APASL clinical practice guidelines on the management of acute kidney injury in acute-on-chronic liver failure.

Acute-on-chronic liver failure (ACLF) is a syndrome that is characterized by the rapid development of organ failures predisposing these patients to a high risk of short-term early death. The main causes of organ failure in these patients are bacterial infections and systemic inflammation, both of which can be severe. For the majority of these patients, a prompt liver transplant is still the only effective course of treatment. Kidneys are one of the most frequent extrahepatic organs that are affected in patients with ACLF, since acute kidney injury (AKI) is reported in 22.8-34% of patients with ACLF. Approach and management of kidney injury could improve overall outcomes in these patients. Importantly, patients with ACLF more frequently have stage 3 AKI with a low rate of response to the current treatment modalities. The objective of the present position paper is to critically review and analyze the published data on AKI in ACLF, evolve a consensus, and provide recommendations for early diagnosis, pathophysiology, prevention, and management of AKI in patients with ACLF. In the absence of direct evidence, we propose expert opinions for guidance in managing AKI in this very challenging group of patients and focus on areas of future research. This consensus will be of major importance to all hepatologists, liver transplant surgeons, and intensivists across the globe.

Evaluation of costs associated with fertility treatment leading to a live birth after one fresh transfer: A global perspective.

Considerable costs are associated with infertility treatment, but little evidence is available on the main drivers of treatment costs. This cost analysis investigated key costs for treatment with assisted reproductive technology (ART) and the proportion of costs attributed to the acquisition of recombinant human follicle-stimulating hormone (r-hFSH) alfa originator for one fresh embryo transfer (ET) leading to a live birth in Spain, Norway, the UK, Germany, Denmark, South Korea, Australia, and New Zealand. The total costs for one ART cycle with a fresh ET leading to a live birth varied between countries (€4108-€12,314). Costs for pregnancy and live birth were the major contributors in European countries, and the costs of oocyte retrieval, monitoring during ovarian stimulation, pregnancy, and live birth were the top contributors in the Asia-Pacific countries, included in this analysis. Acquisition costs for r-hFSH alfa originator contributed to only 5%-17% of the total costs of one ART cycle with one fresh ET leading to a live birth.

Incidence and causes of early hospital readmissions after living donor renal transplant - A single centre study.

Background: Kidney transplantation in spite of being the best modality for the treatment of ESRD remains a complex therapeutic option as it has its own set of problems due to associated morbidity especially in the first month after transplantation. Aim: The primary aim of this study was to find the incidence, causes, and factors responsible for early hospital readmissions (EHRs) and secondary aim was to find the effect of EHR on morbidity, mortality, and graft loss. Patients and Methods: A retrospective analysis of the records of the chronic kidney disease (CKD) patients who underwent living donor renal transplantation. 202 patients were included in the study. Inpatient records and charts were assessed for the medical status of the patients, cause of CKD, comorbidities, admissions 3 months prior to transplant, vintage dialysis, and modality of dialysis. Results: Sixty-one (30.2%) patients were readmitted to the hospital once or more within 30 days of discharge after renal transplantation. Thirty-four (55.7%) patients in the EHR group were admitted once or more in the 90 days prior to transplant as compared to 48 (34%) patients in the no readmission group. Thirty-four (55.7%) patients in the EHR group were hospitalised again within 1 year of EHR and 50 (35.5%) in the no EHR group got admitted within 1 year of discharge. Conclusions: Renal transplant recipients with hospital admissions 90 days before transplant and readmissions within 30 days of discharge after transplantation are at high risk of morbidity and should be treated as high-risk category and should have more stringent follow-up protocols.

Phenomics, genomics of oil palm (Elaeis guineensis Jacq.): way forward for making sustainable and high yielding quality oil palm.

Oil palm (Elaeis guineensis Jacq.) is a heterogeneous, perennial crop having long breeding cycle with a genome size of 1.8 Gb. The demand for vegetable oil is steadily increasing, and expected that nearly 240-250 million tons of vegetable oil may be required by 2050. Genomics and next generation technologies plays crucial role in achieving the sustainable availability of oil palm with good yield and high quality. A successful breeding programme in oil palm depends on the availability of diverse gene pool, ex-situ conservation and their proper utilization for generating elite planting material. The major breeding methods adopted in oil palm are either modified recurrent selection or the modified reciprocal recurrent selection method. The QTLs of yield and related traits are chiefly located on chromosome 4, 10, 12 and 15 which is discussed in the current review. The probable chromosomal regions influencing the less height increment is observed to be on chromosomes 4, 10, 14 and 15. Advanced genomic approaches together with bioinformatics tools were discussed thoroughly for achieving sustainable oil palm where more efforts are needed. Major emphasis is given on oil palm crop improvement using holistic approaches of various genomic tools. Also a road map given on the milestones in the genomics and way forward for making oil palm to high yielding quality oil palm.

Genome-wide association study (GWAS) of major QTLs for bunch and oil yield related traits in Elaeis guineensis L.

Oil palm (Elaeis guineensis Jacq.) is a long breeding cycle perennial crop with a genome size of 1.8 Gb. This is the first report of GWAS on large number of 310 African germplasm using 400 SSR markers till date. Highly significant correlation was found between leaf area (LA) and rachis length (RL) (0.75) followed by bunch weight (BW) and bunch index (BI) (0.65), whereas negative correlation was observed between bunch number (BN) and average bunch weight (ABW). First two principal component analysis (PCA) together explained maximum amount of variation (84.5 %). The PCA1 revealed that group 2 (Guinea Bissau and Cameroon) and group 4 (Zambia and Cameroon) genotypes are best suitable for BN, BI and BW traits. GWAS of six bunch yield and seven bunch oil yield traits with SSRs resulted in the identification 43 significant quantitative trait loci (QTLs) by mixed linear model (MLM) approach. Seven SSR loci were found to be linked to oil to dry mesocarp (ODM) on chromosomes 1,4,7,10,12 and 15. The SSR locus mEgCIR1753 for ODM was significantly linked at a p of ≤0.05 which explained 34.6 % of phenotypic variance. The important parameters like ODM, OWM and OB were located on 4, 10, 11 and 15 chromosomes. The leaf area and ODM were associated with candidate genes representing of low-temperature-induced 65 kDa proteins. The identified markers can be effectively used for marker assisted selection of high yielding oil palm genotypes.

Patient experiences of fertility clinic closure during the COVID-19 pandemic: appraisals, coping and emotions.

STUDY QUESTION: What are appraisals, coping strategies and emotional reactions of patients to coronavirus disease 2019 (COVID-19) fertility clinic closures? SUMMARY ANSWER: Clinic closure was appraised as stressful due to uncertainty and threat to the attainability of the parenthood goal but patients were able to cope using strategies that fit the uncertainty of the situation. WHAT IS KNOWN ALREADY: Psychological research on COVID-19 suggests that people are more anxious than historical norms and moderately to extremely upset about fertility treatment cancellation owing to COVID-19. STUDY DESIGN, SIZE, DURATION: The study was of cross-sectional design, comprising a mixed-methods, English language, anonymous, online survey posted from April 9 to 21 to social media. Eligibility criteria were being affected by COVID-19 fertility clinic closure, 18 years of age or older and able to complete the survey in English. In total, 946 people clicked on the survey link, 76 did not consent, 420 started but did not complete the survey and 450 completed (48% completion, 446 women, four men). PARTICIPANTS/MATERIALS, SETTING, METHODS: Overall 74.7% (n = 336) of respondents were residents in the UK with an average age of 33.6 years (SD = 4.4) and average years trying to conceive, 3.5 years (SD = 2.22). The survey comprised quantitative questions about the intensity of cognitive appraisals and emotions about clinic closure, and ability to cope with clinic closure. Open-text questions covered their understanding of COVID-19 and its effect on reproductive health and fertility plans, concerns and perceived benefits of clinic closure, and knowledge about closure. Sociodemographic information was collected. Descriptive and inferential statistics were used on quantitative data. Thematic qualitative analysis (inductive coding) was performed on the textual data from each question. Deductive coding grouped themes from each question into meta-themes related to cognitive stress and coping theory. MAIN RESULTS AND THE ROLE OF CHANCE: Most patients (81.6%, n = 367) had tests or treatments postponed, with these being self (41.3%, n = 186) or publicly (46.4%, n = 209) funded. Patients appraised fertility clinic closure as having potential for a more negative than positive impact on their lives, and to be very or extremely uncontrollable and stressful (P ≤ 0.001). Most reported a slight to moderate ability to cope with closure. Data saturation was achieved with all open-text questions, with 33 broad themes identified and four meta-themes linked to components of the cognitive stress and coping theory. First, participants understood clinic closure was precautionary due to unknown effects of COVID-19 but some felt clinic closure was unfair relative to advice about getting pregnant given to the public. Second, closure was appraised as a threat to attainability of the parenthood goal largely due to uncertainty of the situation (e.g. re-opening, effect of delay) and intensification of pre-existing hardships of fertility problems (e.g. long time waiting for treatment, history of failed treatment). Third, closure taxed personal coping resources but most were able to cope using thought-management (e.g. distraction, focusing on positives), getting mentally and physically fit for next treatments, strengthening their social network, and keeping up-to-date. Finally, participants reported more negative than positive emotions (P ≤ 0.001) and, almost all participants reported stress, worry and frustration at the situation, while some expressed anger and resentment at the unfairness of the situation. Overall, 11.8% were not at all able to cope, with reports of intense feelings of hopelessness and deteriorating well-being and mental health. LIMITATIONS, REASONS FOR CAUTION: The survey captures patient reactions at a specific point in time, during lockdown and before clinics announced re-opening. Participants were self-selected (e.g. UK residents, women, 48% starting but not completing the survey), which may affect generalisability. WIDER IMPLICATIONS OF THE FINDINGS: Fertility stakeholders (e.g. clinics, patient support groups, regulators, professional societies) need to work together to address the great uncertainty from COVID-19. This goal can be met proactively by setting up transparent processes for COVID-19 eventualities and signposting to information and coping resources. Future psychological research priorities should be on identifying patients at risk of distress with standardised measures and developing digital technologies appropriate for the realities of fertility care under COVID-19. STUDY FUNDING/COMPETING INTEREST(S): University funded research. Outside of the submitted work, Prof. J.B. reports personal fees from Merck KGaA, Merck AB, Theramex, Ferring Pharmaceuticals A/S; grants from Merck Serono Ltd; and that she is co-developer of the Fertility Quality of Life (FertiQoL) and MediEmo apps. Outside of the submitted work, Dr R.M. reports personal or consultancy fees from Manchester Fertility, Gedeon Richter, Ferring and Merck. Outside of the submitted work, Dr S.G. reports consultancy fees from Ferring Pharmaceuticals A/S, Access Fertility and SONA-Pharm LLC, and grants from Merck Serono Ltd. The other authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Impact of UDST: A step forward to end TB.

BACKGROUND: India is determined to eliminate TB by 2025 despite being a high burden country. Revised National Tuberculosis Control Programme (RNTCP) is being strengthened with introduction of Universal Drug Susceptibility Testing (UDST) for Rifampicin to achieve the elimination status. METHODOLOGY: We used a before-after comparison of baseline and intervention periods (12 months each) and analyzed data viz CBNAAT performed and case detection for both drug sensitive and drug resistant TB cases. RESULTS: After implementation of Universal DST, CBNAAT performed raised from 1252 to 3137 (increased by 2.5 times); Rif sensitive cases detected raised from 458 to 1241 (increased by 2.7 times) and Rif resistant cases detected raised from 54 to 82 (increased by 1.5 times) during baseline period (2017) and intervention period (2018). CONCLUSION: We conclude that introduction of UDST for Rifampicin in RNTCP has given a significant impact with increased case detection in our study.

Identification of QTLs in oil palm (Elaeis guineensis Jacq.) using SSR markers through association mapping.

Oil palm (Elaeis guineensis Jacq.) is a perennial vegetable and a high oil-yielding crop (4-6 t/ha). There is a large scope for increasing the oil yield by selecting elite planting material for breeding programme in germplasm evaluation, characterization and utilization. In the present study, a diverse range of 150 oil palm genotypes were characterized using 12 quantitative variables with 54genomic microsatellite markers. A wide variation was observed in the morphological traits among indigenous populations. Highly significantand positive correlations were observed between vegetative dry matter (VDM) and total dry matter (TDM) (0.862), and height and height increment (0.838). The first two principal component analyses explained 67.7% of total variation among morphological traits. The genotypes IC0610001-59 (Pune-2) and IC0610001-60 (Pune-2) were found highly promising based on less height increment, more TDMwith high yield. For the mapping study, general linear model (GLM) approach, quantitative-trait loci (QTL) for annual height increment, number of bunches, bunch yield and bunch index were linked to simple-sequence repeat (SSR) loci mEgCIR3649 with phenotypic variance of 15.08, 10.43, 11.74, 15.39. TDM and VDM were linked to mEgCIR0192 (27.34 and 24.19%), mEgCIR3684 (16.84 and 18.30%), SPSC00163 (18.8 and 15.39%) and mEgCIR0555 (16.47 and 18.81%), with at a significant threshold (P) level of B0.001 and by mixed linear model (MLM) approach. TDM was linked to mEgCIR0555 with phenotypic variance of 20.72%, bunch yield and bunch index were linked to mEgCIR2813 at phenotypic variance of 17.11% and 12.88%, respectively, at a significant threshold (P) level of B0.01.

Development of pepper vein banding virus chimeric virus-like particles for potential diagnostic and therapeutic applications.

Monoclonal antibodies have attracted wide attention in therapeutics owing to their high efficacy, low toxicity, and specific targeting. However, antibodies cannot cross the cell membrane barrier. Therefore, their therapeutic potential is limited to surface-exposed antigens or secreted proteins. In the present investigation, we have developed a chimeric virus-like particle (VLP) of pepper vein banding virus (PVBV) and explored the possibility of using it as a delivery vehicle for antibodies against intracellular antigens as well as for future applications in immunodiagnostics. The chimeric PVBV particles were generated by genetically engineering the B domain of Staphylococcus aureus protein A (SpA) at the N-terminus of the PVBV coat protein (CP). The chimeric VLPs purified by sucrose density gradient centrifugation had ~440-fold higher affinity towards IgG antibody when compared to SpA. Interestingly, the unassembled chimeric CP with the B-domain at the N-terminus (BCP) purified by Ni-NTA chromatography was a monomer, and it had ~45-fold higher affinity towards antibodies compared to SpA. Additionally, the chimeric particles were able to bind and deliver antibodies against both intracellular (α-tubulin) and surface-exposed antigens (CD 20). However, the BCP monomer failed to enter mammalian cells. Thus, for the first time, we have demonstrated that the assembled VLPs are essential for internalization. These results demonstrate the potential of the use of chimeric PVBV VLPs in diagnostics and, more importantly, as nanocarriers for intracellular delivery of antibodies.

Ethnic differences in the severity and clinical management of type 2 diabetes at time of diagnosis: A cohort study in the UK Clinical Practice Research Datalink.

AIMS: To characterize ethnic differences in the severity and clinical management of type 2 diabetes at initial diagnosis. METHODS: An observational cohort study of 179,886 people with incident type 2 diabetes between 2004 and 2017 in the Clinical Practice Research Datalink was undertaken; 63.4% of the cohort were of white ethnicity, 3.9% south Asian, and 1.6% black. Ethnic differences in clinical profile at diagnosis, consultation rates, and risk factor recording were derived from linear and logistic regression. Cox-proportional hazards regression was used to determine ethnic differences in time to initiation of therapeutic and non-therapeutic management following diagnosis. All analyses adjusted for age, sex, deprivation, and clustering by practice. RESULTS: In the 12 months prior to diagnosis, non-white groups had fewer consultations compared to white groups, but risk factor recording was better than or equivalent to white groups for 9/10 risk factors for south Asian groups and 8/10 risk factors for black groups (p < 0.002). Blood pressure, BMI, cholesterol, eGFR, and CVD risk levels were more favourable in non-white groups, and prevalence of macrovascular disease was significantly lower (p < 0.003). Time to initiation of antidiabetic treatment and first risk assessment was faster in non-white groups relative to white groups, while time to risk factor measurement and diabetes review was slower. CONCLUSIONS: We find limited evidence of systematic ethnic inequalities around the time of type 2 diabetes diagnosis. Ethnic disparities in downstream consequences may relate to genetic risk factors, or manifest later in the care pathway, potentially in relation to long-term risk factor control.

Incidence, Risk Factors, and Outcomes of Transition of Acute Kidney Injury to Chronic Kidney Disease in Cirrhosis: A Prospective Cohort Study.

Transition to chronic kidney disease (CKD) after an episode of acute kidney injury (AKI) is known in patients without cirrhosis. We studied the incidence and risk factors for development of CKD in patients with cirrhosis. Competing risk analysis was performed to identify risk factors for CKD development. Of 818 patients with cirrhosis (age, 50.4 ± 11.8 years; 84% males; Model for End-Stage Liver Disease [MELD], 19.9 ± 9.9), 36% had AKI at enrollment, 27% had previous AKI, and 61% developed new episodes of AKI during the follow-up period. CKD developed in 269 (33%) patients. Serum cystatin C (CysC; subdistribution hazard ratio [SHR], 1.58; 1.07-2.33), episodes of previous AKI (SHR, 1.26; 1.02-1.56), and AKI stage at enrollment (no AKI [SHR, 1] vs. stage 1 [SHR, 3.28; 1.30-8.25] vs. stage 2 [SHR, 4.33; 1.76-10.66] vs. stage 3 [SHR, 4.5; 1.59-12.73]) were identified as baseline risk factors for CKD development. On time-varying competing risk analysis, MELD (SHR, 1.01; 1.00-1.03), number of AKI episodes (SHR, 1.25; 1.15-1.37), and CysC (SHR, 1.38; 1.01-1.89) predicted CKD development. Development of CKD was associated with higher risk of death. Reduction in glomerular filtration rate (GFR) not meeting CKD criteria was observed in 66% of patients with cirrhosis, more so in those with previous AKI episodes and a high CysC level and MELD score. Renal histology, available in 55 patients, showed tubulointerstitial injury in 86%, cholemic nephrosis in 29%, and glomerular changes in 38%. Conclusion: Almost two-thirds of patients with cirrhosis develop episodes of AKI and reduction in GFR; one-third progress to CKD, resulting in adverse outcomes. Higher MELD and CysC levels and number of AKI episodes predict development of CKD in patients with cirrhosis.

Genome wide association study (GWAS) and identification of candidate genes for yield and oil yield related traits in oil palm (Eleaeis guineensis) using SNPs by genotyping-based sequencing.

The genotyping-based sequencing (GBS) method used for GWAS of four yield and seven oil yield related traits on highly diverse African oil palm germplasm. GBS generated 325 million-reads covering 50.78Gb of sequence data, with an average of 3.4 million-reads per sample. Finally, 4031 fully informative SNPs with a range between 157 on chromosome 15 to 455 on chromosome 1 were used for GWAS. Association mapping resulted in identification of 40 highly significant loci, where more genetic loci were found to be associated with oil to bunch (OB), followed by average bunch weight (ABW). The loci, SGI|593,593|linked to QTNOB3 explained high amount of phenotypic variance (25.3%). The nucleotide sequences of linked genetic loci for OB were found to be similar to mitogen activated protein kinase-5 (MAPK-5) protein which is an early flowering protein. The significant loci identified can be used to select desirable palms at early stage through marker assisted selection.

Genome-wide association study for leaf area, rachis length and total dry weight in oil palm (Eleaeisguineensis) using genotyping by sequencing.

The marker-trait association for complex traits using genotyping by sequencing (GBS) method is being widely spread in plants. The study aimed to identify significant single nucleotide polymorphism (SNP) associations for rachis length (RL), leaf area (LA) and total dry weight (TrDW) in oil palm among diverse African germplasm. The Illumina NextSeq platform has been used for SNP genotyping and retained 4031 fully informative SNPs after applying the filter criterion. These 4031 SNPs were used for genome wide association study for the above three traits. The LD decay rates of the African germplasm using GBS data of SNP is observed to be 25 Kb at 0.45 of average pair wise correlation coefficient (r2). Association mapping led to the identification of seven significant associations for three traits using MLM approach at a P value of ≤ 0.001. Three associations were identified for total dry weight, two each for leaf area index and rachis length. The qtlLA1 was found to be highly significant at a P value of 7.39E-05 (18.4% phenotypic variance) which is located on chromosome 4. Two QTLs (qtlLA2 and qtlRL1) were located on chromosome 1, which explained 11.9% and 12.4% of phenotypic variance respectively. Three QTLs for total dry weight were located on chromosome 2, 14 and 16, all-together explained 40% phenotypic variance. The results showed that the SNP-trait associations identified in the present study could be used in selection of elite oil palm germplasm for higher yields.

Structural and functional studies on Salmonella typhimurium pyridoxal kinase: the first structural evidence for the formation of Schiff base with the substrate.

A large number of enzymes depend on the ubiquitous cofactor pyridoxal 5' phosphate (PLP) for their activity. Pyridoxal kinase (PLK) is the key enzyme involved in the synthesis of PLP from the three forms of vitamin B6 via the salvage pathway. In the present work, we determined the unliganded structure of StPLK in a monoclinic form and its ternary complex with bound pyridoxal (PL), ADP and Mg2+ in two different tetragonal crystal forms (Form I and Form II). We found that, in the ternary complex structure of StPLK, the active site Lys233 forms a Schiff base linkage with the substrate (PL). Although formation of a Schiff base with the active site Lys229 was demonstrated in the Escherichia coli enzyme based on biochemical studies, the ternary complex of StPLK represents the first crystal structure where the Schiff bond formation has been observed. We also identified an additional site for PLP binding away from the active site in one of the ternary complexes (crystal Form I), suggesting a probable route for the product release. This is the first ternary complex structure where the modeled γ-phosphate of ATP is close enough to PL for the phosphorylation of the substrate. StPLK prefers PL over pyridoxamine as its substrate and follows a sequential mechanism of catalysis. Surface plasmon resonance studies suggest that StPLK interacts with apo-PLP-dependent enzymes with µm affinity supporting the earlier proposed direct transfer mechanism of PLP from PLK to PLP-dependent enzymes.

Development and validation of whole genome-wide and genic microsatellite markers in oil palm (Elaeis guineensis Jacq.): First microsatellite database (OpSatdb).

The availability of large expressed sequence tag (EST) and whole genome databases of oil palm enabled the development of a data base of microsatellite markers. For this purpose, an EST database consisting of 40,979 EST sequences spanning 27 Mb and a chromosome-wise whole genome databases were downloaded. A total of 3,950 primer pairs were identified and developed from EST sequences. The tri and tetra nucleotide repeat motifs were most prevalent (each 24.75%) followed by di-nucleotide repeat motifs. Whole genome-wide analysis found a total of 245,654 SSR repeats across the 16 chromosomes of oil palm, of which 38,717 were compound microsatellite repeats. A web application, OpSatdb, the first microsatellite database of oil palm, was developed using the PHP and MySQL database ( https://ssr.icar.gov.in/index.php ). It is a simple and systematic web-based search engine for searching SSRs based on repeat motif type, repeat type, and primer details. High synteny was observed between oil palm and rice genomes. The mapping of ESTs having SSRs by Blast2GO resulted in the identification of 19.2% sequences with gene ontology (GO) annotations. Randomly, a set of ten genic SSRs and five genomic SSRs were used for validation and genetic diversity on 100 genotypes belonging to the world oil palm genetic resources. The grouping pattern was observed to be broadly in accordance with the geographical origin of the genotypes. The identified genic and genome-wide SSRs can be effectively useful for various genomic applications of oil palm, such as genetic diversity, linkage map construction, mapping of QTLs, marker-assisted selection, and comparative population studies.

Hydatidiform molar pregnancy following assisted reproduction.

INTRODUCTION: The use of assisted reproduction techniques (ART) is increasing; however, reports of molar pregnancy following ART remain scarce. Currently, the Human Fertility and Embryology Authority (HFEA) collates data on the molar pregnancies that have resulted through the use of ART. Recently, they have indicated that they will no longer collect these data. AIM: This paper aimed to examine the incidence of molar pregnancy amongst patients undergoing assisted reproduction. METHODS: We contacted HFEA and placed a request under the Freedom of Information Act (2000) for the number of molar pregnancies that resulted from fresh/frozen embryo transfer since HFEA started collecting data in 1991 to February 2018. We also asked how many patients who had suffered a molar pregnancy went on to have a normal pregnancy and how many had subsequent molar pregnancies, in subsequent treatment cycles. RESULTS: Between 68 and 76 molar pregnancies occurred within this period using ART (n = 274,655). The incidence of molar pregnancy using fresh intracytoplasmic sperm injection (ICSI) (1/4302) and fresh in vitro fertilisation (IVF) (1/4333) was similar. The risk of recurrence of molar pregnancy following a previous molar was higher following ART compared to spontaneous conceptions. CONCLUSION: The use of ICSI should be protective against triploidy; however, the retrospective data suggests that molar pregnancy is not eliminated with the use of ART. It is pertinent to continue to record this data, through the gestational trophoblastic disease centres, in order to ensure no further increase in incidence, appropriate follow-up, and transparency in communication.

Ethnic variations in the risk of hypoglycaemia among people with Type 2 diabetes prescribed insulins and/or sulfonylureas: a historical cohort study using general practice-recorded data.

AIM: To identify ethnic differences in hypoglycaemic risk among people with Type 2 diabetes prescribed insulins and/or sulfonylureas in community settings. METHODS: Using routine general practice-recorded data, two cohorts of adults with Type 2 diabetes from east London were studied between January 2013 and December 2015: (1) adults prescribed insulins ± other antidiabetes medications (n=7269) and (2) adults prescribed sulfonylureas ± other antidiabetes medications excluding insulins (n=12 502). Incidence rate ratios of hypoglycaemia by ethnicity, adjusting for age, sex, socio-economic status and clustering within Clinical Commissioning Groups, were estimated using random effects Poisson regression. RESULTS: Compared with white British people prescribed insulins, those of black Caribbean ethnicity were at increased hypoglycaemic risk [adjusted incidence rate ratio 1.56 (95% CI 1.21,2.01)], while Bangladeshi people had a lower risk [adjusted incidence rate ratio 0.49 (95% CI, 0.38,0.64)]. In the sulfonylurea cohort, black Caribbean, black African and Indian people all had increased risks of hypoglycaemia compared with white British people [adjusted incidence rate ratios 1.63 (95% CI 1.15,2.29), 1.90 (95% CI 1.32,2.75) and 1.93 (95% CI 1.39,2.69), respectively]. CONCLUSION: The differences in hypoglycaemic risk among people with Type 2 diabetes prescribed insulin and/or sulfonylureas warrant further investigation of any differing biological responses and/or cultural attitudes to antidiabetes therapy among ethnic groups, and should be considered by clinicians evaluating the treatment goals of people with Type 2 diabetes using insulins or sulfonylureas.

Key Issues for Seamless Integrated Chemistry-Meteorology Modeling.

Online coupled meteorology-atmospheric chemistry models have greatly evolved in recent years. Although mainly developed by the air quality modeling community, these integrated models are also of interest for numerical weather prediction and climate modeling, as they can consider both the effects of meteorology on air quality and the potentially important effects of atmospheric composition on weather. This paper summarizes the main conclusions from the "Symposium on Coupled Chemistry-Meteorology/Climate Modelling: Status and Relevance for Numerical Weather Prediction, Air Quality and Climate Research," which was initiated by the European COST Action ES1004 "European Framework for Online Integrated Air Quality and Meteorology Modelling (EuMetChem)." It offers a brief review of the current status of online coupled meteorology and atmospheric chemistry modeling and a survey of processes relevant to the interactions between atmospheric physics, dynamics, and composition. In addition, it highlights scientific issues and emerging challenges that require proper consideration to improve the reliability and usability of these models for three main application areas: air quality, meteorology (including weather prediction), and climate modeling. It presents a synthesis of scientific progress in the form of answers to nine key questions, and provides recommendations for future research directions and priorities in the development, application, and evaluation of online coupled models.