New radiocarbon dates from the Bapot-1 site in Saipan and Neolithic dispersal by stratified diffusion

The colonisation of the Mariana Islands in Western Micronesia is likely to represent an early ocean dispersal of more than 2000 km. Establishing the date of human arrival in the archipelago is important for modelling Neolithic expansion in Island Southeast Asia and the Pacific, particularly the role of long-distance dispersals. This paper presents new ¹⁴C results and a ΔR estimate from the Bapot-1 site on Saipan Island, which indicate human arrival at ca. 3400-3200 cal. BP. Archaeological chronologies of long-distance dispersal to Western Micronesia and the Lapita expansion (Bismarcks to Samoa) show that the Neolithic dispersal rate was increasing during the period ca. 3400-2900 cal. BP. The range-versus-time relationship is similar to stratified diffusion whereby a period of relatively slow expansion is succeeded by long-distance movement. An increase in new colonies created by long-distance migrants results in accelerating range expansion

Anxiety in couples undergoing IVF: evidence from E-Freeze randomised controlled trial

Study question What are the risk factors and impacts of anxiety in women and men in heterosexual couples undergoing IVF as part of a randomised trial, with a delay in embryo transfer in one arm? Summary answer Duration of infertility, ethnicity, and male partner’s anxiety levels were associated with women’s anxiety at the start of treatment, while initial anxiety score, partner’s anxiety score at embryo transfer, ethnicity, and clinic location were associated with women’s anxiety levels at embryo transfer; although women undergoing IVF were more anxious than their partners for slightly different reasons, their self-reported state anxiety was not associated with achieving clinical pregnancy, nor with switching from delayed frozen embryo transfer to fresh embryo transfer in an IVF trial. What is known already Use of IVF treatment continues to rise and patients undergoing IVF are anxious. Participating in a randomised controlled trial (RCT) with uncertainty of arm randomisation might increase their anxiety, while a delay in treatment may add further to anxiety. Study design, size, duration A mixed methods study was conducted using data from the multi-centre E-Freeze RCT cohort conducted across 13 clinics in the UK from 2016 to 2019. A regression analysis on anxiety scores of couples undergoing the IVF trial and a qualitative analysis of participant questionnaires were performed. Participants/materials, setting, methods Six hundred and four couples participating in the E-Freeze trial, who had at least one useable State-Trait Anxiety Inventory (STAI) State Anxiety subscale (STAI-S) standardised self-report questionnaire for at least one of the partners, were included in the study. STAI-S scores were measured at consent for trial (T1) and again at embryo transfer (T2). Linear and log-binomial regression were used to explore the association between characteristics and STAI-S scores, and the associations between STAI-S scores and non-compliance and clinical pregnancy, respectively. Responses to the open text question were qualitatively analysed inductively using content analysis. Main results and the role of chance Women’s STAI-S scores at T1 (consent) were associated with their ethnicity, duration of infertility, and their male partner’s STAI-S score at T1. Women’s STAI-S scores at T2 (embryo transfer) were associated with their ethnicity, location of fertility clinic, their STAI-S score at consent, and their male partner’s STAI-S score at embryo transfer. The adjusted coefficient (95% CI) for women’s STAI-S scores at T2 was −4.75 (−7.29, −2.20, P  Limitations, reasons for caution Data were not available on education level or social support, which might influence anxiety scores. Men’s baseline characteristics were not collected. Wider implications of the findings Identifying couples at increased risk of emotional distress may be improved by using standardised anxiety measures at the start of the fertility treatment. Women can be reassured that their self-reported state anxiety does not affect their chances of achieving clinical pregnancy through IVF, and this may help to reduce anxiety levels. The psychological wellbeing and experiences of couples undergoing IVF could be supported by patient-centred care: making information about the whole process of treatment and choices available to both partners in accessible formats; ensuring interactions with staff are kind and supportive; and acknowledging and addressing the different concerns of women undergoing IVF and their partners. Study funding/competing interest(s) This study was an NIHR HTA (National Institute for Health and Care Research Health Technology Assessment) funded study. There are no conflicts of interest to declare. Trial registration number ISRCTN registry: ISRCTN61225414

Electronic cigarette use (vaping) and patterns of tobacco cigarette smoking in pregnancy-evidence from a population-based maternity survey in England.

OBJECTIVES: Exposure to tobacco products during pregnancy presents a potential harm to both mother and baby. This study sought to estimate the prevalence of vaping during pregnancy and to explore the factors and outcomes associated with vaping in pregnancy. SETTING: England. PARTICIPANTS: Women who gave birth between 15th and 28th October 2017. METHODS: A cross-sectional population-based postal survey of maternal and infant health, the National Maternity Survey (NMS) 2018. The prevalence of vaping and patterns of cigarette smoking were estimated, and regression analysis was used to explore associations between maternal characteristics and vaping, and between vaping and birth outcomes. OUTCOME MEASURES: Unweighted and weighted prevalence of vaping with 95% confidence intervals, and unadjusted and adjusted relative risks or difference in means for the association of participant characteristics and secondary outcomes with vaping. Secondary outcome measures were: preterm birth, gestational age at birth, birthweight, and initiation and duration of breastfeeding. RESULTS: A total of 4,509 women responded to the survey. The prevalence of vaping in pregnancy was 2.8% (95%CI 2.4% to 3.4%). This varied according to the pattern of cigarette smoking in pregnancy: 0.3% in never-smokers; 3.3% in ex-smokers; 7.7% in pregnancy-inspired quitters; 9.5% in temporary quitters; and 17.7% in persistent smokers. Younger women, unmarried women, women with fewer years of formal education, women living with a smoker, and persistent smokers were more likely to vape, although after adjusting for pattern of cigarette smoking and maternal characteristics, persistent smoking was the only risk factor. We did not find any association between vaping and preterm birth, birthweight, or breastfeeding. CONCLUSIONS: The prevalence of vaping during pregnancy in the NMS 2018 was low overall but much higher in smokers. Smoking was the factor most strongly associated with vaping. Co-occurrence of vaping with persistent smoking has the potential to increase the harms of tobacco exposure in pregnant women and their infants

Doctors’ perspectives of informed consent for non-emergency surgical procedures: a qualitative interview study

Background The need to involve patients more in decisions about their care, the ethical imperative and concerns about ligation and complaints has highlighted the issue of informed consent and how it is obtained. In order for a patient to make an informed decision about their treatment, they need appropriate discussion of the risks and benefits of the treatment. Objectives To explore doctors’ perspectives of gaining informed consent for routine surgical procedures. Design Qualitative study using semi-structured interviews selected by purposive sampling. Data were analysed thematically. Setting and Participants Twenty doctors in two teaching hospitals in the UK. Results Doctors described that while consent could be taken over a series of consultations, it was common for consent to be taken immediately prior to surgery. Juniors were often taking consent when they were unfamiliar with the procedure. Doctors used a range of communication techniques to inform patients about the procedure and its risks including quantifying risks, personalizing risk, simplification of language and use of drawings. Barriers to effective consent taking were reported to be shortage of time, clinician inexperience and patients’ reluctance to be involved

Tuberculosis IRIS: Pathogenesis, Presentation, and Management across the Spectrum of Disease.

Antiretroviral therapy (ART), while essential in combatting tuberculosis (TB) and HIV coinfection, is often complicated by the TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). Depending on the TB disease site and treatment status at ART initiation, this immune-mediated worsening of TB pathology can take the form of paradoxical TB-IRIS, unmasking TB-IRIS, or CNS TB-IRIS. Each form of TB-IRIS has unique implications for diagnosis and treatment. Recently published studies have emphasized the importance of neutrophils and T cell subtypes in TB-IRIS pathogenesis, alongside the recognized role of CD4 T cells and macrophages. Research has also refined our prognostic understanding, revealing how the disease can impact lung function. While corticosteroids remain the only trial-supported therapy for prevention and management of TB-IRIS, increasing interest has been given to biologic therapies directly targeting the immune pathology. TB-IRIS, especially its unmasking form, remains incompletely described and more data is needed to validate biomarkers for diagnosis. Management strategies remain suboptimal, especially in the highly morbid central nervous system (CNS) form of the disease, and further trials are necessary to refine treatment. In this review we will summarize the current understanding of the immunopathogenesis, the presentation of TB-IRIS and the evidence for management recommendations

'Digital by Default' and the 'hard to reach': Exploring solutions to digital exclusion in remote rural areas

Williams, F., Philip, L., Fairhurst, G., & Farrington, J. (2016). ‘Digital by Default’ and ‘the hard to reach’: exploring solutions to digital exclusion in remote rural areas. Local Economy, 31(7), 757-777. DOI: 10.1177/0269094216670938. Copyright © 2016 SAGE. Reprinted by permission of SAGE Publications.In the UK, the geography of Information and Communication Technology (ICT) infrastructure required for Internet connectivity is such that high speed broadband and mobile phone networks are generally less available in rural areas compared with urban areas or, in other words, as remoteness and population sparsity increase so too does the likelihood of an area having no or very poor broadband connectivity. Against a policy backdrop of UK Government efforts to bring forward network infrastructure upgrades and to improve the accessibility of broadband services in locations where there is a weak commercial investment case, this paper considers the options for the ‘final few’ in the prevailing ‘Digital by Default’ public services context. The paper outlines the Rural Public Access WiFi Services project, a study focused upon enabling Internet connectivity for commercially ‘hard to reach’ rural areas in the UK. The Rural Public Access WiFi Services concept and the experiment are introduced before findings from a pilot deployment of a broadband service to households in a remote rural area, who may be classified as ‘digitally excluded’, are presented. The paper then reflects on our field experiment and the potential of the Rural Public Access WiFi Services model as a solution to overcoming some of the digital participation barriers manifest in the urban–rural divide. Early indications show that the Rural Public Access WiFi Services model has the potential to encourage participation in the Digital Economy and could aid the UK Government’s Digital by Default agenda, although adoption of the model is not without its challenges

Classification of patient-safety incidents in primary care

Primary care lags behind secondary care in the reporting of, and learning from, incidents that put patient safety at risk. In primary care, there is no universally agreed approach to classifying the severity of harm arising from such patient-safety incidents. This lack of an agreed approach limits learning that could lead to the prevention of injury to patients. In a review of research on patient safety in primary care, we identified 21 existing approaches to the classification of harm severity. Using the World Health Organization's (WHO's) International Classification for Patient Safety as a reference, we undertook a framework analysis of these approaches. We then developed a new system for the classification of harm severity. To assess and classify harm, most existing approaches use measures of symptom duration (11/21), symptom severity (11/21) and/or the level of intervention required to manage the harm (14/21). However, few of these approaches account for the deleterious effects of hospitalization or the psychological stress that may be experienced by patients and/or their relatives. The new classification system we developed builds on WHO's International Classification for Patient Safety and takes account not only of hospitalization and psychological stress but also of so-called near misses and uncertain outcomes. The constructs we have outlined have the potential to be applied internationally, across primary-care settings, to improve both the detection and prevention of incidents that cause the most severe harm to patients

Radiotherapy exposure directly damages the uterus and causes pregnancy loss

Female cancer survivors are significantly more likely to experience infertility than the general population. It is well established that chemotherapy and radiotherapy can damage the ovary and compromise fertility, yet the ability of cancer treatments to induce uterine damage, and the underlying mechanisms, have been understudied. Here, we show that in mice total-body γ-irradiation (TBI) induced extensive DNA damage and apoptosis in uterine cells. We then transferred healthy donor embryos into ovariectomized adolescent female mice that were previously exposed to TBI to study the impacts of radiotherapy on the uterus independent from effects to ovarian endocrine function. Following TBI, embryo attachment and implantation were unaffected, but fetal resorption was evident at midgestation in 100% of dams, suggesting failed placental development. Consistent with this hypothesis, TBI impaired the decidual response in mice and primary human endometrial stromal cells. TBI also caused uterine artery endothelial dysfunction, likely preventing adequate blood vessel remodeling in early pregnancy. Notably, when pro-apoptotic protein Puma-deficient (Puma-/-) mice were exposed to TBI, apoptosis within the uterus was prevented, and decidualization, vascular function, and pregnancy were restored, identifying PUMA-mediated apoptosis as a key mechanism. Collectively, these data show that TBI damages the uterus and compromises pregnancy success, suggesting that optimal fertility preservation during radiotherapy may require protection of both the ovaries and uterus. In this regard, inhibition of PUMA may represent a potential fertility preservation strategy.</p

Standardized Urine-Based Tuberculosis (TB) Screening With TB-Lipoarabinomannan and Xpert MTB/RIF Ultra in Ugandan Adults With Advanced Human Immunodeficiency Virus Disease and Suspected Meningitis.

BACKGROUND: Diagnosis of extrapulmonary tuberculosis (TB) remains challenging. We sought to determine the prevalence of disseminated TB by testing urine with TB-lipoarabinomannan (TB-LAM) lateral flow assay and Xpert MTB/RIF Ultra (Ultra) in hospitalized adults. METHODS: We prospectively enrolled human immunodeficiency virus (HIV)-positive adults with suspected meningitis in Uganda during 2018-2020. Participants underwent standardized urine-based TB screening. Urine (60 mcL) was tested with TB-LAM (Alere), and remaining urine was centrifuged with the cell pellet resuspended in 2 mL of urine for Xpert Ultra testing. RESULTS: We enrolled 348 HIV-positive inpatients with median CD4 of 37 cells/mcL (interquartile range, 13-102 cells/mcL). Overall, 26% (90 of 348; 95% confidence interval [CI], 21%-30%) had evidence of disseminated TB by either urine assay. Of 243 participants with both urine TB-LAM and Ultra results, 20% (48 of 243) were TB-LAM-positive, 12% (29 of 243) were Ultra-positive, and 6% (14 of 243) were positive by both assays. In definite and probable TB meningitis, 37% (14 of 38) were TB-LAM-positive and 41% (15 of 37) were Ultra-positive. In cryptococcal meningitis, 22% (40 of 183) were TB-LAM-positive and 4.4% (6 of 135) were Ultra-positive. Mortality trended higher in those with evidence of disseminated TB by either assay (odds ratio = 1.44; 95% CI, 0.83-2.49; P = .19) and was 6-fold higher in those with definite TB meningitis who were urine Ultra-positive (odds ratio = 5.67; 95% CI, 1.13-28.5; P = .04). CONCLUSIONS: In hospitalized Ugandans with advanced HIV disease and suspected meningitis, systematic screening with urine TB-LAM and Ultra found a high prevalence of urine TB test positivity (26%). In those with TB meningitis, urine tests were positive in over one third. There was little concordance between Ultra and TB-LAM, which warrants further investigation