Degradation of temporal contrast from post-pedestal interference with a chirped pulse in an optical parametric amplifier.

Pre-pedestal generation is observed in a 0.35-PW laser front end coming from a post-pedestal via instantaneous gain and pump depletion in an optical parametric amplifier during chirped-pulse amplification. Generalized simulations show how this effect arises from gain nonlinearity and applies to all optical parametric chirped-pulse-amplification systems with a post-pedestal. An experiment minimizing the effect of B-integral is used to isolate and study the newly observed conversion of a continuous post-pedestal into a continuous pre-pedestal. Matching numerical simulations confirm experimental results and additionally reveal how third-order dispersion largely controls the slope of the generated pre-pedestal.

Global forecasts in reservoir computers.

A reservoir computer is a machine learning model that can be used to predict the future state(s) of time-dependent processes, e.g., dynamical systems. In practice, data in the form of an input-signal are fed into the reservoir. The trained reservoir is then used to predict the future state of this signal. We develop a new method for not only predicting the future dynamics of the input-signal but also the future dynamics starting at an arbitrary initial condition of a system. The systems we consider are the Lorenz, Rossler, and Thomas systems restricted to their attractors. This method, which creates a global forecast, still uses only a single input-signal to train the reservoir but breaks the signal into many smaller windowed signals. We examine how well this windowed method is able to forecast the dynamics of a system starting at an arbitrary point on a system's attractor and compare this to the standard method without windows. We find that the standard method has almost no ability to forecast anything but the original input-signal while the windowed method can capture the dynamics starting at most points on an attractor with significant accuracy.

Final amplifier of an ultra-intense all-OPCPA system with 13-J output signal energy and 41% pump-to-signal conversion efficiency.

Optical parametric chirped-pulse amplification (OPCPA) using high-energy Nd:glass lasers has the potential to produce ultra-intense pulses (>1023 W/cm2). We report on the performance of the final high-efficiency amplifier in an OPCPA system based on large-aperture (63 × 63-mm2) partially deuterated potassium dihydrogen phosphate (DKDP) crystals. The seed beam (180-nm bandwidth, 110 mJ) was provided by the preceding OPCPA stages. A maximum pump-to-signal conversion efficiency of 41% and signal energy up to 13 J were achieved with a 52-mm-long DKDP crystal due to the flattop super-Gaussian pump beam profile and flat-in-time pulse shape.

Achieving 100 GW idler pulses from an existing petawatt optical parametric chirped pulse amplifier.

Optical parametric chirped-pulse-amplification produces two broadband pulses, a signal and an idler, that can both provide peak powers >100 GW. In most cases the signal is used, but compressing the longer-wavelength idler opens up opportunities for experiments where the driving laser wavelength is a key parameter. This paper will describe several subsystems that were added to a petawatt class, Multi-Terawatt optical parametric amplifier line (MTW-OPAL) at the Laboratory for Laser Energetics to address two long-standing issues introduced by the use of the idler, angular dispersion, and spectral phase reversal. To the best of our knowledge, this is the first time that compensation of angular dispersion and phase reversal has been achieved in a single system and results in a 100 GW, 120-fs duration, pulse at 1170 nm.

Effect of the pump beam profile and wavefront on the amplified signal wavefront in optical parametric amplifiers.

We present a theoretical and experimental analysis of the signal phase introduced by the pump-beam wavefront and spatial profile during optical parametric amplification (OPA) process. The theory predicts the appearance of an additional wavefront in the amplified signal beam that is proportional to the spatial derivative of the pump-beam wavefront. The effect of the pump-beam profile on the signal-beam wavefront is also investigated. Our experiments tested these theoretical predictions by comparing the wavefront of the signal beam before and after amplification in a multi-joule broadband OPA. The measured signal wavefront was shown to have the expected dependence on the pump-beam profile and wavefront. These results can be considered when designing petawatt-scale ultrabroadband optical parametric chirped-pulse-amplification systems.

Collegiate male athletes exhibit conditions of the Male Athlete Triad.

The primary purpose of this study was to determine prevalence of the Male Athlete Triad (MAT) conditions: low energy availability (EA), low bone mineral density (BMD), and low testosterone in male collegiate athletes from different sports. Participants included 44 collegiate male athletes (age, 20.4 ± 0.2 years; body mass index, 25.3 ± 1.3 kg/m2) from 7 sports (cross country, soccer, basketball, wrestling, track, golf, and baseball). Resting metabolic rate, 3-day food intake, 7-day exercise energy expenditure, body composition, and reproductive and metabolic hormones were assessed. Of the total participants, 15% had low EA, 0% had low BMD, 28% had low total testosterone (TT), and 80% had low calculated free testosterone (cFT). There were no significant correlations between EA, BMD, TT, and cFT. Insulin and sex hormone binding globulin (SHBG) were below and on the upper end of the reference range for healthy male adults, respectively. Insulin was negatively correlated with total (r = -0.330, p = 0.043) and lumbar spine BMD z-scores (r = -0.413, p = 0.010). Low TT and low cFT were the most prevalent MAT conditions among all athletes. Further research should investigate the relationship between insulin and SHBG and the role of these hormones in the MAT. Novelty: Assessment of energy availability alone is not sufficient to identify physiological disturbances in collegiate male athletes. Low total and/or free testosterone may be present in some collegiate male athletes, regardless of BMD status. Low insulin and high SHBG concentration may portray the presence of conditions of the MAT in male collegiate athletes.

Analysis of pump-to-signal noise transfer in two-stage ultra-broadband optical parametric chirped-pulse amplification.

In optical parametric chirped-pulse amplification (OPCPA), pump temporal intensity modulation is transferred to the chirped-signal spectrum via instantaneous parametric gain and results in contrast degradation of the recompressed signal. We investigate, for the first time to our knowledge, the pump-to-signal noise transfer in a two-stage ultra-broadband OPCPA pumped by a single laser and show the dependence of pump-induced signal noise, characterized both before and after pulse compression, on the difference in pump-seed delay in the two stages. We demonstrate an up-to-15-dB reduction of the pump-induced contrast degradation via pump-seed delay optimization. Experiments and simulations show that, even when parametric amplifiers are operated in saturation, the pump-seed delay can be used to minimize the pump-induced contrast degradation that is attributed largely to the noises from the unsaturated edges of the pulse and that of the beam.

Looking down: a model for visual route following in flying insects.

Insect visual navigation is often assumed to depend on panoramic views of the horizon, and how these change as the animal moves. However, it is known that honey bees can visually navigate in flat, open meadows where visual information at the horizon is minimal, or would remain relatively constant across a wide range of positions. In this paper we hypothesise that these animals can navigate using view memories of the ground. We find that in natural scenes, low resolution views from an aerial perspective of ostensibly self-similar terrain (e.g. within a field of grass) provide surprisingly robust descriptors of precise spatial locations. We propose a new visual route following approach that makes use of transverse oscillations to centre a flight path along a sequence of learned views of the ground. We deploy this model on an autonomous quadcopter and demonstrate that it provides robust performance in the real world on journeys of up to 30 m. The success of our method is contingent on a robust view matching process which can evaluate the familiarity of a view with a degree of translational invariance. We show that a previously developed wavelet based bandpass orientated filter approach fits these requirements well, exhibiting double the catchment area of standard approaches. Using a realistic simulation package, we evaluate the robustness of our approach to variations in heading direction and aircraft height between inbound and outbound journeys. We also demonstrate that our approach can operate using a vision system with a biologically relevant visual acuity and viewing direction.

Sentinel lymph node biopsy for melanoma of the head and neck: a multicentre study to examine safety, efficacy, and prognostic value.

Sentinel lymph node biopsy (SLNB) is an accurate staging procedure for malignant melanoma but its use in patients with melanoma of the head and neck has been questioned in the past because of a perceived record of poor safety and accuracy. Technical improvements have sought to redress this. Vital structures and variable lymphatic pathways can make its use in the head and neck challenging. In our study we have examined the data and the experiences of clinicians from University Hospital Southampton and the Royal Surrey County Hospital. We retrospectively analysed the data and case notes of 143 patients who had SLNB to establish its safety, efficacy, and prognostic value. The detection rate of at least one sentinel lymph node was 100%. Nodes positive for metastatic melanoma were found in 20% of patients. Of them, 76% went on to have completion lymphadenectomy. Multivariate Cox regression analysis suggested that positive SLNB was a strong predictor of reduced overall survival for all Breslow-thickness melanomas (HR=3.9, p=0.019) and intermediate melanomas (HR=6.3, p=0.007). It predicted reduced recurrence-free survival for all melanomas (HR=7.4, p<0.001) and was a strong predictor for those of intermediate thickness (HR=8.3, p<0.001). The false negative rate was 9.4% and false omission rate 2.6%. Temporary and permanent morbidity rates were 2.1% and 0%, respectively. SLNB for melanoma in the head and neck is a safe, accurate staging procedure that offers prognostically useful information. The upstaging of disease allows access to trial-based targeted treatments.

Simulation of grating compressor misalignment tolerances and mitigation strategies for chirped-pulse-amplification systems of varying bandwidths and beam sizes.

The effects of pulse compressor grating misalignment on pulse duration and focusability are simulated for chirped-pulse-amplification systems of varying bandwidths, beam sizes, groove densities, and incident angles. Tilt-alignment tolerances are specified based on a 2 drop in focused intensity, illustrating how tolerances scale with bandwidth and compressor beam size, which scales with energy when transformed via known grating damage thresholds. Grating-alignment tolerance scaling with grating groove density and incident/diffracted angles is investigated and applied to compressor design. A correlation between grating tip and in-plane rotation error sensitivity is defined and used to compensate residual out-of-plane angular dispersion, even for ultra-broadband pulses. Simulation of dispersion compensation methods after grating misalignment is shown to mitigate pulse lengthening, limited by temporal contrast degradation and higher-order effects for ultrabroad bandwidths.

Housing: A Case for The Medicalization of Poverty.

"Medicalization" has been a contentious notion since its introduction centuries ago. While some scholars lamented a medical overreach into social domains, others hailed its promise for social justice advocacy. Against the backdrop of a growing commitment to health equity across the nation, this article reviews historical interpretations of medicalization, offers an application of the term to non-biologic risk factors for disease, and presents the case of housing the demonstrate the great potential of medicalizing poverty.

Polygenic risk for severe psychopathology among Europeans is associated with major depressive disorder in Han Chinese women.

BACKGROUND: Previous studies have demonstrated that several major psychiatric disorders are influenced by shared genetic factors. This shared liability may influence clinical features of a given disorder (e.g. severity, age at onset). However, findings have largely been limited to European samples; little is known about the consistency of shared genetic liability across ethnicities. METHOD: The relationship between polygenic risk for several major psychiatric diagnoses and major depressive disorder (MDD) was examined in a sample of unrelated Han Chinese women. Polygenic risk scores (PRSs) were generated using European discovery samples and tested in the China, Oxford, and VCU Experimental Research on Genetic Epidemiology [CONVERGE (maximum N = 10 502)], a sample ascertained for recurrent MDD. Genetic correlations between discovery phenotypes and MDD were also assessed. In addition, within-case characteristics were examined. RESULTS: European-based polygenic risk for several major psychiatric disorder phenotypes was significantly associated with the MDD case status in CONVERGE. Risk for clinically significant indicators (neuroticism and subjective well-being) was also associated with case-control status. The variance accounted for by PRS for both psychopathology and for well-being was similar to estimates reported for within-ethnicity comparisons in European samples. However, European-based PRS were largely unassociated with CONVERGE family history, clinical characteristics, or comorbidity. CONCLUSIONS: The shared genetic liability across severe forms of psychopathology is largely consistent across European and Han Chinese ethnicities, with little attenuation of genetic signal relative to within-ethnicity analyses. The overall absence of associations between PRS for other disorders and within-MDD variation suggests that clinical characteristics of MDD may arise due to contributions from ethnicity-specific factors and/or pathoplasticity.

Comprehensive population screening in the Ashkenazi Jewish population for recurrent disease-causing variants.

The Ashkenazi Jewish (AJ) population has an increased risk for a variety of recessive diseases due to historical founder effects and genetic drift. For some, the disease-causing founder mutations have been identified and well-characterized, but for others, further study is necessary. The purpose of this study is to assess the carrier frequencies of 85 pathogenic variants causative of 29 recessive conditions in the AJ population. Up to 3000 AJ individuals were genotyped by Luminex MagPlex® -TAG™ bead array or Agena Bioscience™ MassARRAY assays. We identified seven conditions with carrier frequencies higher than 1 in 100, nine between 1 in 100 and 1 in 200, and four between 1 in 200 and 1 in 500. Variants in nine conditions had a detected carrier rate of less than 1 in 500 or were not identified in approximately 2000 AJ individuals. We assessed the combined AJ carrier frequency for 18 relatively prevalent diseases to be 1 in 6, and the risk of AJ individuals to be a carrier couple for one of these 18 diseases as 1 in 441. We note additional recessive genetic conditions should be considered for AJ carrier screening panels.

SNP-based heritability estimates of the personality dimensions and polygenic prediction of both neuroticism and major depression: findings from CONVERGE.

Biometrical genetic studies suggest that the personality dimensions, including neuroticism, are moderately heritable (~0.4 to 0.6). Quantitative analyses that aggregate the effects of many common variants have recently further informed genetic research on European samples. However, there has been limited research to date on non-European populations. This study examined the personality dimensions in a large sample of Han Chinese descent (N=10 064) from the China, Oxford, and VCU Experimental Research on Genetic Epidemiology study, aimed at identifying genetic risk factors for recurrent major depression among a rigorously ascertained cohort. Heritability of neuroticism as measured by the Eysenck Personality Questionnaire (EPQ) was estimated to be low but statistically significant at 10% (s.e.=0.03, P=0.0001). In addition to EPQ, neuroticism based on a three-factor model, data for the Big Five (BF) personality dimensions (neuroticism, openness, conscientiousness, extraversion and agreeableness) measured by the Big Five Inventory were available for controls (n=5596). Heritability estimates of the BF were not statistically significant despite high power (>0.85) to detect heritabilities of 0.10. Polygenic risk scores constructed by best linear unbiased prediction weights applied to split-half samples failed to significantly predict any of the personality traits, but polygenic risk for neuroticism, calculated with LDpred and based on predictive variants previously identified from European populations (N=171 911), significantly predicted major depressive disorder case-control status (P=0.0004) after false discovery rate correction. The scores also significantly predicted EPQ neuroticism (P=6.3 × 10-6). Factor analytic results of the measures indicated that any differences in heritabilities across samples may be due to genetic variation or variation in haplotype structure between samples, rather than measurement non-invariance. Findings demonstrate that neuroticism can be significantly predicted across ancestry, and highlight the importance of studying polygenic contributions to personality in non-European populations.

Fecal microbiota transplantation for recurrent Clostridium difficile infection in hematopoietic stem cell transplant recipients.

Recurrent Clostridium difficile infection (CDI) is a consequence of intestinal dysbiosis and is particularly common following hematopoietic stem cell transplantation (HSCT). Fecal microbiota transplantation (FMT) is an effective method of treating CDI by correcting intestinal dysbiosis by passive transfer of healthy donor microflora. FMT has not been widely used in immunocompromised patients, including HSCT recipients, owing to concern for donor-derived infection. Here, we describe initial results of an FMT program for CDI at a US HSCT center. Seven HSCT recipients underwent FMT between February 2015 and February 2016. Mean time post HSCT was 635 days (25-75 interquartile range [IQR] 38-791). Five of the patients (71.4%) were on immunosuppressive therapy at FMT; 4 had required long-term suppressive oral vancomycin therapy because of immediate recurrence after antibiotic cessation. Stool donors underwent comprehensive health and behavioral screening and laboratory testing of serum and stool for 32 potential pathogens. FMT was administered via the naso-jejunal route in 6 of the 7 patients. Mean follow-up was 265 days (IQR 51-288). Minor post-FMT adverse effects included self-limited bloating and urgency. One patient was suspected of having post-FMT small intestinal bacterial overgrowth. No serious adverse events were noted and all-cause mortality was 0%. Six of 7 (85.7%) patients had no recurrence; 1 patient recurred at day 156 post FMT after taking an oral antibiotic and required repeat FMT, after which no recurrence has occurred. Diarrhea was improved in all patients and 1 patient with gastrointestinal graft-versus-host disease was able to taper off systemic immunosuppression after FMT. With careful donor selection and laboratory screening, FMT appears to be a safe and effective therapy for CDI in HSCT patients and may confer additional benefits. Larger studies are necessary to confirm safety and efficacy and explore other possible effects.

Identification of quantitative trait loci and candidate genes for an anxiolytic-like response to ethanol in BXD recombinant inbred strains.

Genetic differences in acute behavioral responses to ethanol contribute to the susceptibility to alcohol use disorder and the reduction of anxiety is a commonly reported motive underlying ethanol consumption among alcoholics. Therefore, we studied the genetic variance in anxiolytic-like responses to ethanol across the BXD recombinant inbred (RI) mouse panel using the light-dark transition model of anxiety. Strain-mean genetic mapping and a mixed-model quantitative trait loci (QTL) analysis replicated several previously published QTL for locomotor activity and identified several novel anxiety-related loci. Significant loci included a chromosome 11 saline anxiety-like QTL (Salanq1) and a chromosome 12 locus (Etanq1) influencing the anxiolytic-like response to ethanol. Etanq1 was successfully validated by studies with BXD advanced intercross strains and fine-mapped to a region comprising less than 3.5 Mb. Through integration of genome-wide mRNA expression profiles of the mesocorticolimbic reward circuit (prefrontal cortex, nucleus accumbens and ventral midbrain) across the BXD RI panel, we identified high priority candidate genes within Etanq1, the strongest of which was Ninein (Nin), a Gsk3ß-interacting protein that is highly expressed in the brain.

The clinical impact of vancomycin-resistant Enterococcus colonization and bloodstream infection in patients undergoing autologous transplantation.

BACKGROUND: Although several studies have documented adverse outcomes for vancomycin-resistant Enterococcus (VRE) colonization and infection in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, data are inadequate for patients undergoing autologous (auto-)HSCT. METHODS: We conducted a retrospective cohort study of 300 consecutive patients receiving an auto-HSCT between 2006 and 2014. Patients had stool cultures for VRE on admission and weekly during hospitalization. RESULTS: Thirty-six percent of patients had VRE gastrointestinal (GI) colonization and 3% developed a VRE bloodstream infection (BSI), all of whom were colonized. VRE strain typing of BSI isolates showed that some patients shared identical patterns. Rates of colonization and BSI in colonized patients were similar to simultaneous patients undergoing allo-HSCT, except that the latter had a higher rate of colonization at admission. A diagnosis of lymphoma was associated with an increased risk of colonization. VRE BSI was associated with longer lengths of stay and possibly higher costs, but no decrease in overall survival, and colonized patients had no VRE infections during the year following discharge. Repeat stool cultures in patients subsequently undergoing allo-HSCT suggested that most, if not all, VRE-positive auto-HSCT patients lose their detectable GI colonization within a few months of discharge. CONCLUSION: VRE colonization is frequent but carries a low risk for infection in patients undergoing auto-HSCT. However, these patients can serve as reservoirs for transmission to higher risk patients. Moreover, patients may remain colonized if proceeding to an allo-HSCT shortly after auto-HSCT, potentially increasing the risk of the allogeneic procedure.

A founder mutation in COL4A3 causes autosomal recessive Alport syndrome in the Ashkenazi Jewish population.

Alport syndrome is an inherited progressive nephropathy arising from mutations in the type IV collagen genes, COL4A3, COL4A4, and COL4A5. Symptoms also include sensorineural hearing loss and ocular lesions. We determined the molecular basis of Alport syndrome in a non-consanguineous Ashkenazi Jewish family with multiple affected females using linkage analysis and next generation sequencing. We identified a homozygous COL4A3 mutation, c.40_63del, in affected individuals with mutant alleles inherited from each parent on partially conserved haplotypes. Large-scale population screening of 2017 unrelated Ashkenazi Jewish samples revealed a carrier frequency of 1 in 183 indicating that COL4A3 c.40_63del is a founder mutation which may be a common cause of Alport syndrome in this population. Additionally, we determined that heterozygous mutation carriers in this family do not meet criteria for a diagnosis of Thin Basement Membrane Nephropathy and concluded that carriers of c.40_63del are not likely to develop benign familial hematuria.