To analyze the geographic inequalities in life expectancy (LE) and the probability of survival up to 40 and 60 years in Brazil between 1991 and 2010, to partition the variance of these indicators by ...including municipalities, states, and macroregions in the analysis, and to test the association between municipal socio-economic and health services indicators with life expectancy.
Multilevel analysis.
Census data from 1991, 2000, and 2010 were used to calculate the outcomes and the socio-economic variables. Municipalities were separated into centiles according to their values in each outcome. Absolute and relative differences were calculated for each year. Multilevel linear regression models were performed, taking into account three levels: regions, states, and municipalities. Municipal socio-economic and health services variables were included in the model with the 2010 data.
All 5545 Brazilian counties showed improvement in the three indicators, but the magnitude varied significantly across the country. The highest gains in LE were observed in the North and Northeast regions. The gap in LE between the 1st and 99th percentile decreased from 19.6 years to 12.2 years. The relative difference also fell, from 1.37 to 1.18. Most counties’ socio-economic and health services indicators were associated with the outcomes and explained 86.7%, 31.2%, and 32.4% of the variation in LE attributable to regions, states, and counties, respectively.
The average life expectancy increased between 1991 and 2010. Concomitantly, a reduction in geographic disparities was observed. The counties’ socio-economic and health services variables explained much of the variation of the outcomes in 2010.
•All Brazilian municipalities showed an increase in life expectancy between 1990 and 2010.•There was a remarkable reduction in geographic inequality in the country.•Counties and regions accounted for the major part of the total variability of life expectancy.•County’s variables explained an expressive proportion of the life expectancy variation.
Species inhabit complex environments and respond to selection imposed by numerous abiotic and biotic conditions that vary in both space and time. Environmental heterogeneity strongly influences trait ...evolution and patterns of adaptive population differentiation. For example, heterogeneity can favor local adaptation, or can promote the evolution of plastic genotypes that alter their phenotypes based on the conditions they encounter. Different abiotic and biotic agents of selection can act synergistically to either accelerate or constrain trait evolution. The environmental context has profound effects on quantitative genetic parameters. For instance, heritabilities measured in controlled conditions often exceed those measured in the field; thus, laboratory experiments could overestimate the potential for a population to respond to selection. Nevertheless, most studies of the genetic basis of ecologically relevant traits are conducted in simplified laboratory environments, which do not reflect the complexity of nature. Here, we advocate for manipulative field experiments in the native ranges of plant species that differ in mating system, life-history strategy and growth form. Field studies are vital to evaluate the roles of disparate agents of selection, to elucidate the targets of selection and to develop a nuanced perspective on the evolution of quantitative traits. Quantitative genetics field studies will also shed light on the potential for natural populations to adapt to novel climates in highly fragmented landscapes. Drawing from our experience with the ecological model system Boechera (Brassicaceae), we discuss advancements possible through dedicated field studies, highlight future research directions and examine the challenges associated with field studies.
Aedes (Hulecoeteomyia) japonicus japonicus (Diptera: Culicidae) (Theobald) is an invasive mosquito species in Central Europe, where it has colonized several areas. In this study, field‐collected ...specimens of Ae. japonicus and Culex pipiens (Diptera: Culicidae) (Linnaeus) from Zürich (Switzerland) were orally exposed to two strains (NY99 and FIN) of the avian zoonotic pathogen West Nile virus (WNV) (family Flaviviridae, genus Flavivirus). Dissemination and transmission of the viruses after incubation for 12–15 days under a fluctuating Central European midsummer temperature regime (24 ± 7 °C) was investigated by detection of viral RNA in homogenates of pools of both head/thorax and saliva by reverse transcription real‐time polymerase chain reaction (PCR). Culex pipiens was susceptible to WNV NY99 only, whereas both virus strains could be detected in Ae. japonicus, with the additional isolation of WNV NY99 in Vero cell culture from one saliva pool. Given the high abundances of Ae. japonicus in many newly colonized areas, its recently demonstrated broad host range, including mammalian and avian blood hosts, and its vector competence, this species is a potential key bridge vector of WNV in Central Europe.
The invasive mosquito Aedes (Hulecoeteomyia) japonicus japonicus from northeastern Switzerland showed high susceptibility to West Nile viruses (NY99 and FIN) after oral exposure and incubation under a fluctuating realistic midsummer temperature regime.
Infectious virus particles of the WNV NY99 strain were isolated from saliva of Ae. japonicus.
The autochthonous species of Culex pipiens was susceptible to WNV NY99 but not to the WNV FIN strain.
Social needs interventions in medical settings aim to mitigate the effects of adverse social circumstances on health outcomes by connecting vulnerable patients with resources. This study examined the ...relationship between intervention dosage and the success of resource connections using data from a social needs intervention in multiple clinical settings across the US.
The intervention uses a case management approach to connect patients with unmet needs to resources and services in the community. Intervention dosage was conceptualized as the number of contacts between the navigator and the patient, categorized as direct contact (phone vs. in person) and indirect contact (initiated by the navigator vs. patient). Success of the intervention was conceptualized as ‘none,’ ‘partial,’ or ‘optimal’ for each patient, based on the number of social needs the resource connections addressed.
Administrative data were extracted for 38,404 unique patients who screened positive for unmet resource needs between 2012 and 2017. Owing to the large sample size, statistical corrections were made to reduce type I error.
Multinomial logistic regression analyses showed that higher intervention dosage was related to greater success of resource connections, after adjusting for the patient and site characteristics, and the number of needs (odds ratios ranged from 1.62 to 2.89). In-person contact, although received by only 25% of the patients, was associated with the highest probability of optimal success.
This study demonstrates a feasible way to conceptualize an intervention dose for a social needs intervention that uses a case management approach and has implications for how intervention delivery may improve success of resource connections.
•There is a dose-response relationship between amount of intervention and resource connection outcomes, after controlling for patient sociodemographic and contextual characteristics.•Higher dose of intervention over the phone leads to a few successful outcomes and a higher dose in person leads to optimal success outcomes.•Patient sociodemographics did not relate consistently or strongly to intervention dosage.•Patients originating as walk-ups when they had signed up for the intervention received a higher dosage of in-person intervention compared with those who arrived at the site indirectly.
Abstract
Medical societies have a social responsibility to disseminate knowledge and inform health authorities on threats to public health posed by various diseases. Advocacy for health protection ...programmes and for medical research funding is now embedded into the missions of most scientific societies. To promote kidney research funding in Europe, the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA), rather than acting as an individual society advocating for the fight against kidney disease, has actively helped to create an alliance of national associations centred on kidney diseases, the European Kidney Health Alliance (EKHA), and joined the Biomedical Alliance (BMA). The ERA-EDTA is fully committed to supporting its working groups (WGs) and consortia of its members to allow them to produce valuable kidney research. The framing and formalization of projects, and the regulatory issues related to submission to the European Commission, are complex. To help WGs to gain expert advice from agencies with specific know-how, the ERA-EDTA has adopted a competitive approach. The best research projects proposed by WGs and consortia of other European investigators will receive seed funding to cover the costs of consultancy by expert agencies. Via its broader platforms, the EKHA and the BMA, the ERA-EDTA will strive towards broader recognition of kidney disease and related clusters of non-communicable diseases, by European and national agencies, as major threats to the qualities of life of their populations and their economies.
Melanoma is a heterogeneous tumor with different subpopulations showing different proliferation rates. Slow-cycling cells were previously identified in melanoma, but not fully biologically ...characterized. Using the label-retention method, we identified a subpopulation of slow-cycling cells, defined as label-retaining cells (LRC), with strong invasive properties. We demonstrate through live imaging that LRC are leaving the primary tumor mass at a very early stage and disseminate to peripheral organs. Through global proteome analyses, we identified the secreted protein SerpinE2/protease nexin-1 as causative for the highly invasive potential of LRC in melanomas.
Abstract Background and aims We have previously shown that the anti-inflammatory and anti-oxidant functions of HDL are impaired in T2D patients. In this study, we examined whether HDL from T2D ...patients contains elevated levels of oxidized fatty acids and whether those levels correlate with cardiovascular disease (CVD). Methods and results HETEs and HODEs on HDL were determined by LC-MS/MS in 40 non-diabetic controls (ND), 40 T2D without CVD (D+ CVD− ) and 38 T2D with known history of CVD (D+ CVD+ ). HDL oxidant index was evaluated by a cell-free assay using dichlorofluorescein. Twenty-six randomly selected subjects from the three groups underwent coronary calcium score evaluation (CAC). Major cardiovascular risk factors were similar among the groups. HETEs and HODEs content were significantly increased in HDL from D+ CVD+ when compared to D+ CVD− and ND patients. HDL oxidant index was not different among the three groups; however, it was significantly higher in patients with CAC score >100 when compared to patients with CAC score <100. Conclusion Patients with D+ CVD− and D+ CVD+ are characterized by a severe, graded enrichment of oxidized fatty acids on HDL. In the present study, a loss of HDL function (as estimated by the HDL oxidant index) is observed only in patients with more advanced atherosclerosis.
Summary
Grass cell walls have hydroxycinnamic acids attached to arabinosyl residues of arabinoxylan (AX), and certain BAHD acyltransferases are involved in their addition. In this study, we ...characterized one of these BAHD genes in the cell wall of the model grass Setaria viridis. RNAi silenced lines of S. viridis (SvBAHD05) presented a decrease of up to 42% of ester‐linked p‐coumarate (pCA) and 50% of pCA‐arabinofuranosyl, across three generations. Biomass from SvBAHD05 silenced plants exhibited up to 32% increase in biomass saccharification after acid pre‐treatment, with no change in total lignin. Molecular dynamics simulations suggested that SvBAHD05 is a p‐coumaroyl coenzyme A transferase (PAT) mainly involved in the addition of pCA to the arabinofuranosyl residues of AX in Setaria. Thus, our results provide evidence of p‐coumaroylation of AX promoted by SvBAHD05 acyltransferase in the cell wall of the model grass S. viridis. Furthermore, SvBAHD05 is a promising biotechnological target to engineer crops for improved biomass digestibility for biofuels, biorefineries and animal feeding.
Significance Statement
A BAHD acyltransferase gene was studied, and it was demonstrated that its suppression causes reduction of ester‐linked p‐coumaric acid in the cell walls of Setaria viridis. RNAi silenced lines had higher biomass digestibility with no alteration in the biomass production. Molecular dynamics simulation reinforced the evidence that SvBAHD05 is mainly responsible for the incorporation of p‐coumaric acid onto arabinoxylan, the main hemicellulose in grass cell walls.
Phospholipase A
2
is the main enzyme in the metabolism of membrane phospholipids. It comprises a family of enzymes divided into iPLA
2
, cPLA
2
and sPLA
2
. Studies have reported increased PLA
2
...activity in psychotic patients, which suggests an accelerated breakdown of membrane phospholipids. In the present study we investigated whether increased PLA
2
activity is also present in individuals at ultra-high risk (UHR) for psychosis. One-hundred fifty adults were included in this study (85 UHR and 65 controls). UHR was assessed using the “structured interview for prodromal syndromes”. PLA
2
activity was determined in platelets by a radio-enzymatic assay. We found in UHR individuals increased activities of iPLA
2
(
p
< 0.001) and cPLA
2
(
p
= 0.012) as compared to controls. No correlations were found between socio-demographic and clinical parameters and PLA
2
activity. Our findings suggest that increased PLA
2
activities may be useful as a biological risk-marker for psychotic disorders.
Tofacitinib is an oral Janus kinase inhibitor. This trial assessed the efficacy and safety of tofacitinib versus placebo in patients with polyarticular course juvenile idiopathic arthritis (JIA).
...This double-blind, withdrawal phase 3 trial enrolled patients with polyarticular course JIA (extended oligoarthritis, rheumatoid factor-positive or rheumatoid factor-negative polyarthritis, or systemic JIA without active systemic features) aged 2 years to younger than 18 years, and was done at 64 centres of the Paediatric Rheumatology International Trials Organisation and Pediatric Rheumatology Collaborative Study Group networks in 14 countries. Patients with psoriatic arthritis or enthesitis-related arthritis were enrolled for exploratory endpoints. During part 1 of the study, patients received oral open-label tofacitinib (weight-based doses; 5 mg twice daily or lower) for 18 weeks. Patients achieving at least JIA/American College of Rheumatology 30 response were randomly assigned (1:1) using an Interactive Response Technology system to continue tofacitinib or switch to placebo in part 2 of the study for 26 weeks. The primary endpoint was JIA flare rate by week 44 in part 2 in patients with polyarticular course JIA; the intention-to-treat principle was applied. Safety was evaluated throughout part 1 and part 2 of the study in all patients who received one dose or more of study medication. This trial is registered with ClinicalTrials.gov, NCT02592434.
Between June 10, 2016, and May 16, 2019, of 225 patients enrolled, 184 (82%) patients had polyarticular course JIA, 20 (9%) had psoriatic arthritis, and 21 (9%) had enthesitis-related arthritis. 147 (65%) of 225 patients received concomitant methotrexate. In part 2, 142 patients with polyarticular course JIA were assigned to tofacitinib (n=72) or placebo (n=70). Flare rate by week 44 was significantly lower with tofacitinib (21 29% of 72 patients) than with placebo (37 53% of 70 patients; hazard ratio 0·46, 95% CI 0·27–0·79; p=0·0031). In part 2 of the study, adverse events occurred in 68 (77%) of 88 patients receiving tofacitinib and 63 (74%) of 85 in the placebo group. Serious adverse events occurred in one (1%) and two (2%), respectively. In the entire tofacitinib exposure period, 107 (48%) of 225 patients had infections or infestations. There were no deaths during this study.
The results of this pivotal trial show that tofacitinib is an effective treatment in patients with polyarticular course JIA. New oral therapies are particularly relevant for children and adolescents, who might prefer to avoid injections.
Pfizer.
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