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Summary: Background: Dengue shows high geographic heterogeneity within and across endemic countries. In the context of increasing burden and predicted outbreaks due to climate change, understanding the heterogeneity will enable us to develop region specific targeted interventions, including vaccination. World Health Organisation (WHO) suggests standard methodologies to study the burden and heterogeneity at national and subnational levels. Regional studies with robust and standard methodology to capture heterogeneity are scarce. We estimated the seroprevalence of dengue in children aged 9–12 years and the force of infection in Kerala, India, from where Zika cases also have been reported recently. Methods: We conducted a school-based cross-sectional survey in 38 clusters; selected by stratified random sampling, representing rural, urban, high burden and low-burden administrative units. Validation of Indirect IgG ELISA was done by Plaque Reduction Neutralization Test (PRNT90) using the local isolates of all four serotypes. Force of infection (FOI) was estimated using the WHO-FOI calculator. We conducted a follow-up survey among a subsample of seronegative children, to estimate the rate of sero-conversion. Results: Among 5236 children tested, 1521 were positive for anti-dengue IgG antibody. The overall seroprevalence in the state was 29% (95% CI 24.1–33.9). The validity corrected seroprevalence was 30.9% in the overall sample, 46.9% in Thiruvananthapuram, 26.9% in Kozhikkode and 24.9% in Kollam. Age-specific seroprevalence increased with age; 25.7% at 9 years, 29.5% at 10 years, 30.9% at 11 years and 33.9% at 12 years. Seroprevalence varied widely across clusters (16.1%–71.4%). The estimated force of infection was 3.3/100 person-years and the seroconversion rate was 4.8/100 person-years. 90% of children who tested positive were not aware of dengue infection. All the four serotypes were identified in PRNT and 40% of positive samples had antibodies against multiple serotypes. Interpretation: The study validates the WHO methodology for dengue serosurveys and confirms its feasibility in a community setting. The overall seroprevalence in the 9–12 year age group is low to moderate in Kerala; there are regional variations; high burden and low burden clusters co-exist in the same districts. The actual burden of dengue exceeds the reported numbers. Heterogeneity in prevalence, the high proportion of inapparent dengue and the hyperendemic situation suggest the need for region-specific and targeted interventions, including vaccination. Funding: World Health Organization.

Asthma is a heterogeneous disease, with multiple underlying inflammatory pathways and structural airway abnormalities that impact disease persistence and severity. Recent progress has been made in developing targeted asthma therapeutics, especially for subjects with eosinophilic asthma. However, there is an unmet need for new approaches to treat patients with severe and exacerbation-prone asthma, who contribute disproportionately to disease burden. Extensive deep phenotyping has revealed the heterogeneous nature of severe asthma and identified distinct disease subtypes. A current challenge in the field is to translate new and emerging knowledge about different pathobiologic mechanisms in asthma into patient-specific therapies, with the ultimate goal of modifying the natural history of disease. Here, we describe the Precision Interventions for Severe and/or Exacerbation-Prone Asthma (PrecISE) Network, a groundbreaking collaborative effort of asthma researchers and biostatisticians from around the United States. The PrecISE Network was designed to conduct phase II/proof-of-concept clinical trials of precision interventions in the population with severe asthma, and is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Using an innovative adaptive platform trial design, the PrecISE Network will evaluate up to 6 interventions simultaneously in biomarker-defined subgroups of subjects. We review the development and organizational structure of the PrecISE Network, and choice of interventions being studied. We hope that the PrecISE Network will enhance our understanding of asthma subtypes and accelerate the development of therapeutics for severe asthma.

Tuberculosis (TB) continues to be a global challenge. Reducing the duration of TB treatment for drug-sensitive TB (DSTB) has direct and distinct advantages. We ventured into the aspect of utilizing linezolid as a pivotal drug in shortening therapy in DSTB. Linezolid has gained prominence as it is faring well in resistant TB management. Only a few studies use the strategy of Linezolid in DS-TB but it seems a lucrative approach, the bactericidal effects have been reported favourably in the studies. There have been concerns about the potential adverse drug effects of Linezolid reported but clinical trials have demonstrated safety and tolerability when administered for shorter periods. If the safety and efficacy of giving Linezolid for a shorter period along with standard drugs for DSTB is established it could lead to newer avenues using Linezolid for shortening the duration of treatment for DSTB as an alternative to treat DSTB.

Abstract Aims With numerous and continuing attempts at adapting diabetes self-management support programmes to better account for underserved populations, its important that the lessons being learned are understood and shared. The work we present here reviews the latest evidence and best practice in designing and embedding culturally and socially sensitive, self-management support programmes. Methods We explored the literature with regard to four key design considerations of diabetes self-management support programmes: Composition - the design and content of written materials and digital tools and interfaces; Structure - the combination of individual and group sessions, their frequency, and the overall duration of programmes; Facilitators - the combination of individuals used to deliver the programme; and Context – the influence and mitigation of a range of individual, socio-cultural, and environmental factors. Results We found useful and recent examples of design innovation within a variety of countries and models of health care delivery including Brazil, Mexico, Netherlands, Spain, United Kingdom, and United States of America. Within Composition we confirmed the importance of retaining best practice in creating readily understood written information and intuitive digital interfaces; Structure the need to offer group, individual, and remote learning options in programmes of flexible duration and frequency; Facilitators where the benefits of using culturally concordant peers and community-based providers were described; and finally in Context the need to integrate self-management support programmes within existing health systems, and tailor their various constituent elements according to the language, resources, and beliefs of individuals and their communities. Conclusions A number of design principles across the four design considerations were identified that together offer a promising means of creating the next generation of self-management support programme more readily accessible for underserved communities. Ultimately, we recommend that the precise configuration should be co-produced by all relevant service and patient stakeholders and its delivery embedded in local health systems.

Abstract Survival outcomes for patients with neuroblastoma vary markedly and reliable prognostic markers and risk stratification tools are lacking. We sought to identify and validate a transcriptomic signature capable of predicting risk of mortality in patients with neuroblastoma. The TARGET NBL dataset (n = 243) was used to develop the model and two independent cohorts, E-MTAB-179 (n = 478) and GSE85047 (n = 240) were used as validation sets. EFS was the primary outcome and OS was the secondary outcome of interest for all analysis. We identified a 21-gene signature capable of stratifying neuroblastoma patients into high and low risk groups in the E-MTAB-179 (HR 5.87 [3.83–9.01], p

This paper explores the role of international partnerships to facilitate low-energy building design, construction, and operations. We present the strategic approach, joint research and development outcomes, and implementation activities of a unique U.S.-India program on buildings energy efficiency, the Center for Building Energy Research and Development. We discuss the collaboration successes in both countries despite their dissimilar building contexts, implementation challenges and opportunities. We highlight a range of R&D outcomes, such as novel tools and technologies developed and tested by the joint teams, with their technical energy savings potential, as well as results of capacity building and technology demonstrations. A deep-dive into key new scientific methods around building energy monitoring and benchmarking that could have a significant impact on high-performanceof buildings in both countries is also provided. Finally, in addition to joint R&D successes, pathways to deployment, and lessons learned are discussed as key takeaways.

This article reports a novel surgical technique in the management of soft posterior polar cataracts. This technique avoids hydro procedures, trenching, and chopping. Viscodissection is avoided or minimal, and polar opacity is removed last. These modifications minimize the risk of intraoperative complications.

The photoresponsive nature of the triazole sensors introduces a dynamic element to biomaterial sensing, enabling precise control and modulation of their response. The investigation explores the innovative application of triazole sensors with photoresponsive properties in biomaterial sensing. Combining the robust binding capabilities of the triazole scaffold with the adaptability conferred by photoresponsive units, these sensors introduce a dynamic element to sensing, enabling precise control and modulation of their response. The study showcases their versatility in various applications, from cellular imaging to biomarker monitoring, within complex biological environments. Through customization based on specific biomolecules of interest, the sensors exhibit high selectivity, making them valuable tools for unraveling cellular processes and disease mechanisms. Activity testing likely involved synthesizing and characterizing these sensors and evaluating their performance through techniques such as spectroscopy, microscopy, and biochemical assays. The results underscore the transformative potential of photoresponsive-based triazole sensors in advancing biomaterials sensing technologies, with implications for diagnostics, drug discovery, and fundamental biological research. Overall, the investigation emphasizes their adaptability and versatility in addressing the evolving landscape of biological sensing challenges.

Introduction: Management of spondylolysis in adolescents is generally successful with conservative management. Uncommonly, surgical fixation is necessary for refractory cases. Direct repair with intralaminar screws is one commonly utilized technique. Recently, less invasive spinal procedures are becoming viable with the enabling of technologies, including robotics. Case description: A 14-year-old baseball player and surfer presented with low back pain, diagnosed by MRI as bony edema and stress fractures of the posterior spinal elements. After 18 months, the pain was unresponsive to rest, physical therapy, and bracing. There was no radicular pain or neurologic symptoms. Computed tomography (CT) revealed bilateral, chronic nonhealing pars defects at L5. He underwent outpatient, robot-assisted percutaneous intralaminar fixation with hydroxyapatite-coated screws through a 2 cm skin incision. Outcome: On postoperative day 1, the patient reported relief of his preoperative pain and he was ambulating without difficulty. At 2 weeks follow-up, the patient was completely pain free and surfing. At 2 months follow-up, low-dose CT demonstrated partial incorporation of the hydroxyapatite-coated screws, and the patient returned to sports. At 6 months follow-up, the patient had no pain and was swinging his baseball bat with full force. Low-dose CT revealed complete healing of the defects with full incorporation of the hydroxyapatite-coated screws. Conclusions: A novel minimally invasive robotic percutaneous approach for direct spondylolysis repair using hydroxyapatite-coated screws is a potential surgical treatment option for non-healing pars defects in adolescent patients.