Understanding the Epidemiology of Heart Failure to Improve Management Practices: An Asia-Pacific Perspective

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Electrical manipulation of spin states in a single electrostatically gated transition-metal complex

We demonstrate an electrically controlled high-spin (S=5/2) to low-spin (S=1/2) transition in a three-terminal device incorporating a single Mn2+ ion coordinated by two terpyridine ligands. By adjusting the gate-voltage we reduce the terpyridine moiety and thereby strengthen the ligand-field on the Mn-atom. Adding a single electron thus stabilizes the low-spin configuration and the corresponding sequential tunnelling current is suppressed by spin-blockade. From low-temperature inelastic cotunneling spectroscopy, we infer the magnetic excitation spectrum of the molecule and uncover also a strongly gate-dependent singlet-triplet splitting on the low-spin side. The measured bias-spectroscopy is shown to be consistent with an exact diagonalization of the Mn-complex, and an interpretation of the data is given in terms of a simplified effective model.Comment: Will appear soon in Nanoletter

Insights into the ceria-catalyzed ketonization reaction for biofuels applications

The ketonization of small organic acids is a valuable reaction for biorenewable applications. Ceria has long been used as a catalyst for this reaction; however, under both liquid and vapor phase conditions, it was found that given the right temperature regime of about 150-300 °C, cerium oxide, which was previously believed to be a stable catalyst for ketonization, can undergo bulk transformations. This result, along with other literature reports, suggest that the long held belief of two separate reaction pathways for either bulk or surface ketonization reactions are not required to explain the interaction of cerium oxide with organic acids. X-ray photon spectroscopy, scanning electron microscopy, and temperature programmed decomposition results supported the formation of metal acetates and explained the occurrence of cerium reduction as well as the formation of cerium oxide/acetate whiskers. After thermogravimetry/mass spectrometry and FT-IR experiments, a single reaction sequence is proposed that can be applied to either surface or bulk reactions with ceria

Thrips-transmitted tobacco streak virus: A growing biotic challenge in sunflower (Helianthus annuus) cultivation and adaptive management strategies in India

Sunflower farming is under serious threat due to necrosis disease, predominantly caused by Tobacco Streak Virus (TSV) and transmitted by thrips. Among the vectors, Thrips palmi have been identified as a major carrier of this devastating disease. A critical component in the epidemiology of sunflower necrosis is the bioecology of thrips. Their complex behaviour such as specialized feeding, rapid reproduction and efficient dispersal-enable swift population build-up and facilitate virus transmission. These dynamics, coupled with environmental factors like temperature and humidity, contribute to seasonal disease outbreaks. Effective management of sunflower necrosis disease requires a comprehensive and integrated approach. Key strategies include adjusting the sowing time to avoid peak thrips activity, cultivating TSV-resistant sunflower varieties and minimizing weed hosts that serve as virus reservoirs. Biological control through the application of plant growth-promoting microbial consortia offers an eco-friendly and sustainable method to suppress vector populations. Additionally, the judicious use of insecticides in combination with biocontrol agents can enhance disease suppression while reducing chemical dependency. Although sunflower necrosis has been extensively studied in regions like India, its global distribution, impact and economic consequences remain underexplored. There is an urgent need for expanded region-specific research to evaluate its prevalence and severity across diverse agroclimatic zones. Multidisciplinary efforts are essential to develop resilient cropping systems, advance vector management strategies and safeguard sunflower production under changing environmental conditions

Effect of treatment of clinical seizures vs electrographic seizures in full-term and near-term neonates : a randomized clinical trial

Importance: Seizures in the neonatal period are associated with increased mortality and morbidity. Bedside amplitude-integrated electroencephalography (aEEG) has facilitated the detection of electrographic seizures; however, whether these seizures should be treated remains uncertain. Objective: To determine if the active management of electrographic and clinical seizures in encephalopathic term or near-term neonates improves survival free of severe disability at 2 years of age compared with only treating clinically detected seizures. Design, Setting, and Participants: This randomized clinical trial was conducted in tertiary newborn intensive care units recruited from 2012 to 2016 and followed up until 2 years of age. Participants included neonates with encephalopathy at 35 weeks’ gestation or more and younger than 48 hours old. Data analysis was completed in April 2021. Interventions: Randomization was to an electrographic seizure group (ESG) in which seizures detected on aEEG were treated in addition to clinical seizures or a clinical seizure group (CSG) in which only seizures detected clinically were treated. Main Outcomes and Measures: Primary outcome was death or severe disability at 2 years, defined as scores in any developmental domain more than 2 SD below the Australian mean assessed with Bayley Scales of Neonate and Toddler Development, 3rd ed (BSID-III), or the presence of cerebral palsy, blindness, or deafness. Secondary outcomes included magnetic resonance imaging brain injury score at 5 to 14 days, time to full suck feeds, and individual domain scores on BSID-III at 2 years. Results: Of 212 randomized neonates, the mean (SD) gestational age was 39.2 (1.7) weeks and 122 (58%) were male; 152 (72%) had moderate to severe hypoxic-ischemic encephalopathy (HIE) and 147 (84%) had electrographic seizures. A total of 86 neonates were included in the ESG group and 86 were included in the CSG group. Ten of 86 (9%) neonates in the ESG and 4 of 86 (4%) in the CSG died before the 2-year assessment. The odds of the primary outcome were not significantly different in the ESG group compared with the CSG group (ESG, 38 of 86 [44%] vs CSG, 27 of 86 [31%]; odds ratio [OR], 1.83; 95% CI, 0.96 to 3.49; P = .14). There was also no significant difference in those with HIE (OR, 1.77; 95% CI, 0.84 to 3.73; P = .26). There was evidence that cognitive outcomes were worse in the ESG (mean [SD] scores, ESG: 97.4 [17.7] vs CSG: 103.8 [17.3]; mean difference, −6.5 [95% CI, −1.2 to −11.8]; P = .01). There was little evidence of a difference in secondary outcomes, including time to suck feeds, seizure burden, or brain injury score. Conclusions and Relevance: Treating electrographic and clinical seizures with currently used anticonvulsants did not significantly reduce the rate of death or disability at 2 years in a heterogeneous group of neonates with seizures

Child, Maternal and Demographic Factors Influencing Caregiver-Reported Autistic Trait Symptomatology in Toddlers.

Current research on children's autistic traits in the general population relies predominantly on caregiver-report, yet the extent to which individual, caregiver or demographic characteristics are associated with informants' ratings has not been sufficiently explored. In this study, caregivers of 396 Singaporean two-year-olds from a birth cohort study completed the Quantitative Checklist for Autism in Toddlers. Children's gender, cognitive functioning and birth order, maternal age, and ethnic group membership were not significant predictors of caregiver-reported autistic traits. Poorer child language development and higher maternal depressive symptoms significantly predicted more social-communicative autistic traits, while lower maternal education predicted more behavioural autistic traits. Children's language and informants' educational level and depressive symptomatology may need to be considered in caregiver-reports of autistic traits.This research is supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Programme and administered by the Singapore Ministry of Health’s National Medical Research Council (NMRC), Singapore—NMRC/TCR/004-NUS/2008 and NMRC/TCR/012-NUHS/2014. Additional funding was provided by the Ministry of Education AcRF Tier 1 funding grant R581000130112 awarded to the corresponding/senior author and Singapore Institute for Clinical Sciences—A*STAR

Two-Year Outcomes After Minimally Invasive Surfactant Therapy in Preterm Infants: Follow-Up of the OPTIMIST-A Randomized Clinical Trial

Importance: The long-term effects of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome remain to be definitively clarified. / Objective: To examine the effect of MIST on death or neurodevelopmental disability (NDD) at 2 years' corrected age. / Design, Setting, and Participants: Follow-up study of a randomized clinical trial with blinding of clinicians and outcome assessors conducted in 33 tertiary-level neonatal intensive care units in 11 countries. The trial included 486 infants with a gestational age of 25 to 28 weeks supported with continuous positive airway pressure (CPAP). Collection of follow-up data at 2 years' corrected age was completed on December 9, 2022. / Interventions: Infants assigned to MIST (n = 242) received exogenous surfactant (200 mg/kg poractant alfa) via a thin catheter; those assigned to the control group (n = 244) received sham treatment. / Main Outcomes and Measures: The key secondary outcome of death or moderate to severe NDD was assessed at 2 years' corrected age. Other secondary outcomes included components of this composite outcome, as well as hospitalizations for respiratory illness and parent-reported wheezing or breathing difficulty in the first 2 years. / Results: Among the 486 infants randomized, 453 had follow-up data available (median gestation, 27.3 weeks; 228 females [50.3%]); data on the key secondary outcome were available in 434 infants. Death or NDD occurred in 78 infants (36.3%) in the MIST group and 79 (36.1%) in the control group (risk difference, 0% [95% CI, -7.6% to 7.7%]; relative risk [RR], 1.0 [95% CI, 0.81-1.24]); components of this outcome did not differ significantly between groups. Secondary respiratory outcomes favored the MIST group. Hospitalization with respiratory illness occurred in 49 infants (25.1%) in the MIST group vs 78 (38.2%) in the control group (RR, 0.66 [95% CI, 0.54-0.81]) and parent-reported wheezing or breathing difficulty in 73 (40.6%) vs 104 (53.6%), respectively (RR, 0.76 [95% CI, 0.63-0.90]). / Conclusions and Relevance: In this follow-up study of a randomized clinical trial of preterm infants with respiratory distress syndrome supported with CPAP, MIST compared with sham treatment did not reduce the incidence of death or NDD by 2 years of age. However, infants who received MIST had lower rates of adverse respiratory outcomes during their first 2 years of life. / Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943

Homologous recombination DNA repair defects in PALB2-associated breast cancers.

Mono-allelic germline pathogenic variants in the Partner And Localizer of BRCA2 (PALB2) gene predispose to a high-risk of breast cancer development, consistent with the role of PALB2 in homologous recombination (HR) DNA repair. Here, we sought to define the repertoire of somatic genetic alterations in PALB2-associated breast cancers (BCs), and whether PALB2-associated BCs display bi-allelic inactivation of PALB2 and/or genomic features of HR-deficiency (HRD). Twenty-four breast cancer patients with pathogenic PALB2 germline mutations were analyzed by whole-exome sequencing (WES, n = 16) or targeted capture massively parallel sequencing (410 cancer genes, n = 8). Somatic genetic alterations, loss of heterozygosity (LOH) of the PALB2 wild-type allele, large-scale state transitions (LSTs) and mutational signatures were defined. PALB2-associated BCs were found to be heterogeneous at the genetic level, with PIK3CA (29%), PALB2 (21%), TP53 (21%), and NOTCH3 (17%) being the genes most frequently affected by somatic mutations. Bi-allelic PALB2 inactivation was found in 16 of the 24 cases (67%), either through LOH (n = 11) or second somatic mutations (n = 5) of the wild-type allele. High LST scores were found in all 12 PALB2-associated BCs with bi-allelic PALB2 inactivation sequenced by WES, of which eight displayed the HRD-related mutational signature 3. In addition, bi-allelic inactivation of PALB2 was significantly associated with high LST scores. Our findings suggest that the identification of bi-allelic PALB2 inactivation in PALB2-associated BCs is required for the personalization of HR-directed therapies, such as platinum salts and/or PARP inhibitors, as the vast majority of PALB2-associated BCs without PALB2 bi-allelic inactivation lack genomic features of HRD.ER

The N3RO trial: a randomised controlled trial of docosahexaenoic acid to reduce bronchopulmonary dysplasia in preterm infants <29 weeks' gestation

Background: Bronchopulmonary dysplasia (BPD) is a major cause of mortality and long-term respiratory and neurological morbidity in very preterm infants. While survival rates of very preterm infants have increased over the past two decades there has been no decrease in the rate of BPD in surviving infants. Evidence from animal and human studies has suggested potential benefits of docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid, in the prevention of chronic lung disease. This randomised controlled trial aims to determine the effectiveness of supplementary DHA in reducing the rate of BPD in infants less than 29 weeks’ gestation. Methods/design: This is a multicentre, parallel group, randomised, blinded and controlled trial. Infants born less than 29 weeks’ gestation, within 3 days of first enteral feed and with parent informed consent are eligible to participate. Infants will be randomised to receive an enteral emulsion containing DHA or a control emulsion without DHA. The DHA emulsion will provide 60 mg/kg/day of DHA. The study emulsions will continue to 36 weeks’ postmenstrual age (PMA). The primary outcome is BPD as assessed by the requirement for supplemental oxygen and/or assisted ventilation at 36 weeks’ PMA. Secondary outcomes include the composite of death or BPD; duration of respiratory support and hospitalisation, major neonatal morbidities. The target sample size is 1244 infants (622 per group), which will provide 90 % power to detect a clinically meaningful absolute reduction of 10 % in the incidence of BPD between the DHA and control emulsion (two tailed α =0.05). Discussion: DHA supplementation has the potential to reduce respiratory morbidity in very preterm infants. This multicentre trial will provide evidence on whether an enteral DHA supplement reduces BPD in very preterm infants. Trial registration: Australia and New Zealand Clinical Trial Registry: ACTRN12612000503820. Registered 09 May 2012. Keywords: Infant Preterm Bronchopulmonary dysplasia Docosahexaenoic acid n-3 long chain polyunsaturated fatty acidsCarmel T. Collins, Robert A. Gibson, Maria Makrides, Andrew J. McPhee, Thomas R. Sullivan, Peter G. Davis, Marta Thio, Karen Simmer, Victor S. Rajadurai and the N3RO Investigative Team (The University of Adelaide members of the N3RO Investigative Team: Philip Ryan and Michael Stark

Comparing very low birth weight versus very low gestation cohort methods for outcome analysis of high risk preterm infants

© 2017 The Author(s). Background: Compared to very low gestational age (<32 weeks, VLGA) cohorts, very low birth weight (<1500 g; VLBW) cohorts are more prone to selection bias toward small-for-gestational age (SGA) infants, which may impact upon the validity of data for benchmarking purposes. Method: Data from all VLGA or VLBW infants admitted in the 3 Networks between 2008 and 2011 were used. Two-thirds of each network cohort was randomly selected to develop prediction models for mortality and composite adverse outcome (CAO: mortality or cerebral injuries, chronic lung disease, severe retinopathy or necrotizing enterocolitis) and the remaining for internal validation. Areas under the ROC curves (AUC) of the models were compared. Results: VLBW cohort (24,335 infants) had twice more SGA infants (20.4% vs. 9.3%) than the VLGA cohort (29,180 infants) and had a higher rate of CAO (36.5% vs. 32.6%). The two models had equal prediction power for mortality and CAO (AUC 0.83), and similarly for all other cross-cohort validations (AUC 0.81-0.85). Neither model performed well for the extremes of birth weight for gestation (<1500 g and ≥32 weeks, AUC 0.50-0.65; ≥1500 g and <32 weeks, AUC 0.60-0.62). Conclusion: There was no difference in prediction power for adverse outcome between cohorting VLGA or VLBW despite substantial bias in SGA population. Either cohorting practises are suitable for international benchmarking