Dominant contribution of atmospheric nonlinearities to ENSO asymmetry and extreme El Niño events.

Extreme El Niño events have outsized impacts and strongly contribute to the El Niño Southern Oscillation (ENSO) warm/cold phase asymmetries. There is currently no consensus on the respective importance of oceanic and atmospheric nonlinearities for those asymmetries. Here, we use atmospheric and oceanic general circulation models that reproduce ENSO asymmetries well to quantify the atmospheric nonlinearities contribution. The linear and nonlinear components of the wind stress response to Sea Surface Temperature (SST) anomalies are isolated using ensemble atmospheric experiments, and used to force oceanic experiments. The wind stress-SST nonlinearity is dominated by the deep atmospheric convective response to SST. This wind-stress nonlinearity contributes to ~ 40% of the peak amplitude of extreme El Niño events and ~ 55% of the prolonged eastern Pacific warming they generate until the following summer. This large contribution arises because nonlinearities consistently drive equatorial westerly anomalies, while the larger linear component is made less efficient by easterly anomalies in the western Pacific during fall and winter. Overall, wind-stress nonlinearities fully account for the eastern Pacific positive ENSO skewness. Our findings underscore the pivotal role of atmospheric nonlinearities in shaping extreme El Niño events and, more generally, ENSO asymmetry.

Indian Academy of Pediatrics (IAP) Advisory Committee on Vaccines and Immunization Practices (ACVIP): Recommended Immunization Schedule (2023) and Update on Immunization for Children Aged 0 Through 18 Years.

JUSTIFICATION: In view of new developments in vaccinology and the availability of new vaccines, there is a need to revise/review the existing immunization recommendations. PROCESS: The Advisory Committee on Vaccines and Immunization Practices (ACVIP) of Indian Academy of Pediatrics (IAP) had a physical meeting on March 25, 2023, at Vaccicon, Kolkata, followed by online meetings to discuss the updates and new recommendations. Opinion of each member was sought on the various recommendations and updates, following which an evidence-based consensus was reached. The contents were finalized on September 8, 2023, during the National Conference of Pediatric - Infectious Diseases (NCPID) at Aurangabad. An online meeting of all members was held on November 15, 2023 and the recommendations were finalized. Objectives: To review and revise the IAP immunization recommendations of 2020-21 and issue recommendations on existing and new vaccines. RECOMMENDATIONS: The major changes include recommendation of HPV vaccine for boys; a 2-dose schedule of 9vHPV for boys and girls aged 9-14 y; a dose of Td vaccine at 16-18 y; guidance for injectable polio vaccine (IPV) for those patients who are changing from National Immunization Program to IAP schedule.

Comprehensive Morpho-Functional and Dental Rehabilitation of a Complete Unilateral Cleft Lip and Palate Patient.

Congenital clefts cause compromised function and esthetics, inadvertently affecting a patient's social and mental health. These defects can be successfully managed by a multidisciplinary team that can provide holistic care from birth till adulthood and beyond. A 17-year-old girl with left side congenital cleft, who had undergone cleft surgeries at our center, reported with a chief complaint of a missing front tooth in the upper region. Clinical and radiographic investigations showed a need for tertiary grafting, which was done using an autologous iliac graft. After six months, a dental implant was placed and immediately loaded after implant stability quotient assessment. Treatment of cleft patients is arduous and technique sensitive and should be done following pre-defined protocols. Each case should be handled by a multidisciplinary team giving attention to each aspect of the treatment requirement. It is an added advantage if the treatment is holistically catered at a single center as it provides patient comfort and avoids patient dependence on past records.

Safety and target engagement of an oral small-molecule sequestrant in adolescents with autism spectrum disorder: an open-label phase 1b/2a trial.

Autism spectrum disorder (ASD) is defined by hallmark behaviors involving reduced communication and social interaction as well as repetitive activities and restricted interests. ASD represents a broad spectrum, from minimally affected individuals to those requiring intense support, with additional manifestations often including anxiety, irritability/aggression and altered sensory processing. Gastrointestinal (GI) issues are also common in ASD, and studies have identified changes in the gut microbiome of individuals with ASD compared to control populations, complementing recent findings of differences in gut-derived metabolites in feces and circulation. However, a role for the GI tract or microbiome in ASD remains controversial. Here we report that an oral GI-restricted adsorbent (AB-2004) that has affinity for small aromatic or phenolic molecules relieves anxiety-like behaviors that are driven by a gut microbial metabolite in mice. Accordingly, a pilot human study was designed and completed to evaluate the safety of AB-2004 in an open-label, single-cohort, multiple-ascending-dose clinical trial that enrolled 30 adolescents with ASD and GI symptoms in New Zealand and Australia. AB-2004 was shown to have good safety and tolerability across all dose levels, and no drug-related serious adverse events were identified. Significant reductions in specific urinary and plasma levels of gut bacterial metabolites were observed between baseline and end of AB-2004 treatment, demonstrating likely target engagement. Furthermore, we observed improvements in multiple exploratory behavioral endpoints, most significantly in post hoc analysis of anxiety and irritability, as well as GI health, after 8 weeks of treatment. These results from an open-label study (trial registration no. ACTRN12618001956291) suggest that targeting gut-derived metabolites with an oral adsorbent is a safe and well-tolerated approach to improving symptoms associated with ASD, thereby emboldening larger placebo-controlled trials.

Safety, quality and efficiency of intra-operative imaging for treatment decisions in patients with suspected choledocholithiasis without pre-operative magnetic resonance cholangiopancreatography.

INTRODUCTION: Cholecystectomy is the accepted treatment for patients with symptomatic gallstones. In this study, we evaluate a simplified strategy for managing suspected synchronous choledocholithiasis by focussing on intra-operative imaging as the primary decision-making tool to target common bile duct (CBD) stone treatment. METHODS: All elective and emergency patients undergoing laparoscopic cholecystectomy (LC) for gallstones with any markers of synchronous choledocholithiasis were included. Patients unfit for surgery or who had pre-operative proof of choledocholithiasis were excluded. Intra-operative imaging was used for evaluation of the CBD. CBD stone treatment was with bile duct exploration (LCBDE) or endoscopic retrograde cholangiopancreatography (LC + ERCP). Outcomes were safety, effectiveness and efficiency. RESULTS: 506 patients were included. 371 (73%) had laparoscopic ultrasound (LUS), 80 (16%) had on-table cholangiography (OTC) and 55 (11%) had both. 164 (32.4%) were found to have CBD stones. There was no increase in length of surgery for LC + LUS compared with average time for LC only in our unit (p = 0.17). 332 patients (65.6%) had clear ducts. Imaging was indeterminate in 10 (2%) patients. Overall morbidity was 10.5%. There was no mortality. 142 (86.6%) patients with stones on intra-operative imaging proceeded to LCBDE. 22 (13.4%) patients had ERCP. Sensitivity and specificity of intra-operative imaging were 93.3 and 99.1%, respectively. Success rate of LCBDE was 95.8%. Effectiveness was 97.8%. CONCLUSIONS: Eliminating pre-operative bile duct imaging in favour of intra-operative imaging is safe and effective. When combined with intra-operative stone treatment, this method becomes a true 'single-stage' approach to managing suspected choledocholithiasis.

Coronavirus Disease 2019 (COVID-19) Vaccination for Children: Position Statement of Indian Academy of Pediatrics Advisory Committee on Vaccination and Immunization Practices.

JUSTIFICATION: Data generated after the first wave has revealed that some children with coronavirus 19 (COVID-19) can become seriously ill. Multi-inflammatory syndrome in children (MIS-C) and long COVID cause significant morbidity in children. Prolonged school closures and quarantine have played havoc with the psychosocial health of children. Many countries in the world have issued emergency use authorisation (EUA) of selected Covid-19 vaccines for use in children. In India, a Subject Expert Committee (SEC) has recommended the use of Covaxin (Bharat Biotech) for children from the ages of 2-18 years. The recommendation has been given to the Drugs Controller General of India (DCGI) for final approval. OBJECTIVE: To provide an evidence-based document to guide the pediatricians on the recommendation to administer COVID vaccines to children, as and when they are available for use. PROCESS: Formulation of key questions was done by the committee, followed by review of literature on epidemiology and burden of Covid-19 in children, review of the studies on COVID vaccines in children, and the IAP stand on Covid-19 vaccination in children. The available data was discussed in the ACVIP focused WhatsApp group followed by an online meeting on 24 October, 2021, wherein the document was discussed in detail and finalized. RECOMMENDATIONS: The IAP supports the Government of India's decision to extend the COVID-19 vaccination program to children between 2-18 years of age. Children with high-risk conditions may be immunized on a priority basis. The IAP and its members should be a partner with the Government of India, in the implementation of this program and the surveillance that is necessary following the roll-out.

Breastfeeding and Coronavirus Disease 2019 (COVID-19) Vaccination: Position Statement of Indian Academy of Pediatrics Advisory Committee on Vaccination and Immunization Practices.

JUSTIFICATION: In India, till recently, breastfeeding women have been excluded from the coronavirus disease (COVID-19) vaccination program, rendering a significant population of the country, including frontline workers, ineligible to derive the benefits of the COVID-19 vaccine rollout. OBJECTIVE: The objective of this recommendation is production of an evidence-based document to guide the pediatricians to give advice to breastfeeding mothers regarding the safety of COVID-19 vaccines in lactating women. PROCESS: Formulation of key question was done under the chairmanship of president of the IAP. It was followed by review of literature regarding efficacy and safety of COVID-19 vaccines in breastfeeding women. The recommendations of other international and national professional bodies were also deliberated in detail. The available data was discussed in the ACVIP focused WhatsApp group. Opinion of all members was taken and the final document was prepared after achieving consensus. RECOMMENDATIONS: The IAP/ACVIP recommends the administration of COVID-19 vaccines to all breastfeeding women. The IAP/ACVIP endorses the recent recommendation of the Government of India, to consider all breastfeeding women as eligible for COVID-19 vaccination.

Ethical rationing of healthcare resources during COVID-19 outbreak: Review.

While rationing of healthcare resources is inevitable even in the most developed economies, particularly on the wake of a pandemic, ethical basis of its implementation needs to be reviewed. With sudden and huge demand for drugs and medical supplies and equipments, the need for rationing arises and thus the concept becomes unavoidable. Thus, we aimed to review and analyse on the key ethical issues in the concept of healthcare rationing. Our search in various PubMed databases resulted articles explaining on the concept of strategizing the priorities based on universal ethical principles of justice, benevolence and ensuring equality rather than wealth, power, geographical location or other personal biases. Concrete and pragmatic regulations and guidelines for systematic rationing have to be framed and followed. In addition, physicians being sensitive and empowered on deciding bedside rationing in coordination with the recommendations of ethicists and healthcare officials, will ensure fair practice.

Indian Academy of Pediatrics (IAP) Advisory Committee on Vaccines and Immunization Practices (ACVIP): Recommended Immunization Schedule (2020-21) and Update on Immunization for Children Aged 0 Through 18 Years.

JUSTIFICATION: In view of new developments in vaccinology and the availability of new vaccines, there is a need to revise/review the existing immunization recommendations. PROCESS: Advisory Committee on Vaccines and Immunization Practices (ACVIP) of Indian Academy of Pediatrics (IAP) had a physical meeting in March, 2020 followed by online meetings (September-October, 2020), to discuss the updates and new recommendations. Opinion of each member was sought on the various recommendations and updates, following which an evidence-based consensus was reached. OBJECTIVES: To review and revise the IAP recommendations for 2020-21 and issue recommendations on existing and new vaccines. RECOMMENDATIONS: The major changes include recommendation of a booster dose of injectable polio vaccine (IPV) at 4-6 years for children who have received the initial IPV doses as per the ACVIP/IAP schedule, re-emphasis on the importance of IPV in the primary immunization schedule, preferred timing of second dose of varicella vaccine at 3-6 months after the first dose, and uniform dosing recommendation of 0.5 mL (15 µg HA) for inactivated influenza vaccines.

Immunization During the COVID-19 Pandemic: Recommendations From Indian Academy of Pediatrics Advisory Committee on Vaccines and Immunization Practices.

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, immunization practices of all age groups, especially routine childhood vaccines, have been interrupted. Immunization is considered an essential health activity, which needs to be resumed as early as possible. This pandemic has created several unique issues related to routine immunization of individual children at clinics, which needs to be addressed. In this communication, the Advisory Committee on Vaccines and Immunization Practices (ACVIP) of Indian Academy of Pediatrics addresses the common questions and issues related to SARS-CoV-2 and routine immunization services. This also includes the recommendations for routine immunization of SARS-CoV-2 suspect and positive children, and for the logistics to be followed for immunization services.

Lung Barrier Function in COVID-19?

The novel coronavirus COVID-19 appears to strike some people more intensely than others. Some people only experience mild symptoms while others require hospitalization and ventilation. With the virus becoming more prevalent day by day, it is not just the elderly, but even young people are falling seriously ill. Various researchers across the world state that specific cells in the nasal passages, intestines, and lungs may be more susceptible to the infection. Shifting the focus and research towards epithelium might provide new insight towards understanding COVID-19. This article is an overview of how epithelium permeability in COVID-19 may associate with comorbidities and other factors.

The influence of boreal summer intra-seasonal oscillations on Indo-western Pacific Ocean surface waves.

The present study examines the influence of Boreal Summer Intra-Seasonal Oscillation (BSISO) on Tropical Indian Ocean surface waves using the latest version of ECMWF reanalysis (ERA5) during summer monsoon months June through August (JJA). BSISO is a distinct mode of ISO during JJA having a northward and eastward movement from the equatorial Indian Ocean to the western Pacific Ocean. Composite analysis of anomalies of significant wave heights (SWH), wind sea, swell, and mean wave period for 8 phases of BSISO has been carried out to understand its influence. SWH anomalies in response to BSISO's are phase-dependent. Negative SWH anomalies are noticed with strong northward and weak eastward propagation during the phases 1-3 in response to the easterly wind anomalies over the north Indian Ocean (NIO). During phases 5-7, high positive SWH anomalies (~ 0.5 m) in response to the westerly wind anomalies with northward and weak eastward propagation over NIO. Phases 4 and 8 behave like transition phases. In addition, enhanced (suppressed) SWH anomalies (~ 0.5 m) are seen during the active (break) spells of BSISO over NIO. Over the southern tip of India, negative (positive) SWH anomalies prevail during the active (break) conditions. This study clearly suggests that the wave forecast advisories during intra-seasonal time scales would be more useful for offshore and coastal activities during the summer monsoon.

Cost effectiveness of intraoperative laparoscopic ultrasound for suspected choledocholithiasis; outcomes from a specialist benign upper gastrointestinal unit.

INTRODUCTION: Common bile duct stones are present in 10% of patients with symptomatic gallstones. One-third of UK patients undergoing cholecystectomy will have preoperative ductal imaging, commonly with magnetic resonance cholangiopancreatography. Intraoperative laparoscopic ultrasound is a valid alternative but is not widely used. The primary aim of this study was to assess cost effectiveness of laparoscopic ultrasound compared with magnetic resonance cholangiopancreatography. MATERIALS AND METHODS: A prospective database of all patients undergoing laparoscopic cholecystectomy between 2015 and 2018 at a district general hospital was assessed. Inclusion criteria were all patients, emergency and elective, with symptomatic gallstones and suspicion of common bile duct stones (derangement of liver function tests with or without dilated common bile duct on preoperative ultrasound, or history of pancreatitis). Patients with known common bile duct stones (magnetic resonance cholangiopancreatography or failed endoscopic retrograde cholangiogram) were excluded. Ninety-day morbidity data were also collected. RESULTS: A total of 420 (334 elective and 86 emergency) patients were suspected to have common bile duct stones and were included in the study. The cost of a laparoscopic ultrasound was £183 per use. The cost of using the magnetic resonance cholangiopancreatography unit was £365 per use. Ten postoperative magnetic resonance cholangiopancreatographies were performed for inconclusive intraoperative imaging. The estimated cost saving was £74,650. Some 128 patients had common bile duct stones detected intraoperatively and treated. There was a false positive rate of 4.7%, and the false negative rate at 90 days was 0.7%. laparoscopic ultrasound use saved 129 bed days for emergency patients and 240 magnetic resonance cholangiopancreatography hours of magnetic resonance imaging. CONCLUSION: The use of laparoscopic ultrasound during laparoscopic cholecystectomy for the detection of common bile duct stone is safe, accurate and cost effective. Equipment and maintenance costs are quickly offset and hospital bed days can be saved with its use.

Containing the first outbreak of COVID-19 in a healthcare setting in India: The sree chitra experience.

The response to the first health worker case in India and novel strategies adopted in the context of evolving pandemic of COVID-19 is presented here. On the same day of confirmation, institutional COVID cell was established, and contact tracing was started. A total of 184 contacts were identified and quarantined. Hospital services were scaled down, and responsibilities were reassigned. In-house digital platforms were used for daily meetings, contact tracing, line listing, risk stratification, and research. Reverse transcription polymerase chain reaction-based severe acute respiratory syndrome-CoV2 testing facility was established in the institute. All high-risk contacts were given hydroxychloroquine prophylaxis. No secondary cases were found. Hospital preparedness, participatory decision-making through institutional COVID cell, optimal use of in-house digital platforms, and coordination with the state health department and national bodies, including Indian Council of Medical Research, were the supporting factors. Rapidly evolving guidelines, trepidation about the disease, logistic delays, and lack of support systems for people under quarantine were the challenges in the containment exercise.

Synthesis, spectral studies, DNA binding, photocleavage, antimicrobial and anticancer activities of isoindol Ru(II) polypyridyl complexes.

Three new Ru(II) polypyridyl complexes [Ru(phen)2CIIP]2+ (1) {CIIP = 2-(5-Chloro-3a H-Isoindol-3-yl)-1H-Imidazo[4,5-f][1, 10]phenantholine} (phen = 1, 10 phenanthroline), [Ru(bpy)2CIIP]2+ (2) (bpy = 2, 2' bipyridine) and [Ru(dmb)2CIIP]2+ (3) (dmb = 4, 4'-dimethyl 2, 2' bipyridine) were synthesized and characterized by different spectral methods. The DNA-binding behavior of these complexes was investigated by absorption, emission spectroscopic titration and viscosity measurements, indicating that these three complexes bind to CT-DNA in an intercalative mode, but binding affinities of these complexes were different. The DNA-binding constants Kb of complexes 1, 2 and 3 were calculated in the order of 106. All three complexes cleave pBR322 DNA in photoactivated cleavage studies and exhibit good antimicrobial activity. Anticancer activity of these Ru(II) complexes was evaluated in MCF7 cells. Cytotoxicity by MTT assay showed growth inhibition in a dose dependent manner. Cell cycle analysis by flow cytometry data showed an increase in Sub G1 population. Annexin V FITC/PI staining confirms that these complexes cause cell death by the induction of apoptosis.

Nonlinear convection of binary liquids in a porous medium.

Thermal convection of binary mixtures in a porous medium is studied with stress-free boundary conditions. The linear stability analysis is studied by using the normal mode method. The effects of the material parameters have been studied at the onset of convection. Using a multiple scale analysis near the onset of the stationary convection, a cubic-quintic amplitude equation is derived. The influence of the Lewis number and the separation ratio on the supercritical-subcritical transition is discussed. Stationary front solutions and localized states are analyzed at the Maxwell point. Near the threshold of the oscillatory convection, a set of two coupled complex cubic-quintic Ginzburg-Landau type amplitude equations is derived, and implicit analytical expressions for the coefficients are given.