Sources of Klebsiella and Raoultella species on dairy farms: Be careful where you walk

Klebsiella spp. are a common cause of mastitis, milk loss, and culling on dairy farms. Control of Klebsiella mastitis is largely based on prevention of exposure of the udder to the pathogen. To identify critical control points for mastitis prevention, potential Klebsiella sources and transmission cycles in the farm environment were investigated, including oro-fecal transmission, transmission via the indoor environment, and transmission via the outdoor environment. A total of 305 samples was collected from 3 dairy farms in upstate New York in the summer of 2007, and included soil, feed crops, feed, water, rumen content, feces, bedding, and manure from alleyways and holding pens. Klebsiella spp. were detected in 100% of rumen samples, 89% of water samples, and approximately 64% of soil, feces, bedding, alleyway, and holding pen samples. Detection of Klebsiella spp. in feed crops and feed was less common. Genotypic identification of species using rpoB sequence data showed that Klebsiella pneumoniae was the most common species in rumen content, feces, and alleyways, whereas Klebsiella oxytoca, Klebsiella variicola, and Raoultella planticola were the most frequent species among isolates from soil and feed crops. Random amplified polymorphic DNA-based strain typing showed heterogeneity of Klebsiella spp. in rumen content and feces, with a median of 4 strains per 5 isolates. Observational and bacteriological data support the existence of an oro-fecal transmission cycle, which is primarily maintained through direct contact with fecal contamination or through ingestion of contaminated drinking water. Fecal shedding of Klebsiella spp. contributes to pathogen loads in the environment, including bedding, alleyways, and holding pens. Hygiene of alleyways and holding pens is an important component of Klebsiella control on dairy farms

Isolated oxygen defects in 3C- and 4H-SiC: A theoretical study

Ab initio calculations in the local-density approximation have been carried out in SiC to determine the possible configurations of the isolated oxygen impurity. Equilibrium geometry and occupation levels were calculated. Substitutional oxygen in 3C-SiC is a relatively shallow effective mass like double donor on the carbon site (O-C) and a hyperdeep double donor on the Si site (O-Si). In 4H-SiC O-C is still a double donor but with a more localized electron state. In 3C-SiC O-C is substantially more stable under any condition than O-Si or interstitial oxygen (O-i). In 4H-SiC O-C is also the most stable one except for heavy n-type doping. We propose that O-C is at the core of the electrically active oxygen-related defect family found by deep level transient spectroscopy in 4H-SiC. The consequences of the site preference of oxygen on the SiC/SiO2 interface are discussed

Studies of Pion Production Near Threshold

This work was supported by National Science Foundation Grant PHY 75-00289 and Indiana Universit

Premenopausal gynecologic surgery and survival among black and white women with breast cancer

Purpose: In the United States, hysterectomies and oophorectomies are frequently performed before menopause for benign conditions. The procedures are associated with reduced breast cancer-specific mortality among White women. The relationship between premenopausal gynecologic surgery and mortality in Black women with breast cancer is unknown. Methods: This investigation used incident invasive cases of breast cancer from Phases 1 and 2 of the Carolina Breast Cancer Study a population-based study that recruited Black and White women in North Carolina between 1993 and 2001. Premenopausal gynecologic surgery was operationalized in three categories: no surgery; hysterectomy with bilateral oophorectomy; hysterectomy with conservation of ≥ 1 ovary. Mortality was ascertained using the National Death Index, last updated in 2016. Multivariable-adjusted Cox Proportional Hazard Models were used to estimate the effect of premenopausal surgery on breast cancer-specific and all-cause mortality Results: Hysterectomy with bilateral oophorectomy was associated with reduced breast cancer-specific mortality (HR 0.68; 95% CI 0.49, 0.96). White and Black women had a similar reduction in breast cancer-specific mortality. (HR among white: 0.66; 95% CI 0.43, 1.02), (HR among Black: 0.67; 95% CI 0.37, 1.21). Conclusions: There was a similar reduction in breast cancer-specific mortality following premenopausal, pre-diagnosis hysterectomy with bilateral oophorectomy across both Black and White women

Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference

The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique\u2014Subtype and Stage Inference (SuStaIn)\u2014able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-sectional patient studies. Results from imaging studies in two neurodegenerative diseases reveal subgroups and their distinct trajectories of regional neurodegeneration. In genetic frontotemporal dementia, SuStaIn identifies genotypes from imaging alone, validating its ability to identify subtypes; further the technique reveals within-genotype heterogeneity. In Alzheimer\u2019s disease, SuStaIn uncovers three subtypes, uniquely characterising their temporal complexity. SuStaIn provides fine-grained patient stratification, which substantially enhances the ability to predict conversion between diagnostic categories over standard models that ignore subtype (p = 7.18 7 10 124 ) or temporal stage (p = 3.96 7 10 125 ). SuStaIn offers new promise for enabling disease subtype discovery and precision medicine

Rapid handheld continuous electroencephalogram (eeg) has the potential to detect delirium in older adults

Background: Delirium-related biochemical derangements lead to electrical changes that can be detected in electroencephalographic (EEG) patterns followed by behavioral signs and symptoms. Studies using limited lead EEG show a large difference between patients with and without delirium while discriminating delirium from other causes. Handheld rapid EEG devices may be capable of detecting delirium before symptom onset, thus providing an objective physiological method to detect delirium when it is most amenable to interventions. Objective: The aimof this studywas to explore the potential for rapid EEG to detect waveform pattern changes consistent with delirium status. Methods: This prospective exploratory pilot study used a correlational design and mixed models to explore the relationships between handheld portable EEG data and delirium status. Results: While being under powered minimized opportunities to detect statistical differences in EEGderived ratios using spectral density analysis, sleep-to-wake ratios tended to be higher in patients with delirium. Conclusions: Limited lead EEG may be useful in predicting adverse outcomes and risk for delirium in older critically ill patients. Although this population is at the highest risk for mortality, delirium is not easily identified by current clinical assessments. Therefore, further investigation of limited lead EEG for delirium detection is warranted. © 2022 Lippincott Williams and Wilkins. All rights reserved