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Gene by environment (GxE) interaction studies have investigated the influence of a number of candidate genes and variants for major depressive disorder (MDD) on the association between childhood trauma and MDD. Most of these studies are hypothesis driven and investigate only a limited number of SNPs in relevant pathways using differing methodological approaches. Here (1) we identified 27 genes and 268 SNPs previously associated with MDD or with GxE interaction in MDD and (2) analyzed their impact on GxE in MDD using a common approach in 3944 subjects of European ancestry from the Psychiatric Genomics Consortium who had completed the Childhood Trauma Questionnaire. (3) We subsequently used the genome-wide SNP data for a genome-wide case-control GxE model and GxE case-only analyses testing for an enrichment of associated SNPs. No genome-wide significant hits and no consistency among the signals of the different analytic approaches could be observed. This is the largest study for systematic GxE interaction analysis in MDD in subjects of European ancestry to date. Most of the known candidate genes/variants could not be supported. Thus, their impact on GxE interaction in MDD may be questionable. Our results underscore the need for larger samples, more extensive assessment of environmental exposures, and greater efforts to investigate new methodological approaches in GxE models for MDD.

Contains fulltext : 169790pub.pdf (publisher's version ) (Closed access), Schizophrenia is associated with brain structural abnormalities including gray and white matter volume reductions. Whether these alterations are caused by genetic risk variants for schizophrenia is unclear. Previous attempts to detect associations between polygenic factors for schizophrenia and structural brain phenotypes in healthy subjects have been negative or remain non-replicated. In this study, we used genetic risk scores that were based on the accumulated effect of selected risk variants for schizophrenia belonging to specific biological systems like synaptic function, neurodevelopment, calcium signaling, and glutamatergic neurotransmission. We hypothesized that this "biologically informed" approach would provide the missing link between genetic risk for schizophrenia and brain structural phenotypes. We applied whole-brain voxel-based morphometry (VBM) analyses in two population-based target samples and subsequent regions of interest (ROIs) analyses in an independent replication sample (total N = 2725). No consistent association between the genetic scores and brain volumes were observed in the investigated samples. These results suggest that in healthy subjects with a higher genetic risk for schizophrenia additional factors apart from common genetic variants (e.g., infection, trauma, rare genetic variants, or gene-gene interactions) are required to induce structural abnormalities of the brain. Further studies are recommended to test for possible gene-gene or gene-environment effects. (c) 2017 Wiley Periodicals, Inc.

Contains fulltext : 169790pub.pdf (publisher's version ) (Closed access), Schizophrenia is associated with brain structural abnormalities including gray and white matter volume reductions. Whether these alterations are caused by genetic risk variants for schizophrenia is unclear. Previous attempts to detect associations between polygenic factors for schizophrenia and structural brain phenotypes in healthy subjects have been negative or remain non-replicated. In this study, we used genetic risk scores that were based on the accumulated effect of selected risk variants for schizophrenia belonging to specific biological systems like synaptic function, neurodevelopment, calcium signaling, and glutamatergic neurotransmission. We hypothesized that this "biologically informed" approach would provide the missing link between genetic risk for schizophrenia and brain structural phenotypes. We applied whole-brain voxel-based morphometry (VBM) analyses in two population-based target samples and subsequent regions of interest (ROIs) analyses in an independent replication sample (total N = 2725). No consistent association between the genetic scores and brain volumes were observed in the investigated samples. These results suggest that in healthy subjects with a higher genetic risk for schizophrenia additional factors apart from common genetic variants (e.g., infection, trauma, rare genetic variants, or gene-gene interactions) are required to induce structural abnormalities of the brain. Further studies are recommended to test for possible gene-gene or gene-environment effects. (c) 2017 Wiley Periodicals, Inc.

Item does not contain fulltext, While research on chronic ankle instability (CAI) and awareness of its impact on society and health care systems has grown substantially in the last 2 decades, the inconsistency in participant/patient selection criteria across studies presents a potential obstacle to addressing the problem properly. This major gap within the literature limits the ability to generalise this evidence to the target patient population. Therefore, there is a need to provide standards for patient/participant selection criteria in research focused on CAI with justifications using the best available evidence. The International Ankle Consortium provides this position paper to present and discuss an endorsed set of selection criteria for patients with CAI based on the best available evidence to be used in future research and study designs. These recommendations will enhance the validity of research conducted in this clinical population with the end goal of bringing the research evidence to the clinician and patient.

Contains fulltext : 136784.pdf (publisher's version ) (Open Access), While research on chronic ankle instability (CAI) and awareness of its impact on society and health care systems has grown substantially in the last 2 decades, the inconsistency in participant or patient selection criteria across studies presents a potential obstacle to addressing the problem properly. This major gap within the literature limits the ability to generalize this evidence to the target patient population. Therefore, there is a need to provide standards for patient or participant selection criteria in research focused on CAI with justifications using the best available evidence. The International Ankle Consortium provides this position paper to present and discuss an endorsed set of selection criteria for patients with CAI based on the best available evidence to be used in future research and study designs. These recommendations will enhance the validity of research conducted in this clinical population with the end goal of bringing the research evidence to the clinician and patient.

Item does not contain fulltext, While research on chronic ankle instability (CAI) and awareness of its impact on society and health care systems has grown substantially in the last 2 decades, the inconsistency in participant/patient selection criteria across studies presents a potential obstacle to addressing the problem properly. This major gap within the literature limits the ability to generalise this evidence to the target patient population. Therefore, there is a need to provide standards for patient/participant selection criteria in research focused on CAI with justifications using the best available evidence. The International Ankle Consortium provides this position paper to present and discuss an endorsed set of selection criteria for patients with CAI based on the best available evidence to be used in future research and study designs. These recommendations will enhance the validity of research conducted in this clinical population with the end goal of bringing the research evidence to the clinician and patient.

Contains fulltext : 136784.pdf (publisher's version ) (Open Access), While research on chronic ankle instability (CAI) and awareness of its impact on society and health care systems has grown substantially in the last 2 decades, the inconsistency in participant or patient selection criteria across studies presents a potential obstacle to addressing the problem properly. This major gap within the literature limits the ability to generalize this evidence to the target patient population. Therefore, there is a need to provide standards for patient or participant selection criteria in research focused on CAI with justifications using the best available evidence. The International Ankle Consortium provides this position paper to present and discuss an endorsed set of selection criteria for patients with CAI based on the best available evidence to be used in future research and study designs. These recommendations will enhance the validity of research conducted in this clinical population with the end goal of bringing the research evidence to the clinician and patient.

Item does not contain fulltext, The International Ankle Consortium is an international community of researchers and clinicians whose primary scholastic purpose is to promote scholarship and dissemination of research-informed knowledge related to pathologies of the ankle complex. The constituents of the International Ankle Consortium and other similar organizations have yet to properly define the clinical phenomenon known as chronic ankle instability (CAI) and its related characteristics for consistent patient recruitment and advancement of research in this area. Although research on CAI and awareness of its impact on society and healthcare systems have grown substantially in the last 2 decades, the inconsistency in participant/patient selection criteria across studies presents a potential obstacle to addressing the problem properly. This major gap within the literature limits the ability to generalize this evidence to the target patient population. Therefore, there is a need to provide standards for patient/participant selection criteria in research focused on CAI, with justifications using the best available evidence.J Orthop Sports Phys Ther 2013;43(8):585-591. doi:10.2519/jospt.2013.0303.

Item does not contain fulltext, The International Ankle Consortium is an international community of researchers and clinicians whose primary scholastic purpose is to promote scholarship and dissemination of research-informed knowledge related to pathologies of the ankle complex. The constituents of the International Ankle Consortium and other similar organizations have yet to properly define the clinical phenomenon known as chronic ankle instability (CAI) and its related characteristics for consistent patient recruitment and advancement of research in this area. Although research on CAI and awareness of its impact on society and healthcare systems have grown substantially in the last 2 decades, the inconsistency in participant/patient selection criteria across studies presents a potential obstacle to addressing the problem properly. This major gap within the literature limits the ability to generalize this evidence to the target patient population. Therefore, there is a need to provide standards for patient/participant selection criteria in research focused on CAI, with justifications using the best available evidence.J Orthop Sports Phys Ther 2013;43(8):585-591. doi:10.2519/jospt.2013.0303.

Item does not contain fulltext, The International Ankle Consortium is an international community of researchers and clinicians whose primary scholastic purpose is to promote scholarship and dissemination of research-informed knowledge related to pathologies of the ankle complex. The constituents of the International Ankle Consortium and other similar organizations have yet to properly define the clinical phenomenon known as chronic ankle instability (CAI) and its related characteristics for consistent patient recruitment and advancement of research in this area. Although research on CAI and awareness of its impact on society and healthcare systems have grown substantially in the last 2 decades, the inconsistency in participant/patient selection criteria across studies presents a potential obstacle to addressing the problem properly. This major gap within the literature limits the ability to generalize this evidence to the target patient population. Therefore, there is a need to provide standards for patient/participant selection criteria in research focused on CAI, with justifications using the best available evidence.J Orthop Sports Phys Ther 2013;43(8):585-591. doi:10.2519/jospt.2013.0303.

BACKGROUND: This study was undertaken to estimate utility values for alternative treatment intervals for long acting antipsychotic intramuscular injections for the treatment of schizophrenia. METHODS: Vignettes were developed using the published literature and an iterative consultation process with expert clinicians and patient representative groups. Four vignettes were developed. The first was a vignette of relapsed/untreated schizophrenia. The other three vignettes presented a standardised picture of well-managed schizophrenia with variations in the intervals between injections: once every 2-weeks, 4-weeks and 3-months. A standardised time trade off (TTO) approach was used to obtain utility values for the vignettes. As a societal perspective was sought, a representative sample of individuals from across the community (Sydney, Australia) was recruited. Ninety-eight people completed the TTO interview. The vignettes were presented in random order to prevent possible ordering effects. RESULTS: A clear pattern of increasing utility was observed with increasing time between injections. Untreated schizophrenia was rated as very poor health-related quality of life with a mean (median) utility of 0.27 (0.20). The treated health states were rated at much higher utilities and were statistically significantly different (p < 0.001) from each other: (1) 2-weekly: mean (median) utility = 0.61 (0.65); (2) 4-weekly: mean (median) utility = 0.65 (0.70); (3) 3-monthly: mean (median) utility = 0.70 (0.75). CONCLUSIONS: This study has provided robust data indicating that approximately a 0.05 utility difference exists between treatment options, with the highest utility assigned to 3-monthly injections.

BACKGROUND: Risperidone long-acting injection (LAI) is mostly administered twice weekly to people with schizophrenia by nurses at community mental health centres (CMHC) or through mobile outreach visits. This study estimates the cost of resource utilisation associated with the administration of risperidone LAI and the potential savings from substituting two-weekly injections with a longer interval product of therapeutic equivalence. METHODS: A survey of mental health staff overseeing the administration of risperidone LAI at 253 distinct Australian CMHCs was undertaken in November 2009. For the two-week period prior to the survey, respondents were asked questions on injection time (and related tasks) and, for mobile outreach visits, distance and time travelled as well as reduction in visits. Results were stratified by Australian Standard Geographical Classification (ASGC) region. Resource use was quantified and valued in Australian dollars. RESULTS: Results are derived from 74 CMHCs, representing approximately 26% of the national average risperidone LAI unit two-week sales. Stratified average injection time (including related tasks) for risperidone LAI ranged from 18-29 minutes, with a national average of 20.12 minutes. For mobile outreach visits, average distance per patient ranged from 19.4 to 55.5 km for One Staff Visits and 15.2 to 218.1 km for More Than One Staff Visits, and average time travelled ranged from 34.1 to 54.5 minutes for One Staff Visits and 29.2 to 136.3 minutes for More Than One Staff visits. The upper range consistently reflected greater resource utilisation in rural areas compared to urban areas. If administration of risperidone LAI had not been required, 20% fewer mobile outreach visits would have occurred. CONCLUSIONS: The national average saving per two-weekly risperidone long-acting injection avoided is $75.14. In 2009 in Australia, this would have saved ~$11 million for injection administration costs alone if all patients taking two-weekly

OBJECTIVE: To conduct a systematic review of the efficacy of single-agent bortezomib vs. single-agent thalidomide in patients with relapsed/refractory multiple. METHODS: Publications in English from 1966 to June 2005 (MEDLINE, EMBASE, Cochrane library), publication reference lists, Janssen-Cilag data-on-file and abstracts from recent multiple myeloma conferences were reviewed. Prospective studies containing at least a single arm of either treatment group with n> or =30 were included. Studies adding dexamethasone for non-responders were excluded. Statistical pooling was performed for response rate and overallsurvival. RESULTS: One bortezomib study (n = 333, NEJM 2005, 352; 2487-98) and 15 thalidomide (n = 1007) studies met these criteria and were included. Patient baseline characteristics including age, gender, IgG : IgA, disease duration and beta-2 microglobulin were well matched except that 48% of bortezomib patients had received prior thalidomide. Response rate, defined as serum M-protein reduction > or =50%, was 53% for patients receiving bortezomib vs. 32% for thalidomide (P < 0.001, n = 10 studies). Response rate determined by European Group for Blood and Marrow Transplantation (EBMT) criteria was 41% for patients receiving bortezomib vs. 22% for thalidomide (P < 0.001, n = 4 studies). CONCLUSION: Bortezomib was associated with a significantly higher response rate and complete remission rate using both M-protein and EBMT criteria.

A new method of separation of single polyprenols (or dolichols) from a mixture of isoprenoid alcohols is described. Application of a high-performance liquid chromatography (HPLC) apparatus equipped with a semipreparative ODS column resulted in preparation of long-chain (dihydro)polyprenols of high purity (>95%). This approach substantially decreases the time scale of the conventional chromatographical preparative procedure. The method can be widely used in chemical and biochemical projects, where single polyprenols or dolichols are required.

AIRWAR II is a deterministic, expected-value simulation of a two-sided air-to-air and air-to-ground campaign fought over an extended period of time. It includes Wild Weasels, ECM, SAMs, air intercepts, reinforcement of weapons and planes, and detailed ground equations at primary and secondary bases which may be degraded by chemical/nuclear/biological effects. Documentation includes: Execution instructions, model description, pertinent equations, logic flowcharts, sample input/output, sample graphics. (Author)

Postural control deficits have been identified among individuals with chronic ankle instability (CAI) compared to healthy controls. Although deficits in static balance have previously been reported using center of pressure (COP) and, more recently, time to boundary (TTB) measures, the underlying mechanism behind these deficits warrants further investigation. It is unclear if there are differences in the spatial distribution of COP and TTBminima data points under the foot. Our purpose was to determine if there are differences in the location of the distribution of the COP and the TTB minima data points between groups with and without CAI. Fifty healthy and 61 CAI subjects participated in this case–control study. The subjects performed three successful 10-s trials of quiet single limb stance on a force plate with eyes-open and -closed conditions. Results showed that during eyes-open trials, the CAI group exhibited more COP and TTB minima data points on the anterolateral aspect of the foot compared to controls. With eyes-closed single limb balance, the CAI group demonstrated significantly more COP and TTB minima data points anterior to the horizontal midline of the foot compared to controls. Overall, the CAI group showed a greater anterior displacement of COP and TTB minima during single limb static stance compared to controls. This alteration may result from the CAI subjects adopting a more dorsiflexed position in an effort to keep the ankle in a more stable, closed pack position and limiting the available degrees of freedom in the distal lower extremity.