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• Hybrid seed inviability (HSI) is an important mechanism of reproductive isolation and speciation. HSI varies in strength among populations of diploid species but it remains to be tested whether similar processes affect natural variation in HSI within ploidy-variable species (triploid block). • Here we used extensive endosperm, seed and F₁-hybrid phenotyping to explore HSI variation within a diploid-autotetraploid species. By leveraging 12 population pairs from three ploidy contact zones, we tested for the effect of interploidy crossing direction (parent of origin), ploidy divergence and spatial arrangement in shaping reproductive barriers in a naturally relevant context. • We detected strong parent-of-origin effects on endosperm development, F₁ germination and survival, which was also reflected in the rates of triploid formation in the field. Endosperm cellularization failure was least severe and F₁-hybrid performance was slightly better in the primary contact zone, with genetically closest diploid and tetraploid lineages. • We demonstrated overall strong parent-of-origin effects on HSI in a ploidy variable species, which translate to fitness effects and contribute to interploidy reproductive isolation in a natural context. Subtle intraspecific variation in these traits suggests the fitness consequences of HSI are predominantly a constitutive property of the species regardless of the evolutionary background of its populations.

•Assessed impact of universal seasonal influenza vaccination policy on seasonal influenza vaccine uptake in Manitoba, Canada.•Significantly increased odds of vaccination 5-years post-policy relative to pre-policy among age groups except ≥65-year-olds.•Mostly homogeneous effect estimates within age groups across strata of assessed socioeconomic/health-related characteristics.•Largely consistent findings irrespective of sex and region of residence. In 2010, the government of the province of Manitoba, Canada introduced universal seasonal influenza vaccination policy (USIVP), providing free-of-charge vaccination to all registered residents of the province at least six months of age. Impact of the policy on seasonal influenza vaccine (SIV) uptake (receipt of vaccine) in Manitoba remains unclear, as there is a lack of published evaluations. We conducted an ecological study, utilizing population-wide data from several linked de-identified Manitoba Health and Seniors Care administrative health databases. The study period was from 2000/01–2019/20 influenza seasons. The primary exposure was USIVP (five influenza seasons pre-policy [2005/06–2009/10] compared with post-policy [2010/11–2014/15]). The outcome was SIV uptake. We conducted pre/post logistic regression analysis stratified by age group (<5-, 5–17-, 18–44-, 45–64-, ≥65-year-olds) and certain population socioeconomic and health-related characteristics. Results are adjusted odds ratios with associated 95 % confidence intervals. We observed significantly increased adjusted odds of SIV uptake post-policy relative to pre-policy in all age groups except ≥65-year-olds already covered from inception of the vaccination programme. The adjusted odds ratios ranged from 0.76 (0.75–0.76) among ≥65-year-olds to 2.15 (2.13–2.18) among 5–17-year-olds, and were largely homogeneous within age groups across sex, income quintiles, regions of residence, and categories of number of visits to primary care physician/hospitalization one year prior to an influenza season except among <5- and 5–17-year-olds. These findings were mostly consistent irrespective of sex and region of residence although there was variability across income quintiles in Northern Manitoba region. Introduction of the USIVP in Manitoba was followed by a significant increase in SIV uptake in the five years post policy among <65-year-olds, with similar increased relative odds of vaccination observed within age groups across subpopulations. The observed variations in the relative odds of vaccination across income quintiles in Northern Manitoba region requires administrative attention.

Inactivated influenza vaccine is recommended in any stage of pregnancy, but evidence of safety in early pregnancy is limited, including for vaccines containing A/H1N1pdm2009 (pH1N1) antigen. We sought to determine if receipt of vaccine containing pH1N1 was associated with spontaneous abortion (SAB). We conducted a case-control study over two influenza seasons (2010–11, 2011–12) in the Vaccine Safety Datalink. Cases had SAB and controls had live births or stillbirths and were matched on site, date of last menstrual period, and age. Of 919 potential cases identified using diagnosis codes, 485 were eligible and confirmed by medical record review. Exposure was defined as vaccination with inactivated influenza vaccine before the SAB date; the primary exposure window was the 1–28days before the SAB. The overall adjusted odds ratio (aOR) was 2.0 (95% CI, 1.1–3.6) for vaccine receipt in the 28-day exposure window; there was no association in other exposure windows. In season-specific analyses, the aOR in the 1–28days was 3.7 (95% CI 1.4–9.4) in 2010–11 and 1.4 (95% CI 0.6–3.3) in 2011–12. The association was modified by influenza vaccination in the prior season (post hoc analysis). Among women who received pH1N1-containing vaccine in the previous influenza season, the aOR in the 1–28days was 7.7 (95% CI 2.2–27.3); the aOR was 1.3 (95% CI 0.7–2.7) among women not vaccinated in the previous season. This effect modification was observed in each season. SAB was associated with influenza vaccination in the preceding 28days. The association was significant only among women vaccinated in the previous influenza season with pH1N1-containing vaccine. This study does not and cannot establish a causal relationship between repeated influenza vaccination and SAB, but further research is warranted.

Dietary fiber intake is associated with a lower risk of diabetes, cardiovascular disease, and cancer. However, it is unknown whether dietary fiber has a beneficial effect on preventing the development of chronic kidney disease (CKD). Using the UK Biobank prospective cohort, 110,412 participants who completed at least one dietary questionnaire and had an estimated glomerular filtration rate ≥60 mL/min/1.73 m2, urinary albumin-to-creatinine ratio <30 mg/g, and no history of CKD were included. The primary exposure was total dietary fiber density, calculated by dividing the absolute amount of daily total fiber intake by total energy intake (g/1,000 kcal). We separately examined soluble and insoluble fiber densities as additional predictors. The primary outcome was incident CKD based on diagnosis codes. A total of 3,507 (3.2%) participants developed incident CKD during a median follow-up of 9.9 years. In a multivariable cause-specific model, the adjusted hazard ratios (aHRs; 95% confidence intervals [CIs]) for incident CKD were 0.85 (0.77–0.94), 0.78 (0.70–0.86), and 0.76 (0.68–0.86), respectively, for the second, third, and highest quartiles of dietary fiber density (reference: lowest quartile). In a continuous model, the aHR for each +Δ1.0g/1,000 kcal increase in dietary fiber density was 0.97 (95% CI, 0.95–0.99). This pattern of associations was similar for both soluble and insoluble fiber densities and did not differ across subgroups of sex, age, body mass index, hypertension, diabetes, smoking, and inflammation. Increased fiber intake was associated with a lower risk of CKD in this large well-characterized cohort.

Parkinson disease (PD) is a neurodegenerative disorder particularly characterized by the loss of dopaminergic neurons in the substantia nigra . Pesticide exposure has been associated with PD occurrence, and we previously reported that the fungicide benomyl interferes with several cellular processes potentially relevant to PD pathogenesis. Here we propose that benomyl, via its bioactivated thiocarbamate sulfoxide metabolite, inhibits aldehyde dehydrogenase (ALDH), leading to accumulation of the reactive dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), preferential degeneration of dopaminergic neurons, and development of PD. This hypothesis is supported by multiple lines of evidence. (i) We previously showed in mice the metabolism of benomyl to S -methyl N -butylthiocarbamate sulfoxide, which inhibits ALDH at nanomolar levels. We report here that benomyl exposure in primary mesencephalic neurons (ii) inhibits ALDH and (iii) alters dopamine homeostasis. It induces selective dopaminergic neuronal damage (iv) in vitro in primary mesencephalic cultures and (v) in vivo in a zebrafish system. (vi) In vitro cell loss was attenuated by reducing DOPAL formation. (vii) In our epidemiology study, higher exposure to benomyl was associated with increased PD risk. This ALDH model for PD etiology may help explain the selective vulnerability of dopaminergic neurons in PD and provide a potential mechanism through which environmental toxicants contribute to PD pathogenesis.

Anticoagulant rodenticides (ARs) are used worldwide for the control of rodent pests and are the main method of control of rat pest populations in agricultural areas. The main aim of this review is to discuss the risk of ARs to non-target wildlife in oil palm areas in Southeast Asia, mainly Indonesia and Malaysia. We discussed AR use in oil palm areas and toxicities of ARs on target and non-target animals. We also reviewed published literature on wildlife species reported in oil palm areas in Southeast Asia and utilizing this information, we assessed the hazard risk of ARs to non-target wildlife in oil palm plantations. ARs are a secondary exposure hazard to rodent-consuming mammalian carnivores, such as leopard cats and civets, and rodent-consuming raptors, such as barn owls. Consumption of dead poisoned prey puts scavengers, such as water monitors, at high risk for AR exposure. Domestic livestock and granivorous birds are at high risk for AR exposure via primary exposure to toxic bait, while omnivores such as macaques and wild pigs are at moderate risk for both primary and secondary exposure to ARs. The effects of ARs on barn owls have been well studied in the field and in laboratory secondary toxicity studies. Thus, the nest-box occupancy and reproductive parameters of local barn owl populations can be monitored as an indicator of the AR exposure level in the area.Clinical Trials RegistrationNo clinical trials were involved in this study.

•Waning protection against influenza A (H3N2) occurred in a 2007–2008 community study.•Patients vaccinated earlier were more likely to develop H3N2 illness.•Effects were seen in young children and older adults, but not working age adults. Recent studies have suggested that vaccine-induced protection against influenza may decline within one season. We reanalyzed data from a study of influenza vaccine effectiveness to determine if time since vaccination was an independent predictor of influenza A (H3N2). Patients with acute respiratory illness were actively recruited during the 2007–2008 season. Respiratory swabs were tested for influenza, and vaccination dates were determined by a validated immunization registry. The association between influenza RT-PCR result and vaccination interval (days) was examined using multivariable logistic regression, adjusting for calendar time, age and other confounders. There were 629 vaccinated participants, including 177 influenza A (H3N2) cases and 452 test negative controls. The mean (SD) interval from vaccination to illness onset was 101.7 (25.9) days for influenza cases and 93.0 (29.9) days for controls. There was a significant association between vaccination interval and influenza result in the main effects model. The adjusted odds ratio (aOR) for influenza was 1.12 (CI 1.01, 1.26) for every 14 day increase in the vaccination interval. Age modified the association between vaccination interval and influenza (p=0.005 for interaction). Influenza was associated with increasing vaccination interval in young children and older adults, but not in adolescents or non-elderly adults. Similar results were found when calendar week of vaccine receipt was assessed as the primary exposure variable. Identification of influenza A (H3N2) was associated with increasing time since vaccination among young children and older adults during a single influenza season.

Muscle weakness is an important indicator of disability, chronic disease and mortality. While we recently proposed sex/race specific grip strength cutpoints for clinical muscle weakness in a diverse, nationally representative sample of older Americans, the extent to which these cutpoints predict physical disability remains unknown. To examine whether sex/race specific muscle weakness cutpoints predict physical disability status in a nationally representative sample of Americans age 65+. We used data from the 2006-2010 Health and Retirement Study. Fully-adjusted, weighted multinomial logistic regression models were used to quantify the odds of experiencing the onset, progression or persistence of disability in activities of daily living (ADL) among weak versus non-weak individuals over a 2-year period. General community, nationally representative sample of older Americans. Population-based, community dwelling sample of older American adults aged 65-years+; 57 percent were women, 91% were White and the mean age was 75 years. The primary outcome of interest was disability dynamics, defined by changes in ADL status across at 2- year period. The primary exposure was clinical muscle weakness as defined by previously identified cutpoints. Hypotheses were formulated before analyses were conducted. In this nationally representative sample (n= 8,725), 44% of individuals were classified as weak at baseline. At follow-up, 55% remained independent with no change in their ADL status, 11% had an onset of disability and 4% progressed in their disability status. The odds of experiencing an onset of ADL disability was 54% higher among weak individuals compared those who were not weak at baseline (OR= 1.54, 95% CI= 1.54, 1.5, p<.0001); the odds of experiencing a progression in physical disability status was 2.16 times higher among those who were weak at baseline compared to non-weak individuals (OR= 2.16, 95% CI= 2.15, 2.16, p<.0001). This is the first study to use grip strength weakness cut-points to identify those who may be at greatest risk for experiencing physical disability in later life. Results underscore the importance of using population-specific cutpoints for clinical weakness in order to identify individuals at greatest risk for adverse health outcomes.

Surface water samples were collected from the sampling sites throughout the Xiangjiang River for investigating spatial variation, risk assessment and source identification of the trace elements. The results indicated that the mean concentrations of the elements were under the permissible limits as prescribed by guidelines except arsenic (As). Based on the health risk indexes, the primary contributor to the chronic risks was arsenic (As), which was suggested to be the most important pollutant leading to non-carcinogenic and carcinogenic concerns. Individuals, who depend on surface water from the Xiangjiang River for potable and domestic use, might be subjected to the integrated health risks for exposure to the mixed trace elements. Children were more sensitive to the risks than the adults, and the oral intake was the primary exposure pathway. Besides, multivariate statistical analyses revealed that arsenic (As), cadmium (Cd), lead (Pb), selenium (Se), and mercury (Hg) mainly derived from the chemical industrial wastewaters and the coal burning, and zinc (Zn) copper (Cu) and chromium (Cr) mainly originated from the natural erosion, the mineral exploitation activities, and the non-point agricultural sources. As a whole, the upstream of the Xiangjiang River was explained as the high polluted region relatively.

Human papillomavirus (HPV) vaccine coverage was high in Denmark until it plunged following negative media coverage. We examined whether the decline in HPV vaccination undermined uptake of another adolescent vaccine, measles, mumps and rubella (MMR). The Danish national health register provided data on uptake of MMR vaccine dose 2 (at age 13) for children born from 1991 to 2003 (n = 827,716). The primary exposure variable comprised three time periods: before HPV vaccine introduction, during high HPV vaccine coverage, and after the drop in HPV vaccine coverage. To examine the effect of HPV vaccination on MMR2 uptake, we estimated MMR2 uptake by age 13 using logistic regression, controlling for gender, birth month, birth year, and maternal education. MMR2 vaccination coverage was high for both girls and boys (86% and 85%) in 2009. Following the introduction of HPV vaccine for girls in 2009, MMR2 coverage increased for girls even as it decreased for boys (gender gap 4·6 percentage points, 95% CI 4·3 to 4·8). Coverage with MMR2 for girls continued to be high over the following four years, and almost all girls (91%) who received MMR2 vaccination also received HPV1 vaccination within the same week. When negative media coverage led to a decline in HPV vaccination, MMR2 uptake for girls also declined. By 2015, MMR2 coverage for girls and boys had become similar again (80% and 79%). Families with the highest level of maternal education showed the strongest decline in MMR2 coverage for girls. Concomitant vaccine provision can increase overall vaccine uptake. However, reduced demand for one vaccine may reduce concomitant vaccination and undermine resiliency of a country’s vaccination program. Drs. Gørtz and Ejrnæs appreciate generous funding from the Novo Nordisk Foundation (grant no. NNF17OC0026542) and from the Danish National Research Foundation through its grant (DNRF-134) to the Center for Economic Behavior and Inequality (CEBI) at the University of Copenhagen.