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Abstract Background Positive pressure ventilation (PPV) is an essential component of neonatal resuscitation. Meta-analytic evidence suggests that, among late preterm and term newborn infants who require resuscitation after birth, a supraglottic airway (SA) device is more effective than a face mask at reducing the probability of PPV failure and reducing the need for endotracheal intubation. However, SA devices are rarely used in routine practice in hospital delivery room settings within the United States. Methods In preparation for a pragmatic hybrid effectiveness-implementation trial, we used implementation mapping to identify barriers and facilitators to SA use; develop a logic model; identify and operationalize implementation strategies targeting key barriers and facilitators; and refine strategies based on iterative feedback from clinicians and administrators (e.g., physicians, nurse practitioners, nurse managers, and respiratory therapists). We used the Consolidated Framework for Implementation Research (CFIR) to organize barriers and implementation strategies. Results Across open-ended survey responses and focus groups, identified barriers included: (1) mixed perceptions of the advantages or disadvantages of SA compared to alternatives; (2) insufficient education and training in SA use; and (3) lack of perceived need for an alternative to intubation as a standard practice. The research team’s understanding of these barriers and selection of implementation strategies to address them were refined throughout the iterative implementation mapping process, which resulted in the selection of two sets of implementation strategies to be tested in a hybrid trial. Conclusions The implementation mapping process described in this paper provides an exemplar of a systematic and partner-engaged process to identify and select implementation strategies for the purpose of hybrid trial design.

Abstract Background Chronic cough has been associated with reduced health-related quality of life, negative impacts on sleep, work, and other daily activities, and increased use of health care resources. Little is known about the prevalence of chronic cough in Italy. In the present study we sought to estimate the prevalence of chronic cough in Italy, describe sociodemographic and clinical characteristics associated with chronic cough, and characterize the impact of chronic cough on overall health and wellness, work and other daily activities, and health care resource use. Methods We conducted a cross-sectional study to collect sociodemographic and health-related data from Italian residents who participated in the 2020 National Health and Wellness Survey (N = 10,026). To assess the characteristics and burden of chronic cough, adults who indicated that they had experienced chronic cough during the prior 12 months were compared with propensity score-matched controls without chronic cough. Results The estimated weighted lifetime and 12-month prevalence of chronic cough were estimated as 9.2% and 6.3%, respectively. Compared with matched controls, respondents with chronic cough had significantly lower measures of overall physical and mental health (P

Background Chronic cough, defined as daily cough for at least 8 weeks, negatively affects quality of life and work productivity and increases healthcare resource utilisation. We aimed to determine the prevalence and burden of chronic cough in the UK. Methods Study participants were general population respondents to the 2018 UK National Health and Wellness Survey (NHWS). Respondents completed survey questions relating to health, quality of life, work productivity and activity impairment, and use of healthcare resources. Prevalence estimates were projected to the UK population using post-stratification sampling weights to adjust for sampling bias. The population with chronic cough was matched 1:3 with a group without chronic cough, using propensity score matchingon age, sex and the modified Charlson Comorbidity Index. Results Of 15 000 NHWS respondents, 715 reported chronic cough in the previous 12 months and 918 during their lifetime. Weighted to the UK adult population, the 12-month prevalence of chronic cough was 4.9% and lifetime prevalence was 6.2%. Prevalence of chronic cough was higher among older respondents and those with smoking histories. Chronic cough respondents experienced higher rates of severe anxiety and depression in the past 2 weeks than matched controls. Poor sleep quality and loss of work productivity were also observed. More chronic cough respondents visited a healthcare provider in the past 6 months than respondents without chronic cough with a mean of 5.8 and 3.7 visits per respondent, respectively. Conclusion Adults with chronic cough report lower quality of life, reduced work productivity and greater healthcare resource utilisation than matched controls without chronic cough.

Background Chronic cough (CC) which is defined ≥8 weeks is a common condition in clinical practice. However, estimates of prevalence and associated comorbidities in German adults and key subgroups of age and gender are lacking. Methods Cross-sectional study based on a representative panel of 15 020 adult subjects of the general population who completed the German National Health and Wellness Survey, reporting CC and questions about comorbidities. Lifetime and 12-month prevalence are presented as unweighted estimates. Results The lifetime CC prevalence was 6.5% (range across age groups 5.1%–8.3%) and the 12-month prevalence was 4.9% (range 3.7–5.7%). The prevalence of diagnosed CC was 2.8% (range 0.9–4.1%) and the prevalence of persons currently on any prescription to treat CC was 0.6% (range 0.2–1.4%). Respondents who experienced CC were 52.0±17.0 years old, with a higher prevalence in those aged 50 years and older. Persons with CC had higher morbidity scores and were diagnosed with an increased number of comorbidities, most frequently diagnoses of the respiratory system (71.0%), followed by digestive tract disorders (34.0%) and sleep disorders (37.6%). Conclusions In a broadly representative sample of German adults, lifetime and 12-month prevalence of CC was greatest in current and former smokers and those older ≥50 years of age. Comorbidities are frequent and may complicate management of these patients.

Introduction Lead exposure has a detrimental effect on child neurodevelopment. (1-3) Although exposure is decreasing, no safe level or threshold has been identified. (3) Moreover, lead exposure is higher among [...], BACKGROUND: Folic acid (FA) supplementation may attenuate the associations between gestational exposure to certain chemicals and autism or autistic-like behaviors, but to our knowledge, this has not been assessed for lead. OBJECTIVES: We examined whether the relationship between gestational blood-lead levels (BLLs) and autistic-like behaviors was modified by gestational plasma total folate concentrations, FA supplementation, and maternal methylenetetrahydrofolate reductase (MTHFR) 677C>T genotype. METHODS: We used data from the Maternal--Infant Research on Environmental Chemicals study (2008-2011), a Canadian pregnancy and birth cohort study. Childhood autistic-like behaviors were documented in 601 children 3-4 y of age with the Social Responsiveness Scale-2 (SRS-2), where higher scores denote more autistic-like behaviors. We measured BLLs and plasma total folate concentrations during the first and third trimesters of pregnancy. We also estimated gestational FA supplementation via surveys and genotyped the maternal MTHFR 677C>T single nucleotide polymorphism (SNP). We estimated the confounder-adjusted associations between [log.sub.2]-transformed BLLs and SRS-2 scores by two indicators of folate exposure and maternal MTHFR 677C>T genotype using linear regression. RESULTS: Third-trimester BLLs were associated with increased SRS-2 scores [[[beta].sub.adj] = 3:3; 95% confidence interval (CI): 1.1, 5.5] among participants with low (T SNP ([[beta].sub.adj] = 0:9; 95% CI: -1:2, 3.1) than those without the T allele ([[beta].sub.adj] = -0:3; 95% CI: -1:3, 0.7), but the difference was not statistically significant (p-interaction = 0:28). DISCUSSION: Folate may modify the associations between gestational lead exposure and childhood autistic-like behaviors, suggesting that it mitigates the neurotoxic effects of prenatal lead exposure. https://doi.org/10.1289/EHP14479

Zika virus (ZIKV) infection during pregnancy in humans is associated with an increased incidence of congenital anomalies including microcephaly as well as fetal death and miscarriage and collectively has been referred to as Congenital Zika Syndrome (CZS). Animal models for ZIKV infection in pregnancy have been developed including mice and non-human primates (NHPs). In macaques, fetal CZS outcomes from maternal ZIKV infection range from none to significant. In the present study we develop the olive baboon (Papio anubis), as a model for vertical transfer of ZIKV during pregnancy. Four mid-gestation, timed-pregnant baboons were inoculated with the French Polynesian ZIKV isolate (104 ffu). This study specifically focused on the acute phase of vertical transfer. Dams were terminated at 7 days post infection (dpi; n = 1), 14 dpi (n = 2) and 21 dpi (n = 1). All dams exhibited mild to moderate rash and conjunctivitis. Viremia peaked at 5-7 dpi with only one of three dams remaining mildly viremic at 14 dpi. An anti-ZIKV IgM response was observed by 14 dpi in all three dams studied to this stage, and two dams developed a neutralizing IgG response by either 14 dpi or 21 dpi, the latter included transfer of the IgG to the fetus (cord blood). A systemic inflammatory response (increased IL2, IL6, IL7, IL15, IL16) was observed in three of four dams. Vertical transfer of ZIKV to the placenta was observed in three pregnancies (n = 2 at 14 dpi and n = 1 at 21 dpi) and ZIKV was detected in fetal tissues in two pregnancies: one associated with fetal death at ~14 dpi, and the other in a viable fetus at 21 dpi. ZIKV RNA was detected in the fetal cerebral cortex and other tissues of both of these fetuses. In the fetus studied at 21 dpi with vertical transfer of virus to the CNS, the frontal cerebral cortex exhibited notable defects in radial glia, radial glial fibers, disorganized migration of immature neurons to the cortical layers, and signs of pathology in immature oligodendrocytes. In addition, indices of pronounced neuroinflammation were observed including astrogliosis, increased microglia and IL6 expression. Of interest, in one fetus examined at 14 dpi without detection of ZIKV RNA in brain and other fetal tissues, increased neuroinflammation (IL6 and microglia) was observed in the cortex. Although the placenta of the 14 dpi dam with fetal death showed considerable pathology, only minor pathology was noted in the other three placentas. ZIKV was detected immunohistochemically in two placentas (14 dpi) and one placenta at 21 dpi but not at 7 dpi. This is the first study to examine the early events of vertical transfer of ZIKV in a NHP infected at mid-gestation. The baboon thus represents an additional NHP as a model for ZIKV induced brain pathologies to contrast and compare to humans as well as other NHPs.

Introduction: Group 2 pulmonary hypertension (PH), defined as a mean pulmonary arterial pressure ≥25 mmHg with elevated pulmonary capillary wedge pressure >15 mmHg, has no approved therapy and patients often die from right ventricular failure (RVF). Alterations in mitochondrial metabolism, notably impaired glucose oxidation, and increased mitochondrial fission, contribute to right ventricle (RV) dysfunction in PH. We hypothesized that the impairment of RV and left ventricular (LV) function in group 2 PH results in part from a proglycolytic isoform switch from pyruvate kinase muscle (PKM) isoform 1 to 2 and from increased mitochondrial fission, due either to upregulation of expression of dynamin-related protein 1 (Drp1) or its binding partners, mitochondrial dynamics protein of 49 or 51 kDa (MiD49 or 51).Methods and Results: Group 2 PH was induced by supra-coronary aortic banding (SAB) in 5-week old male Sprague Dawley rats. Four weeks post SAB, echocardiography showed marked reduction of tricuspid annular plane systolic excursion (2.9 ± 0.1 vs. 4.0 ± 0.1 mm) and pulmonary artery acceleration time (24.3 ± 0.9 vs. 35.4 ± 1.8 ms) in SAB vs. sham rats. Nine weeks post SAB, left and right heart catheterization showed significant biventricular increases in end systolic and diastolic pressure in SAB vs. sham rats (LV: 226 ± 15 vs. 103 ± 5 mmHg, 34 ± 5 vs. 7 ± 1 mmHg; RV: 40 ± 4 vs. 22 ± 1 mmHg, and 4.7 ± 1.5 vs. 0.9 ± 0.5 mmHg, respectively). Picrosirius red staining showed marked biventricular fibrosis in SAB rats. There was increased muscularization of small pulmonary arteries in SAB rats. Confocal microscopy showed biventricular mitochondrial depolarization and fragmentation in SAB vs. sham cardiomyocytes. Transmission electron microscopy confirmed a marked biventricular reduction in mitochondria size in SAB hearts. Immunoblot showed marked biventricular increase in PKM2/PKM1 and MiD51 expression. Mitofusin 2 and mitochondrial pyruvate carrier 1 were increased in SAB LVs.Conclusions: SAB caused group 2 PH. Impaired RV function and RV fibrosis were associated with increases in mitochondrial fission and expression of MiD51 and PKM2. While these changes would be expected to promote increased production of reactive oxygen species and a glycolytic shift in metabolism, further study is required to determine the functional consequences of these newly described mitochondrial abnormalities.

Background: Toxic metals, such as lead (Pb), cadmium (Cd), arsenic (As), and mercury (Hg), may be associated with a higher risk of gestational hypertension and preeclampsia, whereas manganese (Mn) is an essential metal that may be protective. OBJECTIVES: We estimated the individual, independent, and joint associations of Pb, Cd, As, Hg, and Mn on the risk of developing gestational hypertension and preeclampsia in a cohort of Canadian women. Methods: Metal concentrations were analyzed in first and third trimester maternal blood (n = 1,560). We measured blood pressure after 20 wk gestation to diagnose gestational hypertension, whereas proteinuria and other complications defined preeclampsia. We estimated individual and independent (adjusted for coexposure) relative risks (RRs) for each doubling of metal concentrations and examined interactions between toxic metals and Mn. We used quantile g-computation to estimate the joint effect of trimester-specific exposures. Results: Each doubling of third trimester Pb (RR = 1.54; 95% CI: 1.06, 2.22) and first trimester blood As (RR = 1.25; 95% CI: 1.01, 1.58) was independently associated with a higher risk of developing preeclampsia. First trimester blood As (RR = 3.40; 95% CI: 1.40, 8.28) and Mn (RR = 0.63; 95% CI: 0.42, 0.94) concentrations were associated with a higher and lower risk, respectively, of developing gestational hypertension. Mn modified the association with As such that the deleterious association with As was stronger at lower concentrations of Mn. First trimester urinary dimethylarsinic acid concentrations were not associated with gestational hypertension (RR=1.31; 95% CI: 0.60, 2.85) or preeclampsia (RR = 0.92; 95% CI: 0.68, 1.24). We did not observe overall joint effects for blood metals. Discussion: Our results confirm that even low blood Pb concentrations are a risk factor for preeclampsia. Women with higher blood As concentrations combined with lower Mn in early pregnancy were more likely to develop gestational hypertension. These pregnancy complications impact maternal and neonatal health. Understanding the contribution of toxic metals and Mn is of public health importance. https://doi.org/10.1289/EHP10825, Introduction Gestational hypertension and preeclampsia are major contributors to maternal (1,2) and newborn (3,4) morbidity and mortality. Women with these conditions have an increased risk of developing hypertension and other [...]

"Emerging Voices" is a choral series published by Oxford University Press. The aim is to cater for adolescent male voices at various stages of change. Part ranges conform to the 'cambiata' system developed by Irvin Cooper. The paper asks whether a unique, characteristic timbral quality exists in voices at the mid-point of change and can be heard as distinctively different from unchanged 'treble' and newly emerged baritone timbre. The first 12 pieces in the series have been recorded by choirs ranging from beginner school groups to a prestigious national youth choir. During the recording process, samples of individual parts were taken to analyse and evaluate the vocal timbres that 'emerged'. A distinct midvoice timbre was only found in choirs where boys possessed significant choral experience gained as trebles. Such voices were more adaptable to different choir dispositions, able to manoeuver between a low alto part and a high tenor part. The paper concludes that Cooper's ideal of 'fitting the song to the voice, not the voice to the song' is only fully realised in solo singing instruction but where boys lacked significant choral experience, placement in cambiata parts that matched speaking voice pitches could result in pleasing choral tone through skilled blending of midvoice stages.

This paper argues that an anthropocentric fallacy permeates thinking within both technological and ecological approaches to environmentalism. In consequence, sustainable development is an incoherent concept through the weakness of its anthropocentric ethical grounding. Using the Judaeo-Christian tradition as an example, this paper examines the degree to which religion can be an alternative means of grounding an environmental ethic outside anthropocentrism. It concludes that, though religion can also be corrupted by anthropocentrism, insights gained through theology ought not to be wholly dismissed.

An editorial is presented on broad range of UK professionals involved in the care of patients with head and neck cancer. Topics include underpinning the basis of care of patients with head and neck cancer, which apply across the spectrum of management; and guidelines can be also used as an educational resource for clinicians, and for insight into head and neck cancer care for non-clinicians.