PubMed

Oates, Crispian P

2015-02-01

Physics and technology is seen as a difficult subject by those training in medical ultrasound. The reasons for this are discussed. Who should teach the subject and what should be included are considered. Ways to approach the subject so as to make it more relevant and easier to learn are proposed and a basic syllabus is suggested in an appendix.

The Relevance of Objective and Subjective Social Position for Self-Rated Health: A Combined Approach for the Swedish Context

ERIC Educational Resources Information Center

Miething, Alexander

2013-01-01

The study investigates the health effects of subjective class position stratified by objective social position. Four types of subjective class were analysed separately for individuals with manual or non-manual occupational background. The cross-sectional analysis is based on the Swedish Level-of-Living Survey from 2000 and includes 4,139…

Effects of Alcohol on Moral Functioning in Male Social Drinkers.

ERIC Educational Resources Information Center

Fincham, Frank; Barling, Julian

1979-01-01

Alcohol consumption was not found to affect the stage of moral reasoning of the subjects, but an inverse relationship was found between the amount of alcohol consumed and the subjects' discrimination of relevant from irrelevant information in their moral reasoning. (BH)

Autism Bibliography.

ERIC Educational Resources Information Center

MacGregor, Kelly; Sobsey, Dick

The bibliography contains 392 citations relevant to education and related services for children with autism and their families published between 1983 and 1988. Most of the citations are journal articles but a number of relevant books are also included. Citations are alphabetized by title. An author index (by first author) and a subject index are…

The DOD Humanitarian and Civic Assistance Program Concepts, Trends, Medical Challenges

DTIC Science & Technology

1997-03-01

program improvements; measuring program performance and effectiveness; and defining military roles relevant to training, long term benefits, and the...support conclusions relevant to trends, benefits, challenges, suggested improvements, and suggested areas for future research. 15. SUBJECT TERMS 16...a Long Term Medical Benefit ................ 28 CONCLUSION

Feedback of Client-Relevant Information and Clinical Practice

ERIC Educational Resources Information Center

Dana, Richard H.; Graham, E. Diane

1976-01-01

The literature suggests that how one reacts to feedback is influenced by kind of feedback, conditions under which feedback is presented, and a variety of relevant subject variables. The most frequent design has resulted in acceptance of false feedback by college students leading to derogation of instruments and assessors. (Author/MV)

An Etic-Emic Analysis of Individualism and Collectivism.

ERIC Educational Resources Information Center

Triandis, Harry C.; And Others

1993-01-01

An analysis of the responses of 1,614 adult subjects from 10 cultures show that the Leung-Bond procedure provides ways of extracting both strong and weak etics relevant to individualism and weak etics relevant to collectivism. The most complete picture is obtained when both etics and emics are examined. (SLD)

Job Search and Social Cognitive Theory: The Role of Career-Relevant Activities

ERIC Educational Resources Information Center

Zikic, Jelena; Saks, Alan M.

2009-01-01

Social cognitive theory was used to explain the relationships between career-relevant activities (environmental and self career exploration, career resources, and training), self-regulatory variables (job search self-efficacy and job search clarity), variables from the Theory of Planned Behavior (job search attitude, subjective norm, job search…

Effects of Sex, Gender Role Identification, and Gender Relevance of Two Types of Stressors on Cardiovascular and Subjective Responses: Sex and Gender Match and Mismatch Effects

ERIC Educational Resources Information Center

van Well, Sonja; Kolk, Annemarie M.; Klugkist, Irene G.

2008-01-01

The authors tested the hypothesis that a match between the gender relevance of a stressor and one's sex or gender role identification would elicit higher cardiovascular responses. Healthy female and male undergraduates (n = 108) were exposed to two stressors: the Cold Pressor Test (CPT) and the n-back task. Stressor relevance was manipulated to be…

Sleep disruption is related to poor response inhibition in individuals with obsessive-compulsive and repetitive negative thought symptoms.

PubMed

Nota, Jacob A; Schubert, Jessica R; Coles, Meredith E

2016-03-01

Obsessive-compulsive (OC) symptoms and repetitive negative thinking (RNT) are associated with poor inhibitory control. Sleep disruptions may partially mediate these relations and/or act as a "second hit" to individuals with OC symptoms and RNT. Models including habitual (past month) hours slept and bedtimes were tested. We employed a go/no-go task that allowed us to examine the relation between sleep and inhibition with various task contingencies. Sixty-seven unselected individuals were recruited from the participant pool at a public university. Bias-corrected bootstrap estimates did not show that sleep disruption mediated the relation between OC symptoms and response inhibition nor the relation between RNT and response inhibition. Multiple linear regression analyses found significant interactions between hours slept and OC symptom severity and between RNT and hours slept to predict poor response inhibition. Hours slept significantly negatively predicted commission errors when OC symptoms and RNT levels were relatively heightened but not when OC symptoms and RNT levels were relatively low. These effects were present in blocks where task contingencies were designed to shape a no-go bias. No significant relations were found with habitual bedtimes. The cross-sectional study design precludes testing the temporal precedence of symptoms in the "second hit" model. The unselected sample also limits generalization to clinical samples. These findings support a "second hit" model of interaction between sleep disruption and perseverative thoughts and behaviors. Further research on the mechanisms of the relation between sleep disruption and perseverative thought symptoms (OC and RNT) is warranted. Copyright © 2015 Elsevier Ltd. All rights reserved.

Diagnostic profiles of adult psychiatric outpatients with and without attention deficit hyperactivity disorder.

PubMed

Gorlin, Eugenia I; Dalrymple, Kristy; Chelminski, Iwona; Zimmerman, Mark

2016-10-01

Despite growing recognition that attention deficit/hyperactivity disorder (ADHD) is a highly prevalent, impairing, and comorbid disorder that persists into adulthood, reports on the nature and extent of its psychiatric comorbidities have been mixed to date. This study compared the prevalence rates of all major Axis I disorders as well as borderline personality disorder in an unselected sample of adult psychiatric outpatients with and without ADHD. As part of the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we administered a DSM-IV-based semi-structured diagnostic interview assessing ADHD and other psychiatric disorders to 1134 patients presenting for initial evaluation at an outpatient psychiatric practice. Logistic regression analyses were used to compare the rates of each disorder in patients with versus without an ADHD diagnosis (both overall and by Combined and Inattentive type). Patients with (versus without) any ADHD diagnosis had significantly higher rates of bipolar disorder, social phobia, impulse control disorders, eating disorders, and BPD, and significantly lower rates of major depressive disorder and adjustment disorder (all p<.05). Patients with (versus without) ADHD-Inattentive type had significantly higher rates of social phobia and eating disorders, whereas those with (versus without) the ADHD-Combined type had significantly higher rates of bipolar disorder, alcohol dependence, and BPD (all p<.05). In this novel investigation of the psychiatric profiles of an unselected sample of treatment-seeking adult outpatients with versus without ADHD, a distinct pattern of comorbidities emerged across subtypes, with implications for the accurate assessment and treatment of patients presenting for psychiatric care. Copyright © 2016 Elsevier Inc. All rights reserved.

Second- to Third-Trimester Longitudinal Growth Assessment for the Prediction of Largeness for Gestational Age and Macrosomia in an Unselected Population.

PubMed

Caradeux, Javier; Eixarch, Elisenda; Mazarico, Edurne; Basuki, Tri Rahmat; Gratacós, Eduard; Figueras, Francesc

2018-01-01

Prenatal detection of excessive growth remains inaccurate. Most strategies rely on a single cross-sectional evaluation of fetal size during the third trimester. To compare second- to third-trimester longitudinal growth assessment with cross-sectional evaluation at the third trimester in the prediction of largeness for gestational age (LGA) and macrosomia. A cohort of 2,696 unselected singleton pregnancies scanned at 21 ± 2 and 32 ± 2 weeks was created. Abdominal circumference (AC) measurements were transformed to z values according to the INTERGROWTH-21st standards. Longitudinal growth assessment was performed by calculation of z velocity and conditional growth. Both methods were compared to cross-sectional assessment at 32 ± 2 weeks. Predictive performance for LGA and macrosomia was determined by receiver operating characteristic curve analysis. A total of 188 (7%) newborns qualified for LGA and 182 (6.8%) for macrosomia. The areas under the curve (AUCs) for 32-week AC z score, AC z velocity, and conditional AC were 0.78, 0.61, and 0.55, respectively, for the prediction of LGA, and 0.75, 0.61, and 0.55, respectively, for the prediction of macrosomia. Both AUCs of AC z velocity and conditional AC were significantly lower (p < 0.001) than the AUC of cross-sectional AC z scores. In the general population, second- to third-trimester longitudinal assessment of fetal growth is inferior to third-trimester cross-sectional evaluation of size in the prediction of LGA and macrosomia. © 2017 S. Karger AG, Basel.

Cell-based strategies to manage leukemia relapse: efficacy and feasibility of immunotherapy approaches.

PubMed

Rambaldi, A; Biagi, E; Bonini, C; Biondi, A; Introna, M

2015-01-01

When treatment fails, the clinical outcome of acute leukemia patients is usually very poor, particularly when failure occurs after transplantation. A second allogeneic stem cell transplant could be envisaged as an effective and feasible salvage option in younger patients having a late relapse and an available donor. Unmanipulated or minimally manipulated donor T cells may also be effective in a minority of patients but the main limit remains the induction of severe graft-versus-host disease. This clinical complication has brought about a huge research effort that led to the development of leukemia-specific T-cell therapy aiming at the direct recognition of leukemia-specific rather than minor histocompatibility antigens. Despite a great scientific interest, the clinical feasibility of such an approach has proven to be quite problematic. To overcome this limitation, more research has moved toward the choice of targeting commonly expressed hematopoietic specific antigens by the genetic modification of unselected T cells. The best example of this is represented by the anti-CD19 chimeric antigen receptor (CD19.CAR) T cells. As a possible alternative to the genetic manipulation of unselected T cells, specific T-cell subpopulations with in vivo favorable homing and long-term survival properties have been genetically modified by CAR molecules. Finally, the use of naturally cytotoxic effector cells such as natural killer and cytokine-induced killer cells has been proposed in several clinical trials. The clinical development of these latter cells could also be further expanded by additional genetic modifications using the CAR technology.

Symptom severity scale of the DSM5 for schizophrenia, and other psychotic disorders: diagnostic validity and clinical feasibility.

PubMed

Ritsner, Michael S; Mar, Maria; Arbitman, Marina; Grinshpoon, Alexander

2013-06-30

Innovations in DSM5 include dimensional diagnosis of schizophrenia (SZ) and other psychotic (OP) disorders using the symptom severity scale (SS-DSM5). We evaluated the psychometric properties and diagnostic validity of the SS-DSM5 scale using a cross-sectional design and an unselected convenience unselected sample of 314 inpatients and outpatients with SZ/OP and mood disorders who received standard care in routine clinical practice. The SS-DSM5 scale, the Clinical Global Impression-Severity scale (CGI-S), the Positive and Negative Syndrome Scale (PANSS), and the Bech-Rafaelsen Mania Scale (BRMS) were administered. Factor structure, reliability, internal consistency, convergent and diagnostic ability of the DSM5-SS were evaluated. Factor analysis indicated two latent factors underlying the SS-DSM5 (Psychotic and Deficit sub-scales). Cronbach's alpha was >0.70. Convergent validity of the SS-DSM5 was highly significant. Patients with SZ/PO disorders were correctly diagnosed (77.9%) using the SS-DSM5 scale (72% using PANSS). The agreement of the diagnostic decisions between the SS-DSM5 and PANSS was substantial for SZ/PO disorders (Kappa=0.75). Classifying participants with SZ/PO versus mood disorders using SS-DSM5 provided a sensitivity of 95%, and specificity of 34%. Thus, this study suggests that the SS-DSM5 has acceptable psychometric properties and that its use in clinical practice and research is feasible in clinical settings. The dimensional option for the diagnosis of schizophrenia and related disorders using SS-DSM5 is discussed. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chromatic and achromatic monocular deprivation produce separable changes of eye dominance in adults.

PubMed

Zhou, Jiawei; Reynaud, Alexandre; Kim, Yeon Jin; Mullen, Kathy T; Hess, Robert F

2017-11-29

Temporarily depriving one eye of its input, in whole or in part, results in a transient shift in eye dominance in human adults, with the patched eye becoming stronger and the unpatched eye weaker. However, little is known about the role of colour contrast in these behavioural changes. Here, we first show that the changes in eye dominance and contrast sensitivity induced by monocular eye patching affect colour and achromatic contrast sensitivity equally. We next use dichoptic movies, customized and filtered to stimulate the two eyes differentially. We show that a strong imbalance in achromatic contrast between the eyes, with no colour content, also produces similar, unselective shifts in eye dominance for both colour and achromatic contrast sensitivity. Interestingly, if this achromatic imbalance is paired with similar colour contrast in both eyes, the shift in eye dominance is selective, affecting achromatic but not chromatic contrast sensitivity and revealing a dissociation in eye dominance for colour and achromatic image content. On the other hand, a strong imbalance in chromatic contrast between the eyes, with no achromatic content, produces small, unselective changes in eye dominance, but if paired with similar achromatic contrast in both eyes, no changes occur. We conclude that perceptual changes in eye dominance are strongly driven by interocular imbalances in achromatic contrast, with colour contrast having a significant counter balancing effect. In the short term, eyes can have different dominances for achromatic and chromatic contrast, suggesting separate pathways at the site of these neuroplastic changes. © 2017 The Author(s).

Non-optic glioma in adults and children with neurofibromatosis 1.

PubMed

Sellmer, Laura; Farschtschi, Said; Marangoni, Marco; Heran, Manraj K S; Birch, Patricia; Wenzel, Ralph; Friedman, Jan M; Mautner, Victor-Felix

2017-02-15

Non-optic gliomas occur in 5% of children with NF1, but little is known about these tumours in adults. We aimed to investigate progression, spontaneous regression and the natural history of non-optic gliomas in adults and compare these findings to the results found in children. One thousand seven hundred twenty-two brain MRI scans of 562 unselected individuals with NF1 were collected at the NF outpatient department of the University Hospital Hamburg-Eppendorf between 2003 and 2015. The number of scans per patient ranged from one to 12; patients were followed for a median of 3.7 years. We identified 24 patients (4.3%) with non-optic gliomas. Median age at first scan with glioma was 21.2 years, much higher than in previous publications. Only seven of the 24 non-optic glioma patients were symptomatic. Five of 24 patients had multiple non-optic gliomas. Four individuals developed a new tumour, and 4 cases showed progression. The risk of new tumour development was 0.19% (95% confidence interval 0.06% to 0.52%) per patient year of follow-up for patients over 10 years. The rate of progressing non-optic gliomas per patient year of follow-up in the first 5 years after tumour diagnosis was 4.7% (95% confidence interval 1.5% to 12%). Non-optic gliomas are twice as common in an unselected cohort of NF1 patients as previously reported. This is likely due to increased frequency of diagnosis of asymptomatic tumours when routine MRIs are performed and a higher prevalence in older individuals.

Effects of nutritional supplementation during pregnancy on early adult disease risk: follow up of offspring of participants in a randomised controlled trial investigating effects of supplementation on infant birth weight.

PubMed

Macleod, John; Tang, Lie; Hobbs, F D Richard; Wharton, Brian; Holder, Roger; Hussain, Shakir; Nichols, Linda; Stewart, Paul; Clark, Penny; Luzio, Steve; Holly, Jeff; Smith, George Davey

2013-01-01

Observational evidence suggests that improving fetal growth may improve adult health. Experimental evidence from nutritional supplementation trials undertaken amongst pregnant women in the less developed world does not show strong or consistent effects on adult disease risk and no trials from the more developed world have previously been reported. To test the hypothesis that nutritional supplementation during pregnancy influences offspring disease risk in adulthood. Clinical assessment of a range of established diseases risk markers in young adult offspring of 283 South Asian mothers who participated in two trials of nutritional supplementation during pregnancy (protein/energy/vitamins; energy/vitamins or vitamins only) at Sorrento Maternity Hospital in Birmingham UK either unselected or selected on the basis of nutritional status. 236 (83%) offspring were traced and 118 (50%) of these were assessed in clinic. Protein/energy/vitamins supplementation amongst undernourished mothers was associated with increased infant birthweight. Nutritional supplementation showed no strong association with any one of a comprehensive range of markers of adult disease risk and no consistent pattern of association with risk across markers in offspring of either unselected or undernourished mothers. We found no evidence that nutritional supplements given to pregnant women are an important influence on adult disease risk however our study lacked power to estimate small effects. Our findings do not provide support for a policy of nutritional supplementation for pregnant women as an effective means to improve adult health in more developed societies.

Analytical evaluation of point of care cTnT and clinical performances in an unselected population as compared with central laboratory highly sensitive cTnT.

PubMed

Dupuy, Anne Marie; Sebbane, Mustapha; Roubille, François; Coste, Thibault; Bargnoux, Anne Sophie; Badiou, Stéphanie; Kuster, Nils; Cristol, Jean Paul

2015-03-01

To report the analytical performances of the Radiometer AQT90 FLEX® cTnT assay (Neuilly-Plaisance, France) and to evaluate the concordance with hs-cTnT results from central laboratory for the diagnosis of acute myocardial infarction (AMI) at baseline and during a short follow-up among unselected patients admitted in emergency room or cardiology department. Analytical performances of AQT90 FLEX® cTnT immunoassay included imprecision study with determination of a coefficient of variation at 10% and 20%, linearity, and limit of detection. The concordance study was based on samples obtained from 170 consecutive patients with chest pain suggestive of acute coronary syndrome (ACS) admitted in the emergency room or cardiology department. The kinetic study (within 62 additional samples 3h later) was based on absolute delta criterion and the combination of relative change of 30% with absolute change of 7ng/L. The cTnT assay from Radiometer was evaluated as clinically usable, although less sensitive than the Roche hs-cTnT assay as demonstrated by the concordance and the kinetic studies. In non-selected population, the cTnT AQT Flex© assay on AQT90© with kinetic change at 3h, provides similar clinical classification of patients, particularly for AMI group as compared to central laboratory hs-cTnT assay and could be suitable for clinical use. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

TP53 PIN3 and PEX4 polymorphisms and infertility associated with endometriosis or with post-in vitro fertilization implantation failure

PubMed Central

Paskulin, D D; Cunha-Filho, J S L; Souza, C A B; Bortolini, M C; Hainaut, P; Ashton-Prolla, P

2012-01-01

p53 has a crucial role in human fertility by regulating the expression of leukemia inhibitory factor (LIF), a secreted cytokine critical for blastocyst implantation. To examine whether TP53 polymorphisms may be involved with in vitro fertilization (IVF) failure and endometriosis (END), we have assessed the associations between TP53 polymorphism in intron 2 (PIN2; G/C, intron 2), PIN3 (one (N, non-duplicated) or two (D, duplicated) repeats of a 16-bp motif, intron 3) and polymorphism in exon 4 (PEX4; C/G, p.P72R, exon 4) in 98 women with END and 115 women with post-IVF failure. In addition, 134 fertile women and 300 women unselected with respect to fertility-related features were assessed. TP53 polymorphisms and haplotypes were identified by amplification refractory mutation system polymerase chain reaction. TP53 PIN3 and PEX4 were associated with both END (P=0.042 and P=0.007, respectively) and IVF (P=0.004 and P=0.009, respectively) when compared with women both selected and unselected for fertility-related features. Haplotypes D-C and N-C were related to higher risk for END (P=0.002, P=0.001, respectively) and failure of IVF (P=0.018 and P=0.002, respectively) when compared with the Fertile group. These results support that specific TP53 haplotypes are associated with an increased risk of END-associated infertility and with post-IVF failure. PMID:23013791

Outcomes for patients with congenital hepatoblastoma.

PubMed

Trobaugh-Lotrario, Angela D; Chaiyachati, Barbara H; Meyers, Rebecka L; Häberle, Beate; Tomlinson, Gail E; Katzenstein, Howard M; Malogolowkin, Marcio H; von Schweinitz, Dietrich; Krailo, Mark; Feusner, James H

2013-11-01

Congenital hepatoblastoma, diagnosed in the first month of life, has been reported to have a poor prognosis; however, a comprehensive evaluation of this entity is lacking. We retrospectively reviewed two patients from the senior authors' personal series and 25 cases identified in the databases of several multicenter group studies (INT-0098, P9645, 881, P9346, HB 89, HB94, and HB 99). We compared this series with cases of congenital hepatoblastoma previously published in the literature. The 3-year survival in our case series was 86% (18/21) with a follow-up of 44-230 months (median 85.5 months). Presentation and treatment were not substantially different from hepatoblastoma cohorts unselected for age. Survival was comparable to the reported disease free survival for a similar cohort of hepatoblastoma patients unselected for age between 1986 and 2002 (82.5%) [von Schweinitz et al., Eur J Cancer 1997; 33:1243-1249]. The 2-year survival of cases reported in the literature was 0% (0/9) and 42% (10/24) for patients reported before and after 1990, respectively. Congenital hepatoblastoma does not appear to confer a worse prognosis. The improved survival of our current series of patients, collected from the past 20 years of German and American multicenter trials and personal series, suggests that the outcome of hepatoblastoma at this young age is much better than has been historically reported. More rigorous analysis should be conducted in future multicenter trials. It is possible that congenital hepatoblastoma should be treated like all other patients with hepatoblastoma provided that the child is stable enough to proceed with surgery and chemotherapy. Copyright © 2013 Wiley Periodicals, Inc.

Case-finding for coeliac disease in secondary care: a prospective multicentre UK study.

PubMed

Mooney, Peter D; Leeds, John S; Libzo, Nafan; Sidhu, Reina; Evans, Kate E; Hall, Emma J; Jandu, Veerinder S; Hopper, Andrew D; Basumani, Pandurangan; Dear, Keith L; McAlindon, Mark E; Sanders, David S

2014-01-01

Coeliac disease affects 1% of the population. Despite this high prevalence, the majority of individuals are undetected. Many patients present with subtle symptoms which may also contribute to under diagnosis. Our aim was to determine the relative importance of different presenting characteristics. Unselected gastroenterology patients referred to 4 hospitals in South Yorkshire were investigated for coeliac disease. Diagnosis was based on positive serology and the presence of villous atrophy. Odds ratios were calculated for presenting characteristics and multivariate analysis performed to identify independent risk factors. 4089 patients were assessed (41.5% male, mean age 55.8 ± 18.2 years); 129 had coeliac disease (3.2%, 95% CI 2.6-3.7%). Multivariate analysis of patients referred to secondary care showed family history of coeliac disease (OR 1.26, p < 0.0001), anaemia (OR 1.03, p < 0.0001) and osteoporosis (OR 1.1, p = 0.006) were independent risk factors for diagnosis of coeliac disease. When compared to population controls, diarrhoea (OR 4.1, p < 0.0001), weight loss (OR 2.7, p = 0.02), irritable bowel syndrome symptoms (OR 3.2, p = 0.005) thyroid disease (OR 4.4, p = 0.01) and diabetes (OR 3.0, p = 0.05) were also associated with increased coeliac disease risk. Coeliac disease accounts for 1 in 31 referrals in secondary care to unselected gastroenterology clinics. A low threshold for coeliac disease testing should be adopted. Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Impact of severe tricuspid regurgitation on accuracy of systolic pulmonary arterial pressure measured by Doppler echocardiography: Analysis in an unselected patient population.

PubMed

Fei, Beini; Fan, Ting; Zhao, Ling; Pei, Xiaoli; Shu, Xianhong; Fang, Xiaoyan; Cheng, Leilei

2017-07-01

Pulmonary arterial pressure is an important index in cardiovascular disorders, especially for pulmonary hypertension (PH). Doppler echocardiography (DE) is widely used as a noninvasive method to assess pulmonary arterial pressure. However, recent studies have found several hemodynamic factors that affect its accuracy in estimating systolic pulmonary arterial pressure (sPAP). But the effect of tricuspid regurgitation (TR) has not been investigated. Therefore, our study is aimed to determine whether the severity of TR will affect the accuracy of sPAP measured by DE in an unselected patient population. We retrospectively studied 177 patients who underwent DE and right heart catheterization (RHC) examinations. Patients were categorized into 3 groups according to the severity of TR (mild, moderate, and severe). The discrepancy in sPAP measured by DE and RHC was calculated and compared in each group. Determinants of discordant results between two methods were also evaluated. Age, gender, interval between DE and RHC, sequence of DE and RHC were similar among groups (all P>.05). Differences in sPAP, RAP, and tricuspid regurgitation pressure gradient (TR-PG) were similar in group 1 and 2 (all P>.05), while all significantly higher in group 3 (all P<.05). The difference in sPAP between DE and RHC was affected independently by severe TR and severe PH (both P<.05). Severe TR and severe PH affect the accuracy of sPAP measured by DE. Modification of echocardiographic sPAP measurements by taking into consideration of these factors may lead to reduced systemic errors. © 2017, Wiley Periodicals, Inc.

Psychometric properties of the dimensional anxiety scales for DSM-V in an unselected sample of German treatment seeking patients.

PubMed

Beesdo-Baum, Katja; Klotsche, Jens; Knappe, Susanne; Craske, Michelle G; Lebeau, Richard T; Hoyer, Jürgen; Strobel, Anja; Pieper, Lars; Wittchen, Hans-Ulrich

2012-12-01

Dimensional assessments are planned to be included as supplements to categorical diagnoses in DSM-V. The aim of this study was to examine the unidimensionality, reliability, validity, and clinical sensitivity of brief self-rated scales for specific anxiety disorders in an unselected German sample of consecutive attendees to a psychological clinic. These scales use a common template to assess core constructs of fear and anxiety. Dimensional scales for social anxiety disorder, specific phobia, agoraphobia, panic disorder, and generalized anxiety disorder were administered along with established scales to 102 adults seeking treatment for mental health problems at a German university outpatient clinic for psychotherapy. The computer-assisted clinical version of the Munich-Composite International Diagnostic Interview was used to assess mental disorders according to DSM-IV criteria. Dimensionality and scale reliability were examined using confirmatory factor analyses. Convergent and discriminant validity were examined by testing differences in the size of correlations between each dimensional anxiety scale and each of the previously validated scales. Each dimensional scale's ability to correctly differentiate between individuals with versus without an anxiety diagnosis was examined via the area under the curve. Analyses revealed unidimensionality for each scale, high reliability, and convergent and discriminant validity. Classification performance was good to excellent for all scales except for specific phobia. The application of the dimensional anxiety scales may be an effective way to screen for specific anxiety disorders and to supplement categorical diagnoses in DSM-V, although further evaluation and refinement of the scales (particularly the specific phobia scale) is needed. © 2012 Wiley Periodicals, Inc.

Treatment, Outcome and Prognostic Factors in Renal Cell Carcinoma - A Single Center Study (2000-2010)

PubMed Central

Achermann, Christof; Stenner, Frank; Rothschild, Sacha I.

2016-01-01

In Switzerland efficient availability of novel drugs for renal cell cancer (RCC) has been granted early. Since the advent of the targeted agents for RCC the usage of these drugs has been reported to improve progression free survival. Here, we find that patients who are able to receive sequential targeted therapy, including tyrosine kinase inhibitors (TKI) and mTOR inhibitors (mTORi), have a largely better outcome than those who have less exposure to these agents. The value of the prognostic scores developed by Motzer and Heng is fully reflected by the outcomes according to prognostic risk groups in our unselected patient cohort. Also, the use of surgical intervention appears to be an important prognostic factor, however with a somehow diminished effect by novel systemic therapies. The importance of multiple lines of targeted therapies is underlined by this retrospective analysis. For patients with metastatic RCC not receiving targeted therapy the median OS was 22.6 months compared to those with one TKI 25.4 months. Patients receiving a second-line therapy (median overall survival 27.6 months) and those patients with three or more lines of therapy (43.8 months) have the greatest benefit. Also, exposure to a mTORi improves survival versus non-exposure to mTORi (63.3 vs. 22.3 months, p=0.038). In conclusion a trend towards improved survival is confirmed for an unselected population when the full variety of therapeutic options is available and can be used for the individual patient. PMID:27313782

The Task-Relevant Attribute Representation Can Mediate the Simon Effect

PubMed Central

Chen, Antao

2014-01-01

Researchers have previously suggested a working memory (WM) account of spatial codes, and based on this suggestion, the present study carries out three experiments to investigate how the task-relevant attribute representation (verbal or visual) in the typical Simon task affects the Simon effect. Experiment 1 compared the Simon effect between the between- and within-category color conditions, which required subjects to discriminate between red and blue stimuli (presumed to be represented by verbal WM codes because it was easy and fast to name the colors verbally) and to discriminate between two similar green stimuli (presumed to be represented by visual WM codes because it was hard and time-consuming to name the colors verbally), respectively. The results revealed a reliable Simon effect that only occurs in the between-category condition. Experiment 2 assessed the Simon effect by requiring subjects to discriminate between two different isosceles trapezoids (within-category shapes) and to discriminate isosceles trapezoid from rectangle (between-category shapes), and the results replicated and expanded the findings of Experiment 1. In Experiment 3, subjects were required to perform both tasks from Experiment 1. Wherein, in Experiment 3A, the between-category task preceded the within-category task; in Experiment 3B, the task order was opposite. The results showed the reliable Simon effect when subjects represented the task-relevant stimulus attributes by verbal WM encoding. In addition, the response times (RTs) distribution analysis for both the between- and within-category conditions of Experiments 3A and 3B showed decreased Simon effect with the RTs lengthened. Altogether, although the present results are consistent with the temporal coding account, we put forth that the Simon effect also depends on the verbal WM representation of task-relevant stimulus attribute. PMID:24618692

Liquefied natural gas (LNG) safety

NASA Technical Reports Server (NTRS)

Ordin, P. M.

1977-01-01

Bibliography, assembled from computer search of NASA Aerospace Safety Data Bank, including title of report, author, abstract, source, description of figures, key references, and key words or subject terms. Publication is indexed by key subjects and by authors. Items are relevant to design engineers and safety specialists.

Allergenic properties and differential response of walnut subjected to processing treatments

USDA-ARS?s Scientific Manuscript database

Walnut is one of the most frequently involved foods in anaphylactic reactions. We investigated changes in walnut allergenicity after physical treatments by in vitro techniques and physiologically relevant assays. Changes in the allergenicity of walnut subjected to high pressure and thermal/pressur...

Reviewing the curriculum for physics and technology in postgraduate sonography courses

PubMed Central

2015-01-01

Physics and technology is seen as a difficult subject by those training in medical ultrasound. The reasons for this are discussed. Who should teach the subject and what should be included are considered. Ways to approach the subject so as to make it more relevant and easier to learn are proposed and a basic syllabus is suggested in an appendix. PMID:27433234

The clinical relevance of advanced artificial feedback in the control of a multi-functional myoelectric prosthesis.

PubMed

Markovic, Marko; Schweisfurth, Meike A; Engels, Leonard F; Bentz, Tashina; Wüstefeld, Daniela; Farina, Dario; Dosen, Strahinja

2018-03-27

To effectively replace the human hand, a prosthesis should seamlessly respond to user intentions but also convey sensory information back to the user. Restoration of sensory feedback is rated highly by the prosthesis users, and feedback is critical for grasping in able-bodied subjects. Nonetheless, the benefits of feedback in prosthetics are still debated. The lack of consensus is likely due to the complex nature of sensory feedback during prosthesis control, so that its effectiveness depends on multiple factors (e.g., task complexity, user learning). We evaluated the impact of these factors with a longitudinal assessment in six amputee subjects, using a clinical setup (socket, embedded control) and a range of tasks (box and blocks, block turn, clothespin and cups relocation). To provide feedback, we have proposed a novel vibrotactile stimulation scheme capable of transmitting multiple variables from a multifunction prosthesis. The subjects wore a bracelet with four by two uniformly placed vibro-tactors providing information on contact, prosthesis state (active function), and grasping force. The subjects also completed a questionnaire for the subjective evaluation of the feedback. The tests demonstrated that feedback was beneficial only in the complex tasks (block turn, clothespin and cups relocation), and that the training had an important, task-dependent impact. In the clothespin relocation and block turn tasks, training allowed the subjects to establish successful feedforward control, and therefore, the feedback became redundant. In the cups relocation task, however, the subjects needed some training to learn how to properly exploit the feedback. The subjective evaluation of the feedback was consistently positive, regardless of the objective benefits. These results underline the multifaceted nature of closed-loop prosthesis control as, depending on the context, the same feedback interface can have different impact on performance. Finally, even if the closed-loop control does not improve the performance, it could be beneficial as it seems to improve the subjective experience. Therefore, in this study we demonstrate, for the first time, the relevance of an advanced, multi-variable feedback interface for dexterous, multi-functional prosthesis control in a clinically relevant setting.

ERP C250 Shows the Elderly (Cognitively Normal, Alzheimer’s Disease) Store More Stimuli in Short-Term Memory than Young Adults Do

PubMed Central

Chapman, Robert M.; Gardner, Margaret N.; Mapstone, Mark; Klorman, Rafael; Porsteinsson, Anton P.; Dupree, Haley M.; Antonsdottir, Inga M.; Kamalyan, Lily

2016-01-01

Objective To determine how aging and dementia affect the brain’s initial storing of task-relevant and irrelevant information in short-term memory. Methods We used brain Event-Related Potentials (ERPs) to measure short-term memory storage (ERP component C250) in 36 Young Adults, 36 Normal Elderly, and 36 early-stage AD subjects. Participants performed the Number-Letter task, a cognitive paradigm requiring memory storage of a first relevant stimulus to compare it with a second stimulus. Results In Young Adults, C250 was more positive for the first task-relevant stimulus compared to all other stimuli. C250 in Normal Elderly and AD subjects was roughly the same to relevant and irrelevant stimuli in intratrial parts 1–3 but not 4. The AD group had lower C250 to relevant stimuli in part 1. Conclusions Both normal aging and dementia cause less differentiation of relevant from irrelevant information in initial storage. There was a large aging effect involving differences in the pattern of C250 responses of the Young Adult versus the Normal Elderly/AD groups. Also, a potential dementia effect was obtained. Significance C250 is a candidate tool for measuring short-term memory performance on a biological level, as well as a potential marker for memory changes due to normal aging and dementia. PMID:27178862

Effects of Objective and Subjective Competence on the Reliability of Crowdsourced Relevance Judgments

ERIC Educational Resources Information Center

Samimi, Parnia; Ravana, Sri Devi; Webber, William; Koh, Yun Sing

2017-01-01

Introduction: Despite the popularity of crowdsourcing, the reliability of crowdsourced output has been questioned since crowdsourced workers display varied degrees of attention, ability and accuracy. It is important, therefore, to understand the factors that affect the reliability of crowdsourcing. In the context of producing relevance judgments,…

Task Effects in the Interpretation of Pronouns

ERIC Educational Resources Information Center

Sanoudaki, Eirini; Varlokosta, Spyridoula

2015-01-01

Children acquiring a range of languages have difficulties in the interpretation of personal pronouns. Ongoing debates in the relevant literature concern the extent to which different pronoun types are subject to this phenomenon, as well as the role of methodology in relevant research. In this study, we use two different experimental tasks to…

Bradford's Law and Its Relevance to Researchers

ERIC Educational Resources Information Center

Shenton, Andrew K.; Hay-Gibson, Naomi V.

2009-01-01

Bradford's Law has been the subject of much discussion and analysis in library and information science since its formulation in the 1930s and remains frequently debated to this day. It has been applied to various practices within the discipline, especially with regard to collection development, but its relevance to researchers and the potential it…

Situating the Lesotho Secondary School Geography in Curriculum Relevance Debate

ERIC Educational Resources Information Center

Raselimo, Mohaeka

2017-01-01

The issue of curriculum relevance has attracted attention of academics and the general public in Lesotho where there are social, economic, environmental and political challenges confronting the society. To address these challenges education, through various school subjects, is expected to play a pivotal role. However, there are concerns that the…

9/11: Maintaining Relevance for the Classroom Student

ERIC Educational Resources Information Center

Waterson, Robert A.; Rickey, Matt

2011-01-01

The experience of 9/11 prompted a transformation in one secondary teacher's approach to teaching controversial subjects based on the relevance to today's students. Soon after that fateful day, this teacher found a purpose and rationale for developing a very demanding curriculum on 9/11, and relates how his teaching unit has evolved by expanding…

French Immersion Research Relevant to Decisions in Ontario. Review and Evaluation Bulletins, Number 1.

ERIC Educational Resources Information Center

Parkin, Michael; And Others

Canadian research relevant to French immersion program development in Ontario is reviewed and summarized. The review includes studies on six program or instructional aspects: (1) attitudes and motivation of immersion students and parents; (2) achievement of immersion students in English language arts and other subjects; (3) French proficiency and…

An Education Millennium Development Goal for Quality: Complexity and Democracy

ERIC Educational Resources Information Center

Barrett, Angeline M.

2011-01-01

A good quality education is inclusive, relevant and democratic. Of these three characteristics, the author contends that democratic is the most fundamental and underpins the other two. Education can only truly be inclusive and relevant if its goals are continuously the subject of open democratic debate, since education is a value-based,…

Training of Classroom Relevant Behaviors with the "Staats Box." Technical Report #9.

ERIC Educational Resources Information Center

Sueoka, Sarah; And Others

This case study of a kindergarten boy in the Kamehameha Early Education Program (KEEP) suggests that specific operant training in school-relevant behaviors can facilitate classroom adjustment if the training is coordinated with the regular classroom teacher. The subject, considered unmanageable, hyperactive, and aggressive by the staff at his…

Self-harming in depressed patients: pattern analysis.

PubMed

Parker, G; Malhi, Gin; Mitchell, Philip; Kotze, Beth; Wilhelm, Kay; Parker, Kay

2005-10-01

As deliberate self-harm (DSH) is a common concomitant of depressive disorders, we undertook a study examining the relevance of possible determinants and correlates of DSH. Three separate samples of depressed outpatients were studied to determine consistency of identified factors across samples, with principal analyses involving gender, age and diagnosis-matched DSH and non-DSH subjects. Across the samples, some 20% of subjects admitted to episodes of DSH. Women reported higher rates and there was a consistent trend for higher rates in bipolar patients. Univariate analyses examined the relevance of several sociodemographic variables, illicit drug and alcohol use, past deprivational and abusive experiences, past suicidal attempts and disordered personality functioning. Multivariate analyses consistently identified previous suicide attempts and high 'acting out' behaviours across the three samples, suggesting the relevance of an externalizing response to stress and poor impulse control. Results assist the identification and management of depressed patients who are at greater risk of DSH behaviours.

Effect of gender on communication of health information to older adults.

PubMed

Dearborn, Jennifer L; Panzer, Victoria P; Burleson, Joseph A; Hornung, Frederick E; Waite, Harrison; Into, Frances H

2006-04-01

To examine the effect of gender on three key elements of communication with elderly individuals: effectiveness of the communication, perceived relevance to the individual, and effect of gender-stereotyped content. Survey. University of Connecticut Health Center. Thirty-three subjects (17 female); aged 69 to 91 (mean+/-standard deviation 82+/-5.4). Older adults listened to 16 brief narratives randomized in order and by the sex of the speaker (Narrator Voice). Effectiveness was measured according to ability to identify key features (Risks), and subjects were asked to rate the relevance (Plausibility). Number of Risks detected and determinations of plausibility were analyzed according to Subject Gender and Narrator Voice. Narratives were written for either sex or included male or female bias (Neutral or Stereotyped). Female subjects identified a significantly higher number of Risks across all narratives (P=.01). Subjects perceived a significantly higher number of Risks with a female Narrator Voice (P=.03). A significant Voice-by-Stereotype interaction was present for female-stereotyped narratives (P=.009). In narratives rated as Plausible, subjects detected more Risks (P=.02). Subject Gender influenced communication effectiveness. A female speaker resulted in identification of more Risks for subjects of both sexes, particularly for Stereotyped narratives. There was no significant effect of matching Subject Gender and Narrator Voice. This study suggests that the sex of the speaker influences the effectiveness of communication with older adults. These findings should motivate future research into the means by which medical providers can improve communication with their patients.

A New Heterogeneous Multidimensional Unfolding Procedure

ERIC Educational Resources Information Center

Park, Joonwook; Rajagopal, Priyali; DeSarbo, Wayne S.

2012-01-01

A variety of joint space multidimensional scaling (MDS) methods have been utilized for the spatial analysis of two- or three-way dominance data involving subjects' preferences, choices, considerations, intentions, etc. so as to provide a parsimonious spatial depiction of the underlying relevant dimensions, attributes, stimuli, and/or subjects'…

Proband-only medical exome sequencing as a cost-effective first-tier genetic diagnostic test for patients without prior molecular tests and clinical diagnosis in a developing country: the China experience.

PubMed

Hu, Xuyun; Li, Niu; Xu, Yufei; Li, Guoqiang; Yu, Tingting; Yao, Ru-En; Fu, Lijun; Wang, Jiwen; Yin, Lei; Yin, Yong; Wang, Ying; Jin, Xingming; Wang, Xiumin; Wang, Jian; Shen, Yiping

2017-11-02

PurposeTo evaluate the performance of proband-only medical exome sequencing (POMES) as a cost-effective first-tier diagnostic test for pediatric patients with unselected conditions.MethodsA total of 1,323 patients were tested by POMES, which targeted 2,742 known disease-causing genes. Clinical relevant variants were Sanger-confirmed in probands and parents. We assessed the diagnostic validity and clinical utility of POMES by means of a survey questionnaire.ResultsPOMES, ordered by 136 physicians, identified 512 pathogenic or likely pathogenic variants associated with over 200 conditions. The overall diagnostic rate was 28.8%, ranging from 10% in neonatal intensive care unit patients to over 35% in pediatric intensive care unit patients. The test results had an impact on the management of the 45.1% of patients for whom there were positive findings. The average turnaround time was 57 days; the cost was $360/case.ConclusionWe adopted a relatively efficient and cost-effective approach in China for the molecular diagnosis of pediatric patients with suspected genetic conditions. While training for clinical geneticists and other specialists is lagging behind in China POMES is serving as a diagnostic equalizer for patients who do not normally receive extensive clinical evaluation and clinical diagnosis prior to testing. This Chinese experience should be applicable to other developing countries that are lacking clinical, financial, and personnel resources.GENETICS in MEDICINE advance online publication, 2 November 2017; doi:10.1038/gim.2017.195.

Determinants of handicap after stroke: the North East Melbourne Stroke Incidence Study (NEMESIS).

PubMed

Sturm, Jonathan W; Donnan, Geoffrey A; Dewey, Helen M; Macdonell, Richard A L; Gilligan, Amanda K; Thrift, Amanda G

2004-03-01

Handicap, although more relevant to the patient than impairment or disability, has received little attention in people with stroke. The aim of this study was to identify, in an unselected population, factors determining handicap at 2 years after stroke. All first-ever cases of stroke in a population of 306 631 over a 1-year period were assessed. Stroke severity, comorbidity, and demographic information was recorded. Among survivors, 2-year poststroke handicap was assessed with the London Handicap Scale. Disability, physical impairment, depression, anxiety, living arrangements, and recurrent stroke at 2 years were documented. If necessary, proxy assessments were obtained, except for mood. Linear regression analyses were performed to identify factors independently associated with handicap. First, all assessments (proxy and nonproxy) were examined; then, the nonproxy assessments were used to examine the effects of mood. Of 266 patients with incident stroke who were alive at 2 years, 226 (85%) were assessed. Significant determinants of handicap on univariable analysis were age, female sex, socioeconomic status, alcohol intake, stroke subtype, initial stroke severity; 2-year physical impairment, disability, depression and anxiety scores; institutionalization; and recurrent stroke. On multivariable analysis, the independent determinants of handicap were age and 2-year physical impairment and disability. In analysis restricted to nonproxy data, depression and anxiety were also independently associated with handicap. Age, concurrent disability, and physical impairment were more important determinants of handicap than other demographic factors or initial stroke severity. Because depression and anxiety were independently associated with handicap, their treatment may potentially reduce handicap in stroke patients.

Measurement of antinuclear antibodies and their fine specificities: time for a change in strategy?

PubMed

Otten, Henny G; Brummelhuis, Walter J; Fritsch-Stork, Ruth; Leavis, Helen L; Wisse, Bram W; van Laar, Jacob M; Derksen, Ronald H W M

2017-01-01

The current strategy for antinuclear antibody (ANA) analysis involves screening for presence with a subsequent detailed analysis of their specificity. The aim of this study is to compare the clinical and financial efficacy of this strategy between different commercial tests in a large cohort of unselected patients. In all consecutive 1030 patients associations were defined between results from different ANA test systems and the pre-test probability for connective tissue disease (CTDs). Test systems were used for screening (ANA-IIF vs. CTD screen) and definition of their fine specificity (profile 3 line blot vs. CTD single analytes). Positive ANA-IIF and/or CTD screen results were found in 304 sera. Further analysis for ANA-specificity by profile 3 line blot and CTD single analytes showed 86 discrepant results of which more than a third are clinically relevant, with the CTD single analyte assay performing better than the line blot in supporting or confirming the presence of a CTD. Autoantigens present in one test but absent in the other were of minor practical use. The ANA screening and identification strategies currently employed are not cost-effective as 83% of tests were performed in order to find specific autoantibodies in patients without the fitting clinical signs or symptoms. This causes many unexpected positive results and subsequent confusion with regard to interpretation. We advocate that some autoantigens should be excluded from the line blot and CTD assays and propose the use of a cost-effective and selective ANA specificity testing purely based on clinical guidance.

CHEK2 1100delC variant and breast cancer risk in Caucasians: a meta-analysis based on 25 studies with 29,154 cases and 37,064 controls.

PubMed

Yang, Yuan; Zhang, Fan; Wang, Yang; Liu, Sheng-Chun

2012-01-01

Links between the CHEK2 1100delC heterozygote and breast cancer risk have been extensively explored. However, both positive and negative associations with this variant have been reported in individual studies. For a detailed assessment of the CHEK2 1100delC heterozygote and breast cancer risk, relevant studies published as recently as May 2012 were identified using PUBMED and EMBASE and selected using a priori defined criteria. The strength of the relationship between the CHEK2 1100delC variant and breast cancer risks was assessed by odds ratios (ORs) under the fixed effects model. A total of 29,154 cases and 37,064 controls from 25 case-control studies were identified in this meta-analysis. The CHEK2 1100delC heterozygote was more frequently detected in cases than in controls (1.34% versus 0.44%). A significant association was found between CHEK2 1100delC heterozygote and breast cancer risk (OR=2.75, 95% CI: [2.25, 3.36]). The ORs and CIs were 2.33 (95% CI: [1.79, 3.05]), 3.72 (95% CI: [2.61, 5.31]) and 2.78 (95% CI: [2.28, 3.39]) respectively in unselected, family, early-onset breast cancer subgroups. The CHEK2 1100delC variant could be a potential factor for increased breast cancer risk in Caucasians. However, more consideration is needed in order to apply it to allele screening or other clinical work.

Inter-rater reliability of the Full Outline of UnResponsiveness score and the Glasgow Coma Scale in critically ill patients: a prospective observational study

PubMed Central

2010-01-01

Introduction The Glasgow Coma Scale (GCS) is the most widely used scoring system for comatose patients in intensive care. Limitations of the GCS include the impossibility to assess the verbal score in intubated or aphasic patients, and an inconsistent inter-rater reliability. The FOUR (Full Outline of UnResponsiveness) score, a new coma scale not reliant on verbal response, was recently proposed. The aim of the present study was to compare the inter-rater reliability of the GCS and the FOUR score among unselected patients in general critical care. A further aim was to compare the inter-rater reliability of neurologists with that of intensive care unit (ICU) staff. Methods In this prospective observational study, scoring of GCS and FOUR score was performed by neurologists and ICU staff on 267 consecutive patients admitted to intensive care. Results In a total of 437 pair wise ratings the exact inter-rater agreement for the GCS was 71%, and for the FOUR score 82% (P = 0.0016); the inter-rater agreement within a range of ± 1 score point for the GCS was 90%, and for the FOUR score 92% (P = ns.). The exact inter-rater agreement among neurologists was superior to that among ICU staff for the FOUR score (87% vs. 79%, P = 0.04) but not for the GCS (73% vs. 73%). Neurologists and ICU staff did not significantly differ in the inter-rater agreement within a range of ± 1 score point for both GCS (88% vs. 93%) and the FOUR score (91% vs. 88%). Conclusions The FOUR score performed better than the GCS for exact inter-rater agreement, but not for the clinically more relevant agreement within the range of ± 1 score point. Though neurologists outperformed ICU staff with regard to exact inter-rater agreement, the inter-rater agreement of ICU staff within the clinically more relevant range of ± 1 score point equalled that of the neurologists. The small advantage in inter-rater reliability of the FOUR score is most likely insufficient to replace the GCS, a score with a long tradition in intensive care. PMID:20398274

Lymphocytic gastritis, gastric adenocarcinoma, and primary gastric lymphoma.

PubMed Central

Griffiths, A P; Wyatt, J; Jack, A S; Dixon, M F

1994-01-01

A series of primary gastric lymphomas and adenocarcinomas was reviewed to assess the prevalence of lymphocytic gastritis in these conditions. Lymphocytic gastritis was more prevalent in patients with gastric adenocarcinoma (16 of 130 cases; 12.3%) and primary gastric lymphoma (six of 45 cases; 13.7%) than in unselected patients undergoing endoscopy (0.83-2.5%). This suggests that these two disparate gastric tumours may share an immunological dysfunction or a common pathogenesis, and this is of interest given that Helicobacter pylori is thought to have a role in the evolution of gastric adenocarcinoma and lymphoma. PMID:7876391

Whole-genome random sequencing and assembly of Haemophilus influenzae Rd

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

Fleischmann, R.D.; Adams, M.D.; White, O.

1995-07-28

An approach for genome analysis based on sequencing and assembly of unselected pieces of DNA from the whole chromosome has been applied to obtain the complete nucleotide sequence (1,830,137 base pairs) of the genome from the bacterium Haemophilus influenzae Rd. This approach eliminates the need for initial mapping efforts and is therefore applicable to the vast array of microbial species for which genome maps are unavailable. The H. influenzae Rd genome sequence (Genome Sequence DataBase accession number L42023) represents the only complete genome sequence from a free-living organism. 46 refs., 4 figs., 4 tabs.

Beamforming approaches for untethered, ultrasonic neural dust motes for cortical recording: a simulation study.

PubMed

Bertrand, Alexander; Seo, Dongjin; Maksimovic, Filip; Carmena, Jose M; Maharbiz, Michel M; Alon, Elad; Rabaey, Jan M

2014-01-01

In this paper, we examine the use of beamforming techniques to interrogate a multitude of neural implants in a distributed, ultrasound-based intra-cortical recording platform known as Neural Dust. We propose a general framework to analyze system design tradeoffs in the ultrasonic beamformer that extracts neural signals from modulated ultrasound waves that are backscattered by free-floating neural dust (ND) motes. Simulations indicate that high-resolution linearly-constrained minimum variance beamforming sufficiently suppresses interference from unselected ND motes and can be incorporated into the ND-based cortical recording system.

Career Action Pack.

ERIC Educational Resources Information Center

Blum, Robert E.; Raymond, Carolyn D.

One of five McDonald's Action Packs, these instructional materials for ninth and tenth graders (and more able sixth and seventh graders) have incorporated ideas around three career development goals--subject relevance, career awareness, and self-awareness. The action pack contains six units--three units each in the subject areas of language arts…

Objective Academic Achievement and Subjective Personal Well-Being

ERIC Educational Resources Information Center

McDonald, Betty

2012-01-01

This paper examines the relationship between objective academic achievement (OAA) and subjective well-being (SWB). Using a sample of 515 adolescents from ten different high schools across a small country, semi-structured interviews, academic records and observations provided relevant data for the study. OAA was measured from examination results…

Using Visual Information to Determine the Subjective Valuation of Public Space for Transportation : Application to Subway Crowding Costs in NYC

DOT National Transportation Integrated Search

2017-11-30

The objective of this project is to explore the role of visual information in determining the users subjective valuation of multidimensional trip attributes that are relevant in decision-making, but are neglected in standard travel demand models. ...

Genomics-based non-invasive prenatal testing for detection of fetal chromosomal aneuploidy in pregnant women.

PubMed

Badeau, Mylène; Lindsay, Carmen; Blais, Jonatan; Nshimyumukiza, Leon; Takwoingi, Yemisi; Langlois, Sylvie; Légaré, France; Giguère, Yves; Turgeon, Alexis F; Witteman, William; Rousseau, François

2017-11-10

Common fetal aneuploidies include Down syndrome (trisomy 21 or T21), Edward syndrome (trisomy 18 or T18), Patau syndrome (trisomy 13 or T13), Turner syndrome (45,X), Klinefelter syndrome (47,XXY), Triple X syndrome (47,XXX) and 47,XYY syndrome (47,XYY). Prenatal screening for fetal aneuploidies is standard care in many countries, but current biochemical and ultrasound tests have high false negative and false positive rates. The discovery of fetal circulating cell-free DNA (ccfDNA) in maternal blood offers the potential for genomics-based non-invasive prenatal testing (gNIPT) as a more accurate screening method. Two approaches used for gNIPT are massively parallel shotgun sequencing (MPSS) and targeted massively parallel sequencing (TMPS). To evaluate and compare the diagnostic accuracy of MPSS and TMPS for gNIPT as a first-tier test in unselected populations of pregnant women undergoing aneuploidy screening or as a second-tier test in pregnant women considered to be high risk after first-tier screening for common fetal aneuploidies. The gNIPT results were confirmed by a reference standard such as fetal karyotype or neonatal clinical examination. We searched 13 databases (including MEDLINE, Embase and Web of Science) from 1 January 2007 to 12 July 2016 without any language, search filter or publication type restrictions. We also screened reference lists of relevant full-text articles, websites of private prenatal diagnosis companies and conference abstracts. Studies could include pregnant women of any age, ethnicity and gestational age with singleton or multifetal pregnancy. The women must have had a screening test for fetal aneuploidy by MPSS or TMPS and a reference standard such as fetal karyotype or medical records from birth. Two review authors independently carried out study selection, data extraction and quality assessment (using the QUADAS-2 tool). Where possible, hierarchical models or simpler alternatives were used for meta-analysis. Sixty-five studies of 86,139 pregnant women (3141 aneuploids and 82,998 euploids) were included. No study was judged to be at low risk of bias across the four domains of the QUADAS-2 tool but applicability concerns were generally low. Of the 65 studies, 42 enrolled pregnant women at high risk, five recruited an unselected population and 18 recruited cohorts with a mix of prior risk of fetal aneuploidy. Among the 65 studies, 44 evaluated MPSS and 21 evaluated TMPS; of these, five studies also compared gNIPT with a traditional screening test (biochemical, ultrasound or both). Forty-six out of 65 studies (71%) reported gNIPT assay failure rate, which ranged between 0% and 25% for MPSS, and between 0.8% and 7.5% for TMPS.In the population of unselected pregnant women, MPSS was evaluated by only one study; the study assessed T21, T18 and T13. TMPS was assessed for T21 in four studies involving unselected cohorts; three of the studies also assessed T18 and 13. In pooled analyses (88 T21 cases, 22 T18 cases, eight T13 cases and 20,649 unaffected pregnancies (non T21, T18 and T13)), the clinical sensitivity (95% confidence interval (CI)) of TMPS was 99.2% (78.2% to 100%), 90.9% (70.0% to 97.7%) and 65.1% (9.16% to 97.2%) for T21, T18 and T13, respectively. The corresponding clinical specificity was above 99.9% for T21, T18 and T13.In high-risk populations, MPSS was assessed for T21, T18, T13 and 45,X in 30, 28, 20 and 12 studies, respectively. In pooled analyses (1048 T21 cases, 332 T18 cases, 128 T13 cases and 15,797 unaffected pregnancies), the clinical sensitivity (95% confidence interval (CI)) of MPSS was 99.7% (98.0% to 100%), 97.8% (92.5% to 99.4%), 95.8% (86.1% to 98.9%) and 91.7% (78.3% to 97.1%) for T21, T18, T13 and 45,X, respectively. The corresponding clinical specificities (95% CI) were 99.9% (99.8% to 100%), 99.9% (99.8% to 100%), 99.8% (99.8% to 99.9%) and 99.6% (98.9% to 99.8%). In this risk group, TMPS was assessed for T21, T18, T13 and 45,X in six, five, two and four studies. In pooled analyses (246 T21 cases, 112 T18 cases, 20 T13 cases and 4282 unaffected pregnancies), the clinical sensitivity (95% CI) of TMPS was 99.2% (96.8% to 99.8%), 98.2% (93.1% to 99.6%), 100% (83.9% to 100%) and 92.4% (84.1% to 96.5%) for T21, T18, T13 and 45,X respectively. The clinical specificities were above 100% for T21, T18 and T13 and 99.8% (98.3% to 100%) for 45,X. Indirect comparisons of MPSS and TMPS for T21, T18 and 45,X showed no statistical difference in clinical sensitivity, clinical specificity or both. Due to limited data, comparative meta-analysis of MPSS and TMPS was not possible for T13.We were unable to perform meta-analyses of gNIPT for 47,XXX, 47,XXY and 47,XYY because there were very few or no studies in one or more risk groups. These results show that MPSS and TMPS perform similarly in terms of clinical sensitivity and specificity for the detection of fetal T31, T18, T13 and sex chromosome aneuploidy (SCA). However, no study compared the two approaches head-to-head in the same cohort of patients. The accuracy of gNIPT as a prenatal screening test has been mainly evaluated as a second-tier screening test to identify pregnancies at very low risk of fetal aneuploidies (T21, T18 and T13), thus avoiding invasive procedures. Genomics-based non-invasive prenatal testing methods appear to be sensitive and highly specific for detection of fetal trisomies 21, 18 and 13 in high-risk populations. There is paucity of data on the accuracy of gNIPT as a first-tier aneuploidy screening test in a population of unselected pregnant women. With respect to the replacement of invasive tests, the performance of gNIPT observed in this review is not sufficient to replace current invasive diagnostic tests.We conclude that given the current data on the performance of gNIPT, invasive fetal karyotyping is still the required diagnostic approach to confirm the presence of a chromosomal abnormality prior to making irreversible decisions relative to the pregnancy outcome. However, most of the gNIPT studies were prone to bias, especially in terms of the selection of participants.

Can “Model Projects of Need-Adapted Care” Reduce Involuntary Hospital Treatment and the Use of Coercive Measures?

PubMed Central

Wullschleger, Alexandre; Berg, Jürgen; Bermpohl, Felix; Montag, Christiane

2018-01-01

Intensive outpatient models of need-adapted psychiatric care have been shown to reduce the length of hospital stays and to improve retention in care for people with severe mental illnesses. In contrast, evidence regarding the impact of such models on involuntary hospital treatment and other coercive measures in inpatient settings is still sparse, although these represent important indicators of the patients' wellbeing. In Germany, intensive models of care still have not been routinely implemented, and their effectiveness within the German psychiatric system is only studied in a few pioneering regions. An innovative model of flexible, assertive, need-adapted care established in Berlin, Germany, in 2014, treating unselected 14% of the catchment area's patients, was evaluated on the basis of routine clinical data. Records of n = 302 patients diagnosed with severe mental disorders, who had been hospitalized at least once during a 4-year-observational period, were analyzed in a retrospective individual mirror-image design, comparing the 2 years before and after inclusion in the model project regarding the time spent in hospital, the number and duration of involuntary hospital treatments and the use of direct coercive interventions like restraint or isolation. After inclusion to the project, patients spent significantly less time in hospital. Among patients treated on acute wards and patients with a diagnosis of psychosis, the number of patients subjected to provisional detention due to acute endangerment of self or others decreased significantly, as did the time spent under involuntary hospital treatment. The number of patients subjected to mechanical restraint, but not to isolation, on the ward decreased significantly, while the total number of coercive interventions remained unchanged. Findings suggest some potential of intensive models of need-adapted care to reduce coercive interventions in psychiatry. However, results must be substantiated by evidence from randomized-controlled trials and longer observation periods. PMID:29765339

Children's subjective emotional reactivity to affective pictures: gender differences and their antisocial correlates in an unselected sample of 7-11-year-olds.

PubMed

Sharp, Carla; van Goozen, Stephanie; Goodyer, Ian

2006-02-01

Differential responses in terms of gender and antisocial behaviour in emotional reactivity to affective pictures using the International Affective Picture System (IAPS) have been demonstrated in adult and adolescent samples. Moreover, a quadratic relationship between the arousal (intensity) and valence (degree of unpleasantness) has been suggested. The picture perception methodology has rarely been applied to middle school-aged children. We examined the subjective ratings of emotional reactivity in children for: i) the relationship between arousal and valence, ii) gender differences, and iii) its association with measures of antisocial behaviour. Twenty-seven IAPS pictures were selected to cover a wide range of affective content and were individually administered to a non-referred community sample of 659 7-11-year-old children using a paper-and-pencil version. Concurrent symptoms of conduct disorder, oppositional defiance and psychopathy were collected from multiple sources (teacher-, parent- and self-report). A quadratic relationship between arousal and valence, similar to that previously reported in adults, was demonstrated. A gender difference was found for valence ratings, with girls rating aversive pictures more unpleasant than boys. No gender differences for arousal ratings were found. A significant difference was found between groups scoring above and below cut-off scores on measures of antisocial behaviour. Children above cut-off reported lower arousal to unpleasant pictures, but higher arousal to pleasant pictures. We confirmed that a paper-and-pencil version of the IAPS for evaluating emotion response to affectively valent and arousing stimuli can be used in school settings and that comparable gender differences in emotional reactivity can be found in children. The differential emotional reactivity of children above cut-off on measures of antisocial behaviour suggested these symptoms to be associated with a combination of increased reward and decreased punishment sensitivity.

Exercise duration and peak systolic blood pressure are predictive of mortality in ambulatory patients with mild-moderate chronic heart failure.

PubMed

Williams, Simon G; Jackson, Mark; Ng, Leong L; Barker, Diane; Patwala, Ashish; Tan, Lip-Bun

2005-01-01

It is a prevailing concept in chronic heart failure (CHF) that ventricular remodelling (evaluated via imaging) and neurohormonal activation (via biomarkers) exert major influences, such that the need to subject patients to haemodynamic evaluations and exercise testing has been questioned. We sought to investigate whether exercise and haemodynamic parameters lack independent prognostic value in a cohort of unselected ambulatory patients with mild-moderate CHF. Eighty-five consecutive patients with stable CHF in New York Heart Association functional classes I-IV, aged 55 +/- 12 years, 84% males, left ventricular ejection fraction (LVEF) 37 +/- 15%, participated in this study. Survivors were followed for a median of 5.08 years. All subjects underwent cardiopulmonary exercise testing to measure standard parameters including peak oxygen consumption, exercise duration and blood pressure. A sample of venous blood was taken to determine the N-terminal pro-brain natriuretic peptide (N-BNP) level. Echocardiography was performed at rest to measure LVEF. Predictors of mortality were sought using the Cox proportional hazards model. All-cause mortality was 19% (16 deaths, 95% CI 11-29%). Age and LVEF did not independently predict mortality. Although various parameters including New York Heart Association class, peak oxygen consumption and N-BNP level were all predictive of outcome on univariate analysis, multivariate analysis identified reduced exercise duration and peak systolic blood pressure (SBP) to be the only independent predictors of all-cause mortality. Hazard ratios of 0.78 (95% CI 0.65-0.93, p = 0.007) and 0.79 (95% CI 0.66-0.95, p = 0.01) were associated with an increase in exercise duration of 1 min and 10 mm Hg peak SBP, respectively. Two simple parameters (exercise duration and peak SBP) that are easily measured by standard exercise testing are the strongest independent predictors of mortality which outperform LVEF and N-BNP in ambulatory patients with mild-moderate CHF. Copyright (c) 2005 S. Karger AG, Basel.

High Level of Chemokine CCL18 Is Associated With Pulmonary Function Deterioration, Lung Fibrosis Progression, and Reduced Survival in Systemic Sclerosis.

PubMed

Hoffmann-Vold, Anna-Maria; Tennøe, Anders Heiervang; Garen, Torhild; Midtvedt, Øyvind; Abraityte, Aurelija; Aaløkken, Trond Mogens; Lund, May Britt; Brunborg, Cathrine; Aukrust, Pål; Ueland, Thor; Molberg, Øyvind

2016-08-01

Markers for early identification of progressive interstitial lung disease (ILD) in systemic sclerosis (SSc) are in demand. Chemokine CCL18, which has been linked to pulmonary inflammation, is an interesting candidate, but data have not been consistent. We aimed to assess CCL18 levels in a large, prospective, unselected SSc cohort with longitudinal, paired data sets on pulmonary function and lung fibrosis. Sera from the Oslo University Hospital SSc cohort (n = 298) and healthy control subjects (n = 100) were analyzed for CCL18 by enzyme immunoassay. High CCL18 (>53 ng/mL) was defined using the mean value plus 2 SD in sera obtained from healthy control subjects as the cutoff. High serum CCL18 was identified in 35% (105 of 298). Annual decline in FVC differed significantly between high and low CCL18 subsets (13.3% and 4.7%; P = .016), as did the annual progression rate of lung fibrosis (0.9% [SD, 2.9] and 0.2% [SD, 1.9]). Highest rates of annual FVC decline > 10% (21%) and annual fibrosis progression (1.2%) were seen in patients with high CCL18 and early disease (< 3 years). In multivariate analyses, CCL18 was associated with annual FVC decline > 10% (OR, 1.1; 95% CI, 1.01-1.11) and FVC < 70% at follow-up (OR, 3.1; 95% CI, 1.08-8.83). Survival analyses showed that patients with high CCL18 had reduced 5- and 10-year cumulative survival compared with patients with low CCL18 (85% and 74%, compared with 97% and 89%, respectively; P = .001). The results from this prospective cohort reinforce the notion that high CCL18 may serve as a marker for early identification of progressive ILD in SSc. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Impact of risk factors on cardiovascular risk: a perspective on risk estimation in a Swiss population.

PubMed

Chrubasik, Sigrun A; Chrubasik, Cosima A; Piper, Jörg; Schulte-Moenting, Juergen; Erne, Paul

2015-01-01

In models and scores for estimating cardiovascular risk (CVR), the relative weightings given to blood pressure measurements (BPMs), and biometric and laboratory variables are such that even large differences in blood pressure lead to rather low differences in the resulting total risk when compared with other concurrent risk factors. We evaluated this phenomenon based on the PROCAM score, using BPMs made by volunteer subjects at home (HBPMs) and automated ambulatory BPMs (ABPMs) carried out in the same subjects. A total of 153 volunteers provided the data needed to estimate their CVR by means of the PROCAM formula. Differences (deltaCVR) between the risk estimated by entering the ABPM and that estimated with the HBPM were compared with the differences (deltaBPM) between the ABPM and the corresponding HBPM. In addition to the median values (= second quartile), the first and third quartiles of blood pressure profiles were also considered. PROCAM risk values were converted to European Society of Cardiology (ESC) risk values and all participants were assigned to the risk groups low, medium and high. Based on the PROCAM score, 132 participants had a low risk for suffering myocardial infarction, 16 a medium risk and 5 a high risk. The calculated ESC scores classified 125 participants into the low-risk group, 26 into the medium- and 2 into the high-risk group for death from a cardiovascular event. Mean ABPM tended to be higher than mean HBPM. Use of mean systolic ABPM or HBPM in the PROCAM formula had no major impact on the risk level. Our observations are in agreement with the rather low weighting of blood pressure as risk determinant in the PROCAM score. BPMs assessed with different methods had relatively little impact on estimation of cardiovascular risk in the given context of other important determinants. The risk calculations in our unselected population reflect the given classification of Switzerland as a so-called cardiovascular "low risk country".

[Determinants of task preferences when performance is indicative of individual characteristics: self-assessment motivation and self-verification motivation].

PubMed

Numazaki, M; Kudo, E

1995-04-01

The present study was conducted to examine determinants of information-gathering behavior with regard to one's own characteristics. Four tasks with different self-congruent and incongruent diagnosticity were presented to subjects. As self-assessment theory predicted, high diagnostic tasks were preferred to low tasks. And as self-verification theory predicted, self-congruent diagnosticity had a stronger effect on task preference than self-incongruent diagnosticity. In addition, subjects who perceived the relevant characteristics important inclined to choose self-assessment behavior more than who did not. Also, subjects who were certain of their self-concept inclined to choose self-verification behavior more than who were not. These results suggest that both self-assessment and self-verification motivations play important roles in information-gathering behavior regarding one's characteristics, and strength of the motivations is determined by the importance of relevant characteristics or the certainty of self-concept.

Extracting Characteristics of the Study Subjects from Full-Text Articles

PubMed Central

Demner-Fushman, Dina; Mork, James G

2015-01-01

Characteristics of the subjects of biomedical research are important in determining if a publication describing the research is relevant to a search. To facilitate finding relevant publications, MEDLINE citations provide Medical Subject Headings that describe the subjects’ characteristics, such as their species, gender, and age. We seek to improve the recommendation of these headings by the Medical Text Indexer (MTI) that supports manual indexing of MEDLINE. To that end, we explore the potential of the full text of the publications. Using simple recall-oriented rule-based methods we determined that adding sentences extracted from the methods sections and captions to the abstracts prior to MTI processing significantly improved recall and F1 score with only a slight drop in precision. Improvements were also achieved in directly assigning several headings extracted from the full text. These results indicate the need for further development of automated methods capable of leveraging the full text for indexing. PMID:26958181

Rapid Parallel Screening for Strain Optimization

DTIC Science & Technology

2013-08-16

fermentation yields of industrially relevant biological compounds. Screening of the desired chemicals was completed previously. Microbes that can...reporter, and, 2) a yeast TAR cloning shuttle vector for transferring catabolic clusters to E. coli. 15. SUBJECT TERMS NA 16. SECURITY CLASSIFICATION OF... fermentation yields of industrially relevant biological compounds. Screening of the desired chemicals was completed previously. Microbes that can utilize

Rapid Parallel Screening for Strain Optimization

DTIC Science & Technology

2013-05-16

fermentation yields of industrially relevant biological compounds. Screening of the desired chemicals was completed previously. Microbes that can...reporter, and, 2) a yeast TAR cloning shuttle vector for transferring catabolic clusters to E. coli. 15. SUBJECT TERMS NA 16. SECURITY CLASSIFICATION OF... fermentation yields of industrially relevant biological compounds. Screening of the desired chemicals was completed previously. Microbes that can utilize

Challenging the wisdom of puncture at the calyceal fornix in percutaneous nephrolithotripsy: feasibility and safety study with 137 patients operated via a non-calyceal percutaneous track.

PubMed

Kyriazis, Iason; Kallidonis, Panagiotis; Vasilas, Marinos; Panagopoulos, Vasilios; Kamal, Wissam; Liatsikos, Evangelos

2017-05-01

To present our experience with a central, non-calyceal puncture protocol for percutaneous nephrolithotripsy (PCNL) in an attempt to challenge the opinion of worldwide adopted calyceal puncture as the less traumatic site of percutaneous entrance into the collecting system. During 2012, a total of 137 consecutive, unselected patients were subjected to PCNL in our department. Non-calyceal punctures were performed to all cases and followed by subsequent track dilations up to 30 Fr. Perioperative and postoperative data were prospectively collected and analyzed. Mean operative time (from skin puncture to nephrostomy tube placement) was 48 min. Patients with single, multiple and staghorn stones had primary stone-free rates of 89.2, 80.4 and 66.7 % after PCNL, respectively. The overall complication rate was 10.2 %, while bleeding complications were minimal. Only 4 patients (2.9 %) required blood transfusion. Five patients (3.6 %) had Clavien Grade IIIa complications requiring an intervention for their management and none Grade IV or V. Despite the absence of evidence that non-calyceal percutaneous tracts could be a risk factor for complications, the concept of calyceal puncture has been worldwide adopted by PCNL surgeons as the sole safe percutaneous entrance into the collective system. Based on our experience, other pathways than the worldwide recognized rule, calyceal puncture, are possible and probably not as dangerous as has been previously stated.

Sodium phenylbutyrate decreases plasma branched-chain amino acids in patients with urea cycle disorders.

PubMed

Burrage, Lindsay C; Jain, Mahim; Gandolfo, Laura; Lee, Brendan H; Nagamani, Sandesh C S

2014-01-01

Sodium phenylbutyrate (NaPBA) is a commonly used medication for the treatment of patients with urea cycle disorders (UCDs). Previous reports involving small numbers of patients with UCDs have shown that NaPBA treatment can result in lower plasma levels of the branched-chain amino acids (BCAA) but this has not been studied systematically. From a large cohort of patients (n=553) with UCDs enrolled in the Longitudinal Study of Urea Cycle Disorders, a collaborative multicenter study of the Urea Cycle Disorders Consortium, we evaluated whether treatment with NaPBA leads to a decrease in plasma BCAA levels. Our analysis shows that NaPBA use independently affects the plasma BCAA levels even after accounting for multiple confounding covariates. Moreover, NaPBA use increases the risk for BCAA deficiency. This effect of NaPBA seems specific to plasma BCAA levels, as levels of other essential amino acids are not altered by its use. Our study, in an unselected population of UCD subjects, is the largest to analyze the effects of NaPBA on BCAA metabolism and potentially has significant clinical implications. Our results indicate that plasma BCAA levels should to be monitored in patients treated with NaPBA since patients taking the medication are at increased risk for BCAA deficiency. On a broader scale, these findings could open avenues to explore NaPBA as a therapy in maple syrup urine disease and other common complex disorders with dysregulation of BCAA metabolism. Copyright © 2014 Elsevier Inc. All rights reserved.

Sodium Phenylbutyrate Decreases Plasma Branched-Chain Amino Acids in Patients with Urea Cycle Disorders

PubMed Central

Burrage, Lindsay C.; Jain, Mahim; Gandolfo, Laura; Lee, Brendan H.; Nagamani, Sandesh CS.

2014-01-01

Sodium phenylbutyrate (NaPBA) is a commonly used medication for the treatment of patients with urea cycle disorders (UCDs). Previous reports involving small numbers of patients with UCDs have shown that NaPBA treatment can result in lower plasma levels of the branched-chain amino acids (BCAA) but this has not been studied systematically. From a large cohort of patients (n=553) with UCDs enrolled in Longitudinal Study of Urea Cycle Disorders, a collaborative multicenter study of the Urea Cycle Disorders Consortium, we evaluated whether treatment with NaPBA leads to a decrease in plasma BCAA levels. Our analysis shows that NaPBA use independently affects the plasma BCAA levels even after accounting for multiple confounding covariates. Moreover, NaPBA use increases the risk for BCAA deficiency. This effect of NaPBA seems specific to plasma BCAA levels, as levels of other essential amino acids are not altered by its use. Our study, in an unselected population of UCD subjects, is the largest to analyze the effects of NaPBA on BCAA metabolism and potentially has significant clinical implications. Our results indicate that plasma BCAA levels should to be monitored in patients treated with NaPBA since patients taking the medication are at increased risk for BCAA deficiency. On a broader scale, they could open avenues to explore NaPBA as a therapy in maple syrup urine disease and other common complex disorders with dysregulation of BCAA metabolism. PMID:25042691

Subjective knowledge of AIDS and use of HIV testing.

PubMed

Phillips, K A

1993-10-01

Increasing knowledge is an important goal of human immunodeficiency virus (HIV) prevention strategies, although increased knowledge may not be associated with increased preventive behaviors. This study examines the association of (1) objective and subjective acquired immunodeficiency syndrome (AIDS) knowledge, and (2) both objective and subjective AIDS knowledge with HIV testing use. Data are from the 1988 National Health Interview Survey. Objective and subjective knowledge were only moderately correlated. In regression analyses, higher subjective knowledge was significantly associated with higher testing use, but objective knowledge was not. The results are relevant to other preventive behaviors for which knowledge is an important factor.

Outcome quality of in-patient cardiac rehabilitation in elderly patients--identification of relevant parameters.

PubMed

Salzwedel, Annett; Nosper, Manfred; Röhrig, Bernd; Linck-Eleftheriadis, Sigrid; Strandt, Gert; Völler, Heinz

2014-02-01

Outcome quality management requires the consecutive registration of defined variables. The aim was to identify relevant parameters in order to objectively assess the in-patient rehabilitation outcome. From February 2009 to June 2010 1253 patients (70.9 ± 7.0 years, 78.1% men) at 12 rehabilitation clinics were enrolled. Items concerning sociodemographic data, the impairment group (surgery, conservative/interventional treatment), cardiovascular risk factors, structural and functional parameters and subjective health were tested in respect of their measurability, sensitivity to change and their propensity to be influenced by rehabilitation. The majority of patients (61.1%) were referred for rehabilitation after cardiac surgery, 38.9% after conservative or interventional treatment for an acute coronary syndrome. Functionally relevant comorbidities were seen in 49.2% (diabetes mellitus, stroke, peripheral artery disease, chronic obstructive lung disease). In three key areas 13 parameters were identified as being sensitive to change and subject to modification by rehabilitation: cardiovascular risk factors (blood pressure, low-density lipoprotein cholesterol, triglycerides), exercise capacity (resting heart rate, maximal exercise capacity, maximal walking distance, heart failure, angina pectoris) and subjective health (IRES-24 (indicators of rehabilitation status): pain, somatic health, psychological well-being and depression as well as anxiety on the Hospital Anxiety and Depression Scale). The outcome of in-patient rehabilitation in elderly patients can be comprehensively assessed by the identification of appropriate key areas, that is, cardiovascular risk factors, exercise capacity and subjective health. This may well serve as a benchmark for internal and external quality management.

Assessment of the effects of lacosamide on sleep parameters in healthy subjects.

PubMed

Hudson, J Douglas; Guptill, Jeffrey T; Byrnes, William; Yates, Stephen L; Williams, Paulette; D'Cruz, O'Neill

2015-02-01

Seizures and antiepileptic drugs (AED) may disrupt sleep patterns in patients with epilepsy, thus evaluation of lacosamide effects on objective and subjective sleep measures is warranted. A multicenter, interventional, open-label study (NCT01530386) was conducted in healthy subjects without confounding effects of concomitant AED use, co-morbidities, or disease state to determine whether lacosamide impacts sleep parameters after 22 days of lacosamide exposure. After overnight polysomnography (PSG) to assess baseline parameters, lacosamide was initiated at 100mg/day (50mg twice daily) and increased by 100mg/day weekly to 300 mg/day (the mid-range maintenance dose for adjunctive therapy). The primary variable was change from baseline to post-treatment in wake after sleep onset (WASO). Secondary variables included additional objective sleep measures, subject-reported measures of sleep quality, daytime sleepiness, and tolerability. Change from baseline in WASO was analyzed using the Wilcoxon rank-sum test. A total of 27 subjects received ≥1 dose of lacosamide and 25 subjects completed the study. For WASO, median change from baseline was a 6-min reduction (95% confidence interval: -38, 77.5; p=0.1074) after lacosamide treatment; this was considered not clinically relevant. No clinically relevant changes were observed in any secondary variables. Thirteen subjects (48%) reported a treatment-emergent adverse event, none of which was severe or led to study discontinuation. Lacosamide 300 mg/day had no effect on objective or subjective sleep parameters in healthy subjects and was generally well tolerated. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Orangutans (Pongo abelii) seek information about tool functionality in a metacognition tubes task.

PubMed

Mulcahy, Nicholas J

2016-11-01

Nonhuman primates appear to engage in metacognition by knowing when they need to search for relevant information for solving the tubes task. The task involves presenting subjects with a number of tubes with only 1 having food hidden inside. Before choosing, subjects look inside the tubes more often when they do not know which 1 contains the food (hidden trials) compared to when they do know this information (visible trials). It is argued, however, that nonmetacognitive general food searching strategies can explain this looking behavior. To address this issue, 3 orangutans were tested with a novel tubes task in which they were only required to seek information about tool functionality. The results showed that subjects had the ability to search for tool functionality but no subject looked significantly more in hidden trials compared to visible trials. Subjects were retested with the same condition and given a second condition in which the cost of a wrong choice was increased. In both conditions, 2 subjects looked significantly more inside the hidden trials compared to the visible trials. Subjects were also tested with the traditional tubes task in which food was hidden inside 1 tube. All subjects looked inside the tubes significantly more in the hidden trials compared to the visible trials. However, subjects conducted more excessive looks compared to when looking for tool functionality. I suggest that excessive searches may be caused by food being a strong stimulus and discuss the relevance of this possibility for metacognitive research involving the tubes task. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

ERP C250 shows the elderly (cognitively normal, Alzheimer's disease) store more stimuli in short-term memory than Young Adults do.

PubMed

Chapman, Robert M; Gardner, Margaret N; Mapstone, Mark; Klorman, Rafael; Porsteinsson, Anton P; Dupree, Haley M; Antonsdottir, Inga M; Kamalyan, Lily

2016-06-01

To determine how aging and dementia affect the brain's initial storing of task-relevant and irrelevant information in short-term memory. We used brain Event-Related Potentials (ERPs) to measure short-term memory storage (ERP component C250) in 36 Young Adults, 36 Normal Elderly, and 36 early-stage AD subjects. Participants performed the Number-Letter task, a cognitive paradigm requiring memory storage of a first relevant stimulus to compare it with a second stimulus. In Young Adults, C250 was more positive for the first task-relevant stimulus compared to all other stimuli. C250 in Normal Elderly and AD subjects was roughly the same to relevant and irrelevant stimuli in Intratrial Parts 1-3 but not 4. The AD group had lower C250 to relevant stimuli in part 1. Both normal aging and dementia cause less differentiation of relevant from irrelevant information in initial storage. There was a large aging effect involving differences in the pattern of C250 responses of the Young Adult versus the Normal Elderly/AD groups. Also, a potential dementia effect was obtained. C250 is a candidate tool for measuring short-term memory performance on a biological level, as well as a potential marker for memory changes due to normal aging and dementia. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

SF3B1 mutations constitute a novel therapeutic target in breast cancer

PubMed Central

Maguire, Sarah L; Leonidou, Andri; Wai, Patty; Marchiò, Caterina; Ng, Charlotte KY; Sapino, Anna; Salomon, Anne-Vincent; Reis-Filho, Jorge S; Weigelt, Britta; Natrajan, Rachael C

2015-01-01

Mutations in genes encoding proteins involved in RNA splicing have been found to occur at relatively high frequencies in several tumour types including myelodysplastic syndromes, chronic lymphocytic leukaemia, uveal melanoma, and pancreatic cancer, and at lower frequencies in breast cancer. To investigate whether dysfunction in RNA splicing is implicated in the pathogenesis of breast cancer, we performed a re-analysis of published exome and whole genome sequencing data. This analysis revealed that mutations in spliceosomal component genes occurred in 5.6% of unselected breast cancers, including hotspot mutations in the SF3B1 gene, which were found in 1.8% of unselected breast cancers. SF3B1 mutations were significantly associated with ER-positive disease, AKT1 mutations, and distinct copy number alterations. Additional profiling of hotspot mutations in a panel of special histological subtypes of breast cancer showed that 16% and 6% of papillary and mucinous carcinomas of the breast harboured the SF3B1 K700E mutation. RNA sequencing identified differentially spliced events expressed in tumours with SF3B1 mutations including the protein coding genes TMEM14C, RPL31, DYNL11, UQCC, and ABCC5, and the long non-coding RNA CRNDE. Moreover, SF3B1 mutant cell lines were found to be sensitive to the SF3b complex inhibitor spliceostatin A and treatment resulted in perturbation of the splicing signature. Albeit rare, SF3B1 mutations result in alternative splicing events, and may constitute drivers and a novel therapeutic target in a subset of breast cancers. © 2014 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. PMID:25424858

Androgen Concentrations in Umbilical Cord Blood and Their Association with Maternal, Fetal and Obstetric Factors

PubMed Central

Keelan, Jeffrey A.; Mattes, Eugen; Tan, HaiWei; Dinan, Andrew; Newnham, John P.; Whitehouse, Andrew J. O.; Jacoby, Peter; Hickey, Martha

2012-01-01

The aim of this study was to measure umbilical blood androgen concentrations in a birth cohort using a highly specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay and assesses the effects of sex, labor, and gestational age on fetal androgen levels at birth. We performed a prospective cohort study of androgen concentrations in mixed arterial and venous umbilical cord serum from 803 unselected singleton pregnancies from a general obstetric population in Western Australia. Total testosterone (TT), Δ4-androstenedione, and dehydroepiandrosterone were extracted from archived cord serum samples and measured using LC-MS/MS. SHBG was measured by ELISA; free testosterone (FT) and bioavailable testosterone (BioT) values were also calculated. Median values for all three androgens were generally lower than previously published values. Levels of TT, FT, BioT, and SHBG were significantly higher in male verses female neonates (P<0.0001), while dehydroepiandrosterone levels were higher in females (P<0.0001). Labor was associated with a significant (∼15–26%) decrease in median cord blood TT and FT levels (both sexes combined), but a modest (∼16–31%) increase in SHBG, Δ4-androstenedione, and dehydroepiandrosterone concentrations. TT and FT were significantly negatively correlated with gestational age at delivery, while SHBG, Δ4-androstenedione, and dehydroepiandrosterone were positively correlated. Antenatal glucocorticoid administration also had a significant effect in the multiple regression models. This is the first study to report umbilical cord androgen levels in a large unselected population of neonates using LC-MS/MS. Our findings suggest that previous studies have over-estimated cord androgen levels, and that fetal, maternal, and obstetric factors influence cord androgen levels differentially. Caution should be exercised when interpreting previously-published data that have not taken all of these factors into account. PMID:22916165

Real-world heart failure management in 10,910 patients with chronic heart failure in the Netherlands : Design and rationale of the Chronic Heart failure ESC guideline-based Cardiology practice Quality project (CHECK-HF) registry.

PubMed

Brugts, J J; Linssen, G C M; Hoes, A W; Brunner-La Rocca, H P

2018-05-01

Data from patient registries give insight into the management of patients with heart failure (HF), but actual data from unselected real-world HF patients are scarce. Therefore, we performed a cross sectional study of current HF care in the period 2013-2016 among more than 10,000 unselected HF patients at HF outpatient clinics in the Netherlands. In 34 participating centres, all 10,910 patients with chronic HF treated at cardiology centres were included in the CHECK-HF registry. Of these, most (96%) were managed at a specific HF outpatient clinic. Heart failure was typically diagnosed according to the ESC guidelines 2012, based on signs, symptoms and structural and/or functional cardiac abnormalities. Information on diagnostics, treatment and co-morbidities were recorded, with specific focus on drug therapy and devices. In our cohort, the mean age was 73 years (SD 12) and 60% were male. Frequent co-morbidities reported in the patient records were diabetes mellitus 30%, hypertension 43%, COPD 19%, and renal insufficiency 58%. In 47% of the patients, ischaemia was the origin of HF. In our registry, the prevalence of HF with preserved ejection fraction was 21%. The CHECK-HF registry will provide insight into the current, real world management of patient with chronic HF, including HF with reduced ejection fraction, preserved ejection fraction and mid-range ejection fraction, that will help define ways to improve quality of care. Drug and device therapy and guideline adherence as well as interactions with age, gender and co-morbidities will receive specific attention.

Prospective Evaluation of Germline Alterations in Patients With Exocrine Pancreatic Neoplasms.

PubMed

Lowery, Maeve A; Wong, Winston; Jordan, Emmet J; Lee, Jonathan W; Kemel, Yelena; Vijai, Joseph; Mandelker, Diana; Zehir, Ahmet; Capanu, Marinela; Salo-Mullen, Erin; Arnold, Angela G; Yu, Kenneth H; Varghese, Anna M; Kelsen, David P; Brenner, Robin; Kaufmann, Erica; Ravichandran, Vignesh; Mukherjee, Semanti; Berger, Michael F; Hyman, David M; Klimstra, David S; Abou-Alfa, Ghassan K; Tjan, Catherine; Covington, Christina; Maynard, Hannah; Allen, Peter J; Askan, Gokce; Leach, Steven D; Iacobuzio-Donahue, Christine A; Robson, Mark E; Offit, Kenneth; Stadler, Zsofia K; O'Reilly, Eileen M

2018-02-28

Identification of pathogenic germline alterations (PGAs) has important clinical and therapeutic implications in pancreas cancer. We performed comprehensive germline testing (GT) in an unselected prospective cohort of patients with exocrine pancreatic neoplasms with genotype and phenotype association to facilitate identification of prognostic and/or predictive biomarkers and examine potential therapeutic implications. Six hundred fifteen unselected patients with exocrine pancreatic neoplasms were prospectively consented for somatic tumor and matched sample profiling for 410-468 genes. GT for PGAs in 76 genes associated with cancer susceptibility was performed in an "identified" manner in 356 (57.9%) patients and in an "anonymized" manner in 259 (42.1%) patients, using an institutional review board-approved protocol. Detailed clinical and pathological features, response to platinum, and overall survival (OS) were collected for the identified cohort. OS was analyzed with Kaplan-Meier curves. PGAs were present in 122 (19.8%) of 615 patients involving 24 different genes, including BRCA1/2, ATM, PALB2, and multiple additional genes associated with the DNA damage response pathway. Of 122 patients with germline alterations, 41.8% did not meet current guidelines for GT. The difference in median OS was not statistically significant between patients with and without PGA (50.8 months, 95% confidence interval = 34.5 to not reached, two-sided P = .94). Loss of heterozygosity was found in 60.0% of BRCA1/2. PGAs frequently occur in pancreas exocrine neoplasms and involve multiple genes beyond those previously associated with hereditary pancreatic cancer. These PGAs are therapeutically actionable in about 5% to 10% of patients. These data support routinely offering GT in all pancreatic ductal adenocarcimona patients with a broad panel of known hereditary cancer predisposition genes.

Removal of restrictions following primary THA with posterolateral approach does not increase the risk of early dislocation.

PubMed

Gromov, Kirill; Troelsen, Anders; Otte, Kristian Stahl; Ørsnes, Thue; Ladelund, Steen; Husted, Henrik

2015-01-01

Patient education and mobilization restrictions are often used in an attempt to reduce the risk of dislocation following primary THA. To date, there have been no studies investigating the safety of removal of mobilization restrictions following THA performed using a posterolateral approach. In this retrospective non-inferiority study, we investigated the rate of early dislocation following primary THA in an unselected patient cohort before and after removal of postoperative mobilization restrictions. From the Danish National Health Registry, we identified patients with early dislocation in 2 consecutive and unselected cohorts of patients who received primary THA at our institution from 2004 through 2008 (n = 946) and from 2010 through 2014 (n = 1,329). Patients in the first cohort were mobilized with functional restrictions following primary THA whereas patients in the second cohort were allowed unrestricted mobilization. Risk of early dislocation (within 90 days) was compared in the 2 groups and odds ratio (OR)-adjusted for possible confounders-was calculated. Reasons for early dislocation in the 2 groups were identified. When we adjusted for potential confounders, we found no increased risk of early dislocation within 90 days in patients who were mobilized without restrictions. Risk of dislocation within 90 days was lower (3.4% vs 2.8%), risk of dislocation within 30 days was lower (2.1% vs 2.0%), and risk of multiple dislocations (1.8% vs 1.1%) was lower in patients who were mobilized without restrictions, but not statistically significantly so. Increasing age was an independent risk factor for dislocation. Removal of mobilization restrictions from the mobilization protocol following primary THA performed with a posterolateral approach did not lead to an increased risk of dislocation within 90 days.

Prospective assessment of the occurrence of anemia in patients with heart failure: results from the Study of Anemia in a Heart Failure Population (STAMINA-HFP) Registry.

PubMed

Adams, Kirkwood F; Patterson, James H; Patterson, John H; Oren, Ron M; Mehra, Mandeep R; O'Connor, Christopher M; Piña, Ileana L; Miller, Alan B; Chiong, Jun R; Dunlap, Stephanie H; Cotts, William G; Felker, Gary M; Schocken, Douglas D; Schwartz, Todd A; Ghali, Jalal K

2009-05-01

Although a potentially important pathophysiologic factor in heart failure, the prevalence and predictors of anemia have not been well studied in unselected patients with heart failure. The Study of Anemia in a Heart Failure Population (STAMINA-HFP) Registry prospectively studied the prevalence of anemia and the relationship of hemoglobin to health-related quality of life and outcomes among patients with heart failure. A random selection algorithm was used to reduce bias during enrollment of patients seen in specialty clinics or clinics of community cardiologists with experience in heart failure. In this initial report, data on prevalence and correlates of anemia were analyzed in 1,076 of the 1,082 registry patients who had clinical characteristics and hemoglobin determined by finger-stick at baseline. Overall (n = 1,082), the registry patients were 41% female and 73% white with a mean age (+/-SD) of 64 +/- 14 years (68 +/- 13 years in community and 57 +/- 14 years in specialty sites, P < .001). Among the 1,076 patients in the prevalence analysis, mean hemoglobin was 13.3 +/- 2.1 g/dL (median 13.2 g/dL); and anemia (defined by World Health Organization criteria) was present in 34%. Age identified patients at risk for anemia, with 40% of patients >70 years affected. Initial results from the STAMINA-HFP Registry suggest that anemia is a common comorbidity in unselected outpatients with heart failure. Given the strong association of anemia with adverse outcomes in heart failure, this study supports further investigation concerning the importance of anemia as a therapeutic target in this condition.

Frequency of hepatitis B virus 'a' determinant variants in unselected Spanish chronic carriers.

PubMed

Avellón, Ana; Echevarria, José M

2006-01-01

The prevalence in the population of hepatitis B virus (HBV) surface antigen (HBsAg) variants that may impair diagnosis, or allow the virus to escape vaccine-induced immunity or passive immunoglobulin therapy is unknown. A genome fragment encoding HBsAg amino acids 112-212 was amplified and sequenced from the sera of 272 unselected DNA-positive, HBV-chronic carriers from Spain. The genotype and the HBsAg subtype were predicted from the sequences. Analysis of amino-acid positions 112-157 revealed single or multiple substitutions in 39% of the carriers studied. Mutations were not detected for residues 121, 135, 137, 139, 140, 141, 142, 146, 147, 148, 149, 151, 152, 153, 155, 156, and 157. Substitutions reported previously to be in association with failures of diagnostic tests or with vaccine or immunoglobulin therapy escape were found in 12.5%, 6.6%, and 9.2% of carriers, respectively. Met133Thr (2.2%); Gln129His, Met133Ile, Phe/Tyr134Asn (1.8%); Phe/Tyr134Leu, Gly145Ala (1.5%), and Pro120Thr (1.1%) were the most frequent. Other substitutions, including Gly145Arg (0.4%), were found at a frequency of less than 1%. Samples containing HBV mutants were tested with three commercial assays for HBsAg screening. Almost all the mutants reacted to the upper cut-off values of the assays, but six samples with weak reactivity with one or more of the methods were also found. Thus, HBV mutants with a potential impact on clinical and public health issues are moderately frequent among chronic carriers from Spain, although their influence on the performance of diagnostic tests seems to be slight.

Outcomes of Patients Treated with the Everolimus- versus the Paclitaxel-Eluting Stents in a Consecutive Cohort of Patients at a Tertiary Medical Center.

PubMed

Shammas, Nicolas W; Shammas, Gail A; Nader, Elie; Jerin, Michael; Mrad, Luay; Ehrecke, Nicholas; Shammas, Waheeb J; Voelliger, Cara M; Hafez, Alexander; Kelly, Ryan; Reynolds, Emily

2013-09-01

In this study, we compare the outcomes of the paclitaxel-eluting stent (PES) versus the everolimus-eluting stent (EES) treated patients at a tertiary medical center and up to 2 years follow-up. Unselected consecutive patients were retrospectively recruited following stenting with PES (159 patients) or EES (189 patients). The primary endpoint of the study was target lesion failure (TLF), defined as the combined endpoint of cardiac death, nonfatal myocardial infarction (MI), or target lesion revascularization (TLR). Secondary endpoints included target vessel revascularization (TVR), TLR, target vessel failure (TVF), acute stent thrombosis (ST), total death, cardiac death, and nonfatal MI. Patients treated with the PES stent had less congestive heart failure and restenotic lesions, but a higher prevalence of longer lesions, nonleft main bifurcations, required more stents per patient (4.3 ± 2.8 vs. 2.9 ± 2.1). TLF occurred in 32.3% PES versus 21.5% EES (p = 0.027). The secondary unadjusted endpoints for PES versus EES, respectively, were TVF 38.6 versus 30.7% (p = 0.140), TVR 35.7 versus 26.5% (p = 0.079), definite and probable ST 1.2 versus 0.0%, nonfatal MI 4.5 versus 4.2%, and mortality 9.6 versus 4.0%. Logistic regression analysis showed that the numbers of stents per patient (p = 0.001), age (p = 0.01), and renal failure (p = 0.045) were independent predictors of TLF. Using univariate analysis, EES had lower TLF than PES in a cohort of unselected patients undergoing percutaneous coronary intervention at 2 years follow-up. Multivariate analysis showed that the numbers of stents per patient, age, and renal failure, but not stent type, were predictors of TLF.

Chromophobe hepatocellular carcinoma with abrupt anaplasia: a proposal for a new subtype of hepatocellular carcinoma with unique morphological and molecular features

PubMed Central

Wood, Laura D; Heaphy, Christopher M; Daniel, Hubert Darius-J; Naini, Bita V; Lassman, Charles R; Arroyo, May R; Kamel, Ihab R; Cosgrove, David P; Boitnott, John K; Meeker, Alan K; Torbenson, Michael S

2014-01-01

Hepatocellular carcinomas exhibit heterogeneous morphologies by routine light microscopy. Although some morphologies represent insignificant variations in growth patterns, others may represent unrecognized subtypes of hepatocellular carcinoma. Identification of these subtypes could lead to separation of hepatocellular carcinomas into discrete groups with unique underlying genetic changes, prognosis, or therapeutic responses. In order to identify potential subtypes, two pathologists independently screened a cohort of 219 unselected hepatocellular carcinoma resection specimens and divided cases into potential subtypes. One of these promising candidate subtypes was further evaluated using histological and molecular techniques. This subtype was characterized by a unique and consistent set of histological features: smooth chromophobic cytoplasm, abrupt focal nuclear anaplasia (small clusters of tumor cells with marked nuclear anaplasia in a background of tumor cells with bland nuclear cytology), and scattered microscopic pseudocysts—we designate this variant as ‘chromophobe hepatocellular carcinoma with abrupt anaplasia’. Thirteen cases were identified (6% of all hepatocellular carcinomas), including 6 men and 7 women with an average age of 61 years. Six cases occurred in cirrhotic livers. Serum AFP was elevated in 6 out of 10 cases. There were a variety of underlying liver diseases, but cases were enrichment for chronic hepatitis B, P = 0.006. Interestingly, at the molecular level, this variant was strongly associated with the alternative lengthening of telomere (ALT) phenotype by telomere FISH. ALT is a telomerase-independent mechanism of telomere maintenance and is found in approximately 8% of unselected hepatocellular carcinomas. In contrast, 11/12 (92%) of the cases of chromophobe hepatocellular carcinoma with abrupt anaplasia were ALT-positive. In summary, we propose that chromophobe hepatocellular carcinoma with abrupt anaplasia represents a new subtype of hepatocellular carcinoma with unique morphological and molecular features. PMID:23640129

Chromophobe hepatocellular carcinoma with abrupt anaplasia: a proposal for a new subtype of hepatocellular carcinoma with unique morphological and molecular features.

PubMed

Wood, Laura D; Heaphy, Christopher M; Daniel, Hubert Darius-J; Naini, Bita V; Lassman, Charles R; Arroyo, May R; Kamel, Ihab R; Cosgrove, David P; Boitnott, John K; Meeker, Alan K; Torbenson, Michael S

2013-12-01

Hepatocellular carcinomas exhibit heterogeneous morphologies by routine light microscopy. Although some morphologies represent insignificant variations in growth patterns, others may represent unrecognized subtypes of hepatocellular carcinoma. Identification of these subtypes could lead to separation of hepatocellular carcinomas into discrete groups with unique underlying genetic changes, prognosis, or therapeutic responses. In order to identify potential subtypes, two pathologists independently screened a cohort of 219 unselected hepatocellular carcinoma resection specimens and divided cases into potential subtypes. One of these promising candidate subtypes was further evaluated using histological and molecular techniques. This subtype was characterized by a unique and consistent set of histological features: smooth chromophobic cytoplasm, abrupt focal nuclear anaplasia (small clusters of tumor cells with marked nuclear anaplasia in a background of tumor cells with bland nuclear cytology), and scattered microscopic pseudocysts--we designate this variant as 'chromophobe hepatocellular carcinoma with abrupt anaplasia'. Thirteen cases were identified (6% of all hepatocellular carcinomas), including 6 men and 7 women with an average age of 61 years. Six cases occurred in cirrhotic livers. Serum AFP was elevated in 6 out of 10 cases. There were a variety of underlying liver diseases, but cases were enrichment for chronic hepatitis B, P=0.006. Interestingly, at the molecular level, this variant was strongly associated with the alternative lengthening of telomere (ALT) phenotype by telomere FISH. ALT is a telomerase-independent mechanism of telomere maintenance and is found in approximately 8% of unselected hepatocellular carcinomas. In contrast, 11/12 (92%) of the cases of chromophobe hepatocellular carcinoma with abrupt anaplasia were ALT-positive. In summary, we propose that chromophobe hepatocellular carcinoma with abrupt anaplasia represents a new subtype of hepatocellular carcinoma with unique morphological and molecular features.

Use of prophylactic Saccharomyces boulardii to prevent Clostridium difficile infection in hospitalized patients: a controlled prospective intervention study.

PubMed

Carstensen, Jeppe West; Chehri, Mahtab; Schønning, Kristian; Rasmussen, Steen Christian; Anhøj, Jacob; Godtfredsen, Nina Skavlan; Andersen, Christian Østergaard; Petersen, Andreas Munk

2018-05-03

Clostridium difficile infection (CDI) is a common complication to antibiotic use. Saccharomyces boulardii has shown effect as a prophylactic agent. We aimed to evaluate the efficacy of S. boulardii in preventing CDI in unselected hospitalized patients treated with antibiotics. We conducted a 1 year controlled prospective intervention study aiming to prescribe Sacchaflor (S. boulardii 5 × 10 9 , Pharmaforce ApS) twice daily to hospitalized patients treated with antibiotics. Comparable departments from three other hospitals in our region were included as controls. All occurrences of CDI in patients receiving antibiotics were reported and compared to a baseline period defined as 2 years prior to intervention. Results were analyzed using run chart tests for non-random variation in CDI rates. In addition, odds ratios for CDI were calculated. S. boulardii compliance reached 44% at the intervention hospital, and 1389 patients were treated with Sacchaflor. Monthly CDI rates dropped from a median of 3.6% in the baseline period to 1.5% in the intervention period. S. boulardii treatment was associated with a reduced risk of CDI at the intervention hospital: OR = 0.06 (95% CI 0.02-0.16). At two control hospitals, CDI rates did not change. At one control hospital, the median CDI rate dropped from 3.5 to 2.4%, possibly reflecting the effects of simultaneous multifaceted intervention against CDI at that hospital. The results from this controlled prospective interventional study indicate that S. boulardii is effective for the prevention of CDI in an unselected cohort of mainly elderly patients from departments of internal medicine.

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

Mast, Mirjam E., E-mail: m.mast@mchaaglanden.nl; Heijenbrok, Mark W.; Petoukhova, Anna L.

Purpose: Breast cancer radiotherapy has been associated with an increased risk of cardiac toxicity. However, no data are available on the probability of developing coronary artery disease (CAD) in breast cancer patients when compared with healthy women. Therefore, baseline coronary artery calcium (CAC) scores, as an accepted tool to predict CAD, were determined and compared with the CAC scores of a healthy, asymptomatic cohort, the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. Methods and Materials: Eighty consecutive patients with ductal carcinoma in situ or infiltrative breast cancer referred for radiotherapy after breast-conserving surgery were included in our study. Their cardiovascular riskmore » profile was registered, and a 64 multislice CT scan was performed. The CAC scores of an unselected (Caucasian only) Radiotherapy Centre West (RCWEST) cohort, as well as of those of a selected (comorbidity and race adjusted) RCWEST cohort, were determined. The scores of both cohorts were compared with those of the female (Caucasian only) MESA cohort. Results: For the unselected RCWEST cohort (n = 62) we found significant (p < .01) higher scores for women in the 55-64 age category compared with those of the MESA cohort. In the selected cohort (n = 55) the CAC scores of the women in the age category 55-64 were significantly (p = .02) higher compared with the MESA cohort. No significant differences were noted in the other age categories. Conclusion: Both cohorts revealed that CAC scores in the 55-64 age category were significantly higher than the CAC scores in the asymptomatic (female) MESA population. These data suggest that breast cancer patients bear a higher risk of developing coronary heart disease before the start of radiotherapy. Therefore, measures to decrease cardiac dose further in breast cancer radiotherapy are even more important.« less

Symptoms of gonadal dysfunction are more predictive of hypopituitarism than nonspecific symptoms in screening for pituitary dysfunction following moderate or severe traumatic brain injury.

PubMed

Cuesta, Martín; Hannon, Mark J; Crowley, Rachel K; Behan, Lucy Ann; Tormey, William; Rawluk, Daniel; Delargy, Mark; Agha, Amar; Thompson, Christopher J

2016-01-01

The economic and logistic burden of screening for hypopituitarism following moderate/severe traumatic brain injury (TBI) is considerable. A key recommendation in published guidelines is to prioritize for screening those patients with symptoms suggestive of pituitary dysfunction. The purpose of this study was to evaluate the utility of targeted screening for hypopituitarism in long-term survivors after moderate/severe TBI using referrals on the basis of symptoms. In group 1 (G1), consecutive, unselected patients were screened from the Irish National Neurosurgery Centre, whereas in group 2 (G2) patients were targeted based on the presence of symptoms suggestive of pituitary dysfunction. A total of 137 patients (113 male) were systematically screened (G1) and compared to 112 patients (77 male) referred for pituitary evaluation on the basis of suggestive symptoms (G2). The rate of GH, ACTH, gonadotrophin (GT), TSH and ADH deficiency was compared among groups. Patients referred with menstrual dysfunction had more GH (50% vs 11%, P = 0·001), ACTH (60% vs 14%, P < 0·0001), GT (90% vs 16%, P < 0·0001) deficiency and any pituitary hormone deficit (80% vs 33%, P = 0·003) than G1. Men with symptoms of hypogonadism had more GH (33% vs 11%, P = 0·003), GT (58% vs 16%, P < 0·0001) and TSH (16% vs 1%, P = 0·03) deficiency than G1. Patients with nonspecific symptoms were no more likely to have hypopituitarism than those consecutively screened. Symptoms of hypogonadism are sufficiently predictive of hypopituitarism to justify screening for hypopituitarism after moderate/severe TBI. Nonspecific symptoms of hypopituitarism are no more predictive than unselected screening. © 2015 John Wiley & Sons Ltd.

High prey-predator size ratios and unselective feeding in copepods: A seasonal comparison of five species with contrasting feeding modes

NASA Astrophysics Data System (ADS)

Djeghri, Nicolas; Atkinson, Angus; Fileman, Elaine S.; Harmer, Rachel A.; Widdicombe, Claire E.; McEvoy, Andrea J.; Cornwell, Louise; Mayor, Daniel J.

2018-07-01

There has been an upsurge of interest in trait-based approaches to zooplankton, modelling the seasonal changes in the feeding modes of zooplankton in relation to phytoplankton traits such as size or motility. We examined this link at two English Channel plankton monitoring sites south of Plymouth (L4 and E1). At L4 there was a general transition from diatoms in spring to motile microplankton in summer and autumn, but this was not mirrored in the succession of copepod feeding traits; for example the ambushing Oithona similis dominated during the spring diatom bloom. At nearby E1 we measured seasonality of food and grazers, finding strong variation between 2014 and 2015 but overall low mesozooplankton biomass (median 4.5 mg C m-3). We also made a seasonal grazing study of five copepods with contrasting feeding modes (Calanus helgolandicus, Centropages typicus, Acartia clausi, Pseudocalanus elongatus and Oithona similis), counting the larger prey items from the natural seston. All species of copepod fed on all food types and differences between their diets were only subtle; the overriding driver of diet was the composition of the prey field. Even the smaller copepods fed on copepod nauplii at significant rates, supporting previous suggestions of the importance of intra-guild predation. All copepods, including O. similis, were capable of tackling extremely long (>500 μm) diatom chains at clearance rates comparable to those on ciliates. Maximum observed prey:predator length ratios ranged from 0.12 (C. helgolandicus) up to 0.52 (O. similis). Unselective feeding behaviour and the ability to remove highly elongated cells have implications for how copepod feeding is represented in ecological and biogeochemical models.

Financial incentives for smoking cessation in pregnancy: a single-arm intervention study assessing cessation and gaming

PubMed Central

Ierfino, Diana; Mantzari, Eleni; Hirst, Julie; Jones, Tina; Aveyard, Paul; Marteau, Theresa M

2015-01-01

Aims Financial incentives were the single most effective intervention for smoking cessation in pregnancy in a recent Cochrane Review, but based on a few small trials in the United States using only 7-day point prevalence measures of cessation. This study estimates (a) prolonged cessation in an unselected population of English pregnant smokers who are offered financial incentives for quitting and (b) ‘gaming’, i.e. false reporting of smoking status to enter the scheme or gain an incentive. Design Single-arm intervention study Setting Antenatal clinic and community Participants A total of 239 pregnant smokers enrolled into the financial incentive scheme, attending for maternity care at one hospital in an area of high deprivation in England over a 42-week period. Measurements Smoking cessation at delivery and 6 months postpartum, assessed using salivary cotinine; gaming assessed using urinary and salivary cotinine at enrolment, 28 and 36 weeks gestation, and 2 days and 6 months postpartum. Findings Thirty-nine per cent (239 of 615) of smokers were enrolled into the scheme, 60% (143 of 239) of whom made a quit attempt. Of those enrolled, 20% [48 of 239; 95% confidence interval (CI) = 14.9%, 25.1%] were quit at delivery and 10% (25 of 239; 95% CI = 6.2%, 13.8%) at 6 months postpartum. There was no evidence that women gamed to enter the scheme, but evidence that 4% (10 of 239) of those enrolled gamed on one or more occasions to gain vouchers. Conclusions Enrolment on an incentive scheme in an unselected English cohort of pregnant smokers was associated with prolonged cessation rates comparable to those reported in US trials. Rates of gaming were arguably insufficiently high to invalidate the use of such schemes. PMID:25727238

BRCAsearch: written pre-test information and BRCA1/2 germline mutation testing in unselected patients with newly diagnosed breast cancer.

PubMed

Nilsson, Martin P; Törngren, Therese; Henriksson, Karin; Kristoffersson, Ulf; Kvist, Anders; Silfverberg, Barbro; Borg, Åke; Loman, Niklas

2018-02-01

To evaluate a simplified method of pre-test information and germline BRCA1/2 mutation testing. In a prospective, single-arm study, comprehensive BRCA1/2 testing was offered to unselected patients with newly diagnosed breast cancer at three hospitals in south Sweden (BRCAsearch, ClinicalTrials.gov Identifier: NCT02557776). Pre-test information was provided by a standardized invitation letter, but the patients could contact a genetic counselor for telephone genetic counseling if they felt a need for that. Noncarriers were informed about the test result through a letter. Mutation carriers were contacted and offered an appointment for in-person post-test genetic counseling. During the period Feb 2, 2015-Aug 26, 2016, eight hundred and eighteen patients were invited to participate in the study. Through Jan 31, 2017, five hundred and forty-two (66.2%) of them consented to analysis of BRCA1 and BRCA2. Eleven pathogenic mutations were found (BRCA1, n = 2; BRCA2, n = 9), corresponding to a mutation prevalence of 2.0%. Six out of 11 fulfilled the Swedish BRCA testing criteria, and 9 out of 11 fulfilled the NCCN testing criteria. None of the BRCA-associated tumors were of the luminal A-like subtype. Very few patients contacted us for telephone genetic counseling or practical questions, suggesting that a majority felt that the written pre-test information was sufficient for them to make a decision on testing. Streamlining the process of pre-test information, genetic testing, and delivery of test results was feasible and was associated with an uptake of genetic testing in 2/3 of the breast cancer patients.

Impact of extent of resection and recurrent surgery on clinical outcome and overall survival in a consecutive series of 170 patients for glioblastoma in intraoperative high field magnetic resonance imaging.

PubMed

Coburger, Jan; Wirtz, Christian R; König, Ralph W

2017-06-01

In patients with a glioblastoma (GBM), few unselected data exists using actual standard adjuvant treatment and contemporary surgical techniques like iMRI. Aim of study is to assess impact of EoR and recurrent surgery on survival and outcome. We assessed a consecutive unselected series of 170 surgeries for GBM (2008-2014) applying intraoperative MRI (iMRI). All patients received adjuvant radio-chemo-therapy. Overall-survival (OS), progression free survival (PFS), complications and new permanent neurological deficits (nPND) were assessed. Uni- and multivariate-cox-regression-models were calculated. Mean follow-up was 40mo. GTR was intended in 82% and achieved in 77% of these cases. A nPND was found in 7% of patients. In multivariate cox-regression, GTR (HR:0.6, P<0.024) and absence of MGMT methylation (HR:1.6, P<0.042) was significantly associated with PFS. We found no difference in PFS after primary surgery and recurrent surgery. Concerning OS, in multivariate assessment an un-methylated MGMT-promotor (HR2.0, P<0.01) and presence of a complication (HR1.7, P<0.06) were negative prognosticators. Only GTR was significantly beneficial for OS (HR0.4, P<0.028) compared to a failed GTR and a STR. Repeated surgery for recurrent disease was positively associated with OS (HR0.6, P<0.06). Surgery in a contemporary setup using iMRI, brain mapping and modern adjuvant treatment, has a higher OS and lower complication rates as previously published. A maximum but safe resection should be the goal of surgery since a perioperative complication significantly decreases OS. Recurrent surgery has a beneficial effect on OS without an increase of complications.

Population Growth of Varroa destructor (Acari: Varroidae) in Colonies of Russian and Unselected Honey Bee (Hymenoptera: Apidae) Stocks as Related to Numbers of Foragers With Mites.

PubMed

DeGrandi-Hoffman, Gloria; Ahumada, Fabiana; Danka, Robert; Chambers, Mona; DeJong, Emily Watkins; Hidalgo, Geoff

2017-06-01

Varroa (Varroa destructor Anderson and Trueman) is an external parasite of honey bees (Apis mellifera L.) and a leading cause of colony losses worldwide. Varroa populations can be controlled with miticides, but mite-resistant stocks such as the Russian honey bee (RHB) also are available. Russian honey bee and other mite-resistant stocks limit Varroa population growth by affecting factors that contribute to mite reproduction. However, mite population growth is not entirely due to reproduction. Numbers of foragers with mites (FWM) entering and leaving hives also affect the growth of mite populations. If FWM significantly contribute to Varroa population growth, mite numbers in RHB colonies might not differ from unselected lines (USL). Foragers with mites were monitored at the entrances of RHB and USL hives from August to November, 2015, at two apiary sites. At site 1, RHB colonies had fewer FWM than USL and smaller phoretic mite populations. Russian honey bee also had fewer infested brood cells and lower percentages with Varroa offspring than USL. At site 2, FWM did not differ between RHB and USL, and phoretic mite populations were not significantly different. At both sites, there were sharp increases in phoretic mite populations from September to November that corresponded with increasing numbers of FWM. Under conditions where FWM populations are similar between RHB and USL, attributes that contribute to mite resistance in RHB may not keep Varroa population levels below that of USL. Published by Oxford University Press on behalf of Entomological Society of America 2017. This work is written by US Government employees and is in the public domain in the US.

The Spectrum of Renal Allograft Failure

PubMed Central

Chand, Sourabh; Atkinson, David; Collins, Clare; Briggs, David; Ball, Simon; Sharif, Adnan; Skordilis, Kassiani; Vydianath, Bindu; Neil, Desley; Borrows, Richard

2016-01-01

Background Causes of “true” late kidney allograft failure remain unclear as study selection bias and limited follow-up risk incomplete representation of the spectrum. Methods We evaluated all unselected graft failures from 2008–2014 (n = 171; 0–36 years post-transplantation) by contemporary classification of indication biopsies “proximate” to failure, DSA assessment, clinical and biochemical data. Results The spectrum of graft failure changed markedly depending on the timing of allograft failure. Failures within the first year were most commonly attributed to technical failure, acute rejection (with T-cell mediated rejection [TCMR] dominating antibody-mediated rejection [ABMR]). Failures beyond a year were increasingly dominated by ABMR and ‘interstitial fibrosis with tubular atrophy’ without rejection, infection or recurrent disease (“IFTA”). Cases of IFTA associated with inflammation in non-scarred areas (compared with no inflammation or inflammation solely within scarred regions) were more commonly associated with episodes of prior rejection, late rejection and nonadherence, pointing to an alloimmune aetiology. Nonadherence and late rejection were common in ABMR and TCMR, particularly Acute Active ABMR. Acute Active ABMR and nonadherence were associated with younger age, faster functional decline, and less hyalinosis on biopsy. Chronic and Chronic Active ABMR were more commonly associated with Class II DSA. C1q-binding DSA, detected in 33% of ABMR episodes, were associated with shorter time to graft failure. Most non-biopsied patients were DSA-negative (16/21; 76.1%). Finally, twelve losses to recurrent disease were seen (16%). Conclusion This data from an unselected population identifies IFTA alongside ABMR as a very important cause of true late graft failure, with nonadherence-associated TCMR as a phenomenon in some patients. It highlights clinical and immunological characteristics of ABMR subgroups, and should inform clinical practice and individualised patient care. PMID:27649571

The selectivity of responses to red-green colour and achromatic contrast in the human visual cortex: an fMRI adaptation study.

PubMed

Mullen, Kathy T; Chang, Dorita H F; Hess, Robert F

2015-12-01

There is controversy as to how responses to colour in the human brain are organized within the visual pathways. A key issue is whether there are modular pathways that respond selectively to colour or whether there are common neural substrates for both colour and achromatic (Ach) contrast. We used functional magnetic resonance imaging (fMRI) adaptation to investigate the responses of early and extrastriate visual areas to colour and Ach contrast. High-contrast red-green (RG) and Ach sinewave rings (0.5 cycles/degree, 2 Hz) were used as both adapting stimuli and test stimuli in a block design. We found robust adaptation to RG or Ach contrast in all visual areas. Cross-adaptation between RG and Ach contrast occurred in all areas indicating the presence of integrated, colour and Ach responses. Notably, we revealed contrasting trends for the two test stimuli. For the RG test, unselective processing (robust adaptation to both RG and Ach contrast) was most evident in the early visual areas (V1 and V2), but selective responses, revealed as greater adaptation between the same stimuli than cross-adaptation between different stimuli, emerged in the ventral cortex, in V4 and VO in particular. For the Ach test, unselective responses were again most evident in early visual areas but Ach selectivity emerged in the dorsal cortex (V3a and hMT+). Our findings support a strong presence of integrated mechanisms for colour and Ach contrast across the visual hierarchy, with a progression towards selective processing in extrastriate visual areas. © 2015 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Circulating neural antibodies in unselected children with new-onset seizures.

PubMed

Garcia-Tarodo, Stephanie; Datta, Alexandre N; Ramelli, Gian P; Maréchal-Rouiller, Fabienne; Bien, Christian G; Korff, Christian M

2018-05-01

The role of autoimmunity and neural antibodies is increasingly recognized in different forms of seizures and epilepsy. Their prevalence in new-onset epilepsy has also recently been the focus of several clinical cohorts in the adult and pediatric population, with positive titers in 10-11% of cases. Our aim was to determine the seropositivity at the first seizure onset in a non-selective group of children. We conducted a prospective multicenter cohort study recruiting children aged 0-16 years with new-onset seizures presenting at the In- and Outpatient Pediatric Neurology Departments of three Children's Hospitals in Switzerland between September 2013 and April 2016. Neural antibodies were screened within the first 6 months of a first seizure and when positive, repeated at 1 month and 6 months follow-up. A total of 103 children were enrolled with a mean age at presentation of 5 years (range 1 day-15 years 9 months). The majority (n = 75) presented with generalized seizures and 6 had status epilepticus lasting > 30 min. At the time of onset, 55% of patients had fever, 24% required emergency seizure treatment and 27% hospitalization. Epilepsy was diagnosed at follow-up in 18%. No specific antibody was found. Serum antibodies against the VGKC complex, without binding to the specific antigens LGI1 and CASPR2, were found in two patients. Four patients harbored not otherwise characterized antibodies against mouse neuropil. Specific neural antibodies are rarely found in an unselected population of children that present with a first seizure. Applying an extensive neuronal antibody profile in a child with new-onset seizures does not appear to be justified. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Caffeine intake and abstract reasoning among 1374 unselected men and women from general population. Role of the -163C>A polymorphism of CYP1A2 gene.

PubMed

Casiglia, Edoardo; Tikhonoff, Valérie; Albertini, Federica; Favaro, Jacopo; Montagnana, Martina; Danese, Elisa; Finatti, Francesco; Benati, Marco; Mazza, Alberto; Dal Maso, Lucia; Spinella, Paolo; Palatini, Paolo

2017-08-01

The possible effect of caffeine as an enhancer of cognitive performance, particularly that on abstract reasoning, has never been studied in an epidemiological setting, especially in relation to -163C>A polymorphism of CYP1A2 gene, largely controlling caffeine metabolism. Aim of this study was to ascertain whether in general population free chronic caffeine intake modifies abstract reasoning, and if this effect is influenced by the above mentioned genotype, by age, schooling, ethanol intake and smoking habits. We studied 1374 unselected men and women aged 51 ± 15 years (range 18-89) from a general population. Daily caffeine intake deriving from coffee, tea, chocolate or cola was calculated from an anamnestic questionnaire and from a 7-day dietary diary. Abstract reasoning was measured in the frame of a neuropsychological assessment as the ability to find a concept linking two words indicating objects or actions and explaining how they were connected. In age-schooling-adjusted linear regression, the higher the caffeine intake, the better the abstraction score. Abstract reasoning depended on caffeine in the -163C>A CC homozygous only (so-called slow metabolizers), where it was higher in the 3rd tertile of caffeine intake. Age and ethanol reduced while smoking and schooling enhanced this association. The interaction term between caffeine and the -163C>A polymorphism was accepted in linear regressions. Caffeine consumption resulted innocuous for the A-carriers (so-called fast metabolizers). In general population, a positive association between caffeine intake and abstract reasoning exists in the CC homozygous of the -163C>A polymorphism of CYP1A2 gene. Copyright © 2017 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

Terminal differentiation of T cells is strongly associated with CMV infection and increased in HIV-positive individuals on ART and lifestyle matched controls

PubMed Central

Booiman, Thijs; Wit, Ferdinand W.; Girigorie, Arginell F.; Maurer, Irma; De Francesco, Davide; Sabin, Caroline A.; Harskamp, Agnes M.; Prins, Maria; Franceschi, Claudio; Deeks, Steven G.; Winston, Alan; Reiss, Peter

2017-01-01

HIV-1-positive individuals on successful antiretroviral therapy (ART) are reported to have higher rates of age-associated non-communicable comorbidities (AANCCs). HIV-associated immune dysfunction has been suggested to contribute to increased AANCC risk. Here we performed a cross-sectional immune phenotype analysis of T cells in ART-treated HIV-1-positive individuals with undetectable vireamia (HIV-positives) and HIV-1-negative individuals (HIV-negatives) over 45 years of age. In addition, two control groups were studied: HIV negative adults selected based on lifestyle and demographic factors (Co-morBidity in Relation to AIDS, or COBRA) and unselected age-matched donors from a blood bank. Despite long-term ART (median of 12.2 years), HIV-infected adults had lower CD4+ T-cell counts and higher CD8+ T-cell counts compared to well-matched HIV-negative COBRA participants. The proportion of CD38+HLA-DR+ and PD-1+ CD4+ T-cells was higher in HIV-positive cohort compared to the two HIV-negative cohorts. The proportion CD57+ and CD27−CD28− cells of both CD4+ and CD8+ T-cells in HIV-positives was higher compared to unselected adults (blood bank) as reported before but this difference was not apparent in comparison with well-matched HIV-negative COBRA participants. Multiple regression analysis showed that the presence of an increased proportion of terminally differentiated T cells was strongly associated with CMV infection. Compared to appropriately selected HIV-negative controls, HIV-positive individuals on ART with long-term suppressed viraemia exhibited incomplete immune recovery and increased immune activation/exhaustion. CMV infection rather than treated HIV infection appears to have more consistent effects on measures of terminal differentiation of T cells. PMID:28806406

Epigenetic Alterations in Density Selected Human Spermatozoa for Assisted Reproduction.

PubMed

Yu, Bolan; Zhou, Hua; Liu, Min; Zheng, Ting; Jiang, Lu; Zhao, Mei; Xu, Xiaoxie; Huang, Zhaofeng

2015-01-01

Epidemiological evidence indicates that assisted reproductive technologies (ART) may be associated with several epigenetic diseases such as Beckwith-Wiedemann syndrome (BWS) or Silver-Russell syndrome (SRS). Selection of sperm by density-gradients in ART has improved DNA integrity and sperm quality; however, epigenetic alterations associated with this approach are largely unknown. In the present study, we investigated DNA methylation and histone retention profiles in raw sperm and selected sperm derived from the same individual and separated by using density-gradients. Results from a study group consisting of 93 males demonstrated that both global DNA methylation and histone retention levels decreased in density selected sperm. Compared to unselected raw sperm, histone transition rates decreased by an average of 27.2% in selected sperm, and the global methylation rate was 3.8% in unselected sperm and 3.3% in the selected sperm. DNA methylation and histone retention location profiling analyses suggested that these alterations displayed specific location patterns in the human genome. Changes in the pattern of hypomethylation largely occurred in transcriptional factor gene families such as HOX, FOX, and GATA. Histone retention increased in 67 genes, whereas it was significantly clustered in neural development-related gene families, particularly the olfactory sensor gene family. Although a causative relationship could not be established, the results of the present study suggest the possibility that sperm with good density also possess unique epigenetic profiles, particularly for genes involved in neural and olfactory development. As increasing evidence demonstrates that epigenetics plays a key role in embryonic development and offspring growth characteristics, the specific epigenetic alterations we observed in selected sperm may influence the transcriptional process and neural development in embryos.

Epigenetic Alterations in Density Selected Human Spermatozoa for Assisted Reproduction

PubMed Central

Yu, Bolan; Zhou, Hua; Liu, Min; Zheng, Ting; Jiang, Lu; Zhao, Mei; Xu, Xiaoxie; Huang, Zhaofeng

2015-01-01

Epidemiological evidence indicates that assisted reproductive technologies (ART) may be associated with several epigenetic diseases such as Beckwith-Wiedemann syndrome (BWS) or Silver-Russell syndrome (SRS). Selection of sperm by density-gradients in ART has improved DNA integrity and sperm quality; however, epigenetic alterations associated with this approach are largely unknown. In the present study, we investigated DNA methylation and histone retention profiles in raw sperm and selected sperm derived from the same individual and separated by using density-gradients. Results from a study group consisting of 93 males demonstrated that both global DNA methylation and histone retention levels decreased in density selected sperm. Compared to unselected raw sperm, histone transition rates decreased by an average of 27.2% in selected sperm, and the global methylation rate was 3.8% in unselected sperm and 3.3% in the selected sperm. DNA methylation and histone retention location profiling analyses suggested that these alterations displayed specific location patterns in the human genome. Changes in the pattern of hypomethylation largely occurred in transcriptional factor gene families such as HOX, FOX, and GATA. Histone retention increased in 67 genes, whereas it was significantly clustered in neural development-related gene families, particularly the olfactory sensor gene family. Although a causative relationship could not be established, the results of the present study suggest the possibility that sperm with good density also possess unique epigenetic profiles, particularly for genes involved in neural and olfactory development. As increasing evidence demonstrates that epigenetics plays a key role in embryonic development and offspring growth characteristics, the specific epigenetic alterations we observed in selected sperm may influence the transcriptional process and neural development in embryos. PMID:26709917

CHEK2 mutations and the risk of papillary thyroid cancer.

PubMed

Siołek, Monika; Cybulski, Cezary; Gąsior-Perczak, Danuta; Kowalik, Artur; Kozak-Klonowska, Beata; Kowalska, Aldona; Chłopek, Małgorzata; Kluźniak, Wojciech; Wokołorczyk, Dominika; Pałyga, Iwona; Walczyk, Agnieszka; Lizis-Kolus, Katarzyna; Sun, Ping; Lubiński, Jan; Narod, Steven A; Góźdż, Stanisław

2015-08-01

Mutations in the cell cycle checkpoint kinase 2 (CHEK2) tumor suppressor gene are associated with multi-organ cancer susceptibility including cancers of the breast and prostate. A genetic association between thyroid and breast cancer has been suggested, however little is known about the determinants of this association. To characterize the association of CHEK2 mutations with thyroid cancer, we genotyped 468 unselected patients with papillary thyroid cancer and 468 (matched) cancer-free controls for four founder mutations of CHEK2 (1100delC, IVS2 + 1G>A, del5395 and I157T). We compared the family histories reported by patients with a CHEK2 mutation to those of non-carriers. A CHEK2 mutation was seen in 73 of 468 (15.6%) unselected patients with papillary thyroid cancer, compared to 28 of 460 (6.0%) age- and sex-matched controls (OR 3.3; p < 0.0001). A truncating mutation (IVS2 + 1G>A, 1100delC or del5395) was associated with a higher risk of thyroid cancer (OR = 5.7; p = 0.006), than was the missense mutation I157T (OR = 2.8; p = 0.0001). CHEK2 mutation carriers reported a family history of breast cancer 2.2 times more commonly than non-carriers (16.4% vs.8.1%; p = 0.05). A CHEK2 mutation was found in seven of 11 women (63%) with multiple primary cancers of the breast and thyroid (OR = 10; p = 0.0004). These results suggest that CHEK2 mutations predispose to thyroid cancer, familial aggregations of breast and thyroid cancer and to double primary cancers of the breast and thyroid. © 2015 UICC.

Impact of the introduction of a standardised ICD programming protocol: real-world data from a single centre.

PubMed

Sunderland, Nicholas; Kaura, Amit; Li, Anthony; Kamdar, Ravi; Petzer, Ed; Dhillon, Para; Murgatroyd, Francis; Scott, Paul A

2016-09-01

Randomised trials have shown that empiric ICD programming, using long detection times and high detection zones, reduces device therapy in ICD recipients. However, there is less data on its effectiveness in a "real-world" setting, especially secondary prevention patients. Our aim was to evaluate the introduction of a standardised programming protocol in a real-world setting of unselected ICD recipients. We analysed 270 consecutive ICD recipients implanted in a single centre-135 implanted prior to protocol implementation (physician-led group) and 135 after (standardised group). The protocol included long arrhythmia detection times (30/40 or equivalent) and high rate detection zones (primary prevention lower treatment zone 200 bpm). Programming in the physician-led group was at the discretion of the implanter. The primary endpoint was time-to-any therapy (ATP or shocks). Secondary endpoints were time-to-inappropriate therapy and time-to-appropriate therapy. The safety endpoints were syncopal episodes, hospital admissions and death. At 12 months follow-up, 47 patients had received any ICD therapy (physician-led group, n = 31 vs. standardised group, n = 16). There was a 47 % risk reduction in any device therapy (p = 0.04) and an 86 % risk reduction in inappropriate therapy (p = 0.009) in the standardised compared to the physician-led group. There was a non-significant 30 % risk reduction in appropriate therapy (p = 0.32). Results were consistent across primary and secondary prevention patients. There were no significant differences in the rates of syncope, hospitalisation, and death. In unselected patients in a real-world setting, introduction of a standardised programming protocol, using long detection times and high detection zones, significantly reduces the burden of ICD therapy without an increase in adverse outcomes.

Evaluation of the Dutch BRCA1/2 clinical genetic center referral criteria in an unselected early breast cancer population

PubMed Central

van den Broek, Alexandra J; de Ruiter, Karen; van 't Veer, Laura J; Tollenaar, Rob A E M; van Leeuwen, Flora E; Verhoef, Senno; Schmidt, Marjanka K

2015-01-01

In this study, we evaluated the diagnostic value of the Dutch Clinical Genetic Center (CGC) referral guidelines for BRCA1/2 mutation testing in 903 early breast cancer patients, unselected for family history, diagnosed in a cancer hospital before the age of 50 years in 1974–2002; most prevalent Dutch pathogenic BRCA1/2 mutations had been analyzed on coded DNA in a research setting. Forty-nine (5.4%) of the patients were proven to be BRCA1/2 mutation carriers. We found that 78% and 69% of BRCA1 and BRCA2 mutation carriers identified met the criteria for referral to the CGC based on age, family history and synchronous multiple tumors; reflected by a combined sensitivity of 75.5% and specificity of 63.2%. More than half of the BRCA1 mutation carriers, that is, 58% had a triple-negative tumor. The highest AUC was obtained by shifting the age at diagnosis threshold criterion from 40 to 35 years and by adding a ‘triple-negative breast cancer' criterion with an age threshold of 45 years; the specificity increased to 71.2%, whereas the sensitivity remained the same; that is, a referral of fewer patients will lead to the identification of at least the same number of BRCA1/2 mutation carriers. Two-thirds of the BRCA1/2 mutation carriers identified in this research setting had been referred for counseling and testing. Our results indicate that, awaiting a possibly more extended mutation screening of all breast cancer patients, the triple-negative status of a breast cancer should be added to the CGC referral criteria. PMID:25138101

The Importance of Accuracy, Stimulating writing, and Relevance in Middle School Science Textbook Writing

NASA Astrophysics Data System (ADS)

Hubisz, John

2004-05-01

While accuracy in Middle School science texts is most important, the texts should also read well, stimulating the student to want to go on, and the material must be relevant to the subject at hand as the typical student is not yet prepared to ignore that which is irrelevant. We know that children will read if the material is of interest (witness The Lord of the Rings and the Harry Potter book sales) and so we must write in a way that stimulates the student to want to examine the subject further and eliminate that which adds nothing to the discipline. Examples of the good and the bad will be presented.

Reflective Practice in a Capstone Business Internship Subject

ERIC Educational Resources Information Center

Lang, Roselynn; McNaught, Keith

2013-01-01

Purpose: Capstone subjects which link students approaching graduation with significant experiential learning and relevant industry placements, have the potential to be very valuable to students. This is particularly evident if they are able to critically reflect on the experience. In light of this, the School of Business at the University of Notre…

Applications of Tutoring Systems in Specialized Subject Areas: An Analysis of Skills, Methodologies, and Results.

ERIC Educational Resources Information Center

Heron, Timothy E.; Welsch, Richard G.; Goddard, Yvonne L.

2003-01-01

This article reviews how tutoring systems have been applied across specialized subject areas (e.g., music, horticulture, health and safety, social interactions). It summarizes findings, provides an analysis of skills learned within each tutoring system, identifies the respective methodologies, and reports relevant findings, implications, and…

Subject-Matter Determines Method.

ERIC Educational Resources Information Center

Guth, Hans P.

Only the approach that integrates a study of both the "what" and the "how" of a discipline will be relevant to the practicing English teacher. Missing between the two extremes of specialized subject matter research and conventional educational research is research into the structure of a particular discipline, exploring it as a body of knowledge,…

Self-Evaluative Reactions: The Role of Personal Valuation of the Activity.

ERIC Educational Resources Information Center

Simon, Karen M.

The differential activation of self-evaluative reactions to performance attainments on tasks varying on their relevance for subjects' sense of personal adequacy was investigated. All subjects (N=97) spoke extemporaneously on prescribed topics and received the same random sequence of performance scores. The same task was designated as assessing…

Factors Influencing the Accuracy of Verbal Reports of Conversational Behavior.

ERIC Educational Resources Information Center

Benoit, William L.; Benoit, Pamela J.

1989-01-01

Investigates (1) whether subjects consult their memory or relevant implicit theories when making verbal reports, and (2) the effect of recognition criterion on verbal report performance. Finds that subjects occasionally employ implicit theories to develop their verbal reports, but that memory is much more important in determining the reports. (MM)

Cerebral atrophy in elderly with subjective memory complaints.

PubMed

Palm, Walter M; Ferrarini, Luca; van der Flier, Wiesje M; Westendorp, Rudi G J; Bollen, Eduard L E M; Middelkoop, Huub A M; Milles, Julien R; van der Grond, Jeroen; van Buchem, Mark A

2013-08-01

To evaluate ventricular shape differences along the complete surface of the lateral and third ventricles of persons with subjective memory complaints (MC). We included 28 controls and 21 persons with MC. FLAIR, T2, and PD-weighted brain MRI scans were acquired at 1.5 Tesla, followed by semi-automated segmentation of the lateral and third ventricles, and local shape difference analysis based on growing and adaptive meshes. Ventricular meshes were used to highlight local areas with significant differences between controls and persons with MC, determined by permutation tests with a predefined threshold (P = 0.01). Compared with control subjects, relevant differences were found in the shape of the ventricular surface adjacent to the thalamus and corona radiata in persons with MC. Before correction for multiple comparisons, relevant differences were also found in the shape of the ventricular surface adjacent to the corpus callosum, hippocampus, and amydala. Our findings suggest the presence of localized structural brain differences in patients with subjective memory complaints in the thalamus and the corona radiata. Copyright © 2013 Wiley Periodicals, Inc.

Ten Years of Spatial Disorientation in U.S. Army Rotary-Wing Operations (Reprint)

DTIC Science & Technology

2012-10-01

and reinforces the importance and relevance of SD awareness, research, education , and training in RW operations. Aviation, Space, and Environmental...and relevance of SD awareness, research, education , and training in RW operations. Keywords: spatial disorientation , aircraft accidents...generally included the areas of awareness, research, education and training, and technological initiatives. A thorough treatment of this subject is

Hexavalent and trivalent chromium in leather: What should be done?

PubMed

Moretto, Angelo

2015-11-01

Trivalent chromium compounds are used for leather tanning, and chromium may be released during use of leather goods. In certain instances, small amounts of hexavalent chromium can be formed and released. Both trivalent and hexavalent chromium can elicit allergic skin reaction in chromium sensitised subjects, the latter being significantly more potent. Induction of sensitisation only occurs after exposure to hexavalent chromium. A minority of subjects are sensitised to chromium, and in a fraction of these subjects allergic skin reaction have been described after wearing leather shoes or, less frequently, other leather goods. The evidence that in all these cases the reaction is related to hexavalent chromium is not always strong. The content of hexavalent chromium in leather is regulated in European Union, but rate of release rather than content is relevant for allergic skin reaction. The role of trivalent chromium appear much less relevant if at all. Modern tanning procedure do not pose significant risk due to either hexavalent or trivalent chromium. Dismissing bad quality and worn-off leather goods is relevant in reducing or eliminating the skin reaction. It should also be pointed out that shoe components or substances other than chromium in leather may cause allergic/irritative skin reactions. Copyright © 2015 Elsevier Inc. All rights reserved.

Irrelevant Features of a Stimulus Can Either Facilitate or Disrupt Performance in a Working Memory Task: The Role of Fluid Intelligence

PubMed Central

Perfetti, Bernardo; Tesse, Marcello; Varanese, Sara; Saggino, Aristide; Onofrj, Marco

2011-01-01

It has been shown that fluid intelligence (gf) is fundamental to overcome interference due to information of a previously encoded item along a task-relevant domain. However, the biasing effect of task-irrelevant dimensions is still unclear as well as its relation with gf. The present study aimed at clarifying these issues. Gf was assessed in 60 healthy subjects. In a different session, the same subjects performed two versions (letter-detection and spatial) of a three-back working memory task with a set of physically identical stimuli (letters) presented at different locations on the screen. In the letter-detection task, volunteers were asked to match stimuli on the basis of their identity whereas, in the spatial task, they were required to match items on their locations. Cross-domain bias was manipulated by pseudorandomly inserting a match between the current and the three back items on the irrelevant domain. Our findings showed that a task-irrelevant feature of a salient stimulus can actually bias the ongoing performance. We revealed that, at trials in which the current and the three-back items matched on the irrelevant domain, group accuracy was lower (interference). On the other hand, at trials in which the two items matched on both the relevant and irrelevant domains, the group showed an enhancement of the performance (facilitation). Furthermore, we demonstrated that individual differences in fluid intelligence covaries with the ability to override cross-domain interference in that higher gf subjects showed better performance at interference trials than low gf subjects. Altogether, our findings suggest that stimulus features irrelevant to the task can affect cognitive performance along the relevant domain and that gf plays an important role in protecting relevant memory contents from the hampering effect of such a bias. PMID:22022580

Cue-reactivity in behavioral addictions: A meta-analysis and methodological considerations.

PubMed

Starcke, Katrin; Antons, Stephanie; Trotzke, Patrick; Brand, Matthias

2018-05-23

Background and aims Recent research has applied cue-reactivity paradigms to behavioral addictions. The aim of the current meta-analysis is to systematically analyze the effects of learning-based cue-reactivity in behavioral addictions. Methods The current meta-analysis includes 18 studies (29 data sets, 510 participants) that have used a cue-reactivity paradigm in persons with gambling (eight studies), gaming (nine studies), or buying (one study) disorders. We compared subjective, peripheral physiological, electroencephal, and neural responses toward addiction-relevant cues in patients versus control participants and toward addiction-relevant cues versus control cues in patients. Results Persons with behavioral addictions showed higher cue-reactivity toward addiction-relevant cues compared with control participants: subjective cue-reactivity (d = 0.84, p = .01) and peripheral physiological and electroencephal measures of cue-reactivity (d = 0.61, p < .01). Increased neural activation was found in the caudate nucleus, inferior frontal gyrus, median cingulate cortex, subgenual cingulate, and precentral gyrus. Persons with gambling, gaming, or buying disorders also showed higher cue-reactivity toward addiction-relevant cues compared with control cues: subjective cue-reactivity (d = 0.39, p = .11) and peripheral physiological and electroencephal measures of cue-reactivity (d = 0.47, p = .05). Increased neural activation was found in the caudate nucleus, inferior frontal gyrus, angular gyrus, inferior network, and precuneus. Discussion and conclusions Cue-reactivity not only exists in substance-use disorders but also in gambling, gaming, and buying disorders. Future research should differentiate between cue-reactivity in addictive behaviors and cue-reactivity in functional excessive behaviors such as passions, hobbies, or professions.

Classical subjective expected utility.

PubMed

Cerreia-Vioglio, Simone; Maccheroni, Fabio; Marinacci, Massimo; Montrucchio, Luigi

2013-04-23

We consider decision makers who know that payoff-relevant observations are generated by a process that belongs to a given class M, as postulated in Wald [Wald A (1950) Statistical Decision Functions (Wiley, New York)]. We incorporate this Waldean piece of objective information within an otherwise subjective setting à la Savage [Savage LJ (1954) The Foundations of Statistics (Wiley, New York)] and show that this leads to a two-stage subjective expected utility model that accounts for both state and model uncertainty.

The effects of alcohol mixed with energy drink (AMED) on subjective intoxication and alertness: results from a double-blind placebo-controlled clinical trial.

PubMed

van de Loo, Aurora J A E; van Andel, Nienke; van Gelder, Charlotte A G H; Janssen, Boris S G; Titulaer, Joep; Jansen, Jimmy; Verster, Joris C

2016-05-01

The purpose of this double blind placebo controlled study was to examine if specific effects on subjective intoxication and alertness-sleepiness ratings could be demonstrated after consuming alcohol mixed with energy drink (AMED) when compared to consuming alcohol only (AO). 56 healthy volunteers rated their subjective intoxication on a scale ranging from 0 (sober) to 10 (highly intoxicated) at baseline, breath alcohol concentration (BAC) of 0%, and at BAC 0.08%, 0.05%, and 0.02%. Alertness-sleepiness was assessed with the Karolinska sleepiness scale. Scores of the AMED and AO condition, at each BAC level, were compared. Subjective intoxication for AMED and AO did not differ significantly from each other at any BAC level, except for BAC 0.02%. A significant increase in sleepiness scores was found in the AO condition, whereas scores remained stable in the AMED condition. Sleepiness scores at BAC0.08% and 0.05% were significantly lower after AMED when compared to AO. However, the observed differences between AMED and AO were small and have no clinical relevance. Mixing alcohol with energy drink had no overall masking effect on subjective intoxication caused by alcohol, nor had a relevant effect on subjective alertness-sleepiness ratings. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The Future for Mathematics Subject Associations

ERIC Educational Resources Information Center

Pope, Sue

2012-01-01

Subject associations have developed, over the years, to serve the interests of the mathematics education community. We live in changing times, and education is often at the forefront of such change. So, to remain contemporary, relevant, and to have a regard for the future in a world influenced by technology, it is suggested that there is a need…

Physics Practical Work and Its Influence on Students' Academic Achievement

ERIC Educational Resources Information Center

Musasia, Amadalo Maurice; Ocholla, Alphayo Abacha; Sakwa, Thomas Welikhe

2016-01-01

In Kenyan secondary schools, form two is an important class for all students. The students choose relevant subjects to study in form three and four. Physics is compulsory at form one and two but optional thereafter. Performance in the subject at the end of the secondary school is usually dismal. Majority of students lack motivation for most…

One Secondary School's Subject-Area Teachers' Perspectives on Co-Teaching Students with Special Needs

ERIC Educational Resources Information Center

Legutko, Robert S.

2015-01-01

This study is an action research study conducted at one rural northeastern Pennsylvania junior/senior high school to gain secondary education subject-area teacher's perspectives on educating students with special needs in a co-teaching environment. A written open-ended questionnaire was issued to relevant faculty members which determined that…

Instance, Cue, and Dimension Learning in Concept Shift Task.

ERIC Educational Resources Information Center

Prentice, Joan L.; Panda, Kailas C.

Experiment I was designed to demonstrate that young children fail to abstract the positive cue as the relevant stimulus event in a restricted concept-learning task. Sixteen kindergarten and 16 fourth grade subjects were trained to criterion on a Kendler-type task, whereupon each subject was presented a pair of new instances which contrasted only…

Work-Based Learning, Power and Subjectivity: Creating Space for a Foucauldian Research Ethic

ERIC Educational Resources Information Center

Zemblyas, Michalinos

2006-01-01

This paper aims at problematizing the context of power relations and politics while engaging in work-based learning (WBL). The author uses Foucault's ideas on power/knowledge, ethics and subjectivity to show that he has something to say of particular relevance and importance to those engaged in WBL. Foucauldian ideas make possible an interrogation…

77 FR 61028 - Hasbro, Inc.; Hasbro Managerial Services, Inc., Including On-Site Leased Workers of Entegee East...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-05

... relevant period and that the subject firm had sufficient control over the leased workers for the Department to determine that there was operational control of the leased workers by the subject firm. The... Managerial Services, Inc., Including On-Site Leased Workers of Entegee East Longmeadow, MA Amended...

The Need for Inclusion of Entrepreneurship Education in Malaysia Lower and Higher Learning Institutions

ERIC Educational Resources Information Center

Ahmad, Syed Zamberi

2013-01-01

Purpose: The aim of this paper is to focus on relevant issues of entrepreneurship education, such as target groups for the subject. It advocates the need for inclusion of entrepreneurship education as a subject in the curricula of all primary, secondary and tertiary learning institutions in Malaysia and other developing countries.…

Teachers in School Sports: Between the Fields of Education and Sport?

ERIC Educational Resources Information Center

Ferry, Magnus

2016-01-01

According to the cultural sociologist Pierre Bourdieu, gaining access to a social space or a position within a social space requires a specific capital. For teachers, this is normally indicated by a valid teaching certificate with relevant subject knowledge. However, when no qualified teachers are available, which is the case for the subject of…

Fluorescence Imaging/Agents in Tumor Resection.

PubMed

Stummer, Walter; Suero Molina, Eric

2017-10-01

Intraoperative fluorescence imaging allows real-time identification of diseased tissue during surgery without being influenced by brain shift and surgery interruption. 5-Aminolevulinic acid, useful for malignant gliomas and other tumors, is the most broadly explored compound approved for fluorescence-guided resection. Intravenous fluorescein sodium has recently received attention, highlighting tumor tissue based on extravasation at the blood-brain barrier (defective in many brain tumors). Fluorescein in perfused brain, unselective extravasation in brain perturbed by surgery, and propagation with edema are concerns. Fluorescein is not approved but targeted fluorochromes with affinity to brain tumor cells, in development, may offer future advantages. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Exploiting Molecular and Immune Biology of Gastric and Gastroesophageal Adenocarcinomas to Discover Novel Therapeutic Targets.

PubMed

Elimova, Elena; Song, Shumei; Shimodaira, Yusuke; Lin, Quan; Ajani, Jaffer A

2016-11-01

Gastroesophageal carcinomas (GACs) are a significant problem worldwide, and despite many attempts to improve the outcomes of patients with these tumors, little progress has been made over the last several decades. In the past decade, only transtuzumab and ramucirumab, two drugs with marginal clinical benefit, have been approved for the treatment of patients with GACs. After second-line therapy, most treatment options are generally ineffective. Prior studies in this disease have been largely empiric, using unselected patient populations. More recently, detailed somatic genotyping, enrichment of patients based on biomarkers, and pharmacokinetic studies have opened new avenues for developing treatment options in patients with GAC.

Precancerous lesions of the cervix uteri in infertile women.

PubMed Central

Holst, N; Abyholm, T

1983-01-01

A study of 318 patients with tubal infertility and a control group of 200 unselected infertile women yielded 14 (4.4%) and 1 (0.5%), respectively, with precancerous lesions of the cervix uteri. The one patient in the control group with severe dysplasia was later shown to have tubal infertility. The overall incidence of premalignant lesions of the cervix uteri as reported to the National Cancer Registry of Norway was 0.1% for the age group and period studied. Women with tubal infertility represent a small but comparatively high risk group for the development of precancerous lesions of the cervix uteri. PMID:6412931

Estimate of the fetal temperature increase due to UHF RFID exposure.

PubMed

Fiocchi, S; Markakis, I A; Liorni, I; Parazzini, M; Samaras, T; Ravazzani, P

2013-01-01

Exposure from electromagnetic (EM) devices has increased during the last decades due to the rapid development of new technologies. Among them, radiofrequency identification (RFID) applications are used in almost every aspect of everyday life, which could expose people unselectively. This scenario could pose potential risks for certain groups of general population, such as pregnant women, who are more sensitive to thermal effects produced by EM exposure. In this paper, the temperature rise at the steady state in two pregnant women models exposed to UHF RFID has been assessed. Results show that heating of tissues is far from the threshold of biological effects indicated by radiation protection guidelines.

Anosognosia for obvious visual field defects in stroke patients.

PubMed

Baier, Bernhard; Geber, Christian; Müller-Forell, Wiebke; Müller, Notger; Dieterich, Marianne; Karnath, Hans-Otto

2015-01-01

Patients with anosognosia for visual field defect (AVFD) fail to recognize consciously their visual field defect. There is still unclarity whether specific neural correlates are associated with AVFD. We studied AVFD in 54 patients with acute stroke and a visual field defect. Nineteen percent of this unselected sample showed AVFD. By using modern voxelwise lesion-behaviour mapping techniques we found an association between AVFD and parts of the lingual gyrus, the cuneus as well as the posterior cingulate and corpus callosum. Damage to these regions appears to induce unawareness of visual field defects and thus may play a significant role for conscious visual perception.

Brown Nail-bed Arcs and Chronic Renal Disease

PubMed Central

Stewart, W. K.; Raffle, E. J.

1972-01-01

A brown arc affecting the distal part of the fingernail-bed, just proximal to the point of separation of the nail from its bed, has been found in 12 out of 34 patients with chronic renal disease (35%) compared with an incidence of less than 2% in a series of unselected patients. It represents a distinctive form of pigmentation, possibly due to lipochromes. No decisive association could be found between the presence or absence of the pigmented nail arc and the level of impaired renal function. Nevertheless it seems that renal disease predisposes towards the development of brown nail arcs. Imagesp786-a PMID:5014252

An Exploration of the Relevance of the Pedagogy and Academic Content Knowledge That Are Offered to Prospective Science and Mathematics Teachers in Tanzania Teachers' Colleges

ERIC Educational Resources Information Center

Mungure, Daudi Mika

2016-01-01

This paper explored the Relevance of the Pedagogy and Academic Content Knowledge that are offered to Prospective Science and Mathematics Teachers in Tanzania Teachers' colleges. Morogoro Teachers' College and Kleruu Teachers' college were used as a case study. The performance in science and mathematics subjects in form four National examinations…

Resilience Among Students at the Basic Enlisted Submarine School

DTIC Science & Technology

2016-12-01

reported resilience. The Hayes’ Macro in the Statistical Package for the Social Sciences (SSPS) was used to uncover factors relevant to mediation analysis... Statistical Package for the Social Sciences (SPSS) was used to uncover factors relevant to mediation analysis. Findings suggest that the encouragement of...to Stressful Experiences Scale RTC Recruit Training Command SPSS Statistical Package for the Social Sciences SS Social Support SWB Subjective Well

Parallel workflow tools to facilitate human brain MRI post-processing

PubMed Central

Cui, Zaixu; Zhao, Chenxi; Gong, Gaolang

2015-01-01

Multi-modal magnetic resonance imaging (MRI) techniques are widely applied in human brain studies. To obtain specific brain measures of interest from MRI datasets, a number of complex image post-processing steps are typically required. Parallel workflow tools have recently been developed, concatenating individual processing steps and enabling fully automated processing of raw MRI data to obtain the final results. These workflow tools are also designed to make optimal use of available computational resources and to support the parallel processing of different subjects or of independent processing steps for a single subject. Automated, parallel MRI post-processing tools can greatly facilitate relevant brain investigations and are being increasingly applied. In this review, we briefly summarize these parallel workflow tools and discuss relevant issues. PMID:26029043

Application of HRV-CD for estimation of life expectancy in various clinical disorders.

PubMed

Almoznino-Sarafian, Dorit; Sarafian, Gideon; Zyssman, Itzhak; Shteinshnaider, Miriam; Tzur, Irma; Kaplan, Ben-Zion; Berman, Sylvia; Cohen, Natan; Gorelik, Oleg

2009-12-01

Low heart rate variability (HRV) was found in various medical conditions including heart failure and acute myocardial infarction. Decreased HRV in these conditions predicted poor prognosis. HRV was estimated in 133 unselected inpatients with relevant clinical bedside conditions by non-linear analysis derived from chaos theory, which calculates the correlation dimension (CD) of the cardiac electrophysiologic system (HRV-CD). Mean HRV-CD in the entire group was 3.75+/-0.45. Heart failure, coronary artery disease, cardiac arrhythmia, low serum potassium, renal dysfunction, and diabetes mellitus were significantly associated with reduced HRV-CD compared to their counterparts [3.6 vs. 3.9 (P<.001), 3.65 vs. 3.87 (P=.005), 3.58 vs. 3.8 (P=.01), 3.38 vs. 3.81 (P=.02), 3.59 vs. 3.8 (P=.04), and 3.66 vs. 3.82 (P=.04), respectively]. Stepwise logistic regression showed heart failure to be the condition most significantly associated with low HRV-CD (odds ratio 4.2, 95% confidence interval 1.90-9.28, P<.001). In the entire group, decreased HRV-CD (< or =3.75 vs. >3.75) was associated with lower survival (P=.01). Mortality of diabetic patients with HRV-CD < or =3.75 exceeded the mortality in patients with HRV-CD >3.75 (P=.02). Heart failure, renal dysfunction or age over 70 combined with HRV-CD < or =3.75 also appeared to be associated with augmented mortality. Diminished HRV-CD is associated with heart failure, coronary artery disease, cardiac arrhythmia, renal dysfunction, diabetes mellitus and low serum potassium. Among the latter, heart failure is most significantly associated with decreased HRV-CD. Decreased HRV-CD values, especially in diabetics, are also associated with lower survival.

Reproducibility and reliability of the ankle-brachial index as assessed by vascular experts, family physicians and nurses.

PubMed

Holland-Letz, Tim; Endres, Heinz G; Biedermann, Stefanie; Mahn, Matthias; Kunert, Joachim; Groh, Sabine; Pittrow, David; von Bilderling, Peter; Sternitzky, Reinhardt; Diehm, Curt

2007-05-01

The reliability of ankle-brachial index (ABI) measurements performed by different observer groups in primary care has not yet been determined. The aims of the study were to provide precise estimates for all effects influencing the variability of the ABI (patients' individual variability, intra- and inter-observer variability), with particular focus on the performance of different observer groups. Using a partially balanced incomplete block design, 144 unselected individuals aged > or = 65 years underwent double ABI measurements by one vascular surgeon or vascular physician, one family physician and one nurse with training in Doppler sonography. Three groups comprising a total of 108 individuals were analyzed (only two with ABI < 0.90). Errors for two repeated measurements for all three observer groups did not differ (experts 8.5%, family physicians 7.7%, and nurses 7.5%, p = 0.39). There was no relevant bias among observer groups. Intra-observer variability expressed as standard deviation divided by the mean was 8%, and inter-observer variability was 9%. In conclusion, reproducibility of the ABI measurement was good in this cohort of elderly patients who almost all had values in the normal range. The mean error of 8-9% within or between observers is smaller than with established screening measures. Since there were no differences among observers with different training backgrounds, our study confirms the appropriateness of ABI assessment for screening peripheral arterial disease (PAD) and generalized atherosclerosis in the primary case setting. Given the importance of the early detection and management of PAD, this diagnostic tool should be used routinely as a standard for PAD screening. Additional studies will be required to confirm our observations in patients with PAD of various severities.

Stanniocalcin 2 is an estrogen-responsive gene coexpressed with the estrogen receptor in human breast cancer.

PubMed

Bouras, Toula; Southey, Melissa C; Chang, Andy C; Reddel, Roger R; Willhite, Dorian; Glynne, Richard; Henderson, Michael A; Armes, Jane E; Venter, Deon J

2002-03-01

Differences in gene expression are likely to explain the phenotypic variation between hormone-responsive and hormone-unresponsive breast cancers. In this study, DNA microarray analysis of approximately 10,000 known genes and 25,000 expressed sequence tag clusters was performed to identify genes induced by estrogen and repressed by the pure antiestrogen ICI 182 780 in vitro that correlated with estrogen receptor (ER) expression in primary breast carcinomas in vivo. Stanniocalcin (STC) 2 was identified as one of the genes that fulfilled these criteria. DNA microarray hybridization showed a 3-fold induction of STC2 mRNA expression in MCF-7 cells in < or = 3 h of estrogen exposure and a 3-fold repression in the presence of antiestrogen (one-way ANOVA, P < 0.0005). In 13 ER-positive and 12 ER-negative breast carcinomas, the microarray-derived mRNA levels observed for STC2 correlated with tumor ER mRNA (Pearson's correlation, r = 0.85; P < 0.0001) and ER protein status (Spearman's rank correlation, r = 0.73; P < 0.0001). The expression profile of STC2 was further confirmed by in situ hybridization and immunohistochemistry on a larger cohort of 236 unselected breast carcinomas using tissue microarrays. STC2 mRNA and protein expression were found to be associated with tumor ER status (Fisher's exact test, P < 0.005). The related gene, STC1, was also examined and shown to be associated with ER status in breast carcinomas (Fisher's exact test, P < 0.05). This study demonstrates the feasibility of using global gene expression data derived from an in vitro model to pinpoint novel estrogen-responsive genes of potential clinical relevance.

Common variants in genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1/2), adiponectin concentrations, and diabetes incidence in the Diabetes Prevention Program

PubMed Central

Mather, K. J.; Christophi, C. A.; Jablonski, K. A.; Knowler, W. C.; Goldberg, R. B.; Kahn, S. E.; Spector, T.; Dastani, Z.; Waterworth, D.; Richards, J. B.; Funahashi, T.; Pi-Sunyer, F. X.; Pollin, T. I.; Florez, J. C.; Franks, P. W.

2012-01-01

Aims Baseline adiponectin concentrations predict incident Type 2 diabetes mellitus in the Diabetes Prevention Program. We tested the hypothesis that common variants in the genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1, ADIPOR2) would associate with circulating adiponectin concentrations and/or with diabetes incidence in the Diabetes Prevention Program population. Methods Seventy-seven tagging single-nucleotide polymorphisms (SNPs) in ADIPOQ (24), ADIPOR1 (22) and ADIPOR2 (31) were genotyped. Associations of SNPs with baseline adiponectin concentrations were evaluated using linear modelling. Associations of SNPs with diabetes incidence were evaluated using Cox proportional hazards modelling. Results Thirteen of 24 ADIPOQ SNPs were significantly associated with baseline adiponectin concentrations. Multivariable analysis including these 13 SNPs revealed strong independent contributions from rs17366568, rs1648707, rs17373414 and rs1403696 with adiponectin concentrations. However, no ADIPOQ SNPs were directly associated with diabetes incidence. Two ADIPOR1 SNPs (rs1342387 and rs12733285) were associated with ~18% increased diabetes incidence for carriers of the minor allele without differences across treatment groups, and without any relationship with adiponectin concentrations. Conclusions ADIPOQ SNPs are significantly associated with adiponectin concentrations in the Diabetes Prevention Program cohort. This observation extends prior observations from unselected populations of European descent into a broader multi-ethnic population, and confirms the relevance of these variants in an obese/dysglycaemic population. Despite the robust relationship between adiponectin concentrations and diabetes risk in this cohort, variants in ADIPOQ that relate to adiponectin concentrations do not relate to diabetes risk in this population. ADIPOR1 variants exerted significant effects on diabetes risk distinct from any effect of adiponectin concentrations. [Clinical Trials Registry Nos; NCT 00004992 (Diabetes Prevention Program) and NCT 00038727 (Diabetes Prevention Program Outcomes Study)] PMID:22443353

Patient reported outcome in posttraumatic pituitary deficiency: results from The Danish National Study on posttraumatic hypopituitarism.

PubMed

Klose, Marianne; Stochholm, Kirstine; Janukonyté, Jurgita; Christensen, Louise Lehman; Cohen, Arieh S; Wagner, Aase; Laurberg, Peter; Christiansen, Jens Sandahl; Andersen, Marianne; Feldt-Rasmussen, Ulla

2015-06-01

Posttraumatic pituitary hormone deficiency is often suggested. The impact of these predominantly mild and often irreproducible deficiencies on outcome is less clear. The aim of the present study was to describe patient reported outcome in a national a priori unselected cohort of patients with traumatic brain injury (TBI) in relation to deficiencies identified upon pituitary assessment. We conducted a nationwide population-based cohort study. Participants were Danish patients with a head trauma diagnosis recorded in the Danish Board of Health diagnostic code registry; 439 patients (and 124 healthy controls) underwent assessment of anterior pituitary function 2.5 years (median) after TBI. Questionnaires on health-related quality of life (QoL) (SF36, EuroQoL-5D, QoL assessment of GH deficiency in adults) and fatigue (MFI-20) were completed in parallel to pituitary assessment. Patients with TBI had significant detriments in QoL. Impairment (mainly physical scales) related to pituitary deficiency, although only partially confirmed after adjustment for demographic differences. Hypogonadotropic hypogonadism related to several QoL scores. Increasing impairments were observed with declining total testosterone concentrations (men), but not free testosterone concentrations or any other hormone concentrations. Total testosterone was not independently related to impaired QoL and fatigue, after adjustment for demographics, and treatment with antidiabetics, opioids, antidepressants, and anticonvulsants. Only a very limited relationship between pituitary hormone deficiencies and QoL/fatigue was demonstrated. Due to the dominating influence of concurrent comorbidities, pituitary deficiencies were not independently related to QoL/fatigue. Causality is still to be shown, and whether substitution therapy could be of additional relevance in selected patients needs to be proven. © 2015 European Society of Endocrinology.

Advanced ECG in 2016: is there more than just a tracing?

PubMed

Reichlin, Tobias; Abächerli, Roger; Twerenbold, Raphael; Kühne, Michael; Schaer, Beat; Müller, Christian; Sticherling, Christian; Osswald, Stefan

2016-01-01

The 12-lead electrocardiogram (ECG) is the most frequently used technology in clinical cardiology. It is critical for evidence-based management of patients with most cardiovascular conditions, including patients with acute myocardial infarction, suspected chronic cardiac ischaemia, cardiac arrhythmias, heart failure and implantable cardiac devices. In contrast to many other techniques in cardiology, the ECG is simple, small, mobile, universally available and cheap, and therefore particularly attractive. Standard ECG interpretation mainly relies on direct visual assessment. The progress in biomedical computing and signal processing, and the available computational power offer fascinating new options for ECG analysis relevant to all fields of cardiology. Several digital ECG markers and advanced ECG technologies have shown promise in preliminary studies. This article reviews promising novel surface ECG technologies in three different fields. (1) For the detection of myocardial ischaemia and infarction, QRS morphology feature analysis, the analysis of high frequency QRS components (HF-QRS) and methods using vectorcardiography as well as ECG imaging are discussed. (2) For the identification and management of patients with cardiac arrhythmias, methods of advanced P-wave analysis are discussed and the concept of ECG imaging for noninvasive localisation of cardiac arrhythmias is presented. (3) For risk stratification of sudden cardiac death and the selection of patients for medical device therapy, several novel markers including an automated QRS-score for scar quantification, the QRS-T angle or the T-wave peak-to-end-interval are discussed. Despite the existing preliminary data, none of the advanced ECG markers and technologies has yet accomplished the transition into clinical practice. Further refinement of these technologies and broader validation in large unselected patient cohorts are the critical next step needed to facilitate translation of advanced ECG technologies into clinical cardiology.

Medical Student Dissection of Cadavers Improves Performance on Practical Exams but not on the NBME Anatomy Subject Exam.

PubMed

Sargent Jones, Leslie; Paulman, Lance E; Thadani, Raj; Terracio, Louis

2001-12-01

We have examined whether cadaver dissection by first year medical students (MIs) affected their performance in two test measures: the NBME Gross Anatomy and Embryology Subject Exam (dissection-relevant questions only), and practical exams given at the end of each major section within the course. The dissections for the entire course were divided into 18 regional dissection units and each student was assigned to dissect one third of the regional units; the other two-thirds of the material was learned from the partner-prosected cadavers. Performance for each student on the exams was then assessed as a function of the regions those students actually dissected. While the results indicated a small performance advantage for MIs answering questions on material they had dissected on the NBME Subject Exam questions relevant to dissection (78-88% of total exam), the results were not statistically significant. However, a similar, small performance advantage on the course practical exams was highly significant.

Self-deception as pseudo-rational regulation of belief.

PubMed

Michel, Christoph; Newen, Albert

2010-09-01

Self-deception is a special kind of motivational dominance in belief-formation. We develop criteria which set paradigmatic self-deception apart from related phenomena of auto-manipulation such as pretense and motivational bias. In self-deception rational subjects defend or develop beliefs of high subjective importance in response to strong counter-evidence. Self-deceivers make or keep these beliefs tenable by putting prima-facie rational defense-strategies to work against their established standards of rational evaluation. In paradigmatic self-deception, target-beliefs are made tenable via reorganizations of those belief-sets that relate relevant data to target-beliefs. This manipulation of the evidential value of relevant data goes beyond phenomena of motivated perception of data. In self-deception belief-defense is pseudo-rational. Self-deceivers will typically apply a dual standard of evaluation that remains intransparent to the subject. The developed model of self-deception as pseudo-rational belief-defense is empirically anchored. So, we hope to put forward a promising candidate. Copyright © 2010 Elsevier Inc. All rights reserved.

Challenges to tracking subjects for follow-up research: a case study.

PubMed

Fenster, Judy

2009-01-01

This narrative presents issues faced by the author and her research assistants in attempting to locate 40 subjects who had participated in a child welfare research study two decades earlier. The experience of the researchers suggests that attempting to locate subjects, especially where contact has not been maintained over the years, may not be accomplished without considerable time and expense. The author reflects on possible contributors to the difficulties in contacting these participants, highlights some recent developments in techniques for locating subjects after long periods of time have elapsed, and discusses some relevant ethical dilemmas.

[Effect of air-electric fields on driving and reaction patterns. Test subjects in the car driving simulator (author's transl)].

PubMed

Anselm, D; Danner, M; Kirmaier, N; König, H L; Müller-Limmroth, W; Reis, A; Schauerte, W

1977-06-10

In the relevant frequency range of about 10 Hertz cars can be considered very largely as Faraday cages and consequently as screens against air-electric fields. This may have a negative influence on driving and reaction patterns as a result. In an extensive investigation 48 subjects in a driving simulator were exposed to definite artificially produced air-electric fields. The self-rating of the performance and concentration of the subjects, reaction times and driving errors were determined. While the reaction times remained practically constant, the driving behavior of the subjects improved.

CXCR5-Dependent Entry of CD8 T Cells into Rhesus Macaque B-Cell Follicles Achieved through T-Cell Engineering.

PubMed

Ayala, Victor I; Deleage, Claire; Trivett, Matthew T; Jain, Sumiti; Coren, Lori V; Breed, Matthew W; Kramer, Joshua A; Thomas, James A; Estes, Jacob D; Lifson, Jeffrey D; Ott, David E

2017-06-01

Follicular helper CD4 T cells, T FH , residing in B-cell follicles within secondary lymphoid tissues, are readily infected by AIDS viruses and are a major source of persistent virus despite relative control of viral replication. This persistence is due at least in part to a relative exclusion of effective antiviral CD8 T cells from B-cell follicles. To determine whether CD8 T cells could be engineered to enter B-cell follicles, we genetically modified unselected CD8 T cells to express CXC chemokine receptor 5 (CXCR5), the chemokine receptor implicated in cellular entry into B-cell follicles. Engineered CD8 T cells expressing human CXCR5 (CD8 hCXCR5 ) exhibited ligand-specific signaling and chemotaxis in vitro Six infected rhesus macaques were infused with differentially fluorescent dye-labeled autologous CD8 hCXCR5 and untransduced CD8 T cells and necropsied 48 h later. Flow cytometry of both spleen and lymph node samples revealed higher frequencies of CD8 hCXCR5 than untransduced cells, consistent with preferential trafficking to B-cell follicle-containing tissues. Confocal fluorescence microscopy of thin-sectioned lymphoid tissues demonstrated strong preferential localization of CD8 hCXCR5 T cells within B-cell follicles with only rare cells in extrafollicular locations. CD8 hCXCR5 T cells were present throughout the follicles with some observed near infected T FH In contrast, untransduced CD8 T cells were found in the extrafollicular T-cell zone. Our ability to direct localization of unselected CD8 T cells into B-cell follicles using CXCR5 expression provides a strategy to place highly effective virus-specific CD8 T cells into these AIDS virus sanctuaries and potentially suppress residual viral replication. IMPORTANCE AIDS virus persistence in individuals under effective drug therapy or those who spontaneously control viremia remains an obstacle to definitive treatment. Infected follicular helper CD4 T cells, T FH , present inside B-cell follicles represent a major source of this residual virus. While effective CD8 T-cell responses can control viral replication in conjunction with drug therapy or in rare cases spontaneously, most antiviral CD8 T cells do not enter B-cell follicles, and those that do fail to robustly control viral replication in the T FH population. Thus, these sites are a sanctuary and a reservoir for replicating AIDS viruses. Here, we demonstrate that engineering unselected CD8 T cells to express CXCR5, a chemokine receptor on T FH associated with B-cell follicle localization, redirects them into B-cell follicles. These proof of principle results open a pathway for directing engineered antiviral T cells into these viral sanctuaries to help eliminate this source of persistent virus. Copyright © 2017 American Society for Microbiology.

Portable inhaled methoxyflurane is feasible and safe for colonoscopy in subjects with morbid obesity and/or obstructive sleep apnea.

PubMed

Nguyen, Nam Q; Toscano, Leanne; Lawrence, Matthew; Phan, Vinh-An; Singh, Rajvinder; Bampton, Peter; Fraser, Robert J; Holloway, Richard H; Schoeman, Mark N

2015-10-01

Colonoscopy with inhaled methoxyflurane (Penthrox) is well tolerated in unselected subjects and is not associated with respiratory depression. The aim of this prospective study was to compare the feasibility, safety, and post-procedural outcomes of portable methoxyflurane used as an analgesic agent during colonoscopy with those of anesthesia-assisted deep sedation (AADS) in subjects with morbid obesity and/or obstructive sleep apnea (OSA). The outcomes of 140 patients with morbid obesity/OSA who underwent colonoscopy with either Penthrox inhalation (n = 85; 46 men, 39 women; mean age 57.2 ± 1.1 years) or AADS (n = 55; 27 men, 28 women; mean age, 54.9 ± 1.1 years) were prospectively assessed. All Penthrox-assisted colonoscopies were successful, without any requirement for additional intravenous sedation. Compared with AADS, Penthrox was associated with a shorter total procedural time (24 ± 1 vs. 52 ± 1 minutes, P < 0.001), a lower incidence of hypotension (3 /85 vs. 23 /55, P < 0.001), and a lower incidence of respiratory desaturation (0 /85 vs. 14 /55, P < 0.001). The patients in the Penthrox group recovered more rapidly and were discharged much earlier than those in the AADS group (27 ± 2 vs. 97 ± 5 minutes, P < 0.0001). Of those who underwent colonoscopy with Penthrox, 90 % were willing to receive Penthrox again for colonoscopy. More importantly, of the patients who underwent colonoscopy with Penthrox and had had AADS for previous colonoscopy, 82 % (28 /34) preferred to receive Penthrox for future colonoscopies. Penthrox-assisted colonoscopy cost significantly less than colonoscopy with AADS ($ 332 vs. $ 725, P < 0.001), with a cost saving of approximately $ 400 for each additional complication avoided. Compared with AADS, Penthrox is highly feasible and safe in patients with morbid obesity/OSA undergoing colonoscopy and is associated with fewer cardiorespiratory complications. Because of the advantages of this approach in regard to procedural time, recovery time, and cost benefit in comparison with AADS, further evaluation in a randomized trial is warranted.

Clinical relevance in anesthesia journals.

PubMed

Lauritsen, Jakob; Møller, Ann M

2006-04-01

The purpose of this review is to present the latest knowledge and research on the definition and distribution of clinically relevant articles in anesthesia journals. It will also discuss the importance of the chosen methodology and outcome of articles. In the last few years, more attention has been paid to evidence-based medicine in anesthesia. Several articles on the subject have focused on the need to base clinical decisions on sound research employing both methodological rigor and clinically relevant outcomes. The number of systematic reviews in anesthesia literature is increasing as well as the focus on diminishing the number of surrogate outcomes. It has been shown that the impact factor is not a valid measure of establishing the level of clinical relevance to a journal. This review presents definitions of clinically relevant anesthesia articles. A clinically relevant article employs both methodological rigor and a clinically relevant outcome. The terms methodological rigor and clinical outcomes are fully discussed in the review as well as problems with journal impact factors.

Publications in anesthesia journals: quality and clinical relevance.

PubMed

Lauritsen, Jakob; Moller, Ann M

2004-11-01

Clinicians performing evidence-based anesthesia rely on anesthesia journals for clinically relevant information. The objective of this study was to analyze the proportion of clinically relevant articles in five high impact anesthesia journals. We evaluated all articles published in Anesthesiology, Anesthesia & Analgesia, British Journal of Anesthesia, Anesthesia, and Acta Anaesthesiologica Scandinavica from January to June, 2000. Articles were assessed and classified according to type, outcome, and design; 1379 articles consisting of 5468 pages were evaluated and categorized. The most common types of article were animal and laboratory research (31.2%) and randomized clinical trial (20.4%). A clinically relevant article was defined as an article that used a statistically valid method and had a clinically relevant end-point. Altogether 18.6% of the pages had as their subject matter clinically relevant trials. We compared the Journal Impact Factor (a measure of the number of citations per article in a journal) and the proportion of clinically relevant pages and found that they were inversely proportional to each other.

Assessing the Moral Relevance of Peace Education Contents in the Basic Education Social Studies Curricula for Effective Citizenship Participation in Nigeria

ERIC Educational Resources Information Center

Nwaubani, Okechukwu O,; Okafor, Ogochukwu Stella

2015-01-01

Social studies is a core subject at the basic education level in Nigeria which has the potentials of inculcating functional knowledge and desirable morals into pupils for effective citizenship participation through peaceful coexistence. However, despite this positive trend, the moral significance of peace education contents of the subject seem not…

Postgraduate Taught Portfolio Review--The Cluster Approach, Non-Subject-Based Grouping of Courses and Relevant Performance Indicators

ERIC Educational Resources Information Center

Konstantinidis-Pereira, Alicja

2018-01-01

This paper summarises a new method of grouping postgraduate taught (PGT) courses introduced at Oxford Brookes University as a part of a Portfolio Review. Instead of classifying courses by subject, the new cluster approach uses statistical methods to group the courses based on factors including flexibility of study options, level of specialisation,…

Readiness of Educational Activity Subjects for Results-Oriented Cooperation in the Inclusive Educational Practice of Higher School

ERIC Educational Resources Information Center

Tsyrenov, Vladimir Ts.; Erdyneeva, Klavdiya G.; Tudupova, Tuyana Ts.; Boronoyev, Pavel G.; Popova, Nataliya N.

2017-01-01

The relevance of the research is due to the necessity of integration of persons with health limitations and disabilities into the educational space of higher education institutions. With regard to this, the paper is aimed at finding out the extent of readiness of the educational activity subjects for results-oriented cooperation in inclusive…

Research Project "Subject Developing Environment of Preschool Education" for Russian Preschool Bilinguals (By the Example of Textile Educational Materials)

ERIC Educational Resources Information Center

Latipova, Liliya A.; Krapotkina, Irene E.; Koudrjavtseva, Ekaterina L.

2016-01-01

The problem's relevance stated in the article is determined by the following: forming preschool bilinguals' subject developing environment is connected with their active education and development, as well as with flexible preparation for studying at school. The purpose of this article is to develop methodology of textile developing materials' use…

Cardiovascular reactivity in a simulated job interview: the role of gender role self-concept.

PubMed

Sieverding, Monika; Weidner, Gerdi; von Volkmann, Bettina

2005-01-01

This study investigated the relation of gender role self-concept (G-SC) to cardiovascular and emotional reactions to an ecologically relevant stressor in a sample of graduating male and female university students. Thirty-seven men and 37 women completed the Personal Attribute Questionnaire and worked on four tasks designed to reflect common features of a job interview. Blood pressure and heart rate were measured at baseline, during, and after each task; subjective stress was measured at baseline and after each task. Subjective and objective stress scores were averaged across tasks and analyzed by sex and G-SC (i.e., instrumentality, expressiveness). Results indicated that women as a group demonstrated greater emotional reactivity, but did not differ in their physiological reactions when compared to men. Regardless of sex, participants' instrumentality scores contributed significantly to the variation in subjective stress response: those scoring high on instrumentality reported less stress, but evidenced greater blood pressure reactivity than those scoring low on instrumentality. These results suggest that gender roles, particularly an instrumental self-concept, may play an important role in both subjective and objective reactions to an ecologically relevant stressor.

Coping with Novelty and Human Intelligence: The Role of Counterfactual Reasoning

DTIC Science & Technology

1988-01-01

terminating relevance tests. Relevance is determined by checking whether the conceptual relation in the precue matches that in the item of the problem...found that experts tend to conceptualize dumain-related problems in abstract terms, whereas nonexperts apparently rely more on surface-level features...finally, the effects of the two surface-structural rule manipulations might for all subjects be partly due to perceptual, rather than conceptual

The relevance of dietary sodium in hemodialysis

PubMed Central

Mc Causland, Finnian R.; Waikar, Sushrut S.; Brunelli, Steven M.

2013-01-01

Since the earliest days of hemodialysis, dietary sodium restriction has been recommended as a therapeutic means to mitigate problems of extracellular volume overload, hypertension and inter-dialytic weight gain. Recently, there has been a proliferation of human subjects' research examining the potential effects of dietary sodium curtailment. Herein we examine the available evidence with respect to the effects of dietary sodium restriction on clinically relevant endpoints among hemodialysis patients. PMID:23129821

Modeling the Evolution of Beliefs Using an Attentional Focus Mechanism

PubMed Central

Marković, Dimitrije; Gläscher, Jan; Bossaerts, Peter; O’Doherty, John; Kiebel, Stefan J.

2015-01-01

For making decisions in everyday life we often have first to infer the set of environmental features that are relevant for the current task. Here we investigated the computational mechanisms underlying the evolution of beliefs about the relevance of environmental features in a dynamical and noisy environment. For this purpose we designed a probabilistic Wisconsin card sorting task (WCST) with belief solicitation, in which subjects were presented with stimuli composed of multiple visual features. At each moment in time a particular feature was relevant for obtaining reward, and participants had to infer which feature was relevant and report their beliefs accordingly. To test the hypothesis that attentional focus modulates the belief update process, we derived and fitted several probabilistic and non-probabilistic behavioral models, which either incorporate a dynamical model of attentional focus, in the form of a hierarchical winner-take-all neuronal network, or a diffusive model, without attention-like features. We used Bayesian model selection to identify the most likely generative model of subjects’ behavior and found that attention-like features in the behavioral model are essential for explaining subjects’ responses. Furthermore, we demonstrate a method for integrating both connectionist and Bayesian models of decision making within a single framework that allowed us to infer hidden belief processes of human subjects. PMID:26495984

Evaluation of the safety profile of an electronic vapour product used for two years by smokers in a real-life setting.

PubMed

Walele, Tanvir; Bush, Jim; Koch, Annelize; Savioz, Rebecca; Martin, Claire; O'Connell, Grant

2018-02-01

The safety profile of Puritane™, a closed system electronic vapour product (EVP), was evaluated when used by smokers of conventional cigarettes (CCs) for 24 months in a real-life setting. The study was a two-centre ambulatory clinical study with 209 healthy volunteers. Outcome measures included adverse events (AEs), vital signs, electrocardiogram, lung function tests, exposure to nicotine and selected smoke constituents, nicotine withdrawal effects and smoking desire. No serious AEs related to EVP use were observed. The most frequently reported AEs were headache, nasopharyngitis, sore throat and cough, reported by 28.7%, 28.7%, 19.6% and 16.7% of subjects, respectively, which dissipated over time. Small decreases in lung function were not considered clinically relevant. No clinically relevant findings were observed in the other safety parameters. From Month 2, nicotine withdrawal symptoms decreased. Smoking desire and CC consumption steadily decreased over time in all subjects. EVP use was associated with reduced exposure to cigarette smoke constituents, whereas urinary nicotine levels remained close to baseline. Body weight did not increase in CC subjects switching to the EVP. In conclusion, the aerosol of the EVP at study was well tolerated and not associated with any clinically relevant health concerns after usage for up to 24 months. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Multi-parameter comparison of a standardized mixed meal tolerance test in healthy and type 2 diabetic subjects: the PhenFlex challenge.

PubMed

Wopereis, Suzan; Stroeve, Johanna H M; Stafleu, Annette; Bakker, Gertruud C M; Burggraaf, Jacobus; van Erk, Marjan J; Pellis, Linette; Boessen, Ruud; Kardinaal, Alwine A F; van Ommen, Ben

2017-01-01

A key feature of metabolic health is the ability to adapt upon dietary perturbations. Recently, it was shown that metabolic challenge tests in combination with the new generation biomarkers allow the simultaneous quantification of major metabolic health processes. Currently, applied challenge tests are largely non-standardized. A systematic review defined an optimal nutritional challenge test, the "PhenFlex test" (PFT). This study aimed to prove that PFT modulates all relevant processes governing metabolic health thereby allowing to distinguish subjects with different metabolic health status. Therefore, 20 healthy and 20 type 2 diabetic (T2D) male subjects were challenged both by PFT and oral glucose tolerance test (OGTT). During the 8-h response time course, 132 parameters were quantified that report on 26 metabolic processes distributed over 7 organs (gut, liver, adipose, pancreas, vasculature, muscle, kidney) and systemic stress. In healthy subjects, 110 of the 132 parameters showed a time course response. Patients with T2D showed 18 parameters to be significantly different after overnight fasting compared to healthy subjects, while 58 parameters were different in the post-challenge time course after the PFT. This demonstrates the added value of PFT in distinguishing subjects with different health status. The OGTT and PFT response was highly comparable for glucose metabolism as identical amounts of glucose were present in both challenge tests. Yet the PFT reports on additional processes, including vasculature, systemic stress, and metabolic flexibility. The PFT enables the quantification of all relevant metabolic processes involved in maintaining or regaining homeostasis of metabolic health. Studying both healthy subjects and subjects with impaired metabolic health showed that the PFT revealed new processes laying underneath health. This study provides the first evidence towards adopting the PFT as gold standard in nutrition research.

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29 CFR 578.4 - Determination of penalty.

Code of Federal Regulations, 2010 CFR

2010-07-01

... business. (b) Where appropriate, the Administrator may also consider other relevant factors in assessing... legal certainty; (3) The previous history of violations, including whether the employer is subject to...

Waveform shape analysis: extraction of physiologically relevant information from Doppler recordings.

PubMed

Ramsay, M M; Broughton Pipkin, F; Rubin, P C; Skidmore, R

1994-05-01

1. Doppler recordings were made from the brachial artery of healthy female subjects during a series of manoeuvres which altered the pressure-flow characteristics of the vessel. 2. Changes were induced in the peripheral circulation of the forearm by the application of heat or ice-packs. A sphygmomanometer cuff was used to create graded occlusion of the vessel above and below the point of measurement. Recordings were also made whilst the subjects performed a standardized Valsalva manoeuvre. 3. The Doppler recordings were analysed both with the standard waveform indices (systolic/diastolic ratio, pulsatility index and resistance index) and by the method of Laplace transform analysis. 4. The waveform parameters obtained by Laplace transform analysis distinguished the different changes in flow conditions; they thus had direct physiological relevance, unlike the standard waveform indices.

The applied importance of research on the matching law

PubMed Central

Pierce, W. David; Epling, W. Frank

1995-01-01

In this essay, we evaluate the applied implications of two articles related to the matching law and published in the Journal of the Experimental Analysis of Behavior, May 1994. Building on Mace's (1994) criteria for increasing the applied relevance of basic research, we evaluate the applied implications of basic research studies. Research by Elsmore and McBride (1994) and Savastano and Fantino (1994) involve an extension of the behavioral model of choice. Elsmore and McBride used rats as subjects, but arranged a multioperant environment that resembles some of the complex contingencies of human behavior. Savastino and Fantino used human subjects and extended the matching law to ratio and interval contingencies. These experiments contribute to a growing body of knowledge on the matching law and its relevance for human behavior. PMID:16795866

Neural correlates of economic value and valuation context: an event-related potential study.

PubMed

Tyson-Carr, John; Kokmotou, Katerina; Soto, Vicente; Cook, Stephanie; Fallon, Nicholas; Giesbrecht, Timo; Stancak, Andrej

2018-05-01

The value of environmental cues and internal states is continuously evaluated by the human brain, and it is this subjective value that largely guides decision making. The present study aimed to investigate the initial value attribution process, specifically the spatiotemporal activation patterns associated with values and valuation context, using electroencephalographic event-related potentials (ERPs). Participants completed a stimulus rating task in which everyday household items marketed up to a price of £4 were evaluated with respect to their desirability or material properties. The subjective values of items were evaluated as willingness to pay (WTP) in a Becker-DeGroot-Marschak auction. On the basis of the individual's subjective WTP values, the stimuli were divided into high- and low-value items. Source dipole modeling was applied to estimate the cortical sources underlying ERP components modulated by subjective values (high vs. low WTP) and the evaluation condition (value-relevant vs. value-irrelevant judgments). Low-WTP items and value-relevant judgments both led to a more pronounced N2 visual evoked potential at right frontal scalp electrodes. Source activity in right anterior insula and left orbitofrontal cortex was larger for low vs. high WTP at ∼200 ms. At a similar latency, source activity in right anterior insula and right parahippocampal gyrus was larger for value-relevant vs. value-irrelevant judgments. A stronger response for low- than high-value items in anterior insula and orbitofrontal cortex appears to reflect aversion to low-valued item acquisition, which in an auction experiment would be perceived as a relative loss. This initial low-value bias occurs automatically irrespective of the valuation context. NEW & NOTEWORTHY We demonstrate the spatiotemporal characteristics of the brain valuation process using event-related potentials and willingness to pay as a measure of subjective value. The N2 component resolves values of objects with a bias toward low-value items. The value-related changes of the N2 component are part of an automatic valuation process.

BOLD response to semantic and syntactic processing during hypoglycemia is load-dependent.

PubMed

Schafer, Robin J; Page, Kathleen A; Arora, Jagriti; Sherwin, Robert; Constable, R Todd

2012-01-01

This study investigates how syntactic and semantic load factors impact sentence comprehension and BOLD signal under moderate hypoglycemia. A dual session, whole brain fMRI study was conducted on 16 healthy participants using the glucose clamp technique. In one session, they experienced insulin-induced hypoglycemia (plasma glucose at ∼50mg/dL); in the other, plasma glucose was maintained at euglycemic levels (∼100mg/dL). During scans subjects were presented with sentences of contrasting syntactic (embedding vs. conjunction) and semantic (reversibility vs. irreversibility) load. Semantic factors dominated the overall load effects on both performance (p<0.001) and BOLD response (p<0.01, corrected). Differential BOLD signal was observed in frontal, temporal, temporo-parietal and medio-temporal regions. Hypoglycemia and syntactic factors significantly impacted performance (p=0.002) and BOLD response (p<0.01, corrected) in the reversible clause conditions, more extensively in reversible-embedded than in reversible-conjoined clauses. Hypoglycemia resulted in a robust decrease in performance on reversible clauses and exerted attenuating effects on BOLD unselectively across cortical circuits. The dominance of reversibility in all measures underscores the distinction between the syntactic and semantic contrasts. The syntactic is based in a quantitative difference in algorithms interpreting embedded and conjoined structures. We suggest that the semantic is based in a qualitative difference between algorithmic mapping of arguments in reversible clauses and heuristic linking in irreversible clauses. Because heuristics drastically reduce resource demand, the operations they support would resist the load-dependent cognitive consequences of hypoglycemia. © 2011 Elsevier Inc. All rights reserved.

Basic symptoms in the general population and in psychotic and non-psychotic psychiatric adolescents.

PubMed

Meng, Heiner; Schimmelmann, Benno Graf; Koch, Eginhard; Bailey, Barbara; Parzer, Peter; Günter, Michael; Mohler, Beat; Kunz, Natalia; Schulte-Markwort, Michael; Felder, Wilhelm; Zollinger, Rudolf; Bürgin, Dieter; Resch, Franz

2009-06-01

Cognitive-perceptive 'basic symptoms' are used complementary to ultra-high-risk criteria in order to predict onset of psychosis in the pre-psychotic phase. The aim was to investigate the prevalence of a broad selection of 'basic symptoms' in a representative general adolescent population sample (GPS; N=96) and to compare it with adolescents first admitted for early onset psychosis (EOP; N=87) or non-psychotic psychiatric disorders (NP; N=137). Subjects were assessed with the Bonn Scale for the Assessment of Basic Symptoms (BSABS). Prevalence of at least one 'basic symptom' and mean numbers were compared across the three groups. Logistic regression was used to predict group membership by BSABS subscales; risk ratios were calculated to identify 'basic symptoms' which best discriminated between groups. The prevalence of at least any one 'basic symptom' was 30.2% in GPS compared to 81% in NP and 96.5% in EOP. Correct classification of EOP when compared to GPS was high (94.0%) and lower when compared to NP (78.6%). Cognitive symptoms discriminated best between EOP and NP. Alike other prodromal- and psychotic-like experiences, 'basic symptoms' are prevalent in the general adolescent population, yet at a lower rate compared to EOP and NP. The usage of 'at least one basic symptom' as a screening criterion for youth at risk of developing a psychotic disorder is not recommended in the general population or in unselected psychiatrically ill adolescents. However, particularly cognitive 'basic symptoms' may be a valuable criteria to be included in future 'at risk' studies in adolescents.

Comprehensive malnutrition inflammation score as a marker of nutritional status in Chinese peritoneal dialysis patients.

PubMed

Chan, Jessie Ying Wing; Che, Kit I; Lam, Karry Mau Chu; Chow, Kai-Ming; Chung, Kwok-Yi; Li, Philip Kam-Tao; Szeto, Cheuk-Chun

2007-04-01

Malnutrition is common among peritoneal dialysis (PD) patients. However, the ideal marker of nutritional status in PD patients remained controversial. We studied 165 unselected adult PD patients. We compared the comprehensive Malnutrition-Inflammation Score (MIS) and the 7-point Subjective Global Assessment (SGA) score. The mean age was 59.2 +/- 11.5 years. Seventy patients were male. MIS significantly correlated with the SGA score (r =-0.667, P < 0.001). Of the 165 patients, 132 (80.0%) had similar classification of nutritional status by SGA and MIS (Group I); 17 (10.3%) were classified as normal by SGA but moderately malnourished by MIS (Group II), while 16 (9.7%) were classified as normal by MIS but moderately malnourished by SGA (Group III). Group II had been dialysed longer than Group I (71.7 +/- 50.3 vs 40.7 +/- 37.5 months, P = 0.011). As compared with Group I, Group III was more likely to require helper for PD exchange (37.5%vs 9.7%, P = 0.004), marginally more likely to be diabetic (62.5%vs 35.6%, P = 0.085) and had a slightly higher Charlson's comorbidity score (6.13 +/- 1.78 vs 4.98 +/- 2.1, P = 0.085), although the latter two were not statistically significant. MIS has a reasonable correlation with the conventional SGA score in PD patients. Patients with limited self-care capability, diabetes and multiple comorbidities probably had worse score (i.e. worse nutrition) revealed by SGA than by MIS, while patients who had been dialysed longer had worse score revealed by MIS than by SGA.

Chronic lymphocytic leukemia: A prognostic model comprising only two biomarkers (IGHV mutational status and FISH cytogenetics) separates patients with different outcome and simplifies the CLL-IPI.

PubMed

Delgado, Julio; Doubek, Michael; Baumann, Tycho; Kotaskova, Jana; Molica, Stefano; Mozas, Pablo; Rivas-Delgado, Alfredo; Morabito, Fortunato; Pospisilova, Sarka; Montserrat, Emili

2017-04-01

Rai and Binet staging systems are important to predict the outcome of patients with chronic lymphocytic leukemia (CLL) but do not reflect the biologic diversity of the disease nor predict response to therapy, which ultimately shape patients' outcome. We devised a biomarkers-only CLL prognostic system based on the two most important prognostic parameters in CLL (i.e., IGHV mutational status and fluorescence in situ hybridization [FISH] cytogenetics), separating three different risk groups: (1) low-risk (mutated IGHV + no adverse FISH cytogenetics [del(17p), del(11q)]); (2) intermediate-risk (either unmutated IGHV or adverse FISH cytogenetics) and (3) high-risk (unmutated IGHV + adverse FISH cytogenetics). In 524 unselected subjects with CLL, the 10-year overall survival was 82% (95% CI 76%-88%), 52% (45%-62%), and 27% (17%-42%) for the low-, intermediate-, and high-risk groups, respectively. Patients with low-risk comprised around 50% of the series and had a life expectancy comparable to the general population. The prognostic model was fully validated in two independent cohorts, including 417 patients representative of general CLL population and 337 patients with Binet stage A CLL. The model had a similar discriminatory value as the CLL-IPI. Moreover, it applied to all patients with CLL independently of age, and separated patients with different risk within Rai or Binet clinical stages. The biomarkers-only CLL prognostic system presented here simplifies the CLL-IPI and could be useful in daily practice and to stratify patients in clinical trials. © 2017 Wiley Periodicals, Inc.

Out with the old? The role of selective attention in retaining targets in partial report.

PubMed

Lindsey, Dakota R B; Bundesen, Claus; Kyllingsbæk, Søren; Petersen, Anders; Logan, Gordon D

2017-01-01

In the partial-report task, subjects are asked to report only a portion of the items presented. Selective attention chooses which objects to represent in short-term memory (STM) on the basis of their relevance. Because STM is limited in capacity, one must sometimes choose which objects are removed from memory in light of new relevant information. We tested the hypothesis that the choices among newly presented information and old information in STM involve the same process-that both are acts of selective attention. We tested this hypothesis using a two-display partial-report procedure. In this procedure, subjects had to select and retain relevant letters (targets) from two sequentially presented displays. If selection in perception and retention in STM are the same process, then irrelevant letters (distractors) in the second display, which demanded attention because of their similarity to the targets, should have decreased target report from the first display. This effect was not obtained in any of four experiments. Thus, choosing objects to keep in STM is not the same process as choosing new objects to bring into STM.

Treatment modalities in children with teeth affected by molar-incisor enamel hypomineralisation (MIH): A systematic review.

PubMed

Lygidakis, N A

2010-04-01

This was to review the literature concerning the treatment of permanent teeth with molar-incisor hypomineralised enamel (MIH), comment about possible shortcomings and propose areas of future research. A search of MedLine, Scopus, ResearchGate, Isis and Google Scholar databases was conducted using all terms relevant to the subject. Relevant papers published in English were identified after a review of their titles, abstracts or full reading of the papers. Of 189 references initially found, 66 papers were included; 34 directly relevant to the subject. From the latter, only 14 concerned laboratory or clinical studies dealing with treatment for MIH. Since 2000 11 reviews evaluated, to a certain extent, treatment options for affected teeth. Analysis of the proposed treatment modalities indicated options for prevention, restorations, and adhesion to hypomineralised enamel, full coronal coverage and extraction followed by orthodontics. Based on these findings, a treatment decision plan is proposed. Although treatment approaches for MIH have started to be clearer, long-term clinical trials, supported by laboratory studies, should be conducted to further facilitate the clinical management of this dental defect.

Dental students' motivation and the context of learning.

PubMed

Kristensen, Bettina Tjagvad; Netterstrom, Ingeborg; Kayser, Lars

2009-02-01

This qualitative study shows dental students' motives for choosing the dental education and how the motives influence their motivation at the first semester of study. Further the study demonstrates the relevance of the context of learning. This issue is of importance when planning a curriculum for the dental education. The material consists of interviews with eight dental students. The results show that dental students were focused on their future professional role, its practical dimensions and their future working conditions. Their motivation for choosing the dental education was found to influence their motivation for studying and their experience of the relevance of the first semester. The dental students who had co-education with the medical students at the first year of study missed a dental context and courses with clinically relevant contents. In conclusion, our data signify the importance of the context of learning. It is recommended that a future curriculum for the dental school should be designed in a way where basic science subjects are taught with both theoretically as well as practically oriented subjects and in a context which is meaningful for the students.

Reward-related brain response and craving correlates of marijuana cue exposure: a preliminary study in treatment-seeking marijuana-dependent subjects.

PubMed

Goldman, Marina; Szucs-Reed, Regina P; Jagannathan, Kanchana; Ehrman, Ronald N; Wang, Ze; Li, Yin; Suh, Jesse J; Kampman, Kyle; O'Brien, Charles P; Childress, Anna Rose; Franklin, Teresa R

2013-01-01

: Determining the brain substrates underlying the motivation to abuse addictive drugs is critical for understanding and treating addictive disorders. Laboratory neuroimaging studies have demonstrated differential activation of limbic and motivational circuitry (eg, amygdala, hippocampus, ventral striatum, insula, and orbitofrontal cortex) triggered by cocaine, heroin, nicotine, and alcohol cues. The literature on neural responses to marijuana cues is sparse. Thus, the goals of this study were to characterize the brain's response to marijuana cues, a major motivator underlying drug use and relapse, and determine whether these responses are linked to self-reported craving in a clinically relevant population of treatment-seeking marijuana-dependent subjects. : Marijuana craving was assessed in 12 marijuana-dependent subjects using the Marijuana Craving Questionnaire-Short Form. Subsequently, blood oxygen level dependent functional magnetic resonance imaging data were acquired during exposure to alternating 20-second blocks of marijuana-related versus matched nondrug visual cues. : Brain activation during marijuana cue exposure was significantly greater in the bilateral amygdala and the hippocampus. Significant positive correlations between craving scores and brain activation were found in the ventral striatum and the medial and lateral orbitofrontal cortex (P < 0.0001). : This study presents direct evidence for a link between reward-relevant brain responses to marijuana cues and craving and extends the current literature on marijuana cue reactivity. Furthermore, the correlative relationship between craving and brain activity in reward-related regions was observed in a clinically relevant sample (treatment-seeking marijuana-dependent subjects). Results are consistent with prior findings in cocaine, heroin, nicotine, and alcohol cue studies, indicating that the brain substrates of cue-triggered drug motivation are shared across abused substances.

Clinical relevance of IL-6 gene polymorphism in severely injured patients

PubMed Central

Jeremić, Vasilije; Alempijević, Tamara; Mijatović, Srđan; Šijački, Ana; Dragašević, Sanja; Pavlović, Sonja; Miličić, Biljana; Krstić, Slobodan

2014-01-01

In polytrauma, injuries that may be surgically treated under regular circumstances due to a systemic inflammatory response become life-threatening. The inflammatory response involves a complex pattern of humoral and cellular responses and the expression of related factors is thought to be governed by genetic variations. This aim of this paper is to examine the influence of interleukin (IL) 6 single nucleotide polymorphism (SNP) -174C/G and -596G/A on the treatment outcome in severely injured patients. Forty-seven severely injured patients were included in this study. Patients were assigned an Injury Severity Score. Blood samples were drawn within 24 h after admission (designated day 1) and on subsequent days (24, 48, 72 hours and 7days) of hospitalization. The IL-6 levels were determined through ELISA technique. Polymorphisms were analyzed by a method of Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR). Among subjects with different outcomes, no statistically relevant difference was found with regards to the gene IL-6 SNP-174G/C polymorphism. More than a half of subjects who died had the SNP-174G/C polymorphism, while this polymorphism was represented in a slightly lower number in survivors. The incidence of subjects without polymorphism and those with heterozygous and homozygous gene IL-6 SNP-596G/A polymorphism did not present statistically significant variations between survivors and those who died. The levels of IL-6 over the observation period did not present any statistically relevant difference among subjects without the IL-6 SNP-174 or IL-6 SNP -596 gene polymorphism and those who had either a heterozygous or a homozygous polymorphism. PMID:24856384

Pooled population pharmacokinetic model of imipenem in plasma and the lung epithelial lining fluid

PubMed Central

Rizk, Matthew L.; Lala, Mallika; Chavez‐Eng, Cynthia; Visser, Sandra A. G.; Kerbusch, Thomas; Danhof, Meindert; Rao, Gauri; van der Graaf, Piet H.

2016-01-01

Aims Several clinical trials have confirmed the therapeutic benefit of imipenem for treatment of lung infections. There is however no knowledge of the penetration of imipenem into the lung epithelial lining fluid (ELF), the site of action relevant for lung infections. Furthermore, although the plasma pharmacokinetics (PK) of imipenem has been widely studied, most studies have been based on selected patient groups. The aim of this analysis was to characterize imipenem plasma PK across populations and to quantify imipenem ELF penetration. Methods A population model for imipenem plasma PK was developed using data obtained from healthy volunteers, elderly subjects and subjects with renal impairment, in order to identify predictors for inter‐individual variability (IIV) of imipenem PK. Subsequently, a clinical study which measured plasma and ELF concentrations of imipenem was included in order to quantify lung penetration. Results A two compartmental model best described the plasma PK of imipenem. Creatinine clearance and body weight were included as subject characteristics predictive for IIV on clearance. Typical estimates for clearance, central and peripheral volume, and inter‐compartmental clearance were 11.5 l h–1, 9.37 l, 6.41 l, 13.7 l h–1, respectively (relative standard error (RSE) <8%). The distribution of imipenem into ELF was described using a time‐independent penetration coefficient of 0.44 (RSE 14%). Conclusion The identified lung penetration coefficient confirms the clinical relevance of imipenem for treatment of lung infections, while the population PK model provided insights into predictors of IIV for imipenem PK and may be of relevance to support dose optimization in various subject groups. PMID:26852277

Pooled population pharmacokinetic model of imipenem in plasma and the lung epithelial lining fluid.

PubMed

van Hasselt, J G Coen; Rizk, Matthew L; Lala, Mallika; Chavez-Eng, Cynthia; Visser, Sandra A G; Kerbusch, Thomas; Danhof, Meindert; Rao, Gauri; van der Graaf, Piet H

2016-06-01

Several clinical trials have confirmed the therapeutic benefit of imipenem for treatment of lung infections. There is however no knowledge of the penetration of imipenem into the lung epithelial lining fluid (ELF), the site of action relevant for lung infections. Furthermore, although the plasma pharmacokinetics (PK) of imipenem has been widely studied, most studies have been based on selected patient groups. The aim of this analysis was to characterize imipenem plasma PK across populations and to quantify imipenem ELF penetration. A population model for imipenem plasma PK was developed using data obtained from healthy volunteers, elderly subjects and subjects with renal impairment, in order to identify predictors for inter-individual variability (IIV) of imipenem PK. Subsequently, a clinical study which measured plasma and ELF concentrations of imipenem was included in order to quantify lung penetration. A two compartmental model best described the plasma PK of imipenem. Creatinine clearance and body weight were included as subject characteristics predictive for IIV on clearance. Typical estimates for clearance, central and peripheral volume, and inter-compartmental clearance were 11.5 l h(-1) , 9.37 l, 6.41 l, 13.7 l h(-1) , respectively (relative standard error (RSE) <8%). The distribution of imipenem into ELF was described using a time-independent penetration coefficient of 0.44 (RSE 14%). The identified lung penetration coefficient confirms the clinical relevance of imipenem for treatment of lung infections, while the population PK model provided insights into predictors of IIV for imipenem PK and may be of relevance to support dose optimization in various subject groups. © 2016 The British Pharmacological Society.

A historical note on false traumatic memories.

PubMed

Rosen, Gerald M; Sageman, Marc; Loftus, Elizabeth

2004-01-01

Unhampered by current ethical standards and human subject committees, H. Bernheim (1889) created a false memory of a horrific traumatic event. Bernheim also demonstrated his subject's willingness to discuss the implanted memory with a representative of the law. Bernheim's work represents the first documented case of an implanted false traumatic memory, with direct relevance to contemporary debates. Copyright 2003 Wiley Periodicals, Inc. J Clin Psychol.