Do social support and community engagement act as mechanisms in the association between neighbourhood income inequality and the mental health of mothers in Calgary, Canada? A mediation analysis.

PURPOSE: According to the social determinants of health framework, income inequality is a potential risk factor for adverse mental health. However, few studies have explored the mechanisms suspected to mediate this relationship. The current study addresses this gap through a mediation analysis to determine if social support and community engagement act as mediators linking neighbourhood income inequality to maternal anxiety and depressive symptoms within a cohort of new mothers living in the City of Calgary, Canada. METHODS: Data collected at three years postpartum from mothers belonging to the All Our Families (AOF) cohort were used in the current study. Maternal data were collected between 2012 and 2015 and linked to neighbourhood socioeconomic data from the 2006 Canadian Census. Income inequality was measured using Gini coefficients derived from 2006 after-tax census data. Generalized structural equation models were used to quantify the associations between income inequality and mental health symptoms, and to assess the potential direct and indirect mediating effects of maternal social support and community engagement. RESULTS: Income inequality was not significantly associated with higher depressive symptoms (ß = 0.32, 95%CI = -0.067, 0.70), anxiety symptoms (ß = 0.11, 95%CI = -0.39, 0.60), or lower social support. Income inequality was not associated with community engagement. For the depression models, higher social support was significantly associated with lower depressive symptoms (ß = -0.13, 95%CI = -0.15, -0.097), while community engagement was not significantly associated with depressive symptoms (ß = 0.059, 95%CI = -0.15, 0.27). Similarly, for the anxiety models, lower anxiety symptoms were significantly associated with higher levels of social support (ß = -0.17, 95%CI = -0.20, -0.13) but not with higher levels of community engagement (ß = 0.14, 95%CI = -0.14, 0.41). CONCLUSION: The current study did not find clear evidence for social support or community engagement mediating the relationship between neighbourhood income inequality and maternal mental health. Future investigations should employ a broader longitudinal approach to capture changes in income inequality, potential mediators, and mental health symptomatology over time.

Preparedness, Hurricanes Irma and Maria, and Impact on Health in Puerto Rico.

OBJECTIVES: Only few studies evaluated whether hurricane preparedness impacts health. The PREPARE study addresses this gap. METHODS: We recruited participants who had pertinent pre-hurricane data from the San Juan Overweight Adults Longitudinal Study (SOALS: n=364) and 125 patients with diabetes from Federally Qualified Health Center (COSSMA) in Puerto Rico. Participants aged 42-75 years completed interviews 20-34 months after Hurricanes Irma and Maria. We evaluated associations between self-reported hurricane preparedness and health and other related associations using logistic regression controlling for age, location, education and interview date. RESULTS: Only 41% of participants reported high pre-hurricane preparedness; 25% reported gaps (moderate/low availability) in information and 48% reported gaps in resources for hurricane preparedness. Participants reporting lower pre-hurricane preparedness had higher reported hurricane-related detrimental health impact (OR=1.96; 95% CI: 1.31, 2.95) and higher odds (OR=2.07; 95% CI: 0.92, 4.68) of developing new non-communicable disease (NCD) compared to others. Post-hurricane drinking water disruption for ≥ 3 months versus none or less (OR=2.76; 95% CI: 1.39, 5.47) and similarly diet changes due to cooking/refrigeration access (OR=1.96; 95% CI: 1.24, 3.07), and diet changes for ≥ 20 months due to finances/access to shops (OR=2.83; 95% CI: 1.85, 4.32) were also associated with detrimental health impact. CONCLUSION: Lower preparedness was associated with higher detrimental impact of the hurricanes on overall health, and marginally significant impact on NCD. Future preparedness efforts could especially target means of coping with disruption of water services and regular diet, as these were also associated with detrimental health impact.

Donanemab (LY3002813) Phase 1b Study in Alzheimer's Disease: Rapid and Sustained Reduction of Brain Amyloid Measured by Florbetapir F18 Imaging.

BACKGROUND: Donanemab (LY3002813) is an IgG1 antibody directed at an N­terminal pyroglutamate of amyloid beta epitope that is present only in brain amyloid plaques. OBJECTIVES: To assess effects of donanemab on brain amyloid plaque load after single and multiple intravenous doses, as well as pharmacokinetics, safety/tolerability, and immunogenicity. DESIGN: Phase 1b, investigator- and patient-blind, randomized, placebo-controlled study. SETTING: Patients recruited at clinical research sites in the United States and Japan. PARTICIPANTS: 61 amyloid plaque-positive patients with mild cognitive impairment due to Alzheimer's disease and mild-to-moderate Alzheimer's disease dementia. INTERVENTION: Six cohorts were dosed with donanemab: single dose 10-, 20- or 40- mg/kg (N = 18), multiple doses of 10-mg/kg every 2 weeks for 24 weeks (N = 10), and 10- or 20-mg/kg every 4 weeks for 72 weeks (N=18) or placebo (N = 15). MEASUREMENTS: Brain amyloid plaque load, using florbetapir positron emission tomography, was assessed up to 72 weeks. Safety was evaluated by occurrence of adverse events, magnetic resonance imaging, electrocardiogram, vital signs, laboratory testing, neurological monitoring, and immunogenicity. RESULTS: Treatment with donanemab resulted in rapid reduction of amyloid, even after a single dose. By 24 weeks, amyloid positron emission tomography mean changes from baseline for single donanemab doses in Centiloids were: -16.5 (standard error 11.22) 10-mg/kg intravenous; 40.0 (standard error 11.23) 20 mg/kg intravenous; and -49.6 (standard error 15.10) 40-mg/kg intravenous. Mean reduction of amyloid plaque in multiple dose cohorts by 24 weeks in Centiloids were: 55.8 (standard error 9.51) 10-mg/kg every 2 weeks; -50.2 (standard error 10.54) 10-mg/kg every 4 weeks; and -58.4 (standard error 9.66) 20-mg/kg every 4 weeks. Amyloid on average remained below baseline levels up to 72 weeks after a single dose of donanemab. Repeated dosing resulted in continued florbetapir positron emission tomography reductions over time compared to single dosing with 6 out of 28 patients attaining complete amyloid clearance within 24 weeks. Within these, 5 out of 10 patients in the 20 mg/kg every 4 weeks cohort attained complete amyloid clearance within 36 weeks. When dosing with donanemab was stopped after 24 weeks of repeat dosing in the 10 mg every 2 weeks cohort, florbetapir positron emission tomography reductions were sustained up to 72 weeks. For the single dose cohorts on day 1, dose proportional increases in donanemab pharmacokinetics were observed from 10 to 40 mg/kg. Dose proportional increases in pharmacokinetics were also observed at steady state with the multiple dose cohorts. Donanemab clearance was comparable across the dose levels. Mean donanemab elimination-half-life following 20 mg/kg single dose was 9.3 days with range of 5.6 to 16.2 days. Greater than 90% of patients had positive treatment-emergent antidrug antibodies with donanemab. However, overall, the treatment-emergent antidrug antibodies did not have a significant impact on pharmacokinetics. Donanemab was generally well tolerated. Amongst the 46 participants treated with donanemab, the following amyloid-related imaging abnormalities, common to the drug class, were observed: 12 vasogenic cerebral edema events (12 [19.7%] patients), 10 cerebral microhemorrhage events (6 [13.0%] patients), and 2 superficial siderosis events (2 [4.3%] patients). CONCLUSIONS: Single and multiple doses of donanemab demonstrated a rapid, robust, and sustained reduction up to 72 weeks in brain amyloid plaque despite treatment-emergent antidrug antibodies detected in most patients. Amyloid-related imaging abnormalities were the most common treatment-emergent event.

Convergent evolution of pain-inducing defensive venom components in spitting cobras.

Convergent evolution provides insights into the selective drivers underlying evolutionary change. Snake venoms, with a direct genetic basis and clearly defined functional phenotype, provide a model system for exploring the repeated evolution of adaptations. While snakes use venom primarily for predation, and venom composition often reflects diet specificity, three lineages of cobras have independently evolved the ability to spit venom at adversaries. Using gene, protein, and functional analyses, we show that the three spitting lineages possess venoms characterized by an up-regulation of phospholipase A2 (PLA2) toxins, which potentiate the action of preexisting venom cytotoxins to activate mammalian sensory neurons and cause enhanced pain. These repeated independent changes provide a fascinating example of convergent evolution across multiple phenotypic levels driven by selection for defense.

How effective are population health surveys for estimating prevalence of chronic conditions compared to anonymised clinical data?

INTRODUCTION: Population health surveys are used to record person-reported outcome measures for chronic health conditions and provide a useful source of data when evaluating potential disease burdens. The reliability of survey-based prevalence estimates for chronic diseases is unclear nonetheless. This study applied methodological triangulation via a data linkage method to validate prevalence of selected chronic conditions (angina, myocardial infarction, heart failure, and asthma). METHODS: Linked healthcare records were used for a combined cohort of 11,323 adults from the 2013 and 2014 sweeps of the Welsh Health Survey (WHS). The approach utilised consented survey data linked to primary and secondary care electronic health record (EHR) data back to 2002 within the Secure Anonymised Information Linkage (SAIL) Databank. RESULTS: This descriptive study demonstrates validation of survey and clinical data using data linkage for selected chronic cardiovascular conditions and asthma with varied success. The results indicate that identifying cases for separate cardiovascular conditions was limited without specific medication codes for each condition, but more straightforward for asthma, where there was an extensive list of medications available. For asthma there was better agreement between prevalence estimates based on survey and clinical data as a result. CONCLUSION: Whilst the results provide external validity for the WHS as an instrument for estimating the burden of chronic disease, they also indicate that a data linkage appproach can be used to produce comparable prevalence estimates using clinical data if a defined condition-specific set of clinical codes are available.

Key drivers of cloud response to surface-active organics.

Aerosol-cloud interactions constitute the largest source of uncertainty in global radiative forcing estimates, hampering our understanding of climate evolution. Recent empirical evidence suggests surface tension depression by organic aerosol to significantly influence the formation of cloud droplets, and hence cloud optical properties. In climate models, however, surface tension of water is generally assumed when predicting cloud droplet concentrations. Here we show that the sensitivity of cloud microphysics, optical properties and shortwave radiative effects to the surface phase are dictated by an interplay between the aerosol particle size distribution, composition, water availability and atmospheric dynamics. We demonstrate that accounting for the surface phase becomes essential in clean environments in which ultrafine particle sources are present. Through detailed sensitivity analysis, quantitative constraints on the key drivers - aerosol particle number concentrations, organic fraction and fixed updraft velocity - are derived for instances of significant cloud microphysical susceptibilities to the surface phase.

The Revelatory Journey of Fine-tuning the Diagnosis of an Adult Male on the Autistic Spectrum - Asperger Syndrome/High-functioning Autism with Corollary Diagnoses / Viaje revelador al configurar el diagnóstico de un varón adulto en sintonía con el espectro autista - síndrome de Asperger/autismo de alto funcionamiento con diagnósticos corolarios

ABSTRACT This article provides an account of the revelatory experience of diagnosing a high-functioning, autistic, adult male by a non-specialist medical practitioner and its implications for knowledge, attitudes and practice in dealing with the autistic spectrum.

RESUMEN Este artículo ofrece un reporte de la experiencia reveladora del diagnóstico de un varón adulto autista de alto funcionamiento por un médico no especializado y sus implicaciones para el conocimiento, las actitudes y la práctica al tratar con el espectro autista.

Pathways from assaultive violence to post-traumatic stress, depression, and generalized anxiety symptoms through stressful life events: longitudinal mediation models.

BACKGROUND: Assaultive violence events are associated with increased risk for adverse psychiatric outcomes, including post-traumatic stress (PTS), depression, and generalized anxiety. Prior research has indicated that economic, legal, and social stressors that could follow assaultive events may explain the increased risk for adverse psychiatric outcomes, yet longitudinal studies have not adequately examined this pathway. In the current study, we aimed to address this limitation. METHODS: Participants (N = 1360) were part of a longitudinal population-based study of adults living in Detroit. At three waves, participants indicated their exposure to assaultive violence and economic, legal, and social stressors, and completed inventories of PTS, depression, and generalized anxiety. Longitudinal mediation models were used to test the hypothesized pathway from assaultive violence to each psychiatric outcome. RESULTS: The hypothesized models evidenced good fit with the data and, in each, the paths from Wave 1 (W1) assaultive violence to W2 stressors, and from W2 stressors to W3 symptoms were significant (range of Standardized Estimates: 0.09-0.15, all p < 0.01). Additionally, the indirect paths from W1 assaultive violence to W3 symptoms were significant (range of Standardized Estimates: 0.01-0.02, all p < 0.05). CONCLUSIONS: The findings illustrate that the economic, legal, and social stressors that could follow assaultive violence increase risk for a range of psychiatric symptoms. Although future research is needed, the results suggest that investment in interventions that prevent and mitigate assaultive violence survivors' exposure to such stressors may be an effective way to prevent mental illness in the aftermath of violent assaults.

Twin pregnancies complicated by gestational diabetes mellitus: a single centre cohort study.

AIMS: In women with a twin pregnancy, to determine the incidence of, risk factors for and outcomes of women with gestational diabetes mellitus, and assess how these have changed with a change in gestational diabetes screening. METHODS: Retrospective cohort study of women with a twin pregnancy attending an Australian tertiary hospital, 2002-2013. Information on gestational diabetes status, gestational diabetes risk factors and pregnancy outcomes was ascertained. Pregnancy outcomes included hypertensive disorders, twin birthweight centile and a composite adverse pregnancy outcome. Analysis was stratified pre/post screening protocol change (epoch 1: 2002-2009, epoch 2: 2010-2013) and by gestational diabetes status. RESULTS: Gestational diabetes was diagnosed in 86/982 (8.8%) women, increasing from 4.4% to 14.7% between epochs (P = 0.0001). The proportion of women with hypertensive disorders increased (11.7% vs. 13.4%, P = 0.009), but the proportion of infant's birthweight > 90th centile decreased (11.0% vs. 7.6%, P = 0.02) between epochs. Overall, 33.6% of women had ≥ 1 risk factors for gestational diabetes. Three-quarters (73.7%) of women overall had an adverse pregnancy outcome, with a slightly higher proportion in women with gestational diabetes compared with those with no gestational diabetes (79.7% vs. 73.1%, P = 0.06). The rate of the adverse pregnancy outcome did not change by epoch, after adjusting for maternal and pregnancy risk factors (adjusted odds ratio = 0.96, 95% confidence interval 0.73-1.26). CONCLUSIONS: Almost 1 in 10 women with a twin pregnancy were diagnosed with gestational diabetes, with the incidence of gestational diabetes increasing threefold with a new screening protocol. The pregnancy outcomes of women with a twin pregnancy did not change with increased detection and treatment for gestational diabetes.

Cutaneous pseudovasculitis, antiphospholipid syndrome and obstetric misadventure.

We present two women with severe obstetric complications from antiphospholipid (aPL) syndrome associated with a rare dermatological manifestation, cutaneous pseudovasculitis. Both of these women developed a rash on the palmar aspect of the hands during the post partum period, with histology consistent with microthrombotic disease, despite anticoagulation. Cutaneous pseudovasculitis appears to be a maternal manifestation of aPL coagulopathy, possibly reflecting the severity of the underlying pregnancy pathology.

Report on Hyperbaric Oxygen Therapy: An Overlooked Therapeutic Option in Stroke Recovery and a Potential Source of Health Sector Revenue and Health Tourism.

This is a special case report on Jamaica's first use of hyperbaric oxygen therapy (HBOT) in stroke recovery, presented at the 56th Annual Conference of the Association of Surgeons in Jamaica, Kingston, Jamaica. The literature and story behind the trial ‒ covering case history, diagnosis and discussion of outcome ‒ technical issues, costing, insurance and possibilities for income earning and health tourism are explored.

A common functional consequence of tumor-derived mutations within c-MYC.

The relevance of changes to the coding sequence of the c-MYC oncogene to malignancy is controversial. Overexpression of a pristine form of MYC is observed in many cancers and is sufficient to drive tumorigenesis in most contexts. Yet missense changes to MYC are found in ~50% of Burkitt's lymphomas, aggregate within an amino-terminal degron important for proteasomal destruction of MYC, and where examined profoundly enhance the tumorigenic properties of MYC in vitro and in vivo. Much of the controversy surrounding these mutants stems from the limited number of mutations that have been evaluated and their clustering within a single region of the MYC protein; the highly-conserved Myc box I (MbI) element. Here, by analysis of extant genomic data sets, we identify a previously unrecognized hotspot for tumor-associated MYC mutations, located in a conserved central portion of the protein. We show that, despite their distal location in MYC, mutations in this region precisely phenocopy those in MbI in terms of stability, in vitro transformation, growth-promoting properties, in vivo tumorigenesis and ability to escape p53-dependent tumor surveillance mechanisms. The striking parallels between the behavior of tumor-derived mutations in disparate regions of the MYC protein reveals that a common molecular process is disrupted by these mutations, implying an active role for these mutations in tumorigenesis and suggesting that different therapeutic strategies may be needed for treatment of lymphomas expressing wild type versus mutant forms of MYC protein.

The Polycomb complex PRC2 supports aberrant self-renewal in a mouse model of MLL-AF9;Nras(G12D) acute myeloid leukemia.

The Trithorax and Polycomb groups of chromatin regulators are critical for cell-lineage specification during normal development; functions that often become deregulated during tumorigenesis. As an example, oncogenic fusions of the Trithorax-related protein mixed lineage leukemia (MLL) can initiate aggressive leukemias by altering the transcriptional circuitry governing hematopoietic cell differentiation, a process that requires multiple epigenetic pathways to implement. Here we used shRNA screening to identify chromatin regulators uniquely required in a mouse model of MLL-fusion acute myeloid leukemia, which revealed a role for the Polycomb repressive complex 2 (PRC2) in maintenance of this disease. shRNA-mediated suppression of PRC2 subunits Eed, Suz12 or Ezh1/Ezh2 led to proliferation arrest and differentiation of leukemia cells, with a minimal impact on growth of several non-transformed hematopoietic cell lines. The requirement for PRC2 in leukemia is partly because of its role in direct transcriptional repression of genes that limit the self-renewal potential of hematopoietic cells, including Cdkn2a. In addition to implicating a role for PRC2 in the pathogenesis of MLL-fusion leukemia, our results suggest, more generally, that Trithorax and Polycomb group proteins can cooperate with one another to maintain aberrant lineage programs in cancer.

Granule exocytosis mediates immune surveillance of senescent cells.

Senescence is a stable cell cycle arrest program that contributes to tumor suppression, organismal aging and certain wound healing responses. During liver fibrosis, for example, hepatic stellate cells initially proliferate and secrete extracellular matrix components that produce fibrosis; however, these cells eventually senesce and are cleared by immune cells, including natural killer (NK) cells. Here, we examine how NK cells target senescent cells and assess the impact of this process on liver fibrosis. We show that granule exocytosis, but not death-receptor-mediated apoptosis, is required for NK-cell-mediated killing of senescent cells. This pathway bias is due to upregulation of the decoy death receptor, Dcr2, an established senescence marker that attenuates NK-mediated cell death. Accordingly, mice with defects in granule exocytosis accumulate senescent stellate cells and display more liver fibrosis in response to a fibrogenic agent. Our results thus provide new insights into the immune surveillance of senescent cells and reveal how granule exocytosis has a protective role against liver fibrosis.

Report and viewpoint on the Vaccine Safety Conference, Tryall Club, Jamaica, January 3-7, 2011: cautionary tales and implications for the Caribbean.

This paper represents information obtained from a recent conference on vaccination safety and policy: Vaccine Safety: Evaluating the Science Conference, Tryall Club, Jamaica, January 3-7, 2011 and the author's viewpoint on the same. The first section represents a synopsis of recorded information and the second the author's view of Caribbean concerns related to the recorded information.

[Diabetic, neuropathic, arteriopathic foot and dressing choice]. / Pied a risque et choix de pansements.

The definition for the diabetic foot is infection, ulceration or destruction of deep tissues of the foot associated with neuropathy or peripheral vascular disease in the lower extremity of people with diabetes. Non-diabetic patients may suffer the same risks when neuropathy and arteriopathy are present. Knowing that 85% of amputations are preceded by foot ulcers, prevention is primordial. At the onset of an ulcer, immediate treatment must be undertaken and preferably by an interdisciplinary team. Delayed healing and increased risk of infection are often due to an associated vascular disease. While the array of dressings is expansive there is no «gold standard¼ treatment or «miracle dressing¼ described for foot ulcers. The management consists of wound analysis, debridement, woundcare and especially offloading.

Report and viewpoint on the Vaccine Safety Conference, Tryall Club, Jamaica, january 3-7, 2011: cautionary tales and implications for the caribbean / Reporte y puntos de vista sobre la Conferencia de Seguridad de las Vacunas Celebrada en Tryall Club, Jamaica, enero 3-7, 2011: narrativas aleccionadoras e implicaciones para el caribe

This paper represents information obtained from a recent conference on vaccination safety and policy: Vaccine Safety: Evaluating the Science Conference, Tryall Club, Jamaica, January 3-7, 2011 and the author s viewpoint on the same. The first section represents a synopsis of recorded information and the second the author's view of Caribbean concerns related to the recorded information.

El presente trabajo representa información obtenida de una reciente conferencia sobre seguridad y políticas de vacunación: evaluación de la Conferencia Científica en Tryall Club, Jamaica, del 3 al 7 de enero de 2011, y puntod de vista del autor sobre la misma. La primera sección ofrece una sinopsis de la información obtenida, y la segunda ofrece el punto de vista del autor sobre problemas del Caribe en relación con la información obtenida.

Acquired epidermodysplasia verruciformis due to multiple and unusual HPV infection among vertically-infected, HIV-positive adolescents in Zimbabwe.

BACKGROUND: We have previously described the presentation of epidermodysplasia verruciformis (EV)-like eruptions in almost a quarter of hospitalized adolescents with vertically-acquired human immunodeficiency virus (HIV) infection in Harare, Zimbabwe, a region with a high prevalence of HIV infection. METHODS: We performed a clinical case note review and skin biopsy from affected sites in 4 HIV-infected adolescents with EV-like lesions in Harare. Biopsies were processed for histology and for human papillomavirus (HPV) typing. RESULTS: All patients had long-standing skin lesions that pre-dated the diagnosis of HIV by several years. The histology of skin biopsies from all patients was consistent with EV. In each biopsy, EV-associated ß-HPV type 5 was identified (additionally, type 19 was found in 1 biopsy). Cutaneous wart-associated HPV types 1 and 2 were detected in all biopsies, together with genital lesion-associated HPV types 6, 16, and 52, (as well as ≥3 other genital lesion-associated HPV types). Despite immune reconstitution with combination antiretroviral therapy (cART), there was no improvement in EV-like lesions in any patient. CONCLUSIONS: EV is a disfiguring and potentially stigmatizing condition among this patient group and is difficult to treat; cART appears to have no impact on the progression of skin disease. Among adolescents with longstanding HIV-induced immunosuppression and with high levels of sun exposure, close dermatological surveillance for potential skin malignancy is required.

Improving the performance of power plant cooling ponds.

A study was conducted on the effectiveness of using vertical baffles to improve the thermal performance of power plant cooling ponds. A small scale physical model of a rectangular cooling pond was used. A base case was established using traditional horizontal baffles to create a serpentine flow pattern through the pond. The horizontal baffles were then replaced by a series of underflow weirs that spanned the pond. An improvement in cooling of over 30% was realized.