Relationship of the Perceived Social and Physical Environment with Mental Health-Related Quality of Life in Middle-Aged and Older Adults: Mediating Effects of Physical Activity

Background

Mental health conditions are among the leading non-fatal diseases in middle-aged and older adults in Australia. Proximal and distal social environmental factors and physical environmental factors have been associated with mental health, but the underlying mechanisms explaining these associations remain unclear. The study objective was to examine the contribution of different types of physical activity in mediating the relationship of social and physical environmental factors with mental health-related quality of life in middle-aged and older adults.

Methods

Baseline data from the Wellbeing, Eating and Exercise for a Long Life (WELL) study were used. WELL is a prospective cohort study, conducted in Victoria, Australia. Baseline data collection took place in 2010. In total, 3,965 middle-aged and older adults (55–65 years, 47.4% males) completed the SF-36 Health Survey, the International Physical Activity Questionnaire, and a questionnaire on socio-demographic, social and physical environmental attributes. Mediation analyses were conducted using the MacKinnon product-of-coefficients test.

Results

Personal safety, the neighbourhood physical activity environment, social support for physical activity from family or friends, and neighbourhood social cohesion were positively associated with mental health-related quality of life. Active transportation and leisure-time physical activity mediated 32.9% of the association between social support for physical activity from family or friends and mental health-related quality of life. These physical activity behaviours also mediated 11.0%, 3.4% and 2.3% respectively, of the relationship between the neighbourhood physical activity environment, personal safety and neighbourhood social cohesion and mental health-related quality of life.

Conclusions

If these results are replicated in future longitudinal studies, tailored interventions to improve mental health-related quality of life in middle-aged and older adults should use a combined strategy, focusing on increasing physical activity as well as social and physical environmental attributes.     

CO2 and H2O: Understanding Different Stakeholder Perspectives on the Use of Carbon Credits to Finance Household Water Treatment Projects

Background

Carbon credits are an increasingly prevalent market-based mechanism used to subsidize household water treatment technologies (HWT). This involves generating credits through the reduction of carbon emissions from boiling water by providing a technology that reduces greenhouse gas emissions linked to climate change. Proponents claim this process delivers health and environmental benefits by providing clean drinking water and reducing greenhouse gases. Selling carbon credits associated with HWT projects requires rigorous monitoring to ensure households are using the HWT and achieving the desired benefits of the device. Critics have suggested that the technologies provide neither the benefits of clean water nor reduced emissions. This study explores the perspectives of carbon credit and water, sanitation and hygiene (WASH) experts on HWT carbon credit projects.

Methods

Thirteen semi-structured, in-depth interviews were conducted with key informants from the WASH and carbon credit development sectors. The interviews explored perceptions of the two groups with respect to the procedures applied in the Gold Standard methodology for trading Voluntary Emission Reduction (VER) credits.

Results

Agreement among the WASH and carbon credit experts existed for the concept of suppressed demand and parameters in the baseline water boiling test. Key differences, however, existed. WASH experts’ responses highlighted a focus on objectively verifiable data for monitoring carbon projects while carbon credit experts called for contextualizing observed data with the need for flexibility and balancing financial viability with quality assurance.

Conclusions

Carbon credit projects have the potential to become an important financing mechanism for clean energy in low- and middle-income countries. Based on this research we recommend that more effort be placed on building consensus on the underlying assumptions for obtaining carbon credits from HWT projects, as well as the approved methods for monitoring correct and consistent use of the HWT technologies in order to support public health impacts.     

Verbal Autopsy: Evaluation of Methods to Certify Causes of Death in Uganda

To assess different methods for determining cause of death from verbal autopsy (VA) questionnaire data, the intra-rater reliability of Physician-Certified Verbal Autopsy (PCVA) and the accuracy of PCVA, expert-derived (non-hierarchical) and data-driven (hierarchal) algorithms were assessed for determining common causes of death in Ugandan children. A verbal autopsy validation study was conducted from 2008-2009 in three different sites in Uganda. The dataset included 104 neonatal deaths (0-27 days) and 615 childhood deaths (1-59 months) with the cause(s) of death classified by PCVA and physician review of hospital medical records (the ‘reference standard’). Of the original 719 questionnaires, 141 (20%) were selected for a second review by the same physicians; the repeat cause(s) of death were compared to the original,and agreement assessed using the Kappa statistic.Physician reviewers’ refined non-hierarchical algorithms for common causes of death from existing expert algorithms, from which, hierarchal algorithms were developed. The accuracy of PCVA, non-hierarchical, and hierarchical algorithms for determining cause(s) of death from all 719 VA questionnaires was determined using the reference standard. Overall, intra-rater repeatability was high (83% agreement, Kappa 0.79 [95% CI 0.76-0.82]). PCVA performed well, with high specificity for determining cause of neonatal (>67%), and childhood (>83%) deaths, resulting in fairly accurate cause-specific mortality fraction (CSMF) estimates. For most causes of death in children, non-hierarchical algorithms had higher sensitivity, but correspondingly lower specificity, than PCVA and hierarchical algorithms, resulting in inaccurate CSMF estimates. Hierarchical algorithms were specific for most causes of death, and CSMF estimates were comparable to the reference standard and PCVA. Inter-rater reliability of PCVA was high, and overall PCVA performed well. Hierarchical algorithms performed better than non-hierarchical algorithms due to higher specificity and more accurate CSMF estimates. Use of PCVA to determine cause of death from VA questionnaire data is reasonable while automated data-driven algorithms are improved.     

Paleoceanographic Insights on Recent Oxygen Minimum Zone Expansion: Lessons for Modern Oceanography

Climate-driven Oxygen Minimum Zone (OMZ) expansions in the geologic record provide an opportunity to characterize the spatial and temporal scales of OMZ change. Here we investigate OMZ expansion through the global-scale warming event of the most recent deglaciation (18-11 ka), an event with clear relevance to understanding modern anthropogenic climate change. Deglacial marine sediment records were compiled to quantify the vertical extent, intensity, surface area and volume impingements of hypoxic waters upon continental margins. By integrating sediment records (183-2,309 meters below sea level; mbsl) containing one or more geochemical, sedimentary or microfossil oxygenation proxies integrated with analyses of eustatic sea level rise, we reconstruct the timing, depth and intensity of seafloor hypoxia. The maximum vertical OMZ extent during the deglaciation was variable by region: Subarctic Pacific (~600-2,900 mbsl), California Current (~330-1,500 mbsl), Mexico Margin (~330-830 mbsl), and the Humboldt Current and Equatorial Pacific (~110-3,100 mbsl). The timing of OMZ expansion is regionally coherent but not globally synchronous. Subarctic Pacific and California Current continental margins exhibit tight correlation to the oscillations of Northern Hemisphere deglacial events (Termination IA, Bølling-Allerød, Younger Dryas and Termination IB). Southern regions (Mexico Margin and the Equatorial Pacific and Humboldt Current) exhibit hypoxia expansion prior to Termination IA (~14.7 ka), and no regional oxygenation oscillations. Our analyses provide new evidence for the geographically and vertically extensive expansion of OMZs, and the extreme compression of upper-ocean oxygenated ecosystems during the geologically recent deglaciation.     

The Prognostic Significance of Metabolic Response Heterogeneity in Metastatic Colorectal Cancer

Background

Tumoral heterogeneity is a major determinant of resistance in solid tumors. FDG-PET/CT can identify early during chemotherapy non-responsive lesions within the whole body tumor load. This prospective multicentric proof-of-concept study explores intra-individual metabolic response (mR) heterogeneity as a treatment efficacy biomarker in chemorefractory metastatic colorectal cancer (mCRC).

Methods

Standardized FDG-PET/CT was performed at baseline and after the first cycle of combined sorafenib (600mg/day for 21 days, then 800mg/day) and capecitabine (1700 mg/m²/day administered D1-14 every 21 days). MR assessment was categorized according to the proportion of metabolically non-responding (non-mR) lesions (stable FDG uptake with SUVmax decrease <15%) among all measurable lesions.

Results

Ninety-two patients were included. The median overall survival (OS) and progression-free survival (PFS) were 8.2 months (95% CI: 6.8–10.5) and 4.2 months (95% CI: 3.4–4.8) respectively. In the 79 assessable patients, early PET-CT showed no metabolically refractory lesion in 47%, a heterogeneous mR with at least one non-mR lesion in 32%, and a consistent non-mR or early disease progression in 21%. On exploratory analysis, patients without any non-mR lesion showed a significantly longer PFS (HR 0.34; 95% CI: 0.21–0.56, P-value <0.001) and OS (HR 0.58; 95% CI: 0.36–0.92, P-value 0.02) compared to the other patients. The proportion of non-mR lesions within the tumor load did not impact PFS/OS.

Conclusion

The presence of at least one metabolically refractory lesion is associated with a poorer outcome in advanced mCRC patients treated with combined sorafenib-capecitabine. Early detection of treatment-induced mR heterogeneity may represent an important predictive efficacy biomarker in mCRC.

Trial Registration

ClinicalTrials.gov NCT01290926     

Resilience in the General Population: Standardization of the Resilience Scale (RS-11)

Background

The objectives of the study were to generate normative data for the RS-11 for different age groups for men and women and to further investigate the construct validity and factor structure in the general population.

Methods

Nationally representative face-to face household surveys were conducted in Germany in 2006 (n = 5,036).

Results

Normative data for the RS-11 were generated for men and women (53.7% female) and different age levels (mean age (SD) of 48.4 (18.0) years). Men had significantly higher mean scores compared with women (60.0 [SD = 10.2] vs. 59.3 [SD = 11.0]). Results of CFA supported a one-factor model of resilience. Self-esteem (standardized β = .50) and life satisfaction (standardized β =.20) were associated with resilience.

Conclusions

The normative data provide a framework for the interpretation and comparisons of resilience with other populations. Results demonstrate a special importance of self-esteem in the understanding of resilience.     

Integrating Protein Engineering and Bioorthogonal Click Conjugation for Extracellular Vesicle Modulation and Intracellular Delivery

Exosomes are small, cell-secreted vesicles that transfer proteins and genetic information between cells. This intercellular transmission regulates many physiological and pathological processes. Therefore, exosomes have emerged as novel biomarkers for disease diagnosis and as nanocarriers for drug delivery. Here, we report an easy-to-adapt and highly versatile methodology to modulate exosome composition and conjugate exosomes for intracellular delivery. Our strategy combines the metabolic labeling of newly synthesized proteins or glycan/glycoproteins of exosome-secreting cells with active azides and bioorthogonal click conjugation to modify and functionalize the exosomes. The azide-integrated can be conjugated to a variety of small molecules and proteins and can efficiently deliver conjugates into cells. The metabolic engineering of exosomes diversifies the chemistry of exosomes and expands the functions that can be introduced into exosomes, providing novel, powerful tools to study the roles of exosomes in biology and expand the biomedical potential of exosomes.     

Factors Associated with Clinical Research Recruitment in a Pediatric Academic Medical Center—A Web-Based Survey

Background

One of the most difficult aspects of conducting clinical research is the ability to successfully recruit participants. Pediatric clinical research presents unique recruitment challenges that relate to the need for parental consent on behalf of a minor, child assent, and school attendance. Yet, this has been less well studied. We conducted a survey of investigators performing human subjects research in a single large academic pediatric hospital to better understand characteristics of studies with successful recruitment.

Methods

We conducted a web-based survey from September 2011 to December 2011 of all principal investigators with an Institutional Review Board approved human subjects protocol at Boston Children’s Hospital, a pediatric Academic Medical Center. The survey captured various characteristics of the protocols including study design, staffing, resources, and investigator experience and training as well as respondents’ perceived barriers and facilitators to recruitment. We used chi square tests and Mantel-Haenszel test for linear trend to examine the relationship between selected predictor variables and the binary outcome of successful vs. unsuccessful recruitment and multivariable logistic regression analyses to examine the simultaneous influence of potential predictors on each outcome.

Results

Among the 349 eligible investigators, 52% responded to the survey, and 181 with valid data were included in the analyses. Two-thirds of the 87 protocols closed to enrollment reached 80% or more of their target enrollment, whereas, only one-third of the 94 protocols actively recruiting were meeting 80% of their target. Recruitment method appeared to be the only significant and independent factor associated with achieving 80% or more of target enrollment in closed to enrollment protocols. Closed to enrollment protocols that used recruitment in person were 4.55 times (95% CI 1.30 to 15.93; p = 0.02) more likely to achieve 80% or more of their target enrollment when compared to those that used other recruitment methods. Other potentially modifiable factors such as number of study visits, study duration and investigator experience were suggestive of being meaningfully related to recruitment.

Conclusion

Recruiting in person may promote reaching an acceptable target enrollment in pediatric as well as adult clinical research. Future research is needed on larger and more diverse samples to gain a better understanding of how the characteristics and qualifications of the individuals who conduct recruitment influence participant enrollment as well as how best to approach patient and families for their participation.