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The emergence of correlated phenomena arising from the combination of 1T and 1H van der Waals layers is the focus of intense research. Here, we synthesize a self-stacked 6R phase in NbSeTe, showing perfect alternating 1T and 1H layers that grow coherently along the c-direction, as revealed by scanning transmission electron microscopy. Angle-resolved photoemission spectroscopy shows a mixed contribution of the trigonal and octahedral Nb bands to the Fermi level. Diffuse scattering reveals temperature-independent short-range charge fluctuations with propagation vector qCO= (0.25 0), derived from the condensation of a longitudinal mode in the 1T layer, while the long-range charge density wave is quenched by ligand disorder. Magnetization measurements suggest the presence of an inhomogeneous, short-range magnetic order, further supported by the absence of a clear phase transition in the specific heat. These experimental analyses in combination with ab initiocalculations indicate that the ground state of 6R-NbSeTe is described by a statistical distribution of short-range charge-modulated and spin-correlated regions driven by ligand disorder. Our results demonstrate how natural 1T-1H self-stacked bulk heterostructures can be used to engineer emergent phases of matter.

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Climate change adaptation policies are urgently needed, but the large volume and variety of evidence limits the ability of practitioners to make informed decisions. Here, we create an evidence map of adaptation policy research, selecting and categorizing 8,691 documents using state-of-the-art transformers-based machine learning models. We combine policy-relevant categories, such as the NATO-typology and governance levels, with automatically extracted locations and a structural topic model to provide a detailed global assessment of the tools governments are using to address climate change risks and impacts. We find that international-level policies, as well as policies in North America and much of the Global South, emphasize financial instruments, whereas national policies, particularly in Europe and Oceania, favor authority-based legislation. Collaborative approaches are most common at the local level. Despite a rapidly expanding evidence base overall, we note persistent geographic inequalities and limited evidence on information-based policies, policy implementation, and structural reforms.

BackgroundSocial cognition (SC) deficits are included in the amyotrophic lateral sclerosis-frontotemporal spectrum disorder (ALS-FTDS) revised diagnostic criteria. However, the impact of SC assessment on cognitive classification and the cognitive–behavioural correlates of SC remain unclear. This cross-sectional study aimed to assess the impact of SC assessment on ALS-FTDS categorisation and explore the relationship of SC with executive functions (EF) and behaviour changes in a cohort of ALS patients.Methods121 patients and 56 healthy controls from the Turin ALS Centre underwent cognitive/behavioural testing, including the SC subdomains of facial emotion recognition, and cognitive and affective theory of mind (ToM).ResultsPatients performed significantly worse than controls in all SC explored domains, and 45% of patients exhibited a deficit in at least one SC test, dissociated from the presence of EF deficits. In 13% of cases, the SC deficit was isolated and subclinical. SC assessment contributed to the attribution of cognitive impairment in 10% of patients. Through a statistical clustering approach, we found that ToM only partially overlaps with EF while behaviour changes are associated with emotional disorders (anxiety and depression).ConclusionsSC is overall independent of EF in ALS, with ToM only partially associated with specific EF measures, and behaviour changes associated with emotional disorders. The influence of SC on cognitive categorisation and the frequent identification of a subclinical SC impairment have implications in a clinical setting, considering the substantial impact of cognitive impairment on disease burden and therapeutic choices.

ABSTRACTThe aim of our analysis is to give voice to young change agents in tourism host communities. Drawing on a braided narrative analysis, we present the narratives of three young people engaged in advocacy work in three different countries. Our analysis is emergent from research withrather than onyoung people across three countries on three different continents (Canada, Australia, and Scotland). Our analysis explores the nexus between two foundational theories we use as a lens for understanding the narratives shared by our informants, including a feminist ethic of care and ‘childist’ ontological understanding of children as moral agents capable of ethical decision-making and drivers of change. Our braided narrative analysis unearths themes in relation to the work of our informants based on the past, present, and future, including recognising problems in the system; leading and activating change; and young people demonstrating courage, calling for inclusion, and confronting barriers. We conclude with a discussion on the practical implications of our work to intentionally include, make space for, normalise, and compensate the work of young people.

In this article, Javier Canosa discusses the effects of high inflation in Argentina and the tax developments of 2022 in Argentina.

ABSTRACTThere is sufficient evidence in academic scholarship that points to the important role diaspora tourism plays for the economies of homeland communities and countries. Given previous research shows a decreased level of attachment to the homeland in the second generation of immigrants, this research seeks to explore the effects of childhood experiences on adult behaviours and outcomes in relation to diaspora tourism. The research reveals the important role played by families in transmitting knowledge, memories, traditions and other cultural practices to diaspora children. Destination Marketing Organisations (DMOs), however, are neglecting to engage this lucrative market partly because communication strategies are aimed at adults of the diaspora and not at children. Based on these findings, we propose DMOs take a child-centred approach by actively engaging diaspora children to devise tourism marketing strategies that are child-friendly.

VSe2is a layered compound that has attracted great attention due to its proximity to a ferromagnetic state that is quenched by its charge density wave (CDW) phase. In the monolayer limit, unrelated experiments have reported different CDW orders with different transition temperatures, making this monolayer very controversial. Here we perform first-principles nonperturbative anharmonic phonon calculations in monolayer VSe2in order to estimate the CDW order and the corresponding transition temperature. They reveal that monolayer VSe2develops two independent charge density wave orders that compete as a function of strain. Variations of only 1.5% in the lattice parameter are enough to stabilize one order or the other. Moreover, we analyze the impact of external Lennard-Jones interactions, showing that these can act together with anharmonicity to suppress the CDW orders. Our results solve previous experimental contradictions, highlighting the high tunability and substrate dependency of the CDW orders of monolayer VSe2.

Amyotrophic lateral sclerosis (ALS) is known to represent a collection of overlapping syndromes. Various classification systems based on empirical observations have been proposed, but it is unclear to what extent they reflect ALS population substructures. We aimed to use machine-learning techniques to identify the number and nature of ALS subtypes to obtain a better understanding of this heterogeneity, enhance our understanding of the disease, and improve clinical care.

We present the fifth case of candida dubliniensis meningitis in a young immunocompetent host and suggest extracorporeal membrane oxygenation (ECMO) as a potential risk factor for colonization.

Social policy in Australia and internationally, that is focused on improving children's safety and well‐being, increasingly makes implicit or explicit reference to the United Nations Convention on the Rights of the Child. Concomitantly, children and young people's participation is more widely acknowledged as being key to ensuring policies, programmes and services reflect their views and lived experience. The non‐government sector, along with statutory bodies like the National and State‐based Children's Commissions in Australia, have led the way in advocating for children's participation, including the development of resources to assist in facilitating this. Little is known, however, about the nature, scope and extent of such resources nor the evidence informing them. This article reports the findings of a scoping review of rights‐informed resources and academic articles that provide a sound rationale and “good practice” information, education and/or professional learning about children's participation rights, in particular. The findings highlight some of the tensions and possibilities between the rhetorical aspirations of participation and existing practice. The analysis is intended to support the efforts of organisations endeavouring to improve their understanding and approaches to embedding children's rights, including participation in decision making and other matters of interest or concern to them.

Introduction and background: Myocardial revascularization using internal thoracic arteries (ITAs) has been associated with superior clinical outcome. This study addresses the question of whether internal mammary arteries are unsuitable for [...]

Occup Environ Med 2004;61:239-246 Aims: To explore the relation between safety climate (workers' perceptions regarding management's attitudes towards occupational safety and health) and workers' behaviour at work. Methods: Cross sectional [...]

Inherent susceptibility of peptides to enzymatic degradation in the gastrointestinal tract is a key bottleneck in oral peptide drug development. Here, we present a systematic analysis of (i) the gut stability of disulfide-rich peptide scaffolds, orally administered peptide therapeutics, and well-known neuropeptides and (ii) medicinal chemistry strategies to improve peptide gut stability. Among a broad range of studied peptides, cyclotides were the only scaffold class to resist gastrointestinal degradation, even when grafted with non-native sequences. Backbone cyclization, a frequently applied strategy, failed to improve stability in intestinal fluid, but several site-specific alterations proved efficient. This work furthermore highlights the importance of standardized gut stability test conditions and suggests defined protocols to facilitate cross-study comparison. Together, our results provide a comparative overview and framework for the chemical engineering of gut-stable peptides, which should be valuable for the development of orally administered peptide therapeutics and molecular probes targeting receptors within the gastrointestinal tract.

ObjectiveTo detect the clinical characteristics of patients with amyotrophic lateral sclerosis (ALS) carrying an intermediate ATXN2polyQ number of repeats in a large population-based series of Italian patients with ALS.MethodsThe study population includes 1330 patients with ALS identified through the Piemonte and Valle d’Aosta Register for ALS, diagnosed between 2007 and 2019 and not carrying C9orf72, SOD1, TARDBPand FUSmutations. Controls were 1274 age, sex and geographically matched Italian subjects, identified through patients’ general practitioners.ResultsWe found 42 cases and 4 controls with≥31 polyQ repeats, corresponding to an estimated OR of 10.4 (95% CI 3.3 to 29.0). Patients with≥31 polyQ repeats (ATXN2+) compared with those without repeat expansion (ATXN2−) had more frequently a spinal onset (p=0.05), a shorter diagnostic delay (p=0.004), a faster rate of ALSFRS-R progression (p=0.004) and King’s progression (p=0.004), and comorbid frontotemporal dementia (7 (28.0%) vs 121 (13.4%), p=0.037). ATXN2+ patients had a 1-year shorter survival (ATXN2+ patients 1.82 years, 95% CI 1.08 to 2.51; ATXN2− 2.84 years, 95% CI 1.67 to 5.58, p=0.0001). ATXN2polyQ intermediate repeats was independently related to a worse outcome in Cox multivariable analysis (p=0.006).ConclusionsIn our population-based cohort, ATXN2+ patients with ALS have a distinctive phenotype, characterised by a more rapid disease course and a shorter survival. In addition, ATXN2+ patients have a more severe impairment of cognitive functions. These findings have relevant implications on clinical practice, including the possibility of refining the individual prognostic prediction and improving the design of ALS clinical trials, in particular as regards as those targeted explicitly to ATXN2.

BackgroundA genetic diagnosis in Amyotrophic Lateral Sclerosis (ALS) can inform genetic counselling, prognosis and, in the light of incoming gene-targeted therapy, management. However, conventional genetic testing strategies are often costly and time-consuming.ObjectiveTo evaluate the diagnostic yield and advantages of whole-genome sequencing (WGS) as a standard diagnostic genetic test for ALS.MethodsIn this population-based cohort study, 1043 ALS patients from the Piemonte and Valle d’Aosta Register for ALS and 755 healthy individuals were screened by WGS for variants in 42 ALS-related genes and for repeated-expansions in C9orf72 and ATXN2.ResultsA total of 279 ALS cases (26.9%) received a genetic diagnosis, namely 75.2% of patients with a family history of ALS and 21.5% of sporadic cases. The mutation rate among early-onset ALS patients was 43.9%, compared with 19.7% of late-onset patients. An additional 14.6% of the cohort carried a genetic factor that worsen prognosis.ConclusionsOur results suggest that, because of its high diagnostic yield and increasingly competitive costs, along with the possibility of retrospectively reassessing newly described genes, WGS should be considered as standard genetic testing for all ALS patients. Additionally, our results provide a detailed picture of the genetic basis of ALS in the general population.

Although ‘child safety’ is now a national policy priority in Australia, there is little research exploring the practicesin schools that contribute to children and young people’s felt sense of safety and wellbeing. Drawing on a mixed-method Australian Research Council (ARC) Discovery project, this article presents findings from interviews with school staff (N= 10), leaders (N= 5) and nine focus groups with students (N= 58), in primary and secondary schools in three Australian states (New South Wales, Victoria and South Australia). We employ relational ethics, recognition theory and the theory of practice architectures to explore practices at school that support student wellbeing and safety. The findings contribute significantly to understanding the ‘bundled’ nature of current practices and the conditions that enable and constrain these. Close attention to these findings is critical as schools seek to operationalise the National Child Safe Principles and refine ongoing safeguarding procedures. The findings have informed the development of an online survey that is currently testing, on a much larger scale, which elements of ethical practice are most positively associated with students’ safety, wellbeing and recognition at school.

Rates of Hepatitis C virus (HCV) testing and diagnosis are variable among people who use drugs (PWUD). In Puglia in 2018, of 871 subjects screened, 38% had HCV antibodies (HCVAb). Despite sustained virologic response at week 12 Sustained virologic response (SVR12) rates >95%, addiction centers in Italy are not allowed to prescribe direct‐acting antivirals (DAA). To increase testing and linkage to care a dedicated program including “ad hoc” transportation and fast‐track access to care was offered to PWUD from Puglia. Over 12 months, 1,470 individuals seen at 15 Services for Dependence (SERDs) underwent screening. For HCVAb positive, a fast‐track evaluation was offered at our Hepatology Unit. Patients were subsequently taken to their pharmacists to receive the prescribed DAA regimen. Treatment and adherence were supervised by SERDs physicians, SVR12 assessed at our unit. The scalability of the process was based on both, number of patients screened in our region in 2018, and number of PWUD diagnosed and treated at our center during 2018–2019. Of 1,470 individuals screened, 634 (43.1%) tested HCVAb positive. Overall, 231 were RNA positive, 54% of whom on opioid agonist therapy (OAT) and 32% with cirrhosis. Median interval between RNA assessment and treatment start was 22 days (0–300). Patients received 12‐week sofosbuvir/velpatasvir regimen without Ribavirin; in 220 patients who completed treatment, SVR12 was 98.6%. Among GT3, SVR12 was 98%. No re‐infection was observed. Improvements in screening, and linkage to care were registered. A PWUD‐tailored service led to HCV care cascade improvement and high SVR12 rates. Despite history of drug addiction, social instability and logistic barriers, micro‐elimination programs providing dedicated care are key drivers of success.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.

The never-ending demand for more features and better performance is forcing designers to re-evaluate the microprocessors that their products incorporate. Outside forces can also affect processor selection for a next-generation [...]

Assessing global progress on human adaptation to climate change is an urgent priority. Although the literature on adaptation to climate change is rapidly expanding, little is known about the actual extent of implementation. We systematically screened >48,000 articles using machine learning methods and a global network of 126 researchers. Our synthesis of the resulting 1,682 articles presents a systematic and comprehensive global stocktake of implemented human adaptation to climate change. Documented adaptations were largely fragmented, local and incremental, with limited evidence of transformational adaptation and negligible evidence of risk reduction outcomes. We identify eight priorities for global adaptation research: assess the effectiveness of adaptation responses, enhance the understanding of limits to adaptation, enable individuals and civil society to adapt, include missing places, scholars and scholarship, understand private sector responses, improve methods for synthesizing different forms of evidence, assess the adaptation at different temperature thresholds, and improve the inclusion of timescale and the dynamics of responses.

IMPORTANCE: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation. OBJECTIVE: To identify the genetic variants associated with juvenile ALS. DESIGN, SETTING, AND PARTICIPANTS: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism. MAIN OUTCOMES AND MEASURES: De novo variants present only in the index case and not in unaffected family members. RESULTS: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway. CONCLUSIONS AND RELEVANCE: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.

Analizar la incidencia y las características de la lesión medular (LM) traumática en la población geriátrica de Galicia (España), el manejo hospitalario y el pronóstico vital y funcional.

To analyze the incidence and characteristics of traumatic spinal cord injury (SCI) in geriatric population of Galicia (Spain), hospital management and functional prognosis

Heart valve replacement has steadily increased over the past decades due to improved surgical mortality, an aging population, and the increasing use of transcatheter valve technology. With these developments, prosthetic valve complications, including prosthetic valve endocarditis, are increasingly encountered. In this review, we aim to characterize the manifestations of prosthetic valve endocarditis using representative case studies from our institution to highlight the advances and contributions of modern multimodality imaging techniques.

Child safety is now a national policy priority in Australia. Extensive enquiries and reviews have escalated legislative and policy responses focused on developing, maintaining and monitoring “child safe” organisations. The recommendations of the Royal Commission into Institutional Responses to Child Sexual Abuse point to the importance of cultural conditions within organisations in supporting child safety and the need for responsive change in some organisations. Drawing on a recent policy analysis, undertaken as part of a larger Australian Research Council Discovery Project, this article examines how children and safety are constructed, within and across relevant state and federal government policies in Australia, and the implications of this. Distinctions are drawn between conceptualisations of children within the broader education policy context and two specific policy contexts in which children are considered particularly vulnerable to abuse – out‐of‐home care and disability. The findings indicate that policy discourses of “child safe” potentially foster different emphases and approaches in organisations. These have implications for the way children are positioned in relation to their safety, how their rights are recognised and implemented, and what is required to foster cultural conditions within organisations to best support children’s safety and wellbeing.

The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia, and to generate a resource for the scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide gene-aggregation tests implicated mutations in the gene GBA. Genetic risk scores demonstrate that LBD shares risk profiles and pathways with Alzheimer’s disease and Parkinson’s disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition.

Humans settled the Caribbean about 6,000 years ago, and ceramic use and intensified agriculture mark a shift from the Archaic to the Ceramic Age at around 2,500 years ago1–3. Here we report genome-wide data from 174 ancient individuals from The Bahamas, Haiti and the Dominican Republic (collectively, Hispaniola), Puerto Rico, Curaçao and Venezuela, which we co-analysed with 89 previously published ancient individuals. Stone-tool-using Caribbean people, who first entered the Caribbean during the Archaic Age, derive from a deeply divergent population that is closest to Central and northern South American individuals; contrary to previous work4, we find no support for ancestry contributed by a population related to North American individuals. Archaic-related lineages were >98% replaced by a genetically homogeneous ceramic-using population related to speakers of languages in the Arawak family from northeast South America; these people moved through the Lesser Antilles and into the Greater Antilles at least 1,700 years ago, introducing ancestry that is still present. Ancient Caribbean people avoided close kin unions despite limited mate pools that reflect small effective population sizes, which we estimate to be a minimum of 500–1,500 and a maximum of 1,530–8,150 individuals on the combined islands of Puerto Rico and Hispaniola in the dozens of generations before the individuals who we analysed lived. Census sizes are unlikely to be more than tenfold larger than effective population sizes, so previous pan-Caribbean estimates of hundreds of thousands of people are too large5,6. Confirming a small and interconnected Ceramic Age population7, we detect 19 pairs of cross-island cousins, close relatives buried around 75 km apart in Hispaniola and low genetic differentiation across islands. Genetic continuity across transitions in pottery styles reveals that cultural changes during the Ceramic Age were not driven by migration of genetically differentiated groups from the mainland, but instead reflected interactions within an interconnected Caribbean world1,8.

ObjectiveTo identify the metabolic changes related to the various levels of cognitive deficits in amyotrophic lateral sclerosis (ALS) using 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG-PET) imaging.Methods274 ALS patients underwent neuropsychological assessment and brain 18F-FDG-PET at diagnosis. According to the criteria published in 2017, cognitive status was classified as ALS with normal cognition (ALS-Cn, n=132), ALS with behavioural impairment (ALS-Bi, n=66), ALS with cognitive impairment (ALS-Ci, n=30), ALS with cognitive and behavioural impairment (ALS-Cbi, n=26), ALS with frontotemporal dementia (ALS–FTD, n=20). We compared each group displaying some degree of cognitive and/or behavioural impairment to ALS-Cn patients, including age at PET, sex and ALS Functional Rating Scale-Revised as covariates.ResultsWe identified frontal lobe relative hypometabolism in cognitively impaired patients that resulted more extensive and significant across the continuum from ALS-Ci, through ALS-Cbi, to ALS–FTD. ALS–FTD patients also showed cerebellar relative hypermetabolism. ALS-Bi patients did not show any difference compared with ALS-Cn.ConclusionsThese data support the concept that patients with cognitive impairment have a more widespread neurodegenerative process compared with patients with a pure motor disease: the more severe the cognitive impairment, the more diffuse the metabolic changes. Otherwise, metabolic changes related to pure behavioural impairment need further characterisation.

There are emerging data depicting the clinical presentation of coronavirus disease 19 (COVID‐19) in solid organ transplant recipients but negligible data‐driven guidance on clinical management. A biphasic course has been described in some infected with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), beginning with a flu‐like illness followed by an intense inflammatory response characterized by elevated c‐reactive protein (CRP), interleukin 6 (IL‐6), and acute respiratory distress syndrome (ARDS) associated with high mortality. The exuberant and possibly dysregulated immune response has prompted interest in therapeutic agents that target the cytokines involved, particularly IL‐6. Tocilizumab is an IL‐6 receptor antagonist with a record of use for a variety of rheumatologic conditions and cytokine release syndrome due to chimeric antigen receptor T‐cell therapy but experience in solid organ and composite tissue transplant recipients (SOT/CTTRs) with SARS‐CoV‐2‐related ARDS has not been previously reported in detail. We present the clinical course of 5 SOT/CTTRs with SARS‐CoV‐2‐related ARDS that received tocilizumab with favorable short‐term outcomes in 4. Responses were characterized by reductions in CRP, discontinuation of vasopressors, improved oxygenation and respiratory mechanics, and variable duration of ventilator support. Four bacterial infections occurred within 2 weeks of tocilizumab administration. We discuss safety concerns and the need for randomized comparative trials to delineate tocilizumab's clinical utility in this population. The authors describe the clinical course of solid organ and vascularized composite allograft recipients with COVID‐19–related ARDS treated with tocilizumab.

Analizar la supervivencia de los pacientes con insuficiencia cardiaca (IC) tratados en una unidad especializada.

Adaptar la ICU Mobility Scale(IMS) al ámbito de las unidades de cuidados intensivos (UCI) de España y evaluar las propiedades métricas de la IMS versión española (IMS-Es).