Photoreceptor replacement by transplantation is proposed as a treatment for blindness. Transplantation of healthy photoreceptor precursor cells into diseased murine eyes leads to the presence of ...functional photoreceptors within host retinae that express an array of donor-specific proteins. The resulting improvement in visual function was understood to be due to donor cells integrating within host retinae. Here, however, we show that while integration occurs the majority of donor-reporter-labelled cells in the host arises as a result of material transfer between donor and host photoreceptors. Material transfer does not involve permanent donor-host nuclear or cell-cell fusion, or the uptake of free protein or nucleic acid from the extracellular environment. Instead, RNA and/or protein are exchanged between donor and host cells in vivo. These data require a re-evaluation of the mechanisms underlying rescue by photoreceptor transplantation and raise the possibility of material transfer as a strategy for the treatment of retinal disorders.
The treatment gap between the number of people with mental disorders and the number treated represents a major public health challenge. We examine this gap by socio-economic status (SES; indicated by ...family income and respondent education) and service sector in a cross-national analysis of community epidemiological survey data.
Data come from 16 753 respondents with 12-month DSM-IV disorders from community surveys in 25 countries in the WHO World Mental Health Survey Initiative. DSM-IV anxiety, mood, or substance disorders and treatment of these disorders were assessed with the WHO Composite International Diagnostic Interview (CIDI).
Only 13.7% of 12-month DSM-IV/CIDI cases in lower-middle-income countries, 22.0% in upper-middle-income countries, and 36.8% in high-income countries received treatment. Highest-SES respondents were somewhat more likely to receive treatment, but this was true mostly for specialty mental health treatment, where the association was positive with education (highest treatment among respondents with the highest education and a weak association of education with treatment among other respondents) but non-monotonic with income (somewhat lower treatment rates among middle-income respondents and equivalent among those with high and low incomes).
The modest, but nonetheless stronger, an association of education than income with treatment raises questions about a financial barriers interpretation of the inverse association of SES with treatment, although future within-country analyses that consider contextual factors might document other important specifications. While beyond the scope of this report, such an expanded analysis could have important implications for designing interventions aimed at increasing mental disorder treatment among socio-economically disadvantaged people.
ABSTRACT We compute upper limits on the nanohertz-frequency isotropic stochastic gravitational wave background (GWB) using the 9 year data set from the North American Nanohertz Observatory for ...Gravitational Waves (NANOGrav) collaboration. Well-tested Bayesian techniques are used to set upper limits on the dimensionless strain amplitude (at a frequency of 1 yr−1) for a GWB from supermassive black hole binaries of A gw < 1.5 × 10 − 15 . We also parameterize the GWB spectrum with a broken power-law model by placing priors on the strain amplitude derived from simulations of Sesana and McWilliams et al. Using Bayesian model selection we find that the data favor a broken power law to a pure power law with odds ratios of 2.2 and 22 to one for the Sesana and McWilliams prior models, respectively. Using the broken power-law analysis we construct posterior distributions on environmental factors that drive the binary to the GW-driven regime including the stellar mass density for stellar-scattering, mass accretion rate for circumbinary disk interaction, and orbital eccentricity for eccentric binaries, marking the first time that the shape of the GWB spectrum has been used to make astrophysical inferences. Returning to a power-law model, we place stringent limits on the energy density of relic GWs, gw ( f ) h 2 < 4.2 × 10 − 10 . Our limit on the cosmic string GWB, gw ( f ) h 2 < 2.2 × 10 − 10 , translates to a conservative limit on the cosmic string tension with G < 3.3 × 10 − 8 , a factor of four better than the joint Planck and high-l cosmic microwave background data from other experiments.
Background Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, ...the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy. Objectives Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy. Results The addendum provides 3 separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider's office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation. Conclusions Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy.
Background & Aims:
Serotonin (5-HT) is a critical signaling molecule in the gut. 5-HT released from enterochromaffin cells initiates peristaltic, secretory, vasodilatory, vagal, and nociceptive ...reflexes. Despite being pathophysiologically divergent, ulcerative colitis (UC) and irritable bowel syndrome (IBS) are both associated with clinical symptoms that include alterations in the normal patterns of motility, secretion, and sensation. Our aim was to test whether enteric 5-HT signaling is defective in these disorders.
Methods:
Rectal biopsy specimens were obtained from healthy controls and patients with UC, IBS with diarrhea (IBS-D), and IBS with constipation (IBS-C). Key elements of 5-HT signaling, including measures of 5-HT content, release, and reuptake, were analyzed with these samples.
Results:
Mucosal 5-HT, tryptophan hydroxylase 1 messenger RNA, serotonin transporter messenger RNA, and serotonin transporter immunoreactivity were all significantly reduced in UC, IBS-C, and IBS-D. The enterochromaffin cell population was decreased in severe UC samples but was unchanged in IBS-C and IBS-D. When 5-HT release was investigated under basal and mechanical stimulation conditions, no changes were detected in any of the groups relative to controls.
Conclusions:
These data show that UC and IBS are associated with similar molecular changes in serotonergic signaling mechanisms. While UC and IBS have distinct pathophysiologic properties, these data suggest that shared defects in 5-HT signaling may underlie the altered motility, secretion, and sensation. These findings represent the first demonstration of significant molecular alterations specific to the gut in patients with IBS and support the assertion that disordered gastrointestinal function in IBS involves changes intrinsic to the bowel.
The Predicting Risk of Cancer at Screening study in Manchester, UK, is a prospective study of breast cancer risk estimation. It was designed to assess whether mammographic density may help in ...refinement of breast cancer risk estimation using either the Gail model (Breast Cancer Risk Assessment Tool) or the Tyrer-Cuzick model (International Breast Intervention Study model).
Mammographic density was measured at entry as a percentage visual assessment, adjusted for age and body mass index. Tyrer-Cuzick and Gail 10-year risks were based on a questionnaire completed contemporaneously. Breast cancers were identified at the entry screen or shortly thereafter. The contribution of density to risk models was assessed using odds ratios (ORs) with profile likelihood confidence intervals (CIs) and area under the receiver operating characteristic curve (AUC). The calibration of predicted ORs was estimated as a percentage (observed vs expected (O/E) from logistic regression.
The analysis included 50,628 women aged 47-73 years who were recruited between October 2009 and September 2013. Of these, 697 had breast cancer diagnosed after enrolment. Median follow-up was 3.2 years. Breast density interquartile range odds ratio (IQR-OR) 1.48, 95 % CI 1.34-1.63, AUC 0.59 was a slightly stronger univariate risk factor than the Tyrer-Cuzick model IQR-OR 1.36 (95 % CI 1.25-1.48), O/E 60 % (95 % CI 44-74), AUC 0.57 or the Gail model IQR-OR 1.22 (95 % CI 1.12-1.33), O/E 46 % (95 % CI 26-65 %), AUC 0.55. It continued to add information after allowing for Tyrer-Cuzick IQR-OR 1.47 (95 % CI 1.33-1.62), combined AUC 0.61 or Gail IQR-OR 1.45 (95 % CI 1.32-1.60), combined AUC 0.59.
Breast density may be usefully combined with the Tyrer-Cuzick model or the Gail model.
Single-nucleotide polymorphisms (SNPs) have demonstrated an association with breast cancer susceptibility, but there is limited evidence on how to incorporate them into current breast cancer risk ...prediction models.
To determine whether a panel of 18 SNPs (SNP18) may be used to predict breast cancer in combination with classic risk factors and mammographic density.
This cohort study enrolled a subcohort of 9363 women, aged 46 to 73 years, without a previous breast cancer diagnosis from the larger prospective cohort of the PROCAS study (Predicting Risk of Cancer at Screening) specifically to evaluate breast cancer risk-assessment methods. Enrollment took place from October 2009 through June 2015 from multiple population-based screening centers in Greater Manchester, England. Follow-up continued through January 5, 2017.
Genotyping of 18 SNPs, visual-assessment percentage mammographic density, and classic risk assessed by the Tyrer-Cuzick risk model from a self-completed questionnaire at cohort entry.
The predictive ability of SNP18 for breast cancer diagnosis (invasive and ductal carcinoma in situ) was assessed using logistic regression odds ratios per interquartile range of the predicted risk.
A total of 9363 women were enrolled in this study (mean range age, 59 46-73 years). Of these, 466 were found to have breast cancer (271 prevalent; 195 incident). SNP18 was similarly predictive when unadjusted or adjusted for mammographic density and classic factors (odds ratios per interquartile range, respectively, 1.56; 95% CI, 1.38-1.77 and 1.53; 95% CI, 1.35-1.74), with observed risks being very close to expected (adjusted observed-to-expected odds ratio, 0.98; 95% CI, 0.69-1.28). A combined risk assessment indicated 18% of the subcohort to be at 5% or greater 10-year risk, compared with 30% of all cancers, 35% of interval-detected cancers, and 42% of stage 2+ cancers. In contrast, 33% of the subcohort were at less than 2% risk but accounted for only 18%, 17%, and 15% of the total, interval, and stage 2+ breast cancers, respectively.
SNP18 added substantial information to risk assessment based on the Tyrer-Cuzick model and mammographic density. A combined risk is likely to aid risk-stratified screening and prevention strategies.
Lead halide perovskites have proven to be a versatile class of visible light absorbers that allow rapid access to the long minority carrier lifetimes and diffusion lengths desirable for traditional ...single-junction photovoltaics. We explore the extent to which the attractive features of these semiconductors may be extended to include an intermediate density of states for future application in multi-level solar energy conversion systems capable of exceeding the Shockley-Queisser limit. We computationally and experimentally explore the substitution of transition metals on the Pb site of MAPbX3 (MA = methylammonium, X = Br or Cl) to achieve a tunable density of states within the parent gap. Computational screening identified both Fe- and Co-substituted MAPbBr3 as promising absorbers with a mid-gap density of states, and the later films were synthesized via conventional solution-based processing techniques. First-principles density functional theory (DFT) calculations support the existence of mid-gap states upon Co incorporation and enhanced sub-gap absorption, which are consistent with UV-visible-NIR absorption spectroscopy. Strikingly, steady state and time-resolved PL studies reveal no sign of self-quenching for Co-substitution up to 25%, which suggest this class of materials to be a worthy candidate for future application in intermediate band photovoltaics.
Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the ...National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy.
Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy.
The addendum provides 3 separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider's office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation.
Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy.
We report population-based concentrations, stratified by age, sex, and racial/ethnic groups, of dialkyl phosphate (DAP) metabolites of multiple organophosphorus pesticides. We measured ...dimethylphosphate (DMP), dimethylthiophosphate (DMTP), dimethyldithiophosphate (DMDTP), diethylphosphate (DEP), diethylthiophosphate (DETP), and diethyldithiophosphate (DEDTP) concentrations in 1,949 urine samples collected in U.S. residents 6-59 years of age during 1999 and 2000 as a part of the ongoing National Health and Nutrition Examination Survey (NHANES). We detected each DAP metabolite in more than 50% of the samples, with DEP being detected most frequently (71%) at a limit of detection of 0.2 μg/L. The geometric means for the metabolites detected in more than 60% of the samples were 1.85 μg/L for DMTP and 1.04 μg/L for DEP. The 95th percentiles for each metabolite were DMP, 13 μg/L; DMTP, 46 μg/L; DMDTP, 19 μg/L; DETP, 2.2 μg/L; and DEDTP, 0.87 μg/L. We determined the molar sums of the dimethyl-containing and diethyl-containing metabolites; their geometric mean concentrations were 49.4 and 10.5 nmol/L, respectively, and their 95th percentiles were 583 and 108 nmol/L, respectively. These data are also presented as creatinine-adjusted concentrations. Multivariate analyses showed concentrations of DAPs in children 6-11 years of age that were consistently significantly higher than in adults and often higher than in adolescents. Although the concentrations between sexes and among racial/ethnic groups varied, no significant differences were observed. These data will be important in evaluating the impact of organophosphorus pesticide exposure in the U.S. population and the effectiveness of regulatory actions.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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