Explore the vast range of titles available.

Two thirds of all persons with late-onset Alzheimer's disease (AD) are women. Identification of sex-based molecular mechanisms underpinning the female-based prevalence of AD would advance development of therapeutic targets during the prodromal AD phase when prevention or delay in progression is most likely to be effective. This 3-year brain imaging study examines the impact of the menopausal transition on Alzheimer's disease (AD) biomarker changes [brain β-amyloid load via 11C-PiB PET, and neurodegeneration via 18F-FDG PET and structural MRI] and cognitive performance in midlife. Fifty-nine 40-60 year-old cognitively normal participants with clinical, neuropsychological, and brain imaging exams at least 2 years apart were examined. These included 41 women [15 premenopausal controls (PRE), 14 perimenopausal (PERI), and 12 postmenopausal women (MENO)] and 18 men. We used targeted minimum loss-based estimation to evaluate AD biomarker and cognitive changes. Older age was associated with baseline Aβ and neurodegeneration markers, but not with rates of change in these biomarkers. APOE4 status influenced change in Aβ load, but not neurodegenerative changes. Longitudinally, MENO and PERI groups showed declines in estrogen-dependent memory tests as compared to men (p < .04). Adjusting for age, APOE4 status, and vascular risk confounds, the MENO and PERI groups exhibited higher rates of CMRglc decline as compared to males (p ≤ .015). The MENO group exhibited the highest rate of hippocampal volume loss (p's ≤ .001), and higher rates of Aβ deposition than males (p < .01). CMRglc decline exceeded Aβ and atrophy changes in all female groups vs. men. These findings indicate emergence and progression of a female-specific hypometabolic AD-endophenotype during the menopausal transition. These findings suggest that the optimal window of opportunity for therapeutic intervention to prevent or delay progression of AD endophenotype in women is early in the endocrine aging process.

Estimating the causal effect of an intervention on a population typically involves defining parameters in a nonparametric structural equation model (Pearl, 2000, Causality: Models, Reasoning, and Inference) in which the treatment or exposure is deterministically assigned in a static or dynamic way. We define a new causal parameter that takes into account the fact that intervention policies can result in stochastically assigned exposures. The statistical parameter that identifies the causal parameter of interest is established. Inverse probability of treatment weighting (IPTW), augmented IPTW (A‐IPTW), and targeted maximum likelihood estimators (TMLE) are developed. A simulation study is performed to demonstrate the properties of these estimators, which include the double robustness of the A‐IPTW and the TMLE. An application example using physical activity data is presented.

The mechanical properties of fly-ash-based geopolymer concrete (GPC) were studied. Experimentally measured values of the static elastic modulus, Poisson's ratio, compressive strength, and flexural strength of GPC specimens made from 25 fly ash (FA) stockpiles from different sources were recorded and analyzed. The results were studied using regression analysis to identify tendencies and correlations within the mechanical properties of GPC. It was found that the mechanical behavior of GPC is similar to that of ordinary portland cement (OPC) concrete, suggesting that equations, akin to those given by ACI 318-08, could be applied for GPC to determine its flexural strength and static elastic modulus. The validity of an equation to determine the density of GPC as a function of FA fineness was also put forward. [PUBLICATION ABSTRACT]

There has been a noticeable gap in scholarly research concerning managers’ ambidexterity in entrepreneurial firms, particularly in startups. This quantitative study examines the degree of influence of transversal competencies related to ambidexterity in startup managers of Chilean firms. Findings indicate that CEO perseverance, enterprising, business orchestration, and networking positively affect managers’ ability to balance exploration and exploitation activities. The study also suggests that the firm’s age does not moderate the relationship between competencies and ambidexterity except for business orchestration. In addition, the article´s major contribution is to connect transversal competencies in startup CEOs and the micro-foundations theory of ambidexterity, highlighting the importance of individual cognitive predispositions since resilience and motivational dimensions. Indeed, the study identifies perseverance and enterprising as competencies with a higher impact in these entrepreneurial high-tech firms.

Increasing evidence implicates sex and endocrine aging effects on brain bioenergetic aging in the greater lifetime risk of Alzheimer’s disease (AD) in women. We conducted 31 Phosphorus Magnetic Resonance Spectroscopy ( 31 P-MRS) to assess the impact of sex and menopause on brain high-energy phosphates [adenosine triphosphate (ATP), phosphocreatine (PCr), inorganic phosphate (Pi)] and membrane phospholipids [phosphomonoesters/phosphodiesters (PME/PDE)] in 216 midlife cognitively normal individuals at risk for AD, 80% female. Ninety-seven participants completed amyloid-beta (Aβ) 11 C-PiB PET. Women exhibited higher ATP utilization than men in AD-vulnerable frontal, posterior cingulate, fusiform, medial and lateral temporal regions (p < 0.001). This profile was evident in frontal cortex at the pre-menopausal and peri-menopausal stage and extended to the other regions at the post-menopausal stage (p = 0.001). Results were significant after multi-variable adjustment for age, APOE-4 status, midlife health indicators, history of hysterectomy/oophorectomy, use of menopause hormonal therapy, and total intracranial volume. While associations between ATP/PCr and Aβ load were not significant, individuals with the highest Aβ load were post-menopausal and peri-menopausal women with ATP/PCr ratios in the higher end of the distribution. No differences in Pi/PCr, Pi/ATP or PME/PDE were detected. Outcomes are consistent with dynamic bioenergetic brain adaptations that are associated with female sex and endocrine aging.

The world's southernmost tree has been documented along with the condition and growth pattern of the world's southernmost forest on Isla Hornos, Chile. The distribution of trees at broad scales is strongly influenced by the abiotic environment and determining the position and condition of tree limits around the world is an important way to monitor global change. This offers an ideal way to test the relationship between the biogeography of individual species and the effects of climate/climate change. The limits of trees, as all ecotones, are also useful communication points – easily understood signposts of ecosystems and their change through time. The southernmost trees in the world exist at soil temperatures that correspond to the low range of global treeline temperatures, with a climate analogous to equatorial treeline despite the high latitude (56° S). However, their fine‐scale distribution is strongly influenced by wind exposure rather than simply aspect and/or elevation, as one would expect if temperature were limiting the range. Recent establishment further south was found from core forest areas, however significant dieback along wind‐exposed edges of the contiguous forest was also noted. In contrast to the wide extension of land where boreal or subarctic forests grow in the Northern Hemisphere, in the Southern Hemisphere Isla Hornos represents a single point embedded in the ocean under much milder climatic conditions. Documented shifts in wind intensity and direction as result of larger‐scale climate change will likely continue to strongly shape the condition of these unique forests.

Background: Childhood obesity and overweight conditions impact systemic health and craniofacial development. Objectives: This review assessed the influence of elevated body mass index (BMI) on craniofacial morphology, considering age, sex, and ethnicity. Methods: A comprehensive search of Scopus, Web of Science, Embase, Cochrane, PubMed, and OpenGrey was conducted following PRISMA guidelines. Ten cross-sectional studies involving 1383 individuals aged 6 to 18 years were included. The sample comprised 812 females and 571 males, with most studies focusing on adolescents aged 12–18 years of different ethnicities depending on the study. Craniofacial structures were compared between overweight/obese and normal weight groups through cephalometric analysis. Study quality was assessed using the Newcastle–Ottawa Scale (NOS). Results: Overweight and obese individuals showed significant craniofacial changes, including increased anterior cranial base length, maxillary and mandibular dimensions, bimaxillary prognathism, and greater soft tissue thickness. These alterations may be influenced by differences in tissue composition, hormonal fluctuations, fat-to-bone ratio, and metabolic disorders. Variations in skeletal divergence, dental alignment, and airway space were also observed. The methodological quality ranged from moderate to high. Conclusions: Excess weight during growth is linked to distinct craniofacial alterations. Orthodontic diagnostics should integrate metabolic and hormonal considerations to optimize treatment outcomes. These changes should be carefully considered by orthodontists and pediatric dentists. Longitudinal studies are needed to understand the long-term effects of obesity on craniofacial development.

IntroductionNearly one-quarter of patients discharged from the hospital with heart failure (HF) are readmitted within 30 days, placing a significant burden on patients, families and health systems. The objective of the ‘Using Mobile Integrated Health and Telehealth to support transitions of care among patients with Heart failure’ (MIGHTy-Heart) study is to compare the effectiveness of two postdischarge interventions on healthcare utilisation, patient-reported outcomes and healthcare quality among patients with HF.Methods and analysisThe MIGHTy-Heart study is a pragmatic comparative effectiveness trial comparing two interventions demonstrated to improve the hospital to home transition for patients with HF: mobile integrated health (MIH) and transitions of care coordinators (TOCC). The MIH intervention bundles home visits from a community paramedic (CP) with telehealth video visits by emergency medicine physicians to support the management of acute symptoms and postdischarge care coordination. The TOCC intervention consists of follow-up phone calls from a registered nurse within 48–72 hours of discharge to assess a patient’s clinical status, identify unmet clinical and social needs and reinforce patient education (eg, medication adherence and lifestyle changes). MIGHTy-Heart is enrolling and randomising (1:1) 2100 patients with HF who are discharged to home following a hospitalisation in two New York City (NY, USA) academic health systems. The coprimary study outcomes are all-cause 30-day hospital readmissions and quality of life measured with the Kansas City Cardiomyopathy Questionnaire 30 days after hospital discharge. The secondary endpoints are days at home, preventable emergency department visits, unplanned hospital admissions and patient-reported symptoms. Data sources for the study outcomes include patient surveys, electronic health records and claims submitted to Medicare and Medicaid.Ethics and disseminationAll participants provide written or verbal informed consent prior to randomisation in English, Spanish, French, Mandarin or Russian. Study findings are being disseminated to scientific audiences through peer-reviewed publications and presentations at national and international conferences. This study has been approved by: Biomedical Research Alliance of New York (BRANY #20-08-329-380), Weill Cornell Medicine Institutional Review Board (20-08022605) and Mt. Sinai Institutional Review Board (20-01901).Trial registration numberClinicaltrials.gov, NCT04662541.

The purpose of this study is to investigate which dry port services generate the greatest positive impact on stakeholders and their objectives. Stakeholders identified from the literature are the dry ports, the dry port’s municipality/region, the seaport, shippers, shipping lines, rail operators, and road operators. A method based on multi-actor multi-criteria analysis is applied to allow the evaluation of different scenarios considering the objectives and opinions of multiple stakeholders. The findings show that the basic services of the dry ports studied are crucial to establishing initial operations. Expanding the service portfolio by adding a wider range of customer-oriented value-added services generates extra economic and environmental benefits for stakeholders. The results expand the understanding on stakeholder benefits from the diversified range of dry port services, while the inclusion of multiple stakeholders in the analysis acknowledges the heterogeneity in stakeholder perceptions. Finally, this methodology enables the creation of an extensive set of criteria and indicators for dry port evaluations.

A transthoracic infection involving a low dose of Mycobacterium tuberculosis has been used to establish a new model of infection in minipigs. The 20-week monitoring period showed a marked Th1 response and poor humoral response for the whole infection. A detailed histopathological analysis was performed after slicing the formalin-fixed whole lungs of each animal. All lesions were recorded and classified according to their microscopic aspect, their relationship with the intralobular connective network and their degree of maturity in order to obtain a dissemination ratio (DR) between recent and old lesions. CFU counts and evolution of the DR with time showed that the proposed model correlated with a contained infection, decreasing from week 9 onwards. These findings suggest that the infection induces an initial Th1 response, which is followed by local fibrosis and encapsulation of the granulomas, thereby decreasing the onset of new lesions. Two therapeutic strategies were applied in order to understand how they could influence the model. Thus, chemotherapy with isoniazid alone helped to decrease the total number of lesions, despite the increase in DR after week 9, with similar kinetics to those of the control group, whereas addition of a therapeutic M. tuberculosis fragment-based vaccine after chemotherapy increased the Th1 and humoral responses, as well as the number of lesions, but decreased the DR. By providing a local pulmonary structure similar to that in humans, the mini-pig model highlights new aspects that could be key to a better understanding tuberculosis infection control in humans.