A Device for Quantitative Analysis of the Thumb Ulnar Collateral Ligament

A device to quantitatively assess the ulnar collateral ligament of the thumb was developed to facilitate rapid and accurate diagnosis of the ligamentous injury known as Skier’s thumb. Topics: Wound

Good Research Practices for Measuring Drug Costs in Cost-Effectiveness Analyses: A Managed Care Perspective: The ISPOR Drug Cost Task Force Report—Part III

AbstractObjectivesThe objective of this report is to provide guidance and recommendations on how drug costs should be measured for cost-effectiveness analyses conducted from the perspective of a managed care organization (MCO).MethodsThe International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Task Force on Good Research Practices—Use of Drug Costs for Cost Effectiveness Analysis (DCTF) was appointed by the ISPOR Board of Directors. Members were experienced developers or users of CEA models. The DCTF met to develop core assumptions and an outline before preparing a draft report. They solicited comments on drafts from external reviewers and from the ISPOR membership at ISPOR meetings and via the ISPOR Web site.ResultsThe cost of a drug to an MCO equals the amount it pays to the dispenser for the drug's ingredient cost and dispensing fee minus the patient copay and any rebates paid by the drug's manufacturer. The amount that an MCO reimburses for each of these components can differ substantially across a number of factors that include type of drug (single vs. multisource), dispensing site (retail vs. mail order), and site of administration (self-administered vs. physician's office). Accurately estimating the value of cost components is difficult because they are determined by proprietary and confidential contracts.ConclusionEstimates of drug cost from the MCO perspective should include amounts paid for medication ingredients and dispensing fees, and net out copays, rebates, and other drug price reductions. Because of the evolving nature of drug pricing, ISPOR should publish a Web site where current DCTF costing recommendations are updated as new information becomes available

Angiogenic mRNA and microRNA Gene Expression Signature Predicts a Novel Subtype of Serous Ovarian Cancer

Ovarian cancer is the fifth leading cause of cancer death for women in the U.S. and the seventh most fatal worldwide. Although ovarian cancer is notable for its initial sensitivity to platinum-based therapies, the vast majority of patients eventually develop recurrent cancer and succumb to increasingly platinum-resistant disease. Modern, targeted cancer drugs intervene in cell signaling, and identifying key disease mechanisms and pathways would greatly advance our treatment abilities. In order to shed light on the molecular diversity of ovarian cancer, we performed comprehensive transcriptional profiling on 129 advanced stage, high grade serous ovarian cancers. We implemented a, re-sampling based version of the ISIS class discovery algorithm (rISIS: robust ISIS) and applied it to the entire set of ovarian cancer transcriptional profiles. rISIS identified a previously undescribed patient stratification, further supported by micro-RNA expression profiles, and gene set enrichment analysis found strong biological support for the stratification by extracellular matrix, cell adhesion, and angiogenesis genes. The corresponding “angiogenesis signature” was validated in ten published independent ovarian cancer gene expression datasets and is significantly associated with overall survival. The subtypes we have defined are of potential translational interest as they may be relevant for identifying patients who may benefit from the addition of anti-angiogenic therapies that are now being tested in clinical trials

The impact of the COVID-19 pandemic on the delivery of primary percutaneous coronary intervention in STEMI

Objectives: The clinical environment has been forced to adapt to meet the unprecedented challenges posed by the COVID-19 pandemic. Intensive care facilities were expanded in anticipation of the pandemic where the consequences include severe delays in elective procedures. Emergent procedures such as Percutaneous Coronary Intervention (PCI) in acute myocardial infarction (AMI) in which delays in timely delivery have well established adverse prognostic effects must also be explored in the context of changes in procedure and public behaviour associated with the COVID-19 pandemic. The aim for this single centre retrospective cohort study is to determine if door-to-balloon (D2B) times in PCI for ST Elevation Myocardial Infarction (STEMI) during the United Kingdom’s first wave of the COVID-19 pandemic differed from pre-COVID-19 populations. Methods: Data was extracted from our single centre PCI database for all patients that underwent pPCI for STEMI. The reference (Pre-COVID-19) cohort was collected over the period 01-03-2019 to 31-05-2019 and the exposure group (COVID-19) over the period 01-03-2020 to 31-05-2020. Baseline patient characteristics for both populations were extracted. The primary outcome measurement was D2B times. Secondary outcome measurements included: time of symptom onset to call for help, transfer time to first hospital, transfer time from non-PCI to PCI centre, time from call-to-help to PCI centre, time to table and onset of symptoms to balloon time. Categorical and continuous variables were assessed with Chi squared and Mann-Whitney U analysis respectively. Procedural times were calculated and compared in the context of heterogeneity findings. Results: 4 baseline patient characteristics were unbalanced between populations with statistical significance (P<0.05). The pre-covid-19 cohort was more likely to have suffered out of hospital cardiac arrest (OHCA) and had left circumflex disease, whereas the 1st wave cohort were more likely to have been investigated with left ventriculography and be of Afro-Caribbean origin. No statistically significant difference in in-hospital procedural times was found with D2B, C2B, O2B times comparable between groups. Pre-hospital delays were the greatest contributors in missed target times: the 1st wave group had significantly longer delayed time of symptom onset to call for help (Control: 31 mins; IQR [82.5] vs 1st wave: 60 mins; IQR [90.0], P=0.001) and time taken from call for help to arrival at the PCI hospital (control: 72 mins; IQR [23] vs 1st wave: 80 mins; IQR [66.5], P=0.042). Conclusion: Enhanced infection prevention and control procedures considering the COVID-19 pandemic did not impede the delivery of pPCI in our single centre cohort. The public health impact of the pandemic has been demonstrated with times being significantly impacted by patient related delays. The recovery of public engagement in emergency medical services must become the focus for public health initiatives as we emerge from the height of COVID-19 disease burden in the UK.Publisher PDFPeer reviewe

Brain state stability during working memory is explained by network control theory, modulated by dopamine D1/D2 receptor function, and diminished in schizophrenia

Dynamical brain state transitions are critical for flexible working memory but the network mechanisms are incompletely understood. Here, we show that working memory entails brainwide switching between activity states. The stability of states relates to dopamine D1 receptor gene expression while state transitions are influenced by D2 receptor expression and pharmacological modulation. Schizophrenia patients show altered network control properties, including a more diverse energy landscape and decreased stability of working memory representations

BRCC36A is epistatic to BRCA1 in DNA crosslink repair and homologous recombination in Arabidopsis thaliana

BRCA1 is a well-known tumor suppressor protein in mammals, involved in multiple cellular processes such as DNA repair, chromosome segregation and chromatin remodeling. Interestingly, homologs of BRCA1 and several of its complex partners are also found in plants. As the respective mutants are viable, in contrast to mammalian mutants, detailed analyses of their biological role is possible. Here we demonstrate that the model plant Arabidopsis thaliana harbors two homologs of the mammalian BRCA1 interaction partner BRCC36, AtBRCC36A and AtBRCC36B. Mutants of both genes as well as the double mutants are fully fertile and show no defects in development. We were able to show that mutation of one of the homologs, AtBRCC36A, leads to a severe defect in intra- and interchromosomal homologous recombination (HR). A HR defect is also apparent in Atbrca1 mutants. As the Atbrcc36a/Atbrca1 double mutant behaves like the single mutants of AtBRCA1 and AtBRCC36A both proteins seem to be involved in a common pathway in the regulation of HR. AtBRCC36 is also epistatic to AtBRCA1 in DNA crosslink repair. Upon genotoxic stress, AtBRCC36A is transferred into the nucleus

Intergenerational Community-Based Research and Creative Practice: Promoting Environmental Sustainability in Jinja, Uganda

This article critically reflects on the methodological approach developed for a recent project based in Jinja, Uganda, that sought to generate new forms of environmental knowledge and action utilizing diverse forms of creative intergenerational practice embedded within a broader framework of community-based participatory research. This approach provided new opportunities for intergenerational dialogue in Jinja, generated increased civic environmental engagement, and resulted in a participant-led campaign to share knowledge regarding sustainable biomass consumption. We term this approach intergenerational community-based research and creative practice. We discuss the advantages of this model while also reflecting throughout on the challenges of the approach