A rare case of breast carcinoma co-existing with axillary mantle cell lymphoma

BACKGROUND: Mantle cell lymphoma (MCL) is a rare variety of non-Hodgkin's lymphoma which originates from CD5+ B-cell population in the mantle zones of lymphoid follicles. Coexistence of such tumours in the axillary lymph nodes with invasive breast cancers without prior history of adjuvant chemotherapy or radiotherapy has not been previously reported in literature. CASE REPORT: We report a rare case of breast cancer co-existing with stage I mantle cell lymphoma of the ipsilateral axillary lymph node detected fortuitously by population screening. CONCLUSION: Though some studies have tried to prove breast carcinomas and lymphomas to share a common molecular or viral link, more research needs to be done to establish whether such a link truly exists

Understanding and applying practitioner and patient views on the implementation of a novel automated Computer-Aided Risk Score (CARS) predicting the risk of death following emergency medical admission to hospital: qualitative study

Objectives: The Computer-Aided Risk Score (CARS) estimates the risk of death following emergency admission to medical wards using routinely collected vital signs and blood test data. Our aim was to elicit the views of healthcare practitioners (staff) and service users and carers (SU/C) on (1) the potential value, unintended consequences and concerns associated with CARS and practitioner views on (2) the issues to consider before embedding CARS into routine practice. Setting: This study was conducted in two National Health Service (NHS) hospital trusts in the North of England. Both had in-house information technology (IT) development teams, mature IT infrastructure with electronic National Early Warning Score (NEWS) and were capable of integrating NEWS with blood test results. The study focused on emergency medical and elderly admissions units. There were 60 and 39 acute medical/elderly admissions beds at the two NHS hospital trusts. Participants: We conducted eight focus groups with 45 healthcare practitioners and two with 11 SU/Cs in two NHS acute hospitals. Results: Staff and SU/Cs recognised the potential of CARS but were clear that the score should not replace or undermine clinical judgments. Staff recognised that CARS could enhance clinical decision-making/judgments and aid communication with patients. They wanted to understand the components of CARS and be reassured about its accuracy but were concerned about the impact on intensive care and blood tests. Conclusion: Risk scores are widely used in healthcare, but their development and implementation do not usually involve input from practitioners and SU/Cs. We contributed to the development of CARS by eliciting views of staff and SU/Cs who provided important, often complex, insights to support the development and implementation of CARS to ensure successful implementation in routine clinical practice

A high-affinity antibody against the CSP N-terminal domain lacks Plasmodium falciparum inhibitory activity

Malaria is a global health concern and research efforts are ongoing to develop a superior vaccine to RTS,S/AS01. To guide immunogen design, we seek a comprehensive understanding of the protective humoral response against Plasmodium falciparum circumsporozoite protein (PfCSP). In contrast to the well-studied responses to the repeat region and the C-terminus, the antibody response against the N-terminal domain of PfCSP (N-CSP) remains obscure. Here, we characterized the molecular recognition and functional efficacy of the N-CSP-specific monoclonal antibody 5D5. The crystal structure at 1.85 Åresolution revealed that 5D5 binds an α-helical epitope in N-CSP with high affinity through extensive shape and charge complementarity, and the unusual utilization of an N-linked glycan. Nevertheless, functional studies indicated low 5D5 binding to live Pf sporozoites, and lack of sporozoite inhibition in vitro and in mosquitoes. Overall, our data on low recognition and inhibition of sporozoites do not support the inclusion of the 5D5 epitope into the next generation of CSP-based vaccines.Summary Statement The Plasmodium falciparum sporozoite surface protein, PfCSP, is an attractive vaccine target, but the antibody response against the CSP N-terminal domain has remained understudied. Here, to guide immunogen design, Thai et al. provide insights into the binding motif and functional efficacy of the N-terminal domain-specific monoclonal antibody, 5D5

Do binaries in clusters form in the same way as in the field?

We examine the dynamical destruction of binary systems in star clusters of different densities. We find that at high densities (10^4 - 10^5 Msun pc^-3) almost all binaries with separations > 10^3 AU are destroyed after a few crossing times. At low densities (order(10^2) Msun pc^-3) many binaries with separations > 10^3 AU are destroyed, and no binaries with separations > 10^4 AU survive after a few crossing times. Therefore the binary separations in clusters can be used as a tracer of the dynamical age and past density of a cluster. We argue that the central region of the Orion Nebula Cluster was around 100 times denser in the past with a half-mass radius of only 0.1 - 0.2 pc as (a) it is expanding, (b) it has very few binaries with separations > 10^3 AU, and (c) it is well-mixed and therefore dynamically old. We also examine the origin of the field binary population. Binaries with separations < 10^2 AU are not significantly modified in any cluster, therefore at these separations the field reflects the sum of all star formation. Binaries with separations in the range 10^2 - 10^4 AU are progressively more and more heavily affected by dynamical disruption in increasingly dense clusters. If most star formation is clustered, these binaries must be over-produced relative to the field. Finally, no binary with a separation > 10^4 AU can survive in any cluster and so must be produced by isolated star formation, but only if all isolated star formation produces extremely wide binaries.Comment: 12 pages, 6 figures, accepted for publication in MNRA

Management and restoration of crayfish stocks- Phase 2

Crayfish or spiny lobster occur in physically complex reef habitat in shallow waters off the west coast of Ireland. These habitats provide shelter for larvae that are settling out from the overlying water column and for juvenile and adult lobsters that use these areas to shelter and forage. Fisheries for spiny lobster occur in these areas and remove lobsters from the reef. The consequence of this for the structure and function of reef habitat is unknown. In this study the distribution of reef habitat was estimated from multibeam acoustic data collected in previous campaigns by the INFOMAR programme. Sub-sets of this area were re-mapped at higher resolution to provide further detail of the topography of the reef from which terrain variables were derived. Underwater video and SCUBA methods were used to identify the flora and fauna in areas with different topographies. Weak correlations between the terrain variables and the biological data were found. This was used to model the distribution of areas of high and low biodiversity over broader areas where only terrain data were available. Capacity to model the distribution of biological communities and crayfish over broad areas using physical terrain data remains difficult. Other physical variables that may be important in regulating the biology of reef need to be included and the association of crayfish with particular types of reef terrain needs to be established by higher resolution sampling. The benefits of the work reported here include increased capacity to monitor the distribution of biodiversity in marine reef habitats, to detect change that may be brought about by sector activities such as fishing or climate change, to estimate the population size of exploited reef species for fisheries management and to identify positive changes to biodiversity and lobster abundance that may occur through spatial management of reef habitat.European Maritime and Fisheries Fund (EMFF) Operational Programme 2014-2020. Project ref number: MB/2019/0

Effects of gastroprotectant drugs for the prevention and treatment of peptic ulcer disease and its complications: a meta-analysis of randomised trials

Background: Gastroprotectant drugs are used for the prevention and treatment of peptic ulcer disease and might reduce its associated complications, but reliable estimates of the effects of gastroprotectants in different clinical settings are scarce. We aimed to examine the effects of proton-pump inhibitors (PPIs), prostaglandin analogues, and histamine-2 receptor antagonists (H2RAs) in different clinical circumstances by doing meta-analyses of tabular data from all relevant unconfounded randomised trials of gastroprotectant drugs. Background: Gastroprotectant drugs are used for the prevention and treatment of peptic ulcer disease and might reduce its associated complications, but reliable estimates of the effects of gastroprotectants in different clinical settings are scarce. We aimed to examine the effects of proton-pump inhibitors (PPIs), prostaglandin analogues, and histamine-2 receptor antagonists (H2RAs) in different clinical circumstances by doing meta-analyses of tabular data from all relevant unconfounded randomised trials of gastroprotectant drugs. Methods: We searched MEDLINE and Embase from Jan 1, 1950, to Dec 31, 2015, to identify unconfounded, randomised trials of a gastroprotectant drug (defined as a PPI, prostaglandin analogue, or H2RA) versus control, or versus another gastroprotectant. Two independent researchers reviewed the search results and extracted the prespecified outcomes and key characteristics for each trial. We did meta-analyses of the effects of gastroprotectant drugs on ulcer development, bleeding, and mortality overall, according to the class of gastroprotectant, and according to the individual drug within a gastroprotectant class. Findings: We identified comparisons of gastroprotectant versus control in 849 trials (142 485 participants): 580 prevention trials (110 626 participants), 233 healing trials (24 033 participants), and 36 trials for the treatment of acute upper gastrointestinal bleeding (7826 participants). Comparisons of one gastroprotectant drug versus another were available in 345 trials (64 905 participants), comprising 160 prevention trials (32 959 participants), 167 healing trials (28 306 participants), and 18 trials for treatment of acute upper gastrointestinal bleeding (3640 participants). The median number of patients in each trial was 78 (IQR 44·0–210·5) and the median duration was 1·4 months (0·9–2·8). In prevention trials, gastroprotectant drugs reduced development of endoscopic ulcers (odds ratio [OR] 0·27, 95% CI 0·25–0·29; p&lt;0·0001), symptomatic ulcers (0·25, 0·22–0·29; p&lt;0·0001), and upper gastrointestinal bleeding (0·40, 0·32–0·50; p&lt;0·0001), but did not significantly reduce mortality (0·85, 0·69–1·04; p=0·11). Larger proportional reductions in upper gastrointestinal bleeding were observed for PPIs than for other gastroprotectant drugs (PPIs 0·21, 99% CI 0·12–0·36; prostaglandin analogues 0·63, 0·35–1·12; H2RAs 0·49, 0·30–0·80; phet=0·0005). Gastroprotectant drugs were effective in preventing bleeding irrespective of the use of non-steroidal anti-inflammatory drugs (phet=0·56). In healing trials, gastroprotectants increased endoscopic ulcer healing (3·49, 95% CI 3·28–3·72; p&lt;0·0001), with PPIs more effective (5·22, 99% CI 4·00–6·80) than prostaglandin analogues (2·27, 1·91–2·70) and H2RAs (3·80, 3·44–4·20; phet&lt;0·0001). In trials among patients with acute bleeding, gastroprotectants reduced further bleeding (OR 0·68, 95% CI 0·60–0·78; p&lt;0·0001), blood transfusion (0·75, 0·65–0·88; p=0·0003), further endoscopic intervention (0·56, 0·45–0·70; p&lt;0·0001), and surgery (0·72, 0·61–0·84; p&lt;0·0001), but did not significantly reduce mortality (OR 0·90, 0·72–1·11; p=0·31). PPIs had larger protective effects than did H2RAs for further bleeding (phet=0·0107) and blood transfusion (phet=0·0130). Interpretation: Gastroprotectants, in particular PPIs, reduce the risk of peptic ulcer disease and its complications and promote healing of peptic ulcers in a wide range of clinical circumstances. However, this meta-analysis might have overestimated the benefits owing to small study bias

Recombination dynamics of a human Y-chromosomal palindrome:rapid GC-biased gene conversion, multi-kilobase conversion tracts, and rare inversions

The male-specific region of the human Y chromosome (MSY) includes eight large inverted repeats (palindromes) in which arm-to-arm similarity exceeds 99.9%, due to gene conversion activity. Here, we studied one of these palindromes, P6, in order to illuminate the dynamics of the gene conversion process. We genotyped ten paralogous sequence variants (PSVs) within the arms of P6 in 378 Y chromosomes whose evolutionary relationships within the SNP-defined Y phylogeny are known. This allowed the identification of 146 historical gene conversion events involving individual PSVs, occurring at a rate of 2.9-8.4×10(-4) events per generation. A consideration of the nature of nucleotide change and the ancestral state of each PSV showed that the conversion process was significantly biased towards the fixation of G or C nucleotides (GC-biased), and also towards the ancestral state. Determination of haplotypes by long-PCR allowed likely co-conversion of PSVs to be identified, and suggested that conversion tract lengths are large, with a mean of 2068 bp, and a maximum in excess of 9 kb. Despite the frequent formation of recombination intermediates implied by the rapid observed gene conversion activity, resolution via crossover is rare: only three inversions within P6 were detected in the sample. An analysis of chimpanzee and gorilla P6 orthologs showed that the ancestral state bias has existed in all three species, and comparison of human and chimpanzee sequences with the gorilla outgroup confirmed that GC bias of the conversion process has apparently been active in both the human and chimpanzee lineages

UV Circular Polarisation in Star Formation Regions : The Origin of Homochirality?

Ultraviolet circularly polarised light has been suggested as the initial cause of the homochirality of organic molecules in terrestrial organisms, via enantiomeric selection of prebiotic molecules by asymmetric photolysis. We present a theoretical investigation of mechanisms by which ultraviolet circular polarisation may be produced in star formation regions. In the scenarios considered here, light scattering produces only a small percentage of net circular polarisation at any point in space, due to the forward throwing nature of the phase function in the ultraviolet. By contrast, dichroic extinction can produce a fairly high percentage of net circular polarisation (∼10%) and may therefore play a key role in producing an enantiomeric excessPeer reviewe

The formation of very wide binaries during the star cluster dissolution phase

Over the past few decades, numerous wide (>1000 au) binaries in the Galactic field and halo have been discovered. Their existence cannot be explained by the process of star formation or by dynamical interactions in the field, and their origin has long been a mystery. We explain the origin of these wide binaries by formation during the dissolution phase of young star clusters: an initially unbound pair of stars may form a binary when their distance in phase-space is small. Using N-body simulations, we find that the resulting wide binary fraction in the semi-major axis range 1000 au - 0.1 pc for individual clusters is 1-30%, depending on the initial conditions. The existence of numerous wide binaries in the field is consistent with observational evidence that most clusters start out with a large degree of substructure. The wide binary fraction decreases strongly with increasing cluster mass, and the semi-major axis of the newly formed binaries is determined by the initial cluster size. The resulting eccentricity distribution is thermal, and the mass ratio distribution is consistent with gravitationally-focused random pairing. As a large fraction of the stars form in primordial binaries, we predict that a large number of the observed 'wide binaries' are in fact triple or quadruple systems. By integrating over the initial cluster mass distribution, we predict a binary fraction of a few per cent in the semi-major axis range 1000 au - 0.1 pc in the Galactic field, which is smaller than the observed wide binary fraction. However, this discrepancy may be solved when we consider a broad range of cluster morphologies.Comment: 14 pages, 12 figures, accepted by MNRA