Process evaluation of implementation of the early stages of a whole systems approach to obesity in a small Island.

BACKGROUND: The small Atlantic island of St Helena is a United Kingdom Overseas Territory (UKOT) with a high prevalence of childhood obesity (over a quarter of 4-5 and 10-11 year olds) and, anecdotally, adulthood obesity and its associated health detriments. St Helena have taken a whole systems approach to obesity (WSAO) to address the issue. A WSAO recognises the factors that impact obesity as a complex system and requires a 'health in all policies' approach. UK academic and public health technical support was provided to the local St Helena delivery team. This process evaluation sought to explore the early stages of the WSAO implementation and implications for the transferability of the approach to other small island developing states and UKOT. METHODS: Data was collected via eight semi-structured interviews, paper based and online surveys, and document analysis. Thematic analysis was used to analyse the data. RESULTS: The analysis identified three factors which aided the first phase of WSAO implementation: (1) senior leaders support for the approach; (2) the academic support provided to establish and develop the approach; and (3) effective adaptation of UK Government resources to suit the local context. Key challenges of early implementation included: maintaining and broadening stakeholder engagement; limited local workforce capacity and baseline knowledge related to obesity and systems thinking; and limited capacity for support from the UK-based academic team due to contract terms and COVID-19 restrictions. CONCLUSIONS: Early stages of implementation of a WSAO in a UKOT can be successful when using UK's resources as a guide and adapting them to a small island context. All participants recommended other small islands adopt this approach. Continued senior support, dedicated leadership, and comprehensive community engagement is needed to progress implementation and provide the foundation for long-term impact. Small island developing states considering adopting a WSAO should consider political will, senior level buy-in and support, funding, and local workforce knowledge and capacity to enable the best chances of successful and sustainable implementation.

Optic nerve sheath diameter and eyeball transverse diameter in severe head injury and its correlation with intracranial pressure.

BACKGROUND: Gold standard for determining intracranial pressure (ICP), intraventricular catheter, is invasive with associated risks. Non-invasive investigations like magnetic resonance imaging and ultrasonography have demonstrated correlation between optic nerve sheath diameter (ONSD) and raised ICP. However, computed tomography (CT) is accessible and less operator-dependent. Literature shows variable results regarding correlations between ICP and ONSD on CT. The study aimed to investigate correlations between raised ICP and ONSD, eyeball transverse diameter (ETD), and ONSD/ETD ratios on CT scan(s) of severe head injuries. METHODS: A retrospective review of a three-year prospectively-maintained database of severe traumatic head injuries in patients who had ICP measurements and CT scans was conducted. Glasgow Coma Score (GCS), ICP, ONSD 3 mm and 9 mm behind the globe, ETD, ONSD/ETD ratios, CT Marshall Grade, and Glasgow Outcome Score (GOS) were recorded. Statistical analysis assessed correlations between ICP and CT measurements. RESULTS: Seventy-four patients were assessed; mortality rate: 36.5 %. Assault (48.6 %) and pedestrian-vehicle collisions (21.6 %) were the most common mechanisms. CT Marshall Grade correlated significantly with 3 mm and 9 mm ONSD, ONSD/ETD ratios, GCS, and GCS motor score, which correlated significantly with GOS. No significant correlation was found between ICP and ONSD, ETD or ONSD/ETD ratios. Marshall Grade was not significantly associated with ICP measurements but correlated with injury severity. CONCLUSIONS: Unlike previous studies, our study not only investigated the correlation between ICP and single variables (ONSD and ETD) but also the ONSD/ETD ratios. No correlations were observed between raised ICP and ONSD, ETD or ONSD/ETD ratio on CT in neurotrauma patients.

Lessons on food security from the COVID-19 pandemic in Bermuda.

Compared with other OECD countries, Bermuda ranks third globally in terms of income inequality globally. During the COVID-19 pandemic, anecdotal evidence suggested, significant fluctuations in the food demand and supply. We aimed to examine the impact of the COVID-19 pandemic on food insecurity, with a focus on the availability and affordability of various foods in Bermuda. We utilized a cross-sectional study design to investigate potential drivers of food insecurity within the local population. To gauge the level of household food insecurity we relied on the Bermuda Omnibus survey (N = 400) undertaken by Total Research Associates Ltd via telephone. To assess changes in food availability and affordability we conducted semi-structured interviews with key stakeholders who played pivotal roles in shaping food accessibility availability and affordability of food in Bermuda. These interviews were systematically analysed using the framework method. We performed analyses of food retail and import data to evaluate fluctuations in food prices and their impact on food availability and affordability. We found statistically significant associations between changes in food consumption, household income, and government aid. Food aid beneficiaries ate fewer fruits and vegetables by 50% [95% CI:17%-83%] and less fresh meat and fish by 39% [95 CI:3%-75%] compared with residents who did not receive any aid during the COVID-19 period from March 2020 to March 2021. Although we did not identify statistically significant food price increases feeding programmes played a pivotal role in preventing food insecurity during the pandemic in Bermuda. However, a lack of monitoring regarding the nutritional quality within the programmes, allowed a wide availability of foods high in sugar, salts, and fats, disproportionately affected low-income populations. In conclusion, food availability in Bermuda remained largely unaffected during the pandemic. Nevertheless, the surge in demand for feeding programs underscores underlying food security challenges in Bermuda and warrants further attention.

Allogeneic chondrogenic-induced mesenchymal stem cells for the treatment of tarsometatarsal lameness in horses.

OBJECTIVE: To assess the efficacy of commercial intra-articular blood-derived allogeneic-induced mesenchymal stem cells (CIMSCs) to treat tarsometatarsal lameness in horses. STUDY DESIGN: This was a retrospective cohort study. ANIMALS: Records from 167 adult light breed horses with bilateral tarsometatarsal lameness. METHODS: Horses with tarsometatarsal lameness were retrospectively selected from medical records. Diagnosis followed subjective graded lameness assessment before and after intra-articular analgesia, with graded radiographic tarsal examination. Horses were excluded if they were diagnosed or treated for any other concurrent lameness conditions during the study. Time to last follow-up and time of recurrence of lameness was recorded at veterinary re-assessment. RESULTS: A total of 67 horses were recruited to the CIMSC-treated group and 100 to the corticosteroid (CS)-treated group. Median age was 9 years, with no difference in signalment, use or radiographic grade between groups. First re-examination was 38 days (95% CI: 38-49), with no difference between groups, CIMSC 42 (35-45), control 34 (25-42). Median follow-up was 438 days for CIMSC, 546 for controls. Symptoms of lameness recurred in 86/100 controls compared to 17/67 (25%) CIMSC. Median time to lameness recurring in CIMSC was 336 days (95% CI: 239-400), control 90 days (95% CI: 80-108), p < .0001. Cox proportional hazard ratio for treatment was 8.35, 95% CI: 4.67 to 14.92, p < .0001. CONCLUSIONS: Lameness was abolished in all treated horses. It recurred significantly less often, and later, in CIMSC-treated horses. CLINICAL SIGNIFICANCE: Intra-articular CIMSC treatment results in prolonged soundness in horses with tarsometatarsal lameness.

Cable failure tolerant control and planning in a planar reconfigurable cable driven parallel robot.

The addition of geometric reconfigurability in a cable driven parallel robot (CDPR) introduces kinematic redundancies which can be exploited for manipulating structural and mechanical properties of the robot through redundancy resolution. In the event of a cable failure, a reconfigurable CDPR (rCDPR) can also realign its geometric arrangement to overcome the effects of cable failure and recover the original expected trajectory and complete the trajectory tracking task. In this paper we discuss a fault tolerant control (FTC) framework that relies on an Interactive Multiple Model (IMM) adaptive estimation filter for simultaneous fault detection and diagnosis (FDD) and task recovery. The redundancy resolution scheme for the kinematically redundant CDPR takes into account singularity avoidance, manipulability and wrench quality maximization during trajectory tracking. We further introduce a trajectory tracking methodology that enables the automatic task recovery algorithm to consistently return to the point of failure. This is particularly useful for applications where the planned trajectory is of greater importance than the goal positions, such as painting, welding or 3D printing applications. The proposed control framework is validated in simulation on a planar rCDPR with elastic cables and parameter uncertainties to introduce modeled and unmodeled dynamics in the system as it tracks a complete trajectory despite the occurrence of multiple cable failures. As cables fail one by one, the robot topology changes from an over-constrained to a fully constrained and then an under-constrained CDPR. The framework is applied with a constant-velocity kinematic feedforward controller which has the advantage of generating steady-state inputs despite dynamic oscillations during cable failures, as well as a Linear Quadratic Regulator (LQR) feedback controller to locally dampen these oscillations.

Evaluation of a Depression Intervention in People With HIV and/or TB in Eswatini Primary Care Facilities: Implications for Southern Africa.

INTRODUCTION: Depression associated with chronic illnesses is common in Southern Africa, yet there are major treatment gaps. This study assesses the feasibility and acceptability of the Healthy Activity Program intervention for depression among people with HIV and/or TB. The intervention involves training nonspecialist nurses in depression, including identification, counseling based on behavioral activation theory, and structured referral. METHODS: This is a mixed methods evaluation of a pilot counseling service integrated within routine HIV and TB care from 2018 to 2019. Participants included people living with HIV and/or patients with TB in rural Eswatini. RESULTS: A total of 324 people living with HIV and/or TB were screened for depression, with 19% (62/324) screening positive. The median number of sessions attended was 3 (interquartile range: 1-5), with 16/60 (26%) attending the minimum 5 sessions. Qualitative results indicated acceptability, but there were concerns about feasibility. CONCLUSIONS: The Healthy Activity Program is a promising option to manage the treatment gap for depression in people with HIV and/or TB. However, task-shifting to nonspecialist health care professionals without increasing staff capacity is a barrier to implementation. Realistic and pragmatic assessments of capacity and workforce are essential.

Active travel to school: a longitudinal millennium cohort study of schooling outcomes.

OBJECTIVES: Assess longitudinal associations between active travel during the school commute and later educational outcomes. SETTING: England, Wales and Northern Ireland. PARTICIPANTS: 6778 children, surveyed at ages 7, 11, 14 and 17. PRIMARY AND SECONDARY OUTCOMES: School-leaver General Certificate of Secondary Education exam scores summed to provide a single measure of educational success. RESULTS: Controlling a range of sociodemographic and health variables, using active versus passive travel modes during a child's commute to school during earlier years predicted differences in school-leaver exam performance at age 16. These effects were mediated through changes in self-esteem, emotional difficulties and behavioural difficulties. Examples include: being driven to school at 11 was associated with improved exam performance at 16 mediated through enhanced self-esteem at 14 (ab=0.08, 95% CI=0.01 to 0.20, p=0.05) and cycling at 14 was associated with better exam scores at 16 mediated through reduced emotional difficulty at 16 (ab=0.10, 95% CI=0.01 to 0.30, p=0.05). The relationship between travel mode and exam performance was moderated by household income quintile, most notably with poorer exam performance seen in high-income children who were driven to school. Importantly, although our model predicted 21% of variance in exam performance, removing travel mode barely reduced its ability to predict exam scores (ΔR 2=-0.005, F 20,6469 = 2.50, p<0.001). CONCLUSION: There are differences in school-leaver exam performance linked to travel mode choices earlier in the school career, but these differences are extremely small. There appears to be no realistic educational disadvantage from any given travel mode, strengthening the case for cleaner, healthier modes to become the default.

COVID-19 vaccination intentions and subsequent uptake: An analysis of the role of marginalisation in society using British longitudinal data.

COVID-19 vaccine hesitancy has previously been modelled using data on intentions - expressed prior to vaccine availability. Once vaccines became widely available, it became possible to model hesitancy using actual vaccination uptake data. This paper estimates the determinants of the joint distribution of COVID-19 vaccination intentions (declared before the release of any vaccine) and actual vaccination take-up (when it was widely available across the age distribution). We use high quality longitudinal data (UK Household Longitudinal Study) collected during the pandemic in the UK, merged to a wide variety of individual characteristics collected prior to the COVID-19 pandemic. Our estimation draws on pre-Covid values of variables for a sample that includes 10,073 observations from the September 2021 wave. The contribution of this paper is to model hesitancy and uptake jointly. The work shows that people who might be regarded as marginalised in society (measured, before the pandemic began) are less likely to say that they intend to be vaccinated and they go on to also be more likely to actually remain unvaccinated. It also shows that there is a large positive correlation between the unobservable determinants of intention and of uptake. This high positive correlation has an important implication - that information campaigns can be reasonably well profiled to target specific groups on the basis of intention data alone. We also show that changing one's mind is not correlated with observable data. This is consistent with two explanations. Firstly, the new information available on the arrival of vaccines, that they are safe and effective, may be more optimistic than was originally assumed. Secondly, individuals may have been more pessimistic about the effects associated with infection before vaccines became available.

A perspective on plant robotics: from bioinspiration to hybrid systems.

As miscellaneous as the Plant Kingdom is, correspondingly diverse are the opportunities for taking inspiration from plants for innovations in science and engineering. Especially in robotics, properties like growth, adaptation to environments, ingenious materials, sustainability, and energy-effectiveness of plants provide an extremely rich source of inspiration to develop new technologies-and many of them are still in the beginning of being discovered. In the last decade, researchers have begun to reproduce complex plant functions leading to functionality that goes far beyond conventional robotics and this includes sustainability, resource saving, and eco-friendliness. This perspective drawn by specialists in different related disciplines provides a snapshot from the last decade of research in the field and draws conclusions on the current challenges, unanswered questions on plant functions, plant-inspired robots, bioinspired materials, and plant-hybrid systems looking ahead to the future of these research fields.

Cannabinoid hyperemesis syndrome in North America: evaluation of health burden and treatment prevalence.

BACKGROUND: Cannabinoid hyperemesis syndrome (CHS) is a poorly understood vomiting disorder associated with chronic cannabis use. AIMS: To characterise patients experiencing CHS in North America and to obtain a population-based estimate of CHS treatment prevalence in Canada before and during the Covid-19 pandemic METHODS: Internet survey of 157 CHS sufferers in Canada and the United States. Administrative health databases for the province of Alberta (population 5 million) were accessed to measure emergency department (ED) visits for vomiting, with a concurrent diagnostic code for cannabis use. Three time periods of 1 year were assessed: prior to recreational cannabis legalisation (2017-2018), after recreational legalisation (2018-2019) and during the first year of the Covid-19 pandemic (2020-2021). RESULTS: Problematic cannabis use (defined as a CUDIT-R score ≥8) was universal among the survey cohort, and 59% and 68% screening for moderate or worse anxiety or depression, respectively. The overall treatment prevalence of CHS across all ages increased from 15 ED visits per 100,000 population (95% CI, 14-17) prior to legalisation, to 21 (95% CI, 20-23) after legalisation, to 32 (95% CI, 31-35) during the beginning of the Covid-19 pandemic (p < 0.001). Treatment prevalence among chronic cannabis users was as high as 6 per 1000 in the 16-24 age group. CONCLUSION: Survey data suggest patients with CHS almost universally suffer from a cannabis use disorder, which has significant treatment implications. Treatment prevalence in the ED has increased substantially over a very short time period, with the highest rates seen during the Covid-19 pandemic.

Challenges and Opportunities for Mental Health and Psychosocial Support in the COVID-19 Response in Africa: A Mixed-Methods Study.

This research aimed to (1) assess the extent to which mental health and psycho-social support (MHPSS) was included in the national response to the COVID-19 pandemic in African countries, and (2) explore barriers and enablers to MHPSS integration into the COVID-19 response. A mixed-methods study, using an online survey and in-depth interviews, was conducted. Participants included Mental Health Focal Points at the Ministries of Health, the World Health Organization (WHO) country and regional offices, and civil society representatives. Responses were received from 28 countries out of 55 contacted. The implementation level, based on standard guidelines, of MHPSS activities was below 50% in most countries. The most implemented MHPSS activities were establishing coordination groups (57%) and developing MHPSS strategy (45%), while the least implemented activities included implementing the developed MHPSS strategy (32%) and establishing monitoring and evaluation mechanisms (21%). Key factors that hindered implementing MHPSS activities included lack of political commitment and low prioritisation of mental health during emergencies, as it was seen as a "less important" issue during the COVID-19 pandemic, when more importance was given to infection prevention and control (IPC). However, there are signs of optimism, as mental health gained some attention during COVID-19. It is imperative to build on the attention gained by integrating MHPSS in emergency preparedness and response and strengthening mental health systems in the longer term.

Mental health systems in six Caribbean small island developing states: a comparative situational analysis.

BACKGROUND: Small island developing states (SIDS) have particular mental health system needs due to their remoteness and narrow resource base. We conducted situational analyses to support mental health system strengthening in six SIDS: Anguilla, Bermuda, British Virgin Islands, Cayman Islands, Montserrat and Turks and Caicos Islands. METHODS: The situational analyses covered five domains: 1. Socio-economic context and burden of mental disorders, 2. Leadership and governance for mental health 3. Mental health and social care services 4. Strategies for promotion and prevention in mental health and 5. Information systems, evidence and research for mental health. First, a desk-based exercise was conducted, in which data was drawn from the public domain. Second, a field visit was conducted at each site, comprising visits to facilities and consultation meetings with key stakeholders. RESULTS: Our key findings were 1. Despite most of these SIDS being high-income economies, social inequalities within states exist. There was no population-level data on mental health burden. 2. All SIDS have a mental health policy or plan, but implementation is typically limited due to lack of funds or staff shortages. There was minimal evidence of service user involvement in policy or service development. 3. All SIDS have a specialist, multi-disciplinary mental health workforce, however Montserrat and Anguilla rely on visiting psychiatrists. Child and adolescent and dedicated crisis intervention services were found in only two and one SIDS respectively. A recovery-oriented ethos was not identified in any SIDS. 4. Mental illness stigma was prevalent in all SIDS. Promotion and prevention were objectives of mental health strategies for all SIDS, however activities tended to be sporadic. No mental health non-Governmental organisations were identified in three SIDS. 5. Health information systems are generally underdeveloped, with paper-based systems in three SIDS. There has been no rigorous local mental health research. CONCLUSION: Cross-cutting recommendations include: to develop mental health action plans that include clear implementation indicators; to facilitate community surveys to ascertain the prevalence of mental disorders; to explore task-sharing approaches to increase access to primary mental health care; and to develop programmes of mental health promotion and prevention.

Effectiveness of intravenous prostaglandin to reduce digital amputations from frostbite: an observational study.

PURPOSE: We assessed the effectiveness and safety of a 5-day intravenous prostaglandin (iloprost) protocol at reducing digital amputation for patients with severe frostbite injuries at urban emergency departments. METHODS: This retrospective study examines consecutive patients who presented to Calgary emergency departments from April 2017 to April 2020 with Grade 2-4 frostbite injuries. Patients from February 2019 onward were managed using a 5-day iloprost infusion protocol, whereas patients prior to this time were managed with standard care (local best practice without iloprost as a therapeutic option). The primary effectiveness outcome was rate of affected digits amputated, stratified by frostbite severity. The secondary safety outcome was the incidence of serious adverse events associated with iloprost (allergic reactions or symptomatic hypotension requiring treatment or discontinuation of the infusion). RESULTS: 90 patients were included, 26 were treated with iloprost, compared to 64 patients who received usual care. Both the treatment and usual care groups experienced substantial rates of homelessness and substance use. No digital amputations were required for patients with Grade 2 injuries in either group, but significantly lower digital amputation rates were observed for patients with more severe frostbite injuries treated with iloprost versus usual care: Grade 3 (18% vs 44%, p < 0.001), Grade 4 (46% vs 95%, p < 0.001). No serious adverse events were associated with iloprost. CONCLUSION: In this unselected socially complex urban population, administration of iloprost for patients with frostbite was shown to be safe and was associated with lower digital amputation rates, particularly for those with more severe injuries.

RéSUMé: OBJECTIF: Nous avons évalué l'efficacité et la sécurité d'un protocole de 5 jours de prostaglandine intraveineuse (iloprost) pour réduire l'amputation digitale chez les patients souffrant d'engelures graves dans les services d'urgence urbains. MéTHODES: Cette étude rétrospective examine des patients consécutifs qui se sont présentés aux services d'urgence de Calgary d'avril 2017 à avril 2020 avec des engelures de niveau 2 à 4. À compter de février 2019, les patients ont été traités au moyen d'un protocole de perfusion d'iloprost de 5 jours, tandis que les patients avant cette période ont été pris en charge avec des soins standard (meilleures pratiques locales sans iloprost comme option thérapeutique). Le principal résultat d'efficacité était le taux de doigts affectés amputés, stratifié selon la gravité des gelures. Le critère secondaire de sécurité était l'incidence des événements indésirables graves associés à l'iloprost (réactions allergiques ou hypotension symptomatique nécessitant un traitement ou l'arrêt de la perfusion). RéSULTATS: 90 patients ont été inclus, 26 ont été traités avec de l'iloprost, contre 64 patients qui ont reçu les soins habituels. Les groupes de traitement et de soins habituels ont tous deux connu des taux importants de sans-abrisme et de consommation de substances. Aucune amputation digitale n'a été nécessaire pour les patients présentant des lésions de grade 2 dans l'un ou l'autre groupe, mais des taux d'amputation digitale significativement plus faibles ont été observés pour les patients présentant des lésions de gelures plus sévères traités par iloprost par rapport aux soins habituels : Grade 3 (18 % contre 44 %, p < 0,001), Grade 4 (46 % contre 95 %, p < 0,001). Aucun événement indésirable grave n'a été associé à l'iloprost. CONCLUSION: Dans cette population urbaine non sélectionnée et socialement complexe, l'administration d'iloprost pour les patients souffrant d'engelures s'est avérée sûre et a été associée à des taux d'amputation digitale plus faibles, en particulier pour ceux présentant des blessures plus graves.

Non-tremor motor dysfunction in Lewy body dementias is associated with AD biomarkers.

Motor features of Parkinson's disease (PD) are heterogeneous and well-studied; non-tremor features of postural instability and gait dysfunction (PIGD) have been linked to worse outcomes and Alzheimer's disease (AD) co-pathology. However, these features are understudied in Lewy body dementias (LBD). Here we perform retrospective analysis of a unique cohort of LBD (n = 30) with Unified Parkinson's Disease Rating Scale (UPDRS) data collected at baseline in proximity to cerebrospinal fluid collection to test the hypothesis that LBD patients with a positive AD biomarker profile (LBD + AD = 13) would have higher PIGD burden compared with LBD patients without AD biomarker positivity (LBD-AD = 17). We find novel evidence for selective impairment of PIGD burden in LBD + AD vs LBD-AD (OR = 1.95, 95%CI = 1.02-3.70, p = 0.04) and a direct association of increasing CSF tau/Aß1-42 ratio with increasing PIGD disability in the total cohort (ß = 0.23, SE = 0.08, p = 0.01). This unique biomarker stratification approach suggests AD co-pathology may contribute to PIGD motor signs in LBD.

Prevention of Periprosthetic Joint Infection in Total Hip and Knee Replacement: One European Consensus.

Periprosthetic joint infection (PJI) is a devastating complication in total hip and knee replacement. Its prevention is key to decrease the incidence and avoid some consequences that seriously impact patients and health systems. In view of the variety of recommendations and guidelines, we decided to conduct an expert, peer-reviewed European consensus analysis about the pre-, intra-, and postoperative prevention of PJI. A multinational group of practicing orthopedic experts developed a series of 47 consensus statements in 6 main groups of intervention, and a 2-stage Delphi approach was launched with a threshold for agreement at 75% and for very high agreement at more than 90%. A total of 306 orthopedic surgeon responses were gathered from 9 countries. Consensus was reached for 42/47 statements, 31/47 of which achieved a very high consensus. Many preoperative actions gathered strong consensus, although areas like the use of alcoholic chlorhexidine or the timing of hair removal did not attain strong consensus, despite available evidence. Intra- and postoperative actions showed more variability regarding incise drapes, skin suturing techniques, and wound follow-up. This study confirms an important consensus among orthopedic surgeons across Europe in many areas well known to contribute to the prevention of PJI; however, there are still grounds for improvement.

Structural basis for ligand reception by anaplastic lymphoma kinase.

The proto-oncogene ALK encodes anaplastic lymphoma kinase, a receptor tyrosine kinase that is expressed primarily in the developing nervous system. After development, ALK activity is associated with learning and memory1 and controls energy expenditure, and inhibition of ALK can prevent diet-induced obesity2. Aberrant ALK signalling causes numerous cancers3. In particular, full-length ALK is an important driver in paediatric neuroblastoma4,5, in which it is either mutated6 or activated by ligand7. Here we report crystal structures of the extracellular glycine-rich domain (GRD) of ALK, which regulates receptor activity by binding to activating peptides8,9. Fusing the ALK GRD to its ligand enabled us to capture a dimeric receptor complex that reveals how ALK responds to its regulatory ligands. We show that repetitive glycines in the GRD form rigid helices that separate the major ligand-binding site from a distal polyglycine extension loop (PXL) that mediates ALK dimerization. The PXL of one receptor acts as a sensor for the complex by interacting with a ligand-bound second receptor. ALK activation can be abolished through PXL mutation or with PXL-targeting antibodies. Together, these results explain how ALK uses its atypical architecture for its regulation, and suggest new therapeutic opportunities for ALK-expressing cancers such as paediatric neuroblastoma.

National or population level interventions addressing the social determinants of mental health - an umbrella review.

BACKGROUND: Social circumstances in which people live and work impact the population's mental health. We aimed to synthesise evidence identifying effective interventions and policies that influence the social determinants of mental health at national or scaled population level. We searched five databases (Cochrane Library, Global Health, MEDLINE, EMBASE and PsycINFO) between Jan 1st 2000 and July 23rd 2019 to identify systematic reviews of population-level interventions or policies addressing a recognised social determinant of mental health and collected mental health outcomes. There were no restrictions on country, sub-population or age. A narrative overview of results is provided. Quality assessment was conducted using Assessment of Multiple Systematic Reviews (AMSTAR 2). This study was registered on PROSPERO (CRD42019140198). RESULTS: We identified 20 reviews for inclusion. Most reviews were of low or critically low quality. Primary studies were mostly observational and from higher income settings. Higher quality evidence indicates more generous welfare benefits may reduce socioeconomic inequalities in mental health outcomes. Lower quality evidence suggests unemployment insurance, warm housing interventions, neighbourhood renewal, paid parental leave, gender equality policies, community-based parenting programmes, and less restrictive migration policies are associated with improved mental health outcomes. Low quality evidence suggests restriction of access to lethal means and multi-component suicide prevention programmes are associated with reduced suicide risk. CONCLUSION: This umbrella review has identified a small and overall low-quality evidence base for population level interventions addressing the social determinants of mental health. There are significant gaps in the evidence base for key policy areas, which limit ability of national policymakers to understand how to effectively improve population mental health.

Olfaction as an early marker of Parkinson's disease and Alzheimer's disease.

Olfactory impairment is a common and early sign of Parkinson's disease (PD) and Alzheimer's disease (AD), the two most prevalent neurodegenerative conditions in the elderly. This phenomenon corresponds to pathologic processes emerging in the olfactory system prior to the onset of typical clinical manifestations. Clinically available tests can establish hyposmia through odor identification assessment, discrimination, and odor detection threshold. There are significant efforts to develop preventative or disease-modifying therapies that slow down or halt the progression of PD and AD. Due to the convenience and low cost of its assessment, olfactory impairment could be used in these studies as a screening instrument. In the clinical setting, loss of smell may also help to differentiate PD and AD from alternative causes of Parkinsonism and cognitive impairment, respectively. Here, we discuss the pathophysiology of olfactory dysfunction in PD and AD and how it can be assessed in the clinical setting to aid in the early and differential diagnosis of these disorders.