Comparative effectiveness of levetiracetam, valproate and carbamazepine among elderly patients with newly diagnosed epilepsy: subgroup analysis of the randomized, unblinded KOMET study

BACKGROUND: Few clinical trials have evaluated the efficacy and tolerability of antiepileptic drugs (AEDs) as initial monotherapy for elderly patients. METHODS: This post-hoc subgroup analysis of data from an unblinded, randomized, 52-week superiority study (KOMET) compared the effectiveness of levetiracetam (LEV) with extended-release sodium valproate (VPA-ER) and controlled-release carbamazepine (CBZ-CR) as monotherapy in patients aged 60 years with newly diagnosed epilepsy. The physician chose VPA or CBZ as preferred standard treatment; patients were randomized to standard AEDs or LEV. The primary endpoint was time to treatment withdrawal. Results are exploratory, since KOMET was not powered for a subgroup analysis by age. RESULTS: Patients (n = 308) were randomized to LEV (n = 48) or VPA-ER (n = 53) in the VPE-ER stratum or to LEV (n = 104) or CBZ-CR (n = 103) in the CBZ-CR stratum. Mean age was 69.6 years, range 60.2-89.9 years (intention-to-treat population n = 307). Time to treatment withdrawal hazard ratio [HR] (95 % confidence interval [CI]) for LEV vs. standard AEDs was 0.44 (0.28-0.67); LEV vs. VPA-ER: 0.46 (0.16-1.33); LEV vs. CBZ-CR: 0.45 (0.28-0.72). Twelve-month withdrawal rates were: LEV vs. standard AEDs, 20.4 vs. 38.7 %; LEV vs. VPA-ER, 10.4 vs. 23.1 %; LEV vs. CBZ-CR, 25.0 vs. 46.6 %. Time to first seizure was similar between LEV and standard AEDs (HR: 0.92, 95 % CI: 0.63-1.35), LEV and VPA-ER (0.77, 0.38-1.56), and LEV and CBZ-CR (1.02, 0.64-1.63). Adverse events were reported by 76.2, 67.3, and 82.5 % of patients for LEV, VPA-ER, and CBZ-CR, respectively. Discontinuation rates due to AEs were 11.3, 10.2, and 35.0 % for LEV, VPA-ER, and CBZ-CR, respectively.CONCLUSIONS: Time to treatment withdrawal was longer with LEV compared with standard AEDs. This finding was driven primarly by the result in the CBZ-CR stratum, which in turn was likely due to the more favorable tolerability profile of LEV. Results of this post-hoc analysis suggest that LEV(VLID)195291

PRADA: Portable Reusable Accurate Diagnostics with nanostar Antennas for multiplexed biomarker screening

Precise monitoring of specific biomarkers in biological fluids with accurate biodiagnostic sensors is critical for early diagnosis of diseases and subsequent treatment planning. In this work, we demonstrated an innovative biodiagnostic sensor, portable reusable accurate diagnostics with nanostar antennas (PRADA), for multiplexed biomarker detection in small volumes (~50 μl) enabled in a microfluidic platform. Here, PRADA simultaneously detected two biomarkers of myocardial infarction, cardiac troponin I (cTnI), which is well accepted for cardiac disorders, and neuropeptide Y (NPY), which controls cardiac sympathetic drive. In PRADA immunoassay, magnetic beads captured the biomarkers in human serum samples, and gold nanostars (GNSs) “antennas” labeled with peptide biorecognition elements and Raman tags detected the biomarkers via surface‐enhanced Raman spectroscopy (SERS). The peptide‐conjugated GNS‐SERS barcodes were leveraged to achieve high sensitivity, with a limit of detection (LOD) of 0.0055 ng/ml of cTnI, and a LOD of 0.12 ng/ml of NPY comparable with commercially available test kits. The innovation of PRADA was also in the regeneration and reuse of the same sensor chip for ~14 cycles. We validated PRADA by testing cTnI in 11 de‐identified cardiac patient samples of various demographics within a 95% confidence interval and high precision profile. We envision low‐cost PRADA will have tremendous translational impact and be amenable to resource‐limited settings for accurate treatment planning in patients

Infrared based saliva screening test for COVID-19

Abstract: Severe acute respiratory syndrome coronavirus 2 has resulted in an unprecedented need for diagnostic testing that is critical in controlling the spread of COVID-19. We propose a portable infrared spectrometer with purpose-built transflection accessory for rapid point-of-care detection of COVID-19 markers in saliva. Initially, purified virion particles were characterized with Raman spectroscopy, synchrotron infrared (IR) and AFM-IR. A data set comprising 171 transflection infrared spectra from 29 patients testing positive for SARS-CoV-2 by RT-qPCR and 28 testing negative, was modeled using Monte Carlo Double Cross Validation with 50 randomized test and model sets. The testing sensitivity was 93 % (27/29) with a specificity of 82 % (23/28) that included positive samples on the limit of detection for RT-qPCR. Here, we demonstrate a proof-of-concept high throughput infrared COVID-19 test that is rapid, inexpensive, portable and utilizes sample self-collection thus minimizing the risk to healthcare workers and ideally suited to mass screening

A noise-reduction GWAS analysis implicates altered regulation of neurite outgrowth and guidance in autism

<p>Abstract</p> <p>Background</p> <p>Genome-wide Association Studies (GWAS) have proved invaluable for the identification of disease susceptibility genes. However, the prioritization of candidate genes and regions for follow-up studies often proves difficult due to false-positive associations caused by statistical noise and multiple-testing. In order to address this issue, we propose the novel GWAS noise reduction (GWAS-NR) method as a way to increase the power to detect true associations in GWAS, particularly in complex diseases such as autism.</p> <p>Methods</p> <p>GWAS-NR utilizes a linear filter to identify genomic regions demonstrating correlation among association signals in multiple datasets. We used computer simulations to assess the ability of GWAS-NR to detect association against the commonly used joint analysis and Fisher's methods. Furthermore, we applied GWAS-NR to a family-based autism GWAS of 597 families and a second existing autism GWAS of 696 families from the Autism Genetic Resource Exchange (AGRE) to arrive at a compendium of autism candidate genes. These genes were manually annotated and classified by a literature review and functional grouping in order to reveal biological pathways which might contribute to autism aetiology.</p> <p>Results</p> <p>Computer simulations indicate that GWAS-NR achieves a significantly higher classification rate for true positive association signals than either the joint analysis or Fisher's methods and that it can also achieve this when there is imperfect marker overlap across datasets or when the closest disease-related polymorphism is not directly typed. In two autism datasets, GWAS-NR analysis resulted in 1535 significant linkage disequilibrium (LD) blocks overlapping 431 unique reference sequencing (RefSeq) genes. Moreover, we identified the nearest RefSeq gene to the non-gene overlapping LD blocks, producing a final candidate set of 860 genes. Functional categorization of these implicated genes indicates that a significant proportion of them cooperate in a coherent pathway that regulates the directional protrusion of axons and dendrites to their appropriate synaptic targets.</p> <p>Conclusions</p> <p>As statistical noise is likely to particularly affect studies of complex disorders, where genetic heterogeneity or interaction between genes may confound the ability to detect association, GWAS-NR offers a powerful method for prioritizing regions for follow-up studies. Applying this method to autism datasets, GWAS-NR analysis indicates that a large subset of genes involved in the outgrowth and guidance of axons and dendrites is implicated in the aetiology of autism.</p

A Call to Action: Taking the Untenable out of Women Professors’ Pregnancy, Postpartum, and Caregiving Demands

Despite becoming increasingly represented in academic departments, women scholars face a critical lack of support as they navigate demands pertaining to pregnancy, motherhood, and child caregiving. In addition, cultural norms surrounding how faculty and academic leaders discuss and talk about tenure, promotion, and career success have created pressure for women who wish to grow their family and care for their children, leading to questions about whether it is possible for these women to have a family and an academic career. The current paper is a call to action for academia to build structures that support women professors as they navigate the complexities of pregnancy, the postpartum period, and the caregiving demands of their children. We specifically call on those of us in I-O psychology, management, and related departments to lead the way. In making this call, we first present the realistic, moral, and financial cases for why this issue needs to be at the forefront of discussions surrounding success in the academy. We then discuss how in the U.S. and elsewhere, an absence of policies supporting women places two groups of academics—department heads (as the leaders of departments who have discretion outside of formal policies to make work better for women) and other faculty members (as potential allies both in the department and within our professional organizations)—in a critical position to enact support and change. We conclude with our boldest call—to make a cultural shift that shatters the assumption that having a family is not compatible with academic success. Combined, we seek to launch a discussion that leads directly to necessary and overdue changes in how women scholars are supported in academia

Targeted massively parallel sequencing of autism spectrum disorder-associated genes in a case control cohort reveals rare loss-of-function risk variants

BACKGROUND: Autism spectrum disorder (ASD) is highly heritable, yet genome-wide association studies (GWAS), copy number variation screens, and candidate gene association studies have found no single factor accounting for a large percentage of genetic risk. ASD trio exome sequencing studies have revealed genes with recurrent de novo loss-of-function variants as strong risk factors, but there are relatively few recurrently affected genes while as many as 1000 genes are predicted to play a role. As such, it is critical to identify the remaining rare and low-frequency variants contributing to ASD. METHODS: We have utilized an approach of prioritization of genes by GWAS and follow-up with massively parallel sequencing in a case-control cohort. Using a previously reported ASD noise reduction GWAS analyses, we prioritized 837 RefSeq genes for custom targeting and sequencing. We sequenced the coding regions of those genes in 2071 ASD cases and 904 controls of European white ancestry. We applied comprehensive annotation to identify single variants which could confer ASD risk and also gene-based association analysis to identify sets of rare variants associated with ASD. RESULTS: We identified a significant over-representation of rare loss-of-function variants in genes previously associated with ASD, including a de novo premature stop variant in the well-established ASD candidate gene RBFOX1. Furthermore, ASD cases were more likely to have two damaging missense variants in candidate genes than controls. Finally, gene-based rare variant association implicates genes functioning in excitatory neurotransmission and neurite outgrowth and guidance pathways including CACNAD2, KCNH7, and NRXN1. CONCLUSIONS: We find suggestive evidence that rare variants in synaptic genes are associated with ASD and that loss-of-function mutations in ASD candidate genes are a major risk factor, and we implicate damaging mutations in glutamate signaling receptors and neuronal adhesion and guidance molecules. Furthermore, the role of de novo mutations in ASD remains to be fully investigated as we identified the first reported protein-truncating variant in RBFOX1 in ASD. Overall, this work, combined with others in the field, suggests a convergence of genes and molecular pathways underlying ASD etiology. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13229-015-0034-z) contains supplementary material, which is available to authorized users

The Grizzly, November 13, 2003

The Power of Puppets: Spiral Q at Ursinus • Registration Frustration • Philly Re-elects John Street as Mayor • First Injectable Male Contraceptive • Campus Connection: Spotlight on NYU and Student Suicide • Rush Begins at Ursinus • Cellphones Used to Cheat: Will This Technology Tempt Students at Ursinus? • Opinions: John Street: A Better Choice for Philadelphia Mayor; Die in Peace or Stay Alive?; Careers over Children; Why You Should Vote • Academy of Sportfighting • Networking for Holidays • Halloween Extravaganzas: Frightful Night for the Senior Class; Smoking Party • Musical Performances in UC History • Myrin Library now Recycles! • Field Hockey\u27s Season Cut Short • Women\u27s Soccer Team has a Record Breaking Season • UC Football: Skid Continueshttps://digitalcommons.ursinus.edu/grizzlynews/1548/thumbnail.jp

Time to get real: the case for critical action research in purchasing and supply management

In fragile and often complex supply chains, PSM failures continue to be reported in the media, often with severe economic, social and environmental consequences. To encourage organisations to engage in responsible PSM, we need engaged research. In this paper we argue that Action Research (AR) is an influential, participative method to challenge the more dominant versions of PSM impacts, which tend to focus only on the positive, and often only monetised elements of what is valued. AR places change at the core of the research process, requiring critical reflexive practice of the impact of assumptions, values and actions on others. We argue that PSM research has more potential for influence if it starts from a ‘real’ problem anchored in practice, and that crucially, the problem itself should be challenged dialogically by scholars, practitioners and diverse stakeholders. Critical AR can reframe performance from a technical, company-centric notion to explore broader relationships between inputs and outputs over a longer time frame. We explore the risks and rewards of Critical AR for PSM scholars and draw conclusions on our role as engaged advocates of change