Nagel, Zachary D; Engelward, Bevin P; Brenner, David J; Begley, Thomas J; Sobol, Robert W; Bielas, Jason H; Stambrook, Peter J; Wei, Qingyi; Hu, Jennifer J; Terry, Mary Beth; Dilworth, Caroline; McAllister, Kimberly A; Reinlib, Les; Worth, Leroy; Shaughnessy, Daniel T
The rise of advanced technologies for characterizing human populations at the molecular level, from sequence to function, is shifting disease prevention paradigms toward personalized strategies. Because minimization of adverse outcomes is a key driver for treatment decisions for diseased populations, developing personalized therapy strategies represent an important dimension of both precision medicine and personalized prevention. In this commentary, we highlight recently developed enabling technologies in the field of DNA damage, DNA repair, and mutagenesis. We propose that omics approaches and functional assays can be integrated into population studies that fuse basic, translational and clinical research with commercial expertise in order to accelerate personalized prevention and treatment of cancer and other diseases linked to aberrant responses to DNA damage. This collaborative approach is generally applicable to efforts to develop data-driven, individualized prevention and treatment strategies for other diseases. We also recommend strategies for maximizing the use of biological samples for epidemiological studies, and for applying emerging technologies to clinical applications. Copyright © 2017 Elsevier B.V. All rights reserved.
Weber, Marianne; Yap, Sarsha; Goldsbury, David; Manners, David; Tammemagi, Martin; Marshall, Henry; Brims, Fraser; McWilliams, Annette; Fong, Kwun; Kang, Yoon Jung; Caruana, Michael; Banks, Emily; Canfell, Karen
Lung cancer screening with computerised tomography holds promise, but optimising the balance of benefits and harms via selection of a high risk population is critical. PLCOm2012 is a logistic regression model based on U.S. data, incorporating sociodemographic and health factors, which predicts 6-year lung cancer risk among ever-smokers, and thus may better predict those who might benefit from screening than criteria based solely on age and smoking history. We aimed to validate the performance of PLCOm2012 in predicting lung cancer outcomes in a cohort of Australian smokers. Predicted risk of lung cancer was calculated using PLCOm2012 applied to baseline data from 95,882 ever-smokers aged ≥45 years in the 45 and Up Study (2006-2009). Predictions were compared to lung cancer outcomes captured to June 2014 via linkage to population-wide health databases; a total of 1,035 subsequent lung cancer diagnoses were identified. PLCOm2012 had good discrimination (area under the receiver-operating-characteristic-curve; AUC 0.80, 95%CI 0.78-0.81) and excellent calibration (mean and 90th percentiles of absolute risk difference between observed and predicted outcomes: 0.006 and 0.016, respectively). Sensitivity (69.4%, 95%CI, 65.6-73.0%) of the PLCOm2012 criteria in the 55-74 year age group for predicting lung cancers was greater than that using criteria based on ≥30 pack-years smoking and ≤15 years quit (57.3%, 53.3-61.3%; p < 0.0001), but specificity was lower (72.0%, 71.7-72.4% versus 75.2%, 74.8-75.6%, respectively; p < 0.0001). Targeting high risk people for lung cancer screening using PLCOm2012 might improve the balance of benefits versus harms, and cost-effectiveness of lung cancer screening. © 2017 UICC.
Böhm, Monika; Hutchings, Michael R; White, Piran C L
The management of many pathogens, which are of concern to humans and their livestock, is complicated by the pathogens' ability to cross-infect multiple host species, including wildlife. This has major implications for the management of such diseases, since the dynamics of infection are dependent on the rates of both intra- and inter-specific transmission. However, the difficulty of studying transmission networks in free-living populations means that the relative opportunities for intra- versus inter-specific disease transmission have not previously been demonstrated empirically within any wildlife-livestock disease system. Using recently-developed proximity data loggers, we quantify both intra- and inter-specific contacts in a wildlife-livestock disease system, using bovine tuberculosis (bTB) in badgers and cattle in the UK as our example. We assess the connectedness of individuals within the networks in order to identify whether there are certain 'high-risk' individuals or groups of individuals for disease transmission within and between species. Our results show that contact patterns in both badger and cattle populations vary widely, both between individuals and over time. We recorded only infrequent interactions between badger social groups, although all badgers fitted with data loggers were involved in these inter-group contacts. Contacts between badgers and cattle occurred more frequently than contacts between different badger groups. Moreover, these inter-specific contacts involved those individual cows, which were highly connected within the cattle herd. This work represents the first continuous time record of wildlife-host contacts for any free-living wildlife-livestock disease system. The results highlight the existence of specific individuals with relatively high contact rates in both livestock and wildlife populations, which have the potential to act as hubs in the spread of disease through complex contact networks. Targeting testing or preventive
Tao, Sha; Hoffmeister, Michael; Brenner, Hermann
Screening the population for colorectal cancer (CRC) by colonoscopy could reduce the disease burden. However, targeted screening of individuals at high risk could increase its cost effectiveness. We developed a scoring system to identify individuals with at least 1 advanced adenoma, based on easy-to-collect risk factors among 7891 participants of the German screening colonoscopy program. The system was validated in an independent sample of 3519 participants. Multiple logistic regression was used to develop the algorithm, and the regression coefficient-based scores were used to determine individual risks. Relative risk and numbers of colonoscopies needed for detecting one or more advanced neoplasm(s) were calculated for quintiles of the risk score. The predictive ability of the scoring system was quantified by the area under the curve. We identified 9 risk factors (sex, age, first-degree relatives with a history of CRC, cigarette smoking, alcohol consumption, red meat consumption, ever regular use [at least 2 times/wk for at least 1 y] of nonsteroidal anti-inflammatory drugs, previous colonoscopy, and previous detection of polyps) that were associated significantly with risk of advanced neoplasms. The developed score was associated strongly with the presence of advanced neoplasms. In the validation sample, individuals in the highest quintile of scores had a relative risk for advanced neoplasm of 3.86 (95% confidence interval, 2.71-5.49), compared with individuals in the lowest quintile. The number needed to screen to detect 1 or more advanced neoplasm(s) varied from 20 to 5 between quintiles of the risk score. In the validation sample, the scoring system identified patients with CRC or any advanced neoplasm with area under the curve values of 0.68 and 0.66, respectively. We developed a scoring system, based on easy-to-collect risk factors, to identify individuals most likely to have advanced neoplasms. This system might be used to stratify individuals for CRC
Thompson, Elizabeth; Kline, Emily; Reeves, Gloria; Pitts, Steven C; Bussell, Kristin; Schiffman, Jason
Brief self-report screening can help facilitate early identification of individuals at risk for or in early stages of psychosis. Existing screening tools focus on self-reported attenuated positive symptoms to detect potential risk; however, parent reports may also be helpful for assessing symptoms, especially in younger patients. Recent evidence has shown that the "atypicality" scale within the self-report form of the Behavior Assessment System for Children, Second Edition (BASC-2) may be useful for identifying high-risk youth within a more clinically comprehensive and potentially minimally stigmatizing format. The BASC-2 parent report form also includes the atypicality scale, but no research has investigated the relation of this scale to psychosis risk. The aim of the current study is to evaluate the association of parent along with youth reports of BASC-2 atypicality with attenuated positive symptoms as assessed by the Structured Interview for Psychosis-Risk Syndromes (SIPS), in a sample of help-seeking adolescents (n=63). Results indicate that both parent and youth reports of atypicality predict clinician-rated symptoms. Moreover, the combination of parent and youth report significantly improved prediction of SIPS scores over either single-informant scale. These findings suggest that parent report scales, as ascertained through part of a larger, commonly used measure, may help identify youth at risk for psychosis, particularly if used in conjunction with youth self-report. Copyright © 2014 Elsevier B.V. All rights reserved.
Anbalagan, Viknesh Prabu; Venkataraman, Vijayachandrika; Vamsi, Mamilla; Deepa, Mohan; Mohan, Viswanathan
Objective We aim to determine whether a simple Indian diabetes risk score (IDRS) is associated with individuals with non-alcoholic fatty liver disease (NAFLD) among nondiabetic Asian Indians. Methods Nondiabetic participants (n = 409) were selected from the Chennai Urban Rural Epidemiology Study. Mean age was 40 ± 11.9 years, mean body mass index was 23.2 ± 3.9 kg/m2, and 224 (54.8%) were women. The IDRS was classified as high (≥60), medium (30–50), and low (<30) risk. Non-alcoholic fatty liver disease was assessed by high-resolution β mode ultrasonography. To determine the factors associated with NAFLD, a univariate analysis was first done and a stepwise logistic regression analysis was done based on the factors associated with NAFLD. Biochemical and anthropometric measurements were obtained using standardized procedures. Results The overall prevalence of NAFLD was 24.7% (101/409 participants), and it was significantly higher among those with a high (30.4%) and medium IDRS (21%) compared with the low IDRS group (15.8%; trend chi square; p = .022). In stepwise logistic regression, IDRS was associated with NAFLD with an adjusted odds ratio of 1.78 (95% confidence interval 1.04–3.06), even after adjusting for potential confounders. Conclusions The IDRS can be used as the initial step to screen individuals at high risk of NAFLD in the community. PMID:23294790
Boehm, O; Baumgarten, G; Hoeft, A
Postoperative mortality remains alarmingly high with a mortality rate ranging between 0.4% and 4%. A small subgroup of multimorbid and/or elderly patients undergoing different surgical procedures naturally confers the highest risk of complications and perioperative death. Therefore, preoperative assessment should identify these high-risk patients and stratify them to individualized monitoring and treatment throughout all phases of perioperative care. A "tailored" perioperative approach might help further reduce perioperative morbidity and mortality. This article aims to elucidate individual morbidity-specific risks. It further suggests approaches to detect patients at the risk of perioperative complications.
Kinar, Yaron; Akiva, Pinchas; Choman, Eran; Kariv, Revital; Shalev, Varda; Levin, Bernard; Narod, Steven A.; Goshen, Ran
Individuals with colorectal cancer (CRC) have a tendency to intestinal bleeding which may result in mild to severe iron deficiency anemia, but for many colon cancer patients hematological abnormalities are subtle. The fecal occult blood test (FOBT) is used as a pre-screening test whereby those with a positive FOBT are referred to colonscopy. We sought to determine if information contained in the complete blood count (CBC) report coud be processed automatically and used to predict the presence of occult colorectal cancer (CRC) in the setting of a large health services plan. Using the health records of the Maccabi Health Services (MHS) we reviewed CBC reports for 112,584 study subjects of whom 133 were diagnosed with CRC in 2008 and analysed these with the MeScore tool. The odds ratio for being diagnosed with CRC in 2008 was calculated with regards to the MeScore, using cutoff levels of 97% and 99% percentiles. For individuals in the highest one percentile, the odds ratio for CRC was 21.8 (95% CI 13.8 to 34.2). For the majority of the individuals with cancer, CRC was not suspected at the time of the blood draw. Frequent use of anticoagulants, the presence of other gastrointestinal pathologies and non-GI malignancies were assocaitged with false positive MeScores. The MeScore can help identify individuals in the population who would benefit most from CRC screening, including those with no clinical signs or symptoms of CRC. PMID:28182647
Levitt, Naomi S.; Puoane, Thandi; Denman, Catalina A.; Abrahams-Gessel, Shafika; Surka, Sam; Mendoza, Carlos; Khanam, Masuma; Alam, Sartaj; Gaziano, Thomas A.
Background We have found that community health workers (CHWs) with appropriate training are able to accurately identify people at high cardiovascular disease (CVD) risk in the community who would benefit from the introduction of preventative management, in Bangladesh, Guatemala, Mexico, and South Africa. This paper examines the attendance pattern for those individuals who were so identified and referred to a health care facility for further assessment and management. Design Patient records from the health centres in each site were reviewed for data on diagnoses made and treatment commenced. Reasons for non-attendance were sought from participants who had not attended after being referred. Qualitative data were collected from study coordinators regarding their experiences in obtaining the records and conducting the record reviews. The perspectives of CHWs and community members, who were screened, were also obtained. Results Thirty-seven percent (96/263) of those referred attended follow-up: 36 of 52 (69%) were urgent and 60 of 211 (28.4%) were non-urgent referrals. A diagnosis of hypertension (HTN) was made in 69% of urgent referrals and 37% of non-urgent referrals with treatment instituted in all cases. Reasons for non-attendance included limited self-perception of risk, associated costs, health system obstacles, and lack of trust in CHWs to conduct CVD risk assessments and to refer community members into the health system. Conclusions The existing barriers to referral in the health care systems negatively impact the gains to be had through screening by training CHWs in the use of a simple risk assessment tool. The new diagnoses of HTN and commencement on treatment in those that attended referrals underscores the value of having persons at the highest risk identified in the community setting and referred to a clinic for further evaluation and treatment. PMID:25854780
Levitt, Naomi S; Puoane, Thandi; Denman, Catalina A; Abrahams-Gessel, Shafika; Surka, Sam; Mendoza, Carlos; Khanam, Masuma; Alam, Sartaj; Gaziano, Thomas A
We have found that community health workers (CHWs) with appropriate training are able to accurately identify people at high cardiovascular disease (CVD) risk in the community who would benefit from the introduction of preventative management, in Bangladesh, Guatemala, Mexico, and South Africa. This paper examines the attendance pattern for those individuals who were so identified and referred to a health care facility for further assessment and management. Patient records from the health centres in each site were reviewed for data on diagnoses made and treatment commenced. Reasons for non-attendance were sought from participants who had not attended after being referred. Qualitative data were collected from study coordinators regarding their experiences in obtaining the records and conducting the record reviews. The perspectives of CHWs and community members, who were screened, were also obtained. Thirty-seven percent (96/263) of those referred attended follow-up: 36 of 52 (69%) were urgent and 60 of 211 (28.4%) were non-urgent referrals. A diagnosis of hypertension (HTN) was made in 69% of urgent referrals and 37% of non-urgent referrals with treatment instituted in all cases. Reasons for non-attendance included limited self-perception of risk, associated costs, health system obstacles, and lack of trust in CHWs to conduct CVD risk assessments and to refer community members into the health system. The existing barriers to referral in the health care systems negatively impact the gains to be had through screening by training CHWs in the use of a simple risk assessment tool. The new diagnoses of HTN and commencement on treatment in those that attended referrals underscores the value of having persons at the highest risk identified in the community setting and referred to a clinic for further evaluation and treatment.
LDCT screening. Such samples can be classified into two risk classes ( Bach -high, and Bach -low), as determined by a risk model developed at IEO. Under...separate funding, samples from Bach -high subjects are being analyzed using the miR-Test. The DoD-funded project aims to improve the clinical...applicability of the miR-Test blood test by analyzing ~1000 serum samples of Bach -low individuals. A parallel study of 1000 individuals undergoing LDCT
Sankar, Ashwin; Beattie, W Scott; Wijeysundera, Duminda N
Accurate and early identification of high-risk surgical patients allows for targeted use of perioperative monitoring and interventions that may improve their outcomes. This review summarizes current evidence on how information from the preoperative, operative, and immediate postoperative periods can help identify such individuals. Simple risk indices, such as the Revised Cardiac Risk Index or American Society of Anesthesiologists Physical Status scale, and online calculators allow risk to be estimated with moderate accuracy using readily available preoperative clinical information. Both specific specialized tests (i.e., cardiopulmonary exercise testing and cardiac stress testing) and promising novel biomarkers (i.e., troponins and natriuretic peptides) can help refine these risk estimates before surgery. Estimates of perioperative risk can be further informed by information acquired during the operative and immediate postoperative periods, such as risk indices (i.e., surgical Apgar score), individual risk factors (i.e., intraoperative hypotension), or postoperative biomarkers (i.e., troponins and natriuretic peptides). Preoperative clinical risk indices and risk calculators estimate surgical risk with moderate accuracy. Although novel biomarkers, specialized preoperative testing, and immediate postoperative risk indices show promise as methods to refine these risk estimates, more research is needed on how best to integrate risk information from these different sources.
Stoita, Alina; Penman, Ian D; Williams, David B
Pancreatic cancer is difficult to diagnose at an early stage and is associated with a very poor survival. Ten percent of pancreatic cancers result from genetic susceptibility and/or familial aggregation. Individuals from families with multiple affected first-degree relatives and those with a known cancer-causing genetic mutation have been shown to be at much higher risk of developing pancreatic cancer. Recent efforts have focused on detecting disease at an earlier stage to improve survival in these high-risk groups. This article reviews high-risk groups, screening methods, and current screening programs and their results.
Stoita, Alina; Penman, Ian D; Williams, David B
Pancreatic cancer is difficult to diagnose at an early stage and is associated with a very poor survival. Ten percent of pancreatic cancers result from genetic susceptibility and/or familial aggregation. Individuals from families with multiple affected first-degree relatives and those with a known cancer-causing genetic mutation have been shown to be at much higher risk of developing pancreatic cancer. Recent efforts have focused on detecting disease at an earlier stage to improve survival in these high-risk groups. This article reviews high-risk groups, screening methods, and current screening programs and their results. PMID:21633635
Bennett, Antonia V; Lozano, Paula; Richardson, Laura P; McCauley, Elizabeth; Katon, Wayne J
To develop a definition of high-risk asthma that more precisely identifies patients needing case management than the 2006 Healthcare Effectiveness Data and Information Set (HEDIS) definition. Two-year claims-based study, with cross-sectional phone survey data, for a sample of 769 youths (age 11-17 years) with asthma. The 2006 HEDIS measure defines high-risk asthma as meeting any of the following criteria: >1 emergency department (ED) visits, > or =1 hospitalizations for asthma, > or =4 asthma medication prescriptions, or > or =4 ambulatory visits for asthma with > or =2 prescriptions for asthma medication in 1 year. We created a revised definition (> or =1 ED visits or > or =1 hospitalizations for asthma or > or =1 oral steroid prescriptions for asthma) and identified patients with high-risk asthma in year 1 according to each definition. We compared the 2 groups on demographic and clinical characteristics, and healthcare utilization and costs in years 1 and 2. The revised definition identified 29% of the sample as having high-risk asthma, whereas the 2006 definition identified 67%. Compared with the 2006 definition, the revised definition identified patients with significantly greater asthma-related physical health problems and higher medical costs in year 1. In year 2, youths classified as high risk by the revised definition made more ED visits and were more likely to use oral steroids than those classified as high risk by the 2006 definition. The revised high-risk asthma definition identifies half as many individuals and is better able to identify patients with poorly controlled asthma in the subsequent year.
Gill, Kelly Elizabeth; Evans, Elizabeth; Kayser, Jürgen; Ben-David, Shelly; Messinger, Julie; Bruder, Gerard; Malaspina, Dolores; Corcoran, Cheryl Mary
Smell identification deficits exist in schizophrenia, and may be associated with its negative symptoms. Less is known about smell identification and its clinical correlates in individuals at clinical high risk (CHR) for schizophrenia and related psychotic disorders. We examined smell identification, symptoms and IQ in 71 clinical high-risk (CHR) subjects and 36 healthy controls. Smell identification was assessed using both the 40-item University of Pennsylvania Smell Identification Test (UPSIT; Doty et al., 1984) and its extracted 12-item Brief Smell Identification Test (Goudsmit et al., 2003). Smell identification did not significantly differ between CHR subjects and controls. Among CHR subjects, smell identification did not predict schizophrenia (N = 19; 27%) within 2 years, nor was it associated with negative or positive symptoms. This is the third prospective cohort study to examine smell identification in CHR subjects, and overall, findings are inconclusive, similar to what is found for other disorders in adolescents, such as autism spectrum, attention deficit and anxiety disorders. Smell identification deficit may not have clear utility as a marker of emergent schizophrenia and related psychotic disorders. PMID:25066961
Gill, Kelly Elizabeth; Evans, Elizabeth; Kayser, Jürgen; Ben-David, Shelly; Messinger, Julie; Bruder, Gerard; Malaspina, Dolores; Corcoran, Cheryl Mary
Smell identification deficits exist in schizophrenia, and may be associated with its negative symptoms. Less is known about smell identification and its clinical correlates in individuals at clinical high risk (CHR) for schizophrenia and related psychotic disorders. We examined smell identification, symptoms and IQ in 71 clinical high-risk (CHR) subjects and 36 healthy controls. Smell identification was assessed using both the 40-item University of Pennsylvania Smell Identification Test (UPSIT; Doty, R.L., Shaman, P., Kimmelman, C.P., Dann, M.S., 1984. University of Pennsylvania Smell Identification Test: a rapid quantitative olfactory function test for the clinic. Laryngoscope 94, 176-178) and its extracted 12-item Brief Smell Identification Test (Goudsmit, N., Coleman, E., Seckinger, R.A., Wolitzky, R., Stanford, A.D., Corcoran, C., Goetz, R.R., Malaspina, D., 2003. A brief smell identification test discriminates between deficit and non-deficit schizophrenia. Psychiatry Research 120, 155-164). Smell identification did not significantly differ between CHR subjects and controls. Among CHR subjects, smell identification did not predict schizophrenia (N=19; 27%) within 2 years, nor was it associated with negative or positive symptoms. This is the third prospective cohort study to examine smell identification in CHR subjects, and overall, findings are inconclusive, similar to what is found for other disorders in adolescents, such as autism spectrum, attention deficit and anxiety disorders. Smell identification deficit may not have clear utility as a marker of emergent schizophrenia and related psychotic disorders. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Marulanda, Susana; Addington, Jean
It has been suggested that resilience may be a protective factor with respect to mental illness. This may be an important factor for those who are vulnerable to psychiatric illness. Thus, the aims of this paper were to compare levels of resilience between individuals at clinical high risk (CHR) for psychosis and healthy controls, and to examine associations between resilience and clinical measures, functioning and trauma of CHR participants. Eighty participants, 40 CHR and 40 University of Calgary undergraduate students, completed two resilience questionnaires: the Connor-Davidson Resilience Scale and the Child and Youth Resilience Measure. A t-test revealed a significant difference between the groups on levels of resilience (t = 4.34, P < 0.01), demonstrating that CHR participants have lower levels of resilience than healthy controls. In terms of the associations between resilience and measures of mental health of CHR participants, it was found that higher levels of resilience were related to lower negative symptoms, depression and anxiety. Furthermore, resilient CHR participants showed higher levels of role functioning and generally reported higher positive schemas of self and others, as well as lower stress to reported life events. No associations were found between resilience and attenuated psychotic symptoms, social functioning, IQ and trauma. The results of the current study suggest that resilience may be beneficial to other mental issues present in CHR individuals but this may not be the case for attenuated psychotic symptoms. © 2014 Wiley Publishing Asia Pty Ltd.
Marulanda, Susana; Addington, Jean
Background It has been suggested that resilience may be a protective factor with respect to mental illness. This may be an important factor for those who are vulnerable to psychiatric illness. Thus, the aims of this paper were to compare levels of resilience between individuals at clinical high risk (CHR) for psychosis and healthy controls, and to examine associations between resilience and clinical measures, functioning, and trauma of CHR participants. Method Eighty participants, 40 CHR and 40 University of Calgary undergraduate students, completed two resilience questionnaires: the Connor-Davidson Resilience Scale and the Child and Youth Resilience Measure. Results A t-test revealed a significant difference between the groups on levels of resilience (t=4.34, p <0.01), demonstrating that CHR participants have lower levels of resilience than healthy controls. In terms of the associations between resilience and measures of mental health of CHR participants, it was found that higher levels of resilience were related to lower negative symptoms, depression, and anxiety. Furthermore, resilient CHR participants showed higher levels of role functioning and generally reported higher positive schemas of self and others, as well as lower stress to reported life events. No associations were found between resilience and attenuated psychotic symptoms, social functioning, IQ, and trauma. Conclusions The results of the current study suggest that resilience may be beneficial to other mental issues present in CHR individuals but this may not be the case for attenuated psychotic symptoms. PMID:25234104
Colarusso, Ronald P.; And Others
Teacher effectiveness in identifying children "at risk" for learning problems was studied with five Head Start teachers. Results showed that, after training in classroom observation techniques, paraprofessional teachers are capable of identifying developmental delays in children. (PHR)
Cadiz, Fernando; Kuerer, Henry M; Puga, Julio; Camacho, Jamile; Cunill, Eduardo; Arun, Banu
Our need to create a program for individuals at high risk for breast cancer development led us to research the available data on such programs. In this paper, we summarize our findings and our thinking process as we developed our own program. Breast cancer incidence is increasing worldwide. Even though there are known risk factors for breast cancer development, approximately 60% of patients with breast cancer have no known risk factor, although this situation will probably change with further research, especially in genetics. For patients with risk factors based on personal or family history, different models are available for assessing and quantifying risk. Assignment of risk levels permits tailored screening and risk reduction strategies. Potential benefits of specialized programs for women with high breast cancer risk include more cost -effective interventions as a result of patient stratification on the basis of risk; generation of valuable data to advance science; and differentiation of breast programs from other breast cancer units, which can result in increased revenue that can be directed to further improvements in patient care. Guidelines for care of patients at high risk for breast cancer are available from various groups. However, running a high-risk breast program involves much more than applying a guideline. Each high-risk program needs to be designed by its institution with consideration of local resources and country legislation, especially related to genetic issues. Development of a successful high-risk program includes identifying strengths, weaknesses, opportunities, and threats; developing a promotion plan; choosing a risk assessment tool; defining "high risk"; and planning screening and risk reduction strategies for the specific population served by the program. The information in this article may be useful for other institutions considering creation of programs for patients with high breast cancer risk.
Dubowitz, Howard; Kim, Jeongeun; Black, Maureen M.; Weisbart, Cindy; Semiatin, Joshua; Magder, Laurence S.
Objective: To help professionals identify factors that place families at risk for future child maltreatment, to facilitate necessary services and to potentially help prevent abuse and neglect. Method: The data are from a prospective, longitudinal study of 332 low-income families recruited from urban pediatric primary care clinics, followed for…
Cadiz, Fernando; Kuerer, Henry M.; Puga, Julio; Camacho, Jamile; Cunill, Eduardo; Arun, Banu
Our need to create a program for individuals at high risk for breast cancer development led us to research the available data on such programs. In this paper, we summarize our findings and our thinking process as we developed our own program. Breast cancer incidence is increasing worldwide. Even though there are known risk factors for breast cancer development, approximately 60% of patients with breast cancer have no known risk factor, although this situation will probably change with further research, especially in genetics. For patients with risk factors based on personal or family history, different models are available for assessing and quantifying risk. Assignment of risk levels permits tailored screening and risk reduction strategies. Potential benefits of specialized programs for women with high breast cancer risk include more cost -effective interventions as a result of patient stratification on the basis of risk; generation of valuable data to advance science; and differentiation of breast programs from other breast cancer units, which can result in increased revenue that can be directed to further improvements in patient care. Guidelines for care of patients at high risk for breast cancer are available from various groups. However, running a high-risk breast program involves much more than applying a guideline. Each high-risk program needs to be designed by its institution with consideration of local resources and country legislation, especially related to genetic issues. Development of a successful high-risk program includes identifying strengths, weaknesses, opportunities, and threats; developing a promotion plan; choosing a risk assessment tool; defining “high risk”; and planning screening and risk reduction strategies for the specific population served by the program. The information in this article may be useful for other institutions considering creation of programs for patients with high breast cancer risk. PMID:23833688
Rahman, S.M. Jamshedur; Ji, Xiangming; Zimmerman, Lisa J.; Li, Ming; Harris, Bradford K.; Hoeksema, Megan D.; Trenary, Irina A.; Zou, Yong; Qian, Jun; Slebos, Robbert J.C.; Beane, Jennifer; Spira, Avrum; Shyr, Yu; Eisenberg, Rosana; Liebler, Daniel C.; Young, Jamey D.; Massion, Pierre P.
The molecular determinants of lung cancer risk remain largely unknown. Airway epithelial cells are prone to assault by risk factors and are considered to be the primary cell type involved in the field of cancerization. To investigate risk-associated changes in the bronchial epithelium proteome that may offer new insights into the molecular pathogenesis of lung cancer, proteins were identified in the airway epithelial cells of bronchial brushing specimens from risk-stratified individuals by shotgun proteomics. Differential expression of selected proteins was validated by parallel reaction monitoring mass spectrometry in an independent set of individual bronchial brushings. We identified 2,869 proteins, of which 312 proteins demonstrated a trend in expression. Pathway analysis revealed enrichment of carbohydrate metabolic enzymes in high-risk individuals. Glucose consumption and lactate production were increased in human bronchial epithelial BEAS2B cells treated with cigarette smoke condensate for 7 months. Increased lipid biosynthetic capacity and net reductive carboxylation were revealed by metabolic flux analyses of [U-13C5] glutamine in this in vitro model, suggesting profound metabolic reprogramming in the airway epithelium of high-risk individuals. These results provide a rationale for the development of potentially new chemopreventive strategies and selection of patients for surveillance programs. PMID:27882349
strategies that will save more lives (Lyle, 2013). DoD spokewoman, Cynthia O. Smith, said “We are deeply concerned about suicide in the military...assesses an individual’s perceived stress and was designed to measure “the degree to which individuals appraise situations in their lives as...personal lives (18.9%). The most frequently indicated stressors for both men and women were being away from family (16.6%), deployment (13.4%), and
Giampaoli, Simona; Palmieri, Luigi; Mattiello, Amalia; Panico, Salvatore
The identification of high risk individuals is one of the main goals of cardiovascular primary prevention and constitutes the basis for implementing actions oriented toward reducing modifiable risk factors at individual level, from changing life styles to drug interventions. The most appropriate method for identifying high risk individuals is the evaluation of their absolute global risk, a probability indicator of incidence, predictable on the basis of risk factor levels. Risk functions, derived from longitudinal studies, are used to identify persons at high probability to develop cardiovascular diseases. The appropriateness of the use of these risk functions depends upon the characteristics of the population that generated them and of individuals which they are applied to. Risk charts are simply absolute global risks calculated by classes of risk factors; risk scores are more precise evaluation derived from absolute global risks calculated by continuous levels of risk factors. Risk charts and scores are formed through the risk functions derived from different studies: Framingham, PROCAM (Munster), Seven Countries Study, SCORE and Progetto CUORE. A further chart has been created using the Framingham Study and adapted to the guidelines of New Zealand regarding the treatment of dyslipidemias and blood pressure. Major differences can be found in the availability of risk factors in men and women and in the use of fatal and non-fatal coronary and cerebrovascular events as end-points. All these studies use different diagnostic criteria for identification, classification and validation of events. The awareness of the risk charts differences is a key issue to refine tools for prevention of cardiovascular disease in populations with different probabilities of disease frequency.
Lami, Gabriele; Biagini, Maria Rosa; Galli, Andrea
Pancreatic cancer is a highly lethal disease with a genetic susceptibility and familial aggregation found in 3%-16% of patients. Early diagnosis remains the only hope for curative treatment and improvement of prognosis. This can be reached by the implementation of an intensive screening program, actually recommended for individuals at high-risk for pancreatic cancer development. The aim of this strategy is to identify pre-malignant precursors or asymptomatic pancreatic cancer lesions, curable by surgery. Endoscopic ultrasound (EUS) with or without fine needle aspiration (FNA) seems to be the most promising technique for early detection of pancreatic cancer. It has been described as a highly sensitive and accurate tool, especially for small and cystic lesions. Pancreatic intraepithelial neoplasia, a precursor lesion which is highly represented in high-risk individuals, seems to have characteristics chronic pancreatitis-like changes well detected by EUS. Many screening protocols have demonstrated high diagnostic yields for pancreatic pre-malignant lesions, allowing prophylactic pancreatectomies. However, it shows a high interobserver variety even among experienced endosonographers and a low sensitivity in case of chronic pancreatitis. Some new techniques such as contrast-enhanced harmonic EUS, computer-aided diagnostic techniques, confocal laser endomicroscopy miniprobe and the detection of DNA abnormalities or protein markers by FNA, promise improvement of the diagnostic yield of EUS. As the resolution of imaging improves and as our knowledge of precursor lesions grows, we believe that EUS could become the most suitable method to detect curable pancreatic neoplasms in correctly identified asymptomatic at-risk patients. PMID:25031786
Li, JunJie; Jiang, Yizhou; Liu, Yirong; Shao, Zhimin
To demonstrate the patterns of breast cancer-specific mortality (BCSM) in estrogen receptor (ER)-positive diseases and to identify high-risk candidates for extended endocrine therapy. Using the Surveillance, Epidemiology and End Results database, we identified ER-positive patients diagnosed between 1990 and 2000 (cohort 1 [C1]) and between 2001 and 2005 (cohort 2 [C2]). The patterns of BCSM were calculated using Cox proportional hazard regression models. A risk classification model was developed, and X-tile software was used to divide patients with high BCSM rates into 3 risk groups. The annual BCSM rate of C2 was decreased by one-third and was maintained at 10-15 (per 1000 persons per year) from year 2 to year 10. Long-term mortality risks still persisted in C2, especially in patients with node-positive, grade 3 or T3 disease, who should be considered as "clinical-high-risk". These patients were further divided into 3 risk groups through our model: for C1, 42.2% were in the low-risk group, 38.9% in the medium-risk group, and 18.9% in the high-risk group; and for C2, 45.5% were in the low-risk group, 38.2% in the medium-risk group and 16.2% in the high-risk group (p < 0.001). The BCSM rates of the patients in each group within C2 decreased, and fewer patients in C2 were classified into the clinical high-risk group. ER-positive patients with node-positive, grade 3 or T3 diseases had sustained risks of death throughout the 10-year time frame, and our model is helpful to identify patients with high risk who are candidates for extended endocrine therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.
Leynaud, Gerardo C; Reati, Gustavo J
To determine the case distribution of accidental ophidism in the Córdoba province of Argentina, identify high risk areas, and evaluate the usefulness of the SIGEpi software program (Pan American Health Organization, Washington, DC, United States of America). Information regarding the 299 cases of accidental ophidism reported in Córdoba in 1995-2006 was collected from the Provincial Epidemiology Department's official records of incidents involving venomous creatures. The SIGEpi software program was used for geographic mapping. Specific maps were produced to identify, quantify, and visualize the danger zones and areas of high risk for ophidism. The incidents occurred mostly in the northern and western areas of the province. Snakes of the Bothrops genus were responsible for the majority of the incidents (87.7% of the total). The departments with the highest annual incidence rates were Pocho and Río Seco (> 10 incidents per 100,000 residents). Three ophidism high-risk zones were identified: one in far west of the province, another in the far north, and another just north of Bañados del Río Dulce and the Mar Chiquita lagoon. Accidental ophidism constitutes a major health problem in the Córdoba province where incidence rates are higher than those areas with more severe economic issues tied to rural labor. SIGEpi software is a reasonable choice for studying public health challenges and proved to be effective in identifying areas at high risk for ophidism.
Braverman, Julia; Shaffer, Howard J
The goal of this study is to identify betting patterns displayed during the first month of actual Internet gambling on a betting site that can serve as behavioural markers to predict the development of gambling-related problems. Using longitudinal data, k-means clustering analysis identified a small subgroup of high-risk gamblers. Seventy-three percent of the members of this subgroup eventually closed their account due to gambling-related problems. The characteristics of this high-risk subgroup were as follows: (i) frequent and (ii) intensive betting combined with (iii) high variability across wager amount and (iv) an increasing wager size during the first month of betting. This analysis provides important information that can help to identify potentially problematic gamblers during the early stages of gambling-related problems. Public health workers can use these results to develop early interventions that target high-risk Internet gamblers for prevention efforts. However, one study limitation is that the results distinguish only a small proportion of the total sample; therefore, additional research will be necessary to identify markers that can classify larger segments of high-risk gamblers.
McGaw, Sue; Scully, Tamara; Pritchard, Colin
Objectives: This study set out to identify risk factors affecting parents with intellectual disabilities (IDs) by determining: (i) whether perception of family support differs between parents with IDs, referring professionals, and a specialist parenting service; (ii) whether multivariate familial and demographic factors differentiates "high-risk"…
Harrisberger, Fabienne; Buechler, Roman; Smieskova, Renata; Lenz, Claudia; Walter, Anna; Egloff, Laura; Bendfeldt, Kerstin; Simon, Andor E; Wotruba, Diana; Theodoridou, Anastasia; Rössler, Wulf; Riecher-Rössler, Anita; Lang, Undine E; Heekeren, Karsten; Borgwardt, Stefan
Reduction in hippocampal volume is a hallmark of schizophrenia and already present in the clinical high-risk state. Nevertheless, other subcortical structures, such as the thalamus, amygdala and pallidum can differentiate schizophrenia patients from controls. We studied the role of hippocampal and subcortical structures in clinical high-risk individuals from two cohorts. High-resolution T1-weighted structural MRI brain scans of a total of 91 clinical high-risk individuals and 64 healthy controls were collected in two centers. The bilateral volume of the hippocampus, the thalamus, the caudate, the putamen, the pallidum, the amygdala, and the accumbens were automatically segmented using FSL-FIRST. A linear mixed-effects model and a prospective meta-analysis were applied to assess group-related volumetric differences. We report reduced hippocampal and thalamic volumes in clinical high-risk individuals compared to healthy controls. No volumetric alterations were detected for the caudate, the putamen, the pallidum, the amygdala, or the accumbens. Moreover, we found comparable medium effect sizes for group-related comparison of the thalamus in the two analytical methods. These findings underline the relevance of specific alterations in the hippocampal and subcortical volumes in the high-risk state. Further analyses may allow hippocampal and thalamic volumes to be used as biomarkers to predict psychosis. PMID:27738647
Rahman, A K M Anisur; Dirk, Berkvens; Fretin, David; Saegerman, Claude; Ahmed, Muzahed Uddin; Muhammad, Noor; Hossain, Akram; Abatih, Emmanuel
Brucellosis is an occupational hazard of livestock farmers, dairy workers, veterinarians, slaughterhouse workers, and laboratory personnel, all of whom are considered to belong to the high-risk occupational group (HROG). A study was undertaken to determine the seroprevalence of brucellosis, identify risk factors associated with brucellosis seropositivity, and detect Brucella at genus level using real-time polymerase chain reaction (PCR) among people in the HROG in the Dhaka division of Bangladesh. A sample of 500 individuals from the HROG was collected from three districts of Dhaka division of Bangladesh. A multiple random effects logistic regression model was used to identify potential risk factors. Two types of real-time PCR methods were applied to detect Brucella genus-specific DNA using serum from seropositive patients. The prevalence of brucellosis based on the three tests was observed to be 4.4% based on a parallel interpretation. The results of the multiple random effects logistic regression analysis with random intercept for district revealed that the odds of brucellosis seropositivity among individuals who had been in contact with livestock for more than 26 years was about 14 times higher as compared to those who had less than 5 years of contact with livestock. In addition, when the contact was with goats, the odds of brucellosis seropositivity were about 60 times higher as compared to when contact was with cattle only. Noticeable variation in brucellosis seropositivity among humans within the three districts was noted. All of the 13 individuals who tested positive for the serological tests were also positive in two types of real-time PCR using the same serum samples. Livestock farmers of brucellosis positive herds had a significantly higher probability to be seropositive for brucellosis. The study emphasized that contact with livestock, especially goats, is a significant risk factor for the transmission of brucellosis among individuals in the HROG.
Cotter, Jack; Bartholomeusz, Cali; Papas, Alicia; Allott, Kelly; Nelson, Barnaby; Yung, Alison R; Thompson, Andrew
Social and role functioning are compromised for the majority of individuals at ultra-high risk of psychosis, and it is important to identify factors that contribute to this functional decline. This study aimed to investigate social cognitive abilities, which have previously been linked to functioning in schizophrenia, as potential factors that impact social, role and global functioning in ultra-high risk patients. A total of 30 ultra-high risk patients were recruited from an established at-risk clinical service in Melbourne, Australia, and completed a battery of social cognitive, neurocognitive, clinical and functioning measures. We examined the relationships between all four core domains of social cognition (emotion recognition, theory of mind, social perception and attributional style), neurocognitive, clinical and demographic variables with three measures of functioning (the Global Functioning Social and Role scales and the Social and Occupational Functioning Assessment Scale) using correlational and multiple regression analyses. Performance on a visual theory of mind task (visual jokes task) was significantly correlated with both concurrent role ( r = 0.425, p = 0.019) and global functioning ( r = 0.540, p = 0.002). In multivariate analyses, it also accounted for unique variance in global, but not role functioning after adjusting for negative symptoms and stress. Social functioning was not associated with performance on any of the social cognition tasks. Among specific social cognitive abilities, only a test of theory of mind was associated with functioning in our ultra-high risk sample. Further longitudinal research is needed to examine the impact of social cognitive deficits on long-term functional outcome in the ultra-high risk group. Identifying social cognitive abilities that significantly impact functioning is important to inform the development of targeted intervention programmes for ultra-high risk individuals.
Shaikh, Mumtaz Ali; Kumar, Raj; Ghori, Raft Ahmed; Shaikh, Dur-e-Yakta
To assess the body mass index and waist circumferences of high risk non diabetic young individuals and compare them with low risk non diabetic young individuals. A cross sectional, case control comparative study was conducted in the department of medicine, LUMHS from January 2008 to March 2009. Five hundred individuals 20-40 years of age were selected and divided into two groups i.e. Group A: high risk (250 individuals) and Group B: low risk (250 individuals) on the basis of same age and gender. Group A included those who had positive family history of type 2 DM in 1st degree relatives while group B had no family history of type 2 DM in 1st degree relatives. The blood pressure, BMI and Waist Circumference was measured and Fasting Blood Sugar was estimated in each individual. In each group 125 (50%) were males and 125 (50%) were females. In group A 58% and in group B 28.8% individuals represented raised BMI whereas 42% in group A and 36% in group B individuals showed an increased waist circumference. Mean fasting blood glucose was significantly higher in Group A than in Group B (P = 0.001). Impaired Fasting Glucose is strongly associated with family history of type 2 diabetes mellitus. Presence of obesity specially in high risk non-diabetic young individuals emphasize the need for routine health screening for early institution of preventive measures.
Sagrestano, Lynda M.; Heiss-Wendt, Renate M.; Mizan, Ainon N.; Kittleson, Mark J.; Sarvela, Paul D.
Identified the best methods of reaching people at high risk with HIV-prevention messages. Data from men who had sex with men, injection drug users, sex workers, HIV-positive people, heterosexuals, migrant workers, and perinatal women indicated that over 70 percent were exposed to HIV-prevention messages, though sources of exposure varied by risk…
Financial Management Regulation GPC Government Purchase Card OUSD (ATL) Office of the Under Secretary of Defense for Acquisition...Technology, and Logistics PCPMO Purchase Card Program Management Office PCOLS Purchase Card On-Line System U.S.C. United States Code INSPECTOR...FINANCIAL MANAGEMENT AND COMPTROLLER) AUDITOR GENERAL, DEPARTMENT OF THE ARMY SUBJECT: Army Needs to Identify Government Purchase Card High-Risk
Amminger, G Paul; Schäfer, Miriam R; Papageorgiou, Konstantinos; Klier, Claudia M; Schlögelhofer, Monika; Mossaheb, Nilufar; Werneck-Rohrer, Sonja; Nelson, Barnaby; McGorry, Patrick D
Problems in the perception of emotional material, in particular deficits in the recognition of negative stimuli, have been demonstrated in schizophrenia including in first-episode samples. However, it is largely unknown if emotion recognition impairment is present in people with subthreshold psychotic symptoms. Here, we examined the capacity to recognize facially expressed emotion and affective prosody in 79 individuals at ultra high-risk for psychosis, 30 clinically stable individuals with first-episode schizophrenia assessed as outpatients during the early recovery phase of illness, and 30 unaffected healthy control subjects. We compared (1) scores for a combined fear-sadness aggregate index across face and voice modalities, (2) summary scores of specific emotions across modalities, and (3) scores for specific emotions for each sensory modality. Findings supported deficits in recognition of fear and sadness across both modalities for the clinical groups (the ultra high-risk and first-episode group) as compared with the healthy controls. Furthermore, planned contrasts indicated that compared with the healthy control subjects, both clinical groups had a significant deficit for fear and sadness recognition in faces and for anger recognition in voices. Specific impairments in emotion recognition may be apparent in people at clinical high-risk for schizophrenia before the full expression of psychotic illness. The results suggest a trait deficit and an involvement of the amygdala in the pathology of ultra high-risk states.
Papadatou, Ioanna; Spoulou, Vana
Controversy exists regarding the optimal use of the 23-valent pneumococcal conjugate vaccine for the protection of high-risk individuals, such as children and adults with immunocompromising conditions and the elderly. The effectiveness and immunogenicity of 23-valent pneumococcal polysaccharide vaccine (PPV23) are limited in such high-risk populations compared to the healthy, with meta-analyses failing to provide robust evidence on vaccine efficacy against invasive pneumococcal disease (IPD) or pneumonia. Moreover, several studies have demonstrated a PPV23-induced state of immune tolerance or hyporesponsiveness to subsequent vaccination, where the response to revaccination does not reach the levels achieved with primary vaccination. The clinical significance of hyporesponsiveness is not yet clarified, but attenuated humoral and cellular response could lead to reduced levels of protection and increased susceptibility to pneumococcal disease. As disease epidemiology among high-risk groups shows that we are still in need of maximum serotype coverage, the optimal use of PPV23 in the context of combined conjugate/polysaccharide vaccine schedules is an important priority. In this minireview, we discuss PPV23-induced hyporesponsiveness and its implications in designing highly effective vaccination schedules for the optimal protection for high-risk individuals.
Mette, Lindsey A; Saldívar, Anna Maria Pulido; Poullard, Natalie E; Torres, Ivette C; Seth, Sarah G; Pollock, Brad H; Tomlinson, Gail E
Breast and colorectal cancers are common cancers for which genetic risk assessment and counseling are available. However, these services are often limited to metropolitan areas and are not readily accessible to underserved populations. Moreover, ethnic and racial disparities present additional obstacles to identifying and screening high-risk individuals and have a bearing on treatment outcomes. To provide cancer genetic risk assessment and counseling through telemedicine to the remote, underserved primarily Hispanic population of the Texas-Mexico border region. Program participants were mailed a questionnaire to assess their satisfaction with the program so that we could determine the acceptability of video-teleconferencing for cancer risk assessment. The overall level of satisfaction with the program was very high, demonstrating the acceptability of a cancer genetic risk assessment program that relied on telemedicine to reach and underserved minority community. Delivery model requires the availability of and access to communication technologies; trained staff are needed at remote sites for sample collection and patient handling. Video-teleconferencing is an acceptable method of providing cancer risk assessment in a remote, underserved population. ©2016 Frontline Medical Communications.
Webster, Daniel W; Wintemute, Garen J
This article summarizes and critiques available evidence from studies published between 1999 and August 2014 on the effects of policies designed to keep firearms from high-risk individuals in the United States. Some prohibitions for high-risk individuals (e.g., those under domestic violence restraining orders, violent misdemeanants) and procedures for checking for more types of prohibiting conditions are associated with lower rates of violence. Certain laws intended to prevent prohibited persons from accessing firearms-rigorous permit-to-purchase, comprehensive background checks, strong regulation and oversight of gun dealers, and requiring gun owners to promptly report lost or stolen firearms-are negatively associated with the diversion of guns to criminals. Future research is needed to examine whether these laws curtail nonlethal gun violence and whether the effects of expanding prohibiting conditions for firearm possession are modified by the presence of policies to prevent diversion.
Martei, Yehoda M; Matro, Jennifer M
Identifying patients at high risk of breast cancer recurrence has important implications not only for enabling the ability to provide accurate information to patients but also the potential to improve patient outcomes. Patients at high recurrence risk can be offered appropriate treatment to improve the overall survival. However, the major challenge is identifying patients with early-stage breast cancer at lower risk who may be spared potentially toxic therapy. The successful integration of molecular assays into clinical practice may address the problem of overtreatment and improve overall patient outcomes. PMID:26504408
Glenthøj, Louise Birkedal; Hjorthøj, Carsten; Kristensen, Tina Dam; Davidson, Charlie Andrew; Nordentoft, Merete
Cognitive deficits are prominent features of the ultra-high risk state for psychosis that are known to impact functioning and course of illness. Cognitive remediation appears to be the most promising treatment approach to alleviate the cognitive deficits, which may translate into functional improvements. This study systematically reviewed the evidence on the effectiveness of cognitive remediation in the ultra-high risk population. The electronic databases MEDLINE, PsycINFO, and Embase were searched using keywords related to cognitive remediation and the UHR state. Studies were included if they were peer-reviewed, written in English, and included a population meeting standardized ultra-high risk criteria. Six original research articles were identified. All the studies provided computerized, bottom-up-based cognitive remediation, predominantly targeting neurocognitive function. Four out of five studies that reported a cognitive outcome found cognitive remediation to improve cognition in the domains of verbal memory, attention, and processing speed. Two out of four studies that reported on functional outcome found cognitive remediation to improve the functional outcome in the domains of social functioning and social adjustment. Zero out of the five studies that reported such an outcome found cognitive remediation to affect the magnitude of clinical symptoms. Research on the effect of cognitive remediation in the ultra-high risk state is still scarce. The current state of evidence indicates an effect of cognitive remediation on cognition and functioning in ultra-high risk individuals. More research on cognitive remediation in ultra-high risk is needed, notably in large-scale trials assessing the effect of neurocognitive and/or social cognitive remediation on multiple outcomes.
Yang, Yelin; Chen, Li; Yam, Yeung; Achenbach, Stephan; Al-Mallah, Mouaz; Berman, Daniel S; Budoff, Matthew J; Cademartiri, Filippo; Callister, Tracy Q; Chang, Hyuk-Jae; Cheng, Victor Y; Chinnaiyan, Kavitha; Cury, Ricardo; Delago, Augustin; Dunning, Allison; Feuchtner, Gudrun; Hadamitzky, Martin; Hausleiter, Jörg; Karlsberg, Ronald P; Kaufmann, Philipp A; Kim, Yong-Jin; Leipsic, Jonathon; LaBounty, Troy; Lin, Fay; Maffei, Erica; Raff, Gilbert L; Shaw, Leslee J; Villines, Todd C; Min, James K; Chow, Benjamin J W
This study sought to develop a clinical model that identifies patients with and without high-risk coronary artery disease (CAD). Although current clinical models help to estimate a patient's pre-test probability of obstructive CAD, they do not accurately identify those patients with and without high-risk coronary anatomy. Retrospective analysis of a prospectively collected multinational coronary computed tomographic angiography (CTA) cohort was conducted. High-risk anatomy was defined as left main diameter stenosis ≥50%, 3-vessel disease with diameter stenosis ≥70%, or 2-vessel disease involving the proximal left anterior descending artery. Using a cohort of 27,125, patients with a history of CAD, cardiac transplantation, and congenital heart disease were excluded. The model was derived from 24,251 consecutive patients in the derivation cohort and an additional 7,333 nonoverlapping patients in the validation cohort. The risk score consisted of 9 variables: age, sex, diabetes, hypertension, current smoking, hyperlipidemia, family history of CAD, history of peripheral vascular disease, and chest pain symptoms. Patients were divided into 3 risk categories: low (≤7 points), intermediate (8 to 17 points) and high (≥18 points). The model was statistically robust with area under the curve of 0.76 (95% confidence interval [CI]: 0.75 to 0.78) in the derivation cohort and 0.71 (95% CI: 0.69 to 0.74) in the validation cohort. Patients who scored ≤7 points had a low negative likelihood ratio (<0.1), whereas patients who scored ≥18 points had a high specificity of 99.3% and a positive likelihood ratio (8.48). In the validation group, the prevalence of high-risk CAD was 1% in patients with ≤7 points and 16.7% in those with ≥18 points. We propose a scoring system, based on clinical variables, that can be used to identify patients at high and low pre-test probability of having high-risk CAD. Identification of these populations may detect those who may benefit
Ng, Tommy H; Chung, Ka-Fai; Ho, Fiona Yan-Yee; Yeung, Wing-Fai; Yung, Kam-Ping; Lam, Tak-Ho
Over the past decade, researchers have shifted focus from the manic and depressive episodes to the interepisode period in the study of sleep-wake disturbance in bipolar disorder. The objective of this systematic review was to compile and synthesize studies that employed sleep diary, actigraphy, polysomnography, and questionnaires to compare sleep-wake patterns in people with interepisode bipolar disorder or high-risk individuals vs. normal controls and/or people with primary insomnia. We searched key databases until June 2013. Our search identified 21 eligible studies, yielding 24 sleep-wake variables. A total of 531 people with interepisode bipolar disorder, 157 high-risk individuals, 678 normal controls and 67 adults with primary insomnia were evaluated. Using a random-effects model, our analyses suggest that adults with interepisode bipolar disorder appear worse than normal controls in most variables and comparable to adults with primary insomnia in certain aspects. Sleep onset latency, wake after sleep onset, and variability of sleep-wake variables were most consistently impaired in interepisode bipolar disorder. In comparison with controls, high-risk individuals were found to have higher variability in sleep efficiency and lower relative amplitude. The findings provide a foundation for the search for candidate endophenotypes and the development of novel interventions for bipolar disorder. Copyright © 2014 Elsevier Ltd. All rights reserved.
Oreskovic, Nicolas Michel; Maniates, Jennifer; Weilburg, Jeffrey; Choy, Garry
Care coordination programs have traditionally focused on medically complex patients, identifying patients that qualify by analyzing formatted clinical data and claims data. However, not all clinically relevant data reside in claims and formatted data. Recently, there has been increasing interest in including patients with complex psychosocial determinants of health in care coordination programs. Psychosocial risk factors, including social determinants of health, mental health disorders, and substance abuse disorders, are less amenable to rapid and systematic data analyses, as these data are often not collected or stored as formatted data, and due to US Health Insurance Portability and Accountability Act (HIPAA) regulations are often not available as claims data. The objective of our study was to develop a systematic approach using word recognition software to identifying psychosocial risk factors within any part of a patient's electronic health record (EHR). We used QPID (Queriable Patient Inference Dossier), an ontology-driven word recognition software, to scan adult patients' EHRs to identify terms predicting a high-risk patient suitable to be followed in a care coordination program in Massachusetts, USA. Search terms identified high-risk conditions in patients known to be enrolled in a care coordination program, and were then tested against control patients. We calculated precision, recall, and balanced F-measure for the search terms. We identified 22 EHR-available search terms to define psychosocial high-risk status; the presence of 9 or more of these terms predicted that a patient would meet inclusion criteria for a care coordination program. Precision was .80, recall .98, and balanced F-measure .88 for the identified terms. For adult patients insured by Medicaid and enrolled in the program, a mean of 14 terms (interquartile range [IQR] 11-18) were present as identified by the search tool, ranging from 2 to 22 terms. For patients enrolled in the program but
Okun, A; Lentz, T J; Schulte, P; Stayner, L
Approximately one-third (32%) of U.S. workers are employed in small business industries (those with 80% of workers in establishments with fewer than 100 employees), and approximately 53 million persons in private industry work in small business establishments. This study was performed to identify small business industries at high risk for occupational injuries, illnesses, and fatalities. Small business industries were identified from among all three- and four-digit Standard Industrial Classification (SIC) codes and ranked using Bureau of Labor Statistics (BLS) data by rates and numbers of occupational injuries, illnesses, and fatalities. Both incidence rates and number of injury, illness, and fatality cases were evaluated. The 253 small business industries identified accounted for 1,568 work-related fatalities (34% of all private industry). Transportation incidents and violent acts were the leading causes of these fatalities. Detailed injury and illness data were available for 105 small business industries, that accounted for 1,476,400 work-related injuries, and 55,850 occupational illnesses. Many of the small business industries had morbidity and mortality rates exceeding the average rates for all private industry. The highest risk small business industries, based on a combined morbidity and mortality index, included logging, cut stone and stone products, truck terminals, and roofing, siding, and sheet metal work. Identification of high-risk small business industries indicates priorities for those interested in developing targeted prevention programs.
Olvet, Doreen M.; Carrión, Ricardo E.; Auther, Andrea M.; Cornblatt, Barbara A.
Aims A major public health concern associated with schizophrenia is the long-term disability that involves an inability to function independently in the community. An individual’s self-awareness of functional impairment may be a significant factor contributing to long-term disability. In fact, subjective interpretation of one’s illness impacts treatment participation and adherence, and is linked to poor outcomes. However, it remains unclear how illness-related functional impairment is perceived by individuals prior to the onset of psychosis. This study aims to examine the relationship between clinician-based and self-report assessments of functioning, as well as the contribution of clinical symptoms to this relationship in individuals at clinical high-risk for psychosis. Methods The Sheehan Disability Scale, a self-rated instrument, was used to measure disruption in daily functioning in social and role functioning due to symptoms in a sample of 73 treatment-seeking patients at clinical high-risk for psychosis and 50 healthy controls. Results Relative to healthy controls, clinical high-risk patients self-reported significant disruptions in social and role functioning. In addition, a specific relationship emerged in that clinician-rated measures of functioning and depression were related to disability scores. Conclusions These findings suggest that clinical high-risk patients are significantly disturbed by their illness. Self-reported disruption of daily functioning was associated with clinician-rated functioning and depressive symptoms, further highlighting the impact of functional impairments on the level of distress experienced by patients in the early phases of the illness. Intervention strategies that repair functional impairment before the onset of psychosis may prevent long-term disability. PMID:23968457
Oku, Kenji; Amengual, Olga; Yasuda, Shinsuke; Atsumi, Tatsuya
Antiphospholipid syndrome (APS) is a clinical disorder characterised by thrombosis and/or pregnancy morbidity in the persistence of antiphospholipid (aPL) antibodies that are pathogenic and have pro-coagulant activities. Thrombosis in APS tends to recur and require prophylaxis; however, the stereotypical treatment for APS patients is inadequate and stratification of the thrombotic risks is important as aPL are prevalently observed in various diseases or elderly population. It is previously known that the multiple positive aPL or high titre aPL correlate to thrombotic events. To progress the stratification of thrombotic risks in APS patients and to quantitatively analyse those risks, antiphospholipid score (aPL-S) and the Global Anti-phospholipid Syndrome Score (GAPSS) were defined. These scores were raised from the large patient cohort data and either aPL profile classified in detail (aPL-S) or simplified aPL profile with classical thrombotic risk factors (GAPSS) was put into a scoring system. Both the aPL-S and GAPSS have shown a degree of accuracy in identifying high-risk APS patients, especially those at a high risk of thrombosis. However, there are several areas requiring improvement, or at least that clinicians should be aware of, before these instruments are applied in clinical practice. One such issue is standardisation of the aPL tests, including general testing of phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT). Additionally, clinicians may need to be aware of the patient's medical history, particularly with respect to the incidence of SLE, which influences the cutoff value for identifying high-risk patients.
Konings, Ingrid C A W; Sidharta, Grace N; Harinck, Femme; Aalfs, Cora M; Poley, Jan-Werner; Kieffer, Jacobien M; Kuenen, Marianne A; Smets, Ellen M A; Wagner, Anja; van Hooft, Jeanin E; van Rens, Anja; Fockens, Paul; Bruno, Marco J; Bleiker, Eveline M A
When assessing the feasibility of surveillance for pancreatic cancer (PC), it is important to address its psychological burden. The aim of this ongoing study is to evaluate the psychological burden of annual pancreatic surveillance for individuals at high risk to develop PC. This is a multicenter prospective study. High-risk individuals who undergo annual pancreatic surveillance with magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) were invited to complete questionnaires to assess motivations for participating in surveillance, experiences with participation, perceived PC risk, topics of concern, and psychological distress. Questionnaires were sent after intake for participation (T1), after the first MRI and EUS (T2), and after the MRI and EUS 1 (T3), 2 (T4), and 3 years (T5) after first surveillance. In total, 140 out of 152 individuals returned one or more of the questionnaires (response 92%); 477 questionnaires were analyzed. The most frequently reported motivation for participating in surveillance was the possible early detection of (a precursor stage of) cancer (95-100%). Only a minority of respondents experienced MRI and EUS as uncomfortable (10% and 11%, respectively), and respondents dreaded their next EUS investigation less as surveillance progressed. Respondents' cancer worries decreased significantly over time, and both their anxiety and depression scores remained stable and low over the 3-year period of follow-up. The psychological burden of pancreatic surveillance is low at all assessments. Therefore, from a psychological point of view, participation of high-risk individuals in an annual pancreatic surveillance program is feasible.Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
Canto, Marcia Irene; Hruban, Ralph H.; Fishman, Elliot K.; Kamel, Ihab R.; Schulick, Richard; Zhang, Zhe; Topazian, Mark; Takahashi, Naoki; Fletcher, Joel; Petersen, Gloria; Klein, Alison P.; Axilbund, Jennifer; Griffin, Constance; Syngal, Sapna; Saltzman, John R.; Mortele, Koenraad J.; Lee, Jeffrey; Tamm, Eric; Vikram, Raghunandan; Bhosale, Priya; Margolis, Daniel; Farrell, James; Goggins, Michael
BACKGROUND & AIMS The risk of pancreatic cancer is increased in patients with a strong family history of pancreatic cancer or a predisposing germline mutation. Screening can detect curable, non-invasive pancreatic neoplasms, but the optimal imaging approach is not known. We determined the baseline prevalence and characteristics of pancreatic abnormalities using 3 imaging tests to screen asymptomatic, high-risk individuals (HRI). METHODS We screened 225 asymptomatic adult HRI at 5 academic US medical centers once, using computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasonography (EUS). We compared results in a blinded, independent fashion. RESULTS Ninety-two of 216 HRI (42%) were found to have at least 1 pancreatic mass (84 cystic, 3 solid) or a dilated pancreatic duct (n=5) by any of the imaging modalities. Fifty-one of the 84 HRI with a cyst (60.7%) had multiple lesions, typically small (mean 0.55 cm, range 2–39 mm), in multiple locations. The prevalence of pancreatic lesions increased with age; they were detected in 14% of subjects <50 years old, 34% of subjects 50–59 years old, and 53% of subjects 60–69 years old (P<.0001). CT, MRI, and EUS detected a pancreatic abnormality in 11%, 33.3%, and 42.6% of the HRI, respectively. Among these abnormalities, proven or suspected neoplasms were identified in 85 HRI (82 intraductal papillary mucinous neoplasms [IPMN] and 3 pancreatic endocrine tumors). Three of 5 HRI who underwent pancreatic resection had high-grade dysplasia in <3 cm IPMNs and in multiple intraepithelial neoplasias. CONCLUSIONS Screening of asymptomatic HRI frequently detects small pancreatic cysts, including curable, non-invasive high-grade neoplasms. EUS and MRI detect pancreatic lesions better than CT. PMID:22245846
Sakuma, Mio; Bates, David W; Morimoto, Takeshi
Adverse drug events (ADEs) are common health problems worldwide. Developing a prediction rule to identify patients at high risk for ADEs to prevent or ameliorate ADEs could be one attractive strategy. The Japan Adverse Drug Events (JADE) study is a prospective cohort study including 3459 participants. We randomly divided the JADE study cohort into the derivation and the validation sets, using an automated random digit generator. We calculated the probabilities of ADE in each patient in the validation set after applying the prediction rule developed in the derivation set. The actual incidence and area under the receiver operating characteristic curve (AUC) in the validation set were compared with those in the derivation set to evaluate the prognostic ability of our developed prediction rule. The developed prediction rule included eight independent risk factors. Each patient in the validation set was classified into three categories of risk for the ADEs according to the probability of ADEs calculated by the developed prediction rule. Eight percent (137/1730) of patients in the validation set fell into the high-risk group, and 35% of this group (48/137) had at least one ADE. The AUC in the validation set was 0.63 (95%CI 0.60-0.66), and the performance to discriminate the probability of ADE was similar (p = 0.08) compared with that in the derivation set. This prediction rule had the modest predictive ability and could help physicians and other healthcare professionals to make an estimation of patients at high risk for ADEs. Copyright © 2012 John Wiley & Sons, Ltd.
Wu, Jia; Gensheimer, Michael F; Dong, Xinzhe; Rubin, Daniel L; Napel, Sandy; Diehn, Maximilian; Loo, Billy W; Li, Ruijiang
To develop an intratumor partitioning framework for identifying high-risk subregions from (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) imaging and to test whether tumor burden associated with the high-risk subregions is prognostic of outcomes in lung cancer. In this institutional review board-approved retrospective study, we analyzed the pretreatment FDG-PET and CT scans of 44 lung cancer patients treated with radiation therapy. A novel, intratumor partitioning method was developed, based on a 2-stage clustering process: first at the patient level, each tumor was over-segmented into many superpixels by k-means clustering of integrated PET and CT images; next, tumor subregions were identified by merging previously defined superpixels via population-level hierarchical clustering. The volume associated with each of the subregions was evaluated using Kaplan-Meier analysis regarding its prognostic capability in predicting overall survival (OS) and out-of-field progression (OFP). Three spatially distinct subregions were identified within each tumor that were highly robust to uncertainty in PET/CT co-registration. Among these, the volume of the most metabolically active and metabolically heterogeneous solid component of the tumor was predictive of OS and OFP on the entire cohort, with a concordance index or CI of 0.66-0.67. When restricting the analysis to patients with stage III disease (n=32), the same subregion achieved an even higher CI of 0.75 (hazard ratio 3.93, log-rank P=.002) for predicting OS, and a CI of 0.76 (hazard ratio 4.84, log-rank P=.002) for predicting OFP. In comparison, conventional imaging markers, including tumor volume, maximum standardized uptake value, and metabolic tumor volume using threshold of 50% standardized uptake value maximum, were not predictive of OS or OFP, with CI mostly below 0.60 (log-rank P>.05). We propose a robust intratumor partitioning method to identify clinically relevant, high-risk
Syed, Zeeshan; Saeed, Mohammed; Rubinfeld, Ilan
For many clinical conditions, only a small number of patients experience adverse outcomes. Developing risk stratification algorithms for these conditions typically requires collecting large volumes of data to capture enough positive and negative for training. This process is slow, expensive, and may not be appropriate for new phenomena. In this paper, we explore different anomaly detection approaches to identify high-risk patients as cases that lie in sparse regions of the feature space. We study three broad categories of anomaly detection methods: classification-based, nearest neighbor-based, and clustering-based techniques. When evaluated on data from the National Surgical Quality Improvement Program (NSQIP), these methods were able to successfully identify patients at an elevated risk of mortality and rare morbidities following inpatient surgical procedures. PMID:21347083
Syed, Zeeshan; Saeed, Mohammed; Rubinfeld, Ilan
For many clinical conditions, only a small number of patients experience adverse outcomes. Developing risk stratification algorithms for these conditions typically requires collecting large volumes of data to capture enough positive and negative for training. This process is slow, expensive, and may not be appropriate for new phenomena. In this paper, we explore different anomaly detection approaches to identify high-risk patients as cases that lie in sparse regions of the feature space. We study three broad categories of anomaly detection methods: classification-based, nearest neighbor-based, and clustering-based techniques. When evaluated on data from the National Surgical Quality Improvement Program (NSQIP), these methods were able to successfully identify patients at an elevated risk of mortality and rare morbidities following inpatient surgical procedures.
Canto, Marcia Irene
Pancreatic cancer (PC) is a highly lethal disease. Most symptomatic, clinically detected PCs are advanced and not curable. Indeed, the estimated 5-year survival rate is 4%, which is attributable to late diagnosis and low resection rate. Screening of high-risk individuals and early detection of small PCs and precursor lesions might improve the outcome if curative therapy could be offered in the presymptomatic stage. This article summarizes the available published data and preliminary results and discusses the different approaches to screening for pancreatic neoplasia at 2 university-based programs in the United States.
Cassidy, Adrian; Myles, Jonathan P; Liloglou, Triantafillos; Duffy, Stephen W; Field, John K
Within the framework of the Liverpool Lung Project (LLP), population-based case-control and prospective cohort studies are in progress to identify molecular and epidemiological risk factors and define populations and individuals most at risk of developing lung cancer. This report describes a strategy for selection of a high-risk population and further provides support for the inclusion of occupational and genetic risk factors in future models. Data from the case-control study (256 incident cases and 314 population controls) were analysed to define a high-risk population. Detailed lifestyle and occupational information were collected during structured interviews. Models were constructed using conditional logistic regression and included terms for age, tobacco consumption and previous respiratory disease. Smoking duration was chosen as the most important predictor of lung cancer risk [>50 years (OR 15.65, 95% CI 6.10-40.15)]. However, such a model would preclude younger individuals. Several combinations of previous respiratory disease were also considered, of which a history of bronchitis, emphysema or pneumonia (BEP) was the most significant (OR 1.86, 95% CI 1.28-2.69). A high-risk subset (based on combinations of smoking duration and BEP) was identified, which have a 4.5-fold greater risk of developing lung cancer (OR 4.5, 95% CI 2.33-8.68). Future refinement of the risk model to include individuals occupationally exposed to asbestos and with the p21 genotypes is discussed. There is real potential for environmental and genetic factors to improve on risk prediction and targeting of susceptible individuals beyond the traditional models based only on smoking and age. The development of a molecular-epidemiological model will inform the development of effective surveillance, early detection and chemoprevention strategies.
Witte, Tracy K; Holm-Denoma, Jill M; Zuromski, Kelly L; Gauthier, Jami M; Ruscio, John
Although suicide risk is often thought of as existing on a graded continuum, its latent structure (i.e., whether it is categorical or dimensional) has not been empirically determined. Knowledge about the latent structure of suicide risk holds implications for suicide risk assessments, targeted suicide interventions, and suicide research. Our objectives were to determine whether suicide risk can best be understood as a categorical (i.e., taxonic) or dimensional entity, and to validate the nature of any obtained taxon. We conducted taxometric analyses of cross-sectional, baseline data from 16 independent studies funded by the Military Suicide Research Consortium. Participants (N = 1,773) primarily consisted of military personnel, and most had a history of suicidal behavior. The Comparison Curve Fit Index values for MAMBAC (.85), MAXEIG (.77), and L-Mode (.62) all strongly supported categorical (i.e., taxonic) structure for suicide risk. Follow-up analyses comparing the taxon and complement groups revealed substantially larger effect sizes for the variables most conceptually similar to suicide risk compared with variables indicating general distress. Pending replication and establishment of the predictive validity of the taxon, our results suggest the need for a fundamental shift in suicide risk assessment, treatment, and research. Specifically, suicide risk assessments could be shortened without sacrificing validity, the most potent suicide interventions could be allocated to individuals in the high-risk group, and research should generally be conducted on individuals in the high-risk group. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Mosleh, Wassim; Adib, Keenan; Natdanai, Punnanithinont; Carmona-Rubio, Andres; Karki, Roshan; Paily, Jacienta; Ahmed, Mohamed Abdel-Aal; Vakkalanka, Sujit; Madam, Narasa; Gudleski, Gregory D; Chung, Charles; Sharma, Umesh C
Prior studies identified the incremental value of non-invasive imaging by CT-angiogram (CTA) to detect high-risk coronary atherosclerotic plaques. Due to their superficial locations, larger calibers and motion-free imaging, the carotid arteries provide the best anatomic access for the non-invasive characterization of atherosclerotic plaques. We aim to assess the ability of predicting obstructive coronary artery disease (CAD) or acute myocardial infarction (MI) based on high-risk carotid plaque features identified by CTA. We retrospectively examined carotid CTAs of 492 patients that presented with acute stroke to characterize the atherosclerotic plaques of the carotid arteries and examined development of acute MI and obstructive CAD within 12-months. Carotid lesions were defined in terms of calcifications (large or speckled), presence of low-attenuation plaques, positive remodeling, and presence of napkin ring sign. Adjusted relative risks were calculated for each plaque features. Patients with speckled (<3 mm) calcifications and/or larger calcifications on CTA had a higher risk of developing an MI and/or obstructive CAD within 1 year compared to patients without (adjusted RR of 7.51, 95%CI 1.26-73.42, P = 0.001). Patients with low-attenuation plaques on CTA had a higher risk of developing an MI and/or obstructive CAD within 1 year than patients without (adjusted RR of 2.73, 95%CI 1.19-8.50, P = 0.021). Presence of carotid calcifications and low-attenuation plaques also portended higher sensitivity (100 and 79.17%, respectively) for the development of acute MI. Presence of carotid calcifications and low-attenuation plaques can predict the risk of developing acute MI and/or obstructive CAD within 12-months. Given their high sensitivity, their absence can reliably exclude 12-month events.
Watkins, Rochelle E; Mak, Donna B; Connelly, Crystal
Prisoners frequently engage in high risk behaviours for sexually transmitted infections (STIs) and blood borne viruses (BBVs) and effective interventions are required to control the transmission of STIs and BBVs among prisoners. The variation in engagement in high risk behaviours among prisoner sociodemographic sub-groups in Western Australia, including differences between prisoners admitted to metropolitan and regional prisons, has not been systematically described. The objective of this article was to describe self-reported engagement in unprotected sex and sharing injecting equipment among prisoners on admission to prison in Western Australia, using routinely collected data. A retrospective medical record audit was conducted for a total of 946 individuals admitted to prisons in Western Australia. Quota sampling was used to ensure adequate sampling of females, juveniles, and individuals from regional prisons. Initial health assessment records completed on admission to prison in Western Australia were audited to evaluate self-reported engagement in unprotected sex and the sharing of injecting equipment among prison entrants. Unprotected sex in the previous 12 months was reported by 48% of prisoners, and ever sharing injecting equipment was reported by 16% of prisoners. Adults were more likely to report both unprotected sex (52%) and sharing injecting equipment (18%) than juveniles (40% and 11%, respectively). Adults admitted to a metropolitan prison were significantly more likely to report sharing injecting equipment (23%) than adults admitted to a regional prison (10%). Associations between risk behaviours, sex and Aboriginality differed among prisoners admitted to metropolitan and regional prisons. There is distinct sociodemographic patterning of high risk behaviours among prisoners in Western Australia by age, sex, Aboriginality and prison location. The effectiveness of interventions to prevent STI and BBV transmission in prisoners may be enhanced by addressing
García-García, Guillermo; Gutiérrez-Padilla, Alfonso J; Chávez-Iñiguez, Jonathan; Pérez-Gómez, Héctor R; Mendoza-García, Martha; González-De la Peña, Ma Del Mar; Tonelli, Marcello
Chronic kidney disease (CKD) is a major public health problem in Mexico. Current guidelines recommend routine CKD testing in patients at increased risk for CKD. We undertook this study to examine the diagnostic yield of targeted screening (case-finding) for CKD in high-risk populations in rural and urban communities in Jalisco, Mexico. In a cross-sectional study, we did laboratory tests searching for CKD and its risk factors and compared the characteristics of participants with those reported by the National Health and Nutrition Survey 2006 (NHNS). Individuals who were aware that they had CKD and those <18 years of age were excluded. There were 9,169 participants assessed: 28.7% were men and mean age was 55.6 ± 13.7 years. They were predominantly female (71.3 vs. 55.6%, p = 0.0001) and older (55.59 ± 0.1 vs. 42.5 ± 0.3 years, p = 0.0001) than the NHNS population. Self-reported diabetes (41.9 vs. 7.3%, p = 0001) and fasting blood sugar >126 mg/dl (56.1 vs. 14.4%, p = 0.0001) were more prevalent among the participants; self-reported hypertension (41.9 vs. 7.3%, p = 0.0001), systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg (52.5 vs. 43.2%, p = 0.0001), and obesity (42.8. vs. 29.3%, p = 0.0001) were also more frequent among participants. There were 19.7% with proteinuria; CKD was more prevalent among the high risk participants in our study (31.3 vs. 8.0%, p = 0.0001) than in the general population. CKD was detected frequently in high-risk Mexican populations. Trials of case-finding and intervention are feasible and warranted in Mexico. Copyright © 2013 IMSS. Published by Elsevier Inc. All rights reserved.
Goghari, Vina M; Brett, Caroline; Tabraham, Paul; Johns, Louise; Valmaggia, Lucia; Broome, Matthew; Woolley, James; Bramon, Elvira; Howes, Oliver; Byrne, Majella; McGuire, Philip
The goal of this investigation was to clarify the nature of spatial working memory difficulties in individuals at ultra high risk (UHR) for psychosis. We evaluated spatial working memory and intelligence in 96 individuals at UHR for psychosis, 28 patients with first episode psychosis (FEP), and 23 healthy controls. Fourteen UHR individuals developed a psychotic disorder during follow-up. Compared to controls, the UHR group was impaired in both the short-term maintenance of material and in the effective use of strategy, but not more immediate memory. These impairments were not as severe as those in the FEP group, as the UHR group performed better than the FEP group. A similar pattern of results was found for the intelligence measures. Discriminant function analyses demonstrated short-term maintenance of material significantly differentiated the UHR and healthy control groups even when accounting for full scale intelligence quotient (IQ); whereas full scale IQ significantly differentiated the UHR and FEP groups and FEP and control groups. Notably, within the UHR group, impaired spatial working memory performance was associated with lower global functioning, but not full scale IQ. The subgroup of UHR individuals who later developed psychosis was not significantly more impaired on any aspect of working memory performance than the group of UHR individuals who did not develop psychosis. Given, the relationship between spatial working memory deficits and functional outcome, these results indicate that cognitive remediation could be useful in individuals at UHR for psychosis to potentially improve functioning. Copyright © 2013 Elsevier Ltd. All rights reserved.
Sugimoto, Mitsushige; Ban, Hiromitsu; Ichikawa, Hitomi; Sahara, Shu; Otsuka, Taketo; Inatomi, Osamu; Bamba, Shigeki; Furuta, Takahisa; Andoh, Akira
Objective The Kyoto gastritis classification categorizes the endoscopic characteristics of Helicobacter pylori (H. pylori) infection-associated gastritis and identifies patterns associated with a high risk of gastric cancer. We investigated its efficacy, comparing scores in patients with H. pylori-associated gastritis and with gastric cancer. Methods A total of 1,200 patients with H. pylori-positive gastritis alone (n=932), early-stage H. pylori-positive gastric cancer (n=189), and successfully treated H. pylori-negative cancer (n=79) were endoscopically graded according to the Kyoto gastritis classification for atrophy, intestinal metaplasia, fold hypertrophy, nodularity, and diffuse redness. Results The prevalence of O-II/O-III-type atrophy according to the Kimura-Takemoto classification in early-stage H. pylori-positive gastric cancer and successfully treated H. pylori-negative cancer groups was 45.1%, which was significantly higher than in subjects with gastritis alone (12.7%, p<0.001). Kyoto gastritis scores of atrophy and intestinal metaplasia in the H. pylori-positive cancer group were significantly higher than in subjects with gastritis alone (all p<0.001). No significant differences were noted in the rates of gastric fold hypertrophy or diffuse redness between the two groups. In a multivariate analysis, the risks for H. pylori-positive gastric cancer increased with intestinal metaplasia (odds ratio: 4.453, 95% confidence interval: 3.332-5.950, <0.001) and male sex (1.737, 1.102-2.739, p=0.017). Conclusion Making an appropriate diagnosis and detecting patients at high risk is crucial for achieving total eradication of gastric cancer. The scores of intestinal metaplasia and atrophy of the scoring system in the Kyoto gastritis classification may thus be useful for detecting these patients.
Sugimoto, Mitsushige; Ban, Hiromitsu; Ichikawa, Hitomi; Sahara, Shu; Otsuka, Taketo; Inatomi, Osamu; Bamba, Shigeki; Furuta, Takahisa; Andoh, Akira
Objective The Kyoto gastritis classification categorizes the endoscopic characteristics of Helicobacter pylori (H. pylori) infection-associated gastritis and identifies patterns associated with a high risk of gastric cancer. We investigated its efficacy, comparing scores in patients with H. pylori-associated gastritis and with gastric cancer. Methods A total of 1,200 patients with H. pylori-positive gastritis alone (n=932), early-stage H. pylori-positive gastric cancer (n=189), and successfully treated H. pylori-negative cancer (n=79) were endoscopically graded according to the Kyoto gastritis classification for atrophy, intestinal metaplasia, fold hypertrophy, nodularity, and diffuse redness. Results The prevalence of O-II/O-III-type atrophy according to the Kimura-Takemoto classification in early-stage H. pylori-positive gastric cancer and successfully treated H. pylori-negative cancer groups was 45.1%, which was significantly higher than in subjects with gastritis alone (12.7%, p<0.001). Kyoto gastritis scores of atrophy and intestinal metaplasia in the H. pylori-positive cancer group were significantly higher than in subjects with gastritis alone (all p<0.001). No significant differences were noted in the rates of gastric fold hypertrophy or diffuse redness between the two groups. In a multivariate analysis, the risks for H. pylori-positive gastric cancer increased with intestinal metaplasia (odds ratio: 4.453, 95% confidence interval: 3.332-5.950, <0.001) and male sex (1.737, 1.102-2.739, p=0.017). Conclusion Making an appropriate diagnosis and detecting patients at high risk is crucial for achieving total eradication of gastric cancer. The scores of intestinal metaplasia and atrophy of the scoring system in the Kyoto gastritis classification may thus be useful for detecting these patients. PMID:28321054
Spiva, LeeAnna; Hand, Marti; VanBrackle, Lewis; McVay, Frank
Hospital readmission is an adverse patient outcome that is serious, common, and costly. For hospitals, identifying patients at risk for hospital readmission is a priority to reduce costs and improve care. The purposes were to validate a predictive algorithm to identify patients at a high risk for preventable hospital readmission within 30 days after discharge and determine if additional risk factors enhance readmission predictability. A retrospective study was conducted on a randomized sample of 598 patients discharged from a Southeast community hospital. Data were collected from the organization's database and manually abstracted from the electronic medical record using a structured tool. Two separate logistic regression models were fit for the probability of readmission within 30 days after discharge. The first model used the LACE index as the predictor variable, and the second model used the LACE index with additional risk factors. The two models were compared to determine if additional risk factors increased the model's predictive ability. The results indicate both models have reasonable prognostic capability. The LACE index with additional risk factors did little to improve prognostication, while adding to the model's complexity. Findings support the use of the LACE index as a practical tool to identify patients at risk for readmission.
Addington, Jean; Addington, Donald; Abidi, Sabina; Raedler, Thomas; Remington, Gary
Young people who are at clinical high risk (CHR) of developing psychosis are often help seeking and have significant distress and dysfunction. There are limited guidelines for the assessment and treatment for this population. The aim of this guideline was to develop treatment recommendations for this at-risk group. A systematic search was conducted for published guidelines for CHR. All current guidelines for schizophrenia were reviewed for treatment guidelines on individuals at CHR. The recommendations adopted were primarily drawn from the European Psychiatric Association (EPA) guidance on the early intervention in clinical high-risk states of psychoses and the 2014 National Institute for Health and Care Excellence (NICE) guidelines on the treatment and management of those at CHR for psychosis. After the guideline development process described, 9 recommendations were developed based on the quality of evidence, appropriateness for the Canadian health care system, and clinical expert consensus. Assessment by an expert in the field was the first recommendation. It was recommended that treatment follow a staged approach with psychological treatments being the first-line treatment and pharmacotherapy reserved for adults, those who did not respond to psychological interventions, and those who had more severe symptoms.
Watts, C G; Dieng, M; Morton, R L; Mann, G J; Menzies, S W; Cust, A E
Understanding how individuals at high-risk of primary cutaneous melanoma are best identified, screened and followed up will help optimize melanoma prevention strategies and clinical management. We conducted a systematic review of international clinical practice guidelines and documented the quality of supporting evidence for recommendations for clinical management of individuals at high risk of melanoma. Guidelines published between January 2000 and July 2014 were identified from a systematic search of Medline, Embase and four guideline databases; 34 guidelines from 20 countries were included. High-risk characteristics that were consistently reported included many melanocytic naevi, dysplastic naevi, family history, large congenital naevi, and Fitzpatrick Type I and II skin types. Most guidelines identify risk factors and recommend that individuals at high risk of cutaneous melanoma be monitored, but only half of the guidelines provide recommendations for screening based on level of risk. There is disagreement in screening and follow-up recommendations for those with an increased risk of future melanoma. High-level evidence supports long-term screening of individuals at high risk and monitoring using dermoscopy. Evidence is low for defining screening intervals and duration of follow-up, and for skin self-examination, although education about skin self-examination is widely encouraged. Clinical practice guidelines would benefit from a dedicated section for identification, screening and follow-up of individuals at high risk of melanoma. Guidelines could be improved with clear definitions of multiple naevi, family history and frequency of follow-up. Research examining the benefits and costs of alternative management strategies for groups at high risk will enhance the quality of recommendations.
Andrews, Brian T; Jackson, Anee Sophia; Nazir, Niaman; Hromas, Alan; Sokol, Jason A; Thurston, Todd E
Maxillofacial trauma frequently involves the bony orbit that surrounds the ocular globe. Concomitant globe injury is a concern whenever orbit trauma occurs and in severe cases can occasionally result in vision loss. The mechanism of injury, physical exam findings, and radiographic imaging can provide useful information concerning the severity of the injury and concerns for vision loss. Using these three tools, it is hypothesized that the patient's history, physical exam, and radiographic findings can identify high-risk maxillofacial trauma patients with concomitant ocular injury. Identification of high risk patients who require comprehensive ophthalmologic evaluation may alter management and possibly preserve or restore vision. A retrospective clinical chart review was performed at a tertiary academic medical center. Subjects were identified using the institutional trauma registry. Data collected included subject demographics, patient medical records and notes, ophthalmologic testing, and radiographic imaging. The incidence of orbit fracture and concomitant ocular injury associated with the mechanism of injury, physical exam findings, and radiographic imaging was determined. Statistical analysis was performed using a chi-square and Fisher exact test. In this study, 279 subjects with orbit fractures were identified and the incidence of concomitant ocular injury was 27.6% (77 of 279). Mechanism of injury was statistically associated with an increased risk of ocular injury (P = 0.0340), with penetrating trauma being the most likely etiology. The physical exam findings of visual acuity and an afferent pupillary defect were statistically associated with ocular injury (P = 0.0029 and 0.0001, respectively). Depth of orbit fracture on radiographic imaging was statistically associated with ocular injury (P = 0.0024), with fractures extending to the posterior third of the orbit being most likely to have associated ocular injury. Maxillofacial trauma patients with orbit
Fahey, Erin; Lehna, Carlee; Hanchette, Carol; Coty, Mary-Beth
The purpose of this study was to evaluate whether the sample of older adults in a home fire safety (HFS) study captured participants living in the areas at highest risk for fire occurrence. The secondary aim was to identify high risk areas to focus future HFS interventions. Geographic information systems software was used to identify census tracts where study participants resided. Census data for these tracts were compared with participant data based on seven risk factors (ie, age greater than 65 years, nonwhite race, below high school education, low socioeconomic status, rented housing, year home built, home value) previously identified in a fire risk model. The distribution of participants and census tracts among risk categories determined how well higher risk census tracts were sampled. Of the 46 census tracts where the HFS intervention was implemented, 78% (n = 36) were identified as high or severe risk according to the fire risk model. Study participants' means for median annual family income (P < .0001) and median home value (P < .0001) were significantly lower than the census tract means (n = 46), indicating participants were at higher risk of fire occurrence. Of the 92 census tracts identified as high or severe risk in the entire county, the study intervention was implemented in 39% (n = 36), indicating 56 census tracts as potential areas for future HFS interventions. The Geographic information system-based fire risk model is an underutilized but important tool for practice that allows community agencies to develop, plan, and evaluate their outreach efforts and ensure the most effective use of scarce resources.
Fusar-Poli, Paolo; Cappucciati, Marco; Borgwardt, Stefan; Woods, Scott W; Addington, Jean; Nelson, Barnaby; Nieman, Dorien H; Stahl, Daniel R; Rutigliano, Grazia; Riecher-Rössler, Anita; Simon, Andor E; Mizuno, Masafumi; Lee, Tae Young; Kwon, Jun Soo; Lam, May M L; Perez, Jesus; Keri, Szabolcs; Amminger, Paul; Metzler, Sibylle; Kawohl, Wolfram; Rössler, Wulf; Lee, Jimmy; Labad, Javier; Ziermans, Tim; An, Suk Kyoon; Liu, Chen-Chung; Woodberry, Kristen A; Braham, Amel; Corcoran, Cheryl; McGorry, Patrick; Yung, Alison R; McGuire, Philip K
Individuals can be classified as being at clinical high risk (CHR) for psychosis if they meet at least one of the ultra-high-risk (UHR) inclusion criteria (brief limited intermittent psychotic symptoms [BLIPS] and/or attenuated psychotic symptoms [APS] and/or genetic risk and deterioration syndrome [GRD]) and/or basic symptoms [BS]. The meta-analytical risk of psychosis of these different subgroups is still unknown. To compare the risk of psychosis in CHR individuals who met at least one of the major inclusion criteria and in individuals not at CHR for psychosis (CHR-). Electronic databases (Web of Science, MEDLINE, Scopus) were searched until June 18, 2015, along with investigation of citations of previous publications and a manual search of the reference lists of retrieved articles. We included original follow-up studies of CHR individuals who reported the risk of psychosis classified according to the presence of any BLIPS, APS and GRD, APS alone, GRD alone, BS, and CHR-. Independent extraction by multiple observers and random-effects meta-analysis of proportions. Moderators were tested with meta-regression analyses (Bonferroni corrected). Heterogeneity was assessed with the I2 index. Sensitivity analyses tested robustness of results. Publication biases were assessed with funnel plots and the Egger test. The proportion of each subgroup with any psychotic disorder at 6, 12, 24, 36, and 48 or more months of follow-up. Thirty-three independent studies comprising up to 4227 individuals were included. The meta-analytical proportion of individuals meeting each UHR subgroup at intake was: 0.85 APS (95%CI, 0.79-0.90), 0.1 BLIPS (95%CI, 0.06-0.14), and 0.05 GRD (95%CI, 0.03-0.07). There were no significant differences in psychosis risk at any time point between the APS and GRD and the APS-alone subgroups. There was a higher risk of psychosis in the any BLIPS greater than APS greater than GRD-alone subgroups at 24, 36, and 48 or more months of follow-up. There was no
Hartz, Sarah M; Olfson, Emily; Culverhouse, Robert; Cavazos-Rehg, Patricia; Chen, Li-Shiun; DuBois, James; Fisher, Sherri; Kaphingst, Kimberly; Kaufman, David; Plunk, Andrew; Ramnarine, Shelina; Solomon, Stephanie; Saccone, Nancy L; Bierut, Laura J
The goal of this study was to examine participant responses to disclosure of genetic results in a minority population at high risk for depression and anxiety. Eighty-two subjects in a genetic study of nicotine dependence were offered personalized genetic results. All were nicotine-dependent and 64% self-identified as African American. Pathway Genomics was used to evaluate genetic risks for five complex diseases. Participants returned 4-8 weeks after enrollment for in-person genetic counseling interviews and evaluation of baseline measures. A telephone follow-up was performed 4-8 weeks later to assess responses to results. Fifty of the 82 subjects (61%) were interested in receiving genetic results. These participants had multiple risk factors, including high baseline measures of depression (66%) and anxiety (32%), as well as low rates of employment (46%), adequate health literacy (46%), and health insurance (45%). Pathway Genomics reported "increased risk" for at least one disease in 77% of subjects. Ninety-five percent of participants reported that they appreciated the genetic results, and receiving these results was not associated with changes in symptoms of depression or anxiety. Furthermore, after return of genetic results, smoking cessation attempts increased (P = 0.003). Even in an underserved population at high risk for adverse psychological reactions, subjects responded positively to personalized genetic results.
Marrett, L D; King, W D; Walter, S D; From, L
OBJECTIVE: To determine which host characteristics are risk factors for cutaneous malignant melanoma in order to aim prevention and early detection programs at people at high risk. DESIGN: Case-control study. SETTING: Southern Ontario. SUBJECTS: The 583 case subjects were aged 20 to 69 years and had had malignant melanoma newly diagnosed between Oct. 1, 1984, and Sept. 30, 1986. The 608 control subjects were randomly selected from a list of residents in the study area and were stratum matched for age, sex and municipality. INTERVENTION: Through in-person interviews the interviewer ascertained exposure to putative external risk factors and assessed skin colour and number of nevi on the arm, and the subject reported his or her natural hair colour at age 20 years, eye colour, skin reaction to repeated sun exposure, and freckle and whole-body nevus densities. RESULTS: Although all the host factors mentioned were significantly associated with melanoma risk when considered separately, only hair colour, skin reaction to repeated sun exposure, and self-reported freckle and nevus densities remained significant after backward logistic regression analysis. The odds ratio for melanoma was estimated to be 10.7 in people who had many nevi compared with those who had none (95% confidence interval [CI] 6.6 to 17.4), 4.0 in people who had red hair compared with those who had black hair (95% CI 1.9 to 8.2), 1.9 in people who had many freckles compared with those who had none or few (95% CI 1.3 to 2.8) and 1.4 respectively in people who burned and had a subsequent increase in tan and those who burned and had no increase in tan after repeated sun exposure compared with those who did not burn [corrected]. CONCLUSIONS: Four risk factors for malignant melanoma have been identified. Prospective evaluation of their predictive value should be done. In the meantime, however, these factors should be used to identify people apparently at high risk for malignant melanoma, who can then be
Introduction: Negative affect, alcohol consumption, and presence of others smoking have consistently been implicated as risk factors for smoking lapse and relapse. What is not known, however, is how these factors work together to affect smoking outcomes. This paper uses ecological momentary assessment (EMA) collected during the first 7 days of a smoking cessation attempt to test the individual and combined effects of high-risk triggers on smoking urge and lapse. Methods: Participants were 300 female smokers who enrolled in a study that tested an individually tailored smoking cessation treatment. Participants completed EMA, which recorded negative affect, alcohol consumption, presence of others smoking, smoking urge, and smoking lapse, for 7 days starting on their quit date. Results: Alcohol consumption, presence of others smoking, and negative affect were, independently and in combination, associated with increase in smoking urge and lapse. The results also found that the relationship between presence of others smoking and lapse and the relationship between negative affect and lapse were moderated by smoking urge. Conclusions: The current study found significant individual effects of alcohol consumption, presence of other smoking, and negative affect on smoking urge and lapse. Combing the triggers increased smoking urge and the risk for lapse to varying degrees, and the presence of all 3 triggers resulted in the highest urge and lapse risk. PMID:24323569
Kimhy, D; Corcoran, C; Harkavy-Friedman, JM; Ritzler, B; Javitt, DC; Malaspina, D
Schizophrenia has been associated with deficits in visual perception and processing, but there is little information about their temporal development and stability. We assessed visual form perception using the Rorschach Comprehensive System (RCS) in 23 individuals at clinical high risk for psychosis, 15 individuals with recent onset schizophrenia (≤2 years since onset), and 34 with chronic schizophrenia (≥3 years since onset). All three groups demonstrated reduced conventional form perception (X+%), as compared with published norms, but did not differ significantly from one another. In contrast, the high-risk group had significantly better performance on an index of clarity of conceptual thinking (WSUM6) compared to the chronic schizophrenia patients, with the recent-onset group scoring intermediate to the high risk and chronic schizophrenia groups. The results suggest that individuals at clinical high risk for psychosis display substantial deficits in visual form perception prior to the onset of psychosis and that these deficits are comparable in severity to those observed in individuals with schizophrenia. Therefore, visual form perception deficits may constitute a trait-like risk factor for psychosis in high risk individuals and may potentially serve as an endophenotype of risk for development of psychosis. Clarity of conceptual thinking was relatively preserved among high risk patients, consistent with a relationship to disease expression, not risk. These deficits are discussed in the context of the putative neurobiological underpinnings of visual deficits and the developmental pathophysiology of psychosis in schizophrenia. PMID:17884347
Zwaigenbaum, Lonnie; Bryson, Susan E.; Szatmari, Peter; Brian, Jessica; Smith, Isabel M.; Roberts, Wendy; Vaillancourt, Tracy; Roncadin, Caroline
Sex differences were examined in 3-year-olds with autism spectrum disorders (ASD) ascertained from a high-risk cohort, and high- and low-risk comparison groups. Participants included 319 high-risk siblings and 129 low-risk controls. Eighty-five siblings were diagnosed with ASD, including 57 of 176 boys (32.4%) and 28 of 143 girls (19.6%), implying…
Zwaigenbaum, Lonnie; Bryson, Susan E.; Szatmari, Peter; Brian, Jessica; Smith, Isabel M.; Roberts, Wendy; Vaillancourt, Tracy; Roncadin, Caroline
Sex differences were examined in 3-year-olds with autism spectrum disorders (ASD) ascertained from a high-risk cohort, and high- and low-risk comparison groups. Participants included 319 high-risk siblings and 129 low-risk controls. Eighty-five siblings were diagnosed with ASD, including 57 of 176 boys (32.4%) and 28 of 143 girls (19.6%), implying…
Remington, Austin C; Hernandez-Boussard, Tina; Warstadt, Nicholus M; Finnegan, Micaela A; Shaffer, Robyn; Kwong, Jereen Z; Curtin, Catherine
Rates of diabetes and its associated comorbidities have been increasing in the United States, with diabetic foot ulcer treatment representing a large cost to the patient and healthcare system. These ulcers often result in multiple hospital admissions. This study examined readmissions following inpatient care for a diabetic foot ulcer and identified modifiable factors associated with all-cause 30-day readmissions to the inpatient or emergency department (ED) setting. We hypothesized that patients undergoing aggressive treatment would have lower 30-day readmission rates. We identified patient discharge records containing International Classification of Disease ninth revision codes for both diabetes mellitus and distal foot ulcer in the State Inpatient and Emergency Department databases from the Agency for Healthcare Research and Quality, Healthcare Cost and Utilization Project in Florida and New York, 2011-2012. All-cause 30-day return to care visits (ED or inpatient) were analyzed. Patient demographics and treatment characteristics were evaluated using univariate and multivariable regression models. The cohort included 25,911 discharges, having a mean age of 63 and an average of 3.8 comorbidities. The overall rate of return to care was 30%, and 21% of subjects underwent a toe or midfoot amputation during their index stay. The most common diagnosis codes upon readmission were diabetes mellitus (19%) and infection (13%). Patients with a toe or midfoot amputation procedure were less likely to be readmitted within 30 days (odds ratio: 0.78; 95% confidence interval: 0.73, 0.84). Presence of comorbidities, black and Hispanic ethnicities, and Medicare and Medicaid payer status were also associated with higher odds of readmission following initial hospitalization (p < 0.05). The study suggests that there are many factors that affect readmission rates for diabetic foot ulcer patients. Understanding patients at high-risk for readmission can improve counseling and
Shaikh, Madiha; Ellett, Lyn; Dutt, Anirban; Day, Fern; Laing, Jennifer; Kroll, Jasmine; Petrella, Sabrina; McGuire, Philip; Valmaggia, Lucia R
Despite a consensus that psychosocial adversity plays a role in the onset of psychosis, the nature of this role in relation to persecutory paranoia remains unclear. This study examined the complex relationship between perceived ethnic discrimination and paranoid ideation in individuals at Ultra High Risk (UHR) for psychosis using a virtual reality paradigm to objectively measure paranoia. Data from 64 UHR participants and 43 healthy volunteers were analysed to investigate the relationship between perceived ethnic discrimination and persecutory ideation in a virtual reality environment. Perceived ethnic discrimination was higher in young adults at UHR in comparison to healthy controls. A positive correlation was observed between perceived ethnic discrimination and paranoid persecutory ideation in the whole sample. Perceived ethnic discrimination was not a significant predictor of paranoid persecutory ideation in the VR environment. Elevated levels of perceived ethnic discrimination are present in individuals at UHR and are consistent with current biopsychosocial models in which psychosocial adversity plays a key role in the development of psychosis and attenuated symptomatology.
Woodberry, Kristen A.; Seidman, Larry J.; Giuliano, Anthony J.; Verdi, Mary B.; Cook, William L.; McFarlane, William R.
Background Characterizing neuropsychological (NP) functioning of individuals at clinical high risk (CHR) for psychosis may be useful for prediction of psychosis and understanding functional outcome. The degree to which NP impairments are associated with general cognitive ability and/or later emergence of full psychosis in CHR samples requires study with well-matched controls. Methods We assessed NP functioning across eight cognitive domains in a sample of 73 CHR youth, 13 of whom developed psychotic-level symptoms after baseline assessment, and 34 healthy comparison (HC) subjects. Groups were matched on age, sex, ethnicity, handedness, subject and parent grade attainment, and median family income, and were comparable on WRAT-3 Reading, an estimate of premorbid IQ. Profile analysis was used to examine group differences and the role of IQ in profile shape. Results The CHR sample demonstrated a significant difference in overall magnitude of NP impairment but only a small and nearly significant difference in profile shape, primarily due to a large impairment in olfactory identification. Individuals who subsequently developed psychotic-level symptoms demonstrated large impairments in verbal IQ, verbal memory and olfactory identification comparable in magnitude to first episode samples. Conclusions CHR status may be associated with moderate generalized cognitive impairments marked by some degree of selective impairment in olfaction and verbal memory. Impairments were greatest in those who later developed psychotic symptoms. Future study of olfaction in CHR samples may enhance early detection and specification of neurodevelopmental mechanisms of risk. PMID:20692125
Darweesh, Sirwan K L; Wolters, Frank J; Hofman, Albert; Stricker, Bruno H; Koudstaal, Peter J; Ikram, M Arfan
Early identification of individuals at high risk of developing neurodegenerative diseases is essential for timely preventive intervention. However, simple methods that can be used for risk assessment in general practice are lacking. Within the population-based Rotterdam Study, we used the Purdue Pegboard Test (PPT) to assess manual dexterity in 4,856 persons (median age 70 years, 58% women) free of parkinsonism and dementia between 2000 and 2004. We followed these persons until January 1, 2012 for the onset of neurodegenerative diseases (defined as first diagnosis of parkinsonism or dementia). We determined the association of PPT scores with incident neurodegenerative disease, adjusting for age, sex, study cohort, level of education, smoking, preferred hand, parental history, memory complaints, and Mini-Mental State Examination. Furthermore, we determined the incremental predictive value of PPT, expressed as change in risk classification and discrimination. During follow-up (median 9.2 years), 277 participants were diagnosed with a neurodegenerative disease (227 with dementia and 50 with parkinsonism). Lower PPT scores were associated with higher risk of incident neurodegenerative diseases (hazard ratio [HR] = 1.28, 95% confidence interval [CI]: 1.18-1.41) and improved discrimination of incident neurodegenerative diseases. We also observed significant associations of PPT scores separately with incident dementia (HR = 1.25; 95% CI: 1.14-1.39]) and incident parkinsonism (HR = 1.41; 95% CI: 1.19-1.67). A rapid, nonlaboratory test of manual dexterity may help to identify persons at high risk for neurodegenerative diseases. This highlights the importance of motor function in the preclinical phase of both dementia and parkinsonism and may aid in selecting individuals for refined screening and neuroprotective trials. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e
Rhee, Mary K; Safo, Sandra E; Jackson, Sandra L; Xue, Wenqiong; Olson, Darin E; Long, Qi; Barb, Diana; Haw, J Sonya; Tomolo, Anne M; Phillips, Lawrence S
Many individuals with diabetes remain undiagnosed, leading to delays in treatment and higher risk for subsequent diabetes complications. Despite recommendations for diabetes screening in high risk groups, the optimal approach is not known. We evaluated the utility of inpatient glucose levels as an opportunistic screening tool for identifying patients at high risk for diabetes. We retrospectively examined 462,421 patients in the national VA healthcare system, hospitalized on medical/surgical services in 2000-2010, for ≥3 days, with ≥2 inpatient random plasma glucose (RPG) measurements. All had continuity of care - ≥1 primary care visit and ≥1 glucose measure within 2 years before hospitalization and yearly for ≥3 years after discharge. Glucose levels during hospitalization and incidence of diabetes within 3 years after discharge in patients without diabetes were evaluated. Patients had mean age 65.0 years, BMI 29.9, and were 96% male, 71% white, and 18% black. Preexisting diabetes was present in 39.4%, 1.3% were diagnosed during hospitalization, 8.1% diagnosed <5 years post-discharge, and 51.3% never diagnosed (NonDM). The NonDM group had the lowest mean hospital RPG (112 mg/dl [6.2 mmol/L]). Having at least two RPGs >140 mg/dl (>7.8 mmol/L), the 95(th) percentile of NonDM hospital glucose, provided 81% specificity for identifying incident diabetes <3 years post-discharge. Screening for diabetes could be considered in patients with at least two hospital glucoses at/above the 95th percentile of the nondiabetic range (141 mg/dl [7.8 mmol/L]). Copyright © 2017. Published by Elsevier Inc.
Mechelli, Andrea; Lin, Ashleigh; Wood, Stephen; McGorry, Patrick; Amminger, Paul; Tognin, Stefania; McGuire, Philip; Young, Jonathan; Nelson, Barnaby; Yung, Alison
Recent studies have reported an association between psychopathology and subsequent clinical and functional outcomes in people at ultra-high risk (UHR) for psychosis. This has led to the suggestion that psychopathological information could be used to make prognostic predictions in this population. However, because the current literature is based on inferences at group level, the translational value of the findings for everyday clinical practice is unclear. Here we examined whether psychopathological information could be used to make individualized predictions about clinical and functional outcomes in people at UHR. Participants included 416 people at UHR followed prospectively at the Personal Assessment and Crisis Evaluation (PACE) Clinic in Melbourne, Australia. The data were analysed using Support Vector Machine (SVM), a supervised machine learning technique that allows inferences at the individual level. SVM predicted transition to psychosis with a specificity of 60.6%, a sensitivity of 68.6% and an accuracy of 64.6% (p<0.001). In addition, SVM predicted functioning with a specificity of 62.5%, a sensitivity of 62.5% and an accuracy of 62.5% (p=0.008). Prediction of transition was driven by disorder of thought content, attenuated positive symptoms and functioning, whereas functioning was best predicted by attention disturbances, anhedonia-asociality and disorder of thought content. These results indicate that psychopathological information allows individualized prognostic predictions with statistically significant accuracy. However, this level of accuracy may not be sufficient for clinical translation in real-world clinical practice. Accuracy might be improved by combining psychopathological information with other types of data using a multivariate machine learning framework.
Apuzzo, Mah-rya L.; Yoshinaga-Itano, Christine
This study examined developmental characteristics of 82 deaf and hard-of-hearing children identified through the high-risk registry in Colorado either before or after 6 months of age. Children identified early and receiving intervention two to three months after identification had significantly higher levels of receptive and expressive language,…
Pumper, Megan A; Moreno, Megan A
It is challenging to identify older adolescents at risk for alcohol dependence. This study investigated first-year college students who scored as dependent alcohol users (DAU), and examined their alcohol use and Facebook displays. This longitudinal study recruited college students at two universities to complete a phone interview prior to college (Time 1) and one year later (Time 2). Interviews assessed lifetime and current alcohol use, and attitude (scale of 0=very negative to 6=very positive) and intention (scale of 0=not at all likely to 5=very likely) toward alcohol use. The alcohol use disorders identification test (AUDIT) was administered at Time 2. Facebook profiles were evaluated for the presence of references to alcohol use and intoxication/problematic drinking (I/PD) prior to and throughout the participants first year at the university. Analyses included Chi-squared tests and Wilcoxon sign rank tests. Of 315 participants in the study, a total of 21 (6.7%) of participants met criteria as a DAU at Time 2. DAUs were 54.5% female, 86.4% Caucasian, and 73.7% from University A. At Time 1 all DAUs reported lifetime alcohol use and 91.1% were current drinkers. At Time 2, 95.7% were current drinkers. At Time 1, DAU's mean attitude toward alcohol was 4.0 (SD=1.0) and mean intention was 4.0 (SD=1.4); by Time 2 attitude was 4.6 (SD=0.9), p=0.02, and intention was 4.9 (SD=0.3). At Time 1, 39.1% of DAUs displayed alcohol references on Facebook but only one referenced I/PD. By Time 2, 20 DAU profile owners (90.4%) displayed some reference to alcohol and 52.2% referenced I/PD. Findings suggest areas in which dependence could be identified early, specifically attitude towards alcohol and assessment of Facebook profiles for references to alcohol. These findings have the potential to guide future intervention efforts for this high-risk population.
Deighton, Stephanie; Addington, Jean
Recent research suggests aerobic exercise has a positive impact on symptoms and cognition in psychosis. Because individuals with psychosis are at risk of weight gain and the resultant metabolic side-effects, developing effective exercise programmes is of interest. Furthermore, this may be a useful intervention for those who are at risk of developing psychosis, that is, those at clinical high risk (CHR). The aim of this initial exploratory project was to examine the role of exercise in participants at CHR for psychosis. A comprehensive questionnaire was developed to assess current physical activity involvement; exercise levels in terms of frequency, intensity and duration; and perceived fitness levels. Reported barriers to exercise and reasons for exercising were also considered. Eighty participants, 40 CHR and 40 healthy controls, were assessed with this questionnaire. Overall, both groups were involved in a wide range of physical activity. Healthy controls reported higher levels of participation in indoor/outdoor activities and strength and/or flexibility training. They also exercised more frequently, more intensely and reported higher perceived fitness levels than CHR participants. Levels of exercise were unrelated to clinical symptoms and functioning in CHR participants. CHR youth reported more barriers to exercise and less positive reasons for exercising that were related to self-perception. The results suggest that exercise should be investigated further in the CHR population as it may have treatment implications. © 2013 Wiley Publishing Asia Pty Ltd.
Barbato, Mariapaola; Addington, Jean
In the last decade the interest in the role of the visual system in schizophrenia has grown, with evidence pointing to dysfunction in bottom-up visual processing that leads to early visual processing deficits. A fundamental component of visual perception is binocular depth perception (BDP), that is, depth perception derived by the difference between the images impressed upon the left and right retina. Two studies reported impaired BDP in schizophrenia and suggested a possible developmental deficit of brain structures involved in early visual processing. The aim of this study was to examine BDP in a young population at clinical high risk (CHR) of developing psychosis to determine whether this dysfunction is present in this potentially prepsychotic period. Forty-two CHR participants and 44 healthy controls were assessed using a computerized test of depth perception; a subsample completed a test of stereopsis. The computerized test comprised two trial blocks, with four conditions at increasing level of difficulty, in which participants were asked to discriminate the relative depth of two stimuli simultaneously presented on the screen. BDP was not impaired in the CHR group, whose performance was similar to that of the control group on both measures. For the CHR group performance in both tests was not correlated to positive symptoms. These results indicate that BDP is preserved in individuals at CHR for psychosis, and impaired BDP should not be considered a vulnerability marker for schizophrenia. Nevertheless future studies should verify BDP's potential power in predicting schizophrenia.
van Donkersgoed, R. J. M.; Wunderink, L.; Nieboer, R.; Aleman, A.; Pijnenborg, G. H. M.
Objective Treatment in the ultra-high risk stage for a psychotic episode is critical to the course of symptoms. Markers for the development of psychosis have been studied, to optimize the detection of people at risk of psychosis. One possible marker for the transition to psychosis is social cognition. To estimate effect sizes for social cognition based on a quantitative integration of the published evidence, we conducted a meta-analysis of social cognitive performance in people at ultra high risk (UHR). Methods A literature search (1970-July 2015) was performed in PubMed, PsychINFO, Medline, Embase, and ISI Web of Science, using the search terms ‘social cognition’, ‘theory of mind’, ‘emotion recognition’, ‘attributional style’, ‘social knowledge’, ‘social perception’, ‘empathy’, ‘at risk mental state’, ‘clinical high risk’, ‘psychosis prodrome’, and ‘ultra high risk’. The pooled effect size (Cohen’s D) and the effect sizes for each domain of social cognition were calculated. A random effects model with 95% confidence intervals was used. Results Seventeen studies were included in the analysis. The overall significant effect was of medium magnitude (d = 0.52, 95% Cl = 0.38–0.65). No moderator effects were found for age, gender and sample size. Sub-analyses demonstrated that individuals in the UHR phase show significant moderate deficits in affect recognition and affect discrimination in faces as well as in voices and in verbal Theory of Mind (TOM). Due to an insufficient amount of studies, we did not calculate an effect size for attributional bias and social perception/ knowledge. A majority of studies did not find a correlation between social cognition deficits and transition to psychosis, which may suggest that social cognition in general is not a useful marker for the development of psychosis. However some studies suggest the possible predictive value of verbal TOM and the recognition of specific emotions in faces
Bouchard, Danielle R; Langlois, Marie-France; Domingue, Marie-Ève; Brown, Christine; LeBrun, Vicki; Baillargeon, Jean-Patrice
The main objective of this study was to determine whether expectations and readiness to modify eating habits and physical activity (PA) level are different between young and older individuals with prediabetes who agreed to participate in a lifestyle modification program. Cross-sectional analysis. Primary care or referral center. Adults between ages 27 and 78 years (N=74) were tested before starting a 12-month lifestyle intervention. Not applicable. The visual analog scale questionnaire was used to assess expectations and readiness (ie, intentions, conviction, and self-confidence) to modify the PA level and eating habits. The PA level was assessed with a pedometer and eating habits with a questionnaire. Analyses were stratified by the age group: <60 years old versus ≥60 years old. Body mass loss expectations in terms of goal (-22.9% vs -17.9% of the current body mass; P=.04), acceptable (-15.6% vs -9.4%; P=.01), and failure (-7.6% vs -3.8%; P=.05) in future body mass loss were all greater for the younger group. Despite no significant age group difference in the initial PA level and eating habits, the youngest group had a greater intention to increase the PA level (89% vs 81%; P=.004) and to eat healthier (90% vs 85%; P=.001). Finally, the PA level and the consumption of fruits and vegetables, but not body mass, were associated with intentions or self-confidence to make some lifestyle modifications within age groups. In individuals at high risk for diabetes, increasing age is associated with lower expectations and reduced readiness with regard to lifestyle modifications. Thus, age should be considered when planning a lifestyle modification program. Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
Reniers, Renate L E P; Lin, Ashleigh; Yung, Alison R; Koutsouleris, Nikolaos; Nelson, Barnaby; Cropley, Vanessa L; Velakoulis, Dennis; McGorry, Patrick D; Pantelis, Christos; Wood, Stephen J
Most individuals at ultra-high risk (UHR) for psychosis do not transition to frank illness. Nevertheless, many have poor clinical outcomes and impaired psychosocial functioning. This study used voxel-based morphometry to investigate if baseline grey and white matter brain densities at identification as UHR were associated with functional outcome at medium- to long-term follow-up. Participants were help-seeking UHR individuals (n = 109, 54M:55F) who underwent magnetic resonance imaging at baseline; functional outcome was assessed an average of 9.2 years later. Primary analysis showed that lower baseline grey matter density, but not white matter density, in bilateral frontal and limbic areas, and left cerebellar declive were associated with poorer functional outcome (Social and Occupational Functioning Assessment Scale [SOFAS]). These findings were independent of transition to psychosis or persistence of the at-risk mental state. Similar regions were significantly associated with lower self-reported levels of social functioning and increased negative symptoms at follow-up. Exploratory analyses showed that lower baseline grey matter densities in middle and inferior frontal gyri were significantly associated with decline in Global Assessment of Functioning (GAF) score over follow-up. There was no association between baseline grey matter density and IQ or positive symptoms at follow-up. The current findings provide novel evidence that those with the poorest functional outcomes have the lowest grey matter densities at identification as UHR, regardless of transition status or persistence of the at-risk mental state. Replication and validation of these findings may allow for early identification of poor functional outcome and targeted interventions. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: firstname.lastname@example.org.
Yang, Lawrence H; Link, Bruce G; Ben-David, Shelly; Gill, Kelly E; Girgis, Ragy R; Brucato, Gary; Wonpat-Borja, Ahtoy J; Corcoran, Cheryl M
Despite advances that the psychosis "clinical high-risk" (CHR) identification offers, risk of stigma exists. Awareness of and agreement with stereotypes has not yet been evaluated in CHR individuals. Furthermore, the relative stigma associated with symptoms, as opposed to the label of risk, is not known, which is critical because CHR identification may reduce symptom-related stigma. Thirty-eight CHR subjects were ascertained using standard measures from the Center of Prevention and Evaluation/New York State Psychiatric Institute/ Columbia University. Labeling-related measures adapted to the CHR group included "stereotype awareness and self-stigma" ("Stereotype awareness", "Stereotype Agreement", "Negative emotions [shame]"), and a parallel measure of "Negative emotions (shame)" for symptoms. These measures were examined in relation to symptoms of anxiety and depression, adjusting for core CHR symptoms (e.g. attenuated psychotic symptoms). CHR participants endorsed awareness of mental illness stereotypes, but largely did not themselves agree with these stereotypes. Furthermore, CHR participants described more stigma associated with symptoms than they did with the risk-label itself. Shame related to symptoms was associated with depression, while shame related to the risk-label was associated with anxiety. Both stigma of the risk-label and of symptoms contribute to the experience of CHR individuals. Stereotype awareness was relatively high and labeling-related shame was associated with increased anxiety. Yet limited agreement with stereotypes indicated that labeling-related stigma had not fully permeated self-conceptions. Furthermore, symptom-related stigma appeared more salient overall and was linked with increased depression, suggesting that alleviating symptom-related shame via treating symptoms might provide major benefit. Copyright © 2015. Published by Elsevier B.V.
Heinze, Kareen; Reniers, Renate L E P; Nelson, Barnaby; Yung, Alison R; Lin, Ashleigh; Harrison, Ben J; Pantelis, Christos; Velakoulis, Dennis; McGorry, Patrick D; Wood, Stephen J
Investigation of aberrant large-scale brain networks offers novel insight into the role these networks play in diverse psychiatric disorders such as schizophrenia. Although studies report altered functional brain connectivity in participants at ultra-high risk (UHR) for psychosis, it is unclear whether these alterations extend to structural brain networks. Whole-brain structural covariance patterns of 133 participants at UHR for psychosis (51 of whom subsequently developed psychosis) and 65 healthy control (HC) subjects were studied. Following data preprocessing (using VBM8 toolbox), the mean signal in seed regions relating to specific networks (visual, auditory, motor, speech, semantic, executive control, salience, and default-mode) were extracted, and voxel-wise analyses of covariance were conducted to compare the association between whole-brain signal and each seed region for UHR and HC individuals. The UHR participants who transitioned to psychosis were compared with the UHR participants who did not. Significantly reduced structural covariance was observed in the UHR sample compared with the HC sample for the default-mode network, and increased covariance was observed for the motor and executive control networks. When the UHR participants who transitioned to psychosis were compared with the UHR participants who did not, aberrant structural covariance was observed in the salience, executive control, auditory, and motor networks. Whole-brain structural covariance analyses revealed subtle changes of connectivity of the default-mode, executive control, salience, motor, and auditory networks in UHR individuals for psychosis. Although we found significant differences, these are small changes and tend to reflect largely intact structural networks. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Kerlikowske, Karla; Zhu, Weiwei; Tosteson, Anna N A; Sprague, Brian L; Tice, Jeffrey A; Lehman, Constance D; Miglioretti, Diana L
Twenty-one states have laws requiring that women be notified if they have dense breasts and that they be advised to discuss supplemental imaging with their provider. To better direct discussions of supplemental imaging by determining which combinations of breast cancer risk and Breast Imaging Reporting and Data System (BI-RADS) breast density categories are associated with high interval cancer rates. Prospective cohort. Breast Cancer Surveillance Consortium (BCSC) breast imaging facilities. 365,426 women aged 40 to 74 years who had 831,455 digital screening mammography examinations. BI-RADS breast density, BCSC 5-year breast cancer risk, and interval cancer rate (invasive cancer ≤12 months after a normal mammography result) per 1000 mammography examinations. High interval cancer rate was defined as more than 1 case per 1000 examinations. High interval cancer rates were observed for women with 5-year risk of 1.67% or greater and extremely dense breasts or 5-year risk of 2.50% or greater and heterogeneously dense breasts (24% of all women with dense breasts). The interval rate of advanced-stage disease was highest (>0.4 case per 1000 examinations) among women with 5-year risk of 2.50% or greater and heterogeneously or extremely dense breasts (21% of all women with dense breasts). Five-year risk was low to average (0% to 1.66%) for 51.0% of women with heterogeneously dense breasts and 52.5% with extremely dense breasts, with interval cancer rates of 0.58 to 0.63 and 0.72 to 0.89 case per 1000 examinations, respectively. The benefit of supplemental imaging was not assessed. Breast density should not be the sole criterion for deciding whether supplemental imaging is justified because not all women with dense breasts have high interval cancer rates. BCSC 5-year risk combined with BI-RADS breast density can identify women at high risk for interval cancer to inform patient-provider discussions about alternative screening strategies. National Cancer Institute.
Gundersen, Craig; Engelhard, Emily E; Crumbaugh, Amy S; Seligman, Hilary K
To facilitate the introduction of food insecurity screening into clinical settings, we examined the test performance of two-item screening questions for food insecurity against the US Department of Agriculture's Core Food Security Module. We examined sensitivity, specificity and accuracy of various two-item combinations of questions assessing food insecurity in the general population and high-risk population subgroups. 2013 Current Population Survey December Supplement, a population-based US survey. All survey participants from the general population and high-risk subgroups. The test characteristics of multiple two-item combinations of questions assessing food insecurity had adequate sensitivity (>97 %) and specificity (>70 %) for widespread adoption as clinical screening measures. We recommend two specific items for clinical screening programmes based on their widespread current use and high sensitivity for detecting food insecurity. These items query how often the household 'worried whether food would run out before we got money to buy more' and how often 'the food that we bought just didn't last and we didn't have money to get more'. The recommended items have sensitivity across high-risk population subgroups of ≥97 % and a specificity of ≥74 % for food insecurity.
Barbato, Mariapaola; Addington, Jean
Objective In the last decade the interest in the role of the visual system in schizophrenia has grown, with evidence pointing to dysfunction in bottom-up visual processing that leads to early visual processing deficits. A fundamental component of visual perception is binocular depth perception (BDP), i.e. depth perception derived by the difference between the images impressed upon the left and right retina. Two studies reported impaired BDP in schizophrenia and suggested a possible developmental deficit of brain structures involved in early visual processing. The aim of this study was to examine BDP in a young population at clinical high risk (CHR) of developing psychosis to determine if this dysfunction is present in this potentially pre-psychotic period. Methods Forty-two CHR participants and 44 healthy controls were assessed using a computerized test of depth perception; a subsample completed a test of stereopsis. The computerized test was comprised of two trial blocks, with four conditions at increasing level of difficulty, where participants were asked to discriminate the relative depth of two stimuli simultaneously presented on the screen. Results BDP was not impaired in the CHR group, whose performance was similar to that of the control group on both measures. For the CHR group performance in both tests was not correlated to positive symptoms. Conclusions These results indicate that BDP is preserved in individuals at CHR for psychosis and impaired BDP should not be considered a vulnerability marker for schizophrenia. Nevertheless future studies should verify BDP's potential power in predicting schizophrenia. PMID:24188117
Weitzel, Jeffrey N; Lagos, Veronica I; Herzog, Josef S; Judkins, Thaddeus; Hendrickson, Brant; Ho, Jason S; Ricker, Charité N; Lowstuter, Katrina J; Blazer, Kathleen R; Tomlinson, Gail; Scholl, Tom
Large rearrangements account for 8% to 15% of deleterious BRCA mutations, although none have been characterized previously in individuals of Mexican ancestry. DNA from 106 Hispanic patients without an identifiable BRCA mutation by exonic sequence analysis was subjected to multiplexed quantitative differential PCR. One case of Native American and African American ancestry was identified via multiplex ligation-dependent probe amplification. Long-range PCR was used to confirm deletion events and to clone and sequence genomic breakpoints. Splicing patterns were derived by sequencing cDNA from reverse transcription-PCR of lymphoblastoid cell line RNA. Haplotype analysis was conducted for recurrent mutations. The same deletion of BRCA1 exons 9 through 12 was identified in five unrelated families. Long-range PCR and sequencing indicated a deletion event of 14.7 kb. A 3-primer PCR assay was designed based on the deletion breakpoints, identified within an AluSp element in intron 8 and an AluSx element in intron 12. Haplotype analysis confirmed common ancestry. Analysis of cDNA showed direct splicing of exons 8 to 13, resulting in a frameshift mutation and predicted truncation of the BRCA1 protein. We identified and characterized a novel large BRCA1 deletion in five unrelated families-four of Mexican ancestry and one of African and Native American ancestry, suggesting the possibility of founder effect of Amerindian or Mestizo origin. This BRCA1 rearrangement was detected in 3.8% (4 of 106) of BRCA sequence-negative Hispanic families. An assay for this mutation should be considered for sequence-negative high-risk Hispanic patients.
Pre-clinical research by investigators at the Center for Cancer Research and their colleagues have identified a number of novel epigenetic targets for high-risk neuroblastoma and validated a promising new targeted inhibitor in pre-clinical models. Read more...
Elam, Angela R; Lee, Paul P
Purpose. To understand barriers facing high-risk individuals and to solicit the suggestions of these individuals, especially nonusers, on how to change the eye care delivery system to better meet their needs. Methods. Four focus groups were conducted. All discussion was audiotaped and transcribed. Content analysis was performed by the authors and with the assistance of qualitative software, NUD(*)IST Vivo. Results. The most frequently cited barriers include (1) cost, (2) trust, (3) communication, (4) clinic accessibility (transportation/distance), and (5) doctor-patient relationship. In underutilizers, trust was the most identified barrier to care. Suggestions on increasing educational opportunities/awareness of eye care and addressing cost and insurance issues as a means of improving trust and communications were most frequently offered, including using the Department of Social Services as a focal point for eye care education and assessment. Discussion. Trust is a major barrier to eye care, especially among underutilizers of disadvantaged populations. Increasing trust and eye care education at the community and individual levels is essential to increasing eye care utilization.
Heflinger, Craig Anne; Hoffman, Cheri
Youth with Serious Emotional Disturbances (SED) face many challenges as they approach the transition to adulthood and adult services. This study examines publicly funded transition-age youth in order to describe the numbers and type of youth in need of policy and service planning in one state. Using Medicaid enrollment and claims/encounter data, youth with high risk of transition difficulties were identified in the following groups: SED, state custody/foster care or risk of custody, users of intensive or frequent mental health services, or having diagnoses of major mental disorders, conduct disorders, or developmental disabilities. Almost one quarter of all enrolled 14 to 17-year olds met criteria for at least one of the high risk groups, and three-quarters of these were youth with SED. High risk youth are described, with greater detail on those with SED, and implications for policy, services, and research are discussed.
Lewis, Geraint H
Context: Predictive models can be used to identify people at high risk of unplanned hospitalization, although some of the high-risk patients they identify may not be amenable to preventive care. This study describes the development of “impactibility models,” which aim to identify the subset of at-risk patients for whom preventive care is expected to be successful. Methods: This research used semistructured interviews with representatives of thirty American organizations that build, use, or appraise predictive models for health care. Findings: Impactibility models may refine the output of predictive models by (1) giving priority to patients with diseases that are particularly amenable to preventive care; (2) excluding patients who are least likely to respond to preventive care; or (3) identifying the form of preventive care best matched to each patient's characteristics. Conclusions: Impactibility models could improve the efficiency of hospital-avoidance programs, but they have important implications for equity and access. PMID:20579284
Li, Zhenjun; Wang, Ligui; Sun, Weige; Hou, Xuexin; Yang, Haiyan; Sun, Lina; Xu, Shuai; Sun, Qiangzheng; Zhang, Jingshan; Song, Hongbin; Lin, Hualiang
Spatial distribution of bacillary dysentery incidence was mapped at the district level in Wuhan, China. And a generalized additive time series model was used to examine the effect of daily weather factors on bacillary dysentery in the high-risk areas, after controlling for potential confounding factors. Central districts were found to be the high-risk areas. The time series analysis found an acute effect of meteorological factors on bacillary dysentery occurrence. A positive association was found for mean temperature (excess risk (ER) for 1°C increase being 0.94% (95% confidence interval (CI): 0.46% to 1.43% on the lag day 2), while a negative effect was observed for relative humidity and rainfall, the ER for 1% increase in relative humidity was -0.21% (95% CI: -0.34% to -0.08%), and the ER for 1 mm increase in rainfall was -0.23% (95% CI: -0.37% to -0.09%). This study suggests that bacillary dysentery prevention and control strategy should consider local weather variations.
Li, Zhenjun; Wang, Ligui; Sun, Weige; Hou, Xuexin; Yang, Haiyan; Sun, Lina; Xu, Shuai; Sun, Qiangzheng; Zhang, Jingshan; Song, Hongbin; Lin, Hualiang
Spatial distribution of bacillary dysentery incidence was mapped at the district level in Wuhan, China. And a generalized additive time series model was used to examine the effect of daily weather factors on bacillary dysentery in the high-risk areas, after controlling for potential confounding factors. Central districts were found to be the high-risk areas. The time series analysis found an acute effect of meteorological factors on bacillary dysentery occurrence. A positive association was found for mean temperature (excess risk (ER) for 1°C increase being 0.94% (95% confidence interval (CI): 0.46% to 1.43% on the lag day 2), while a negative effect was observed for relative humidity and rainfall, the ER for 1% increase in relative humidity was −0.21% (95% CI: −0.34% to −0.08%), and the ER for 1 mm increase in rainfall was −0.23% (95% CI: −0.37% to −0.09%). This study suggests that bacillary dysentery prevention and control strategy should consider local weather variations. PMID:24257434
Combariza, Juan F; Lombana, Milton; Pino, Luis E; Arango, Marcos
The objective of this study is to assess the prognostic usefulness of the Multinational Association of Supportive Care in Cancer (MASCC) risk score in association with the value of C-reactive protein (CRP) to identify high-risk patients with febrile neutropenia and hematologic neoplasms. A retrospective cohort study in which the MASCC score and the CRP values were used to assess the mortality risk at 30 days among patients with febrile neutropenia and hematologic malignancies was performed. Two hundred thiry-seven patients with febrile neutropenia were analyzed; the mortality rate within 30 days was 9 %. High-risk patients according to the MASCC score were significantly more likely to experience adverse outcomes, such as being transferred to the intensive care unit (RR 3.55; CI 95 % 2.73-6.62, p < 0.001) and death (RR 2.21; CI 95 % 1.74-2.79, p < 0.001). Multivariate analysis showed a strong association between the high-risk group identified by the MASCC score (HR 3.0; CI 95 % 1.12-13.54, p = 0.032) and the mean levels of CRP (HR 17; CI 95 % 2.21-136.48, p = 0.007) and survival. The survival rate within 30 days was 100 % for the patients with a low-risk MASCC score and a mean CRP less than 15 mg/dL. This rate was only 64 % for high-risk patients with a mean CRP greater than 15 mg/dL. The MASCC risk score combined with the mean CRP value successfully identifies patients with febrile neutropenia and hematological malignancies and a high risk of death.
Bennett, K J; Lipman, E L; Brown, S; Racine, Y; Boyle, M H; Offord, D R
Externalizing behavior symptoms (EBS) in childhood are a strong predictor of future conduct problems. This study evaluated their predictive accuracy using logistic regression and receiver operating characteristic curve techniques. EBS, alone and in combination with other child and familial risk factors, were used to predict conduct problems 30 months later in a nonclinic population of kindergartners and Grade 1 children. The sensitivity (Sn) and positive predictive value (PPV) of EBS alone were below preset criteria of > or = 50% for each (prevalence < or = 15%). Sn and PPV increased when other child and familial factors were combined with symptoms but did not exceed the preset criteria. From a developmental perspective, substantial stability of EBS exists over time. However, from the perspective of prevention science, significant levels of misclassification will occur when EBS are used to designate high-risk status under the low-prevalence conditions of normal populations.
Briand, Lionel C.; Basili, Victor R.; Hetmanski, Christopher J.
Applying equal testing and verification effort to all parts of a software system is not very efficient, especially when resources are limited and scheduling is tight. Therefore, one needs to be able to differentiate low/high fault frequency components so that testing/verification effort can be concentrated where needed. Such a strategy is expected to detect more faults and thus improve the resulting reliability of the overall system. This paper presents the Optimized Set Reduction approach for constructing such models, intended to fulfill specific software engineering needs. Our approach to classification is to measure the software system and build multivariate stochastic models for predicting high risk system components. We present experimental results obtained by classifying Ada components into two classes: is or is not likely to generate faults during system and acceptance test. Also, we evaluate the accuracy of the model and the insights it provides into the error making process.
Moshki, Mahdi; Dehnoalian, Atefeh; Alami, Ali
This study sought to assess the effect of precede-proceed model on preventive behaviors for type 2 diabetes mellitus (DM) in high-risk individuals. In this semi-experimental study, 164 high-risk individuals for type 2 DM were selected and were randomly divided into two groups of intervention and control ( n = 85). Educational intervention was performed as a single session face-to-face instruction for 1.5 hr for the intervention group participants. Data were collected before (baseline) and immediately and 1 month after the intervention in the two groups. The mean score of predisposing (knowledge) factors ( p = .001), reinforcing factors ( p = .001), and enabling factors ( p = .02) were significantly different at baseline and 1 month after the intervention in the intervention group compared with the control group ( p < .05). A significant improvement occurred in the nutritional habits of high-risk participants in the intervention group at 1 month after the intervention compared with controls ( p = .001). The precede-proceed model can be effective for promoting the preventive behaviors for type 2 DM in high-risk individuals.
Corcoran, Cheryl M; Kimhy, David; Stanford, Arielle; Khan, Shamir; Walsh, Julie; Thompson, Judy; Schobel, Scott; Harkavy-Friedman, Jill; Goetz, Ray; Colibazzi, Tiziano; Cressman, Victoria; Malaspina, Dolores
Background Cannabis use is reported to increase the risk for psychosis, but no prospective study has longitudinally examined drug use and symptoms concurrently in clinical high risk cases. Method We prospectively followed for up to 2 years 32 cases who met research criteria for prodromal psychosis to examine the relationship between substance use and clinical measures. Results Cases with a baseline history of cannabis use (41%) were older, but did not differ in clinical measures. Longitudinal assessments showed these cases had significantly more perceptual disturbances and worse functioning during epochs of increased cannabis use that were unexplained by concurrent use of other drugs or medications. Conclusions These data demonstrate that cannabis use may be a risk factor for the exacerbation of sub-threshold psychotic symptoms, specifically perceptual disturbances, in high risk cases. PMID:18809298
Cao, Yin; Rosner, Bernard A.; Ma, Jing; Tamimi, Rulla M.; Chan, Andrew T.; Fuchs, Charles S.
Assessing risk of colorectal adenoma at first-time colonoscopy that are of higher likelihood of developing advanced neoplasia during surveillance could help tailor first-line colorectal cancer screening. We developed prediction models for high-risk colorectal adenoma (at least one adenoma ≥1 cm, or with advanced histology, or ≥3 adenomas) among 4,881 asymptomatic white men and 17,970 women who underwent colonoscopy as their first-time screening for colorectal cancer in two prospective U.S. studies using logistic regressions. C-statistics and Hosmer-Lemeshow tests were used to evaluate discrimination and calibration. Ten-fold cross-validation was used for internal validation. A total of 330 (6.7%) men and 678 (3.8%) women were diagnosed with high-risk adenoma at first-time screening colonoscopy. The model for men included age, family history of colorectal cancer, BMI, smoking, sitting watching TV/VCR, regular aspirin/NSAID use, physical activity, and a joint term of multivitamin and alcohol. For women, the model included age, family history of colorectal cancer, BMI, smoking, alcohol, beef/pork/lamb as main dish, regular aspirin/NSAID, calcium, and oral contraceptive use. The C-statistic of the model for men was 0.67 and 0.60 for women (0.64 and 0.57 in cross-validation). Both models calibrated well. The predicted risk of high-risk adenoma for men in the top decile was 15.4% vs 1.8% for men in the bottom decile (Odds Ratio[OR]=9.41), and 6.6% vs 2.1% for women (OR=3.48). In summary, we developed and internally validated an absolute risk assessment tool for high-risk colorectal adenoma among the U.S. population that may provide guidance for first-time colorectal cancer screening. PMID:25820865
Cao, Yin; Rosner, Bernard A; Ma, Jing; Tamimi, Rulla M; Chan, Andrew T; Fuchs, Charles S; Wu, Kana; Giovannucci, Edward L
Assessing risk of colorectal adenoma at first-time colonoscopy that are of higher likelihood of developing advanced neoplasia during surveillance could help tailor first-line colorectal cancer screening. We developed prediction models for high-risk colorectal adenoma (at least one adenoma ≥1 cm, or with advanced histology, or ≥3 adenomas) among 4,881 asymptomatic white men and 17,970 women who underwent colonoscopy as their first-time screening for colorectal cancer in two prospective US studies using logistic regressions. C-statistics and Hosmer-Lemeshow tests were used to evaluate discrimination and calibration. Ten-fold cross-validation was used for internal validation. A total of 330 (6.7%) men and 678 (3.8%) women were diagnosed with high-risk adenoma at first-time screening colonoscopy. The model for men included age, family history of colorectal cancer, BMI, smoking, sitting watching TV/VCR, regular aspirin/NSAID use, physical activity, and a joint term of multivitamin and alcohol. For women, the model included age, family history of colorectal cancer, BMI, smoking, alcohol, beef/pork/lamb as main dish, regular aspirin/NSAID, calcium, and oral contraceptive use. The C-statistic of the model for men was 0.67 and 0.60 for women (0.64 and 0.57 in cross-validation). Both models calibrated well. The predicted risk of high-risk adenoma for men in the top decile was 15.4% vs. 1.8% for men in the bottom decile (Odds Ratio [OR] = 9.41), and 6.6% vs. 2.1% for women (OR = 3.48). In summary, we developed and internally validated an absolute risk assessment tool for high-risk colorectal adenoma among the US population that may provide guidance for first-time colorectal cancer screening.
Fox, A S; Bonacci, J; McLean, S G; Saunders, N
Screening methods sensitive to movement strategies that increase anterior cruciate ligament (ACL) loads are likely to be effective in identifying athletes at-risk of ACL injury. Current ACL injury risk screening methods are yet to be evaluated for their ability to identify athletes' who exhibit high-risk lower limb mechanics during sport-specific maneuvers associated with ACL injury occurrences. The purpose of this study was to examine the efficacy of two ACL injury risk screening methods in identifying high-risk lower limb mechanics during a sport-specific landing task. Thirty-two female athletes were screened using the Landing Error Scoring System (LESS) and Tuck Jump Assessment. Participants' also completed a sport-specific landing task, during which three-dimensional kinematic and kinetic data were collected. One-dimensional statistical parametric mapping was used to examine the relationships between screening method scores, and the three-dimensional hip and knee joint rotation and moment data from the sport-specific landing. Higher LESS scores were associated with reduced knee flexion from 30 to 57 ms after initial contact (P = 0.003) during the sport-specific landing; however, no additional relationships were found. These findings suggest the LESS and Tuck Jump Assessment may have minimal applicability in identifying athletes' who exhibit high-risk landing postures in the sport-specific task examined.
McFarlane, William R.; Cook, William L.; Downing, Donna; Verdi, Mary B.; Woodberry, Kristen A.; Ruff, Anita
Objective The Portland [Maine] Identification and Early Referral (PIER) Program was established in 2001 as a prevention system for identifying and treating youths at high risk of an initial psychotic episode. Methods During six years, 7,270 professionals from the educational, general medical, and mental health sectors were provided information on prodromal symptoms and means for rapid referral of at-risk youth, which resulted in referral of 780 youths who met eligibility criteria. Results After screening, 37% of the community referrals were found to be at high risk of psychosis, and another 20% had untreated psychosis, yielding an efficiency ratio of 57%. Prodromal cases identified were 46% of the expected incidence of psychosis in the catchment area. Community educational presentations were significantly associated with referrals six months later; half of referrals were from outside the mental health system. Conclusions Community-based identification is an efficient public health strategy, offering the opportunity for preventive intervention. PMID:20439374
Katapodi, Maria C; Northouse, Laurel L; Milliron, Kara J; Liu, Guipeng; Merajver, Sofia D
Little is known about family members' interrelated decisions to seek genetic testing for breast cancer susceptibility. The specific aims of this cross-sectional, descriptive, cohort study were (i) to examine whether individual and family characteristics have a direct effect on women's decisions to use genetic testing for hereditary susceptibility to breast cancer and (ii) to explore whether family characteristics moderate the relationships between individual characteristics and the decision to use genetic testing. Participants were women (>18 years old) who (i) received genetic testing for hereditary breast cancer and who agreed to invite one of their female relatives into the study and (ii) female relatives who had NOT obtained genetic testing and were identified by pedigree analysis as having >10% chances of hereditary susceptibility to breast cancer. The final sample consisted of 168 English-speaking, family dyads who completed self-administered, mailed surveys with validated instruments. Multivariate conditional logistic regression analyses showed that the proposed model explained 62% of the variance in genetic testing. The factors most significantly associated with genetic testing were having a personal history of cancer; perceiving genetic testing to have more benefits than barriers; having greater family hardiness; and perceiving fewer negative consequences associated with a breast cancer diagnosis. No significant interaction effects were observed. Findings suggest that both individual and family characteristics are associated with the decision to obtain genetic testing for hereditary breast cancer; hence, there is a need for interventions that foster a supportive family environment for patients and their high-risk relatives. Copyright © 2012 John Wiley & Sons, Ltd.
Velthorst, Eva; Derks, Eske M; Schothorst, Patricia; Becker, Hiske; Durston, Sarah; Ziermans, Tim; Nieman, Dorien H; de Haan, Lieuwe
Patients at Ultra-High Risk (UHR) for developing a first psychosis vary widely in their symptom presentation and illness course. An important aim in UHR research concerns the characterization of the clinical heterogeneity in this population. We aimed to identify qualitatively and quantitatively different clinical symptom profiles at baseline and at 2-year follow-up in a group of UHR subjects and healthy controls. We employed a Latent Class Factor Analysis (LCFA) to the 19 items of the Structured Interview for Prodromal Syndromes (SIPS) ratings at baseline and at 2-year follow-up in a sample of 147 UHR subjects and 141 controls from the Dutch Prediction of Psychosis Study (DUPS) in the Netherlands. Additionally, a stepwise logistic regression analysis was performed with transition to psychosis as a dependent variable and baseline latent variable scores as predictors. Variation in symptomatology at baseline was explained by both quantitative and qualitative differences; at 2-year follow-up qualitative differences between individuals were no longer observed. Quantitative differences showed moderate stability over time (range=0.109-0.42). Within the UHR sample, transition to psychosis was significantly associated with quantitative differences in baseline SIPS scores. The results of our study suggest a 'quasi'-continuous extended psychosis phenotype, a finding that merits replication in other samples.
Bendfeldt, Kerstin; Smieskova, Renata; Koutsouleris, Nikolaos; Klöppel, Stefan; Schmidt, André; Walter, Anna; Harrisberger, Fabienne; Wrege, Johannes; Simon, Andor; Taschler, Bernd; Nichols, Thomas; Riecher-Rössler, Anita; Lang, Undine E; Radue, Ernst-Wilhelm; Borgwardt, Stefan
The psychosis high-risk state is accompanied by alterations in functional brain activity during working memory processing. We used binary automatic pattern-classification to discriminate between the at-risk mental state (ARMS), first episode psychosis (FEP) and healthy controls (HCs) based on n-back WM-induced brain activity. Linear support vector machines and leave-one-out-cross-validation were applied to fMRI data of matched ARMS, FEP and HC (19 subjects/group). The HC and ARMS were correctly classified, with an accuracy of 76.2% (sensitivity 89.5%, specificity 63.2%, p = 0.01) using a verbal working memory network mask. Only 50% and 47.4% of individuals were classified correctly for HC vs. FEP (p = 0.46) or ARMS vs. FEP (p = 0.62), respectively. Without mask, accuracy was 65.8% for HC vs. ARMS (p = 0.03) and 65.8% for HC vs. FEP (p = 0.0047), and 57.9% for ARMS vs. FEP (p = 0.18). Regions in the medial frontal, paracingulate, cingulate, inferior frontal and superior frontal gyri, inferior and superior parietal lobules, and precuneus were particularly important for group separation. These results suggest that FEP and HC or FEP and ARMS cannot be accurately separated in small samples under these conditions. However, ARMS can be identified with very high sensitivity in comparison to HC. This might aid classification and help to predict transition in the ARMS.
Dunn, Charlotte E; Edwards, Adrian; Carter, Ben; Field, John K; Brain, Kate; Lifford, Kate J
This study aimed to examine the relationship between pre-screening expectations and psychological responses to low-dose computerised tomography (LDCT) screening among high-risk individuals in the United Kingdom Lung Cancer Screening (UKLS) pilot trial. Prior to screening, high-risk individuals randomised into the intervention arm of the UKLS were asked about their expected screening test result. Their actual LDCT scan result was compared with their baseline screening expectation to determine the level of congruence. Levels of concern about and perceived accuracy of the result were assessed in a questionnaire two weeks following receipt of their test result. The sample included 1589 participants. Regardless of their expected results, patients who required follow-up investigations after their initial LDCT scan were the most concerned about their result (p<0.001). Participants who expected to require follow-up, but did not need it, perceived the test to be least accurate (p=0.006). Lung cancer screening participants who require follow-up or who have unexpected negative results can be identified for supportive interventions. These findings can be used to ensure that any future LDCT lung cancer screening programme is tailored to identify and support those high-risk individuals who may benefit from additional help. Copyright © 2017 Elsevier B.V. All rights reserved.
Dunkler, Daniela; Dehghan, Mahshid; Teo, Koon K; Heinze, Georg; Gao, Peggy; Kohl, Maria; Clase, Catherine M; Mann, Johannes F E; Yusuf, Salim; Oberbauer, Rainer
among individuals with type 2 diabetes. Sodium intake, within a wide range, and normal protein intake are not associated with CKD. clinicaltrials.gov Identifier: NCT00153101.
Low, Lian Leng; Liu, Nan; Ong, Marcus Eng Hock; Ng, Eileen Yining; Ho, Andrew Fu Wah; Thumboo, Julian; Lee, Kheng Hock
Unplanned readmissions may be avoided by accurate risk prediction and appropriate resources could be allocated to high risk patients. The Length of stay, Acuity of admission, Charlson comorbidity index, Emergency department visits in past six months (LACE) index was developed to predict hospital readmissions in Canada. In this study, we assessed the performance of the LACE index in a Singaporean cohort by identifying elderly patients at high risk of 30-day readmissions. We further investigated the use of additional risk factors in improving readmission prediction performance.Data were extracted from the hospital's electronic health records (EHR) for all elderly patients ≥ 65 years, with alive-discharge episodes from Singapore General Hospital in 2014. In addition to LACE, we also collected patients' data during the index admission, including demographics, medical history, laboratory results, and previous medical utilization.Among the 17,006 patients analyzed, 2051 or 12.1% of them were observed 30-day readmissions. The final predictive model was better than the LACE index in terms of discriminative ability; c-statistic of LACE index and final logistic regression model was 0.595 and 0.628, respectively.The LACE index had poor discriminative ability in identifying elderly patients at high risk of 30-day readmission, even if it was augmented with additional risk factors. Further studies should be conducted to discover additional factors that may enable more accurate and timely identification of patients at elevated risk of readmissions, so that necessary preventive actions can be taken.
Holla, Bharath; Panda, Rajanikant; Venkatasubramanian, Ganesan; Biswal, Bharat; Bharath, Rose Dawn; Benegal, Vivek
Familial susceptibility to alcoholism is likely to be linked to the externalizing diathesis seen in high-risk offspring from high-density alcohol use disorder (AUD) families. The present study aimed at comparing resting brain functional connectivity and their association with externalizing symptoms and alcoholism familial density in 40 substance-naive high-risk (HR) male offspring from high-density AUD families and 30 matched healthy low-risk (LR) males without a family history of substance dependence using graph theory-based network analysis. The HR subjects from high-density AUD families compared with LR, showed significantly reduced clustering, small-worldness, and local network efficiency. The frontoparietal, cingulo-opercular, sensorimotor and cerebellar networks exhibited significantly reduced functional segregation. These disruptions exhibited independent incremental value in predicting the externalizing symptoms over and above the demographic variables. The reduction of functional segregation in HR subjects was significant across both the younger and older age groups and was proportional to the family loading of AUDs. Detection and estimation of these developmentally relevant disruptions in small-world architecture at critical brain regions sub-serving cognitive, affective, and sensorimotor processes are vital for understanding the familial risk for early onset alcoholism as well as for understanding the pathophysiological mechanism of externalizing behaviors. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.
Barajas, Ana; Ochoa, Susana; Obiols, Jordi E.; Lalucat-Jo, Lluís
Introduction. To date, few studies have focused on the characterization of clinical phenomenology regarding gender in population at high-risk of psychosis. This paper is an attempt to summarize the findings found in the scientific literature regarding gender differences in high-risk populations, taking into account parameters studied in populations with schizophrenia and other psychotic disorders, such as incidence, clinical expression, duration of untreated illness (DUI), social functioning, and cognitive impairment prior to full-blown psychosis development. Method. Studies were systematically searched in PubMed. Studies using gender variable as a control variable were excluded. 12 studies met inclusion criteria. Results. Most of the studies found a differential pattern between women and men as regards clinical, social, and cognitive variables in the prodromal phase, with worse performance in men except in cognitive functioning (more severe negative symptoms, worse social functioning, and longer DUI in men). Similar conversion rates over time were found between men and women. Conclusions. Many of the studies analyzed suggest that differences between men and women in the expression of psychosis extend across a continuum, from the subclinical forms of illness to the debut of psychosis. However, the small number of studies and their significant methodological and clinical limitations do not allow for firm conclusions. PMID:25685840
Kanavakis, E; Efthymiadou, A; Strofalis, S; Doudounakis, S; Traeger-Synodinos, J; Tzetis, M
Cystic fibrosis (CF) mutation analysis on 437 CF patients, characterized 80 different mutations (20 so far specific to our population) accounting for 91% of CF genes and generating 103 different genotypes. Eight mutations were common [F508del (53.4%), 621+1G>T (5.7%), G542X (3.9%), N1303K (2.6%), 2789+5G>A (1.7%), 2183AA>G (1.4%), E822X (1.4%), R1158X (1%)], 12 showed frequencies between 0.5% and 1%, while the remaining (60) were very rare (1 to 3 alleles). Denaturing gradient gel electrophoresis (DGGE) screening of 12 exons (3, 4, 7, 10, 11, 13, 14b, 16, 17b 20 and 21) detected 85.5% of CF alleles. Haplotypes for eight diallelic and three microsatellite markers have been characterized for the common, a few rare and novel Greek mutations. Results of 165 prenatal diagnoses (including 49 due to bowel hyperechogenicity), testing a total of 41 different parental genotypes, are reported. One hundred and sixteen prenatal tests resulted in 22 affected, 59 heterozygous, 34 normal fetuses and one incomplete diagnosis. Of the 49 echogenic bowel fetuses, 3 were heterozygotes. Carrier screening was initiated, with emphasis on individuals and couples in high-risk groups - with a family history of CF, one partner with CF, and couples with male infertility seeking in vitro fertilization (IVF). Mutation analysis on 672 individuals (120 couples, 91 unaffected CF siblings, 283 CF family relatives and 58 general population subjects), identified a total of 176 heterozygotes and 7 couples where both partners were CF heterozygotes. Prenatal diagnosis was performed in 4 cases and 3 were counseled on the availability of a prenatal test.
Mayo, Danessa; Corey, Sarah; Kelly, Leah H; Yohannes, Seghel; Youngquist, Alyssa L; Stuart, Barbara K; Niendam, Tara A; Loewy, Rachel L
The experience of childhood trauma (CT) and stressful life events (SLEs) is associated with subsequent development of a variety of mental health conditions, including psychotic illness. Recent research identifying adolescents and young adults at clinical high risk (CHR) for psychosis allows for prospective evaluation of the impact of trauma and adverse life events on psychosis onset and other outcomes, addressing etiological questions that cannot be answered in studies of fully psychotic or non-clinical populations. This article provides a comprehensive review of the current emerging literature on trauma and adverse life events in the CHR population. Up to 80% of CHR youth endorse a lifetime history of childhood traumatic events and victimization (e.g., bullying). Several studies have shown that the experience of CT predicts psychosis onset among CHR individuals, while the literature on the influence of recent SLEs (e.g., death of a loved one) remains inconclusive. Multiple models have been proposed to explain the link between trauma and psychosis, including the stress-vulnerability and stress-sensitivity hypotheses, with emphases on both cognitive processes and neurobiological mechanisms (e.g., the hypothalamic-pituitary-adrenal axis). Despite the preponderance of CHR individuals who endorse either CT or SLEs, no clinical trials have been conducted evaluating interventions for trauma in CHR youth to date. Furthermore, the current process of formal identification and assessment of trauma, SLEs, and their impact on CHR youth is inconsistent in research and clinical practice. Recommendations for improving trauma assessment, treatment, and future research directions in the CHR field are provided.
Zarogianni, Eleni; Storkey, Amos J; Johnstone, Eve C; Owens, David G C; Lawrie, Stephen M
To date, there are no reliable markers for predicting onset of schizophrenia in individuals at high risk (HR). Substantial promise is, however, shown by a variety of pattern classification approaches to neuroimaging data. Here, we examined the predictive accuracy of support vector machine (SVM) in later diagnosing schizophrenia, at a single-subject level, using a cohort of HR individuals drawn from multiply affected families and a combination of neuroanatomical, schizotypal and neurocognitive variables. Baseline structural magnetic resonance imaging (MRI), schizotypal and neurocognitive data from 17 HR subjects, who subsequently developed schizophrenia and a matched group of 17 HR subjects who did not make the transition, yet had psychotic symptoms, were included in the analysis. We employed recursive feature elimination (RFE), in a nested cross-validation scheme to identify the most significant predictors of disease transition and enhance diagnostic performance. Classification accuracy was 94% when a self-completed measure of schizotypy, a declarative memory test and structural MRI data were combined into a single learning algorithm; higher than when either quantitative measure was used alone. The discriminative neuroanatomical pattern involved gray matter volume differences in frontal, orbito-frontal and occipital lobe regions bilaterally as well as parts of the superior, medial temporal lobe and cerebellar regions. Our findings suggest that an early SVM-based prediction of schizophrenia is possible and can be improved by combining schizotypal and neurocognitive features with neuroanatomical variables. However, our predictive model needs to be tested by classifying a new, independent HR cohort in order to estimate its validity.
Algee-Hewitt, Bridget F B; Edge, Michael D; Kim, Jaehee; Li, Jun Z; Rosenberg, Noah A
Highly polymorphic genetic markers with significant potential for distinguishing individual identity are used as a standard tool in forensic testing [1, 2]. At the same time, population-genetic studies have suggested that genetically diverse markers with high individual identifiability also confer information about genetic ancestry [3-6]. The dual influence of polymorphism levels on ancestry inference and forensic desirability suggests that forensically useful marker sets with high levels of individual identifiability might also possess substantial ancestry information. We study a standard forensic marker set-the 13 CODIS loci used in the United States and elsewhere [2, 7-9]-together with 779 additional microsatellites , using direct population structure inference to test whether markers with substantial individual identifiability also produce considerable information about ancestry. Despite having been selected for individual identification and not for ancestry inference , the CODIS markers generate nontrivial model-based clustering patterns similar to those of other sets of 13 tetranucleotide microsatellites. Although the CODIS markers have relatively low values of the F(ST) divergence statistic, their high heterozygosities produce greater ancestry inference potential than is possessed by less heterozygous marker sets. More generally, we observe that marker sets with greater individual identifiability also tend toward greater population identifiability. We conclude that population identifiability regularly follows as a byproduct of the use of highly polymorphic forensic markers. Our findings have implications for the design of new forensic marker sets and for evaluations of the extent to which individual characteristics beyond identification might be predicted from current and future forensic data.
Villalpando, Aimee Hilado; Leow, Christine; Hornstein, John
This research report examines the Baby TALK model, an innovative early childhood intervention approach used to identify, recruit, and serve young children who are at-risk for developmental delays, mental health needs, and/or school failure, and their families. The report begins with a description of the model. This description is followed by an…
Hall, Amanda; And Others
The report reviews assessment guidelines developed for visually impaired infants (birth-24 months). Project staff examined research on the assessment of infants with vision loss and identified material relevant to their needs. Following a review of existing assessment tools, guidelines were prepared in the following areas: social competence,…
Mannucci, Pier Mannuccio; Franchini, Massimo
Thrombophilia is defined as a condition predisposing to the development of venous thromboembolic complications. Over the past decades, there have been great advances in the understanding of the pathogenesis of venous thromboembolism (VTE) through the identification of several inherited and acquired risk factors. However, in spite of such progress, a number of questions remain unanswered. In particular, it is well known that some subjects carrying several risk factors for VTE will never experience a thrombotic episode while other individuals developed recurrent thromboembolic events with no known risk factor. In this review, we summarize the current knowledge on the various thrombophilia markers, and also discuss their role in the development of thrombotic complications.
Briend, A.; Bari, A.
OBJECTIVE--To see whether change in weight was a more useful index than weight for age in assessing the risk of dying among malnourished children. DESIGN--Prospective cohort study. SETTING--Rural community in Bangladesh being served by international health organisation. PARTICIPANTS--1011 Children aged under 5, of whom 66 died. END POINT--Efficient screening method for identifying malnourished children at risk of dying. MEASUREMENTS AND MAIN RESULTS--Weight was measured every month. Weight for age and monthly change in weight averaged over one and three months were calculated. Sensitivity and specificity curves were used to compare the values of these two variables in identifying children with a high risk of dying. Weight for age was more sensitive than change in weight at all levels of specificity. Changes in weight, however, were independently related to the risk of dying even when intercurrent diseases and low weight for age were taken into account. CONCLUSIONS--For identifying children with a high risk of dying weight for age is a more efficient screening tool than a recent change in weight. Growth monitoring as currently recommended for primary health care programmes in developing countries does not seem to be the most effective approach in identifying children in need of urgent help. PMID:2503147
Whalley, Heather C; Sussmann, Jessika E; Chakirova, Goultchira; Mukerjee, Prerona; Peel, Anna; McKirdy, James; Hall, Jeremy; Johnstone, Eve C; Lawrie, Stephen M; McIntosh, Andrew M
Bipolar disorder is a highly heritable psychiatric disorder characterized by episodic elevation or depression of mood. Bipolar disorder is associated with structural and functional brain abnormalities but it is unclear whether these are present in relatives of affected individuals and if they are associated with subclinical symptoms or traits associated with the disorder. Functional magnetic resonance imaging scans were conducted on 93 unrelated relatives of bipolar disorder patients and 70 healthy comparison subjects performing the Hayling sentence completion paradigm. Examination of comparison subjects versus high-risk individuals was followed by assessments of associations with depression scores and measures of cyclothymic temperament. Examination of comparison subjects versus high-risk subjects revealed increased activation in the high-risk group in the left amygdala. No interaction effects were observed between the groups for scores of depression or cyclothymia and activation in any region. Significant associations were found across the groups with depression ratings and activation in the ventral striatum and with cyclothymia and activation in ventral prefrontal regions, however no interaction effects were observed between the groups. Differences in activation in the left amygdala in those at familial risk may represent a heritable endophenotype of bipolar disorder. Activation in striatal and ventral prefrontal regions may, in contrast, represent a distinct biological basis of subclinical features of the illness regardless of the presence of familial risk. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Brookes, V J; Ward, M P
The proximity of Papua New Guinea (PNG) to canine rabies-endemic countries in South-East Asia presents a risk of incursion of this disease into PNG and the rest of the Oceanic region. The objective of this study was to identify the highest risk routes for entry of dogs - associated with movement of people - into PNG from canine rabies-endemic countries. A structured, in-country expert-elicitation workshop was used, and 20 entry routes were identified. The highest risk routes were three land routes from Papua, Indonesia (hunters, traditional border crossers and unregulated, unchecked 'shopper-crossers') and two sea routes (fishing and logging). These results will be used to direct more detailed risk assessments to develop surveillance strategies and incursion response plans.
Thapar, Ajay K; Hood, Kerenza; Collishaw, Stephan; Hammerton, Gemma; Mars, Becky; Sellers, Ruth; Potter, Robert; Craddock, Nick; Thapar, Anita; Rice, Frances
Adolescent offspring of depressed parents are at particularly heightened risk of developing early onset Major Depressive Disorder (MDD) yet are unlikely to access services. We therefore aimed to identify a parsimonious combination of parent-reported symptoms that accurately detected offspring MDD. We used a multi-sample study comprising a development sample of 335 offspring of adults with recurrent MDD assessed on three occasions (mean age 12.4-14.8 years) and an independent validation sub-sample of 807 adolescents from a general population cohort (mean age 13.1 years). Parent ratings of psychiatric symptoms in adolescent offspring were assessed using established questionnaires. The best performing four-item combination of symptoms was identified. Accuracy in detecting concurrent DSM-IV MDD diagnosis, assessed by direct adolescent and parent interviews, was compared to the well-established 13-item short Moods and Feelings Questionnaire (sMFQ) using ROC curve analysis. The combination identified (concentration problems, anhedonia, worrying excessively and feeling unloved) performed equivalently to the sMFQ both in the development dataset and in the validation dataset. We concluded that a combination of four parent-reported mental health items performs equivalently to an established, longer depression questionnaire measure in detecting a diagnosis of adolescent major depressive disorder among offspring of parents with recurrent MDD and needs further evaluation.
Carrión, Ricardo E.; McLaughlin, Danielle; Goldberg, Terry E.; Auther, Andrea M.; Olsen, Ruth H.; Olvet, Doreen M.; Correll, Christoph U.; Cornblatt, Barbara A.
Importance A major public health concern associated with schizophrenia and psychotic disorders is the long-term disability that involves impaired cognition, lack of social support, and an inability to function independently in the community. A critical goal of early detection and intervention studies in psychosis is therefore to understand the factors leading to this often profound impairment. Objective To develop a predictive model of functional (social and role) outcome in a clinical high-risk sample for psychosis. Design Prospective, naturalistic, longitudinal 3- to 5-year follow-up study. Setting The Recognition and Prevention Program in New York, a research clinic located in the Zucker Hillside Hospital in New York. Participants One hundred one treatment-seeking patients at clinical high risk for psychosis. Ninety-two (91%) were followed up prospectively for a mean (SD) of 3 (1.6) years. Intervention Neurocognitive and clinical assessment. Main Outcomes and Measures The primary outcome variables were social and role functioning at the last follow-up visit. Results Poor social outcome was predicted by reduced processing speed (odds ratio [OR], 1.38; 95% CI, 1.050-1.823; P = .02), impaired social functioning at baseline (OR, 1.85; 95% CI, 1.258-2.732; P = .002), and total disorganized symptoms (OR, 5.06; 95% CI, 1.548-16.527; P = .007). Reduced performance on tests for verbal memory (OR, 1.74; 95% CI, 1.169-2.594; P = .006), role functioning at baseline (OR, 1.34; 95% CI, 1.053-1.711; P = .02), and motor disturbances (OR, 1.77; 95% CI, 1.060-2.969; P = .03) predicted role outcome. The areas under the curve for the social and role prediction models were 0.824 (95% CI, 0.736-0.913; P < .001) and 0.77 (95% CI, 0.68-0.87; P < .001), respectively, demonstrating a high discriminative ability. In addition, poor functional outcomes were not entirely dependent on the development of psychosis, because 40.3% and 45.5% of nonconverters at clinical high risk had poor social
Nam, Soohyun; Whittemore, Robin; Jeon, Sangchoon; Davey-Rothwell, Melissa A.; Latkin, Carl
Data from a social network-based HIV/STI prevention study with a total of 330 men and women at high risk of HIV/STIs were used to examine the relationships of substance use, depressive symptoms, general health, cardiovascular disease risk factors, sociodemographic characteristics, and systolic/diastolic blood pressure (SBP/DBP). Approximately 60% of the participants had prehypertension to stage 2 hypertension. In the base model, older subjects (p<.0001), men (p=.003), and with poorer self-reported health (p=.029) were significantly associated with high SBP, whereas older age (p<.001) and higher body mass index (p<.001) were significantly associated with higher DBP. After adjusting for the base model, high frequency of alcohol drinking and high frequency of binge drinking remained significant for high SBP and DBP. Our data suggest that future cardiovascular disease programs should target moderate alcohol consumption to improve blood pressure among individuals at high risk of HIV/STIs. PMID:26514661
Carney, R; Cotter, J; Firth, J; Bradshaw, T; Yung, A R
We aimed to assess whether individuals at ultra high risk (UHR) for psychosis have higher rates of cannabis use and cannabis use disorders (CUDs) than non-UHR individuals and determine whether UHR cannabis users have more severe psychotic experiences than non-users. We conducted a meta-analysis of studies reporting cannabis use in the UHR group and/or positive or negative symptoms among UHR cannabis users and non-users. Logit event rates were calculated for cannabis use, in addition to odds ratios to assess the difference between UHR and controls. Severity of clinical symptoms in UHR cannabis users and non-users was compared using Hedges' g. Thirty unique studies were included (UHR n = 4205, controls n = 667) containing data from cross-sectional and longitudinal studies, and randomised control trials. UHR individuals have high rates of current (26.7%) and lifetime (52.8%) cannabis use, and CUDs (12.8%). Lifetime use and CUDs were significantly higher than controls (lifetime OR: 2.09; CUD OR: 5.49). UHR cannabis users had higher rates of unusual thought content and suspiciousness than non-users. Ultra high risk individuals have high rates of cannabis use and CUDs, and cannabis users had more severe positive symptoms. Targeting substance use during the UHR phase may have significant benefits to an individual's long-term outcome. © 2017 The Authors Acta Psychiatrica Scandinavica Published by John Wiley & Sons Ltd.
Fernández-Nogueira, Patricia; Bragado, Paloma; Almendro, Vanessa; Ametller, Elisabet; Rios, Jose; Choudhury, Sibgat
The nervous system is now recognized to be a relevant component of the tumor microenvironment. Receptors for neuropeptides and neurotransmitters have been identified in breast cancer. However, very little is known about the role of neurogenes in regulating breast cancer progression. Our purpose was to identify neurogenes associated with breast cancer tumorigenesis with a potential to be used as biomarker and/or targets for treatment. We used three databases of human genes: GeneGo, GeneCards and Eugenes to generate a list of 1266 relevant neurogenes. Then we used bioinformatics tools to interrogate two published breast cancer databases SAGE and MicMa (n=96) and generated a list of 7 neurogenes that are differentially express among breast cancer subtypes. The clinical potential was further investigated using the GOBO database (n=1881). We identified 6 neurogenes that are differentially expressed among breast cancer subtypes and whose expression correlates with prognosis. Histamine receptor1 (HRH1), neuropilin2 (NRP2), ephrin-B1 (EFNB1), neural growth factor receptor (NGFR) and amyloid precursor protein (APP) were differentially overexpressed in basal and HER2-enriched tumor samples and syntaxin 1A (STX1A) was overexpressed in HER2-enriched and luminal B tumors. Analysis of HRH1, NRP2, and STX1A expression using the GOBO database showed that their expression significantly correlated with a shorter overall survival (p < 0.0001) and distant metastasis-free survival (p < 0.0001). In contrast, elevated co-expression of NGFR, EFNB1 and APP was associated with longer overall (p < 0.0001) and metastasis-free survival (p < 0.0001). We propose that HRH1, NRP2, and STX1A can be used as prognostic biomarkers and therapeutic targets for basal and HER2-enriched breast cancer subtypes. PMID:26673618
Kirchner, Aimee T; Ladd, D Alan; Elshaw, John J; Schlub, James F
Unhealthy lifestyles cost businesses, governmental organizations, and the U.S. military billions of dollars every year, not to mention intangible costs associated with increased mortality. This study implemented a low-cost cognitive-behavioral motivational intervention to effect behavioral change in high-risk civilian employees working for a U.S. military organization, with accompanying improvement in certain health indicators after 120 days compared with a control group. Our analysis of these results led to two conclusions: first, low-cost cognitive-behavioral motivational treatments can improve both behavior and health, and second, tentative results indicate a fully mediated relationship may exist among the cognitive variables of locus of control and self-efficacy, vice the predicted parallel relationship. Overall, we assert that effective implementation of an intervention like the one used in this study might lower the U.S. Air Force's health care bill by as much as $40 million, improve employee efficiency and mission capability, enable healthier lives, and prevent premature death. Reprint & Copyright © 2013 Association of Military Surgeons of the U.S.
Butt, Jawad H; Dalsgaard, Søren; Torp-Pedersen, Christian; Køber, Lars; Gislason, Gunnar H; Kruuse, Christina; Fosbøl, Emil L
Beta-blockers relieve the autonomic symptoms of exam-related anxiety and may be beneficial in exam-related and performance anxiety, but knowledge on related psychiatric outcomes is unknown. We hypothesized that beta-blocker therapy for exam-related anxiety identifies young students at risk of later psychiatric events. Using Danish nationwide administrative registries, we studied healthy students aged 14-30 years (1996-2012) with a first-time claimed prescription for a beta-blocker during the exam period (May-June); students who were prescribed a beta-blocker for medical reasons were excluded. We matched these students on age, sex, and time of year to healthy and study active controls with no use of beta-blockers. Risk of incident use of antidepressants, incident use of other psychotropic medications, and suicide attempts was examined by cumulative incidence curves for unadjusted associations and multivariable cause-specific Cox proportional hazard analyses for adjusted hazard ratios (HRs). We identified 12,147 healthy students with exam-related beta-blocker use and 12,147 matched healthy students with no current or prior use of beta-blockers (median age, 19 years; 80.3% women). Among all healthy students, 0.14% had a first-time prescription for a beta-blocker during the exam period with the highest proportion among students aged 19 years (0.39%). Eighty-one percent of the students filled only that single prescription for a beta-blocker during follow-up. During follow-up, 2225 (18.3%) beta-blocker users and 1400 (11.5%) nonbeta-blocker users were prescribed an antidepressant (p < 0.0001); 1225 (10.1%) beta-blocker users and 658 (5.4%) nonbeta-blocker users were prescribed a psychotropic drug (p < 0.0001); and 16 (0.13%) beta-blocker users and 6 (0.05%) nonbeta-blocker users attempted suicide (p = 0.03). Exam-related beta-blocker use was associated with an increased risk of antidepressant use (adjusted HRs, 1.68 [95% confidence intervals (CIs), 1
Ali, Noor; Lifford, Kate J; Carter, Ben; McRonald, Fiona; Yadegarfar, Ghasem; Baldwin, David R; Weller, David; Hansell, David M; Duffy, Stephen W; Field, John K; Brain, Kate
The current study aimed to identify the barriers to participation among high-risk individuals in the UK Lung Cancer Screening (UKLS) pilot trial. The UKLS pilot trial is a randomised controlled trial of low-dose CT (LDCT) screening that has recruited high-risk people using a population approach in the Cambridge and Liverpool areas. High-risk individuals aged 50-75 years were invited to participate in UKLS. Individuals were excluded if a LDCT scan was performed within the last year, if they were unable to provide consent, or if LDCT screening was unable to be carried out due to coexisting comorbidities. Statistical associations between individual characteristics and UKLS uptake were examined using multivariable regression modelling. In those who completed a non-participation questionnaire (NPQ), thematic analysis of free-text data was undertaken to identify reasons for not taking part, with subsequent exploratory linkage of key themes to risk factors for non-uptake. Comparative data were available from 4061 high-risk individuals who consented to participate in the trial and 2756 who declined participation. Of those declining participation, 748 (27.1%) completed a NPQ. Factors associated with non-uptake included: female gender (OR=0.64, p<0.001), older age (OR=0.73, p<0.001), current smoking (OR=0.70, p<0.001), lower socioeconomic group (OR=0.56, p<0.001) and higher affective risk perception (OR=0.52, p<0.001). Among non-participants who provided a reason, two main themes emerged reflecting practical and emotional barriers. Smokers were more likely to report emotional barriers to participation. A profile of risk factors for non-participation in lung screening has emerged, with underlying reasons largely relating to practical and emotional barriers. Strategies for engaging high-risk, hard-to-reach groups are critical for the equitable uptake of a potential future lung cancer screening programme. The UKLS trial was registered with the International Standard
Swann, R E; Mandalou, P; Robinson, M W; Ow, M M; Foung, S K H; McLauchlan, J; Patel, A H; Cramp, M E
Injection drug users uninfected by hepatitis C virus (HCV) despite likely repeated exposure through high-risk behaviour are well documented. Factors preventing infection in these individuals are incompletely understood. Here, we looked for anti-HCV-envelope antibody responses in a cohort of repeatedly exposed but uninfected subjects. Forty-two hepatitis C diagnostic antibody- and RNA-negative injection drug users at high risk of exposure were studied and findings compared to healthy controls and cases with chronic HCV infection. Purified IgGs from sera were tested by ELISA for binding to genotype 1a and 3a envelope glycoproteins E1E2 with further testing for IgG and IgM reactivity against soluble E2. Virus-neutralizing activity was assessed using an HCV pseudoparticle system. Uninfected subjects demonstrated significantly greater IgG and IgM reactivities to envelope glycoproteins than healthy controls with IgG from 6 individuals additionally showing significant neutralization. This study is the first to describe humoral immunological responses targeting the HCV envelope, important for viral neutralization, in exposed uninfected individuals. A subset of these cases also had evidence of viral neutralization via anti-envelope antibodies. In addition to confirming viral exposure, the presence of specific anti-envelope antibodies may be a factor that helps these individuals resist HCV infection.
Egner, Patricia A.; Wang, Jin-Bing; Zhu, Yuan-Rong; Zhang, Bao-Chu; Wu, Yan; Zhang, Qi-Nan; Qian, Geng-Sun; Kuang, Shuang-Yuan; Gange, Stephen J.; Jacobson, Lisa P.; Helzlsouer, Kathy J.; Bailey, George S.; Groopman, John D.; Kensler, Thomas W.
Residents of Qidong, People's Republic of China, are at high risk for development of hepatocellular carcinoma, in part from consumption of foods contaminated with aflatoxins. Chlorophyllin, a mixture of semisynthetic, water-soluble derivatives of chlorophyll that is used as a food colorant and over-the-counter medicine, has been shown to be an effective inhibitor of aflatoxin hepatocarcinogenesis in animal models by blocking carcinogen bioavailability. In a randomized, double-blind, placebo-controlled chemoprevention trial, we tested whether chlorophyllin could alter the disposition of aflatoxin. One hundred and eighty healthy adults from Qidong were randomly assigned to ingest 100 mg of chlorophyllin or a placebo three times a day for 4 months. The primary endpoint was modulation of levels of aflatoxin-N7-guanine adducts in urine samples collected 3 months into the intervention measured by using sequential immunoaffinity chromatography and liquid chromatography–electrospray mass spectrometry. This aflatoxin–DNA adduct excretion product serves as a biomarker of the biologically effective dose of aflatoxin, and elevated levels are associated with increased risk of liver cancer. Adherence to the study protocol was outstanding, and no adverse events were reported. Aflatoxin-N7-guanine could be detected in 105 of 169 available samples. Chlorophyllin consumption at each meal led to an overall 55% reduction (P = 0.036) in median urinary levels of this aflatoxin biomarker compared with those taking placebo. Thus, prophylactic interventions with chlorophyllin or supplementation of diets with foods rich in chlorophylls may represent practical means to prevent the development of hepatocellular carcinoma or other environmentally induced cancers. PMID:11724948
Egner, P A; Wang, J B; Zhu, Y R; Zhang, B C; Wu, Y; Zhang, Q N; Qian, G S; Kuang, S Y; Gange, S J; Jacobson, L P; Helzlsouer, K J; Bailey, G S; Groopman, J D; Kensler, T W
Residents of Qidong, People's Republic of China, are at high risk for development of hepatocellular carcinoma, in part from consumption of foods contaminated with aflatoxins. Chlorophyllin, a mixture of semisynthetic, water-soluble derivatives of chlorophyll that is used as a food colorant and over-the-counter medicine, has been shown to be an effective inhibitor of aflatoxin hepatocarcinogenesis in animal models by blocking carcinogen bioavailability. In a randomized, double-blind, placebo-controlled chemoprevention trial, we tested whether chlorophyllin could alter the disposition of aflatoxin. One hundred and eighty healthy adults from Qidong were randomly assigned to ingest 100 mg of chlorophyllin or a placebo three times a day for 4 months. The primary endpoint was modulation of levels of aflatoxin-N(7)-guanine adducts in urine samples collected 3 months into the intervention measured by using sequential immunoaffinity chromatography and liquid chromatography-electrospray mass spectrometry. This aflatoxin-DNA adduct excretion product serves as a biomarker of the biologically effective dose of aflatoxin, and elevated levels are associated with increased risk of liver cancer. Adherence to the study protocol was outstanding, and no adverse events were reported. Aflatoxin-N(7)-guanine could be detected in 105 of 169 available samples. Chlorophyllin consumption at each meal led to an overall 55% reduction (P = 0.036) in median urinary levels of this aflatoxin biomarker compared with those taking placebo. Thus, prophylactic interventions with chlorophyllin or supplementation of diets with foods rich in chlorophylls may represent practical means to prevent the development of hepatocellular carcinoma or other environmentally induced cancers.
Lemiale, Virginie; Lambert, Jérôme; Canet, Emmanuel; Mokart, Djamel; Pène, Frederic; Rabbat, Antoine; Kouatchet, Achille; Vincent, François; Bruneel, Fabrice; Gruson, Didier; Chevret, Sylvie; Azoulay, Elie
We sought to identify risk factors for mechanical ventilation in patients with malignancies and acute respiratory failure (ARF). We analyzed data from a previous randomized controlled trial in which nonintubated oncology and hematology subjects with ARF were randomized to early bronchoalveolar lavage or routine care in 16 ICUs in France. Consecutive patients with malignancies were admitted to the ICU for ARF in 2005 and 2006 with no intervention. During the study period, 219 patients were admitted to the ICU for ARF, and 8 patients were not included due to a nonintubation order. Data on the underlying disease, pulmonary involvement, and extrapulmonary organ dysfunctions were recorded at admission in the 211 remaining subjects. Ventilatory support included oxygen only (49 subjects), noninvasive ventilation (NIV) only (81 subjects), NIV followed by invasive mechanical ventilation (49 subjects), and first-line invasive mechanical ventilation (32 subjects). The 81 subjects who required invasive mechanical ventilation were compared with the 130 subjects who remained on oxygen or NIV. Factors associated with invasive mechanical ventilation by multivariate analysis were the oxygen flow required at ICU admission, the number of quadrants involved on chest x-ray, and hemodynamic dysfunction. Mortality rates for subjects who had NIV failure were 65.3% compared with 50% for subjects who were first-line intubated (P = .34). In cancer patients with ARF, hypoxemia, extent of pulmonary infiltration on chest x-ray, or hemodynamic dysfunction are risk factors for invasive mechanical ventilation. Mortality was not significantly different between NIV failure and first-line intubation. Copyright © 2014 by Daedalus Enterprises.
Beck, Louisa R.; Rodriquez, Mario H.; Dister, Sheri W.; Rodriquez, Americo D.; Rejmankova, Eliska; Ulloa, Armando; Meza, Rosa A.; Roberts, Donald R.; Paris, Jack F.; Spanner, Michael A.; Washino, Robert K.; Hacker, Carl; Legters, Llewellyn F.
A landscape approach using remote sensing and Geographic Information System (GIS) technologies was developed to discriminate between villages at high and low risk for malaria transmission, as defined by adult Anopheles albimanus abundance. Satellite data for an area in southern Chiapas, Mexico were digitally processed to generate a map of landscape elements. The GIS processes were used to determine the proportion of mapped landscape elements surrounding 40 villages where An. albimanus data had been collected. The relationships between vector abundance and landscape element proportions were investigated using stepwise discriminant analysis and stepwise linear regression. Both analyses indicated that the most important landscape elements in terms of explaining vector abundance were transitional swamp and unmanaged pasture. Discriminant functions generated for these two elements were able to correctly distinguish between villages with high ind low vector abundance, with an overall accuracy of 90%. Regression results found both transitional swamp and unmanaged pasture proportions to be predictive of vector abundance during the mid-to-late wet season. This approach, which integrates remotely sensed data and GIS capabilities to identify villages with high vector-human contact risk, provides a promising tool for malaria surveillance programs that depend on labor-intensive field techniques. This is particularly relevant in areas where the lack of accurate surveillance capabilities may result in no malaria control action when, in fact, directed action is necessary. In general, this landscape approach could be applied to other vector-borne diseases in areas where: 1. the landscape elements critical to vector survival are known and 2. these elements can be detected at remote sensing scales.
Kerr, Zachary Y.; Pollack, Lance M.; Woods, William J.; Blair, Johnny; Binson, Diane
The National HIV/AIDS Strategy emphasizes the importance of bringing prevention to the most at-risk populations. Interventions targeting all men who have sex with men (MSM) fail in that respect because only a minority engages in behavior that is likely to lead to HIV infection. Previous studies have shown that MSM who seek male sexual partners in more than one venue type (e.g., bathhouse, cruising area, online) are most likely to engage in unprotected anal intercourse (UAI), compared to men who only meet partners in any one of these setting types or who do not use venues. The present study reports differences in prevalence of UAI among MSM by their use of venue sites to meet sexual partners. A probability sample of 459 bathhouse patrons completed exit surveys. In the three months before the current bathhouse visit, 63.5% visited a bathhouse (not including the visit at which they were recruited), 46.7% visited a cruising area, 46.5% used online cruise sites to find sex partners, and 30.9% reported UAI. While UAI was associated with online cruise site use, prevalence of UAI with men met online was relatively low. The odds of UAI among men who used all three venues was significantly higher compared to men using zero [Odds Ratio (OR)=4.4; 95% Confidence Interval (CI): 1.6, 12.1)] one (OR=5.3; 95% CI: 2.2, 12.8) or two venues (OR=4.3; 95% CI: 1.9, 9.6). The findings suggest that prevention would benefit from screening for venue use to help identify men with the greatest behavioral risk. PMID:25245930
Du, Changzheng; Xue, Weicheng; Dou, Fangyuan; Peng, Yifan; Yao, Yunfeng; Zhao, Jun; Gu, Jin
High-risk patients with stage II colon cancer may benefit from adjuvant chemotherapy, but identifying this patient population can be difficult. We assessed the prognosis value for predicting tumor progression in patients with stage II colon cancer, of a panel of 2 biomarkers for colon cancer: tumor budding and preoperative carcinoembryonic antigen (CEA). Consecutive patients (N = 134) with stage II colon cancer who underwent curative surgery from 2000 to 2007 were included. Multivariate analysis was used to evaluate the association of CEA and tumor budding grade with 5-year disease-free survival (DFS). The prognostic accuracy of CEA, tumor budding grade and the combination of both (CEA-budding panel) was determined. The study found that both CEA and tumor budding grade were associated with 5-year DFS. The prognostic accuracy for disease progression was higher for the CEA-budding panel (82.1%) than either CEA (70.9%) or tumor budding grade (72.4%) alone. The findings indicate that the combination of CEA levels and tumor budding grade has greater prognostic value for identifying patients with stage II colon cancer who are at high-risk for disease progression, than either marker alone.
Baker, Susan P
The Frank A Calderone Prize in Public Health, the pre-eminent award in the field, is overseen by Columbia University's Mailman School of Public Health and presented to an individual who has made 'a transformational contribution in the field of public health'. The Prize recognises an individual who has accomplished extraordinary distinction in public health and/or who has made a specific contribution which has had long-term national or global implications. On 6 May 2010, the prize was awarded to Susan Baker. This is the first time the Prize has been bestowed upon an injury control researcher.
Carrión, Ricardo E; Cornblatt, Barbara A; McLaughlin, Danielle; Chang, Jeremy; Auther, Andrea M; Olsen, Ruth H; Javitt, Daniel C
There is a growing recognition that individuals at clinical high risk need intervention for functional impairments, along with emerging psychosis, as the majority of clinical high risk (CHR) individuals show persistent deficits in social and role functioning regardless of transition to psychosis. Recent studies have demonstrated reduced reading ability as a potential cause of functional disability in schizophrenia, related to underlying deficits in generation of mismatch negativity (MMN). The present study extends these findings to subjects at CHR. The sample consisted of 34 CHR individuals and 33 healthy comparison subjects (CNTLs) from the Recognition and Prevention (RAP) Program at the Zucker Hillside Hospital in New York. At baseline, reading measures were collected, along with MMN to pitch, duration, and intensity deviants, and measures of neurocognition, and social and role (academic/work) functioning. CHR subjects showed impairments in reading ability, neurocognition, and MMN generation, relative to CNTLs. Lower-amplitude MMN responses were correlated with worse reading ability, slower processing speed, and poorer social and role functioning. However, when entered into a simultaneous regression, only reduced responses to deviance in sound duration and volume predicted poor social and role functioning, respectively. Deficits in reading ability exist even prior to illness onset in schizophrenia and may represent a decline in performance from prior abilities. As in schizophrenia, deficits are related to impaired MMN generation, suggesting specific contributions of sensory-level impairment to neurocognitive processes related to social and role function. Copyright © 2015 Elsevier B.V. All rights reserved.
Carrión, Ricardo E.; Cornblatt, Barbara A.; McLaughlin, Danielle; Chang, Jeremy; Auther, Andrea M.; Olsen, Ruth H.; Javitt, Daniel C.
Background There is a growing recognition that individuals at clinical high risk need intervention for functional impairments, along with emerging psychosis, as the majority of clinical high risk (CHR) individuals show persistent deficits in social and role functioning regardless of transition to psychosis. Recent studies have demonstrated reduced reading ability as a potential cause of functional disability in schizophrenia, related to underlying deficits in generation of mismatch negativity (MMN). The present study extends these findings to subjects at CHR. Methods The sample consisted of 34 CHR individuals and 33 healthy comparisons subjects (CNTLs) from the Recognition and Prevention (RAP) Program at the Zucker Hillside Hospital in New York. At baseline, reading measures were collected, along with MMN to pitch, duration, and intensity deviants, and measures of neurocognition, and social and role (academic/work) functioning. Results CHR subjects showed impairments in reading ability, neurocognition, and MMN generation, relative to CNTLs. Lower-amplitude MMN responses were correlated with worse reading ability, slower processing speed, and poorer social and role functioning. However, when entered into a simultaneous regression, only reduced responses to deviance in sound duration and volume predicted poor social and role functioning, respectively. Conclusions Deficits in reading ability exist even prior to illness onset in schizophrenia and may represent a decline in performance from prior abilities. As in schizophrenia, deficits are related to impaired MMN generation, suggesting specific contributions of sensory-level impairment to neurocognitive processes related to social and role function. PMID:25728833
Despite major advances in medical therapies late mortality after myocardial infarction (MI) is still high. A substantial proportion of post-MI patients die from sudden cardiac death. Prophylactic implantable-cardioverter defibrillator (ICD) therapy has been established for post-MI patients with reduced left ventricular ejection fraction (LVEF ≤35%). However, most patients who die after MI have an LVEF >35%. For this large group of patients, no specific prophylactic strategies exist. There is strong evidence that measures of cardiac autonomic dysfunction after MI provide important prognostic information in post-MI patients with preserved LVEF. Combinations of autonomic markers can identify high-risk patients after MI with LVEF >35% whose prognosis is equally worse than that of patients with LVEF ≤35%. The ongoing REFINE-ICD (NCT00673842) and SMART-MI trials (NCT02594488) test different preventive strategies in high-risk post-MI patients with cardiac autonomic dysfunction and LVEF 36-50%. While REFINE-ICD follows the traditional concept of ICD-implantation, SMART-MI uses implantable cardiac monitors with remote monitoring capabilities to sensitively detect asymptomatic, but prognostically relevant arrhythmias that could trigger specific diagnostic and therapeutic interventions.
Natsubori, Tatsunobu; Hashimoto, Ryu-Ichiro; Yahata, Noriaki; Inoue, Hideyuki; Takano, Yosuke; Iwashiro, Norichika; Koike, Shinsuke; Gonoi, Wataru; Sasaki, Hiroki; Takao, Hidemasa; Abe, Osamu; Kasai, Kiyoto; Yamasue, Hidenori
Disturbances in semantic and phonological aspects of language processing are indicated in patients with schizophrenia, and in high-risk individuals for schizophrenia. To uncover neural correlates of the disturbances, a previous functional magnetic resonance imaging (fMRI) study using a visual lexical decision task in block design reported less leftward lateralization in the inferior frontal cortices, in patients with schizophrenia and individuals with high genetic risk for psychosis compared with normal control subjects. However, to our knowledge, no previous study has investigated contrasts between word and non-word processing that allow dissociation between semantic and phonological processing using event-related design visual lexical decision fMRI tasks in subjects with ultra-high-risk for psychosis (UHR) and patients with schizophrenia. In the current study, 20 patients with schizophrenia, 11 UHR, and 20 demographically matched controls underwent lexical decision fMRI tasks. Compared with controls, both schizophrenia and UHR groups showed significantly decreased activity in response to non-words compared with words in the inferior frontal regions. Additionally, decreased leftward lateralization in the non-word compared with word activity contrast was found in subjects with UHR compared with controls, which was not evident in patients with schizophrenia. The present findings suggest neural correlates of difficulty in phonological aspects of language processing during non-word processing in contrast to word, which at least partially commonly underlies the pathophysiology of schizophrenia and UHR. Together with a previous study in genetic high-risk subjects, the current results also suggest that reduced functional lateralization in the language-related frontal cortex may be a vulnerability marker for schizophrenia. Furthermore, the current result may suggest that the genetic basis of psychosis is presumed to be related to the evolution of the language capacity
Coyle, Hannah; Traynor, Victoria; Solowij, Nadia
The aim of this study was to assess the efficacy of cognitive training, specifically computerized cognitive training (CCT) and virtual reality cognitive training (VRCT), programs for individuals living with mild cognitive impairment (MCI) or dementia and therefore at high risk of cognitive decline. After searching a range of academic databases (CINHAL, PSYCinfo, and Web of Science), the studies evaluated (N = 16) were categorized as CCT (N = 10), VRCT (N = 3), and multimodal interventions (N = 3). Effect sizes were calculated, but a meta-analysis was not possible because of the large variability of study design and outcome measures adopted. The cognitive domains of attention, executive function, and memory (visual and verbal) showed the most consistent improvements. The positive effects on psychological outcomes (N = 6) were significant reductions on depressive symptoms (N = 3) and anxiety (N = 2) and improved perceived use of memory strategy (N = 1). Assessments of activities of daily living demonstrated no significant improvements (N = 8). Follow-up studies (N = 5) demonstrated long-term improvements in cognitive and psychological outcomes (N = 3), and the intervention groups showed a plateau effect of cognitive functioning compared with the cognitive decline experienced by control groups (N = 2). CCT and VRCT were moderately effective in long-term improvement of cognition for those at high risk of cognitive decline. Total intervention time did not mediate efficacy. Future research needs to improve study design by including larger samples, longitudinal designs, and a greater range of outcome measures, including functional and quality of life measures, to assess the wider effect of cognitive training on individuals at high risk of cognitive decline. Copyright © 2015. Published by Elsevier Inc.
Seidman, Larry J.; Meyer, Eric C.; Giuliano, Anthony J.; Breiter, Hans C.; Goldstein, Jill M.; Kremen, William S.; Thermenos, Heidi W.; Toomey, Rosemary; Stone, William S.; Tsuang, Ming T.; Faraone, Stephen V.
Objectives The search for predictors of schizophrenia has accelerated with a growing focus on early intervention and prevention of psychotic illness. Studying nonpsychotic relatives of individuals with schizophrenia enables identification of markers of vulnerability for the illness independent of confounds associated with psychosis. The goal of these studies was to develop new auditory continuous performance tests (ACPTs) and evaluate their effects in individuals with schizophrenia and their relatives. Methods We carried out two studies of auditory vigilance with tasks involving working memory (WM) and interference control with increasing levels of cognitive load to discern the information processing vulnerabilities in a sample of schizophrenia patients, and two samples of nonpsychotic relatives of individuals with schizophrenia and controls. Study 1 assessed adults (mean age = 41), and Study 2 assessed teenagers and young adults age 13-25 (mean =19). Results Patients with schizophrenia were impaired on all five versions of the ACPTs, while relatives were impaired only on WM tasks, particularly the two interference tasks that maximize cognitive load. Across all groups, the interference tasks were more difficult to perform than the other tasks. Schizophrenia patients performed worse than relatives who performed worse than controls. For patients, the effect sizes were large (Cohen’s d =1.5), whereas for relatives, they were moderate (d = ~0.40-0.50). There was no age by group interaction in the relatives –control comparison except for participants <31 years of age. Conclusions Novel WM tasks that manipulate cognitive load and interference control index an important component of the vulnerability to schizophrenia. PMID:22563872
Salerno, Jennifer; Darling-Fisher, Cindy; Hawkins, Nicole M.; Fraker, Elizabeth
Background: This article describes a school-wide sexually transmitted infection (STI) screening to identify adolescent high-risk sexual behaviors, STI history/incidence, and presence of chlamydia and gonorrhea, and examines relationships between high-risk behaviors and screening positive for chlamydia and gonorrhea in an alternative high school…
Salerno, Jennifer; Darling-Fisher, Cindy; Hawkins, Nicole M.; Fraker, Elizabeth
Background: This article describes a school-wide sexually transmitted infection (STI) screening to identify adolescent high-risk sexual behaviors, STI history/incidence, and presence of chlamydia and gonorrhea, and examines relationships between high-risk behaviors and screening positive for chlamydia and gonorrhea in an alternative high school…
Poulos, Roslyn G; Hayen, Andrew; Chong, Shanley S S; Finch, Caroline F
Burns are a significant cause of morbidity and mortality in children. Although industrialized countries have achieved significant declines in deaths and hospitalizations for these injuries in recent decades, the benefits have not been shared equally by children across all socioeconomic groups. We used Bayesian methods to map posterior expected relative risks, as an estimate of smoothed hospital separation ratios for fire and burns in children, across local government areas in New South Wales, Australia. The geographic pattern of relative risk varied by age group; higher than average risks were observed for children residing in rural and remote areas, as well as in scattered local government areas closer to the coast and in some metropolitan regions. Mapping the occurrence of injury gives injury practitioners the opportunity to identify high risk communities for further investigation of risk factors and implementation of targeted interventions within a defined area.
Gilbert, Rebecca; Martin, Richard M.; Evans, David M.; Tilling, Kate; Davey Smith, George; Kemp, John P.; Lane, J. Athene; Hamdy, Freddie C.; Neal, David E.; Donovan, Jenny L.; Metcalfe, Chris
Introduction Prostate-specific antigen (PSA) testing is a widely accepted screening method for prostate cancer, but with low specificity at thresholds giving good sensitivity. Previous research identified four single nucleotide polymorphisms (SNPs) principally associated with circulating PSA levels rather than with prostate cancer risk (TERT rs2736098, FGFR2 rs10788160, TBX3 rs11067228, KLK3 rs17632542). Removing the genetic contribution to PSA levels may improve the ability of the remaining biologically-determined variation in PSA to discriminate between high and low risk of progression within men with identified prostate cancer. We investigate whether incorporating information on the PSA-SNPs improves the discrimination achieved by a single PSA threshold in men with raised PSA levels. Materials and Methods Men with PSA between 3-10ng/mL and histologically-confirmed prostate cancer were categorised as high or low risk of progression (Low risk: Gleason score≤6 and stage T1-T2a; High risk: Gleason score 7–10 or stage T2C). We used the combined genetic effect of the four PSA-SNPs to calculate a genetically corrected PSA risk score. We calculated the Area under the Curve (AUC) to determine how well genetically corrected PSA risk scores distinguished men at high risk of progression from low risk men. Results The analysis includes 868 men with prostate cancer (Low risk: 684 (78.8%); High risk: 184 (21.2%)). Receiver operating characteristic (ROC) curves indicate that including the 4 PSA-SNPs does not improve the performance of measured PSA as a screening tool for high/low risk prostate cancer (measured PSA level AU C = 59.5% (95% CI: 54.7,64.2) vs additionally including information from the 4 PSA-SNPs AUC = 59.8% (95% CI: 55.2,64.5) (p-value = 0.40)). Conclusion We demonstrate that genetically correcting PSA for the combined genetic effect of four PSA-SNPs, did not improve discrimination between high and low risk prostate cancer in men with raised PSA levels (3-10ng
Stefanescu, Ada; Macklin, Eric A; Lin, Elaine; Dudzinski, David M; Johnson, Jacob; Kennedy, Kevin F; Jacoby, Daniel; DeFaria Yeh, Doreen; Lewis, Gregory D; Yeh, Robert W; Liberthson, Richard; Lui, George; Bhatt, Ami B
Our objective was to determine whether the Seattle Heart Failure Model (SHFM) differentiates patients with adult congenital heart disease (ACHD) at high versus low risk for cardiovascular outcomes and poor exercise capacity. The ACHD population is growing and presents increasingly for care in the community and at tertiary centers. Few strategies exist to identify the patients with ACHD at high risk for heart failure and mortality.We studied 153 adults with transposition of the great arteries, Ebstein anomaly, tetralogy of Fallot, double outlet right ventricle, and single ventricle from 2 ACHD centers. The primary outcome was cardiovascular death, with a secondary composite outcome of death, transplant, ventricular assist device, cardiovascular admission, and treatment for arrhythmia. We defined risk groups based on SHFM 5-year predicted survival: high (predicted survival <70%), intermediate (70% to 85%), and low risk (>85%). Ten patients had the primary outcome of death, and 46 the combined end point. The hazard of death in the SHFM high- versus the intermediate-risk group was 7.09 (95% confidence interval 1.5 to 33.4, p = 0.01; no deaths in the low-risk group) and the hazard of the composite outcome between the high- versus low-risk group was 6.64 (95% confidence interval 2.5 to 17.6, p = 0.0001). Kaplan-Meier survival analysis showed greater probability of all-cause mortality (p = 0.003) in the high-risk group. In conclusion, the SHFM can help identify subjects with ACHD at risk for adverse outcome and poor cardiopulmonary efficiency. This may add to the care of patients with ACHD in the community and streamline care at tertiary centers.
Fusar-Poli, Paolo; Cappucciati, Marco; De Micheli, Andrea; Rutigliano, Grazia; Bonoldi, Ilaria; Tognin, Stefania; Ramella-Cravaro, Valentina; Castagnini, Augusto; McGuire, Philip
Background: Brief Limited Intermittent Psychotic Symptoms (BLIPS) are key inclusion criteria to define individuals at ultra high risk for psychosis (UHR). Their diagnostic and prognostic significance is unclear. Objectives: To address the baseline diagnostic relationship between BLIPS and the ICD-10 categories and examine the longitudinal prognostic impact of clinical and sociodemographic factors. Methods: Prospective long-term study in UHR individuals meeting BLIPS criteria. Sociodemographic and clinical data, including ICD-10 diagnoses, were automatically drawn from electronic health records and analyzed using Kaplan–Meier failure function (1-survival), Cox regression models, bootstrapping methods, and Receiver Operating Characteristics (ROC) curve. Results: Eighty BLIPS were included. At baseline, two-thirds (68%) of BLIPS met the diagnostic criteria for ICD-10 Acute and Transient Psychotic Disorder (ATPD), most featuring schizophrenic symptoms. The remaining individuals met ICD-10 diagnostic criteria for unspecified nonorganic psychosis (15%), mental and behavioral disorders due to use of cannabinoids (11%), and mania with psychotic symptoms (6%). The overall 5-year risk of psychosis was 0.54. Recurrent episodes of BLIPS were relatively rare (11%) but associated with a higher risk of psychosis (hazard ratio [HR] 3.98) than mono-episodic BLIPS at the univariate analysis. Multivariate analysis revealed that seriously disorganizing or dangerous features increased greatly (HR = 4.39) the risk of psychosis (0.89 at 5-year). Bootstrapping confirmed the robustness of this predictor (area under the ROC = 0.74). Conclusions: BLIPS are most likely to fulfill the ATPD criteria, mainly acute schizophrenic subtypes. About half of BLIPS cases develops a psychotic disorder during follow-up. Recurrent BLIPS are relatively rare but tend to develop into psychosis. BLIPS with seriously disorganizing or dangerous features have an extreme high risk of psychosis. PMID:28053130
Nam, Soohyun; Whittemore, Robin; Jeon, Sangchoon; Davey-Rothwell, Melissa A; Latkin, Carl
Data from a social network-based human immunodeficiency virus (HIV)/sexually transmitted infection (STI) prevention study with a total of 330 men and women at high risk for HIV/STIs were used to examine the relationships between substance use, depressive symptoms, general health, cardiovascular disease risk factors, sociodemographic characteristics, and systolic/diastolic blood pressure (SBP/DBP). Approximately 60% of the participants had prehypertension to stage 2 hypertension. In the base model, older patients (P<.0001), men (P=.003), and patients with poorer self-reported health (P=.029) were significantly associated with high SBP, whereas older age (P<.001) and higher body mass index (P<.001) were significantly associated with higher DBP. After adjusting for the base model, high frequency of alcohol drinking and high frequency of binge drinking remained significant for high SBP and DBP. These data suggest that future cardiovascular disease programs should target moderate alcohol consumption to improve blood pressure among individuals at high risk for HIV/STIs. © 2015 Wiley Periodicals, Inc.
Chuang, Jung-Fang; Rau, Cheng-Shyuan; Wu, Shao-Chun; Liu, Hang-Tsung; Hsu, Shiun-Yuan; Hsieh, Hsiao-Yun; Chen, Yi-Chun; Hsieh, Ching-Hua
The ratio of systolic blood pressure (SBP) to heart rate (HR), called the reverse shock index (RSI), is used to evaluate the hemodynamic stability of trauma patients. To minimize undertriage in emergency departments (EDs), we evaluated whether RSI < 1 (i.e., SBP lower than HR) could be used as an additional variable to identify patients at high risk for more severe injury within a level category of the five-level Taiwan Triage and Acuity Scales (TTAS) system. Data obtained from the Trauma Registry System, including triage level according to the TTAS system, were retrospectively reviewed for trauma admissions from January 2009 through December 2013 in a Level I trauma center. In our study, the primary outcomes were injury severity as measured using different scoring systems, including the Glasgow coma scale (GCS), abbreviated injury scale scores, and the injury severity score (ISS), and in-hospital mortality. The secondary outcomes were hospital and intensive care unit (ICU) length of stay (LOS). Of 10,814 trauma patients, 348 patients (3.2%) had RSI < 1, whereas 10,466 (96.8%) had RSI ≥ 1. Those with RSI < 1 had greater injury severity, a higher incidence of commonly associated injuries, lower GCS scores, greater deterioration of vital signs, and a higher incidence of procedures those with RSI ≥ 1. Patients with RSI < 1 also worse outcomes including hospital and ICU LOS, a greater frequency of ICU admission, and higher in-hospital mortality. Although the five-level TTAS system provides good prioritization of patients with major trauma, using the additional criterion of RSI < 1 could identify the patients at higher risk within the same triage level (I-III). The alert of a trauma patient's SBP being lower than his/her HR (RSI < 1) without the requirement of any additional equipment makes the concept of RSI particularly valuable in crowded EDs for identifying high-risk patients. RSI < 1 may serve as a principle trigger for action in the
Kang, Dae Ryong; Yadav, Dhananjay; Koh, Sang Baek; Kim, Jang Young; Ahn, Song Vogue
The ratio of serum leptin to adiponectin (L/A ratio) could be used as a marker for insulin resistance. However, few prospective studies have investigated the impact of L/A ratio on improvement of metabolic components in high-risk individuals with metabolic syndrome. We examined the association between L/A ratio and the regression of metabolic syndrome in a population-based longitudinal study. A total of 1017 subjects (431 men and 586 women) with metabolic syndrome at baseline (2005-2008) were examined and followed (2008-2011). Baseline serum levels of leptin and adiponectin were analyzed by radioimmunoassay. Area under the receiver operating characteristics curve (AUROC) analyses were used to assess the predictive ability of L/A ratio for the regression of metabolic syndrome. During an average of 2.8 years of follow-up, metabolic syndrome disappeared in 142 men (32.9%) and 196 women (33.4%). After multivariable adjustment, the odds ratios (95% confidence interval) for regression of metabolic syndrome in comparisons of the lowest to the highest tertiles of L/A ratio were 1.84 (1.02-3.31) in men and 2.32 (1.37-3.91) in women. In AUROC analyses, L/A ratio had a greater predictive power than serum adiponectin for the regression of metabolic syndrome in both men (p=0.024) and women (p=0.019). Low L/A ratio is a predictor for the regression of metabolic syndrome. The L/A ratio could be a useful clinical marker for management of high-risk individuals with metabolic syndrome.
Kang, Dae Ryong; Yadav, Dhananjay; Koh, Sang-Baek; Kim, Jang-Young
Purpose The ratio of serum leptin to adiponectin (L/A ratio) could be used as a marker for insulin resistance. However, few prospective studies have investigated the impact of L/A ratio on improvement of metabolic components in high-risk individuals with metabolic syndrome. We examined the association between L/A ratio and the regression of metabolic syndrome in a population-based longitudinal study. Materials and Methods A total of 1017 subjects (431 men and 586 women) with metabolic syndrome at baseline (2005–2008) were examined and followed (2008–2011). Baseline serum levels of leptin and adiponectin were analyzed by radioimmunoassay. Area under the receiver operating characteristics curve (AUROC) analyses were used to assess the predictive ability of L/A ratio for the regression of metabolic syndrome. Results During an average of 2.8 years of follow-up, metabolic syndrome disappeared in 142 men (32.9%) and 196 women (33.4%). After multivariable adjustment, the odds ratios (95% confidence interval) for regression of metabolic syndrome in comparisons of the lowest to the highest tertiles of L/A ratio were 1.84 (1.02–3.31) in men and 2.32 (1.37–3.91) in women. In AUROC analyses, L/A ratio had a greater predictive power than serum adiponectin for the regression of metabolic syndrome in both men (p=0.024) and women (p=0.019). Conclusion Low L/A ratio is a predictor for the regression of metabolic syndrome. The L/A ratio could be a useful clinical marker for management of high-risk individuals with metabolic syndrome. PMID:28120564
Villamor, N; Conde, L; Martínez-Trillos, A; Cazorla, M; Navarro, A; Beà, S; López, C; Colomer, D; Pinyol, M; Aymerich, M; Rozman, M; Abrisqueta, P; Baumann, T; Delgado, J; Giné, E; González-Díaz, M; Hernández, J M; Colado, E; Payer, A R; Rayon, C; Navarro, B; José Terol, M; Bosch, F; Quesada, V; Puente, X S; López-Otín, C; Jares, P; Pereira, A; Campo, E; López-Guillermo, A
NOTCH1 has been found recurrently mutated in a subset of patients with chronic lymphocytic leukemia (CLL). To analyze biological features and clinical impact of NOTCH1 mutations in CLL, we sequenced this gene in 565 patients. NOTCH1 mutations, found in 63 patients (11%), were associated with unmutated IGHV, high expression of CD38 and ZAP-70, trisomy 12, advanced stage and elevated lactate dehydrogenase. Sequential analysis in 200 patients demonstrated acquisition of mutation in one case (0.5%) and disappearance after treatment in two. Binet A and B patients with NOTCH1-mutated had a shorter time to treatment. NOTCH1-mutated patients were more frequently refractory to therapy and showed shorter progression-free and overall survival after complete remission. Overall survival was shorter in NOTCH1-mutated patients, although not independently from IGHV. NOTCH1 mutation increased the risk of transformation to diffuse large B-cell lymphoma independently from IGHV, with this being validated in resampling tests of replicability. In summary, NOTCH1 mutational status, that was rarely acquired during the course of the disease, identify a genetic subgroup with high risk of transformation and poor outcome. This recently identified genetic subgroup of CLL patients deserves prospective studies to define their best management.
García-Alcalá, Hector; Genestier-Tamborero, Christelle Nathalie; Hirales-Tamez, Omara; Salinas-Palma, Jorge; Soto-Vega, Elena
mellitus in those aged over 50 years than in younger subjects (46.15% versus 15.88%, respectively). Conclusion The FINDRISC survey is a very useful tool for identifying individuals at high risk of developing diabetes and prediabetic states, especially in those older than 50 years. PMID:23204848
García-Alcalá, Hector; Genestier-Tamborero, Christelle Nathalie; Hirales-Tamez, Omara; Salinas-Palma, Jorge; Soto-Vega, Elena
than in younger subjects (46.15% versus 15.88%, respectively). The FINDRISC survey is a very useful tool for identifying individuals at high risk of developing diabetes and prediabetic states, especially in those older than 50 years.
Piskulic, Danijela; Liu, Lu; Cadenhead, Kristin S.; Cannon, Tyrone D.; Cornblatt, Barbara A.; McGlashan, Thomas H.; Perkins, Diana O.; Seidman, Larry J.; Tsuang, Ming T.; Walker, Elaine F.; Woods, Scott W.; Bearden, Carrie E.; Mathalon, Daniel H.; Addington, Jean
Deficits in social cognition are well established in schizophrenia and have been observed prior to the illness onset. Compared to healthy controls (HCs), individuals at clinical high risk of psychosis (CHR) are said to show deficits in social cognition similar to those observed in patients experiencing a first episode of psychosis. These deficits have been observed in several domains of social cognition, such as theory of mind (ToM), emotion perception and social perception. In the current study, the stability of three domains of social cognition (ToM, social perception and facial emotion perception) was assessed over time along and their association with both clinical symptoms and the later development of psychosis. Six hundred and seventy-five CHR individuals and 264 HC participants completed four tests of social cognition at baseline. Of those, 160 CHR and 155 HC participants completed assessments at all three time points (baseline, 1 year and 2 years) as part of their participation in the North American Prodrome Longitudinal Study. The CHR group performed poorer on all tests of social cognition across all time points compared to HCs. Social cognition was not associated with attenuated positive symptoms at any time point in the study. CHR individuals who developed a psychotic disorder during the course of the study did not differ in social cognition compared to those who did not develop psychosis. This longitudinal study demonstrated mild to moderate, but persistent ToM and social perception impairments in those at CHR for psychosis compared to HCs. PMID:26785807
Piskulic, Danijela; Liu, Lu; Cadenhead, Kristin S; Cannon, Tyrone D; Cornblatt, Barbara A; McGlashan, Thomas H; Perkins, Diana O; Seidman, Larry J; Tsuang, Ming T; Walker, Elaine F; Woods, Scott W; Bearden, Carrie E; Mathalon, Daniel H; Addington, Jean
Deficits in social cognition are well established in schizophrenia and have been observed prior to the illness onset. Compared to healthy controls (HCs), individuals at clinical high risk of psychosis (CHR) are said to show deficits in social cognition similar to those observed in patients experiencing a first episode of psychosis. These deficits have been observed in several domains of social cognition, such as theory of mind (ToM), emotion perception and social perception. In the current study, the stability of three domains of social cognition (ToM, social perception and facial emotion perception) was assessed over time along and their association with both clinical symptoms and the later development of psychosis. Six hundred and seventy-five CHR individuals and 264 HC participants completed four tests of social cognition at baseline. Of those, 160 CHR and 155 HC participants completed assessments at all three time points (baseline, 1year and 2years) as part of their participation in the North American Prodrome Longitudinal Study. The CHR group performed poorer on all tests of social cognition across all time points compared to HCs. Social cognition was not associated with attenuated positive symptoms at any time point in the study. CHR individuals who developed a psychotic disorder during the course of the study did not differ in social cognition compared to those who did not develop psychosis. This longitudinal study demonstrated mild to moderate, but persistent ToM and social perception impairments in those at CHR for psychosis compared to HCs.
Falasca, Pasquale; Berardo, Arianna; Di Tommaso, Francesca
The prospective historical cohort study develops and validates a method of identifying patients at high risk of emergency admission to hospital in the population of the Province of Ravenna (no. = 296 641). The main outcome measure is: emergency hospital admission analyzed using multivariate logistic regression (MoSaiCo - Modello Statistico Combinato). To validate the findings, the coefficients for 30 most powerful variables found on half of the population (derivation data set) were then applied to the rest of the population (validation data set). The key predicting factors included some demographic variables, social variables, clinical variables and use of health/social services. Discriminatory power and validation both reached good results. Risk score increases when variables indicating the individual vulnerability raise. The predictive frailty risk resulting from MoSaiCo allows to stratify the population, to organize care services, to provide a practical planning tool in the field of case management and management of frail patients.
Nabiwemba, E; Marchant, T; Namazzi, G; Kadobera, D; Waiswa, P
Low birthweight and prematurity are risk factors for neonatal mortality. Identifying low birthweight and premature babies at birth and giving them appropriate care could increase their chances of survival. This study aimed at assessing the use of foot length as a surrogate for low birthweight and prematurity, and recommending an operational cut-off for identifying high-risk babies at the community level in low resource settings. A hospital-based cross-sectional study was carried out between 1 September and 17 December 2009 in Uganda. Foot length of 711 newborns was measured using three different methods and their weight taken using a digital salter scale within 24 h of life. Gestational age of the newborns was also estimated using the Eregie method. Non-parametric receiver operating characteristic curve analysis was carried out to determine the foot length method with the highest predictive value to predict low birthweight and premature newborns. Sensitivity, specificity and predictive values for a range of foot lengths were estimated to determine the optimal cut-off to predict low birthweight and prematurity in this setting. Of the 711 babies recruited on day 1, 85 (12%) babies were low birthweight (<2500 g) and 29 (4%) premature (<37 weeks). The operational cut-off for foot length to detect small babies was defined as 7.6 cm, with sensitivity 85% [95% confidence interval (CI) 75-92] and specificity 81% (95% CI 78-84) for low birthweight, and sensitivity 96% (95% CI 82-100) and specificity 76% (95% CI 73-79) for premature babies. Foot length in the first days of life can predict low birthweight and prematurity among newborn babies in this setting. Further evaluation is needed to assess the feasibility of its use by community health workers to identify babies that need extra care. © 2012 Blackwell Publishing Ltd.
Bédard, Emilie; Fey, Stéphanie; Charron, Dominique; Lalancette, Cindy; Cantin, Philippe; Dolcé, Patrick; Laferrière, Céline; Déziel, Eric; Prévost, Michèle
Legionella pneumophila is frequently detected in hot water distribution systems and thermal control is a common measure implemented by health care facilities. A risk assessment based on water temperature profiling and temperature distribution within the network is proposed, to guide effective monitoring strategies and allow the identification of high risk areas. Temperature and heat loss at control points (water heater, recirculation, representative points-of-use) were monitored in various sections of five health care facilities hot water distribution systems and results used to develop a temperature-based risk assessment tool. Detailed investigations show that defective return valves in faucets can cause widespread temperature losses because of hot and cold water mixing. Systems in which water temperature coming out of the water heaters was kept consistently above 60 °C and maintained above 55 °C across the network were negative for Legionella by culture or qPCR. For systems not meeting these temperature criteria, risk areas for L. pneumophila were identified using temperature profiling and system's characterization; higher risk was confirmed by more frequent microbiological detection by culture and qPCR. Results confirmed that maintaining sufficiently high temperatures within hot water distribution systems suppressed L. pneumophila culturability. However, the risk remains as shown by the persistence of L. pneumophila by qPCR. Copyright © 2015 Elsevier Ltd. All rights reserved.
Dodell-Feder, David; DeLisi, Lynn E.; Hooker, Christine I.
Unaffected first-degree relatives of individuals with schizophrenia (i.e., those at familial high-risk [FHR]), demonstrate social dysfunction qualitatively similar though less severe than that of their affected relatives. These social difficulties may be the consequence of genetically conferred disruption to aspects of the default mode network (DMN), such as the dMPFC subsystem, which overlaps with the network of brain regions recruited during social cognitive processes. In the present study, we investigate this possibility, testing DMN connectivity and its relationship to social functioning in FHR using resting-state fMRI. Twenty FHR individuals and 17 controls underwent fMRI during a resting-state scan. Hypothesis-driven functional connectivity analyses examined ROI-to-ROI correlations between the DMN’s hubs, and regions of the dMPFC subsystem and MTL subsystem. Connectivity values were examined in relationship to a measure of social functioning and empathy/perspective-taking. Results demonstrate that FHR exhibit reduced connectivity specifically within the dMPFC subsystem of the DMN. Certain ROI-to-ROI correlations predicted aspects of social functioning and empathy/perspective-taking across all participants. Together, the data indicate that disruption to the dMPFC subsystem of the DMN may be associated with familial risk for schizophrenia, and that these intrinsic connections may carry measurable consequences for social functioning. PMID:24768131
Kraan, T; Velthorst, E; Koenders, L; Zwaart, K; Ising, H K; van den Berg, D; de Haan, L; van der Gaag, M
Previous research has established the relationship between cannabis use and psychotic disorders. Whether cannabis use is related to transition to psychosis in patients at ultra-high risk (UHR) for psychosis remains unclear. The present study aimed to review the existing evidence on the association between cannabis use and transition to psychosis in UHR samples. A search of PsychInfo, Embase and Medline was conducted from 1996 to August 2015. The search yielded 5559 potentially relevant articles that were selected on title and abstract. Subsequently 36 articles were screened on full text for eligibility. Two random-effects meta-analyses were performed. First, we compared transition rates to psychosis of UHR individuals with lifetime cannabis use with non-cannabis-using UHR individuals. Second, we compared transition rates of UHR individuals with a current DSM-IV cannabis abuse or dependence diagnosis with lifetime users and non-using UHR individuals. We found seven prospective studies reporting on lifetime cannabis use in UHR subjects (n = 1171). Of these studies, five also examined current cannabis abuse or dependence. Lifetime cannabis use was not significantly associated with transition to psychosis [odds ratio (OR) 1.14, 95% confidence interval (CI) 0.856-1.524, p = 0.37]. A second meta-analysis yielded an OR of 1.75 (95% CI 1.135-2.710, p = 0.01), indicating a significant association between current cannabis abuse or dependence and transition to psychosis. Our results show that cannabis use was only predictive of transition to psychosis in those who met criteria for cannabis abuse or dependence, tentatively suggesting a dose-response relationship between current cannabis use and transition to psychosis.
Fusar-Poli, Paolo; De Micheli, Andrea; Cappucciati, Marco; Rutigliano, Grazia; Davies, Cathy; Ramella-Cravaro, Valentina; Oliver, Dominic; Bonoldi, Ilaria; Rocchetti, Matteo; Gavaghan, Lauren; Patel, Rashmi; McGuire, Philip
The diagnostic and prognostic significance of the DSM-5-defined Attenuated Psychosis Syndrome (DSM-5-APS) in individuals undergoing an ultra high risk (UHR) clinical assessment for suspicion of psychosis risk is unknown. Prospective cohort study including all consecutive help-seeking individuals undergoing both a DSM-5-APS and a Comprehensive Assessment of At Risk Mental States (CAARMS 12/2006) assessment for psychosis risk at the Outreach and Support in South London (OASIS) UHR service (March 2013-April 2014). The diagnostic significance of DSM-5-APS was assessed with percent overall agreement, prevalence bias adjusted kappa, Bowker's test, Stuart-Maxwell test, residual analysis; the prognostic significance with Cox regression, Kaplan-Meier failure function, time-dependent area under the curve (AUC) and net benefits analysis. The impact of specific revisions of the DSM-5-APS was further tested. In 203 help-seeking individuals undergoing UHR assessment, the agreement between the DSM-5-APS and the CAARMS 12/2006 was only moderate (kappa 0.59). Among 142 nonpsychotic cases, those meeting DSM-5-APS criteria had a 5-fold probability (HR = 5.379) of developing psychosis compared to those not meeting DSM-5-APS criteria, with a 21-month cumulative risk of psychosis of 28.17% vs 6.49%, respectively. The DSM-5-APS prognostic accuracy was acceptable (AUC 0.76 at 24 months) and similar to the CAARMS 12/2006. The DSM-5-APS designation may be clinically useful to guide the provision of indicated interventions within a 7%-35% (2-year) range of psychosis risk. The removal of the criterion E or C of the DSM-5-APS may improve its prognostic performance and transdiagnostic value. The DSM-5-APS designation may be clinically useful in individuals accessing clinical services for psychosis prevention.
Clemm von Hohenberg, Christian; Pasternak, Ofer; Kubicki, Marek; Ballinger, Thomas; Vu, Mai-Anh; Swisher, Tali; Green, Katie; Giwerc, Michelle; Dahlben, Brian; Goldstein, Jill M.; Woo, Tsung-Ung W.; Petryshen, Tracey L.; Mesholam-Gately, Raquelle I.; Woodberry, Kristen A.; Thermenos, Heidi W.; Mulert, Christoph; McCarley, Robert W.; Seidman, Larry J.; Shenton, Martha E.
Background: The study of individuals at clinical high risk (CHR) for psychosis provides an important opportunity for unraveling pathological mechanisms underlying schizophrenia and related disorders. A small number of diffusion tensor magnetic resonance imaging (DTI) studies in CHR samples have yielded anatomically inconsistent results. The present study is the first to apply tract-based spatial statistics (TBSS) to perform a whole-brain DTI analysis in CHR subjects. Methods: A total of 28 individuals meeting CHR criteria and 34 healthy controls underwent DTI. TBSS was used for a group comparison of fractional anisotropy (FA), as well as axial, radial, and mean diffusivity (AD, RD, and MD). Conversion to psychosis was monitored during a mean follow-up period of 12.3 months. Results: The rate of conversion to psychosis was relatively low (4%). TBSS revealed increased MD in several clusters in the right hemisphere, most notably in the superior longitudinal fasciculus (SLF), posterior corona radiata, and corpus callosum (splenium and body). Increased RD was restricted to a smaller area in the posterior parietal lobe. Conclusion: We present further evidence that white matter microstructure is abnormal in CHR individuals, even in a sample in which the vast majority do not transition to psychosis over the following year. In accord with previous studies on CHR individuals and patients with early-onset schizophrenia, our findings suggest an important pathological role for the parietal lobe and especially the SLF. The latter is known to undergo particularly dynamic microstructural changes during adolescence and early adulthood, a critical phase for the development of psychotic illness. PMID:23737549
Tice, Jeffrey A; Miglioretti, Diana L; Li, Chin-Shang; Vachon, Celine M; Gard, Charlotte C; Kerlikowske, Karla
Women with proliferative breast lesions are candidates for primary prevention, but few risk models incorporate benign findings to assess breast cancer risk. We incorporated benign breast disease (BBD) diagnoses into the Breast Cancer Surveillance Consortium (BCSC) risk model, the only breast cancer risk assessment tool that uses breast density. We developed and validated a competing-risk model using 2000 to 2010 SEER data for breast cancer incidence and 2010 vital statistics to adjust for the competing risk of death. We used Cox proportional hazards regression to estimate the relative hazards for age, race/ethnicity, family history of breast cancer, history of breast biopsy, BBD diagnoses, and breast density in the BCSC. We included 1,135,977 women age 35 to 74 years undergoing mammography with no history of breast cancer; 17% of the women had a prior breast biopsy. During a mean follow-up of 6.9 years, 17,908 women were diagnosed with invasive breast cancer. The BCSC BBD model slightly overpredicted risk (expected-to-observed ratio, 1.04; 95% CI, 1.03 to 1.06) and had modest discriminatory accuracy (area under the receiver operator characteristic curve, 0.665). Among women with proliferative findings, adding BBD to the model increased the proportion of women with an estimated 5-year risk of 3% or higher from 9.3% to 27.8% (P<.001). The BCSC BBD model accurately estimates women's risk for breast cancer using breast density and BBD diagnoses. Greater numbers of high-risk women eligible for primary prevention after BBD diagnosis are identified using the BCSC BBD model. © 2015 by American Society of Clinical Oncology.
White, Kellee; Rudolph, Abby E; Jones, Kandice C; Latkin, Carl; Benjamin, Ebele O; Crawford, Natalie D; Fuller, Crystal M
HIV testing services and research among drug users has largely focused on injection drug users (IDUs); yet noninjection drug users (NIDUs) are also at increased risk for HIV due to high-risk sexual behaviors and overlapping networks with IDUs. This study examined drug use, sexual risk, and social network characteristics associated with recent HIV testing (testing within past year) among NIDUs. Interviewer-administered questionnaires were conducted among 418 NIDUs and log-binomial regression models were used to identify correlates of recent HIV testing. Prevalence ratios (PR) with 95% confidence intervals (CI) were reported. Nearly 97% of NIDUs reported having ever been tested for HIV and most participants (85.7%) indicated testing for HIV within the past year. Factors independently associated with recent HIV testing were higher educational attainment (PR: 1.86; 95% CI: 1.03, 3.34) and networks to discuss health and medical services (PR: 1.84; 95% CI: 1.06, 1.20). A prior positive sexually transmitted infection was associated with decreased likelihood of recent HIV test (PR: 0.43; 95% CI 0.25, 0.74). Identifying specific social network characteristics may be effective in facilitating HIV testing and prevention strategies targeting NIDUs.
Bard, Robert L; Gillespie, Brenda W; Lange, David C; Pinter, Agnes; Nicklas, John M
Ventilatory inefficiency (high volume of expired air/volume of carbon dioxide eliminated [Ve/Vco2] slope), and impaired exercise tolerance (low peak volume of oxygen consumption) obtained from cardiopulmonary exercise testing (CPX) strongly predict mortality in heart failure (HF) patients; however, other CPX variables may also contain prognostic information. Therefore, the purpose of this study was to determine the prognostic power of the aggregate of CPX data. The study prospectively monitored 390 patients referred for cardiac transplantation evaluation for 10 years for events (death, urgent transplant, left ventricular assist devices). Cox regression was used to analyze 18 CPX variables to identify the best survival model. Ve/Vco2 slope was the most powerful mortality predictor, and only resting systolic blood pressure (SBP) added additional independent prognostic power when expressed at its threshold effect value as SBP ≤ 100 mm Hg. Patients with low SBP had a greater risk than those who were within the next higher quartile of Ve/Vco2 slope with SBP > 100 mm Hg. A very high-risk cohort included 9% of the population that had a Ve/Vco2 slope > 41 and SBP ≤ 100 mm Hg and an associated 2-year event rate of 67%; conversely, a low-risk cohort had a Ve/Vco2 slope ≤ 30 and SBP >100 mm Hg and associated 2-, 5-, and 10-year event rates of 5%, 12%, and 30%, respectively. Ve/Vco2 slope was the best individual predictive CPX variable and its interpretation was significantly altered by the presence of hypotension. An algorithm combining these CPX variables identifies a HF population at very high risk of early death and warranting advanced therapies. Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
Dodell-Feder, David; DeLisi, Lynn E; Hooker, Christine I
Theory-of-mind (ToM) ability is foundational for successful social relationships, and dependent on a neurocognitive system, which includes temporoparietal junction and medial prefrontal cortex. Schizophrenia is associated with ToM impairments, and initial studies demonstrate similar, though more subtle deficits, in unaffected first-degree relatives, indicating that ToM deficits are a potential biomarker for the disorder. Importantly, the social consequences of ToM deficits could create an additional vulnerability factor for individuals at familial high risk (FHR). However, behavioral studies of ToM are inconsistent and virtually nothing is known about the neural basis of ToM in FHR or the relationship between ToM and social functioning. Here, FHR and non-FHR control participants underwent functional MRI scanning while reasoning about a story character's thoughts, emotions or physical appearance. Afterwards, participants completed a 28-day online 'daily-diary' questionnaire in which they reported daily social interactions and degree of ToM reasoning. FHR participants demonstrated less neural activity in bilateral temporoparietal junction when reasoning about thoughts and emotions. Moreover, across all participants, the degree of neural activity during ToM reasoning predicted several aspects of daily social behavior. Results suggest that vulnerability for schizophrenia is associated with neurocognitive deficits in ToM and the degree of deficit is related to day-to-day social functioning. © The Author (2014). Published by Oxford University Press. For Permissions, please email: email@example.com.
Ives, Natalie J; Suciu, Stefan; Eggermont, Alexander M M; Kirkwood, John; Lorigan, Paul; Markovic, Svetomir N; Garbe, Claus; Wheatley, Keith
Many randomised trials assessing interferon-α (IFN-α) as adjuvant therapy for high-risk malignant melanoma have been undertaken. To better assess the role of IFN-α, an individual patient data (IPD) meta-analysis of these trials was undertaken. IPD was sought from all randomised trials of adjuvant IFN-α versus no IFN-α for high-risk melanoma. Primary outcomes were event-free survival (EFS) and overall survival (OS). Standard methods for quantitative IPD meta-analysis were used. Subgroup analyses by dose, duration of treatment and various patient and disease-specific parameters were performed. Fifteen trials were included in the analysis (eleven with IPD). EFS was significantly improved with IFN-α (hazard ratio [HR] = 0.86, CI 0.81-0.91; P < 0.00001), as was OS (HR = 0.90, CI 0.85-0.97; P = 0.003). The absolute differences in EFS at 5 and 10 years were 3.5% and 2.7%, and for OS were 3.0% and 2.8% respectively in favour of IFN-α. There was no evidence that the benefit of IFN-α differed depending on dose or duration of treatment, or by age, gender, site of primary tumour, disease stage, Breslow thickness, or presence of clinical nodes. Only for ulceration was there evidence of an interaction (test for heterogeneity: P = 0.04 for EFS; P = 0.002 for OS); only patients with ulcerated tumours appeared to obtain benefit from IFN-α. This meta-analysis provides clear evidence that adjuvant IFN-α significantly reduces the risk of relapse and improves survival and shows no benefit for higher doses compared to lower doses. The increased benefit in patients with ulcerated tumours, and lack of benefit in patients without ulceration, needs further investigation. Copyright © 2017 Elsevier Ltd. All rights reserved.
Barbato, Mariapaola; Liu, Lu; Penn, David L.; Keefe, Richard S.E.; Perkins, Diana O.; Woods, Scott W.; Addington, Jean
In schizophrenia, neurocognition, social cognition and functional outcome are all inter-related, with social cognition mediating the impact that impaired neurocognition has on functional outcome. Less clear is the nature of the relationship between neurocognition, social cognition and functional outcome in individuals at clinical high risk (CHR) for psychosis. 137 CHR participants completed a neurocognitive test battery, a battery of social cognition tasks and the Social Functioning Scale. Confirmatory factor analysis showed that all social cognition tasks were reliable and valid measures of the latent variable. The path from neurocognition to functioning was statistically significant (standardized coefficient β = 0.22, p <0.01). The path from social cognition to functioning was also statistically significant (β= 0.27, p<0.05). In the mediation model the bootstrapping estimate revealed a nonsignificant indirect effect that was the association of social cognition with neurocognition and with functional outcome (β =0.20, 95% CI =−0.07 to 0.52, p=0.11). However, social cognition was significantly associated with neurocognition (β = 0.80, p < 0.001) and the path from neurocognition to functioning was no longer significant as soon as the mediator (social cognition) was entered into the mediation model (β = 0.02, p = 0.92). All of the model fit indices were very good. Unlike what has been observed with psychotic patients, social cognition does not seem to mediate the pathway from neurocognition to functional outcome when assessed with a measure of social attainment in individuals at CHR for psychosis. PMID:24012459
Chan, Raymond C. K.; Di, Xin; McAlonan, Grainne M.; Gong, Qi-yong
Objective: The present study reviewed voxel-based morphometry (VBM) studies on high-risk individuals with schizophrenia, patients experiencing their first-episode schizophrenia (FES), and those with chronic schizophrenia. We predicted that gray matter abnormalities would show progressive changes, with most extensive abnormalities in the chronic group relative to FES and least in the high-risk group. Method: Forty-one VBM studies were reviewed. Eight high-risk studies, 14 FES studies, and 19 chronic studies were analyzed using anatomical likelihood estimation meta-analysis. Results: Less gray matter in the high-risk group relative to controls was observed in anterior cingulate regions, left amygdala, and right insula. Lower gray matter volumes in FES compared with controls were also found in the anterior cingulate and right insula but not the amygdala. Lower gray matter volumes in the chronic group were most extensive, incorporating similar regions to those found in FES and high-risk groups but extending to superior temporal gyri, thalamus, posterior cingulate, and parahippocampal gryus. Subtraction analysis revealed less frontotemporal, striatal, and cerebellar gray matter in FES than the high-risk group; the high-risk group had less gray matter in left subcallosal gyrus, left amygdala, and left inferior frontal gyrus compared with FES. Subtraction analysis confirmed lower gray matter volumes through ventral-dorsal anterior cingulate, right insula, left amygdala and thalamus in chronic schizophrenia relative to FES. Conclusions: Frontotemporal brain structural abnormalities are evident in nonpsychotic individuals at high risk of developing schizophrenia. The present meta-analysis indicates that these gray matter abnormalities become more extensive through first-episode and chronic illness. Thus, schizophrenia appears to be a progressive cortico-striato-thalamic loop disorder. PMID:19633214
Du Toit, George; Roberts, Graham; Sayre, Peter H; Plaut, Marshall; Bahnson, Henry T; Mitchell, Herman; Radulovic, Suzana; Chan, Susan; Fox, Adam; Turcanu, Victor; Lack, Gideon
Peanut allergy (PA) is rare in countries in which peanuts are introduced early into infants' diets. Learning Early About Peanut Allergy (LEAP) is an interventional study aiming to assess whether PA can be prevented by oral tolerance induction. We sought to characterize a population screened for the risk of PA. Subjects screened for the LEAP interventional trial comprise the LEAP screening study cohort. Infants were aged 4 to 10 months and passed a prescreening questionnaire. This analysis includes 834 infants (mean age, 7.8 months). They were split into the following: group I, patients with mild eczema and no egg allergy (n = 118); group II, patients with severe eczema, egg allergy, or both but 0-mm peanut skin prick test (SPT) wheal responses (n = 542); group III, patients with severe eczema, egg allergy, or both and 1- to 4-mm peanut wheal responses (n = 98); and group IV, patients with greater than 4-mm peanut wheal responses (n = 76). Unexpectedly, many (17%) in group II had peanut-specific IgE sensitization (≥ 0.35 kU/L); 56% of group III were similarly sensitized. In contrast, none of the patients in group I and 91% of those in group IV had peanut-specific IgE sensitization. Sensitization on skin testing to peanut (SPT response of 1-4 mm vs 0 mm) was associated with egg allergy and severe eczema (odds ratio [OR], 2.31 [95% CI, 1.39-3.86] and 2.47 [95% CI, 1.14-5.34], respectively). Similar associations were observed with specific IgE sensitization. Black race was associated with a significantly higher risk of peanut-specific IgE sensitization (OR, 5.30 [95% CI, 2.85-9.86]). Paradoxically, for a given specific IgE level, black race was protective against cutaneous sensitization (OR, 0.15 [95% CI, 0.04-0.61]). Egg allergy, severe eczema, or both appear to be useful criteria for identifying high-risk infants with an intermediate level of peanut sensitization for entry into a PA prevention study. The relationship between specific IgE level and SPT sensitization
Makiani, Mahin Jamshidi; Davoodian, Parivash; Abedi, Farshid; Hossini, Mahtab; Zare, Shahram; Rahimi, Shafea; Jahanshahi, Keramat Allah; Eftekhari, Tasnim Eqbal
AIDS and hepatitis are two of the most important health issues in the world. Adolescents and individuals in their reproductive years are important population for interventions in order to reduce high risk behaviors for transmission of sexually transmitted disease. However the prevalence of AIDS and hepatitis B and C is high in Bandar Abbas, no study is available about high risk behaviors related to these diseases in Bandar Abbas. The aim of the current study was to investigate high risk behaviors related to AIDS and hepatitis B and C among 15- to 45 year old individuals in Bandar Abbas, Southern Iran. In this analytical study, 1938 participants between 15- and 45 years of age in Bandar Abbas in 2012 were selected to participate in this study. For each individual, the following information was sought: shared syringes, phlebotomy, tattoos, prisoning, drug abuse, amphetamine, alcohol, smoking, unsafe sexual contacts, as well as demographic information including age, sex, marital status, and education level. Data were analysed using SPSS version 16 (SPSS Inc. Chicago, Illinois, United States) using descriptive statistics and chi-square tests. A total of 8.4% reported having had tattoos; 10.3% reported previous phlebotomy. Individuals with prison history included 7.3% of our study population and their mean age was 31.4 years. Unsafe sexual contact was reported in 10.7% of the study sample. High risk behaviors were more common among individuals with a low educational level, and in alcohol users and amphetamine users (P<0.05). High risk behaviors are more common among individuals in their reproductive years. Increasing educational level and knowledge translation are effective in preventing AIDS and hepatitis high risk behaviors.
Makiani, Mahin Jamshidi; Davoodian, Parivash; Abedi, Farshid; Hossini, Mahtab; Zare, Shahram; Rahimi, Shafea; Jahanshahi, Keramat Allah; Eftekhari, Tasnim Eqbal
Background: AIDS and hepatitis are two of the most important health issues in the world. Adolescents and individuals in their reproductive years are important population for interventions in order to reduce high risk behaviors for transmission of sexually transmitted disease. However the prevalence of AIDS and hepatitis B and C is high in Bandar Abbas, no study is available about high risk behaviors related to these diseases in Bandar Abbas. The aim of the current study was to investigate high risk behaviors related to AIDS and hepatitis B and C among 15- to 45 year old individuals in Bandar Abbas, Southern Iran. Method: In this analytical study, 1938 participants between 15- and 45 years of age in Bandar Abbas in 2012 were selected to participate in this study. For each individual, the following information was sought: shared syringes, phlebotomy, tattoos, prisoning, drug abuse, amphetamine, alcohol, smoking, unsafe sexual contacts, as well as demographic information including age, sex, marital status, and education level. Data were analysed using SPSS version 16 (SPSS Inc. Chicago, Illinois, United States) using descriptive statistics and chi-square tests. Results: A total of 8.4% reported having had tattoos; 10.3% reported previous phlebotomy. Individuals with prison history included 7.3% of our study population and their mean age was 31.4 years. Unsafe sexual contact was reported in 10.7% of the study sample. High risk behaviors were more common among individuals with a low educational level, and in alcohol users and amphetamine users (P<0.05). Conclusion: High risk behaviors are more common among individuals in their reproductive years. Increasing educational level and knowledge translation are effective in preventing AIDS and hepatitis high risk behaviors. PMID:25763163
Corcoran, C M; Keilp, J G; Kayser, J; Klim, C; Butler, P D; Bruder, G E; Gur, R C; Javitt, D C
Schizophrenia is characterized by profound and disabling deficits in the ability to recognize emotion in facial expression and tone of voice. Although these deficits are well documented in established schizophrenia using recently validated tasks, their predictive utility in at-risk populations has not been formally evaluated. The Penn Emotion Recognition and Discrimination tasks, and recently developed measures of auditory emotion recognition, were administered to 49 clinical high-risk subjects prospectively followed for 2 years for schizophrenia outcome, and 31 healthy controls, and a developmental cohort of 43 individuals aged 7-26 years. Deficit in emotion recognition in at-risk subjects was compared with deficit in established schizophrenia, and with normal neurocognitive growth curves from childhood to early adulthood. Deficits in emotion recognition significantly distinguished at-risk patients who transitioned to schizophrenia. By contrast, more general neurocognitive measures, such as attention vigilance or processing speed, were non-predictive. The best classification model for schizophrenia onset included both face emotion processing and negative symptoms, with accuracy of 96%, and area under the receiver-operating characteristic curve of 0.99. In a parallel developmental study, emotion recognition abilities were found to reach maturity prior to traditional age of risk for schizophrenia, suggesting they may serve as objective markers of early developmental insult. Profound deficits in emotion recognition exist in at-risk patients prior to schizophrenia onset. They may serve as an index of early developmental insult, and represent an effective target for early identification and remediation. Future studies investigating emotion recognition deficits at both mechanistic and predictive levels are strongly encouraged.
Corcoran, C. M.; Keilp, J. G.; Kayser, J.; Klim, C.; Butler, P. D.; Bruder, G. E.; Gur, R. C.; Javitt, D. C.
Background Schizophrenia is characterized by profound and disabling deficits in the ability to recognize emotion in facial expression and tone of voice. Although these deficits are well documented in established schizophrenia using recently validated tasks, their predictive utility in at-risk populations has not been formally evaluated. Method The Penn Emotion Recognition and Discrimination tasks, and recently developed measures of auditory emotion recognition, were administered to 49 clinical high-risk subjects prospectively followed for 2 years for schizophrenia outcome, and 31 healthy controls, and a developmental cohort of 43 individuals aged 7–26 years. Deficit in emotion recognition in at-risk subjects was compared with deficit in established schizophrenia, and with normal neurocognitive growth curves from childhood to early adulthood. Results Deficits in emotion recognition significantly distinguished at-risk patients who transitioned to schizophrenia. By contrast, more general neurocognitive measures, such as attention vigilance or processing speed, were non-predictive. The best classification model for schizophrenia onset included both face emotion processing and negative symptoms, with accuracy of 96%, and area under the receiver-operating characteristic curve of 0.99. In a parallel developmental study, emotion recognition abilities were found to reach maturity prior to traditional age of risk for schizophrenia, suggesting they may serve as objective markers of early developmental insult. Conclusions Profound deficits in emotion recognition exist in at-risk patients prior to schizophrenia onset. They may serve as an index of early developmental insult, and represent an effective target for early identification and remediation. Future studies investigating emotion recognition deficits at both mechanistic and predictive levels are strongly encouraged. PMID:26040537
Rasam, A. R. Abdul; Shariff, N. M.; Dony, J. F.
Development of an innovative method to enhance the detection of tuberculosis (TB) in Malaysia is the latest agenda of the Ministry of Health. Therefore, a geographical information system (GIS) based index model is proposed as an alternative method for defining potential high-risk areas of local TB cases at Section U19, Shah Alam. It is adopted a spatial multi-criteria decision making (MCDM) method for ranking environmental risk factors of the disease in a standardised five-score scale. Scale 1 and 5 illustrate the lowest and the highest risk of the TB spread respectively, while scale from 3 to 5 is included as a potential risk level. These standardised scale values are then combined with expert normalised weights (0 to 1) to calculate the overall index values and produce a TB ranked map using a GIS overlay analysis and weighted linear combination. It is discovered that 71.43% of the Section is potential as TB high risk areas particularly at urban and densely populated settings. This predictive result is also reliable with the current real cases in 2015 by 76.00% accuracy. A GIS based MCDM method has demonstrated analytical capabilities in targeting high-risk spots and TB surveillance monitoring system of the country, but the result could be strengthened by applying other uncertainty assessment method.
Ho, New Fei; Holt, Daphne J; Cheung, Mike; Iglesias, Juan Eugenio; Goh, Alex; Wang, Mingyuan; Lim, Joseph KW; de Souza, Joshua; Poh, Joann S; See, Yuen Mei; Adcock, Alison R; Wood, Stephen J; Chee, Michael WL; Lee, Jimmy; Zhou, Juan
Most individuals identified as ultra-high-risk (UHR) for psychosis do not develop frank psychosis. They continue to exhibit subthreshold symptoms, or go on to fully remit. Prior work has shown that the volume of CA1, a subfield of the hippocampus, is selectively reduced in the early stages of schizophrenia. Here we aimed to determine whether patterns of volume change of CA1 are different in UHR individuals who do or do not achieve symptomatic remission. Structural MRI scans were acquired at baseline and at 1–2 follow-up time points (at 12-month intervals) from 147 UHR and healthy control subjects. An automated method (based on an ex vivo atlas of ultra-high-resolution hippocampal tissue) was used to delineate the hippocampal subfields. Over time, a greater decline in bilateral CA1 subfield volumes was found in the subgroup of UHR subjects whose subthreshold symptoms persisted (n=40) and also those who developed clinical psychosis (n=12), compared with UHR subjects who remitted (n=41) and healthy controls (n=54). No baseline differences in volumes of the overall hippocampus or its subfields were found among the groups. Moreover, the rate of volume decline of CA1, but not of other hippocampal subfields, in the non-remitters was associated with increasing symptom severity over time. Thus, these findings indicate that there is deterioration of CA1 volume in persistently symptomatic UHR individuals in proportion to symptomatic progression. PMID:28079061
Haegeli, Pascal; Gunn, Matt; Haider, Wolfgang
The development of effective prevention initiatives requires a detailed understanding of the characteristics and needs of the target audience. To properly identify at-risk individuals, it is crucial to clearly delineate risky from acceptable behavior. Whereas health behavior campaigns commonly use single conditions (e.g., lack of condom use) to identify high-risk cohorts, many risk behaviors are more complex and context dependent, rendering a single condition approach inadequate. Out-of-bounds skiing, an activity associated with voluntary exposure to avalanche hazard, is an example of such a multifaceted risk-taking activity. Using a dataset from an extensive online survey on out-of-bounds skiing, we present an innovative approach for identifying at-risk individuals in complex risk environments. Based on a risk management framework, we first examine risk-taking preferences of out-of-bounds skiers with respect to exposure and preparedness--the two main dimensions of risk management--separately. Our approach builds on existing person-centered research and uses Latent Class Analysis to assign survey participants to mutually exclusive behavioral classes on these two dimensions. Discrete Choice Experiments are introduced as a useful method for examining exposure preferences in the context of variable external conditions. The two class designations are then combined using a risk matrix to assign overall risk levels to each survey participant. The present approach complements existing person-centered prevention research on the antecedents of risk-taking by offering a process-oriented method for examining behavioral patterns with respect to the activity itself. Together, the two approaches can offer a much richer perspective for informing the design of effective prevention initiatives.
Sanders, Perry R.; Conti, Gary J.
Although One-Stop Career Centers are mandated to promote client-centered services, patrons are ordinarily funneled through a standard procedure. Adult education principles suggest that these centers should be learner-centered and address individual differences. Therefore, the purpose of the this study was to describe the interaction of the…
Allison, Kevin W., Comp.; Richardson, Kathy A., Comp.
The bibliography lists English-language journal articles, book sections, a dissertation, and an official State of Wisconsin report, addressing the topic of substance abuse among handicapped and high-risk individuals. The entries are arranged in five sections according to handicapping condition and provide basic bibliographic information and a…
Milner, Joel S.; Rabenhorst, Mandy M.; McCanne, Thomas R.; Crouch, Julie L.; Skowronski, John J.; Fleming, Matthew T.; Hiraoka, Regina; Risser, Heather J.
Objective: The present investigation used event-related potentials (ERPs, N400 and N300) to determine the extent to which individuals at low and high risk for child physical abuse (CPA) have pre-existing positive and negative child-related schemata that can be automatically activated by ambiguous child stimuli. Methods: ERP data were obtained from…
Milner, Joel S.; Rabenhorst, Mandy M.; McCanne, Thomas R.; Crouch, Julie L.; Skowronski, John J.; Fleming, Matthew T.; Hiraoka, Regina; Risser, Heather J.
Objective: The present investigation used event-related potentials (ERPs, N400 and N300) to determine the extent to which individuals at low and high risk for child physical abuse (CPA) have pre-existing positive and negative child-related schemata that can be automatically activated by ambiguous child stimuli. Methods: ERP data were obtained from…
Jewell, Zoe C.; Alibhai, Sky K.; Weise, Florian; Munro, Stuart; Van Vuuren, Marlice; Van Vuuren, Rudie
The cheetah (Acinonyx jubatus) is Africa's most endangered large felid and listed as Vulnerable with a declining population trend by the IUCN1. It ranges widely over sub-Saharan Africa and in parts of the Middle East. Cheetah conservationists face two major challenges, conflict with landowners over the killing of domestic livestock, and concern over range contraction. Understanding of the latter remains particularly poor2. Namibia is believed to support the largest number of cheetahs of any range country, around 30%, but estimates range from 2,9053 to 13,5204. The disparity is likely a result of the different techniques used in monitoring. Current techniques, including invasive tagging with VHF or satellite/GPS collars, can be costly and unreliable. The footprint identification technique5 is a new tool accessible to both field scientists and also citizens with smartphones, who could potentially augment data collection. The footprint identification technique analyzes digital images of footprints captured according to a standardized protocol. Images are optimized and measured in data visualization software. Measurements of distances, angles, and areas of the footprint images are analyzed using a robust cross-validated pairwise discriminant analysis based on a customized model. The final output is in the form of a Ward's cluster dendrogram. A user-friendly graphic user interface (GUI) allows the user immediate access and clear interpretation of classification results. The footprint identification technique algorithms are species specific because each species has a unique anatomy. The technique runs in a data visualization software, using its own scripting language (jsl) that can be customized for the footprint anatomy of any species. An initial classification algorithm is built from a training database of footprints from that species, collected from individuals of known identity. An algorithm derived from a cheetah of known identity is then able to classify free
Jewell, Zoe C; Alibhai, Sky K; Weise, Florian; Munro, Stuart; Van Vuuren, Marlice; Van Vuuren, Rudie
The cheetah (Acinonyx jubatus) is Africa's most endangered large felid and listed as Vulnerable with a declining population trend by the IUCN(1). It ranges widely over sub-Saharan Africa and in parts of the Middle East. Cheetah conservationists face two major challenges, conflict with landowners over the killing of domestic livestock, and concern over range contraction. Understanding of the latter remains particularly poor(2). Namibia is believed to support the largest number of cheetahs of any range country, around 30%, but estimates range from 2,905(3) to 13,520(4). The disparity is likely a result of the different techniques used in monitoring. Current techniques, including invasive tagging with VHF or satellite/GPS collars, can be costly and unreliable. The footprint identification technique(5) is a new tool accessible to both field scientists and also citizens with smartphones, who could potentially augment data collection. The footprint identification technique analyzes digital images of footprints captured according to a standardized protocol. Images are optimized and measured in data visualization software. Measurements of distances, angles, and areas of the footprint images are analyzed using a robust cross-validated pairwise discriminant analysis based on a customized model. The final output is in the form of a Ward's cluster dendrogram. A user-friendly graphic user interface (GUI) allows the user immediate access and clear interpretation of classification results. The footprint identification technique algorithms are species specific because each species has a unique anatomy. The technique runs in a data visualization software, using its own scripting language (jsl) that can be customized for the footprint anatomy of any species. An initial classification algorithm is built from a training database of footprints from that species, collected from individuals of known identity. An algorithm derived from a cheetah of known identity is then able to classify
Cullen, Alexis E; Jewell, Amelia; Tully, John; Coghlan, Suzanne; Dean, Kimberlie; Fahy, Tom
substance use, are strong predictors of absconsion in forensic settings; the absence of these factors may enable clinical teams to identify unnecessarily restricted low-risk individuals.
Rosellini, Anthony J; Monahan, John; Street, Amy E; Hill, Eric D; Petukhova, Maria; Reis, Ben Y; Sampson, Nancy A; Benedek, David M; Bliese, Paul; Stein, Murray B; Ursano, Robert J; Kessler, Ronald C
Growing concerns exist about violent crimes perpetrated by U.S. military personnel. Although interventions exist to reduce violent crimes in high-risk populations, optimal implementation requires evidence-based targeting. The goal of the current study was to use machine learning methods (stepwise and penalized regression; random forests) to develop models to predict minor violent crime perpetration among U.S. Army soldiers. Predictors were abstracted from administrative data available for all 975,057 soldiers in the U.S. Army 2004-2009, among whom 25,966 men and 2728 women committed a first founded minor violent crime (simple assault, blackmail-extortion-intimidation, rioting, harassment). Temporally prior administrative records measuring socio-demographic, Army career, criminal justice, medical/pharmacy, and contextual variables were used to build separate male and female prediction models that were then tested in an independent 2011-2013 sample. Final model predictors included young age, low education, early career stage, prior crime involvement, and outpatient treatment for diverse emotional and substance use problems. Area under the receiver operating characteristic curve was 0.79 (for men and women) in the 2004-2009 training sample and 0.74-0.82 (men-women) in the 2011-2013 test sample. 30.5-28.9% (men-women) of all administratively-recorded crimes in 2004-2009 were committed by the 5% of soldiers having highest predicted risk, with similar proportions (28.5-29.0%) when the 2004-2009 coefficients were applied to the 2011-2013 test sample. These results suggest that it may be possible to target soldiers at high-risk of violence perpetration for preventive interventions, although final decisions about such interventions would require weighing predicted effectiveness against intervention costs and competing risks.
Patterson, Mark E.; Miranda, Derick; Schuman, Greg; Eaton, Christopher; Smith, Andrew; Silver, Brad
Background: Leveraging “big data” as a means of informing cost-effective care holds potential in triaging high-risk heart failure (HF) patients for interventions within hospitals seeking to reduce 30-day readmissions. Objective: Explore provider’s beliefs and perceptions about using an electronic health record (EHR)-based tool that uses unstructured clinical notes to risk-stratify high-risk heart failure patients. Methods: Six providers from an inpatient HF clinic within an urban safety net hospital were recruited to participate in a semistructured focus group. A facilitator led a discussion on the feasibility and value of using an EHR tool driven by unstructured clinical notes to help identify high-risk patients. Data collected from transcripts were analyzed using a thematic analysis that facilitated drawing conclusions clustered around categories and themes. Results: From six categories emerged two themes: (1) challenges of finding valid and accurate results, and (2) strategies used to overcome these challenges. Although employing a tool that uses electronic medical record (EMR) unstructured text as the benchmark by which to identify high-risk patients is efficient, choosing appropriate benchmark groups could be challenging given the multiple causes of readmission. Strategies to mitigate these challenges include establishing clear selection criteria to guide benchmark group composition, and quality outcome goals for the hospital. Conclusion: Prior to implementing into practice an innovative EMR-based case-finder driven by unstructured clinical notes, providers are advised to do the following: (1) define patient quality outcome goals, (2) establish criteria by which to guide benchmark selection, and (3) verify the tool’s validity and reliability. Achieving consensus on these issues would be necessary for this innovative EHR-based tool to effectively improve clinical decision-making and in turn, decrease readmissions for high-risk patients. PMID:27683666
Patterson, Mark E; Miranda, Derick; Schuman, Greg; Eaton, Christopher; Smith, Andrew; Silver, Brad
Leveraging "big data" as a means of informing cost-effective care holds potential in triaging high-risk heart failure (HF) patients for interventions within hospitals seeking to reduce 30-day readmissions. Explore provider's beliefs and perceptions about using an electronic health record (EHR)-based tool that uses unstructured clinical notes to risk-stratify high-risk heart failure patients. Six providers from an inpatient HF clinic within an urban safety net hospital were recruited to participate in a semistructured focus group. A facilitator led a discussion on the feasibility and value of using an EHR tool driven by unstructured clinical notes to help identify high-risk patients. Data collected from transcripts were analyzed using a thematic analysis that facilitated drawing conclusions clustered around categories and themes. From six categories emerged two themes: (1) challenges of finding valid and accurate results, and (2) strategies used to overcome these challenges. Although employing a tool that uses electronic medical record (EMR) unstructured text as the benchmark by which to identify high-risk patients is efficient, choosing appropriate benchmark groups could be challenging given the multiple causes of readmission. Strategies to mitigate these challenges include establishing clear selection criteria to guide benchmark group composition, and quality outcome goals for the hospital. Prior to implementing into practice an innovative EMR-based case-finder driven by unstructured clinical notes, providers are advised to do the following: (1) define patient quality outcome goals, (2) establish criteria by which to guide benchmark selection, and (3) verify the tool's validity and reliability. Achieving consensus on these issues would be necessary for this innovative EHR-based tool to effectively improve clinical decision-making and in turn, decrease readmissions for high-risk patients.
Dennis, Ann M; Murillo, Wendy; de Maria Hernandez, Flor; Guardado, Maria Elena; Nieto, Ana Isabel; Lorenzana de Rivera, Ivette; Eron, Joseph J; Paz-Bailey, Gabriela
HIV in Central America is concentrated among certain groups such as men who have sex with men (MSM) and female sex workers (FSWs). We compared social recruitment chains and HIV transmission clusters from 699 MSM and 787 FSWs to better understand factors contributing to ongoing HIV transmission in El Salvador. Phylogenies were reconstructed using pol sequences from 119 HIV-positive individuals recruited by respondent-driven sampling (RDS) and compared with RDS chains in 3 cities in El Salvador. Transmission clusters with a mean pairwise genetic distance ≤ 0.015 and Bayesian posterior probabilities =1 were identified. Factors associated with cluster membership were evaluated among MSM. Sequences from 34 (43%) MSM and 4 (10%) FSW grouped in 14 transmission clusters. Clusters were defined by risk group (12 MSM clusters) and geographic residence (only 1 spanned separate cities). In 4 MSM clusters (all n = 2), individuals were also members of the same RDS chain, but only 2 had members directly linked through recruitment. All large clusters (n ≥ 3) spanned >1 RDS chain. Among MSM, factors independently associated with cluster membership included recent infection by BED assay (P = 0.02), sex with stable male partners (P = 0.02), and sex with ≥ 3 male partners in the past year (P = 0.04). We found few HIV transmissions corresponding directly with the social recruitment. However, we identified clustering in nearly one-half of MSM suggesting that RDS recruitment was indirectly but successfully uncovering transmission networks, particularly among recent infections. Interrogating RDS chains with phylogenetic analyses may help refine methods for identifying transmission clusters.
Dennis, Ann M.; Murillo, Wendy; de Maria Hernandez, Flor; Guardado, Maria Elena; Nieto, Ana Isabel; de Rivera, Ivette Lorenzana; Eron, Joseph J.; Paz-Bailey, Gabriela
Objective HIV in Central America is concentrated among certain groups such as men who have sex with men (MSM) and female sex workers (FSW). We compared social recruitment chains and HIV transmission clusters from 699 MSM and 757 FSW to better understand factors contributing to ongoing HIV transmission in El Salvador. Methods Phylogenies were reconstructed using pol sequences from 119 HIV-positive individuals recruited by respondent driven sampling (RDS) and compared to RDS chains in three cities in El Salvador. Transmission clusters with a mean pairwise genetic distance ≤0.015 and Bayesian posterior probabilities=1 were identified. Factors associated with cluster membership were evaluated among MSM. Results Sequences from 34 (43%) MSM and 4 (10%) FSW grouped in 14 transmission clusters. Clusters were defined by risk group (12 MSM clusters) and geographic residence (only one spanned separate cities). In 4 MSM clusters (all n=2), individuals were also members of the same RDS chain but only 2 had members directly linked through recruitment. All large clusters (n≥3) spanned more than one RDS chain. Among MSM, factors independently associated with cluster membership included recent infection by BED assay (P=0.02), sex with stable male partners (P=0.02), and sex with ≥3 male partners in past year (P=0.04). Conclusions We found few HIV transmissions corresponding directly with the social recruitment. However, we identified clustering in nearly one half of MSM suggesting RDS recruitment was indirectly but successfully uncovering transmission networks, particularly among recent infections. Interrogating RDS chains with phylogenetic analyses may help refine methods for identifying transmission clusters. PMID:23364512
Cullen, Alexis E.; Jewell, Amelia; Tully, John; Coghlan, Suzanne; Dean, Kimberlie; Fahy, Tom
inpatient verbal aggression and substance use, are strong predictors of absconsion in forensic settings; the absence of these factors may enable clinical teams to identify unnecessarily restricted low-risk individuals. PMID:26401653
Veschi, Veronica; Liu, Zhihui; Voss, Ty C; Ozbun, Laurent; Gryder, Berkley; Yan, Chunhua; Hu, Ying; Ma, Anqi; Jin, Jian; Mazur, Sharlyn J; Lam, Norris; Souza, Barbara K; Giannini, Giuseppe; Hager, Gordon L; Arrowsmith, Cheryl H; Khan, Javed; Appella, Ettore; Thiele, Carol J
Given the paucity of druggable mutations in high-risk neuroblastoma (NB), we undertook chromatin-focused small interfering RNA and chemical screens to uncover epigenetic regulators critical for the differentiation block in high-risk NB. High-content Opera imaging identified 53 genes whose loss of expression led to a decrease in NB cell proliferation and 16 also induced differentiation. From these, the secondary chemical screen identified SETD8, the H4(K20me1) methyltransferase, as a druggable NB target. Functional studies revealed that SETD8 ablation rescued the pro-apoptotic and cell-cycle arrest functions of p53 by decreasing p53(K382me1), leading to activation of the p53 canonical pathway. In pre-clinical xenograft NB models, genetic or pharmacological (UNC0379) SETD8 inhibition conferred a significant survival advantage, providing evidence for SETD8 as a therapeutic target in NB. Published by Elsevier Inc.
Giuliani, Massimo; Cordiali-Fei, Paola; Castilletti, Concetta; Di Carlo, Aldo; Palamara, Guido; Boros, Stefano; Rezza, Giovanni
Background The occurrence of, and risk factors for, HHV-8 infection have yet to be definitively determined, particularly among heterosexual individuals with at-risk behavior for sexually transmitted infections (STI). The objective of this study was to estimate the incidence and determinants of HHV-8 infection among HIV-uninfected individuals repeatedly attending an urban STI clinic. Methods Sera from consecutive HIV-uninfected individuals repeatedly tested for HIV-1 antibodies were additionally tested for HHV-8 antibodies using an immunofluorescence assay. To identify determinants of HHV-8 infection, a nested case-control study and multivariate logistic regression analysis were performed. Results Sera from 456 HIV-uninfected individuals (224 multiple-partner heterosexuals and 232 men who have sex with men (MSM]) were identified for inclusion in the study. The HHV-8 seroprevalence at enrollment was 9.4% (21/224; 95% C.I.: 6.0–14.2%) among heterosexuals with multiple partners and 22.0% (51/232; 95% C.I.: 16.9–28.0%) among MSM. Among the 203 multiple-partner heterosexuals and 181 MSM who were initially HHV-8-negative, 17 (IR = 3.0/100 p-y, 95% C.I.: 1.9 – 4.8) and 21 (IR = 3.3/100 p-y, 95% C.I:.2.1 – 5.1) seroconversions occurred, respectively. HHV-8 seroconversion tended to be associated with a high number of sexual partners during the follow-up among MSM (> 10 partners: AOR = 3.32 95% CI:0.89–12.46) and among the multiple-partner heterosexuals (> 10 partner; AOR = 3.46, 95% CI:0.42–28.2). Moreover, among MSM, HHV-8 seroconversion tended to be associated with STI (AOR = 1.80 95%CI: 0.52–7.96). During the study period the HIV-1 incidence was lower than that of HHV-8 among both groups (0.89/100 p-y among MSM and 0.95/100 p-y among multiple-partner heterosexuals). Conclusion The large difference between the incidence of HHV-8 and the incidence of HIV-1 and other STIs may suggest that the circulation of HHV-8 is sustained by practices other than classical
Ho, New Fei; Holt, Daphne J; Cheung, Mike; Iglesias, Juan Eugenio; Goh, Alex; Wang, Mingyuan; Lim, Joseph Kw; de Souza, Joshua; Poh, Joann S; See, Yuen Mei; Adcock, Alison R; Wood, Stephen J; Chee, Michael Wl; Lee, Jimmy; Zhou, Juan
Most individuals identified as ultra-high-risk (UHR) for psychosis do not develop frank psychosis. They continue to exhibit subthreshold symptoms, or go on to fully remit. Prior work has shown that the volume of CA1, a subfield of the hippocampus, is selectively reduced in the early stages of schizophrenia. Here we aimed to determine whether patterns of volume change of CA1 are different in UHR individuals who do or do not achieve symptomatic remission. Structural MRI scans were acquired at baseline and at 1-2 follow-up time points (at 12-month intervals) from 147 UHR and healthy control subjects. An automated method (based on an ex vivo atlas of ultra-high-resolution hippocampal tissue) was used to delineate the hippocampal subfields. Over time, a greater decline in bilateral CA1 subfield volumes was found in the subgroup of UHR subjects whose subthreshold symptoms persisted (n=40) and also those who developed clinical psychosis (n=12), compared with UHR subjects who remitted (n=41) and healthy controls (n=54). No baseline differences in volumes of the overall hippocampus or its subfields were found among the groups. Moreover, the rate of volume decline of CA1, but not of other hippocampal subfields, in the non-remitters was associated with increasing symptom severity over time. Thus, these findings indicate that there is deterioration of CA1 volume in persistently symptomatic UHR individuals in proportion to symptomatic progression.Neuropsychopharmacology advance online publication, 1 February 2017; doi:10.1038/npp.2017.5.
Bai, Chuan; Zhou, Qian; Wei, Shengnan; Jiang, Xiaowei; Geng, Haiyang; Zhou, Yifang; Tang, Yanqing; Wang, Fei
Background Understanding morphologic changes in vulnerable and early disease state of schizophrenia (SZ) may provide further insight into the development of psychosis. Method Whole brain voxel-based morphometry was performed to identify gray matter (GM) regional differences in 60 individuals with SZ during their first psychotic episode (FE-SZ), 31 individuals at genetic high risk for SZ (GHR-SZ) individuals, and 71 healthy controls. Results Significant differences were found in several regions including the prefrontal cortex, parietal lobe, temporal lobe, hippocampus, occipital lobe, and cerebellum among the three groups (p<0.05, corrected). Compared to the HC group, the FE-SZ group had significantly decreased GM volumes in several regions including the cerebellum, hippocampus, fusiform gyrus, lingual gyrus, supramarginal gyrus, and superior, middle, and inferior temporal gyri and significantly increased GM volumes in the middle frontal gyrus and inferior operculum frontal gyrus (p<0.05). The GHR-SZ group had significant decreases in GM volumes in the supramaginal gyrus, precentral gyrus, and rolandic operculum and significant increases in GM volumes in the cerebellum, fusiform gyrus, middle frontal gyrus, inferior operculum frontal gyrus, and superior, middle, and inferior temporal gyri when compared to the HC group (p<0.05). Compared to the GHR-SZ group, the FE-SZ group had significant decreases in GM volumes in several regions including the cerebellum, fusiform gyrus, supramarginal gyrus, and superior, middle, and inferior temporal gyri (p<0.05). Conclusions The findings herein implicate the involvement of multisensory integration in SZ development and pathophysiology. Additionally, the patterns of observed differences suggest possible indicators of disease, vulnerability, and resiliency in SZ. PMID:27723806
Moradi, Ali; Soori, Hamid; Kavousi, Amir; Eshghabadi, Farshid; Jamshidi, Ensiyeh; Zeini, Salahdien
Background: More than 20% of deaths from traffic crashes are related to pedestrians. This figure in Tehran, the capital of Iran, reaches to 40%. This study aimed to determine the high-risk areas and spatially analyze the traffic crashes, causing death to pedestrians in Tehran. Methods: Mapping was used to display the distribution of the crashes. Determining the distribution pattern of crashes and the hot spots/ low-risk areas were done, using Moran's I index and Getis-Ord G, respectively. Results: A total of 198 crashes were studied; 92 of which, (46.4%) occurred in 2013 to 2014 and other 106 cases (63.6%) occurred in 2014 to 2015. The highest and the lowest frequency of crashes was related to January (26 cases) and June (10 cases), respectively. One hundred fifty- eight cases (79.8%) of crashes occurred in Tehran highways. Moran's index showed that the studied traffic crashes had a cluster distribution (p<0.001). Getis- Ord General G index indicated that the distribution of hot and cold spots of the studied crashes was statistically significant (p<0.001). Conclusion: The majority of traffic crashes causing death to pedestrians occurred in highways located in the main entrances and exits of Tehran. Given the important role of environmental factors in the occurrence of traffic crashes related to pedestrians, identification of these factors requires more studies with casual inferences.
Moradi, Ali; Soori, Hamid; Kavousi, Amir; Eshghabadi, Farshid; Jamshidi, Ensiyeh; Zeini, Salahdien
Background: More than 20% of deaths from traffic crashes are related to pedestrians. This figure in Tehran, the capital of Iran, reaches to 40%. This study aimed to determine the high-risk areas and spatially analyze the traffic crashes, causing death to pedestrians in Tehran. Methods: Mapping was used to display the distribution of the crashes. Determining the distribution pattern of crashes and the hot spots/ low-risk areas were done, using Moran’s I index and Getis-Ord G, respectively. Results: A total of 198 crashes were studied; 92 of which, (46.4%) occurred in 2013 to 2014 and other 106 cases (63.6%) occurred in 2014 to 2015. The highest and the lowest frequency of crashes was related to January (26 cases) and June (10 cases), respectively. One hundred fifty- eight cases (79.8%) of crashes occurred in Tehran highways. Moran’s index showed that the studied traffic crashes had a cluster distribution (p<0.001). Getis- Ord General G index indicated that the distribution of hot and cold spots of the studied crashes was statistically significant (p<0.001). Conclusion: The majority of traffic crashes causing death to pedestrians occurred in highways located in the main entrances and exits of Tehran. Given the important role of environmental factors in the occurrence of traffic crashes related to pedestrians, identification of these factors requires more studies with casual inferences. PMID:28210615
Weitlauf, Amy S; Vehorn, Alison C; Stone, Wendy L; Fein, Deborah; Warren, Zachary E
Given the high autism spectrum disorder (ASD) recurrence risk in younger siblings, it is important to identify early ASD markers within this high-risk population. Although there is increasing evidence that the Modified Checklist for Autism in Toddlers-Revised, with Follow-Up Interview can identify many low-risk children during the second year of life, there has yet to be a study of how the M-CHAT-R/F functions in a high-risk sibling population at very young ages. As part of a larger population-based study, the authors screened 74 infant siblings with the Modified Checklist for Autism in Toddlers-Revised, with Follow-Up Interview at 18 months and assessed diagnoses between the ages of 18 and 43 months. The M-CHAT-R/F had the highest positive predictive value for identifying children at risk of any developmental concern (i.e., ASD, language delay). Overall, 33% of siblings who presented for follow-up evaluations received ASD diagnoses with an additional 22% showing other developmental concerns. Failing the M-CHAT-R/F at 18 months of age raises significant concern that a child will show some degree of developmental difference or delay over time. These findings highlight the need for close developmental monitoring of this high-risk sample.
Payaprom, Yupares; Bennett, Paul; Alabaster, Erica; Tantipong, Hutsaya
Influenza vaccination rates remain suboptimal in many countries, including Thailand. This study compared the effect of a theory-based educational leaflet, based on the Health Action Process Approach (HAPA), and action planning intervention with a standard government information leaflet designed to increase influenza vaccination uptake among high-risk Thai adults. A controlled before and after trial was conducted. Participants in the intervention (n = 99) received a leaflet based on the HAPA and asking them to form an action plan identifying where, when, and how they would seek vaccination. Those in the comparison condition (n = 102) received a standard government information leaflet. There are 2 sets of outcome measures: (a) process measures of HAPA related variables taken at T1 and T2, and (b) vaccination rates during the subsequent 2 months. The HAPA intervention resulted in greater changes on measures of risk perception, outcome expectancies, self-efficacy, and intention than the comparison condition. Stronger intentions to obtain vaccination were explained by changes in outcome expectancies, perceived self-efficacy for arranging time and transportation, and planning. No significant difference in vaccination rates was observed between two groups. Influenza vaccination was directly predicted by self-efficacy and intention. Results demonstrate that a HAPA-based leaflet may be a useful tool to enhance individual's vaccination intention, but larger trials are required to confirm these findings.
Garrido, Pilar; Sánchez, Marcelo; Belda Sanchis, José; Moreno Mata, Nicolás; Artal, Ángel; Gayete, Ángel; Matilla González, José María; Galbis Caravajal, José Marcelo; Isla, Dolores; Paz-Ares, Luis; Seijo, Luis M
Lung cancer (LC) is a major public health issue. Despite recent advances in treatment, primary prevention and early diagnosis are key to reducing the incidence and mortality of this disease. A recent clinical trial demonstrated the efficacy of selective screening by low-dose computed tomography (LDCT) in reducing the risk of both lung cancer mortality and all-cause mortality in high-risk individuals. This article contains the reflections of an expert group on the use of LDCT for early diagnosis of LC in high-risk individuals, and how to evaluate its implementation in Spain. The expert group was set up by the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR), the Spanish Society of Thoracic Surgery (SECT), the Spanish Society of Radiology (SERAM) and the Spanish Society of Medical Oncology (SEOM). Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.
Reid, Brian J.; Levine, Douglas S.; Longton, Gary; Blount, Patricia L.; Rabinovitch, Peter S.
OBJECTIVE Barrett’s esophagus develops in 5–20% of patients with gastroesophageal reflux disease and predisposes to esophageal adenocarcinoma. The value of endoscopic biopsy surveillance is questioned because most patients do not develop cancer. Furthermore, observer variation in histological diagnosis makes validation of surveillance guidelines difficult because varying histological interpretations may lead to different estimated rates of progression. Thus, objective biomarkers need to be validated for use with histology to stratify patients according to their risk for progression to cancer. METHODS We prospectively evaluated patients using a systematic endoscopic biopsy protocol with baseline histological and flow cytometric abnormalities as predictors and cancer as the outcome. RESULTS Among patients with negative, indefinite, or low-grade dysplasia, those with neither aneuploidy nor increased 4N fractions had a 0% 5-yr cumulative cancer incidence compared with 28% for those with either aneuploidy or increased 4N. Patients with baseline increased 4N, aneuploidy, and high-grade dysplasia had 5-yr cancer incidences of 56%, 43%, and 59%, respectively. Aneuploidy, increased 4N, or HGD were detected at baseline in all 35 patients who developed cancer within 5 yr. CONCLUSIONS A systematic baseline endoscopic biopsy protocol using histology and flow cytometry identifies subsets of patients with Barrett’s esophagus at low and high risk for progression to cancer. Patients whose baseline biopsies are negative, indefinite, or low-grade displasia without increased 4N or aneuploidy may have surveillance deferred for up to 5 yr. Patients with cytometric abnormalities merit more frequent surveillance, and management of high-grade displasia can be individualized. PMID:10925966
Sekine, Yasuo; Yanagibori, Ryoko; Suzuki, Kiminori; Sugiyama, Sonomi; Yamaji, Haruko; Ishibashi, Michiko; Fujisawa, Takehiko
Patients with chronic obstructive pulmonary disease (COPD) are at risk for lung cancer; the diseases have common etiologies, including cigarette smoking. We aimed to clarify the effectiveness of COPD detection using a regional mass-screening program for lung cancer. A total of 7,067 residents of Togane, Chiba, Japan received lung cancer screening between May and July, 2011. We defined four groups of possible COPD candidates: group A (n=358), positive smoking history, positive chronic respiratory symptoms; group B (n=766), positive smoking history, positive lifestyle-related disease; group C (n=75), passive smoking history, positive chronic respiratory symptoms; and group D (n=301), passive smoking history, positive lifestyle-related disease. Candidates underwent on-site pulmonary function testing (PFT). The criteria for COPD candidates were fulfilled in 1,686 of 7,067 individuals (23.9%); 1,500 participants underwent PFT (89%), and 171 (11.4%) were diagnosed with COPD. The overall COPD detection rate was 2.4%. The frequency of COPD was significantly higher in groups A and B than in groups C and D (P=0.048); however, the distribution of COPD grades was similar among the groups (P=0.372). Multiple logistic regression analysis identified male sex, age 60 years or greater, and positive smoking history as risk factors for COPD. COPD screening using a community-based lung cancer-screening program may be effective for disease detection. Individuals who are 60 years of age or older with a positive smoking history should undergo PFT to detect COPD.
Koblin, Beryl A.; Metch, Barbara; Novak, Richard M.; Morgan, Cecilia; Lucy, Debbie; Dunbar, Debora; Graham, Parrie; Swann, Edith; Madenwald, Tamra; Escamilia, Gina; Frank, Ian
Background Identifying cohorts of US women with HIV infection rates sufficient for inclusion in vaccine efficacy trials has been challenging. Using geography and sexual network characteristics to inform recruitment strategies, HVTN 906 determined the feasibility of recruiting a cohort of women at high risk for HIV acquisition. Methods HIV uninfected women who reported unprotected sex in the prior six months, resided or engaged in risk behavior in local geographical high-risk pockets and/or had a male partner who had been incarcerated, injected drugs or had concurrent partners were eligible. Behavioral risk assessment, HIV counseling and testing and pregnancy testing were done at baseline, 6, 12 and 18 months. Results Among 799 women, 71% were from local high-risk pockets and had high-risk male partners. Median age was 37 years; 79% were Black; 15% Latina. Over half (55%) reported a new partner in the prior six months, 57% reported a male partner who had concurrent female sexual partners and 37% reported a male partner who had been incarcerated. Retention at 18 months was 79.5%. Annual pregnancy incidence was 12%. Annual HIV incidence was 0.31% (95% CI: 0.06, 0.91). Risk behaviors decreased between screening and six months with smaller changes thereafter. Discussion This cohort of women recruited using new strategies based on geography and sexual network characteristics did not have an HIV incidence high enough for HIV vaccine efficacy trials, despite high baseline levels of risk and a high pregnancy rate. New strategies to identify cohorts of US women for efficacy trials are needed. PMID:23446497
Fisher, Brian T; Ross, Rachael K; Roilides, Emmanuel; Palazzi, Debra L; Abzug, Mark J; Hoffman, Jill A; Berman, David M; Prasad, Priya A; Localio, A Russell; Steinbach, William J; Vogiatzi, Lambrini; Dutta, Ankhi; Zaoutis, Theoklis E
We attempted to validate a previously derived clinical prediction rule for candidemia in the pediatric intensive care unit. This multicenter case control study did not identify significant association of candidemia with most of the previously identified predictors. Additional study in larger cohorts with other predictor variables is needed. © The Author 2015. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: firstname.lastname@example.org.
Wong, Robert J; Campbell, Brendan; Liu, Benny; Baden, Rachel; Bhuket, Taft
Sub-optimal screening for chronic hepatitis C virus (HCV) and chronic hepatitis B virus (HBV) among high risk groups delays diagnosis and treatment. We aimed to evaluate overall rates of HCV and HBV screening and patient knowledge of their testing result. Adults age ≥18 years undergoing elective outpatient endoscopy at a large, urban safety-net hospital from July 2015 to July 2016 were prospectively evaluated to determine rates of HCV and HBV testing, the results of those completed tests, and patient knowledge of test results among high risk individuals (as determined by U.S. Preventative Services Task Force). Among 1125 patients (52.3% male, 70.4% foreign-born), 66.5% were high risk for chronic HCV; only 30.9% received prior testing. 14.7% had positive chronic HCV infection. Patients born in the 1945-1965 cohort were more likely to have received prior HCV testing compared to those born outside of this cohort (32.7 vs. 16.9%, p = 0.01). Among patients who received HCV screening, 29.3% were aware of test results. Overall, 61.6% were high risk for chronic HBV; only 25.1% received prior testing. 4.1% were positive for chronic HBV. Compared to Caucasians, Asians (19.0 vs. 44.4%, p < 0.001) and Hispanics (20.0 vs. 44.4%, p < 0.001) were less likely to have previous HBV testing. Among patients who received prior HBV screening, 18.4% were aware of test results. Less than one-third of high risk patients received HCV and HBV screening among an ethnically diverse safety-net population. Equally low rates of patient knowledge of testing results were observed.
Heilbron, Nicole; Goldston, David; Walrath, Christine; Rodi, Michael; McKeon, Richard
Several agencies have emphasized the importance of establishing clear protocols or procedures to address the needs of youths who are identified as suicidal through suicide prevention programs or in emergency department settings. What constitutes optimal guidelines for developing and implementing such protocols, however, is unclear. At the request…
Cuadros, Diego F; Awad, Susanne F; Abu-Raddad, Laith J
The geographical structure of an epidemic is ultimately a consequence of the drivers of the epidemic and the population susceptible to the infection. The 'know your epidemic' concept recognizes this geographical feature as a key element for identifying populations at higher risk of HIV infection where prevention interventions should be targeted. In an effort to clarify specific drivers of HIV transmission and identify priority populations for HIV prevention interventions, we conducted a comprehensive mapping of the spatial distribution of HIV infection across sub-Saharan Africa (SSA). The main source of data for our study was the Demographic and Health Survey conducted in 20 countries from SSA. We identified and compared spatial clusters with high and low numbers of HIV infections in each country using Kulldorff spatial scan test. The test locates areas with higher and lower numbers of HIV infections than expected under spatial randomness. For each identified cluster, a likelihood ratio test was computed. A P-value was determined through Monte Carlo simulations to evaluate the statistical significance of each cluster. Our results suggest stark geographic variations in HIV transmission patterns within and across countries of SSA. About 14% of the population in SSA is located in areas of intense HIV epidemics. Meanwhile, another 16% of the population is located in areas of low HIV prevalence, where some behavioral or biological protective factors appear to have slowed HIV transmission. Our study provides direct evidence for strong geographic clustering of HIV infection across SSA. This striking pattern of heterogeneity at the micro-geographical scale might reflect the fact that most HIV epidemics in the general population in SSA are not far from their epidemic threshold. Our findings identify priority geographic areas for HIV programming, and support the need for spatially targeted interventions in order to maximize the impact on the epidemic in SSA.
Breast Cancer Predisposition PRINCIPAL INVESTIGATOR: Mary-Claire King, PhD CONTRACTING ORGANIZATION: University of Washington Seattle, WA, 98195...Families to Identify New Mutational Mechanisms of Breast Cancer Predisposition 5b. GRANT NUMBER W81XWH-13-1-0336 5c. PROGRAM ELEMENT NUMBER 6...regulatory regions. Our hypothesis for this proposal is that much of the substantial remaining familial risk of breast cancer is due to a large number
Gautam, R; Srinath, I; Clavijo, A; Szonyi, B; Bani-Yaghoub, M; Park, S; Ivanek, R
Coccidioidomycosis or Valley Fever (VF) is an emerging soil-borne fungal zoonosis affecting humans and animals. Most non-human cases of VF are found in dogs, which we hypothesize may serve as sentinels for estimating the human exposure risk. The objective of this study is to use the spatial and temporal distribution and clusters of dogs seropositive for VF to define the geographic area in Texas where VF is endemic, and thus presents a higher risk of exposure to humans. The included specimens were seropositive dogs tested at a major diagnostic laboratory between 1999 and 2009. Data were aggregated by zip code and smoothed by empirical Bayesian estimation to develop an isopleth map of VF seropositive rates using kriging. Clusters of seropositive dogs were identified using the spatial scan test. Both the isopleth map and the scan test identified an area with a high rate of VF-seropositive dogs in the western and southwestern parts of Texas (relative risk = 31). This location overlapped an area that was previously identified as a potential endemic region based on human surveys. Together, these data suggest that dogs may serve as sentinels for estimating the risk of human exposure to VF. © 2012 Blackwell Verlag GmbH.
Jenkins, P; Scaife, J; Freeman, S
We have previously developed a predictive model that identifies patients at increased risk of febrile neutropaenia (FN) following chemotherapy, based on pretreatment haematological indices. This study was designed to validate our earlier findings in a separate cohort of patients undergoing more myelosuppressive chemotherapy supported by growth factors. We conducted a retrospective analysis of 263 patients who had been treated with adjuvant docetaxel, adriamycin and cyclophosphamide (TAC) chemotherapy for breast cancer. All patients received prophylactic pegfilgrastim and the majority also received prophylactic antibiotics. Thirty-one patients (12%) developed FN. Using our previous model, patients in the highest risk group (pretreatment absolute neutrophil count≤3.1 10(9)/l and absolute lymphocyte count≤1.5 10(9)/l) comprised 8% of the total population and had a 33% risk of developing FN. Compared with the rest of the cohort, this group had a 3.4-fold increased risk of developing FN (P=0.001) and a 5.2-fold increased risk of cycle 1 FN (P<0.001). A simple model based on pretreatment differential white blood cell count can be applied to pegfilgrastim-supported patients to identify those who are at higher risk of FN.
Reisner, Sari L; Mimiaga, Matthew J; Case, Patricia; Johnson, Carey V; Safren, Steven A; Mayer, Kenneth H
Studies have found that between 14% and 46% of US men who have sex with men (MSM) consistently report "barebacking" behavior (i.e., intentional unprotected anal intercourse) with other men. This is of public health significance because MSM continue to constitute more than 50% of new HIV infections in the USA. Men who self-identify as barebackers may represent a different and unique subset of MSM with distinct HIV prevention needs. In 2007, 227 HIV seronegative MSM recruited through modified respondent-driven sampling completed an interviewer-administered survey which assessed barebacker identity (i.e., personally identifying with the barebacker scene), demographics, sexual risk behaviors, psychosocial variables, and drug/alcohol use. Bivariate and multivariable logistic regression procedures were used to examine predictors of barebacker identity in relation to HIV risk behavior. Overall, 31% of participants identified as a barebacker. In bivariate analyses, lower education (OR = 1.76; 95% CI = 0.99-3.13; p < 0.05), a current drinking problem (OR = 2.34, 95% CI = 1.29-4.23; p < 0.01), higher levels of HIV treatment optimism (OR = 1.06; 95% CI = 1.01-1.12; p < 0.05), meeting sexual partners at private sex parties (OR = 2.47; 95% CI = 1.28-4.74; p < 0.01) or at bars/cubs (OR = 1.97; 95% CI = 1.10-3.52; p < 0.05), and engaging in serodiscordant unprotected insertive anal sex (OR = 3.42; 95% CI = 1.27-9.21; p < 0.01) significantly predicted barebacker identification compared to those with no barebacker identification. In a multivariable model, barebackers were more likely to screen in for alcohol abuse (adjusted OR = 2.16; 95% CI = 1.09-4.27; p < 0.05) and engage in serodiscordant unprotected insertive anal sex (adjusted OR = 3.17; 95% CI = 1.09-9.20; p < 0.05) compared to their non-barebacker counterparts. No significant differences were found in serodiscordant unprotected receptive anal sex between barebackers and non-barebackers. These findings suggest that
Smesny, Stefan; Milleit, Berko; Schaefer, Miriam R; Hesse, Jana; Schlögelhofer, Monika; Langbein, Kerstin; Hipler, Uta-Christina; Berger, Maximus; Cotter, David R; Sauer, Heinrich; McGorry, Patrick D; Amminger, G Paul
Alterations of immune function have been reported in ultra-high risk (UHR) for psychosis patients causing expectations in terms of predictive meaningfulness and benefits of anti-inflammatory agents. According to a RCT in UHR-patients supplementation of omega-3 polyunsaturated fatty acids (PUFA) was effective in reducing transition to psychosis risk and to improve symptomatology. Based on preclinical findings, we now investigated state marker properties of and the influence of PUFA on immune markers in a RCT (clinical trials.gov Identifier: NCT00396643). In a longitudinal design we measured plasma levels of the pro-inflammatory interleukin 6 (IL-6), the soluble alpha (Tac) subunit of the interleukin 2 receptor (sIL-2r), and the circulating soluble form of the intercellular adhesion molecule one (sICAM-1), in 79 help-seeking UHR individuals (13-25years of age). Using linear mixed model (LMM) analysis, we investigated the effects of 12weeks supplementation of either 1.2g/d PUFA (n=38) or Placebo (n=41). At baseline, inflammatory markers were not altered in patients who later suffered transition to psychosis within one year (n=12; 11 PUFA-group, 1 PL-group). IL-6 was weakly inverse associated with omega-6 PUFA, and highly increased in nicotine users. In univariate tests of the LMM omega-3 PUFA caused a significant increase of sICAM-1 (p=0.022). PUFA did not significantly influence IL-6 or sIL-2r. The enhancement of sICAM-1 in the PUFA condition is suggestive for supportive effects on vascular immune response and immediate Th1 helper cell mediated immune answer, which was found disturbed in manifest schizophrenia, e.g. by facilitating the leukocyte adhesion and migration across the endothelium.
Puig, Susana; Potrony, Miriam; Cuellar, Francisco; Puig-Butille, Joan Anton; Carrera, Cristina; Aguilera, Paula; Nagore, Eduardo; Garcia-Casado, Zaida; Requena, Celia; Kumar, Rajiv; Landman, Gilles; Costa Soares de Sá, Bianca; Gargantini Rezze, Gisele; Facure, Luciana; de Avila, Alexandre Leon Ribeiro; Achatz, Maria Isabel; Carraro, Dirce Maria; Duprat Neto, João Pedreira; Grazziotin, Thais C; Bonamigo, Renan R; Rey, Maria Carolina W; Balestrini, Claudia; Morales, Enrique; Molgo, Montserrat; Bakos, Renato Marchiori; Ashton-Prolla, Patricia; Giugliani, Roberto; Larre Borges, Alejandra; Barquet, Virginia; Pérez, Javiera; Martínez, Miguel; Cabo, Horacio; Cohen Sabban, Emilia; Latorre, Clara; Carlos-Ortega, Blanca; Salas-Alanis, Julio C; Gonzalez, Roger; Olazaran, Zulema; Malvehy, Josep; Badenas, Celia
CDKN2A is the main high-risk melanoma-susceptibility gene, but it has been poorly assessed in Latin America. We sought to analyze CDKN2A and MC1R in patients from Latin America with familial and sporadic multiple primary melanoma (SMP) and compare the data with those for patients from Spain to establish bases for melanoma genetic counseling in Latin America. CDKN2A and MC1R were sequenced in 186 Latin American patients from Argentina, Brazil, Chile, Mexico, and Uruguay, and in 904 Spanish patients. Clinical and phenotypic data were obtained. Overall, 24 and 14% of melanoma-prone families in Latin America and Spain, respectively, had mutations in CDKN2A. Latin American families had CDKN2A mutations more frequently (P = 0.014) than Spanish ones. Of patients with SMP, 10% of those from Latin America and 8.5% of those from Spain had mutations in CDKN2A (P = 0.623). The most recurrent CDKN2A mutations were c.-34G>T and p.G101W. Latin American patients had fairer hair (P = 0.016) and skin (P < 0.001) and a higher prevalence of MC1R variants (P = 0.003) compared with Spanish patients. The inclusion criteria for genetic counseling of melanoma in Latin America may be the same criteria used in Spain, as suggested in areas with low to medium incidence, SMP with at least two melanomas, or families with at least two cases among first- or second-degree relatives.Genet Med 18 7, 727-736.
Puig, Susana; Potrony, Miriam; Cuellar, Francisco; Puig-Butille, Joan Anton; Carrera, Cristina; Aguilera, Paula; Nagore, Eduardo; Garcia-Casado, Zaida; Requena, Celia; Kumar, Rajiv; Landman, Gilles; Costa Soares de Sá, Bianca; Gargantini Rezze, Gisele; Facure, Luciana; de Avila, Alexandre Leon Ribeiro; Achatz, Maria Isabel; Carraro, Dirce Maria; Duprat Neto, João Pedreira; Grazziotin, Thais C.; Bonamigo, Renan R.; Rey, Maria Carolina W.; Balestrini, Claudia; Morales, Enrique; Molgo, Montserrat; Bakos, Renato Marchiori; Ashton-Prolla, Patricia; Giugliani, Roberto; Larre Borges, Alejandra; Barquet, Virginia; Pérez, Javiera; Martínez, Miguel; Cabo, Horacio; Cohen Sabban, Emilia; Latorre, Clara; Carlos-Ortega, Blanca; Salas-Alanis, Julio C; Gonzalez, Roger; Olazaran, Zulema; Malvehy, Josep; Badenas, Celia
Purpose: CDKN2A is the main high-risk melanoma-susceptibility gene, but it has been poorly assessed in Latin America. We sought to analyze CDKN2A and MC1R in patients from Latin America with familial and sporadic multiple primary melanoma (SMP) and compare the data with those for patients from Spain to establish bases for melanoma genetic counseling in Latin America. Genet Med 18 7, 727–736. Methods: CDKN2A and MC1R were sequenced in 186 Latin American patients from Argentina, Brazil, Chile, Mexico, and Uruguay, and in 904 Spanish patients. Clinical and phenotypic data were obtained. Genet Med 18 7, 727–736. Results: Overall, 24 and 14% of melanoma-prone families in Latin America and Spain, respectively, had mutations in CDKN2A. Latin American families had CDKN2A mutations more frequently (P = 0.014) than Spanish ones. Of patients with SMP, 10% of those from Latin America and 8.5% of those from Spain had mutations in CDKN2A (P = 0.623). The most recurrent CDKN2A mutations were c.-34G>T and p.G101W. Latin American patients had fairer hair (P = 0.016) and skin (P < 0.001) and a higher prevalence of MC1R variants (P = 0.003) compared with Spanish patients. Genet Med 18 7, 727–736. Conclusion: The inclusion criteria for genetic counseling of melanoma in Latin America may be the same criteria used in Spain, as suggested in areas with low to medium incidence, SMP with at least two melanomas, or families with at least two cases among first- or second-degree relatives. Genet Med 18 7, 727–736. PMID:26681309
Kraan, Tamar; Velthorst, Eva; Smit, Filip; de Haan, Lieuwe; van der Gaag, Mark
Childhood trauma and recent life-events have been related to psychotic disorders. The aim of the present study was to examine whether childhood trauma and recent life-events are significantly more prevalent in patients at Ultra High Risk (UHR) of developing a psychotic disorder compared to healthy controls. A search of PsychInfo and Embase was conducted, relevant papers were reviewed, and three random-effects meta-analyses were performed. One meta-analysis assessed the prevalence rate of childhood trauma in UHR subjects and two meta-analyses were conducted to compare UHR subjects and healthy control subjects on the experience of childhood trauma and recent life-events. We found 12 studies on the prevalence of (childhood) trauma in UHR populations and 4 studies on recent life-events in UHR populations. We performed a meta-analysis on 6 studies (of which trauma prevalence rates were available) on childhood trauma in UHR populations, yielding a mean prevalence rate of 86.8% (95% CI 77%-93%). Childhood trauma was significantly more prevalent in UHR subjects compared to healthy control groups (Random effects Hedges' g=1.09; Z=4.60, p<.001). In contrast to our hypothesis, life-event rates were significantly lower in UHR subjects compared to healthy controls (Random effects Hedges' g=-0.53; Z=-2.36, p<.02). Our meta-analytic results illustrate that childhood trauma is highly prevalent among UHR subjects and that childhood trauma is related to UHR status. These results are in line with studies on childhood trauma in psychotic populations. In contrast to studies on recent life-events in psychotic populations, our results show that recent life-events are not associated with UHR status. Copyright © 2014 Elsevier B.V. All rights reserved.
Identifying Aboriginal-specific AUDIT-C and AUDIT-3 cutoff scores for at-risk, high-risk, and likely dependent drinkers using measures of agreement with the 10-item Alcohol Use Disorders Identification Test.
Calabria, Bianca; Clifford, Anton; Shakeshaft, Anthony P; Conigrave, Katherine M; Simpson, Lynette; Bliss, Donna; Allan, Julaine
The Alcohol Use Disorders Identification Test (AUDIT) is a 10-item alcohol screener that has been recommended for use in Aboriginal primary health care settings. The time it takes respondents to complete AUDIT, however, has proven to be a barrier to its routine delivery. Two shorter versions, AUDIT-C and AUDIT-3, have been used as screening instruments in primary health care. This paper aims to identify the AUDIT-C and AUDIT-3 cutoff scores that most closely identify individuals classified as being at-risk drinkers, high-risk drinkers, or likely alcohol dependent by the 10-item AUDIT. Two cross-sectional surveys were conducted from June 2009 to May 2010 and from July 2010 to June 2011. Aboriginal Australian participants (N = 156) were recruited through an Aboriginal Community Controlled Health Service, and a community-based drug and alcohol treatment agency in rural New South Wales (NSW), and through community-based Aboriginal groups in Sydney NSW. Sensitivity, specificity, and positive and negative predictive values of each score on the AUDIT-C and AUDIT-3 were calculated, relative to cutoff scores on the 10-item AUDIT for at-risk, high-risk, and likely dependent drinkers. Receiver operating characteristic (ROC) curve analyses were conducted to measure the detection characteristics of AUDIT-C and AUDIT-3 for the three categories of risk. The areas under the receiver operating characteristic (AUROC) curves were high for drinkers classified as being at-risk, high-risk, and likely dependent. Recommended cutoff scores for Aboriginal Australians are as follows: at-risk drinkers AUDIT-C ≥ 5, AUDIT-3 ≥ 1; high-risk drinkers AUDIT-C ≥ 6, AUDIT-3 ≥ 2; and likely dependent drinkers AUDIT-C ≥ 9, AUDIT-3 ≥ 3. Adequate sensitivity and specificity were achieved for recommended cutoff scores. AUROC curves were above 0.90.
Wang, Tianjiao; Feldman, Andrew L; Wada, David A; Lu, Ye; Polk, Avery; Briski, Robert; Ristow, Kay; Habermann, Thomas M; Thomas, Dafydd; Ziesmer, Steven C; Wellik, Linda E; Lanigan, Thomas M; Witzig, Thomas E; Pittelkow, Mark R; Bailey, Nathanael G; Hristov, Alexandra C; Lim, Megan S; Ansell, Stephen M; Wilcox, Ryan A
The cell of origin and the tumor microenvironment's role remain elusive for the most common peripheral T-cell lymphomas (PTCLs). As macrophages promote the growth and survival of malignant T cells and are abundant constituents of the tumor microenvironment, their functional polarization was examined in T-cell lymphoproliferative disorders. Cytokines that are abundant within the tumor microenvironment, particularly interleukin (IL)-10, were observed to promote alternative macrophage polarization. Macrophage polarization was signal transducer and activator of transcription 3 dependent and was impaired by the Janus kinase inhibitor ruxolitinib. In conventional T cells, the production of T helper (Th)2-associated cytokines and IL-10, both of which promote alternative macrophage polarization, is regulated by the T-cell transcription factor GATA-binding protein 3 (GATA-3). Therefore, its role in the T-cell lymphomas was examined. GATA-3 expression was observed in 45% of PTCLs, not otherwise specified (PTCL, NOS) and was associated with distinct molecular features, including the production of Th2-associated cytokines. In addition, GATA-3 expression identified a subset of PTCL, NOS with distinct clinical features, including inferior progression-free and overall survival. Collectively, these data suggest that further understanding the cell of origin and lymphocyte ontogeny among the T-cell lymphomas may improve our understanding of the tumor microenvironment's pathogenic role in these aggressive lymphomas.
Skowron, K. B.; Pitroda, S. P.; Namm, J. P.; Balogun, O.; Beckett, M. A.; Zenner, M. L.; Fayanju, O.; Huang, X.; Fernandez, C.; Zheng, W.; Qiao, G.; Chin, R.; Kron, S. J.; Khodarev, N. N.; Posner, M. C.; Steinberg, G. D.; Weichselbaum, R. R.
Strategies to identify tumors at highest risk for treatment failure are currently under investigation for patients with bladder cancer. We demonstrate that flow cytometric detection of poorly differentiated basal tumor cells (BTCs), as defined by the co-expression of CD90, CD44 and CD49f, directly from patients with early stage tumors (T1-T2 and N0) and patient-derived xenograft (PDX) engraftment in locally advanced tumors (T3-T4 or N+) predict poor prognosis in patients with bladder cancer. Comparative transcriptomic analysis of bladder tumor cells isolated from PDXs indicates unique patterns of gene expression during bladder tumor cell differentiation. We found cell division cycle 25C (CDC25C) overexpression in poorly differentiated BTCs and determined that CDC25C expression predicts adverse survival independent of standard clinical and pathologic features in bladder cancer patients. Taken together, our findings support the utility of BTCs and bladder cancer PDX models in the discovery of novel molecular targets and predictive biomarkers for personalizing oncology care for patients. PMID:27775025
Individual heterogeneity in detection probabilities is a far more serious problem for capture-recapture modeling than has previously been recognized. In this note, I illustrate that population size is not an identifiable parameter under the general closed population mark-recapture model Mh. The problem of identifiability is obvious if the population includes individuals with pi = 0, but persists even when it is assumed that individual detection probabilities are bounded away from zero. Identifiability may be attained within parametric families of distributions for pi, but not among parametric families of distributions. Consequently, in the presence of individual heterogeneity in detection probability, capture-recapture analysis is strongly model dependent.
Holmberg, K; Sundelin, C; Hjern, A
Recent studies have demonstrated the beneficial long-term effects of an indicated parent support programme for acting out behaviour in pre-school children with attention-deficit/hyperactivity disorder (ADHD) traits. In this study we wanted to assess different thresholds for screening with the Conners scale for hyperactive-inattentive behaviours in first grade for ADHD in grade four. The study population consisted of 422 first graders (6- to 7-year-olds) in one municipality in Stockholm County who were screened with Conners 10-item scale and followed up by ADHD assessment in grade four. Sensitivity, specificity, likelihood ratios, and positive predictive value (PPV) of the screening by parents and teachers in first grade for being diagnosed with ADHD in fourth grade were calculated. The prevalence of pervasive and situational ADHD was 5.7% and 5.9% respectively. A score ≥ 10 on the Conners scale in first grade in teachers' reports identified 63% [95% confidence interval (CI): 43-79] of children diagnosed with pervasive ADHD in grade four (P < 0.001) with a PPV of 29% and a positive likelihood ratio (LR+) of 6.72. Parental reports of a score ≥ 10 yielded a lower sensitivity (29%; 95% CI: 15-49), PPV of 20% and LR+ of 4.24 for pervasive ADHD. The best predictor was a combination of parent and teacher scores ≥ 10 with a PPV of 50% and LR+ of 16.63. Associations with situational ADHD were weak with LR+ of 1.81 and 2.49, respectively, for teachers' and parental scores ≥ 10. This study indicates a strong association between a teacher's report of a score ≥ 10 on the Conners scale in first grade and pervasive ADHD in grade four, while parental reports were less predictive. © 2012 Blackwell Publishing Ltd.
Leedahl, David D; Frazee, Erin N; Schramm, Garrett E; Dierkhising, Ross A; Bergstralh, Eric J; Chawla, Lakhmir S; Kashani, Kianoush B
To promote early detection of AKI, recently proposed pretest probability models combine sub-Kidney Disease Improving Global Outcomes (KDIGO) AKI criteria with baseline AKI risk. The primary objective of this study was to determine sub-KDIGO thresholds that identify patients with septic shock at highest risk for AKI. This was a retrospective analysis of 390 adult patients admitted to the medical intensive care unit (ICU) of a tertiary, academic medical center with septic shock between January 2008 and December 2010. Hourly urine output was collected from the time of septic shock recognition (hour 0) to hour 96, urine catheter removal, or ICU discharge (whichever occurred first). All available serum creatinine (SCr) measurements were collected until hour 96. The AKI pretest probability model was assessed during the first 12 hours of resuscitation and included the initial episode of oliguria, increase from baseline to peak SCr level, and Acute Physiology and Chronic Health Evaluation (APACHE) III score in a multivariable receiver-operator characteristic (ROC) analysis. The primary outcome was the incidence of stage II or III (stage II+) AKI defined by KDIGO criteria. Secondary outcomes included the need for RRT and 28-day mortality. Ninety-eight (25%) patients developed stage II+ AKI after septic shock recognition. APACHE III score and increase in SCr level in the first 12 hours were not statistically associated with stage II+ AKI in multivariable ROC analysis. Consecutive oliguria for 3 hours had fair predictive ability for achieving stage II+ AKI criteria (area under ROC curve, 0.73; 95% confidence interval [95% CI], 0.68 to 0.78), and oliguria for 5 hours demonstrated optimal accuracy (82%; 95% CI, 79% to 86%). Three to 5 hours of consecutive oliguria in patients with septic shock may provide a valuable measure of AKI risk. Further validation to support this finding is needed. Copyright © 2014 by the American Society of Nephrology.
Sweeting, Arianne N; Ross, Glynis P; Hyett, Jon; Molyneaux, Lynda; Tan, Kris; Constantino, Maria; Harding, Anna Jane; Wong, Jencia
The increasing prevalence of gestational diabetes mellitus (GDM) necessitates risk stratification directing limited antenatal resources to those at greatest risk. Recent evidence demonstrates that an early pregnancy glycated hemoglobin (HbA1c ≥5.9% (41 mmol/mol) predicts adverse pregnancy outcomes. To determine the optimal HbA1c threshold for adverse pregnancy outcomes in GDM in a treated multiethnic cohort and whether this differs in women diagnosed <24 vs ≥24 weeks' gestation (early vs standard GDM). This was a retrospective cohort study undertaken at the Royal Prince Alfred Hospital Diabetes Antenatal Clinic, Australia, between 1991 and 2011. Pregnant women (N = 3098) underwent an HbA1c (single-laboratory) measurement at the time of GDM diagnosis. Maternal clinical and pregnancy outcome data were collected prospectively. The association between baseline HbA1c and adverse pregnancy outcomes in early vs standard GDM. HbA1c was measured at a median of 17.6 ± 3.3 weeks' gestation in early GDM (n = 844) and 29.4 ± 2.6 weeks' gestation in standard GDM (n = 2254). In standard GDM, HbA1c >5.9% (41 mmol/mol) was associated with the greatest risk of large-for-gestational-age (odds ratio [95% confidence interval] = 2.7 [1.5-4.9]), macrosomia (3.5 [1.4-8.6]), cesarean section (3.6 [2.1-6.2]), and hypertensive disorders (2.6 [1.1-5.8]). In early GDM, similar HbA1c associations were seen; however, lower HbA1c correlated with the greatest risk of small-for-gestational-age (P trend = 0.004) and prevalence of neonatal hypoglycemia. Baseline HbA1c >5.9% (41 mmol/mol) identifies an increased risk of large-for-gestational-age, macrosomia, cesarean section, and hypertensive disorders in standard GDM. Although similar associations are seen in early GDM, higher HbA1c levels do not adequately capture risk-limiting utility as a triage tool in this cohort.
Lakatos, M.; Móring, A.; Szentimrey, T.; Németh, Á.; Bihari, Z.; Kovács, T.; Vincze, E.
could be defined with the probability of the events exceeding a specific high threshold. This level was determined by the average of the yearly mean 99% percentile for each settlement. The interpolated daily fields resulted in time series for each geographical position. With using the empirical probability distribution functions the threshold of the events with less than 1% probability is designed. The ordered probabilities of the exceeding of these thresholds made possible to assess categories for ranking the Hungarian settlements according to the degree of the exposure to either the wind storm or heavy rain. In the case of hail the categories were stated simply according to the measure of the interpolated empirical probabilities of the hail occurrence. The risky locations regarding of wind, rain, hail or theirs combinations can be identified by combining the results. Category maps illustrate the Hungarian locations according to the exposure to the analysed risks.
Shaughnessy, John D; Qu, Pingping; Usmani, Saad; Heuck, Christoph J; Zhang, Qing; Zhou, Yiming; Tian, Erming; Hanamura, Ichiro; van Rhee, Frits; Anaissie, Elias; Epstein, Joshua; Nair, Bijay; Stephens, Owen; Williams, Ryan; Waheed, Sarah; Alsayed, Yazan; Crowley, John; Barlogie, Bart
Gene expression profiling (GEP) of purified plasma cells 48 hours after thalidomide and dexamethasone test doses showed these agents' mechanisms of action and provided prognostic information for untreated myeloma patients on Total Therapy 2 (TT2). Bortezomib was added in Total Therapy 3 (TT3), and 48 hours after bortezomib GEP analysis identified 80 highly survival-discriminatory genes in a training set of 142 TT3A patients that were validated in 128 patients receiving TT3B. The 80-gene GEP model (GEP80) also distinguished outcomes when applied at baseline in both TT3 and TT2 protocols. In context of our validated 70-gene model (GEP70), the GEP80 model identified 9% of patients with a grave prognosis among those with GEP70-defined low-risk disease and 41% of patients with favorable prognosis among those with GEP70-defined high-risk disease. PMSD4 was 1 of 3 genes common to both models. Residing on chromosome 1q21, PSMD4 expression is highly sensitive to copy number. Both higher PSMD4 expression levels and higher 1q21 copy numbers affected clinical outcome adversely. GEP80 baseline-defined high risk, high lactate dehydrogenase, and low albumin were the only independent adverse variables surviving multivariate survival model. We are investigating whether second-generation proteasome inhibitors (eg, carfilzomib) can overcome resistance associated with high PSMD4 levels.
Stevens, Angela K; Littlefield, Andrew K; Talley, Amelia E; Brown, Jennifer L
Extant literature has established a strong relation between individual differences in "impulsivity" and alcohol consumption. However, the relation between "impulsivity," intentions-to-drink, and alcohol consumption has remained understudied. As a part of a larger study, 77 participants (60.5% female, 76.3% White, M age=20.8) completed 10days of daily diary reports regarding their intention to use alcohol and alcohol consumption. Hierarchical linear modeling (HLM) was used to estimate within-person relations between intentions-to-drink and subsequent alcohol use. All models were adjusted for participant age, biological sex, and day of the week. Results showed a strong positive association between daily intention to consume alcohol and self-reported alcohol use (β=0.50, p<0.01). Importantly, tests of interactions indicated that individuals higher in impulsivity were not significantly more likely to engage in unplanned drinking. Multilevel mediation analyses indicated significant indirect effects between impulsivity-like constructs, including positive urgency, lack-of-planning, and self-report delay discounting, and reported daily alcohol consumption via higher overall (i.e., between-person) levels of intentions-to-drink; that is, individuals who reported higher levels of these impulsivity-related constructs were more likely to intend to drink across the 10-days and, in turn, consumed more alcohol. Findings from the study suggest that treatment providers could address drinking intentions among individuals higher in impulsivity and work to establish potential replacement behaviors to reduce alcohol consumption in this population.
Wu, J; Gensheimer, M; Dong, X; Rubin, D; Napel, S; Diehn, M; Loo, B; Li, R
Purpose: To develop an intra-tumor partitioning framework for identifying high-risk subregions from 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and CT imaging, and to test whether tumor burden associated with the high-risk subregions is prognostic of outcomes in lung cancer. Methods: In this institutional review board-approved retrospective study, we analyzed the pre-treatment FDG-PET and CT scans of 44 lung cancer patients treated with radiotherapy. A novel, intra-tumor partitioning method was developed based on a two-stage clustering process: first at patient-level, each tumor was over-segmented into many superpixels by k-means clustering of integrated PET and CT images; next, tumor subregions were identified by merging previously defined superpixels via population-level hierarchical clustering. The volume associated with each of the subregions was evaluated using Kaplan-Meier analysis regarding its prognostic capability in predicting overall survival (OS) and out-of-field progression (OFP). Results: Three spatially distinct subregions were identified within each tumor, which were highly robust to uncertainty in PET/CT co-registration. Among these, the volume of the most metabolically active and metabolically heterogeneous solid component of the tumor was predictive of OS and OFP on the entire cohort, with a concordance index or CI = 0.66–0.67. When restricting the analysis to patients with stage III disease (n = 32), the same subregion achieved an even higher CI = 0.75 (HR = 3.93, logrank p = 0.002) for predicting OS, and a CI = 0.76 (HR = 4.84, logrank p = 0.002) for predicting OFP. In comparison, conventional imaging markers including tumor volume, SUVmax and MTV50 were not predictive of OS or OFP, with CI mostly below 0.60 (p < 0.001). Conclusion: We propose a robust intra-tumor partitioning method to identify clinically relevant, high-risk subregions in lung cancer. We envision that this approach will be applicable to identifying useful
Zhou, Yifang; Liu, Jie; Driesen, Naomi; Womer, Fay; Chen, Kaiyuan; Wang, Ye; Jiang, Xiaowei; Zhou, Qian; Bai, Chuan; Wang, Dahai
White matter (WM) neuroimaging studies have shown varied findings at different stages of schizophrenia (SZ). Understanding these variations may elucidate distinct markers of genetic vulnerability and conversion to psychosis. To examine the similarities and differences in WM connectivity between those at-risk for and in early stages of SZ, a cross-sectional diffusion tensor imaging study of 48 individuals diagnosed with first-episode SZ (FE-SZ), 37 nonpsychotic individuals at a high genetic risk of SZ (GHR-SZ), and 67 healthy controls (HC) was conducted. Decreased fractional anisotropy (FA) in the corpus callosum (CC), anterior cingulum (AC), and uncinate fasciculus (UF) was observed in both the GHR-SZ and FE-SZ groups, while decreased FAs in the superior longitudinal fasciculus (SLF) and the fornix were only seen in the FE-SZ participants. Additionally, both GHR-SZ and FE-SZ showed worse executive performance than HC. The left SLF III FA was significantly positively correlated with hallucinations, and right SLF II was positively correlated with thought disorder. The presence of shared WM deficits in both FE-SZ and GHR-SZ individuals may reflect the genetic liability to SZ, while the disparate FA changes in the FE-SZ group may represent symptom-generating circuitry that mediates perceptual and cognitive disturbances of SZ and ultimately culminates in the onset of psychotic episodes. PMID:28401151
Newgard, Craig D; Rudser, Kyle; Atkins, Dianne L; Berg, Robert; Osmond, Martin H; Bulger, Eileen M; Davis, Daniel P; Schreiber, Martin A; Warden, Craig; Rea, Thomas D; Emerson, Scott
The validity of using adult physiologic criteria to triage injured children in the out-of-hospital setting remains unproven. Among children meeting adult field physiologic criteria, we assessed the availability of physiologic information, the incidence of death or prolonged hospitalization, and whether age-specific criteria would improve the specificity of the physiologic triage step. We analyzed a prospective, out-of-hospital cohort of injured children aged < or =14 years collected from December 2005 through February 2007 by 237 emergency medical services (EMS) agencies transporting to 207 acute care hospitals (trauma and nontrauma centers) in 11 sites across the United States and Canada. Inclusion criteria were standard adult physiologic values: systolic blood pressure (SBP) < or =90 mmHg, respiratory rate < 10 or > 29 breaths/min, Glasgow Coma Scale (GCS) score < or =12, and field intubation attempt. Seven physiologic variables (including age-specific values) and three demographic and mechanism variables were included in the analysis. "High-risk" children included those who died (field or in-hospital) or were hospitalized > 2 days. The decision tree was derived and validated using binary recursive partitioning. Nine hundred fifty-five children were included in the analysis, of whom 62 (6.5%) died and 117 (12.3%) were hospitalized > 2 days. Missing values were common, ranging from 6% (respiratory rate) to 53% (pulse oximetry), and were associated with younger age and high-risk outcome. The final decision rule included four variables (assisted ventilation, GCS score < 11, pulse oximetry < 95%, and SBP > 96 mmHg), which demonstrated improved specificity (71.7% [95% confidence interval (CI) 66.7-76.6%]) at the expense of missing high-risk children (sensitivity 76.5% [95% CI 66.4-86.6%]). The incidence of high-risk injured children meeting adult physiologic criteria is relatively low and the findings from this sample do not support using age-specific values to better
Lee, C Christine; Perkins, Bruce A; Kayaniyil, Sheena; Harris, Stewart B; Retnakaran, Ravi; Gerstein, Hertzel C; Zinman, Bernard; Hanley, Anthony J
Emerging evidence suggests that peripheral neuropathy begins in the early stages of diabetes pathogenesis. Our objective was to describe the prevalence of peripheral neuropathy and nerve dysfunction according to glucose tolerance and metabolic syndrome status and examine how these conditions are associated with neurological changes in individuals at risk for type 2 diabetes. We studied 467 individuals in the longitudinal PROMISE (Prospective Metabolism and Islet Cell Evaluation) cohort. Peripheral neuropathy was defined by Michigan Neuropathy Screening Instrument (MNSI) scores (>2), and the severity of nerve dysfunction was measured objectively by vibration perception thresholds (VPTs) using a neurothesiometer. Metabolic syndrome was defined using the International Diabetes Federation/American Heart Association harmonized criteria. The prevalence of peripheral neuropathy was 29%, 49%, and 50% for normal glycemia, prediabetes, and new-onset diabetes, respectively (P < 0.001 for trend). The mean VPT was 6.5 V for normal glycemia, 7.9 V for prediabetes, and 7.6 V for new-onset diabetes (P = 0.024 for trend). Prediabetes was associated with higher MNSI scores (P = 0.01) and VPTs (P = 0.004) versus normal glycemia, independent of known risk factors. Additionally, progression of glucose intolerance over 3 years predicted a higher risk of peripheral neuropathy (P = 0.007) and nerve dysfunction (P = 0.002). Metabolic syndrome was not independently associated with MNSI scores or VPTs. In individuals with multiple risk factors for diabetes, prediabetes was associated with similar risks of peripheral neuropathy and severity of nerve dysfunction as new-onset diabetes. Prediabetes, but not metabolic syndrome, was independently associated with both the presence of peripheral neuropathy and the severity of nerve dysfunction. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit
Rautio, Nina; Jokelainen, Jari; Saaristo, Timo; Oksa, Heikki; Keinänen-Kiukaanniemi, Sirkka; Peltonen, Markku; Vanhala, Mauno; Korpi-Hyövälti, Eeva; Moilanen, Leena; Saltevo, Juha; Niskanen, Leo; Tuomilehto, Jaakko; Uusitupa, Matti
The authors assessed the predictors of success of a lifestyle intervention (weight loss ≥ 5% and improved glucose tolerance) in individuals at high risk for type 2 diabetes in a 1-year follow-up in a primary health care setting. High-risk individuals for type 2 diabetes were identified by opportunistic screening in the implementation of the Finnish National Diabetes Prevention Program (FIN-D2D). All together, 3880 individuals participated in the 1-year follow-up. Sociodemographic characteristics, health status and behavior, family history of diabetes, clinical factors, and health care provider were considered possible predictors of lifestyle intervention success. In sum, 19.3% of individuals lost at least 5% of weight, and 32.6% with abnormal glucose tolerance at baseline showed improvement in glucose tolerance. Abnormal glucose tolerance was the strongest predictor of weight loss and improvement in glucose tolerance. High attendance at lifestyle intervention visits, being outside of labor force, and high body mass index at baseline were also related to weight loss, and high education was related to improvement in glucose tolerance. In "real-life settings," glucose tolerance status, number of intervention visits, employment status, education, and body mass index explained the success of lifestyle intervention. These factors may help in targeting interventions, although they may not be generalized to other cultural settings.
Fusar-Poli, Paolo; Crossley, Nicolas; Woolley, James; Carletti, Francesco; Perez-Iglesias, Rocio; Broome, Matthew; Johns, Louise; Tabraham, Paul; Bramon, Elvira; McGuire, Philip
Background Psychosis onset is characterized by white matter and electrophysiologic abnormalities. The relation between these factors in the development of illness is almost unknown. We studied the relation between white matter volumes and P300 in prodromal psychosis. Methods We assessed white matter volume (detected using magnetic resonance imaging) and electrophysiologic response during an oddball task (P300) in healthy controls and individuals at high clinical risk for psychosis (with an “at-risk mental state” [ARMS]). Results We included 41 controls and 39 patients with an ARMS in our study. A psychotic disorder developed in 26% of the ARMS group within the follow-up period of 2 years. The P300 amplitude was significantly lower in the ARMS group than in the control group. The ARMS group showed reduced volume of white matter underlying the left superior temporal gyrus and the left superior frontal gyrus and increased volume of white matter underlying the right insula and the right angular gyrus compared with controls. Relative to individuals who did not later become psychotic, the subgroup in whom psychosis subsequently developed had a smaller volume of white matter underlying the left precuneus and the right middle temporal gyrus and increased volume in the white matter underlying the right middle frontal gyrus. We observed a significant interaction in the right middle frontal gyrus: white matter volume was negatively associated with P300 amplitude in the ARMS group and positively associated with P300 amplitude in the control group. Limitations The voxel-based morphometry method alone cannot determine whether abnormal white matter volumes are due to an altered number of axonal connections or decreased myelination. Conclusion P300 abnormalities precede the onset of psychosis and are directly related to white matter alterations, representing a correlate of an increased vulnerability to disease. PMID:21299920
Deschamps, Marie Marcelle; Metch, Barbara; Morgan, Cecilia A; Zorrilla, Carmen D; Donastorg, Yeycy; Swann, Edith; Taina, Dadaille; Patrice, Joseph; JW, Pape
Background Identifying cohorts of Caribbean women with HIV infection rates sufficient for inclusion in HIV vaccine efficacy trials has been challenging. HVTN 907 determined the feasibility of identifying and retaining a cohort of women at high risk for HIV acquisition by focusing recruitment on female sex workers (FSW). Methods HIV uninfected FSWs, residing in Haiti, Dominican Republic (DR) and Puerto Rico (PR), who reported unprotected sex and met previously described more stringent site-specific eligibility criteria14, were eligible. Behavioral risk assessment, HIV counseling and testing and pregnancy testing were done at baseline, 6, 12, and 18 months. Results Among 799 FSWs (264 from DR, 334 from Haiti, 201 from PR), the median age was 26 years, with 54% having less than a high school education and 45% having a monthly household income of less than $US100. Median number of male partners six months prior to screening was 200. Retention at 18 months was 93%. Twelve women became HIV infected, nine from Haiti. The annualized HIV incidence was 1.07 % (95% CI 0.55%, 1.87%). Pregnancy incidence was 22.5% (95% CI 21.9, 29.5%). Statistically significant declines in risk behaviors occurred between screening and the 18 month visit assessment. Discussion The HVTN 907 study identified a high risk cohort of women with excellent retention for all 3 sites, despite major challenges especially in Haiti. These results show that a bridging study of a vaccine shown to be efficacious in other clade settings would be possible among FSW in the region, particularly in Haiti. PMID:26761272
Dillon, Ronna F.; Osborne, Susan S.
In this article we describe the nature of attention deficit disorders (ADDs) within an individual differences model of abilities. In so doing, a model-based explanation for the sources of learning and performance difficulties among individuals identified with ADDs is provided. Earlier models of ADDs are discussed, and the proposed loci of ADDs…
Dillon, Ronna F.; Osborne, Susan S.
In this article we describe the nature of attention deficit disorders (ADDs) within an individual differences model of abilities. In so doing, a model-based explanation for the sources of learning and performance difficulties among individuals identified with ADDs is provided. Earlier models of ADDs are discussed, and the proposed loci of ADDs…
Müller, Arndt-Christian; Eckert, Franziska; Paulsen, Frank; Zips, Daniel; Stenzl, Arnulf; Schilling, David; Alber, Markus; Bares, Roland; Martus, Peter; Weckermann, Dorothea; Belka, Claus; Ganswindt, Ute
To assess the efficacy of individual sentinel node (SN)-guided pelvic intensity modulated radiation therapy (IMRT) by determining nodal clearance rate [(n expected nodal involvement - n observed regional recurrences)/n expected nodal involvement] in comparison with surgically staged patients. Data on 475 high-risk prostate cancer patients were examined. Sixty-one consecutive patients received pelvic SN-based IMRT (5 × 1.8 Gy/wk to 50.4 Gy [pelvic nodes + individual SN] and an integrated boost with 5 × 2.0 Gy/wk to 70.0 Gy to prostate + [base of] seminal vesicles) and neo-/adjuvant long-term androgen deprivation therapy; 414 patients after SN-pelvic lymph node dissection were used to calculate the expected nodal involvement rate for the radiation therapy sample. Biochemical control and overall survival were estimated for the SN-IMRT patients using the Kaplan-Meier method. The expected frequency of nodal involvement in the radiation therapy group was estimated by imputing frequencies of node-positive patients in the surgical sample to the pattern of Gleason, prostate-specific antigen, and T category in the radiation therapy sample. After a median follow-up of 61 months, 5-year OS after SN-guided IMRT reached 84.4%. Biochemical control according to the Phoenix definition was 73.8%. The nodal clearance rate of SN-IMRT reached 94%. Retrospective follow-up evaluation is the main limitation. Radiation treatment of pelvic nodes individualized by inclusion of SNs is an effective regional treatment modality in high-risk prostate cancer patients. The pattern of relapse indicates that the SN-based target volume concept correctly covers individual pelvic nodes. Thus, this SN-based approach justifies further evaluation, including current dose-escalation strategies to the prostate in a larger prospective series. Copyright © 2016 Elsevier Inc. All rights reserved.
Scott, S E; Weinman, J; Grunfeld, E A
The aim of this pilot research was to improve understanding of individuals at risk of oral cancer, to determine their attitudes towards and responses to early detection interventions. In-depth interviews with the target group (n = 25) were used to determine their views, attitudes and requirements for an intervention to encourage early detection of oral cancer. This data was used in combination with theory-based constructs to develop written material that aimed to increase awareness of oral cancer, encourage mouth self-examination (MSE) and early presentation. A second pilot study used a think-aloud protocol to assess the target groups' (n = 14) reactions to the written information. In both studies the tape-recorded responses were analysed using framework analysis. The target group had limited knowledge about oral cancer, particularly the signs and symptoms. Participants saw benefits in performing MSE but noted the main barriers were not knowing what signs to look for or where to look. The written information was generally well-received but required some modifications. In particular, the target group required further persuasion that their lifestyle contributed to an increased risk of oral cancer. The results of these pilot studies have informed the development of a theory-based intervention for the early detection of oral cancer.
Kratz, Johannes R; Mann, Michael J; Jablons, David M
There is widespread agreement amongst clinical oncologists that more refined risk-stratification in early-stage lung cancer patients beyond conventional TNM staging is needed. Over the past decade, a number of molecular prognostic signatures have been designed to meet this need by correlating patterns in the differences in gene expression or modification to patient prognosis. Unfortunately, the majority of proposed signatures are not amenable to practical widespread implementation or have not yet undergone large-scale, rigorous clinical validation. A practical 14-gene prognostic signature that has undergone large-scale blinded independent validation is now ready for widespread clinical use. An international clinical trial is underway that has been designed to document the precise degree of benefit derived from adjuvant therapy in high-risk stage I patients identified by the 14-gene prognostic assay.
Hayakawa, Takehito; Hashimoto, Shigeatsu; Kanda, Hideyuki; Hirano, Noriko; Kurihara, Yumi; Kawashima, Takako; Fukushima, Tetsuhito
Objectives To clarify the risk factors for falls in hospital settings and to propose the use of such factors to identify high-risk persons at admission. Design Prospective cohort study. Setting Fukushima Medical University Hospital, Japan, from August 2008 and September 2009. Participants 9957 adult consecutive inpatients admitted to our hospital. Methods Information was collected at admission from clinical records obtained from a structured questionnaire conducted in face-to-face interviews with subjects by nurses and doctors and fall events were collected from clinical records. Results The proportion of patients who fell during follow-up was 2.5% and the incidence of falls was 3.28 per 100 person-days. There were significant differences in age, history of falling, cognitive dysfunction, planned surgery, wheelchair use, need for help to move, use of a remote caring system, rehabilitation, use of laxative, hypnotic or psychotropic medications and need for help with activities of daily living (ADL) between patients who did and did not fall. Multivariable adjusted ORs for falls showed that age, history of falls and need for help with ADL were common risk factors in both men and women. Using psychotropic medication also increased the risk of falling in men while cognitive dysfunction and use of hypnotic medication increased the risk of falling in women. Planned surgery was associated with a low risk of falls in women. Conclusions To prevent falls in inpatients it is important to identify high-risk persons. Age, history of falling and the need for help with ADL are the most important pieces of information to be obtained at admission. Care plans for patients including fall prevention should be clear and considered. PMID:25232563
Hayakawa, Takehito; Hashimoto, Shigeatsu; Kanda, Hideyuki; Hirano, Noriko; Kurihara, Yumi; Kawashima, Takako; Fukushima, Tetsuhito
To clarify the risk factors for falls in hospital settings and to propose the use of such factors to identify high-risk persons at admission. Prospective cohort study. Fukushima Medical University Hospital, Japan, from August 2008 and September 2009. 9957 adult consecutive inpatients admitted to our hospital. Information was collected at admission from clinical records obtained from a structured questionnaire conducted in face-to-face interviews with subjects by nurses and doctors and fall events were collected from clinical records. The proportion of patients who fell during follow-up was 2.5% and the incidence of falls was 3.28 per 100 person-days. There were significant differences in age, history of falling, cognitive dysfunction, planned surgery, wheelchair use, need for help to move, use of a remote caring system, rehabilitation, use of laxative, hypnotic or psychotropic medications and need for help with activities of daily living (ADL) between patients who did and did not fall. Multivariable adjusted ORs for falls showed that age, history of falls and need for help with ADL were common risk factors in both men and women. Using psychotropic medication also increased the risk of falling in men while cognitive dysfunction and use of hypnotic medication increased the risk of falling in women. Planned surgery was associated with a low risk of falls in women. To prevent falls in inpatients it is important to identify high-risk persons. Age, history of falling and the need for help with ADL are the most important pieces of information to be obtained at admission. Care plans for patients including fall prevention should be clear and considered.
Jacobs, Chris; Patch, Christine
This is the second in a series of articles on genetics. This article focuses on competency 1 of the revised framework for genetics/genomics for nurses. The authors discuss the importance of nurses identifying individuals who may benefit from genetic services. Recording a family history and drawing a family tree are useful skills that will help to identify these individuals and inform the healthcare team. The article explains when to refer individuals to genetic services and what they may expect from these referrals.
Ell, Kathleen; Katon, Wayne; Lee, Pey-Jiuan; Guterman, Jeffrey; Wu, Shinyi
Identify biopsychosocial factors associated with depression for patients with Type 2 diabetes. A quasi-experimental clinical trial of 1293 patients was predominantly Hispanic (91%) female (62%), mean age 53 and average diabetes duration 10 years; 373 (29%) patients were depressed and assessed by Patient Health Questionnaire-9. Demographic, baseline clinical and psychosocial variables were compared between depressed and nondepressed patients. Bivariate analyses found depression significantly associated (p<0.05) with female gender, diabetes emotional burden and regimen distress, BMI ≥ 30, lack of an A1C test, diabetes duration, poor self-care, number of diabetes symptoms and complications, functional and physical characteristics (pain, self-rated health condition, Short-Form Health Survey SF-physical, disability score and comorbid illnesses), as well as higher number of ICD-9 diagnoses and emergency room use. A multivariable regression model with stepwise selection identified six key risk factors: greater disability, diabetes symptoms and regimen distress, female gender, less diabetes self-care and lack of A1C. In addition, after controlling for identified six factors, the number of psychosocial stressors significantly associated with increased risk of depression (adjusted odds ratio=1.37, 95% confidence intervals: 1.18-1.58, p<.0001). Knowing biopsychosocial factors could help primary care physicians and endocrinologists identify a high-risk group of patients needing depression screening. Copyright © 2015 Elsevier Inc. All rights reserved.
Cha, Seon-Ah; Lim, Sun-Young; Kim, Kook-Rye; Lee, Eun-Young; Kang, Borami; Choi, Yoon-Hee; Yoon, Kun-Ho; Ahn, Yu-Bae; Lee, Jin-Hee; Ko, Seung-Hyun
The trend of increasing numbers of patients with type 2 diabetes emphasizes the need for active screening of high-risk individuals and intensive lifestyle modification (LSM). The community-based Korean Diabetes Prevention Study (C-KDPS) is a randomized controlled clinical trial to prevent type 2 diabetes by intensive LSM using a web-based program. The two public healthcare centers in Korea are involved, and 420 subjects are being recruited for 6 months and will be followed up for 22 months. The participants are allocated randomly to intensive LSM (18 individual sessions for 24 weeks) and usual care (control group). The major goals of the C-KDPS lifestyle intervention program are: 1) a minimum of 5-7% loss of initial body weight in 6 months and maintenance of this weight loss, 2) increased physical activity (≥ 150 min/week of moderate intensity activity), 3) balanced healthy eating, and 4) quitting smoking and alcohol with stress management. The web-based program includes education contents, video files, visit schedules, and inter-communicable keeping track sites. Primary outcomes are the diagnoses of newly developed diabetes. A 75-g oral glucose tolerance test with hemoglobin A1c level determination and cardiovascular risk factor assessment is scheduled at 6, 12, 18, and 22 months. Active screening of high-risk individuals and an effective LSM program are an essential prerequisite for successful diabetes prevention. We hope that our C-KDPS program can reduce the incidence of newly developed type 2 diabetes and be implemented throughout the country, merging community-based public healthcare resources and a web-based system. Clinical Research Information Service (CRIS), Republic of Korea (No. KCT0001981 ). Date of registration; July 28, 2016.
O'Brien, Mary P; Miklowitz, David J; Cannon, Tyrone D
Perceived criticism (PC) is a measure of how much criticism from 1 family member "gets through" to another. PC ratings have been found to predict the course of psychotic disorders, but questions remain regarding whether psychosocial treatment can effectively decrease PC, and whether reductions in PC predict symptom improvement. In a sample of individuals at high risk for psychosis, we examined a) whether Family Focused Therapy for Clinical High-Risk (FFT-CHR), an 18-session intervention that consists of psychoeducation and training in communication and problem solving, brought about greater reductions in perceived maternal criticism, compared to a 3-session family psychoeducational intervention; and b) whether reductions in PC from baseline to 6-month reassessment predicted decreases in subthreshold positive symptoms of psychosis at 12-month follow-up. This study was conducted within a randomized controlled trial across 8 sites. The perceived criticism scale was completed by 90 families prior to treatment and by 41 families at 6-month reassessment. Evaluators, blind to treatment condition, rated subthreshold symptoms of psychosis at baseline, 6- and 12-month assessments. Perceived maternal criticism decreased from pre- to posttreatment for both treatment groups, and this change in criticism predicted decreases in subthreshold positive symptoms at 12-month follow-up. This study offers evidence that participation in structured family treatment is associated with improvement in perceptions of the family environment. Further, a brief measure of perceived criticism may be useful in predicting the future course of attenuated symptoms of psychosis for CHR youth.
Valli, I; Crossley, N A; Day, F; Stone, J; Tognin, S; Mondelli, V; Howes, O; Valmaggia, L; Pariante, C; McGuire, P
The onset of psychosis is thought to involve interactions between environmental stressors and the brain, with cortisol as a putative mediator. We examined the relationship between the cortisol stress response and brain structure in subjects at ultra-high risk (UHR) for psychosis. Waking salivary cortisol was measured in 22 individuals at UHR for psychosis and 17 healthy controls. Grey matter volume was assessed using magnetic resonance imaging at 3 T. The relationship between the stress response and grey matter volume was investigated using voxel-based analyses. Our predictions of the topography of cortisol action as a structural brain modulator were informed by measures of brain glucocorticoid and mineralcorticoid receptor distribution obtained from the multimodal neuroanatomical and genetic Allen Brain Atlas. Across all subjects, reduced responsivity of the hypothalamus–pituitary–adrenal (HPA) axis was correlated with smaller grey matter volumes in the frontal, parietal and temporal cortex and in the hippocampus. This relationship was particularly marked in the UHR subjects in the right prefrontal, left parahippocampal/fusiform and parietal cortices. The subgroup that subsequently developed psychosis showed a significant blunting of HPA stress response, observed at trend level also in the whole UHR sample. Altered responses to stress in people at high risk of psychosis are related to reductions in grey matter volume in areas implicated in the vulnerability to psychotic disorders. These areas may represent the neural components of a stress vulnerability model. PMID:27138796
Valli, I; Crossley, N A; Day, F; Stone, J; Tognin, S; Mondelli, V; Howes, O; Valmaggia, L; Pariante, C; McGuire, P
The onset of psychosis is thought to involve interactions between environmental stressors and the brain, with cortisol as a putative mediator. We examined the relationship between the cortisol stress response and brain structure in subjects at ultra-high risk (UHR) for psychosis. Waking salivary cortisol was measured in 22 individuals at UHR for psychosis and 17 healthy controls. Grey matter volume was assessed using magnetic resonance imaging at 3 T. The relationship between the stress response and grey matter volume was investigated using voxel-based analyses. Our predictions of the topography of cortisol action as a structural brain modulator were informed by measures of brain glucocorticoid and mineralcorticoid receptor distribution obtained from the multimodal neuroanatomical and genetic Allen Brain Atlas. Across all subjects, reduced responsivity of the hypothalamus-pituitary-adrenal (HPA) axis was correlated with smaller grey matter volumes in the frontal, parietal and temporal cortex and in the hippocampus. This relationship was particularly marked in the UHR subjects in the right prefrontal, left parahippocampal/fusiform and parietal cortices. The subgroup that subsequently developed psychosis showed a significant blunting of HPA stress response, observed at trend level also in the whole UHR sample. Altered responses to stress in people at high risk of psychosis are related to reductions in grey matter volume in areas implicated in the vulnerability to psychotic disorders. These areas may represent the neural components of a stress vulnerability model.
Deichgræber, Pia; Witte, Daniel R; Møller, Holger J; Skriver, Mette V; Richelsen, Bjørn; Jørgensen, Marit E; Johansen, Nanna B; Sandbæk, Annelli
Our aim was to investigate the association between the macrophage-activation marker soluble CD163 (sCD163), adiponectin, C-reactive protein (CRP) and changes in glycaemia, insulin resistance and insulin secretion in individuals at high risk of type 2 diabetes mellitus. This prospective study included 1014 individuals at high risk of type 2 diabetes mellitus participating in the Danish arm of the Anglo-Danish-Dutch study of Intensive Treatment In PeOple with ScreeN-detected Diabetes in Primary Care (ADDITION-Europe trial) baseline examination in 2001-2006 and follow-up examination (ADDITION-Progression [ADDITION-PRO]) in 2009-2011. Baseline serum samples were analysed for sCD163, adiponectin and CRP. The associations between sCD163, adiponectin and CRP per doubling of concentration, and changes per year in HbA1c, fasting plasma glucose, 2 h glucose, fasting insulin, HOMA-IR and HOMA-β were assessed using a mixed-effects model. A doubling of sCD163 concentration was positively associated with changes in HOMA-β (β = 1.160 per year, 95% CI 0.345, 1.975) as well as a doubling of CRP concentration (β = 0.410 per year, 95% CI 0.051, 0.769) after adjustment for age and sex. A doubling of adiponectin was inversely associated with changes in 2 h glucose (β =-0.063 per year, 95% CI -0.111, -0.014), HOMA-IR (β =-0.038 per year, 95% CI -0.060, -0.015) and HOMA-β (β =-1.028 per year, 95% CI -1.635, -0.421) after adjustment for age and sex. The associations were robust to adjustment for baseline waist circumference and smoking. Adjustment for CRP did not change the associations for sCD163 or adiponectin. Our findings indicate that mechanisms related to inflammation, including macrophage activation and adipocyte metabolism, may play a role in changes in glucose homeostasis in individuals at high risk of type 2 diabetes mellitus.
Newgard, Craig D.; Rudser, Kyle; Atkins, Dianne L.; Berg, Robert; Osmond, Martin H.; Bulger, Eileen M.; Davis, Daniel P.; Schreiber, Martin A.; Warden, Craig; Rea, Thomas D.; Emerson, Scott
Objective The validity of using adult physiologic criteria to triage injured children in the out-of-hospital setting remains unproven. Among children meeting adult field physiologic criteria, we assessed the availability of physiologic information, the incidence of death or prolonged hospitalization, and whether age-specific criteria would improve the specificity of the physiologic triage step. Methods We analyzed a prospective, out-of-hospital cohort of injured children aged ≤14 years collected from December 2005 through February 2007 by 237 emergency medical services (EMS) agencies transporting to 207 acute care hospitals (trauma and nontrauma centers) in 11 sites across the United States and Canada. Inclusion criteria were standard adult physiologic values: systolic blood pressure (SBP) ≤90 mmHg, respiratory rate <10 or >29 breaths/min, Glasgow Coma Scale (GCS) score ≤12, and field intubation attempt. Seven physiologic variables (including age-specific values) and three demographic and mechanism variables were included in the analysis. “High-risk” children included those who died (field or in-hospital) or were hospitalized >2 days. The decision tree was derived and validated using binary recursive partitioning. Results Nine hundred fifty-five children were included in the analysis, of whom 62 (6.5%) died and 117 (12.3%) were hospitalized >2 days. Missing values were common, ranging from 6% (respiratory rate) to 53% (pulse oximetry), and were associated with younger age and high-risk outcome. The final decision rule included four variables (assisted ventilation, GCS score <11, pulse oximetry <95%, and SBP >96 mmHg), which demonstrated improved specificity (71.7% [95% confidence interval (CI) 66.7–76.6%]) at the expense of missing high-risk children (sensitivity 76.5% [95% CI 66.4–86.6%]). Conclusions The incidence of high-risk injured children meeting adult physiologic criteria is relatively low and the findings from this sample do not support using
Barbaro, Brunella; Leccisotti, Lucia; Vecchio, Fabio M; Di Matteo, Marialuisa; Serra, Teresa; Salsano, Marco; Poscia, Andrea; Coco, Claudio; Persiani, Roberto; Alfieri, Sergio; Gambacorta, Maria Antonietta; Valentini, Vincenzo; Giordano, Alessandro; Bonomo, Lorenzo
To correlate imaging parameters from baseline MRI diffusion-weighted imaging (DWI) and fludeoxyglucose (FDG) positron emission tomography (PET)-CT with synchronous and metachronous metastases in mucinous carcinoma (MC) and non-mucinous carcinoma (NMC) rectal cancer. 111 patients with extraperitoneal locally advanced rectal cancer, who underwent pelvic MRI, DWI and FDG PET-CT, were stratified into MC (n = 23) and NMC (n = 88). We correlated adverse morphologic features on MRI [mT4, mesorectal fascia involvement, extramural venous invasion (mEMVI), mN2] and quantitative imaging parameters [minimum apparent diffusion coefficient (ADCmin), maximum standardized uptake value, total lesion glycolysis, metabolic tumour volume, T2 weighted and DWI tumour volumes] with the presence of metastatic disease. All patients underwent pre-operative chemoradiation therapy (CRT); 100/111 patients underwent surgery after CRT and were classified as pathological complete response (PCR) and no PCR [tumour regression grade (TRG)1 vs TRG2-5] and as ypN0 and ypN1-2. Median follow-up time was 48 months. Metastases were confirmed on FDG PET-CT and contrast-enhanced multidetector CT. The percentage of mucin measured by MRI correlates with that quantified by histology. On multivariate analysis, the synchronous metastases were correlated with mEMVI [odds ratio (OR) = 21.48, p < 0.01] and low ADCmin (OR = 0.04, p = 0.038) in NMC. The difference of metachronous recurrence between the MC group (10-90% mucin) and NMC group was significant (p < 0.01) (OR = 21.67, 95% confidence interval 3.8-120.5). Metachronous metastases were correlated with ypN2 (OR = 8.24, p = 0.01) in MC and in NMC. In NMC, mEMVI correlated with no PCR (p = 0.018) and ypN2 (p < 0.01). mEMVI could identify patients with NMC, who are at high risk of synchronous metastases. The MC group is at a high risk of developing metachronous metastases. Advances in knowledge: Patients at high risk of
Bendifallah, Sofiane; Canlorbe, Geoffroy; Laas, Enora; Huguet, Florence; Coutant, Charles; Hudry, Delphine; Graesslin, Olivier; Raimond, Emilie; Touboul, Cyril; Collinet, Pierre; Cortez, Annie; Bleu, Géraldine; Daraï, Emile; Ballester, Marcos
This study aimed to develop a predictive model using histopathologic characteristics of early-stage type 1 endometrial cancer (EC) to identify patients at high risk for lymph node (LN) metastases. The data of 523 patients who received primary surgical treatment between January 2001 and December 2012 were abstracted from a prospective multicenter database (training set). A multivariate logistic regression analysis of selected prognostic features was performed to develop a nomogram predicting LN metastases. To assess its accuracy, an internal validation technique with a bootstrap approach was adopted. The optimal threshold in terms of clinical utility, sensitivity, specificity, negative predictive values (NPVs), and positive predictive values (PPVs) was evaluated by the receiver-operating characteristics (ROC) curve area and the Youden Index. Overall, the LN metastasis rate was 12.4 % (65/523). Lymph node metastases were associated with histologic grade, tumor diameter, depth of myometrial invasion, and lymphovascular space involvement status. These variables were included in the nomogram. Discrimination of the model was 0.83 [95 % confidence interval (CI) 0.80-0.85] in the training set. The area under the curve ROC for predicting LN metastases after internal validation was 0.82 (95 % CI 0.80-0.84). The Youden Index provided a value of 0.2, corresponding to a cutoff of 140 points (total score in the algorithm). At this threshold, the model had a sensitivity of 0.73 (95 % CI 0.62-0.83), a specificity of 0.84 (95 % CI 0.82-0.85), a PPV of 0.40 (95 % CI 0.34-0.45), and an NPV of 0.95 (95 % CI 0.94-0.97). The results show that the risk of LN metastases can be predicted correctly so that patients at high risk can benefit from adapted surgical treatment.
Martinelli, Sara; Cuneo, Antonio; Formigaro, Luca; Cavallari, Maurizio; Lista, Enrico; Quaglia, Francesca Maria; Ciccone, Maria; Bardi, Antonella; Volta, Eleonora; Tammiso, Elisa; Saccenti, Elena; Sofritti, Olga; Daghia, Giulia; Negrini, Massimo; Dabusti, Melissa; Tomasi, Paolo; Moretti, Sabrina; Cavazzini, Francesco; Rigolin, Gian Matteo
Chronic lymphocytic leukemia (CLL) displays an extremely variable clinical behaviour. Accurate prognostication and prediction of response to treatment are important in an era of effective first-line regimens and novel molecules for high risk patients. Because a plethora of prognostic biomarkers were identified, but few of them were validated by multivariable analysis in comprehensive prospective studies, we applied in this survey stringent criteria to select papers from the literature in order to identify the most reproducible prognostic/predictive markers. Each biomarker was analysed in terms of reproducibility across the different studies with respect to its impact on time to first treatment (TTFT), progression free survival (PFS), overall survival (OS) and response to treatment. We were able to identify the following biomarkers as the most reliable in guiding risk stratification in the daily clinical practice: 17p-/TP53 mutations, IGHV unmutated configuration, short telomeres and 11q-. However, the method for measuring telomere length was not validated yet and 11q- was predictive of inferior OS only in those patients who did not receive FCR-like combinations. Stage and lymphocytosis were predictive of shorter TTFT and age, high serum thymidine kinase levels and poor performance status were predictive of shorter OS. Using our criteria no parameter was found to independently predict for inferior response to treatment. PMID:27872727
Pluijm, S M F; Smit, J H; Tromp, E A M; Stel, V S; Deeg, D J H; Bouter, L M; Lips, P
The aim of the prospective study reported here was to develop a risk profile that can be used to identify community-dwelling elderly at a high risk of recurrent falling. The study was designed as a 3-year prospective cohort study. A total of 1365 community-dwelling persons, aged 65 years and older, of the population-based Longitudinal Aging Study Amsterdam participated in the study. During an interview in 1995/1996, physical, cognitive, emotional and social aspects of functioning were assessed. A follow-up on the number of falls and fractures was conducted during a 3-year period using fall calendars that participants filled out weekly. Recurrent fallers were identified as those who fell at least twice within a 6-month period during the 3-year follow-up. The incidence of recurrent falls at the 3-year follow-up point was 24.9% in women and 24.4% in men. Of the respondents, 5.5% reported a total of 87 fractures that resulted from a fall, including 20 hip fractures, 21 wrist fractures and seven humerus fractures. Recurrent fallers were more prone to have a fall-related fracture than those who were not defined as recurrent fallers (11.9% vs. 3.4%; OR: 3.8; 95% CI: 2.3-6.1). Backward logistic regression analysis identified the following predictors in the risk profile for recurrent falling: two or more previous falls, dizziness, functional limitations, weak grip strength, low body weight, fear of falling, the presence of dogs/cats in the household, a high educational level, drinking 18 or more alcoholic consumptions per week and two interaction terms (high education x 18 or more alcohol consumptions per week and two or more previous falls x fear of falling) (AUC=0.71). At a cut-off point of 5 on the total risk score (range 0-30), the model predicted recurrent falling with a sensitivity of 59% and a specificity of 71%. At a cut-off point of 10, the sensitivity and specificity were 31% and 92%, respectively. A risk profile including nine predictors that can easily be
Lavoie, Suzie; Whitford, Thomas J; Benninger, Franz; Feucht, Martha; Kim, Sung-Wan; Klier, Claudia M; McNamara, Robert K; Rice, Simon; Schäfer, Miriam R; Amminger, G Paul
Abnormal levels of polyunsaturated fatty acids (PUFAs) have been reported in individuals suffering from schizophrenia. The main aim of the present study was to investigate the relationship between erythrocyte membrane fatty acid levels and resting-state brain activity occurring in individuals at ultra-high risk (UHR) of psychosis. The association between erythrocyte membrane fatty acids levels and resting-state brain activity and its value in predicting psychosis was examined in 72 UHR individuals. In the frontal area, the activity in the fast frequency band Beta2 was positively associated with docosahexaenoic acid (DHA) levels (R = 0.321, P = 0.017), and in the fronto-central area, Beta2 activity showed a positive correlation with eicosapentaenoic acid (EPA) levels (R = 0.305, P = 0.009), regardless of psychosis transition status. Conversely, the slow frequency band Theta was significantly negatively associated with EPA levels in the parieto-occipital region (R = -0.251, P = 0.033. Results also showed that Alpha power was negatively correlated with DHA levels in UHR individuals who did not transition to psychosis, while this correlation was not present in individuals who later transitioned. Our results suggest that individuals at UHR for psychosis who have higher basal omega-3 fatty acids levels present with resting EEG features associated with better states of alertness and vigilance. Furthermore, the improvement in the Alpha synchrony observed along with increased DHA levels in participants who did not transition to psychosis is disturbed in those who did transition. However, these interesting results are limited by the small sample size and low statistical power of the study. © The Royal Australian and New Zealand College of Psychiatrists 2015.
Identifying Aboriginal-specific AUDIT-C and AUDIT-3 cutoff scores for at-risk, high-risk, and likely dependent drinkers using measures of agreement with the 10-item Alcohol Use Disorders Identification Test
Background The Alcohol Use Disorders Identification Test (AUDIT) is a 10-item alcohol screener that has been recommended for use in Aboriginal primary health care settings. The time it takes respondents to complete AUDIT, however, has proven to be a barrier to its routine delivery. Two shorter versions, AUDIT-C and AUDIT-3, have been used as screening instruments in primary health care. This paper aims to identify the AUDIT-C and AUDIT-3 cutoff scores that most closely identify individuals classified as being at-risk drinkers, high-risk drinkers, or likely alcohol dependent by the 10-item AUDIT. Methods Two cross-sectional surveys were conducted from June 2009 to May 2010 and from July 2010 to June 2011. Aboriginal Australian participants (N = 156) were recruited through an Aboriginal Community Controlled Health Service, and a community-based drug and alcohol treatment agency in rural New South Wales (NSW), and through community-based Aboriginal groups in Sydney NSW. Sensitivity, specificity, and positive and negative predictive values of each score on the AUDIT-C and AUDIT-3 were calculated, relative to cutoff scores on the 10-item AUDIT for at-risk, high-risk, and likely dependent drinkers. Receiver operating characteristic (ROC) curve analyses were conducted to measure the detection characteristics of AUDIT-C and AUDIT-3 for the three categories of risk. Results The areas under the receiver operating characteristic (AUROC) curves were high for drinkers classified as being at-risk, high-risk, and likely dependent. Conclusions Recommended cutoff scores for Aboriginal Australians are as follows: at-risk drinkers AUDIT-C ≥ 5, AUDIT-3 ≥ 1; high-risk drinkers AUDIT-C ≥ 6, AUDIT-3 ≥ 2; and likely dependent drinkers AUDIT-C ≥ 9, AUDIT-3 ≥ 3. Adequate sensitivity and specificity were achieved for recommended cutoff scores. AUROC curves were above 0.90. PMID:25179547
A genome-wide investigation of microRNA expression identifies biologically-meaningful microRNAs that distinguish between high-risk and low-risk intraductal papillary mucinous neoplasms of the pancreas.
Permuth-Wey, Jennifer; Chen, Y Ann; Fisher, Kate; McCarthy, Susan; Qu, Xiaotao; Lloyd, Mark C; Kasprzak, Agnieszka; Fournier, Michelle; Williams, Vonetta L; Ghia, Kavita M; Yoder, Sean J; Hall, Laura; Georgeades, Christina; Olaoye, Funmilayo; Husain, Kazim; Springett, Gregory M; Chen, Dung-Tsa; Yeatman, Timothy; Centeno, Barbara Ann; Klapman, Jason; Coppola, Domenico; Malafa, Mokenge
Intraductal papillary mucinous neoplasms (IPMNs) are pancreatic ductal adenocarcinoma (PDAC) precursors. Differentiating between high-risk IPMNs that warrant surgical resection and low-risk IPMNs that can be monitored is a significant clinical problem, and we sought to discover a panel of mi(cro)RNAs that accurately classify IPMN risk status. In a discovery phase, genome-wide miRNA expression profiling was performed on 28 surgically-resected, pathologically-confirmed IPMNs (19 high-risk, 9 low-risk) using Taqman MicroRNA Arrays. A validation phase was performed in 21 independent IPMNs (13 high-risk, 8 low-risk). We also explored associations between miRNA expression level and various clinical and pathological factors and examined genes and pathways regulated by the identified miRNAs by integrating data from bioinformatic analyses and microarray analysis of miRNA gene targets. Six miRNAs (miR-100, miR-99b, miR-99a, miR-342-3p, miR-126, miR-130a) were down-regulated in high-risk versus low-risk IPMNs and distinguished between groups (P<10-3, area underneath the curve (AUC) = 87%). The same trend was observed in the validation phase (AUC = 74%). Low miR-99b expression was associated with main pancreatic duct involvement (P = 0.021), and serum albumin levels were positively correlated with miR-99a (r = 0.52, P = 0.004) and miR-100 expression (r = 0.49, P = 0.008). Literature, validated miRNA:target gene interactions, and pathway enrichment analysis supported the candidate miRNAs as tumor suppressors and regulators of PDAC development. Microarray analysis revealed that oncogenic targets of miR-130a (ATG2B, MEOX2), miR-342-3p (DNMT1), and miR-126 (IRS-1) were up-regulated in high- versus low-risk IPMNs (P<0.10). This pilot study highlights miRNAs that may aid in preoperative risk stratification of IPMNs and provides novel insights into miRNA-mediated progression to pancreatic malignancy. The miRNAs identified here and in other recent investigations warrant evaluation in
Wilkins, David; Leung, Marcus H Y; Lee, Patrick K H
Humans host individually unique skin microbiota, suggesting that microbiota traces transferred from skin to surfaces could serve as forensic markers analogous to fingerprints. While it is known that individuals leave identifiable microbiota traces on surfaces, it is not clear for how long these traces persist. Moreover, as skin and surface microbiota change with time, even persistent traces may lose their forensic potential as they would cease to resemble the microbiota of the person who left them. We followed skin and surface microbiota within households for four seasons to determine whether accurate microbiota-based matching of individuals to their households could be achieved across long time delays. While household surface microbiota traces could be matched to the correct occupant or occupants with 67% accuracy, accuracy decreased substantially when skin and surface samples were collected in different seasons, and particularly when surface samples were collected long after skin samples. Most OTUs persisted on skin or surfaces for less than one season, indicating that OTU loss was the major cause of decreased matching accuracy. OTUs that were more useful for individual identification persisted for less time and were less likely to be deposited from skin to surface, suggesting a trade-off between the longevity and identifying value of microbiota traces. While microbiota traces have potential forensic value, unlike fingerprints they are not static and may degrade in a way that preferentially erases features useful in identifying individuals.
O'Brien, Jessica W; Lichenstein, Sarah D; Hill, Shirley Y
Individuals with multiple alcohol-dependent (AD) relatives are at increased risk for substance use disorders (SUDs). Prospective, longitudinal studies of high-risk (HR) individuals afford the opportunity to determine potential risk markers of SUDs. The current study assessed the effect of familial risk and genetic variation on Iowa Gambling Task (IGT) performance and tested for an association between IGT performance and SUD outcomes. Individuals from multiplex AD families (n = 63) and low-risk (LR; n = 45) control families, ages 16-34 years, were tested using a computerized version of the IGT. SUD outcomes were assessed at approximately yearly intervals. 5-HTTLPR and COMT genotypes were available for the majority of participants (n = 86). HR offspring showed poorer performance overall on the IGT and especially poor performance on the final trial block (Block 5), indicating a failure to improve decision making with previous experience. The 5-HTTLPR short-allele homozygote participants performed worse than long-allele carriers, with HR S/S carriers exhibiting particularly poor performance. There was no main effect of COMT on IGT performance and no significant COMT by Risk interaction. Significantly more individuals in the HR than LR group met criteria for SUD. Importantly, disadvantageous performance on IGT Block 5 was significantly associated with an earlier age at SUD onset. This is the first study to show that both familial risk of SUD and 5-HTTLPR variation impact performance on the IGT. Poorer IGT performance was associated with earlier onset of SUD, suggesting that HR individuals who fail to appropriately attend to long-term costs and benefits during a decision-making task are especially at risk for developing SUD in adolescence and young adulthood.
Coble, Jamie B.; Hines, Wes
The ultimate goal of most prognostic systems is accurate prediction of the remaining useful life of individual systems or components based on their use and performance. Traditionally, individual-based prognostic methods use a measure of degradation to make lifetime estimates. Degradation measures may include sensed measurements, such as temperature or vibration level, or inferred measurements, such as model residuals or physics-based model predictions. Often, it is beneficial to combine several measures of degradation into a single parameter. Parameter features such as trendability, monotonicity, and prognosability can be used to compare candidate prognostic parameters to determine which is most useful for individual-based prognosis. By quantifying these features for a given parameter, the metrics can be used with any traditional optimization technique to identify an appropriate parameter. This parameter may be used with a parametric extrapolation model to make prognostic estimates for an individual unit. The proposed methods are illustrated with an application to simulated turbofan engine data.
Fuller, Trevon; Havers, Fiona; Xu, Cuiling; Fang, Li-Qun; Cao, Wu-Chun; Shu, Yuelong; Widdowson, Marc-Alain; Smith, Thomas B.
Summary Objectives The rapid emergence, spread, and disease severity of avian influenza A(H7N9) in China has prompted concerns about a possible pandemic and regional spread in the coming months. The objective of this study was to predict the risk of future human infections with H7N9 in China and neighboring countries by assessing the association between H7N9 cases at sentinel hospitals and putative agricultural, climatic, and demographic risk factors. Methods This cross-sectional study used the locations of H7N9 cases and negative cases from China’s influenza-like illness surveillance network. After identifying H7N9 risk factors with logistic regression, we used Geographic Information Systems (GIS) to construct predictive maps of H7N9 risk across Asia. Results Live bird market density was associated with human H7N9 infections reported in China from March-May 2013. Based on these cases, our model accurately predicted the virus’ spread into Guangxi autonomous region in February 2014. Outside China, we find there is a high risk that the virus will spread to northern Vietnam, due to the import of poultry from China. Conclusions Our risk map can focus efforts to improve surveillance in poultry and humans, which may facilitate early identification and treatment of human cases. PMID:24642206
Gonsalves, W I; Rajkumar, S V; Dispenzieri, A; Dingli, D; Timm, M M; Morice, W G; Lacy, M Q; Buadi, F K; Go, R S; Leung, N; Kapoor, P; Hayman, S R; Lust, J A; Russell, S J; Zeldenrust, S R; Hwa, L; Kourelis, T V; Kyle, R A; Gertz, M A; Kumar, S K
The presence of high numbers of circulating clonal plasma cells (cPCs) in patients with smoldering multiple myeloma (SMM), detected by a slide-based immunofluorescence assay, has been associated with a shorter time to progression (TTP) to MM. The significance of quantifying cPCs via multiparameter flow cytometry, a much more readily available diagnostic modality, in patients with SMM has not been evaluated. This study evaluated 100 patients with a known or new diagnosis of SMM who were seen at the Mayo Clinic, Rochester from January 2008 until December 2013. Patients with ⩾150 cPCs (N=9) were considered to have high number of cPCs based on the 97% specificity and 78% PPV of progression to MM within 2 years of cPC assessment. The median TTP of patients with ⩾150 cPCs was 9 months compared with not reached for patients with <150 cPCs (P<0.001). Thus, quantification of cPCs via multiparametric flow cytometry identifies patients with SMM at very high risk of progression to MM within 2 years and warrants confirmation in larger studies. In the future, this may allow reclassification of such patients as having MM requiring therapy prior to them enduring end-organ damage.
Barbato, Mariapaola; Liu, Lu; Cadenhead, Kristin S; Cannon, Tyrone D; Cornblatt, Barbara A; McGlashan, Thomas H; Perkins, Diana O; Seidman, Larry J; Tsuang, Ming T; Walker, Elaine F; Woods, Scott W; Bearden, Carrie E; Mathalon, Daniel H; Heinssen, Robert; Addington, Jean
Social cognition, the mental operations that underlie social interactions, is a major construct to investigate in schizophrenia. Impairments in social cognition are present before the onset of psychosis, and even in unaffected first-degree relatives, suggesting that social cognition may be a trait marker of the illness. In a large cohort of individuals at clinical high risk for psychosis (CHR) and healthy controls, three domains of social cognition (theory of mind, facial emotion recognition and social perception) were assessed to clarify which domains are impaired in this population. Six-hundred and seventy-five CHR individuals and 264 controls, who were part of the multi-site North American Prodromal Longitudinal Study, completed The Awareness of Social Inference Test, the Penn Emotion Recognition task, the Penn Emotion Differentiation task, and the Relationship Across Domains, measures of theory of mind, facial emotion recognition, and social perception, respectively. Social cognition was not related to positive and negative symptom severity, but was associated with age and IQ. CHR individuals demonstrated poorer performance on all measures of social cognition. However, after controlling for age and IQ, the group differences remained significant for measures of theory of mind and social perception, but not for facial emotion recognition. Theory of mind and social perception are impaired in individuals at CHR for psychosis. Age and IQ seem to play an important role in the arising of deficits in facial affect recognition. Future studies should examine the stability of social cognition deficits over time and their role, if any, in the development of psychosis.
Barbato, Mariapaola; Liu, Lu; Cadenhead, Kristin S.; Cannon, Tyrone D.; Cornblatt, Barbara A.; McGlashan, Thomas H.; Perkins, Diana O.; Seidman, Larry J.; Tsuang, Ming T.; Walker, Elaine F.; Woods, Scott W.; Bearden, Carrie E.; Mathalon, Daniel H.; Heinssen, Robert; Addington, Jean
Social cognition, the mental operations that underlie social interactions, is a major construct to investigate in schizophrenia. Impairments in social cognition are present before the onset of psychosis, and even in unaffected first-degree relatives, suggesting that social cognition may be a trait marker of the illness. In a large cohort of individuals at clinical high risk for psychosis (CHR) and healthy controls, three domains of social cognition (theory of mind, facial emotion recognition and social perception) were assessed to clarify which domains are impaired in this population. Six-hundred and seventy-five CHR individuals and 264 controls, who were part of the multi-site North American Prodromal Longitudinal Study, completed The Awareness of Social Inference Test, the Penn Emotion Recognition task, the Penn Emotion Differentiation task, and the Relationship Across Domains, measures of theory of mind, facial emotion recognition, and social perception, respectively. Social cognition was not related to positive and negative symptom severity, but was associated with age and IQ. CHR individuals demonstrated poorer performance on all measures of social cognition. However, after controlling for age and IQ, the group differences remained significant for measures of theory of mind and social perception, but not for facial emotion recognition. Theory of mind and social perception are impaired in individuals at CHR for psychosis. Age and IQ seem to play an important role in the arising of deficits in facial affect recognition. Future studies should examine the stability of social cognition deficits over time and their role, if any, in the development of psychosis. PMID:27695675
Trepanier, Pier-Yves; Fortin, Israel; Lambert, Carole; Lacroix, Frederic
The strategy currently used to treat glioblastoma multiforme (GBM) patients, which mostly relies on population-based failure patterns, does not consider the important variability in such patterns reported in the literature. As part of the multidisciplinary efforts being made to develop personalized therapeutic approaches, numerical models of tumor growth and treatment are increasingly being used by different groups around the world. In this study, a new formalism relying on the proliferation-invasion model is developed to identify potential locations of GBM recurrences. The authors assess the sensitivity of the location of potential tumor recurrences to the input parameter values predicted for a given patient by varying those values using a Monte-Carlo based approach. Our approach is designed to be prospective in the sense that it relies on patient-specific imaging data that can be gathered in one single preradiotherapy imaging session. The authors modeled the infiltration paths of glial cells using patient-specific diffusion tensor imaging (DTI) data. Nine GBM patients with preradiotherapy DTI data are considered in this study. The possible locations of tumor recurrences are determined by randomly selecting many ensembles of values for each of the growth and radiobiological parameters in the GBM growth model. A novel concept, the occurrence probability (OP), is introduced to assess the sensitivity of potential tumor recurrence locations to the input parameter values. For a given patient, the OP map is derived from a superposition of all potential tumor recurrence locations obtained with all sets of parameter values. For eight out of nine of patients, the authors have identified a statistically significant region where the OP is above 50%. For two patients, these high risk regions are found to be located at a distance greater than 3.9 cm from the border of the gross tumor volume highlighting the inaccuracy of current margins for some patients. The exact location
Wan, Tao; Bloch, B. Nicolas; Plecha, Donna; Thompson, Cheryi L.; Gilmore, Hannah; Jaffe, Carl; Harris, Lyndsay; Madabhushi, Anant
To identify computer extracted imaging features for estrogen receptor (ER)-positive breast cancers on dynamic contrast en-hanced (DCE)-MRI that are correlated with the low and high OncotypeDX risk categories. We collected 96 ER-positivebreast lesions with low (<18, N = 55) and high (>30, N = 41) OncotypeDX recurrence scores. Each lesion was quantitatively charac-terize via 6 shape features, 3 pharmacokinetics, 4 enhancement kinetics, 4 intensity kinetics, 148 textural kinetics, 5 dynamic histogram of oriented gradient (DHoG), and 6 dynamic local binary pattern (DLBP) features. The extracted features were evaluated by a linear discriminant analysis (LDA) classifier in terms of their ability to distinguish low and high OncotypeDX risk categories. Classification performance was evaluated by area under the receiver operator characteristic curve (Az). The DHoG and DLBP achieved Az values of 0.84 and 0.80, respectively. The 6 top features identified via feature selection were subsequently combined with the LDA classifier to yield an Az of 0.87. The correlation analysis showed that DHoG (ρ = 0.85, P < 0.001) and DLBP (ρ = 0.83, P < 0.01) were significantly associated with the low and high risk classifications from the OncotypeDX assay. Our results indicated that computer extracted texture features of DCE-MRI were highly correlated with the high and low OncotypeDX risk categories for ER-positive cancers.
Krumrei, Kirk; Flanagan, Molly; Bruner, Josh; Durall, Chris
Injuries are somewhat commonplace in highly active populations. One strategy for reducing injuries is to identify individuals with an elevated injury risk before participation so that remediative interventions can be provided. Preparticipation screenings have traditionally entailed strength and flexibility measures thought to be indicative of inflated injury risk. Some researchers, however, have suggested that functional movements/tasks should be assessed to help identify individuals with a high risk of future injury. One assessment tool used for this purpose is the Functional Movement Screen (FMS). The FMS generates a numeric score based on performance attributes during 7 dynamic tasks; this score is purported to reflect future injury risk. Expanding interest in the FMS has led researchers to investigate how accurately it can identify individuals with an increased risk of injury. Can the Functional Movement Screen accurately identify highly active individuals with an elevated risk of injury?
Spratt, Daniel E; Yousefi, Kasra; Deheshi, Samineh; Ross, Ashley E; Den, Robert B; Schaeffer, Edward M; Trock, Bruce J; Zhang, Jingbin; Glass, Andrew G; Dicker, Adam P; Abdollah, Firas; Zhao, Shuang G; Lam, Lucia L C; du Plessis, Marguerite; Choeurng, Voleak; Haddad, Zaid; Buerki, Christine; Davicioni, Elai; Weinmann, Sheila; Freedland, Stephen J; Klein, Eric A; Karnes, R Jeffrey; Feng, Felix Y
Purpose To perform the first meta-analysis of the performance of the genomic classifier test, Decipher, in men with prostate cancer postprostatectomy. Methods MEDLINE, EMBASE, and the Decipher genomic resource information database were searched for published reports between 2011 and 2016 of men treated by prostatectomy that assessed the benefit of the Decipher test. Multivariable Cox proportional hazards models fit to individual patient data were performed; meta-analyses were conducted by pooling the study-specific hazard ratios (HRs) using random-effects modeling. Extent of heterogeneity between studies was determined with the I(2) test. Results Five studies (975 total patients, and 855 patients with individual patient-level data) were eligible for analysis, with a median follow-up of 8 years. Of the total cohort, 60.9%, 22.6%, and 16.5% of patients were classified by Decipher as low, intermediate, and high risk, respectively. The 10-year cumulative incidence metastases rates were 5.5%, 15.0%, and 26.7% ( P < .001), respectively, for the three risk classifications. Pooling the study-specific Decipher HRs across the five studies resulted in an HR of 1.52 (95% CI, 1.39 to 1.67; I(2) = 0%) per 0.1 unit. In multivariable analysis of individual patient data, adjusting for clinicopathologic variables, Decipher remained a statistically significant predictor of metastasis (HR, 1.30; 95% CI, 1.14 to 1.47; P < .001) per 0.1 unit. The C-index for 10-year distant metastasis of the clinical model alone was 0.76; this increased to 0.81 with inclusion of Decipher. Conclusion The genomic classifier test, Decipher, can independently improve prognostication of patients postprostatectomy, as well as within nearly all clinicopathologic, demographic, and treatment subgroups. Future study of how to best incorporate genomic testing in clinical decision-making and subsequent treatment recommendations is warranted.
Chaubert-Pereira, Florence; Caraglio, Yves; Lavergne, Christian; Guédon, Yann
Background and Aims This study aimed to identify and characterize the ontogenetic, environmental and individual components of forest tree growth. In the proposed approach, the tree growth data typically correspond to the retrospective measurement of annual shoot characteristics (e.g. length) along the trunk. Methods Dedicated statistical models (semi-Markov switching linear mixed models) were applied to data sets of Corsican pine and sessile oak. In the semi-Markov switching linear mixed models estimated from these data sets, the underlying semi-Markov chain represents both the succession of growth phases and their lengths, while the linear mixed models represent both the influence of climatic factors and the inter-individual heterogeneity within each growth phase. Key Results On the basis of these integrative statistical models, it is shown that growth phases are not only defined by average growth level but also by growth fluctuation amplitudes in response to climatic factors and inter-individual heterogeneity and that the individual tree status within the population may change between phases. Species plasticity affected the response to climatic factors while tree origin, sampling strategy and silvicultural interventions impacted inter-individual heterogeneity. Conclusions The transposition of the proposed integrative statistical modelling approach to cambial growth in relation to climatic factors and the study of the relationship between apical growth and cambial growth constitute the next steps in this research. PMID:19684021
Shen, Yi; Zhang, Jian; Cai, Hui; Shao, Jian-Guo; Zhang, You-Yi; Liu, Yan-Mei; Qin, Gang; Qin, Yan
The presence of diabetes mellitus (DM) is associated with increased liver morbidity and mortality risk in patients with chronic hepatitis B (CHB). Aim of this study was to identify factors associated with type 2 diabetes mellitus (T2DM) in CHB patients. A cross-sectional study with pair-matched controls was conducted in Nantong Third People's Hospital, Nantong University, China. From January 2008 to December 2012, a total of 1783 CHB patients were screened for study subjects, among whom 207 patients with T2DM were enrolled as cases and 207 sex- and age-matched non-DM patients as controls. Demographic, anthropometric, lifestyle, clinical, and laboratory data were obtained from each subject. In the univariate model, thirteen variables showed marked differences between the DM group and non-DM group. Patients with longer duration of CHB (≥15 years) and alcoholic steatosis showed the highest likelihood of T2DM (odds ratio = 5.39 and 4.95; 95% confidence intervals 2.76-10.53 and 1.65-14.91). In the multivariate adjusted analysis, three CHB-related factors, namely high viral load, long duration of illness, and presence of cirrhosis, contributed to substantially increase the likelihood of T2DM, in addition to the other five risk factors including family history of DM, low education level, elevated triglycerides (TG), gamma-glutamyl transferase (GGT) levels, and presence of alcoholic steatosis. Our findings suggest that high viral load, long duration of CHB, presence of cirrhosis, alcoholic steatosis and several other factors may be potential risk factors for development of T2DM in CHB patients. It is of vital importance to monitor glucose in high-risk CHB patients and aggressively intervene on modifiable risk factors.
Muratori, Leonardo; Petroni, Giulia; Antonuzzo, Lorenzo; Boni, Luca; Iorio, Jessica; Lastraioli, Elena; Bartoli, Gianluca; Messerini, Luca; Di Costanzo, Francesco; Arcangeli, Annarosa
Background The identification of early-stage colorectal cancer (CRC) with high risk of progression is one major clinical challenge, mainly due to lack of validated biomarkers. The aims of the present study were to analyze the prognostic impact of three molecular markers belonging to the ion channels and transporters family: the ether-à-go-go-related gene 1 (hERG1) and the calcium-activated KCa3.1 potassium channels, as well as the glucose transporter 1 (Glut-1); and to define the impact of adjuvant chemotherapy in conjunction with the abovementioned biomarkers, in a cohort of radically resected stage I–III CRC patients. Patients and methods The expressions of hERG1, KCa3.1, and Glut-1 were tested by immunohistochemistry on 162 surgical samples of nonmetastatic, stage I–III CRC patients. The median follow-up was 32 months. The association between biological markers, clinicopathological features, and survival outcomes was investigated by evaluating both disease-free survival and overall survival. Results Although no prognostic valence emerged for KCa3.1, evidence of a negative impact of hERG1 expression on survival outcomes was provided. On the contrary, Glut-1 expression had a positive impact. According to the results of the multivariate analysis, patients were stratified in four risk groups, based on TNM stage and hERG1/Glut-1 expression. After adjusting for adjuvant therapy, stage I and II, Glut-1-negative, and hERG1-positive patients showed the worst survival experience. Conclusion This study strongly indicates that the combination of hERG1 positivity and Glut-1 negativity behaves as a prognostic biomarker in radically resected CRC patients. This combination identifies a group of stage I and II CRC patients with a bad prognosis, even worse than that of stage III patients, regardless of adjuvant therapy accomplishment. PMID:27789963
Spyridou, Andria; Schauer, Maggie; Ruf-Leuschner, Martina
KINDEX Greek version can be considered a valid tool, which can be used by non-trained medical staff providing obstetrical care to identify high-risk women and refer them to adequate mental health and social services. These kind of assessments are indispensable for the promotion of a healthy family environment and child development.
Carrión, Ricardo E; Demmin, Docia; Auther, Andrea M; McLaughlin, Danielle; Olsen, Ruth; Lencz, Todd; Correll, Christoph U; Cornblatt, Barbara A
Research in individuals at clinical high-risk (CHR) for psychosis has focused on subjects with no more than 12 months of present or worsened attenuated positive symptoms. However, the impact of long duration attenuated positive and/or negative prodromal symptoms on outcomes is unclear. Seventy-six CHR subjects with attenuated positive symptoms and at least moderate severity level negative symptoms rated on the Scale of Prodromal Symptoms (SOPS) were prospectively followed for a mean of 3.0 ± 1.6 years. Social and Role functioning was assessed with the Global Functioning: Social and Role scales. Correlations between attenuated positive and negative symptom duration and severity and conversion to psychosis and functional outcomes were analyzed. The average onset of SOPS rated negative symptoms (M = 53.24 months, SD = 48.90, median = 37.27) was approximately twelve months prior to the emergence of attenuated positive symptom (M = 40.15 months, SD = 40.33, median = 24.77, P < 0.05). More severe positive symptoms (P = 0.004), but not longer duration of positive (P = 0.412) or negative (P = 0.754) symptoms, predicted conversion to psychosis. Neither positive symptom duration (P = 0.181) nor severity (P = 0.469) predicted role or social functioning at study endpoint. Conversely, longer negative symptom duration predicted poor social functioning (P = 0.004). Overall, our findings suggest that the severity of attenuated positive symptoms at baseline may be more important than symptom duration for determining individuals at increased risk of developing psychosis. In contrast, long-standing negative symptoms may be associated with persistent social difficulties and therefore have an important position in the treatment of disability.
Lim, Stephen S; Gaziano, Thomas A; Gakidou, Emmanuela; Reddy, K Srinath; Farzadfar, Farshad; Lozano, Rafael; Rodgers, Anthony
In 2005, a global goal of reducing chronic disease death rates by an additional 2% per year was established. Scaling up coverage of evidence-based interventions to prevent cardiovascular disease in high-risk individuals in low-income and middle-income countries could play a major part in reaching this goal. We aimed to estimate the number of deaths that could be averted and the financial cost of scaling up, above current coverage levels, a multidrug regimen for prevention of cardiovascular disease (a statin, aspirin, and two blood-pressure-lowering medicines) in 23 such countries. Identification of individuals was limited to those already accessing health services, and treatment eligibility was based on the presence of existing cardiovascular disease or absolute risk of cardiovascular disease by use of easily measurable risk factors. Over a 10-year period, scaling up this multidrug regimen could avert 17.9 million deaths from cardiovascular disease (95% uncertainty interval 7.4 million-25.7 million). 56% of deaths averted would be in those younger than 70 years, with more deaths averted in women than in men owing to larger absolute numbers of women at older ages. The 10-year financial cost would be US$47 billion ($33 billion-$61 billion) or an average yearly cost per head of $1.08 ($0.75-1.40), ranging from $0.43 to $0.90 across low-income countries and from $0.54 to $2.93 across middle-income countries. This package could effectively meet three-quarters of the proposed global goal with a moderate increase in health expenditure.
Diderich, Hester M; Fekkes, Minne; Verkerk, Paul H; Pannebakker, Fieke D; Velderman, Mariska Klein; Sorensen, Peggy J G; Baeten, Paul; Oudesluys-Murphy, Anne Marie
Identifying child abuse and neglect solely on the grounds of child characteristics leaves many children undetected. We developed a new approach (Hague protocol) based on characteristics of parents who attend the Emergency Department (ED) because they have the following problems: (1) intimate partner violence, (2) substance abuse, or (3) suicide attempt or other serious psychiatric problems. The goal of this protocol is to enable the Reporting Center for Child Abuse and Neglect (RCCAN) to rapidly assess family problems and offer voluntary community based support to these parents. The aim of this study is to assess whether this protocol for screening adults presenting for care in the Emergency Department can identify children at high risk for maltreatment. A before and after study was conducted at 9 EDs in 3 regions in the Netherlands (one intervention region and 2 control regions). During the period January 2006 to November 2007, prior to the introduction of the Hague protocol, from a total of 385,626 patients attending the ED in the intervention region 4 parents (1 per 100,000) were referred to the RCCAN. In the period after introduction of the protocol (December 2007 to December 2011), the number rose to 565 parents from a total of 885,301 patients attending the ED (64 per 100,000). In the control region, where the protocol was not implemented, these figures were 2 per 163,628 (1 per 100,000) and 10 per 371,616 (3 per 100,000) respectively (OR=28.0 (95 CI 4.6-170.7)). At assessment, child abuse was confirmed in 91% of referred cases. The protocol has a high positive predictive value of 91% and can substantially increase the detection rate of child abuse in an ED setting. Parental characteristics are strong predictors of child abuse. Implementing guidelines to detect child abuse based on parental characteristics of parents attending the adult section of the ED can increase the detection rate of child abuse and neglect allowing appropriate aid to be initiated for
Perrodin, Catherine; Kayser, Christoph; Abel, Taylor J.; Logothetis, Nikos K.; Petkov, Christopher I.
Social animals can identify conspecifics by many forms of sensory input. However, whether the neuronal computations that support our ability to identify individuals rely on modality-independent convergence or involve ongoing synergistic interactions along the multiple sensory streams remains controversial. Direct neuronal measurements at relevant brain sites could address such questions, but this requires better bridging the work in humans and animal models. We overview recent studies in nonhuman primates on voice- and face-identity sensitive pathways and evaluate the correspondences to relevant findings in humans. This synthesis provides insights into converging sensory streams in the primate anterior temporal lobe for identity processing. Furthermore, we advance a model and suggest how alternative neuronal mechanisms could be tested. PMID:26454482
Scheiman, M; Blaskey, P; Ciner, E B; Gallaway, M; Parisi, M; Pollack, K; Selznick, R
Individuals with "scotopic sensitivity syndrome" have been reported to have visual symptoms including eye strain, headaches, blurred vision, double vision and words moving on the page. This study was designed to investigate Irlen's claims that these symptoms are unrelated to vision anomalies. She suggests that the use of Irlen tinted lenses/filters relieves these symptoms and results in improved reading performance. Thirty nine subjects (age 10-49) were recruited by advertising for a study of Irlen Filters/Lenses. Before the Irlen screening all subjects received an optometric examination. The results of this study demonstrate that 95 percent of the subjects identified as candidates for Irlen Filters did have significant and readily identifiable vision anomalies. Fifty seven percent of the subjects had received vision care within the past year, yet testing revealed that 90 percent of these subjects had significant vision problems that had not been corrected.
Doret, Muriel; Gaucherand, Pascal
Antenatal care is aiming to reduce maternal land foetal mortality and morbidity. Maternal and foetal mortality can be due to different causes. Their knowledge allows identifying pregnancy (high risk pregnancy) with factors associated with an increased risk for maternal and/or foetal mortality and serious morbidity. Identification of high risk pregnancies and initiation of appropriate treatment and/or surveillance should improve maternal and/or foetal outcome. New risk factors are continuously described thanks to improvement in antenatal care and development in biology and cytopathology, increasing complexity in identifying high risk pregnancies. Level of risk can change all over the pregnancy. Ideally, it should be evaluated prior to the pregnancy and at each antenatal visit. Clinical examination is able to screen for intra-uterin growth restriction, pre-eclampsia, threatened for preterm labour; ultrasounds help in the diagnosis of foetal morphological anomalies, foetal chromosomal anomalies, placenta praevia and abnormal foetal growth; biological exams are used to screen for pre-eclampsia, gestational diabetes, trisomy 21 (for which screening method just changed), rhesus immunisation, seroconversion for toxoplasmosis or rubeola, unknown infectious disease (syphilis, hepatitis B, VIH). During pregnancy, most of the preventive strategies have to be initiated during the first trimester or even before conception. Prevention for neural-tube defects, neonatal hypocalcemia and listeriosis should be performed for all women. On the opposite, some measures are concerning only women with risk factors such as prevention for toxoplasmosis, rhesus immunization (which recently changed), tobacco complications and pre-eclampsia and intra-uterine growth factor restriction.
Gershon, A S; Wang, C; Guan, J; Vasilevska-Ristovska, J; Cicutto, L; To, T
Chronic Obstructive Pulmonary Disease (COPD) is a common chronic respiratory disease responsible for significant morbidity and mortality. Population-based health administrative databases provide a powerful and unbiased way of studying COPD in the population, however, their ability to accurately identify patients with this disease must first be confirmed. The objective was to validate population-based health administrative definitions of COPD. Previously abstracted medical records of adults over the age of 35 randomly selected from primary care practices in Ontario, Canada were reviewed by an expert panel to establish if an individual did or did not have a diagnosis of COPD. These reference designations were then linked to each individual's respective health administrative database record and compared with predefine health administrative data definitions of COPD. Concepts of diagnostic test evaluation were used to calculate and compare their test characteristics. The most sensitive health administrative definition of COPD was 1 or more ambulatory claims and/or 1 or more hospitalizations for COPD that yielded a sensitivity of 85.0% (95% confidence interval 77.0 to 91.0) and a specificity of 78.4% (95% confidence interval 73.6 to 82.7). As number of ambulatory claims in the definition increased, sensitivity decreased and specificity increased. Individuals with COPD can be accurately identified in health administrative data, and therefore it may be used to create an unbiased population cohort for surveillance and research. This offers a powerful means of generating evidence to inform strategies that optimize the prevention and management of COPD.
Lai, Wei-Hung; Rau, Cheng-Shyuan; Hsu, Shiun-Yuan; Wu, Shao-Chun; Kuo, Pao-Jen; Hsieh, Hsiao-Yun; Chen, Yi-Chun; Hsieh, Ching-Hua
The ratio of systolic blood pressure (SBP) to heart rate (HR), called the reverse shock index (RSI), is used to evaluate the hemodynamic stability of trauma patients. A SBP lower than the HR (RSI < 1) indicates the probability of hemodynamic shock. The objective of this study was to evaluate whether the RSI as evaluated by emergency medical services (EMS) personnel at the injury scene (EMS RSI) and the physician in the emergency department (ED RSI) could be used as an additional variable to identify patients who are at high risk of more severe injury. Data obtained from all 16,548 patients added to the trauma registry system at a Level I trauma center between January 2009 and December 2013 were retrospectively reviewed. Only patients transferred by EMS were included in this study. A total of 3715 trauma patients were enrolled and subsequently divided into four groups: group I patients had an EMS RSI ≥1 and an ED RSI ≥1 (n = 3485); group II an EMS RSI ≥ 1 and an ED RSI < 1 (n = 85); group III an EMS RSI < 1 and an ED RSI ≥ 1 (n = 98); and group IV an EMS RSI < 1 and a ED RSI < 1 (n = 47). A Pearson's χ² test, Fisher's exact test, or independent Student's t-test was conducted to compare trauma patients in groups II, III, and IV with those in group I. Group II and IV patients had a higher injury severity score, a higher incidence of commonly associated injuries, and underwent more procedures (including intubation, chest tube insertion, and blood transfusion in the ED) than patients in group I. Group II and IV patients were also more likely to receive a severe injury to the thoracoabdominal area. These patients also had worse outcomes regarding the length of stay in hospital and intensive care unit (ICU), the proportion of patients admitted to ICU, and in-hospital mortality. Group II patients had a higher adjusted odds ratio for mortality (5.8-times greater) than group I patients. Using an RSI < 1 as a threshold to evaluate the hemodynamic condition of the
Carrión, R. E.; McLaughlin, D.; Auther, A. M.; Olsen, R.; Correll, C. U.; Cornblatt, B. A.
Background Although cognitive deficits in patients with schizophrenia are rooted early in development, the impact of psychosis on the course of cognitive functioning remains unclear. In this study a nested case-control design was used to examine the relationship between emerging psychosis and the course of cognition in individuals ascertained as clinical high-risk (CHR) who developed psychosis during the study (CHR+T). Method Fifteen CHR+T subjects were administered a neurocognitive battery at baseline and post-psychosis onset (8.04 months, S.D. = 10.26). CHR+T subjects were matched on a case-by-case basis on age, gender, and time to retest with a group of healthy comparison subjects (CNTL, n = 15) and two groups of CHR subjects that did not transition: (1) subjects matched on medication treatment (i.e. antipsychotics and antidepressants) at both baseline and retesting (Meds-matched CHR+NT, n = 15); (2) subjects unmedicated at both assessments (Meds-free CHR+NT, n = 15). Results At baseline, CHR+T subjects showed large global neurocognitive and intellectual impairments, along with specific impairments in processing speed, verbal memory, sustained attention, and executive function. These impairments persisted after psychosis onset and did not further deteriorate. In contrast, CHR+NT subjects demonstrated stable mild to no impairments in neurocognitive and intellectual performance, independent of medication treatment. Conclusions Cognition appears to be impaired prior to the emergence of psychotic symptoms, with no further deterioration associated with the onset of psychosis. Cognitive deficits represent trait risk markers, as opposed to state markers of disease status and may therefore serve as possible predictors of schizophrenia prior to the onset of the full illness. PMID:26169626
Sahin, Seda; Yüksel, Çağrı; Güler, Julide; Karadayı, Gülşah; Akturan, Elçin; Göde, Evrim; Özhan, Amber Alix; Üçok, Alp
Childhood trauma (CT) is more common in patients with psychosis than in general population and is found to be related to the severity of symptoms. The objective of this study was to investigate the severity of CT, and its relationship with clinical features in two different groups: first-episode schizophrenia (FES) and ultra high risk for psychosis (UHR) groups. In this cross-sectional study, 83 patients with FES, 41 individuals with UHR and 69 healthy controls were included. Clinical features were evaluated with the Brief Psychiatric Rating Scale, the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms (SAPS). We evaluated CT with the Childhood Trauma Questionnaire (CTQ). UHR group was also assessed with the Calgary Depression Scale for Schizophrenia. The emotional and physical abuse, physical and emotionalneglect subscale scores and CTQ total score of both the UHR group and FES group were higher than the control group. However, the CTQ total score and subscale scores did not differ between FES and UHR groups. UHR group had more Schneiderian symptoms in terms of both number and severity, and severity of sexual abuse was found to be correlated with SAPS scores especially for the 'commenting voices' item. The CTQ emotional abuse and neglect scores were correlated with the severity of depression. FES patients with higher CTQ scores obtained higher total scores on SAPS and higher total scores on Schneiderian items. We found that CT is related to the severity of psychotic symptoms in both FES and UHR groups. Therefore, it is possible that interventions aimed at preventing CT in children would reduce the manifestation of psychosis among young people. © 2013 Wiley Publishing Asia Pty Ltd.
Kuusisto, Kirsi M; Bebel, Aleksandra; Vihinen, Mauno; Schleutker, Johanna; Sallinen, Satu-Leena
Two major high-penetrance breast cancer genes, BRCA1 and BRCA2, are responsible for approximately 20% of hereditary breast cancer (HBC) cases in Finland. Additionally, rare mutations in several other genes that interact with BRCA1 and BRCA2 increase the risk of HBC. Still, a majority of HBC cases remain unexplained which is challenging for genetic counseling. We aimed to analyze additional mutations in HBC-associated genes and to define the sensitivity of our current BRCA1/2 mutation analysis protocol used in genetic counseling. Eighty-two well-characterized, high-risk hereditary breast and/or ovarian cancer (HBOC) BRCA1/2-founder mutation-negative Finnish individuals, were screened for germline alterations in seven breast cancer susceptibility genes, BRCA1, BRCA2, CHEK2, PALB2, BRIP1, RAD50, and CDH1. BRCA1/2 were analyzed by multiplex ligation-dependent probe amplification (MLPA) and direct sequencing. CHEK2 was analyzed by the high resolution melt (HRM) method and PALB2, RAD50, BRIP1 and CDH1 were analyzed by direct sequencing. Carrier frequencies between 82 (HBOC) BRCA1/2-founder mutation-negative Finnish individuals and 384 healthy Finnish population controls were compared by using Fisher's exact test. In silico prediction for novel missense variants effects was carried out by using Pathogenic-Or-Not -Pipeline (PON-P). Three previously reported breast cancer-associated variants, BRCA1 c.5095C > T, CHEK2 c.470T > C, and CHEK2 c.1100delC, were observed in eleven (13.4%) individuals. Ten of these individuals (12.2%) had CHEK2 variants, c.470T > C and/or c.1100delC. Fourteen novel sequence alterations and nine individuals with more than one non-synonymous variant were identified. One of the novel variants, BRCA2 c.72A > T (Leu24Phe) was predicted to be likely pathogenic in silico. No large genomic rearrangements were detected in BRCA1/2 by multiplex ligation-dependent probe amplification (MLPA). In this study, mutations in previously known breast cancer
Neskey, David M; Osman, Abdullah A; Ow, Thomas J; Katsonis, Panagiotis; McDonald, Thomas; Hicks, Stephanie C; Hsu, Teng-Kuei; Pickering, Curtis R; Ward, Alexandra; Patel, Ameeta; Yordy, John S; Skinner, Heath D; Giri, Uma; Sano, Daisuke; Story, Michael D; Beadle, Beth M; El-Naggar, Adel K; Kies, Merrill S; William, William N; Caulin, Carlos; Frederick, Mitchell; Kimmel, Marek; Myers, Jeffrey N; Lichtarge, Olivier
TP53 is the most frequently altered gene in head and neck squamous cell carcinoma, with mutations occurring in over two-thirds of cases, but the prognostic significance of these mutations remains elusive. In the current study, we evaluated a novel computational approach termed evolutionary action (EAp53) to stratify patients with tumors harboring TP53 mutations as high or low risk, and validated this system in both in vivo and in vitro models. Patients with high-risk TP53 mutations had the poorest survival outcomes and the shortest time to the development of distant metastases. Tumor cells expressing high-risk TP53 mutations were more invasive and tumorigenic and they exhibited a higher incidence of lung metastases. We also documented an association between the presence of high-risk mutations and decreased expression of TP53 target genes, highlighting key cellular pathways that are likely to be dysregulated by this subset of p53 mutations that confer particularly aggressive tumor behavior. Overall, our work validated EAp53 as a novel computational tool that may be useful in clinical prognosis of tumors harboring p53 mutations. ©2015 American Association for Cancer Research.
Neskey, David M.; Osman, Abdullah A.; Ow, Thomas J.; Katsonis, Panagiotis; McDonald, Thomas; Hicks, Stephanie C.; Hsu, Teng-Kuei; Pickering, Curtis R.; Ward, Alexandra; Patel, Ameeta; Yordy, John S.; Skinner, Heath D.; Giri, Uma; Sano, Daisuke; Story, Michael D.; Beadle, Beth M.; El-Naggar, Adel K.; Kies, Merrill S.; William, William N.; Caulin, Carlos; Frederick, Mitchell; Kimmel, Marek; Myers, Jeffrey N.; Lichtarge, Olivier
TP53 is the most frequently altered gene in head and neck squamous cell carcinoma (HNSCC) with mutations occurring in over two third of cases, but the prognostic significance of these mutations remains elusive. In the current study, we evaluated a novel computational approach termed Evolutionary Action (EAp53) to stratify patients with tumors harboring TP53 mutations as high or low risk, and validated this system in both in vivo and in vitro models. Patients with high risk TP53 mutations had the poorest survival outcomes and the shortest time to the development of distant metastases. Tumor cells expressing high risk TP53 mutations were more invasive and tumorigenic and they exhibited a higher incidence of lung metastases. We also documented an association between the presence of high risk mutations and decreased expression of TP53 target genes, highlighting key cellular pathways that are likely to be dysregulated by this subset of p53 mutations which confer particularly aggressive tumor behavior. Overall, our work validated EAp53 as a novel computational tool that may be useful in clinical prognosis of tumors harboring p53 mutations. PMID:25634208
Mathotaarachchi, Sulantha; Pascoal, Tharick A; Shin, Monica; Benedet, Andrea L; Kang, Min Su; Beaudry, Thomas; Fonov, Vladimir S; Gauthier, Serge; Rosa-Neto, Pedro
Identifying individuals destined to develop Alzheimer's dementia within time frames acceptable for clinical trials constitutes an important challenge to design studies to test emerging disease-modifying therapies. Although amyloid-β protein is the core pathologic feature of Alzheimer's disease, biomarkers of neuronal degeneration are the only ones believed to provide satisfactory predictions of clinical progression within short time frames. Here, we propose a machine learning-based probabilistic method designed to assess the progression to dementia within 24 months, based on the regional information from a single amyloid positron emission tomography scan. Importantly, the proposed method was designed to overcome the inherent adverse imbalance proportions between stable and progressive mild cognitive impairment individuals within a short observation period. The novel algorithm obtained an accuracy of 84% and an under-receiver operating characteristic curve of 0.91, outperforming the existing algorithms using the same biomarker measures and previous studies using multiple biomarker modalities. With its high accuracy, this algorithm has immediate applications for population enrichment in clinical trials designed to test disease-modifying therapies aiming to mitigate the progression to Alzheimer's disease dementia. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
Levey, Douglas J.; Londoño, Gustavo A.; Ungvari-Martin, Judit; Hiersoux, Monique R.; Jankowski, Jill E.; Poulsen, John R.; Stracey, Christine M.; Robinson, Scott K.
Practically all animals are affected by humans, especially in urban areas. Although most species respond negatively to urbanization, some thrive in human-dominated settings. A central question in urban ecology is why some species adapt well to the presence of humans and others do not. We show that Northern Mockingbirds (Mimus polyglottos) nesting on the campus of a large university rapidly learn to assess the level of threat posed by different humans, and to respond accordingly. In a controlled experiment, we found that as the same human approached and threatened a nest on 4 successive days, mockingbirds flushed from their nest at increasingly greater distances from that human. A different human approaching and threatening the nest identically on the fifth day elicited the same response as the first human on the first day. Likewise, alarm calls and attack flights increased from days 1–4 with the first human, and decreased on day 5 with the second human. These results demonstrate a remarkable ability of a passerine bird to distinguish one human from thousands of others. Also, mockingbirds learned to identify individual humans extraordinarily quickly: after only 2 30-s exposures of the human at the nest. More generally, the varying responses of mockingbirds to intruders suggests behavioral flexibility and a keen awareness of different levels of threat posed by individuals of another species: traits that may predispose mockingbirds and other species of urban wildlife to successful exploitation of human-dominated environments. PMID:19451622
Levey, Douglas J; Londoño, Gustavo A; Ungvari-Martin, Judit; Hiersoux, Monique R; Jankowski, Jill E; Poulsen, John R; Stracey, Christine M; Robinson, Scott K
Practically all animals are affected by humans, especially in urban areas. Although most species respond negatively to urbanization, some thrive in human-dominated settings. A central question in urban ecology is why some species adapt well to the presence of humans and others do not. We show that Northern Mockingbirds (Mimus polyglottos) nesting on the campus of a large university rapidly learn to assess the level of threat posed by different humans, and to respond accordingly. In a controlled experiment, we found that as the same human approached and threatened a nest on 4 successive days, mockingbirds flushed from their nest at increasingly greater distances from that human. A different human approaching and threatening the nest identically on the fifth day elicited the same response as the first human on the first day. Likewise, alarm calls and attack flights increased from days 1-4 with the first human, and decreased on day 5 with the second human. These results demonstrate a remarkable ability of a passerine bird to distinguish one human from thousands of others. Also, mockingbirds learned to identify individual humans extraordinarily quickly: after only 2 30-s exposures of the human at the nest. More generally, the varying responses of mockingbirds to intruders suggests behavioral flexibility and a keen awareness of different levels of threat posed by individuals of another species: traits that may predispose mockingbirds and other species of urban wildlife to successful exploitation of human-dominated environments.
Mancia, G; Cha, G; Gil-Extremera, B; Harvey, P; Lewin, A J; Villa, G; Kjeldsen, S E
The DISTINCT study (reDefining Intervention with Studies Testing Innovative Nifedipine GITS-Candesartan Therapy) investigated the efficacy and safety of nifedipine GITS/candesartan cilexetil combinations vs respective monotherapies and placebo in patients with hypertension. This descriptive sub-analysis examined blood pressure (BP)-lowering effects in high-risk participants, including those with renal impairment (estimated glomerular filtration rate<90 ml min(-1), n=422), type 2 diabetes mellitus (n=202), hypercholesterolaemia (n=206) and cardiovascular (CV) risk factors (n=971), as well as the impact of gender, age and body mass index (BMI). Participants with grade I/II hypertension were randomised to treatment with nifedipine GITS (N) 20, 30, 60 mg and/or candesartan cilexetil (C) 4, 8, 16, 32 mg or placebo for 8 weeks. Mean systolic BP and diastolic BP reductions after treatment in high-risk participants were greater, overall, with N/C combinations vs respective monotherapies or placebo, with indicators of a dose-response effect. Highest rates of BP control (ESH/ESC 2013 guideline criteria) were also achieved with highest doses of N/C combinations in each high-risk subgroup. The benefits of combination therapy vs monotherapy were additionally observed in patient subgroups categorised by gender, age or BMI. All high-risk participants reported fewer vasodilatory adverse events in the pooled N/C combination therapy than the N monotherapy group. In conclusion, consistent with the DISTINCT main study outcomes, high-risk participants showed greater reductions in BP and higher control rates with N/C combinations compared with respective monotherapies and lesser vasodilatory side-effects compared with N monotherapy.
Mancia, G; Cha, G; Gil-Extremera, B; Harvey, P; Lewin, A J; Villa, G; Kjeldsen, S E
The DISTINCT study (reDefining Intervention with Studies Testing Innovative Nifedipine GITS—Candesartan Therapy) investigated the efficacy and safety of nifedipine GITS/candesartan cilexetil combinations vs respective monotherapies and placebo in patients with hypertension. This descriptive sub-analysis examined blood pressure (BP)-lowering effects in high-risk participants, including those with renal impairment (estimated glomerular filtration rate<90 ml min−1, n=422), type 2 diabetes mellitus (n=202), hypercholesterolaemia (n=206) and cardiovascular (CV) risk factors (n=971), as well as the impact of gender, age and body mass index (BMI). Participants with grade I/II hypertension were randomised to treatment with nifedipine GITS (N) 20, 30, 60 mg and/or candesartan cilexetil (C) 4, 8, 16, 32 mg or placebo for 8 weeks. Mean systolic BP and diastolic BP reductions after treatment in high-risk participants were greater, overall, with N/C combinations vs respective monotherapies or placebo, with indicators of a dose–response effect. Highest rates of BP control (ESH/ESC 2013 guideline criteria) were also achieved with highest doses of N/C combinations in each high-risk subgroup. The benefits of combination therapy vs monotherapy were additionally observed in patient subgroups categorised by gender, age or BMI. All high-risk participants reported fewer vasodilatory adverse events in the pooled N/C combination therapy than the N monotherapy group. In conclusion, consistent with the DISTINCT main study outcomes, high-risk participants showed greater reductions in BP and higher control rates with N/C combinations compared with respective monotherapies and lesser vasodilatory side-effects compared with N monotherapy. PMID:27511476
Stange, Jonathan P.; Boccia, Angelo S.; Shapero, Benjamin G.; Molz, Ashleigh R.; Flynn, Megan; Matt, Lindsey M.; Abramson, Lyn Y.; Alloy, Lauren B.
Recent work has identified Behavioral Approach System (BAS) sensitivity as a risk factor for the first onset and recurrence of mood episodes in bipolar disorder, but little work has evaluated risk factors for depression in individuals at risk for, but without a history of, bipolar disorder. The present study evaluated cognitive styles and the emotion-regulatory characteristics of emotional clarity and ruminative brooding as prospective predictors of depressive symptoms in individuals with high versus moderate BAS sensitivity. Three separate regressions indicated that the associations between dysfunctional attitudes, self-criticism, and neediness with prospective increases in depressive symptoms were moderated by emotional clarity and brooding. Whereas brooding interacted with these cognitive styles to exacerbate their impact on depressive symptoms, emotional clarity buffered against their negative impact. These interactions were specific to high-BAS individuals for dysfunctional attitudes, but were found across the full sample for self-criticism and neediness. These results indicate that emotion-regulatory characteristics and cognitive styles may work in conjunction to confer risk for and resilience against depression, and that some of these relationships may be specific to individuals at risk for bipolar disorder. PMID:22775344
Eggink, Florine A; Van Gool, Inge C; Leary, Alexandra; Pollock, Pamela M; Crosbie, Emma J; Mileshkin, Linda; Jordanova, Ekaterina S; Adam, Julien; Freeman-Mills, Luke; Church, David N; Creutzberg, Carien L; De Bruyn, Marco; Nijman, Hans W; Bosse, Tjalling
High-risk endometrial cancer (EC) is an aggressive disease for which new therapeutic options are needed. Aims of this study were to validate the enhanced immune response in highly mutated ECs and to explore immune profiles in other EC subgroups. We evaluated immune infiltration in 116 high-risk ECs from the TransPORTEC consortium, previously classified into four molecular subtypes: (i) ultramutated POLE exonuclease domain-mutant ECs (POLE-mutant); (ii) hypermutated microsatellite unstable (MSI); (iii) p53-mutant; and (iv) no specific molecular profile (NSMP). Within The Cancer Genome Atlas (TCGA) EC cohort, significantly higher numbers of predicted neoantigens were demonstrated in POLE-mutant and MSI tumors compared with NSMP and p53-mutants. This was reflected by enhanced immune expression and infiltration in POLE-mutant and MSI tumors in both the TCGA cohort (mRNA expression) and the TransPORTEC cohort (immunohistochemistry) with high infiltration of CD8(+) (90% and 69%), PD-1(+) (73% and 69%) and PD-L1(+) immune cells (100% and 71%). Notably, a subset of p53-mutant and NSMP cancers was characterized by signs of an antitumor immune response (43% and 31% of tumors with high infiltration of CD8(+) cells, respectively), despite a low number of predicted neoantigens. In conclusion, the presence of enhanced immune infiltration, particularly high numbers of PD-1 and PD-L1 positive cells, in highly mutated, neoantigen-rich POLE-mutant and MSI endometrial tumors suggests sensitivity to immune checkpoint inhibitors.
Butts, Alissa M; Weigand, Stephen; Brown, Paul D; Petersen, Ronald C; Jack, Clifford R; Machulda, Mary M; Cerhan, Jane H
Meningiomas are primary intracranial tumors that are often asymptomatic. To our knowledge, no study has attempted to describe neurocognitive function in patients with incidentally-discovered meningioma. We utilized the Mayo Clinic Study of Aging (MCSA), which is a population-based sample of Olmsted County, Minnesota residents that includes neuropsychological testing and brain MRI approximately every 15 months. Using a text search of radiologists' notes of 2402 MCSA individuals (mean age 77 years, scanned between 2004 and 2014) we identified 48 eligible subjects (2%) who had at least one meningioma. Most meningiomas were small (90% <3 cm). We matched each of the 48 subjects to 5 non-demented MCSA controls (n = 240) on age, sex, and education. Cognitive domains assessed included memory, attention-executive function, language, and visuospatial. More women (67%) had a meningioma than men (33%). Groups did not differ on prevalence of Mild Cognitive Impairment (Meningioma = 19%, Controls = 13%). Across cognitive domains, we observed similar performance for the two groups (p's ≥ 0.21). Subtle differences emerged in memory and language domains (p = 0.05 and p = 0.11) when we divided the Meningioma group by tumor location, wherein the small group with an infratentorial tumor performed more poorly than controls globally as well as on select memory and language measures. Our findings suggest that small meningiomas are generally cognitively benign, but that may change as the tumor evolves, and might be impacted by other factors such as meningioma location.
Hou, Wei-Peng; Wang, Ya-Jie; Qiao, Li-Hong; Shen, Hui-Li
To investigate the clinical value of combined determination of in vitro allergens and fractional exhaled nitric oxide (FeNO) in indentifying children at a high risk of asthma among those with recurrent wheezing. A total of 148 children with recurrent wheezing (0.5-6 years old) were enrolled as study subjects, and 80 healthy children who underwent physical examination were enrolled as the control group. Pharmacia UniCAP immunoassay analyzer was used to measure specific immunoglobulin E (sIgE). Nano Coulomb Nitric Oxide Analyzer was used to measure FeNO. The asthma predictive index (API) was evaluated. The recurrent wheezing group had a significantly higher proportion of children with positive sIgE than the control group [68.9% (102/148) vs 11.3% (9/80); P<0.05]. The recurrent wheezing group also had significantly higher levels and positive rate of FeNO than the control group (P<0.05). The overall positive rate of API in children with wheezing was 32.4%, and the API-positive children had a significantly higher FeNO value than the API-negative children (51±6 ppb vs 13±5 ppb; P<0.05). The detection rate of API was 40.2% (41/102) in positive-sIgE children and 50.1% (38/73) in FeNO-positive children, and there was no significant difference between these two groups. The children with positive sIgE and FeNO had a significantly higher detection rate of API (81.4%) than those with positive sIgE or FeNO (P<0.05). Combined determination of FeNO and in vitro allergens is more sensitive in detecting children at a high risk of asthma than FeNO or in vitro allergens determination alone and provides a good method for early identification, diagnosis, and intervention of asthma in children.
Hempler, Nana Folmann; Krasnik, Allan; Pisinger, Charlotta; Jørgensen, Torben
It has been hypothesised that health conscious individuals tend to take better care of themselves by greater adherence to preventive medications. We examined, whether long-term changes in dietary habits and physical activity were associated with initiation of lipid-lowering and antihypertensive medications. The study population consisted of two subsamples from the population-based cohort Inter99 study (1999-2006) in Copenhagen, Denmark: one with systolic blood pressure > 140 mmHg (N = 557) and one with total cholesterol > 7 mmol/L (N = 314). At a health examination, individuals completed a questionnaire about health behaviour and had their blood pressure and cholesterol measured at baseline and after five years. Data on medications were obtained through linkage to the Registry of Medical Product Statistics. Positive changes in physical activity (odds ratio =3.50; 95% CI 1.23-7.54) and in dietary habits (odds ratio = 2.08; 95% CI 1.03-4.21) were associated with an increased initiation of lipid-lowering medications. With respect to antihypertensives, no association was observed in terms of physical activity, but for diet, a positive trend in terms of initiation was observed among those with positive changes in dietary habits (odds ratio = 1.58; 95% CI 0.96-2.59). Generally, we observed health conscious behaviour in terms of increased initiation of preventive medications among those who reported positive changes in health behaviour. This study therefore suggests that more attention should be given to identifying individuals and groups, who are less health conscious and thereby less likely to engage in either preventive medications or changes in health behaviours.
General Accounting Office, Washington, DC.
This report provides an overview of efforts undertaken by the U.S. General Accounting Office (GAO) in 1990 to review and report on federal program areas its work identified as high risk because of vulnerabilities to waste, fraud, abuse, and mismanagement. It reviews the current status of efforts to address these concerns. The six categories of…
General Accounting Office, Washington, DC.
This report provides an overview of efforts undertaken by the U.S. General Accounting Office (GAO) in 1990 to review and report on federal program areas its work identified as high risk because of vulnerabilities to waste, fraud, abuse, and mismanagement. It reviews the current status of efforts to address these concerns. The six categories of…
Mutational analysis of FANCL, FANCM and the recently identified FANCI suggests that among the 13 known Fanconi Anemia genes, only FANCD1/BRCA2 plays a major role in high-risk breast cancer predisposition.
García, María J; Fernández, Victoria; Osorio, Ana; Barroso, Alicia; Fernández, Fernando; Urioste, Miguel; Benítez, Javier
Fanconi Anemia (FA) is a rare recessive syndrome characterized by cellular hypersensitivity to DNA-cross-linking agents. To date, 13 FA complementation groups have been described and all 13 genes associated to each of these groups have been currently identified. Three of the known FA genes are also high-risk (FANCD1/BRCA2) or moderate-risk (FANCN/PALB2 and FANCJ/BRIP1) breast cancer susceptibility genes, which makes all members of the FA pathway particularly attractive breast cancer candidate genes. Most FA genes have been screened for mutations in breast cancer families negative for BRCA1/2 mutations but the role of FANCL, FANCM and the recently identified FANCI has not been evaluated to date. This fact and novel data sustaining greater functional relevance of the three genes within the FA pathway prompted us to scrutinize all coding sequences and splicing sites of FANCI, FANCL and FANCM in 95 BRCA1/2-negative index cases from Spanish high-risk breast cancer families. We identified 68 sequence variants of which 24 were coding and 44 non-coding. Six exonic and 26 non-coding variants had not been described previously. None of the coding changes caused clearly pathogenic changes and computational analysis of all non-described intronic variants did not revealed major impact in splicing. With the present study, all known FA genes have been evaluated within the context of breast cancer high-risk predisposition. Our results rule out a major role of FANCI, FANCL and FANCM in familial breast cancer susceptibility, suggesting that among the 13 known FA genes, only FANCD1/BRCA2 plays a major role in high-risk breast cancer predisposition.
Laures-Gore, Jacqueline S.; DuBay, Michaela F.; Duff, Melissa C.; Buchanan, Tony W.
Purpose: To develop valid indicators of stress in individuals with aphasia (IWA) by examining the relationship between certain language variables (error frequency [EF] and word productivity [WP]) and cortisol reactivity. Method: Fourteen IWA and 10 controls participated in a speaking task. Salivary cortisol was collected pre- and posttask. WP and…
Laures-Gore, Jacqueline S.; DuBay, Michaela F.; Duff, Melissa C.; Buchanan, Tony W.
Purpose: To develop valid indicators of stress in individuals with aphasia (IWA) by examining the relationship between certain language variables (error frequency [EF] and word productivity [WP]) and cortisol reactivity. Method: Fourteen IWA and 10 controls participated in a speaking task. Salivary cortisol was collected pre- and posttask. WP and…
Ioup, Juliette W.; Ioup, George E.
The Littoral Acoustic Demonstration Center (LADC) is a consortium at Stennis Space Center comprising the University of New Orleans, the University of Southern Mississippi, the Naval Research Laboratory, and the University of Louisiana at Lafayette. LADC deployed three Environmental Acoustic Recording System (EARS) buoys in the northern Gulf of Mexico during the summer of 2001 to study ambient noise and marine mammals. Each LADC EARS was an autonomous, self-recording buoy capable of 36 days of continuous recording of a single channel at an 11.7-kHz sampling rate (bandwidth to 5859 Hz). The hydrophone selected for this analysis was approximately 50 m from the bottom in a water depth of 800 m on the continental slope off the Mississippi River delta. This paper contains recent analysis results for sperm whale codas recorded during a 3-min period. Results are presented for the identification of individual sperm whales from their codas, using the acoustic properties of the clicks within each coda. The recorded time series, the Fourier transform magnitude, and the wavelet transform coefficients are each used separately with a self-organizing map procedure for 43 codas. All show the codas as coming from four or five individual whales. [Research supported by ONR.
Lan, Lan; Fang, Yong; Lin, Xiaodong; Chen, Jianguo; Li, Dayi; Feng, Guoying
First-order approximations have been used to study the recursion expressions of the reflection and transmission coefficients of a weakly absorptive multilayer mirror. It has been proved that in the proximity of the central frequency ω0 of a quarter-wave mirror, contributions of an individual layer to the reflection delay time and absorption-induced reflectivity reduction can be quantitatively specified with a single weighting factor pertinent to that layer. Derivations have indicated that the absorption-induced reductions of mirror reflectivity and reflection delay can be reduced by selecting an odd layer number and a large index ratio between alternating high and low refractive index coating materials. Calculations have also suggested that the absorbed incident light is not distributed, among the reflected and transmitting parts, according to the ratio between the reflectivity and potential transmission.
Kraan, Tamar C; Ising, Helga K; Fokkema, Marjolein; Velthorst, Eva; van den Berg, David P G; Kerkhoven, Margot; Veling, Wim; Smit, Filip; Linszen, Don H; Nieman, Dorien H; Wunderink, Lex; Boonstra, Nynke; Klaassen, Rianne M C; Dragt, Sara; Rietdijk, Judith; de Haan, Lieuwe; van der Gaag, Mark
Childhood adversity is associated with a range of mental disorders, functional impairment and higher health care costs in adulthood. In this study we evaluated if childhood adversity was predictive of adverse clinical and functional outcomes and health care costs in a sample of patients at ultra-high risk (UHR) for developing a psychosis. Structural Equation Modeling was used to examine the effect of childhood adversity on depression, anxiety, transition to psychosis and overall functioning at 4-year follow-up. In addition, we evaluated economic costs of childhood adversity in terms of health care use and productivity loss. Data pertain to 105 UHR participants of the Dutch Early Detection and Intervention Evaluation (EDIE-NL). Physical abuse was associated with higher depression rates (b=0.381, p=0.012) and lower social functional outcome (b=-0.219, p=0.017) at 4-year follow-up. In addition, emotional neglect was negatively associated with social functioning (b=-0.313, p=0.018). We did not find evidence that childhood adversity was associated with transition to psychosis, but the experience of childhood adversity was associated with excess health care costs at follow-up. The data indicate long-term negative effects of childhood adversity on depression, social functioning and health care costs at follow-up in a sample of UHR patients.
Hines, Jacqueline H. (Inventor); Solie, Leland P. (Inventor); Tucker, Dana Y. G. (Inventor); Hines, Andrew T. (Inventor)
A surface-launched acoustic wave sensor tag system for remotely sensing and/or providing identification information using sets of surface acoustic wave (SAW) sensor tag devices is characterized by acoustic wave device embodiments that include coding and other diversity techniques to produce groups of sensors that interact minimally, reducing or alleviating code collision problems typical of prior art coded SAW sensors and tags, and specific device embodiments of said coded SAW sensor tags and systems. These sensor/tag devices operate in a system which consists of one or more uniquely identifiable sensor/tag devices and a wireless interrogator. The sensor device incorporates an antenna for receiving incident RF energy and re-radiating the tag identification information and the sensor measured parameter(s). Since there is no power source in or connected to the sensor, it is a passive sensor. The device is wirelessly interrogated by the interrogator.
Ginther, C; Issel-Tarver, L; King, M C
Mitochondrial DNA (mtDNA) was extracted from teeth stored from 3 months to 20 years, including teeth from the semi-skeletonized remains of a murder victim which had been buried for 10 months. Tooth donors and/or their maternal relatives provided blood or buccal cells, from which mtDNA was also extracted. Enzymatic amplification and direct sequencing of roughly 650 nucleotides from two highly polymorphic regions of mtDNA yielded identical sequences for each comparison of tooth and fresh DNA. Our results suggest that teeth provide an excellent source for high molecular weight mtDNA that can be valuable for extending the time in which decomposed human remains can be genetically identified.
Ferreira, Daniel; Falahati, Farshad; Linden, Cecilia; Buckley, Rachel F; Ellis, Kathryn A; Savage, Greg; Villemagne, Victor L; Rowe, Christopher C; Ames, David; Simmons, Andrew; Westman, Eric
Subjective memory decline (SMD) is a heterogeneous condition. While SMD might be the earliest sign of Alzheimer's disease (AD), it also occurs in aging and various neurological, medical, and psychiatric conditions. Identifying those with higher risk to develop dementia is thus a major challenge. We tested a novel disease severity index generated by multivariate data analysis with numerous structural MRI measures as input. The index was used to identify SMD individuals with high risk of progression to mild cognitive impairment (MCI) or AD. A total of 69 healthy controls, 86 SMD, 45 MCI, and 38 AD patients were included. Subjects were followed up for 7.5 years. Clinical, cognitive, PET amyloid imaging and APOE ε4 data were used as outcome variables. The results showed that SMD evidenced cognitive performance intermediate between healthy controls and MCI. The disease severity index identified eleven (13%) SMD individuals with an AD-like pattern of brain atrophy. These individuals showed lower cognitive performance, increased CDR-SOB, higher amyloid burden and worse clinical progression (6.2 times higher likelihood to develop MCI, dementia or die than healthy controls). The current disease severity index may have relevance for clinical practice, as well as for selecting appropriate individuals for clinical trials.
Robinson, Alexandra R.
An updated global survey of radioisotope production and distribution was completed and subjected to a revised "down-selection methodology" to determine those radioisotopes that should be classified as potential national security risks based on availability and key physical characteristics that could be exploited in a hypothetical radiological dispersion device. The potential at-risk radioisotopes then were used in a modeling software suite known as Turbo FRMAC, developed by Sandia National Laboratories, to characterize plausible contamination maps known as Protective Action Guideline Zone Maps. This software also was used to calculate the whole body dose equivalent for exposed individuals based on various dispersion parameters and scenarios. Derived Response Levels then were determined for each radioisotope using: 1) target doses to members of the public provided by the U.S. EPA, and 2) occupational dose limits provided by the U.S. Nuclear Regulatory Commission. The limiting Derived Response Level for each radioisotope also was determined.
Gakidou, Emmanuela; Roth, Gregory
Background Increasing attention is being paid to the marked disparities in diabetes prevalence and health outcomes in the United States. There is a need to identify the small-area geographic variation in diabetes risk and related outcomes, a task that current health surveillance methods, which often rely on a self-reported diagnosis of diabetes, are not detailed enough to achieve. Broad adoption of electronic health records (EHR) and routine centralized reporting of patient-level data offers a new way to examine diabetes risk and highlight hotspots for intervention. Methods and Findings We examined small-area geographic variation in hemoglobin A1c (HgbA1C) levels in three counties though a retrospective observational analysis of the complete population of diabetic patients receiving at least two ambulatory care visits for diabetes in three counties (two urban, one rural) in Minnesota in 2013, with clinical performance measures re-aggregated to patient home zip code area. Patient level performance measures included HgbA1c, blood pressure, low-density lipoprotein cholesterol and smoking. Diabetes care was provided to 63,053 patients out of a total population of 1.48 million people aged 18–74. Within each zip code area, on average 4.1% of the population received care for diabetes. There was significant and largely consistent geographic variation in the proportion of patients within their zip code area of residence attaining HgbA1C <8.0%, ranging from 59–90% of patients within each zip code area (interquartile range (IQR) 72.0%-78.1%). Attainment of performance measures for a zip code area were correlated with household income, educational attainment and insurance coverage for the same zip code area (all p < .001). Conclusions We identified small geographic areas with the least effective control of diabetes. Centrally-aggregated EHR provides a new means of identifying and targeting at-risk neighborhoods for community-based interventions. PMID:27463641
With the increasing amount of people traveling to high altitude regions, the number of people at risk of acquiring altitude illness increases. Altitude illness entails three syndromes; acute mountain sickness, high-altitude cerebral edema, and high-altitude pulmonary edema. These syndromes are potentially lethal acquired medical conditions that in most cases are preventable. Health care providers need to inform travelers of the risks associated with mountaineering and the prophylactic measures available as well as identify underlying conditions that require specific considerations. This article provides a summary of the pathophysiology, symptoms and treatment of altitude illness and aims to be an orientation for general practitioners.
Khoury, Michael; Manlhiot, Cedric; Gibson, Don; Chahal, Nita; Stearne, Karen; Dobbin, Stafford; McCrindle, Brian W
Universal screening of children for dyslipidemia and other cardiovascular risk factors has been recommended. Given the clustering of cardiovascular risk factors within families, one benefit of screening adolescents may be to identify "at-risk" families in which adult members might also be at elevated risk and potentially benefit from medical evaluation. Cross-sectional study of grade 9 students evaluating adiposity, lipids and blood pressure. Data collected by Heart Niagara Inc. through the Healthy Heart Schools' Program. Parents completed questionnaires, evaluating family history of dyslipidemia, hypertension, diabetes and early cardiovascular disease events in parents and siblings (first-degree relatives), and grandparents (second-degree relatives). Associations between positive risk factor findings in adolescents and presence of a positive family history were assessed in logistic regression models. N = 4014 adolescents ages 14-15 years were screened; 3467 (86 %) provided family medical history. Amongst adolescents, 4.7 % had dyslipidemia, 9.5 % had obesity, and 3.5 % had elevated blood pressure. Central adiposity (waist-to-height ratio ≥0.5) in the adolescent was associated with increased odds of diabetes in first- (OR:2.0 (1.6-2.6), p < 0.001) and second-degree relatives (OR:1.3 (1.1-1.6), p = 0.002). Dyslipidemia was associated with increased odds of diabetes (OR:1.6 (1.1-2.3), p < 0.001), hypertension (OR:2.2 (1.5-3.2), p < 0.001) and dyslipidemia (OR:2.2 (1.5-3.2),p < 0.001) in first degree relatives. Elevated blood pressure did not identify increased odds of a positive family history. Presence of obesity and/or dyslipidemia in adolescents identified through a universal school-based screening program is associated with risk factor clustering within families. Universal pediatric cardiometabolic screening may be an effective entry into reverse cascade screening.
Vana, Kimberly D; Silva, Graciela E; Goldberg, Rochelle
This study compared the predictive abilities of the STOP-Bang and Epworth Sleepiness Scale (ESS) for screening sleep clinic patients for obstructive sleep apnea (OSA) and sleep-disordered breathing (SDB). Forty-seven new adult patients without previous diagnoses of OSA or SDB were administered the STOP-Bang and ESS and were assigned to OSA or SDB risk groups based on their scores. STOP-Bang responses were scored with two Body Mass Index cut points of 35 and 30 kg/m(2) (SB35 and SB30). The tools' predictive abilities were determined by comparing patients' predicted OSA and SDB risks to their polysomnographic results. The SB30 correctly identified more patients with OSA and SDB than the ESS alone. The ESS had the highest specificity for OSA and SDB.
Masson, Lindi; Arnold, Kelly B; Little, Francesca; Mlisana, Koleka; Lewis, David A; Mkhize, Nonhlanhla; Gamieldien, Hoyam; Ngcapu, Sinaye; Johnson, Leigh; Lauffenburger, Douglas A; Abdool Karim, Quarraisha; Abdool Karim, Salim S; Passmore, Jo-Ann S
Untreated sexually transmitted infections (STIs) and bacterial vaginosis (BV) cause genital inflammation and increase the risk of HIV infection. WHO-recommended syndromic STI and BV management is severely limited as many women with asymptomatic infections go untreated. The purpose of this cross-sectional study was to evaluate genital cytokine profiles as a biomarker of STIs and BV to identify women with asymptomatic, treatable infections. Concentrations of 42 cytokines in cervicovaginal lavages from 227 HIV-uninfected women were measured using Luminex. All women were screened for BV by microscopy and STIs using molecular assays. Multivariate analyses were used to identify cytokine profiles associated with STIs/BV. A multivariate profile of seven cytokines (interleukin (IL)-1α, IL-1β, tumour necrosis factor-β, IL-4, fractalkine, macrophage-derived chemokine, and interferon-γ) most accurately predicted the presence of a treatable genital condition, with 77% classification accuracy and 75% cross-validation accuracy (sensitivity 72%; specificity 81%, positive predictive value (PPV) 86%, negative predictive value (NPV) 64%). Concomitant increased IL-1β and decreased IP-10 concentrations predicted the presence of a treatable genital condition without a substantial reduction in predictive value (sensitivity 77%, specificity 72%, PPV 82% and NPV 65%), correctly classifying 75% of the women. This approach performed substantially better than clinical signs (sensitivity 19%, specificity 92%, PPV 79% and NPV 40%). Supplementing syndromic management with an assessment of IL-1β and IP-10 as biomarkers of genital inflammation may improve STI/BV management for women, enabling more effective treatment of asymptomatic infections and potentially reducing their risk of HIV infection. 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/
Poli, Daniela; Antonucci, Emilia; Dentali, Francesco; Testa, Sophie; Palareti, Gualtiero
The most feared complication of vitamin K antagonists (VKAs) treatment is intracranial hemorrhage (ICH). The previously published CHIRONE Study fails to identify risk factors associated with ICH recurrence after VKAs resumption. The aim of this secondary analysis of the study is to evaluate if patients who need surgery or with severe neurological sequelae after the first episode show a higher risk of ICH recurrence. The HASBLED score was used to stratify bleeding risk and to evaluate the distribution of recurrence in relation to each class of risk. The study included 267 patients from 27 Italian centers. The treatment of the index ICH, surgical or medical was recorded; modified Rankin Scale score of 3 or more was used to define patients with severe neurological impairment; HASBLED score of 3 or more was used to identify high bleeding risk patients. During follow-up, 20 patients (7.5%) had ICH recurrence (rate of 2.56 × 100 patient-years). No difference in the type of treatment [hazard ratio = 1.5; 95% confidence interval (CI): 0.49-4.74] and neurological impairment with modified Rankin Scale 3 or more (hazard ratio = 0.9; 95% CI: 0.31-2.83) were found in relation to ICH recurrence. The mean HASBLED score was similar between the two groups (P = 0.54). In conclusion, the results of our study suggest that neither the severity of the index ICH at presentation nor the HASBLED clinical prediction rule should be used to assess the risk of recurrence in patients who need VKAs resumption after a previous ICH.
Gur, David; Zheng, Bin; Lederman, Dror; Dhurjaty, Sreeram; Sumkin, Jules; Zuley, Margarita
A new resonance-frequency based electronic impedance spectroscopy (REIS) system with multi-probes, including one central probe and six external probes that are designed to contact the breast skin in a circular form with a radius of 60 millimeters to the central ("nipple") probe, has been assembled and installed in our breast imaging facility. We are conducting a prospective clinical study to test the performance of this REIS system in identifying younger women (< 50 years old) at higher risk for having or developing breast cancer. In this preliminary analysis, we selected a subset of 100 examinations. Among these, 50 examinations were recommended for a biopsy due to detection of a highly suspicious breast lesion and 50 were determined negative during mammography screening. REIS output signal sweeps that we used to compute an initial feature included both amplitude and phase information representing differences between corresponding (matched) EIS signal values acquired from the left and right breasts. A genetic algorithm was applied to reduce the feature set and optimize a support vector machine (SVM) to classify the REIS examinations into "biopsy recommended" and "non-biopsy" recommended groups. Using the leave-one-case-out testing method, the classification performance as measured by the area under the receiver operating characteristic (ROC) curve was 0.816 +/- 0.042. This pilot analysis suggests that the new multi-probe-based REIS system could potentially be used as a risk stratification tool to identify pre-screened young women who are at higher risk of having or developing breast cancer.
Lanzi, Robin Gaines; Ramey, Sharon Landesman; Bert, Shannon Carothers
OBJECTIVE To test the ability of a 3-item screening tool (Parenting Responsibility and Emotional Preparedness [PREP]) to detect adolescent mothers at elevated risk for nonoptimal parenting and poor child development outcomes at 2 years of age. DESIGN A 4-site prospective cohort study conducted from December 2001 to August 2007 of adolescent mothers recruited in the third trimester of pregnancy and followed up at 4, 8, 18, and 24 months post partum. SETTING Community clinics and home settings in Birmingham, Alabama; Kansas City, Kansas and Missouri; South Bend, Indiana; and Washington, DC. PARTICIPANTS A total of 270 first-time adolescent mothers (aged 15-19 years) and their infants (birth to 2 years of age). MAIN EXPOSURES Naturalistic observations of parent-child interactions and quality of home environment during the first 2 years of life. OUTCOME MEASURES Maternal mental health and cognitive indicators, positive mother-child interactions, quality of home environment, child social-emotional development, and child cognitive development (Bayley scales). RESULTS PREP scores identified adolescent mothers with significantly elevated depressive symptoms and childhood trauma and lower scores of knowledge of infant development and maternal IQ. PREP predicted significantly lower quality of home environments and higher levels of nonoptimal mother-child interactions at 4, 8, and 18 months. PREP also predicted significantly lower child outcomes at 2 years of age for cognitive scores and higher levels of depressive and withdrawal symptoms and dysregulation and negative emotionality. CONCLUSIONS PREP is a low-cost, easily administered, nonstigmatizing screening tool that identifies adolescent mothers who self-recognize that they need help to meet their infants' social, emotional, and cognitive needs.
Russo, Vincenzo; Rago, Anna; Pannone, Bruno; Papa, Andrea A; Di Meo, Federica; Mayer, Maria C; Spasiano, Anna; Russo, Maria G; Golino, Paolo; Calabrò, Raffaele; Nigro, Gerardo
Patients with beta-thalassemia major (β-TM) are at increased risk for sudden cardiac death (SCD). Heterogeneity of ventricular repolarization is considered to provide an electrophysiological substrate for malignant arrhythmias. QT dispersion (QTc-D) and JT dispersion (JTc-D) are electrocardiographic parameters indicative of heterogeneity of ventricular repolarization. The aim of our study was to evaluate the heterogeneity of ventricular repolarization in patients with beta-thalassemia and to test the hypothesis that an abnormal QTc and JTc dispersion may predict SCD in this population. The study involved 51 patients with β-TM (age 33.9±8.4; 33M) and 51 healthy subjects used as controls, matched for age, gender, and body mass index (BMI). Among the β-TM group, 14 patients with β-TM (age 27±6.64; 11M) died from SCD during follow-up. For each patient, QTD and JTD intervals were calculated. Compared to the healthy control group, β-TM group presented increased values of the QTc-D (65.36±33.95 vs. 37, 62±17.65; P<0.003) and JTc-D (74.64±33.27 vs. 40.32±12.45; P<0.001). In the β-TM sudden death group, QTc-D and JTc-D were significantly greater than in survived β-TM group (92.70±44.24 vs. 56.14±23.80, P=0.0001; 101.54±47.93 vs. 64.47±17.90, P=0.0001). A cutoff value of 70ms for QTc-D had a sensitivity and specificity of 77% in identifying patients at risk for SCD. A cutoff value of 100ms for JTc-D had a sensitivity of 65% and a specificity of 94% in identifying this category of patients. β-TM is associated with significant changes in heterogeneity of ventricular repolarization. QTc and JTc dispersion are useful markers of risk of SCD in patients with β-TM. © 2011 John Wiley & Sons A/S.
Qian, Jing; Zhu, Weiyou; Wang, Keming; Ma, Lin; Xu, Jin; Xu, Tongpeng; Røe, Oluf Dimitri; Li, Aiping; Zhou, Jianwei; Shu, Yongqian
Background and Aims JWA, a microtubule-associated protein (MAP) involved in apoptosis, has been identified as a suppressor of metastasis, and it affects cell migration in melanoma and its downregulation in tumor is an idependent negative prognostic factor in resectable gastric cancer. HER2 overexpression has been observed in gastric cancer (GC) cells and implicated in the metastatic phenotype. However, the biological role of JWA in migration and its clinical value in HER2-positive GC remain elusive. Results JWA suppresses EGF-induced cell migration and actin cytoskeletal rearrangement by abrogating HER2 expression and downstream PI3K/AKT signaling in HER2-overexpressing GC cell lines. The modulation of HER2 by JWA is dependent on ERK activation and consequent PEA3 upregulation and activation. Reduced JWA expression is associated with high HER2 expression and with poor survival in patients with AGC, whereas HER2 expression alone is not associated with survival. However, concomitant low JWA and high HER2 expression is associated with unfavorable outcomes. Additionally, when patients were stratified by JWA expression, those with higher HER2 expression in the low JWA expression subgroup exhibited worse survival. Methods The impact of JWA on the EGF-induced migration of HER2-positive GC cells was studied using transwell assays and G-LISA assays. Western blotting, real-time PCR, electrophoretic mobility shift assays and luciferase assays were utilized to investigate the mechanisms by which JWA affects HER2. The association of JWA with HER2 and its clinical value were further analyzed by IHC in 128 pairs of advanced gastric cancer (AGC) and adjacent normal tissue samples. Conclusions This study characterizes a novel mechanism for regulating cell motility in HER2-overexpressing GC cells involving JWA-mediated MEK/ERK/PEA3 signaling activation and HER2 downregulation. Furthermore, JWA may be a useful prognostic indicator for advanced GC and may help stratify HER2-positive
Martínez-López, B; Perez, A M; Sánchez-Vizcaíno, J M
The identification of premises that may play an important role in the introduction or spread of animal diseases is fundamental to the development of risk-based surveillance and control programs. A combination of geo-statistical and cluster analysis methods was used to identify geographical areas and periods of time at highest risk for introduction of the African horse sickness virus (AHSV) into the Castile and Leon (CyL) region of Spain. Risk was estimated based on the predicted premises-specific abundance of Culicoides spp., a vector for AHSV, and on the frequency of equine introductions from outside regions. The largest abundance of Culicoides spp. was observed between May and September in the northern region of CyL. Six significant (P-value <0.01) space-time clusters of equine premises were found, at which presence of Culicoides spp. was predicted and live equidae were introduced from outside CyL. The clusters included 37 equine premises and took place between April and December. These results will contribute to updating plans for prevention of AHSV introduction and spread in Spain. The methodological approach developed here may be adapted and applied to design and establish risk-based surveillance and control programs for Spain and other European countries.
Bruyère, Olivier; Cooper, Cyrus; Arden, Nigel; Branco, Jaime; Brandi, Maria Luisa; Herrero-Beaumont, Gabriel; Berenbaum, Francis; Dennison, Elaine; Devogelaer, Jean-Pierre; Hochberg, Marc; Kanis, John; Laslop, Andrea; McAlindon, Tim; Reiter, Susanne; Richette, Pascal; Rizzoli, René; Reginster, Jean-Yves
Osteoarthritis is a syndrome affecting a variety of patient profiles. A European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis and the European Union Geriatric Medicine Society working meeting explored the possibility of identifying different patient profiles in osteoarthritis. The risk factors for the development of osteoarthritis include systemic factors (e.g., age, sex, obesity, genetics, race, and bone density) and local biomechanical factors (e.g., obesity, sport, joint injury, and muscle weakness); most also predict disease progression, particularly joint injury, malalignment, and synovitis/effusion. The characterization of patient profiles should help to better orientate research, facilitate trial design, and define which patients are the most likely to benefit from treatment. There are a number of profile candidates. Generalized, polyarticular osteoarthritis and local, monoarticular osteoarthritis appear to be two different profiles; the former is a feature of osteoarthritis co-morbid with inflammation or the metabolic syndrome, while the latter is more typical of post-trauma osteoarthritis, especially in cases with severe malalignment. Other biomechanical factors may also define profiles, such as joint malalignment, loss of meniscal function, and ligament injury. Early- and late-stage osteoarthritis appear as separate profiles, notably in terms of treatment response. Finally, there is evidence that there are two separate profiles related to lesions in the subchondral bone, which may determine benefit from bone-active treatments. Decisions on appropriate therapy should be made considering clinical presentation, underlying pathophysiology, and stage of disease. Identification of patient profiles may lead to more personalized healthcare, with more targeted treatment for osteoarthritis.
Das, Marco; Mühlenbruch, Georg; Mahnken, Andreas H; Hering, K G; Sirbu, H; Zschiesche, W; Knoll, Lars; Felten, Michael K; Kraus, Thomas; Günther, Rolf W; Wildberger, Joachim E
The purpose of this study was to assess the prevalence of lung cancer in a high-risk asbestos-exposed cohort using low-dose MDCT. Of a population of 5,389 former power-plant workers, 316 were characterized as individuals at highest risk for lung cancer according to a lung-cancer risk model including age, asbestos exposure and smoking habits. Of these 316, 187 (mean age: 66.6 years) individuals were included in a prospective trial. Mean asbestos exposure time was 29.65 years and 89% were smokers. Screening was performed on a 16-slice MDCT (Siemens) with low-dose technique (10/20 mAs(eff.); 1 mm/0.5 mm increment). In addition to soft copy PACS reading analysis on a workstation with a dedicated lung analysis software (LungCARE; Siemens) was performed. One strongly suspicious mass and eight cases of histologically proven lung cancer were found plus 491 additional pulmonary nodules (average volume: 40.72 ml, average diameter 4.62 mm). Asbestos-related changes (pleural plaques, fibrosis) were visible in 80 individuals. Lung cancer screening in this high-risk cohort showed a prevalence of lung cancer of 4.28% (8/187) at baseline screening with an additional large number of indeterminate pulmonary nodules. Low-dose MDCT proved to be feasible in this highly selected population.
Chen, Haitao; Liu, Xu; Brendler, Charles B; Ankerst, Donna P; Leach, Robin J; Goodman, Phyllis J; Lucia, M Scott; Tangen, Catherine M; Wang, Li; Hsu, Fang-Chi; Sun, Jielin; Kader, A Karim; Isaacs, William B; Helfand, Brian T; Zheng, S Lilly; Thompson, Ian M; Platz, Elizabeth A; Xu, Jianfeng
While family history (FH) has been widely used to provide risk information, it captures only a small proportion of subjects with higher genetic susceptibility. Our objective is to assess whether a genetic risk score (GRS) calculated from prostate cancer (PCa) risk-associated single nucleotide polymorphisms (SNPs) can supplement FH for more effective risk stratification for PCa screening decision-making. A GRS was calculated based on 29 PCa risk-associated SNPs for 4,528 men of European descent in the placebo arm of the Prostate Cancer Prevention Trial (PCPT). At study entry, participants were free of PCa diagnosis. Performance of FH and GRS were measured by observed detection rate of PCa and high-grade PCa (Gleason score ≥7) during the 7-year study. GRS was a significant predictor of PCa in men with or without a positive FH (P = 1.18 × 10(-4) and P = 4.50 × 10(-16) , respectively). Using FH alone, as expected, the 17% of men who were FH+ had a PCa detection rate that was significantly higher (29.02%) than FH- men (23.43%, P = 0.001). When both FH+ or GRS >1.4 are considered, more than twice as many men (36%) can be classified as higher risk, as evidenced by a significantly higher PCa detection rate (30.98%) than in the remaining men (20.61%, P = 5.30 × 10(-15) ). If targeting only FH+ men, four out of five PCa cases would go undetected, as would a similarly large fraction (∼80%) of high-grade PCa cases. In comparison, if targeting FH+ or GRS >1.4 men, almost half of all PCa cases would be detected, including 45% of high-grade PCa cases. A prostate cancer GRS can supplement family history to better identify higher risk men for targeted intervention. Prostate 76:1120-1129, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
McNamara, Robert K.; Strawn, Jeffrey R.; Chang, Kiki D.; DelBello, Melissa P.
Synopsis Increasing evidence from retrospective and prospective studies is beginning to validate criteria to identify individuals at high risk for developing bipolar disorder or schizophrenia. In parallel, intervention trials are evaluating the efficacy and tolerability of pharmacological and non-pharmacological approaches for the treatment of sub-threshold and possibly prodromal presentations in these high-risk populations with the ultimate objective of mitigating illness progression. This article reviews current evidence for candidate interventions for high-risk individuals in an effort to guide future research in this rapidly emerging field. PMID:23040899
McMahon, M A; Peterson, C; Schilke, J
Osteoporosis is the most common systemic bone disorder causing thousands of injuries and deaths each year. The pathogenesis of osteoporosis is a complex puzzle that contains many interlocking pieces involving both genetic and environmental factors. The prevention of age-related bone loss, which could be gained through health teaching by the nurse, should be optimized. Nurses and other caregivers can make significant contributions toward the initial identification of those persons at risk or who may already have the debilitating disease by using the Osteoporosis Risk Questionnaire.
Bora, Emre; Pantelis, Christos
Theory of mind (ToM) deficit is a well-established feature of schizophrenia and has been suggested as a vulnerability marker of this disorder. However, as most of this evidence is based on studies in chronic patients, it is less clear whether ToM is impaired prior to or following the onset of a first-episode and whether it is evident in unaffected relatives of patients. In this meta-analysis, ToM performance of 3005 individuals with first-episode psychosis (FEP), individuals at ultra-high risk for psychosis (UHR) and unaffected relatives were compared with 1351 healthy controls. ToM was substantially impaired in first-episode psychosis (Cohen d=1.0) and this deficit was comparable to findings in chronic patients. ToM was also impaired in unaffected relatives (d=0.37) and UHR subjects (d=0.45) and performances of these groups were intermediate between FES and healthy controls. Severity of ToM deficits in unaffected relatives and UHR subjects was similar to other cognitive deficits observed in these groups. Longitudinal studies of clinical and genetic high-risk subjects are necessary to investigate the trajectory of development of ToM deficits in schizophrenia. Copyright © 2013 Elsevier B.V. All rights reserved.
Karyadi, Danielle M; Geybels, Milan S; Karlins, Eric; Decker, Brennan; McIntosh, Laura; Hutchinson, Amy; Kolb, Suzanne; McDonnell, Shannon K; Hicks, Belynda; Middha, Sumit; FitzGerald, Liesel M; DeRycke, Melissa S; Yeager, Meredith; Schaid, Daniel J; Chanock, Stephen J; Thibodeau, Stephen N; Berndt, Sonja I; Stanford, Janet L; Ostrander, Elaine A
Prostate cancer (PCa) susceptibility is defined by a continuum from rare, high-penetrance to common, low-penetrance alleles. Research to date has concentrated on identification of variants at the ends of that continuum. Taking an alternate approach, we focused on the important but elusive class of low-frequency, moderately penetrant variants by performing disease model-based variant filtering of whole exome sequence data from 75 hereditary PCa families. Analysis of 341 candidate risk variants identified nine variants significantly associated with increased PCa risk in a population-based, case-control study of 2,495 men. In an independent nested case-control study of 7,121 men, there was risk association evidence for TANGO2 p.Ser17Ter and the established HOXB13 p.Gly84Glu variant. Meta-analysis combining the case-control studies identified two additional variants suggestively associated with risk, OR5H14 p.Met59Val and CHAD p.Ala342Asp. The TANGO2 and HOXB13 variants co-occurred in cases more often than expected by chance and never in controls. Finally, TANGO2 p.Ser17Ter was associated with aggressive disease in both case-control studies separately. Our analyses identified three new PCa susceptibility alleles in the TANGO2, OR5H14 and CHAD genes that not only segregate in multiple high-risk families but are also of importance in altering disease risk for men from the general population. This is the first successful study to utilize sequencing in high-risk families for the express purpose of identifying low-frequency, moderately penetrant PCa risk mutations.
Karyadi, Danielle M.; Geybels, Milan S.; Karlins, Eric; Decker, Brennan; McIntosh, Laura; Hutchinson, Amy; Kolb, Suzanne; McDonnell, Shannon K.; Hicks, Belynda; Middha, Sumit; FitzGerald, Liesel M.; DeRycke, Melissa S.; Yeager, Meredith; Schaid, Daniel J.; Chanock, Stephen J.; Thibodeau, Stephen N.; Berndt, Sonja I.; Stanford, Janet L.; Ostrander, Elaine A.
Prostate cancer (PCa) susceptibility is defined by a continuum from rare, high-penetrance to common, low-penetrance alleles. Research to date has concentrated on identification of variants at the ends of that continuum. Taking an alternate approach, we focused on the important but elusive class of low-frequency, moderately penetrant variants by performing disease model-based variant filtering of whole exome sequence data from 75 hereditary PCa families. Analysis of 341 candidate risk variants identified nine variants significantly associated with increased PCa risk in a population-based, case-control study of 2,495 men. In an independent nested case-control study of 7,121 men, there was risk association evidence for TANGO2 p.Ser17Ter and the established HOXB13 p.Gly84Glu variant. Meta-analysis combining the case-control studies identified two additional variants suggestively associated with risk, OR5H14 p.Met59Val and CHAD p.Ala342Asp. The TANGO2 and HOXB13 variants co-occurred in cases more often than expected by chance and never in controls. Finally, TANGO2 p.Ser17Ter was associated with aggressive disease in both case-control studies separately. Our analyses identified three new PCa susceptibility alleles in the TANGO2, OR5H14 and CHAD genes that not only segregate in multiple high-risk families but are also of importance in altering disease risk for men from the general population. This is the first successful study to utilize sequencing in high-risk families for the express purpose of identifying low-frequency, moderately penetrant PCa risk mutations. PMID:27902461
... 49 Transportation 8 2010-10-01 2010-10-01 false Procedures for identifying the individual making the request. 1007.4 Section 1007.4 Transportation Other Regulations Relating to Transportation... CONTAINING INFORMATION ABOUT INDIVIDUALS § 1007.4 Procedures for identifying the individual making...
Sybill K. Amelon; Sarah E. Hooper; Kathryn M. Womack
The ability to recognize individuals within an animal population is fundamental to conservation and management. Identification of individual bats has relied on artificial marking techniques that may negatively affect the survival and alter the behavior of individuals. Biometric systems use biological characteristics to identify individuals. The field of animal...
Osondu, Chukwuemeka U; Aneni, Ehimen C; Shaharyar, Sameer; Roberson, Lara; Rouseff, Maribeth; Das, Sankalp; Spatz, Erica; Younus, Adnan; Guzman, Henry; Brown, Doris; Santiago-Charles, Joann; Ochoa, Teresa; Mora, Joseph; Gilliam, Cynthia; Lehn, Virginia; Sherriff, Shoshana; Tran, Thinh; Gonzalez, Anthony; Virani, Salim; Feldman, Theodore; Agatston, Arthur S; Nasir, Khurram
This is a single-arm, pre and post effectiveness study that evaluated the impact of a comprehensive workplace lifestyle program on severe obesity among high cardiovascular disease risk individuals in a large, diverse employee population. Employees of Baptist Health South Florida were considered eligible to participate if they had 2 or more of the following cardiometabolic risk factors: total cholesterol ≥200 mg/dL, systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg, hemoglobin A1c ≥6.5%, body mass index ≥30kg/m(2). Participants received a personalized diet plan and physical activity intervention, and were followed for 1 year. Data on anthropometric measurements, blood pressure, blood glucose, and other biochemical measures were collected. Participants' body mass index was calculated and their eligibility for bariatric surgery (BS) also assessed. A total of 297 persons participated in the program; 160 participants completed all procedures through 12 months of follow-up. At baseline, 34% (n = 100) of all participants were eligible for BS. In an intention-to-treat analysis, 27% (n = 27) of BS eligible participants at baseline became ineligible after 12 months. Considering program completers only, 46% of BS eligible participants at baseline became ineligible. Irrespective of BS eligibility at 12 months, mean values of cardiometabolic risk factors among program completers improved after the follow-up period. Workplace wellness programs provide an important option for weight loss that can obviate the need for BS, reduce cardiovascular disease risk, and potentially reduce costs. However, in designing future worksite lifestyle interventions, measures should be taken to improve participation and retention rates in such programs.
Kettunen, Eeva; Salmenkivi, Kaisa; Vuopala, Katri; Toljamo, Tuula; Kuosma, Eeva; Norppa, Hannu; Knuutila, Sakari; Kaleva, Simo; Huuskonen, Matti S; Anttila, Sisko
Lung cancer specimens display recurrent copy number aberrations in distinguished chromosomal regions as compared with normal lung cells. Such alterations have been utilized in design of fluorescence in situ hybridization (FISH) probe sets in attempts to improve the cytological diagnosis of lung cancer. One of such probe sets, LAVysion, detects copy number changes in the centromeric region of chromosome 6 (CEP6), and regions 5p15, 8q24, and 7p12, often gained in lung cancer. We evaluated the feasibility of the LAVysion multi-color probe set in detection of individuals at high risk of lung cancer by applying the FISH probe set on smears prepared of induced sputa obtained from 20 lung cancer patients, 43 asbestos-exposed workers, 21 heavy tobacco smokers, and 15 healthy never-smokers. The hybridized sputum smears were examined using fluorescence microscopy and the number of signals in epithelial cells was examined throughout the hybridized area. Additionally, we review here the previous studies using LAVysion probe set. The FISH probe set was slightly more sensitive than cytology alone in detecting lung cancer. No significant differences in copy number gain were found between high-risk individuals and healthy never-smokers. The proportions of individuals with copy number gains in sputa among the lung cancer patients, asbestos-exposed workers, tobacco smokers, and never-smokers were 50, 20, 12, and 27%, respectively, when three or more cells with a copy number gain detected by at least two different probes was used as the cut-off point. In comparison, the sensitivity of cytology in detecting lung cancer was 44%. In the lung cancer patients the number of abnormal cells by FISH correlated well with the cytologic atypia class (Spearman rank correlation coefficient 0.77, p<0.01). Using multivariant variance analysis, gains in CEP6, 5p15, 8q24 and 7p12 were not associated with smoking or asbestos exposure. FISH did not significantly exceed the sensitivity of sputum cytology
Ompad, Danielle C; Galea, Sandro; Vlahov, David
Vaccine distribution programs have historically targeted individuals at high risk of complications due to influenza. Despite recommendations from the Advisory Committee on Immunization Practices, vaccination coverage among high-risk populations has been generally low. This review systematically summarizes the recent literature evaluating programs in different settings, from within medical settings to venue-based and community-based approaches, in an effort to identify successful program components. The published literature was identified by using the MEDLINE database from 1990 to 2006 covering studies that reported on interventions or programs aimed at vaccinating high-risk populations. The authors reviewed 56 studies. In the United States, the Healthy People 2010 goals included 90% vaccination coverage for adults aged > or = 65 years and 60% for high-risk adults aged 18-64 years. Only a handful of the studies reviewed managed to meet those goals. Interventions that increased vaccination coverage to Healthy People 2010 goals included advertising, provider and patient mailings, registry-based telephone calls, patient and staff education, standing orders coupled with standardized forms, targeting of syringe exchange customers, and visiting nurses. Few studies evaluated the impact of vaccination programs by race/ethnicity and socioeconomic status. Few studies targeted individuals outside of the health-care and social services sectors. Given the growing disparities in health and health-care access, understanding the way in which interventions can remedy disparities is crucial.
Mueck, Krislynn M; Kao, Lillian S
Surgical site infections (SSIs) are a significant healthcare quality issue, resulting in increased morbidity, disability, length of stay, resource utilization, and costs. Identification of high-risk patients may improve pre-operative counseling, inform resource utilization, and allow modifications in peri-operative management to optimize outcomes. Review of the pertinent English-language literature. High-risk surgical patients may be identified on the basis of individual risk factors or combinations of factors. In particular, statistical models and risk calculators may be useful in predicting infectious risks, both in general and for SSIs. These models differ in the number of variables; inclusion of pre-operative, intra-operative, or post-operative variables; ease of calculation; and specificity for particular procedures. Furthermore, the models differ in their accuracy in stratifying risk. Biomarkers may be a promising way to identify patients at high risk of infectious complications. Although multiple strategies exist for identifying surgical patients at high risk for SSIs, no one strategy is superior for all patients. Further efforts are necessary to determine if risk stratification in combination with risk modification can reduce SSIs in these patient populations.
Peer, Nasheeta; Balakrishna, Yusentha; de Villiers, Anniza; Crickmore, Christelle; Mungal-Singh, Vash
To determine the proportion of participants identified with previously undiagnosed diabetes and untreated hypertension in the Heart and Stroke Foundation South Africa's screening programme. This cross-sectional study was conducted nationally in 2013 among ≥18-year-old adults self-selected for screening. Data collection included medical history and behaviours related to diet, physical activity, smoking and alcohol use. Clinical measurements comprised blood pressure, anthropometry and point-of-care random blood glucose and cholesterol assessments. Among the 7711 participants, 2488 men and 5223 women, mean ages were 47.6 years and 48.6 years, respectively. Prevalence of diabetes was 13.8% in men and 12.8% in women but only 1.8% (45) and 0.9% (47), respectively, were newly diagnosed. Another 14.5% (men) and 12.4% (women) had impaired glycaemia. Only 32.9% and 36.3% with known diabetes were controlled. Hypertension was prevalent in 51.8% of men and 48.9% of women, 52.0% and 63.1% of whom were using anti-hypertensive medication; 43.2% of men and 45.5% of women on anti-hypertensive medication were controlled. Very few individuals with newly diagnosed diabetes were identified, which underscores the need for cost-effective targeted screening of high-risk individuals to optimize diagnosis. Furthermore, the suboptimal levels of diabetes and hypertension control highlights the need for improved care.
The Relationship of Neurocognition and Negative Symptoms to Social and Role Functioning Over Time in Individuals at Clinical High Risk in the First Phase of the North American Prodrome Longitudinal Study
Meyer, Eric C.; Carrión, Ricardo E.; Cornblatt, Barbara A.; Addington, Jean; Cadenhead, Kristin S.; Cannon, Tyrone D.; McGlashan, Thomas H.; Perkins, Diana O.; Tsuang, Ming T.; Walker, Elaine F.; Woods, Scott W.; Heinssen, Robert; Seidman, Larry J.
Objectives: Impaired social, role, and neurocognitive functioning are preillness characteristics of people who later develop psychosis. In people with schizophrenia, neurocognition and negative symptoms are associated with functional impairment. We examined the relative contributions of neurocognition and symptoms to social and role functioning over time in clinically high-risk (CHR) individuals and determined if negative symptoms mediated the influence of cognition on functioning. Methods: Social, role, and neurocognitive functioning and positive, negative, and disorganized symptoms were assessed in 167 individuals at CHR for psychosis in the North American Prodrome Longitudinal Study Phase 1 (NAPLS-1), of whom 96 were reassessed at 12 months. Results: Regression analyses indicated that negative symptoms accounted for unique variance in social and role functioning at baseline and follow-up. Composite neurocognition accounted for unique, but modest, variance in social and role functioning at baseline and in role functioning at follow-up. Negative symptoms mediated the relationship between composite neurocognition and social and role functioning across time points. In exploratory analyses, individual tests (IQ estimate, Digit Symbol/Coding, verbal memory) selectively accounted for social and role functioning at baseline and follow-up after accounting for symptoms. When negative symptom items with content overlapping with social and role functioning measures were removed, the relationship between neurocognition and social and role functioning was strengthened. Conclusion: The modest overlap among neurocognition, negative symptoms, and social and role functioning indicates that these domains make substantially separate contributions to CHR individuals. PMID:24550526
... TRADING COMMISSION RECORDS MAINTAINED ON INDIVIDUALS § 146.4 Procedures for identifying the individual making the request. When a request for information or for access to records has been made pursuant to... information is given and records are disclosed only to the proper person. (a) An individual may establish...
Ichikawa, Kazunobu; Konta, Tsuneo; Ikeda, Ami; Fujimoto, Shouichi; Iseki, Kunitoshi; Moriyama, Toshiki; Yamagata, Kunihiro; Tsuruya, Kazuhiko; Yoshida, Hideaki; Asahi, Koichi; Kurahashi, Issei; Ohashi, Yasuo; Watanabe, Tsuyoshi
Clinical information regarding risk factors may be helpful in the detection of various diseases. This cross-sectional study examined the characteristics of subjects with past history of renal failure, and assessed whether this information would be useful for the efficient detection of high-risk individuals for chronic kidney disease (CKD) and cardiovascular disease (CVD) at health checkup. This study utilized data from a nationwide health checkup, "The Specific Health Check and Guidance in Japan," and data for 250,130 adult subjects were analyzed. Subjects with self-reported history of renal failure and receiving dialysis therapy were defined as having a history of renal failure. Among total participants, there were 1,400 (0.6%) with a history of renal failure. The prevalence of a history of renal failure was higher in subjects with CKD than in those without CKD (1.5 vs. 0.3%, P < 0.001) and increased with progression of the stage of CKD (0.9-43.5%). Subjects with a history of renal failure had a reduced estimated glomerular filtration rate (44.6 ± 20.3 ml/min/1.73 m(2)) and a higher prevalence of CKD (50.5%) and CVD (31.9%), compared with subjects with hypertension, diabetes or metabolic syndrome. Multivariate logistic regression analysis showed an independent association between a history of CVD and renal failure (odds ratio 3.68, 95% confidence interval 3.26-4.15), after adjustment for confounding factors. A history of renal failure was strongly associated with advanced CKD and CVD. Information regarding history of renal failure could be utilized to efficiently detect high-risk individuals at health checkup.
Yoon, Hyuk; Kim, Nayoung
Gastric cancer is associated with high morbidity and mortality worldwide. To reduce the socioeconomic burden related to gastric cancer, it is very important to identify and manage high risk group for gastric cancer. In this review, we describe the general risk factors for gastric cancer and define high risk group for gastric cancer. We discuss strategies for the effective management of patients for the prevention and early detection of gastric cancer. Atrophic gastritis (AG) and intestinal metaplasia (IM) are the most significant risk factors for gastric cancer. Therefore, the accurate selection of individuals with AG and IM may be a key strategy for the prevention and/or early detection of gastric cancer. Although endoscopic evaluation using enhanced technologies such as narrow band imaging-magnification, the serum pepsinogen test, Helicobacter pylori serology, and trefoil factor 3 have been evaluated, a gold standard method to accurately select individuals with AG and IM has not emerged. In terms of managing patients at high risk of gastric cancer, it remains uncertain whether H. pylori eradication reverses and/or prevents the progression of AG and IM. Although endoscopic surveillance in high risk patients is expected to be beneficial, further prospective studies in large populations are needed to determine the optimal surveillance interval. PMID:25547086
Costa, Bernardo; Cabré, Joan J; Sagarra, Ramon; Solà-Morales, Oriol; Barrio, Francisco; Piñol, Josep L; Cos, Xavier; Bolíbar, Bonaventura; Castell, Conxa; Kissimova-Skarbek, Katarzyna; Tuomilehto, Jaakko
Type 2 diabetes is an important preventable disease and a growing public health problem. Based on information provided by clinical trials, we know that Type 2 diabetes can be prevented or delayed by lifestyle intervention. In view of translating the findings of diabetes prevention research into real-life it is necessary to carry out community-based evaluations so as to learn about the feasibility and effectiveness of locally designed and implemented programmes. The aim of this project was to assess the effectiveness of an active real-life primary care strategy in high-risk individuals for developing diabetes, and then evaluate its efficiency. Cost-Effectiveness analysis of the DE-PLAN (Diabetes in Europe - Prevention using Lifestyle, physical Activity and Nutritional intervention) project when applied to a Mediterranean population in Catalonia (DE-PLAN-CAT). Multicenter, longitudinal cohort assessment (4 years) conducted in 18 primary health-care centres (Catalan Health Institute). Individuals without diabetes aged 45-75 years were screened using the Finnish Diabetes Risk Score - FINDRISC - questionnaire and a 2-h oral glucose tolerance test. All high risk tested individuals were invited to participate in either a usual care intervention (information on diet and cardiovascular health without individualized programme), or the intensive DE-PLAN educational program (individualized or group) periodically reinforced. Oral glucose tolerance test was repeated yearly to determine diabetes incidence. Besides measuring the accumulated incidence of diabetes, information was collected on economic impact of the interventions in both cohorts (using direct and indirect cost questionnaires) and information on utility measures (Quality Adjusted Life Years). A cost-utility and a cost-effectiveness analysis will be performed and data will be modelled to predict long-term cost-effectiveness. The project was intended to evidence that a substantial reduction in Type 2 diabetes incidence
Background Type 2 diabetes is an important preventable disease and a growing public health problem. Based on information provided by clinical trials, we know that Type 2 diabetes can be prevented or delayed by lifestyle intervention. In view of translating the findings of diabetes prevention research into real-life it is necessary to carry out community-based evaluations so as to learn about the feasibility and effectiveness of locally designed and implemented programmes. The aim of this project was to assess the effectiveness of an active real-life primary care strategy in high-risk individuals for developing diabetes, and then evaluate its efficiency. Methods/Design Cost-Effectiveness analysis of the DE-PLAN (Diabetes in Europe - Prevention using Lifestyle, physical Activity and Nutritional intervention) project when applied to a Mediterranean population in Catalonia (DE-PLAN-CAT). Multicenter, longitudinal cohort assessment (4 years) conducted in 18 primary health-care centres (Catalan Health Institute). Individuals without diabetes aged 45-75 years were screened using the Finnish Diabetes Risk Score - FINDRISC - questionnaire and a 2-h oral glucose tolerance test. All high risk tested individuals were invited to participate in either a usual care intervention (information on diet and cardiovascular health without individualized programme), or the intensive DE-PLAN educational program (individualized or group) periodically reinforced. Oral glucose tolerance test was repeated yearly to determine diabetes incidence. Besides measuring the accumulated incidence of diabetes, information was collected on economic impact of the interventions in both cohorts (using direct and indirect cost questionnaires) and information on utility measures (Quality Adjusted Life Years). A cost-utility and a cost-effectiveness analysis will be performed and data will be modelled to predict long-term cost-effectiveness. Discussion The project was intended to evidence that a substantial
Fletcher, Kathryn; Parker, Gordon; Paterson, Amelia; Synnott, Howe
Risk-taking behaviours during hypomanic states are recognised, however the high-risk nature of some behaviours-including the potential for harm to both the individual and others-has not been detailed in the research literature. The current study examines risk-taking behaviours and their consequences (including their potential for impairment) in those with a bipolar II condition. Participants were recruited from the Sydney-based Black Dog Institute Depression Clinic. Diagnostic assignment of bipolar II disorder was based on clinician judgement and formal DSM-IV criteria. Participants completed a series of detailed questions assessing previous risk-taking behaviours during hypomanic states. The sample comprised a total of 93 participants. Risk-taking behaviours during hypomania included spending significant amounts of money, excessive alcohol or drug use, dangerous driving and endangering sexual activities. Key consequences included interpersonal conflict, substantial financial burden and feelings of guilt, shame and remorse. Despite recognition of the risks and consequences associated with hypomanic behaviours, less than one-fifth of participants agreed that hypomania should be treated because of the associated risks. Study limitations included a cross-sectional design, reliance on self-report information, lack of controlling for current mood state, and comprised a tertiary referral sample that may be weighted to more severe cases. Findings may therefore not be generalisable and require replication. Risk-taking behaviours during hypomania are common, and often linked with serious consequences. Whilst hypomania is often enjoyed and romanticised by patients-leading to ambivalence around treatment of such states-careful consideration of the impact of risk-taking behaviour is necessary, while the study raises the question as to what is 'impairment' in hypomania. Findings should advance clinical management by identifying those high-risk behaviours that would benefit from
The relationship of neurocognition and negative symptoms to social and role functioning over time in individuals at clinical high risk in the first phase of the North American Prodrome Longitudinal Study.
Meyer, Eric C; Carrión, Ricardo E; Cornblatt, Barbara A; Addington, Jean; Cadenhead, Kristin S; Cannon, Tyrone D; McGlashan, Thomas H; Perkins, Diana O; Tsuang, Ming T; Walker, Elaine F; Woods, Scott W; Heinssen, Robert; Seidman, Larry J
Impaired social, role, and neurocognitive functioning are preillness characteristics of people who later develop psychosis. In people with schizophrenia, neurocognition and negative symptoms are associated with functional impairment. We examined the relative contributions of neurocognition and symptoms to social and role functioning over time in clinically high-risk (CHR) individuals and determined if negative symptoms mediated the influence of cognition on functioning. Social, role, and neurocognitive functioning and positive, negative, and disorganized symptoms were assessed in 167 individuals at CHR for psychosis in the North American Prodrome Longitudinal Study Phase 1 (NAPLS-1), of whom 96 were reassessed at 12 months. Regression analyses indicated that negative symptoms accounted for unique variance in social and role functioning at baseline and follow-up. Composite neurocognition accounted for unique, but modest, variance in social and role functioning at baseline and in role functioning at follow-up. Negative symptoms mediated the relationship between composite neurocognition and social and role functioning across time points. In exploratory analyses, individual tests (IQ estimate, Digit Symbol/Coding, verbal memory) selectively accounted for social and role functioning at baseline and follow-up after accounting for symptoms. When negative symptom items with content overlapping with social and role functioning measures were removed, the relationship between neurocognition and social and role functioning was strengthened. The modest overlap among neurocognition, negative symptoms, and social and role functioning indicates that these domains make substantially separate contributions to CHR individuals. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: email@example.com.
Hajek, Tomas; Cooke, Christopher; Kopecek, Miloslav; Novak, Tomas; Hoschl, Cyril; Alda, Martin
Background Brain imaging is of limited diagnostic use in psychiatry owing to clinical heterogeneity and low sensitivity/specificity of between-group neuroimaging differences. Machine learning (ML) may better translate neuroimaging to the level of individual participants. Studying unaffected offspring of parents with bipolar disorders (BD) decreases clinical heterogeneity and thus increases sensitivity for detection of biomarkers. The present study used ML to identify individuals at genetic high risk (HR) for BD based on brain structure. Methods We studied unaffected and affected relatives of BD probands recruited from 2 sites (Halifax, Canada, and Prague, Czech Republic). Each participant was individually matched by age and sex to controls without personal or family history of psychiatric disorders. We applied support vector machines (SVM) and Gaussian process classifiers (GPC) to structural MRI. Results We included 45 unaffected and 36 affected relatives of BD probands matched by age and sex on an individual basis to healthy controls. The SVM of white matter distinguished unaffected HR from control participants (accuracy = 68.9%, p = 0.001), with similar accuracy for the GPC (65.6%, p = 0.002) or when analyzing data from each site separately. Differentiation of the more clinically heterogeneous affected familiar group from healthy controls was less accurate (accuracy = 59.7%, p = 0.05). Machine learning applied to grey matter did not distinguish either the unaffected HR or affected familial groups from controls. The regions that most contributed to between-group discrimination included white matter of the inferior/middle frontal gyrus, inferior/middle temporal gyrus and precuneus. Limitations Although we recruited 126 participants, ML benefits from even larger samples. Conclusions Machine learning applied to white but not grey matter distinguished unaffected participants at high and low genetic risk for BD based on regions previously implicated in the
Hajek, Tomas; Cooke, Christopher; Kopecek, Miloslav; Novak, Tomas; Hoschl, Cyril; Alda, Martin
Brain imaging is of limited diagnostic use in psychiatry owing to clinical heterogeneity and low sensitivity/specificity of between-group neuroimaging differences. Machine learning (ML) may better translate neuroimaging to the level of individual participants. Studying unaffected offspring of parents with bipolar disorders (BD) decreases clinical heterogeneity and thus increases sensitivity for detection of biomarkers. The present study used ML to identify individuals at genetic high risk (HR) for BD based on brain structure. We studied unaffected and affected relatives of BD probands recruited from 2 sites (Halifax, Canada, and Prague, Czech Republic). Each participant was individually matched by age and sex to controls without personal or family history of psychiatric disorders. We applied support vector machines (SVM) and Gaussian process classifiers (GPC) to structural MRI. We included 45 unaffected and 36 affected relatives of BD probands matched by age and sex on an individual basis to healthy controls. The SVM of white matter distinguished unaffected HR from control participants (accuracy = 68.9%, p = 0.001), with similar accuracy for the GPC (65.6%, p = 0.002) or when analyzing data from each site separately. Differentiation of the more clinically heterogeneous affected familiar group from healthy controls was less accurate (accuracy = 59.7%, p = 0.05). Machine learning applied to grey matter did not distinguish either the unaffected HR or affected familial groups from controls. The regions that most contributed to between-group discrimination included white matter of the inferior/middle frontal gyrus, inferior/middle temporal gyrus and precuneus. Although we recruited 126 participants, ML benefits from even larger samples. Machine learning applied to white but not grey matter distinguished unaffected participants at high and low genetic risk for BD based on regions previously implicated in the pathophysiology of BD.
Because identifiable factors contribute to allograft loss, and because no consensus has been reached on the definition of high risk, an interdisciplinary group of nurses, physicians, pharmacists, and social workers was convened in May 2008. Participants sought to reach consensus about the current state of science and best practices related to the definition and management of high-risk kidney transplant recipients. An expert facilitator with extensive experience in leading consensus teams guided consensus-building activities, which included discussion and small-group work. This consensus group conceptualized the definition of the "high-risk" kidney transplant recipient and provided information to guide the multidisciplinary team in their assessment of these patients before and after transplant. Three key areas, which were conceptualized as independent scales, had a substantial impact on outcomes: (1) transplant recipient medical factors, (2) donor and recipient immunological factors, and (3) transplant recipient psychosocial factors. Though depicted separately, alteration of a specific risk on one scale could influence some risk factors on another scale. In addition, the kidney allograft itself must be considered in the assessment of high risk. The continuum of risk described here should be useful to transplant clinicians in their assessment of high-risk adult kidney transplant patients, may aid centers in developing a more complete definition of high risk, and may lead to risk-reduction efforts.
Cotrina Luque, J; Guerrero Aznar, M D; Alvarez del Vayo Benito, C; Jimenez Mesa, E; Guzman Laura, K P; Fernández Fernández, L
«High-risk drugs» are those that have a very high «risk» of causing death or serious injury if an error occurs during its use. The Institute for Safe Medication Practices (ISMP) has prepared a high-risk drugs list applicable to the general population (with no differences between the pediatric and adult population). Thus, there is a lack of information for the pediatric population. The main objective of this work is to develop a high-risk drug list adapted to the neonatal or pediatric population as a reference model for the pediatric hospital health workforce. We made a literature search in May 2012 to identify any published lists or references in relation to pediatric and/or neonatal high-risk drugs. A total of 15 studies were found, from which 9 were selected. A model list was developed mainly based on the ISMP one, adding strongly perceived pediatric risk drugs and removing those where the pediatric use was anecdotal. There is no published list that suits pediatric risk management. The list of pediatric and neonatal high-risk drugs presented here could be a «reference list of high-risk drugs » for pediatric hospitals. Using this list and training will help to prevent medication errors in each drug supply chain (prescribing, transcribing, dispensing and administration). Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.
Corcoran, Cheryl; Davidson, Larry; Sills-Shahar, Rachel; Nickou, Connie; Malaspina, Dolores; Miller, Tandy; McGlashan, Thomas
Because schizophrenia is difficult to treat and exacts large personal and societal costs, there is an effort underway to identify adolescents and young adults at high risk for psychosis. Theory-derived criteria of subthreshold positive symptoms identify a “prodromal” or clinically at-risk population who have conversion rates to psychosis of 40 to 50% within one to two years. However, further characterization of the psychosis prodrome by qualitative research methods could increase the predictive value of the “prodromal” designation. We conducted open-ended interviews with 20 parents of prodromal adolescents that focused on changes observed. The narratives fell into two thematically distinct subgroups, identified as “declining” and “never normal.” The prodromal adolescents described as “declining” had a higher subsequent rate of conversion to psychosis than did the “never normal” group. Although preliminary, these results suggest that a trajectory of change in personality, relationships, and behavior from an essentially normal baseline may be consistent with increased risk for psychosis among prodromal adolescents. PMID:14686457
Rautio, Nina; Jokelainen, Jari; Oksa, Heikki; Saaristo, Timo; Peltonen, Markku; Niskanen, Leo; Saltevo, Juha; Korpi-Hyövälti, Eeva; Uusitupa, Matti; Tuomilehto, Jaakko; Keinänen-Kiukaanniemi, Sirkka
To describe socioeconomic characteristics of participants and their effect on uptake and completion of the implementation project (FIN-D2D) for the National Type 2 Diabetes Prevention Programme. Furthermore, to assess the effectiveness of individual vs. group intervention during one-year follow-up. At baseline, 2820 men and 5764 women aged <65 years participated in the non-randomized implementation project in primary health care setting; one-year follow-up was available for 1067 men and 2122 women. Socioeconomic status included education and occupation. Interventions were individual and/or group-based. The changes in cardiovascular risk factors and glucose tolerance were used as measures of the effectiveness of intervention. 68.4% of the men and 69.8% of the women participated in some of the intervention modalities offered. Low education and not working were related to active participation in the intervention in men. 88.2% of men and 76.1% of women selected the individual instead of group intervention. The effectiveness of individual vs. group interventions did not differ, except for minor changes in systolic blood pressure in women and glucose tolerance in men. Socioeconomic status modulated participation in interventions. Both types of intervention worked equally well, but participation in group intervention was low. Copyright © 2012 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.
DeSalvo, Karen; Lurie, Nicole; Finne, Kristen; Worrall, Chris; Bogdanov, Alina; Dinkler, Ayame; Babcock, Sarah; Kelman, Jeffrey
During a disaster or prolonged power outage, individuals who use electricity-dependent medical equipment are often unable to operate it and seek care in acute care settings or local shelters. Public health officials often report that they do not have proactive and systematic ways to rapidly identify and assist these individuals. In June 2013, we piloted a first-in-the-nation emergency preparedness drill in which we used Medicare claims data to identify individuals with electricity-dependent durable medical equipment during a disaster and securely disclosed it to a local health department. We found that Medicare claims data were 93% accurate in identifying individuals using a home oxygen concentrator or ventilator. The drill findings suggest that claims data can be useful in improving preparedness and response for electricity-dependent populations.
DeSalvo, Karen; Finne, Kristen; Worrall, Chris; Bogdanov, Alina; Dinkler, Ayame; Babcock, Sarah; Kelman, Jeffrey
During a disaster or prolonged power outage, individuals who use electricity-dependent medical equipment are often unable to operate it and seek care in acute care settings or local shelters. Public health officials often report that they do not have proactive and systematic ways to rapidly identify and assist these individuals. In June 2013, we piloted a first-in-the-nation emergency preparedness drill in which we used Medicare claims data to identify individuals with electricity-dependent durable medical equipment during a disaster and securely disclosed it to a local health department. We found that Medicare claims data were 93% accurate in identifying individuals using a home oxygen concentrator or ventilator. The drill findings suggest that claims data can be useful in improving preparedness and response for electricity-dependent populations. PMID:24832404
Ilin, Yelena; Kraft, Mary L
The cellular and matrix cues that induce stem cell differentiation into distinct cell lineages must be identified to permit the ex vivo expansion of desired cell populations for clinical applications. Combinatorial biomaterials enable screening multiple different microenvironments while using small numbers of rare stem cells. New methods to identify the phenotypes of individual cells in cocultures with location specificity would increase the efficiency and throughput of these screening platforms. Here, we demonstrate that partial least-squares discriminant analysis (PLS-DA) models of calibration Raman spectra from cells in pure cultures can be used to identify the lineages of individual cells in more complex culture environments. The calibration Raman spectra were collected from individual cells of four different lineages, and a PLS-DA model that captured the Raman spectral profiles characteristic of each cell line was created. The application of these models to Raman spectra from test sets of cells indicated individual, fixed and living cells in separate monocultures, as well as those in more complex culture environments, such as cocultures, could be identified with low error. Cells from populations with very similar biochemistries could also be identified with high accuracy. We show that these identifications are based on reproducible cell-related spectral features, and not spectral contributions from the culture environment. This work demonstrates that PLS-DA of Raman spectra acquired from pure monocultures provides an objective, noninvasive, and label-free approach for accurately identifying the lineages of individual, living cells in more complex coculture environments.
Velema, J P; van Wijnen, G; Bult, P; van Naerssen, T; Jota, S
We performed a hospital-based case-control study to identify high risk groups and routes of transmission of typhoid fever in the city of Ujung Pandang on the island of Sulawesi, Indonesia. The annual incidence of this disease in southern Sulawesi is estimated at 3.1/1000 and the case fatality at 5.1% Cases were 50 patients over 13 years of age admitted to Stella Maris Hospital with a diagnosis of typhoid fever between June and September 1991. Diagnosis was made on clinical grounds and in 90% of cases confirmed by a Widal test. Controls were 42 patients admitted for non-infectious disorders during the same period and individually matched by age and sex. Controls did not have a history of typhoid fever. Interviews took place in hospital. Analysis was by unconditional logistic regression. High-risk groups consisted of those who were single, unemployed and those who had a university education. Median age of cases was 22 years. Consumption of food from warungs (food stalls in the street) was strongly associated with risk (OR = 45). Both cases and controls washed hands after use of the toilet and before meals, but cases used soap significantly less often (OR = 30). The results of this study can be used to take preventive measures against this severe disease of educated and single young adults by targetting them for IEC-activities emphasizing the importance of thorough hand-washing and the need to take care in the selection of street-foods.
Elena, Paillaud; Sylvie, Bastuji-Garin; Anne, Plonquet; Emile, Foucat; Bénédicte, Fournier; Emmanuelle, Boutin; Aurélie, Le Thuaut; Yves, Levy; Sophie, Hue
We hypothesized that low-grade inflammation was driven by microbial translocation and associated with an increased risk of healthcare-associated infections (HAIs). We included 121 patients aged 75 years or over in this prospective cohort study. High-sensitivity C-reactive protein (hs-CRP), I-FABP, and sCD14 -- as markers for low-grade inflammation, intestinal epithelial barrier integrity, and monocyte activation, respectively -- were measured at admission. HAIs occurred during hospitalization in 62 (51%) patients. Elevated hs-CRP (≥6.02 mg/L, i.e., the median) was associated with a significantly higher HAI risk when I-FABP was in the highest quartile (odds ratio [OR], 4; 95% confidence interval [95%CI], 1.39-11.49; P=0.010). In patients with hs-CRP elevation and highest-quartile I-FABP, sCD14 elevation (≥0.65 pg/mL, i.e., the median) was associated with an 11-fold higher HAI risk (OR, 10.8; 95%CI, 2.28-51.1; P=0.003). Multivariate analyses adjusted for invasive procedures and comorbidities did not change the associations linking the three markers to the HAI risk. Increased levels of hs-CRP, I-FABP, and sCD14 may reflect loss of intestinal epithelial barrier integrity with microbial translocation leading to monocyte activation and low-grade inflammation. In our cohort, these markers identified patients at high risk for HAIs.
Singh, Jay P.; Fazel, Seena; Gueorguieva, Ralitza; Buchanan, Alec
Background Rates of violence in persons identified as high risk by structured risk assessment instruments (SRAIs) are uncertain and frequently unreported by validation studies. Aims To analyse the variation in rates of violence in individuals identified as high risk by SRAIs. Method A systematic search of databases (1995-2011) was conducted for studies on nine widely used assessment tools. Where violence rates in high-risk groups were not published, these were requested from study authors. Rate information was extracted, and binomial logistic regression was used to study heterogeneity. Results Information was collected on 13 045 participants in 57 samples from 47 independent studies. Annualised rates of violence in individuals classified as high risk varied both across and within instruments. Rates were elevated when population rates of violence were higher, when a structured professional judgement instrument was used and when there was a lower proportion of men in a study. Conclusions After controlling for time at risk, the rate of violence in individuals classified as high risk by SRAIs shows substantial variation. In the absence of information on local base rates, assigning predetermined probabilities to future violence risk on the basis of a structured risk assessment is not supported by the current evidence base. This underscores the need for caution when such risk estimates are used to influence decisions related to individual liberty and public safety. PMID:24590974
Gordon, Evan M; Laumann, Timothy O; Adeyemo, Babatunde; Gilmore, Adrian W; Nelson, Steven M; Dosenbach, Nico U F; Petersen, Steven E
Recent work has made important advances in describing the large-scale systems-level organization of human cortex by analyzing functional magnetic resonance imaging (fMRI) data averaged across groups of subjects. However, new findings have emerged suggesting that individuals' cortical systems are topologically complex, containing small but reliable features that cannot be observed in group-averaged datasets, due in part to variability in the position of such features along the cortical sheet. This previous work has reported only specific examples of these individual-specific system features; to date, such features have not been comprehensively described. Here we used fMRI to identify cortical system features in individual subjects within three large cross-subject datasets and one highly sampled within-subject dataset. We observed system features that have not been previously characterized, but 1) were reliably detected across many scanning sessions within a single individual, and 2) could be matched across many individuals. In total, we identified forty-three system features that did not match group-average systems, but that replicated across three independent datasets. We described the size and spatial distribution of each non-group feature. We further observed that some individuals were missing specific system features, suggesting individual differences in the system membership of cortical regions. Finally, we found that individual-specific system features could be used to increase subject-to-subject similarity. Together, this work identifies individual-specific features of human brain systems, thus providing a catalog of previously unobserved brain system features and laying the foundation for detailed examinations of brain connectivity in individuals.
Purcell, Jeremy J.; Rapp, Brenda
Previous research has shown that damage to the neural substrates of orthographic processing can lead to functional reorganization during reading (Tsapkini et al., 2011); in this research we ask if the same is true for spelling. To examine the functional reorganization of spelling networks we present a novel three-stage Individual Peak Probability Comparison (IPPC) analysis approach for comparing the activation patterns obtained during fMRI of spelling in a single brain-damaged individual with dysgraphia to those obtained in a set of non-impaired control participants. The first analysis stage characterizes the convergence in activations across non-impaired control participants by applying a technique typically used for characterizing activations across studies: Activation Likelihood Estimate (ALE) (Turkeltaub et al., 2002). This method was used to identify locations that have a high likelihood of yielding activation peaks in the non-impaired participants. The second stage provides a characterization of the degree to which the brain-damaged individual's activations correspond to the group pattern identified in Stage 1. This involves performing a Mahalanobis distance statistics analysis (Tsapkini et al., 2011) that compares each of a control group's peak activation locations to the nearest peak generated by the brain-damaged individual. The third stage evaluates the extent to which the brain-damaged individual's peaks are atypical relative to the range of individual variation among the control participants. This IPPC analysis allows for a quantifiable, statistically sound method for comparing an individual's activation pattern to the patterns observed in a control group and, thus, provides a valuable tool for identifying functional reorganization in a brain-damaged individual with impaired spelling. Furthermore, this approach can be applied more generally to compare any individual's activation pattern with that of a set of other individuals. PMID:24399981
Purcell, Jeremy J; Rapp, Brenda
Previous research has shown that damage to the neural substrates of orthographic processing can lead to functional reorganization during reading (Tsapkini et al., 2011); in this research we ask if the same is true for spelling. To examine the functional reorganization of spelling networks we present a novel three-stage Individual Peak Probability Comparison (IPPC) analysis approach for comparing the activation patterns obtained during fMRI of spelling in a single brain-damaged individual with dysgraphia to those obtained in a set of non-impaired control participants. The first analysis stage characterizes the convergence in activations across non-impaired control participants by applying a technique typically used for characterizing activations across studies: Activation Likelihood Estimate (ALE) (Turkeltaub et al., 2002). This method was used to identify locations that have a high likelihood of yielding activation peaks in the non-impaired participants. The second stage provides a characterization of the degree to which the brain-damaged individual's activations correspond to the group pattern identified in Stage 1. This involves performing a Mahalanobis distance statistics analysis (Tsapkini et al., 2011) that compares each of a control group's peak activation locations to the nearest peak generated by the brain-damaged individual. The third stage evaluates the extent to which the brain-damaged individual's peaks are atypical relative to the range of individual variation among the control participants. This IPPC analysis allows for a quantifiable, statistically sound method for comparing an individual's activation pattern to the patterns observed in a control group and, thus, provides a valuable tool for identifying functional reorganization in a brain-damaged individual with impaired spelling. Furthermore, this approach can be applied more generally to compare any individual's activation pattern with that of a set of other individuals.
Fries, J F; McShane, D
We undertook this study to identify persons with high medical use to target them for health promotion and self-management interventions specific to their problems. We compared the reductions in cost and health risk of a health education program aimed at high-risk persons with a similar program addressed to all risk levels. We compared health risk and use in 2,586 high-risk persons with those of employee (N = 50,576) and senior (N = 39,076) groups and contrasted results in specific high-risk disease or behavior categories (modules)--arthritis, back pain, high blood pressure, diabetes mellitus, heart disease, smoking, and obesity--against each other, using validated self-report measures, over a 6-month period. Interventions were a standard generic health education program and a similar program directed at high risk individuals (Healthtrac). Health risk scores improved by 11% in the overall high-risk group compared with 9% in the employee group and 6% in the senior group. Physician use decreased by 0.8 visits per 6 months in the high-risk group compared with 0.05 and 0.15 visits, respectively, per 6 months in the employee and senior groups. Hospital stays decreased by 0.2 days per 6 months in the high-risk group compared with 0.05 days in the comparison groups. The duration of illness or confinement to home decreased by 0.9 days per 6 months in the high-risk group and 0.15 and 0.25, respectively, in the employee and senior groups. Using imputed costs of $130 per physician visit, $1,000 per hospital day, and $200 per sick day, previous year costs were $1,138 in direct costs for the high-risk groups compared with $352 and $995 in the employee and senior groups, respectively. At 6 months, direct costs were reduced by $304 in the high-risk group compared with $57 and $70 in the comparison groups. Total costs were reduced $484 in the high-risk groups compared with $87 in the employee group and $120 in the senior group. The return on investment was about 6:1 in the high-risk
Moro, Dorian; MacAulay, Isobel
For large species, the capture and handling of individuals in capture-mark-recapture studies introduces nonhuman animal welfare issues associated with handling, physical marking, and possible wounding due to tag loss. The use of photographic identification for these species offers an alternative and less invasive marking technique. This study investigated the opportunity offered by photo identification to individually mark individuals of a large reptile, the perentie (Varanus giganteus), in Australia and therefore avoid the stress of physically capturing and handling. Photographs submitted by a remotely located community were first validated to confirm whether perenties could be individually identified from their spots electronically using a computer program. Computer-aided selection of unique patterns was found to be appropriate for the identification of individuals and confirmed 38 individuals during the sampling period. The value of this approach is 2-fold: There is a benefit to animal welfare in that handling an animal is not required to capture him or her, thus reducing capture-related stress; and confirmation that photo identification of distinctive patterns of the perentie is valid and offers a useful option to identify individuals of this large species.
Guarana, Cristiano L; Hernandez, Morela
In this article we investigate the functional effects of ambivalence on decision-making processes. We build on the misattribution literature and recent work on ambivalence to propose that individuals who properly identify the causes of their ambivalence (i.e., identified ambivalence) can systematically process relevant situational cues to make more effective decisions. The results of 4 studies demonstrate that individuals experiencing identified ambivalence are less influenced by cognitive biases (i.e., the framing effect, availability bias, and conjunction bias) than individuals experiencing no ambivalence or felt ambivalence. Notably, we find that contextual awareness accounts for the effect of identified ambivalence on decision effectiveness. We then investigate the role of trait self-control as a specific contingency in our model; our results indicate that identified ambivalence leads to effective decisions when individuals are low in trait self-control. Taken together, we advance theory and offer robust, consistent empirical evidence that explains why and how ambivalence can result in functional outcomes. (PsycINFO Database Record (c) 2016 APA, all rights reserved).
McManus, Beth M.
Research suggests that early self-regulatory difficulties among high-risk newborns can lead to poor interactional difficulties and negative long-term cognitive and social-emotional outcomes if not identified and treated early. This article describes why an individualized, developmentally supportive, relationship-based program, such as the Newborn…
McManus, Beth M.
Research suggests that early self-regulatory difficulties among high-risk newborns can lead to poor interactional difficulties and negative long-term cognitive and social-emotional outcomes if not identified and treated early. This article describes why an individualized, developmentally supportive, relationship-based program, such as the Newborn…
This article explores the impact of the mapping work of the Human Genome Project on individuals with mental retardation and the negative effects of genetic testing. The potential to identify disabilities and the concept of eugenics are discussed, along with ethical issues surrounding potential genetic therapies. (Contains references.) (CR)
This article explores the impact of the mapping work of the Human Genome Project on individuals with mental retardation and the negative effects of genetic testing. The potential to identify disabilities and the concept of eugenics are discussed, along with ethical issues surrounding potential genetic therapies. (Contains references.) (CR)
Gard, Eric Evan; Fergenson, David Philip
A method and system of identifying individual aerosol particles in real time. Sample aerosol particles are compared against and identified with substantially matching known particle types by producing positive and negative test spectra of an individual aerosol particle using a bipolar single particle mass spectrometer. Each test spectrum is compared to spectra of the same respective polarity in a database of predetermined positive and negative spectra for known particle types and a set of substantially matching spectra is obtained. Finally the identity of the individual aerosol particle is determined from the set of substantially matching spectra by determining a best matching one of the known particle types having both a substantially matching positive spectrum and a substantially matching negative spectrum associated with the best matching known particle type.
Kanki, Barbara G.
Mountaineering expeditions combine a number of factors which make them potentially good analogs to the planetary exploration facet of long-duration space missions. A study of mountain climbing teams was conducted in order to evaluate the usefulness of the environment as a space analog and to specifically identify the factors and issues surrounding teamwork and 'successful' team performance in two mountaineering environments. This paper focuses on social/organizational factors, including team size and structure, leadership styles and authority structure which were found in the sample of 22 climb teams (122 individuals). The second major issue discussed is the construction of a valid performance measure in this high-risk environment.
Fong, Allan; Clark, Lindsey; Cheng, Tianyi; Franklin, Ella; Fernandez, Nicole; Ratwani, Raj; Parker, Sarah Henrickson
The objective of this paper is to identify attribute patterns of influential individuals in intensive care units using unsupervised cluster analysis. Despite the acknowledgement that culture of an organisation is critical to improving patient safety, specific methods to shift culture have not been explicitly identified. A social network analysis survey was conducted and an unsupervised cluster analysis was used. A total of 100 surveys were gathered. Unsupervised cluster analysis was used to group individuals with similar dimensions highlighting three general genres of influencers: well-rounded, knowledge and relational. Culture is created locally by individual influencers. Cluster analysis is an effective way to identify common characteristics among members of an intensive care unit team that are noted as highly influential by their peers. To change culture, identifying and then integrating the influencers in intervention development and dissemination may create more sustainable and effective culture change. Additional studies are ongoing to test the effectiveness of utilising these influencers to disseminate patient safety interventions. This study offers an approach that can be helpful in both identifying and understanding influential team members and may be an important aspect of developing methods to change organisational culture. © 2017 John Wiley & Sons Ltd.
Tüchsen, F; Andersen, O; Costa, G; Filakti, H; Marmot, M G
Four longitudinal studies of mortality and morbidity by occupation based on individual record linkage of information and two cross-sectional studies of mortality were compared in order to identify occupations at high risk of ischemic heart disease. In more than one country an increased risk of ischemic heart disease was found in drivers of buses, taxies, and lorries, in bakers, in naval officers and fishermen, in hotel and restaurant workers, in senior police, customs, and other uniformed men, in barbers and hairdressers, in warehouse and wholesale staff, as well as in laboratory assistants and in radio and telegraph operators. Occupations found at high risk in Denmark were also found at high risk in Great Britain and Italy. These occupations may be at genuine high risk. None of these groups work day-work only and several of the groups have psychologically demanding work but unsatisfactory decision authority. Identification of occupations at high risk may help to develop focused preventive strategies.
Ferreira, Daniel; Falahati, Farshad; Linden, Cecilia; Buckley, Rachel F.; Ellis, Kathryn A.; Savage, Greg; Villemagne, Victor L.; Rowe, Christopher C.; Ames, David; Simmons, Andrew; Westman, Eric
Subjective memory decline (SMD) is a heterogeneous condition. While SMD might be the earliest sign of Alzheimer’s disease (AD), it also occurs in aging and various neurological, medical, and psychiatric conditions. Identifying those with higher risk to develop dementia is thus a major challenge. We tested a novel disease severity index generated by multivariate data analysis with numerous structural MRI measures as input. The index was used to identify SMD individuals with high risk of progression to mild cognitive impairment (MCI) or AD. A total of 69 healthy controls, 86 SMD, 45 MCI, and 38 AD patients were included. Subjects were followed up for 7.5 years. Clinical, cognitive, PET amyloid imaging and APOE ε4 data were used as outcome variables. The results showed that SMD evidenced cognitive performance intermediate between healthy controls and MCI. The disease severity index identified eleven (13%) SMD individuals with an AD-like pattern of brain atrophy. These individuals showed lower cognitive performance, increased CDR-SOB, higher amyloid burden and worse clinical progression (6.2 times higher likelihood to develop MCI, dementia or die than healthy controls). The current disease severity index may have relevance for clinical practice, as well as for selecting appropriate individuals for clinical trials. PMID:28287184
Kim, Jongwan; Wang, Jing; Wedell, Douglas H.
Recent research has demonstrated that affective states elicited by viewing pictures varying in valence and arousal are identifiable from whole brain activation patterns observed with functional magnetic resonance imaging (fMRI). Identification of affective states from more naturalistic stimuli has clinical relevance, but the feasibility of identifying these states on an individual trial basis from fMRI data elicited by dynamic multimodal stimuli is unclear. The goal of this study was to determine whether affective states can be similarly identified when participants view dynamic naturalistic audiovisual stimuli. Eleven participants viewed 5s audiovisual clips in a passive viewing task in the scanner. Valence and arousal for individual trials were identified both within and across participants based on distributed patterns of activity in areas selectively responsive to audiovisual naturalistic stimuli while controlling for lower level features of the stimuli. In addition, the brain regions identified by searchlight analyses to represent valence and arousal were consistent with previously identified regions associated with emotion processing. These findings extend previous results on the distributed representation of affect to multimodal dynamic stimuli. PMID:27598534
Kim, Jongwan; Wang, Jing; Wedell, Douglas H; Shinkareva, Svetlana V
Recent research has demonstrated that affective states elicited by viewing pictures varying in valence and arousal are identifiable from whole brain activation patterns observed with functional magnetic resonance imaging (fMRI). Identification of affective states from more naturalistic stimuli has clinical relevance, but the feasibility of identifying these states on an individual trial basis from fMRI data elicited by dynamic multimodal stimuli is unclear. The goal of this study was to determine whether affective states can be similarly identified when participants view dynamic naturalistic audiovisual stimuli. Eleven participants viewed 5s audiovisual clips in a passive viewing task in the scanner. Valence and arousal for individual trials were identified both within and across participants based on distributed patterns of activity in areas selectively responsive to audiovisual naturalistic stimuli while controlling for lower level features of the stimuli. In addition, the brain regions identified by searchlight analyses to represent valence and arousal were consistent with previously identified regions associated with emotion processing. These findings extend previous results on the distributed representation of affect to multimodal dynamic stimuli.
Horst, F; Kramer, F; Schäfer, B; Eekhoff, A; Hegen, P; Nigg, B M; Schöllhorn, W I
Despite the common knowledge about the individual character of human gait patterns and about their non-repeatability, little is known about their stability, their interactions and their changes over time. Variations of gait patterns are typically described as random deviations around a stable mean curve derived from groups, which appear due to noise or experimental insufficiencies. The purpose of this study is to examine the nature of intrinsic inter-session variability in more detail by proving separable characteristics of gait patterns between individuals as well as within individuals in repeated measurement sessions. Eight healthy subjects performed 15 gait trials at a self-selected speed on eight days within two weeks. For each trial, the time-continuous ground reaction forces and lower body kinematics were quantified. A total of 960 gait patterns were analysed by means of support vector machines and the coefficient of multiple correlation. The results emphasise the remarkable amount of individual characteristics in human gait. Support vector machines results showed an error-free assignment of gait patterns to the corresponding individual. Thus, differences in gait patterns between individuals seem to be persistent over two weeks. Within the range of individual gait patterns, day specific characteristics could be distinguished by classification rates of 97.3% and 59.5% for the eight-day classification of lower body joint angles and ground reaction forces, respectively. Hence, gait patterns can be assumed not to be constant over time and rather exhibit discernible daily changes within previously stated good repeatability. Advantages for more individual and situational diagnoses or therapy are identified. Copyright © 2016 Elsevier B.V. All rights reserved.
Thompson, Vicki S; Lacey, Jeffrey A; Gentillon, Cynthia A; Apel, William A
A method for determining a plurality of proteins for discriminating and positively identifying an individual based from a biological sample. The method may include profiling a biological sample from a plurality of individuals against a protein array including a plurality of proteins. The protein array may include proteins attached to a support in a preselected pattern such that locations of the proteins are known. The biological sample may be contacted with the protein array such that a portion of antibodies in the biological sample reacts with and binds to the proteins forming immune complexes. A statistical analysis method, such as discriminant analysis, may be performed to determine discriminating proteins for distinguishing individuals. Proteins of interest may be used to form a protein array. Such a protein array may be used, for example, to compare a forensic sample from an unknown source with a sample from a known source.
Apel, William A.; Thompson, Vicki S; Lacey, Jeffrey A.; Gentillon, Cynthia A.
A method for determining a plurality of proteins for discriminating and positively identifying an individual based from a biological sample. The method may include profiling a biological sample from a plurality of individuals against a protein array including a plurality of proteins. The protein array may include proteins attached to a support in a preselected pattern such that locations of the proteins are known. The biological sample may be contacted with the protein array such that a portion of antibodies in the biological sample reacts with and binds to the proteins forming immune complexes. A statistical analysis method, such as discriminant analysis, may be performed to determine discriminating proteins for distinguishing individuals. Proteins of interest may be used to form a protein array. Such a protein array may be used, for example, to compare a forensic sample from an unknown source with a sample from a known source.
Voskoboinik, Lev; Ayers, Sheri B; LeFebvre, Aaron K; Darvasi, Ariel
Common forensic and mass disaster scenarios present DNA evidence that comprises a mixture of several contributors. Identifying the presence of an individual in such mixtures has proven difficult. In the current study, we evaluate the practical usefulness of currently available "off-the-shelf" SNP microarrays for such purposes. We found that a set of 3000 SNPs specifically selected for this purpose can accurately identify the presence of an individual in complex DNA mixtures of various compositions. For example, individuals contributing as little as 5% to a complex DNA mixture can be robustly identified even if the starting DNA amount was as little as 5.0ng and had undergone whole-genome amplification (WGA) prior to SNP analysis. The work presented in this study represents proof-of-principle that our previously proposed approach, can work with real "forensic-type" samples. Furthermore, in the absence of a low-density focused forensic SNP microarray, the use of standard, currently available high-density SNP microarrays can be similarly used and even increase statistical power due to the larger amount of available information.
Hui, Yiang; Manna, Pradip; Ou, Joyce J; Kerley, Spencer; Zhang, Cunxian; Sung, C James; Lawrence, W Dwayne; Quddus, M Ruhul
High-risk human papillomavirus infection usually is seen at one anatomic site in an individual. Rarely, infection at multiple anatomic sites of the female lower genital tract in the same individual is encountered either simultaneously and/or at a later date. The current study identifies the various subtypes of high-risk human papillomavirus infection in these scenarios and analyzes the potential significance of these findings. High-risk human papillomavirus infection involving 22 anatomic sites from 7 individuals was identified after institutional review board approval. Residual paraffin-embedded tissue samples were retrieved, and all 15 high-risk human papillomavirus were identified and viral load quantified using multiplex real-time polymerase chain reaction-based method. Multiple high-risk human papillomavirus subtypes were identified in 32% of the samples and as many as 5 different subtypes of high-risk human papillomavirus infection in a single anatomic site. In general, each anatomic site has unique combination of viral subtypes, although one individual showed overlapping subtypes in the vagina, cervix, and vulvar samples. Higher viral load and rare subtypes are more frequent in younger patients and in dysplasia compared with carcinoma. Follow-up ranging from 3 to 84 months revealed persistent high-risk human papillomavirus infection in 60% of cases. Copyright © 2015 Elsevier Inc. All rights reserved.
Hansson, Mats G; Lochmüller, Hanns; Riess, Olaf; Schaefer, Franz; Orth, Michael; Rubinstein, Yaffa; Molster, Caron; Dawkins, Hugh; Taruscio, Domenica; Posada, Manuel; Woods, Simon
There is a growing concern in the ethics literature and among policy makers that de-identification or coding of personal data and biospecimens is not sufficient for protecting research subjects from privacy invasions and possible breaches of confidentiality due to the possibility of unauthorized re-identification. At the same time, there is a need in medical science to be able to identify individual patients. In particular for rare disease research there is a special and well-documented need for research collaboration so that data and biosamples from multiple independent studies can be shared across borders. In this article, we identify the needs and arguments related to de-identification and re-identification of patients and research subjects and suggest how the different needs may be balanced within a framework of using unique encrypted identifiers. PMID:27222291
Vannucci, Anna; Kass, Andrea E.; Sinton, Meghan M.; Aspen, Vandana; Weisman, Hannah; Bailey, Jakki O.; Wilfley, Denise E.; Taylor, C. Barr
Identifying measures that reliably and validly assess clinical impairment has important implications for eating disorder (ED) diagnosis and treatment. The current study examined the psychometric properties of the Clinical Impairment Assessment (CIA) in women at high risk for ED onset. Participants were 543 women (20.6 ± 2.0 years) who were classified into one of three ED categories: clinical ED, high risk for ED onset, and low risk control. Among high risk women, the CIA demonstrated high internal consistency (α = 0.93) and good convergent validity with disordered eating attitudes (rs = 0.27–0.68, ps < 0.001). Examination of the CIA’s discriminant validity revealed that CIA global scores were highest among women with a clinical ED (17.7 ± 10.7) followed by high risk women (10.6 ± 8.5) and low risk controls (3.0 ± 3.3), respectively (p < 0.001). High risk women reporting behavioral indices of ED psychopathology (objective and/or subjective binge episodes, purging behaviors, driven exercise, and ED treatment history) had higher CIA global scores than those without such indices (ps < 0.05), suggesting good criterion validity. These data establish the first norms for the CIA in a United States sample. The CIA is psychometrically sound among high risk women, and heightened levels of impairment among these individuals as compared to low risk women verify the relevance of early intervention efforts. PMID:22516320
Oyewumi, L K
A critical review of various high risk situations in which neuroleptics could be used and have been used in clinical practice is presented. These high risk situations include: women of child bearing age (pregnant women, lactating and/or nursing mothers), the two extremes of life (children and the elderly), patients with sexual dysfunction, patients with tardive dyskinesia, non-psychotic psychiatric patients, physically ill and suicidal patients. The extraordinary applications of these drugs, such as for rapid tranquilization and megadose regimens are examined. The author provides guidelines for the use of neuroleptics in these clinical situations.
Wiley, Christopher D; Flynn, James M; Morrissey, Christapher; Lebofsky, Ronald; Shuga, Joe; Dong, Xiao; Unger, Marc A; Vijg, Jan; Melov, Simon; Campisi, Judith
Senescent cells play important roles in both physiological and pathological processes, including cancer and aging. In all cases, however, senescent cells comprise only a small fraction of tissues. Senescent phenotypes have been studied largely in relatively homogeneous populations of cultured cells. In vivo, senescent cells are generally identified by a small number of markers, but whether and how these markers vary among individual cells is unknown. We therefore utilized a combination of single-cell isolation and a nanofluidic PCR platform to determine the contributions of individual cells to the overall gene expression profile of senescent human fibroblast populations. Individual senescent cells were surprisingly heterogeneous in their gene expression signatures. This cell-to-cell variability resulted in a loss of correlation among the expression of several senescence-associated genes. Many genes encoding senescence-associated secretory phenotype (SASP) factors, a major contributor to the effects of senescent cells in vivo, showed marked variability with a subset of highly induced genes accounting for the increases observed at the population level. Inflammatory genes in clustered genomic loci showed a greater correlation with senescence compared to nonclustered loci, suggesting that these genes are coregulated by genomic location. Together, these data offer new insights into how genes are regulated in senescent cells and suggest that single markers are inadequate to identify senescent cells in vivo. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
Neto, O L; Barros, M B; Martelli, C M; Silva, S A; Cavenaghi, S M; Siqueira, J B
The aim of this study was to investigate the spatial pattern of neonatal and post-neonatal mortality in the city of Goiânia, Central Brazil. Analyses were based on linked birth and death certificates relating to 101,000 in-hospital live births from mothers residing in the city of Goiânia over the 1992-1996 period. Overall neonatal and post-neonatal mortality probabilities were calculated using the linked database. The empirical Bayes method was applied to smooth the estimated rates and minimize random fluctuation. Spatial units of analysis were 65 urban districts, corresponding to the urban planning sectors. The following exploratory spatial analyses were applied: "global" Moran's I statistic, local Moran LISA map, and Gi* local statistics. For both neonatal and post-neonatal mortality there was statistically significant spatial autocorrelation. Results of post-neonatal mortality showed a high-risk cluster located on the outskirts of the city. For the neonatal period, a heterogeneous mortality pattern was found with high-risk districts in all regions, including central areas.
Schaafsma, Dilana; Kok, Gerjo; Stoffelen, Joke M. T.; Curfs, Leopold M. G.
Sex education for individuals with intellectual disabilities is important. However, our knowledge about effective methods for teaching sex education to this population is limited. We report the results of a systematic review identifying methods for sex education programs aimed at individuals with intellectual disabilities. In all, 20 articles were included that met the criteria set in terms of topic—the effectiveness of sex education programs—and population of interest—individuals with intellectual disabilities. In these articles, methods for increasing knowledge and for improving skills and attitudes were reported. However, the studies revealed that generalization of skills to real-life situations was often not achieved. There are indications that the maintenance of knowledge and skills still needs extra attention. Moreover, detailed descriptions of the program materials, program goals, and methods used in the programs were often lacking in the reports. Although there is some evidence for methods that may improve knowledge, attitudes, and skills with regard to sex education aimed at individuals with intellectual disabilities, due to the lack of detailed descriptions provided it is unclear under which conditions these methods work. We therefore suggest that authors provide additional detail about methods in future publications or in online supplements. PMID:25085114
Schaafsma, Dilana; Kok, Gerjo; Stoffelen, Joke M T; Curfs, Leopold M G
Sex education for individuals with intellectual disabilities is important. However, our knowledge about effective methods for teaching sex education to this population is limited. We report the results of a systematic review identifying methods for sex education programs aimed at individuals with intellectual disabilities. In all, 20 articles were included that met the criteria set in terms of topic--the effectiveness of sex education programs--and population of interest--individuals with intellectual disabilities. In these articles, methods for increasing knowledge and for improving skills and attitudes were reported. However, the studies revealed that generalization of skills to real-life situations was often not achieved. There are indications that the maintenance of knowledge and skills still needs extra attention. Moreover, detailed descriptions of the program materials, program goals, and methods used in the programs were often lacking in the reports. Although there is some evidence for methods that may improve knowledge, attitudes, and skills with regard to sex education aimed at individuals with intellectual disabilities, due to the lack of detailed descriptions provided it is unclear under which conditions these methods work. We therefore suggest that authors provide additional detail about methods in future publications or in online supplements.
Audesirk, G; Audesirk, T
Although chronic exposure to lead has been correlated with a variety of behavioral and neurochemical deficits in humans and other mammals, little is known of the mechanisms of action of chronic lead at the level of the individual nerve cell. We have used the individually identifiable neurons of the freshwater pond snail Lymnaea stagnalis as a model system to investigate the effects of chronic low level (5 microM) lead exposure on neuronal physiology. Thirteen neuronal parameters were measured with intracellular microelectrode recording in each of six different identifiable neurons or homogeneous neuron clusters. Results were analyzed by a multivariate analysis of variance (MANOVA). MANOVA analysis indicates that there is a significant overall effect of lead exposure (p = 0.0001) and a significant interaction between lead and neuron type (p = 0.01). In most neuron types, chronic lead causes an increase in the resting potential, a slowing of recovery of the membrane potential after the undershoot of a spike, a decrease in spontaneous spiking activity, and a decrease in the input resistance. Lead also has differential effects on identifiable neurons, depressing excitability in some neuron types while not altering excitability in others.
Vanderwood, Karl K; Kramer, Mary Kaye; Miller, Rachel G.; Arena, Vincent C.; Kriska, Andrea M.
Aims Because blood-based screening to identify those with prediabetes to take part in Diabetes Prevention Program (DPP) translation efforts can be costly and time-consuming, non-invasive methods are needed. The aims of this paper are to evaluate the ability of the American Diabetes Association (ADA) risk test in identifying individuals with prediabetes, as well as the use of body composition measures for this purpose. In addition the utility of these alternate methods to ascertain the presence of the metabolic syndrome was assessed. Methods Potential participants were recruited from a worksite and three community centers to take part in a DPP translation study. Participants completed onsite screening where anthropometric measures, fasting lipids and glucose, and hemoglobin A1c were assessed. Those with a BMI ≥24kg/m2 and prediabetes and/or the metabolic syndrome were eligible to participate. Non-invasive screening methods were evaluated for their ability to identify those with prediabetes and the metabolic syndrome based on clinically measured values. Results All non-invasive methods were highly sensitive (68.9% to 98.5%) in the detection of prediabetes, but specificity was low (6.7% to 44.5%). None of the alternatives evaluated achieved acceptable discrimination levels in ROC analysis. Similar results were noted in identifying the metabolic syndrome. Conclusions The non-invasive methods evaluated in this study effectively identify participants with prediabetes, but would also allow for enrollment of a large number of individuals who do not have prediabetes. Deciding whether to use these alternatives, blood-based measures, or a combination of both will ultimately depend on the purpose of the program and the level of flexibility regarding participant eligibility. PMID:25441924
Keitel, Anne; Gross, Joachim
The human brain can be parcellated into diverse anatomical areas. We investigated whether rhythmic brain activity in these areas is characteristic and can be used for automatic classification. To this end, resting-state MEG data of 22 healthy adults was analysed. Power spectra of 1-s long data segments for atlas-defined brain areas were clustered into spectral profiles (“fingerprints”), using k-means and Gaussian mixture (GM) modelling. We demonstrate that individual areas can be identified from these spectral profiles with high accuracy. Our results suggest that each brain area engages in different spectral modes that are characteristic for individual areas. Clustering of brain areas according to similarity of spectral profiles reveals well-known brain networks. Furthermore, we demonstrate task-specific modulations of auditory spectral profiles during auditory processing. These findings have important implications for the classification of regional spectral activity and allow for novel approaches in neuroimaging and neurostimulation in health and disease. PMID:27355236
Hammarlund, Erika; Lewis, Matthew W; Carter, Shirley V; Amanna, Ian; Hansen, Scott G; Strelow, Lisa I; Wong, Scott W; Yoshihara, Paul; Hanifin, Jon M; Slifka, Mark K
Approximately 50% of the US population received smallpox vaccinations before routine immunization ceased in 1972 for civilians and in 1990 for military personnel. Several studies have shown long-term immunity after smallpox vaccination, but skepticism remains as to whether this will translate into full protection against the onset of orthopoxvirus-induced disease. The US monkeypox outbreak of 2003 provided the opportunity to examine this issue. Using independent and internally validated diagnostic approaches with >or=95% sensitivity and >or=90% specificity for detecting clinical monkeypox infection, we identified three previously unreported cases of monkeypox in preimmune individuals at 13, 29 and 48 years after smallpox vaccination. These individuals were unaware that they had been infected because they were spared any recognizable disease symptoms. Together, this shows that the US monkeypox outbreak was larger than previously realized and, more importantly, shows that cross-protective antiviral immunity against West African monkeypox can potentially be maintained for decades after smallpox vaccination.
Landisch, Rachel M; Hanson, Sheila J; Cassidy, Laura D; Braun, Kristin; Punzalan, Rowena C; Gourlay, David M
Pharmacologic prophylaxis for venous thromboembolism (VTE) is a widely accepted practice in adult trauma patients to prevent associated morbidity and mortality. However, VTE prophylaxis has not been standardized in injured pediatric patients. Our institution identified factors potentially associated with a high risk of VTE in critically injured children that led to prospective implementation of VTE prophylaxis guidelines. We hypothesize the guidelines are accurate in predicting children at risk for VTE. Data were prospectively collected on injured children from 8/2010-8/2015. Pharmacologic prophylaxis was indicated for patients identified by the guidelines as high risk for VTE. Prophylaxis was deferred and a screening ultrasound (US) performed if the high risk VTE patients were also at high risk for bleeding. To assess the accuracy of predicting confirmed cases of VTE, stepwise logistic regression analysis was used to measure the association of individual risk factors with VTE controlling for age (≥13 years). A receiver operating characteristic (ROC) curve measured the accuracy of the final model to predict a VTE. Of 4061 trauma patients, 588 were admitted to the ICU, with the guidelines identifying 199 as high risk for VTE. VTE occurred in 3.9% (23/588) of the ICU population and 10% (20/199) of the high risk group. The median age of VTE patients in the ICU was 9.7 years. Statistically significant predictors (p<0.05) of VTE in the multivariate model included presence of a central venous catheter (OR=5.2), inotropes (OR=7.7), immobilization (OR=5.5) and a Glasgow Coma Scale (GCS) < 9 (OR=1.3). The area under ROC curve of this model was 0.92, demonstrating its excellent predictive ability. Specific clinical factors in critically injured children are associated with a high risk for VTE. Incorporating these risk factors in VTE prophylaxis guidelines facilitates more accurate risk stratification and may allow for improved VTE prevention in pediatric trauma. Prognostic
Gittman, Elizabeth; Cassata, Marian
A 5-year federally funded substance abuse prevention program targeted 426 high risk middle-school youth from 4 school districts in Nassau County, New York. Combining a child-centered model with a systemic approach, the program's goal was to prevent or delay the onset of alcohol and other drug use. High-risk youth were identified by school…
Pedersen, D M
High risk sports were rated as to risk, appeal, and likelihood of participation by 282 men and 162 women. Ascending order of perceived risk was skiing, scuba diving, bungee jumping, rock climbing, motorcycle racing, hang gliding, cliff jumping, and skydiving. Profile analysis showed stated likelihood of participation to be directly related to appeal and inversely related to perceived risk.
Xu, X; Tao, S; Ying, Y; Hong, X; He, Y; Zhu, F; Lv, H; Yan, L
The para-Bombay phenotype is characterised by H-deficient or H partially deficient red blood cells (RBCs) in individuals who secrete ABH antigens in their saliva. Samples from an individual whose RBCs had an apparent para-Bombay phenotype and his family members were investigated and a novel FUT1 allele was identified. RBCs' phenotype was characterised by standard serologic technique. Genomic DNA was sequenced with primers that amplified the coding sequence of FUT1 and FUT2, respectively. Routine ABO genotyping analysis was performed. Haplotypes of FUT1 were identified by TOPO cloning sequencing. Recombination expression vectors of FUT1 mutation alleles were constructed and transfected into COS-7 cells. The pα-(1,2)-fucosyltransferase activity of expression protein was determined. B101/O02 genotype of the proband was correlated with ABH substances in saliva. The proband carried a new FUT1 allele which showed 35C/T, 235G/C and 682A/G heterozygote by directly DNA sequencing. Two haplotypes, 235C and 35T+682G, were identified by TOPO cloning sequencing and COS-7 cells transfected with five recombination vectors including wild-type, 35T, 235C, 682G and 35T+682G alleles were established respectively. The α-(1,2)-fucosyltransferase activities of cell lysates which had transfected with 35T, 235C, 682G and 35T+682G recombination vectors showed 79·45, 16·23, 80·32 and 24·59%, respectively, compared with that of the wild-type FUT1-transfected cell lysates. A novel FUT1 allele 235C was identified, which greatly diminished the activity of α-(1,2)-fucosyltransferase. © 2011 The Authors. Transfusion Medicine © 2011 British Blood Transfusion Society.
Comptroller General of the U.S., Washington, DC.
This report reviews the status of government agencies and operations that have been identified as at "high risk" for waste, fraud, abuse, and mismanagement; describes successful progress in some agencies; and looks at recent reform legislation. Six categories being targeted include accountability of defense programs, ensuring that all…
Alimoradi, Zainab; Kariman, Nourossadat; Simbar, Masoumeh; Ahmadi, Fazlollah
ABSTRACT Background: Adolescence is a period of overwhelming changes and challenges, which expose the adolescents to high-risk behaviors. Risky sexual relationship is one of these behaviors that entails physical risks and psychosocial harms. Various factors have been recognized to shape sexual behaviors in adolescents. This paper is an attempt to investigate the factors contributing to high-risk sexual behaviors in Iranian adolescent girls. Methods: A literature review of the research published by Iranian authors, in Farsi or English language in local and foreign journals, was conducted using PubMed, Science Direct, Scopus, Scientific Information Database (SID), IranMedex, IranDoc, and Google Scholar. The search in each database included all the years covered at that time using keywords such as “sexual, adolescents, and Iran”, and continued using other keywords such as “sexual behavior, high-risk behavior, sexual risk and reproductive behavior” individually and in combination Results: Sixteen published articles were identified. Factors contributing to high-risk sexual behaviors in girls can be divided into four general groups including personal, family, peer, school and community. Conclusion: Regarding the identified risk and protective factors, appropriate individual, family and school-based interventions can be designed and implemented to strengthen protective factors. While individual and family factors are considered more in research, factors related to peers, school and community have received less attention. Since social values, beliefs and norms are important factors in formation of sexual behaviors, further research regarding these factors is suggested. PMID:28097173
Parasuraman, Raja; de Visser, Ewart; Lin, Ming-Kuan; Greenwood, Pamela M.
Computerized aiding systems can assist human decision makers in complex tasks but can impair performance when they provide incorrect advice that humans erroneously follow, a phenomenon known as “automation bias.” The extent to which people exhibit automation bias varies significantly and may reflect inter-individual variation in the capacity of working memory and the efficiency of executive function, both of which are highly heritable and under dopaminergic and noradrenergic control in prefrontal cortex. The dopamine beta hydroxylase (DBH) gene is thought to regulate the differential availability of dopamine and norepinephrine in prefrontal cortex. We therefore examined decision-making performance under imperfect computer aiding in 100 participants performing a simulated command and control task. Based on two single nucleotide polymorphism (SNPs) of the DBH gene, −1041 C/T (rs1611115) and 444 G/A (rs1108580), participants were divided into groups of low and high DBH enzyme activity, where low enzyme activity is associated with greater dopamine relative to norepinephrine levels in cortex. Compared to those in the high DBH enzyme activity group, individuals in the low DBH enzyme activity group were more accurate and speedier in their decisions when incorrect advice was given and verified automation recommendations more frequently. These results indicate that a gene that regulates relative prefrontal cortex dopamine availability, DBH, can identify those individuals who are less susceptible to bias in using computerized decision-aiding systems. PMID:22761865
Achkar, Jacqueline M.; Cortes, Laetitia; Croteau, Pascal; Yanofsky, Corey; Mentinova, Marija; Rajotte, Isabelle; Schirm, Michael; Zhou, Yiyong; Junqueira-Kipnis, Ana Paula; Kasprowicz, Victoria O.; Larsen, Michelle; Allard, René; Hunter, Joanna; Paramithiotis, Eustache
Biomarkers for active tuberculosis (TB) are urgently needed to improve rapid TB diagnosis. The objective of this study was to identify serum protein expression changes associated with TB but not latent Mycobacterium tuberculosis infection (LTBI), uninfected states, or respiratory diseases other than TB (ORD). Serum samples from 209 HIV uninfected (HIV−) and co-infected (HIV+) individuals were studied. In the discovery phase samples were analyzed via liquid chromatography and mass spectrometry, and in the verification phase biologically independent samples were analyzed via a multiplex multiple reaction monitoring mass spectrometry (MRM-MS) assay. Compared to LTBI and ORD, host proteins were significantly differentially expressed in TB, and involved in the immune response, tissue repair, and lipid metabolism. Biomarker panels whose composition differed according to HIV status, and consisted of 8 host proteins in HIV− individuals (CD14, SEPP1, SELL, TNXB, LUM, PEPD, QSOX1, COMP, APOC1), or 10 host proteins in HIV+ individuals (CD14, SEPP1, PGLYRP2, PFN1, VASN, CPN2, TAGLN2, IGFBP6), respectively, distinguished TB from ORD with excellent accuracy (AUC = 0.96 for HIV− TB, 0.95 for HIV+ TB). These results warrant validation in larger studies but provide promise that host protein biomarkers could be the basis for a rapid, blood-based test for TB. PMID:26501113
Miyagawa-Yamaguchi, Arisa; Kotani, Norihiro; Honke, Koichi
Lipid rafts that are enriched in glycosylphosphatidylinositol (GPI)-anchored proteins serve as a platform for important biological events. To elucidate the molecular mechanisms of these events, identification of co-clustering molecules in individual raft domains is required. Here we describe an approach to this issue using the recently developed method termed enzyme-mediated activation of radical source (EMARS), by which molecules in the vicinity within 300 nm from horseradish peroxidase (HRP) set on the probed molecule are labeled. GPI-anchored HRP fusion proteins (HRP-GPIs), in which the GPI attachment signals derived from human decay accelerating factor and Thy-1 were separately connected to the C-terminus of HRP, were expressed in HeLa S3 cells, and the EMARS reaction was catalyzed by these expressed HRP-GPIs under a living condition. As a result, these different HRP-GPIs had differences in glycosylation and localization and formed distinct clusters. This novel approach distinguished molecular clusters associated with individual GPI-anchored proteins, suggesting that it can identify co-clustering molecules in individual raft domains. PMID:24671047
Beaton-Green, Lindsay A; Rodrigues, Matthew A; Lachapelle, Sylvie; Wilkins, Ruth C
Biodosimetry is an important tool for triage in the case of large-scale radiological or nuclear emergencies, but traditional microscope-based methods can be tedious and prone to scorer fatigue. While the dicentric chromosome assay (DCA) has been adapted for use in triage situations, it is still time-consuming to create and score slides. Recent adaptations of traditional biodosimetry assays to imaging flow cytometry (IFC) methods have dramatically increased throughput. Additionally, recent improvements in image analysis algorithms in the IFC software have resulted in improved specificity for spot counting of small events. In the IFC method for the dicentric chromosome analysis (FDCA), lymphocytes isolated from whole blood samples are cultured with PHA and Colcemid. After incubation, lymphocytes are treated with a hypotonic solution and chromosomes are isolated in suspension, labelled with a centromere marker and stained for DNA content with DRAQ5. Stained individual chromosomes are analyzed on the ImageStream®(X) (EMD-Millipore, Billerica, MA) and mono- and dicentric chromosome populations are identified and enumerated using advanced image processing techniques. Both the preparation of the isolated chromosome suspensions as well as the image analysis methods were fine-tuned in order to optimize the FDCA. In this paper we describe the method to identify and score centromeres in individual chromosomes by IFC and show that the FDCA method may further improve throughput for triage biodosimetry in the case of large-scale radiological or nuclear emergencies.
Campbell, Catarina D.; Mohajeri, Kiana; Malig, Maika; Hormozdiari, Fereydoun; Nelson, Benjamin; Du, Gaixin; Patterson, Kristen M.; Eng, Celeste; Torgerson, Dara G.; Hu, Donglei; Herman, Catherine; Chong, Jessica X.; Ko, Arthur; O'Roak, Brian J.; Krumm, Niklas; Vives, Laura; Lee, Choli; Roth, Lindsey A.; Rodriguez-Cintron, William; Rodriguez-Santana, Jose; Brigino-Buenaventura, Emerita; Davis, Adam; Meade, Kelley; LeNoir, Michael A.; Thyne, Shannon; Jackson, Daniel J.; Gern, James E.; Lemanske, Robert F.; Shendure, Jay; Abney, Mark; Burchard, Esteban G.; Ober, Carole; Eichler, Evan E.
Asthma is a complex genetic disease caused by a combination of genetic and environmental risk factors. We sought to test classes of genetic variants largely missed by genome-wide association studies (GWAS), including copy number variants (CNVs) and low-frequency variants, by performing whole-genome sequencing (WGS) on 16 individuals from asthma-enriched and asthma-depleted families. The samples were obtained from an extended 13-generation Hutterite pedigree with reduced genetic heterogeneity due to a small founding gene pool and reduced environmental heterogeneity as a result of a communal lifestyle. We sequenced each individual to an average depth of 13-fold, generated a comprehensive catalog of genetic variants, and tested the most severe mutations for association with asthma. We identified and validated 1960 CNVs, 19 nonsense or splice-site single nucleotide variants (SNVs), and 18 insertions or deletions that were out of frame. As follow-up, we performed targeted sequencing of 16 genes in 837 cases and 540 controls of Puerto Rican ancestry and found that controls carry a significantly higher burden of mutations in IL27RA (2.0% of controls; 0.23% of cases; nominal p = 0.004; Bonferroni p = 0.21). We also genotyped 593 CNVs in 1199 Hutterite individuals. We identified a nominally significant association (p = 0.03; Odds ratio (OR) = 3.13) between a 6 kbp deletion in an intron of NEDD4L and increased risk of asthma. We genotyped this deletion in an additional 4787 non-Hutterite individuals (nominal p = 0.056; OR = 1.69). NEDD4L is expressed in bronchial epithelial cells, and conditional knockout of this gene in the lung in mice leads to severe inflammation and mucus accumulation. Our study represents one of the early instances of applying WGS to complex disease with a large environmental component and demonstrates how WGS can identify risk variants, including CNVs and low-frequency variants, largely untested in GWAS. PMID:25116239
Campbell, Catarina D; Mohajeri, Kiana; Malig, Maika; Hormozdiari, Fereydoun; Nelson, Benjamin; Du, Gaixin; Patterson, Kristen M; Eng, Celeste; Torgerson, Dara G; Hu, Donglei; Herman, Catherine; Chong, Jessica X; Ko, Arthur; O'Roak, Brian J; Krumm, Niklas; Vives, Laura; Lee, Choli; Roth, Lindsey A; Rodriguez-Cintron, William; Rodriguez-Santana, Jose; Brigino-Buenaventura, Emerita; Davis, Adam; Meade, Kelley; LeNoir, Michael A; Thyne, Shannon; Jackson, Daniel J; Gern, James E; Lemanske, Robert F; Shendure, Jay; Abney, Mark; Burchard, Esteban G; Ober, Carole; Eichler, Evan E
Asthma is a complex genetic disease caused by a combination of genetic and environmental risk factors. We sought to test classes of genetic variants largely missed by genome-wide association studies (GWAS), including copy number variants (CNVs) and low-frequency variants, by performing whole-genome sequencing (WGS) on 16 individuals from asthma-enriched and asthma-depleted families. The samples were obtained from an extended 13-generation Hutterite pedigree with reduced genetic heterogeneity due to a small founding gene pool and reduced environmental heterogeneity as a result of a communal lifestyle. We sequenced each individual to an average depth of 13-fold, generated a comprehensive catalog of genetic variants, and tested the most severe mutations for association with asthma. We identified and validated 1960 CNVs, 19 nonsense or splice-site single nucleotide variants (SNVs), and 18 insertions or deletions that were out of frame. As follow-up, we performed targeted sequencing of 16 genes in 837 cases and 540 controls of Puerto Rican ancestry and found that controls carry a significantly higher burden of mutations in IL27RA (2.0% of controls; 0.23% of cases; nominal p = 0.004; Bonferroni p = 0.21). We also genotyped 593 CNVs in 1199 Hutterite individuals. We identified a nominally significant association (p = 0.03; Odds ratio (OR) = 3.13) between a 6 kbp deletion in an intron of NEDD4L and increased risk of asthma. We genotyped this deletion in an additional 4787 non-Hutterite individuals (nominal p = 0.056; OR = 1.69). NEDD4L is expressed in bronchial epithelial cells, and conditional knockout of this gene in the lung in mice leads to severe inflammation and mucus accumulation. Our study represents one of the early instances of applying WGS to complex disease with a large environmental component and demonstrates how WGS can identify risk variants, including CNVs and low-frequency variants, largely untested in GWAS.
Nead, Kevin T.; Cooke, John P.; Olin, Jeffrey W.; Leeper, Nicholas J.
Objectives To determine whether utilization of an alternative ankle-brachial index (ABI) calculation method improves mortality risk prediction compared to traditional methods. Background The ABI is used to diagnose peripheral arterial disease (PAD), and to identify those at risk for cardiovascular events. Traditionally, the ABI is calculated using the higher of the dorsalis pedis and posterior tibial ankle arteries. Studies directly comparing calculation methods are limited. Methods The ABI was calculated at baseline in 1,413 study participants undergoing non-emergent coronary angiography subsequently followed for all-cause and cardiovascular mortality. There were 224 individuals assigned to the traditional-PAD group (ABI < 0.90) using the traditional ABI method. Of those remaining, an alternative ABI method utilizing the lower of the two ankle pressures assigned 282 patients to the alternative-PAD group. The 862 individuals not assigned to PAD by either method were the no-PAD group. Results There were 163 mortalities during a median follow-up of 5.0 years. Adjusted Cox regression models showed that the alternative-PAD group had an increased risk for all-cause (HR=1.49; 95% CI, 1.01-2.19) and cardiovascular mortality (HR=3.21; 95% CI, 1.53-6.37) versus the no-PAD group. Additionally, in the no-PAD group, there was an 11% (HR=1.11; 95% CI, 1.05-1.17) increased risk of all-cause mortality per 1mm Hg increased difference between the left and right brachial systolic pressures. Conclusion The implementation of an alternative ABI method and use of the brachial difference identifies individuals at an increased risk for mortality who are currently missed using traditional ABI methods. Current ABI protocols may need to be evaluated. PMID:23707317
Kalmbach, David A.; Pillai, Vivek; Arnedt, J. Todd; Drake, Christopher L.
Study Objectives: A primary focus of the National Institute of Mental Health's current strategic plan is “predicting” who is at risk for disease. As such, the current investigation examined the utility of premorbid sleep reactivity in identifying a specific and manageable population at elevated risk for future insomnia. Methods: A community-based sample of adults (n = 2,892; 59.3% female; 47.9 ± 13.3 y old) with no lifetime history of insomnia or depression completed web-based surveys across three annual assessments. Participants reported parental history of insomnia, demographic characteristics, sleep reactivity on the Ford Insomnia in Response to Stress Test (FIRST), and insomnia symptoms. DSM-IV diagnostic criteria were used to determine insomnia classification. Results: Baseline FIRST scores were used to predict incident insomnia at 1-y follow-up. Two clinically meaningful FIRST cutoff values were identified: FIRST ≥ 16 (sensitivity 77%; specificity 50%; odds ratio [OR] = 2.88, P < 0.001); and FIRST ≥ 18 (sensitivity 62%; specificity 67%; OR = 3.32, P < 0.001). Notably, both FIRST cut-points outperformed known maternal (OR = 1.49–1.59, P < 0.01) and paternal history (P = NS) in predicting insomnia onset, even after controlling for stress exposure and demographic characteristics. Of the incident cases, insomniacs with highly reactive sleep systems reported longer sleep onset latencies (FIRST ≥ 16: 65 min; FIRST ≥ 18: 68 min) than participants with nonreactive insomnia (FIRST < 16: 37 min; FIRST < 18: 44 min); these groups did not differ on any other sleep parameters. Conclusions: The current study established a cost- and time-effective strategy for identifying individuals at elevated risk for insomnia based on trait sleep reactivity. The FIRST accurately identifies a focused target population in which the psychobiological processes complicit in insomnia onset and progression can be better investigated, thus improving future preventive efforts
Kershaw, Trace S.; Lewis, Jessica; Westdahl, Claire; Wang, Yun F.; Rising, Sharon Schindler; Massey, Zohar; Ickovics, Jeannette
CONTEXT Few studies have used classification tree analysis to produce empirically driven decision tools that identify subgroups of women at risk of STDs during pregnancy. Such tools can guide care, treatment and prevention efforts in clinical settings. METHODS A sample of 647 women aged 14−25 attending two urban obstetrics and gynecology clinics in 2001−2004 were surveyed in their second and third trimesters. Baseline predictors at the individual, dyad, and family and community levels were used to develop a classification tree that differentiated subgroups of women by STD incidence at 35 weeks' gestation. Logistic regression analyses were conducted to assess whether the classification tree groups or commonly used risk factors better predicted STD incidence. RESULTS Nineteen percent of women had an incident STD during pregnancy. Classification tree analysis identified three subgroups with a high STD incidence (33−61%), one with a moderate incidence (16%) and three with a low incidence (6−11%). Women in subgroups with high STD incidence included those not living with the partner with whom they conceived and those who had a moderate or a high level of depression, a history of STDs and a low level of social support. A logistic regression model using groups defined by the classification tree analysis had better predictive ability than one using common demographic and sexual risk predictors. CONCLUSION This classification tree identified risk factors not captured by traditional risk screenings, and could be used to guide STD treatment, care and prevention within the prenatal care setting. PMID:17845525
Parham, L Diane; Roush, Sean; Downing, Donna T; Michael, Paul G; McFarlane, William R
To identify and compare the sensory characteristics of young people at clinical high risk (CHR) for psychosis to those of peers at clinical low risk (CLR), and to national normative data. CHR and CLR participants were recruited from 6 US regions. A descriptive cohort design was used to analyse baseline data collected as part of the Early Detection and Intervention for the Prevention of Psychosis Program (EDIPPP). Raw scores on the Adolescent/Adult Sensory Profile (AASP) were analysed for 205 young people with CHR and 87 with CLR in 2 age groups: 12 to 17 years (N = 203) and 18 to 25 years (N = 89). ANOVA procedures were used to determine whether differences in AASP scores existed across CLR, CHR, and normative groups by age group. CHR participants differed significantly from the normative group for all 4 AASP quadrant scores (Low Registration, Sensory Seeking, Sensory Sensitivity and Sensory Avoiding) in both age groups. CLR participants were similar to norms, except for Sensory Seeking scores that were significantly lower than norms in both age ranges. Young people with CHR demonstrate active avoidance, heightened sensitivity, reduced seeking, and reduced registration of sensations in everyday life compared to typical peers. This pattern of differences may be a valuable marker for identifying individuals who are at high risk for developing a psychotic illness, and may also inform interventions designed to prevent or minimize the illness process and accompanying dysfunction. © 2017 John Wiley & Sons Australia, Ltd.
Lindau, Stacy Tessler; Drum, Melinda L.; Gaumer, Elyzabeth; Surawska, Hanna; Jordan, Jeanne A.
Objective To estimate the prevalence, genotypes, and individual-level correlates of high-risk human papillomavirus (HPV) among women aged 57–85. Methods Community-residing women (n=1550), aged 57–85, were drawn from a nationally-representative probability sample. In-home interviews and biomeasures, including a self-collected vaginal specimen, were obtained between 2005 and 2006. Specimens were analyzed for high-risk HPV DNA using probe hybridization and signal amplification (hc2); of 1,028 specimens provided, 1,010 were adequate for analysis. All samples testing positive were analyzed for HPV DNA by L1 consensus polymerase chain reaction followed by type-specific hybridization. Results The overall population-based weighted estimate of high-risk HPV prevalence by hc2 was 6.0% (95% confidence interval [CI] = 4.5 to 7.9). Current marital and smoking status, frequency of sexual activity, history of cancer, and hysterectomy were associated with high-risk HPV positivity. Among high-risk HPV+ women, 63% had multiple type infections. HPV 16 or 18 was present in 17.4% of all high-risk HPV+ women. The most common high-risk genotypes among high-risk HPV+ women were HPV 61 (19.1%), 31 (13.1%), 52 (12.9%), 58 (12.5%), 83 (12.3%), 66(12.0%), 51 (11.7%), 45 (11.2%), 56 (10.3%), 53 (10.2%), 16 (9.7%), and 62 (9.2%). Being married and having an intact uterus were independently associated with lower prevalence of high-risk HPV. Among unmarried women, current sexual activity and smoking were independently and positively associated with high-risk HPV infection. Conclusions In this nationally representative population, nearly 1 in 16 women aged 57–85 were found to have high-risk HPV and prevalence was stable across older age groups. PMID:18978096
Eicher, John D; Chami, Nathalie; Kacprowski, Tim; Nomura, Akihiro; Chen, Ming-Huei; Yanek, Lisa R; Tajuddin, Salman M; Schick, Ursula M; Slater, Andrew J; Pankratz, Nathan; Polfus, Linda; Schurmann, Claudia; Giri, Ayush; Brody, Jennifer A; Lange, Leslie A; Manichaikul, Ani; Hill, W David; Pazoki, Raha; Elliot, Paul; Evangelou, Evangelos; Tzoulaki, Ioanna; Gao, He; Vergnaud, Anne-Claire; Mathias, Rasika A; Becker, Diane M; Becker, Lewis C; Burt, Amber; Crosslin, David R; Lyytikäinen, Leo-Pekka; Nikus, Kjell; Hernesniemi, Jussi; Kähönen, Mika; Raitoharju, Emma; Mononen, Nina; Raitakari, Olli T; Lehtimäki, Terho; Cushman, Mary; Zakai, Neil A; Nickerson, Deborah A; Raffield, Laura M; Quarells, Rakale; Willer, Cristen J; Peloso, Gina M; Abecasis, Goncalo R; Liu, Dajiang J; Deloukas, Panos; Samani, Nilesh J; Schunkert, Heribert; Erdmann, Jeanette; Fornage, Myriam; Richard, Melissa; Tardif, Jean-Claude; Rioux, John D; Dube, Marie-Pierre; de Denus, Simon; Lu, Yingchang; Bottinger, Erwin P; Loos, Ruth J F; Smith, Albert Vernon; Harris, Tamara B; Launer, Lenore J; Gudnason, Vilmundur; Velez Edwards, Digna R; Torstenson, Eric S; Liu, Yongmei; Tracy, Russell P; Rotter, Jerome I; Rich, Stephen S; Highland, Heather M; Boerwinkle, Eric; Li, Jin; Lange, Ethan; Wilson, James G; Mihailov, Evelin; Mägi, Reedik; Hirschhorn, Joel; Metspalu, Andres; Esko, Tõnu; Vacchi-Suzzi, Caterina; Nalls, Mike A; Zonderman, Alan B; Evans, Michele K; Engström, Gunnar; Orho-Melander, Marju; Melander, Olle; O'Donoghue, Michelle L; Waterworth, Dawn M; Wallentin, Lars; White, Harvey D; Floyd, James S; Bartz, Traci M; Rice, Kenneth M; Psaty, Bruce M; Starr, J M; Liewald, David C M; Hayward, Caroline; Deary, Ian J; Greinacher, Andreas; Völker, Uwe; Thiele, Thomas; Völzke, Henry; van Rooij, Frank J A; Uitterlinden, André G; Franco, Oscar H; Dehghan, Abbas; Edwards, Todd L; Ganesh, Santhi K; Kathiresan, Sekar; Faraday, Nauder; Auer, Paul L; Reiner, Alex P; Lettre, Guillaume; Johnson, Andrew D
Platelet production, maintenance, and clearance are tightly controlled processes indicative of platelets' important roles in hemostasis and thrombosis. Platelets are common targets for primary and secondary prevention of several conditions. They are monitored clinically by complete blood counts, specifically with measurements of platelet count (PLT) and mean platelet volume (MPV). Identifying genetic effects on PLT and MPV can provide mechanistic insights into platelet biology and their role in disease. Therefore, we formed the Blood Cell Consortium (BCX) to perform a large-scale meta-analysis of Exomechip association results for PLT and MPV in 157,293 and 57,617 individuals, respectively. Using the low-frequency/rare coding variant-enriched Exomechip genotyping array, we sought to identify genetic variants associated with PLT and MPV. In addition to confirming 47 known PLT and 20 known MPV associations, we identified 32 PLT and 18 MPV associations not previously observed in the literature across the allele frequency spectrum, including rare large effect (FCER1A), low-frequency (IQGAP2, MAP1A, LY75), and common (ZMIZ2, SMG6, PEAR1, ARFGAP3/PACSIN2) variants. Several variants associated with PLT/MPV (PEAR1, MRVI1, PTGES3) were also associated with platelet reactivity. In concurrent BCX analyses, there was overlap of platelet-associated variants with red (MAP1A, TMPRSS6, ZMIZ2) and white (PEAR1, ZMIZ2, LY75) blood cell traits, suggesting common regulatory pathways with shared genetic architecture among these hematopoietic lineages. Our large-scale Exomechip analyses identified previously undocumented associations with platelet traits and further indicate that several complex quantitative hematological, lipid, and cardiovascular traits share genetic factors.
Kalmbach, David A; Pillai, Vivek; Arnedt, J Todd; Drake, Christopher L
A primary focus of the National Institute of Mental Health's current strategic plan is "predicting" who is at risk for disease. As such, the current investigation examined the utility of premorbid sleep reactivity in identifying a specific and manageable population at elevated risk for future insomnia. A community-based sample of adults (n = 2,892; 59.3% female; 47.9 ± 13.3 y old) with no lifetime history of insomnia or depression completed web-based surveys across three annual assessments. Participants reported parental history of insomnia, demographic characteristics, sleep reactivity on the Ford Insomnia in Response to Stress Test (FIRST), and insomnia symptoms. DSM-IV diagnostic criteria were used to determine insomnia classification. Baseline FIRST scores were used to predict incident insomnia at 1-y follow-up. Two clinically meaningful FIRST cutoff values were identified: FIRST ≥ 16 (sensitivity 77%; specificity 50%; odds ratio [OR] = 2.88, P < 0.001); and FIRST ≥ 18 (sensitivity 62%; specificity 67%; OR = 3.32, P < 0.001). Notably, both FIRST cut-points outperformed known maternal (OR = 1.49-1.59, P < 0.01) and paternal history (P = NS) in predicting insomnia onset, even after controlling for stress exposure and demographic characteristics. Of the incident cases, insomniacs with highly reactive sleep systems reported longer sleep onset latencies (FIRST ≥ 16: 65 min; FIRST ≥ 18: 68 min) than participants with nonreactive insomnia (FIRST < 16: 37 min; FIRST < 18: 44 min); these groups did not differ on any other sleep parameters. The current study established a cost- and time-effective strategy for identifying individuals at elevated risk for insomnia based on trait sleep reactivity. The FIRST accurately identifies a focused target population in which the psychobiological processes complicit in insomnia onset and progression can be better investigated, thus improving future preventive efforts. © 2016 Associated Professional Sleep Societies, LLC.
Gard, Eric E.; Coffee, Keith R.; Frank, Matthias; Tobias, Herbert J.; Fergenson, David P.; Madden, Norm; Riot, Vincent J.; Steele, Paul T.; Woods, Bruce W.
An improved method and system of identifying individual aerosol particles in real time. Sample aerosol particles are collimated, tracked, and screened to determine which ones qualify for mass spectrometric analysis based on predetermined qualification or selection criteria. Screening techniques include one or more of determining particle size, shape, symmetry, and fluorescence. Only qualifying particles passing all screening criteria are subject to desorption/ionization and single particle mass spectrometry to produce corresponding test spectra, which is used to determine the identities of each of the qualifying aerosol particles by comparing the test spectra against predetermined spectra for known particle types. In this manner, activation cycling of a particle ablation laser of a single particle mass spectrometer is reduced.
Alexander, Cici; Korstjens, Amanda H.; Hill, Ross A.
Mapping and monitoring tropical rainforests and quantifying their carbon stocks are important, both for devising strategies for their conservation and mitigating the effects of climate change. Airborne Laser Scanning (ALS) has advantages over other remote sensing techniques for describing the three-dimensional structure of forests. This study identifies forest patches using ALS-based structural attributes in a tropical rainforest in Sumatra, Indonesia. A method to group trees with similar attributes into forest patches based on Thiessen polygons and k-medoids clustering is developed, combining the advantages of both raster and individual tree-based methods. The structural composition of the patches could be an indicator of habitat type and quality. The patches could also be a basis for developing allometric models for more accurate estimation of carbon stock than is currently possible with generalised models.
Lambert, J C; Ibrahim-Verbaas, C A; Harold, D; Naj, A C; Sims, R; Bellenguez, C; DeStafano, A L; Bis, J C; Beecham, G W; Grenier-Boley, B; Russo, G; Thorton-Wells, T A; Jones, N; Smith, A V; Chouraki, V; Thomas, C; Ikram, M A; Zelenika, D; Vardarajan, B N; Kamatani, Y; Lin, C F; Gerrish, A; Schmidt, H; Kunkle, B; Dunstan, M L; Ruiz, A; Bihoreau, M T; Choi, S H; Reitz, C; Pasquier, F; Cruchaga, C; Craig, D; Amin, N; Berr, C; Lopez, O L; De Jager, P L; Deramecourt, V; Johnston, J A; Evans, D; Lovestone, S; Letenneur, L; Morón, F J; Rubinsztein, D C; Eiriksdottir, G; Sleegers, K; Goate, A M; Fiévet, N; Huentelman, M W; Gill, M; Brown, K; Kamboh, M I; Keller, L; Barberger-Gateau, P; McGuiness, B; Larson, E B; Green, R; Myers, A J; Dufouil, C; Todd, S; Wallon, D; Love, S; Rogaeva, E; Gallacher, J; St George-Hyslop, P; Clarimon, J; Lleo, A; Bayer, A; Tsuang, D W; Yu, L; Tsolaki, M; Bossù, P; Spalletta, G; Proitsi, P; Collinge, J; Sorbi, S; Sanchez-Garcia, F; Fox, N C; Hardy, J; Deniz Naranjo, M C; Bosco, P; Clarke, R; Brayne, C; Galimberti, D; Mancuso, M; Matthews, F; Moebus, S; Mecocci, P; Del Zompo, M; Maier, W; Hampel, H; Pilotto, A; Bullido, M; Panza, F; Caffarra, P; Nacmias, B; Gilbert, J R; Mayhaus, M; Lannefelt, L; Hakonarson, H; Pichler, S; Carrasquillo, M M; Ingelsson, M; Beekly, D; Alvarez, V; Zou, F; Valladares, O; Younkin, S G; Coto, E; Hamilton-Nelson, K L; Gu, W; Razquin, C; Pastor, P; Mateo, I; Owen, M J; Faber, K M; Jonsson, P V; Combarros, O; O'Donovan, M C; Cantwell, L B; Soininen, H; Blacker, D; Mead, S; Mosley, T H; Bennett, D A; Harris, T B; Fratiglioni, L; Holmes, C; de Bruijn, R F; Passmore, P; Montine, T J; Bettens, K; Rotter, J I; Brice, A; Morgan, K; Foroud, T M; Kukull, W A; Hannequin, D; Powell, J F; Nalls, M A; Ritchie, K; Lunetta, K L; Kauwe, J S; Boerwinkle, E; Riemenschneider, M; Boada, M; Hiltuenen, M; Martin, E R; Schmidt, R; Rujescu, D; Wang, L S; Dartigues, J F; Mayeux, R; Tzourio, C; Hofman, A; Nöthen, M M; Graff, C; Psaty, B M; Jones, L; Haines, J L; Holmans, P A; Lathrop, M; Pericak-Vance, M A; Launer, L J; Farrer, L A; van Duijn, C M; Van Broeckhoven, C; Moskvina, V; Seshadri, S; Williams, J; Schellenberg, G D; Amouyel, P
Eleven susceptibility loci for late-onset Alzheimer's disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer's disease cases and 37,154 controls. In stage 2, 11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer's disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 × 10(-8)) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.
Li, X.; Tao, W.; Collis, S. M.; Varble, A.
Cumulus parameterizations in GCMs depend strongly on the vertical velocity structures of convective updraft cores, or plumes. There hasn't been an accurate way of identifying these cores. The majority of previous studies treat the updraft as a single grid column entity, thus missing many intrinsic characteristics, e.g., the size, strength and spatial orientation of an individual core, its life cycle, and the time variations of the entrainment/detrainment rates associated with its life cycle. In this study, we attempt to apply an innovative algorithm based on the centroid-based k-means cluster analysis to improve our understanding of convection and its associated updraft cores. Both 3-D Doppler radar retrievals and cloud-resolving model simulations of a TWP-ICE campaign case during the monsoon period will be used to test and improve this algorithm. This will provide for more in-depth comparisons between CRM simulations and observations that were not possible previously using the traditional piecewise analysis with each updraft column. The first step is to identify the strongest cores (maximum velocity >10 m/s), since they are well defined and produce definite answers when the cluster analysis algorithm is applied. The preliminary results show that the radar retrieved updraft cores are smaller in size and with the maximum velocity located uniformly at higher levels compared with model simulations. Overall, the model simulations produce much stronger cores compared with the radar retrievals. Within the model simulations, the bulk microphysical scheme simulation produces stronger cores than the spectral bin microphysical scheme. Planned researches include using high temporal-resolution simulations to further track the life cycle of individual updraft cores and study their characteristics.
Coderch, Jordi; Sánchez-Pérez, Inma; Ibern, Pere; Carreras, Marc; Pérez-Berruezo, Xavier; Inoriza, José M
To develop a predictive model for the risk of high consumption of healthcare resources, and assess the ability of the model to identify complex chronic patients. A cross-sectional study was performed within a healthcare management organization by using individual data from 2 consecutive years (88,795 people). The dependent variable consisted of healthcare costs above the 95th percentile (P95), including all services provided by the organization and pharmaceutical consumption outside of the institution. The predictive variables were age, sex, morbidity-based on clinical risk groups (CRG)-and selected data from previous utilization (use of hospitalization, use of high-cost drugs in ambulatory care, pharmaceutical expenditure). A univariate descriptive analysis was performed. We constructed a logistic regression model with a 95% confidence level and analyzed sensitivity, specificity, positive predictive values (PPV), and the area under the ROC curve (AUC). Individuals incurring costs >P95 accumulated 44% of total healthcare costs and were concentrated in ACRG3 (aggregated CRG level 3) categories related to multiple chronic diseases. All variables were statistically significant except for sex. The model had a sensitivity of 48.4% (CI: 46.9%-49.8%), specificity of 97.2% (CI: 97.0%-97.3%), PPV of 46.5% (CI: 45.0%-47.9%), and an AUC of 0.897 (CI: 0.892 to 0.902). High consumption of healthcare resources is associated with complex chronic morbidity. A model based on age, morbidity, and prior utilization is able to predict high-cost risk and identify a target population requiring proactive care. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.
Hewagalamulage, S D; Lee, T K; Clarke, I J; Henry, B A
There is a strong inter-relationship between activation of the hypothalamo-pituitary-adrenal axis and energy homeostasis. Patients with abdominal obesity have elevated cortisol levels. Furthermore, stress and glucocorticoids act to control both food intake and energy expenditure. In particular, glucocorticoids are known to increase the consumption of foods enriched in fat and sugar. It is well-known that, in all species, the cortisol response to stress or adrenocorticotropin is highly variable. It has now emerged that cortisol responsiveness is an important determinant in the metabolic sequelae to stress. Sheep that are characterized as high-cortisol responders (HRs) have greater propensity to weight gain and obesity than low-cortisol responders (LRs). This difference in susceptibility to become obese is associated with a distinct metabolic, neuroendocrine, and behavioral phenotype. In women and ewes, HR individuals eat more in response to stress than LR. Furthermore, HR sheep have impaired melanocortin signaling and reduced skeletal muscle thermogenesis. High-cortisol responder sheep exhibit reactive coping strategies, whereas LRs exhibit proactive coping strategies. This complex set of traits leads to increased food intake and reduced energy expenditure in HR and thus, predisposition to obesity. We predict that cortisol responsiveness may be used as a marker to identify individuals who are at risk of weight gain and subsequent obesity. Copyright © 2016 Elsevier Inc. All rights reserved.
Stanger, James D; Vo, Long; Yovich, John L; Almahbobi, Ghanim
One concern during intracytoplasmic sperm injection (ICSI) is that selected spermatozoa may have increased levels of DNA damage; however, the available testing for this is largely destructive in nature and therefore unsuitable as a tool for sperm selection. One alternative selection process that has previously achieved pregnancies is the hypo-osmotic swelling test (HOST). This study reports that low HOST values of neat semen samples were significantly (P<0.001) associated with increased DNA damage identified by the DNA fragmentation index (DFI) from the sperm chromatin structure assay as well as the TdT-mediated dUTP nick-end labelling (TUNEL) assay. The HOST value was highly predictive of an abnormal DFI value by receiver operating characteristic curve analysis (P<0.001). Furthermore, when individual spermatozoa were assessed for both HOST status and DNA fragmentation by TUNEL, the key HOST-induced tail-swelling grades D, E and F were most commonly associated with high HOST values and were significantly (P<0.001) associated with minimal DNA damage regardless of the DNA status of the ejaculate. The application of HOST may be a valuable tool in the routine identification and selection of viable, DNA-intact individual spermatozoa for ICSI after further research to demonstrate its efficacy and safety. Copyright © 2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
Lamster, Ira B; Cheng, Bin; Burkett, Sandra; Lalla, Evanthia
To assess the periodontal status and number of missing teeth in patients with newly identified pre-diabetes or diabetes mellitus. A total of 1097 subjects with previously undiagnosed diabetes were available for study, and were categorized into normoglycaemic, potentially pre-diabetes or potentially diabetes groups based on a point-of-care (POC) HbA1c test. In fully adjusted models, significant differences were observed between all groups for the per cent of teeth with at least one site with a probing depth of ≥5 mm. For bleeding on probing, there were significant differences between diabetes and pre-diabetes (p = 0.001), and between diabetes and normoglycaemic groups (p = 0.002). For missing teeth, there were significant differences between the pre-diabetes and normoglycaemic groups (p = 0.034), and the diabetes and normoglycaemic groups (p = 0.004). Individuals with previously unidentified pre-diabetes demonstrate a level of periodontal destruction between that observed for normoglycaemic individuals and persons with diabetes. These data emphasize the association of oral findings to dysglycaemia, and suggest that periodontal disease and tooth loss can be early complications of diabetes mellitus. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Meskin, Lawrence H.; And Others
A dental health program in an elementary school succeeded in identifying children considered to be "high risk" in oral health and, through treatment and education, significantly improved their dental health. (JD)
Chang, W.; Stein, M.; Wang, J.; Kotamarthi, V. R.; Moyer, E. J.
A growing body of literature suggests that human-induced climate change may cause significant changes in precipitation patterns, which could in turn influence future flood levels and frequencies and water supply and management practices. Although climate models produce full three-dimensional simulations of precipitation, analyses of model precipitation have focused either on time-averaged distributions or on individual timeseries with no spatial information. We describe here a new approach based on identifying and characterizing individual rainstorms in either data or model output. Our approach enables us to readily characterize important spatio-temporal aspects of rainstorms including initiation location, intensity (mean and patterns), spatial extent, duration, and trajectory. We apply this technique to high-resolution precipitation over the continental U.S. both from radar-based observations (NCEP Stage IV QPE product, 1-hourly, 4 km spatial resolution) and from model runs with dynamical downscaling (WRF regional climate model, 3-hourly, 12 km spatial resolution). In the model studies we investigate the changes in storm characteristics under a business-as-usual warming scenario to 2100 (RCP 8.5). We find that in these model runs, rainstorm intensity increases as expected with rising temperatures (approximately 7%/K, following increased atmospheric moisture content), while total precipitation increases by a lesser amount (3%/K), consistent with other studies. We identify for the first time the necessary compensating mechanism: in these model runs, individual precipitation events become smaller. Other aspects are approximately unchanged in the warmer climate. Because these spatio-temporal changes in rainfall patterns would impact regional hydrology, it is important that they be accurately incorporated into any impacts assessment. For this purpose we have developed a methodology for producing scenarios of future precipitation that combine observational data and
Osteen, Philip J; Frey, Jodi J; Ko, Jungyai
Research and training on suicide is critical given the fact that the majority of suicide deaths are preventable with accurate identification of risk and intervention by trained individuals. However, implementing and evaluating training is difficult because of the multiple factors involved, including, but not limited to, the heterogeneity of trainees, their diverse roles in suicide prevention, absence of clear guidelines for training content across settings, and limited methods for assessing outcomes. Here, three groups of trainees are discussed: community and professional gatekeepers and behavioral health providers. The roles each group plays in managing suicide risk and the training content it needs to be effective are addressed. A staged training approach is proposed, building on the core components of currently used suicide training: knowledge, attitudes, and skills/behaviors. Limitations of current assessment methods are identified and recommendations for alternative methods are provided. The article concludes with a discussion of next steps in moving the field forward, including overcoming challenges and identifying and engaging opportunities. Copyright © 2014 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.
Westfall, Andrew O.; Chamot, Eric; Saag, Michael; Walcott, Melonie; Ritchie, Christine; Kertesz, Stefan
Abstract A method to rapidly identify the presence of chronic pain would enhance the care of HIV-infected individuals, but such an instrument has not been assessed in this population to date. We assessed the construct validity of the two-question Brief Chronic Pain Questionnaire (BCPQ) in HIV-infected patients by assessing the association between BCPQ responses and known correlates of chronic pain. Participants in the University of Alabama Center for AIDS Research Network of Integrated Clinical Systems cohort completed the BCPQ, along with the EuroQOL to assess physical function, the PHQ-9 to assess depression, and the PHQ-anxiety module to assess anxiety. Among 100 participants, 25% were female, the mean age was 45 (SD 12), 63% were African American, 27% were publicly insured, the median CD4+ T cell count was 572 cells/mm3 (IQR 307–788), and 82% had an undetectable viral load. Participants with chronic pain were more likely to have impaired mobility (43% vs. 12%, p=0.001), difficulty with usual activities (47% vs. 12%, p<0.001), lower overall health state (70 vs. 84, p=0.002), pain today (80% vs. 27%, p<0.001), depression (30% vs. 15%, p=0.10), and anxiety (43% vs. 10%, p<0.001) than those without chronic pain. This study provides preliminary evidence for the BCPQ as a brief questionnaire to identify the presence of chronic pain in HIV care settings. PMID:25693683
Goffin, Karolien E; Joniau, Steven; Tenke, Peter; Slawin, Kevin; Klein, Eric A; Stambler, Nancy; Strack, Thomas; Babich, John; Armor, Thomas; Wong, Vivien
(99m)Tc-trofolastat ((99m)Tc-MIP-1404), a small-molecule inhibitor of prostate-specific membrane antigen, shows high potential to detect prostate cancer (PCa) noninvasively using SPECT. We therefore wanted to assess the performance of (99m)Tc-trofolastat SPECT/CT in a phase 2 multicenter, multireader prospective study in patients with intermediate- and high-grade PCa, before radical prostatectomy and extended pelvic lymph node (LN) dissection, with histopathology as the gold standard. Methods: PCa patients (n = 105) with an increased risk of LN involvement (LNI) underwent pelvic (99m)Tc-trofolastat SPECT/CT before radical prostatectomy with extended pelvic LN dissection. The sensitivity of (99m)Tc-trofolastat for detection of PCa on a patient and lobe basis, using visual and semiquantitative (tumor-to-background ratio [TBR]) scores, and of LNI was evaluated as well as the correlation of uptake within the gland to Gleason scores (GS) and assessment of the predictive potential of (99m)Tc-trofolastat uptake for LNI. Results: PCa was detected in 98 patients (94%) with acceptable variability between readers. There was a significantly higher visual score and TBR in positive lobes compared with tumor-negative lobes. Receiver-operating characteristic analysis showed that visual scores more accurately discriminated lobes with GS ≤ 3 + 3 from ≥ 3 + 4, whereas TBRs discriminated high-grade disease from normal lobes better. Visual scores and TBRs correlated significantly with GS. (99m)Tc-trofolastat SPECT/CT detected LNI with a sensitivity of 50% and specificity of 87%, and TBR values significantly predicted LNI with a sensitivity of 90%. Conclusion:(99m)Tc-trofolastat SPECT/CT detects PCa with high sensitivity in patients with intermediate- and high-risk PCa compared with histology. It has the potential to be used as a surrogate marker for GS and predict LNI. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.
Houfflin-Debarge, V; Closset, E; Deruelle, P
Intrapartum asphyxia is increased in several situations such as intrauterine growth retardation, preterm labor, postdate pregnancy or maternal diabetes. In all these cases, fetal heart rate monitoring should be preferred to intermittent auscultation. Fetal scalp blood pH or lactates can be used to identify fetuses at risk of intrapartum asphyxia. However, fetal scalp blood sampling should not delay delivery in case of severe abnormal fetal heart rate as fetal asphyxia could occur rapidly in theses high-risk pregnancies. Data is insufficient to recommend fetal pulse oximetry or ECG analysis. Research should be undertaken to evaluate their performance in these situations.
Knopf, D. A.; Alpert, P. A.; Wang, B.; OBrien, R. E.; Moffet, R. C.; Aller, J. Y.; Laskin, A.; Gilles, M.
Atmospheric ice formation represents one of the least understood atmospheric processes with important implications for the hydrological cycle and climate. Current freezing descriptions assume that ice active sites on the particle surface initiate ice nucleation, however, the nature of these sites remains elusive. Here, we present a new experimental method that allows us to relate physical and chemical properties of individual particles with observed water uptake and ice nucleation ability using a combination of micro-spectroscopic and optical single particle analytical techniqu