Measuring DHEA-S in saliva: time of day differences and positive correlations between two different types of collection methods

<p>Abstract</p> <p>Background</p> <p>The anabolic steroid, dehydroepiandosterone sulfate (DHEA-S), is secreted from the adrenal cortex. It plays a significant role in the body as a precursor to sex steroids as well as a lesser known role in the hypothalamic pituitary adrenal axis (HPA) response to stress. DHEA-S can be measured reliably in saliva, making saliva collection a valuable tool for health research because it minimizes the need for invasive sampling procedures (e.g., blood draws). Typical saliva collection methods include the use of plain cotton swab collection devices (e.g., Salivette^®) or passive drool. There has been some speculation that the plain saliva cotton collection device may interfere with determination of DHEA-S by enzyme immunoassay (EIA) bringing this saliva collection method into question. Because of the increasing popularity of salivary biomarker research, we sought to determine whether the cotton swab interferes with DHEA-S determination through EIA techniques.</p> <p>Findings</p> <p>Fifty-six healthy young adult men and women aged 18-30 years came to the lab in the morning (0800 hrs; 14 men, 14 women) or late afternoon (1600 hrs; 14 men, 14 women) and provided saliva samples via cotton Salivette and passive drool. Passive drool collection was taken first to minimize particle cross contamination from the cotton swab. Samples were assayed for DHEA-S in duplicate using a commercially available kit (DSL, Inc., Webster, TX). DHEA-S levels collected via Salivette and passive drool were positively correlated (r = + 0.83, p < 0.05). Mean DHEA-S levels were not significantly different between collection methods. Salivary DHEA-S levels were significantly higher in males than in females, regardless of saliva collection method (p < 0.05), and morning DHEA-S values were higher than evening levels (p < 0.05).</p> <p>Conclusions</p> <p>Results suggest that DHEA-S can be measured accurately using passive drool or cotton Salivette collection methods. Results also suggest that DHEA-S levels change across the day and that future studies need to take this time of day difference into account when measuring DHEA-S.</p

Automatic Generation of Test Cases based on Bug Reports: a Feasibility Study with Large Language Models

Software testing is a core discipline in software engineering where a large array of research results has been produced, notably in the area of automatic test generation. Because existing approaches produce test cases that either can be qualified as simple (e.g. unit tests) or that require precise specifications, most testing procedures still rely on test cases written by humans to form test suites. Such test suites, however, are incomplete: they only cover parts of the project or they are produced after the bug is fixed. Yet, several research challenges, such as automatic program repair, and practitioner processes, build on the assumption that available test suites are sufficient. There is thus a need to break existing barriers in automatic test case generation. While prior work largely focused on random unit testing inputs, we propose to consider generating test cases that realistically represent complex user execution scenarios, which reveal buggy behaviour. Such scenarios are informally described in bug reports, which should therefore be considered as natural inputs for specifying bug-triggering test cases. In this work, we investigate the feasibility of performing this generation by leveraging large language models (LLMs) and using bug reports as inputs. Our experiments include the use of ChatGPT, as an online service, as well as CodeGPT, a code-related pre-trained LLM that was fine-tuned for our task. Overall, we experimentally show that bug reports associated to up to 50% of Defects4J bugs can prompt ChatGPT to generate an executable test case. We show that even new bug reports can indeed be used as input for generating executable test cases. Finally, we report experimental results which confirm that LLM-generated test cases are immediately useful in software engineering tasks such as fault localization as well as patch validation in automated program repair

Development of a syngeneic mouse model of epithelial ovarian cancer

Background Most cases of ovarian cancer are epithelial in origin and diagnosed at advanced stage when the cancer is widely disseminated in the peritoneal cavity. The objective of this study was to establish an immunocompetent syngeneic mouse model of disseminated epithelial ovarian cancer (EOC) to facilitate laboratory-based studies of ovarian tumor biology and preclinical therapeutic strategies. Methods Individual lines of TgMISIIR-TAg transgenic mice were phenotypically characterized and backcrossed to inbred C57BL/6 mice. In addition to a previously described line of EOC-prone mice, two lines (TgMISIIR-TAg-Low) were isolated that express the oncogenic transgene, but have little or no susceptibility to tumor development. Independent murine ovarian carcinoma (MOVCAR) cell lines were established from the ascites of tumor-bearing C57BL/6 TgMISIIR-TAg transgenic mice, characterized and tested for engraftment in the following recipient mice: 1) severe immunocompromised immunodeficient (SCID), 2) wild type C57BL/6, 3) oophorectomized tumor-prone C57BL/6 TgMISIIR-TAg transgenic and 4) non-tumor prone C57BL/6 TgMISIIR-TAg-Lowtransgenic. Lastly, MOVCAR cells transduced with a luciferase reporter were implanted in TgMISIIR-TAg-Low mice and in vivo tumor growth monitored by non-invasive optical imaging. Results Engraftment of MOVCAR cells by i.p. injection resulted in the development of disseminated peritoneal carcinomatosis in SCID, but not wild type C57BL/6 mice. Oophorectomized tumor-prone TgMISIIR-TAg mice developed peritoneal carcinomas with high frequency, rendering them unsuitable as allograft recipients. Orthotopic or pseudo-orthotopic implantation of MOVCAR cells in TgMISIIR-TAg-Low mice resulted in the development of disseminated peritoneal tumors, frequently accompanied by the production of malignant ascites. Tumors arising in the engrafted mice bore histopathological resemblance to human high-grade serous EOC and exhibited a similar pattern of peritoneal disease spread. Conclusions A syngeneic mouse model of human EOC was created by pseudo-orthotopic and orthotopic implantation of MOVCAR cells in a susceptible inbred transgenic host. This immunocompetent syngeneic mouse model presents a flexible system that can be used to study the consequences of altered gene expression (e.g., by ectopic expression or RNA interference strategies) in an established MOVCAR tumor cell line within the ovarian tumor microenvironment and for the development and analysis of preclinical therapeutic agents including EOC vaccines and immunotherapeutic agents

Measurement of scintillation efficiency for nuclear recoils in liquid argon

The scintillation light yield of liquid argon from nuclear recoils relative to electronic recoils has been measured as a function of recoil energy from 10 keVr up to 250 keVr at zero electric field. The scintillation efficiency, defined as the ratio of the nuclear recoil scintillation response to the electronic recoil response, is 0.25±0.01+0.01 (correlated) above 20 keVr. © 2012 American Physical Society

Infant RSV immunoprophylaxis changes nasal epithelial DNA methylation at 6 years of age

BackgroundRespiratory syncytial virus (RSV) infection has been associated with childhood wheeze and asthma, and potential mechanisms include persistent epigenetic effects.MethodsIn the randomized, placebo-controlled MAKI trial, 429 preterm infants randomly received RSV immunoprophylaxis with palivizumab or placebo during their first RSV season. Children were followed until age 6 for asthma evaluation. DNA methylation in cells obtained by nasal brushes at age 6 was measured by Illumina MethylationEPIC array.ResultsRSV immunoprophylaxis in infancy had a significant impact on global methylation patterns in nasal cells at age 6. The first principal component (PC) related to the immunoprophylaxis intervention was enriched for the pathway "detection of chemical stimulus involved in sensory perception of smell" and "T cell differentiation." Subsequent analysis of these PCs indicated an effect of RSV immunoprophylaxis on cell type composition of nasal brushed cells. Three CpG sites, cg18040241, cg08243963, and cg19555973 which are annotated to genes GLB1L2, SC5D, and BPIFB1, were differentially methylated at genome-wide significance, but were not associated with asthma. ConclusionThe study provides the first proof of concept that RSV immunoprophylaxis during infancy has long-term effects on nasal epigenetic signatures at age 6, relating to host sensory perception, epidermal growth factor receptor signaling, and adaptive immune responses.</p

The balloon-borne large-aperture submillimeter telescope for polarimetry: BLAST-Pol

The Balloon-borne Large Aperture Submillimeter Telescope for Polarimetry (BLAST-Pol) is a suborbital mapping experiment designed to study the role played by magnetic fields in the star formation process. BLAST-Pol is the reconstructed BLAST telescope, with the addition of linear polarization capability. Using a 1.8 m Cassegrain telescope, BLAST-Pol images the sky onto a focal plane that consists of 280 bolometric detectors in three arrays, observing simultaneously at 250, 350, and 500 um. The diffraction-limited optical system provides a resolution of 30'' at 250 um. The polarimeter consists of photolithographic polarizing grids mounted in front of each bolometer/detector array. A rotating 4 K achromatic half-wave plate provides additional polarization modulation. With its unprecedented mapping speed and resolution, BLAST-Pol will produce three-color polarization maps for a large number of molecular clouds. The instrument provides a much needed bridge in spatial coverage between larger-scale, coarse resolution surveys and narrow field of view, and high resolution observations of substructure within molecular cloud cores. The first science flight will be from McMurdo Station, Antarctica in December 2010.Comment: 14 pages, 9 figures Submitted to SPIE Astronomical Telescopes and Instrumentation Conference 201

Geriatric Screening, Triage Urgency, and 30-Day Mortality in Older Emergency Department Patients

BACKGROUND: Urgency triage in the emergency department (ED) is important for early identification of potentially lethal conditions and extensive resource utilization. However, in older patients, urgency triage systems could be improved by taking geriatric vulnerability into account. We investigated the association of geriatric vulnerability screening in addition to triage urgency levels with 30-day mortality in older ED patients. DESIGN: Secondary analysis of the observational multicenter Acutely Presenting Older Patient (APOP) study. SETTING: EDs within four Dutch hospitals. PARTICIPANTS: Consecutive patients, aged 70 years or older, who were prospectively included. MEASUREMENTS: Patients were triaged using the Manchester Triage System (MTS). In addition, the APOP screener was used as a geriatric screening tool. The primary outcome was 30-day mortality. Comparison was made between mortality within the geriatric high- and low-risk screened patients in every urgency triage category. We calculated the difference in explained variance of mortality by adding the geriatric screener (APOP) to triage urgency (MTS) by calculating Nagelkerke R2. RESULTS: We included 2,608 patients with a median age of 79 (interquartile range = 74-84) years, of whom 521 (20.0%) patients were categorized as high risk accor

Fostering implementation of health services research findings into practice: a consolidated framework for advancing implementation science

Abstract Background Many interventions found to be effective in health services research studies fail to translate into meaningful patient care outcomes across multiple contexts. Health services researchers recognize the need to evaluate not only summative outcomes but also formative outcomes to assess the extent to which implementation is effective in a specific setting, prolongs sustainability, and promotes dissemination into other settings. Many implementation theories have been published to help promote effective implementation. However, they overlap considerably in the constructs included in individual theories, and a comparison of theories reveals that each is missing important constructs included in other theories. In addition, terminology and definitions are not consistent across theories. We describe the Consolidated Framework For Implementation Research (CFIR) that offers an overarching typology to promote implementation theory development and verification about what works where and why across multiple contexts. Methods We used a snowball sampling approach to identify published theories that were evaluated to identify constructs based on strength of conceptual or empirical support for influence on implementation, consistency in definitions, alignment with our own findings, and potential for measurement. We combined constructs across published theories that had different labels but were redundant or overlapping in definition, and we parsed apart constructs that conflated underlying concepts. Results The CFIR is composed of five major domains: intervention characteristics, outer setting, inner setting, characteristics of the individuals involved, and the process of implementation. Eight constructs were identified related to the intervention (e.g., evidence strength and quality), four constructs were identified related to outer setting (e.g., patient needs and resources), 12 constructs were identified related to inner setting (e.g., culture, leadership engagement), five constructs were identified related to individual characteristics, and eight constructs were identified related to process (e.g., plan, evaluate, and reflect). We present explicit definitions for each construct. Conclusion The CFIR provides a pragmatic structure for approaching complex, interacting, multi-level, and transient states of constructs in the real world by embracing, consolidating, and unifying key constructs from published implementation theories. It can be used to guide formative evaluations and build the implementation knowledge base across multiple studies and settings.http://deepblue.lib.umich.edu/bitstream/2027.42/78272/1/1748-5908-4-50.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/2/1748-5908-4-50-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/3/1748-5908-4-50-S3.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/4/1748-5908-4-50-S4.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/5/1748-5908-4-50.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/6/1748-5908-4-50-S2.PDFPeer Reviewe