A Pennsylvania State University/General Electric Get Away Special (GAS) experiment

We describe four student-designed experiments by the Pennsylvania State University, which are planned for a GAS canister. The four experiments will measure: the effects of radiation on semiconductors; orbital debris impacts; the Space Shuttle's magnetic field; and the photoelectric yield of several different materials. These experiments are the result of the efforts of more than one hundred students

The depositional history and evaluation of two late quaternary, diamondiferous pocket beaches, south-western Namibia

The two Late Quaternary, diamondiferous pocket beach deposits studied here are situated along a 10 km stretch of the storm-dominated, Atlantic coastline of the Sperrgebiet, south-western Namibia. The pocket beaches are approximately 130 km north of the Orange River mouth, which is widely accepted as a long-lived point source for diamonds sourced from the interior of southern Africa. A total of fourteen pocket beach deposits were recently evaluated in this area, but only two of these, namely Site 2 (to the south) and Site 3 (to the north), are considered here. The main diamondbearing horizons are beach gravels, which occur within, and form part of, the pocket beach sequences. The beach gravels are mostly blanketed by sand overburden, meaning that exposures available for study were limited, and much reliance was placed on borehole logging and observations of evaluation sample tailings. The main aims are to unravel the depositional history of the pocket beach sequences, identify the controls on diamond mineralisation in the beach gravels, and critically examine two different methods of estimating average diamond size for the deposits. In pursuit of these aims, sedimentological characteristics of the unconsolidated pocket beach deposits were recorded using small diameter drill holes, hydraulic grab bulk samples, trench exposures and surface outcrops. The surface geology, geomorphology and modern wave patterns were mapped using high-resolution, Airborne Laser Survey imagery coupled with extensive field checking. Three-dimensional geological modeling software was used to gain insight into the subsurface morphology of the deposits. Fossil shell samples were used to aid interpretation of ancient depositional environments and to date parts of the pocket beach sequences. Variations in diamond concentration and the size of diamonds were recorded using bulk samples, some of which were taken from a trench, but most of which were excavated using a hydraulic grab tool called the GB50. Finally, by using diamond size data from Site 3, sample data from diamondiferous beach gravels to the south of the study area and sample campaign simulations, two alternative methods of evaluating average diamond size in marine gravel deposits were appraised.The pocket beach sequences occur within north-south trending valleys of a major deflation basin and are separated from one another by rocky headlands. The ridge-and-valley topography of the deflation basin has resulted from differential erosion of Late Proterozoic basement rock units, alternating layers of which differ greatly in their resistance to the long-lived, local denudationalprocesses. On the basis of the stratigraphic information collected from the unconsolidated pocket beach valley fills, interpreted within the context of global, Late Pleistocene sea level records, the following depositional history is deduced : a) Deposition of sheetflood gravels by ephemeral streams, activated during a regressive phase. b) Transgression, culminating in the deposition of a gravel beach, representing a sea level highstand of +4 metres above mean sea level (mamsl) at between 120 000 and 130 000 BP. c)A regressive phase, resulting in deflation of former valley fills to the bedrock valley floor and accompanied by re-activation of ephemeral stream activity to form sheetflood deposits; this represents a protracted period of subaerial exposure of the +4 m gravel beach deposit. d) Deposition of a great volume of sediment in the valleys during the latter stages of the transgression from the Last Glacial Maximum (LGM). The sequence generated during this phase, which started at ca. 9 000 BP, contains : i) pan/coastal sabkha sediments, ii) shallow, sheltered bay sediments, iii) back-barrier lagoonal sediments, iv) a gravel beach deposit representing a sea level stillstand at -5 mamsl, laid down between 7 600 and 5 600 BP, v) another gravel beach deposit representing the well-known Middle Holocene sea level highstand at +2 to +3 mamsl, laid down at ca. 5 000 BP, and which terminated the transgression from the LGM. e) A minor regression to the current sea level, accompanied by progradation of the shoreline to its current position. This progradational marine unit consists almost entirely of sand and grit, reflecting the lack of gravel supply to this part of the coastline in the most recent past. f) Deposition of modern coastal dunes, which cap the pocket beach sequence and are the youngest sediments in the study area. Using trench and hydraulic grab evaluation sample results, in combination with analysis of wave patterns and field observations, the following local controls on the density distribution (ie. concentration) and size distribution of diamonds in the gravel beach deposits (+4, -5 and +2 to +3 mamsl stands) are recognised: a) Gravel beach depositional processes, which are responsible for clast sorting on the beach, have influenced the density and size distribution of diamonds. The infill zone, or beach toe, favours maximum diamond concentration while diamond size decreases from the imbricate zone (intertidal) to the infill zone (subtidal). b) Wave energy is identified as the dominant local control on diamond size distribution, but has also influenced diamond concentration to a limited degree. Larger diamonds are intimately associated with coarser beach gravels, both of which are a reflection of increased wave energy. Higher concentrations of diamonds are sometimes associated with zones of coarser gravel and therefore greater wave energy. c) The time of deposition of the host gravel beach is seen to be the dominant controlling factor with respect to diamond concentration. This is seen as evidence of significant temporal variation in the availability of diamonds in the littoral evironment. A significant reduction (20%) in average diamond size from Site 2 to Site 3, over a distance of only 6 km, is evident. The following were identified as reasons for this reduction in diamond size : a) Longshore sorting processes, of which the long-lived northerly littoral drift is a key part, are known to have played a role in the diminution of diamond size northwards from the Orange River mouth point source. However, it is believed that this can only partly account for the observed 20% reduction in diamond size. b) Input of sediment and smaller diamonds at Site 3, reworked out of an older, Eocene-aged marine succession in the hinterland, is recognised as a possible additional reason for the large reduction in diamond size from Site 2 to Site 3. It is also speculated that the large size of the pocket beach at Site 3, relative to Site 2, may have resulted in lower average wave energy at Site 3, with consequent reduced average diamond size. Diamond size in the beach gravels of Site 3, as well as in beach gravels elsewhere in the Sperrgebiet, is seen to be lognormally-distributed within geologically homogeneous zones. In theory, lognormal mean estimators represent the best method of estimating average diamond size in such cases, whereas the arithmetic mean estimator has the tendency to overestimate when large outlier values occur. Lognormal mean estimators have the added benefit of providing for the calculation of confidence limits, which are becoming increasingly more important as financial lending institutions insist on better quantification of the risk involved in resource estimates. Sample campaign simulations demonstrate, for the kinds of diamond size-frequency distributions typical of beach gravel deposits at Site 3, that there is no significant improvement in the accuracy of average diamond size estimates when lognormal mean estimators are used instead of the arithmetic mean estimator. This is because the variance (a ) of the diamond populations is low, and large outlier values are extremely unlikely to occur. However, simulation of a diamond population with high variance, drawn from a sample of beach gravels near the Orange River mouth, shows that lognormal estimators produce significantly more accurate results when a is large. Since individual diamond weights were not recorded during evaluation sampling of Site 3, numerical solution of lognormal estimators is not possible, and these would need to be solved using a less accurate graphical method. It is therefore recommended that individual diamond weights are recorded in future sampling campaigns, allowing for the use of lognormal mean estimators, and the calculation of confidence limits for average diamond size estimates.Thesis (MSc) -- Science, Geology, 200

Hybrid Processing Design for Multipair Massive MIMO Relaying with Channel Spatial Correlation

Massive multiple-input multiple-output (MIMO) avails of simple transceiver design which can tackle many drawbacks of relay systems in terms of complicated signal processing, latency, and noise amplification. However, the cost and circuit complexity of having one radio frequency (RF) chain dedicated to each antenna element are prohibitive in practice. In this paper, we address this critical issue in amplify-and-forward (AF) relay systems using a hybrid analog and digital (A/D) transceiver structure. More specifically, leveraging the channel long-term properties, we design the analog beamformer which aims to minimize the channel estimation error and remain invariant over a long timescale. Then, the beamforming is completed by simple digital signal processing, i.e., maximum ratio combining/maximum ratio transmission (MRC/MRT) or zero-forcing (ZF) in the baseband domain. We present analytical bounds on the achievable spectral efficiency taking into account the spatial correlation and imperfect channel state information at the relay station. Our analytical results reveal that the hybrid A/D structure with ZF digital processor exploits spatial correlation and offers a higher spectral efficiency compared to the hybrid A/D structure with MRC/MRT scheme. Our numerical results showcase that the hybrid A/D beamforming design captures nearly 95% of the spectral efficiency of a fully digital AF relaying topology even by removing half of the RF chains. It is also shown that the hybrid A/D structure is robust to coarse quantization, and even with 2-bit resolution, the system can achieve more than 93% of the spectral efficiency offered by the same hybrid A/D topology with infinite resolution phase shifters.Comment: 17 pages, 13 figures, to appear in IEEE Transactions on Communication

Genetic susceptibility, elevated blood pressure and risk of atrial fibrillation:A Mendelian randomization study

Background: Whether elevated blood pressure (BP) is a modifiable risk factor for atrial fibrillation (AF) is not established. We tested (1) whether the association between BP and risk of AF is causal, (2) whether it varies according to individual’s genetic susceptibility for AF, and (3) the extent to which specific BP-lowering drugs are expected to reduce this risk. Methods: First, causality of association was assessed through two-sample Mendelian randomization, using data from two independent genome-wide association studies that included a total of one million European population. Second, the UK Biobank data of 329,237 participants at baseline was used to study the effect of BP on AF according to genetic susceptibility of developing AF. Third, a possible treatment effect with major BP-lowering drug classes on AF risk was predicted through genetic variants in genes encode the therapeutic targets of each drug class. Estimated drug effects were compared with effects on incident coronary heart disease, for which direct trial evidence exists. Results: The two-sample Mendelian randomization analysis indicated that, on average, exposure to a higher systolic BP increased the risk of AF by 19% (odds ratio per each 10-mm Hg [OR]: 1.19 [1.12 to 1.27]). This association was replicated in the UK biobank using individual participant data. However, in a further genetic risk-stratified analysis, there was evidence for a linear gradient in the relative effects of systolic BP on AF; while there was no conclusive evidence of an effect in those with low genetic risk, a strong effect was observed among those with high genetic susceptibility for AF. The comparison of predicted treatment effects using genetic proxies for three main drug classes (angiotensin-converting enzyme inhibitors, beta-blockers and calcium channel blockers) suggested similar average effects for the prevention of atrial fibrillation and coronary heart disease. Conclusions: The effect of elevated BP on the risk of AF is likely to be causal, suggesting that BP-lowering treatment may be effective in AF prevention. However, average effects masked clinically important variations, with a more pronounced effect in individuals with high genetic susceptibility risk for AF

Blood pressure lowering and risk of new-onset type 2 diabetes:an individual participant data meta-analysis

Background Blood pressure lowering is an established strategy for preventing microvascular and macrovascular complications of diabetes, but its role in the prevention of diabetes itself is unclear. We aimed to examine this question using individual participant data from major randomised controlled trials. Methods We performed a one-stage individual participant data meta-analysis, in which data were pooled to investigate the effect of blood pressure lowering per se on the risk of new-onset type 2 diabetes. An individual participant data network meta-analysis was used to investigate the differential effects of five major classes of antihypertensive drugs on the risk of new-onset type 2 diabetes. Overall, data from 22 studies conducted between 1973 and 2008, were obtained by the Blood Pressure Lowering Treatment Trialists' Collaboration (Oxford University, Oxford, UK). We included all primary and secondary prevention trials that used a specific class or classes of antihypertensive drugs versus placebo or other classes of blood pressure lowering medications that had at least 1000 persons-years of followup in each randomly allocated arm. Participants with a known diagnosis of diabetes at baseline and trials conducted in patients with prevalent diabetes were excluded. For the one-stage individual participant data meta-analysis we used stratified Cox proportional hazards model and for the individual participant data network meta-analysis we used logistic regression models to calculate the relative risk (RR) for drug class comparisons. Findings 145 939 participants (88 500 [60.6%] men and 57 429 [39.4%] women) from 19 randomised controlled trials were included in the one-stage individual participant data meta-analysis. 22 trials were included in the individual participant data network meta-analysis. After a median follow-up of 4.5 years (IQR 2.0), 9883 participants were diagnosed with new-onset type 2 diabetes. Systolic blood pressure reduction by 5 mm Hg reduced the risk of type 2 diabetes across all trials by 11% (hazard ratio 0.89 [95% CI 0.84-0.95]). Investigation of the effects of five major classes of antihypertensive drugs showed that in comparison to placebo, angiotensin-converting enzyme inhibitors (RR 0.84 [95% 0.76-0.93]) and angiotensin II receptor blockers (RR 0.84 [0.76-0.92]) reduced the risk of new-onset type 2 diabetes; however, the use of beta blockers (RR 1.48 [1.27-1.72]) and thiazide diuretics (RR 1.20 [1.07-1.35]) increased this risk, and no material effect was found for calcium channel blockers (RR 1.02 [0.92-1.13]). Interpretation Blood pressure lowering is an effective strategy for the prevention of new-onset type 2 diabetes. Established pharmacological interventions, however, have qualitatively and quantitively different effects on diabetes, likely due to their differing off-target effects, with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers having the most favourable outcomes. This evidence supports the indication for selected classes of antihypertensive drugs for the prevention of diabetes, which could further refine the selection of drug choice according to an individual's clinical risk of diabetes

Comparing the Phenylalanine/Tyrosine Pathway and Related Factors between Keratopathy and No-Keratopathy Groups as Well as between Genders in Alkaptonuria during Nitisinone Treatment

Nitisinone (NIT) causes tyrosinaemia and corneal keratopathy (KP), especially in men. However, the adaptation within the phenylalanine (PHE)/tyrosine (TYR) catabolic pathway during KP is not understood. The objective of this study is to assess potential differences in the PHE/TYR pathway during KP and the influence of gender in NIT-induced tyrosinaemia in alkaptonuria (AKU). Samples of serum and 24 h urine collected from patients treated with NIT during a 4-year randomized study in NIT vs. no-treatment controls (SONIA 2; Suitability Of Nitisinone In Alkaptonuria 2; EudraCT no. 2013-001633-41) at months 3 (V2), 12 (V3), 24 (V4), 36 (V5) and 48 (V6) were included in these analyses. Homogentisic acid (HGA), TYR, PHE, hydroxyphenylpyruvate (HPPA), hydroxyphenyllactate (HPLA) and sNIT were analysed at all time-points in serum and urine in the NIT-group. All statistical analyses were post hoc. Keratopathy occurred in 10 out of 69 AKU patients, eight of them male. Thirty-five sampling points (serum and 24 h urine) were analysed in patients experiencing KP and 272 in those with no-KP (NKP) during NIT therapy. The KP group had a lower HPLA/TYR ratio and a higher TYR/PHE ratio compared with the NKP group (p < 0.05 for both). There were 24, 45, 100 and 207 sampling points (serum and 24 h urine) in the NIT group which were pre-NIT female, pre-NIT male, NIT female and NIT male, respectively. The PHE/TYR ratio and the HPLA/TYR ratio were lower in males (p < 0.001 and p < 0.01, respectively). In the KP group and in the male group during NIT therapy, adaptive responses to minimise TYR formation were impaired compared to NKP group and females, respectively

Using positional information to provide context for biological image analysis with MorphoGraphX 2.0

Positional information is a central concept in developmental biology. In developing organs, positional information can be idealized as a local coordinate system that arises from morphogen gradients controlled by organizers at key locations. This offers a plausible mechanism for the integration of the molecular networks operating in individual cells into the spatially-coordinated multicellular responses necessary for the organization of emergent forms. Understanding how positional cues guide morphogenesis requires the quantification of gene expression and growth dynamics in the context of their underlying coordinate systems. Here we present recent advances in the MorphoGraphX software (Barbier de Reuille et al., 2015)⁠ that implement a generalized framework to annotate developing organs with local coordinate systems. These coordinate systems introduce an organ-centric spatial context to microscopy data, allowing gene expression and growth to be quantified and compared in the context of the positional information thought to control them

LEARN: A multi-centre, cross-sectional evaluation of Urology teaching in UK medical schools

OBJECTIVE: To evaluate the status of UK undergraduate urology teaching against the British Association of Urological Surgeons (BAUS) Undergraduate Syllabus for Urology. Secondary objectives included evaluating the type and quantity of teaching provided, the reported performance rate of General Medical Council (GMC)-mandated urological procedures, and the proportion of undergraduates considering urology as a career. MATERIALS AND METHODS: LEARN was a national multicentre cross-sectional study. Year 2 to Year 5 medical students and FY1 doctors were invited to complete a survey between 3rd October and 20th December 2020, retrospectively assessing the urology teaching received to date. Results are reported according to the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). RESULTS: 7,063/8,346 (84.6%) responses from all 39 UK medical schools were included; 1,127/7,063 (16.0%) were from Foundation Year (FY) 1 doctors, who reported that the most frequently taught topics in undergraduate training were on urinary tract infection (96.5%), acute kidney injury (95.9%) and haematuria (94.4%). The most infrequently taught topics were male urinary incontinence (59.4%), male infertility (52.4%) and erectile dysfunction (43.8%). Male and female catheterisation on patients as undergraduates was performed by 92.1% and 73.0% of FY1 doctors respectively, and 16.9% had considered a career in urology. Theory based teaching was mainly prevalent in the early years of medical school, with clinical skills teaching, and clinical placements in the later years of medical school. 20.1% of FY1 doctors reported no undergraduate clinical attachment in urology. CONCLUSION: LEARN is the largest ever evaluation of undergraduate urology teaching. In the UK, teaching seemed satisfactory as evaluated by the BAUS undergraduate syllabus. However, many students report having no clinical attachments in Urology and some newly qualified doctors report never having inserted a catheter, which is a GMC mandated requirement. We recommend a greater emphasis on undergraduate clinical exposure to urology and stricter adherence to GMC mandated procedures

COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records

BACKGROUND: Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. METHODS: In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. FINDINGS: Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12·7% during the study period. Of 7 244 925 individuals, 460 737 (6·4%) were admitted to hospital and 158 020 (2·2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10·6%) were admitted to the intensive care unit (ICU), 69 090 (15·0%) received non-invasive ventilation, and 25 928 (5·6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30·4%] of 77 202 patients) than wave 2 (44 220 [23·1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50·7%] of 5063 patients). 15 486 (9·8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6·9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1. INTERPRETATION: Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources. FUNDING: British Heart Foundation Data Science Centre, led by Health Data Research UK