Prenatal exome sequencing and impact on perinatal outcome: cohort study.

OBJECTIVES: First, to determine the uptake of prenatal exome sequencing (pES) and the diagnostic yield of pathogenic (causative) variants in a UK tertiary fetal medicine unit following the introduction of the NHS England Rapid Exome Sequencing Service for fetal anomalies testing (R21 pathway). Second, to identify how the decision to proceed with pES and identification of a causative variant affect perinatal outcomes, specifically late termination of pregnancy (TOP) at or beyond 22 weeks' gestation. METHODS: This was a retrospective cohort study of anomalous fetuses referred to the Liverpool Women's Hospital Fetal Medicine Unit between 1 March 2021 and 28 February 2022. pES was performed as part of the R21 pathway. Trio exome sequencing was performed using an Illumina next-generation sequencing platform assessing coding and splice regions of a panel of 974 prenatally relevant genes and 231 expert reviewed genes. Data on demographics, phenotype, pES result and perinatal outcome were extracted and compared. Descriptive statistics and the χ-square or Fisher's exact test were performed using IBM SPSS version 28.0.1.0. RESULTS: In total, 72 cases were identified and two-thirds of eligible women (n = 48) consented to trio pES. pES was not feasible in one case owing to a low DNA yield and, therefore, was performed in 47 cases. In one-third of cases (n = 24), pES was not proposed or agreed. In 58.3% (14/24) of these cases, this was because invasive testing was declined and, in 41.7% (10/24) of cases, women opted for testing and underwent chromosomal microarray analysis only. The diagnostic yield of pES was 23.4% (11/47). There was no overall difference in the proportion of women who decided to have late TOP in the group in which pES was agreed compared with the group in which pES was not proposed or agreed (25.0% (12/48) vs 25.0% (6/24); P = 1.0). However, the decision to have late TOP was significantly more frequent when a causative variant was detected compared with when pES was uninformative (63.6% (7/11) vs 13.9% (5/36); P < 0.0009). The median turnaround time for results was longer in cases in which a causative variant was identified than in those in which pES was uninformative (22 days (interquartile range (IQR), 19-34) days vs 14 days (IQR, 10-15 days); P < 0.0001). CONCLUSIONS: This study demonstrates the potential impact of identification of a causative variant by pES on decision to have late TOP. As the R21 pathway continues to evolve, we urge clinicians and policymakers to consider introducing earlier screening for anomalies, developing robust guidance for late TOP and ensuring optimized support for couples. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Predicting the Risk of Human Immunodeficiency Virus Type 1 (HIV-1) Acquisition in Rural South Africa Using Geospatial Data.

BACKGROUND: Accurate human immunodeficiency virus (HIV) risk assessment can guide optimal HIV prevention. We evaluated the performance of risk prediction models incorporating geospatial measures. METHODS: We developed and validated HIV risk prediction models in a population-based cohort in South Africa. Individual-level covariates included demographic and sexual behavior measures, and geospatial covariates included community HIV prevalence and viral load estimates. We trained models on 2012-2015 data using LASSO Cox models and validated predictions in 2016-2019 data. We compared full models to simpler models restricted to only individual-level covariates or only age and geospatial covariates. We compared the spatial distribution of predicted risk to that of high incidence areas (≥ 3/100 person-years). RESULTS: Our analysis included 19 556 individuals contributing 44 871 person-years and 1308 seroconversions. Incidence among the highest predicted risk quintile using the full model was 6.6/100 person-years (women) and 2.8/100 person-years (men). Models using only age group and geospatial covariates had similar performance (women: AUROC = 0.65, men: AUROC = 0.71) to the full models (women: AUROC = 0.68, men: AUROC = 0.72). Geospatial models more accurately identified high incidence regions than individual-level models; 20% of the study area with the highest predicted risk accounted for 60% of the high incidence areas when using geospatial models but only 13% using models with only individual-level covariates. CONCLUSIONS: Geospatial models with no individual measures other than age group predicted HIV risk nearly as well as models that included detailed behavioral data. Geospatial models may help guide HIV prevention efforts to individuals and geographic areas at highest risk.

Exosome-based liquid biopsies in cancer: opportunities and challenges.

Liquid biopsy in cancer has gained momentum in clinical research and is experiencing a boom for a variety of applications. There are significant efforts to utilize liquid biopsies in cancer for early detection and treatment stratification, as well as residual disease and recurrence monitoring. Although most efforts have used circulating tumor cells and circulating tumor DNA for this purpose, exosomes and other extracellular vesicles have emerged as a platform with potentially broader and complementary applications. Exosomes/extracellular vesicles are small vesicles released by cells, including cancer cells, into the surrounding biofluids. These exosomes contain tumor-derived materials such as DNA, RNA, protein, lipid, sugar structures, and metabolites. In addition, exosomes carry molecules on their surface that provides clues regarding their origin, making it possible to sort vesicle types and enrich signatures from tissue-specific origins. Exosomes are part of the intercellular communication system and cancer cells frequently use them as biological messengers to benefit their growth. Since exosomes are part of the disease process, they have become of tremendous interest in biomarker research. Exosomes are remarkably stable in biofluids, such as plasma and urine, and can be isolated for clinical evaluation even in the early stages of the disease. Exosome-based biomarkers have quickly become adopted in the clinical arena and the first exosome RNA-based prostate cancer test has already helped >50 000 patients in their decision process and is now included in the National Comprehensive Cancer Network guidelines for early prostate cancer detection. This review will discuss the advantages and challenges of exosome-based liquid biopsies for tumor biomarkers and clinical implementation in the context of circulating tumor DNA and circulating tumor cells.

Associations between social and behavioural factors and the risk of late stillbirth - findings from the Midland and North of England Stillbirth case-control study.

OBJECTIVE: To investigate behavioural and social characteristics of women who experienced a late stillbirth compared with women with ongoing live pregnancies at similar gestation. DESIGN: Case-control study. SETTING: 41 maternity units in the UK. POPULATION: Women who had a stillbirth ≥28 weeks' gestation (n = 287) and women with an ongoing pregnancy at the time of interview (n = 714). METHODS: Data were collected using an interviewer-administered questionnaire which included questions regarding women's behaviours (e.g. alcohol intake and household smoke exposure) and social characteristics (e.g. ethnicity, employment, housing). Stress was measured by the 10-item Perceived Stress Scale. MAIN OUTCOME MEASURE: Late stillbirth. RESULTS: Multivariable analysis adjusting for co-existing social and behavioural factors showed women living in the most deprived quintile had an increased risk of stillbirth compared with the least deprived quintile (adjusted odds ratio [aOR] 3.16; 95% CI 1.47-6.77). There was an increased risk of late stillbirth associated with unemployment (aOR 2.32; 95% CI 1.00-5.38) and women who declined to answer the question about domestic abuse (aOR 4.12; 95% CI 2.49-6.81). A greater number of antenatal visits than recommended was associated with a reduction in stillbirth (aOR 0.26; 95% CI 0.16-0.42). CONCLUSIONS: This study demonstrates associations between late stillbirth and socio-economic deprivation, perceived stress and domestic abuse, highlighting the need for strategies to prevent stillbirth to extend beyond maternity care. Enhanced antenatal care may be able to mitigate some of the increased risk of stillbirth. TWEETABLE ABSTRACT: Deprivation, unemployment, social stress & declining to answer about domestic abuse increase risk of #stillbirth after 28 weeks' gestation.

Vaginal bacterial load in the second trimester is associated with early preterm birth recurrence: a nested case-control study.

OBJECTIVE: To assess the association between vaginal microbiome (VMB) composition and recurrent early spontaneous preterm birth (sPTB)/preterm prelabour rupture of membranes (PPROM). DESIGN: Nested case-control study. SETTING: UK tertiary referral hospital. SAMPLE: High-risk women with previous sPTB/PPROM <34+0 weeks' gestation who had a recurrence (n = 22) or delivered at ≥37+0 weeks without PPROM (n = 87). METHODS: Vaginal swabs collected between 15 and 22 weeks' gestation were analysed by 16S rRNA gene sequencing and 16S quantitative PCR. MAIN OUTCOME MEASURE: Recurrent early sPTB/PPROM. RESULTS: Of the 109 high-risk women, 28 had anaerobic vaginal dysbiosis, with the remainder dominated by lactobacilli (Lactobacillus iners 36/109, Lactobacillus crispatus 23/109, or other 22/109). VMB type and diversity were not associated with recurrence. Women with a recurrence, compared to those without, had a higher median vaginal bacterial load (8.64 versus 7.89 log10 cells/mcl, adjusted odds ratio [aOR] 1.90, 95% CI 1.01-3.56, P = 0.047) and estimated Lactobacillus concentration (8.59 versus 7.48 log10 cells/mcl, aOR 2.35, (95% CI 1.20-4.61, P = 0.013). A higher recurrence risk was associated with higher median bacterial loads for each VMB type after stratification, although statistical significance was reached only for L. iners domination (aOR 3.44, 95% CI 1.06-11.15, P = 0.040). Women with anaerobic dysbiosis or L. iners domination had a higher median vaginal bacterial load than women with a VMB dominated by L. crispatus or other lactobacilli (8.54, 7.96, 7.63, and 7.53 log10 cells/mcl, respectively). CONCLUSIONS: Vaginal bacterial load is associated with early sPTB/PPROM recurrence. Domination by lactobacilli other than L. iners may protect women from developing high bacterial loads. Future PTB studies should quantify vaginal bacteria and yeasts. TWEETABLE ABSTRACT: Increased vaginal bacterial load in the second trimester may be associated with recurrent early spontaneous preterm birth.

Narrow pH tolerance found for a microbial fuel cell treating winery wastewater.

AIMS: The use of microbial fuel cells (MFC) to treat winery wastewater is promising; however, an initial acidic pH, fluctuating chemical oxygen demand (COD) levels and a lack of natural buffering in these wastewaters make providing a suitable buffer system at an ideal buffer to COD ratio. METHODS AND RESULTS: A lab scale MFC was designed, inoculated with anaerobic winery sludge and fed with synthetic winery wastewater. It was observed that at pH 6·5, the MFC performed best, the maximum output voltage was 0·63 ± 0·01 V for 60 ± 3 h, and the COD removal efficiency reached 77 ± 7%. The electrogens were affected by pH much more than the bulk COD degrading organisms. Fluorescent in situ hybridization suggested Betaproteobacteria played a significant role in electron transfer. CONCLUSIONS: A ratio of 1 mmol l-1 phosphate buffer to 100 mg l-1 COD was ideal to maintain a stable pH for MFCs treating synthetic winery wastewater. SIGNIFICANCE AND IMPACT OF THE STUDY: The results find the narrow pH tolerance for MFCs treating winery wastewater and demonstrate the significance of pH and buffer to COD ratio for steady performance of MFCs.

Male factor infertility and placental pathology in singleton live births conceived with in vitro fertilization.

PURPOSE: We sought to determine whether pregnancies conceived in those with male factor infertility have unique placental pathology profiles compared to those undergoing infertility treatments for other indications. METHODS: This was a retrospective cohort study of placental pathology from 464 live births conceived from autologous fresh IVF cycles at an academic fertility center from 2004 to 2017. Placental pathology was compared between live births arising from patients with male factor infertility alone and those with another infertility diagnosis. Placental outcomes were compared with parametric or non-parametric tests; logistic regression was performed to account for potential confounders. RESULTS: Compared to cycles performed for a non-male factor diagnosis, male factor infertility cycles had a higher mean paternal age (38.2 years vs. 36.5 years, p < 0.001), a higher female mean BMI (24.3 vs. 23.3 kg/m2, p = 0.01), and a lower day 3 follicle stimulating hormone (FSH) level (6.8 vs. 7.3 IU/mL, p = 0.02). The mean numbers of embryos transferred, and day of transfer were similar between groups, and more cycles used ICSI in the male factor infertility group (90.6% vs. 22.5%, p < 0.001). Placental pathology in our adjusted model was similar between the male factor and non-male factor groups. In our unadjusted subgroup analysis, cycles for male factor using ICSI appeared to lead to more small placentas by weight compared to cycles performed with conventional insemination (45.8% < 10th percentile vs. 18.8%, p = 0.04). CONCLUSION: Male factor infertility is not associated with significantly different placental pathology compared to other infertility diagnoses.

Quantifying movement of multiple threatened species to inform adaptive management of environmental flows.

There is a growing need for water managers to refine and optimise environmental flow strategies (e-flows) to balance water requirements for humans and nature. With increasing demands for freshwater and consequent declines in biodiversity, managers are faced with the problem of how to adaptively manage e-flows for multiple stakeholders and species whose flow requirements may overlap or vary. This study assessed the effectiveness of a regulated e-flow release strategy from a dam, aimed at providing movement opportunities and facilitating reproductive processes for multiple threatened species. Movements of 24 Mary River cod (Maccullochella mariensis), 20 Australian lungfish (Neoceratodus forsteri) and 13 Mary River turtle (Elusor macrurus) were quantified using acoustic telemetry over a three-year period. The influence of regulated e-flow releases, season, river depth, water temperature and rainfall on animal movements was assessed using Generalised linear mixed models (GLMMs). Models showed that hydraulic connectivity provided by both natural flows and regulated e-flow releases facilitated movement of all three species between pool habitats, throughout the year. Mary River turtles made extensive use of regulated e-flow releases when moving between habitats, whereas Mary River cod and Australian lungfish required additional natural rises in river height above the regulated e-flows to trigger movements. Significant movement activity was also recorded for cod and turtles during the dry season (winter and spring), broadly coinciding with breeding periods for these species. The effectiveness of, and potential improvements to, current e-flow strategies to sustain key life-history requirements of these species is discussed. Findings suggest a revised e-flow strategy with relatively minor increases in the magnitude of e-flow releases throughout winter and spring, would be effective in providing movement opportunities and supporting reproductive success for all three species. This study demonstrates that by quantifying movement behaviour in an e-flow context, ecological risk assessment frameworks can then be used to assess and provide for critical life-history requirements of multiple species within the context of a highly regulated system under increasing water use demands.

Trends in Reported Sexual Behavior and Y-Chromosomal DNA Detection Among Female Sex Workers in the Senegal Preexposure Prophylaxis Demonstration Project.

BACKGROUND: Preexposure prophylaxis (PrEP) can reduce HIV acquisition among female sex workers (FSWs). However, changes in condomless sex frequency after PrEP initiation could reduce PrEP effectiveness when PrEP adherence is suboptimal as well as increase the risk of acquiring other sexually transmitted infections. Objective measures of condomless sex may be more accurate for determining changes in sexual behavior than self-reported measures. METHODS: We longitudinally measured self-reported condom use, number of clients, and presence of Y-chromosomal DNA (Yc-DNA) in vaginal swabs among 267 FSWs accessing PrEP at 4 clinics in Senegal between 2015 and 2016. We assessed trends in sexual behavior over time since PrEP initiation using generalized estimating equations and evaluated predictors of Yc-DNA detection. RESULTS: We found no increase in self-reported condomless sex with clients (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.89-1.00), main partners (OR, 0.99; 95% CI, 0.96-1.02), or Yc-DNA detection (OR, 0.99; 95% CI, 0.90-1.08) over time since initiation. Y-chromosomal DNA was detected in 34 (22%) of 154 swabs tested and in 15 (26%) of 58 swabs from FSW reporting consistent condom use among both clients and main partners. Self-reported condom use with clients or main partners did not predict Yc-DNA detection. CONCLUSIONS: In a FSW PrEP demonstration project in Senegal, we found no evidence of risk compensation among FSWs on PrEP as measured by self-reported behavior or through Yc-DNA detection. Y-chromosomal DNA detection was frequently detected among FSWs reporting consistent condom use, highlighting limitations of self-reported sexual behavioral measures.

Case epidemiology from the first three years of a pilot laboratory-based surveillance system for elevated blood-lead concentrations among children in England, 2014-17: implications for public health action.

BACKGROUND: Children incur lead toxicity even at low blood-lead concentrations (BLCs), and testing in England is opportunistic. We described epidemiology of cases notified to a passive laboratory-based surveillance system (SS), the Lead Poisoning in Children (LPIC) SS to inform opportunities to prevent lead exposure in children in England. METHODS: Surveillance population: children <16 years of age and resident in England during the reporting period September 2014-17. Case definition: children with BLC ≥0.48 µmol/l (10 µg/dl). We extracted case demographic/location data and linked it with laboratory, area-level population and socio-economic status (SES) data. We described case BLCs and calculated age-, gender- and SES-specific notification rates, and age-sex standardised regional notification rates. RESULTS: Between 2014 and 2017 there were 86 newly notified cases, giving an annual average notification rate of 2.76 per million children aged 0-15 years. Regionally, rates varied from 0.36 to 9.89 per million. Rates were highest in the most deprived quintile (5.38 per million), males (3.75 per million) and children aged 1-4 years (5.89 per million). CONCLUSIONS: Males, children aged 1-4 years, and children in deprived areas may be at higher risk, and could be targeted for primary prevention. Varied regional notification rates suggest differences in clinician awareness of lead exposure and risk factors; guidelines standardising the indications for BLC-testing may assist secondary prevention.

The efficacy of microlearning in improving self-care capability: a systematic review of the literature.

OBJECTIVE: To determine the effectiveness of microlearning in improving an individual's capability for self-care. STUDY DESIGN: Systematic review of the literature. BACKGROUND: The routine adoption of health seeking self-care behaviours can prevent or delay the appearance of various lifestyle diseases including type 2 diabetes and cardiovascular disease. Microlearning delivers complex knowledge in fragments or bite-size 'nuggets' of information and has been applied as a novel intervention to improve individual's self-care capabilities. The aim of this research was to systematically review the literature to determine the effectiveness of microlearning in improving individual self-care capability. METHODS: A search was conducted on 15 July 2019 across five electronic bibliographic databases: EMBASE, MEDLINE, PsycINFO, CINAHL and Scopus. Randomised and non-randomised controlled trials, controlled before-after studies and interrupted time series studies, published between 1 January 1990 and 15 July 2019 and looking at individuals of all ages were included in the search. The search strategy included a keyword search and a string of "(modality) AND (learning) AND (micro)", which broadly described microlearning to cover all available articles that have used microformat learning interventions. The search was combined with keywords and Medical Subject Headings (MeSH) terms for self-care to identify studies of interests. Studies were screened by two reviewers independently and reported using a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart. Data from included articles were extracted using Cochran Data Collection Form. Risk of bias was assessed using Version 2 of the Cochrane Risk-of-bias or Risk Of Bias In Non-Randomised Studies of Interventions (ROBINS-I). RESULTS: 1310 articles were identified in the initial search. A total of 26 manuscripts were included in the narrative synthesis after title and abstract and full text screening was performed by two reviewers. Outcomes of studies were categorised. A total of 23 studies measured cognitive level self-care capabilities-related changes, and 91% showed statistically significant improvements. Only 11 studies measured actual self-care behaviour changes, from which only 36% showed statistically significant results. From the 26 manuscripts included, 25 articles were evaluated as having moderate-to-high risk of bias. CONCLUSION: Under certain conditions, or when combined with monitoring such as tracking daily medicine intake, microlearning can be effective in improving actual self-care behaviours. Microlearning can also positively influence individuals' cognitive self-care capabilities but was largely ineffective in triggering actual self-care behaviour change. More studies are needed to investigate the effectiveness of microlearning in improving self-care capabilities amongst the general population at scale.

Effect of QUiPP prediction algorithm on treatment decisions in women with a previous preterm birth: a prospective cohort study.

OBJECTIVE: The QUiPP algorithm combines cervical length, quantitative fetal fibronectin (qfFN) and medical history to quantify risk of preterm birth. We assessed the utility of QUiPP to inform preterm birth prevention treatment decisions. DESIGN: A prospective cohort study with a subsequent impact assessment using the QUiPP risk of birth before 34 weeks' gestation. SETTING: A UK tertiary referral hospital. SAMPLE: In all, 119 women with previous spontaneous preterm birth (sPTB) or preterm premature rupture of membranes (PPROM) before 34 weeks' gestation. METHODS: Cervical length and qfFN were measured at 19+0 to 23+0  weeks' gestation. Clinical management was based on history and cervical length. After birth, clinicians were unblinded to qfFN results and QUiPP analysis was undertaken. MAIN OUTCOME MEASURES: Predictive statistics of QUiPP algorithm using 10% risk of sPTB before 34+0  weeks as treatment threshold. RESULTS: Fifteen of 119 women (13%) had PPROM or sPTB before 34 weeks. Of these, 53% (8/15) had QUiPP risk of sPTB before 34+0  weeks above 10%. Applying this treatment threshold in practice would have doubled our treatment rate (20 versus 42%). QUIPP threshold of 10% had positive likelihood ratio (LR) of 1.3 (95% CI 0.76-2.18), and negative LR of 0.8 (95% CI 0.45-1.40) for predicting sPTB before 34+0  weeks. CONCLUSIONS: Use of the QUiPP algorithm in this population may lead to substantial increase in interventions without evidence that currently available treatment options are beneficial for this particular group. TWEETABLE ABSTRACT: Independent study finds that the QUiPP algorithm could lead to substantial increases in treatment without evidence of benefit.

Gestational diabetes and the risk of late stillbirth: a case-control study from England, UK.

OBJECTIVE: To explore the separate effects of being 'at risk' of gestational diabetes mellitus (GDM) and screening for GDM, and of raised fasting plasma glucose (FPG) and clinical diagnosis of GDM, on the risk of late stillbirth. DESIGN: Prospective case-control study. SETTING: Forty-one maternity units in the UK. POPULATION: Women who had a stillbirth ≥28 weeks of gestation (n = 291) and women with an ongoing pregnancy at the time of interview (n = 733). METHODS: Causal mediation analysis explored the joint effects of (i) 'at risk' of GDM and screening for GDM and (ii) raised FPG (≥5.6 mmol/l) and clinical diagnosis of GDM on the risks of late stillbirth. Adjusted odds ratios (aOR) were estimated by logistic regression adjusted for confounders identified by directed acyclic graphs. MAIN OUTCOME MEASURES: Screening for GDM and FPG levels RESULTS: Women 'at risk' of GDM, but not screened, experienced 44% greater risk of late stillbirth than those not 'at risk' (aOR 1.44, 95% CI 1.01-2.06). Women 'at risk' of GDM who were screened experienced no such increase (aOR 0.98, 95% CI 0.70-1.36). Women with raised FPG not diagnosed with GDM experienced four-fold greater risk of late stillbirth than women with normal FPG (aOR 4.22, 95% CI 1.04-17.02). Women with raised FPG who were diagnosed with GDM experienced no such increase (aOR 1.10, 95% CI 0.31-3.91). CONCLUSIONS: Optimal screening and diagnosis of GDM mitigate the higher risks of late stillbirth in women 'at risk' of GDM and/or with raised FPG. Failure to diagnose GDM leaves women with raised FPG exposed to avoidable risk of late stillbirth. TWEETABLE ABSTRACT: Risk of #stillbirth in gestational diabetes is mitigated by effective screening and diagnosis.

Six-month outcomes after restrictive or liberal transfusion for cardiac surgery (TRICS III trial).

CLINICAL QUESTION: Is transfusing red cell components using a restrictive transfusion threshold (Hb < 75 g L-1 ) as safe as a liberal transfusion threshold (Hb < 95 g L-1 in intensive care and < 85 g L-1 outside intensive care) during and after cardiac surgery for adults at moderate to high risk of death? EVIDENCE FROM TRIAL: In adults undergoing cardiac surgery who were at moderate to high risk for death, using a restrictive red-cell transfusion threshold was as safe as a liberal red cell transfusion threshold (composite outcome of death from any cause, myocardial infarction, stroke or new-onset renal failure with dialysis at 6 months after surgery).

Cost-effectiveness of alternative changes to a national blood collection service.

OBJECTIVES: To evaluate the cost-effectiveness of changing opening times, introducing a donor health report and reducing the minimum inter-donation interval for donors attending static centres. BACKGROUND: Evidence is required about the effect of changes to the blood collection service on costs and the frequency of donation. METHODS/MATERIALS: This study estimated the effect of changes to the blood collection service in England on the annual number of whole-blood donations by current donors. We used donors' responses to a stated preference survey, donor registry data on donation frequency and deferral rates from the INTERVAL trial. Costs measured were those anticipated to differ between strategies. We reported the cost per additional unit of blood collected for each strategy versus current practice. Strategies with a cost per additional unit of whole blood less than £30 (an estimate of the current cost of collection) were judged likely to be cost-effective. RESULTS: In static donor centres, extending opening times to evenings and weekends provided an additional unit of whole blood at a cost of £23 and £29, respectively. Introducing a health report cost £130 per additional unit of blood collected. Although the strategy of reducing the minimum inter-donation interval had the lowest cost per additional unit of blood collected (£10), this increased the rate of deferrals due to low haemoglobin (Hb). CONCLUSION: The introduction of a donor health report is unlikely to provide a sufficient increase in donation frequency to justify the additional costs. A more cost-effective change is to extend opening hours for blood collection at static centres.

Real-Time PCR and LAMP Assays for the Detection of Spores of Alternaria solani and Sporangia of Phytophthora infestans to Inform Disease Risk Forecasting.

Real-time loop-mediated isothermal amplification (LAMP) assays for the detection of sporangia of the causal pathogen of late blight, Phytophthora infestans, and spores of the main causal pathogen of early blight, Alternaria solani, were developed to facilitate the in-field detection of airborne inoculum to improve disease forecasting. These assays were compared with an existing real-time PCR assay for P. infestans and a newly developed real-time PCR assay for A. solani. Primers were designed for real-time LAMP of P. infestans and A. solani. The specificity of the P. infestans real-time LAMP assay was similar to that of an existing real-time PCR assay: DNA of P. infestans was consistently amplified as was DNA of the taxonomically closely related species Phytophthora mirabilis, Phytophthora phaseoli, and Phytophthora ipomoea; no amplification of DNA from the potato pathogens Phytophthora erythroseptica or Phytophthora nicotianae occurred. Real-time LAMP and PCR assays were developed for A. solani, and the specificity was compared with an existing conventional PCR assay. Importantly, the A. solani real-time LAMP and PCR assays did not amplify the species Alternaria alternata. However, cross-reactivity with Alternaria dauci was observed with the real-time PCR assay and Alternaria brassicae with the real-time LAMP assay. The sensitivity of all assays for the detection of DNA extracted from sporangia/spores of the target pathogens was evaluated. The P. infestans real-time LAMP assay reliably detected 5 pg of DNA, equivalent to ∼1 sporangia per reaction. By comparison, 20 fg of DNA was detectable with the existing real-time PCR assay. In the case of A. solani, real-time LAMP detected 4.4 pg of DNA, equivalent to ∼1 spore per reaction, and real-time PCR detected 200 fg of DNA. In-field air samplers were deployed in two trial plots planted with potato: one infected with P. infestans, and the other infected with A. solani. Four additional samplers were located in commercial potato fields. Air samples were taken through the season, and detection of airborne inoculum of P. infestans and A. solani with both real-time PCR and LAMP was assessed.

Development of a Cryopreservation Protocol for Vanilla Siamensis: An Endangered Orchid Species in Thailand.

BACKGROUND: Vanilla siamensis is listed in Appendix-II of Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) as an endangered species in Thailand. OBJECTIVE: To develop an optimum cryopreservation protocol for V. siamensis. MATERIALS AND METHODS: Protocorms were precultured on solid ½ MS medium with 0.5 M sucrose for 0-7 d. For encapsulation-dehydration, encapsulated protocorms (beads) were dehydrated for 0-6 h. In the case of encapsulation-vitrification, the beads were loaded with a plant vitrification solution 2 (PVS2) at 0 ˚C for 0-90 min. RESULTS: Protocorms precultured for 3 d gave the highest post-cryopreservation survival of 17%. Dehydration of the encapsulated protocorm beads for 4 h gave the highest survival of 33% and a regrowth of 25%. Protocorms subjected to the encapsulation-vitrification method did not survive at all. CONCLUSION: Protocorms precultured with 0.5 M sucrose for 3 d, encapsulated with 3% sodium alginate and dehydrated to a moisture content c. 14% before plunging into LN was a suitable method for the successful cryopreservation of V. siamensis protocorms.

Small area estimation of under-5 mortality in Bangladesh, Cameroon, Chad, Mozambique, Uganda, and Zambia using spatially misaligned data.

BACKGROUND: The under-5 mortality rate (U5MR) is an important metric of child health and survival. Country-level estimates of U5MR are readily available, but efforts to estimate U5MR subnationally have been limited, in part, due to spatial misalignment of available data sources (e.g., use of different administrative levels, or as a result of historical boundary changes). METHODS: We analyzed all available complete and summary birth history data in surveys and censuses in six countries (Bangladesh, Cameroon, Chad, Mozambique, Uganda, and Zambia) at the finest geographic level available in each data source. We then developed small area estimation models capable of incorporating spatially misaligned data. These small area estimation models were applied to the birth history data in order to estimate trends in U5MR from 1980 to 2015 at the second administrative level in Cameroon, Chad, Mozambique, Uganda, and Zambia and at the third administrative level in Bangladesh. RESULTS: We found substantial variation in U5MR in all six countries: there was more than a two-fold difference in U5MR between the area with the highest rate and the area with the lowest rate in every country. All areas in all countries experienced declines in U5MR between 1980 and 2015, but the degree varied both within and between countries. In Cameroon, Chad, Mozambique, and Zambia we found areas with U5MRs in 2015 that were higher than in other parts of the same country in 1980. Comparing subnational U5MR to country-level targets for the Millennium Development Goals (MDG), we find that 12.8% of areas in Bangladesh did not meet the country-level target, although the country as whole did. A minority of areas in Chad, Mozambique, Uganda, and Zambia met the country-level MDG targets while these countries as a whole did not. CONCLUSIONS: Subnational estimates of U5MR reveal significant within-country variation. These estimates could be used for identifying high-need areas and positive deviants, tracking trends in geographic inequalities, and evaluating progress towards international development targets such as the Sustainable Development Goals.

Association between maternal sleep practices and late stillbirth - findings from a stillbirth case-control study.

OBJECTIVE: To report maternal sleep practices in women who experienced a stillbirth compared with controls with ongoing live pregnancies at similar gestation. DESIGN: Prospective case-control study. SETTING: Forty-one maternity units in the United Kingdom. POPULATION: Women who had a stillbirth after ≥ 28 weeks' gestation (n = 291) and women with an ongoing pregnancy at the time of interview (n = 733). METHODS: Data were collected using an interviewer-administered questionnaire that included questions on maternal sleep practices before pregnancy, in the four weeks prior to, and on the night before the interview/stillbirth. MAIN OUTCOME MEASURES: Maternal sleep practices during pregnancy. RESULTS: In multivariable analysis, supine going-to-sleep position the night before stillbirth had a 2.3-fold increased risk of late stillbirth [adjusted Odds Ratio (aOR) 2.31, 95% CI 1.04-5.11] compared with the left side. In addition, women who had a stillbirth were more likely to report sleep duration less than 5.5 hours on the night before stillbirth (aOR 1.83, 95% CI 1.24-2.68), getting up to the toilet once or less (aOR 2.81, 95% CI 1.85-4.26), and a daytime nap every day (aOR 2.22, 95% CI 1.26-3.94). No interaction was detected between supine going-to-sleep position and a small-for-gestational-age infant, maternal body mass index, or gestational age. The population-attributable risk for supine going-to-sleep position was 3.7% (95% CI 0.5-9.2). CONCLUSIONS: This study confirms that supine going-to-sleep position is associated with late stillbirth. Further work is required to determine whether intervention(s) can decrease the frequency of supine going-to-sleep position and the incidence of late stillbirth. TWEETABLE ABSTRACT: Supine going-to-sleep position is associated with 2.3× increased risk of stillbirth after 28 weeks' gestation. PLAIN LANGUAGE SUMMARY: Stillbirth, the death of a baby before birth, is a tragedy for mothers and families. One approach to reduce stillbirths is to identify factors that are associated with stillbirth. There are few risk factors for stillbirth that can be easily changed, but this study is looking at identifying how mothers may be able to reduce their risk. In this study, we interviewed 291 women who had a stillbirth and 733 women who had a live-born baby from 41 maternity units throughout the UK. The mothers who had a stillbirth were interviewed as soon as practical after their baby died. Mothers who had a live birth were interviewed during their pregnancies at the same times in pregnancy as when the stillbirths occurred. We did not interview mothers who had twins or who had a baby with a major abnormality. Mothers who went to sleep on their back had at least twice the risk of stillbirth compared with mothers who went to sleep on their left-hand side. This study suggests that 3.7% of stillbirths after 28 weeks of pregnancy were linked with going to sleep lying on the back. This study also shows that the link between going-to-sleep position and late stillbirth was not affected by the duration of pregnancy after 28 weeks, the size of the baby, or the mother's weight. Women who got up to the toilet once or more at night had a reduced risk of stillbirth. This is the largest of four similar studies that have all shown the same link between the position in which a mother goes to sleep and stillbirth after 28 weeks of pregnancy. Further studies are needed to see whether women can easily change their sleep position in late pregnancy and whether changing the position a mother goes to sleep in reduces stillbirth.

Potential biological control of Erwinia tracheiphila by internal alimentary canal interactions in Acalymma vittatum with Pseudomonas fluorescens.

AIMS: We aim to determine if Pseudomonas fluorescens is a viable biological control for Erwinia tracheiphila within the insect vector, Acalymma vittatum. METHODS AND RESULTS: Pseudomonas fluorescens secreted fluorescein and inhibited growth of E. tracheiphila in disc diffusion assays. To determine if this antagonism was conserved within the insect vector, we performed in vivo assays by orally injecting beetles with bacterial treatments and fluorescent in situ hybridization to determine bacterial presence within the alimentary canal. CONCLUSIONS: Pseudomonas fluorescens inhibited the growth of E. tracheiphila on a nutrient-limiting medium. In situ experiments demonstrated that P. fluorescens is maintained within the alimentary canal of the beetle for at least 4 days, and co-occurred with E. tracheiphila. When beetles were first presented with Pseudomonas and then challenged with E. tracheiphila, E. tracheiphila was not recovered via FISH after 4 days. These data suggest that P. fluorescens has potential as a biological control agent to limit E. tracheiphila within the insect vector. SIGNIFICANCE AND IMPACT OF THE STUDY: This is a novel approach for controlling E. tracheiphila that has the potential to decrease reliance on insecticides, providing a safer environment for pollinators and growers.