The HLA class II allele DRB1*1501 is over-represented in patients with idiopathic pulmonary fibrosis

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and medically refractory lung disease with a grim prognosis. Although the etiology of IPF remains perplexing, abnormal adaptive immune responses are evident in many afflicted patients. We hypothesized that perturbations of human leukocyte antigen (HLA) allele frequencies, which are often seen among patients with immunologic diseases, may also be present in IPF patients. Methods/Principal Findings: HLA alleles were determined in subpopulations of IPF and normal subjects using molecular typing methods. HLA-DRB1*15 was over-represented in a discovery cohort of 79 Caucasian IPF subjects who had lung transplantations at the University of Pittsburgh (36.7%) compared to normal reference populations. These findings were prospectively replicated in a validation cohort of 196 additional IPF subjects from four other U.S. medical centers that included both ambulatory patients and lung transplantation recipients. High-resolution typing was used to further define specific HLA-DRB1*15 alleles. DRB1*1501 prevalence in IPF subjects was similar among the 143 ambulatory patients and 132 transplant recipients (31.5% and 34.8%, respectively, p = 0.55). The aggregate prevalence of DRB1*1501 in IPF patients was significantly greater than among 285 healthy controls (33.1% vs. 20.0%, respectively, OR 2.0; 95%CI 1.3-2.9, p = 0.0004). IPF patients with DRB1*1501 (n = 91) tended to have decreased diffusing capacities for carbon monoxide (DLCO) compared to the 184 disease subjects who lacked this allele (37.8±1.7% vs. 42.8±1.4%, p = 0.036). Conclusions/Significance: DRB1*1501 is more prevalent among IPF patients than normal subjects, and may be associated with greater impairment of gas exchange. These data are novel evidence that immunogenetic processes can play a role in the susceptibility to and/or manifestations of IPF. Findings here of a disease association at the HLA-DR locus have broad pathogenic implications, illustrate a specific chromosomal area for incremental, targeted genomic study, and may identify a distinct clinical phenotype among patients with this enigmatic, morbid lung disease

Cold Hardiness and Supercooling Capacity in the Overwintering Larvae of the Codling Moth, Cydia pomonella

The codling moth, Cydia pomonella L. (Lepidoptera: Tortricidae), a worldwide apple pest, is classified as a freeze-intolerant organism and one of the most cold-tolerant pests. The objectives of this study were to examine the supercooling point of overwintering and non-diapausing larvae of C. pomonella as an index of its cold hardiness, and to assess larval mortality following 24 h exposure to extreme low temperatures ranging from -5 to -25°C. The mean (±SE) supercooling point for feeding larvae (third through fifth instars) was -12.4 ± 1.1°C. The mean supercooling point for cocooned, non-diapausing larvae (i.e., non-feeding stages) decreased as the days that the arvae were cocooned increased and changed between -15.1 ± 1.2°C for one to two day cocooned arvae and -19.2 ± 1.8°C for less than five day cocooned larvae. The mean (±SE) supercooling point for other non-feeding stages containing pupae and overwintering larvae were -19.9 ± 1.0°C and -20.2 ± 0.2°C, respectively. Mean supercooling points of C. pomonella larvae were significantly lower during the winter months than the summer months, and sex had no effect on the supercooling point of C. pomonella larvae. The mortality of larvae increased significantly after individuals were exposed to temperatures below the mean supercooling point of the population. The supercooling point was a good predictor of cold hardiness

Meeting the home-care needs of disabled older persons living in the community: does integrated services delivery make a difference?

<p>Abstract</p> <p>Background</p> <p>The PRISMA Model is an innovative coordination-type integrated-service-delivery (ISD) network designed to manage and better match resources to the complex and evolving needs of elders. The goal of this study was to examine the impact of this ISD network on unmet needs among disabled older persons living in the community.</p> <p>Methods</p> <p>Using data from the PRISMA study, we compared unmet needs of elders living in the community in areas with or without an ISD network. Disabilities and unmet needs were assessed with the Functional Autonomy Measurement System (SMAF). We used growth-curve analysis to examine changes in unmet needs over time and the variables associated with initial status and change. Sociodemographic characteristics, level of disability, self-perceived health status, cognitive functioning, level of empowerment, and the hours of care received were investigated as covariates. Lastly, we report the prevalence of needs and unmet needs for 29 activities in both areas at the end of the study.</p> <p>Results</p> <p>On average, participants were 83 years old; 62% were women. They had a moderate level of disability and mild cognitive problems. On average, they received 2.07 hours/day (SD = 1.08) of disability-related care, mostly provided by family. The findings from growth-curve analysis suggest that elders living in the area where ISD was implemented and those with higher levels of disability experience better fulfillment of their needs over time. Besides the area, being a woman, living alone, having a higher level of disability, more cognitive impairments, and a lower level of empowerment were linked to initial unmet needs (r²= 0.25; p < 0.001). At the end of the study, 35% (95% CI: 31% to 40%) of elders with needs living in the ISD area had at least one unmet need, compared to 67% (95% CI: 62% to 71%) in the other area. In general, unmet needs were highest for bathing, grooming, urinary incontinence, walking outside, seeing, hearing, preparing meals, and taking medications.</p> <p>Conclusions</p> <p>In spite of more than 30 years of home-care services in the province of Quebec, disabled older adults living in the community still have unmet needs. ISD networks such as the PRISMA Model, however, appear to offer an effective response to the long-term-care needs of the elderly.</p

Higher risk of gastrointestinal parasite infection at lower elevation suggests possible constraints in the distributional niche of Alpine marmots

Alpine marmots Marmota marmota occupy a narrow altitudinal niche within high elevation alpine environments. For animals living at such high elevations where resources are limited, parasitism represents a potential major cost in life history. Using occupancy models, we tested if marmots living at higher elevation have a reduced risk of being infected with gastrointestinal helminths, possibly compensating the lower availability of resources (shorter feeding season, longer snow cover and lower temperature) than marmots inhabiting lower elevations. Detection probability of eggs and oncospheres of two gastro-intestinal helminthic parasites, Ascaris laevis and Ctenotaenia marmotae, sampled in marmot feces, was used as a proxy of parasite abundance. As predicted, the models showed a negative relationship between elevation and parasite detectability (i.e. abundance) for both species, while there appeared to be a negative effect of solar radiance only for C. marmotae. Site-occupancy models are used here for the first time to model the constrains of gastrointestinal parasitism on a wild species and the relationship existing between endoparasites and environmental factors in a population of free-living animals. The results of this study suggest the future use of site-occupancy models as a viable tool to account for parasite imperfect detection in ecoparasitological studies, and give useful insights to further investigate the hypothesis of the contribution of parasite infection in constraining the altitudinal niche of Alpine marmots

Variability of Intensive Care Admission Decisions for the Very Elderly

Although increasing numbers of very elderly patients are requiring intensive care, few large sample studies have investigated ICU admission of very elderly patients. Data on pre triage by physicians from other specialities is limited. This observational cohort study aims at examining inter-hospital variability of ICU admission rates and its association with patients' outcomes. All patients over 80 years possibly qualifying for ICU admission who presented to the emergency departments (ED) of 15 hospitals in the Paris (France) area during a one-year period were prospectively included in the study. Main outcome measures were ICU eligibility, as assessed by the ED and ICU physicians; in-hospital mortality; and vital and functional status 6 months after the ED visit. 2646 patients (median age 86; interquartile range 83–91) were included in the study. 94% of participants completed follow-up (n = 2495). 12.4% (n = 329) of participants were deemed eligible for ICU admission by ED physicians and intensivists. The overall in-hospital and 6-month mortality rates were respectively 27.2% (n = 717) and 50.7% (n = 1264). At six months, 57.5% (n = 1433) of patients had died or had a functional deterioration. Rates of patients deemed eligible for ICU admission ranged from 5.6% to 38.8% across the participating centers, and this variability persisted after adjustment for patients' characteristics. Despite this variability, we found no association between level of ICU eligibility and either in-hospital death or six-month death or functional deterioration. In France, the likelihood that a very elderly person will be admitted to an ICU varies widely from one hospital to another. Influence of intensive care admission on patients' outcome remains unclear