Insights into the complementarity of natural disaster insurance purchases and risk reduction behavior.

While flooding is the costliest natural disaster risk, public-sector investments provide incomplete protection. Moreover, individuals are in general reluctant to voluntarily invest in measures which limit damage costs from natural disasters. The moral hazard hypothesis argues that insured individuals take fewer other preparedness measures based on their assumption that their losses will be covered anyway.

Phase 3 Open-Label Clinical Trial of Elexacaftor/Tezacaftor/Ivacaftor in Children Aged 2-5 Years with Cystic Fibrosis and at Least One Allele.

Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) has been shown to be safe and effective in people with cystic fibrosis (CF) aged ⩾6 years with at least one allele but has not been studied in younger children. To evaluate the safety, pharmacokinetics, pharmacodynamics, and efficacy of ELX/TEZ/IVA in children with CF aged 2-5 years. In this phase 3, open-label, two-part study (parts A and B), children weighing <14 kg (on Day 1) received ELX 80 mg once daily (qd), TEZ 40 mg qd, and IVA 60 mg each morning and 59.

Education of the public health workforce and the Sustainable Development Goals: An analysis of existing competency sets.

Objectives: This paper describes a project designed to quantify the extent to which existing competency frameworks used for educating the public health workforce contribute to achieving the Sustainable Development Goals (SDGs) directly relevant to public health.

Study Design: This was a qualitative study involving a content and thematic analysis and mapping of nine available public health competency sets against the World Federation of Public Health Association's Global Charter for the Public's Health and the SDGs.

Methods: First, the SDG targets directly relevant to public health were selected, then mapped against the elements of the Global Charter to illustrate their alignment with aspects of public health practice.

GA4GH Phenopackets: A Practical Introduction.

The Global Alliance for Genomics and Health (GA4GH) is developing a suite of coordinated standards for genomics for healthcare. The Phenopacket is a new GA4GH standard for sharing disease and phenotype information that characterizes an individual person, linking that individual to detailed phenotypic descriptions, genetic information, diagnoses, and treatments. A detailed example is presented that illustrates how to use the schema to represent the clinical course of a patient with retinoblastoma, including demographic information, the clinical diagnosis, phenotypic features and clinical measurements, an examination of the extirpated tumor, therapies, and the results of genomic analysis.

Physiological tipping points in the relationship between foraging success and lifetime fitness of a long-lived mammal.

Although anthropogenic change is often gradual, the impacts on animal populations may be precipitous if physiological processes create tipping points between energy gain, reproduction or survival. We use 25 years of behavioural, diet and demographic data from elephant seals to characterise their relationships with lifetime fitness. Survival and reproduction increased with mass gain during long foraging trips preceding the pupping seasons, and there was a threshold where individuals that gained an additional 4.

Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients.

Background: Bempedoic acid, an ATP citrate lyase inhibitor, reduces low-density lipoprotein (LDL) cholesterol levels and is associated with a low incidence of muscle-related adverse events; its effects on cardiovascular outcomes remain uncertain.

Methods: We conducted a double-blind, randomized, placebo-controlled trial involving patients who were unable or unwilling to take statins owing to unacceptable adverse effects ("statin-intolerant" patients) and had, or were at high risk for, cardiovascular disease. The patients were assigned to receive oral bempedoic acid, 180 mg daily, or placebo.

The dilemma of improving rational antibiotic use in pediatric community-acquired pneumonia.

Pneumonia is the number one cause of disease and deaths in children under five years old, outside the neonatal period, with the greatest number of cases reported from resource-limited settings. The etiology is variable, with not much information on the local etiology drug resistance profile in many countries. Recent studies suggest an increasing contribution from respiratory viruses, also in children with severe pneumonia, with an increased relative contribution in settings that have good vaccine coverage against common bacterial pathogens.

Patterns of Change in the Severity of Airway Obstruction with Robin Sequence in Early Infancy.

Unlabelled: Previous studies suggest that infants with Robin sequence show a pattern of steady improvement in the severity of airway obstruction, and of their treatment requirements, during infancy.

Methods: Three infants with Robin sequence and severe obstructive sleep apnea were managed with nasal continuous positive airways pressure (CPAP). Multiple measures of airway obstruction were made during infancy, including CPAP pressure evaluations and sleep studies (screening and polysomnography studies).

Assessing the calculation of conductive and acinar ventilatory heterogeneity indices and from multiple-breath washout data.

Sensor errors resulting in elevated values of N concentration [N] in commercial multiple-breath washout (MBW) devices have been shown to prolong the washout and result in erroneously high functional residual capacity (FRC) and lung clearance index (LCI) values. The errors also affect the indices of conductive and acinar ventilatory heterogeneity ( and ) although the mechanism by which this change in values occurs remains unclear. Exploring these effects also provides a timely opportunity to examine the appropriateness of the algorithm used to calculate these indices.

The Environmental Conditions, Treatments, and Exposures Ontology (ECTO): connecting toxicology and exposure to human health and beyond.

Background: Evaluating the impact of environmental exposures on organism health is a key goal of modern biomedicine and is critically important in an age of greater pollution and chemicals in our environment. Environmental health utilizes many different research methods and generates a variety of data types. However, to date, no comprehensive database represents the full spectrum of environmental health data.

Nasal nitric oxide measurement in children for the diagnosis of primary ciliary dyskinesia: European Respiratory Society technical standard.

Nasal nitric oxide (nNO) is extremely low in most people with primary ciliary dyskinesia (PCD) and its measurement is an important contributor to making the diagnosis. Existing guidelines and technical standards focus on nNO measurements in older, cooperative children using chemiluminescence analysers. However, measurements of nNO in pre-school-age children (age 2-5 years) may facilitate early diagnosis and electrochemical rather than chemiluminescence analysers are widely used.

Clinical practice guideline recommendation summaries for pediatric oncology health care professionals: A qualitative study.

Objective: To develop a summary format of clinical practice guideline (CPG) recommendations to improve understandability among health care professionals.

Methods: We developed a summary format based on current research and used the "Think Aloud" technique in one-on-one cognitive interviews to iteratively improve it. Interviews of health care professionals from Children's Oncology Group-member, National Cancer Institute Community Oncology Research Program sites were conducted.

Characteristics associated with poor COVID-19 outcomes in people with psoriasis, psoriatic arthritis and axial spondyloarthritis: data from the COVID-19 PsoProtect and Global Rheumatology Alliance physician-reported registries.

Objectives: To investigate factors associated with severe COVID-19 in people with psoriasis (PsO), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA).

Methods: Demographic data, clinical characteristics and COVID-19 outcome severity of adults with PsO, PsA and axSpA were obtained from two international physician-reported registries. A three-point ordinal COVID-19 severity scale was defined: no hospitalisation, hospitalisation (and no death) and death.

The Ontology of Biological Attributes (OBA) - Computational Traits for the Life Sciences.

Existing phenotype ontologies were originally developed to represent phenotypes that manifest as a character state in relation to a wild-type or other reference. However, these do not include the phenotypic trait or attribute categories required for the annotation of genome-wide association studies (GWAS), Quantitative Trait Loci (QTL) mappings or any population-focused measurable trait data. Moreover, variations in gene expression in response to environmental disturbances even without any genetic alterations can also be associated with particular biological attributes.

Seasonal habitat preference and foraging behaviour of post-moult Weddell seals in the western Ross Sea.

Weddell seals () are important predators in the Southern Ocean and are among the best-studied pinnipeds on Earth, yet much still needs to be learned about their year-round movements and foraging behaviour. Using biologgers, we tagged 62 post-moult Weddell seals in McMurdo Sound and vicinity between 2010 and 2012. Generalized additive mixed models were used to (i) explain and predict the probability of seal presence and foraging behaviour from eight environmental variables, and (ii) examine foraging behaviour in relation to dive metrics.

APOBEC mutagenesis is a common process in normal human small intestine.

APOBEC mutational signatures SBS2 and SBS13 are common in many human cancer types. However, there is an incomplete understanding of its stimulus, when it occurs in the progression from normal to cancer cell and the APOBEC enzymes responsible. Here we whole-genome sequenced 342 microdissected normal epithelial crypts from the small intestines of 39 individuals and found that SBS2/SBS13 mutations were present in 17% of crypts, more frequent than most other normal tissues.

Five-Year Follow-up of Third-Generation Percutaneous Chevron and Akin Osteotomies (PECA) for Hallux Valgus.

Background: Recent large studies of third-generation minimally invasive hallux valgus surgery (MIS) have demonstrated significant improvement in clinical and radiologic outcomes. It remains unknown whether these clinical and radiologic outcomes are maintained in the medium to long term. The aim of this study was to investigate the minimum 5-year clinical and radiologic outcomes following third-generation MIS hallux valgus surgery in the hands of a high-volume MIS surgeon.

Inherited deletion of 9p22.3-p24.3 and duplication of 18p11.31-p11.32 associated with neurodevelopmental delay: Phenotypic matching of involved genes.

We describe a 3.5-year-old Iranian female child and her affected 10-month-old brother with a maternally inherited derivative chromosome 9 [der(9)]. The postnatally detected rearrangement was finely characterized by aCGH analysis, which revealed a 15.

Guideline for the Management of Fever and Neutropenia in Pediatric Patients With Cancer and Hematopoietic Cell Transplantation Recipients: 2023 Update.

Purpose: To update a clinical practice guideline (CPG) for the empiric management of fever and neutropenia (FN) in pediatric patients with cancer and hematopoietic cell transplantation recipients.

Methods: The International Pediatric Fever and Neutropenia Guideline Panel reconvened to conduct the second update of this CPG. We updated the previous systematic review to identify new randomized controlled trials (RCTs) evaluating any strategy for the management of FN in pediatric patients.

Distinct role of ERp57 and ERdj5 as a disulfide isomerase and reductase during ER protein folding.

Proteins entering the secretory pathway need to attain native disulfide pairings to fold correctly. For proteins with complex disulfides, this process requires the reduction and isomerisation of non-native disulfides. Two key members of the protein disulfide isomerase (PDI) family, ERp57 and ERdj5 (also known as PDIA3 and DNAJC10, respectively), are thought to be required for correct disulfide formation but it is unknown whether they act as a reductase, an isomerase or both.

Using Patient Perspectives to Inform Better Clinical Trial Design and Conduct: Current Trends and Future Directions.

The approach to patient engagement (PE) in drug development has changed rapidly due to many factors, including the complexity of innovative drugs and the need to demonstrate outcomes of relevance to patients, the desire to show 'value add' of PE, and the pandemic-related changes to how clinical trials are run, e.g., decentralised studies.

Outcomes of COVID-19 in people with rheumatic and musculoskeletal disease in Ireland over the first 2 years of the pandemic.

Background: Poor COVID-19 outcomes occur with higher frequency in people with rheumatic and musculoskeletal diseases (RMD). Better understanding of the factors involved is crucial to informing patients and clinicians regarding risk mitigation.

Aim: To describe COVID-19 outcomes for people with RMD in Ireland over the first 2 years of the pandemic.

What you need to know about gallstone disease.

Gallstone disease is becoming increasingly common in the UK, with one in six people developing gallstones and over 100 000 cholecystectomies being performed annually. The gallbladder stores bile produced by the liver and, in the presence of fat in the stomach, releases bile into the duodenum to promote the emulsification and absorption of fats and fat-soluble vitamins from the small bowel. Although most people with gallstones remain asymptomatic throughout their lifetime, approximately 20% go on to develop complications of varying severity, ranging from biliary colic to ascending cholangitis, which can be fatal if left untreated.