Rapid detection of BRCA1/2 recurrent mutations in Chinese breast and ovarian cancer patients with multiplex SNaPshot genotyping panels.

BRCA1/2 mutations are significant risk factors for hereditary breast and ovarian cancer (HBOC), its mutation frequency in HBOC of Chinese ethnicity is around 9%, in which nearly half are recurrent mutations. In Hong Kong and China, genetic testing and counseling are not as common as in the West. To reduce the barrier of testing, a multiplex SNaPshot genotyping panel that targeted 25 Chinese BRCA1/2 mutation hotspots was developed, and its feasibility was evaluated in a local cohort of 441 breast and 155 ovarian cancer patients. For those who tested negative, they were then subjected to full-gene testing with next-generation sequencing (NGS). BRCA mutation prevalence in this cohort was 8.05% and the yield of the recurrent panel was 3.52%, identifying over 40% of the mutation carriers. Moreover, from 79 Chinese breast cancer cases recruited overseas, 2 recurrent mutations and one novel BRCA2 mutation were detected by the panel and NGS respectively. The developed genotyping panel showed to be an easy-to-perform and more affordable testing tool that can provide important contributions to improve the healthcare of Chinese women with cancer as well as family members that harbor high risk mutations for HBOC

Improving quality of care and outcome at very preterm birth: the Preterm Birth research programme, including the Cord pilot RCT

BACKGROUND: Being born very premature (i.e. before 32 weeks’ gestation) has an impact on survival and quality of life. Improving care at birth may improve outcomes and parents’ experiences. OBJECTIVES: To improve the quality of care and outcomes following very preterm birth. DESIGN: We used mixed methods, including a James Lind Alliance prioritisation, a systematic review, a framework synthesis, a comparative review, qualitative studies, development of a questionnaire tool and a medical device (a neonatal resuscitation trolley), a survey of practice, a randomised trial and a protocol for a prospective meta-analysis using individual participant data. SETTING: For the prioritisation, this included people affected by preterm birth and health-care practitioners in the UK relevant to preterm birth. The qualitative work on preterm birth and the development of the questionnaire involved parents of infants born at three maternity hospitals in southern England. The medical device was developed at Liverpool Women’s Hospital. The survey of practice involved UK neonatal units. The randomised trial was conducted at eight UK tertiary maternity hospitals. PARTICIPANTS: For prioritisation, 26 organisations and 386 individuals; for the interviews and questionnaire tool, 32 mothers and seven fathers who had a baby born before 32 weeks’ gestation for interviews evaluating the trolley, 30 people who had experienced it being used at the birth of their baby (19 mothers, 10 partners and 1 grandmother) and 20 clinicians who were present when it was being used; for the trial, 261 women expected to have a live birth before 32 weeks’ gestation, and their 276 babies. INTERVENTIONS: Providing neonatal care at very preterm birth beside the mother, and with the umbilical cord intact; timing of cord clamping at very preterm birth. MAIN OUTCOMES MEASURES: Research priorities for preterm birth; feasibility and acceptability of the trolley; feasibility of a randomised trial, death and intraventricular haemorrhage. REVIEW METHODS: Systematic review of Cochrane reviews (umbrella review); framework synthesis of ethics aspects of consent, with conceptual framework to inform selection criteria for empirical and analytical studies. The comparative review included studies using a questionnaire to assess satisfaction with care during childbirth, and provided psychometric information. RESULTS: Our prioritisation identified 104 research topics for preterm birth, with the top 30 ranked. An ethnographic analysis of decision-making during this process suggested ways that it might be improved. Qualitative interviews with parents about their experiences of very preterm birth identified two differences with term births: the importance of the staff appearing calm and of staff taking control. Following a comparative review, this led to the development of a questionnaire to assess parents’ views of care during very preterm birth. A systematic overview summarised evidence for delivery room neonatal care and revealed significant evidence gaps. The framework synthesis explored ethics issues in consent for trials involving sick or preterm infants, concluding that no existing process is ideal and identifying three important gaps. This led to the development of a two-stage consent pathway (oral assent followed by written consent), subsequently evaluated in our randomised trial. Our survey of practice for care at the time of birth showed variation in approaches to cord clamping, and that no hospitals were providing neonatal care with the cord intact. We showed that neonatal care could be provided beside the mother using either the mobile neonatal resuscitation trolley we developed or existing equipment. Qualitative interviews suggested that neonatal care beside the mother is valued by parents and acceptable to clinicians. Our pilot randomised trial compared cord clamping after 2 minutes and initial neonatal care, if needed, with the cord intact, with clamping within 20 seconds and initial neonatal care after clamping. This study demonstrated feasibility of a large UK randomised trial. Of 135 infants allocated to cord clamping ≥ 2 minutes, 7 (5.2%) died and, of 135 allocated to cord clamping ≤ 20 seconds, 15 (11.1%) died (risk difference –5.9%, 95% confidence interval –12.4% to 0.6%). Of live births, 43 out of 134 (32%) allocated to cord clamping ≥ 2 minutes had intraventricular haemorrhage compared with 47 out of 132 (36%) allocated to cord clamping ≤ 20 seconds (risk difference –3.5%, 95% CI –14.9% to 7.8%). LIMITATIONS: Small sample for the qualitative interviews about preterm birth, single-centre evaluation of neonatal care beside the mother, and a pilot trial. CONCLUSIONS: Our programme of research has improved understanding of parent experiences of very preterm birth, and informed clinical guidelines and the research agenda. Our two-stage consent pathway is recommended for intrapartum clinical research trials. Our pilot trial will contribute to the individual participant data meta-analysis, results of which will guide design of future trials. FUTURE WORK: Research in preterm birth should take account of the top priorities. Further evaluation of neonatal care beside the mother is merited, and future trial of alternative policies for management of cord clamping should take account of the meta-analysis. STUDY REGISTRATION: This study is registered as PROSPERO CRD42012003038 and CRD42013004405. In addition, Current Controlled Trials ISRCTN21456601. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 7, No. 8. See the NIHR Journals Library website for further project information

Lysine-91 of the tetraheme c-type cytochrome CymA is essential for quinone interaction and arsenate respiration in Shewanella sp. strain ANA-3

The tetraheme c-type cytochrome, CymA, is essential for arsenate respiratory reduction in Shewanella sp. ANA-3, a model arsenate reducer. CymA is predicted to mediate electron transfer from quinols to the arsenate respiratory reductase (ArrAB). Here, we present biochemical and physiological evidence that CymA interacts with menaquinol (MQH2) substrates. Fluorescence quench titration with the MQH2 analog, 2-n-heptyl-4-hydroxyquinoline-N-oxide (HOQNO), was used to demonstrate quinol binding of E. coli cytoplasmic membranes enriched with various forms of CymA. Wild-type CymA bound HOQNO with a Kd of 0.1–1 μM. It was also shown that the redox active MQH2 analog, 2,3-dimethoxy-1,4-naphthoquinone (DMNH2), could reduce CymA in cytoplasmic membrane preparations. Based on a CymA homology model made from the NrfH tetraheme cytochrome structure, it was predicted that Lys91 would be involved in CymA-quinol interactions. CymA with a K91Q substitution showed little interaction with HOQNO. In addition, DMNH2-dependent reduction of CymA-K91Q was diminished by 45% compared to wild-type CymA. A ΔcymA ANA-3 strain containing a plasmid copy of cymA-K91Q failed to grow with arsenate as an electron acceptor. These results suggest that Lys91 is physiologically important for arsenate respiration and support the hypothesis that CymA interacts with menaquinol resulting in the reduction of the cytochrome

Optimal measurement of visual motion across spatial and temporal scales

Sensory systems use limited resources to mediate the perception of a great variety of objects and events. Here a normative framework is presented for exploring how the problem of efficient allocation of resources can be solved in visual perception. Starting with a basic property of every measurement, captured by Gabor's uncertainty relation about the location and frequency content of signals, prescriptions are developed for optimal allocation of sensors for reliable perception of visual motion. This study reveals that a large-scale characteristic of human vision (the spatiotemporal contrast sensitivity function) is similar to the optimal prescription, and it suggests that some previously puzzling phenomena of visual sensitivity, adaptation, and perceptual organization have simple principled explanations.Comment: 28 pages, 10 figures, 2 appendices; in press in Favorskaya MN and Jain LC (Eds), Computer Vision in Advanced Control Systems using Conventional and Intelligent Paradigms, Intelligent Systems Reference Library, Springer-Verlag, Berli

Informing the design of a national screening and treatment programme for chronic viral hepatitis in primary care: qualitative study of at-risk immigrant communities and healthcare professionals

n Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise statedThis paper presents independent research funded by the National Institute for Health Research (NIHR) under the Programme Grants for Applied Research programme (RP-PG-1209-10038).

Corporate governance compliance and disclosure in the banking sector: using data from Japan

Using regression model this study investigates which characteristics of a bank is associated with the extent of corporate governance disclosure in Japan. The findings suggest that on average 8 banks out of a sample of 46 disclose optimal corporate governance information. The regression model results reveal in general that non-executive directors, cross-ownership, capital adequacy ratio and type of auditors are associated with the extent of corporate governance disclosure. Of these four variables, non-executive directors have a more significant impact on the extent of disclosure contrary to total assets and audit firms of banks in the context of Japan. The findings of this paper are relevant for corporate regulators, professional associations and developers of corporate governance code when designing or updating corporate governance code

Cervical epidural steroid injections in the management of cervical radiculitis: interlaminar versus transforaminal. A review

There has been recent concern regarding the safety of cervical epidural steroid injections. The decision to proceed with treatment requires balancing the risk and benefits. This article is an in depth review of the efficacy, complications, and technique of both interlaminar and transforaminal cervical epidural steroid injections in the management of cervical radiculitis

Charged-Higgs phenomenology in the Aligned two-Higgs-doublet model

The alignment in flavour space of the Yukawa matrices of a general two-Higgs-doublet model results in the absence of tree-level flavour-changing neutral currents. In addition to the usual fermion masses and mixings, the aligned Yukawa structure only contains three complex parameters, which are potential new sources of CP violation. For particular values of these three parameters all known specific implementations of the model based on discrete Z_2 symmetries are recovered. One of the most distinctive features of the two-Higgs-doublet model is the presence of a charged scalar. In this work, we discuss its main phenomenological consequences in flavour-changing processes at low energies and derive the corresponding constraints on the parameters of the aligned two-Higgs-doublet model.Comment: 46 pages, 19 figures. Version accepted for publication in JHEP. References added. Discussion slightly extended. Conclusions unchange

Cross-sector, sessional employment of pharmacists in rural hospitals in Australia and New Zealand: a qualitative study exploring pharmacists’ perceptions and experiences

Background: Many rural hospitals in Australia and New Zealand do not have an on-site pharmacist. Sessional employment of a local pharmacist offers a potential solution to address the clinical service needs of non-pharmacist rural hospitals. This study explored sessional service models involving pharmacists and factors (enablers and challenges) impacting on these models, with a view to informing future sessional employment. Methods: A series of semi-structured one-on-one interviews was conducted with rural pharmacists with experience, or intention to practise, in a sessional employment role in Australia and New Zealand. Participants were identified via relevant newsletters, discussion forums and referrals from contacts. Interviews were conducted during August 2012-January 2013 via telephone or Skype™, for approximately 40–55 minutes each, and recorded.Results: Seventeen pharmacists were interviewed: eight with ongoing sessional roles, five with sessional experience, and four working towards sessional employment. Most participants provided sessional hospital services on a weekly basis, mainly focusing on inpatient medication review and consultation. Recognition of the value of pharmacists’ involvement and engagement with other healthcare providers facilitated establishment and continuity of sessional services. Funds pooled from various sources supplemented some pharmacists’ remuneration in the absence of designated government funding. Enhanced employment opportunities, district support and flexibility in services facilitated the continuous operation of the sessional service. Conclusions: There is potential to address clinical pharmacy service needs in rural hospitals by cross-sector employment of pharmacists. The reported sessional model arrangements, factors impacting on sessional employment of pharmacists and learnings shared by the participants should assist development of similar models in other rural communities