Prenatal exposures and exposomics of asthma

This review examines the causal investigation of preclinical development of childhood asthma using exposomic tools. We examine the current state of knowledge regarding early-life exposure to non-biogenic indoor air pollution and the developmental modulation of the immune system. We examine how metabolomics technologies could aid not only in the biomarker identification of a particular asthma phenotype, but also the mechanisms underlying the immunopathologic process. Within such a framework, we propose alternate components of exposomic investigation of asthma in which, the exposome represents a reiterative investigative process of targeted biomarker identification, validation through computational systems biology and physical sampling of environmental medi

Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma

Contains fulltext : 79699.pdf (publisher's version ) (Closed access)BACKGROUND: We evaluated the efficacy of imatinib mesylate in addition to hydroxyurea in patients with recurrent glioblastoma (GBM) who were either on or not on enzyme-inducing anti-epileptic drugs (EIAEDs). METHODS: A total of 231 patients with GBM at first recurrence from 21 institutions in 10 countries were enrolled. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 600 mg per day for patients not on EIAEDs and at 500 mg twice a day if on EIAEDs. The primary end point was radiographic response rate and secondary end points were safety, progression-free survival at 6 months (PFS-6), and overall survival (OS). RESULTS: The radiographic response rate after centralised review was 3.4%. Progression-free survival at 6 months and median OS were 10.6% and 26.0 weeks, respectively. Outcome did not appear to differ based on EIAED status. The most common grade 3 or greater adverse events were fatigue (7%), neutropaenia (7%), and thrombocytopaenia (7%). CONCLUSIONS: Imatinib in addition to hydroxyurea was well tolerated among patients with recurrent GBM but did not show clinically meaningful anti-tumour activity

Estimating the social value of higher education: willingness to pay for community and technical colleges

Much is known about private financial returns to education in the form of higher earnings. Less is known about how much social value exceeds this private value. Associations between education and socially-desirable outcomes are strong, but disentangling the effect of education from other causal factors is challenging. The purpose of this paper is to estimate the social value of one form of higher education. We elicit willingness to pay for the Kentucky Community and Technical College System (KCTCS) directly and compare our estimate of total social value to our estimates of private value in the form of increased earnings. Our earnings estimates are based on two distinct data sets, one administrative and one from the U.S. Census. The difference between the total social value and the increase in earnings is our measure of the education externality and the private, non-market value combined. Our work differs from previous research by focusing on education at the community college level and by eliciting values directly through a stated-preferences survey in a way that yields a total value including any external benefits. Our preferred estimates indicate the social value of expanding the system exceeds private financial value by at least 25% with a best point estimate of nearly 90% and exceeds total private value by at least 15% with a best point estimate of nearly 60%.Kentucky Community and Technical College Syste

Surge of lower respiratory tract group A streptococcal infections in England in winter 2022:epidemiology and clinical profile

AbstractBackgroundFollowing low incidence of invasive group A streptococcal (iGAS) infections during the COVID-19 pandemic, marked increases were noted in many countries during 2022, particularly in children. In November 2022, severe presentations of lower respiratory tract infections (LRTIs), including empyema, were notified by clinicians across the UK. UKHSA investigated this rise with the aim of informing clinical management and public health response.MethodsWe undertook a case-series analysis using multiple routine data sources, exempted from ethics approval or patient consent. We identified iGAS cases in England in children younger than 15 years with an LRTI reported between Oct 1 and Dec 21, 2022, using UKHSA laboratory surveillance data (GAS detected in LRT specimens) and notifications by clinicians and Health Protection Teams (HPTs). Symptoms, diagnoses, health-care interactions, and outcome (death or recovery) data were obtained from HPT case management notes, the National Child Mortality Database, and the NHS Digital Emergency Care Dataset.FindingsWe identified 147 cases of LRTI iGAS in children across England (77 [52%] male, 70 [48%] female; median age 4 years [IQR 2–6]). Predominant ethnicities were White (74 [65%] of 113 with known ethnicity) and Asian (18 [16%] of 113). Most reported symptoms were fever (90 [75%] of 120 children with ≥1 symptom) and cough (60 [50%] of 120), and 71 (48%) of all 147 children had a diagnosed respiratory viral coinfection (most commonly hMPV and RSV). 127 (86%) of children attended an emergency department, 31% (n=36/114 with onset date) at least twice within 21 days after symptom onset. 37 (25%) of 147 children died, with a median time from symptom onset to death of 4 days (IQR 3–7). Of 32 children with sample dates, 16 (84%) were tested for GAS on or after the day they died. Over half of deaths (21 [57%] of 37 deaths) occurred in the community after rapid deterioration, of whom 18 had previous contact with health-care services documented.InterpretationThe UK saw an unusual rise in iGAS LRTIs in children in late 2022. One in four cases died, over half in the community. Non-specific symptoms, viral symptoms, or positive virology might have lowered suspicion of bacterial infection. Although the use of multiple available data sources expedited the analysis, varying data completeness limited interpretation. Our study highlights the need for earlier detection and identification of effective measures to prevent death

Surface modification of polyaniline nanorods with thiol-terminated poly(ethylene oxide)

Electrochemically grown polyaniline (PAni) thin films have been shown to react efficiently with thiols, which can dramatically change the surface properties of the material without significantly impacting bulk conductivity. Such films, however, are difficult to process and are unsuitable for many applications. Here, we demonstrate the grafting of thiol-terminated poly(ethylene oxide) (PEG-SH) of various molecular weights onto PAni nanorods. The resulting materials are characterized by spectroscopic, microscopic, and thermal analytical methods to demonstrate the covalent attachment of the PEG polymers to the nanorods. The derivatized nanorods are water dispersible and maintain their original morphology and electroactivity. The number of thiols bound to the nanoparticles under a given set of conditions decreases as the size increases, but the total mass of PEG increases with increasing size. The reaction proceeds at room temperature, but is much faster at higher temperature and greater PEG density is observed