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The World Health Organisation (WHO) and others have identified, as a priority, the need to improve antimicrobial stewardship (AMS) interventions as part of the effort to tackle antimicrobial resistance (AMR). An international health partnership model, the Commonwealth Partnerships for Antimicrobial Stewardship (CwPAMS) programme, was established between selected countries in Africa (Ghana, Tanzania, Zambia and Uganda) and the UK to support AMS. This was funded by UK aid under the Fleming Fund and managed by the Commonwealth Pharmacists Association (CPA) and Tropical Health and Education Trust (THET). The primary aims were to develop local AMS teams and generate antimicrobial consumption surveillance data, quality improvement initiatives, infection prevention and control (IPC) and education/training to reduce AMR. Education and training were key components in achieving this, with pharmacists taking a lead role in developing and leading AMS interventions. Pharmacist-led interventions in Ghana improved access to national antimicrobial prescribing guidelines via the CwPAMS mobile app and improved compliance with policy from 18% to 70% initially for patients with pneumonia in one outpatient clinic. Capacity development on AMS and IPC were achieved in both Tanzania and Zambia, and a train-the-trainer model on the local production of alcohol hand rub in Uganda and Zambia. The model of pharmacy health partnerships has been identified as a model with great potential to be used in other low and middle income countries (LMICs) to support tackling AMR.

Abstract Objectives To determine the prevalence of overweight and obesity among patients with type 2 diabetes who are attending diabetes clinics in northern Tanzania. Results In total 227 type 2 diabetic patients attending diabetes clinics were enrolled. Majority of patients 193 (85.0%) were overweight (44.9%) or obese (40.1%). Of them, 65 (33.7%) were overweight/obese after diagnosis of type 2 diabetes. The prevalence of overweight/obesity was significantly higher in female participants than the males [92.2% vs. 69.2%; OR = 5.10; 95% CI 2.22–11.05]. Regarding the region of residence, Kilimanjaro (100.0%) and Arusha (89.8%) regions had significantly highest prevalence of overweight/obesity compared to Tanga region (69.2%) [χ2 = 32.455, P

Metabolic remodelling of the tumour microenvironment is a major mechanism by which cancer cells survive and resist treatment. The pro-oncogenic inflammatory cascade released by adipose tissue promotes oncogenic transformation, proliferation, angiogenesis, metastasis and evasion of apoptosis. STAT3 has emerged as an important mediator of metabolic remodelling. As a downstream effector of adipocytokines and cytokines, its canonical and non-canonical activities affect mitochondrial functioning and cancer metabolism. In this review, we examine the central role played by the crosstalk between the transcriptional and mitochondrial roles of STAT3 to promote survival and further oncogenesis within the tumour microenvironment with a particular focus on adipose-breast cancer interactions.

The National Root Crops Research Institution (NRCRI) Umudike embarked on massive capacity building and extension of technologies of new and improved food forms of cocoyam to rural farmers/women groups from 2005 to date in this country generally and south-east agricultural zone in particular. This study investigated how this training and extension of the technologies has empowered rural women to become entrepreneurs at various levels. A structured interview scheduled, were administered to 120 farmers in 2 agricultural zones of Abia (Ohafia and Umuahia). Data collected were analysed using descriptive and inferential statistics like linear regression model and t-test was used to test the hypothesis. The result revealed that majority of the respondents were married (88%) while 12% were single and were reasonably aware of the technologies. However, on the utilization of the technologies, out of the 5 processing technologies, only 3 had high level of utilization, processing of cocoyam into cake (=3.7) Bread (3.5 and Chin-chin (=3.2). Also a tangible impact was made in the livelihood of the respondents as there was a reasonable difference in income of the respondents after the training. The major challenges associated with the utilization were no extension agents to answer their questions (=3.90) lack of commitment = (Â =3.25 and marketing of product = (=3.17) among others. It is therefore recommended that re-training and provision of market facilities should be intensified to enhance the utilization of the processing technologies and their impact among the respondents.

INTRODUCTION: rotavirus is the leading cause of severe diarrhoea among infants and young children. Each year more than 611 000 children die from rotavirus gastroenteritis, and two million are hospitalized, worldwide. In Kenya, the impact of recent rotavirus vaccinations on morbidities has not been estimated. The study aimed at determining the prevalence and identity of rotavirus strains isolated from rotavirus-associated diarrhoea in vaccinated children presenting with acute gastroenteritis. METHODS: two hundred and ninety eight specimen from children presented at Gertrude Childrens' Hospital from January to June 2012 were tested by EIA (Enzyme-linked Immunosorbent Assay) for rotavirus antigens. Molecular characterization was conducted on rotavirus-positive specimens. Extracted viral RNA was separated by polyacrylamide gel electrophoresis (PAGE) and the specific rotavirus VP4 (P-types) and VP7 (G-types) determined. RESULTS: the prevalence rate of rotavirus was 31.5% (94/298). Of the rotavirus dsRNA, 57 (60.1%) gave visible RNA profiles, 38 (40.4%) assigned long electropherotypes while 19 (20.2%) were short electropherotypes. The strains among the vaccinated were G3P [4], G12P [6], G3P [6], G9P [4], G mixed G9/3P [4] and G1/3P [4]. Specifically, the G genotypes were G9/3 (5.3%), G9 (4.3%), G3 (4.3%), G12 (2.1%) and mixed G1/3 (1.1%). The P genotypes detected were P [4] (5.3%) and P [6] (5.3%). CONCLUSION: the present study demonstrates diversity in circulating genotypes with emergence of genotypes G3, G9, G12 and mixed genotypes G9/3 and recommends that vaccines should be formulated with a broad range of strains to include G9 and G12.

A ovariohisterectomia (OH) eletiva em cadelas é o procedimento mais realizado na cirurgia de pequenos animais. No presente trabalho, foram utilizados três grupos de sete animais (GI, GII e GIII), submetidos a três técnicas de OH eletiva: por celiotomia ("técnica convencional"), por miniceliotomia ("técnica do gancho de Snook"), via cirurgia endoscópica transluminal por orifícios naturais (NOTES) híbrida. Na comparação, foram considerados o tempo de cirurgia, as complicações e dificuldades técnicas trans e pós-operatórias, a avaliação de dor pós-operatória, a quantidade (g) de sangramento cirúrgico estimado, além da determinação de determinados parâmetros vitais, como: frequência cardíaca (FC), frequência respiratória (ƒ), temperatura retal, pressão arterial (média) invasiva (PAI) e a pressão venosa central (PVC). A OH via NOTES vaginal híbrida foi a técnica que apresentou menor escore de desconforto pós-operatório, menor sangramento cirúrgico, porém com maior tempo cirúrgico, comparado com as modalidade convencional e por miniceliotomia.

Background: The importance of tackling economic, social and health-related inequities is increasingly accepted as a core concern for the post-Millennium Development Goal framework. However, there is a global dearth of high-quality, policy-relevant and actionable data on inequities within populations, which means that development solutions seldom focus on the people who need them most. INTREC (INDEPTH Training and Research Centres of Excellence) was established with this concern in mind. It aims to provide training for researchers from the INDEPTH network on associations between health inequities, the social determinants of health (SDH), and health outcomes, and on presenting their findings in a usable form to policy makers. Objective: As part of a baseline situation analysis for INTREC, this paper assesses the current status of SDH training in three of the African INTREC countries – Ghana, Tanzania, and South Africa – as well as the gaps, barriers, and opportunities for training. Methods: SDH-related courses from the three countries were identified through personal knowledge of the researchers, supplemented by snowballing and online searches. Interviews were also conducted with, among others, academics engaged in SDH and public health training in order to provide context and complementary material. Information regarding access to the Internet, as a possible INTREC teaching medium, was gathered in each country through online searches. Results: SDH-relevant training is available, but 1) the number of places available for students is limited; 2) the training tends to be public-health-oriented rather than inclusive of the broader, multi-sectoral issues associated with SDH; and 3) insufficient funding places limitations on both students and on the training institutions themselves, thereby affecting participation and quality. We also identified rapidly expanding Internet connectivity in all three countries, which opens up opportunities for e-learning on SDH, though the current quality of the Internet services remains mixed. Conclusions: SDH training is currently in short supply, and there is a clear role for INTREC to contribute to the training of a critical mass of African researchers on the topic. This work will be accomplished most effectively by building on pre-existing networks, institutions, and methods.

Agnes Binagwaho and colleagues describe how Rwanda achieved country ownership of its HIV programs.

Background A critical need exists for effective electronic tools that facilitate multidisciplinary care for complex patients in patient-centered medical homes. Objective To identify the essential components of a primary care (PC) based electronic care plan (ECP) tool that facilitates coordination of care for complex patients. Methods Three focus groups and nine semi-structured interviews were conducted at an academic PC practice in order to identify the ideal components of an ECP. Results Critical components of an ECP identified included: 1) patient background information, including patient demographics, care team member designation and key patient contacts, 2) user- and patient-centric task management functionalities, 3) a summary of a patient’s care needs linked to the responsible member of the care team and 4) integration with the electronic medical record. We then designed an ECP mockup incorporating these components. Conclusion Our investigation identified key principles that healthcare software developers can integrate into PC and patient-centered ECP tools.

Background The prevalence of allergic diseases in infants, whose parents and siblings do not have allergy, is approximately 10 % and reaches 20–30 % in those with an allergic first-degree relative. Intestinal microbiota may modulate immunologic and inflammatory systemic responses and, thus, influence development of sensitization and allergy. Prebiotics – non-digestible oligosaccharides that stimulate growth of probiotic bacteria – have been reported to modulate immune responses and their supplementation has been proposed as a preventive intervention.Objective The World Allergy Organization (WAO) convened a guideline panel to develop evidence-based recommendations about the use of prebiotics in the prevention of allergy.Methods The WAO guideline panel identified the most relevant clinical questions about the use of prebiotics for the prevention of allergy. We performed a systematic review of randomized controlled trials of prebiotics, and reviewed the evidence about patient values and preferences, and resource requirements (up to January 2015, with an update on July 29, 2015). We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations.Results Based on GRADE evidence to decision frameworks, the WAO guideline panel suggests using prebiotic supplementation in not-exclusively breastfed infants and not using prebiotic supplementation in exclusively breastfed infants. Both recommendations are conditional and based on very low certainty of the evidence. We found no experimental or observational study of prebiotic supplementation in pregnant women or in breastfeeding mothers. Thus, the WAO guideline panel chose not to provide a recommendation about prebiotic supplementation in pregnancy or during breastfeeding, at this time.Conclusions WAO recommendations about prebiotic supplementation for the prevention of allergy are intended to support parents, clinicians and other health care professionals in their decisions whether or not to use prebiotics for the purpose of preventing allergies in healthy, term infants.

Background The prevalence of allergic diseases is approximately 10 % in infants whose parents and siblings do not have allergic diseases and 20–30 % in those with an allergic first-degree relative. Vitamin D is involved in the regulation of the immune system and it may play a role in the development, severity and course of asthma and other allergic diseases.Objective The World Allergy Organization (WAO) convened a guideline panel to develop evidence-based recommendations addressing the use of vitamin D in primary prevention of allergic diseases.Methods Our WAO guideline panel identified the most relevant clinical questions and performed a systematic review of randomized controlled trials and non-randomized studies (NRS), specifically cohort and case-control studies, of vitamin D supplementation for the prevention of allergic diseases. We also reviewed the evidence about values and preferences, and resource requirements (up to January 2015, with an update on January 30, 2016). We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations.Results Having reviewed the currently available evidence, the WAO guideline panel found no support for the hypothesis that vitamin D supplementation reduces the risk of developing allergic diseases in children. The WAO guideline panel suggest not using vitamin D in pregnant women, breastfeeding mothers, or healthy term infants as a means of preventing the development of allergic diseases. This recommendation does not apply to those mothers and infants who have other indications for prophylactic or therapeutic use of vitamin D. The panel’s recommendations are conditional and supported by very low certainty evidence.Conclusions WAO recommendations about vitamin D supplementation for the prevention of allergic diseases support parents, clinicians and other health care professionals in their decisions whether or not to use vitamin D in preventing allergic diseases in healthy, term infants. Keywords: Allergic Diseases, Prevention, Vitamin D, Practice guidelines, GRADE

Background Prevalence of allergic diseases in infants, whose parents and siblings do not have allergy, is approximately 10% and reaches 20–30% in those with an allergic first-degree relative. Intestinal microbiota may modulate immunologic and inflammatory systemic responses and, thus, influence development of sensitization and allergy. Probiotics have been reported to modulate immune responses and their supplementation has been proposed as a preventive intervention.Objective The World Allergy Organization (WAO) convened a guideline panel to develop evidence-based recommendations about the use of probiotics in the prevention of allergy.Methods We identified the most relevant clinical questions and performed a systematic review of randomized controlled trials of probiotics for the prevention of allergy. We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. We searched for and reviewed the evidence about health effects, patient values and preferences, and resource use (up to November 2014). We followed the GRADE evidence-to-decision framework to develop recommendations.Results Currently available evidence does not indicate that probiotic supplementation reduces the risk of developing allergy in children. However, considering all critical outcomes in this context, the WAO guideline panel determined that there is a likely net benefit from using probiotics resulting primarily from prevention of eczema. The WAO guideline panel suggests: a) using probiotics in pregnant women at high risk for having an allergic child; b) using probiotics in women who breastfeed infants at high risk of developing allergy; and c) using probiotics in infants at high risk of developing allergy. All recommendations are conditional and supported by very low quality evidence.Conclusions WAO recommendations about probiotic supplementation for prevention of allergy are intended to support parents, clinicians and other health care professionals in their decisions whether to use probiotics in pregnancy and during breastfeeding, and whether to give them to infants. Keywords: Allergy, Prevention, Probiotics, Practice guidelines, GRADE

OBJECTIVE: To evaluate multimodal MRI of the spinal cord in predicting disease progression and one-year clinical status in amyotrophic lateral sclerosis (ALS) patients. MATERIALS AND METHODS: After a first MRI (MRI1), 29 ALS patients were clinically followed during 12 months; 14/29 patients underwent a second MRI (MRI2) at 11±3 months. Cross-sectional area (CSA) that has been shown to be a marker of lower motor neuron degeneration was measured in cervical and upper thoracic spinal cord from T2-weighted images. Fractional anisotropy (FA), axial/radial/mean diffusivities (λ⊥, λ//, MD) and magnetization transfer ratio (MTR) were measured within the lateral corticospinal tract in the cervical region. Imaging metrics were compared with clinical scales: Revised ALS Functional Rating Scale (ALSFRS-R) and manual muscle testing (MMT) score. RESULTS: At MRI1, CSA correlated significantly (P

Background. Nutritional status is an important determinant of HIV outcomes. Objective. To assess the nutrient intake and nutrient status of HIV seropositive patients attending an AIDS outpatient clinic, to improve the nutritional management of HIV-infected patients. Design. Prospective cohort study. Setting. Comprehensive care clinic in Chulaimbo Sub-District Hospital, Kenya. Subjects. 497 HIV sero-positive adults attending the clinic. Main Outcome Measures. Evaluation of nutrient intake using 24-hour recall, food frequency checklist, and nutrient status using biochemical assessment indicators (haemoglobin, creatinine, serum glutamate pyruvate (SGPT) and mean corpuscular volume (MCV)). Results. Among the 497 patients recruited (M : F sex ratio: 1.4, mean age: 39 years ± 10.5 y), Generally there was inadequate nutrient intake reported among the HIV patients, except iron (10.49 ± 3.49 mg). All the biochemical assessment indicators were within normal range except for haemoglobin 11.2 g/dL (11.4 ± 2.60 male and 11.2 ± 4.25 female). Conclusions. Given its high frequency, malnutrition should be prevented, detected, monitored, and treated from the early stages of HIV infection among patients attending AIDS clinics in order to improve survival and quality of life.

BACKGROUND: Nevirapine (NVP) single-dose is still a widely used antiretroviral prophylaxis for the prevention of vertical HIV-1 transmission in resource-limited settings. However, the main disadvantage of the Non-nucleoside Reverse Transcriptase Inhibitor (NNRTI) NVP is the rapid selection of NVP-resistant virus with negative implications for subsequent NNRTI-based long-term antiretroviral therapy (ART). Here, we analysed the emergence of drug-resistant HIV-1 including minor variants in the early phase after NVP single-dose prophylaxis and the persistence of drug-resistant virus over time. METHODS AND FINDINGS: NVP-resistant HIV-1 harbouring the K103N and/or Y181C resistance mutations in the HIV-1 reverse transcriptase gene was measured from 1 week up to 18 months after NVP single-dose prophylaxis in 29 Ugandan women using allele-specific PCR assays capable of detecting drug-resistant variants representing less than 1% of the whole viral population. In total, drug-resistant HIV-1 was identified in 18/29 (62%) women; rates increased from 18% to 38% and 44% at week 1, 2, 6, respectively, and decreased to 18%, 25%, 13% and 4% at month 3, 6, 12 and 18, respectively. The proportion of NVP-resistant virus of the total viral population was significantly higher in women infected with subtype D (median 40.5%) as compared to subtype A (median 1.3%; p = 0.032, Mann-Whitney U test). 33% of resistant virus was not detectable at week 2 but was for the first time measurable 6-12 weeks after NVP single-dose prophylaxis. Three (10%) women harboured resistant virus in proportions >10% still at month 6. CONCLUSIONS: Current WHO guidelines recommend an additional postnatal intake of AZT and 3TC for one week to avoid NVP resistance formation. Our findings indicate that a 1-week medication might be too short to impede the emergence of NVP resistance in a substantial proportion of women. Furthermore, subsequent NNRTI-based ART should not be started earlier than 12 months after NVP single-dose prophylaxis.

Abstract Background The first mammalian protein histidine phosphatase (PHP) was discovered in the late 90s of the last century. One of the known substrates of PHP is ATP-citrate lyase (ACL), which is responsible - amongst other functions - for providing acetyl-CoA for acetylcholine synthesis in neuronal tissues. It has been shown in previous studies that PHP downregulates the activity of ACL by dephosphorylation. According to this our present work focused on the influence of PHP activity on the acetylcholine level in cholinergic neurons. Results The amount of PHP in SN56 cholinergic neuroblastoma cells was increased after overexpression of PHP by using pIRES2-AcGFP1-PHP as a vector. We demonstrated that PHP overexpression reduced the acetylcholine level and induced cell death. The acetylcholine content of SN56 cells was measured by fast liquid chromatography-tandem mass spectrometry method. Overexpression of the inactive H53A-PHP mutant also induced cell damage, but in a significantly reduced manner. However, this overexpression of the inactive PHP mutant did not change the acetylcholine content of SN56 cells significantly. In contrast, PHP downregulation, performed by RNAi-technique, did not induce cell death, but significantly increased the acetylcholine content in SN56 cells. Conclusions We could show for the first time that PHP downregulation increased the acetylcholine level in SN56 cells. This might be a potential therapeutic strategy for diseases involving cholinergic deficits like Alzheimer's disease.

Abstract Background Pharmacologic treatments are efficacious in reducing post-myocardial infarction (MI) morbidity and mortality. The potential influence of socioeconomic factors on the receipt of pharmacologic therapy has not been systematically examined, even though healthcare utilization likely influences morbidity and mortality post-MI. This study aims to investigate the association between socioeconomic factors and receipt of evidence-based treatments post-MI in a community surveillance setting. Methods We evaluated the association of census tract-level neighborhood household income (nINC) and Medicaid coverage with pharmacologic treatments (aspirin, beta [β]-blockers and angiotensin converting enzyme [ACE] inhibitors; optimal therapy, defined as receipt of two or more treatments) received during hospitalization or at discharge among 9,608 MI events in the ARIC community surveillance study (1993-2002). Prevalence ratios (PR, 95% CI), adjusted for the clustering of hospitalized MI events within census tracts and within patients, were estimated using Poisson regression. Results Seventy-eight percent of patients received optimal therapy. Low nINC was associated with a lower likelihood of receiving β-blockers (0.93, 0.87-0.98) and a higher likelihood of receiving ACE inhibitors (1.13, 1.04-1.22), compared to high nINC. Patients with Medicaid coverage were less likely to receive aspirin (0.92, 0.87-0.98), compared to patients without Medicaid coverage. These findings were independent of other key covariates. Conclusions nINC and Medicaid coverage may be two of several socioeconomic factors influencing the complexities of medical care practice patterns.

Abstract Background Transcription factor 7-like 2 (TCF7L2) has emerged as a consistently replicated susceptibility gene for type 2 diabetes, however, whether the TCF7L2 gene also has similar effects on the retinal microvasculature is less clear. We therefore aimed to investigate the association between the transcription factor 7-like 2 (TCF7L2) rs7903146 polymorphism and retinal microvascular phenotypes in the Atherosclerosis Risk in Communities (ARIC) Study (1993-1995). Methods This was a population-based, cross-sectional study of 10,320 middle-aged African American (n = 2,199) and Caucasian (n = 8,121) men and women selected from four United States communities to examine the association between TCF7L2 rs7903146 polymorphism and retinal microvascular signs (retinopathy, focal arteriolar narrowing, arteriovenous nicking, arteriolar and venular calibers). Photographs on one randomly selected eye were graded for presence of retinal microvascular signs and used to measure retinal vessel calibres. Results After adjusting for age, sex, study center, mean arterial blood pressure, total serum cholesterol, triglycerides, and other covariates, few associations of TCF7L2 rs7903146 and retinal microvascular signs were noted. TCF7L2 rs7903146 T risk allele was significantly associated with focal arteriolar narrowing in Caucasians with hypertension [odds ratio (OR)CT vs. CC (95% CI) = 1.25 (1.09-1.44); ORTT vs. CC = 1.56 (1.18-2.06); P = 0.002] and in Caucasians without diabetes [OR CT vs. CC = 1.18 (1.06-1.32); OR TT vs. CC = 1.40 (1.12, 1.75); P = 0.003]. No significant association of the TCF7L2 rs7903146 polymorphism and retinal vascular signs was noted among African American individuals. Conclusions TCF7L2 rs7903146 is not consistently associated with retinal microvascular signs. However, we report an association between the TCF7L2 rs7903146 polymorphism and focal arteriolar narrowing in Caucasians with hypertension or without diabetes. Further research in other large, population-based studies is needed to replicate these findings.

Abstract Background Arterial diameter and intima-media thickness (IMT) enlargement may each be related to the atherosclerotic process. Their separate or combined enlargement may indicate different arterial phenotypes with different atherosclerosis risk. Methods We investigated cross-sectional (baseline 1987–89: n = 7956) and prospective (median follow-up = 5.9 years: n = 4845) associations between baseline right common carotid artery (RCCA) external diameter and IMT with existing and incident carotid atherosclerotic lesions detected by B-mode ultrasound in any right or left carotid segments. Logistic regression models (unadjusted, adjusted for IMT, or adjusted for IMT and risk factors) were used to relate baseline diameter to existing carotid lesions while comparably adjusted parametric survival models assessed baseline diameter associations with carotid atherosclerosis progression (incident carotid lesions). Four baseline arterial phenotypes were categorized as having 1) neither IMT nor diameter enlarged (reference), 2) isolated IMT thickening, 3) isolated diameter enlargement, and 4) enlargement of both IMT and diameter. The association between these phenotypes and progression to definitive carotid atherosclerotic lesions was assessed over the follow-up period. Results Each standard deviation increment of baseline RCCA diameter was associated with increasing carotid lesion prevalence (unadjusted odds ratio [OR] = 1.54, 95% confidence interval [CI] = 1.47–1.62) and with progression of carotid atherosclerosis (unadjusted hazards ratio (HR) = 1.37, 95% CI = 1.28–1.46); and the associations remained significant even after adjustment for IMT and risk factors (prevalence OR = 1.11, 95% CI = 1.04–1.18; progression HR = 1.11, 95% CI = 1.03–1.19). Controlling for gender, age and race, persons with both RCCA IMT and diameter in the upper 50th percentiles had the greatest risk of progressing to clearly defined carotid atherosclerotic lesions (all HR = 1.71, 95% CI = 1.47–2.0; men HR = 1.88, 95% CI = 1.48–2.39; women HR = 1.59, 95% CI = 1.31–1.95) while RCCA IMT or diameter alone in the upper 50th percentile produced significantly lower estimated risks. Conclusion RCCA IMT and external diameter provide partially overlapping information relating to carotid atherosclerotic lesions. More importantly, the RCCA phenotype of coexistent wall thickening with external diameter enlargement indicates higher atherosclerotic risk than isolated wall thickening or diameter enlargement.

Abstract Background Death certificates are a potential source of sociodemographic data for decedents in epidemiologic research. However, because this information is provided by the next-of-kin or other proxies, there are concerns about validity. Our objective was to assess the agreement of job titles and occupational categories derived from death certificates with that self-reported in mid and later life. Methods Occupation was abstracted from 431 death certificates from North Carolina Atherosclerosis Risk in Communities Study participants who died between 1987 and 2001. Occupations were coded according to 1980 Bureau of Census job titles and then grouped into six 1980 census occupational categories. This information was compared with the self-reported occupation at midlife as reported at the baseline examination (1987–89). We calculated percent agreement using standard methods. Chance-adjusted agreement was assessed by kappa coefficients, with 95% confidence intervals. Results Agreement between death certificate and self-reported job titles was poor (32%), while 67% of occupational categories matched the two sources. Kappa coefficients ranged from 0.53 for technical/sales/administrative jobs to 0.68 for homemakers. Agreement was lower, albeit nonsignificant, for women (kappa = 0.54, 95% Confidence Interval, CI = 0.44–0.63) than men (kappa = 0.62, 95% CI = 0.54–0.69) and for African-Americans (kappa = 0.47, 95% CI = 0.34–0.61) than whites (kappa = 0.63, 95% CI = 0.57–0.69) but varied only slightly by educational attainment. Conclusion While agreement between self- and death certificate reported job titles was poor, agreement between occupational categories was good. This suggests that while death certificates may not be a suitable source of occupational data where classification into specific job titles is essential, in the absence of other data, it is a reasonable source for constructing measures such as occupational SES that are based on grouped occupational data.

Abstract Background Arterial diameters enlarge in response to wall thickening, plaques, and many atherosclerotic risk factors. We hypothesized that right common carotid artery (RCCA) diameter would be independently associated with cardiac disease and improve risk discrimination. Methods In a middle-aged, biracial population (baseline n = 11225), we examined associations between 1 standard deviation increments of baseline RCCA diameter with prevalent myocardial infarction (MI) and incident cardiac events (MI or cardiac death) using logistic regression and Cox proportional hazards models, respectively. Areas under the receiver operator characteristic curve (AUC) were used to estimate model discrimination. Results MI was present in 451 (4%) participants at baseline (1987–89), and incident cardiac events occurred among 646 (6%) others through 1999. Adjusting for IMT, RCCA diameter was associated with prevalent MI (female OR = 2.0, 95%CI = 1.61–2.49; male OR = 1.16, 95% CI = 1.04–1.30) and incident cardiac events (female HR = 1.75, 95% CI = 1.51–2.02; male HR = 1.27, 95% CI = 1.15–1.40). Associations were attenuated but persisted after adjustment for risk factors (not including IMT) (prevalent MI: female OR = 1.73, 95% CI = 1.40–2.14; male OR = 1.14, 95% CI = 1.02–1.28, and incident cardiac events: female HR = 1.26, 95% CI = 1.08–1.48; male HR = 1.19, 95% CI = 1.08–1.32). After additional adjustment for IMT, diameter was associated with incident cardiac events in women (HR = 1.18, 95% CI = 1.00–1.40) and men (HR = 1.17, 95% CI = 1.06–1.29), and with prevalent MI only in women (OR = 1.73; 95% CI = 1.37–2.17). In women, when adjustment was limited, diameter models had larger AUC than other models. Conclusion RCCA diameter is an important correlate of cardiac events, independent of IMT, but adds little to overall risk discrimination after risk factor adjustment.

Abstract Background The effect of age on common carotid artery diameter is unclear for varying atherosclerosis risk levels. Methods Cross-sectional data from the Atherosclerosis Risk in Communities Limited Access Data set were used to estimate the association of age with B-mode ultrasound common carotid artery diameter for three atherosclerosis risk levels. Based on information from clinical examinations, B-mode ultrasounds, questionnaires, blood and other tests, participants were categorized into three groups: pre-existing disease (prevalent stroke and/or coronary heart disease), high risk group (no pre-existing disease, but prevalent diabetes, hypertension, plaques/shadowing, body mass index >= 30, current smoking, or hyperlipidemia), and a low risk group (no pre-existing disease, no plaques/shadowing, and no major elevated risk factors). Multivariable linear regression analyses modeled the common carotid artery diameter relationship with age. Results Age was positively and significantly associated with common carotid artery diameter after risk factor adjustment in the overall sample, but age had a larger effect among persons with evidence of atherosclerosis (interaction p < 0.05). Each year of older age was associated with 0.03 mm larger diameter/year among persons with pre-existing disease, with 0.027 mm larger diameter/year in the high risk group, but only 0.017 mm/year among the low risk group. Results were qualitatively similar using plaques/shadowing status to indicate atherosclerosis severity. Conclusion The significant impact of age on common carotid artery diameter among low risk, middle-aged, black and white men and women suggests arterial remodelling may occur in the absence of identified risk factors. The significantly larger impact of age among persons with, compared to persons without identified atherosclerosis or its risk factors, suggests that arterial remodelling may be an indicator of exposure duration.

Abstract Background A relatively consistent body of research supports an inverse graded relationship between socioeconomic status (SES) and cardiovascular disease (CVD). More recently, researchers have proposed various life course SES hypotheses, which posit that the combination, accumulation, and/or interactions of different environments and experiences throughout life can affect adult risk of CVD. Different life course designs have been utilized to examine the impact of SES throughout the life course. This systematic review describes the four most common life course hypotheses, categorizes the studies that have examined the associations between life course SES and CVD according to their life course design, discusses the strengths and weaknesses of the different designs, and summarizes the studies' findings. Methods This research reviewed 49 observational studies in the biomedical literature that included socioeconomic measures at a time other than adulthood as independent variables, and assessed subclinical CHD, incident CVD morbidity and/or mortality, and/or the prevalence of traditional CVD risk factors as their outcomes. Studies were categorized into four groups based upon life course design and analytic approach. The study authors' conclusions and statistical tests were considered in summarizing study results. Results Study results suggest that low SES throughout the life course modestly impacts CVD risk factors and CVD risk. Specifically, studies reviewed provided moderate support for the role of low early-life SES and elevated levels of CVD risk factors and CVD morbidity and mortality, little support for a unique influence of social mobility on CVD, and consistent support for the detrimental impact of the accumulation of negative SES experiences/conditions across the life course on CVD risk. Conclusions While the basic life course SES study designs have various methodologic and conceptual limitations, they provide an important approach from which to examine the influence of social factors on CVD development. Some limitations may be addressed through the analysis of study cohorts followed from childhood, the evaluation of CVD risk factors in early and middle adulthood, and the use of multiple SES measures and multiple life course analysis approaches in each life course study.

Abstract Background There is evidence of a contribution of early life socioeconomic exposures to the risk of chronic diseases in adulthood. However, extant studies investigating the impact of the neighborhood social environment on health tend to characterize only the current social environment. This in part may be due to complexities involved in obtaining and geocoding historical addresses. The Life Course Socioeconomic Status, Social Context, and Cardiovascular Disease Study collected information on childhood (1930–1950) and early adulthood (1960–1980) place of residence from 12,681 black and white middle-aged and older men and women from four U.S. communities to link participants with census-based socioeconomic indicators over the life course. Results Most (99%) participants were linked to 1930–50 county level socioeconomic census data (the smallest level of aggregation universally available during this time period) corresponding to childhood place of residence. Linkage did not vary by race, gender, birth cohort, or level of educational attainment. A commercial geocoding vendor processed participants' self-reported street addresses for ages 30, 40, and 50. For 1970 and 1980 censuses, spatial coordinates were overlaid onto shape files containing census tract boundaries; for 1960 no shape files existed and comparability files were used. Several methods were tested for accuracy and to increase linkage. Successful linkage to historical census tracts varied by census (66% for 1960, 76% for 1970, 85% for 1980). This compares to linkage rates of 94% for current addresses provided by participants over the course of the ARIC examinations. Conclusion There are complexities and limitations in characterizing the past social context. However, our results suggest that it is feasible to characterize the earlier social environment with known levels of measurement error and that such an approach should be considered in future studies.

BACKGROUND: Manipulative treatment for ankylosing spondylitis is a controversial subject, and no literature on using this therapy for advanced cases with fusion of the spine could be found. OBJECTIVE: To discuss the case presentation of a patient with advanced ankylosing spondylitis who was treated with chiropractic manipulation and mobilization.Clinical features The patient was a 30-year-old Asian male who was first diagnosed with ankylosing spondylitis at age 12. Despite medical intervention, a series of exacerbations had fused his sacroiliac joints and the facet joints in his lumbar and cervical spine. He presented with local moderate-to-severe pain in his low back and neck and lack of mobility.Intervention and outcome The patient was treated with grade 5 manipulation of his thoracic spine and grade 3 mobilization of his lumbar and cervical spine, along with physical therapy and stretches for a period of 12 weeks. He reported some improvement of his condition as measured by the SF-36 Health Survey and several measures of spinal flexibility. CONCLUSIONS: This case shows that even advanced cases of ankylosing spondylitis may show a favorable response to chiropractic manipulative therapy. [ABSTRACT FROM AUTHOR]

OBJETIVO: Investigar os efeitos da remoção da adventícia da aorta em suínos. MÉTODOS: O experimento foi realizado com oito suínos. Removeu-se a camada adventícia da aorta descendente. Após a eutanásia com duas, quatro, seis e oito semanas, o segmento aórtico era removido. Após, eram feitos cortes histológicos com a coloração de hematoxilina e eosina (HE) e pelo método de Weigert - Van Gieson. RESULTADOS: Após duas semanas identificou-se um leve desarranjo do terço externo da túnica média. Nos animais sacrificados após quatro semanas observou-se um desarranjo estrutural dos terços externos da túnica média. Após seis semanas observou-se necrose da parede aórtica. Finalmente, após oito semanas além da fibrose da parede aórtica identificou-se a destruição da lâmina elástica interna. CONCLUSÃO: A remoção da adventícia da aorta em suínos levou à alterações degenerativas da média, determinando perda da estrutura da parede aórtica que é variável em sua localização, intensidade e forma, dependendo do tempo a partir do qual se estabeleceu a lesão isquêmica.

A central concept of evolutionary biology, supported by broad scale allometric analyses, asserts that changing morphology should induce downstream changes in locomotor kinematics and energetics, and by inference selective fitness. However, if these mechanistic relationships exist at local intraspecific scales, where they could provide substrate for fundamental microevolutionary processes, is unknown. Here, analyses of selectively-bred duck breeds demonstrate that distinct body shapes incur kinematic shifts during walking, but these do not translate into differences in energetics. A combination of modular relationships between anatomical regions, and a trade-off between limb flexion and trunk pitching, are shown to homogenise potential functional differences between the breeds, accounting for this discrepancy between form and function. This complex interplay between morphology, motion and physiology indicates that understanding evolutionary links between the avian body plan and locomotor diversity requires studying locomotion as an integrated whole and not key anatomical innovations in isolation., (© 2024. The Author(s).)

Naked carp (Gymnocypris przewalskii) is the only fish species commercially harvested in Qinghai Lake, which is the largest inland saltwater lake in China. Multiple ecological stresses such as long-term overfishing, drying-up of riverine inflows, and decreases in spawning habitat caused the naked carp population to decrease from 320,000 tons before the 1950s to only 3000 tons by the early 2000s. We used matrix projection population modeling to quantitatively simulate the dynamics of the naked carp population from the 1950s to the 2020s. Five versions of the matrix model were developed from the field and laboratory information that represented different population states (high but declining, low abundance, very low abundance, initial recovery, pristine). Equilibrium analysis was applied to density-independent versions of the matrices and population growth rate, age composition, and elasticities were compared among versions. Stochastic, density-dependent version of the most recent decade (recovering) version was used to simulate the time-dependent responses to a range of levels of artificial reproduction (addition of age-1 from hatchery) and of the pristine version to simulate combinations of fishing rate and minimum age of harvest. Results showed the major role of overfishing in the population decline and that the population growth rate was most sensitive to the survival of juveniles and the spawning success of early-age adults. Dynamic simulations showed a rapid population response to artificial reproduction when population abundance was low and that if artificial reproduction continues at its current level, then population biomass would reach 75% of its pristine biomass after 50 years. Simulations with the pristine version identified sustainable fishing levels and the importance of protecting the first few ages of maturity. Overall, modeling results showed that artificial reproduction under conditions of no fishing is an effective approach to restoring the naked carp population. Further effectiveness should consider maximizing survival in the months just after release and maintaining genetic and phenotypic diversity. More information on density-dependent growth, survival, and reproduction, as well as on the genetic diversity and growth and migratory behavior (phenotypic variation) of released and native-spawned fish, would help inform management and conservation strategies and practices going forward., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Chubin Weng, Mengzhen Xu, Fakai Lei reports financial support was provided by National Natural Science Foundation of China (NSFC). Chubin Weng, Mengzhen Xu, Fakai Lei reports financial support was provided by Second Tibetan Plateau Scientific Expedition and Research Program (STEP)., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: To explore the relationship between outdoor time and academic performance among school-aged children., Methods: This study was designed as a cross-sectional study. Data were derived from a school-based prospective children myopia intervention study (STORM). Outdoor time was recorded by self-developed algorithm-validated wristwatches in real-time and calculated as the cumulative average of 10 months. The academic performance was recorded and provided by the participating schools and further standardized. Other information was collected using an online standardized questionnaire. Mixed-effects model and B-Spline method were used to investigate the association between time spent on different types of daily activity, including outdoor activity and academic performance., Results: A total of 3291 children with mean age 9.25 years were included in the final analysis. Overall, outdoor time was associated with academic performance in a non-linear manner; specifically, not exceeding 2.3 h per day, outdoor time was positively associated with academic performance; exceeding 2.3 h per day, this association became non-significant. Likewise, daily sleep duration and out-of-school learning time were associated with academic performance in a non-linear manner, resulting in turning points of 11.3 and 1.4 h per day, respectively. Separate analysis showed that outdoor time and sleep duration but not out-of-school learning time were positively associated with academic performance in Chinese, mathematics and English., Conclusion: Outdoor time, sleep duration and out-of-school learning time were associated with academic performance in a non-linear manner. Promotion of outdoor time may not negatively impact on academic performance., Trial Registration: Our study was registered in ClinicalTrials.gov (Identifier: NCT02980445)., (© 2023. The Author(s).)

Introduction: This study aimed to evaluate the habitual reading distance among non-myopic children and also myopic children with undercorrection and with full correction., Methods: This was a population-based cross-sectional study with a total of 2363 children aged 6-8 years who were recruited from the Hong Kong Children Eye Study. Cycloplegic autorefraction, subjective refraction, habitual visual acuity, and best corrected visual acuity were measured. The entire reading process (9 min) was recorded using a hidden video camera placed 5 m away from the reading desk. Reading distances were taken at 6, 7, 8, and 9 min after the child began reading and were measured using a customized computer program developed in MATLAB. The main outcome was the association of habitual reading distances with refraction status. Habitual reading distances of children were documented via video camera footage., Results: The habitual reading distances of undercorrected myopic children (23.37 ± 4.31 cm) were the shortest when compared to non-myopic children (24.20 ± 4.73 cm, P = 0.002) and fully corrected myopic children (24.81 ± 5.21 cm, P < 0.001), while there was no significant difference between the last two children groups (P = 0.17). A shorter reading distance was associated with myopia (OR 1.67; 95% CI 1.11-2.51; P = 0.013) after adjusting for age, sex, height, near work time, outdoor time, and parental myopia. The association of reading distance with myopia did not hold after undercorrected myopic children were excluded (OR 0.97, 95% CI 0.55-1.73; P = 0.92). A shorter reading distance correlated with poorer vision under habitual correction (β = - 0.003, P < 0.001)., Conclusion: A shorter reading distance was present among undercorrected myopic children. Myopia undercorrection is not recommended as a strategy for slowing myopic progression., (© 2022. The Author(s).)

Polymer adsorption at the solid/liquid interface depends not only on the chemical composition of the polymer but also on the specific placement of the monomers along the polymer sequence. However, challenges in designing polymers with well-controlled sequences have limited explorations into the role of polymer sequence on adsorption behavior to molecular simulations. Here, we demonstrate how the sequence control offered by polypeptide synthesis can be utilized to study the effects small changes in polymer sequence have on polymer adsorption behavior at the solid/liquid interface. Through a combination of quartz crystal microbalance with dissipation monitoring and total internal reflection ellipsometry, we study the adsorption behavior of three polypeptides, consisting of 90% lysine and 10% cysteine, onto a gold surface. We find different mechanisms are responsible for the adsorption of polypeptides and the resulting conformation on the surface. The initial adsorption of the polypeptides is driven by electrostatic interactions between the polylysine and the gold surface. Once adsorbed, the cysteine undergoes a thiol-Au reaction with the surface, altering the conformation of the polymer layer. Our findings suggest the conformation of the polypeptide layer is dependent on the placement of the cysteines within the sequence; polypeptide chains with evenly spaced cysteine groups adopt a more tightly bound "train" conformation as compared to polypeptides with closely grouped cysteine groups. We envision that the methodologies presented here to study sequence specific adsorption behaviors using polypeptides could be a valuable tool to complement molecular simulations studies.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and often fatal disorder. Two U.S. Food and Drug Administration-approved antifibrotic drugs, nintedanib and pirfenidone, slow the rate of decline in lung function, but responses are variable and side effects are common. Objectives: Using an in silico data-driven approach, we identified a robust connection between the transcriptomic perturbations in IPF disease and those induced by saracatinib, a selective Src kinase inhibitor originally developed for oncological indications. Based on these observations, we hypothesized that saracatinib would be effective at attenuating pulmonary fibrosis. Methods: We investigated the antifibrotic efficacy of saracatinib relative to nintedanib and pirfenidone in three preclinical models: 1 ) in vitro in normal human lung fibroblasts; 2 ) in vivo in bleomycin and recombinant Ad-TGF-β (adenovirus transforming growth factor-β) murine models of pulmonary fibrosis; and 3 ) ex vivo in mice and human precision-cut lung slices from these two murine models as well as patients with IPF and healthy donors. Measurements and Main Results: In each model, the effectiveness of saracatinib in blocking fibrogenic responses was equal or superior to nintedanib and pirfenidone. Transcriptomic analyses of TGF-β-stimulated normal human lung fibroblasts identified specific gene sets associated with fibrosis, including epithelial-mesenchymal transition, TGF-β, and WNT signaling that was uniquely altered by saracatinib. Transcriptomic analysis of whole-lung extracts from the two animal models of pulmonary fibrosis revealed that saracatinib reverted many fibrogenic pathways, including epithelial-mesenchymal transition, immune responses, and extracellular matrix organization. Amelioration of fibrosis and inflammatory cascades in human precision-cut lung slices confirmed the potential therapeutic efficacy of saracatinib in human lung fibrosis. Conclusions: These studies identify novel Src-dependent fibrogenic pathways and support the study of the therapeutic effectiveness of saracatinib in IPF treatment.

The effect of nanoscale defects on nanoparticle dynamics in defective tetra-poly(ethylene glycol) (tetra-PEG) hydrogels is investigated using single particle tracking. In a swollen nearly homogeneous hydrogel, PEG-functionalized quantum dot (QD) probes with a similar hydrodynamic diameter ( d h = 15.1 nm) to the mesh size (〈 ξ s 〉 = 16.3 nm), are primarily immobile. As defects are introduced to the network by reaction-tuning, both the percentage of mobile QDs and the size of displacements increase as the number and size of the defects increase with hydrolysis time, although a large portion of the QDs remain immobile. To probe the effect of nanoparticle size on dynamics in defective networks, the transport of d h = 47.1 nm fluorescent polystyrene (PS) and d h = 9.6 nm PEG-functionalized QDs is investigated. The PS nanoparticles are immobile in all hydrogels, even in highly defective networks with an open structure. Conversely, the smaller QDs are more sensitive to perturbations in the network structure with an increased percentage of mobile particles and larger diffusion coefficients compared to the larger QDs and PS nanoparticles. The differences in nanoparticle mobility as a function of size suggests that particles of different sizes probe different length scales of the defects, indicating that metrics such as the confinement ratio alone cannot predict bulk dynamics in these systems. This study provides insight into designing hydrogels with controlled transport properties, with particular importance for degradable hydrogels for drug delivery applications.

Purpose: To evaluate the efficacy of time outdoors per school day over 2 years on myopia onset and shift., Design: A prospective, cluster-randomized, examiner-masked, 3-arm trial., Participants: A total of 6295 students aged 6 to 9 years from 24 primary schools in Shanghai, China, stratified and randomized by school in a 1:1:1 ratio to control (n = 2037), test I (n = 2329), or test II (n = 1929) group., Methods: An additional 40 or 80 minutes of outdoor time was allocated to each school day for test I and II groups. Children in the control group continued their habitual outdoor time. Objective monitoring of outdoor and indoor time and light intensity each day was measured with a wrist-worn wearable during the second-year follow-up., Main Outcome Measures: The 2-year cumulative incidence of myopia (defined as cycloplegic spherical equivalent [SE] of ≤-0.5 diopters [D] in the right eye) among the students without myopia at baseline and changes in SE and axial length (AL) after 2 years., Results: The unadjusted 2-year cumulative incidence of myopia was 24.9%, 20.6%, and 23.8% for control, test I, and II groups, respectively. The adjusted incidence decreased by 16% (incidence risk ratio [IRR], 0.84; 95% confidence interval [CI], 0.72-0.99; P = 0.035) in test I and 11% (IRR = 0.89; 95% CI, 0.79-0.99; P = 0.041) in test II when compared with the control group. The test groups showed less myopic shift and axial elongation compared with the control group (test I: -0.84 D and 0.55 mm, test II: -0.91 D and 0.57 mm, control: -1.04 D and 0.65 mm). There was no significant difference in the adjusted incidence of myopia and myopic shift between the 2 test groups. The test groups had similar outdoor time and light intensity (test I: 127 ± 30 minutes/day and 3557 ± 970 lux/minute; test II: 127 ± 26 minutes/day and 3662 ± 803 lux/minute) but significantly more outdoor time and higher light intensity compared with the control group (106 ± 27 minutes/day and 2984 ± 806 lux/minute). Daily outdoor time of 120 to 150 minutes at 5000 lux/minutes or cumulative outdoor light intensity of 600 000 to 750 000 lux significantly reduced the IRR by 15%～ 24%., Conclusions: Increasing outdoor time reduced the risk of myopia onset and myopic shifts, especially in nonmyopic children. The protective effect of outdoor time was related to the duration of exposure and light intensity. The dose-response effect between test I and test II was not observed probably because of insufficient outdoor time achieved in the test groups, which suggests that proper monitoring on the compliance on outdoor intervention is critical if one wants to see the protective effect., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

The blind troglobite cavefish Sinocyclocheilus rhinocerous lives in oligotrophic, phreatic subterranean waters and possesses a unique cranial morphology including a pronounced supra-occipital horn. We used a combined approach of laboratory observations and Computational Fluid Dynamics modeling to characterize the swimming behavior and other hydrodynamic aspects, i.e., drag coefficients and lateral line sensing distance of S. rhinocerous. Motion capture and tracking based on an Artificial Neural Network, complemented by a Particle Image Velocimetry system to map out water velocity fields, were utilized to analyze the motion of a live specimen in a laboratory aquarium. Computational Fluid Dynamics simulations on flow fields and pressure fields, based on digital models of S. rhinocerous, were also performed. These simulations were compared to analogous simulations employing models of the sympatric, large-eyed troglophile cavefish S. angustiporus. Features of the cavefish swimming behavior deduced from the both live-specimen experiments and simulations included average swimming velocities and three dimensional trajectories, estimates for drag coefficients and potential lateral line sensing distances, and mapping of the flow field around the fish. As expected, typical S. rhinocerous swimming speeds were relatively slow. The lateral line sensing distance was approximately 0.25 body lengths, which may explain the observation that specimen introduced to a new environment tend to swim parallel and near to the walls. Three-dimensional simulations demonstrate that just upstream from the region under the supra-occipital horn the equipotential of the water pressure and velocity fields are nearly vertical. Results support the hypothesis that the conspicuous cranial horn of S. rhinocerous may lead to greater stimulus of the lateral line compared to fish that do not possess such morphology., Competing Interests: VZ is employed by Commercial Space Technologies Ltd. There are no patents, products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Animal-attached devices have transformed our understanding of vertebrate ecology. To minimize any associated harm, researchers have long advocated that tag masses should not exceed 3% of carrier body mass. However, this ignores tag forces resulting from animal movement. Using data from collar-attached accelerometers on 10 diverse free-ranging terrestrial species from koalas to cheetahs, we detail a tag-based acceleration method to clarify acceptable tag mass limits. We quantify animal athleticism in terms of fractions of animal movement time devoted to different collar-recorded accelerations and convert those accelerations to forces (acceleration × tag mass) to allow derivation of any defined force limits for specified fractions of any animal's active time. Specifying that tags should exert forces that are less than 3% of the gravitational force exerted on the animal's body for 95% of the time led to corrected tag masses that should constitute between 1.6% and 2.98% of carrier mass, depending on athleticism. Strikingly, in four carnivore species encompassing two orders of magnitude in mass ( ca 2-200 kg), forces exerted by '3%' tags were equivalent to 4-19% of carrier body mass during moving, with a maximum of 54% in a hunting cheetah. This fundamentally changes how acceptable tag mass limits should be determined by ethics bodies, irrespective of the force and time limits specified.

Background: Cellular diversity of the lung endothelium has not been systematically characterized in humans. We provide a reference atlas of human lung endothelial cells (ECs) to facilitate a better understanding of the phenotypic diversity and composition of cells comprising the lung endothelium., Methods: We reprocessed human control single-cell RNA sequencing (scRNAseq) data from 6 datasets. EC populations were characterized through iterative clustering with subsequent differential expression analysis. Marker genes were validated by fluorescent microscopy and in situ hybridization. scRNAseq of primary lung ECs cultured in vitro was performed. The signaling network between different lung cell types was studied. For cross-species analysis or disease relevance, we applied the same methods to scRNAseq data obtained from mouse lungs or from human lungs with pulmonary hypertension., Results: Six lung scRNAseq datasets were reanalyzed and annotated to identify >15 000 vascular EC cells from 73 individuals. Differential expression analysis of EC revealed signatures corresponding to endothelial lineage, including panendothelial, panvascular, and subpopulation-specific marker gene sets. Beyond the broad cellular categories of lymphatic, capillary, arterial, and venous ECs, we found previously indistinguishable subpopulations; among venous EC, we identified 2 previously indistinguishable populations: pulmonary-venous ECs (COL15A1 neg ) localized to the lung parenchyma and systemic-venous ECs (COL15A1 pos ) localized to the airways and the visceral pleura; among capillary ECs, we confirmed their subclassification into recently discovered aerocytes characterized by EDNRB , SOSTDC1 , and TBX2 and general capillary EC. We confirmed that all 6 endothelial cell types, including the systemic-venous ECs and aerocytes, are present in mice and identified endothelial marker genes conserved in humans and mice. Ligand-receptor connectome analysis revealed important homeostatic crosstalk of EC with other lung resident cell types. scRNAseq of commercially available primary lung ECs demonstrated a loss of their native lung phenotype in culture. scRNAseq revealed that endothelial diversity is maintained in pulmonary hypertension. Our article is accompanied by an online data mining tool (www.LungEndothelialCellAtlas.com)., Conclusions: Our integrated analysis provides a comprehensive and well-crafted reference atlas of ECs in the normal lung and confirms and describes in detail previously unrecognized endothelial populations across a large number of humans and mice.

Habitat loss and alteration are two of the biggest threats facing insular flying-foxes. Altered habitats are often re-vegetated with introduced or domestic plant species on which flying-foxes may forage. However, these alien food plants may not meet the nutritional requirements of flying-foxes. The critically endangered Christmas Island flying-fox (CIFF; Pteropus natalis) is subject to habitat alteration and the introduction of alien food plants, and therefore is a good model species to evaluate the potential impact of alien plant species on insular flying-foxes. In this study, we evaluated nutritional content of native food plants to determine how flying-foxes historically met their nutritional requirements. Furthermore, we compared the nutritional content of native and alien fruits to predict possible impacts of alien plants on insular flying-foxes. Native and alien fruits and flowers, and native foliage (leaves, petals, and petioles) commonly consumed by the CIFF were collected and evaluated for soluble sugars, crude protein, non-fiber carbohydrates, and nine minerals. Evaluation of native food plants suggests that flying-foxes meet energy requirements by consuming fruit and nectar. However, fruit and nectar are low in protein and essential minerals required for demanding life periods; therefore, flying-foxes likely supplement their diets with pollen and foliage. Thus, flying-foxes require a diverse array of plants to meet their nutritional requirements. Compared to native fruits, alien fruits contained significantly higher non-fiber carbohydrates, and this may provide an important energy source, particularly from species that bear fruit year-round. Median mineral concentrations in alien fruit species, however, were deficient compared to native fruits, suggesting major (or even seasonal) shifts in the proportion of alien species in the CIFF diet could lead to nutritional imbalances. This study confirms the need to quantify nutritional parameters in addition to feeding ecology when evaluating habitat quality to inform conservation actions that can be applied both locally and globally., Competing Interests: The authors have declared that no competing interests exist.

Risk factor analysis provides an important basis for developing interventions for any condition. In the case of myopia, evidence for a large number of risk factors has been presented, but they have not been systematically tested for confounding. To be useful for designing preventive interventions, risk factor analysis ideally needs to be carried through to demonstration of a causal connection, with a defined mechanism. Statistical analysis is often complicated by covariation of variables, and demonstration of a causal relationship between a factor and myopia using Mendelian randomization or in a randomized clinical trial should be aimed for. When strict analysis of this kind is applied, associations between various measures of educational pressure and myopia are consistently observed. However, associations between more nearwork and more myopia are generally weak and inconsistent, but have been supported by meta-analysis. Associations between time outdoors and less myopia are stronger and more consistently observed, including by meta-analysis. Measurement of nearwork and time outdoors has traditionally been performed with questionnaires, but is increasingly being pursued with wearable objective devices. A causal link between increased years of education and more myopia has been confirmed by Mendelian randomization, whereas the protective effect of increased time outdoors from the development of myopia has been confirmed in randomized clinical trials. Other proposed risk factors need to be tested to see if they modulate these variables. The evidence linking increased screen time to myopia is weak and inconsistent, although limitations on screen time are increasingly under consideration as interventions to control the epidemic of myopia.

The effect of static silica particles on the dynamics of quantum dot (QD) nanoparticles grafted with a poly(ethylene glycol) (PEG) brush in hydrogel nanocomposites is investigated using single particle tracking (SPT). At a low volume fraction of homogeneously dispersed silica (Φ = 0.005), two distinct populations of PEG-QDs are observed, localized and mobile, whereas almost all PEG-QDs are mobile in neat hydrogel (Φ = 0.0). Increasing the silica particle concentration (Φ = 0.01, 0.1) results in an apparent change in the network structure, confounding the impact of silica on PEG-QD dynamics. The localized behavior of PEG-QDs is attributed to pH-mediated attraction between the PEG brush on the probe and surface silanol groups of silica. Using quartz crystal microbalance with dissipation (QCM-D), the extent of this interaction is investigated as a function of pH. At pH 5.8, the PEG brush on the probe can hydrogen bond with the silanol groups on silica, leading to adsorption of PEG-QDs. In contrast, at pH 9.2, silanol groups are deprotonated and PEG-QD is unable to hydrogen bond with silica leading to negligible adsorption. To test the effect of pH, PEG-QD dynamics are further investigated in hydrogel nanocomposites at Φ = 0.005. SPT agrees with the QCM-D results; at pH 5.8, PEG-QDs are localized whereas at pH 9.2 the PEG-QDs are mobile. This study provides insight into controlling probe transport through hydrogel nanocomposites using pH-mediated interactions, with implications for tuning transport of nanoparticles underlying drug delivery and nanofiltration.

Myopia (near-sightedness) is an important public health issue. Spending more time outdoors can prevent myopia but the long-term association between this exposure and myopia has not been well characterised. We investigated the relationship between time spent outdoors in childhood, adolescence and young adulthood and risk of myopia in young adulthood. The Kidskin Young Adult Myopia Study (KYAMS) was a follow-up of the Kidskin Study, a sun exposure-intervention study of 1776 children aged 6-12 years. Myopia status was assessed in 303 (17.6%) KYAMS participants (aged 25-30 years) and several subjective and objective measures of time spent outdoors were collected in childhood (8-12 years) and adulthood. Index measures of total, childhood and recent time spent outdoors were developed using confirmatory factor analysis. Logistic regression was used to assess the association between a 0.1-unit change in the time outdoor indices and risk of myopia after adjusting for sex, education, outdoor occupation, parental myopia, parental education, ancestry and Kidskin Study intervention group. Spending more time outdoors during childhood was associated with reduced risk of myopia in young adulthood (multivariable odds ratio [OR] 0.82, 95% confidence interval [CI] 0.69, 0.98). Spending more time outdoors in later adolescence and young adulthood was associated with reduced risk of late-onset myopia (≥ 15 years of age, multivariable OR 0.79, 95% CI 0.64, 0.98). Spending more time outdoors in both childhood and adolescence was associated with less myopia in young adulthood.

Purpose: To determine the effects on childhood myopia of parental myopia, parental education, children's outdoor time, and children's near work., Design: Population-based cross-sectional study., Methods: A total of 6,155 subjects in 2,055 family trios (1 child and both parents). Cycloplegic autorefraction was measured for children and noncycloplegic autorefraction for parents. Parental education, children's outdoor time, and near work were collected by questionnaires. Children were categorized into 10 groups based on parental myopia levels. Associations of the above factors with myopia were evaluated by regression analyses. The areas under the receiver operating characteristic curve (AUROCs) for myopia were evaluated., Results: Mild parental myopia did not increase childhood myopia's risk, but the risk was 11.22-folds when both parents were highly myopic. Higher parental education (Father: OR 1.08, P = .046; Mother: OR 1.11, P = .001) and more reading time of children were risk factors (OR 1.21, P = .044). Reduced odds of myopia were associated with more time spent on outdoor activities (OR 0.78, P = .017). Notably, all these factors became insignificant after adjustment, except for parental myopia. Children with more severe parental myopia spent more time on reading, but less on electronic devices. Parental myopic status alone accounted for 11.82% of myopia variation in children. With age and parental myopia, the AUROC for myopia was 0.731., Conclusions: Among parental and environmental factors, parental myopia confers, in a dose-related manner, the strongest independent effect on childhood myopia. Therefore children with high risk of myopia can be identified for early prevention, based on parental myopia data., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The purpose of our web-based, semi-virtual reality simulation was to raise baccalaureate nursing students' awareness of civility and incivility. Educators know civility in nursing is crucial to safe and effective patient care. However, nursing students have reported physiological and psychological distress after experiencing incivility. If nurse educators are unable to better promote civility, the quality of nursing education, and ultimately nursing practice, is threatened., Method: We implemented an innovative civility-related, semi-virtual reality, simulation with senior-level nursing students. After attending a faculty-led discussion on the importance of civility and incivility, students participated in a web-based, semi-virtual reality simulation, followed by a synchronous debriefing session., Results: Students reported that the intervention raised their awareness of civility and incivility., Conclusion: This article describes the intervention and shares the lessons learned in implementing it so nurse educators may replicate this innovative strategy to raise awareness of civility in nursing education. [J Nurs Educ. 2020;59(8):461-464.]., (Copyright 2020, SLACK Incorporated.)

Introduction: The transition from pediatric to adult care is under-studied in primary care. Electronic health record-integrated transition planning tools (ETPTs) can facilitate the transition. We tested whether ETPTs and clinician reminders increase the frequency of transition discussions during adolescent well-visits., Methods: In an academic adolescent medicine primary care practice serving a predominantly African American, Medicaid-insured population, we developed 4 ETPTs-readiness assessment, plan template, information handout, and diagnosis code. We used Plan-Do-Study-Act quality improvement cycles to implement ETPTs and measure outcomes. Each cycle added a new layer of clinician support: (1) ETPT training, (2) visual reminders, (3) incentives, and (4) daily reminders. The primary outcome was the proportion of well-visits in which "any ETPT use" occurred. We collected data via chart review and used run charts and regression analyses with multiple comparisons to detect differences between cycles. Clinicians-provided feedback was elicited., Results: Any ETPT use increased from 0% to 45% between baseline and cycle 4. The odds of any ETPT use was ten times larger in cycle 4 compared to cycle 1 (odds ratio 10.09, 95% confidence interval 2.29-44.44, P = 0.002) and 22 times larger in cycle 4 than cycle 2 (odds ratio 21.99, 95% confidence interval 3.96-122.00, P < 0.001). Clinicians identified time constraints and lack of sociocultural relevance as barriers to uptake., Conclusions: Daily reminders combined with training and visual reminders were effective in increasing the use of ETPTs in primary care. Future interventions should adapt existing transition tools to the needs of target populations and create regular reminders to facilitate uptake., (Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.)