Physics Opportunities with Meson Beams

Over the past two decades, meson photo- and electro-production data of unprecedented quality and quantity have been measured at electromagnetic facilities worldwide. By contrast, the meson-beam data for the same hadronic final states are mostly outdated and largely of poor quality, or even nonexistent, and thus provide inadequate input to help interpret, analyze, and exploit the full potential of the new electromagnetic data. To reap the full benefit of the high-precision electromagnetic data, new high-statistics data from measurements with meson beams, with good angle and energy coverage for a wide range of reactions, are critically needed to advance our knowledge in baryon and meson spectroscopy and other related areas of hadron physics. To address this situation, a state of-the-art meson-beam facility needs to be constructed. The present paper summarizes unresolved issues in hadron physics and outlines the vast opportunities and advances that only become possible with such a facility.Comment: 46 pages, 10 figures, 4 table

Ethnic diversification and neighbourhood mixing : a rapid response analysis of the 2021 Census of England and Wales

Funding from the Economic and Social Research Council (ESRC) is acknowledged gratefully, for the project ‘Geographies of Ethnic Diversity and Inequalities (GEDI)’ (award ES/W012499/1).This paper provides a rapid response analysis of the changing geographies of ethnic diversity and segregation in England and Wales using Census data covering the last 30 years (1991, 2001, 2011 and 2021), a period of significant social, economic and political change. Presenting the first detailed analysis of 2021 Census small area ethnic group data, we find that the growth of ethnic diversity at the national level is mirrored across residential neighbourhoods. Increasing numbers of neighbourhoods are home to a substantial mix of people from different ethnic groups, and this growing neighbourhood ethnic diversity has been spatially diffusing across all regions of England and Wales. We argue that to understand the ethnic mosaic across England and Wales, it is more illuminating to consider mix than majority: places labelled as 'minority-majority' are, in fact, ethnically diverse spaces, home to sizable proportions of people from many ethnic groups. Increasing ethnic diversity is matched by decreasing residential segregation, for all ethnic groups-majority and minority.Publisher PDFPeer reviewe

An ethnic group specific deprivation index for measuring neighbourhood inequalities in England and Wales

The Economic and Social Research Council (ESRC) is thanked for funding for the project Geographies of Ethnic Diversity and Inequalities (GEDI) (award ES/W012499/1).The measurement of deprivation for small areas in the UK has provided the basis for the development of policies and targeting of resources aimed at reducing spatial inequalities. Most measures summarise the aggregate level of deprivation across all people in a given area, and no account is taken of differences between people with differing characteristics, such as age, sex or ethnic group. In recognition of the marked inequalities between ethnic groups in the UK, and the distinctive geographies of these inequalities, this paper presents a new ethnic group-specific neighbourhood deprivation measure—the Ethnic Group Deprivation Index (EGDI). This index, using a custom cross-tabulated 2021 Census dataset on employment, housing tenure, education and health by ethnic group, reveals the small area geographies of ethnic inequalities that have to date received scant attention, and yet have profound impacts on life chances and well-being. Drawing on the methodological framework of the widely used English Index of Multiple Deprivation (IMD) and for the same geographies (Lower Layer Super Output Areas), the EGDI measures deprivation for each ethnic group using data from the 2021 Census of England and Wales. The EGDI reveals the complex geographies of ethnic inequality and demonstrates that while one ethnic group in a neighbourhood may have high relative levels of deprivation, another ethnic group in that same neighbourhood may experience very low relative levels. The EGDI explores ethnic inequalities within and between neighbourhoods, complementing and augmenting existing measures by offering an important means of better understanding ethnic inequalities. The EGDI can be used to help shape locally and culturally sensitive policy development and resource allocation.Publisher PDFPeer reviewe

The polycomb group protein EZH2 is involved in progression of prostate cancer

Prostate cancer is a leading cause of cancer-related death in males and is second only to lung cancer. Although effective surgical and radiation treatments exist for clinically localized prostate cancer, metastatic prostate cancer remains essentially incurable. Here we show, through gene expression profiling(1), that the polycomb group protein enhancer of zeste homolog 2 (EZH2)(2,3) is overexpressed in hormone-refractory, metastatic prostate cancer. Small interfering RNA (siRNA) duplexes(4) targeted against EZH2 reduce the amounts of EZH2 protein present in prostate cells and also inhibit cell proliferation in vitro. Ectopic expression of EZH2 in prostate cells induces transcriptional repression of a specific cohort of genes. Gene silencing mediated by EZH2 requires the SET domain and is attenuated by inhibiting histone deacetylase activity. Amounts of both EZH2 messenger RNA and EZH2 protein are increased in metastatic prostate cancer; in addition, clinically localized prostate cancers that express higher concentrations of EZH2 show a poorer prognosis. Thus, dysregulated expression of EZH2 may be involved in the progression of prostate cancer, as well as being a marker that distinguishes indolent prostate cancer from those at risk of lethal progression.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62896/1/nature01075.pd

Cluster K Mycobacteriophages: Insights into the Evolutionary Origins of Mycobacteriophage TM4

Five newly isolated mycobacteriophages –Angelica, CrimD, Adephagia, Anaya, and Pixie – have similar genomic architectures to mycobacteriophage TM4, a previously characterized phage that is widely used in mycobacterial genetics. The nucleotide sequence similarities warrant grouping these into Cluster K, with subdivision into three subclusters: K1, K2, and K3. Although the overall genome architectures of these phages are similar, TM4 appears to have lost at least two segments of its genome, a central region containing the integration apparatus, and a segment at the right end. This suggests that TM4 is a recent derivative of a temperate parent, resolving a long-standing conundrum about its biology, in that it was reportedly recovered from a lysogenic strain of Mycobacterium avium, but it is not capable of forming lysogens in any mycobacterial host. Like TM4, all of the Cluster K phages infect both fast- and slow-growing mycobacteria, and all of them – with the exception of TM4 – form stable lysogens in both Mycobacterium smegmatis and Mycobacterium tuberculosis; immunity assays show that all five of these phages share the same immune specificity. TM4 infects these lysogens suggesting that it was either derived from a heteroimmune temperate parent or that it has acquired a virulent phenotype. We have also characterized a widely-used conditionally replicating derivative of TM4 and identified mutations conferring the temperature-sensitive phenotype. All of the Cluster K phages contain a series of well conserved 13 bp repeats associated with the translation initiation sites of a subset of the genes; approximately one half of these contain an additional sequence feature composed of imperfectly conserved 17 bp inverted repeats separated by a variable spacer. The K1 phages integrate into the host tmRNA and the Cluster K phages represent potential new tools for the genetics of M. tuberculosis and related species

A High Throughput Screen Identifies Chemical Modulators of the Laminin-Induced Clustering of Dystroglycan and Aquaporin-4 in Primary Astrocytes

Background: Aquaporin-4 (AQP4) constitutes the principal water channel in the brain and is clusteredat the perivascular astrocyte endfeet. This specific distribution of AQP4 plays a major role in maintaining water homeostasis in the brain. A growing body of evidence points to a role ofthe dystroglycan complex and its interaction with perivascular laminin in the clusteringof AQP4 atperivascular astrocyte endfeet. Indeed, mice lacking components of this complex or in which laminindystroglycan interaction is disrupted show a delayed onset of brain edema due to a redistribution of AQP4 away from astrocyte endfeet. It is therefore important to identify inhibitory drugs of laminin-dependent AQP4 clustering which may prevent or reduce brain edema. Methodolgy/Principal Findings: In the present study we used primary rat astrocyte cultures toscreen a library of.3,500 chemicals and identified 6 drugs that inhibit the laminin-induced clustering of dystroglycan and AQP4. Detailed analysis of the inhibitory drug, chloranil, revealed that its inhibition of the clustering is due to the metalloproteinase-2-mediated ß-dystroglycan shedding and subsequent loss of laminin interaction with dystroglycan. Furthermore, chemical variants of chloranil induced a similar effect on ß-dystroglycan and this was prevented by the antioxidant N-acetylcysteine. Conclusion/Significance: These findings reveal the mechanism of action of chloranil in preventing the laminin-induced clustering of dystroglycan and AQP4 and validate the use of high-throughput screening as a tool to identify drugs tha

Rethinking childhood ependymoma: a retrospective, multi-center analysis reveals poor long-term overall survival

Ependymoma is the third most common brain tumor in children, but there is a paucity of large studies with more than 10 years of follow-up examining the long-term survival and recurrence patterns of this disease. We conducted a retrospective chart review of 103 pediatric patients with WHO Grades II/III intracranial ependymoma, who were treated at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and Chicago’s Ann & Robert H. Lurie Children’s Hospital between 1985 and 2008, and an additional 360 ependymoma patients identified from the Surveillance Epidemiology and End Results (SEER) database. For the institutional cohort, we evaluated clinical and histopathological prognostic factors of overall survival (OS) and progression-free survival (PFS) using the log-rank test, and univariate and multivariate Cox proportional-hazards models. Overall survival rates were compared to those of the SEER cohort. Median follow-up time was 11 years. Ten-year OS and PFS were 50 ± 5% and 29 ± 5%, respectively. Findings were validated in the independent SEER cohort, with 10-year OS rates of 52 ± 3%. GTR and grade II pathology were associated with significantly improved OS. However, GTR was not curative for all children. Ten-year OS for patients treated with a GTR was 61 ± 7% and PFS was 36 ± 6%. Pathological examination confirmed most recurrent tumors to be ependymoma, and 74% occurred at the primary tumor site. Current treatment paradigms are not sufficient to provide long-term cure for children with ependymoma. Our findings highlight the urgent need to develop novel treatment approaches for this devastating disease. Electronic supplementary material The online version of this article (doi:10.1007/s11060-017-2568-8) contains supplementary material, which is available to authorized users

The American Congress of Rehabilitation Medicine Diagnostic Criteria for Mild Traumatic Brain Injury

Objective: To develop new diagnostic criteria for mild traumatic brain injury (TBI) that are appropriate for use across the lifespan and in sports, civilian trauma, and military settings. Design: Rapid evidence reviews on 12 clinical questions and Delphi method for expert consensus. Participants: The Mild Traumatic Brain Injury Task Force of the American Congress of Rehabilitation Medicine Brain Injury Special Interest Group convened a Working Group of 17 members and an external interdisciplinary expert panel of 32 clinician-scientists. Public stakeholder feedback was analyzed from 68 individuals and 23 organizations. Results: The first 2 Delphi votes asked the expert panel to rate their agreement with both the diagnostic criteria for mild TBI and the supporting evidence statements. In the first round, 10 of 12 evidence statements reached consensus agreement. Revised evidence statements underwent a second round of expert panel voting, where consensus was achieved for all. For the diagnostic criteria, the final agreement rate, after the third vote, was 90.7%. Public stakeholder feedback was incorporated into the diagnostic criteria revision prior to the third expert panel vote. A terminology question was added to the third round of Delphi voting, where 30 of 32 (93.8%) expert panel members agreed that ‘the diagnostic label ‘concussion’ may be used interchangeably with ‘mild TBI’ when neuroimaging is normal or not clinically indicated.’ Conclusions: New diagnostic criteria for mild TBI were developed through an evidence review and expert consensus process. Having unified diagnostic criteria for mild TBI can improve the quality and consistency of mild TBI research and clinical care.</p