Being Breathed: from King Lear to clinical medicine

This essay explores the therapeutic possibilities opened up by literature for breathless patients today. Focusing on King Lear, it considers Shakespeare’s suggestion that we do not breathe as isolated agents but are instead ‘breathed’ by those who know and observe us. Breath emerges as fundamental to early modern personhood. Many breathless patients today still experience the inseparability of breath and aliveness, and breathlessness becomes ‘a way of life’ as they adapt their sense of what is possible in order to accommodate their condition. This life belongs not only to sufferers, however, but also to those who care for them. Considering recent clinical research on vicarious dyspnoea alongside King Lear reveals the existential and therapeutic potential of breath’s intimate, under-recognised relationality

Forgotten but not gone in rural South Africa: Urinary schistosomiasis and implications for chronic kidney disease screening in endemic countries

Background: Urinary schistosomiasis caused by infection with Schistosoma haematobium (S. haematobium) remains endemic in Africa and is associated with haematuria and albuminuria/proteinuria. Kidney Disease Improving Global Outcomes clinical guidelines recommend evaluating proteinuria/albuminuria and glomerular filtration rate for chronic kidney disease (CKD) diagnosis. The guidelines are informed by population data outside of Africa but have been adopted in many African countries with little validation. Our study aimed to characterise the burden of urinary schistosomiasis in rural South Africa (SA) and evaluate its relationship with markers of kidney dysfunction with implications for CKD screening. Methods: In this population-based cohort study, we recruited 2021 adults aged 20 – 79 years in the Mpumalanga Province, SA. Sociodemographic data were recorded, urinalysis performed, and serum creatinine and urine albumin and creatinine measured. Kidney dysfunction was defined as an estimated glomerular filtration rate (eGFR) 3.0mg/mmol. S. haematobium infection was determined by urine microscopy. Multivariable analyses were performed to determine relationships between S. haematobium and markers of kidney dysfunction. Results: Data were available for 1226 of 2021 participants. 717 (58.5%) were female and the median age was 35 years (IQR 27 – 47). Prevalence of kidney dysfunction and S. haematobium was 20.2% and 5.1% respectively. S. haematobium was strongly associated with kidney dysfunction (OR 8.66; 95% CI 4.10 – 18.3) and related to albuminuria alone (OR 8.69; 95% CI 4.11 – 18.8), with no evidence of an association with eGFR <90ml/min/1.73m2 (OR 0.43; 95% CI 0.05 – 3.59). Discussion: The strong association between urinary schistosomiasis and albuminuria requires careful consideration when screening for CKD. Screening for, and treatment of, schistosomiasis should be a routine part of initial work-up for CKD in S. haematobium endemic areas. Urinary schistosomiasis, a neglected tropical disease, remains a public health concern in the Mpumulanga province of SA

Langmuir turbulence and surface heating in the ocean surface boundary layer

This study uses large-eddy simulation to investigate the structure of the ocean surface boundary layer (OSBL) in the presence of Langmuir turbulence and stabilizing surface heat fluxes. The OSBL consists of a weakly stratified layer, despite a surface heat flux, above a stratified thermocline. The weakly stratified (mixed) layer is maintained by a combination of a turbulent heat flux produced by the wave-driven Stokes drift and downgradient turbulent diffusion. The scaling of turbulence statistics, such as dissipation and vertical velocity variance, is only affected by the surface heat flux through changes in the mixed layer depth. Diagnostic models are proposed for the equilibrium boundary layer and mixed layer depths in the presence of surface heating. The models are a function of the initial mixed layer depth before heating is imposed and the Langmuir stability length. In the presence of radiative heating, the models are extended to account for the depth profile of the heating

The prediction of preference for unfamiliar urban places

Preferences for unfamiliar urban environments were studied as a function of urban categories, viewing time, and four predictor variables: complexity, coherence, identifiability, and mystery. A nonmetric factor analysis of the preference ratings for the longest viewing-time condition yielded five dimensions: Contemporary Life, Alley/Factory, Urban Nature, Unusual Architecture, and Older Buildings. The five categories differed significantly in preference, with Urban Nature by far the most preferred and Alley/Factory distinctly disliked. The combination of low coherence and high complexity characterizes the least liked Alley/Factory category, while the role of mystery in the urban setting is highlighted by the most preferred Urban Nature category. The results point to various ways in which the urban environment could be more responsive to people's preferences.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43513/1/11111_2005_Article_BF01359051.pd

Preeclampsia and COVID-19: results from the INTERCOVID prospective longitudinal study

Background: It is unclear whether the suggested link between COVID-19 during pregnancy and preeclampsia is an independent association or if these are caused by common risk factors. Objective: This study aimed to quantify any independent association between COVID-19 during pregnancy and preeclampsia and to determine the effect of these variables on maternal and neonatal morbidity and mortality. Study Design: This was a large, longitudinal, prospective, unmatched diagnosed and not-diagnosed observational study assessing the effect of COVID-19 during pregnancy on mothers and neonates. Two consecutive not-diagnosed women were concomitantly enrolled immediately after each diagnosed woman was identified, at any stage during pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed until hospital discharge using the standardized INTERGROWTH-21st protocols and electronic data management system. A total of 43 institutions in 18 countries contributed to the study sample. The independent association between the 2 entities was quantified with the risk factors known to be associated with preeclampsia analyzed in each group. The outcomes were compared among women with COVID-19 alone, preeclampsia alone, both conditions, and those without either of the 2 conditions. Results: We enrolled 2184 pregnant women; of these, 725 (33.2%) were enrolled in the COVID-19 diagnosed and 1459 (66.8%) in the COVID-19 not-diagnosed groups. Of these women, 123 had preeclampsia of which 59 of 725 (8.1%) were in the COVID-19 diagnosed group and 64 of 1459 (4.4%) were in the not-diagnosed group (risk ratio, 1.86; 95% confidence interval, 1.32–2.61). After adjustment for sociodemographic factors and conditions associated with both COVID-19 and preeclampsia, the risk ratio for preeclampsia remained significant among all women (risk ratio, 1.77; 95% confidence interval, 1.25–2.52) and nulliparous women specifically (risk ratio, 1.89; 95% confidence interval, 1.17–3.05). There was a trend but no statistical significance among parous women (risk ratio, 1.64; 95% confidence interval, 0.99–2.73). The risk ratio for preterm birth for all women diagnosed with COVID-19 and preeclampsia was 4.05 (95% confidence interval, 2.99–5.49) and 6.26 (95% confidence interval, 4.35–9.00) for nulliparous women. Compared with women with neither condition diagnosed, the composite adverse perinatal outcome showed a stepwise increase in the risk ratio for COVID-19 without preeclampsia, preeclampsia without COVID-19, and COVID-19 with preeclampsia (risk ratio, 2.16; 95% confidence interval, 1.63–2.86; risk ratio, 2.53; 95% confidence interval, 1.44–4.45; and risk ratio, 2.84; 95% confidence interval, 1.67–4.82, respectively). Similar findings were found for the composite adverse maternal outcome with risk ratios of 1.76 (95% confidence interval, 1.32–2.35), 2.07 (95% confidence interval, 1.20–3.57), and 2.77 (95% confidence interval, 1.66–4.63). The association between COVID-19 and gestational hypertension and the direction of the effects on preterm birth and adverse perinatal and maternal outcomes, were similar to preeclampsia, but confined to nulliparous women with lower risk ratios. Conclusion: COVID-19 during pregnancy is strongly associated with preeclampsia, especially among nulliparous women. This association is independent of any risk factors and preexisting conditions. COVID-19 severity does not seem to be a factor in this association. Both conditions are associated independently of and in an additive fashion with preterm birth, severe perinatal morbidity and mortality, and adverse maternal outcomes. Women with preeclampsia should be considered a particularly vulnerable group with regard to the risks posed by COVID-19

Association between fetal abdominal growth trajectories, maternal metabolite signatures early in pregnancy, and childhood growth and adiposity : prospective observational multinational INTERBIO-21st fetal study

Background Obesity predominantly affects populations in high-income countries and those countries facing epidemiological transition. The risk of childhood obesity is increased among infants who had overweight or obesity at birth, but in low-resource settings one in five infants are born small for gestational age. We aimed to study the relationships between: (1) maternal metabolite signatures; (2) fetal abdominal growth; and (3) postnatal growth, adiposity, and neurodevelopment. Methods In the prospective, multinational, observational INTERBIO-21st fetal study, conducted in maternity units in Pelotas (Brazil), Nairobi (Kenya), Karachi (Pakistan), Soweto (South Africa), Mae Sot (Thailand), and Oxford (UK), we enrolled women (≥18 years, with a BMI of less than 35 kg/m2, natural conception, and a singleton pregnancy) who initiated antenatal care before 14 weeks’ gestation. Ultrasound scans were performed every 5±1 weeks until delivery to measure fetal growth and feto–placental blood flow, and we used finite mixture models to derive growth trajectories of abdominal circumference. The infants’ health, growth, and development were monitored from birth to age 2 years. Early pregnancy maternal blood and umbilical cord venous blood samples were collected for untargeted metabolomic analysis. Findings From Feb 8, 2012, to Nov 30, 2019, we enrolled 3598 pregnant women and followed up their infants to 2 years of age. We identified four ultrasound-derived trajectories of fetal abdominal circumference growth that accelerated or decelerated within a crucial 20–25 week gestational age window: faltering growth, early accelerating growth, late accelerating growth, and median growth tracking. These distinct phenotypes had matching feto–placental blood flow patterns throughout pregnancy, and different growth, adiposity, vision, and neurodevelopment outcomes in early childhood. There were 709 maternal metabolites with positive effect for the faltering growth phenotype and 54 for the early accelerating growth phenotype; 31 maternal metabolites had a negative effect for the faltering growth phenotype and 76 for the early accelerating growth phenotype. Metabolites associated with the faltering growth phenotype had statistically significant odds ratios close to 1·5 (ie, suggesting upregulation of metabolic pathways of impaired fetal growth). The metabolites had a reciprocal relationship with the early accelerating growth phenotype, with statistically significant odds ratios close to 0.6 (ie, suggesting downregulation of fetal growth acceleration). The maternal metabolite signatures included 5-hydroxy-eicosatetraenoic acid, and 11 phosphatidylcholines linked to oxylipin or saturated fatty acid sidechains. The fungicide, chlorothalonil, was highly abundant in the early accelerating growth phenotype group. Interpretation Early pregnancy lipid biology associated with fetal abdominal growth trajectories is an indicator of patterns of growth, adiposity, vision, and neurodevelopment up to the age of 2 years. Our findings could contribute to the earlier identification of infants at risk of obesity. Funding Bill & Melinda Gates Foundation

Association Between Preterm-Birth Phenotypes and Differential Morbidity, Growth, and Neurodevelopment at Age 2 Years: Results From the INTERBIO-21st Newborn Study.

Importance: The etiologic complexities of preterm birth remain inadequately understood, which may impede the development of better preventative and treatment measures. Objective: To examine the association between specific preterm-birth phenotypes and clinical, growth, and neurodevelopmental differences among preterm newborns compared with term newborns up to age 2 years. Design, Setting, and Participants: The INTERBIO-21st study included a cohort of preterm and term newborn singletons enrolled between March 2012 and June 2018 from maternity hospitals in 6 countries worldwide who were followed up from birth to age 2 years. All pregnancies were dated by ultrasonography. Data were analyzed from November 2019 to October 2020. Exposures/Interventions: Preterm-birth phenotypes. Main Outcomes and Measures: Infant size, health, nutrition, and World Health Organization motor development milestones assessed at ages 1 and 2 years; neurodevelopment evaluated at age 2 years using the INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) tool. Results: A total of 6529 infants (3312 boys [50.7%]) were included in the analysis. Of those, 1381 were preterm births (mean [SD] gestational age at birth, 34.4 [0.1] weeks; 5148 were term births (mean [SD] gestational age at birth, 39.4 [0] weeks). Among 1381 preterm newborns, 8 phenotypes were identified: no main maternal, fetal, or placental condition detected (485 infants [35.1%]); infections (289 infants [20.9%]); preeclampsia (162 infants [11.7%]); fetal distress (131 infants [9.5%]); intrauterine growth restriction (110 infants [8.0%]); severe maternal disease (85 infants [6.2%]); bleeding (71 infants [5.1%]); and congenital anomaly (48 infants [3.5%]). For all phenotypes, a previous preterm birth was a risk factor for recurrence. Each phenotype displayed differences in neonatal morbidity and infant outcomes. For example, infants with the no main condition detected phenotype had low neonatal morbidity but increased morbidity and hospitalization incidence at age 1 year (odds ratio [OR], 2.2; 95% CI, 1.8-2.7). Compared with term newborns, the highest risk of scoring lower than the 10th centile of INTER-NDA normative values was observed in the fine motor development domain among newborns with the fetal distress (OR, 10.6; 95% CI, 5.1-22.2) phenotype. Conclusions and Relevance: Results of this study suggest that phenotypic classification may provide a better understanding of the etiologic factors and mechanisms associated with preterm birth than continuing to consider it an exclusively time-based entity