Optical Efficiency Calibration for Inhomogeneous IACT Arrays and a Detailed Study of the Highly Extended Pulsar Wind Nebula HESS J1825-137

Very High Energy (VHE) Gamma-ray astronomy using Imaging Atmospheric Cherenkov Telescopes (IACTs) is entering an era of hybrid arrays (such as H.E.S.S. II and CTA), comprising telescopes of varied specifications to enhance the accessible energy range and angular resolution. New algorithms for telescope optical efficiency calibration are developed and adapted for multi-type arrays, for both absolute light yield calibration using muons, and for relative calibration through comparison of shower images. In comparison to previous methods, the stability and flexibility of these algorithms are considerably improved. These will play an important role for the future CTA observatory. The use of multi-type IACT arrays in providing an increased understanding of astrophysical objects and environments is demonstrated through an in-depth study of the Pulsar Wind Nebula HESS J1825-137, known to be highly extended with the presence of strong energy dependent morphology. In particular, measurements of HESS J1825-137 across the entire available energy range allow the particle transport inside the nebula to be constrained, favouring advection over diffusion as the dominant mechanism. Together with X-ray data, a map of the magnetic field of the nebula can be made through spectral modelling. It will also be shown that HESS J1825-137, at 100 pc across, is one of the biggest pulsar wind nebulae to have been discovered yet

The legal recognition particularly by international law and European community law of special economic dependency and preferential rights as claimed in relation to fisheries

An analysis of special economic dependency and preferential rights as claimed in respect of fishery resources is the topic of this thesis. The overall purpose of the study is to assess the legal recognition which has been accorded to the concepts by international law and European Community law respectively. Initially the concepts are examined within the context of international law. The development and recognition of special economic dependency and preferential rights by the international community are examined in detail, especially as the International Court of Justice confidently asserted, in the Fisheries Jurisdiction (United Kingdom v Iceland) Case in.1974, that both concepts were international customary law. The conclusion drawn from the examination is, however, that neither concept has attained the status of international law. Nevertheless, because it has proved politically expedient, the concepts have been recognised as important considerations to be taken account of in fishery negotiations. Similarly, under European Community law the conclusion again is that while both concepts have been recognised they are not recognised as legal concepts which may be invoked as of right. The concepts accordingly cannot be dismissed and the question as to when claims of special economic dependency and preferential rights may be successful is considered. Considered, that is, by reference to international law, European Community law and occasionally municipal law. The raison d'etre for this, as constantly stressed throughout the text, is that although a concept adopted by one legal system need not necessarily be characterised in the same way by another legal, system, legal systems do interrelate. Interrelation will be all the more probable if concepts of the same name are utilised to express similar factual situations. Special dependency claims are, therefore, examined to see whether a factual resemblance may be identified between claimants in different legal systems. In respect of preferential rights, possible ways of their being articulated so as to give expression to special dependency are considered, with the conclusion being drawn that preferential rights should not be defined only in terms of preferential rights of access to fish stocks. A broad definition is required if specially dependent regions are to reap any long-term benefit from being granted preferential rights. The relevance of this study may be thought by some to be minimal in respect of international law. However, although claims of special economic dependency and preferential rights have receded with the establishment of 200 mile fishing/economic zones, Article 71 of the 1981 Draft Convention on the Law of the Sea does provide that a coastal State may derogate from granting access to other States if its "economy is overwhelmingly dependent on the exploitation of the living resources of its exclusive economic zone." It is anticipated, therefore, that in the light of such a provision, special economic dependency and preferential rights will gain fresh relevance under international law. As far as European Community law is concerned, any study of the concepts should be welcome because although it does not solve the problems currently confronting those responsible for negotiating a common fisheries policy, it does at least highlight those ways in which the concepts may be accommodated within the Community system and how through the interrelation of legal systems acceptable means of expression may be found. The law is as of 31 December 1981

Inducing labour in the United Kingdom: A feminist critical discourse analysis of policy and guidance

Induction of labour (IOL), the process of starting labour artificially, is one of the most commonly performed procedures in maternity care in the United Kingdom (UK), yet there is debate whether inducing labour at ‘term’, in the absence of specific medical indication, is beneficial and reduces risk of stillbirth. Moreover, rates of routine IOL are rapidly rising in the UK, despite uncertainty about the evidence base and parents reporting receiving a lack of balanced information about the process. As a contested area of maternity care, the language used to debate, describe and discuss IOL takes on added significance and requires in-depth examination and analysis. To address this, we conducted a feminist critical discourse analysis on policy and professional writing about IOL in the UK, focusing on how these both reflect and construct social practices of pregnancy and birth. Our analysis identified a double discourse about IOL, which we term ‘explicit-implicit discourse of care’, revealing the differences between what is expected to be said and what is really said. Though most texts displayed an explicit discourse of care, which espoused women-centred care and informed choice, they also conveyed an implicit discourse of care, primarily composed of three key dimensions: women as absent actors, disembodiment, and evidence as a primary actor. We argue that this explicit-implicit discourse functions to preserve healthcare professionals' control over maternity care and further alienate women from their own bodies while maintaining a discursive position of women-centred care and informed choice.Output Status: Forthcoming/Available Onlin

Clinicians’ perspectives and experiences of providing cervical ripening at home or in-hospital in the United Kingdom

Acknowledgements We are grateful to those who gave their time for interviews and focus groups despite the severe workload pressures and ongoing COVID-19 pandemic. CHOICE is funded by the National Institute of Healthcare Research Health Technology and Assessment (NIHR HTA) NIHR 127569. SJS is funded by a Wellcome Trust Clinical Career Development Fellowship (209560/Z/17/Z). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The views expressed are those of the authors and not necessarily those of the National Institute of Healthcare Research or the Department of Health and Social Care.Peer reviewedPublisher PD

Fission yeast 26S proteasome mutants are multi-drug resistant due to stabilization of the pap1 transcription factor

Here we report the result of a genetic screen for mutants resistant to the microtubule poison methyl benzimidazol-2-yl carbamate (MBC) that were also temperature sensitive for growth. In total the isolated mutants were distributed in ten complementation groups. Cloning experiments revealed that most of the mutants were in essential genes encoding various 26S proteasome subunits. We found that the proteasome mutants are multi-drug resistant due to stabilization of the stress-activated transcription factor Pap1. We show that the ubiquitylation and ultimately the degradation of Pap1 depend on the Rhp6/Ubc2 E2 ubiquitin conjugating enzyme and the Ubr1 E3 ubiquitin-protein ligase. Accordingly, mutants lacking Rhp6 or Ubr1 display drug-resistant phenotypes

Nedd8 processing enzymes in Schizosaccharomyces pombe

BACKGROUND: Conjugation of the ubiquitin-like modifier Nedd8 to cullins is critical for the function of SCF-type ubiquitin ligases and thus facilitates ubiquitin conjugation and ultimately degradation of SCF substrates, including several cell cycle regulators. Like ubiquitin, Nedd8 is produced as a precursor that must first be processed before it becomes active. In Saccharomyces cerevisiae this is carried out exclusively by the enzyme Yuh1. RESULTS: Here we show that in the fission yeast, Schizosaccharomyces pombe, the Yuh1 orthologue, Uch1, is not the sole Nedd8 processing enzyme. Instead it appears that deubiquitylating enzymes can efficiently process the Nedd8 precursor in vivo. CONCLUSIONS: Several enzymes contribute to Nedd8 precursor processing including a number of deubiquitylating enzymes

Dynamic Gene Regulatory Networks Drive Hematopoietic Specification and Differentiation.

Metazoan development involves the successive activation and silencing of specific gene expression programs and is driven by tissue-specific transcription factors programming the chromatin landscape. To understand how this process executes an entire developmental pathway, we generated global gene expression, chromatin accessibility, histone modification, and transcription factor binding data from purified embryonic stem cell-derived cells representing six sequential stages of hematopoietic specification and differentiation. Our data reveal the nature of regulatory elements driving differential gene expression and inform how transcription factor binding impacts on promoter activity. We present a dynamic core regulatory network model for hematopoietic specification and demonstrate its utility for the design of reprogramming experiments. Functional studies motivated by our genome-wide data uncovered a stage-specific role for TEAD/YAP factors in mammalian hematopoietic specification. Our study presents a powerful resource for studying hematopoiesis and demonstrates how such data advance our understanding of mammalian development.This work was funded by a Longer Larger (LoLa) consortium grant from the Biotechnology and Biological Sciences Research Council, UK, to the senior authors and the corresponding author, computing infrastructure grants from the Wellcome Trust and National Institute for Health Research to B.G., grants from Cancer Research UK to G.L. and V.K., and funding from the Bloodwise charity to C.B.This is the final version of the article. It first appeared from Cell Press via http://dx.doi.org/10.1016/j.devcel.2016.01.02

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

Exposing racial bias in midwifery education: a content analysis of images and text in Myles Textbook for Midwives

Background Race is well documented as a factor in perinatal outcomes. Inherent racial bias has been identified in healthcare learning materials. Myles Textbook for Midwives is used by thousands of midwives globally. Aims To determine how people of different skin colours are represented within Myles. Methods Content analysis of text and images in Myles Textbook for Midwives 17th Edition, 2020 Findings The images overwhelmingly depict light skinned people of White European appearance. Descriptions of skin colour in context of clinical assessment often applied mostly or solely to people with light colour skin. This text often referred to conditions associated with severe morbidity or mortality. Key conclusions Myles Textbook for Midwives presents a light skinned White European norm and often fails to include information that is clinically relevant to the assessment of people with darker skin colours. This may lead to disparity in midwifery education and contribute to poorer outcomes for women and babies

Exposing racial bias in midwifery education: a content analysis of images and text in Myles Textbook for Midwives

Background Race is well documented as a factor in perinatal outcomes. Inherent racial bias has been identified in healthcare learning materials. Myles Textbook for Midwives is used by thousands of midwives globally. Aims To determine how people of different skin colours are represented within Myles. Methods Content analysis of text and images in Myles Textbook for Midwives 17th Edition, 2020 Findings The images overwhelmingly depict light skinned people of White European appearance. Descriptions of skin colour in context of clinical assessment often applied mostly or solely to people with light colour skin. This text often referred to conditions associated with severe morbidity or mortality. Key conclusions Myles Textbook for Midwives presents a light skinned White European norm and often fails to include information that is clinically relevant to the assessment of people with darker skin colours. This may lead to disparity in midwifery education and contribute to poorer outcomes for women and babies