Burden of SARS-CoV-2 infection prior to vaccine eligibility among immunocompromised children aged 1-11 years at a pediatric tertiary referral hospital in Toronto, Canada.

SARS-CoV-2 seroprevalence reflects the efficacy of pandemic infection prevention and control measures. We performed anti-spike IgG serological testing on residual sera of children 1-11 years old at a tertiary care referral center between October and November 2021. Immunocompromised patients had the highest SARS-CoV-2 seroprevalence, at 40.5%, compared to 19.3% in non-immunocompromised patients. Targeted infection prevention and public health interventions are warranted for pediatric immunocompromised patients in future pandemics.

Rechargeable Batteries for Grid Scale Energy Storage.

Ever-increasing global energy consumption has driven the development of renewable energy technologies to reduce greenhouse gas emissions and air pollution. Battery energy storage systems (BESS) with high electrochemical performance are critical for enabling renewable yet intermittent sources of energy such as solar and wind. In recent years, numerous new battery technologies have been achieved and showed great potential for grid scale energy storage (GSES) applications. However, their practical applications have been greatly impeded due to the gap between the breakthroughs achieved in research laboratories and the industrial applications. In addition, various complex applications call for different battery performances. Matching of diverse batteries to various applications is required to promote practical energy storage research achievement. This review provides in-depth discussion and comprehensive consideration in the battery research field for GSES. The overall requirements of battery technologies for practical applications with key parameters are systematically analyzed by generating standards and measures for GSES. We also discuss recent progress and existing challenges for some representative battery technologies with great promise for GSES, including metal-ion batteries, lead-acid batteries, molten-salt batteries, alkaline batteries, redox-flow batteries, metal-air batteries, and hydrogen-gas batteries. Moreover, we emphasize the importance of bringing emerging battery technologies from academia to industry. Our perspectives on the future development of batteries for GSES applications are provided.

Rhodanine-benzamides as potential hits for α-amylase enzyme inhibitors and radical (DPPH and ABTS) scavengers.

A series of 3-substituted and 3,5-disubstituted rhodanine-based derivatives were synthesized from 3-aminorhodanine and examined for α-amylase inhibitory, DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activities in vitro. These derivatives displayed significant α-amylase inhibitory potential with IC50 values of 11.01-56.04 µM in comparison to standard acarbose (IC50 = 9.08 ± 0.07 µM). Especially, compounds 7 (IC50 = 11.01 ± 0.07 µM) and 8 (IC50 = 12.01 ± 0.07 µM) showed highest α-amylase inhibitory activities among the whole series. In addition to α-amylase inhibitory activity, all compounds also demonstrated significant scavenging activities against DPPH and ABTS radicals, with IC50 values ranging from 12.24 to 57.33 and 13.29-59.09 µM, respectively, as compared to the standard ascorbic acid (IC50 = 15.08 ± 0.03 µM for DPPH; IC50 = 16.09 ± 0.17 µM for ABTS). These findings reveal that the nature and position of the substituents on the phenyl ring(s) are crucial for variation in the activities. The structure-activity relationship (SAR) revealed that the compounds bearing an electron-withdrawing group (EWG) at para substitution possessed the highest activity. In kinetic studies, only the km value was changed, with no observed changes in Vmax, indicating a competitive inhibition. Molecular docking studies revealed important interactions between compounds and the α-amylase active pocket. Further advanced research needs to perform on the identified compounds in order to obtain potential antidiabetic agents.

An efficient RP-HPLC-based approach for simultaneous determination of sitagliptin and metformin HCl in pharmaceutical drug formulation.

This study introduces an innovative, and rapid HPLC method using reverse phase elution for the simultaneous analysis of Sitagliptin and Metformin HCl in pharmaceutical formulations. This combination was explored in bulk and solid dosage forms using Luna Phenomenex C8 column (4.6 x 250 mm, 5 µm) at ambient temperature in isocratic elution. It was found that the mobile phase comprising of 0.1% ortho-phosphoric acid, potassium dihydrogen phosphate buffer (pH 3.0) and acetonitrile in ratios 35:35:30, showed a symmetrical peak for Sitagliptin and Metformin HCl. The detection was carried out at 210nm, using a flow rate of 1.0mL/min. The method was linear over the concentration range for Sitagliptin 2.5-7.5 ppm and Metformin HCl 25-75 ppm. The assay recoveries of Sitagliptin and Metformin were found to be 100.36% and 100.20%, respectively. The LOD and LOQ for the Sitagliptin were found to be 0.201 ppm and 0.301 ppm and for Metformin HCl 0.101 ppm and 0.303 ppm, respectively. The proposed methods can be implemented for controlling quality in bulk and solid dosage forms. The analytical methods were validated as per the guideline of ICH Q2 (R2). The developed HPLC methods were effectively employed for the determination of combined dosage forms in pharmaceutical formulations.

Racial and Ethnic Differences in Length of Stay for US Children Hospitalized for Acute Osteomyelitis.

OBJECTIVE: To examine the associations between race and ethnicity and length of stay (LOS) for US children with acute osteomyelitis. STUDY DESIGN: Using the Kids' Inpatient Database, we conducted a cross-sectional study of children <21 years old hospitalized in 2016 or 2019 with acute osteomyelitis. Using survey-weighted negative binomial regression, we modeled LOS by race and ethnicity, adjusting for clinical and hospital characteristics and socioeconomic status. Secondary outcomes included prolonged LOS, defined as LOS of >7 days (equivalent to LOS in the highest quartile). RESULTS: We identified 2388 children discharged with acute osteomyelitis. The median LOS was 5 days (IQR, 3-7). Compared with White children, children of Black race (adjusted incidence rate ratio [aIRR] 1.15; 95% CI, 1.05-1.27), Hispanic ethnicity (aIRR 1.11; 95% CI, 1.02-1.21), and other race and ethnicity (aIRR 1.12; 95% CI, 1.01-1.23) had a significantly longer LOS. The odds of Black children experiencing prolonged LOS was 46% higher compared with White children (aOR, 1.46; 95% CI, 1.01-2.11). CONCLUSIONS: Children of Black race, Hispanic ethnicity, and other race and ethnicity with acute osteomyelitis experienced longer LOS than White children. Elucidating the mechanisms underlying these race- and ethnicity-based differences, including social drivers such as access to care, structural racism, and bias in provision of inpatient care, may improve management and outcomes for children with acute osteomyelitis.

Race and Ethnicity and the Utilization of Security Responses in a Hospital Setting.

BACKGROUND: Security emergency responses (SERs) are utilized by hospitals to ensure the safety of patients and staff but can cause unintended morbidity. The presence of racial and ethnic inequities in SER utilization has not been clearly elucidated. OBJECTIVE: To determine whether Black and Hispanic patients experience higher rates of SER and physical restraints in a non-psychiatric inpatient setting. DESIGN: Retrospective cohort study. PARTICIPANTS: All patients discharged from September 2018 through December 2019. EXPOSURE: Race and ethnicity, as reported by patients at time of registration. MAIN OUTCOMES: The primary outcome was whether a SER was called on a patient. The secondary outcome was the incidence of physical restraints among patients who experienced a SER. KEY RESULTS: Among 24,212 patients, 18,755 (77.5%) patients identified as white, 2,346 (9.7%) as Black, and 2,425 (10.0%) identified with another race. Among all patients, 1,827 (7.6%) identified as Hispanic and 21,554 (89.0%) as non-Hispanic. Sixty-six (2.8%) Black patients had a SER activated during their first admission, compared to 295 (1.6%) white patients. In a Firth logit multivariable model, Black patients had higher adjusted odds of a SER than white patients (adjusted odds ratio (aOR) 1.37 [95% confidence interval: 1.02, 1.81], p = 0.037). Hispanic patients did not have higher odds of having a SER called than non-Hispanic patients. In a Poisson multivariable model among patients who had a SER called, race and ethnicity were not found to be significant predictors of restraint. CONCLUSION: Black patients had higher odds of a SER compared to white patients. No significant differences were found between Hispanic and non-Hispanic patients. Future efforts should focus on assessing the generalizability of these findings, the underlying mechanisms driving these inequities, and effective interventions to address them.

Strengthening Nutrition Interventions during Antenatal Care Improved Maternal Dietary Diversity and Child Feeding Practices in Urban Bangladesh: Results of a Quasi-Experimental Evaluation Study.

BACKGROUND: Bangladesh is urbanizing rapidly, facing challenges of malnutrition, low coverage and poor quality of urban nutrition services. OBJECTIVES: We assessed the effect of integrating maternal, infant, and young child nutrition interventions, delivered at urban Maternal Neonatal and Child Health facilities, on maternal dietary diversity, iron and folic acid (IFA) and calcium consumption, and child feeding practices. METHODS: We used a quasi-experimental design with a nonrandom assignment of 20 health care facilities in Dhaka to intensive and standard service arms. We conducted facility-based observations and community-based surveys at baseline (2020) and endline (2022) (n = 2455 observations and surveys with 1678 pregnant women [PW] or recently delivered women [RDW] at endline). We derived difference-in-difference (DID) estimates, adjusted for characteristics that differed at baseline or endline, and accounted for clustering. RESULTS: Exposure to antenatal care (ANC) was similar in both arms: two-thirds of RDW received ANC during the first trimester and three-fourths received ≥4 ANC checkups. Compared to the standard arm, a higher proportion of PW in the intensive arm received counseling on dietary diversity (DID: 45 percentage points [pp]), and a higher proportion of RDW received IFA (25 pp) and calcium supplementation (19 pp), showed adequate weight gain (44 pp), and recorded appropriate child feeding (27 pp). Improvements were greater in the intensive than the standard arm for the number of food groups consumed (DID: 1.1 food groups) and minimum dietary diversity (23 pp); no effect was observed for IFA and calcium consumption during pregnancy. However, effects were observed for early initiation of (20 pp) and exclusive breastfeeding (45 pp), introduction of solid or semisolid foods (28 pp), and egg and/or flesh food consumption (33 pp) among children. Minimum dietary diversity and acceptable diet remained low in both arms. CONCLUSIONS: Intensifying nutrition in government-aligned health care services delivered by experienced nongovernmental organization-run facilities is a feasible model to address the urban health gap, nutrition services coverage, and improve practices. The trial was registered at clinicaltrials.gov as NCT03882268.

Spectrum Evaluation in CR-Based Smart Healthcare Systems Using Optimizable Tree Machine Learning Approach.

The rapid technological advancements in the current modern world bring the attention of researchers to fast and real-time healthcare and monitoring systems. Smart healthcare is one of the best choices for this purpose, in which different on-body and off-body sensors and devices monitor and share patient data with healthcare personnel and hospitals for quick and real-time decisions about patients' health. Cognitive radio (CR) can be very useful for effective and smart healthcare systems to send and receive patient's health data by exploiting the primary user's (PU) spectrum. In this paper, tree-based algorithms (TBAs) of machine learning (ML) are investigated to evaluate spectrum sensing in CR-based smart healthcare systems. The required data sets for TBAs are created based on the probability of detection (Pd) and probability of false alarm (Pf). These data sets are used to train and test the system by using fine tree, coarse tree, ensemble boosted tree, medium tree, ensemble bagged tree, ensemble RUSBoosted tree, and optimizable tree. Training and testing accuracies of all TBAs are calculated for both simulated and theoretical data sets. The comparison of training and testing accuracies of all classifiers is presented for the different numbers of received signal samples. Results depict that optimizable tree gives the best accuracy results to evaluate the spectrum sensing with minimum classification error (MCE).

Malicious Vehicle Detection Using Layer-Based Paradigm and the Internet of Things.

Deep learning algorithms have a wide range of applications, including cancer diagnosis, face and speech recognition, object recognition, etc. It is critical to protect these models since any changes to them can result in serious losses in a variety of ways. This article proposes the consortium blockchain-enabled conventional neural network (CBCNN), a four-layered paradigm for detecting malicious vehicles. Layer-1 is a convolutional neural network-enabled Internet-of-Things (IoT) model for the vehicle; Layer-2 is a spatial pyramid polling layer for the vehicle; Layer-3 is a fully connected layer for the vehicle; and Layer-4 is a consortium blockchain for the vehicle. The first three layers accurately identify the vehicles, while the final layer prevents any malicious attempts. The primary goal of the four-layered paradigm is to successfully identify malicious vehicles and mitigate the potential risks they pose using multi-label classification. Furthermore, the proposed CBCNN approach is employed to ensure tamper-proof protection against a parameter manipulation attack. The consortium blockchain employs a proof-of-luck mechanism, allowing vehicles to save energy while delivering accurate information about the vehicle's nature to the "vehicle management system." C++ coding is employed to implement the approach, and the ns-3.34 platform is used for simulation. The ns3-ai module is specifically utilized to detect anomalies in the Internet of Vehicles (IoVs). Finally, a comparative analysis is conducted between the proposed CBCNN approach and state-of-the-art methods. The results confirm that the proposed CBCNN approach outperforms competing methods in terms of malicious label detection, average accuracy, loss ratio, and cost reduction.

Effects of Saccharomyces cerevisiae live cells and culture on growth and productive performance in lactating Nili-Ravi buffaloes.

An experimental work was conducted to evaluate the effects of Saccharomyces cerevisiae live cells and its culture on dry matter intake (DMI), milk yield, milk composition, body condition score, selected blood metabolites, feed conversion efficiency (FCE), nutrient digestibility, body weight gain, and economics of milk production in lactating multiparous Nili-Ravi buffaloes. In total, 20 buffaloes of age 5 years ± 6 months and weighing 550 ± 20 kg were selected and assigned to four dietary treatments (n=5 buffalo/treatment) under completely randomized design. The dietary treatments include treatment 1 (T1) control, treatment 2 (T2) 5g/head live yeast, treatment 3 (T3) 5g/head yeast culture, and treatment 4 (T4) 10 g/head yeast culture per day for 60 days excluding 14 days as an adjustment period. The results indicated that T4 showed significant (p<0.05) improvement in DMI, milk yield and components, blood glucose level, digestibility of nutrients, and body weight gain while significant decrease in blood urea nitrogen as compared to other treatment groups. Body condition score was not affected among treatments. In conclusion, yeast culture supplementation significantly improved (p <0.05) milk yield, milk composition, DMI, body weight gain, blood glucose level, and digestibility while significantly decreased blood urea level as compare to control. Economic return was also improved. BCS was not improved. Comparatively, yeast culture showed significant improvement in growth and productive performance as compare to live yeast. Meanwhile, 10-g yeast culture showed better results as compare to 5-g yeast culture.

Genetic networks underlying salinity tolerance in wheat uncovered with genome-wide analyses and selective sweeps.

KEY MESSAGE: A genetic framework underpinning salinity tolerance at reproductive stage was revealed by genome-wide SNP markers and major adaptability genes in synthetic-derived wheats, and trait-associated loci were used to predict phenotypes. Using wild relatives of crops to identify genes related to improved productivity and resilience to climate extremes is a prioritized area of crop genetic improvement. High salinity is a widespread crop production constraint, and development of salt-tolerant cultivars is a sustainable solution. We evaluated a panel of 294 wheat accessions comprising synthetic-derived wheat lines (SYN-DERs) and modern bread wheat advanced lines under control and high salinity conditions at two locations. The GWAS analysis revealed a quantitative genetic framework of more than 200 loci with minor effect underlying salinity tolerance at reproductive stage. The significant trait-associated SNPs were used to predict phenotypes using a GBLUP model, and the prediction accuracy (r2) ranged between 0.57 and 0.74. The r2 values for flag leaf weight, days to flowering, biomass, and number of spikes per plant were all above 0.70, validating the phenotypic effects of the loci discovered in this study. Furthermore, the germplasm sets were compared to identify selection sweeps associated with salt tolerance loci in SYN-DERs. Six loci associated with salinity tolerance were found to be differentially selected in the SYN-DERs (12.4 Mb on chromosome (chr)1B, 7.1 Mb on chr2A, 11.2 Mb on chr2D, 200 Mb on chr3D, 600 Mb on chr6B, and 700.9 Mb on chr7B). A total of 228 reported markers and genes, including 17 well-characterized genes, were uncovered using GWAS and EigenGWAS. A linkage disequilibrium (LD) block on chr5A, including the Vrn-A1 gene at 575 Mb and its homeologs on chr5D, were strongly associated with multiple yield-related traits and flowering time under salinity stress conditions. The diversity panel was screened with more than 68 kompetitive allele-specific PCR (KASP) markers of functional genes in wheat, and the pleiotropic effects of superior alleles of Rht-1, TaGASR-A1, and TaCwi-A1 were revealed under salinity stress. To effectively utilize the extensive genetic information obtained from the GWAS analysis, a genetic interaction network was constructed to reveal correlations among the investigated traits. The genetic network data combined with GWAS, selective sweeps, and the functional gene survey provided a quantitative genetic framework for identifying differentially retained loci associated with salinity tolerance in wheat.

Transporters and transcription factors gene families involved in improving nitrogen use efficiency (NUE) and assimilation in rice (Oryza sativa L.).

Nitrogen (N) as a macronutrient is an important determinant of plant growth. The excessive usage of chemical fertilizers is increasing environmental pollution; hence, the improvement of crop's nitrogen use efficiency (NUE) is imperative for sustainable agriculture. N uptake, transportation, assimilation, and remobilization are four important determinants of plant NUE. Oryza sativa L. (rice) is a staple food for approximately half of the human population, around the globe and improvement in rice yield is pivotal for rice breeders. The N transporters, enzymes indulged in N assimilation, and several transcription factors affect the rice NUE and subsequent yield. Although, a couple of improvements have been made regarding rice NUE, the knowledge about regulatory mechanisms operating NUE is scarce. The current review provides a precise knowledge of how rice plants detect soil N and how this detection is translated into the language of responses that regulate the growth. Additionally, the transcription factors that control N-associated genes in rice are discussed in detail. This mechanistic insight will help the researchers to improve rice yield with minimized use of chemical fertilizers.

Entailing the Next-Generation Sequencing and Metabolome for Sustainable Agriculture by Improving Plant Tolerance.

Crop production is a serious challenge to provide food for the 10 billion individuals forecasted to live across the globe in 2050. The scientists' emphasize establishing an equilibrium among diversity and quality of crops by enhancing yield to fulfill the increasing demand for food supply sustainably. The exploitation of genetic resources using genomics and metabolomics strategies can help generate resilient plants against stressors in the future. The innovation of the next-generation sequencing (NGS) strategies laid the foundation to unveil various plants' genetic potential and help us to understand the domestication process to unmask the genetic potential among wild-type plants to utilize for crop improvement. Nowadays, NGS is generating massive genomic resources using wild-type and domesticated plants grown under normal and harsh environments to explore the stress regulatory factors and determine the key metabolites. Improved food nutritional value is also the key to eradicating malnutrition problems around the globe, which could be attained by employing the knowledge gained through NGS and metabolomics to achieve suitability in crop yield. Advanced technologies can further enhance our understanding in defining the strategy to obtain a specific phenotype of a crop. Integration among bioinformatic tools and molecular techniques, such as marker-assisted, QTLs mapping, creation of reference genome, de novo genome assembly, pan- and/or super-pan-genomes, etc., will boost breeding programs. The current article provides sequential progress in NGS technologies, a broad application of NGS, enhancement of genetic manipulation resources, and understanding the crop response to stress by producing plant metabolites. The NGS and metabolomics utilization in generating stress-tolerant plants/crops without deteriorating a natural ecosystem is considered a sustainable way to improve agriculture production. This highlighted knowledge also provides useful research that explores the suitable resources for agriculture sustainability.

Development of extended-release metformin core tablet and synergistic coating of sitagliptin for the treatment of type-II diabetes mellitus - A comparative drug release evaluation with reference product.

Diabetes is getting a common disease and is spreading rapidly, affecting 6.6 percent world's population. Metformin HCl is an effective pharmacological treatment for type 2 diabetic patients because of its lowering blood glucose level ability, better weight-neutral effects and reduced risk of hypoglycemia. Nevertheless, gastrointestinal (GI) sensitivities are a concern in many patients using its immediate-release formulations. This study aimed to develop extended-release (ER) formulations to control the release into the body and minimize the dosage-related side effects of metformin and to develop an effective method of coating Sitagliptin immediate-release (IR) formulation over the core tablet. This study evaluated different formulations of Metformin HCl ER tablet using hydrophilic polymers. Different concentrations of Sitagliptin were used to develop immediate release coating. The dissolution profile of the designed formulation was compared with the reference 50/500mg tablet. In vitro dissolution of Metformin HCl (MT5), containing Methocel K4M and Methocel K100 polymer, showed 37.62% release at 1hr, 53.46% at 2hr, 84.75% at 6hr and 94.81% at 10hr. The Sitagliptin (ST8) with 10% excess released 103.64% in 30min. Similarity factor values suggested that developed Metformin ER and Sitagliptin IR formulation were like the reference product.

Achievements and Challenges of Genomics-Assisted Breeding in Forest Trees: From Marker-Assisted Selection to Genome Editing.

Forest tree breeding efforts have focused mainly on improving traits of economic importance, selecting trees suited to new environments or generating trees that are more resilient to biotic and abiotic stressors. This review describes various methods of forest tree selection assisted by genomics and the main technological challenges and achievements in research at the genomic level. Due to the long rotation time of a forest plantation and the resulting long generation times necessary to complete a breeding cycle, the use of advanced techniques with traditional breeding have been necessary, allowing the use of more precise methods for determining the genetic architecture of traits of interest, such as genome-wide association studies (GWASs) and genomic selection (GS). In this sense, main factors that determine the accuracy of genomic prediction models are also addressed. In turn, the introduction of genome editing opens the door to new possibilities in forest trees and especially clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9). It is a highly efficient and effective genome editing technique that has been used to effectively implement targetable changes at specific places in the genome of a forest tree. In this sense, forest trees still lack a transformation method and an inefficient number of genotypes for CRISPR/Cas9. This challenge could be addressed with the use of the newly developing technique GRF-GIF with speed breeding.

Diversity and Taxonomic Distribution of Endophytic Bacterial Community in the Rice Plant and Its Prospective.

Endophytic bacterial communities are beneficial communities for host plants that exist inside the surfaces of plant tissues, and their application improves plant growth. They benefit directly from the host plant by enhancing the nutrient amount of the plant's intake and influencing the phytohormones, which are responsible for growth promotion and stress. Endophytic bacteria play an important role in plant-growth promotion (PGP) by regulating the indirect mechanism targeting pest and pathogens through hydrolytic enzymes, antibiotics, biocontrol potential, and nutrient restriction for pathogens. To attain these benefits, firstly bacterial communities must be colonized by plant tissues. The nature of colonization can be achieved by using a set of traits, including attachment behavior and motility speed, degradation of plant polymers, and plant defense evasion. The diversity of bacterial endophytes colonization depends on various factors, such as plants' relationship with environmental factors. Generally, each endophytic bacteria has a wide host range, and they are used as bio-inoculants in the form of synthetic applications for sustainable agriculture systems and to protect the environment from chemical hazards. This review discusses and explores the taxonomic distribution of endophytic bacteria associated with different genotypes of rice plants and their origin, movement, and mechanism of PGP. In addition, this review accentuates compressive meta data of endophytic bacteria communities associated with different genotypes of rice plants, retrieves their plant-growth-promoting properties and their antagonism against plant pathogens, and discusses the indication of endophytic bacterial flora in rice plant tissues using various methods. The future direction deepens the study of novel endophytic bacterial communities and their identification from rice plants through innovative techniques and their application for sustainable agriculture systems.

Provision and utilisation of health and nutrition services during COVID-19 pandemic in urban Bangladesh.

The COVID-19 pandemic is expected to have profound effects on healthcare systems, but little evidence exists on service provision, utilisation, or adaptations. This study aimed to (1) examine the changes to health and nutrition service delivery and utilisation in urban Bangladesh during and after enforcement of COVID-19 restrictions and (2) identify adaptations and potential solutions to strengthen delivery and uptake. We conducted longitudinal surveys with health care providers (n = 45), pregnant women (n = 40), and mothers of children <2 years (n = 387) in February 2020 (in-person) and September 2020 (by phone). We used Wilcoxon matched-pairs signed-rank tests to compare the changes before and during the pandemic. Services delivery for women and children which require proximity were severely affected; weight and height measurements fell by 20-29 percentage points (pp) for pregnant women and 37-57 pp for children, and child immunisations fell by 38 pp. Declines in service utilisation were large, including drops in facility visitations (35 pp among pregnant women and 67 pp among mothers), health and nutrition counselling (up to 73 pp), child weight measurements (50 pp), and immunisations (61 pp). The primary method of adaptation was provision of services over phone (37% for antenatal care services, 44%-49% for counselling). Despite adaptations to service provision, continued availability of routine maternal and child health services did not translate into service utilisation. Further investments are needed to provide timely and accurate information on COVID-19 to the general public, improve COVID-19 training and provide incentives for health care providers and ensure availability of personal protective equipment for providers and beneficiaries.

Appraisal of wheat genomics for gene discovery and breeding applications: a special emphasis on advances in Asia.

KEY MESSAGE: We discussed the most recent efforts in wheat functional genomics to discover new genes and their deployment in breeding with special emphasis on advances in Asian countries. Wheat research community is making significant progress to bridge genotype-to-phenotype gap and then applying this knowledge in genetic improvement. The advances in genomics and phenomics have intrigued wheat researchers in Asia to make best use of this knowledge in gene and trait discovery. These advancements include, but not limited to, map-based gene cloning, translational genomics, gene mapping, association genetics, gene editing and genomic selection. We reviewed more than 57 homeologous genes discovered underpinning important traits and multiple strategies used for their discovery. Further, the complementary advancements in wheat phenomics and analytical approaches to understand the genetics of wheat adaptability, resilience to climate extremes and resistance to pest and diseases were discussed. The challenge to build a gold standard reference genome sequence of bread wheat is now achieved and several de novo reference sequences from the cultivars representing different gene pools will be available soon. New pan-genome sequencing resources of wheat will strengthen the foundation required for accelerated gene discovery and provide more opportunities to practice the knowledge-based breeding.

A continued method performance monitoring approach for the determination of pediatric renin samples - application within a European clinical trial.

Background Plasma renin levels were determined in the academia-driven, EU-funded "Labeling of Enalapril from Neonates up to Adolescents" (LENA) project to evaluate its role in pediatric heart failure. Quality-controlled bioanalysis is crucial to ensure reliable data generation. However, a comprehensive bioanalytical quality control (QC) concept to monitor the method performance within an academic environment was lacking. Methods Thus, a QC concept was designed encompassing regulatory guidance, international recommendations and current scientific discussions. The concept included (1) a system-suitability test, (2) verification of single bioanalytical runs by calibration curve performance and evaluation of QCs, (3) assessment of the inter-run accuracy according to Clinical Laboratory Standards Institute (CLSI) guideline, (4) monitoring of reproducibility by pediatric incurred samples, (5) blank-sample analysis and (6) participation in interlaboratory testing. Results The concept was successfully applied to the academic project. About 11% of single runs were identified as invalid and triggered a re-analysis of unknown samples being included in those runs. The usefulness of the customized inter-run monitoring was demonstrated and proved the good accuracy from the first to the last run. All 147 reanalyzed incurred sample pairs complied with regulatory requirements. Conclusions The regulatory complied QC concept was customized for the demands of academia-driven pediatric trials and contributed to the reliable quantification of 965 pediatric renin samples.

Infections due to multidrug-resistant organisms following heart transplantation: Epidemiology, microbiology, and outcomes.

BACKGROUND: Infections secondary to multidrug-resistant organisms (MDRO) have emerged as a growing problem in solid organ transplantation (SOT). Most of the published data on MDRO infections in SOT pertains to abdominal organ transplantation and data specific to heart transplantation (HT) are limited. METHODS: This is a retrospective review of HT recipients at our institution from 2011 to 2016; with the aim to investigate the epidemiology, microbiologic spectrum, and outcomes in patients with post-HT MDRO infections, classified as multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) using standardized definitions. RESULTS: Of the 149 HT recipients, 82 episodes of bacterial infection were seen in 46 patients (31%) in the year following HT. Thirty (37%) were due to MDR pathogens and 13 (16%) were XDR. The most common gram-negative MDR pathogens were extended-spectrum beta-lactamase (ESBL) Escherichia coli and Klebsiella pneumoniae; while XDR pathogens were most commonly Pseudomonas aeruginosa followed by carbapenem-resistant Klebsiella pneumoniae. Majority of infection episodes were bloodstream (54, 66%) followed by pulmonary infection (20, 24%). Within a year after transplant, HT recipients with any bacterial infection had significantly higher mortality versus those without infection; and XDR infections were associated with a 26-fold greater hazard of death on average compared to those without infection (adjusted HR, 26.1; 95% CI, 6.4-107.0; P < .001). There were no PDR infections. CONCLUSION: Bacterial infections were a significant predictor of 1-year post-HT mortality, which was highest among those with XDR infections. This study highlights the burden of MDRO infections in HT recipients and identifies an area of future research.