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Objectives To investigate associations between number of children and partnership with depressive symptoms among older Europeans and assess whether associations are greater in Eastern than Western countries. We further analyze whether associations are mediated by provision and receipt of emotional and financial support. Methods Using cross-sectional data for five Eastern (Bulgaria, Czech Republic, Georgia, Romania, and Russia) and four Western European countries (Belgium, France, Norway, and Sweden) (n = 15,352), we investigated variation in depressive symptoms using linear regression. We fitted conditional change score models for depressive symptoms using longitudinal data for four countries (Bulgaria, Czech Republic, Georgia, and France) (n = 3,978). Results Unpartnered women and men had more depressive symptoms than the partnered. In Eastern, but not Western, European countries childlessness and having one compared with two children were associated with more depressive symptoms. Formal tests indicated that partnership and number of children were more strongly associated with depressive symptoms in Eastern than Western Europe. Discussion Availability of close family is more strongly associated with older people's depressive symptoms in Eastern than Western Europe. The collapse of previous state supports and greater economic stress in Eastern Europe may mean that having a partner and children has a greater psychological impact than in Western countries. [ABSTRACT FROM AUTHOR]

An essay is presented on the influence of American poet Anne Sexton on the poetry of American poet Sylvia Plath. It traces Sexton's influence on Plath by citing several of her poems including many of Plath's final poems such as "Ariel," "Daddy," and "Lady Lazarus." The author also explores some of their writings having similarities that became famous.

Lilian Vaughan Morgan was an important geneticist of the first part of the 20th century. She discovered both the attached-X and closed-X chromosomes as part of her extensive research on the X chromosome of . She received A.B and M.S. degrees in Biology from Bryn Mawr College and became an independent investigator in the 1890s at the Marine Biological Laboratory, Woods Hole, Massachusetts. Although her research at the turn of the century was in embryology, she made the successful transition to genetics. In 1904 she married T. H. Morgan, raised four children, managed the Morgan household, and when the children were grown resumed full time research. She always worked independently, and in her lifetime published 16 single author papers. [ABSTRACT FROM PUBLISHER]

Related Article: This is a corrected version. See correction statement: http://publichealth.jmir.org/2019/3/e15902/ Background: Annually, there are approximately 25 million unsafe abortions, and this remains a leading cause of maternal morbidity and mortality. In settings where abortion is restricted, women are increasingly able to self-manage abortions by purchasing abortion medications such as misoprostol and mifepristone (RU-486) from pharmacies or other drug sellers. Better availability of these drugs has been shown to be associated with reductions in complications from unsafe abortions. In Bangladesh, abortion is restricted; however, menstrual regulation (MR) was introduced in the 1970s as an interim method of preventing pregnancy. Pharmacy provision of medications for MR is widespread, but customers purchasing these drugs from pharmacies often do not have access to quality information on dosage and potential complications. Objective: This study aimed to describe a call center intervention in Bangladesh, and assess call center use over time and how this changed when a new MR product (combined mifepristone-misoprostol) was introduced into the market. Methods: In 2010, Marie Stopes Bangladesh established a care provider–assisted call center to reduce potential harm from self-administration of MR medications. The call center number was advertised widely in pharmacies and on MR product packaging. We conducted a secondary analysis of routine data collected by call center workers between July 2012 and August 2016. We investigated the reported types of callers, the reason for call, and reported usage of MR products before and after November 2014. We used an interrupted time series (ITS) analysis to formally assess levels of change in caller characteristics and reasons for calling. Results: Over the 4-year period, 287,095 calls about MR were received and the number of users steadily increased over time. The most common callers (of 287,042 callers) were MR users (67,438, 23.49%), their husbands (65,999, 22.99%), pharmacy workers (65,828, 22.93%), and village doctors (56,036, 19.52%). Most MR calls were about misoprostol, but after November 2014, a growing proportion of calls were about the mifepristone-misoprostol regimen. The most common reasons (of 287,042 reasons) for calling were to obtain information about the regimen (208,605, 72.66%), to obtain information about side effects (208,267, 72.54%), or to report side effects (49,930, 17.39%). The ITS analyses showed that after November 2014, an increasing number of calls were from MR users who had taken the complete regimen (P =.02 and who were calling to discuss reported side effects (P =.01) and pain medication (P =.01), and there were fewer calls asking about dosages (P <.001). Conclusions: The high call volume suggests that this call center intervention addressed an unmet demand for information about MR medications from both MR users and health care providers. Call center interventions may improve the quality of information available by providing information directly to MR users and drug sellers, and thus reducing the potential harm from self-management of MR medications. [ABSTRACT FROM AUTHOR]

Background: Despite persistent concerns about only children's disadvantage relative to individuals with siblings, existing health-related evidence is inconsistent. Recent evidence from Nordic countries about only children having poorer health outcomes may not apply elsewhere because selection processes differ across contexts. We investigate the midlife health of only children in the UK where one-child families tend to be socio-economically advantaged relative to large families., Methods: Using the 1946, 1958 and 1970 British birth cohort studies, we examine various biomarkers and self-reported measures of chronic disease by sibship size when respondents are aged in their mid-40s, mid-50s and mid-60s. We estimate separate linear probability models for each cohort, age and outcome, adjusting for childhood and early adulthood circumstances., Results: We found no evidence of only children differing from those with one, two or three or more siblings, at any age, in any of the cohorts, on: heart problems, hypertension, high triglycerides, high glycated haemoglobin or high C-reactive protein. However, compared with only children, the probability for cancer (0.019, 95% confidence interval [CI]: 0.002, 0.035; age 46/1970) and poor general health (0.060, CI: 0.015, 0.127; age 55/1958; and 0.110, CI: 0.052, 0.168; age 63/1946) was higher among those with three or more siblings., Conclusions: There is no consistent pattern of only child health disadvantage for midlife chronic disease outcomes across ages or cohorts in the UK. Research should focus on better understanding how sibship size differentials are contingent on context., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Question: Pseudomonas aeruginosa ( Pa ) is a common pathogen that contributes to progressive lung disease in Cystic Fibrosis (CF). Genetic factors other than CF-causing CFTR variations contribute approximately 85% of the variation in chronic Pa infection age in CF according to twin studies, but the susceptibility loci remain unknown. Our objective is to advance understanding of the genetic basis of host susceptibility to Pa infection., Materials and Methods: We conducted a genome-wide association study (GWAS) of chronic Pa infection age in 1037 Canadians with CF. We subsequently assessed the genetic correlation between chronic Pa infection age and lung function through polygenic risk score (PRS) analysis and inferred their causal relationship through bi-directional Mendelian Randomization analysis., Results: Two novel genome-wide significant loci with lead SNPs rs62369766 (chr5p12; p-value= 1.98 ×10 -8 ) and rs927553 (chr13q12.12; p-value= 1.91 × 10 -8 ) were associated with chronic Pa infection age. The rs62369766 locus was validated using an independent French cohort (N=501). Furthermore, PRS constructed from CF lung function-associated SNPs was significantly associated with chronic Pa infection age (p-value=0.002). Finally, our analysis presented evidence for a causal effect of lung function on the chronic Pa infection age (Beta=0.782 years, p-value= 4.24 × 10 -4 ). In the reverse direction, we observed a moderate effect (Beta=0.002, p-value=0.012)., Conclusions: We identified two novel loci that are associated with chronic Pa infection age in individuals with CF. Additionally, we provided evidence of common genetic contributors and a potential causal relationship between Pa infection susceptibility and lung function in CF. Therapeutics targeting these genetic factors may delay the onset of chronic infections which accounts for significant remaining morbidity in CF., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Antibacterial resistance (ABR) is a major public health threat. An important accelerating factor is treatment-seeking behaviour, including inappropriate antibiotic (AB) use. In many low- and middle-income countries (LMICs) this includes taking ABs with and without prescription sourced from various providers, including health facilities and community drug sellers. However, investigations of complex treatment-seeking, AB use and drug resistance in LMICs are scarce. The Holistic Approach to Unravel Antibacterial Resistance in East Africa (HATUA) Consortium collected questionnaire and microbiological data from adult outpatients with urinary tract infection (UTI)-like symptoms presenting at healthcare facilities in Kenya, Tanzania and Uganda. Using data from 6,388 patients, we analysed patterns of self-reported treatment seeking behaviours ('patient pathways') using process mining and single-channel sequence analysis. Among those with microbiologically confirmed UTI (n = 1,946), we used logistic regression to assess the relationship between treatment seeking behaviour, AB use, and the likelihood of having a multi-drug resistant (MDR) UTI. The most common treatment pathway for UTI-like symptoms in this sample involved attending health facilities, rather than other providers like drug sellers. Patients from sites in Tanzania and Uganda, where over 50% of patients had an MDR UTI, were more likely to report treatment failures, and have repeat visits to providers than those from Kenyan sites, where MDR UTI proportions were lower (33%). There was no strong or consistent relationship between individual AB use and likelihood of MDR UTI, after accounting for country context. The results highlight the hurdles East African patients face in accessing effective UTI care. These challenges are exacerbated by high rates of MDR UTI, suggesting a vicious cycle of failed treatment attempts and sustained selection for drug resistance. Whilst individual AB use may contribute to the risk of MDR UTI, our data show that factors related to context are stronger drivers of variations in ABR., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sado et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: There is still little empirical evidence on how the outbreak of coronavirus disease 2019 (COVID-19) and associated regulations may have disrupted care-seeking for non-COVID-19 conditions or affected antibiotic behaviours in low- and middle-income countries (LMICs). We aimed to investigate the differences in treatment-seeking behaviours and antibiotic use for urinary tract infection (UTI)-like symptoms before and during the pandemic at recruitment sites in two East African countries with different COVID-19 control policies: Mbarara, Uganda and Mwanza, Tanzania., Methods: In this repeated cross-sectional study, we used data from outpatients (pregnant adolescents aged >14 and adults aged >18) with UTI-like symptoms who visited health facilities in Mwanza, Tanzania and Mbarara, Uganda. We assessed the prevalence of self-reported behaviours (delays in care-seeking, providers visited, antibiotics taken) at three different time points, labelled as 'pre-COVID-19 phase' (February 2019 to February 2020), 'COVID-19 phase 1' (March 2020 to April 2020), and 'COVID-19 phase 2' (July 2021 to February 2022)., Results: In both study sites, delays in care-seeking were less common during the pandemic than they were in the pre-COVID phase. Patients in Mwanza, Tanzania had shorter care-seeking pathways during the pandemic compared to before it, but this difference was not observed in Mbarara, Uganda. Health centres were the dominant sources of antibiotics in both settings. Over time, reported antibiotic use for UTI-like symptoms became more common in both settings. During the COVID-19 phases, there was a significant increase in self-reported use of antibiotics like metronidazole (<30% in the pre-COVID-19 phase to 40% in COVID phase 2) and doxycycline (30% in the pre-COVID-19 phase to 55% in COVID phase 2) that were not recommended for treating UTI-like symptoms in the National Treatment Guidelines in Mbarara, Uganda., Conclusions: There was no clear evidence that patients with UTI-like symptoms attending health care facilities had longer or more complex treatment pathways despite strict government-led interventions related to COVID-19. However, antibiotic use increased over time, including some antibiotics not recommended for treating UTI, which has implications for future antimicrobial resistance., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Background: Evidence-based empirical antibiotic prescribing requires knowledge of local antimicrobial resistance patterns. The spectrum of pathogens and their susceptibility strongly influences guidelines for empirical therapies for urinary tract infections (UTI) management., Objective: This study aimed to determine the prevalence of UTI causative bacteria and their corresponding antibiotic resistance profiles in three counties of Kenya. Such data could be used to determine the optimal empirical therapy., Methods: In this cross-sectional study, urine samples were collected from patients who presented with symptoms suggestive of UTI in the following healthcare facilities; Kenyatta National Hospital, Kiambu Hospital, Mbagathi, Makueni, Nanyuki, Centre for Microbiology Research, and Mukuru Health Centres. Urine cultures were done on Cystine Lactose Electrolyte Deficient (CLED) to isolate UTI bacterial etiologies, while antibiotic sensitivity testing was done using the Kirby-Bauer disk diffusion using CLSI guidelines and interpretive criteria., Results: A total of 1,027(54%) uropathogens were isolated from the urine samples of 1898 participants. Staphylococcus spp. and Escherichia coli were the main uropathogens at 37.6% and 30.9%, respectively. The percentage resistance to commonly used drugs for the treatment of UTI were as follows: trimethoprim (64%), sulfamethoxazole (57%), nalidixic acid(57%), ciprofloxacin (27%), amoxicillin-clavulanic acid (5%), and nitrofurantoin (9%) and cefixime (9%). Resistance rates to broad-spectrum antimicrobials, such as ceftazidime, gentamicin, and ceftriaxone, were 15%, 14%, and 11%, respectively. Additionally, the proportion of Multidrug-resistant (MDR) bacteria was 66%., Conclusion: High resistance rates toward fluoroquinolones, sulfamethoxazole, and trimethoprim were reported. These antibiotics are commonly used drugs as they are inexpensive and readily available. Based on these findings, more robust standardised surveillance is needed to confirm the patterns observed while recognising the potential impact of sampling biases on observed resistance rates., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2023 Kiiru et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Phasing of heterozygous alleles is critical for interpretation of cis -effects of disease-relevant variation. We sequenced 477 individuals with cystic fibrosis (CF) using linked-read sequencing, which display an average phase block N50 of 4.39 Mb. We use these samples to construct a graph representation of CFTR haplotypes, demonstrating its utility for understanding complex CF alleles. These are visualized in a Web app, CFTbaRcodes, that enables interactive exploration of CFTR haplotypes present in this cohort. We perform fine-mapping and phasing of the chr7q35 trypsinogen locus associated with CF meconium ileus, an intestinal obstruction at birth associated with more severe CF outcomes and pancreatic disease. A 20-kb deletion polymorphism and a PRSS2 missense variant p.Thr8Ile (rs62473563) are shown to independently contribute to meconium ileus risk (p = 0.0028, p = 0.011, respectively) and are PRSS2 pancreas eQTLs (p = 9.5 × 10 -7 and p = 1.4 × 10 -4 , respectively), suggesting the mechanism by which these polymorphisms contribute to CF. The phase information from linked reads provides a putative causal explanation for variation at a CF-relevant locus, which also has implications for the genetic basis of non-CF pancreatitis, to which this locus has been reported to contribute., Competing Interests: D.M.-C. received an honorarium for teaching module development for Vertex Pharmaceuticals. N.M. is doing contract research trials for Vertex Phaemaceuticals and Abbvie. A.L.S. has received speaking fees for educational programs sponsored by Vertex Pharmaceuticals. B.S.Q. has received speaker fees from Vertex Pharmaceuticals and has served as site principal investigator for several Vertex-sponsored clinical trials. W.M.L. is a study investigator for Vertex Pharmaceuticals. E.T. and F.R. act as consultants for Vertex Pharmaceuticals. M.S. participated in Vertex clinical trials and received payment for education modules. S.M., A.C., J.G., F.L., B.T., W.W.L.S., J.W., Z.W., R.V.P., K.K., A.H., N.P., J.A., C.W., G.C.M., S.B., D.A., E.B., C.B., M.C., A.P., M.P., R.V.W., D.H., M.J.S., E.T., P.W., L.S., F.R., and L.J.S. declare no competing interests., (© 2022 The Authors.)

Introduction: Antimicrobial resistance (AMR) is a global health threat that requires urgent research using a multidisciplinary approach. The biological drivers of AMR are well understood, but factors related to treatment seeking and the social contexts of antibiotic (AB) use behaviours are less understood. Here we describe the Holistic Approach to Unravel Antibacterial Resistance in East Africa, a multicentre consortium that investigates the diverse drivers of drug resistance in urinary tract infections (UTIs) in East Africa., Methods and Analysis: This study will take place in Uganda, Kenya and Tanzania. We will conduct geospatial mapping of AB sellers, and conduct mystery client studies and in-depth interviews (IDIs) with drug sellers to investigate AB provision practices. In parallel, we will conduct IDIs with doctors, alongside community focus groups. Clinically diagnosed patients with UTI will be recruited from healthcare centres, provide urine samples and complete a questionnaire capturing retrospective treatment pathways, sociodemographic characteristics, attitudes and knowledge. Bacterial isolates from urine and stool samples will be subject to culture and antibiotic sensitivity testing. Genomic DNA from bacterial isolates will be extracted with a subset being sequenced. A follow-up household interview will be conducted with 1800 UTI-positive patients, where further environmental samples will be collected. A subsample of patients will be interviewed using qualitative tools. Questionnaire data, microbiological analysis and qualitative data will be linked at the individual level. Quantitative data will be analysed using statistical modelling, including Bayesian network analysis, and all forms of qualitative data analysed through iterative thematic content analysis., Ethics and Dissemination: Approvals have been obtained from all national and local ethical review bodies in East Africa and the UK. Results will be disseminated in communities, with local and global policy stakeholders, and in academic circles. They will have great potential to inform policy, improve clinical practice and build regional pathogen surveillance capacity., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Objectives: To prospectively study infants with an inconclusive diagnosis of cystic fibrosis (CF) identified by newborn screening (NBS; "CF screen positive, inconclusive diagnosis" [CFSPID]) for disease manifestations., Methods: Infants with CFSPID and CF based on NBS from 8 CF centers were prospectively evaluated and monitored. Genotype, phenotype, repeat sweat test, serum trypsinogen, and microbiology data were compared between subjects with CF and CFSPID and between subjects with CFSPID who did (CFSPID→CF) and did not (CFSPID→CFSPID) fulfill the criteria for CF during the first 3 years of life., Results: Eighty-two subjects with CFSPID and 80 subjects with CF were enrolled. The ratio of CFSPID to CF ranged from 1:1.4 to 1:2.9 in different centers. CFTR mutation rates did not differ between groups; 96% of subjects with CFSPID and 93% of subjects with CF had 2 mutations. Subjects with CFSPID had significantly lower NBS immunoreactive trypsinogen (median [interquartile range]:77 [61-106] vs 144 [105-199] μg/L; P < .0001) than did subjects with CF. Pseudomonas aeruginosa and Stenotrophomonas maltophilia were isolated in 12% and 5%, respectively, of subjects with CFSPID. CF was diagnosed in 9 of 82 (11%) subjects with CFSPID (genotype and abnormal sweat chloride = 3; genotype alone = 4; abnormal sweat chloride only = 2). Sweat chloride was abnormal in CFSPID→CF patients at a mean (SD) age of 21.3 (13.8) months. CFSPID→CF patients had significantly higher serial sweat chloride (P < .0001) and serum trypsinogen (P = .009) levels than did CFSPID→CFSPID patients., Conclusions: A proportion of infants with CFSPID will be diagnosed with CF within the first 3 years. These findings underscore the need for clinical monitoring, repeat sweat testing at age 2 to 3 years, and extensive genotyping., (Copyright © 2015 by the American Academy of Pediatrics.)

Objective: To determine the value of monitoring blood pressure by quantifying the probability that observed changes in blood pressure reflect true changes., Design: Analysis of blood pressure measurements of patients in the perindopril protection against recurrent stroke study (PROGRESS)., Setting: Randomised placebo controlled trial carried out in 172 centres in Asia, Australasia, and Europe., Participants: 1709 patients with history of stroke or transient ischaemic attack randomised to fixed doses of perindopril and indapamide. Measurements Mean of two blood pressure measurements in patients receiving treatment recorded to the nearest 2 mm Hg with a standard mercury sphygmomanometer at baseline and then at three months, six months, nine months, and 15 months and then every six months to 33 months., Results: There was no change in the mean blood pressure of the cohort during the 33 month follow-up. Six months after blood pressure was stabilised on treatment, if systolic blood pressure was measured as having increased by >10 mm Hg, six of those measurements would be false positives for every true increase of >or=10 mm Hg. The corresponding value for an increase of 20 mm Hg was over 200. Values for 5 mm Hg and 10 mm Hg increases in diastolic blood pressure were 3.5 and 39, respectively. The likelihood that observed increases in blood pressure reflected true increases rose with the time between measurements such that the ratio of true positives to false positives reached parity at 21 months., Conclusions: Usual clinical approaches to the monitoring of patients taking drugs to lower blood pressure have a low probability of yielding reliable information about true changes in blood pressure. Evidence based guidelines for monitoring treatment response are urgently required to guide clinical practice. Trial registration Australia and New Zealand Clinical Trial Registry.