Order-disorder transition in nanoscopic semiconductor quantum rings

Using the path integral Monte Carlo technique we show that semiconductor quantum rings with up to six electrons exhibit a temperature, ring diameter, and particle number dependent transition between spin ordered and disordered Wigner crystals. Due to the small number of particles the transition extends over a broad temperature range and is clearly identifiable from the electron pair correlation functions.Comment: 4 pages, 5 figures, For recent information on physics of small systems see http://www.smallsystems.d

A Cell Permeable Peptide Targeting the Intracellular Loop 2 of Endothelin B Receptor Reduces Pulmonary Hypertension in a Hypoxic Rat Model

Cell permeable peptides (CPP) aid cellular uptake of targeted cargo across the hydrophobic plasma membrane. CPP-mediated cargo delivery of receptor signaling motifs provides an opportunity to regulate specific receptor initiated signaling cascades. Both endothelin-1 receptors, ETA and ETB, have been targets of antagonist therapies for individuals with pulmonary arterial hypertension (PAH). These therapies have had success but have been accompanied by adverse reactions. Also, unlike the CPP which target specific signaling cascades, the antagonists target the entire function of the receptor. Using the CPP strategy of biased antagonism of the ETB receptor’s intracellular loop 2 (ICB2), we demonstrate blunting of hypoxic pulmonary hypertension (HPH) in the rat, including indices of pulmonary arterial pressure, right ventricular hypertrophy and pulmonary vascular remodeling. Further, ex vivo analysis of the pulmonary artery treated with the IC2B peptide upon injection manifests marked reductions in Akt and ERK activation. Both kinases have been intimately related to cell proliferation and vascular contraction, the hallmarks of PAH. These observations in sum illustrate an involvement of the ETB receptor in HPH and furthermore provide a basis for a novel, CPP-based, strategy in the treatment of PAH, ultimately able to target not only ET-1, but also other factors involved in the development of PAH

Study protocol for a randomised controlled trial of invasive versus conservative management of primary spontaneous pneumothorax

INTRODUCTION: Current management of primary spontaneous pneumothorax (PSP) is variable, with little evidence from randomised controlled trials to guide treatment. Guidelines emphasise intervention in many patients, which involves chest drain insertion, hospital admission and occasionally surgery. However, there is evidence that conservative management may be effective and safe, and it may also reduce the risk of recurrence. Significant questions remain regarding the optimal initial approach to the management of PSP

The prognostic impact of circulating tumour dna in melanoma patients treated with systemic therapies—beyond braf mutant detection

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. In this study, we evaluated the predictive value of circulating tumour DNA (ctDNA) to inform therapeutic outcomes in metastatic melanoma patients receiving systemic therapies. We analysed 142 plasma samples from metastatic melanoma patients prior to commencement of systemic therapy: 70 were treated with BRAF/MEK inhibitors and 72 with immunotherapies. Patient-specific droplet digital polymerase chain reaction assays were designed for ctDNA detection. Plasma ctDNA was detected in 56% of patients prior to first-line anti-PD1 and/or anti-CTLA-4 treatment. The detection rate in the immunotherapy cohort was comparably lower than those with BRAF inhibitors (76%, p = 0.0149). Decreasing ctDNA levels within 12 weeks of treatment was strongly concordant with treatment response (Cohen’s k = 0.798, p \u3c 0.001) and predictive of longer progression free survival. Notably, a slower kinetic of ctDNA decline was observed in patients treated with immunotherapy compared to those on BRAF/MEK inhibitors. Whole exome sequencing of ctDNA was also conducted in 9 patients commencing anti-PD-1 therapy to derive tumour mutational burden (TMB) and neoepitope load measurements. The results showed a trend of high TMB and neoepitope load in responders compared to non-responders. Overall, our data suggest that changes in ctDNA can serve as an early indicator of outcomes in metastatic melanoma patients treated with systemic therapies and therefore may serve as a tool to guide treatment decisions

Indistinguishable and efficient single photons from a quantum dot in a planar nanobeam waveguide

We demonstrate a high-purity source of indistinguishable single photons using a quantum dot embedded in a nanophotonic waveguide. The source features a near-unity internal coupling efficiency and the collected photons are efficiently coupled off chip by implementing a taper that adiabatically couples the photons to an optical fiber. By quasiresonant excitation of the quantum dot, we measure a single-photon purity larger than 99.4% and a photon indistinguishability of up to 94±1% by using p-shell excitation combined with spectral filtering to reduce photon jitter. A temperature-dependent study allows pinpointing the residual decoherence processes, notably the effect of phonon broadening. Strict resonant excitation is implemented as well as another means of suppressing photon jitter, and the additional complexity of suppressing the excitation laser source is addressed. The paper opens a clear pathway towards the long-standing goal of a fully deterministic source of indistinguishable photons, which is integrated on a planar photonic chip

Conservative versus interventional treatment for spontaneous pneumothorax

BACKGROUND: Whether conservative management is an acceptable alternative to interventional management for uncomplicated, moderate-to-large primary spontaneous pneumothorax is unknown. METHODS: In this open-label, multicenter, noninferiority trial, we recruited patients 14 to 50 years of age with a first-known, unilateral, moderate-to-large primary spontaneous pneumothorax. Patients were randomly assigned to immediate interventional management of the pneumothorax (intervention group) or a conservative observational approach (conservative-management group) and were followed for 12 months. The primary outcome was lung reexpansion within 8 weeks. RESULTS: A total of 316 patients underwent randomization (154 patients to the intervention group and 162 to the conservative-management group). In the conservative-management group, 25 patients (15.4%) underwent interventions to manage the pneumothorax, for reasons prespecified in the protocol, and 137 (84.6%) did not undergo interventions. In a complete-case analysis in which data were not available for 23 patients in the intervention group and 37 in the conservative-management group, reexpansion within 8 weeks occurred in 129 of 131 patients (98.5%) with interventional management and in 118 of 125 (94.4%) with conservative management (risk difference, -4.1 percentage points; 95% confidence interval [CI], -8.6 to 0.5; P = 0.02 for noninferiority); the lower boundary of the 95% confidence interval was within the prespecified noninferiority margin of -9 percentage points. In a sensitivity analysis in which all missing data after 56 days were imputed as treatment failure (with reexpansion in 129 of 138 patients [93.5%] in the intervention group and in 118 of 143 [82.5%] in the conservative-management group), the risk difference of -11.0 percentage points (95% CI, -18.4 to -3.5) was outside the prespecified noninferiority margin. Conservative management resulted in a lower risk of serious adverse events or pneumothorax recurrence than interventional management. CONCLUSIONS: Although the primary outcome was not statistically robust to conservative assumptions about missing data, the trial provides modest evidence that conservative management of primary spontaneous pneumothorax was noninferior to interventional management, with a lower risk of serious adverse events. (Funded by the Emergency Medicine Foundation and others; PSP Australian New Zealand Clinical Trials Registry number, ACTRN12611000184976.)

Nucleotide diversity maps reveal variation in diversity among wheat genomes and chromosomes

<p>Abstract</p> <p>Background</p> <p>A genome-wide assessment of nucleotide diversity in a polyploid species must minimize the inclusion of homoeologous sequences into diversity estimates and reliably allocate individual haplotypes into their respective genomes. The same requirements complicate the development and deployment of single nucleotide polymorphism (SNP) markers in polyploid species. We report here a strategy that satisfies these requirements and deploy it in the sequencing of genes in cultivated hexaploid wheat (<it>Triticum aestivum</it>, genomes AABBDD) and wild tetraploid wheat (<it>Triticum turgidum </it>ssp. <it>dicoccoides</it>, genomes AABB) from the putative site of wheat domestication in Turkey. Data are used to assess the distribution of diversity among and within wheat genomes and to develop a panel of SNP markers for polyploid wheat.</p> <p>Results</p> <p>Nucleotide diversity was estimated in 2114 wheat genes and was similar between the A and B genomes and reduced in the D genome. Within a genome, diversity was diminished on some chromosomes. Low diversity was always accompanied by an excess of rare alleles. A total of 5,471 SNPs was discovered in 1791 wheat genes. Totals of 1,271, 1,218, and 2,203 SNPs were discovered in 488, 463, and 641 genes of wheat putative diploid ancestors, <it>T. urartu</it>, <it>Aegilops speltoides</it>, and <it>Ae. tauschii</it>, respectively. A public database containing genome-specific primers, SNPs, and other information was constructed. A total of 987 genes with nucleotide diversity estimated in one or more of the wheat genomes was placed on an <it>Ae. tauschii </it>genetic map, and the map was superimposed on wheat deletion-bin maps. The agreement between the maps was assessed.</p> <p>Conclusions</p> <p>In a young polyploid, exemplified by <it>T. aestivum</it>, ancestral species are the primary source of genetic diversity. Low effective recombination due to self-pollination and a genetic mechanism precluding homoeologous chromosome pairing during polyploid meiosis can lead to the loss of diversity from large chromosomal regions. The net effect of these factors in <it>T. aestivum </it>is large variation in diversity among genomes and chromosomes, which impacts the development of SNP markers and their practical utility. Accumulation of new mutations in older polyploid species, such as wild emmer, results in increased diversity and its more uniform distribution across the genome.</p

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Change in physical activity level and clinical outcomes in older adults with knee pain: a secondary analysis from a randomised controlled trial

BACKGROUND: Exercise interventions improve clinical outcomes of pain and function in adults with knee pain due to osteoarthritis and higher levels of physical activity are associated with lower severity of pain and higher levels of physical functioning in older adults with knee osteoarthritis in cross-sectional studies. However, to date no studies have investigated if change in physical activity level during exercise interventions can explain clinical outcomes of pain and function. This study aimed to investigate if change in physical activity during exercise interventions is associated with future pain and physical function in older adults with knee pain. METHODS: Secondary longitudinal data analyses of a three armed exercise intervention randomised controlled trial. Participants were adults with knee pain attributed to osteoarthritis, over the age of 45 years old (n = 514) from Primary Care Services in the Midlands and Northwest regions of England. Crude and adjusted associations between absolute change in physical activity from baseline to 3 months (measured by the self-report Physical Activity Scale for the Elderly (PASE)) and i) pain ii) physical function (Western Ontario and McMaster Universities Osteoarthritis Index) and iii) treatment response (OMERACT-OARSI responder criteria) at 3 and 6 months follow-up were investigated using linear and logistic regression. RESULTS: Change in physical activity level was not associated with future pain, function or treatment response outcomes in crude or adjusted models at 3 or 6 months (P > 0.05). A 10 point increase in PASE was not associated with pain β = - 0.01 (- 0.05, 0.02), physical function β = - 0.09 (- 0.19, 0.02) or likelihood (odds ratio) of treatment response 1.02 (0.99, 1.04) at 3 months adjusting for sociodemographics, clinical covariates and the trial intervention arm. Findings were similar for 6 month outcome models. CONCLUSIONS: Change in physical activity did not explain future clinical outcomes of pain and function in this study. Other factors may be responsible for clinical improvements following exercise interventions. However, the PASE may not be sufficiently responsive to measure change in physical activity level. We also recommend further investigation into the responsiveness of commonly used physical activity measures. TRIAL REGISTRATION: ( ISRCTN93634563 ). Registered 29th September 2011