Impaired Hyperemic Response to Exercise Post Stroke

Individuals with chronic stroke have reduced perfusion of the paretic lower limb at rest; however, the hyperemic response to graded muscle contractions in this patient population has not been examined. This study quantified blood flow to the paretic and non-paretic lower limbs of subjects with chronic stroke after submaximal contractions of the knee extensor muscles and correlated those measures with limb function and activity. Ten subjects with chronic stroke and ten controls had blood flow through the superficial femoral artery quantified with ultrasonography before and immediately after 10 second contractions of the knee extensor muscles at 20, 40, 60, and 80% of the maximal voluntary contraction (MVC) of the test limb. Blood flow to the paretic and non-paretic limb of stroke subjects was significantly reduced at all load levels compared to control subjects even after normalization to lean muscle mass. Of variables measured, increased blood flow after an 80% MVC was the single best predictor of paretic limb strength, the symmetry of strength between the paretic and non-paretic limbs, coordination of the paretic limb, and physical activity. The impaired hemodynamic response to high intensity contractions was a better predictor of lower limb function than resting perfusion measures. Stroke-dependent weakness and atrophy of the paretic limb do not explain the reduced hyperemic response to muscle contraction alone as the response is similarly reduced in the non-paretic limb when compared to controls. These data may suggest a role for perfusion therapies to optimize rehabilitation post stroke

The high-energy spectrum of the nearby planet-hosting inactive mid-M dwarf LHS 3844

To fully characterize the atmospheres, or lack thereof, of terrestrial exoplanets we must include the high-energy environments provided by their host stars. The nearby mid-M dwarf LHS 3844 hosts a terrestrial world which lacks a substantial atmosphere. We present a time series UV spectrum of LHS 3844 from 1131-3215A captured by HST/COS. We detect one flare in the FUV, which has an absolute energy of 8.96+/-0.79e28 erg and an equivalent duration of 355+/-31 s. We extract the flare and quiescent UV spectra separately. For each spectrum we estimate the Ly-alpha flux using correlations between UV line strengths. We use Swift-XRT to place an upper limit on the soft X-ray flux and construct a differential emission model (DEM) to estimate flux that is obscured by the interstellar medium. We compare the DEM flux estimates in the XUV to other methods that rely on scaling from the Ly-alpha, Si IV, and N V lines in the UV. The XUV, FUV, and NUV flux of LHS 3844 relative to its bolometric luminosity is log10(Lband/LBol) = -3.65, -4.16, and -4.56, respectively, for the quiescent state. These values agree with trends in high-energy flux as a function of stellar effective temperature found by the MUSCLES survey for a sample of early-M dwarfs. Many of the most spectroscopically accessible terrestrial exoplanets orbit inactive mid- to late-M dwarfs like LHS 3844. Measurements of M dwarf high-energy spectra are preferable for exoplanet characterization, but are not always possible. The spectrum of LHS 3844 is a useful proxy for the current radiation environment for these worlds.Comment: Published in AJ; HLSPs now availabl

Impact of an integrated disease management program in reducing exacerbations in patients with severe asthma and COPD

SummaryBackgroundConflicting data exists on the effectiveness of integrated programs in reducing recurrent exacerbations and hospitalizations in patients with Asthma and chronic obstructive lung disease (COPD). We developed a Pulmonologist-led Chronic Lung Disease Program (CLDP) for patients with severe asthma and COPD and analyzed its impact on healthcare utilization and predictors of its effectiveness.MethodsCLDP elements included clinical evaluation, onsite pulmonary function testing, health education, and self-management action plan along with close scheduled and on-demand follow-up. Patients with ≥2 asthma or COPD exacerbations requiring emergency room visit or hospitalization within the prior year were enrolled, and followed for respiratory related ER visits (RER) and hospitalizations (RHA) over the year (357 ± 43 days) after CLDP interventions.ResultsA total of 106 patients were enrolled, and 104 patients were subject to analyses. During the year of follow-up after CLDP enrollment, there was a significant decrease in mean RER (0.56 ± 1.48 versus 2.62 ± 2.81, p < 0.0001), mean RHA (0.39 ± 0.08 versus 1.1 ± 1.62, p < 0.0001), and 30 day rehospitalizations (0.05 ± 0.02 versus 0.28 ± 0.07, p < 0.0001). Reduction of healthcare utilization was strongly associated with GERD and sinusitis therapy, and was independent of pulmonary rehabilitation. Direct variable cost analyses estimated annual savings at $1.17 million. Multivariate logistic regression analysis revealed lack of spirometry utilization as an independent risk factor for severe exacerbations.ConclusionsA Pulmonologist-led disease management program integrating key elements of care is cost effective and significantly decreases severe exacerbations. Integrated programs should be encouraged for care of frequent exacerbators of asthma and COPD

Implementation of the national antimicrobial stewardship competencies for UK undergraduate healthcare professional education within undergraduate pharmacy programmes: a survey of UK schools of pharmacy.

Pharmacists play a key role in antimicrobial stewardship (AMS). Consensus-based national AMS competencies for undergraduate healthcare professionals in the UK reflect the increasing emphasis on competency-based healthcare professional education. However, the extent to which these are included within undergraduate pharmacy education programmes in the UK is unknown. To explore which of the AMS competencies are delivered, including when and at which level, within UK undergraduate MPharm programmes. A cross-sectional online questionnaire captured the level of study of the MPharm programme in which each competency was taught, the method of delivery and assessment of AMS education, and examples of student feedback. Ten institutions completed the survey (33% response rate). No institution reported covering all 54 AMS competencies and 5 of these were taught at half or fewer of the institutions. Key gaps were identified around taking samples, communication, outpatient parenteral antimicrobial therapy and surgical prophylaxis. The minimum time dedicated to AMS teaching differed between institutions (range 9–119 h), teaching was generally through didactic methods, and assessment was generally through knowledge recall and objective structured clinical examinations. Feedback from students suggests they find AMS and antimicrobial resistance (AMR) to be complex yet important topics. UK schools of pharmacy should utilize the competency framework to identify gaps in their AMS, AMR and infection teaching. To prepare newly qualified pharmacists to be effective at delivering AMS and prescribing antimicrobials, schools of pharmacy should utilize more simulated environments and clinical placements for education and assessment of AMS

Decline in CD4 T lymphocytes with monotherapy bridging strategy for non-adherent adolescents living with HIV infection: Results of the IMPAACT P1094 randomized trial

Introduction Management of persistently non-adherent youth living with HIV (YLHIV) with virologic failure (VF) on combination antiretroviral therapy (cART) remains challenging. One strategy has been using 3TC/ FTC monotherapy (3TC/FTC), which in the presence of the M184V resistance mutation, does not suppress viral replication nor select for additional drug resistance mutations, and reduces viral fitness with limited side effects. P1094 compared the immunologic outcome of continuing failing cART vs. switching to 3TC/FTC as a “bridging strategy” to subsequent suppressive cART for non-adherent YLHIV with pre-existing M184V resistance. Materials & methods Participants with documented nonadherence, M184V mutation, CD4+ T cell count ≥100 cells/mm3 and VF (HIV-1 plasma RNA ≥400 copies/mL (2.6 log10 HIV-1 RNA) were enrolled and randomized to continue failing cART vs. switch to 3TC/FTC. The primary endpoint (time to ≥30% CD4+ T cell decline or development of CDC class C events) at 28-weeks were assessed by Kaplan-Meier (K-M) curves in an intent-to-treat analysis. Results Thirty-three perinatally acquired YLHIV participants (16 continuing cART and 17 3TC/FTC) enrolled in the study. The median age, entry CD4+ T cell count, and viral load were 15 years (Inter-quartile range (IQR) 14–20), 472 cells/mm3 (IQR 384–651), and 4.0 log10HIV-1 RNA copies/ml (IQR 3.2–4.5), respectively. Five participants, all in the 3TC/FTC arm, reached the primary endpoint for absolute CD4+ T cell decline (p = 0.02, exact log-rank test comparing monotherapy to cART). The Kaplan-Meier estimate of probability of primary endpoint on 3TC/FTC at 28 weeks was 0.41 (standard error 0.14). There were no CDC class C events or deaths and no statistically significant difference in frequencies of adverse events between the arms. Conclusions Non-adherent participants randomized to 3TC/FTC were more likely than those maintained on failing cART to experience a confirmed decline in CD4+ count of ≥30%. Although this study suffers from limitations of small sample size and premature discontinuation, the randomized comparison to continuing failing cART indicates that 3TC/FTC provides inferior protection from immunologic deterioration for non-adherent youth with M184V resistance. Better alternatives to 3TC/FTC such as ART with higher barriers to resistance and novel adherence and treatment strategies for nonadherent youth are urgently needed

Identifying Motor, Emotional-Behavioral, and Cognitive Deficits that Comprise the Triad of HD Symptoms from Patient, Caregiver, and Provider Perspectives

Background: The objective of this study was to identify important attributes associated with the triad of symptoms (cognition, emotional–behavioral, and motor) of Huntington's disease (HD) from patient, caregiver, and medical provider perspectives to facilitate development of a new disease‐specific, health‐related quality of life (HRQOL) instrument. Methods: We conducted a targeted literature review of HD and HRQOL instruments, expert surveys, and patient and caregiver phone‐based interviews to extract information on the symptoms and issues most relevant to the HD symptom triad (HD triad). The data collected from these sources were used to generate themes and subdomains and to develop an integrated schema that highlights the key dimensions of the triad. Results: The search identified the following areas: emotional functioning/behavioral changes (e.g., positive emotions, sadness/depression); cognitive functioning (e.g., memory/learning, attention/comprehension); physical functioning (e.g., motor functioning, medication); social functioning (e.g., leisure, interpersonal relationships); end‐of‐life concerns/planning; and gene testing. Fifteen individuals diagnosed with HD and 16 HD caregivers, recruited from several Huntington's Disease Society of America support group networks, completed phone interviews. Nineteen US medical providers who specialize in HD completed the online survey. Twenty‐six subdomains of the HD symptom triad (seven cognition, 12 emotional–behavioral, and seven motor) emerged relatively consistently across patient, caregiver, and provider samples. These included movements/chorea, memory impairment, depression, and anxiety. Discussion: Based on an integrated, mixed‐methods approach, important HD triad symptom were identified and organized into a guiding schema. These patient‐, caregiver‐, and provider‐triangulated data served as the basis for development of a HD‐specific HRQOL instrument, the HD‐PRO‐TRIAD™

Secular trends in the association between nativity/length of US residence with body mass index and waist circumference among Mexican-Americans, 1988–2008

We investigated whether associations between nativity/length of US residence and body mass index (BMI) and waist circumference (WC) varied over the past two decades

Gene-metabolite annotation with shortest reactional distance enhances metabolite genome-wide association studies results

Metabolite genome-wide association studies (mGWAS) have advanced our understanding of the genetic control of metabolite levels. However, interpreting these associations remains challenging due to a lack of tools to annotate gene-metabolite pairs beyond the use of conservative statistical significance threshold. Here, we introduce the shortest reactional distance (SRD) metric, drawing from the comprehensive KEGG database, to enhance the biological interpretation of mGWAS results. We applied this approach to three independent mGWAS, including a case study on sickle cell disease patients. Our analysis reveals an enrichment of small SRD values in reported mGWAS pairs, with SRD values significantly correlating with mGWAS p values, even beyond the standard conservative thresholds. We demonstrate the utility of SRD annotation in identifying potential false negatives and inaccuracies within current metabolic pathway databases. Our findings highlight the SRD metric as an objective, quantitative and easy-to-compute annotation for gene-metabolite pairs, suitable to integrate statistical evidence to biological networks

Search for anomalous t t-bar production in the highly-boosted all-hadronic final state

A search is presented for a massive particle, generically referred to as a Z', decaying into a t t-bar pair. The search focuses on Z' resonances that are sufficiently massive to produce highly Lorentz-boosted top quarks, which yield collimated decay products that are partially or fully merged into single jets. The analysis uses new methods to analyze jet substructure, providing suppression of the non-top multijet backgrounds. The analysis is based on a data sample of proton-proton collisions at a center-of-mass energy of 7 TeV, corresponding to an integrated luminosity of 5 inverse femtobarns. Upper limits in the range of 1 pb are set on the product of the production cross section and branching fraction for a topcolor Z' modeled for several widths, as well as for a Randall--Sundrum Kaluza--Klein gluon. In addition, the results constrain any enhancement in t t-bar production beyond expectations of the standard model for t t-bar invariant masses larger than 1 TeV.Comment: Submitted to the Journal of High Energy Physics; this version includes a minor typo correction that will be submitted as an erratu