The Upstream Sequence Transcription Complex dictates nucleosome positioning and promoter accessibility at piRNA genes in the C. elegans germ line.

The piRNA pathway is a conserved germline-specific small RNA pathway that ensures genomic integrity and continued fertility. In C. elegans and other nematodes, Type-I piRNAs are expressed from >10,000 independently transcribed genes clustered within two discrete domains of 1.5 and 3.5 MB on Chromosome IV. Clustering of piRNA genes contributes to their germline-specific expression, but the underlying mechanisms are unclear. We analyze isolated germ nuclei to demonstrate that the piRNA genomic domains are located in a heterochromatin-like environment. USTC (Upstream Sequence Transcription Complex) promotes strong association of nucleosomes throughout piRNA clusters, yet organizes the local nucleosome environment to direct the exposure of individual piRNA genes. Localization of USTC to the piRNA domains depends upon the ATPase chromatin remodeler ISW-1, which maintains high nucleosome density across piRNA clusters and ongoing production of piRNA precursors. Overall, this work provides insight into how chromatin states coordinate transcriptional regulation over large genomic domains, with implications for global genome organization.

Sense of coherence moderates job demand-resources and impact on burnout among nurses and midwives in the context of the COVID-19 pandemic: A cross-sectional survey.

AIM: This study aimed to test the propositions using the job demands-resources (JD-R) model for main/moderation/mediation effects of a sense of coherence and practice environment support on mental well-being (anxiety, depression and burnout) outcomes in nurses and midwives in Australia during the COVID-19 pandemic. DESIGN: Cross-sectional quantitative survey. DATA SOURCES: The study was a cross-sectional design using self-report questionnaires reported as per the Reporting of Observational Studies in Epidemiology Guidelines. Following human research ethics approval (2020.ETH.00121) participants were recruited to take part in an online anonymous survey using self-report instruments to test the JD-R model in Australia. RESULTS: 156 participant nurses and midwives experienced anxiety, depression and emotional burnout during COVID-19. While a considerable proportion of participants indicated high levels of emotional exhaustion, their responses showed low levels of depersonalization (detached response to other people) and high levels of personal accomplishment (high levels of work performance and competence). A sense of coherence was a significant protective factor for mental health well-being for the participants, which is to say, high levels of sense of coherence were predictive of lower levels of anxiety, depression and burnout in this study sample. CONCLUSION: It is evident that both nursing and midwifery professions require psychosocial support to preserve their health both in the short and long term. Ensuring individualized tailored support will require a layered response within organizations aimed at individual self-care and collegial peer support. PATIENT OR PUBLIC CONTRIBUTION: There was no patient or public contribution in this study, as the focus was on nurses and midwives.

Understanding the needs and preferences for cancer care among First Nations people: An integrative review.

AIM: This systematic review aimed to identify the needs and preferences for cancer care services among Australian First Nations people. DESIGN: Integrative review. DATA SOURCES: An integrative review was conducted. A wide range of search terms were used to increase the sensitivity and specificity of the searches in electronic databases. Methodological quality assessment, data extraction, was conducted independently by two reviewers, and a narrative synthesis was conducted. RESULTS: Forty-two studies were included. A total of 2965 Australian First Nations adults, both men and women of various ages across the lifespan, were represented; no First Nations children affected by cancer were represented in the studies. Three themes emerged which included: (1) discrimination, racism and trauma, resulting from colonization, directly impacted First National people's cancer care experience; (2) cultural ways of knowing, being and doing are fundamental to how First Nations people engage with cancer care services; and (3) First Nations people need culturally safe person-centred cancer care services that address practical needs. CONCLUSION: Most participants represented in this review experienced discrimination, racism and trauma, resulting from colonization, which directly negatively impacted Aboriginal peoples' cancer care experience. While the Optimal Cancer Pathway (OCP) was launched in Australia several years ago, people with cancer may continue to experience distressing unmet care needs. PATIENT OR PUBLIC CONTRIBUTION: Our team includes both First Nations people, non-First Nations researchers and healthcare professionals with expertise in cancer care. The researchers employed decolonizing restorative approaches to ensure voice, respect, accountability and reciprocity in this review work. IMPLICATIONS FOR NURSING PRACTICE: Members of the multidisciplinary team including nurses and policymakers should reflect on these findings, ensure that they have up-to-date cultural safety training and stand together with Indigenous and non-Indigenous cancer leaders to take proactive steps to stamp out and dismantle oppression in health, and safely implement the OCP.

Tailored psychological intervention for anxiety or depression in COPD (TANDEM): a randomised controlled trial.

BACKGROUND: The TANDEM multicentre, pragmatic, randomised controlled trial evaluated whether a tailored psychological intervention based on a cognitive behavioural approach for people with COPD and symptoms of anxiety and/or depression improved anxiety or depression compared with usual care (control). METHODS: People with COPD and moderate to very severe airways obstruction and Hospital Anxiety and Depression Scale subscale scores indicating mild to moderate anxiety (HADS-A) and/or depression (HADS-D) were randomised 1.25:1 (242 intervention and 181 control). Respiratory health professionals delivered the intervention face-to-face over 6-8 weeks. Co-primary outcomes were HADS-A and HADS-D measured 6 months post-randomisation. Secondary outcomes at 6 and 12 months included: HADS-A and HADS-D (12 months), Beck Depression Inventory II, Beck Anxiety Inventory, St George's Respiratory Questionnaire, social engagement, the EuroQol instrument five-level version (EQ-5D-5L), smoking status, completion of pulmonary rehabilitation, and health and social care resource use. RESULTS: The intervention did not improve anxiety (HADS-A mean difference -0.60, 95% CI -1.40-0.21) or depression (HADS-D mean difference -0.66, 95% CI -1.39-0.07) at 6 months. The intervention did not improve any secondary outcomes at either time-point, nor did it influence completion of pulmonary rehabilitation or healthcare resource use. Deaths in the intervention arm (13/242; 5%) exceeded those in the control arm (3/181; 2%), but none were associated with the intervention. Health economic analysis found the intervention highly unlikely to be cost-effective. CONCLUSION: This trial has shown, beyond reasonable doubt, that this cognitive behavioural intervention delivered by trained and supervised respiratory health professionals does not improve psychological comorbidity in people with advanced COPD and depression or anxiety.

Does pay-for-performance improve patient outcomes in acute exacerbation of COPD admissions?

BACKGROUND: The COPD Best Practice Tariff (BPT) is a pay-for-performance scheme in England that incentivises review by a respiratory specialist within 24 hours of admission and completion of a list of key care components prior to discharge, known as a discharge bundle, for patients admitted with acute exacerbation of COPD (AECOPD). We investigated whether the two components of the COPD BPT were associated with lower 30-day mortality and readmission in people discharged following AECOPD. METHODS: Longitudinal study of national audit data containing details of AECOPD admissions in England and Wales between 01 February 2017 and 13 September 2017. Data were linked with national admissions and mortality data. Mixed-effects logistic regression, using a random intercept for hospital to adjust for clustering of patients, was used to determine the relationship between the COPD BPT criteria (combined and separately) and 30-day mortality and readmission. Models were adjusted for age, sex, socioeconomic status, length of stay, smoking status, Charlson comorbidity index, mental illness and requirement for oxygen or noninvasive ventilation during admission. RESULTS: 28 345 patients discharged from hospital following AECOPD were included. 37% of admissions conformed to the two COPD BPT criteria. No relationship was observed between BPT conforming admissions and 30-day mortality (OR: 1.09 (95% CI 0.92 to 1.29)) or readmissions (OR: 0.96 (95% CI 0.90 to 1.02)). No relationship was observed between either of the individual COPD BPT components and 30-day mortality or readmissions. However, a specialist review at any time during admission was associated with lower inpatient mortality (OR: 0.69 (95% CI 0.58 to 0.81)). CONCLUSION: Completion of the combined COPD BPT criteria does not appear associated with a reduction in 30-day mortality or readmission. However, specialist review was associated with reduced inpatient mortality. While it is difficult to argue that discharge bundles do not improve care, this analysis questions whether the pay-for-performance model improves mortality or readmissions.

Pityriasis rubra pilaris-like eruption following administration of the BNT163b2 (Pfizer-BioNTech) mRNA COVID-19 vaccine.

We describe a case of a pityriasis rubra pilaris (PRP)-like eruption occurring following administration of the Pfizer-Biontech mRNA COVID-19 vaccine, with worsening of the condition following the second dose. To our knowledge, this is the first reported case of a PRP-like eruption as a cutaneous adverse event of the Pfizer-Biontech mRNA COVID-19 vaccine.

Evaluating phytochemical and microbial contributions to atrazine degradation.

The inclusion of warm-season grasses, such as switchgrass (Panicum virgatum) and eastern gamagrass (EG) (Tripsacum dactyloides), in vegetated buffer strips has been shown to mitigate herbicide contamination in runoff and increase herbicide degradation in soil. The mode of action by which buffer strip rhizospheres enhance herbicide degradation remains unclear, but microorganisms and phytochemicals are believed to facilitate degradation processes. The objectives of this study were to: 1) screen root extracts from seven switchgrass cultivars for the ability to degrade the herbicide atrazine (ATZ) in solution; 2) determine sorption coefficients (Kd) of the ATZ-degrading phytochemical 2-ß-D-glucopyranosyloxy-4-hydroxy-1,4-benzoxazin-3-one (DBG) to soil and Ca-montmorillonite, and investigate if DBG or ATZ sorption alters degradation processes; and 3) quantify ATZ degradation rates and soil microbial response to ATZ application in mesocosms containing soil and select warm-season grasses. Phytochemicals extracted from the roots of switchgrass cultivars degraded 44-85% of ATZ in 16-h laboratory assays, demonstrating that some switchgrass cultivars could rapidly degrade ATZ under laboratory conditions. However, attempts to isolate ATZ-degrading phytochemicals from plant roots were unsuccessful. Sorption studies revealed that DBG was strongly sorbed to soil (Kd = 87.2 L kg-1) and Ca-montmorillonite (Kd = 31.7 L kg-1), and DBG driven hydrolysis of ATZ was entirely inhibited when either ATZ or DBG were sorbed to Ca-montmorillonite. Atrazine degradation rates in mesocosm soils were rapid (t0.5 = 8.2-11.2 d), but not significantly different between soils collected from the two switchgrass cultivar mesocosms, the eastern gamagrass cultivar mesocosm, and the unvegetated mesocosm (control). Significant changes in three phospholipid fatty acid biomarkers were observed among the treatments. These changes indicated that different ATZ-degrading microbial consortia resulted in equivalent ATZ degradation rates between treatments. Results demonstrated that soil microbial response was the dominant mechanism controlling ATZ degradation in the soil studied, rather than root phytochemicals.

Improving practice in radiology: a quality-improvement project examining CT colonography patient dose and scanning technique.

AIM: To audit scanning technique and patient doses for computed tomography (CT) colonography (CTC) examinations in a large UK region and to identify opportunities for quality improvement. MATERIALS AND METHODS: Scanning technique and patient dose data were gathered for both contrast-enhanced and unenhanced CTC examinations from 33 imaging protocols across 27 scanners. Measurements of patient weight and effective diameter were also obtained. Imaging protocols were compared to identify technique differences between similar scanners. Scanner average doses were calculated and combined to generate regional diagnostic reference limits (DRLs) for both examinations. RESULTS: The regional DRLs for contrast-enhanced examinations were volume CT dose index (CTDIvol) of 11 and 5 mGy for the two scan phases (contrast-enhanced and either delayed phase or non-contrast enhanced respectively), and dose-length product (DLP) of 740 mGy·cm. For unenhanced examinations, these were 5 mGy and 450 mGy·cm. These are notably lower than the national DRLs of 11 mGy and 950 mGy·cm. Substantial differences in scan technique and doses on similar scanners were identified as areas for quality-improvement action. CONCLUSION: A regional CTC dose audit has demonstrated compliance with national DRLs but marked variation in practice between sites for the dose delivered to patients, notably when scanners of the same type were compared for the same indication. This study demonstrates that the national DRL is too high for current scanner technology and should be revised.

Evidence for the impact of the 8.2-kyBP climate event on Near Eastern early farmers.

The 8.2-thousand years B.P. event is evident in multiple proxy records across the globe, showing generally dry and cold conditions for ca. 160 years. Environmental changes around the event are mainly detected using geochemical or palynological analyses of ice cores, lacustrine, marine, and other sediments often distant from human settlements. The Late Neolithic excavated area of the archaeological site of Çatalhöyük East [Team Poznan (TP) area] was occupied for four centuries in the ninth and eighth millennia B.P., thus encompassing the 8.2-thousand years B.P. climatic event. A Bayesian analysis of 56 radiocarbon dates yielded a high-resolution chronological model comprising six building phases, with dates ranging from before 8325-8205 to 7925-7815 calibrated years (cal) B.P. Here, we correlate an onsite paleoclimate record constructed from δ2H values of lipid biomarkers preserved in pottery vessels recovered from these buildings with changes in architectural, archaeozoological, and consumption records from well-documented archaeological contexts. The overall sequence shows major changes in husbandry and consumption practices at ca. 8.2 thousand years B.P., synchronous with variations in the δ2H values of the animal fat residues. Changes in paleoclimate and archaeological records seem connected with the patterns of atmospheric precipitation during the occupation of the TP area predicted by climate modeling. Our multiproxy approach uses records derived directly from documented archaeological contexts. Through this, we provide compelling evidence for the specific impacts of the 8.2-thousand years B.P. climatic event on the economic and domestic activities of pioneer Neolithic farmers, influencing decisions relating to settlement planning and food procurement strategies.

COVID-19 vaccine-readiness for anti-CD20-depleting therapy in autoimmune diseases.

Although most autoimmune diseases are considered to be CD4 T cell- or antibody-mediated, many respond to CD20-depleting antibodies that have limited influence on CD4 and plasma cells. This includes rituximab, oblinutuzumab and ofatumumab that are used in cancer, rheumatoid arthritis and off-label in a large number of other autoimmunities and ocrelizumab in multiple sclerosis. Recently, the COVID-19 pandemic created concerns about immunosuppression in autoimmunity, leading to cessation or a delay in immunotherapy treatments. However, based on the known and emerging biology of autoimmunity and COVID-19, it was hypothesised that while B cell depletion should not necessarily expose people to severe SARS-CoV-2-related issues, it may inhibit protective immunity following infection and vaccination. As such, drug-induced B cell subset inhibition, that controls at least some autoimmunities, would not influence innate and CD8 T cell responses, which are central to SARS-CoV-2 elimination, nor the hypercoagulation and innate inflammation causing severe morbidity. This is supported clinically, as the majority of SARS-CoV-2-infected, CD20-depleted people with autoimmunity have recovered. However, protective neutralizing antibody and vaccination responses are predicted to be blunted until naive B cells repopulate, based on B cell repopulation kinetics and vaccination responses, from published rituximab and unpublished ocrelizumab (NCT00676715, NCT02545868) trial data, shown here. This suggests that it may be possible to undertake dose interruption to maintain inflammatory disease control, while allowing effective vaccination against SARS-CoV-29, if and when an effective vaccine is available.

Cardio-metabolic risk factors among young infertile women: a systematic review and meta-analysis.

BACKGROUND: There is currently no concise systematic review or meta-analysis addressing cardio-metabolic risk factors in women experiencing infertility. OBJECTIVES: To determine whether infertile women have higher levels of cardiovascular risk factors compared with fertile women. SEARCH STRATEGY: We performed a systematic literature search using PubMed, Embase and CINAHL, Scopus and additional manual and bibliographic searches for relevant articles (end search date 6 November 2019). SELECTION CRITERIA: We selected studies that compared cardio-metabolic risk factors in fertile and infertile women of reproductive age. DATA COLLECTION AND ANALYSIS: At least two authors independently screened potentially eligible studies. MAIN RESULTS: There was an increased presence of several cardio-metabolic risk factors in infertile women compared with fertile women. Infertile women had statistically significant higher body mass index (BMI), increased total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) compared with fertile women. Fasting glucose, fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR) and mean arterial pressure were not found to be different between fertile and infertile women. A subgroup analysis revealed that TC, fasting glucose and fasting insulin were increased, and high-density lipoprotein was decreased only in women with polycystic ovarian syndrome compared with fertile women, whereas BMI, TG and LDL-C were statistically significantly increased in women with any indication of infertility compared with fertile women. CONCLUSIONS: Infertile women have a higher level of cardio-metabolic risk factors compared with fertile women. This finding has clinical implications for infertile women in general, and those attempting to conceive through medically assisted reproduction. TWEETABLE ABSTRACT: Infertile women appear to have a higher level of cardio-metabolic risk factors compared with fertile women.

Glycosylated fibronectin point-of-care test for diagnosis of pre-eclampsia in a low-resource setting: a prospective Southeast Asian population study.

OBJECTIVE: To determine the performance of a glycosylated fibronectin (GlyFn) point-of-care (POC) test for pre-eclampsia (PE) in a large Southeast Asian cohort (India) in comparison to previously described biomarkers. DESIGN: A total of 798 pregnant women at ≥20 weeks of gestation were enrolled in a prospective case-control study. Study participants included 469 normotensive women with urinary mg protein/mmol creatinine ratio <0.3, 135 with PE (hypertension with urinary mg protein/mmol creatinine ratio ≥0.3) and 194 with gestational hypertension (hypertension with urinary mg protein/mmol creatinine ratio <0.3). METHODS: GlyFn levels were determined using a POC device and PIGF, sFlt-1 and PAPPA2 levels were determined by immunoassay. Performance was assessed using logistic regression modelling and receiver-operating characteristic (ROC) curves. Classification performance and positive and negative predictive values are reported at specific thresholds. RESULTS: Increased levels of GlyFn, soluble fms-like tyrosine kinase-1 (sFlt-1) and pregnancy-associated placental protein A2 (PAPPA2), and decreased levels of placental growth factor (PlGF) were significantly associated (P < 0.01) with clinically defined PE. Area under the ROC (AUROC) values with 95% confidence intervals were: GlyFn, 0.99 (0.98-0.99); PlGF, 0.96 (0.94-0.98); sFlt-1, 0.86 (0.83-0.89); and PAPPA2, 0.96 (0.94-0.97). Of subjects with GH, 48% were positive for more than two PE biomarkers, and 70% of these delivered preterm. CONCLUSIONS: The Lumella™ GlyFn POC test has been validated in a low/middle-income country setting for PE diagnosis and may be a useful adjunctive tool for early identification, appropriate triage, and improved outcomes. TWEETABLE ABSTRACT: The Lumella™ point-of-care test had excellent performance in diagnosing PE in a large Southeast Asian cohort.

Using online tools at the Bovine Genome Database to manually annotate genes in the new reference genome.

With the availability of a new highly contiguous Bos taurus reference genome assembly (ARS-UCD1.2), it is the opportune time to upgrade the bovine gene set by seeking input from researchers. Furthermore, advances in graphical genome annotation tools now make it possible for researchers to leverage sequence data generated with the latest technologies to collaboratively curate genes. For many years the Bovine Genome Database (BGD) has provided tools such as the Apollo genome annotation editor to support manual bovine gene curation. The goal of this paper is to explain the reasoning behind the decisions made in the manual gene curation process while providing examples using the existing BGD tools. We will describe the sources of gene annotation evidence provided at the BGD, including RNA-seq and Iso-Seq data. We will also explain how to interpret various data visualizations when curating gene models, and will demonstrate the value of manual gene annotation. The process described here can be applied to manual gene curation for other species with similar tools. With a better understanding of manual gene annotation, researchers will be encouraged to edit gene models and contribute to the enhancement of livestock gene sets.

First report of Meloidogyne enterolobii infecting Japanese blue berry tree (Elaeocarpus decipiens) in Florida, USA.

In October 2019, samples of galled roots with rhizosphere soil were collected from declining Elaeocarpus decipiens in Hernando County, Florida. Extracted root-knot nematodes were identified by both molecular and morphological methods as Meloidogyne enterolobii. This is a first report of this regulated root-knot nematode on Elaeocarpus decipiens in Florida.In October 2019, samples of galled roots with rhizosphere soil were collected from declining Elaeocarpus decipiens in Hernando County, Florida. Extracted root-knot nematodes were identified by both molecular and morphological methods as Meloidogyne enterolobii. This is a first report of this regulated root-knot nematode on Elaeocarpus decipiens in Florida.

First report of root-knot nematodes (Meloidogyne species) infecting Chinese Elm (Ulmus parvifolia) in Florida, USA.

Samples of galled roots, resembling those induced by root-knot nematodes, and rhizosphere soil were collected from potted plants of Ulmus parvifolia cvs. Allee and Drake in Lake County, Florida. Nematode species were identified using both molecular analysis and morphology of perineal patterns. Meloidogyne enterolobii and M. javanica were identified from U. parvifolia cv. Allee. Meloidogyne arenaria and M. javanica were identified from U. parvifolia cv. Drake. This is a first report of these nematode species infecting Chinese Elm in Florida.Samples of galled roots, resembling those induced by root-knot nematodes, and rhizosphere soil were collected from potted plants of Ulmus parvifolia cvs. Allee and Drake in Lake County, Florida. Nematode species were identified using both molecular analysis and morphology of perineal patterns. Meloidogyne enterolobii and M. javanica were identified from U. parvifolia cv. Allee. Meloidogyne arenaria and M. javanica were identified from U. parvifolia cv. Drake. This is a first report of these nematode species infecting Chinese Elm in Florida.

Development and first validation of a patient-reported experience measure in chronic obstructive pulmonary disease (PREM-C9).

We developed a chronic obstructive pulmonary disease (COPD) patient-reported experience measure (PREM-C9). 174 patients with COPD (86 [49%] with a confirmed diagnosis and 88 [51%] with a self-reported diagnosis of COPD) completed a 38-item list, COPD Assessment Test (CAT) and Hospital Anxiety and Depression Scale (HADS). Hierarchical and Rasch analysis produced a 9-item list (PREM-C9). It demonstrated fit to the Rasch model (χ² p=0.33) and correlated moderately with CAT (r=0.42), HAD-anxiety (r=0.30) and HAD-depression (r=0.41) (p<0.05). A substudy confirmed its ability to detect change prepulmonary and postpulmonary rehabilitation. The PREM-C9 is a simple, valid measure of experience of patients living with COPD, validated in this study population with mild to very severe disease; it may be a useful measure in research and clinical audits.

The effects of monoclonal anti-CD47 on RBCs, compatibility testing, and transfusion requirements in refractory acute myeloid leukemia.

BACKGROUND: CD47 is a novel therapeutic target in the treatment of solid-organ and hematologic malignancies. CD47 is also expressed on RBCs. Here, we report our experience of the RBC effects and the impact on blood bank testing and transfusion management in a Phase 1 trial of the humanized anti-CD47 monoclonal antibody Hu5F9-G4 in relapsed or primary refractory acute myeloid leukemia (AML) (NCT02678338). STUDY DESIGN AND METHODS: Nineteen patients with relapsed or primary refractory AML treated across five UK centers were included for analysis. Patients received escalating doses of Hu5F9-G4. Serial laboratory data were collected to evaluate impact on hemoglobin (Hb), markers of hemolysis (bilirubin, lactate dehydrogenase, reticulocyte count), transfusion requirements, and blood compatibility testing. RESULTS: A decline in Hb was observed with drug administration (median Hb change, -1.0 g/dL; range, 0.4-1.6) with associated increase in transfusion requirements. Patients responded to transfusion with a median Hb increment per unit of 1.0 g/dL. RBC agglutination was seen in all cases without associated change in Hb, lactate dehydrogenase, bilirubin, or reticulocyte count. Nine of 19 (47%) patients developed a newly positive antibody screen with a pan-agglutinin identified in plasma. Invalid ABO blood grouping occurred in 4 of 12 (33%) non-group O patients due to anomalous reactivity in the reverse ABO-type results. CONCLUSIONS: Treatment with Hu5F9-G4 in patients with AML resulted in an Hb decline and increased transfusion requirements. Problems with ABO blood typing and compatibility testing were widely observed and should be expected by centers treating recipients of Hu5F9-G4.

Metabolic syndrome and time to pregnancy: a retrospective study of nulliparous women.

OBJECTIVE: To determine: (1) the association between metabolic syndrome (MetS), time to pregnancy (TTP), and infertility; (2) associations between individual and an increasing number of MetS components, TTP, and infertility; and (3) whether these relationships differ by body mass index (BMI < 30 kg/m2 versus BMI ≥ 30 kg/m2 ). DESIGN: Retrospective cohort study. SETTING: Multiple centres (in Australia, Ireland, New Zealand, and the UK). POPULATION: Five thousand five hundred and nineteen low-risk nulliparous pregnant women. METHODS: Data on retrospectively reported TTP (number of months to conceive) and a blood sample to assess metabolic health were collected between 14 and 16 weeks of gestation. MetS was defined according to the International Diabetes Federation criteria. Accelerated failure time models with log-normal distribution were conducted to estimate time ratios (TRs) and 95% CIs. Differences in MetS on infertility (TTP > 12 months) were compared using a generalised linear model (Poisson distribution) with robust variance estimates (relative risks, RRs; 95% CIs). All analyses (entire cohort and split by BMI) were controlled for a range of maternal and paternal confounding factors. MAIN OUTCOME MEASURES: Time to pregnancy and infertility. RESULTS: Of the 5519 women included, 12.4% (n = 684) had MetS. Compared with women without MetS, women with MetS had a longer TTP (adjusted TR 1.30; 95% CI 1.15-1.46), which was similar in women who were obese and in women who were not obese. Marginal estimates for median TTP in women with MetS versus without MetS was 3.1 months (3.0-3.3 months) versus 4.1 months (3.6-4.5 months), respectively. Women with MetS were at a 62% greater risk for infertility and were at a greater risk for infertility whether they were obese (adjusted RR 1.62; 95% CI 1.15-2.29) or not (adjusted RR 1.73; 95% CI 1.33-2.23). Reduced high-density lipoprotein cholesterol (HDL-C) and raised triglycerides (TGs) were the main individual components associated with risk for infertility. CONCLUSION: Metabolic syndrome is associated with longer TTP and infertility, independent of obesity. Additional studies, before pregnancy, are required to support our findings and to determine the applicability of which combinations of metabolic abnormalities pose the greatest risk to delayed fertility, or whether individual components are amenable to modification. TWEETABLE ABSTRACT: Metabolic syndrome is associated with longer time to pregnancy and infertility, independent of obesity.

Thymopoiesis following HSCT; a retrospective review comparing interventions for aGVHD in a pediatric cohort.

Acute graft-versus-host disease (aGVHD) complicates allogeneic hematopoietic stem cell transplantation (HSCT), and is treated with topical and/or systemic corticosteroids. Systemic corticosteroids and aGVHD damage thymic tissue. We compared thymopoietic effect of topical steroid therapy, corticosteroids and extracorporeal photopheresis (ECP) in 102 pediatric allogeneic HSCT patients. We categorized patients into 4 groups: - no aGVHD, aGVHD treated with topical or systemic steroid, or ECP. Naïve CD4+CD45RA+CD27+ T-lymphocyte values at 3, 6, 9, 12months post-HSCT were recorded: for ECP patients, values were recorded at 3, 6, 9, 12months during ECP. Differences were compared using the Kruskal-Wallis test. 41 patients had no aGVHD, 23 had aGVHD treated topically or systemically (25), 13 received ECP. Rate of thymopoiesis was significantly different between all groups at all time-points post-transplant (p=0.002, p<0.001, p<0.001, p=0.001 respectively). Even mild aGVHD impairs thymopoiesis. Worst recovery was in ECP patients. Earlier institution of ECP may speed thymic recovery.

Correction to: Testing for medical school selection: What are prospective doctors' experiences and perceptions of the GAMSAT and what are the consequences of testing?

The wrong acknowledgement and funding information were provided in the original publication.