Physiological measurement of the push-pull effect during flight

The Push-pull In-flight Research Program was a Canadian Forces sponsored set of experiments conducted during flight to investigate the bodily responses to +gz exposure when preceded by low, or negative, gz exposure. This type of exposure is known as the push-pull manoeuvre. It has been hypothesized that the physiological responses of the human body to this manoeuvre can lessen an individual pilot\u27s g tolerance, thereby making him or her more susceptible to g-induced loss of consciousness. The overall aim of this thesis was to instrument an aircraft and perform in-flight research to collect data for evaluation of this hypothesis. As a joint research venture, the Aerospace Engineering Test Establishment, in conjunction with the Defence and Civil Institute of Environmental Medicine, performed a series of in-flight trials using a highly-instrumented CF-18 aircraft to gather physiological data on a wide spectrum of test subjects. The end-goal of this flight testing and follow-on research is to design a microprocessor controlled anti-g valve for future use in high-performance aircraft. This thesis evaluates the instrumentation approach, test procedures, and data gathering conducted during this test program. Preliminary results indicate the existence of a push-pull effect. Specific attention is given to the difficulties encountered with conducting experimental physiological research in an ejection seat equipped, high-performance fighter aircraft, and the methods and equipment developed to overcome these challenges

Surface passivation of c-Si by atmospheric pressure chemical vapor deposition of Al2O3

Atmospheric pressure chemical vapor deposition of Al₂O₃ is shown to provide excellent passivation of crystalline silicon surfaces.Surface passivation,permittivity, and refractive index are investigated before and after annealing for deposition temperatures between 330 and 520 °C. Deposition temperatures >440 °C result in the best passivation, due to both a large negative fixed charge density (∼2 × 10¹² cm⁻²) and a relatively low interface defect density (∼1 × 10¹¹ eV⁻¹ cm⁻²), with or without an anneal. The influence of deposition temperature on film properties is found to persist after subsequent heat treatment. Correlations between surface passivation properties and the permittivity are discussed

On effective surface recombination parameters

This paper examines two effective surface recombination parameters: the effective surface recombination velocity Seff and the surface saturation current density J0 s . The dependence of Seff and J0 s on surface charge Q, surface dopant concentration Ns , and interface parameters is derived. It is shown that for crystalline silicon at 300 K in low-injection, Seff is independent of Ns only when Q²/Ns   1.5 × 10⁷ cm for accumulation and Q¹˙⁸⁵ /Ns  > 1.5 × 10⁶ cm for inversion. These conditions are commonly satisfied in undiffused wafers but rarely in diffused wafers. We conclude that for undiffused silicon, J0 s is superior to the conventional Seff as a metric for quantifying the surface passivation, whereas for diffused silicon, the merit in using J0 s or Seff (or neither) depends on the sample. Experimental examples are given that illustrate the merits and flaws of J0 s and Seff

Effect of boron concentration on recombination at the p-Si–Al2O3 interface

We examine the surface passivation properties of Al₂O₃ deposited on boron-doped planar crystalline silicon surfaces as a function of the boron concentration. Both uniformly doped and diffused surfaces are studied, with surface boron concentrations ranging from 9.2 × 10¹⁵ to 5.2 × 10¹⁹ cm⁻³. Atmospheric pressure chemical vapor deposition and thermal atomic layer deposition are used to deposit the Al₂O₃ films. The surface recombination rate of each sample is determined from photoconductance measurements together with the measured dopant profiles via numerical simulation, using the latest physical models. These values are compared with calculations based on the interface properties determined from capacitance–voltage and conductance measurements. It is found that the fundamental surface recombination velocity of electrons, Sn 0 , which describes the chemical passivation of the interface, is independent of the surface boron concentration Ns for Ns  ≤ 3 × 10¹⁹ cm⁻³, and in excellent agreement with values calculated from the interface state density Dit and capture coefficients cn and cp measured on undiffused boron-doped surfaces. We conclude that the physical properties of the Si– Al₂O₃ interface are independent of the boron dopant concentration over this range

Improved silicon surface passivation of APCVD Al2O3 by rapid thermal annealing

Short-duration post-deposition thermal treatments at temperatures above those normally used for annealing activation have the potential to further improve the already excellent passivation of crystalline silicon (c-Si) achieved by Al2O3, but have so far received little attention. In this work we investigate the influence of rapid thermal annealing (RTA) on the surface passivation of c-Si by Al2O3 deposited by atmospheric pressure chemical vapour deposition (APCVD) as a function of RTA peak temperature between 500 and 900 °C, and for Al2O3 deposition temperatures between 325 and 440 °C. The saturation current density J0 of undiffused p-type surfaces is observed either to increase or decrease following RTA depending on the Al2O3 deposition temperature and the RTA peak temperature. The optimum deposition temperature depends on the post-deposition thermal processing to be applied. Films deposited at lower temperatures provide worse passivation after low temperature heat treatment, but maintain this passivation better at higher RTA temperatures. An exceptionally low J0 of 7 fA cm−2, due to the combination of a very low interface state density Dit and unusually high negative fixed charge density Qf, is achieved by the use of a short 500–550 °C RTA combined with optimised deposition conditions

Evolution of late-stage metastatic melanoma is dominated by aneuploidy and whole genome doubling

Although melanoma is initiated by acquisition of point mutations and limited focal copy number alterations in melanocytes-of-origin, the nature of genetic changes that characterise lethal metastatic disease is poorly understood. Here, we analyze the evolution of human melanoma progressing from early to late disease in 13 patients by sampling their tumours at multiple sites and times. Whole exome and genome sequencing data from 88 tumour samples reveals only limited gain of point mutations generally, with net mutational loss in some metastases. In contrast, melanoma evolution is dominated by whole genome doubling and large-scale aneuploidy, in which widespread loss of heterozygosity sculpts the burden of point mutations, neoantigens and structural variants even in treatment-naïve and primary cutaneous melanomas in some patients. These results imply that dysregulation of genomic integrity is a key driver of selective clonal advantage during melanoma progression

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Genetic architecture of subcortical brain structures in 38,851 individuals

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease