Association Between Sedentary Time and Quality of Life From the Osteoarthritis Initiative: Who Might Benefit Most From Treatment?

Objective To investigate the relationship between sedentary behavior and quality-adjusted life years (QALYs) among participants in the Osteoarthritis Initiative. Design Longitudinal, observational design. Setting Osteoarthritis Initiative cohort. Participants Individuals (N=1794) from a prospective, multicenter longitudinal cohort were classified into quantile groups based on average daily sedentary time (most sedentary, quartile 1 [Q1] ≥11.6h; 10.7h≤ Q2 Interventions Not applicable. Main Outcome Measures Individual QALYs were estimated over 2 years from the area under the curve of health-related utility scores derived from the Medical Outcomes Study 12-Item Short-Form Health Survey versus time. The relationship between baseline sedentary behavior and median 2-year QALYs was estimated using quantile regression adjusted for socioeconomic factors and body mass index. Results Lower QALYs over 2 years were more frequently found among the most sedentary (Q1, median 1.59), and QALYs increased as time spent in baseline sedentary behavior decreased (median QALYs for Q2, 1.64; Q3, 1.65; Q4, 1.65). The relationship of sedentary time and median QALY change was only significant for the most sedentary Q1 group, where an additional hour of sedentary behavior significantly reduced QALYs by −.072 (95% confidence interval, −.121 to −.020). Conclusions Our findings suggest that individuals with the most extreme sedentary profiles may be vulnerable to additional losses of quality of life if they become more sedentary. Targeting these individuals to decrease sedentary behavior has the potential to be cost-effective

UC-15 Malware Analysis Using Reverse Engineering

The motivation for this project is driven by evaluation of the different tools on the market that allow for breaking down executables or binary files, and understanding what the malware is doing. By reverse-engineering the malware, we can understand its impact and how to protect against it. Our focus is to understand where different tools are stronger than others, as well as understand the evolving landscape of malware and security overall. For this capstone project, we utilized two different tools and many sample malware files. The methods used to debug the malware are detailed in our milestone two report and will be expanded upon in our final presentation. At this point, we\u27ve found the tool WinDbg to be the most versatile for binary and executable debugging. We also evaluated IDA Pro, and understand the many ways in which its graphical display of data and relationships, equips a researcher with the necessary tools and information to walk through an executable. Our focus in milestone 3 is to expand our documentation and guide on malware debugging to the point that it provides a user the full breadth of information and steps needed to start from scratch and end with a broken apart piece of malware. We provided much of this as part of the milestone 2 presentation and report, but we will continue to build on it so it\u27s a useful how-to guide for anyone trying to debug a piece of malicious code.Advisors(s): Dr. Ying Xie [email protected](s): SecurityIT 498

Physical Activity Minimum Threshold Predicting Improved Function in Adults With Lower‐Extremity Symptoms

Objective To identify an evidence‐based minimum physical activity threshold to predict improved or sustained high function for adults with lower‐extremity joint symptoms. Methods Prospective multisite data from 1,629 adults, age ≥49 years with symptomatic lower‐extremity joint pain/aching/stiffness, participating in the Osteoarthritis Initiative accelerometer monitoring substudy were clinically assessed 2 years apart. Improved/high function in 2‐year gait speed and patient‐reported outcomes (PROs) were based on improving or remaining in the best (i.e., maintaining high) function quintile compared to baseline status. Optimal thresholds predicting improved/high function were investigated using classification trees for the legacy federal guideline metric requiring 150 minutes/week of moderate‐vigorous (MV) activity in bouts lasting 10 minutes or more (MV‐bout) and other metrics (total MV, sedentary, light intensity activity, nonsedentary minutes/week). Results Optimal thresholds based on total MV minutes/week predicted improved/high function outcomes more strongly than the legacy or other investigated metrics. Meeting the 45 total MV minutes/week threshold had increased relative risk (RR) for improved/high function (gait speed RR 1.8, 95% confidence interval [95% CI] 1.6, 2.1 and PRO physical function RR 1.4, 95% CI 1.3, 1.6) compared to less active adults. Thresholds were consistent across sex, body mass index, knee osteoarthritis status, and age. Conclusion These results supported a physical activity minimum threshold of 45 total MV minutes/week to promote improved or sustained high function for adults with lower‐extremity joint symptoms. This evidence‐based threshold is less rigorous than federal guidelines (≥150 MV‐bout minutes/week) and provides an intermediate goal towards the federal guideline for adults with lower‐extremity symptoms

Natural killer cells during acute HIV-1 infection: clues for HIV-1 prevention and therapy

Despite progress in preexposure prophylaxis, the number of newly diagnosed cases with HIV-1 remains high, highlighting the urgent need for preventive and therapeutic strategies to reduce HIV-1 acquisition and limit disease progression. Early immunological events, occurring during acute infection, are key determinants of the outcome and course of disease. Understanding early immune responses occurring before viral set-point is established, is critical to identify potential targets for prophylactic and therapeutic approaches. Natural killer (NK) cells represent a key cellular component of innate immunity and contribute to the early host defence against HIV-1 infection, modulating the pathogenesis of acute HIV-1 infection (AHI). Emerging studies have identified tools for harnessing NK cell responses and expanding specialized NK subpopulations with adaptive/memory features, paving the way for development of novel HIV-1 therapeutics. This review highlights the knowns and unknowns regarding the role of NK cell subsets in the containment of acute HIV-1 infection, and summarizes recent advances in selectively augmenting NK cell functions through prophylactic and therapeutic interventions

The Banathy Conversation Methodology

Context: Thirty years ago, members of the systems science community discovered that at their conferences, more was being accomplished in the breaks than in the sessions. Led by Bela H. Banathy, they cancelled the sessions and created a conversation methodology that has proven far more effective. Dozens of conversations have now been held around the world. Problem: At a recent conversation in Linz, Austria, a team devoted its inquiry to the Banathy Conversation Methodology (BCM) itself, asking, in particular, how to develop and spread the methodology further, beyond the systems science community. Method: The team captured key features and benefits of BCM and developed new tools. Results: Described herein are the development of the methodology, its theoretical underpinnings, the methodology itself, heuristics for successful conversations, and an example of how the methodology is spreading. Implications: Ultimately, the hope is to develop the methodology in such ways that communities could apply it to meet significant challenges and co-create their futures

Chronic lung disease in HIV-infected children established on antiretroviral therapy.

Respiratory disease is a major cause of morbidity and mortality in HIV-infected children. Despite antiretroviral therapy (ART), children suffer chronic symptoms. We investigated symptom prevalence, lung function, and exercise capacity among older children established on ART, and an age-matched HIV-uninfected group. A cross-sectional study in Zimbabwe of: 1) HIV-infected children aged 6-16 years receiving ART for over six months; 2) HIV-uninfected children attending primary health clinics from the same area. Standardised questionnaire, spirometry, Incremental Shuttle Walk Testing (ISWT), CD4 count, HIV viral load, and sputum culture for tuberculosis were performed. 202 HIV-infected and 150 uninfected participants (median age 11.1 years in each group) were recruited. Median age at HIV diagnosis and ART initiation was 5.5 (IQR 2.8-7.5) and 6.1 years (IQR 3.6-8.4) respectively. Median CD4 count was 726 cells/μl, and 79% had HIV viral load<400copies/ml. Chronic respiratory symptoms were rare in HIV-uninfected children (n = 1 [0.7%]), but common in HIV-infected participants (51 [25%]), especially cough (30 [15%]) and dyspnoea (30 [15%]). HIV-infected participants were more commonly previously treated for tuberculosis (76 [38%] versus 1 [0.7%], p < 0.001), had lower exercise capacity (mean ISWT distance 771m versus 889m respectively, p < 0.001), and more frequently abnormal spirometry (43 [24.3%] versus 15 [11.5%], p = 0.003) compared to HIV-uninfected participants. HIV diagnosis at an older age was associated with lung function abnormality (p = 0.025). No participant tested positive for M. tuberculosis. In children, despite ART, HIV is associated with significant respiratory symptoms and functional impairment. Understanding pathogenesis is key, as new treatment strategies are urgently required

Longitudinal investigation of training status and cardiopulmonary responses in pre- and early-pubertal children

PurposeThe presence of a maturational threshold that modulates children’s physiological responses to exercise training continues to be debated, not least due to a lack of longitudinal evidence to address this question. The purpose of this study was to investigate the interaction between swim-training status and maturity in nineteen trained (T, 10 ± 1 years, −2.4 ± 1.9 years pre-peak height velocity, 8 boys) and fifteen untrained (UT, 10 ± 1 years, −2.3 ± 0.9 years pre-peak height velocity, 5 boys) children, at three annual measurements.MethodsIn addition to pulmonary gas exchange measurements, stroke volume (SV) and cardiac output ( Q˙) were estimated by thoracic bioelectrical impedance during incremental ramp exercise.ResultsAt baseline and both subsequent measurement points, trained children had significantly (P < 0.05) higher peak oxygen uptake (year 1 T 1.75 ± 0.34 vs. UT 1.49 ± 0.22; year 2 T 2.01 ± 0.31 vs. UT 1.65 ± 0.08; year 3 T 2.07 ± 0.30 vs. UT 1.77 ± 0.16 l min−1) and Q˙ (year 1 T 15.0 ± 2.9 vs. UT 13.2 ± 2.2; year 2 T 16.1 ± 2.8 vs. UT 13.8 ± 2.9; year 3 T 19.3 ± 4.4 vs. UT 16.0 ± 2.7 l min−1). Furthermore, the SV response pattern differed significantly with training status, demonstrating the conventional plateau in UT but a progressive increase in T. Multilevel modelling revealed that none of the measured pulmonary or cardiovascular parameters interacted with maturational status, and the magnitude of the difference between T and UT was similar, irrespective of maturational status.ConclusionThe results of this novel longitudinal study challenge the notion that differences in training status in young people are only evident once a maturational threshold has been exceeded

The immune evasion roles of Staphylococcus aureus protein A and impact on vaccine development

While Staphylococcus aureus (S. aureus) bacteria are part of the human commensal flora, opportunistic invasion following breach of the epithelial layers can lead to a wide array of infection syndromes at both local and distant sites. Despite ubiquitous exposure from early infancy, the life-long risk of opportunistic infection is facilitated by a broad repertoire of S. aureus virulence proteins. These proteins play a key role in inhibiting development of a long-term protective immune response by mechanisms ranging from dysregulation of the complement cascade to the disruption of leukocyte migration. In this review we describe the recent progress made in dissecting S. aureus immune evasion, focusing on the role of the superantigen, staphylococcal protein A (SpA). Evasion of the normal human immune response drives the ability of S. aureus to cause infection, often recurrently, and is also thought to be a major hindrance in the development of effective vaccination strategies. Understanding the role of S. aureus virulence protein and determining methods overcoming or subverting these mechanisms could lead to much-needed breakthroughs in vaccine and monoclonal antibody development

Consumption of New Zealand blackcurrant extract improves recovery from exercise-induced muscle damage in non-resistance trained men and women: A double-blind randomised trial

Background: Blackcurrant is rich in anthocyanins that may protect against exercise-induced muscle damage (EIMD) and facilitate a faster recovery of muscle function. We examined the effects of New Zealand blackcurrant (NZBC) extract on indices of muscle damage and recovery following a bout of strenuous isokinetic resistance exercise. Methods: Using a double-blind, randomised, placebo controlled, parallel design, twenty-seven healthy participants received either a 3 g·day−1 NZBC extract (n = 14) or the placebo (PLA) (n = 13) for 8 days prior to and 4 days following 60 strenuous concentric and eccentric contractions of the biceps brachii muscle on an isokinetic dynamometer. Muscle soreness (using a visual analogue scale), maximal voluntary contraction (MVC), range of motion (ROM) and blood creatine kinase (CK) were assessed before (0 h) and after (24, 48, 72 and 96 h) exercise. Results: Consumption of NZBC extract resulted in faster recovery of baseline MVC (p = 0.04), attenuated muscle soreness at 24 h (NZBC: 21 ± 10 mm vs. PLA: 40 ± 23 mm, p = 0.02) and 48 h (NZBC: 22 ± 17 vs. PLA: 44 ± 26 mm, p = 0.03) and serum CK concentration at 96 h (NZBC: 635 ± 921 UL vs. PLA: 4021 ± 4319 UL, p = 0.04) following EIMD. Conclusions: Consumption of NZBC extract prior to and following a bout of eccentric exercise attenuates muscle damage and improves functional recovery. These findings are of practical importance in recreationally active and potentially athletic populations, who may benefit from accelerated recovery following EIMD