Optimal Media for Use in Air Sampling To Detect Cultivable Bacteria and Fungi in the Pharmacy

Current guidelines for air sampling for bacteria and fungi in compounding pharmacies require the use of a medium for each type of organism. U.S. Pharmacopeia (USP) chapter <797> (http://www.pbm.va.gov/linksotherresources/docs/USP797PharmaceuticalCompoundingSterileCompounding.pdf) calls for tryptic soy agar with polysorbate and lecithin (TSApl) for bacteria and malt extract agar (MEA) for fungi. In contrast, the Controlled Environment Testing Association (CETA), the professional organization for individuals who certify hoods and clean rooms, states in its 2012 certification application guide (http://www.cetainternational.org/reference/CAG-009v3.pdf?sid=1267) that a single-plate method is acceptable, implying that it is not always necessary to use an additional medium specifically for fungi. In this study, we reviewed 5.5 years of data from our laboratory to determine the utility of TSApl versus yeast malt extract agar (YMEA) for the isolation of fungi. Our findings, from 2,073 air samples obtained from compounding pharmacies, demonstrated that the YMEA yielded >2.5 times more fungal isolates than TSApl

A brother and sister with the same karyotype: Case report of two siblings with partial 3p duplication and partial 9p deletion and sex reversal

Two siblings with the same male unbalanced karyotype demonstrate sex reversal. The older sib appeared phenotypically female and the younger sib demonstrated a male gender. The female had gonadal dysgenesis with bilateral ovatestes. The male had bilateral testes. The report discusses the phenotypical differences and genes associated with sex reversal

Strong Interaction Physics at the Luminosity Frontier with 22 GeV Electrons at Jefferson Lab

This document presents the initial scientific case for upgrading the Continuous Electron Beam Accelerator Facility (CEBAF) at Jefferson Lab (JLab) to 22 GeV. It is the result of a community effort, incorporating insights from a series of workshops conducted between March 2022 and April 2023. With a track record of over 25 years in delivering the world's most intense and precise multi-GeV electron beams, CEBAF's potential for a higher energy upgrade presents a unique opportunity for an innovative nuclear physics program, which seamlessly integrates a rich historical background with a promising future. The proposed physics program encompass a diverse range of investigations centered around the nonperturbative dynamics inherent in hadron structure and the exploration of strongly interacting systems. It builds upon the exceptional capabilities of CEBAF in high-luminosity operations, the availability of existing or planned Hall equipment, and recent advancements in accelerator technology. The proposed program cover various scientific topics, including Hadron Spectroscopy, Partonic Structure and Spin, Hadronization and Transverse Momentum, Spatial Structure, Mechanical Properties, Form Factors and Emergent Hadron Mass, Hadron-Quark Transition, and Nuclear Dynamics at Extreme Conditions, as well as QCD Confinement and Fundamental Symmetries. Each topic highlights the key measurements achievable at a 22 GeV CEBAF accelerator. Furthermore, this document outlines the significant physics outcomes and unique aspects of these programs that distinguish them from other existing or planned facilities. In summary, this document provides an exciting rationale for the energy upgrade of CEBAF to 22 GeV, outlining the transformative scientific potential that lies within reach, and the remarkable opportunities it offers for advancing our understanding of hadron physics and related fundamental phenomena.Comment: Updates to the list of authors; Preprint number changed from theory to experiment; Updates to sections 4 and 6, including additional figure

Measurement of prompt hadron production ratios in pppp collisions at s=\sqrt{s} = 0.9 and 7 TeV

The charged-particle production ratios $\bar{p}/p$, $K^-/K^+$, $\pi^-/\pi^+$, $(p + \bar{p})/(\pi^+ + \pi^-)$, $(K^+ + K^-)/(\pi^+ + \pi^-)$ and $(p + \bar{p})/(K^+ + K^-)$ are measured with the LHCb detector using $0.3 {\rm nb^{-1}}$ of $pp$ collisions delivered by the LHC at $\sqrt{s} = 0.9$ TeV and $1.8 {\rm nb^{-1}}$ at $\sqrt{s} = 7$ TeV. The measurements are performed as a function of transverse momentum $p_{\rm T}$ and pseudorapidity $\eta$. The production ratios are compared to the predictions of several Monte Carlo generator settings, none of which are able to describe adequately all observables. The ratio $\bar{p}/p$ is also considered as a function of rapidity loss, $\Delta y \equiv y_{\rm beam} - y$, and is used to constrain models of baryon transport.Comment: Incorrect entries in Table 2 corrected. No consequences for rest of pape

BacHBerry: BACterial Hosts for production of Bioactive phenolics from bERRY fruits

BACterial Hosts for production of Bioactive phenolics from bERRY fruits (BacHBerry) was a 3-year project funded by the Seventh Framework Programme (FP7) of the European Union that ran between November 2013 and October 2016. The overall aim of the project was to establish a sustainable and economically-feasible strategy for the production of novel high-value phenolic compounds isolated from berry fruits using bacterial platforms. The project aimed at covering all stages of the discovery and pre-commercialization process, including berry collection, screening and characterization of their bioactive components, identification and functional characterization of the corresponding biosynthetic pathways, and construction of Gram-positive bacterial cell factories producing phenolic compounds. Further activities included optimization of polyphenol extraction methods from bacterial cultures, scale-up of production by fermentation up to pilot scale, as well as societal and economic analyses of the processes. This review article summarizes some of the key findings obtained throughout the duration of the project

Clostridium difficile Testing in the Clinical Laboratory by Use of Multiple Testing Algorithms ▿

The incidence of Clostridium difficile infection (CDI) has risen almost 3-fold in the United States over the past decade, emphasizing the need for rapid and accurate tests for CDI. The Cepheid Xpert C. difficile assay is an integrated, closed, nucleic acid amplification system that automates sample preparation and real-time PCR detection of the toxin B gene (tcdB). A total of 432 stool specimens from symptomatic patients were tested by a glutamate dehydrogenase (GDH) assay, a toxin A and B enzyme immunoassay (EIA), the Xpert C. difficile assay, and a cell culture cytotoxicity neutralization assay (CCCN). The results of these methods, used individually and in combination, were compared to those of toxigenic culture. Results for the Xpert C. difficile assay alone showed a sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of 94.4, 96.3, 84.0, and 98.8%, while the EIA alone gave corresponding values of 58.3, 94.7, 68.9, and 91.9%, respectively. An algorithm using the GDH assay and the EIA (plus the CCCN if the EIA was negative) showed corresponding values of 83.1, 96.7, 83.1, and 96.1%. The Xpert C. difficile assay was statistically superior to the EIA (P, <0.001 by Fisher's exact test) and to the GDH-EIA-CCCN algorithm (P, 0.0363). Combining the GDH and Xpert C. difficile assays lowered both the sensitivity and the NPV of the Xpert assay. The GDH-EIA-CCCN procedure required, on average, 2 days to complete testing on GDH-positive results, while testing by the Xpert C. difficile assay was completed, on average, in less than 1 h. Xpert C. difficile testing yielded the highest sensitivity and NPV, in the least amount of time, of the individual- and multiple-test algorithms evaluated in this study

Longitudinal assessment of cognitive decline in the Amish

Background The Modified Mini‐Mental State (3MS) is a widely used measure of global cognition. The Old Order Amish are both genetically and environmentally homogeneous, with similar years of formal education across the population. Here, we investigated the longitudinal course of cognitive function as measured by the distribution of 3MS in the Mid‐Western Amish. Method After extensive QC, the 919 subjects with both baseline 3MS and AD status were analyzed. The change from 1st to 2nd measurement was used as the main longitudinal trait of interest. Mean decline differences in 4 baseline age groups (=90) were assessed. The differences in the average longitudinal decline of 3MS between AD cases and controls was assessed using Kolmogorov‐Smirnov tests and ANCOVA adjusted for age at exam and sibship. Result The overall baseline mean 3MS score was 89.52 [42, 100] at the mean age of exam 75.52 [60, 99]. The overall annual rate of decline was ‐0.3 [‐5, 5] from 1st to 2nd measurement (n=242) and ‐0.6 [‐2.1, 1.3] from 2nd to 3rd measurement (n = 23). The annual rate of decline was ‐0.96 [‐4, 1.7] in AD cases (n=18), ‐0.01 [‐5, 5] in AD controls (n=180) and ‐1.08 [‐5, 0.7] in an ‘Unclear’ group (n = 44). The most rapid annual decline of the 3MS was in age 80 to 90 group and the decline rate was significant (p‐value=0.004) compared to the lowest age group (<70) overall and in AD cases. In the Unclear group, the rate of decline was greatest in age 70 to 80. However, in the control group, cognition improved, with a 1.29 [‐1, 5] annual increase in age 80 to 90. The age and sibship adjusted differences in decline were significant (p‐value<2e‐10) between AD cases vs. controls as well as between Unclear vs. controls. Conclusion We explored the changes of 3MS scores over time and demonstrated different patterns of decline by age and AD status in the Amish. Our study is the first in this homogeneous Amish population, providing a better understanding and insight into the cognitive decline examining the change in 3MS over time

Joint linkage and association mapping of preserved cognition in the old‐order Amish

Background Most studies on Alzheimer Disease (AD) have focused on the identification of variants associated with increased risk. The Amish is a genetically homogeneous population ideal to investigate susceptibility genes for complex traits such as AD. This study aims to use family‐based linkage and association approaches to identify genetic variants that protect against the development of cognitive impairment (CI), the central feature of AD. Method A total of 800 adults from Amish communities in Indiana and Ohio were screened for CI using the 3MS test. Individuals were classified as cognitively normal (CN) if the 3MS score was ≥87 at age 75 and cognitively impaired if < 87 at any age. Samples were genotyped on the Illumina Infinium Global Screening or Expanded Multi‐Ethnic Genotyping Array. Over 7 Million common and rare variants were then imputed using the HRC reference panel. For the linkage analysis 75 nuclear families containing at least two CN individuals were analyzed using Merlin to fit multipoint non‐parametric linkage models and parametric affected‐only (AO) dominant and recessive models using a map of more than 40,000 genotyped markers. The genome‐wide association study (GWAS) of imputed variants utilized the program Genesis to fit a logistic regression model 426 CN to 360 CI, associating each variant with cognitive status while adjusting for sex, pc1, pc2 and relatedness. Result The top linkage peaks were seen in the parametric multipoint AO dominant model: Chr3 (HLOD = 2.6) ∼3.9 mb region (21.0 mb – 24.9 mb) and Chr11 (HLOD 2.1) ∼6.5 mb (11.0 mb – 17.5 mb). In the GWAS analysis, no variants reached genome wide significance (5 × 10−8). However, using a lower significance threshold for regional association under a linkage peak (p < 10−5), 7 associated variants were identified in two regions under the Chr11 peak. Conclusion We identified a 6.5 mb area of interest on chromosome 11 associated with preserved cognitive function in Amish adults over age 75, which is near OTOG a previously reported gene associated with AD. This region merits further investigation for functional variants that might slow or prevent the development of cognitive impairment in older adults