Comment on ‘Tumour-infiltrating inflammation and prognosis in colorectal cancer: systematic review and meta-analysis’

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Public perceptions of the UK marine environment

The damaging effects of human activities on marine health suggest that a major shift is required in the way marine systems are used by individuals. Identifying how to engage society in this shift is an ongoing debate. This includes strengthening the positive connections between society and the sea. This study uses a survey (n¼1047) to investigate UK public perceptions of subtidal species and marine health to assess whether it is possible to build more positive connections between society and the sea. Respondents showed considerable interest in traditionally charismatic species (puffins, seals and seahorses) although many respondents thought these species did not live in UK seas. Gender and experience of marine environments influenced public perceptions of species. Public perceptions of marine health showed issues such as litter to be considered as the greatest indicator of poor health. Ecological concepts of habitat integrity and biodiversity were also rated as important to marine health. Social values were found to influence public perceptions of marine health. The results show that perceptions are far from uniform across the population, and such diversity of perceptions is likely impact upon methods to catalyse societal engagement with marine conservation. These findings reinforce previous research on public perceptions of UK seas, and identify opportunities for building positive connections between society and the sea. Research priorities to further the debate of engaging society with the sea are identified

Performance optimization of a leagility inspired supply chain model: a CFGTSA algorithm based approach

Lean and agile principles have attracted considerable interest in the past few decades. Industrial sectors throughout the world are upgrading to these principles to enhance their performance, since they have been proven to be efficient in handling supply chains. However, the present market trend demands a more robust strategy incorporating the salient features of both lean and agile principles. Inspired by these, the leagility principle has emerged, encapsulating both lean and agile features. The present work proposes a leagile supply chain based model for manufacturing industries. The paper emphasizes the various aspects of leagile supply chain modeling and implementation and proposes a new Hybrid Chaos-based Fast Genetic Tabu Simulated Annealing (CFGTSA) algorithm to solve the complex scheduling problem prevailing in the leagile environment. The proposed CFGTSA algorithm is compared with the GA, SA, TS and Hybrid Tabu SA algorithms to demonstrate its efficacy in handling complex scheduling problems

Gene transfer: anything goes in plant mitochondria

Parasitic plants and their hosts have proven remarkably adept at exchanging fragments of mitochondrial DNA. Two recent studies provide important mechanistic insights into the pattern, process and consequences of horizontal gene transfer, demonstrating that genes can be transferred in large chunks and that gene conversion between foreign and native genes leads to intragenic mosaicism. A model involving duplicative horizontal gene transfer and differential gene conversion is proposed as a hitherto unrecognized source of genetic diversity

Dating of the oldest continental sediments from the Himalayan foreland basin

A detailed knowledge of Himalayan development is important for our wider understanding of several global processes, ranging from models of plateau uplift to changes in oceanic chemistry and climate(1-4). Continental sediments 55 Myr old found in a foreland basin in Pakistan(5) are, by more than 20 Myr, the oldest deposits thought to have been eroded from the Himalayan metamorphic mountain belt. This constraint on when erosion began has influenced models of the timing and diachrony of the India-Eurasia collision(6-8), timing and mechanisms of exhumation(9,10) and uplift(11), as well as our general understanding of foreland basin dynamics(12). But the depositional age of these basin sediments was based on biostratigraphy from four intercalated marl units(5). Here we present dates of 257 detrital grains of white mica from this succession, using the Ar-40-(39) Ar method, and find that the largest concentration of ages are at 36-40 Myr. These dates are incompatible with the biostratigraphy unless the mineral ages have been reset, a possibility that we reject on the basis of a number of lines of evidence. A more detailed mapping of this formation suggests that the marl units are structurally intercalated with the continental sediments and accordingly that biostratigraphy cannot be used to date the clastic succession. The oldest continental foreland basin sediments containing metamorphic detritus eroded from the Himalaya orogeny therefore seem to be at least 15-20 Myr younger than previously believed, and models based on the older age must be re-evaluated

Application of the speed-duration relationship to normalize the intensity of high-intensity interval training

The tolerable duration of continuous high-intensity exercise is determined by the hyperbolic Speed-tolerable duration (S-tLIM) relationship. However, application of the S-tLIM relationship to normalize the intensity of High-Intensity Interval Training (HIIT) has yet to be considered, with this the aim of present study. Subjects completed a ramp-incremental test, and series of 4 constant-speed tests to determine the S-tLIM relationship. A sub-group of subjects (n = 8) then repeated 4 min bouts of exercise at the speeds predicted to induce intolerance at 4 min (WR4), 6 min (WR6) and 8 min (WR8), interspersed with bouts of 4 min recovery, to the point of exercise intolerance (fixed WR HIIT) on different days, with the aim of establishing the work rate that could be sustained for 960 s (i.e. 4×4 min). A sub-group of subjects (n = 6) also completed 4 bouts of exercise interspersed with 4 min recovery, with each bout continued to the point of exercise intolerance (maximal HIIT) to determine the appropriate protocol for maximizing the amount of high-intensity work that can be completed during 4×4 min HIIT. For fixed WR HIIT tLIM of HIIT sessions was 399±81 s for WR4, 892±181 s for WR6 and 1517±346 s for WR8, with total exercise durations all significantly different from each other (P<0.050). For maximal HIIT, there was no difference in tLIM of each of the 4 bouts (Bout 1: 229±27 s; Bout 2: 262±37 s; Bout 3: 235±49 s; Bout 4: 235±53 s; P>0.050). However, there was significantly less high-intensity work completed during bouts 2 (153.5±40. 9 m), 3 (136.9±38.9 m), and 4 (136.7±39.3 m), compared with bout 1 (264.9±58.7 m; P>0.050). These data establish that WR6 provides the appropriate work rate to normalize the intensity of HIIT between subjects. Maximal HIIT provides a protocol which allows the relative contribution of the work rate profile to physiological adaptations to be considered during alternative intensity-matched HIIT protocols

The Overall Coefficient of the Two-loop Superstring Amplitude Using Pure Spinors

Using the results recently obtained for computing integrals over (non-minimal) pure spinor superspace, we compute the coefficient of the massless two-loop four-point amplitude from first principles. Contrasting with the mathematical difficulties in the RNS formalism where unknown normalizations of chiral determinant formulae force the two-loop coefficient to be determined only indirectly through factorization, the computation in the pure spinor formalism can be smoothly carried out.Comment: 29 pages, harvmac TeX. v2: add reference

Clustering and Alignment of Polymorphic Sequences for HLA-DRB1 Genotyping

Located on Chromosome 6p21, classical human leukocyte antigen genes are highly polymorphic. HLA alleles associate with a variety of phenotypes, such as narcolepsy, autoimmunity, as well as immunologic response to infectious disease. Moreover, high resolution genotyping of these loci is critical to achieving long-term survival of allogeneic transplants. Development of methods to obtain high resolution analysis of HLA genotypes will lead to improved understanding of how select alleles contribute to human health and disease risk. Genomic DNAs were obtained from a cohort of n = 383 subjects recruited as part of an Ulcerative Colitis study and analyzed for HLA-DRB1. HLA genotypes were determined using sequence specific oligonucleotide probes and by next-generation sequencing using the Roche/454 GSFLX instrument. The Clustering and Alignment of Polymorphic Sequences (CAPSeq) software application was developed to analyze next-generation sequencing data. The application generates HLA sequence specific 6-digit genotype information from next-generation sequencing data using MUMmer to align sequences and the R package diffusionMap to classify sequences into their respective allelic groups. The incorporation of Bootstrap Aggregating, Bagging to aid in sorting of sequences into allele classes resulted in improved genotyping accuracy. Using Bagging iterations equal to 60, the genotyping results obtained using CAPSeq when compared with sequence specific oligonucleotide probe characterized 4-digit genotypes exhibited high rates of concordance, matching at 759 out of 766 (99.1%) alleles. © 2013 Ringquist et al

Oral beclomethasone dipropionate is an effective treatment for immune checkpoint inhibitor induced colitis.

INTRODUCTION: Systemic corticosteroids are the mainstay of treatment for immune checkpoint inhibitor induced (CPI) colitis but are associated with complications including life-threatening infection. The topically acting oral corticosteroid beclomethasone dipropionate (BD) is an effective treatment for mild to moderate flares of ulcerative colitis, and has fewer side effects than systemic corticosteroids. We hypothesized that BD would be an effective treatment for CPI-induced colitis. METHODS: We performed a retrospective analysis of all patients who started BD for CPI-induced colitis at three UK cancer centers between November 2017 and October 2020. All patients underwent endoscopic assessment and biopsy. The initial regimen of BD was 5 mg once daily for 28 days. Data were collected from electronic patient records. Clinical outcomes were assessed at 28 days after initiation of treatment. RESULTS: Twenty-two patients (14 male) with a median age of 64 (range 45-84) with CPI-induced colitis were treated with BD. At baseline, the median number of loose stools in a 24-hour period was six (common terminology criteria for adverse events, CTCAE grade diarrhea=2). Thirteen patients (59%) were dependent on systemic corticosteroids prior to starting BD. Baseline sigmoidoscopy showed moderate inflammation (Mayo Endoscopic Score (MES) = 2) in two patients (9%), mild inflammation (MES=1) in nine patients (41%) and normal findings (MES=0) in eleven patients (50%). Twenty patients (91%) had histopathological features of inflammation. All 22 patients (100%) had a clinical response to BD and 21 (95%) achieved clinical remission with a return to baseline stool frequency (CTCAE diarrhea=0). Ten patients (45%) had symptomatic relapse on cessation of BD, half within 7 days of stopping. All patients recaptured response on restarting BD. No adverse events were reported in patients treated with BD. CONCLUSIONS: Topical BD represents an appealing alternative option to systemic immunosuppressive treatments to treat colonic inflammation. In this study, BD was effective and safe at inducing remission in CPI-induced colitis, which was refractory to systemic corticosteroids. Further randomized studies are needed to confirm these findings and determine the optimum dosing regimen