USING TRANSFER PATH ANALYSIS AND FREQUENCY BASED SUBSTRUCTURING TO DEVELOP A ROBUST VIBRATION LABORATORY DYNAMIC TEST FIXTURE DESIGN PROCESS

The objective of this research is to determine a robust method for designing shock and vibration laboratory test fixtures that accurately reproduce the field environment for the component of interest. The methods presented in this research examine the boundary conditions presented unto the component of interest through transfer path analysis with the intent of reproducing the next-structure attachment impedance with a laboratory test fixture of one and two attachments. The first method includes only using the next-structure relative motion and stiffness to design a test fixture, while the second method uses an optimization algorithm to develop a lumped parameter model that produces equivalent attachment FRFs. Both methods are conducted and validated using the Box Assembly with Removable Component structure with two attachment locations fashioned by the Department of Energy’s Kansas City National Security Campus, operated and managed by Honeywell Federal Manufacturing & Technologies, LLC and Sandia National Laboratories

Once a feminist: Lynne Segal on Grace Paley’s The Little Disturbances of Man

The following contributions came in response to a request, sent to a number of key figures in feminism today, to write on a text that had been formative for their thinking as feminists. The chosen text could be a theory, a novel, an artwork, a performance, a poem: one that had stimulated, or even revolutionised, their ideas. As we hoped, this project has created a selection of texts central to our many and different experiences as feminists. I used to say that Margaret Drabble's The Garrick Year was the story of my life, in my early twenties, as if I was just a creature of time and circumstance. I read The Garrick Year sometime between October 1965, when my first child was born, and the end of 1967, before my marriage disintegrated. Like the heroine Emma Evans, I married a successful actor, had a child, and followed his career—which in the novel led Emma to Hereford for a summer season of plays

Multi-component Transparent Conducting Oxides: Progress in Materials Modelling

Transparent conducting oxides (TCOs) play an essential role in modern optoelectronic devices through their combination of electrical conductivity and optical transparency. We review recent progress in our understanding of multi-component TCOs formed from solid-solutions of ZnO, In2O3, Ga2O3 and Al2O3, with a particular emphasis on the contributions of materials modelling, primarily based on Density Functional Theory. In particular, we highlight three major results from our work: (i) the fundamental principles governing the crystal structures of multi-component oxide structures including (In2O3)(ZnO)n, named IZO, and (In2O3)m(Ga2O3)l(ZnO)n, named IGZO; (ii) the relationship between elemental composition and optical and electrical behaviour, including valence band alignments; (iii) the high-performance of amorphous oxide semiconductors. From these advances, the challenge of the rational design of novel electroceramic materials is discussed.Comment: Part of a themed issue of Journal of Physics: Condensed Matter on "Semiconducting Oxides". In Press (2011

Embedding clinical interventions into observational studies

Novel approaches to observational studies and clinical trials could improve the cost-effectiveness and speed of translation of research. Hybrid designs that combine elements of clinical trials with observational registries or cohort studies should be considered as part of a long-term strategy to transform clinical trials and epidemiology, adapting to the opportunities of big data and the challenges of constrained budgets. Important considerations include study aims, timing, breadth and depth of the existing infrastructure that can be leveraged, participant burden, likely participation rate and available sample size in the cohort, required sample size for the trial, and investigator expertise. Community engagement and stakeholder (including study participants) support are essential for these efforts to succeed

Этапные операции "damage control" при тяжелых повреждениях печени

Показана эффективность применения при тяжелых травмах печени этапных оперативных вмешательств "damage control", направленных на профилактику коагулопатии, полиорганной недостаточности, а также на уменьшение числа послеоперационных гнойно−септических осложнений и летальности.The efficacy of staged surgical procedures "damage control" aimed at prevention of coagulopathy, polyorgan insufficiency as well as the changes in the number of post−operative purulent septic complications and death is shown

Identification of a BRCA2-Specific modifier locus at 6p24 related to breast cancer risk

Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9×10−8). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer

Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic

BACKGROUND: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study\u27s objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines. METHODS: We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation. FINDINGS: There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p\u3c0.0001). Embolisation of ruptured aneurysms declined with 1170-1035 procedures, respectively, representing an 11.5% (95%CI -13.5% to -9.8%, p=0.002) relative drop. Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations, a 24.9% relative decline (95% CI -28.0% to -22.1%, p\u3c0.0001). A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1% (95% CI 32.3% to 50.6%, p=0.008) despite a decrease in SAH admissions in this tertile. INTERPRETATION: There was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways