Stable isotopes of carbon, nitrogen, and sulfur are used as ecological tracers for a variety of applications, such as studies of animal migrations, energy sources, and food web pathways. Yet ...uncertainty relating to the time period integrated by isotopic measurement of animal tissues can confound the interpretation of isotopic data. There have been a large number of experimental isotopic diet shift studies aimed at quantifying animal tissue isotopic turnover rate λ (%·day(-1), often expressed as isotopic half-life, ln(2)/λ, days). Yet no studies have evaluated or summarized the many individual half-life estimates in an effort to both seek broad-scale patterns and characterize the degree of variability. Here, we collect previously published half-life estimates, examine how half-life is related to body size, and test for tissue- and taxa-varying allometric relationships. Half-life generally increases with animal body mass, and is longer in muscle and blood compared to plasma and internal organs. Half-life was longest in ecotherms, followed by mammals, and finally birds. For ectotherms, different taxa-tissue combinations had similar allometric slopes that generally matched predictions of metabolic theory. Half-life for ectotherms can be approximated as: ln (half-life) = 0.22*ln (body mass) + group-specific intercept; n = 261, p<0.0001, r2 = 0.63. For endothermic groups, relationships with body mass were weak and model slopes and intercepts were heterogeneous. While isotopic half-life can be approximated using simple allometric relationships for some taxa and tissue types, there is also a high degree of unexplained variation in our models. Our study highlights several strong and general patterns, though accurate prediction of isotopic half-life from readily available variables such as animal body mass remains elusive.
Survivors of sexual violence have high rates of depression, anxiety, and post-traumatic stress disorder (PTSD). Although treatment for symptoms related to sexual violence has been shown to be ...effective in high-income countries, evidence is lacking in low-income, conflict-affected countries.
In this trial in the Democratic Republic of Congo, we randomly assigned 16 villages to provide cognitive processing therapy (1 individual session and 11 group sessions) or individual support to female sexual-violence survivors with high levels of PTSD symptoms and combined depression and anxiety symptoms. One village was excluded owing to concern about the competency of the psychosocial assistant, resulting in 7 villages that provided therapy (157 women) and 8 villages that provided individual support (248 women). Assessments of combined depression and anxiety symptoms (average score on the Hopkins Symptom Checklist range, 0 to 3, with higher scores indicating worse symptoms), PTSD symptoms (average score on the PTSD Checklist range, 0 to 3, with higher scores indicating worse symptoms), and functional impairment (average score across 20 tasks range, 0 to 4, with higher scores indicating greater impairment) were performed at baseline, at the end of treatment, and 6 months after treatment ended.
A total of 65% of participants in the therapy group and 52% of participants in the individual-support group completed all three assessments. Mean scores for combined depression and anxiety improved in the individual-support group (2.2 at baseline, 1.7 at the end of treatment, and 1.5 at 6 months after treatment), but improvements were significantly greater in the therapy group (2.0 at baseline, 0.8 at the end of treatment, and 0.7 at 6 months after treatment) (P<0.001 for all comparisons). Similar patterns were observed for PTSD and functional impairment. At 6 months after treatment, 9% of participants in the therapy group and 42% of participants in the individual-support group met criteria for probable depression or anxiety (P<0.001), with similar results for PTSD.
In this study of sexual-violence survivors in a low-income, conflict-affected country, group psychotherapy reduced PTSD symptoms and combined depression and anxiety symptoms and improved functioning. (Funded by the U.S. Agency for International Development Victims of Torture Fund and the World Bank; ClinicalTrials.gov number, NCT01385163.).
The objective of this study was to identify and appraise evidence on the direct and indirect impacts of high indoor temperatures on health; the indoor temperature threshold at which the identified ...health impacts are observed; and to summarise the evidence for establishing a maximum indoor temperature threshold for health.
This is a systematic literature review and narrative synthesis.
A review of the published literature using MEDLINE, EMBASE, Global Health, PsycINFO, Maternity and Infant Care, Cochrane Library, CINAHL and GreenFILE databases was conducted. The search criteria were kept broad to capture evidence from all countries and contexts; no date or study design limits were applied, except English language limits. We included studies that specifically measured indoor temperature and examined its effect on physical or mental health outcomes. Evidence was graded using the National Institutes of Health framework.
Twenty-two articles were included in the review, including 11 observational, seven cross-sectional and three longitudinal cohort studies and one prospective case–control study. Eight main health effects were described: respiratory, blood pressure, core temperature, blood glucose, mental health and cognition, heat-health symptoms, physical functioning and influenza transmission. Five studies found respiratory symptoms worsened in warm indoor environments, with one reporting indoor temperatures higher than 26 °C, which was associated with increased respiratory distress calls being made to paramedics (odds ratio = 1.63, P = 0.056). Core symptoms of schizophrenia and dementia were found to be significantly exacerbated by indoor heat (the latter above a 26 °C cumulative exposure threshold). The absorption of insulin doses in people with type one diabetes was also significantly accelerated in hot indoor environments. Only five studies reported the temperatures at which health outcomes worsened, with thresholds ranging between 26 °C and 32 °C. However, owing to insufficient data and the heterogeneity of the included studies (design, population, setting, exposure measures, outcomes and location), meta-analysis and an upper threshold determination was not feasible.
High indoor temperatures affect aspects of human health, with the strongest evidence for respiratory health, diabetes management and core schizophrenia and dementia symptoms. Exacerbation of symptoms in warm indoor environments has clinical relevance to at-risk groups and those caring for them. Care staff and facility managers need to be vigilant of high temperatures in care environments and should incorporate indoor overheating into their risk management and sustainability and/or climate change adaptation plans. The indoor temperature threshold at which adverse effects begin to occur remains unclear as studies seldom report the exposure–response relationship over a temperature continuum. Until there is extensive scientific data to support a maximum indoor temperature threshold, 26 °C may be the most suitable indoor temperature for at-risk groups in keeping with the existing guidance documents.
•Significant gaps in understanding the impact of indoor heat on health are addressed.•The strongest evidence found exists for increased respiratory morbidity in high indoor temperatures.•Symptoms of mental health disorders are exacerbated by high indoor temperatures.•Insulin absorption in people with type one diabetes is accelerated by heat, potentially affecting medication regimes.•Sparse and heterogeneous data limited the ability to define a robust maximum indoor temperature threshold for health.
The glymphatic system, that is aquaporin 4 (AQP4) facilitated exchange of CSF with interstitial fluid (ISF), may provide a clearance pathway for protein species such as amyloid-β and tau, which ...accumulate in the brain in Alzheimer's disease. Further, tau protein transference via the extracellular space, the compartment that is cleared by the glymphatic pathway, allows for its neuron-to-neuron propagation, and the regional progression of tauopathy in the disorder. The glymphatic system therefore represents an exciting new target for Alzheimer's disease. Here we aim to understand the involvement of glymphatic CSF-ISF exchange in tau pathology. First, we demonstrate impaired CSF-ISF exchange and AQP4 polarization in a mouse model of tauopathy, suggesting that this clearance pathway may have the potential to exacerbate or even induce pathogenic accumulation of tau. Subsequently, we establish the central role of AQP4 in the glymphatic clearance of tau from the brain; showing marked impaired glymphatic CSF-ISF exchange and tau protein clearance using the novel AQP4 inhibitor, TGN-020. As such, we show that this system presents as a novel druggable target for the treatment of Alzheimer's disease, and possibly other neurodegenerative diseases alike.
Both intimate partner violence (IPV) and alcohol misuse are highly prevalent, and partner alcohol misuse is a significant contributor to women's risk for IPV. There are few evidence-based ...interventions to address these problems in low- and middle-income countries (LMICs). We evaluated the effectiveness of an evidence-based, multi-problem, flexible, transdiagnostic intervention, the Common Elements Treatment Approach (CETA) in reducing (a) women's experience of IPV and (b) their male partner's alcohol misuse among couples in urban Zambia.
This was a single-blind, parallel-assignment randomized controlled trial in Lusaka, Zambia. Women who reported moderate or higher levels of IPV and their male partners with hazardous alcohol use were enrolled as a couple and randomized to CETA or treatment as usual plus safety checks (TAU-Plus). The primary outcome, IPV, was assessed by the Severity of Violence Against Women Scale (SVAWS) physical/sexual violence subscale, and the secondary outcome, male alcohol misuse, by the Alcohol Use Disorders Identification Test (AUDIT). Assessors were blinded. Analyses were intent-to-treat. Primary outcome assessments were planned at post-treatment, 12 months post-baseline, and 24 months post-baseline. Enrollment was conducted between May 23, 2016, and December 17, 2016. In total, 123 couples were randomized to CETA, 125 to TAU-Plus. The majority of female (66%) and a plurality of male (48%) participants were between 18 and 35 years of age. Mean reduction in IPV (via SVAWS subscale score) at 12 months post-baseline was statistically significantly greater among women who received CETA compared to women who received TAU-Plus (-8.2, 95% CI -14.9 to -1.5, p = 0.02, Cohen's d effect size = 0.49). Similarly, mean reduction in AUDIT score at 12 months post-baseline was statistically significantly greater among men who received CETA compared to men who received TAU (-4.5, 95% CI -6.9 to -2.2, p < 0.001, Cohen's d effect size = 0.43). The Data and Safety Monitoring Board recommended the trial be stopped early due to treatment effectiveness following the 12-month post-baseline assessment, and CETA was offered to control participants. Limitations of the trial included the lack of a true control condition (i.e., that received no intervention), self-reported outcomes that may be subject to social desirability bias, and low statistical power for secondary IPV outcomes.
Results showed that CETA was more effective than TAU-Plus in reducing IPV and hazardous alcohol use among high-risk couples in Zambia. Future research and programming should include tertiary prevention approaches to IPV, such as CETA, rather than offering only community mobilization and primary prevention.
The trial was registered on ClinicalTrials.gov (NCT02790827).
Shifting consumer preferences towards ‘green’ consumption is promoted by many governments and environmental groups. Rebound effects, which reduce the effectiveness of such actions, are estimated for ...cost-saving ‘green’ consumption choices using Australian data.
Cases examined are: reduced vehicle use, reduced electricity use, changing to smaller passenger vehicles, and utilising fluorescent lighting. It is found that if rebound effects are ignored when evaluating ‘green’ consumption, environmental benefits will be overstated by around 20% for reduced vehicle use, and 7% for reduced electricity use. Rebound effects are higher, and environmental benefits lower, when more efficient vehicles or lighting are utilised rather than simple conservation actions of forgoing use. In addition, lower income households have higher rebound effects, suggesting that environmental policy directed at changing consumer behaviour is most effective when targeted at high income households. An inherent trade-off between economic and environmental benefits of ‘green’ consumption choices is demonstrated.
The size of the rebound effect, and the observed variation with household income, is attributed to Life-Cycle Analysis (LCA) methodologies associated with the calculation of embodied GHG emissions of consumption goods. These results should be therefore be interpreted as the minimum rebound effect to include in policy evaluation.
► Rebound effects are estimated for cost-saving ‘green’ consumption choices. ► Household demand model utilised with LCA embodied GHG emissions data. ► Rebound effects are 4–24% for electricity and motor fuel conservation. ► Rebound effect declines with household income, increases with more cost savings. ► Conservation choices better than replacing household capital.
Inflammatory bowel disease negatively affects the quality of life of millions of patients around the world. Although the precise etiology of the disease remains elusive, aberrant immune system ...activation is an underlying cause. As such, therapies that selectively inhibit immune cell activation without broad immunosuppression are desired. Inhibition of immune cell activation preventing pro‐inflammatory cytokine production through neural stimulation has emerged as one such treatment. These therapeutics are based on the discovery of the cholinergic anti‐inflammatory pathway, a reflex arc that induces efferent vagal nerve signaling to reduce immune cell activation and consequently mortality during septic shock. Despite the success of preclinical and clinical trials, the neural circuitry and mechanisms of action of these immune‐regulatory circuits are controversial. At the heart of this controversy is the protective effect of vagal nerve stimulation despite an apparent lack of neuroanatomical connections between the vagus and target organs. Additional studies have further emphasized the importance of sympathetic innervation of these organs, and that alternative neural circuits could be involved in neural regulation of the immune system. Such controversies also extend to the regulation of intestinal inflammation, with the importance of efferent vagus nerve signals in question. Experiments that better characterize these pathways have now been performed by Willemze et al. in this issue of Neurogastroenterology & Motility. These continued efforts will be critical to the development of better neurostimulator based therapeutics for inflammatory bowel disease.
Several countries restricted the administration of ChAdOx1 to older age groups in 2021 over safety concerns following case reports and observed versus expected analyses suggesting a possible ...association with cerebral venous sinus thrombosis (CVST). Large datasets are required to precisely estimate the association between Coronavirus Disease 2019 (COVID-19) vaccination and CVST due to the extreme rarity of this event. We aimed to accomplish this by combining national data from England, Scotland, and Wales.
We created data platforms consisting of linked primary care, secondary care, mortality, and virological testing data in each of England, Scotland, and Wales, with a combined cohort of 11,637,157 people and 6,808,293 person years of follow-up. The cohort start date was December 8, 2020, and the end date was June 30, 2021. The outcome measure we examined was incident CVST events recorded in either primary or secondary care records. We carried out a self-controlled case series (SCCS) analysis of this outcome following first dose vaccination with ChAdOx1 and BNT162b2. The observation period consisted of an initial 90-day reference period, followed by a 2-week prerisk period directly prior to vaccination, and a 4-week risk period following vaccination. Counts of CVST cases from each country were tallied, then expanded into a full dataset with 1 row for each individual and observation time period. There was a combined total of 201 incident CVST events in the cohorts (29.5 per million person years). There were 81 CVST events in the observation period among those who a received first dose of ChAdOx1 (approximately 16.34 per million doses) and 40 for those who received a first dose of BNT162b2 (approximately 12.60 per million doses). We fitted conditional Poisson models to estimate incidence rate ratios (IRRs). Vaccination with ChAdOx1 was associated with an elevated risk of incident CVST events in the 28 days following vaccination, IRR = 1.93 (95% confidence interval (CI) 1.20 to 3.11). We did not find an association between BNT162b2 and CVST in the 28 days following vaccination, IRR = 0.78 (95% CI 0.34 to 1.77). Our study had some limitations. The SCCS study design implicitly controls for variables that are constant over the observation period, but also assumes that outcome events are independent of exposure. This assumption may not be satisfied in the case of CVST, firstly because it is a serious adverse event, and secondly because the vaccination programme in the United Kingdom prioritised the clinically extremely vulnerable and those with underlying health conditions, which may have caused a selection effect for individuals more prone to CVST. Although we pooled data from several large datasets, there was still a low number of events, which may have caused imprecision in our estimates.
In this study, we observed a small elevated risk of CVST events following vaccination with ChAdOx1, but not BNT162b2. Our analysis pooled information from large datasets from England, Scotland, and Wales. This evidence may be useful in risk-benefit analyses of vaccine policies and in providing quantification of risks associated with vaccination to the general public.
As a result of their unique compositions and properties, nanomaterials have recently seen a tremendous increase in use for novel cancer therapies. By taking advantage of the optical absorption of ...near-infrared light, researchers have utilized nanostructures such as carbon nanotubes, gold nanorods, and graphene oxide sheets to enhance photothermal therapies and target the effect on the tumor tissue. However, new uses for nanomaterials in targeted cancer therapy are coming to light, and the efficacy of photothermal therapy has increased dramatically. In this work, we review some of the current applications of nanomaterials to enhance photothermal therapy, specifically as photothermal absorbers, drug delivery vehicles, photoimmunological agents, and theranostic tools.
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