85 research outputs found
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Ambulatory measurement of knee motion and physical activity: preliminary evaluation of a smart activity monitor
BACKGROUND: There is currently a paucity of devices available for continuous, long-term monitoring of human joint motion. Non-invasive, inexpensive devices capable of recording human activity and joint motion have many applications for medical research. Such a device could be used to quantify range of motion outside the gait laboratory. The purpose of this study was to test the accuracy of the modified Intelligent Device for Energy Expenditure and Activity (IDEEA) in measuring knee flexion angles, to detect different physical activities, and to quantify how often healthy subjects use deep knee flexion in the ambulatory setting. METHODS: We compared Biomotion Laboratory (BML) "gold standard" data to simultaneous IDEEA measures of knee motion and gait, step up/down, and stair descent in 5 healthy subjects. In addition, we used a series of choreographed physical activities outside the BML to confirm the IDEEA's ability to accurately measure 7 commonly-performed physical activities. Subjects then continued data collection during ordinary activities outside the gait laboratory. RESULTS: Pooled correlations between the BML and IDEEA knee flexion angles were .97 +/- .03 for step up/down, .98 +/- .02 for stair descent, and .98 +/- .01 for gait. In the BML protocol, the IDEEA accurately identified gait, but was less accurate in identifying step up/down and stair descent. During sampling outside the BML, the IDEEA accurately detected walking, running, stair ascent, stair descent, standing, lying, and sitting. On average, subjects flexed their knees >120° for 0.17% of their data collection periods outside the BML. CONCLUSION: The modified IDEEA system is a useful clinical tool for evaluating knee motion and multiple physical activities in the ambulatory setting. These five healthy subjects rarely flexed their knees >120°
Mental health diversion courts : some directions for further development
Recent years have seen a growth in the number of specialist courts operating in Australia, including those which aim to address the needs of mentally disordered offenders. This article describes some of the key characteristics of mental health courts, using case studies from the most established court in Australia, the South Australian Magistrates Court Diversion Program (MCDP). This is followed by a consideration of some factors that may affect the future development of this type of program. It is concluded that there is a need to pay careful attention to issues of risk assessment and risk management if the dual goals of improving both the health of individual and the safety of the community are to be realised.<br /
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Long-term follow-up of glycemic and neurological outcomes in an international series of patients with sulfonylurea-treated ABCC8 permanent neonatal diabetes
This is the author accepted manuscript. The final version is available from the American Diabetes Association via the DOI in this record OBJECTIVE ABCC8 mutations cause neonatal diabetes mellitus that can be transient (TNDM) or, less commonly, permanent (PNDM); ∼90% of individuals can be treated with oral sulfonylureas instead of insulin. Previous studies suggested that people with ABCC8-PNDM require lower sulfonylurea doses and have milder neurological features than those with KCNJ11-PNDM. However, these studies were short-term and included combinations of ABCC8-PNDM and ABCC8-TNDM. We aimed to assess the long-term glycemic and neurological outcomes in sulfonylurea-treated ABCC8-PNDM.
RESEARCH DESIGN AND METHODS We studied all 24 individuals with ABCC8-PNDM diagnosed in the U.K., Italy, France, and U.S. known to transfer from insulin to sulfonylureas before May 2010. Data on glycemic control, sulfonylurea dose, adverse effects including hypoglycemia, and neurological features were analyzed using nonparametric statistical methods.
RESULTS Long-term data were obtained for 21 of 24 individuals (median follow-up 10.0 [range 4.1–13.2] years). Eighteen of 21 remained on sulfonylureas without insulin at the most recent follow-up. Glycemic control improved on sulfonylureas (presulfonylurea vs. 1-year posttransfer HbA1c 7.2% vs. 5.7%, P = 0.0004) and remained excellent long-term (1-year vs. 10-year HbA1c 5.7% vs. 6.5%, P = 0.04), n = 16. Relatively high doses were used (1-year vs. 10-year dose 0.37 vs. 0.25 mg/kg/day glyburide, P = 0.50) without any severe hypoglycemia. Neurological features were reported in 13 of 21 individuals; these improved following sulfonylurea transfer in 7 of 13. The most common features were learning difficulties (52%), developmental delay (48%), and attention deficit hyperactivity disorder (38%).
CONCLUSIONS Sulfonylurea treatment of ABCC8-PNDM results in excellent long-term glycemic control. Overt neurological features frequently occur and may improve with sulfonylureas, supporting early, rapid genetic testing to guide appropriate treatment and neurodevelopmental assessment.Wellcome Trus
Filovirus RefSeq Entries: Evaluation and Selection of Filovirus Type Variants, Type Sequences, and Names
Sequence determination of complete or coding-complete genomes of viruses is becoming common practice for supporting the work of epidemiologists, ecologists, virologists, and taxonomists. Sequencing duration and costs are rapidly decreasing, sequencing hardware is under modification for use by non-experts, and software is constantly being improved to simplify sequence data management and analysis. Thus, analysis of virus disease outbreaks on the molecular level is now feasible, including characterization of the evolution of individual virus populations in single patients over time. The increasing accumulation of sequencing data creates a management problem for the curators of commonly used sequence databases and an entry retrieval problem for end users. Therefore, utilizing the data to their fullest potential will require setting nomenclature and annotation standards for virus isolates and associated genomic sequences. The National Center for Biotechnology Information’s (NCBI’s) RefSeq is a non-redundant, curated database for reference (or type) nucleotide sequence records that supplies source data to numerous other databases. Building on recently proposed templates for filovirus variant naming [ ()////-], we report consensus decisions from a majority of past and currently active filovirus experts on the eight filovirus type variants and isolates to be represented in RefSeq, their final designations, and their associated sequences
AI is a viable alternative to high throughput screening: a 318-target study
: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery
Interleukin-6 receptor pathways in abdominal aortic aneurysm
We conducted a systematic review and meta-analysis of studies reporting circulating IL-6 in AAA, and new investigations of the association between a common non-synonymous functional variant (Asp358Ala) in the IL-6R gene (IL6R) and AAA, followed the analysis of the variant both in vitro and in vivo. Inflammation may play a role in the development of abdominal aortic aneurysms (AAA). Interleukin-6 (IL-6) signalling through its receptor (IL-6R) is one pathway that could be exploited pharmacologically. We investigated this using a Mendelian randomization approach
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