Kinetochore assembly: if you build it, they will come

Accurate chromosome segregation requires the interaction of chromosomes with the microtubules from the mitotic spindle. This interaction is mediated by the macro-molecular kinetochore complex, which assembles only at the centromeric region of each chromosome. However, how this site is specified and how assembly of the kinetochore structure is regulated in coordination with cell cycle progression remains unclear. Recent studies have begun to shed light on the mechanisms underlying assembly of this complex structure

Mobilization for Low Intensity Conflict

On 22 July 1982 President Reagan revised US mobilization policy through NSDD 47. His goal was to develop an emergency mobilization preparedness capability that will ensure that government at all levels, in partnership with the private sector and the American people, can respond decisively and effectively to any major national emergency, with defense of the United States as the first priority

Elle sera personage : Nicole Brossard’s writing of the self

La résistance de Brossard aux genres autobiographiques est assez notoire pour que frappe ce je mutable et fluide qui circule dans ses textes hybrides. Cet article retrace l’intérêt de Brossard pour les questions de subjectivité narrative depuis sa phrase célèbre, “Écrire ‘je suis une femme’ est plein de conséquences”. Nous avons choisi de lire Brossard non seulement en tant que théoricienne féministe de l’identité mais aussi comme une auteure qui se fictionnalise dans des “autofictions” qui —paradoxalement— remettent en cause cette catégorie. L’analyse se concentre sur ses préoccupations littéraires et philosophiques qui touchent au "personnage” ; ses jeux constants aux frontières de la fiction ; ses pronoms errants mettant en scène les relations complexes entre la narration et la vie ; et son exploration de la façon dont le soi qui écrit semble penser la construction d’un sujet parlant et sexué

Obstructive sleep apnoea (OSA) in regional and remote Indigenous Australians

Background: Despite Aboriginal and Torres Strait Islander people having increased risk factors for OSA (diabetes, obesity) and high levels of comorbid associated conditions (chronic non-communicable diseases), there are currently no published data relating to the nature of sleep related breathing disorders affecting Indigenous adults. Aims/Objectives: The aim of this study was to compare the use of sleep diagnostic tests, the risks, and cofactors, and outcomes of the care of Indigenous and non-indigenous Australian adults in regional and remote Australia in whom sleep related breathing disorders have been diagnosed. Methods: A retrospective cohort study of 200 sequential subjects: 100 Aboriginal and/or Torres Strait Islander people and 100 non-Indigenous Australians in northern Queensland and Central Australia. Results: Results showed overall Indigenous Australians were 1.8 times more likely to have a positive diagnostic sleep study performed compared with non-indigenous patients, 1.6 times less likely in central Australia and 3.4 times more likely in far north Queensland. All regional and remote residents accessed diagnostic sleep studies at a rate less than Australia overall (31/100,000/y compared with 575/100,000/y). Discussion: Appropriate and more accessible diagnostic and treatment sleep services are required in regional and remote Australia. Further research is required to validate appropriate screening tools and pathways of care especially for Aboriginal and Torres Strait Islander peoples

Relativistic ionization-rescattering with tailored laser pulses

The interaction of relativistically strong tailored laser pulses with an atomic system is considered. Due to a special tailoring of the laser pulse, the suppression of the relativistic drift of the ionized electron and a dramatic enhancement of the rescattering probability is shown to be achievable. The high harmonic generation rate in the relativistic regime is calculated and shown to be increased by several orders of magnitude compared to the case of conventional laser pulses. The energies of the revisiting electron at the atomic core can approach the MeV domain, thus rendering hard x-ray harmonics and nuclear reactions with single atoms feasible

Effectiveness and cost-effectiveness of basic versus biofeedback-mediated intensive pelvic floor muscle training for female stress or mixed urinary incontinence: protocol for the OPAL randomised trial

This is the final version. Available on open access from BMJ Publishing Group via the DOI in this recordIntroduction Accidental urine leakage is a distressing problem that affects around one in three women. The main types of urinary incontinence (UI) are stress, urgency and mixed, with stress being most common. Current UK guidelines recommend that women with UI are offered at least 3 months of pelvic floor muscle training (PFMT). There is evidence that PFMT is effective in treating UI, however it is not clear how intensively women have to exercise to give the maximum sustained improvement in symptoms, and how we enable women to achieve this. Biofeedback is an adjunct to PFMT that may help women exercise more intensively for longer, and thus may improve continence outcomes when compared with PFMT alone. A Cochrane review was inconclusive about the benefit of biofeedback, indicating the need for further evidence. Methods and analysis This multicentre randomised controlled trial will compare the effectiveness and cost-effectiveness of PFMT versus biofeedback-mediated PFMT for women with stress UI or mixed UI. The primary outcome is UI severity at 24 months after randomisation. The primary economic outcome measure is incremental cost per quality-adjusted life-year at 24 months. Six hundred women from UK community, outpatient and primary care settings will be randomised and followed up via questionnaires, diaries and pelvic floor assessment. All participants are offered six PFMT appointments over 16 weeks. The use of clinic and home biofeedback is added to PFMT for participants in the biofeedback group. Group allocation could not be masked from participants and healthcare staff. An intention-to-treat analysis of the primary outcome will estimate the mean difference between the trial groups at 24 months using a general linear mixed model adjusting for minimisation covariates and other important prognostic covariates, including the baseline score. Ethics and dissemination Approval granted by the West of Scotland Research Ethics Committee 4 (16/LO/0990). Written informed consent will be obtained from participants by the local research team. Serious adverse events will be reported to the data monitoring and ethics committee, the ethics committee and trial centres as required. A Standard Protocol Items: Recommendations for Interventional Trials checklist and figure are available for this protocol. The results will be published in international journals and included in the relevant Cochrane review. Trial registration number ISRCTN57746448; Pre-results.National Institute for Health Research (NIHR

Pathogenic Mutations in Cancer-Predisposing Genes: A Survey of 300 Patients with Whole-Genome Sequencing and Lifetime Electronic Health Records

Background: It is unclear whether and how whole-genome sequencing (WGS) data can be used to implement genomic medicine. Our objective is to retrospectively evaluate whether WGS can facilitate improving prevention and care for patients with susceptibility to cancer syndromes. Methods and Findings: We analyzed genetic mutations in 60 autosomal dominant cancer-predisposition genes in 300 deceased patients with WGS data and nearly complete long-term (over 30 years) medical records. To infer biological insights from massive amounts of WGS data and comprehensive clinical data in a short period of time, we developed an in-house analysis pipeline within the SeqHBase software framework to quickly identify pathogenic or likely pathogenic variants. The clinical data of the patients who carried pathogenic and/or likely pathogenic variants were further reviewed to assess their clinical conditions using their lifetime EHRs. Among the 300 participants, 5 (1.7%) carried pathogenic or likely pathogenic variants in 5 cancer-predisposing genes: one in APC, BRCA1, BRCA2, NF1, and TP53 each. When assessing the clinical data, each of the 5 patients had one or more different types of cancers, fully consistent with their genetic profiles. Among these 5 patients, 2 died due to cancer while the others had multiple disorders later in their lifetimes; however, they may have benefited from early diagnosis and treatment for healthier lives, had the patients had genetic testing in their earlier lifetimes. Conclusions: We demonstrated a case study where the discovery of pathogenic or likely pathogenic germline mutations from population-wide WGS correlates with clinical outcome. The use of WGS may have clinical impacts to improve healthcare delivery

Vers un horizon déontologique: une étude qualitative multicontextuelle des pratiques déontologiques au sein de la profession infirmière

This paper reports the results of a qualitative study of nurses' ethical decisionmaking. Focus groups of nurses in diverse practice contexts were used as a means to explore the meaning of ethics and the enactment of ethical practice. The findings centre on the metaphor of a moral horizon - the horizon representing "the good" towards which the nurses were navigating. The findings suggest that currents within the moral climate of nurses' work significantly influence nurses' progress towards their moral horizon. All too often the nurses found themselves navigating against a current characterized by the privileging of biomedicine and a corporate ethos. Conversely, a current of supportive colleagues as well as professional guidelines and standards and ethics education helped them to move towards their horizon. The implications for nursing practice and for our understanding of ethical decision-making are discussed