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Summary: Background: Little is known about the practices and resources employed by general practitioners (GPs) in Singapore to manage late-life depression. As the country is stepping up its efforts to promote collaborative care across community mental health and geriatric care, understanding GPs’ current practices when managing late-life depression appears timely. Methods: This qualitative descriptive study explored the perspectives on late-life depression of 28 private GPs practicing in Singapore through online semi-structured group and individual interviews. GPs were purposively sampled across age, gender, and ethnicity. Analysis followed a reflexive thematic approach and focused on physician- and system-related factors. Findings: Clinical instinct, experience, and knowledge of appropriate resources for specific patients played an important role for GPs during late-life depression care. GPs paid particular attention to communicating with patients tactfully during initial assessments and diagnosis, although some GPs chose to be upfront with patients with whom they had already established rapport. Using non-English languages when communicating about depression could mitigate stigma in some cases but added confusion in others. GPs relied primarily on their own professional support network to manage late-life depression. Although GPs acknowledged the usefulness of public care services, they felt that collaborative care was hindered by a lack of efficient communication channels between providers and appropriate financial coverage to coordinate the frequently complex care of depressed older adults. Interpretation: Current resources and practices to manage late-life depression vary greatly between private GPs in Singapore. This needs to be considered during ongoing reforms to achieve effective collaborative care. Funding: This work was funded by the Division of Family Medicine Research Capabilities Building Budget under the project “Technology and Compassion: Improving Patient Outcomes Through Data Analytics and Patients’ Voice in Primary Care” [NUHSRO/2022/049/NUSMed/DFM].

Monitoring reproductive physiology in wildlife can be a useful tool for assessing population dynamics for conservation and management purposes. Utilizing non-invasive approaches for this, such as quantifying reproductive hormone metabolites from faeces, can be challenging when defaecation events are not observed, or when cryptic species like African clawless otters (Aonyx capensis) are involved. Additionally, test systems for quantifying hormone metabolites in a species for the first time must first be reliably validated prior to use. Our results indicate that Epiandrosterone and Progesterone EIAs are most suitable for determining fAM and fPM concentrations in African clawless otter spraints. The fAM:fPM ratio and respective thresholds are more reliable in sex identification compared to the separate use of individual hormone classes. Sex-related hormone metabolite concentrations remained comparable for up to 12hrs post-defaecation in both sexes. • We screened two androgen and two progestagen enzyme-immunoassays (EIAs) for suitability and reliable quantification of faecal androgen metabolites (fAM) and faecal progestagen metabolites (fPM) in African clawless otters. • We assessed whether the ratio of fAM:fPM concentrations can be used to assign sex to faecal samples from unknown individuals. • We tested the stability of fAM and fPM concentrations post-defaecation to determine the effects of environmental exposure and bacterial metabolism.

Background: Contradictory findings link trait conscientiousness in mid- and late life to increased healthspan and lifespan, as well as to death by suicide. It remains unclear whether conscientiousness is associated with higher odds of attempting suicide or with more severe suicidal behavior among attempters, and whether its relationship to suicide risk varies with aging-related stressors, such as declining health. Methods: In this cross-sectional study comprising 313 depressed adults aged ≥40 years and participating in the Longitudinal Research Program in Late-Life Suicide (Pittsburgh, USA), we employed logistic and linear regression to test whether conscientiousness was associated with the presence of recent suicidal behavior (≤2 years) and with intent severity in recent attempters (n = 84). We further tested whether the above relationships varied based on mental, cognitive, and physical health status, measured as depression severity, cognitive functioning, and the presence/absence of severe physical illness. Results: Participants were 62.1 years old on average (SD = 7.6), 85% White, and 53% female. Recent attempters had a mean age of 61.8 years at their most recent attempt (SD = 8.5), had lower cognitive functioning and were more likely severely physically ill than comparisons. Conscientiousness was positively associated with a higher likelihood of recent suicidal behavior overall (adjusted OR = 1.44, 95% CI = 1.09, 1.90, p = .010), but not in case of co-occurring severe physical illness (interaction OR = 0.54, 95% CI = 0.30, 0.97, p = .039). Conscientiousness was also positively associated with suicidal intent at the most recent attempt (adjusted β = 1.60, SE = 0.62, p = .012), explaining 7% of its variance, although this association lost significance after adjusting for other personality dimensions. Conclusions: Highly conscientious middle-aged and older adults may be at increased risk of resolute suicidal behavior, although conscientiousness may not confer additional suicide risk among those severely physically ill.

Summary: Background: Detection and management of late-life depression largely relies on primary care. Yet in Singapore, older adults are unlikely to seek help for their mental health from their primary care providers. This qualitative descriptive study explores how late-life depression manifests to general practitioners (GPs) in the Singaporean primary care setting. Methods: Twenty-eight private GPs practicing in Singapore were asked about their clinical experience with late-life depression during semi-structured group and individual discussions conducted online. Participants were purposively sampled across age, gender, and ethnicity (Chinese, Malay, Indian). Transcripts were analysed with reflexive thematic analysis. Findings: To GPs, depression in older patients often manifests through somatic symptoms or subtle behavioural changes, only detectable through follow-ups or collateral history. GPs reported that older patients attribute depressive symptoms to normal ageing or do not mention them, particularly within an Asian culture encouraging stoic endurance. GPs perceived late-life depression as reactions to ageing-related stressors, with male, low-income, or institutionalised patients being at particular risk of insidious, severe depression. GPs noted ethnic differences regarding families’ involvement in care, which they described as helpful, but sometimes stress-provoking for patients. Fear of burdensomeness or loss of autonomy/social role could prompt rejection of diagnosis and treatment in patients. GPs considered good patient-doctor rapport as a facilitator at every step of the care process, noting more favourable prognosis in care-concordant patients. Interpretation: Depression in older adults in Singapore can be covert, with favourable outcomes relying on GPs’ ability to pick up on subtle changes, assess patients holistically, and build rapport with patients and families. Funding: This work was funded by the Division of Family Medicine Research Capabilities Building Budget under the project “Technology and Compassion: Improving Patient Outcomes Through Data Analytics and Patients’ Voice in Primary Care” [NUHSRO/2022/049/NUSMed/DFM].

Complementing discourse following a February 2023 event on dietary protein needs in Southeast Asia (SEA), this symposium report summarizes the region’s protein intake, while simultaneously examining the impact of dietary shift toward complementary and alternative proteins and their health implications. It highlights the importance of protein quality in dietary evaluations, optimal intake, and sustainability, advocating for environmentally conscious protein production and innovation in future foods. Discussion points, expert opinions, national nutrition data, and relevant literature, addressing protein intake and quality, their impact on human health, and various technologies for future foods production, have been included. Despite increased protein supply in SEA, protein requirements, particularly during crucial life stages, are often unmet owing to insufficient focus on protein quality. Factoring in amino acids content and bioaccessibility are crucial for assessing nutritional requirement and sustainability evaluations, rather than solely relying on protein quantity alone. Different food sources of protein also have different key conutrients for health relevance such as vitamin B-12 and ω-3 fatty acids. Innovations in food structure, processing, and technology are key to developing nutritious, sustainable, and appealing future foods, including from complementary and alternative protein sources, while considering safety aspects, especially allergenicity. Addressing protein needs in SEA requires a dual focus on protein quantity and quality, underlining the role of public health policies and guidelines that consider key nutritional differences of animal-source and plant-based proteins. To address regional demands, future food innovations should aim at creating unique yet needful food categories or supplementing current existing sources, rather than mimicking current products.

Background: Orthostatic hypotension (OH) is common in older adults with hypertension. Antihypertensive treatment (AHT) prevents cardio- and cerebrovascular events. However, physicians are concerned to cause OH, making them hesitant to initiate or augment AHT in older adults with hypertension. Methods: We systematically researched electronic databases for trials with older participants (≥65 years) with hypertension and OH assessment after initiating, discontinuing, or augmenting AHT. Study quality was assessed using the ROBINS-I tool. Meta-analyses on OH prevalence and postural blood pressure (BP) drop were performed. Results: Twenty-five studies (26,695 participants) met inclusion criteria, of which fifteen could be included in the meta-analyses. OH prevalence decreased after AHT initiation or augmentation (risk ratio 0.39 (95 % CI = 0.21–0.72; I2 = 47 %; p

Importance: The burgeoning landscape of wearable devices warrants a guide for the selection of devices. Existing guidelines and recommendations provide evaluation frameworks with theoretical principles but tend to lack a pragmatic application and systematic approach for device selection. While fitness trackers exemplify the convenience of wearable technologies, their selection for specific health monitoring purposes demands a nuanced understanding of varying functionalities and user compatibilities. Objective: The objective is to develop and present a practical guide for researchers, healthcare professionals, and device users to systematically select wearable devices for continuous monitoring in community-dwelling adults. Methods & results: Based on diverse sources, such as the United States Food and Drug Administration (FDA), the Clinical Trials Transformation Initiative (CTTI), the Electronic Patient-Reported Outcome (ePRO) Consortium, and comparative analyses of wearable technology performances from feasibility and usability studies, the guide incorporates five core criteria: continuous monitoring capability, device availability and suitability, technical performance (accuracy and precision), feasibility of use, and cost evaluation. The structured criteria can be applied in device selection as well as device evaluation. Conclusions: This practical guide provides a step-by-step solution for researchers, healthcare professionals, and device users to choose suitable wearable devices for continuous monitoring. It provides a comprehensive starting point, outlining how to effectively navigate the selection process for wearable devices amidst a plethora of similar options.

Background: Accelerated biological ageing is a major underlying mechanism of frailty development. This study aimed to investigate if the biological age measured by a blood biochemistry-based ageing clock is associated with frailty in geriatric rehabilitation inpatients. Methods: Within the REStORing health of acutely unwell adulTs (RESORT) cohort, patients' biological age was measured by an ageing clock based on completed data of 30 routine blood test variables measured at rehabilitation admission. The delta of biological age minus chronological age (years) was calculated. Ordinal logistic regression and multinomial logistic regression were performed to evaluate the association of the delta of ages with frailty assessed by the Clinical Frailty Scale. Effect modification of Cumulative Illness Rating Scale (CIRS) score was tested. Results: A total of 1187 geriatric rehabilitation patients were included (median age: 83.4 years, IQR: 77.7–88.5; 57.4 % female). The biochemistry-based biological age was strongly correlated with chronological age (Spearman r = 0.883). After adjustment for age, sex and primary reasons for acute admission, higher biological age (per 1 year higher in delta of ages) was associated with more severe frailty at admission (OR: 1.053, 95 % CI:1.012–1.096) in patients who had a CIRS score of 12. The delta of ages was not associated with frailty change from admission to discharge. The specific frailty manifestations as cardiac, hematological, respiratory, renal, and endocrine conditions were associated with higher biological age. Conclusion: Higher biological age was associated with severe frailty in geriatric rehabilitation inpatients with less comorbidity burden.

Background: Emotion dysregulation is a characteristic central to borderline personality disorder (BPD). Valuably, verbal behaviour can provide a unique perspective for studying emotion dysregulation in BPD, with recent research suggesting that the varieties of emotion words one actively uses (i.e., active emotion vocabularies [EVs]) reflect habitual experience and potential dysregulation therein. Accordingly, the present research examined associations between BPD and active EVs across two studies. Methods: Study 1 (N = 530) comprised a large non-clinical sample recruited from online forums, whereby BPD traits were measured via self-report. Study 2 (N = 64 couples) consisted of mixed-gender romantic couples in which the woman had a BPD diagnosis, as well as a control group of couples. In both studies, participants’ verbal behaviours were analysed to calculate their active EVs. Results: Results from both studies revealed BPD to be associated with larger negative EV (i.e., using a broad variation of unique negative emotion words), which remained robust when controlling for general vocabulary size and negative affect word frequency in Study 2. The association between BPD and negative EV was insensitive to context. Limitations: Limitations of this research include: 1) the absence of a clinical control group; 2) typical constraints surrounding word-counting approaches; and 3) the cross-sectional design (causality cannot be inferred). Conclusions: Our findings contribute to BPD theory as well as the broader language and emotion literature. Importantly, these findings provide new insight into how individuals manifesting BPD attend to and represent their emotional experiences, which could be used to inform clinical practice.

Background: Developing context-specific, evidence-informed, and implementable injury-prevention programs is challenging. Women playing in the elite Australian Football League for Women are at high risk of serious knee injuries, and no specific injury-prevention program exists. The objective of the study was to describe the collaborative process used to create a context-specific injury-prevention program. Methods: A previously used intervention-development process was modified to incorporate a partnership with the sport's governing organization and focus on engaging program implementers. The Reach Effectiveness Adoption Implementation and Maintenance (RE-AIM) Sports Setting Matrix guided program development and implementation strategies. Results: The 7-step process, aligned with the RE-AIM Sports Setting Matrix, was applied to develop the injury-prevention program and was titled Prep to Play PRO. The steps were: (Step 1) gaining organizational support and establishing a project partnership; (Step 2) using research evidence and clinical experience; (Step 3) consulting content and context experts; (Step 4) engaging the organization, experts, program implementers, and end-users to concreate the intervention and develop implementation strategies; (Step 5) testing the intervention acceptability and feasibility; (Step 6) evaluating the intervention and implementation strategies against theory; and (Step 7) obtaining feedback from early implementers and end-users. Conclusion: Engaging critical stakeholders at multiple ecological levels (organization, team, and athlete) throughout program development and implementation planning support real-world use. The processes and activities described can guide future sports injury-prevention program development and implementation.

Introduction: There is evidence that supports the association of dense tumor infiltrating lymphocyte (TILs) with an increased risk of ipsilateral recurrence in ductal carcinoma in situ (DCIS). However, the association of cellular composition of DCIS immune microenvironment with the histopathologic parameters and outcome is not well understood. Methods: We queried our institutional database for patients with pure DCIS diagnosed between 2010 and 2019. Immunohistochemical studies for CD8, CD4, CD68, CD163, and FOXP3 were performed and evaluated in the DCIS microenvironment using tissue microarrays. Statistical methods included Fisher's exact test for categorical variables and the two-sample t-test or the Wilcoxon Rank-Sum test for continuous variables. Results: The analytic sample included 67 patients. Median age was 62 years (range = 53 to 66) and median follow up was 6.7 years (range = 5.3 to 7.8). Thirteen patients had ipsilateral recurrence. Of all the clinicopathologic variables, only the DCIS size and TIL density were significantly associated with recurrence (p = 0.023 and 0.006, respectively). After adjusting for age and TIL density, only high CD68 (>50) and high CD68/CD163 ratio (>0.46) correlated with ipsilateral recurrence (p = 0.026 and 0.013, respectively) and shorter time to recurrence [hazard ratio 4.87 (95% CI: 1.24–19, p = 0.023) and 10.32 (95% CI: 1.34–80, p = 0.025), respectively]. Conclusions: In addition to DCIS size and TIL density, high CD68+ tumor-associated macrophages predict ipsilateral recurrence in DCIS. High CD68+ macrophage density and CD68/CD163 ratio also predict a shorter time to recurrence.

Sex differences in human navigation and orientation skills are among the most recognized and studied in human cognition. Numerous findings have shown sex biases on various spatial tasks, with males typically outperforming females on popular tasks such as those measuring mental rotation. Other robust sex differences can be found in video game experience and genre preference, where males tend to play more games and prefer to play games with a stronger navigational component compared to females. To date, little is known about how experience playing video games with a specific navigation component affects spatial ability. In this study we explored how sex effects are impacted when controlling for navigation-style video game experience. In a group of 1305 participants, we first analyzed sex effects on a variety of spatial tasks without controlling for video game experience. Following this, we used case-control matching to create groups for each task that did not differ significantly in their age or video game experience. We then used these matched groups to analyze the sex effects for each task while controlling for video game experience. We found that before controlling for video game experience, males significantly outperformed females on our measure of mental rotation ability. However, after accounting for video game experience, there was no significant difference in mental rotation accuracy between females and males. We also found that before controlling for video game experience, there was no significant difference between males and female accuracy on a measure of spatial perspective taking. After controlling for video game experience, we found that females significantly outperformed males in perspective taking accuracy. Our findings suggest that video game experience does change how sex effects in spatial skills are interpreted and should be considered as a relevant confounding variable.

The projected increase in ‘water scarcity – water reuse’ situations, the associated risks and sustainability challenges, and trends towards holistic approaches motivate the development of integrated assessment for decision-making. The integrated Risk and Sustainability Assessment (RSA) Framework combines the analysis and evaluation of both risk and sustainability of ‘water scarcity – water reuse’ situations. This work aims to test the RSA Framework in a case study in Chile. The analysis uses a multi-layer approach and lane-based approach to translate the real-world system into an information system and to determine interlinkages between indicators. The evaluation involves thresholds and weights to calculate risk and sustainability sub-indices and an RSA index applying TOPSIS. The results indicate low interlinkage between risk and sustainability indicators, visibilising the importance of which and how indicators are considered and what they measure. They show a higher than tolerable degree of risk but an acceptable degree of sustainability. The relevance of spatial and temporal scales for the assessment becomes evident. Spatial aspects are key in determining the degree of water scarcity and how the impact of water reuse can be included in its calculation. Temporal aspects complicate the integration of risk (scenario-based) and sustainability (snapshot mode) assessments. The TOPSIS method appears to be suitable for the aggregation of risk and sustainability performance indicators. Altogether, the results show the potential of the RSA Framework for organising and processing information required to support decision-makers addressing ‘water scarcity – water reuse’ situations from the perspectives of risk and sustainability.

Introduction: The spatial distribution of white matter hyperintensities (WMH) on MRI is often considered in the diagnostic evaluation of patients with cognitive problems. In some patients, clinicians may classify WMH patterns as “unusual”, but this is largely based on expert opinion, because detailed quantitative information about WMH distribution frequencies in a memory clinic setting is lacking. Here we report voxel wise 3D WMH distribution frequencies in a large multicenter dataset and also aimed to identify individuals with unusual WMH patterns. Methods: Individual participant data (N = 3525, including 777 participants with subjective cognitive decline, 1389 participants with mild cognitive impairment and 1359 patients with dementia) from eleven memory clinic cohorts, recruited through the Meta VCI Map Consortium, were used. WMH segmentations were provided by participating centers or performed in Utrecht and registered to the Montreal Neurological Institute (MNI)-152 brain template for spatial normalization. To determine WMH distribution frequencies, we calculated WMH probability maps at voxel level. To identify individuals with unusual WMH patterns, region-of-interest (ROI) based WMH probability maps, rule-based scores, and a machine learning method (Local Outlier Factor (LOF)), were implemented. Results: WMH occurred in 82% of voxels from the white matter template with large variation between subjects. Only a small proportion of the white matter (1.7%), mainly in the periventricular areas, was affected by WMH in at least 20% of participants. A large portion of the total white matter was affected infrequently. Nevertheless, 93.8% of individual participants had lesions in voxels that were affected in less than 2% of the population, mainly located in subcortical areas. Only the machine learning method effectively identified individuals with unusual patterns, in particular subjects with asymmetric WMH distribution or with WMH at relatively rarely affected locations despite common locations not being affected. Discussion: Aggregating data from several memory clinic cohorts, we provide a detailed 3D map of WMH lesion distribution frequencies, that informs on common as well as rare localizations. The use of data-driven analysis with LOF can be used to identify unusual patterns, which might serve as an alert that rare causes of WMH should be considered.

Objective: Collate the perceptions and experience of relevant key stakeholders to develop reporting guidelines for epidemiological injury and physical performance data within law enforcement agencies recruit training programs. Design: An augmented Delphi consensus process. Methods: Initial item generation occurred via online, one-on-one, semi-structured interviews, and followed by one survey round. Items generated from interviews were categorised within three main categories: i) Demographic data, ii) Injury data, and iii) Physical performance data. Participants represented one-of-six target groups: Police officers; Police physical training staff; Police occupational health and safety staff; Elite sport high performance staff; Military high-performance staff; Physical activity injury epidemiologists. Results: A total of 15 representatives (53% women) from six stakeholder groups were included. Other than responses directly related to item generation, three main themes emerged from round one: i) recruits are not likely to report all data being requested truthfully, ii) data that is recorded must be acted upon, and iii) body fat assessments should not be included in this population with focus instead being placed on performance. Three separate reporting databases were generated. Conclusion: Our study established clear demographic, mental health/physical injury, and physical performance data to be collected in a law enforcement recruit training program for injury surveillance and performance monitoring. Furthermore, we identified several items that were classified as relevant, but unlikely to be reported truthfully. These items can help inform current practice and assist clinicians to determine the trustfulness of information received by patients when working within law enforcement environments.

Summary: The 9th FIFA Women's World Cup (FWWC) marked several milestones: the first hosted by two Nations, held in the Southern Hemisphere, comprising 32 teams, and >1.9million spectators (FWWC attendance record). The overwhelming success of the tournament stimulated huge public interest in women's football. The importance of maximising player health was apparent throughout the tournament with injuries and illnesses affecting team selection and performance, emphasising the need for continued focus on women's football player health. This short report summarises the key takeaway messages from the Women's Football Medicine Conference held online during the round stages of the 2023 FWWC.

Over the past 15 years, deep brain stimulation (DBS) has been actively investigated as a groundbreaking therapy for patients with treatment-resistant depression (TRD); nevertheless, outcomes have varied from patient to patient, with an average response rate of ∼50%. The engagement of specific fiber tracts at the stimulation site has been hypothesized to be an important factor in determining outcomes, however, the resulting individual network effects at the whole-brain scale remain largely unknown. Here we provide a computational framework that can explore each individual's brain response characteristics elicited by selective stimulation of fiber tracts. We use a novel personalized in-silico approach, the Virtual Big Brain, which makes use of high-resolution virtual brain models at a mm-scale and explicitly reconstructs more than 100,000 fiber tracts for each individual. Each fiber tract is active and can be selectively stimulated. Simulation results demonstrate distinct stimulus-induced event-related potentials as a function of stimulation location, parametrized by the contact positions of the electrodes implanted in each patient, even though validation against empirical patient data reveals some limitations (i.e., the need for individual parameter adjustment, and differential accuracy across stimulation locations). This study provides evidence for the capacity of personalized high-resolution virtual brain models to investigate individual network effects in DBS for patients with TRD and opens up novel avenues in the personalized optimization of brain stimulation.

Purpose: To describe steps taken that enabled a high rate of retention and early resumption of enrollment in the Zoster Eye Disease Study (ZEDS), a randomized controlled trial funded by the National Eye Institute, during the first 13 months (3/1/2020–3/31/2021) of the COVID–19 pandemic. Methods: A number of responses were implemented in ZEDS when the focus shifted to retention of study participants at the beginning of the pandemic including frequent communication with the participating clinical centers (PCCs) about remote visits, local lab work, shipping study medication, and completion of revised case report forms. Additional payments were provided to the PCCs. Remote activation of PCCs continued. Screening and enrollment visits gradually resumed when allowed. Results: Communication with PCCs increased, and average attendance at monthly coordinator teleconferences went up from 17 to 47. Remote visits peaked in April 2020, accounting for 75% (33/44) of study visits, then declined to less than 10% of study visits beginning August 2020. Overall, 97% (590/609) of study visits were completed. Only 5.5% (9/165) of study participants withdrew consent, and 2.4% (4/165) were lost to follow-up. Enrollment returned to pre-pandemic levels by September 2020. Discussion: Strong communication and unwavering commitment, combined with the technological capability for remote work, visits, and shipment of study medication, were key to the successful retention of study participants and resumption of enrollment. Conclusions: Rapid responses to challenges to trials caused by the COVID-19 pandemic can enable them to continue successfully and provide insights into the planning of future trials.

Gaucher disease is renowned for extreme phenotypic diversity that does not show consistent genotype/phenotype correlations. In Argentina, a national collaborative group, Grupo Argentino de Diagnóstico y Tratamiento de la Enfermedad de Gaucher, GADTEG, delineated uniformly severe type 1 Gaucher disease manifestations presenting in childhood with large burden of irreversible skeletal disease. Here using Long-Read Single Molecule Real-Time (SMRT) Sequencing of GBA1 locus, we show that the RecNciI allele is highly prevalent and it is associated with severe skeletal manifestations with onset in childhood or in young adults. Additionally, we described novel GBA1 variants not previously described.

Intra-individual transient temporal fluctuations in brain signal, as measured by fMRI blood oxygenation level dependent (BOLD) variability, is increasingly considered an important signal rather than measurement noise. Evidence from computational and cognitive neuroscience suggests that signal variability is a good proxy-measure of brain functional integrity and information processing capacity. Here, we sought to explore across-participant and longitudinal relationships between BOLD variability, age, and white matter structure in early childhood. We measured standard deviation of BOLD signal, total white matter volume, global fractional anisotropy (FA) and mean diffusivity (MD) during passive movie viewing in a sample of healthy children (aged 2–8 years; N = 83). We investigated how age and white matter development related to changes in BOLD variability both across- and within-participants. Our across-participant analyses using behavioural partial least squares (bPLS) revealed that the influence of age and white matter maturation on BOLD variability was highly interrelated. BOLD variability increased in widespread frontal, temporal and parietal regions, and decreased in the hippocampus and parahippocampal gyrus with age and white matter development. Our longitudinal analyses using linear mixed effects modelling revealed significant associations between BOLD variability, age and white matter microstructure. Analyses using artificial neural networks demonstrated that BOLD variability and white matter micro and macro-structure at earlier ages were strong predictors of BOLD variability at later ages. By characterizing the across-participant and longitudinal features of the association between BOLD variability and white matter micro- and macrostructure in early childhood, our results provide a novel perspective to understand structure-function relationships in the developing brain.

The effect of different doses of UV-C light (5.3, 8.3 and 11.4 kJ/m2) on native mycobiota and Botrytis cinerea incidence, micro and ultrastructure, biomechanical properties and weight loss of blueberry fruit cv. O'Neal during 20 days of storage at 8 ± 1 °C was evaluated. Decay incidence was significantly reduced by all UV-C light doses for both, native mycobiota and inoculated B. cinerea. The highest UV-C dose studied (11.4 kJ/m2) was the most effective indelaying the onset of fungal and B. cinerea infection (6 and 4 days, respectively). UV-C irradiation caused some distinctive changes in fruit structure characterized by redistribution, alteration and partial removal of epicuticular waxes, reinforcement of epicarp cell walls, and modifications in the cuticle. Biomechanical parameters were not affected by UV-C treatments excepting at day 15 where irradiated samples showed higher values of rupture force (FR) and deformation (D). Structure changes partially explained the significant increase in weight loss, FR and D values in irradiated fruit after 15 days of storage. UV-C irradiation could be an alternative for delaying and reducing fungal infection. However, postharvest shelf-life of irradiated blueberries could be limited by the negative effect on weight loss.

Background: Initial orthostatic hypotension is a clinically relevant syndrome in older adults which has been associated with symptoms of orthostatic intolerance. The aim of this systematic review was to determine the prevalence of orthostatic intolerance symptoms in older adults with initial orthostatic hypotension. Methods: MEDLINE (from 1946), EMBASE (from 1974) and Cochrane were searched to December 6th, 2019 using the terms “initial orthostatic hypotension”, “postural hypotension” and “older adults”. Study selection involved the following criteria: published in English; mean or median age ≥65 years and diagnosis of initial orthostatic hypotension encompassed a decrease in systolic blood pressure by ≥ 40 mmHg and/or diastolic blood pressure by ≥ 20 mmHg within a maximum of 1 min following a postural change. Results: Of 8311 articles, 12 articles reporting initial orthostatic hypotension prevalence in 3446 participants with a mean age of 75 (6 SD) years (56.5% female) were included. Five initial orthostatic hypotension definition variations were utilised and symptoms were reported in six articles (968 participants, mean age 73.4 (6.1 SD) years, 56% female). The prevalence of symptoms in older adults with initial orthostatic hypotension ranged from 24 to 100% and was dependent on variations in timing or the inclusion of symptoms in the initial orthostatic hypotension definition. Conclusions: Where orthostatic intolerance symptoms were reported, a large proportion of older adults with a diagnosis of initial orthostatic hypotension were symptomatic. However, the literature on initial orthostatic hypotension and orthostatic intolerance symptoms is scarce and a variety of definitions of initial orthostatic hypotension are utilised.

Pollution is a key threat to biodiversity and ecosystem health within protected areas. Using a non-invasive, multi-matrix approach, sediment, vegetation and faecal material from lion (Panthera leo) and giraffe (Giraffa camelopardalis) were collected and assessed for the simultaneous quantification of 20 trace elements using an optimised method for Inductively Coupled Plasma-–Mass Spectrometry (ICP-MS). Method Linearity was confirmed over an analytical range of 0.1–50 mg/kg for aluminium (Al) and iron (Fe); 0.4–400 µg/kg for vanadium (V), cobalt (Co), molybdenum (Mo), and cadmium (Cd); 0.5–5 µg/kg for mercury (Hg); and 1–1 000 µg/kg for elements arsenic (As), boron (B), barium (Ba), chromium (Cr), copper (Cu), manganese (Mn), nickel (Ni), lead (Pb), antimony (Sb), selenium (Se), tin (Sn), strontium (Sr) and zinc (Zn). Coefficient of determination (R2) was above 0.99 for all elements. Accuracy (% recovery) and precision (% RSD) of replicate measurements for certified reference material controls fell within 20% of expected value at lower concentrations and 15% at higher concentrations for all elements except Al. Results for instrument and method limit of detections (LOD), method limit of quantification (LOQ) and expanded uncertainty were satisfactory. Preliminary data indicate As, Cd, Cr, Cu, Hg, Ni, Pb, Se, and Zn were present in all matrices evaluated. This raises concerns regarding the combined action of multiple elements at concentrations that can adversely affect ecosystem and wildlife integrity. • Sample quantity is reduced due to the power and sensitivity of ICP-MS. • The optimised method is capable of detecting differences in trace element concentrations over large orders of magnitude in animal faeces containing different amounts of organic content. • The method can be applied to the quantification of essential and potentially toxic elements in faeces across a wide range of terrestrial species.

Introduction: Although three randomized control trials have proven mortality benefit of CT lung cancer screening (CTLS),

Objective: To improve quality of life (QOL) in patients at risk for post–intensive care syndrome (PICS). Patients and Methods: We conducted a mixed-method, prospective, observational, pre-post interventional study in an adult medical and mixed medical/surgical/transplant intensive care unit (ICU) at a tertiary academic hospital. Preintervention included patients admitted from October 1 through October 31, 2016, and postintervention included patients admitted from January 15 through February 14, 2017. First, a multidisciplinary team of stakeholders identified barriers associated with decreased QOL in patients at risk for PICS. Next, interventions were designed and implemented. The effect of interventions was assessed using a mixed-method analysis. The qualitative analysis used a modified grounded theory approach. The quantitative analysis included assessment of preexisting symptoms and risk factors associated with PICS. The 36-Item Short-Form Health Status Survey (SF-36), which surveys physical and mental composite scores, was used to assess QOL. Results: Barriers identified were lack of awareness and understanding of PICS. Interventions included educational videos, paper and online education and treatment materials, and online and in-person support groups for education and treatment. After interventions, the qualitative analysis found that patients who participated in the interventions after hospital discharge showed improved QOL, whereas education during hospitalization alone was not effective. The quantitative analysis did not find improvement in QOL, as defined by SF-36 physical or mental composite scores. Conclusion: Interventions targeted to patients after hospitalization may offer subjective improvement in QOL for those at risk for PICS.

Background: Previous work suggests that major depressive disorder (MDD) is associated with disturbances in global connectivity among brain regions, as well as local connectivity within regions. However, the relative importance of these global versus local changes for successful antidepressant treatment is unknown. We used multiscale entropy (MSE), a measure of brain signal variability, to examine how the propensity for local (fine scale MSE) versus global (coarse scale MSE) neural processing measured prior to antidepressant treatment is related to subsequent treatment response. Methods: We collected resting-state EEG activity during eyes-open and closed conditions from unmedicated individuals with MDD prior to antidepressant pharmacotherapy (N=36) as well as from non-depressed controls (N=36). Treatment response was assessed after 12weeks of treatment using the Montgomery-Åsberg Depression Rating Scale (MADRS), at which time participants with MDD were characterized as either responders (≥50% MADRS decrease) or non-responders. MSE was calculated from baseline EEG, and compared between controls, future treatment responders and non-responders. Putative interactions with the well-documented age effect on signal variability (increased reliance on local neural communication with increasing age, indexed by greater finer-scale variability) were assessed. Results: Only in responders, we found that reduced MSE at fine temporal scales (especially fronto-centrally) and increased MSE diffusely at coarser temporal scales was related to the magnitude of the antidepressant response. In controls and MDD non-responders, but not MDD responders, there was an increase in MSE with age at fine temporal scales and a decrease in MSE with age at coarse temporal scales. Conclusion: Our results suggest that an increased propensity toward global processing, indexed by greater MSE at coarser timescales, at baseline appears to facilitate eventual antidepressant treatment response. Keywords: Depression, Treatment, Response, Multi-scale entropy (MSE), Electroencephalography (EEG), Signal variability, Spectral power density (SPD)

There is growing interest in using financial incentives for patients to improve medication adherence, but few studies have evaluated whether financial incentives are associated with patients' activation and motivation. We analyzed survey data collected as part of a randomized clinical trial conducted from 2011 to 2014 of four financial incentive interventions to reduce low density lipoprotein cholesterol (LDL-C) among patients at risk for atherosclerotic cardiovascular disease. The main trial included 1503 patients aged 18–80 and recruited from primary care practices affiliated with three health systems. Participants were randomized into four groups: patient financial incentives, primary care physicians (PCPs) incentives, patients and PCPs shared incentives, or no incentives for LDL-C control. Patient Activation Measure (PAM) and Treatment Self Regulation Questionnaire (TSRQ) surveys were administered at baseline and 12 months. Clinical outcomes were change in LDL-C at 12 and 15 months and average medication adherence as measured by electronic pill bottle opening. Mean changes in PAM and TSRQ scores were compared between patients eligible and not eligible for incentives. Clinical outcomes were tested against baseline and change in psychosocial measures using bivariate and multivariate regression. Change in PAM score and TSRQ autonomous subscore did not differ significantly between patients eligible and not eligible for incentives. Lower baseline and greater increase in TSRQ autonomous subscore were predictive of greater 15-month decrease in LDL-C. A financial incentive intervention to improve LDL-C control was not associated with changes in patients' activation or autonomous motivation. Increases in patient autonomous motivation are predictive of long-term LDL-C control. Keywords: Patient activation, Incentives, Motivation, Behavioral economics, Cholesterol

Computational models predict that focal damage to the Default Mode Network (DMN) causes widespread decreases and increases of functional DMN connectivity. How such alterations impact functioning in a specific cognitive domain such as episodic memory remains relatively unexplored. Here, we show in patients with unilateral medial temporal lobe epilepsy (mTLE) that focal structural damage leads indeed to specific patterns of DMN functional connectivity alterations, specifically decreased connectivity between both medial temporal lobes (MTLs) and the posterior part of the DMN and increased intrahemispheric anterior–posterior connectivity. Importantly, these patterns were associated with better and worse episodic memory capacity, respectively. These distinct patterns, shown here for the first time, suggest that a close dialogue between both MTLs and the posterior components of the DMN is required to fully express the extensive repertoire of episodic memory abilities.

Background: The eastern Mediterranean region is comprised of 22 countries: Afghanistan, Bahrain, Djibouti, Egypt, Iran, Iraq, Jordan, Kuwait, Lebanon, Libya, Morocco, Oman, Pakistan, Palestine, Qatar, Saudi Arabia, Somalia, Sudan, Syria, Tunisia, the United Arab Emirates, and Yemen. Since our Global Burden of Disease Study 2010 (GBD 2010), the region has faced unrest as a result of revolutions, wars, and the so-called Arab uprisings. The objective of this study was to present the burden of diseases, injuries, and risk factors in the eastern Mediterranean region as of 2013. Methods: GBD 2013 includes an annual assessment covering 188 countries from 1990 to 2013. The study covers 306 diseases and injuries, 1233 sequelae, and 79 risk factors. Our GBD 2013 analyses included the addition of new data through updated systematic reviews and through the contribution of unpublished data sources from collaborators, an updated version of modelling software, and several improvements in our methods. In this systematic analysis, we use data from GBD 2013 to analyse the burden of disease and injuries in the eastern Mediterranean region specifically. Findings: The leading cause of death in the region in 2013 was ischaemic heart disease (90·3 deaths per 100 000 people), which increased by 17·2% since 1990. However, diarrhoeal diseases were the leading cause of death in Somalia (186·7 deaths per 100 000 people) in 2013, which decreased by 26·9% since 1990. The leading cause of disability-adjusted life-years (DALYs) was ischaemic heart disease for males and lower respiratory infection for females. High blood pressure was the leading risk factor for DALYs in 2013, with an increase of 83·3% since 1990. Risk factors for DALYs varied by country. In low-income countries, childhood wasting was the leading cause of DALYs in Afghanistan, Somalia, and Yemen, whereas unsafe sex was the leading cause in Djibouti. Non-communicable risk factors were the leading cause of DALYs in high-income and middle-income countries in the region. DALY risk factors varied by age, with child and maternal malnutrition affecting the younger age groups (aged 28 days to 4 years), whereas high bodyweight and systolic blood pressure affected older people (aged 60–80 years). The proportion of DALYs attributed to high body-mass index increased from 3·7% to 7·5% between 1990 and 2013. Burden of mental health problems and drug use increased. Most increases in DALYs, especially from non-communicable diseases, were due to population growth. The crises in Egypt, Yemen, Libya, and Syria have resulted in a reduction in life expectancy; life expectancy in Syria would have been 5 years higher than that recorded for females and 6 years higher for males had the crisis not occurred. Interpretation: Our study shows that the eastern Mediterranean region is going through a crucial health phase. The Arab uprisings and the wars that followed, coupled with ageing and population growth, will have a major impact on the region's health and resources. The region has historically seen improvements in life expectancy and other health indicators, even under stress. However, the current situation will cause deteriorating health conditions for many countries and for many years and will have an impact on the region and the rest of the world. Based on our findings, we call for increased investment in health in the region in addition to reducing the conflicts. Funding: Bill & Melinda Gates Foundation.