Attitudes to self-sampling for HPV among Indian, Pakistani, African-Caribbean and white British women in Manchester, UK

Objective: To examine attitudes to self-sampling for human papillomavirus (HPV) testing among women from contrasting ethnic groups.Setting: Manchester, UK.Methods: Two hundred women of Indian, Pakistani, African-Caribbean and white British origin were recruited from social and community groups to participate in a questionnaire survey. The questionnaire included items on attitudes to self-sampling and intention to use the test.Results: Willingness to try to use the test was high, and women did not foresee religious or cultural barriers to self-sampling; however, a large proportion of women were concerned about doing the test properly. This concern was greatest in the Indian and African-Caribbean groups.Conclusions: Although women's willingness to try self-sampling for HPV is encouraging, worries about carrying out the procedure correctly must be addressed if women are to feel confident about the results of self-sampling methods and reassured by a negative result

Mitochondrial mislocalization and altered assembly of a cluster of Barth syndrome mutant tafazzins

None of the 28 identified point mutations in tafazzin (Taz1p), which is the mutant gene product associated with Barth syndrome (BTHS), has a biochemical explanation. In this study, endogenous Taz1p was localized to mitochondria in association with both the inner and outer mitochondrial membranes facing the intermembrane space (IMS). Unexpectedly, Taz1p does not contain transmembrane (TM) segments. Instead, Taz1p membrane association involves a segment that integrates into, but not through, the membrane bilayer. Residues 215–232, which were predicted to be a TM domain, were identified as the interfacial membrane anchor by modeling four distinct BTHS mutations that occur at conserved residues within this segment. Each Taz1p mutant exhibits altered membrane association and is nonfunctional. However, the basis for Taz1p dysfunction falls into the following two categories: (1) mistargeting to the mitochondrial matrix or (2) correct localization associated with aberrant complex assembly. Thus, BTHS can be caused by mutations that alter Taz1p sorting and assembly within the mitochondrion, indicating that the lipid target of Taz1p is resident to IMS-facing leaflets

Mitofusins and OPA1 Mediate Sequential Steps in Mitochondrial Membrane Fusion

Mitochondrial fusion requires the coordinated fusion of the outer and inner membranes. Three large GTPases—OPA1 and the mitofusins Mfn1 and Mfn2—are essential for the fusion of mammalian mitochondria. OPA1 is mutated in dominant optic atrophy, a neurodegenerative disease of the optic nerve. In yeast, the OPA1 ortholog Mgm1 is required for inner membrane fusion in vitro; nevertheless, yeast lacking Mgm1 show neither outer nor inner membrane fusion in vivo, because of the tight coupling between these two processes. We find that outer membrane fusion can be readily visualized in OPA1-null mouse cells in vivo, but these events do not progress to inner membrane fusion. Similar defects are found in cells lacking prohibitins, which are required for proper OPA1 processing. In contrast, double Mfn-null cells show neither outer nor inner membrane fusion. Mitochondria in OPA1-null cells often contain multiple matrix compartments bounded together by a single outer membrane, consistent with uncoupling of outer versus inner membrane fusion. In addition, unlike mitofusins and yeast Mgm1, OPA1 is not required on adjacent mitochondria to mediate membrane fusion. These results indicate that mammalian mitofusins and OPA1 mediate distinct sequential fusion steps that are readily uncoupled, in contrast to the situation in yeast

Hybrid Software Development Approaches in Practice: A European Perspective

Agile and traditional development approaches are used in combination in todays software development. To improve the understanding and to provide better guidance for selecting appropriate development approaches, it is important to analyze such combinations in practice. Results obtained from an online survey strongly confirm that hybrid development approaches are widely used in industry. Our results show that hybrid development approaches: (i) have become reality for nearly all companies; (ii) are applied to specific projects even in the presence of company-wide policies for process usage; (iii) are neither planned nor designed but emerge from the evolution of different work practices; and, (iv) are consistently used regardless of company size or industry secto

Residency Times and Patterns of Movement of Postbreeding Dunlin on a Subarctic Staging Area in Alaska

Understanding how individuals use key resources is critical for effective conservation of a population. The Yukon-Kuskokwim Delta (YKD) in western Alaska is the most important postbreeding staging area for shorebirds in the subarctic North Pacific, yet little is known about movements of shorebirds there during the postbreeding period. To address this information gap, we studied residency times and patterns of movement of 17 adult and 17 juvenile radio-marked Dunlin (Calidris alpina) on the YKD between early August and early October 2005. Throughout this postbreeding period, during which Dunlin were molting, most birds were relocated within a 130 km radius of their capture site on the YKD, but three birds were relocated more than 600 km to the south at estuaries along the Alaska Peninsula. On average, juvenile Dunlin were relocated farther away from the banding site (median relocation distance = 36.3 km) than adult Dunlin (median relocation distance = 8.8 km). Post-capture, minimum lengths of stay by Dunlin on the YKD were not significantly different between juveniles (median = 19 days) and adults (median = 23 days), with some birds staging for more than 50 days. Body mass at time of capture was the best single variable explaining length of stay on the YKD, with average length of stay decreasing by 2.5 days per additional gram of body mass at time of capture. Conservation efforts for postbreeding shorebirds should consider patterns of resource use that may differ not only by age cohort but also by individual condition.Pour donner lieu à la conservation efficace d’une population, il est essentiel de comprendre comment les individus se servent des ressources importantes. Le delta Yukon-Kuskokwim, dans l’ouest de l’Alaska, est l’escale de post-reproduction la plus importante des oiseaux de rivage du Pacifique Nord subarctique. Pourtant, on en sait peu sur les déplacements des oiseaux de rivage à cet endroit pendant la période de post-reproduction. Afin de combler ce manque d’information, nous avons étudié les durées de résidence et les habitudes de déplacement de 17 bécasseaux variables (Calidris alpina) adultes et de 17 bécasseaux variables juvéniles radio-marqués dans le delta Yukon-Kuskokwim du début août au début octobre 2005. Pendant la période de post-reproduction pendant laquelle les bécasseaux variables muaient, la plupart des oiseaux ont été déplacés dans un rayon de 130 km de leur lieu de capture dans le delta Yukon-Kuskokwim, mais trois oiseaux ont été relocalisés à plus de 600 km vers le sud, aux estuaires le long de la péninsule de l’Alaska. En moyenne, les bécasseaux variables juvéniles ont été déplacés plus loin du lieu de baguage (distance de déplacement médiane = 36,3 km) que les bécasseaux variables adultes (distance de déplacement médiane = 8,8 km). Par bécasseau variable, les durées de séjour minimales après la capture au delta Yukon-Kuskokwim ne différaient pas considérablement entre les juvéniles (médiane = 19 jours) et les adultes (médiane = 23 jours), certains oiseaux faisant escale pendant plus de 50 jours. La masse corporelle au moment de la capture était la meilleure et la seule variable expliquant la durée du séjour au delta Yukon-Kuskokwim, la durée moyenne du séjour diminuant de 2,5 jours par gramme supplémentaire de masse corporelle au moment de la capture. Les efforts de conservation des oiseaux de rivage en période de post-reproduction devraient tenir compte des modèles d’utilisation des ressources qui risquent de différer non seulement en fonction de la cohorte d’âge, mais également en fonction de l’état de l’individu

The Expression and Roles of Nde1 and Ndel1 in the Adult Mammalian Central Nervous System

Open Access funded by Wellcome Trust Under a Creative Commons license Acknowledgments We thank Prof Angelo Sementilli, Department of Pathology, Universidade Metropolitana de Santos, SP, Brazil, for the human sample collection. This study is funded by Scottish Universities Life Sciences Alliance (HR07019 to S. Shen and C.D. McCaig), Medical Research Scotland (384 FRG to B. Lang, United Kingdom), Tenovus Scotland (G12/25 to B. Lang), Sino-UK Higher Education Research Partnership for PhD Studies (C.D. McCaig and Y.Q. Ding) and Wellcome Trust (WT081633MA-NCE to P.J.A. McCaffery, United Kingdom).Peer reviewedPublisher PD

APPARENT SURVIVAL OF BREEDING WESTERN SANDPIPERS ON THE YUKON-KUSKOKWIM RIVER DELTA, ALASKA

We used 8 years of live recapture data (1998–2005) to estimate apparent annual survival for male (n = 237) and female (n = 296) Western Sandpipers (Calidris mauri) breeding on a 36-ha plot on the Yukon-Kuskokwim River Delta, western Alaska. Apparent annual survival (Φ) is the product of true survival and site fidelity, and estimates of Φ were corrected for the probability of encounter. Overall return rates (individual returned to the study site in a subsequent season) were lower for females (40%) than males (65%), as was Φ (± SE, females = 0.65 ± 0.05, males = 0.78 ± 0.03), and encounter rate (females = 0.51 ± 0.07, males = 0.74 ± 0.04). Results differed from previous estimates of Φ for this species as our estimates of Φ were higher for both males and females compared to estimates from another breeding site and two nonbreeding locations. Disparity among Φ estimates from breeding and nonbreeding areas highlights the need to delineate site-specific factors throughout the annual cycle that influence population dynamics of the Western Sandpiper

APPARENT SURVIVAL OF BREEDING WESTERN SANDPIPERS ON THE YUKON-KUSKOKWIM RIVER DELTA, ALASKA

We used 8 years of live recapture data (1998–2005) to estimate apparent annual survival for male (n = 237) and female (n = 296) Western Sandpipers (Calidris mauri) breeding on a 36-ha plot on the Yukon-Kuskokwim River Delta, western Alaska. Apparent annual survival (Φ) is the product of true survival and site fidelity, and estimates of Φ were corrected for the probability of encounter. Overall return rates (individual returned to the study site in a subsequent season) were lower for females (40%) than males (65%), as was Φ (± SE, females = 0.65 ± 0.05, males = 0.78 ± 0.03), and encounter rate (females = 0.51 ± 0.07, males = 0.74 ± 0.04). Results differed from previous estimates of Φ for this species as our estimates of Φ were higher for both males and females compared to estimates from another breeding site and two nonbreeding locations. Disparity among Φ estimates from breeding and nonbreeding areas highlights the need to delineate site-specific factors throughout the annual cycle that influence population dynamics of the Western Sandpiper

Clinicians' perspectives on diagnosing polycystic ovary syndrome in Australia: a qualitative study

STUDY QUESTION: What are clinicians' views about the diagnosis of polycystic ovary syndrome (PCOS), and how do they handle any complexities and uncertainties in practice?SUMMARY ANSWER: Clinicians have to navigate many areas of complexity and uncertainty regarding the diagnosis of PCOS, related to the diagnostic criteria, limitations in current evidence and misconceptions surrounding diagnosis, and expressed concern about the risk and consequences of both under- and overdiagnosis.WHAT IS KNOWN ALREADY: PCOS is a complex, heterogeneous condition with many areas of uncertainty, raising concerns about both underdiagnosis and overdiagnosis. Quantitative studies with clinicians have found considerable variation in diagnostic criteria used and care provided, as well as a lack of awareness around the breadth of PCOS features and poor uptake of recommended screening for metabolic complications. Clinicians' views about the uncertainties and complexities of diagnosing PCOS have not been explored.STUDY DESIGN, SIZE, DURATION: Semi-structured telephone interviews were conducted with clinicians from September 2017 to July 2018 to explore their perceptions about the diagnosis of PCOS, including how they handle any complexities and uncertainties in practice.PARTICIPANTS/MATERIALS, SETTING, METHODS: A group of 36 clinicians (15 general practitioners, 10 gynaecologists and 11 endocrinologists) currently practicing in Australia, were recruited through advertising via professional organisations, contacting a random sample of endocrine and gynaecology teams across Australia and snowballing. Transcribed audio-recordings were analysed thematically using Framework analysis.MAIN RESULTS AND THE ROLE OF CHANCE: Clinicians expressed a range of uncertainties and complexities regarding the diagnosis of PCOS, which were organised into three areas: (i) establishing diagnosis (e.g. lack of standardisation regarding diagnostic cut-offs, risk of misdiagnosis), (ii) factors influencing the diagnostic process (e.g. awareness of limitations in evidence and consideration of the benefits and harms) and (iii) strategies for handling challenges and uncertainties (e.g. using caution and communication of uncertainties). Clinicians also varied in their concerns regarding under- and overdiagnosis. Overall, most felt the diagnosis was beneficial for women provided that it was the correct diagnosis and time was taken to assess patient expectations and dispel misconceptions, particularly concerning fertility.LIMITATIONS, REASONS FOR CAUTION: There is possible selection bias, as clinicians who are more knowledgeable about PCOS may have been more likely to participate. Clinicians' views may also differ in other countries.WIDER IMPLICATIONS OF THE FINDINGS: These findings underscore the vital need to first consider PCOS a diagnosis of exclusion and use caution before giving a diagnosis in order to reduce misdiagnosis, as suggested by clinicians in our study. Until there is greater standardisation of diagnostic criteria, more transparent conversations with women may help them understand the uncertainties surrounding the criteria and limitations in the evidence. Additionally, clinicians emphasised the importance of education and reassurance to minimise the potential harmful impact of the diagnosis and improve patient-centred outcomes

The benefits and harms of receiving a polycystic ovary syndrome diagnosis: a qualitative study of women's experiences

Study Question: What are the benefits and harms of receiving a polycystic ovary syndrome (PCOS) diagnosis in a community sample of women, including impact on psychosocial wellbeing, lifestyle choices and behaviour? Summary Answer: Although some women benefit considerably from the diagnosis, such as through increased awareness and reassurance, women with minimal symptoms may experience more harm than benefit, including long-lasting anxiety and altered life plans. What Is Known Already: Disease labels can validate symptoms and play a vital role in understanding and coping with illness; however, they can also cause harm by evoking illness schemas about severity and permanence. Regarding PCOS, the diagnostic criteria have expanded over time to include women with milder phenotypes (such as those without signs of androgen excess). This has occurred despite limited investigation of the benefits and harms of the diagnosis and has increased the number of women diagnosed. Study Design, Size, Duration: Semi-structured interviews were conducted face-to-face or by telephone with 26 participants from April-July 2018 to explore women's experiences with the diagnosis, including the benefits and harms of receiving the diagnosis and the impact on their life. Participants/Materials, Setting, Methods: In total, 26 women in the community self-reporting a diagnosis of PCOS (reporting mild to severe symptoms) made by a medical doctor, aged 18-45 years and living in Australia were recruited through social media. Data were analysed thematically using Framework analysis. Main Results and the Role of Chance: The study identified a range of both positive and negative effects of a PCOS diagnosis in the immediate, short and long-term, which were influenced by symptom severity, expectations and experience. For women with previously unexplained and bothersome symptoms, it was a relief to receive a diagnosis, and this resulted in an increased understanding about the importance of a healthy lifestyle. By contrast, women with milder symptoms often reported feeling shocked and overwhelmed by the diagnosis, consequently experiencing anxiety about the associated long-term risks. The majority of women, regardless of symptom severity, experienced prolonged worry and anxiety about infertility, resulting for some in risk taking with contraception, unintended pregnancies, pressure to conceive early or altered life plans. With time, many women developed positive coping strategies and perceived the diagnosis to be valuable, including those who felt they had experienced minimal benefit or even harm. Limitations, Reasons for Caution: PCOS diagnosis was self-reported and the sample was highly educated. Wider Implications of the Findings: Fear of infertility was salient for many women, underscoring the need for accurate information, counselling and reassurance of fertility potential. Given the risk of significant consequences, health professionals should use a tailored approach to PCOS diagnosis to increase the benefits of appropriate and timely diagnosis for women affected by significant symptoms, while reducing the harms of unnecessarily labelling healthy women for whom the benefits of a diagnosis are small.T. Copp, J. Hersch, D.M. Muscat, K.J. McCaffery, J. Doust, A. Dokras, B.W. Mol, and J. Janse