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Encouragingly, better elucidation of the pathophysiological mechanisms underpinning epilepsies and drug resistance by concerted preclinical and clinical efforts have recently enabled a revised approach to the development of more promising therapies, including numerous potential etiology-specific drugs ("precision medicine") for severe pediatric (monogenetic) epilepsies and novel multitargeted ASDs for acquired partial epilepsies, suggesting that the long hoped-for breakthrough in therapy for as-yet ASD-resistant patients is a feasible goal. SIGNIFICANCE STATEMENT Drug resistance provides a major challenge in epilepsy management. Here, we will review the current understanding of the molecular, genetic, and structural mechanisms of drug resistance in epilepsy and discuss how the problem might be overcome.Long-range sequencing information is required for haplotype phasing, de novo assembly and structural variation detection. Current long-read sequencing technologies can provide valuable long-range information but at a high cost with low accuracy and high DNA input requirement. RK-701 GLP inhibitor We have developed a single-tube Transposase Enzyme Linked Long-read Sequencing (TELL-seqTM) technology, which enables a low-cost, high-accuracy and high-throughput short-read second-generation sequencer to generate over 100 kb long-range sequencing information with as little as 0.1 ng input material. In a PCR tube, millions of clonally barcoded beads are used to uniquely barcode long DNA molecules in an open bulk reaction without dilution and compartmentation. The barcode linked reads are used to successfully assemble genomes ranging from microbes to human. These linked-reads also generate mega-base-long phased blocks and provide a cost-effective tool for detecting structural variants in a genome, which are important to identify compound heterozygosity in recessive Mendelian diseases and discover genetic drivers and diagnostic biomarkers in cancers.The latest results from the CodeBreak 100 trial evaluating AMG 510 indicate that this first-in-class KRAS inhibitor, having shown promise in non-small cell lung cancer, is modestly active in several other types of solid tumors, including colorectal cancer.Autologous T cells engineered to target the MAGE-A4 cancer testis antigen successfully shrank a wide range of solid tumors with a manageable toxicity profile. In a phase I trial, the therapy, ADP-A2M4, showed the most promise in synovial sarcoma, yielding a disease control rate of around 90%.Many genetic variants identified in genome-wide association studies (GWAS) are associated with multiple, sometimes seemingly unrelated traits. This motivates multi-trait association analyses, which have successfully identified novel associated loci for many complex diseases. While appealing, most existing methods focus on analyzing a relatively small number of traits and may yield inflated Type I error rates when a large number of traits need to be analyzed jointly. As deep phenotyping data are becoming rapidly available, we develop a novel method, referred to as aMAT (adaptive multi-trait association test), for multi-trait analysis of any number of traits. We applied aMAT to GWAS summary statistics for a set of 58 volumetric imaging derived phenotypes from the UK Biobank. aMAT had a genomic inflation factor of 1.04, indicating the Type I error rate was well controlled. More important, aMAT identified 24 distinct risk loci, 13 of which were ignored by standard GWAS. In comparison, the competing methods either had a suspicious genomic inflation factor or identified much fewer risk loci. Finally, four additional sets of traits have been analyzed and provided similar conclusions.Background Implementation of integrated primary care is considered an important strategy to overcome fragmentation and improve quality of dementia care. However, current quality indicator (QI) sets, to assess and improve quality of care, do not address the interprofessional context. The aim of this research was to construct a feasible and content-wise valid minimum dataset (MDS) to measure the quality of integrated primary dementia care. Methods A modified Delphi method in four rounds was performed. Stakeholders (n=15) (1) developed a preliminary QI set and (2) assessed relevance and feasibility of QIs via a survey (n=84); thereafter, (3) results were discussed for content validity during a stakeholder and (4) expert consensus meeting (n=8 and n=7, respectively). The stakeholders were professionals, informal caregivers, and care organisation managers or policy officers; the experts were professionals and researchers. The final set was pilot-tested for feasibility by multidisciplinary dementia care networks. Results The preliminary set consisted of 40 QIs. In the survey, mean scores for relevance ranged from 5.8 (SD=2.7) to 8.5 (SD=0.7) on a 9-point Likert scale, and 25% of all QIs were considered feasible to collect. Consensus panels reduced the set to 15 QIs to be used for pilot testing 5 quality of care, 3 well-being, 4 network-based care, and 3 cost-efficiency QIs. During pilot testing, all QIs were fully completed, except for well-being QIs. Conclusion A valid and feasible MDS of QIs for primary dementia care was developed, containing innovative QIs on well-being, network-based care and cost-efficiency, in addition to quality of care QIs. Application of the MDS may contribute to development and implementation of integrated care service delivery for primary dementia care.Medical inpatients often have important risk factors for venous thromboembolism (VTE). In our institution, VTE prophylaxis in this group was underused. The main barriers identified were inattention to VTE prophylaxis, competing priorities and lack of confidence in the decision-making. We aimed to improve the rate of VTE prophylaxis use by introducing a paper-based risk assessment tool, with actionable management recommendations within the prescription chart. The rationale was that an assessment tool at the point of prescribing can reduce steps between decision-making and prescribing process, thus promoting confidence and acting as a reminder. A total of 552 prescription charts completed over a period of 29 weeks were examined during the baseline period. In the postintervention period, 871 charts completed over 40 weeks period were examined. The risk assessment tool was completed in 51% of the cases examined in the postintervention period. The introduction of the risk assessment tool was associated with a significant change in the pattern of VTE pharmacological prophylaxis use.