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

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

A Randomized Trial of a Motivational Interviewing Intervention to Increase Lifestyle Physical Activity and Improve Self-Reported Function in Adults with Arthritis

Background Arthritis is a leading cause of chronic pain and functional limitations. Exercise is beneficial for improving strength and function and decreasing pain. We evaluated the effect of a motivational interviewing-based lifestyle physical activity intervention on self-reported physical function in adults with knee osteoarthritis (KOA) or rheumatoid arthritis (RA). Methods Participants were randomized to intervention or control. Control participants received a brief physician recommendation to increase physical activity to meet national guidelines. Intervention participants received the same brief baseline physician recommendation in addition to motivational interviewing sessions at baseline, 3, 6, and 12 months. These sessions focused on facilitating individualized lifestyle physical activity goal setting. The primary outcome was change in self-reported physical function. Secondary outcomes were self-reported pain and accelerometer-measured physical activity. Self-reported KOA outcomes were evaluated by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for KOA (WOMAC scores range from 0 to 68 for function and 0 to 20 for pain) and the Health Assessment Questionnaire (HAQ) for RA. Outcomes were measured at baseline, 3, 6, 12, and 24 months. Multiple regression accounting for repeated measures was used to evaluate the overall intervention effect on outcomes controlling for baseline values. Results Participants included 155 adults with KOA (76 intervention and 79 control) and 185 adults with RA (93 intervention and 92 control). Among KOA participants, WOMAC physical function improvement was greater in the intervention group compared to the control group [difference = 2.21 (95% CI: 0.01, 4.41)]. WOMAC pain improvement was greater in the intervention group compared to the control group [difference = 0.70 (95% CI: −0.004, 1.41)]. There were no significant changes in physical activity. Among RA participants, no significant intervention effects were found. Conclusion Participants with KOA receiving the lifestyle intervention experienced modest improvement in self-reported function and a trend toward improved pain compared to controls. There was no intervention effect for RA participants. Further refinement of this intervention is needed for more robust improvement in function, pain, and physical activity

A smartphone-supported weight loss program: design of the ENGAGED randomized controlled trial

Background Obesity remains a major public health challenge, demanding cost-effective and scalable weight management programs. Delivering key treatment components via mobile technology offers a potential way to reduce expensive in-person contact, thereby lowering the cost and burden of intensive weight loss programs. The ENGAGED study is a theory-guided, randomized controlled trial designed to examine the feasibility and efficacy of an abbreviated smartphone-supported weight loss program. Methods/design Ninety-six obese adults (BMI 30–39.9 kg/m2) will be randomized to one of three treatment conditions: (1) standard behavioral weight loss (STND), (2) technology-supported behavioral weight loss (TECH); or (3) self-guided behavioral weight loss (SELF). All groups will aim to achieve a 7% weight loss goal by reducing calorie and fat intake and progressively increasing moderate intensity physical activity to 175 minutes/week. STND and TECH will attend 8 group sessions and receive regular coaching calls during the first 6 months of the intervention; SELF will receive the Group Lifestyle Balance Program DVD’s and will not receive coaching calls. During months 1–6, TECH will use a specially designed smartphone application to monitor dietary intake, body weight, and objectively measured physical activity (obtained from a Blue-tooth enabled accelerometer). STND and SELF will self-monitor on paper diaries. Linear mixed modeling will be used to examine group differences on weight loss at months 3, 6, and 12. Self-monitoring adherence and diet and activity goal attainment will be tested as mediators. Discussion ENGAGED is an innovative weight loss intervention that integrates theory with emerging mobile technologies. We hypothesize that TECH, as compared to STND and SELF, will result in greater weight loss by virtue of improved behavioral adherence and goal achievement. Trial registration NCT0105171

The Origins of [CII] Emission in Local Star-forming Galaxies

The [CII] 158um fine-structure line is the brightest emission line observed in local star-forming galaxies. As a major coolant of the gas-phase interstellar medium, [CII] balances the heating, including that due to far-ultraviolet photons, which heat the gas via the photoelectric effect. However, the origin of [CII] emission remains unclear, because C+ can be found in multiple phases of the interstellar medium. Here we measure the fractions of [CII] emission originating in the ionized and neutral gas phases of a sample of nearby galaxies. We use the [NII] 205um fine-structure line to trace the ionized medium, thereby eliminating the strong density dependence that exists in the ratio of [CII]/[NII] 122um. Using the FIR [CII] and [NII] emission detected by the KINGFISH and Beyond the Peak Herschel programs, we show that 60-80% of [CII] emission originates from neutral gas. We find that the fraction of [CII] originating in the neutral medium has a weak dependence on dust temperature and the surface density of star formation, and a stronger dependence on the gas-phase metallicity. In metal-rich environments, the relatively cooler ionized gas makes substantially larger contributions to total [CII] emission than at low abundance, contrary to prior expectations. Approximate calibrations of this metallicity trend are provided.Comment: 8 pages, accepted for publication in Ap

Lentiviral Vector Delivery of Human Interleukin-7 (hIL-7) to Human Immune System (HIS) Mice Expands T Lymphocyte Populations

Genetically modified mice carrying engrafted human tissues provide useful models to study human cell biology in physiologically relevant contexts. However, there remain several obstacles limiting the compatibility of human cells within their mouse hosts. Among these is inadequate cross-reactvitiy between certain mouse cytokines and human cellular receptors, depriving the graft of important survival and growth signals. To circumvent this problem, we utilized a lentivirus-based delivery system to express physiologically relevant levels of human interleukin-7 (hIL-7) in Rag2-/-γc-/- mice following a single intravenous injection. hIL-7 promoted homeostatic proliferation of both adoptively transferred and endogenously generated T-cells in Rag2-/-γc-/- Human Immune System (HIS) mice. Interestingly, we found that hIL-7 increased T lymphocyte numbers in the spleens of HIV infected HIS mice without affecting viral load. Taken together, our study unveils a versatile approach to deliver human cytokines to HIS mice, to both improve engraftment and determine the impact of cytokines on human diseases

Technology Interventions to Curb Obesity: A Systematic Review of the Current Literature

Abstract Obesity is a public health crisis that has reached epidemic proportions. Although intensive behavioral interventions can produce clinically significant weight loss, their cost to implement, coupled with resource limitations, pose significant barriers to scalability. To overcome these challenges, researchers have made attempts to shift intervention content to the Internet and other mobile devices. This article systematically reviews the recent literature examining technology-supported interventions for weight loss and maintenance among overweight and obese adults. Thirteen studies were identified that satisfied our inclusion criteria (12 weight loss trials, 1 weight maintenance trial). Our findings suggest that technology interventions may be efficacious at producing weight loss. However, several studies are limited by methodologic shortcomings. There are insufficient data to evaluate their efficacy for weight maintenance. Further research is needed that employs state-ofthe-art methodology, with careful attention being paid to adherence and fidelity to intervention protocols

Beyond aggression: Androgen-receptor blockade modulates social interaction in wild meerkats

In male vertebrates, androgens are inextricably linked to reproduction, social dominance, and aggression, often at the cost of paternal investment or prosociality. Testosterone is invoked to explain rank-related reproductive differences, but its role within a status class, particularly among subordinates, is underappreciated. Recent evidence, especially for monogamous and cooperatively breeding species, suggests broader androgenic mediation of adult social interaction. We explored the actions of androgens in subordinate, male members of a cooperatively breeding species, the meerkat (Suricata suricatta). Although male meerkats show no rank-related testosterone differences, subordinate helpers rarely reproduce. We blocked androgen receptors, in the field, by treating subordinate males with the antiandrogen, flutamide. We monitored androgen concentrations (via baseline serum and time-sequential fecal sampling) and recorded behavior within their groups (via focal observation). Relative to controls, flutamide-treated animals initiated less and received more high-intensity aggression (biting, threatening, feeding competition), engaged in more prosocial behavior (social sniffing, grooming, huddling), and less frequently initiated play or assumed a ‘dominant’ role during play, revealing significant androgenic effects across a broad range of social behavior. By contrast, guarding or vigilance and measures of olfactory and vocal communication in subordinate males appeared unaffected by flutamide treatment. Thus, androgens in male meerkat helpers are aligned with the traditional trade-off between promoting reproductive and aggressive behavior at a cost to affiliation. Our findings, based on rare endocrine manipulation in wild mammals, show a more pervasive role for androgens in adult social behavior than is often recognized, with possible relevance for understanding tradeoffs in cooperative systems

Sequence Similarity Network Reveals Common Ancestry of Multidomain Proteins

We address the problem of homology identification in complex multidomain families with varied domain architectures. The challenge is to distinguish sequence pairs that share common ancestry from pairs that share an inserted domain but are otherwise unrelated. This distinction is essential for accuracy in gene annotation, function prediction, and comparative genomics. There are two major obstacles to multidomain homology identification: lack of a formal definition and lack of curated benchmarks for evaluating the performance of new methods. We offer preliminary solutions to both problems: 1) an extension of the traditional model of homology to include domain insertions; and 2) a manually curated benchmark of well-studied families in mouse and human. We further present Neighborhood Correlation, a novel method that exploits the local structure of the sequence similarity network to identify homologs with great accuracy based on the observation that gene duplication and domain shuffling leave distinct patterns in the sequence similarity network. In a rigorous, empirical comparison using our curated data, Neighborhood Correlation outperforms sequence similarity, alignment length, and domain architecture comparison. Neighborhood Correlation is well suited for automated, genome-scale analyses. It is easy to compute, does not require explicit knowledge of domain architecture, and classifies both single and multidomain homologs with high accuracy. Homolog predictions obtained with our method, as well as our manually curated benchmark and a web-based visualization tool for exploratory analysis of the network neighborhood structure, are available at http://www.neighborhoodcorrelation.org. Our work represents a departure from the prevailing view that the concept of homology cannot be applied to genes that have undergone domain shuffling. In contrast to current approaches that either focus on the homology of individual domains or consider only families with identical domain architectures, we show that homology can be rationally defined for multidomain families with diverse architectures by considering the genomic context of the genes that encode them. Our study demonstrates the utility of mining network structure for evolutionary information, suggesting this is a fertile approach for investigating evolutionary processes in the post-genomic era

The Origins of [C II] Emission in Local Star-forming Galaxies

The [C ii] 158 μm fine-structure line is the brightest emission line observed in local star-forming galaxies. As a major coolant of the gas-phase interstellar medium, [C ii] balances the heating, including that due to far-ultraviolet photons, which heat the gas via the photoelectric effect. However, the origin of [C ii] emission remains unclear because C+ can be found in multiple phases of the interstellar medium. Here we measure the fractions of [C ii] emission originating in the ionized and neutral gas phases of a sample of nearby galaxies. We use the [N ii] 205 μm fine-structure line to trace the ionized medium, thereby eliminating the strong density dependence that exists in the ratio of [C ii]/[N ii] 122 μm. Using the FIR [C ii] and [N ii] emission detected by the KINGFISH (Key Insights on Nearby Galaxies: a Far- Infrared Survey with Herschel) and Beyond the Peak Herschel programs, we show that 60%–80% of [C ii] emission originates from neutral gas. We find that the fraction of [C ii] originating in the neutral medium has a weak dependence on dust temperature and the surface density of star formation, and has a stronger dependence on the gas-phase metallicity. In metal-rich environments, the relatively cooler ionized gas makes substantially larger contributions to total [C ii] emission than at low abundance, contrary to prior expectations. Approximate calibrations of this metallicity trend are providedK.V.C. acknowledges support from the Deutsche Forschungsgemeinschaft Priority Program ISM-SPP 1573 and the MPIA, and thanks the KINGFISH & BTP teams for their support. J.D.S. acknowledges visiting support from the Alexander von Humboldt Foundation and the MPIA. B.G. acknowledges the support of the Australian Research Council via a Future Fellowship (FT140101202). A.D.B. acknowledges partial support from NSFAST0955836 and 1412419. B.T.D. acknowledges partial support from NSF-AST1408723. M.B. was supported by MINEDUC-UA project, code ANT 1655. Beyond the Peak research has been supported by a NASA/JPL grant (RSA 1427378)