Relationship Between Extreme Rainfall Occurrences and Galactic Cosmic Rays over Natal/RN, Brazil: A Case Study.

The increase in Galactic Cosmic Rays (GCR) flux intensity induces the Condensation Nuclei (CN) production, which intensifies rainfall occurrences. Then, the objective of this study was to analyze the rainfall distribution in the NEB and the impact of GCR flux on extreme rainfall events occurred in July 1998 in Natal/RN, Brazil. We used historical rainfall, Sea Surface Temperature (SST) and GCR flux data for Natal/RN. We used R software for statistical analysis. The results indicate that the GCR flux is important for intensifying extremes rainfall occurrences. This fact is observed when analyzing the relationship between rainfall greater than 10 mm and GCR flux above 6,390 counts/min. Pearson correlation coefficient between rainfall and GCR flux was 0.94 (p-value = 0.0005) and SST was -0.76 (p-value = 0.0263), both statistically significant. The rate between GCR flux and rainfall was +2.87 mm/count/min, while the rate between SST and rainfall was -7.91 mm/°C. The variance proportion explained by regression was 94.41%, with relative importance degree corresponding to 62.0% for GCR flux and 32.4% for SST, respectively. The results show that GCR flux had a greater contribution to extreme rainfall occurrence in the metropolitan region of Natal/RN and it is important in climatological studies.

The genomic landscape of familial glioma.

Glioma is a rare brain tumor with a poor prognosis. Familial glioma is a subset of glioma with a strong genetic predisposition that accounts for approximately 5% of glioma cases. We performed whole-genome sequencing on an exploratory cohort of 203 individuals from 189 families with a history of familial glioma and an additional validation cohort of 122 individuals from 115 families. We found significant enrichment of rare deleterious variants of seven genes in both cohorts, and the most significantly enriched gene was HERC2 (P = 0.0006). Furthermore, we identified rare noncoding variants in both cohorts that were predicted to affect transcription factor binding sites or cause cryptic splicing. Last, we selected a subset of discovered genes for validation by CRISPR knockdown screening and found that DMBT1, HP1BP3, and ZCH7B3 have profound impacts on proliferation. This study performs comprehensive surveillance of the genomic landscape of familial glioma.

Genome sequencing reveals underdiagnosis of primary ciliary dyskinesia in bronchiectasis.

BACKGROUND: Bronchiectasis can result from infectious, genetic, immunological and allergic causes. 60-80% of cases are idiopathic, but a well-recognised genetic cause is the motile ciliopathy, primary ciliary dyskinesia (PCD). Diagnosis of PCD has management implications including addressing comorbidities, implementing genetic and fertility counselling and future access to PCD-specific treatments. Diagnostic testing can be complex; however, PCD genetic testing is moving rapidly from research into clinical diagnostics and would confirm the cause of bronchiectasis. METHODS: This observational study used genetic data from severe bronchiectasis patients recruited to the UK 100,000 Genomes Project and patients referred for gene panel testing within a tertiary respiratory hospital. Patients referred for genetic testing due to clinical suspicion of PCD were excluded from both analyses. Data were accessed from the British Thoracic Society audit, to investigate whether motile ciliopathies are underdiagnosed in people with bronchiectasis in the UK. RESULTS: Pathogenic or likely pathogenic variants were identified in motile ciliopathy genes in 17 (12%) out of 142 individuals by whole-genome sequencing. Similarly, in a single centre with access to pathological diagnostic facilities, 5-10% of patients received a PCD diagnosis by gene panel, often linked to normal/inconclusive nasal nitric oxide and cilia functional test results. In 4898 audited patients with bronchiectasis, <2% were tested for PCD and <1% received genetic testing. CONCLUSIONS: PCD is underdiagnosed as a cause of bronchiectasis. Increased uptake of genetic testing may help to identify bronchiectasis due to motile ciliopathies and ensure appropriate management.

Magseed localisation of non-palpable breast lesions: experience from a single centre.

AIM: To prospectively analyse patients undergoing magnetic seed (Magseed) localisation (MSL) to evaluate the outcome, and to retrospectively compare re-excision rates for MSL with previous wire-guided localisation (WGL) to assess the hypothesis that the introduction of MSL may lead to a lower re-excision rate. MATERIALS AND METHODS: MSL commenced at University Hospital Crosshouse in December 2017. No other changes were made to radiological or surgical practice during this time. Data were collected prospectively on all patients undergoing MSL between December 2017 and December 2019, in a single breast unit. Data were gathered retrospectively on patients who had undergone localised breast procedures between January 2016 and December 2019 for comparison of re-excision rates. RESULTS: Two hundred and fifty-five patients underwent MSL surgery between December 2017 and December 2019. Of those, 98% (n=250) patients underwent successful MSL at the first attempt. The Magseed was identified intraoperatively in 100% patients and surgical excision was performed. The re-excision rate reduced from 18.9% in 2016/2017, to 11.6% in 2018/2019 (p=0.098). CONCLUSION: In conclusion, Magseed localisation has proved to be a safe and effective way of localising breast lesions, with the advantage of high accuracy. The reduction in re-excision rates at University Hospital Crosshouse with the introduction of Magseed® localisation is a potential benefit, which requires further study.

Improved Constraints on Primordial Gravitational Waves using Planck, WMAP, and BICEP/Keck Observations through the 2018 Observing Season.

We present results from an analysis of all data taken by the BICEP2, Keck Array, and BICEP3 CMB polarization experiments up to and including the 2018 observing season. We add additional Keck Array observations at 220 GHz and BICEP3 observations at 95 GHz to the previous 95/150/220 GHz dataset. The Q/U maps now reach depths of 2.8, 2.8, and 8.8 µK_{CMB} arcmin at 95, 150, and 220 GHz, respectively, over an effective area of ≈600 square degrees at 95 GHz and ≈400 square degrees at 150 and 220 GHz. The 220 GHz maps now achieve a signal-to-noise ratio on polarized dust emission exceeding that of Planck at 353 GHz. We take auto- and cross-spectra between these maps and publicly available WMAP and Planck maps at frequencies from 23 to 353 GHz and evaluate the joint likelihood of the spectra versus a multicomponent model of lensed ΛCDM+r+dust+synchrotron+noise. The foreground model has seven parameters, and no longer requires a prior on the frequency spectral index of the dust emission taken from measurements on other regions of the sky. This model is an adequate description of the data at the current noise levels. The likelihood analysis yields the constraint r_{0.05}<0.036 at 95% confidence. Running maximum likelihood search on simulations we obtain unbiased results and find that σ(r)=0.009. These are the strongest constraints to date on primordial gravitational waves.

Real-time feedback control of the impurity emission front in tokamak divertor plasmas.

In magnetic confinement thermonuclear fusion the exhaust of heat and particles from the core remains a major challenge. Heat and particles leaving the core are transported via open magnetic field lines to a region of the reactor wall, called the divertor. Unabated, the heat and particle fluxes may become intolerable and damage the divertor. Controlled 'plasma detachment', a regime characterized by both a large reduction in plasma pressure and temperature at the divertor target, is required to reduce fluxes onto the divertor. Here we report a systematic approach towards achieving this critical need through feedback control of impurity emission front locations and its experimental demonstration. Our approach comprises a combination of real-time plasma diagnostic utilization, dynamic characterization of the plasma in proximity to the divertor, and efficient, reliable offline feedback controller design.

Norwich COVID-19 testing initiative pilot: evaluating the feasibility of asymptomatic testing on a university campus.

BACKGROUND: There is a high prevalence of COVID-19 in university-age students, who are returning to campuses. There is little evidence regarding the feasibility of universal, asymptomatic testing to help control outbreaks in this population. This study aimed to pilot mass COVID-19 testing on a university research park, to assess the feasibility and acceptability of scaling up testing to all staff and students. METHODS: This was a cross-sectional feasibility study on a university research park in the East of England. All staff and students (5625) were eligible to participate. All participants were offered four PCR swabs, which they self-administered over two weeks. Outcome measures included uptake, drop-out rate, positivity rates, participant acceptability measures, laboratory processing measures, data collection and management measures. RESULTS: 798 (76%) of 1053 who registered provided at least one swab; 687 (86%) provided all four; 792 (99%) of 798 who submitted at least one swab had all negative results and 6 participants had one inconclusive result. There were no positive results. 458 (57%) of 798 participants responded to a post-testing survey, demonstrating a mean acceptability score of 4.51/5, with five being the most positive. CONCLUSIONS: Repeated self-testing for COVID-19 using PCR is feasible and acceptable to a university population.

First Direct Measurement of

Type-I x-ray bursts can reveal the properties of an accreting neutron star system when compared with astrophysics model calculations. However, model results are sensitive to a handful of uncertain nuclear reaction rates, such as ^{22}Mg(α,p). We report the first direct measurement of ^{22}Mg(α,p), performed with the Active Target Time Projection Chamber. The corresponding astrophysical reaction rate is orders of magnitude larger than determined from a previous indirect measurement in a broad temperature range. Our new measurement suggests a less-compact neutron star in the source GS1826-24.

New Measurement of

Carbon and oxygen burning reactions, in particular, ^{12}C+^{12}C fusion, are important for the understanding and interpretation of the late phases of stellar evolution as well as the ignition and nucleosynthesis in cataclysmic binary systems such as type Ia supernovae and x-ray superbursts. A new measurement of this reaction has been performed at the University of Notre Dame using particle-γ coincidence techniques with SAND (a silicon detector array) at the high-intensity 5U Pelletron accelerator. New results for ^{12}C+^{12}C fusion at low energies relevant to nuclear astrophysics are reported. They show strong disagreement with a recent measurement using the indirect Trojan Horse method. The impact on the carbon burning process under astrophysical scenarios will be discussed.

Filament identification in wide-angle high speed imaging of the mega amp spherical tokamak.

A new tomographic inversion technique is presented for the identification of plasma filaments in wide-angle visible camera data. The technique works on the assumption that background subtracted images of filaments can be represented as a superposition of uniformly emitting magnetic equilibrium field lines. A large collection of equilibrium magnetic field lines is traced and projected onto the camera field of view and combined to form a geometry matrix describing the coordinate transformation from magnetic field aligned coordinates to image pixel coordinates. Inverting this matrix enables the reprojection of the emission in the camera images onto a field aligned basis, from which filaments are readily identifiable. The inversion is a poorly conditioned problem which is overcome using a least-squares approach with Laplacian regularization. Blobs are identified using the "watershed" algorithm and 2D Gaussians are fitted to get the positions, widths, and amplitudes of the filaments. A synthetic camera diagnostic generating images containing experimentally representative filaments is utilized to rigorously benchmark the accuracy and reliability of the technique. 74% of synthetic filaments above the detection amplitude threshold are successfully detected, with 98.8% of detected filaments being true positives. The accuracy with which filament properties and their probability density functions are recovered is discussed, along with sources of error and methods to minimize them.

Physically principled reflection models applied to filtered camera imaging inversions in metal walled fusion machines.

Ray-tracing techniques are applied to filtered divertor imaging, a diagnostic that has long suffered from artifacts due to the polluting effect of reflected light in metal walled fusion machines. Physically realistic surface reflections were modeled using a Cook-Torrance micro-facet bi-directional reflection distribution function applied to a high resolution mesh of the vessel geometry. In the absence of gonioreflectometer measurements, a technique was developed to fit the free parameters of the Cook-Torrance model against images of the JET in-vessel light sources. By coupling this model with high fidelity plasma fluid simulations, photo-realistic renderings of a number of tokamak plasma emission scenarios were generated. Finally, a sensitivity matrix describing the optical coupling of a JET divertor camera and the emission profile of the plasma was obtained, including full reflection effects. These matrices are used to perform inversions on measured data and shown to reduce the level of artifacts in inverted emission profiles.

Immune response to temperature stress in three bivalve species: Pacific oyster Crassostrea gigas, Mediterranean mussel Mytilus galloprovincialis and mud cockle Katelysia rhytiphora.

Summer mortality of some bivalve species is often associated with the change of environmental temperature. This study compares the response of immunological parameters to temperature change in three marine bivalves: Pacific oyster Crassostrea gigas, Mediterranean mussel Mytilus galloprovincialis and mud cockle Katelysia rhytiphora. Each species was exposed to three temperatures, 15 °C, 20 °C and 25 °C for 14 days. The total haemocyte count (THC), phagocytosis, reactive oxygen species (ROS) and the activity of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) were used as indicators to measure the response of each species to different temperatures. The highest temperature (25 °C) significantly increased the THC and phagocysis of haemocytes in all species. The SOD and CAT activities in the haemocytes of M. galloprovincialis and K. rhytiphora rapidly increased with temperature elevation, concomitantly with the increase of ROS ions. In contrast, the increases of ROS and SOD in C. gigas only occurred from 20 °C to 25 °C, suggesting that this intertidal species is more adaptive to different temperature levels. This study indicates that the activities of antioxidant enzymes can reflect the immune response of marine bivalves to thermal stress. Intertidal species such as Pacific oysters have a greater tolerance to thermal stress than subtidal species (e.g. Mediterranean mussel) and demersal species buried in sand (e.g. cockle).

Description of complex viewing geometries of fusion tomography diagnostics by ray-tracing.

Ray-tracing techniques are applied to bolometry, a diagnostic where the finite collection volume is particularly sensitive to the machine and detector configuration. A technique is presented that can handle arbitrarily complex aperture and collimator geometries, neglecting reflection effects. Sight lines from the ASDEX Upgrade bolometer foils were ray-traced with a path tracing algorithm, where the optical path is represented by a statistical bundle of ray paths connecting the foil surface with the slit geometry. By using the full 3D machine model for the detector box and first wall, effects such as occlusion and vignetting were included in the calculation of the bolometer's étendue. Inversion matrices calculated with the ray-tracing technique were compared with the more conventional single-ray approach and shown to be naturally more constrained, requiring less regularisation. The two models were tested on a sample radiation scenario, and the common single-ray approximation is shown to be insufficient. These results are particularly relevant for the divertor where strong emission gradients may be present. The technique developed generalises well to arbitrarily complex viewing geometries and collimators, opening up a new design space for bolometer configurations that might not normally have been considered.

Identification of pathological complete response after neoadjuvant chemotherapy for breast cancer: comparison of greyscale ultrasound, shear wave elastography, and MRI.

AIM: To assess the value of post-treatment shear-wave elastography (SWE) parameters (maximum stiffness [Emax], mean stiffness [Emean], and standard deviation [SD]) compared to greyscale ultrasonography (US) and magnetic resonance imaging (MRI) in identifying pathological complete response (pCR) to neoadjuvant chemotherapy (NACT) in breast cancer. MATERIALS AND METHODS: In a prospective cohort study, 80 patients receiving NACT for breast cancer underwent baseline and post-treatment US, SWE, and MRI examinations. Four SWE images in two orthogonal planes were obtained. Maximum greyscale US diameter and maximum diameter of lesion enhancement on MRI were measured. Percentage reductions between baseline and post-treatment scans were calculated for MRI and greyscale US diameter, and Emean, Emax, and SD. The percentage reduction in Emean and US diameter were also analysed as a combination. Analysis was undertaken using receiver operating characteristic (ROC) curves and the chi-squared test. RESULTS: pCR occurred in 21 of 80 (26%) women. The area under the ROC curve (AUC) for pCR of percentage reductions in Emean, Emax, SD, and greyscale US diameter were 0.89, 0.85, 0.75, and 0.86, respectively. The combination of percentage reductions in Emean and greyscale ultrasound diameter yielded an AUC of 0.92, which is similar to the AUC for MRI of 0.96 (p=0.28). CONCLUSIONS: SWE combined with greyscale US shows promise for end-of-treatment identification of response to NACT in women with breast cancer, with accuracies similar to breast MRI. This technique could be used to inform surgical decision-making after NACT.

A systematic review of interventions to increase physical activity among South Asian adults.

OBJECTIVES: To identify interventions aimed at increasing physical activity (PA) levels among South Asian (SA) adults and identify the specific changes in the content and delivery mode of interventions designed to increase PA levels among SA people aged ≥18 years. DESIGN: A systematic review of quantitative studies. DATA SYNTHESIS: Extracted data were synthesized using a narrative approach. DATA SOURCES: ASSIA, CINHAL, EMBASE, Medline, SPORTDiscus and PsychINFO were searched. Included articles met the following criteria: (1) population: community-dwelling SA adults aged ≥18 years and (2) outcome: reporting determinants of PA, exercise, or a combination of the two, measured objectively or using self-report. The search was restricted to articles published in the English language up to 31 January 2017. RESULTS: Fifteen trials/programmes (16 articles) met the review criteria. The findings show that involving the target community in developing culturally appropriate interventions appears to be important in their acceptability, delivery and uptake. Using community-based participation in intervention planning, evaluation and research appears to produce culturally and linguistically tailored interventions that address core values, attitudes, beliefs and norms, and encourage participation in PA. Furthermore, the use of community health workers and underpinning the interventions with a psychological theory show promise in increasing PA uptake. CONCLUSIONS: This systematic review suggests that making cultural adaptations to PA interventions shows promise, but the evidence base presented is not strong. This does not mean that adopting such an approach is ineffective but that the evidence base is currently lacking.

Fibrinolysis: strategies to enhance the treatment of acute ischemic stroke.

Stroke is a major cause of disability worldwide, and is the second leading cause of death after ischemic heart disease. Until recently, tissue-type plasminogen activator (t-PA) was the only treatment for acute ischemic stroke. If administered within 4.5 h of symptom onset, t-PA improves the outcome in stroke patients. Mechanical thrombectomy is now the preferred treatment for patients with acute ischemic stroke resulting from a large-artery occlusion in the anterior circulation. However, the widespread use of mechanical thrombectomy is limited by two factors. First, only ⁓ 10% of patients with acute ischemic stroke have a proximal large-artery occlusion in the anterior circulation and present early enough to undergo mechanical thrombectomy within 6 h; an additional 9-10% of patients presenting within the 6-24-h time window may also qualify for the procedure. Second, not all stroke centers have the resources or expertise to perform mechanical thrombectomy. Nonetheless, patients who present to hospitals where thrombectomy is not an option can receive intravenous t-PA, and those with qualifying anterior circulation strokes can then be transferred to tertiary stroke centers where thrombectomy is available. Therefore, despite the advances afforded by mechanical thrombectomy, there remains a need for treatments that improve the efficacy and safety of thrombolytic therapy. In this review, we discuss: (i) current treatment options for acute ischemic stroke; (ii) the mechanism of action of fibrinolytic agents; and (iii) potential strategies to manipulate the fibrinolytic system to promote endogenous fibrinolysis or to enhance the efficacy of fibrinolytic therapy.

Long-term satellite tracking reveals variable seasonal migration strategies of basking sharks in the north-east Atlantic.

Animal migration is ubiquitous in nature with individuals within a population often exhibiting varying movement strategies. The basking shark (Cetorhinus maximus) is the world's second largest fish species, however, a comprehensive understanding of their long-term wider-ranging movements in the north-east Atlantic is currently lacking. Seventy satellite tags were deployed on basking sharks over four years (2012-2015) off the west coast of Scotland and the Isle of Man. Data from 28 satellite tags with attachment durations of over 165 days reveal post-summer ranging behaviours. Tagged sharks moved a median minimum straight-line distance of 3,633 km; achieving median displacement of 1,057 km from tagging locations. Tagged individuals exhibited one of three migration behaviours: remaining in waters of UK, Ireland and the Faroe Islands; migrating south to the Bay of Biscay or moving further south to waters off the Iberian Peninsula, and North Africa. Sharks used both continental shelf areas and oceanic habitats, primarily in the upper 50-200 m of the water column, spanning nine geo-political zones and the High Seas, demonstrating the need for multi-national cooperation in the management of this species across its range.

A narrative meta-review of a series of systematic and meta-analytic reviews on the intervention outcome for children with developmental co-ordination disorder.

BACKGROUND: Systematic reviews and meta-analyses are considered to be the 'gold standards' for synthesizing research evidence in particular areas of enquiry. However, such reviews are only useful if they themselves are conducted to a sufficiently high standard. The aim of this study was to conduct a narrative meta-review of existing analyses of the effectiveness of interventions designed for children with developmental co-ordination disorder (DCD). METHODS: A narrative meta-review of systematic and meta-analytic reviews aimed at evaluating the effectiveness of intervention for children with DCD was conducted on studies published between 1950 and 2014. We identified suitable reviews, using a modification of the Population, Intervention, Comparison, Outcome (PICO) system and evaluated their methodological quality using the Assessment of Multiple Systematic Reviews (AMSTAR). In addition, the consistency of the quality of evidence and classification of intervention approaches was assessed independently by two assessors. RESULTS: The literature search yielded a total of four appropriate reviews published in the selected time span. The Assessment of Multiple Systematic Reviews percentage quality scores assigned to each review ranged from 0% (low quality) to 55% (medium quality). Evaluation of the quality of evidence and classification of intervention approaches yielded a discrepancy rate of 25%. All reviews concluded that some kind of intervention was better than none at all. CONCLUSIONS: Although the quality of the reviews progressively improved over the years, the shortcomings identified need to be addressed before concrete evidence regarding the best approach to intervention for children with DCD can be specified.

Activated macrophages utilize glycolytic ATP to maintain mitochondrial membrane potential and prevent apoptotic cell death.

This corrects the article DOI: 10.1038/cdd.2010.27.

Robust anti-obesity and metabolic effects of a dual GLP-1/glucagon receptor peptide agonist in rodents and non-human primates.

AIMS: To characterize the pharmacology of MEDI0382, a peptide dual agonist of glucagon-like peptide-1 (GLP-1) and glucagon receptors. MATERIALS AND METHODS: MEDI0382 was evaluated in vitro for its ability to stimulate cAMP accumulation in cell lines expressing transfected recombinant or endogenous GLP-1 or glucagon receptors, to potentiate glucose-stimulated insulin secretion (GSIS) in pancreatic ß-cell lines and stimulate hepatic glucose output (HGO) by primary hepatocytes. The ability of MEDI0382 to reduce body weight and improve energy balance (i.e. food intake and energy expenditure), as well as control blood glucose, was evaluated in mouse models of obesity and healthy cynomolgus monkeys following single and repeated daily subcutaneous administration for up to 2 months. RESULTS: MEDI0382 potently activated rodent, cynomolgus and human GLP-1 and glucagon receptors and exhibited a fivefold bias for activation of GLP-1 receptor versus the glucagon receptor. MEDI0382 produced superior weight loss and comparable glucose lowering to the GLP-1 peptide analogue liraglutide when administered daily at comparable doses in DIO mice. The additional fat mass reduction elicited by MEDI0382 probably results from a glucagon receptor-mediated increase in energy expenditure, whereas food intake suppression results from activation of the GLP-1 receptor. Notably, the significant weight loss elicited by MEDI0382 in DIO mice was recapitulated in cynomolgus monkeys. CONCLUSIONS: Repeated administration of MEDI0382 elicits profound weight loss in DIO mice and non-human primates, produces robust glucose control and reduces hepatic fat content and fasting insulin and glucose levels. The balance of activities at the GLP-1 and glucagon receptors is considered to be optimal for achieving weight and glucose control in overweight or obese Type 2 diabetic patients.