An analysis of space power system masses

Various space electrical power system masses are analyzed with particular emphasis on the power management and distribution (PMAD) portion. The electrical power system (EPS) is divided into functional blocks: source, interconnection, storage, transmission, distribution, system control and load. The PMAD subsystem is defined as all the blocks between the source, storage and load, plus the power conditioning equipment required for the source, storage and load. The EPS mass of a wide range of spacecraft is then classified as source, storage or PMAD and tabulated in a database. The intent of the database is to serve as a reference source for PMAD masses of existing and in-design spacecraft. The PMAD masses in the database range from 40 kg/kW to 183 kg/kW across the spacecraft systems studied. Factors influencing the power system mass are identified. These include the total spacecraft power requirements, total amount of load capacity and physical size of the spacecraft. It is found that a new utility class of power systems, represented by Space Station Freedom, is evolving

Prosthetic thigh arteriovenous access: outcome with SVS/AAVS reporting standards

AbstractPurposeDifferences in the reporting methods of results for arteriovenous (AV) access can dramatically affect apparent outcome. To enable meaningful comparisons in the literature, the Society for Vascular Surgery and the American Association for Vascular Surgery (SVS/AAVS) recently published reporting standards for dialysis access. The purpose of the present study was to determine infection rates, patency rates, and possible predictive factors for prosthetic thigh AV access outcomes with the reporting standards of the SVS/AAVS.MethodsA retrospective analysis was performed of all patients who underwent placement of thigh AV access by the Surgical Teaching Service at Greenville Memorial Hospital between 1989 and 2001. Outcomes were determined based on SVS/AAVS Standards for Reports Dealing with AV Accesses. The rate of revision per year of access patency was also determined; this end point more accurately reflects the true cost and morbidity associated with AV access than do patency or infection rates alone.ResultsOne hundred twenty-five polytetrafluoroethylene thigh AV accesses were placed in 100 patients. Nine accesses were excluded from the study, six because there was no patient follow-up and 3 as a result of deaths unrelated to the access procedure and which occurred less than 30 days after access placement. There were six (4%) late access-related deaths. There were 18 (15%) early access failures, related to infection in 14 cases (12%), thrombosis in three cases (2%), and steal in one case (1%). Early failure was more common in patients with diabetes mellitus (P = .036). The primary and secondary functional patency rates were 19% and 54%, respectively, at 2 years. Infection occurred in 48 (41%) accesses. The patency and infection rates were not influenced by patient age, gender, body mass index, or diabetes mellitus. The median number of interventions per year of access patency was 1.68, and this outcome was positively correlated with body mass index (P < .001).ConclusionsProsthetic AV access in the thigh is associated with higher morbidity compared with that reported for the upper extremity, and should be considered only if no upper extremity AV access option is available. Early access failure and the requirement for an increased number of interventions to reestablish and maintain access patency are more common in patients with diabetes mellitus and obesity. The number of interventions per year of access patency is a valuable end point when assessing the outcome of AV access procedures

Description and outcomes of a simple surgical technique to treat thrombosed autogenous accesses

ObjectiveOwing to the difficulty of removing acute and chronic thrombus from autogenous accesses (AA) by standard surgical and endovascular techniques, many surgeons consider efforts to salvage a thrombosed AA as being futile. We describe a simple technique to extract acute and chronic thrombus from a failed AA. This technique involves making an incision adjacent to the anastomosis, directly extracting the arterial plug, and manually milking thrombus from the access. This report details the outcomes of a series of thrombosed AAs treated by surgical thrombectomy/intervention using this technique for manual clot extraction.MethodsA total of 146 surgical thrombectomies/interventions were performed in 102 patients to salvage a thrombosed AA. Mean follow-up was 15.6 months. Office, hospital, and dialysis unit records were reviewed to identify patient demographics, define procedure type, and determine functional patency rates. Kaplan-Meier survival analysis was used to estimate primary and secondary functional patency rates.ResultsComplete extraction of thrombus from the AA was achieved in 140 of 146 cases (95%). The studied procedure itself was technically successful in 127 cases (87%). Reasons for failure were the inability to completely extract thrombus from the AA in six, failed angioplasty due to long segment vein stenosis or sclerosis in seven or vein rupture in two, and central vein occlusion in one. Three failures occurred for unknown causes ≤3 days of successful thrombectomy. No single factor analyzed (age, sex, race, diabetes status, access type or location) was associated with technical failure. The estimated primary and secondary functional patency rates were 27% ± 5% and 61% ± 6% at 12 months.ConclusionsThe manual clot extraction technique described in this report effectively removed acute and chronic thrombus from failed AAs. Its use, combined with an intervention to treat the underlying cause for AA failure, significantly extended access durability

Escherichia coli O26 in feedlot cattle: Fecal prevalence, isolation, characterization, and effects of an E. coli O157 vaccine and a direct-fed microbial

Escherichia coli O26 is second only to O157 in causing foodborne, Shiga toxin–producing E. coli (STEC) infections. Our objectives were to determine fecal prevalence and characteristics of E. coli O26 in commercial feedlot cattle (17,148) that were enrolled in a study to evaluate an E. coli O157:H7 siderophore receptor and porin (SRP®) vaccine (VAC) and a direct-fed microbial (DFM; 106 colony-forming units [CFU]/animal/day of Lactobacillus acidophilus and 109 CFU/animal/day of Propionibacterium freudenreichii). Cattle were randomly allocated to 40 pens within 10 complete blocks; pens were randomly assigned to control, VAC, DFM, or VAC+DFM treatments. Vaccine was administered on days 0 and 21, and DFM was fed throughout the study. Pen-floor fecal samples (30/pen) were collected weekly for the last 4 study weeks. Samples were enriched in E. coli broth and subjected to a multiplex polymerase chain reaction (PCR) designed to detect O26-specific wzx gene and four major virulence genes (stx1, stx2, eae, and ehxA) and to a culture-based procedure that involved immunomagnetic separation and plating on MacConkey agar. Ten presumptive E. coli colonies were randomly picked, pooled, and tested by the multiplex PCR. Pooled colonies positive for O26 serogroup were streaked on sorbose MacConkey agar, and 10 randomly picked colonies per sample were tested individually by the multiplex PCR. The overall prevalence of E. coli O26 was higher (p<0.001) by the culture-based method compared to the PCR assay (22.7 versus 10.5%). The interventions (VAC and or DFM) had no impact on fecal shedding of O26. Serogroup O26 was recovered in pure culture from 23.9% (260 of 1089) of O26 PCR-positive pooled colonies. Only 7 of the 260 isolates were positive for the stx gene and 90.1% of the isolates possessed an eaeβ gene that codes for intimin subtype β, but not the bfpA gene, which codes for bundle-forming pilus. Therefore, the majority of the O26 recovered from feedlot cattle feces was atypical enteropathogenic E. coli, and not STEC

Molecular mechanisms contributing to TARP regulation of channel conductance and polyamine block of calcium-permeable AMPA receptors.

Many properties of fast synaptic transmission in the brain are influenced by transmembrane AMPAR regulatory proteins (TARPs) that modulate the pharmacology and gating of AMPA-type glutamate receptors (AMPARs). Although much is known about TARP influence on AMPAR pharmacology and kinetics through their modulation of the extracellular ligand-binding domain (LBD), less is known about their regulation of the ion channel region. TARP-induced modifications in AMPAR channel behavior include increased single-channel conductance and weakened block of calcium-permeable AMPARs (CP-AMPARs) by endogenous intracellular polyamines. To investigate how TARPs modify ion flux and channel block, we examined the action of γ-2 (stargazin) on GluA1 and GluA4 CP-AMPARs. First, we compared the permeation of organic cations of different sizes. We found that γ-2 increased the permeability of several cations but not the estimated AMPAR pore size, suggesting that TARP-induced relief of polyamine block does not reflect altered pore diameter. Second, to determine whether residues in the TARP intracellular C-tail regulate polyamine block and channel conductance, we examined various γ-2 C-tail mutants. We identified the membrane proximal region of the C terminus as crucial for full TARP-attenuation of polyamine block, whereas complete deletion of the C-tail markedly enhanced the TARP-induced increase in channel conductance; thus, the TARP C-tail influences ion permeation. Third, we identified a site in the pore-lining region of the AMPAR, close to its Q/R site, that is crucial in determining the TARP-induced changes in single-channel conductance. This conserved residue represents a site of TARP action, independent of the AMPAR LBD

Wildcat wellness coaching feasibility trial: protocol for home-based health behavior mentoring in girls

Citation: Cull, B. J., Rosenkranz, S. K., Dzewaltowski, D. A., Teeman, C. S., Knutson, C. K., & Rosenkranz, R. R. (2016). Wildcat wellness coaching feasibility trial: protocol for home-based health behavior mentoring in girls. Pilot and Feasibility Studies, 2(1), 26. https://doi.org/10.1186/s40814-016-0066-yChildhood obesity is a major public health problem, with one third of America’s children classified as either overweight or obese. Obesity prevention and health promotion programs using components such as wellness coaching and home-based interventions have shown promise, but there is a lack of published research evaluating the impact of a combined home-based and wellness coaching intervention for obesity prevention and health promotion in young girls. The main objective of this study is to test the feasibility of such an intervention on metrics related to recruitment, intervention delivery, and health-related outcome assessments. The secondary outcome is to evaluate the possibility of change in health-related psychosocial, behavioral, and biomedical outcomes in our sample of participants

Emerging genetic technologies informing personalized medicine in SDS and other inherited bone marrow failure disorders

The ribosomopathy Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive inherited bone marrow failure syndrome (IBMFS) caused by mutations in the Shwachman-Bodian-Diamond syndrome (SBDS) gene, that is associated with an increased risk of myeloid malignancy. Tracking how hematopoietic stem cell (HSC) clonal dynamics change over time, assessing whether somatic genetic rescue mechanisms affect these dynamics, and mapping out when leukemic driver mutations are acquired is important to understand which individuals with SDS may go on to develop leukemia. In this review, we will discuss how new technologies that allow researchers to map mutations at the level of single HSC clones are generating important insights into genetic rescue mechanisms and their relative risk for driving evolution to leukemia, and how these data can inform the future development of personalized medicine approaches in SDS and other IBMFSs

Zero-shot interpretable phenotyping of postpartum hemorrhage using large language models

Many areas of medicine would benefit from deeper, more accurate phenotyping, but there are limited approaches for phenotyping using clinical notes without substantial annotated data. Large language models (LLMs) have demonstrated immense potential to adapt to novel tasks with no additional training by specifying task-specific instructions. Here we report the performance of a publicly available LLM, Flan-T5, in phenotyping patients with postpartum hemorrhage (PPH) using discharge notes from electronic health records (n = 271,081). The language model achieves strong performance in extracting 24 granular concepts associated with PPH. Identifying these granular concepts accurately allows the development of interpretable, complex phenotypes and subtypes. The Flan-T5 model achieves high fidelity in phenotyping PPH (positive predictive value of 0.95), identifying 47% more patients with this complication compared to the current standard of using claims codes. This LLM pipeline can be used reliably for subtyping PPH and outperforms a claims-based approach on the three most common PPH subtypes associated with uterine atony, abnormal placentation, and obstetric trauma. The advantage of this approach to subtyping is its interpretability, as each concept contributing to the subtype determination can be evaluated. Moreover, as definitions may change over time due to new guidelines, using granular concepts to create complex phenotypes enables prompt and efficient updating of the algorithm. Using this language modelling approach enables rapid phenotyping without the need for any manually annotated training data across multiple clinical use cases

Exploiting Single-Cell Tools in Gene and Cell Therapy.

Single-cell molecular tools have been developed at an incredible pace over the last five years as sequencing costs continue to drop and numerous molecular assays have been coupled to sequencing readouts. This rapid period of technological development has facilitated the delineation of individual molecular characteristics including the genome, transcriptome, epigenome, and proteome of individual cells, leading to an unprecedented resolution of the molecular networks governing complex biological systems. The immense power of single-cell molecular screens has been particularly highlighted through work in systems where cellular heterogeneity is a key feature, such as stem cell biology, immunology, and tumor cell biology. Single-cell-omics technologies have already contributed to the identification of novel disease biomarkers, cellular subsets, therapeutic targets and diagnostics, many of which would have been undetectable by bulk sequencing approaches. More recently, efforts to integrate single-cell multi-omics with single cell functional output and/or physical location have been challenging but have led to substantial advances. Perhaps most excitingly, there are emerging opportunities to reach beyond the description of static cellular states with recent advances in modulation of cells through CRISPR technology, in particular with the development of base editors which greatly raises the prospect of cell and gene therapies. In this review, we provide a brief overview of emerging single-cell technologies and discuss current developments in integrating single-cell molecular screens and performing single-cell multi-omics for clinical applications. We also discuss how single-cell molecular assays can be usefully combined with functional data to unpick the mechanism of cellular decision-making. Finally, we reflect upon the introduction of spatial transcriptomics and proteomics, its complementary role with single-cell RNA sequencing (scRNA-seq) and potential application in cellular and gene therapy

Unraveling the molecular interactions between α7 nicotinic receptor and a RIC3 variant associated with backward speech

Recent work putatively linked a rare genetic variant of the chaperone Resistant to Inhibitors of acetylcholinesterase (RIC3) (NM_024557.4:c.262G &gt; A, NP_078833.3:p.G88R) to a unique ability to speak backwards, a language skill that is associated with exceptional working memory capacity. RIC3 is important for the folding, maturation, and functional expression of α7 nicotinic acetylcholine receptors (nAChR). We compared and contrasted the effects of RIC3G88R on assembly, cell surface expression, and function of human α7 receptors using fluorescent protein tagged α7 nAChR and Förster resonance energy transfer (FRET) microscopy imaging in combination with functional assays and 125I-α-bungarotoxin binding. As expected, the wild-type RIC3 protein was found to increase both cell surface and functional expression of α7 receptors. In contrast, the variant form of RIC3 decreased both. FRET analysis showed that RICG88R increased the interactions between RIC3 and α7 protein in the endoplasmic reticulum. These results provide interesting and novel data to show that a RIC3 variant alters the interaction of RIC3 and α7, which translates to decreased cell surface and functional expression of α7 nAChR