884 research outputs found

    Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis

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    Background Parenterally administered ascorbic acid modulates sepsis-induced inflammation and coagulation in experimental animal models. The objective of this randomized, double-blind, placebo-controlled, phase I trial was to determine the safety of intravenously infused ascorbic acid in patients with severe sepsis. Methods Twenty-four patients with severe sepsis in the medical intensive care unit were randomized 1:1:1 to receive intravenous infusions every six hours for four days of ascorbic acid: Lo-AscA (50 mg/kg/24 h, n = 8), or Hi-AscA (200 mg/kg/24 h, n = 8), or Placebo (5% dextrose/water, n = 8). The primary end points were ascorbic acid safety and tolerability, assessed as treatment-related adverse-event frequency and severity. Patients were monitored for worsened arterial hypotension, tachycardia, hypernatremia, and nausea or vomiting. In addition Sequential Organ Failure Assessment (SOFA) scores and plasma levels of ascorbic acid, C-reactive protein, procalcitonin, and thrombomodulin were monitored. Results Mean plasma ascorbic acid levels at entry for the entire cohort were 17.9 ± 2.4 μM (normal range 50-70 μM). Ascorbic acid infusion rapidly and significantly increased plasma ascorbic acid levels. No adverse safety events were observed in ascorbic acid-infused patients. Patients receiving ascorbic acid exhibited prompt reductions in SOFA scores while placebo patients exhibited no such reduction. Ascorbic acid significantly reduced the proinflammatory biomarkers C-reactive protein and procalcitonin. Unlike placebo patients, thrombomodulin in ascorbic acid infused patients exhibited no significant rise, suggesting attenuation of vascular endothelial injury. Conclusions Intravenous ascorbic acid infusion was safe and well tolerated in this study and may positively impact the extent of multiple organ failure and biomarkers of inflammation and endothelial injury

    From diagnosis of colorectal cancer to diagnosis of Lynch syndrome: The RM Partners quality improvement project.

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    AIM: The UK National Institute for Health and Care Excellence guideline DG27 recommends universal testing for Lynch syndrome (LS) in all newly diagnosed colorectal cancer (CRC) patients. However, DG27 guideline implementation varies significantly by geography. This quality improvement project (QIP) was developed to measure variation and deliver an effective diagnostic pathway from diagnosis of CRC to diagnosis of LS within the RM Partners (RMP) West London cancer alliance. METHOD: RM Partners includes a population of 4 million people and incorporates nine CRC multidisciplinary teams (MDTs), overseen by a Pathway Group, and three regional genetic services, managing approximately 1500 new CRC cases annually. A responsible LS champion was nominated within each MDT. A regional project manager and nurse practitioner were appointed to support the LS champions, to develop online training packages and patient consultation workshops. MDTs were supported to develop an 'in-house' mainstreaming service to offer genetic testing in their routine oncology clinics. Baseline data were collected through completion of the LS pathway audit of the testing pathway in 30 consecutive CRC patients from each CRC MDT, with measurement of each step of the testing pathway. Areas for improvement in each MDT were identified, delivered by the local champion and supported by the project team. RESULTS: Overall, QIP measurables improved following the intervention. The Wilcoxon signed rank test revealed significant differences with strong effect sizes on the percentile of CRC cases undergoing mismatch repair (MMR) testing in endoscopic biopsies (p = 0.008), further testing with either methylation or BRAF V600E (p = 0/03) and in effective referral for genetic testing (from 10% to 74%; p = 0.02). During the QIP new mainstreaming services were developed, alongside the implementation of systematic and robust testing pathways. These pathways were tailored to the needs of each CRC team to ensure that patients with a diagnosis of CRC had access to testing for LS. Online training packages were produced which remain freely accessible for CRC teams across the UK. CONCLUSION: The LS project was completed by April 2022. We have implemented a systematic approach with workforce transformation to facilitate identification and 'mainstreamed' genetic diagnosis of LS. This work has contributed to the development of a National LS Transformation Project in England which recommends local leadership within cancer teams to ensure delivery of diagnosis of LS and integration of genomics into clinical practice

    Age differences in upper extremity joint moments and strength during a laboratory-based tether-release forward fall arrest in older women

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    Age-related declines in upper extremity muscle strength may affect an older adult’s ability to land and control a simulated forward fall impact. The role of individual upper extremity joints during a forward fall impact has not been examined. The purpose was to evaluate the age differences in upper extremity joint moment contributions during a simulated forward fall and upper extremity muscle strength in older women. A convenience sample of 68 older women (70 (8) yrs) performed three trials of a simulated forward fall. Percentage joint moments of the upper extremity were recorded. Upper extremity muscle strength was collected via handgrip, hand-held dynamometry of the shoulder and elbow and a custom multi-joint concentric and eccentric strength isokinetic dynamometer protocol. Percentage joint moment contributions differed between women in their sixties and seventies with significantly greater relative shoulder joint involvement (P = .008), coupled with lower elbow joint contributions (P = .004) in comparison to 80 year olds. An increase in each year of age was associated with a 4% increase in elbow contribution (Beta = -0.421, r2 = 17.9, P = 0.0001) and a 3.7% decrease in shoulder contribution (Beta = 0.373, r2 = 14.6, P = 0.002). Older women exhibit different landing strategies as they age. Fall injury prevention research should consider interventions focused on these differences taking into account the contributions of upper extremity strength

    Tracking elusive and shifting identities of the global fishing fleet

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    Illegal, unreported, and unregulated (IUU) fishing costs billions of dollars per year and is enabled by vessels obfuscating their identity. Here, we combine identities of ~35,000 vessels with a decade of GPS data to provide a global assessment of fishing compliance, reflagging patterns, and fishing by foreign-owned vessels. About 17% of high seas fishing is by potentially unauthorized or internationally unregulated vessels, with hot spots of this activity in the west Indian and the southwest Atlantic Oceans. In addition, reflagging, a tactic often used to obscure oversight, occurs in just a few ports primarily by fleets with high foreign ownership. Fishing by foreign-owned vessels is concentrated in parts of high seas and certain national waters, often flying flags of convenience. These findings can address the global scope of potential IUU fishing and enable authorities to improve oversight

    Contralateral effects of unilateral strength and skill training: Modified Delphi consensus to establish key aspects of cross-education

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    © 2020, The Author(s). Background: Cross-education refers to increased motor output (i.e., force generation, skill) of the opposite, untrained limb following a period of unilateral exercise training. Despite extensive research, several aspects of the transfer phenomenon remain controversial. Methods: A modified two-round Delphi online survey was conducted among international experts to reach consensus on terminology, methodology, mechanisms of action, and translational potential of cross-education, and to provide a framework for future research. Results: Through purposive sampling of the literature, we identified 56 noted experts in the field, of whom 32 completed the survey, and reached consensus (75% threshold) on 17 out of 27 items. Conclusion: Our consensus-based recommendations for future studies are that (1) the term ‘cross-education’ should be adopted to refer to the transfer phenomenon, also specifying if transfer of strength or skill is meant; (2) functional magnetic resonance imaging, short-interval intracortical inhibition and interhemispheric inhibition appear to be promising tools to study the mechanisms of transfer; (3) strategies which maximize cross-education, such as high-intensity training, eccentric contractions, and mirror illusion, seem worth being included in the intervention plan; (4) study protocols should be designed to include at least 13–18 sessions or 4–6 weeks to produce functionally meaningful transfer of strength, and (5) cross-education could be considered as an adjuvant treatment particularly for unilateral orthopedic conditions and sports injuries. Additionally, a clear gap in views emerged between the research field and the purely clinical field. The present consensus statement clarifies relevant aspects of cross-education including neurophysiological, neuroanatomical, and methodological characteristics of the transfer phenomenon, and provides guidance on how to improve the quality and usability of future cross-education studies

    Contralateral Effects of Unilateral Strength and Skill Training:Modified Delphi Consensus to Establish Key Aspects of Cross-Education

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    Background Cross-education refers to increased motor output (i.e., force generation, skill) of the opposite, untrained limb following a period of unilateral exercise training. Despite extensive research, several aspects of the transfer phenomenon remain controversial. Methods A modified two-round Delphi online survey was conducted among international experts to reach consensus on terminology, methodology, mechanisms of action, and translational potential of cross-education, and to provide a framework for future research. Results Through purposive sampling of the literature, we identified 56 noted experts in the field, of whom 32 completed the survey, and reached consensus (75% threshold) on 17 out of 27 items. Conclusion Our consensus-based recommendations for future studies are that (1) the term 'cross-education' should be adopted to refer to the transfer phenomenon, also specifying if transfer of strength or skill is meant; (2) functional magnetic resonance imaging, short-interval intracortical inhibition and interhemispheric inhibition appear to be promising tools to study the mechanisms of transfer; (3) strategies which maximize cross-education, such as high-intensity training, eccentric contractions, and mirror illusion, seem worth being included in the intervention plan; (4) study protocols should be designed to include at least 13-18 sessions or 4-6 weeks to produce functionally meaningful transfer of strength, and (5) cross-education could be considered as an adjuvant treatment particularly for unilateral orthopedic conditions and sports injuries. Additionally, a clear gap in views emerged between the research field and the purely clinical field. The present consensus statement clarifies relevant aspects of cross-education including neurophysiological, neuroanatomical, and methodological characteristics of the transfer phenomenon, and provides guidance on how to improve the quality and usability of future cross-education studies

    Fall arrest strategy training improves upper body response time compared to standard fall prevention exercise in older women: A randomized trial

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    Introduction: Exercise can decrease fall risk in older adults but less is known about training to reduce injury risk in the event a fall is unavoidable. The purpose of this study was to compare standard fall prevention exercises to novel Fall Arrest Strategy Training (FAST); exercises designed to improve upper body capacity to reduce fall-injury risk in older women. Method: Forty women (mean age 74.5 years) participated in either Standard (n=19) or FAST (n=21) twice per week for 12 weeks. Both interventions included lower body strength, balance, walking practice, agility and education. FAST added exercises designed to enhance forward landing and descent control such as upper body strengthening, speed and practice of landing and descent on outstretched hands. Results: Both FAST and Standard significantly improved strength, mobility, balance, and fall risk factors from pre to post-intervention. There was a significant time by group interaction effect for upper body response time where FAST improved but Standard did not (p = .038). Discussion: FAST resulted in similar gains in factors that reduce fall risk as a standard fall prevention program; with the additional benefit of improving speed of arm protective responses; a factor that may help enhance landing position and reduce injury risks such as head impact during a forward fall

    Magnetospheric multiprobes: Investigations and instrumentation

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    The multiprobe scientific objectives are to: (1) determine the spatial structure of plasma phenomena such as the aurora, convection reversals, and ion troughs; (2) separate spatial and temporal variations in these phenomena; (3) determine field aligned current densities; (4) perform multiple point analysis of particle beams, wave fields, and plasma clouds that are injected into the ionosphere and magnetosphere by Spacelab active experiment facilities. Trade studies described include: instrument accommodations, power, attitude determination, electric field antennas, storage and ejection, thermal control, tracking communications, command and data management, payload and mission specialist support, functional objectives, and orbital analysis

    Tonic Shock Induces Detachment of Giardia lamblia

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    The single-celled organism Giardia lamblia colonizes the small intestine of a wide variety of hosts, including humans. Giardiasis infections can cause severe gastrointestinal symptoms and pose a major health concern in the developing world. Giardia are known to attach robustly to a variety of surfaces, but the conditions that influence this attachment are not known. In this study, we examined the behavior of attached Giardia parasites exposed to rapid changes in solution properties, like those Giardia might encounter in the intestine. After systematically varying media concentration and composition, we found that only one solution property caused rapid detachment of Giardia cells: tonicity, which is a measure of the total concentration of solutes in the solution that are unable to pass through a semi-permeable membrane (here, the cell membrane of Giardia). We found similar results for Giardia initially attached to monolayers of intestinal cells. Giardia cells remaining attached after a change in tonicity are able to adapt to the change, highlighting the general ability of this organism to weather normal changes in the intestinal environment. We propose that Giardia's susceptibility to large changes in tonicity could be explored as a possible new route for treatment of giardiasis
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