Plasma-tail activity and the interplanetary medium at Halley's Comet during Armada Week: 6-14 March 1986

The encounters of five spacecraft with Halley's Comet during 6-14 March 1986 offered a unique opportunity to calibrate the solar-wind interaction with cometary plasmas as recorded by remote wide-field and narrow-field/narrowband imaging. Perhaps not generally recognized in the comet community is the additional opportunity offered by the Halley Armada to study the structure of the solar-wind and interplanetary magnetic field (IMF) in three dimensions using five sets of data obtained over similar time intervals and heliocentric distances, but at somewhat different heliolatitudes. In fact, the two problems, i.e., comet physics and the structure of the interplanetary medium, are coupled if one wants to understand what conditions pertained at the comet between the encounters. This relationship is discussed

NASA Standard GAS Can Satellite

This paper describes a new direction in small low cost spacecraft. This 150 pound satellite provides access to conduct experiments in space on an economical and short term basis. It can be used by commercial as well as scientific institutions. Currently called the XSAT, it was developed by NASA in cooperation with Defense Systems Inc. (DSI) of McLean, Virginia. XSAT provides for experimental payloads up to 50 pounds, 50 watt hours per day, one megabyte data storage, three day command memory and packetized protocol. Structural and thermal designs can handle worst case loads of the STS manned launch vehicle. XSAT can be operated by an experimenter using a personal computer from a ground-based station either locally or over normal telephone lines. An Attitude Control System (ACS) and/or propulsion system is added to XSAT on a mission peculiar basis in order to accommodate the requirements of each specific payload

Chromosomes 4 and 8 implicated in a genome wide SNP linkage scan of 762 prostate cancer families collected by the ICPCG

BACKGROUND In spite of intensive efforts, understanding of the genetic aspects of familial prostate cancer (PC) remains largely incomplete. In a previous microsatellite‐based linkage scan of 1,233 PC families, we identified suggestive evidence for linkage (i.e., LOD ≥ 1.86) at 5q12, 15q11, 17q21, 22q12, and two loci on 8p, with additional regions implicated in subsets of families defined by age at diagnosis, disease aggressiveness, or number of affected members. METHODS In an attempt to replicate these findings and increase linkage resolution, we used the Illumina 6000 SNP linkage panel to perform a genome‐wide linkage scan of an independent set of 762 multiplex PC families, collected by 11 International Consortium for Prostate Cancer Genetics (ICPCG) groups. RESULTS Of the regions identified previously, modest evidence of replication was observed only on the short arm of chromosome 8, where HLOD scores of 1.63 and 3.60 were observed in the complete set of families and families with young average age at diagnosis, respectively. The most significant linkage signals found in the complete set of families were observed across a broad, 37 cM interval on 4q13–25, with LOD scores ranging from 2.02 to 2.62, increasing to 4.50 in families with older average age at diagnosis. In families with multiple cases presenting with more aggressive disease, LOD scores over 3.0 were observed at 8q24 in the vicinity of previously identified common PC risk variants, as well as MYC , an important gene in PC biology. CONCLUSIONS These results will be useful in prioritizing future susceptibility gene discovery efforts in this common cancer. Prostate 72:410–426, 2012. © 2011 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90245/1/21443_ftp.pd

The relevance of rich club regions for functional outcome post-stroke is enhanced in women

This study aimed to investigate the influence of stroke lesions in predefined highly interconnected (rich-club) brain regions on functional outcome post-stroke, determine their spatial specificity and explore the effects of biological sex on their relevance. We analyzed MRI data recorded at index stroke and similar to 3-months modified Rankin Scale (mRS) data from patients with acute ischemic stroke enrolled in the multisite MRI-GENIE study. Spatially normalized structural stroke lesions were parcellated into 108 atlas-defined bilateral (sub)cortical brain regions. Unfavorable outcome (mRS > 2) was modeled in a Bayesian logistic regression framework. Effects of individual brain regions were captured as two compound effects for (i) six bilateral rich club and (ii) all further non-rich club regions. In spatial specificity analyses, we randomized the split into "rich club" and "non-rich club" regions and compared the effect of the actual rich club regions to the distribution of effects from 1000 combinations of six random regions. In sex-specific analyses, we introduced an additional hierarchical level in our model structure to compare male and female-specific rich club effects. A total of 822 patients (age: 64.7[15.0], 39% women) were analyzed. Rich club regions had substantial relevance in explaining unfavorable functional outcome (mean of posterior distribution: 0.08, area under the curve: 0.8). In particular, the rich club-combination had a higher relevance than 98.4% of random constellations. Rich club regions were substantially more important in explaining long-term outcome in women than in men. All in all, lesions in rich dub regions were associated with increased odds of unfavorable outcome. These effects were spatially specific and more pronounced in women.Peer reviewe

Clinical Trials in Head Injury

Traumatic brain injury (TBI) remains a major public health problem globally. In the United States the incidence of closed head injuries admitted to hospitals is conservatively estimated to be 200 per 100,000 population, and the incidence of penetrating head injury is estimated to be 12 per 100,000, the highest of any developed country in the world. This yields an approximate number of 500,000 new cases each year, a sizeable proportion of which demonstrate signficant long-term disabilities. Unfortunately, there is a paucity of proven therapies for this disease. For a variety of reasons, clinical trials for this condition have been difficult to design and perform. Despite promising pre-clinical data, most of the trials that have been performed in recent years have failed to demonstrate any significant improvement in outcomes. The reasons for these failures have not always been apparent and any insights gained were not always shared. It was therefore feared that we were running the risk of repeating our mistakes. Recognizing the importance of TBI, the National Institute of Neurological Disorders and Stroke (NINDS) sponsored a workshop that brought together experts from clinical, research, and pharmaceutical backgrounds. This workshop proved to be very informative and yielded many insights into previous and future TBI trials. This paper is an attempt to summarize the key points made at the workshop. It is hoped that these lessons will enhance the planning and design of future efforts in this important field of research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63185/1/089771502753754037.pd

Evidence for exercise-based interventions across 45 different long-term conditions: an overview of systematic reviews

Background: Almost half of the global population face significant challenges from long-term conditions (LTCs) resulting in substantive health and socioeconomic burden. Exercise is a potentially key intervention in effective LTC management. Methods: In this overview of systematic reviews (SRs), we searched six electronic databases from January 2000 to October 2023 for SRs assessing health outcomes (mortality, hospitalisation, exercise capacity, disability, frailty, health-related quality of life (HRQoL), and physical activity) related to exercise-based interventions in adults (aged >18 years) diagnosed with one of 45 LTCs. Methodological quality was assessed using AMSTAR-2. International Prospective Resister of Systematic Reviews (PROSPERO) ID: CRD42022319214. Findings: Forty-two SRs plus three supplementary RCTs were included, providing 990 RCTs in 936,825 people across 39 LTCs. No evidence was identified for six LTCs. Predominant outcome domains were HRQoL (82% of SRs/RCTs) and exercise capacity (66%); whereas disability, mortality, physical activity, and hospitalisation were less frequently reported (≤25%). Evidence supporting exercise-based interventions was identified in 25 LTCs, was unclear for 13 LTCs, and for one LTC suggested no effect. No SRs considered multimorbidity in the delivery of exercise. Methodological quality varied: critically-low (33%), low (26%), moderate (26%), and high (12%). Interpretation: Exercise-based interventions improve HRQoL and exercise capacity across numerous LTCs. Key evidence gaps included limited mortality and hospitalisation data and consideration of multimorbidity impact on exercise-based interventions

Development of a diagnostic protocol for dizziness in elderly patients in general practice: a Delphi procedure

<p>Abstract</p> <p>Background</p> <p>Dizziness in general practice is very common, especially in elderly patients. The empirical evidence for diagnostic tests in the evaluation of dizziness is scarce. Aim of our study was to determine which set of diagnostic tests should be part of a diagnostic protocol for evaluating dizziness in elderly patients in general practice.</p> <p>Methods</p> <p>We conducted a Delphi procedure with a panel of 16 national and international experts of all relevant medical specialities in the field of dizziness. A selection of 36 diagnostic tests, based on a systematic review and practice guidelines, was presented to the panel. Each test was described extensively, and data on test characteristics and methodological quality (assessed with the Quality Assessment of Diagnostic Accuracy Studies, QUADAS) were presented. The threshold for in- or exclusion of a diagnostic test was set at an agreement of 70%.</p> <p>Results</p> <p>During three rounds 21 diagnostic tests were selected, concerning patient history (4 items), physical examination (11 items), and additional tests (6 items). Five tests were excluded, although they are recommended by existing practice guidelines on dizziness. Two tests were included, although several practice guidelines question their diagnostic value. Two more tests were included that have never been recommended by practice guidelines on dizziness.</p> <p>Conclusion</p> <p>In this study we successfully combined empirical evidence with expert opinion for the development of a set of diagnostic tests for evaluating dizziness in elderly patients. This comprehensive set of tests will be evaluated in a cross-sectional diagnostic study.</p

Association of latent class analysis-derived multimorbidity clusters with adverse health outcomes in patients with multiple long-term conditions: comparative results across three UK cohorts

Background: It remains unclear how to meaningfully classify people living with multimorbidity (multiple long-term conditions (MLTCs)), beyond counting the number of conditions. This paper aims to identify clusters of MLTCs in different age groups and associated risks of adverse health outcomes and service use. Methods: Latent class analysis was used to identify MLTCs clusters in different age groups in three cohorts: Secure Anonymised Information Linkage Databank (SAIL) (n = 1,825,289), UK Biobank (n = 502,363), and the UK Household Longitudinal Study (UKHLS) (n = 49,186). Incidence rate ratios (IRR) for MLTC clusters were computed for: all-cause mortality, hospitalisations, and general practice (GP) use over 10 years, using &lt;2 MLTCs as reference. Information on health outcomes and service use were extracted for a ten year follow up period (between 01st Jan 2010 and 31st Dec 2019 for UK Biobank and UKHLS, and between 01st Jan 2011 and 31st Dec 2020 for SAIL). Findings: Clustering MLTCs produced largely similar results across different age groups and cohorts. MLTC clusters had distinct associations with health outcomes and service use after accounting for LTC counts, in fully adjusted models. The largest associations with mortality, hospitalisations and GP use in SAIL were observed for the “Pain+” cluster in the age-group 18–36 years (mortality IRR = 4.47, hospitalisation IRR = 1.84; GP use IRR = 2.87) and the “Hypertension, Diabetes &amp; Heart disease” cluster in the age-group 37–54 years (mortality IRR = 4.52, hospitalisation IRR = 1.53, GP use IRR = 2.36). In UK Biobank, the “Cancer, Thyroid disease &amp; Rheumatoid arthritis” cluster in the age group 37–54 years had the largest association with mortality (IRR = 2.47). Cardiometabolic clusters across all age groups, pain/mental health clusters in younger groups, and cancer and pulmonary related clusters in older age groups had higher risk for all outcomes. In UKHLS, MLTC clusters were not significantly associated with higher risk of adverse outcomes, except for the hospitalisation in the age-group 18–36 years. Interpretation: Personalising care around MLTC clusters that have higher risk of adverse outcomes may have important implications for practice (in relation to secondary prevention), policy (with allocation of health care resources), and research (intervention development and targeting), for people living with MLTCs. Funding: This study was funded by the National Institute for Health and Care Research (NIHR; Personalised Exercise-Rehabilitation FOR people with Multiple long-term conditions (multimorbidity)—NIHR202020)