Cost-effective use of liquid nitrogen in cryogenic wind tunnels, phase 2

Cryogenic seal tests were performed and Rulon A was selected for the subject nutating positive displacement expander. A four-chamber expander was designed and fabricated. A nitrogen reliquefier flow system was also designed and constructed for testing the cold expander. Initial tests were unsatisfactory because of high internal friction attributed to nutating Rulon inlet and outlet valve plates. Replacement of the nutating valves with cam-actuated poppet valves improved performance. However, no net nitrogen reliquefaction was achieved due to high internal friction. Computer software was developed for accurate calculation of nitrogen reliquefaction from a system such as that proposed. These calculations indicated that practical reliquefaction rates of 15 to 19 percent could be obtained. Due to mechanical problems, the nutating expander did not demonstrate its feasibility nor that of the system. It was concluded that redesign and testing of a smaller nutating expander was required to prove concept feasibility

Summary of second annual MCBK public meeting: Mobilizing Computable Biomedical Knowledge—A movement to accelerate translation of knowledge into action

The volume of biomedical knowledge is growing exponentially and much of this knowledge is represented in computer executable formats, such as models, algorithms and programmatic code. There is a growing need to apply this knowledge to improve health in Learning Health Systems, health delivery organizations, and other settings. However, most organizations do not yet have the infrastructure required to consume and apply computable knowledge, and national policies and standards adoption are not sufficient to ensure that it is discoverable and used safely and fairly, nor is there widespread experience in the process of knowledge implementation as clinical decision support. The Mobilizing Computable Biomedical Knowledge (MCBK) community formed in 2016 to address these needs. This report summarizes the main outputs of the Second Annual MCBK public meeting, which was held at the National Institutes of Health on July 18‐19, 2019 and brought together over 150 participants from various domains to frame and address important dimensions for mobilizing CBK.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154970/1/lrh2-sup-0001-supinfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154970/2/lrh210222.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154970/3/lrh210222_am.pd

Electronic nutritional intake assessment in patients with urolithiasis: A decision impact analysis

Purpose: To evaluate a physician’s impression of a urinary stone patient’s dietary intake and whether it was dependent on the medium through which the nutritional data were obtained. Furthermore, we sought to determine if using an electronic food frequency questionnaire (FFQ) impacted dietary recommendations for these patients. Materials and Methods: Seventy-six patients attended the Stone Clinic over a period of 6 weeks. Seventy-five gave consent for enrollment in our study. Patients completed an office-based interview with a fellowship-trained endourologist, and a FFQ administered on an iPad. The FFQ assessed intake of various dietary components related to stone development, such as oxalate and calcium. The urologists were blinded to the identity of patients’ FFQ results. Based on the office-based interview and the FFQ results, the urologists provided separate assessments of the impact of nutrition and hydration on the patient’s stone disease (nutrition impact score and hydration impact score, respectively) and treatment recommendations. Multivariate logistic regressions were used to compare pre-FFQ data to post-FFQ data. Results: Higher FFQ scores for sodium (odds ratio [OR], 1.02; p=0.02) and fluids (OR, 1.03, p=0.04) were associated with a higher nutritional impact score. None of the FFQ parameters impacted hydration impact score. A higher FFQ score for oxalate (OR, 1.07; p=0.02) was associated with the addition of at least one treatment recommendation. Conclusions: Information derived from a FFQ can yield a significant impact on a physician’s assessment of stone risks and decision for management of stone disease

High Efficiency Planar Geometry Germanium-on-silicon Single-photon Avalanche Diode Detectors

This paper presents the performance of 26 μm and 50 μm diameter planar Ge-on-Si single-photon avalanche diode (SPAD) detectors. The addition of germanium in these detectors extends the spectral range into the short-wave infrared (SWIR) region, beyond the capability of already well-established Si SPAD devices. There are several advantages for extending the spectral range into the SWIR region including: reduced eye-safety laser threshold, greater attainable ranges, and increased depth resolution in range finding applications, in addition to the enhanced capability to image through obscurants such as fog and smoke. The time correlated single-photon counting (TCSPC) technique has been utilized to observe record low dark count rates, below 100 kHz at a temperature of 125 K for up to a 6.6 % excess bias, for the 26 μm diameter devices. Under identical experimental conditions, in terms of excess bias and temperature, the 50 μm diameter device consistently demonstrates dark count rates a factor of 4 times greater than 26 μm diameter devices, indicating that the dark count rate is proportional to the device volume. Single-photon detection efficiencies of up to ~ 29 % were measured at a wavelength of 1310 nm at 125 K. Noise equivalent powers (NEP) down to 9.8 × 10-17 WHz-1/2 and jitters < 160 ps are obtainable, both significantly lower than previous 100 μm diameter planar geometry devices, demonstrating the potential of these devices for highly sensitive and high-speed imaging in the SWIR

Toward System Change to Tackle Antimicrobial Resistance: Improving the Voluntary Stewardship of Antimicrobials in US Agriculture

From Executive Summary:This report presents the details of a research study looking at the potential for improving voluntary stewardship of antimicrobials in US agriculture, in the interests of tackling antimicrobial resistance (AMR). Failure to address AMR could lead to significant impacts on both human and animal health. Voluntary stewardship is an approach that relies on the willingness of food-animal producers and supportive industries (e.g., veterinary services and pharmaceutical companies), as well as broader stakeholders (e.g., public health policymakers and consumer advocates), to ensure the judicious use of antimicrobials without the need for regulation, legislation, mandatory compliance or statutory enforcement

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study

It is well known that inbreeding increases the risk of recessive monogenic diseases, but it is less certain whether it contributes to the etiology of complex diseases such as schizophrenia. One way to estimate the effects of inbreeding is to examine the association between disease diagnosis and genome-wide autozygosity estimated using runs of homozygosity (ROH) in genome-wide single nucleotide polymorphism arrays. Using data for schizophrenia from the Psychiatric Genomics Consortium (n = 21,868), Keller et al. (2012) estimated that the odds of developing schizophrenia increased by approximately 17% for every additional percent of the genome that is autozygous (β = 16.1, CI(β) = [6.93, 25.7], Z = 3.44, p = 0.0006). Here we describe replication results from 22 independent schizophrenia case-control datasets from the Psychiatric Genomics Consortium (n = 39,830). Using the same ROH calling thresholds and procedures as Keller et al. (2012), we were unable to replicate the significant association between ROH burden and schizophrenia in the independent PGC phase II data, although the effect was in the predicted direction, and the combined (original + replication) dataset yielded an attenuated but significant relationship between Froh and schizophrenia (β = 4.86,CI(β) = [0.90,8.83],Z = 2.40,p = 0.02). Since Keller et al. (2012), several studies reported inconsistent association of ROH burden with complex traits, particularly in case-control data. These conflicting results might suggest that the effects of autozygosity are confounded by various factors, such as socioeconomic status, education, urbanicity, and religiosity, which may be associated with both real inbreeding and the outcome measures of interest

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Age at first birth in women is genetically associated with increased risk of schizophrenia

Prof. Paunio on PGC:n jäsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe