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ABSTRACT In this column, the author describes the vaginal birth of her twin daughters. Despite impending complications in the last weeks of her pregnancy that might have required a cesarean, this mother was committed to doing everything possible to give birth naturally. With the support of her husband as well as the obstetrician and the nurse, she was able to give birth to her daughters vaginally.

Cable bacteria are centimeter-long filamentous bacteria that conduct electrons via internal wires, thus coupling sulfide oxidation in deeper, anoxic sediment with oxygen reduction in surface sediment. This activity induces geochemical changes in the sediment, and other bacterial groups appear to benefit from the electrical connection to oxygen. Here, we report that diverse bacteria swim in a tight flock around the anoxic part of oxygen-respiring cable bacteria and disperse immediately when the connection to oxygen is disrupted (by cutting the cable bacteria with a laser). Raman microscopy shows that flocking bacteria are more oxidized when closer to the cable bacteria, but physical contact seems to be rare and brief, which suggests potential transfer of electrons via unidentified soluble intermediates. Metagenomic analysis indicates that most of the flocking bacteria appear to be aerobes, including organotrophs, sulfide oxidizers, and possibly iron oxidizers, which might transfer electrons to cable bacteria for respiration. The association and close interaction with such diverse partners might explain how oxygen via cable bacteria can affect microbial communities and processes far into anoxic environments. Cable bacteria are centimeter-long filamentous microbes that conduct electrons via internal wires, thus coupling sulfide oxidation between sediment layers. Here, Bjerg et al. show that the anoxic part of oxygen-respiring cable bacteria attracts swarms of other bacteria, which appear to transfer electrons to cable bacteria via soluble metabolites.

Research suggests that economic declines contribute to mortality risks from suicide and drug poisoning, but how the economy impacts individuals’ risks of these deaths has been challenging to specify. Building on recent theoretical advances, we investigate how adolescent occupational expectations and preparation contribute to suicide and drug poisoning deaths in a shifting economy. We use High School and Beyond data linked to adult mortality records for men that were exposed to a decline in labor market share and wages in predominantly blue-collar occupations during early adulthood. We find that adolescent men who expected these occupations had increased risks of suicide and drug poisoning death as adults net of educational and occupational attainment in early adulthood. Family background and occupational preparation are risk factors for death by drug poisoning but not suicide. Our findings improve our understanding of how labor market uncertainty shapes individuals’ vulnerability to suicide and drug poisoning death.

Indoor residual spraying (IRS) is an important part of malaria control. There is a growing list of insecticide classes; pyrethroids remain the principal insecticide used in bednets but recently, novel non-pyrethroid IRS products, with contrasting impacts, have been introduced. There is an urgent need to better assess product efficacy to help decision makers choose effective and relevant tools for mosquito control. Here we use experimental hut trial data to characterise the entomological efficacy of widely-used, novel IRS insecticides. We quantify their impact against pyrethroid-resistant mosquitoes and use a Plasmodium falciparum transmission model to predict the public health impact of different IRS insecticides. We report that long-lasting IRS formulations substantially reduce malaria, though their benefit over cheaper, shorter-lived formulations depends on local factors including bednet use, seasonality, endemicity and pyrethroid resistance status of local mosquito populations. We provide a framework to help decision makers evaluate IRS product effectiveness. Indoor residual spraying is a commonly used method for mosquito, and malaria, control and there are a number of available insecticides that are available for this. Here, the authors evaluate the efficacy of widely-used and novel insecticides against pyrethroid-resistant mosquitoes.

In Fuchs endothelial corneal dystrophy (FECD), mitochondrial and oxidative stresses in corneal endothelial cells (HCEnCs) contribute to cell demise and disease progression. FECD is more common in women than men, but the basis for this observation is poorly understood. To understand the sex disparity in FECD prevalence, we studied the effects of the sex hormone 17-β estradiol (E2) on growth, oxidative stress, and metabolism in primary cultures of HCEnCs grown under physiologic ([O 2 ] 2.5 ) and hyperoxic ([O 2 ] A ) conditions. We hypothesized that E2 would counter the damage of oxidative stress generated at [O 2 ] A . HCEnCs were treated with or without E2 (10 nM) for 7–10 days under both conditions. Treatment with E2 did not significantly alter HCEnC density, viability, ROS levels, oxidative DNA damage, oxygen consumption rates, or extracellular acidification rates in either condition. E2 disrupted mitochondrial morphology in HCEnCs solely from female donors in the [O 2 ] A condition. ATP levels were significantly higher at [O 2 ] 2.5 than at [O 2 ] A in HCEnCs from female donors only, but were not affected by E2. Our findings demonstrate the resilience of HCEnCs against hyperoxic stress. The effects of hyperoxia and E2 on HCEnCs from female donors suggest cell sex-specific mechanisms of toxicity and hormonal influences.

Background: Increased posterior tibial slope (PTS) is a risk factor for knee pathology. Accurate measurement of PTS is predicated on a quality lateral knee radiograph; however, little is known about how the quality of the radiograph affects the measured PTS. Purposes: To (1) describe a method for measuring malalignment on lateral knee radiographs, (2) assess the effects of malpositioning of the knee on radiographic measures of malalignment, and (3) determine any correlations between malalignment and the measured PTS. Study Design: Descriptive laboratory study. Methods: Using a setup similar to that of a standard radiology suite, 25 sets of radiographs were taken using 5 sawbone models. Each set included a true lateral view and separate malpositioned radiographs at 5°, 10°, and 15° of adduction, abduction, internal rotation, and external rotation. Malalignment for each radiograph was quantified as the anterior-posterior distance (APD) and proximal-distal distance (PDD) between femoral condyles. The medial PTS was measured in duplicate, and the interrater reliability was calculated. Results: The interrater reliability was excellent, with intraclass correlation coefficients of 0.92, 0.91, and 0.96 for the APD, PDD, and PTS, respectively. Malrotation significantly affected the APD (P < .001), with a mean change of 5.6 mm per 5°. Malpositioning in abduction/adduction significantly affected the PDD (P < .001), with a mean change of 5.1 mm per 5°. There was no significant impact of rotation or APD on the PTS. Abduction/adduction did affect the PTS (P < .001) above a threshold of 5° of malpositioning. The PTS decreased as the PDD increased, moving from adduction to abduction (R 2 = 0.5687). Conclusion: The measured PTS was more sensitive to malpositioning by abduction/adduction than by malrotation. Malrotation affected the APD, while abduction/adduction affected the PDD. Thus, the accuracy of the measured PTS was compromised more by poorly aligned distal femoral condyles than it was by poorly aligned posterior femoral condyles. Clinical Relevance: To minimize the effects of malpositioning, we recommend utilizing radiographs with a |PDD| of <5 mm and an |APD| of <15 mm when measuring the PTS.

Somatic mutations are a hallmark of tumorigenesis and may be useful for non-invasive diagnosis of cancer. We analyzed whole-genome sequencing data from 2,511 individuals in the Pan-Cancer Analysis of Whole Genomes (PCAWG) study as well as 489 individuals from four prospective cohorts and found distinct regional mutation type-specific frequencies in tissue and cell-free DNA from patients with cancer that were associated with replication timing and other chromatin features. A machine-learning model using genome-wide mutational profiles combined with other features and followed by CT imaging detected >90% of patients with lung cancer, including those with stage I and II disease. The fixed model was validated in an independent cohort, detected patients with cancer earlier than standard approaches and could be used to monitor response to therapy. This approach lays the groundwork for non-invasive cancer detection using genome-wide mutation features that may facilitate cancer screening and monitoring. Somatic mutations are identified from circulating cell-free DNA using a single-molecule-based lowpass whole-genome sequencing method. The regional distribution of mutations can identify a tumor-specific mutational profile in patients with cancer and can be used to monitor patients through treatment.

Deaths from self-injury are increasing. Understanding the sources of risk is important for prevention and treatment. To estimate the risks of suicide and drug poisoning deaths among adult men whose adolescent occupational expectations were not met in adulthood. This cohort study included a sample of men interviewed as part of the High School and Beyond study, a nationally representative study of US high school sophomores and seniors in 1980, who were interviewed every 2 years through 1986; those who were sophomores in 1980 were reinterviewed in 1992. Men who survived to 1992 and reported occupational expectations were included in the present study. Death records prior to 2018 were linked to mortality databases and released in 2019. Data analysis was conducted from May to October 2020. Occupational expectations. Survival or death by suicide, drug poisoning, chronic liver disease, heart disease, cancer, or some other cause, categorized from International Classification of Diseases, Ninth Revision and Tenth Revision codes. Competing risk Fine-Gray survival models regressed cause of death on adolescent occupational expectations and covariates. The 11 680 men in the High School and Beyond cohort study had a median (interquartile range) age of 29 (28-30) years in 1992, when the analysis of their future mortality began. Most men survived until 2015 (11 060 [weighted percentage, 95.0%]). Reported causes of death were suicide (60 [weighted percentage, 0.5%]), drug poisoning (40 [weighted percentage, 0.4%]), chronic liver disease (20 [weighted percentage, 0.2%]), heart disease (130 [weighted percentage, 1.0%]), cancer (100 [weighted percentage, 1.0%]), and other (280 [weighted percentage, 2.0%]). Subhazard ratios for death by suicide and drug poisoning were 2.91 (95% CI, 1.07-7.88; P = .04) and 2.62 (95% CI, 1.15-5.94; P = .02) times higher, respectively, among those who in 1980 expected to hold a subbaccalaureate occupation that later declined in labor market share compared with those with professional occupational expectations. The actual job held by men did not attenuate the hazards of deaths from suicide and drug poisoning. In this cohort study, men whose occupational expectations were not met because of labor market declines were at a higher risk of death from suicide or drug poisoning than men with different occupational expectations. Interventions to mitigate labor market changes should account for individuals' expectational ideals.

Background Clinicians and researchers should consider the expected benefits and potential harms of an intervention. Parenting programmes are a widely used evidence-based intervention for child behaviour problems. However, few data are available on potential negative effects. The aims of this paper were to increase systematic knowledge of adverse event (AE) assessment in parenting programmes and to provide an AE assessment tool. Methods As part of the RISE project (prevention of child mental health problems in South-eastern Europe—adapt, optimise, test and extend parenting for lifelong health), we developed and tested an AE assessment procedure in three sequential studies for parents of children with child behaviour problems aged 2 to 9 years in North Macedonia, Republic of Moldova, and Romania. This paper reports on the development of the assessment tool in phase 1 ( N  = 140), phase 2 ( N  = 835), and the final experiences with using the optimised procedures in phase 3 (multisite randomised controlled trial, N  = 823) in which AEs were assessed before, three times during intervention delivery, and at 1 year follow-up. At each time point, the participants completed a 12-item AE checklist. If moderate-to-severe problems of parent or child were reported, a structured follow-up interview was conducted. Results The response rate on the AE assessment tool increased from 6% (phase 1) to 100% (phase 3) indicating improvement in collecting these data based on the experiences of each phase. Results of the RCT (phase 3) showed generally low (S)AE frequencies with the finally optimised procedure: During the intervention, no serious adverse events (SAE) were registered; at least one AE was reported by 10% (after the first session), 7% (after the third session), and 4% (after the last fifth session) of participants. None of the identified (S)AEs was causally related to the study or intervention. Cost–benefit considerations are needed to determine the best way to ensure participant safety in parenting programmes. Conclusion The applied active AE assessment procedure provides a comprehensive AE assessment tool that can be used by others—with adaptations for the specific context, if needed. Based on our experiences, we outline recommendations for future studies. Trial registration ClinicalTrials.gov, registration number phase 1: NCT03552250; phase 2: NCT03865485, phase 3: NCT04721730 . Registered on 13 January 2021.