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Managing multinational enterprise subsidiaries is a core facet of international business research. A shifting reality on the ground has triggered concerns around the waning relevance of the subsidiary because the MNE and its structure and processes have become increasingly complex. Consequently, more decentralized, responsive, and fluid organizational designs are now at the core of IB research. Juxtaposing recent arguments questioning subsidiary research altogether, we argue that IB scholars can explore and explain complex realities in the contemporary MNE without unnecessarily restricting the breadth of the field and giving up links to established research and theory. We reframe conversations around inward- and outward-looking perspectives, providing a path forward that emphasizes the importance of embracing the subsidiary concept in research reflecting today's complex business environment.La gestion des filiales des entreprises multinationales (Multinational Enterprise - MNE) constitue une facette essentielle de la recherche en affaires internationales (International Business - IB). L'évolution de la réalité sur le terrain a suscité des inquiétudes quant à la perte de pertinence des filiales, étant donné que la MNE, sa structure et ses processus sont devenus de plus en plus complexes. Par conséquent, sont désormais au cœur de la recherche en IB les conceptions organisationnelles plus décentralisées, plus réactives et plus fluides. En juxtaposant les récents arguments remettant en cause la recherche portée sur les filiales, nous argumentons que les chercheurs en IB peuvent explorer et expliquer les réalités complexes des MNEs contemporaines sans restreindre inutilement l'étendue du domaine et sans renoncer aux liens avec la recherche et la théorie établies. Nous recadrons les conversations autour des perspectives autocentrées et orientées vers l’extérieur, tout en proposant une voie à suivre qui souligne l'importance d'inclure le concept de filiale dans la recherche reflétant l'environnement commercial complexe d'aujourd'hui.La gestión de filiales de las empresas multinacionales (MNE por sus siglas en ingles) es una faceta central en la investigación en negocios internacionales. Una realidad cambiante en el terreno ha desencadenado preocupaciones sobre la disminución de la relevancia de la filial debido a que la empresa multinacional y su estructura y procesos se han vuelto cada vez más complejos. En consecuencia, los diseños organizacionales más descentralizados, receptivos y fluidos constituyen ahora el núcleo de la investigación sobre las empresas internacionales. Frente a los recientes argumentos que cuestionan la investigación sobre las filiales, sostenemos que los estudiosos de negocios internacionales pueden explorar y explicar las complejas realidades de las empresas multinacionales contemporáneas sin restringir innecesariamente la amplitud del campo ni renunciar a los vínculos con la investigación y la teoría establecidas. Replanteamos las conversaciones en torno a las perspectivas hacia adentro y hacia afuera, proporcionando un camino a seguir que subraya la importancia de adoptar el concepto de filial en la investigación que refleja el complejo entorno empresarial actual.Gerenciar subsidiárias de empresas multinacionais (MNE) é uma faceta fundamental da pesquisa em negócios internacionais (IB). Uma realidade mutante no terreno desencadeou preocupações em torno da diminuição da relevância da subsidiária porque a MNE e sua estrutura e processos se tornaram cada vez mais complexos. Consequentemente, designs organizacionais mais descentralizados, responsivos e fluidos estão agora no cerne da pesquisa em IB. Justapondo argumentos recentes que questionam a pesquisa sobre subsidiárias como um todo, argumentamos que estudiosos de IB podem explorar e explicar realidades complexas na MNE contemporânea sem restringir desnecessariamente a amplitude do campo e abrir mão de relações com a pesquisas e a teoria estabelecidas. Reestruturamos conversas em torno de perspectivas que vislumbram o exterior e o interior, fornecendo um caminho a seguir que enfatiza a importância de adotar o conceito de subsidiária na pesquisa que reflita o complexo ambiente de negócios de hoje.管理跨国企业 (MNE) 子公司是国际商务 (IB) 研究的一个核心方面。由于MNE及其结构和流程变得越来越复杂， 当地不断变化的现实引发了人们对子公司相关性减弱的担忧。因此， 更加去中心化、反应灵敏和流动的组织设计现在是 IB 研究的核心。我们将最近质疑子公司研究的论点并列在一起， 认为 IB 学者可以探索和解释当代MNE中的复杂现实， 而不会不必要地限制该领域的广度和放弃与既定研究和理论的联系。我们围绕内向和外向观点重新构建对话， 提供了一条前进的道路， 强调了在反映当今复杂商业环境的研究中采用子公司概念的重要性。.

Background Longleaf pine (Pinus palustris Mill.) ecosystems were historically widespread in the North American Coastal Plain and in some southeastern piedmont and montane settings. The naval stores industry, deforestation, and other human activities resulted in an extensive loss (c. 97% loss) of the original woodlands and savannas. Longleaf pine ecosystems are maintained by frequent surface fire which promotes successful regeneration and maintains open canopy conditions and a largely herbaceous understory. Fire regimes (including the frequency and seasonality of fire) likely varied across the entire range of longleaf pine and through time; further research is needed to elucidate this variability. Results We used fire scars in stumps and snags to reconstruct fire history in a piedmont longleaf pine ecosystem in North Carolina. For each tree sampled, we examined multiple cross sections to avoid omission of fire events recorded by smaller fire scars. Our samples revealed evidence of frequent fire (c. 3–4-year fire interval) beginning in the early eighteenth century and extending to the mid-nineteenth century. Fires occurred in the dormant and early earlywood positions of annual rings and were likely human ignited. Conclusions To our knowledge, this is the first tree-ring-based fire history in longleaf pine of the piedmont. As such, it offers a rare glimpse into historical fire activity in a now scarce but important ecological setting. More research is needed to develop additional fire chronologies in the piedmont region, including for longer periods of time and for larger spatial areas.

Die Mitglieder der Osterreichischen Gesellschaft fur Rheumatologie (OGR) wurden aufgefordert, die Bedeutung eines stationaren Rehabilitationsaufenthalts fur Patientinnen und Patienten mit axialer Spondylarthritis (SpA; inkl. Morbus Bechterew) in der heutigen Zeit in einer Onlinebefragung zu beurteilen. Als Vergleichsgruppe wurden die Bewertungen von Rehabilitationsexperten des Arbeitskreises (AK) fur Rehabilitation der OGR herangezogen. Zwei Themenblocke wurden ausgearbeitet und zwar 1) betreffend die Relevanz verschiedener Interventionen im Rahmen der Rehabilitation und 2) zum Nutzen der Rehabilitationsmasnahmen hinsichtlich verschiedener Erkrankungszeitpunkte bei SpA. Bei allen Fragen wurde eine 11-teilige Rating Scale (von 0 = trifft gar nicht zu bis 10 = trifft in sehr hohem Mas zu) verwendet. Am hochsten bewerteten beide Gruppen an 1. Stelle die ergo- und physiotherapeutische Bewegungstherapie (9,3 ± 1,2 bzw. 9,6 ± 0,7). Auch Gelenkschutzberatung und Ruckenschule (Rankingplatz 2) sowie Schulung/Information uber die Erkrankung und Therapie (Rankingplatz 3) erwiesen sich im Ranking bei allen als sehr bedeutsam. Auch wurde klar von allen festgehalten, dass Patienten mit Funktionseinschrankung am meisten von einem Rehabilitationsaufenthalt profitieren konnen; direkt nach einem SpA-Schub der Erkrankung wird der Nutzen am geringsten eingestuft. Auch der Nutzen einer regelmasigen Rehabilitation bei SpA im Abstand weniger Jahre wurde hoch bewertet. Insgesamt hat ein Rehabilitationsaufenthalt bei SpA auch in Zeiten moderner medikamentoser Therapieformen immer noch eine grose Bedeutung.

In the Covid-19 pandemic, being older means being in a special focus: Probabilities for severe infections and mortality rise with increasing age and protective measures for this population group have been increased. This was accompanied by public discourse that portrayed older adults stereotypically as vulnerable and frail but also highlighted the hardships younger people have to endure to protect them. Given the possibly detrimental effects of ageism on individuals and societies, we were interested in older adults’ perception of ageism in the Corona-crisis and its relation to their health and well-being. Furthermore, we were interested in subjective aging variables as moderators in the ageism–health relationship. In June 2020, N = 611 independently living people aged 60 + from the Grand Duchy of Luxembourg were recruited via a survey research institute and interviewed online or by phone. They reported on perceived ageism in different contexts, their life satisfaction, subjective health, subjective age and self-perceptions of aging. Depending on context, ageism was perceived by around 20% of participants, and overall negatively related to subjective health and life satisfaction after the onset of the pandemic. Moderated hierarchical regressions showed that a younger subjective age buffered the negative effect of ageism on subjective health, while perceiving aging as social loss increased its effect on life satisfaction. We discuss the importance of addressing and reducing ageism (not only) in times of crisis and the consequences for individuals and societies.

This paper presents the results of archaeological fieldwork conducted at the request of elders from Barunga, a remote Aboriginal community in the Northern Territory, Australia. The aim of the project was to use archaeological methods to help people from the community relocate and identify each person buried in the Barunga Graveyard and to develop a system where this information would not be forgotten. In the past, the location of burials and the identities of the buried have been known only through memory, as well as repeat visits to the graveyard. Overcrowding within the graveyard has made this practice difficult. To add to this problem, the vast majority of graves of Aboriginal people in remote Northern Territory communities are not recorded in any register. While there is a legislative requirement for a burial register to be kept in non-Aboriginal communities, this has not been a requirement for those within Aboriginal communities. Instead, families must rely on the memories of those in attendance at the burial, and in time the remembering generation also dies and the identities of people in these graves become more and more blurred. This makes it difficult to mourn properly, or to care for that person by caring for their grave. During our fieldwork, we located 175 graves, and we identified 85 individuals. Of those that could be identified, 29 were identified by an associated plaque or headstone, and 56 were identified through oral histories that were recorded during several field visits with elders from the community. Beyond the archaeological results of this research, we found there is an opportunity to build sustainable development in this community that would see local people employed to locate and identify currently unidentified burials. Drawing on comparative cases from other countries such as India, this study addresses the challenge identified by UNESCO (United Nations Educational, Scientific and Cultural Organisation (UNESCO) (2015) introducing cultural heritage into the sustainable development agenda. Retrieved February 19, 2020, from http://www.unesco.org/new/en/culture/themes/culture-and-development/hangzhou-congress/introducing-cultural-heritage-into-the-sustainable-development-agenda/ ), to identify the concrete actions needed to integrate cultural heritage conservation and promotion into the sustainable development debate.

Magnetically shielded rooms (MSRs) use multiple layers of materials such as MuMetal to screen external magnetic fields that would otherwise interfere with high precision magnetic field measurements such as magnetoencephalography (MEG). Optically pumped magnetometers (OPMs) have enabled the development of wearable MEG systems which have the potential to provide a motion tolerant functional brain imaging system with high spatiotemporal resolution. Despite significant promise, OPMs impose stringent magnetic shielding requirements, operating around a zero magnetic field resonance within a dynamic range of ± 5 nT. MSRs developed for OPM-MEG must therefore effectively shield external sources and provide a low remnant magnetic field inside the enclosure. Existing MSRs optimised for OPM-MEG are expensive, heavy, and difficult to site. Electromagnetic coils are used to further cancel the remnant field inside the MSR enabling participant movements during OPM-MEG, but present coil systems are challenging to engineer and occupy space in the MSR limiting participant movements and negatively impacting patient experience. Here we present a lightweight MSR design (30% reduction in weight and 40–60% reduction in external dimensions compared to a standard OPM-optimised MSR) which takes significant steps towards addressing these barriers. We also designed a ‘window coil’ active shielding system, featuring a series of simple rectangular coils placed directly onto the walls of the MSR. By mapping the remnant magnetic field inside the MSR, and the magnetic field produced by the coils, we can identify optimal coil currents and cancel the remnant magnetic field over the central cubic metre to just |B|= 670 ± 160 pT. These advances reduce the cost, installation time and siting restrictions of MSRs which will be essential for the widespread deployment of OPM-MEG.

Background Globally, hearing loss is the second leading cause of disability, affecting approximately 18.7% of the world’s population. However, the burden of hearing loss is unequally distributed, with the majority of affected individuals located in Asia or Sub-Saharan Africa. Following the 2014 West African Ebola Outbreak, disease survivors began to describe hearing loss as part of the constellation of symptoms known as Post-Ebola Syndrome. The goal of this study was to more fully characterize hearing loss among Ebola Virus Disease (EVD) survivors. Methodology and principal findings EVD survivors and their household contacts were recruited (n = 1,12) from Eastern Sierra Leone. Each individual completed a symptom questionnaire, physical exam, and a two-step audiometry process measuring both air and bone conduction thresholds. In comparison to contacts, EVD survivors were more likely to have complaints or abnormal findings affecting every organ system. A significantly greater percentage of EVD survivors were found to have hearing loss in comparison to contacts (23% vs. 9%, p Conclusions and significance This study is the first to use an objective and standardized measurement to report hearing loss among EVD survivors in a clinically meaningful manner. In this study it was found that greater than 1/5th of EVD survivors develop hearing loss. The association between hearing impairment and symptoms affecting the eye and nervous system may indicate a similar mechanism of pathogenesis, which should be investigated further. Due to the quality of life and socioeconomic detriments associated with untreated hearing loss, a greater emphasis must be placed on understanding and mitigating hearing loss following survival to aid in economic recovery following infectious disease epidemics.

Strong for Surgery (S4S) is a public health campaign focused on optimizing patient health prior to surgery by identifying evidence-based modifiable risk factors. The potential impact of S4S bundled risk factors on outcomes after major surgery has not been previously studied. This study tested the hypothesis that a higher number of S4S risk factors is associated with an escalating risk of complications and mortality after major elective surgery in the VA population. The Veterans Affairs Surgical Quality Improvement Program (VASQIP) database was queried for patients who underwent major non-emergent general, thoracic, vascular, urologic, and orthopedic surgeries between the years 2008 and 2015. Patients with complete data pertaining to S4S risk factors, specifically preoperative smoking status, HbA1c level, and serum albumin level, were stratified by number of positive risk factors, and perioperative outcomes were compared. A total of 31,285 patients comprised the study group, with 16,630 (53.2%) patients having no S4S risk factors (S4S0), 12,323 (39.4%) having one (S4S1), 2,186 (7.0%) having two (S4S2), and 146 (0.5%) having three (S4S3). In the S4S1 group, 60.3% were actively smoking, 35.2% had HbA1c > 7, and 4.4% had serum albumin 7, and 27.4% had albumin

Es wird uber den Fall einer 29-jahrigen Patientin mit einer unilateralen Mydriasis nach Anwendung eines Scopolaminpflasters bei ausgepragter PONV-Anamnese berichtet. Das Pflaster wurde zur Narkoseeinleitung erganzt und vor Verlegung auf die Station entfernt. Nach einer elektiven Metallentfernung und Narkose mittels TIVA trat am ersten postoperativen Tag eine unilaterale Mydriasis des linken Auges mit Akkommodationsstorung auf. In der Folge wurden zur Abklarung der Symptomatik neurologische sowie augenarztliche Untersuchungen durchgefuhrt. Zusatzlich erfolgte eine MRT mit Kontrastmittel zum Ausschluss eines zentralen Geschehens. Es wurden keine Ursachen fur das klinische Bild erfasst, sodass die Verdachtsdiagnose einer pharmakologisch induzierten Anisokorie durch den Wirkstoff Scopolamin erhoben wurde. Der Ausloser schien dabei ein Verwischen des Wirkstoffs von der Klebestelle in das betroffene Auge zu sein. Die Symptomatik und das klinische Bild hoben sich bei der Patientin nach 24 h ohne weitere Therapiemasnahmen wieder auf. Fruhe emetische Symptome konnen durch ein Scopolaminpflaster signifikant reduziert werden. Viele Kliniker raten jedoch aufgrund der oben beschriebenen Problematik von der Verwendung von Scopolaminpflastern zur PONV-Prophylaxe ab, da eine intraoperative oder postoperative Anisokorie bei einem neurologisch nichtbeurteilbaren Patienten den zwingenden Ausschluss eines zentralen Ereignisses zur Folge hat.

There is little research on the study success factors of refugee students in higher education. One approach to meeting the growing global demands is to provide online education specifically for refugees. This study examines specific personal characteristics of refugee students and their influence on success and retention in online education. Individual factors such as intrinsic motivation and language proficiency, cognitive functioning, and sociodemographic factors such as gender and country of residence influence retention of refugee students during online studies. The results indicate that sociodemographic factors (e.g., gender), cognitive factors (e.g., English proficiency), and external factors (e.g., country of residence) have a significant influence on study retention on refugee students.

The Athabasca Oil Sands Region (AOSR) in northeast Alberta contains Canada’s largest reserve of hydrocarbons, and the third largest in the world. Extraction and processing operations generate contaminants and nutrients that are aerially deposited across the region. However, structured environmental monitoring efforts were only initiated decades following the establishment (1967) and escalation (~ 1980) of commercial operations. We examined whether diatom assemblages preserved in 210Pb-dated sediment cores retrieved from strategically selected lakes have responded to aerial deposition of contaminants. The relative amount of contaminant inputs was tracked using sedimentary dibenzothiophene (DBT) concentrations and DBT enrichment factors, which are established proxies for AOSR activities. We observed no relationship between diatom assemblage changes and DBT enrichment. The nature of the diatom changes differed among lakes, regardless of DBT enrichment, suggesting that diatom responses were related to site-specific conditions. Moreover, diatom assemblage changes at several sites tracked trends in whole-lake primary production. Collectively, these records indicate that regional warming is likely the primary driver of recent diatom assemblage changes in these shallow, closed-basin lakes.

The SARS-CoV-2 Omicron variant was first identified in November 2021 in Botswana and South Africa1-3. It has since spread to many countries and is expected to rapidly become dominant worldwide. The lineage is characterized by the presence of around 32 mutations in spike-located mostly in the N-terminal domain and the receptor-binding domain-that may enhance viral fitness and enable antibody evasion. Here we isolated an infectious Omicron virus in Belgium from a traveller returning from Egypt. We examined its sensitivity to nine monoclonal antibodies that have been clinically approved or are in development4, and to antibodies present in 115 serum samples from COVID-19 vaccine recipients or individuals who have recovered from COVID-19. Omicron was completely or partially resistant to neutralization by all monoclonal antibodies tested. Sera from recipients of the Pfizer or AstraZeneca vaccine, sampled five months after complete vaccination, barely inhibited Omicron. Sera from COVID-19-convalescent patients collected 6 or 12 months after symptoms displayed low or no neutralizing activity against Omicron. Administration of a booster Pfizer dose as well as vaccination of previously infected individuals generated an anti-Omicron neutralizing response, with titres 6-fold to 23-fold lower against Omicron compared with those against Delta. Thus, Omicron escapes most therapeutic monoclonal antibodies and, to a large extent, vaccine-elicited antibodies. However, Omicron is neutralized by antibodies generated by a booster vaccine dose. ispartof: NATURE vol:602 issue:7898 pages:671-+ ispartof: location:England status: published

Background Intra-regional cultural and linguistic differences are common in low- and middle-income countries. To sensitise undergraduate medical students to the social and contextual determinants of health to achieve the ‘health for all’ goal, these countries must focus on innovative teaching methods. The early introduction of a Community Orientation Program (COP) as a Community-based Medical Education (CBME) method could be a game changing strategy. In this paper the methods, evaluation, and implication of the COP in an Indian setting are described. Methods The curriculum of the COP was developed based on the analysis, design, development, implementation, and evaluation (ADDIE) model for educational intervention. In this learner-centric and supervised educational program, the key aim was to focus on developing students’ communication skills, observation power and enhancing their motivation for learning through collaborative learning. To meet the objectives of the COP, a situated learning model under the constructivism theory was adopted. Results Between 2016 and 2019, 557 students were trained through the COP by visiting more than 1300 households in ten villages. To supplement the students’ observations in the community, more than 150 small group discussions, a health education programme for the community and summary presentations were conducted. The students’ feedback indicated the need to improve the clinical examinations demonstration quality and increase the number of instruments for clinical examinations. More than 80% of students felt that the program would assist them to improve their communication skills, their understanding of the various socio-demographic factors associated with the common diseases, and it will enable them to respect the local culture during their clinical practice. Conclusions Early initiation of the COP as a CBME method in the undergraduate medical curriculum in an Indian setting has shown promising results. Further evidence is required to adopt such a program routinely for under-graduate medical teaching in the low- and middle- income settings.

Purpose of review The Covid-19 pandemic forced residency programs to drastically change their interview processes and adopt virtual interviewing for the 2020-2021 match cycle. Recent findings While virtual interviewing decreased cost and increased convenience for applicants and programs involved in the match, it also introduced several potential disadvantages. Maximizing technological capabilities was an area of utmost concern at the start of the interview cycle, and multiple medical education organizations quickly recommended ways to move to virtual process, and to prevent and troubleshoot technical problems. However, other issues were less straightforward, such as how to address new sources of bias introduced by virtual interviewing, and how to ensure that programs and applicants could make informed decisions about their rank lists after only limited virtual interactions. Additionally, the increased convenience of interviewing raised concerns that students would accept more interviews, disrupting the established calculus programs used to determine how many interviews to offer per spot available. Summary In this review, we examine the benefits and disadvantages of virtual interviewing, review recommendations from the current literature on how to improve the process, and discuss what we learned from our own experience at an academic general surgery residency program over the course of this unprecedented interview season.

The unsymmetrical bidentate phosphine ligands (Me)2PCH2CH2CH2P(Et)2 (14), (Me)2PCH2CH2CH2P(iPr)2 (15), (Me)2PCH2CH2CH2P(Cy)2 (16), and (Me)2PCH2CH2CH2P(Ph)2 (17) were synthesized using air–stable phosphine oxide intermediates. In the first step, sodium phosphinites formed by deprotonation of (Me)2P(O)H, (Et)2P(O)H, and (iPr)2P(O)H were alkylated by 1-bromo-3-chloropropane. The different substitution rates of the chloride and bromide groups allowed the isolation of the intermediates (Me)2P(O)CH2CH2CH2Cl (2), (Et)2P(O)CH2CH2CH2Cl (3), and (iPr)2P(O)CH2CH2CH2Cl (4). Subsequent reaction of (Me)2P(O)CH2CH2CH2Cl (2) with the sodium phosphinites generated from (Et)2P(O)H, (iPr)2P(O)H, (tBu)2P(O)H, (Cy)2P(O)H, or (Ph)2P(O)H gave unsymmetrical bidentate phosphine oxides; reduction of these oxides yielded the unsymmetrical phosphines. The unsymmetrical bidentate phosphines react with metal salts to form complexes. X-ray crystal structures of cis-Pt((Me)2P(CH2CH2CH2)P(iPr)2)Cl2 (20) and racemic [CuI((Me)2P(CH2CH2CH2)P(Ph)2)]Cl (21) were obtained. The kinetics and scope of the synthetic route were also explored. Experiments showed that the rate of substitution of the alkyl chloride group in (R)2P(O)CH2CH2CH2Cl-type oxides increases relative to unsubstituted alkyl chlorides due to the presence of the phosphonyl group on one end of the molecule. The scope of the reaction involving 1,2-dihaloalkanes was also investigated, and it was found that the reaction mixture of sodium dimethylphosphinite and 1,2-dihaloalkanes formed tetramethylbis(phosphine) monoxide (22), which decomposes on work-up to give complex reaction mixtures.

Fragile X syndrome (FXS), a disorder of synaptic development and function, is the most prevalent genetic form of intellectual disability and autism spectrum disorder. FXS mouse models display clinically-relevant phenotypes, such as increased anxiety and hyperactivity. Despite their availability, so far advances in drug development have not yielded new treatments. Therefore, testing novel drugs that can ameliorate FXS’ cognitive and behavioral impairments is imperative. ANAVEX2-73 (blarcamesine) is a sigma-1 receptor (S1R) agonist with a strong safety record and preliminary efficacy evidence in patients with Alzheimer’s disease and Rett syndrome, other synaptic neurodegenerative and neurodevelopmental disorders. S1R’s role in calcium homeostasis and mitochondrial function, cellular functions related to synaptic function, makes blarcamesine a potential drug candidate for FXS. Administration of blarcamesine in 2-month-old FXS and wild type mice for 2 weeks led to normalization in two key neurobehavioral phenotypes: open field test (hyperactivity) and contextual fear conditioning (associative learning). Furthermore, there was improvement in marble-burying (anxiety, perseverative behavior). It also restored levels of BDNF, a converging point of many synaptic regulators, in the hippocampus. Positron emission tomography (PET) and ex vivo autoradiographic studies, using the highly selective S1R PET ligand [18F]FTC-146, demonstrated the drug’s dose-dependent receptor occupancy. Subsequent analyses also showed a wide but variable brain regional distribution of S1Rs, which was preserved in FXS mice. Altogether, these neurobehavioral, biochemical, and imaging data demonstrates doses that yield measurable receptor occupancy are effective for improving the synaptic and behavioral phenotype in FXS mice. The present findings support the viability of S1R as a therapeutic target in FXS, and the clinical potential of blarcamesine in FXS and other neurodevelopmental disorders.

Background The Central African Republic (CAR) suffers a protracted conflict and has the second lowest human development index in the world. Available mortality estimates vary and differ in methodology. We undertook a retrospective mortality study in the Ouaka prefecture to obtain reliable mortality data. Methods We conducted a population-based two-stage cluster survey from 9 March to 9 April, 2020 in Ouaka prefecture. We aimed to include 64 clusters of 12 households for a required sample size of 3636 persons. We assigned clusters to communes proportional to population size and then used systematic random sampling to identify cluster starting points from a dataset of buildings in each commune. In addition to the mortality survey questions, we included an open question on challenges faced by the household. Results We completed 50 clusters with 591 participating households including 4000 household members on the interview day. The median household size was 7 (interquartile range (IQR): 4—9). The median age was 12 (IQR: 5—27). The birth rate was 59.0/1000 population (95% confidence interval (95%-CI): 51.7—67.4). The crude and under-five mortality rates (CMR & U5MR) were 1.33 (95%-CI: 1.09—1.61) and 1.87 (95%-CI: 1.37–2.54) deaths/10,000 persons/day, respectively. The most common specified causes of death were malaria/fever (16.0%; 95%-CI: 11.0–22.7), violence (13.2%; 95%-CI: 6.3–25.5), diarrhoea/vomiting (10.6%; 95%-CI: 6.2–17.5), and respiratory infections (8.4%; 95%-CI: 4.6–14.8). The maternal mortality ratio (MMR) was 2525/100,000 live births (95%-CI: 825—5794). Challenges reported by households included health problems and access to healthcare, high number of deaths, lack of potable water, insufficient means of subsistence, food insecurity and violence. Conclusions The CMR, U5MR and MMR exceed previous estimates, and the CMR exceeds the humanitarian emergency threshold. Violence is a major threat to life, and to physical and mental wellbeing. Other causes of death speak to poor living conditions and poor access to healthcare and preventive measures, corroborated by the challenges reported by households. Many areas of CAR face similar challenges to Ouaka. If these results were generalisable across CAR, the country would suffer one of the highest mortality rates in the world, a reminder that the longstanding “silent crisis” continues.

Background Together with poor biodegradability and insufficient recycling, the massive production and use of plastics have led to widespread environmental contamination by nano- and microplastics. These particles accumulate across ecosystems - even in the most remote habitats - and are transferred through food chains, leading to inevitable human ingestion, that adds to the highest one due to food processes and packaging. Objective The present review aimed at providing a comprehensive overview of current knowledge regarding the effects of nano- and microplastics on intestinal homeostasis. Methods We conducted a literature search focused on the in vivo effects of nano- and microplastics on gut epithelium and microbiota, as well as on immune response. Results Numerous animal studies have shown that exposure to nano- and microplastics leads to impairments in oxidative and inflammatory intestinal balance, and disruption of the gut’s epithelial permeability. Other notable effects of nano- and microplastic exposure include dysbiosis (changes in the gut microbiota) and immune cell toxicity. Moreover, microplastics contain additives, adsorb contaminants, and may promote the growth of bacterial pathogens on their surfaces: they are potential carriers of intestinal toxicants and pathogens that can potentially lead to further adverse effects. Conclusion Despite the scarcity of reports directly relevant to human, this review brings together a growing body of evidence showing that nano- and microplastic exposure disturbs the gut microbiota and critical intestinal functions. Such effects may promote the development of chronic immune disorders. Further investigation of this threat to human health is warranted. 17;1

This study examined narrative ability in ASD and parents across two contexts differing in structure and emotional content, and explored gaze patterns that may underlie narrative differences by presenting narrative tasks on an eye tracker. Participants included 37 individuals with ASD and 38 controls, 151 parents of individuals with ASD and 63 parent controls. The ASD and ASD parent groups demonstrated lower narrative quality than controls in the less structured narrative task only. Subtler, context-dependent differences emerged in gaze and showed some associations with narrative quality. Results indicate a narrative ability profile that may reflect genetic liability to ASD, and subtle links between visual attention and complex language skills that may be influenced by ASD genetic risk.

In stainless steel production, slag from argon oxygen decarburization (AOD) converters is dumped on to the ground and then slowly cooled. The slag undergoes phase transformation from β-dicalcium silicate (β-C2S) to γ-dicalcium silicate (γ-C2S) at approximately 500 °C to 450 °C, resulting in slag volume expansion, disintegration, and dust generation. The dusty slag leads to challenges in material handling, metals recovery, and emissions control. Some operations use slag additives to stabilize slag, but this solution is expensive and can limit the end use of slag due to inclusion of toxic elements. Air granulation was hypothesized as a water-free method for stabilizing AOD slag via rapid quenching. Pilot-scale experiments at Sandvik Materials Technology (SMT) with silicon-reduced AOD slags confirmed that air granulation can produce products which are stable and dust free. Mineralogical analyses further indicated that these air-granulated stainless slags contained either no or low content of γ-C2S and are therefore stable.

Children with autism spectrum disorder (ASD) are at an increased risk to develop problem behavior, which can have deleterious effects on child and parental well-being. Because of this, parents are often provided with Behavioral Parent Training (BPT). However, attrition rates in BPT are high, and there is a relative dearth of research investigating factors that influence parental engagement in BPT. We ran seven semi-structured online focus groups with a total of 30 parents of children with ASD and related disabilities. Parents were interviewed in order to gain a greater understanding of variables that enable or pose barriers to parental engagement in BPT. An inductive qualitative analysis was conducted by two independent authors. Our analyses revealed three themes indicating the need for (a) supportive, professional feedback; (b) accessible, flexible, and affordable training; and (c) social-emotional support and community connection in BPT for parents of children with ASD. Results from this study suggest that parental engagement in BPT for children with ASD may be enhanced if it is relevant to the needs of families, facilitated by responsive professionals, flexible, and readily accessible. Additionally, parents may benefit from BPT that includes social and emotional support, such as assistance connecting with other families and evidence-based strategies to manage the stress associated with parenting a child with ASD and challenging behavior.