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OBJECTIVE: Tooth growth and wear are commonly used tools for determining the age of mammals. The most speciose order of marsupials, Diprotodontia, is characterised by a pair of procumbent incisors within the lower jaw. This study examines the growth and wear of these incisors to understand their relationship with age and sex. DESIGN: Measurements of mandibular incisor crown and root length were made for two sister species of macropodid (kangaroos and wallabies); Macropus giganteus and Macropus fuliginosus. Histological analysis examined patterns of dentine and cementum deposition within these teeth. Broader generalisability within Diprotodontia was tested using dentally reduced Tarsipes rostratus - a species disparate in body size and incisor function to the studied macropodids. RESULTS: In the macropodid sample it is demonstrated that the hypsodont nature of these incisors makes measurements of their growth (root length) and wear (crown length) accurate indicators of age and sex. Model fitting finds that root growth proceeds according to a logarithmic function across the lifespan, while crown wear follows a pattern of exponential reduction for both macropodid species. Histological results find that secondary dentine deposition and cementum layering are further indicators of age. Incisor measurements are shown to correlate with age in the sample of T. rostratus. CONCLUSIONS: The diprotodontian incisor is a useful tool for examining chronological age and sex, both morphologically and microstructurally. This finding has implications for population ecology, palaeontology and marsupial evolution.

A phylogeny describes the evolutionary history of an evolving population. Evolutionary search algorithms can perfectly track the ancestry of candidate solutions, illuminating a population's trajectory through the search space. However, phylogenetic analyses are typically limited to post-hoc studies of search performance. We introduce phylogeny-informed subsampling, a new class of subsampling methods that exploit runtime phylogenetic analyses for solving test-based problems. Specifically, we assess two phylogeny-informed subsampling methods -- individualized random subsampling and ancestor-based subsampling -- on three diagnostic problems and ten genetic programming (GP) problems from program synthesis benchmark suites. Overall, we found that phylogeny-informed subsampling methods enable problem-solving success at extreme subsampling levels where other subsampling methods fail. For example, phylogeny-informed subsampling methods more reliably solved program synthesis problems when evaluating just one training case per-individual, per-generation. However, at moderate subsampling levels, phylogeny-informed subsampling generally performed no better than random subsampling on GP problems. Our diagnostic experiments show that phylogeny-informed subsampling improves diversity maintenance relative to random subsampling, but its effects on a selection scheme's capacity to rapidly exploit fitness gradients varied by selection scheme. Continued refinements of phylogeny-informed subsampling techniques offer a promising new direction for scaling up evolutionary systems to handle problems with many expensive-to-evaluate fitness criteria., Comment: Conference submission

Purpose Campylobacter is a frequent cause of enteric infections with common antimicrobial resistance issues. The most recent reports of campylobacteriosis in Italy include data from 2013 to 2016. We aimed to provide national epidemiological and microbiological data on human Campylobacter infections in Italy during the period 2017–2021. Methods Data was collected from 19 Hospitals in 13 Italian Regions. Bacterial identification was performed by mass spectrometry. Antibiograms were determined with Etest or Kirby-Bauer (EUCAST criteria). Results In total, 5419 isolations of Campylobacter spp. were performed. The most common species were C. jejuni (n = 4535, 83.7%), followed by C. coli (n = 732, 13.5%) and C. fetus (n = 34, 0.6%). The mean age of patients was 34.61 years and 57.1% were males. Outpatients accounted for 54% of the cases detected. Campylobacter were isolated from faeces in 97.3% of cases and in 2.7% from blood. C. fetus was mostly isolated from blood (88.2% of cases). We tested for antimicrobial susceptibility 4627 isolates (85.4%). Resistance to ciprofloxacin and tetracyclines was 75.5% and 54.8%, respectively; resistance to erythromycin was 4.8%; clarithromycin 2% and azithromycin 2%. 50% of C. jejuni and C. coli were resistant to ≥ 2 antibiotics. Over the study period, resistance to ciprofloxacin and tetracyclines significantly decreased (p < 0.005), while resistance to macrolides remained stable. Conclusion Campylobacter resistance to fluoroquinolones and tetracyclines in Italy is decreasing but is still high, while macrolides retain good activity.

Activation-induced cytidine deaminase, AICDA or AID, is a driver of somatic hypermutation and class-switch recombination in immunoglobulins. In addition, this deaminase belonging to the APOBEC family may have off-target effects genome-wide, but its effects at pan-cancer level are not well elucidated. Here, we used different pan-cancer datasets, totaling more than 50,000 samples analyzed by whole-genome, whole-exome, or targeted sequencing. AID mutations are present at pan-cancer level with higher frequency in hematological cancers and higher presence at transcriptionally active TAD domains. AID synergizes initial hotspot mutations by a second composite mutation. AID mutational load was found to be independently associated with a favorable outcome in immune-checkpoint inhibitors (ICI) treated patients across cancers after analyzing 2000 samples. Finally, we found that AID-related neoepitopes, resulting from mutations at more frequent hotspots if compared to other mutational signatures, enhance CXCL13/CCR5 expression, immunogenicity, and T-cell exhaustion, which may increase ICI sensitivity.

To examine illicit substance use across young adulthood and explore the extent to which social skills moderate the relationship between use and harm. 1,404 (761 women) from the Australian Temperament Project (est. 1983) participated across young adulthood (age 19–20, 23–24, and 27–28 years). Measures included self-reported illicit substance use/harm and social skills (i.e., assertion, empathy, responsibility, and self-control). The number and type of illicit substances used changed across young adulthood. Greater illicit substance use was associated with peer (OR = 4.96) and partner use (OR = 3.60). Moderation analyses suggested the risk relationship between the number of illicit substances used and harm was lower in those with high levels of assertion/self-control (ORassertion = 2.34, ORself-control = 2.60) compared to low levels (ORassertion = 4.43, ORself-control = 3.72). Evidence based programmes designed to strengthen individual social skills for young adults may play a role in protecting against the adverse effects of illicit substance use.

The mainstay of treatment for adult patients with gliomas, glioneuronal and neuronal tumors consists of combinations of surgery, radiotherapy, and chemotherapy. For many systemic cancers, targeted treatments are a part of the standard of care, however, the predictive significance of most of these targets in central nervous system (CNS) tumors remains less well-studied. Despite that, there is increasing use of advanced molecular diagnostics that identify potential targets, and tumor-agnostic regulatory approvals on targets also present in CNS tumors have been granted. This raises the question of when and for which targets it is meaningful to test in adult patients with CNS tumors. This evidence-based guideline reviews the evidence available for targeted treatment for alterations in the RAS/MAPK pathway (BRAF, NF1), in growth factor receptors (EGFR, ALK, fibroblast growth factor receptor (FGFR), neurotrophic tyrosine receptor kinase (NTRK), platelet-derived growth factor receptor alpha, and ROS1), in cell cycle signaling (CDK4/6, MDM2/4, and TSC1/2) and altered genomic stability (mismatch repair, POLE, high tumor mutational burden (TMB), homologous recombination deficiency) in adult patients with gliomas, glioneuronal and neuronal tumors. At present, targeted treatment for BRAF p.V600E alterations is to be considered part of the standard of care for patients with recurrent gliomas, pending regulatory approval. For approved tumor agnostic treatments for NTRK fusions and high TMB, the evidence for efficacy in adult patients with CNS tumors is very limited, and treatment should preferably be given within prospective clinical registries and trials. For targeted treatment of CNS tumors with FGFR fusions or mutations, clinical trials are ongoing to confirm modest activity so far observed in basket trials. For all other reviewed targets, evidence of benefit in CNS tumors is currently lacking, and testing/treatment should be in the context of available clinical trials.

Item does not contain fulltext, BACKGROUND: Telemedicine (TM) contributes to bridge the gap between healthcare facilities and patients' homes with neuromuscular disease (NMD) because of mobility issues. However, its deployment is limited due to difficulties evaluating subtle neurological signs such as mild weakness or sensory deficits. The COVID-19 pandemic has disrupted healthcare delivery worldwide, necessitating rapid measures implementation by health care providers (HCPs) to protect patients from acquiring SARS-CoV-2 while maintaining the best care and treatment. OBJECTIVES: Given the challenges faced by remote healthcare assistance of NMD patients, we aim to evaluate the use of TM in NMD during the COVID-19 pandemic. METHODS: Based on the Model for Assessment-of-Telemedicine-Applications (MAST), we conducted a survey amongst clinicians of the ERN EURO NMD (European-Reference-Network-for-Rare-Neuromuscular-Diseases). RESULTS: Based on 42 responses over 76 expected ones, our results show that the COVID-19 pandemic significantly increased the number of HCPs using TM (from 60% to 100%). The TM types most used during the COVID-19 period are teleconsultation and consultation by phone, particularly in the context of symptoms worsening in NMD patients with COVID-19 infection. Most European HCPs were satisfied when using TM but as a complementary option to physical consultations. Many responses addressed the issue of technical aspects needing improvement, particularly for elderly patients who need caregivers' assistance for accessing the TM platform. CONCLUSIONS: TM has been essential during COVID-19, but its use still presents some limitations for NMD patients with cognitive deficits or for first-time diagnosis. Thus, TM should be used as complement to, rather than substitute, for face-to-face consultations.

Findings from longitudinal research, globally, repeatedly emphasise the importance of taking an early life course approach to mental health promotion; one that invests in the formative years of development, from early childhood to young adulthood, just prior to the transition to parenthood for most. While population monitoring systems have been developed for this period, they are typically designed for use within discrete stages (i.e., childhood or adolescent or young adulthood). No system has yet captured development across all ages and stages (i.e., from infancy through to young adulthood). Here we describe the development, and pilot implementation, of a new Australian Comprehensive Monitoring System (CMS) designed to address this gap by measuring social and emotional development (strengths and difficulties) across eight census surveys, separated by three yearly intervals (infancy, 3-, 6-, 9- 12-, 15-, 18 and 21 years). The system also measures the family, school, peer, digital and community social climates in which children and young people live and grow. Data collection is community-led and built into existing, government funded, universal services (Maternal Child Health, Schools and Local Learning and Employment Networks) to maximise response rates and ensure sustainability. The first system test will be completed and evaluated in rural Victoria, Australia, in 2022. CMS will then be adapted for larger, more socio-economically diverse regional and metropolitan communities, including Australian First Nations communities. The aim of CMS is to guide community-led investments in mental health promotion from early childhood to young adulthood, setting secure foundations for the next generation.

We examined the factor structure of parental sensitivity to infants as assessed by the Mini-Maternal Behavior Q-Sort (Mini-MBQS), a 25-item short-form of the original 90-item MBQS. We aimed to: (1) identify latent factors of the Mini-MBQS; and (2) validate each factor by testing associations with infant attachment classifications. Data on parent-infant dyads (n = 313; 222 mothers with 281 children, 29 fathers with 32 children) were drawn from a three-generation Australian cohort study. Exploratory Factor Analysis and Exploratory Structural Equation Modelling examined the structure of the Mini-MBQS. Two latent Mini-MBQS factors were identified, requiring 8 of 25 original items: (1) Attention and Responsiveness and (2) Contingency in Interactions. Infants with insecure attachment classifications had parents with lower sensitivity across both factors relative to infants classified secure. In particular, infants with resistant attachment classifications had parents with notably low Contingency in Interactions scores. Infants with disorganised attachment classifications had parents with the lowest relative sensitivity across both factors, and in these dyads Attention and Responsiveness scores were especially low. Results provide an empirically derived factor structure for the Mini-MBQS. Two subscales, each with significant infant attachment associations, may improve precision in clinical intervention and research translation.

Ceramic membranes operating at high-temperatures are a key-technology for hydrogen separation processes. Cer-cer composites based on BaCe0.65Zr0.20Y0.15O3-d-Gd0.2Ce0.8O2-d have gained increasing attention as asymmetric membranes for H2 purification, for their high proton-electron conductivity, 100% selectivity, temperature and chemical stability, and intrinsic lower costs compared with the Pd–based technologies. Here, BCZY-GDC composite parts were successfully fabricated for the first time by microextrusion. Water-based pastes with different solid loadings and suitable rheological properties were formulated and printed in single or multilayer structures without nozzle clogging. After deposition, the samples were osmotically dried in concentrated PEG solutions in order to obtain cracks-free green bodies. The further process optimization allowed the production of planar BCZY-GDC ceramics to be potentially applied in asymmetric membrane structures. The mechanical properties of the as-obtained single and multilayer structures as well as of the interface between filaments were assessed through different nanoindentation techniques., Peer Reviewed, Postprint (published version)

A better understanding of transcriptional evolution of IDH-wild-type glioblastoma may be crucial for treatment optimization. Here, we perform RNA sequencing (RNA-seq) (n = 322 test, n = 245 validation) on paired primary-recurrent glioblastoma resections of patients treated with the current standard of care. Transcriptional subtypes form an interconnected continuum in a two-dimensional space. Recurrent tumors show preferential mesenchymal progression. Over time, hallmark glioblastoma genes are not significantly altered. Instead, tumor purity decreases over time and is accompanied by co-increases in neuron and oligodendrocyte marker genes and, independently, tumor-associated macrophages. A decrease is observed in endothelial marker genes. These composition changes are confirmed by single-cell RNA-seq and immunohistochemistry. An extracellular matrix-associated gene set increases at recurrence and bulk, single-cell RNA, and immunohistochemistry indicate it is expressed mainly by pericytes. This signature is associated with significantly worse survival at recurrence. Our data demonstrate that glioblastomas evolve mainly by microenvironment (re-)organization rather than molecular evolution of tumor cells.

A better understanding of transcriptional evolution of IDH-wild-type glioblastoma may be crucial for treatment optimization. Here, we perform RNA sequencing (RNA-seq) (n = 322 test, n = 245 validation) on paired primary-recurrent glioblastoma resections of patients treated with the current standard of care. Transcriptional subtypes form an interconnected continuum in a two-dimensional space. Recurrent tumors show preferential mesenchymal progression. Over time, hallmark glioblastoma genes are not significantly altered. Instead, tumor purity decreases over time and is accompanied by co-increases in neuron and oligodendrocyte marker genes and, independently, tumor-associated macrophages. A decrease is observed in endothelial marker genes. These composition changes are confirmed by single-cell RNA-seq and immunohistochemistry. An extracellular matrix-associated gene set increases at recurrence and bulk, single-cell RNA, and immunohistochemistry indicate it is expressed mainly by pericytes. This signature is associated with significantly worse survival at recurrence. Our data demonstrate that glioblastomas evolve mainly by microenvironment (re-)organization rather than molecular evolution of tumor cells., Micro and Nano Engineering

The mainstay of treatment for adult patients with gliomas, glioneuronal and neuronal tumors consists of combinations of surgery, radiotherapy, and chemotherapy. For many systemic cancers, targeted treatments are a part of the standard of care, however, the predictive significance of most of these targets in central nervous system (CNS) tumors remains less well-studied. Despite that, there is increasing use of advanced molecular diagnostics that identify potential targets, and tumor-agnostic regulatory approvals on targets also present in CNS tumors have been granted. This raises the question of when and for which targets it is meaningful to test in adult patients with CNS tumors. This evidence-based guideline reviews the evidence available for targeted treatment for alterations in the RAS/MAPK pathway (BRAF, NF1), in growth factor receptors (EGFR, ALK, fibroblast growth factor receptor (FGFR), neurotrophic tyrosine receptor kinase (NTRK), platelet-derived growth factor receptor alpha, and ROS1), in cell cycle signaling (CDK4/6, MDM2/4, and TSC1/2) and altered genomic stability (mismatch repair, POLE, high tumor mutational burden (TMB), homologous recombination deficiency) in adult patients with gliomas, glioneuronal and neuronal tumors. At present, targeted treatment for BRAF p.V600E alterations is to be considered part of the standard of care for patients with recurrent gliomas, pending regulatory approval. For approved tumor agnostic treatments for NTRK fusions and high TMB, the evidence for efficacy in adult patients with CNS tumors is very limited, and treatment should preferably be given within prospective clinical registries and trials. For targeted treatment of CNS tumors with FGFR fusions or mutations, clinical trials are ongoing to confirm modest activity so far observed in basket trials. For all other reviewed targets, evidence of benefit in CNS tumors is currently lacking, and testing/treatment should be in the context of available clinical trials.

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect

Introduction: The Clinical Care Classification (CCC) system is one of the standard nursing terminologies recognized by the American Nurses Association, developed to describe nursing care through electronic documentation in different healthcare settings. The translation of the CCC system into languages other than English is useful to promote its widespread use in different countries and to provide the standard nursing data necessary for interoperable health information exchange. The aim of this study was to translate the CCC system from English to Italian and to test its clinical validity. Methods: A translation with cross-cultural adaptation was performed in four phases: forward-translation, back-translation, review, and dissemination. Subsequently a pilot cross-mapping study between nursing activities in free-text nursing documentation and the CCC interventions was conducted. Results: All elements of the CCC system were translated into Italian. Semantic and conceptual equivalences were achieved. Altogether 77.8% of the nursing activities were mapped into CCC interventions. Conclusions: The CCC system, and its integration into electronic health records, has the potential to support Italian nurses in describing and providing outcomes and costs of their care in different healthcare settings. Future studies are needed to strengthen the impact of the CCC system on clinical practice.

Incorporating sustainable aspects into supply chain management means developing activities that do not cause damage to natural and social systems, while ensuring the organization's efficiency and performance. In this sense, reducing material losses, especially medicines, can be a way to promote sustainability in the hospital area. In this context, the analysis of the sustainable management of the supply chain at the Hospital de Clinicas de Porto Alegre was carried out through the case study, measuring the stock losses of medicines, which are a source of chemical waste generation, in the period of 2010 to 2019. Losses were measured according to the pharmaceutical form, the drug class and the values ​​for disposal. Most of the loss inventory adjustments occurred due to maturity at the Central Warehouse, with pills as the main pharmaceutical form. Through the results, it can also be inferred that the destination of the medicine before the loss is carried out effectively contributes to the elimination of waste and the consequent generation of waste, being in line with the concept of sustainability. These results provide greater efficiency in the management of the supply chain in Public Administration, especially with regard to stock control and sustainability. In addition, the research contributes to the construction of comparative parameters for measuring drug stock losses, in view of their scarcity in academia., Incorporar aspectos sustentáveis à gestão da cadeia de suprimentos significa desenvolver atividades que não causem danos aos sistemas naturais e sociais, garantindo a eficiência e o desempenho da organização. Nesse sentido, reduzir as perdas de materiais, especialmente medicamentos, pode ser uma forma de promover a sustentabilidade na área hospitalar. Nesse contexto, foi realizada por meio do estudo de caso, a análise do gerenciamento sustentável da cadeia de suprimentos no Hospital de Clínicas de Porto Alegre, mensurando as perdas de estoque de medicamentos, que são fonte de geração de resíduos químicos, do período de 2010 a 2019. As perdas foram mensuradas de acordo com a forma farmacêutica, a classe farmacológica e os valores para descarte. A maior parte dos ajustes de estoque de perda ocorreu devido ao vencimento no Almoxarifado Central, tendo como principal forma farmacêutica, os comprimidos. Por meio dos resultados, também se pode inferir que a destinação do medicamento antes de ser realizada a perda contribui efetivamente para eliminação do desperdício e consequente geração de resíduos, estando alinhado ao conceito de sustentabilidade. Esses resultados proporcionam maior eficiência na gestão da cadeia de suprimentos na Administração Pública, principalmente no que se refere ao controle de estoque e a sustentabilidade. Além disso, a pesquisa contribui para a construção de parâmetros comparativos para mensuração das perdas de estoque de medicamentos, tendo em vista sua escassez no meio acadêmico.

This chapter calls for a more multi-valent engagement with screen media labor that weaves the macro-level complexities of flexible capitalism into the quotidian, even mundane, realities of how a vast network of screen media workers actually work to sustain a mobile regime of accumulation. This approach makes explicit how the division of labor is structured across geography and how power operates within and across those divisions. It also pays attention to work routines and working conditions that now constitute the contemporary “workplace” for film and television workers. These are not discrete tasks but constitute an integrated frame through which industry scholars can interrogate the operations of global capital without resorting to a level of abstraction when discussing the consequences of structural change on the personal and professional livelihoods of screen media workers.

AbstractYouth gambling is associated with a range of harms. This study aimed to examine, among Australian adolescents, the prevalence of gambling (ever, in the last month, at-risk and problem), the most frequent gambling types and modalities, and to explore the student characteristics associated with gambling in the last month and with at-risk or problem gambling. Students aged 12–17 years from Victoria and Queensland answered gambling questions as part of the Australian Secondary School Alcohol and Drug (ASSAD) Survey in 2017. The ASSAD also included a series of questions about smoking, alcohol and other drug use, and mental health. A total of 6377 students from 93 schools were included in analysis. The prevalence of ever gambling and gambling in the last month was 31% and 6% respectively. Of students who had gambled in the last month, 34% were classified as at-risk and 15% were classified as problem gamblers. The most frequent types of gambling in the last month were horse or dog race and sports betting. Students who gambled in the last month did so most frequently via a parent or guardian purchasing or playing for them, at home or at a friends’ house, and online or using an app. Regression analysis indicated that male gender, having money available to spend on self, alcohol consumption in the last seven days, the number of types of advertisements seen in the last month, and the number of peer or family members who gambled in the last month, were significantly associated with the likelihood of students gambling in the last month. Male gender, some age categories, and exposure to more types of gambling advertising were also significant predictors of being classified as an at-risk or problem gambler. This large study of youth gambling provides data on gambling behaviours and related variables from a large sample of Australian secondary school students. Student characteristics, including male gender and exposure to mo

Background Junior medical doctors have a key role in discussions and decisions about treatment and end-of-life care for people with dementia in hospital. Little is known about junior doctors’ decision-making processes when treating people with dementia who have advance care directives (ACDs), or the factors that influence their decisions. To describe among junior doctors in relation to two hypothetical vignettes involving patients with dementia: (1) their legal compliance and decision-making process related to treatment decisions; (2) the factors influencing their clinical decision-making; and (3) the factors associated with accurate responses to one hypothetical vignette. Method A cross-sectional survey of junior doctors, including trainees, interns, registrars and residents, on clinical rotation in five public hospitals located in one Australian state. The anonymous, investigator-developed survey was conducted between August 2018 and June 2019. Two hypothetical vignettes describing patients with dementia presenting to hospital with an ACD and either: (1) bacterial pneumonia; or (2) suspected stroke were presented in the survey. Participants were asked to indicate whether they would commence treatment, given the ACD instructions described in each vignette. Results Overall, 116 junior doctors responded (35% consent rate). In Vignette 1, 58% of respondents (n = 67/116) selected the legally compliant option (i.e. not commence treatment). Participants who chose the legally compliant option perceived ‘following patient wishes’ (n = 32/67; 48%) and ‘legal requirements to follow ACDs’ (n = 32/67; 48%) as equally important reasons for complying with the ACD. The most common reason for not selecting the legally compliant option in Vignette 1 was the ‘ACD is relevant in my decision-making process, but other factors are more relevant’ (n = 14/37; 38%). In Vignette 2, 72% of respondents (n = 83/116) indicated they would commence treatment (i.e. no

Background: For the benefits of advance care planning to be realised during a hospital admission, the treating team must have accurate knowledge of the law pertaining to implementation of advance care directives (ACDs) and substitute decision making. Aims: To determine in a sample of Junior Medical Officers (JMOs): (1) knowledge of the correct order to approach people as substitute decision makers if a patient does not have capacity to consent to treatment; (2) knowledge of the legal validity of ACDs when making healthcare decisions for persons without capacity to consent to treatment, including the characteristics associated with higher knowledge; and (3) barriers to enacting ACDs. Methods: A cross-sectional survey was conducted at five public hospitals in New South Wales, Australia. Interns, residents, registrars, and trainees on clinical rotation during the recruitment period were eligible to participate. Consenting participants completed an anonymous pen-and-paper survey. Results: A total of 118 JMOs completed a survey (36% return rate). Fifty-five percent of participants were female and 56.8% were aged 20–29 years. Seventy-five percent of JMOs correctly identified a Guardian as the first person to approach if a patient did not have decision-making capacity, and 74% correctly identified a person’s spouse or partner as the next person to approach. Only 16.5% identified all four persons in the correct order, and 13.5% did not identify any in the correct order. The mean number of correct responses to the questions assessing knowledge of the legal validity of ACDs was 2.6 (SD = 1.1) out of a possible score of 6. Only 28 participants (23.7%) correctly answered four or more knowledge statements correctly. None of the explored variables were significantly associated with higher knowledge of the legal validity of ACDs. Uncertainty about the currency of ACDs and uncertainty about the legal implications of relying on an ACD when a patient’s family or substitute decisio

Futibatinib, a highly selective, irreversible FGFR1-4 inhibitor, was evaluated in a large multihistology phase I dose-expansion trial that enrolled 197 patients with advanced solid tumors. Futibatinib demonstrated an objective response rate (ORR) of 13.7%, with responses in a broad spectrum of tumors (cholangiocarcinoma and gastric, urothelial, central nervous system, head and neck, and breast cancer) bearing both known and previously uncharacterized FGFR1-3 aberrations. The greatest activity was observed in FGFR2 fusion/rearrangement-positive intrahepatic cholangiocarcinoma (ORR, 25.4%). Some patients with acquired resistance to a prior FGFR inhibitor also experienced responses with futibatinib. Futibatinib demonstrated a manageable safety profile. The most common treatment-emergent adverse events were hyperphosphatemia (81.2%), diarrhea (33.5%), and nausea (30.4%). These results formed the basis for ongoing futibatinib phase II/III trials and demonstrate the potential of genomically selected early-phase trials to help identify molecular subsets likely to benefit from targeted therapy. SIGNIFICANCE: This phase I dose-expansion trial demonstrated clinical activity and tolerability of the irreversible FGFR1-4 inhibitor futibatinib across a broad spectrum of FGFR-aberrant tumors. These results formed the rationale for ongoing phase II/III futibatinib trials in cholangiocarcinoma, breast cancer, gastroesophageal cancer, and a genomically selected disease-agnostic population.This article is highlighted in the In This Issue feature, p. 275.

In a post hoc analysis of the CATNON trial (NCT00626990), we explored whether adding temozolomide to radiotherapy improves outcome in patients with IDH1/2 wildtype (wt) anaplastic astrocytomas with molecular features of glioblastoma [redesignated as glioblastoma, isocitrate dehydrogenase-wildtype (IDH-wt) in the 2021 World Health Organization (WHO) classification of central nervous system tumors]. From the randomized phase III CATNON study examining the addition of adjuvant and concurrent temozolomide to radiotherapy in anaplastic astrocytomas, we selected a subgroup of IDH1/2wt and H3F3Awt tumors with presence of TERT promoter mutations and/or EGFR amplifications and/or combined gain of chromosome 7 and loss of chromosome 10. Molecular abnormalities including MGMT promoter methylation status were determined by next-generation sequencing, DNA methylation profiling, and SNaPshot analysis. Of the 751 patients entered in the CATNON study, 670 had fully molecularly characterized tumors. A total of 159 of these tumors met the WHO 2021 molecular criteria for glioblastoma, IDH-wt. Of these patients, 47 received radiotherapy only and 112 received a combination of radiotherapy and temozolomide. There was no added effect of temozolomide on either overall survival [HR, 1.19; 95% confidence interval (CI), 0.82-1.71] or progression-free survival (HR, 0.87; 95% CI, 0.61-1.24). MGMT promoter methylation was prognostic for overall survival, but was not predictive for outcome to temozolomide treatment either with respect to overall survival or progression-free survival. In this cohort of patients with glioblastoma, IDH-wt temozolomide treatment did not add benefit beyond that observed from radiotherapy, regardless of MGMT promoter status. These findings require a new well-powered prospective clinical study to explore the efficacy of temozolomide treatment in this patient population.

PURPOSE: The Australian Temperament Project Generation 3 Study (ATPG3) was established to examine the extent to which offspring social and emotional development is shaped in the decades prior to conception, in parent and grandparent histories of psychosocial adjustment (eg, emotional regulation, relationship quality and prosociality) and maladjustment (eg, depressive symptoms, substance use and antisociality). PARTICIPANTS: The Australian Temperament Project (ATP) commenced in 1983 as a population representative survey of the social and emotional health of 2443 young Australians (Generation 2: 4-8 months old) and their parents (Generation 1). Since then, families have been followed from infancy to young adulthood (16 waves). Between 2012 and 2018, the cohort was screened biannually for pregnancies (Generation 3), with assessments conducted in the third trimester of pregnancy, and at 8 weeks and 1 year postpartum. FINDINGS TO DATE: A total of 1167 offspring (607 female) born to 703 Generation 2 parents (400 mothers) were recruited into the ATPG3 Study. Findings to date highlight: (1) strong continuities in depressive symptoms and substance use from adolescence through to becoming a parent; (2) a role for persistent preconception mental health problems in risk for parent-child bonding difficulties, as well as infant emotional reactivity and behaviour problems; (3) the importance of secure attachments in adolescence in reducing long-term risk for postpartum mental health problems; and (4) the protective nature of perceived social support, both preconception and postpartum, in strengthening relationship quality and social support during the COVID-19 pandemic. FUTURE PLANS: Assessments of ATPG3 families in preschool and middle childhood are currently funded and underway. We intend to maintain the offspring cohort through childhood, adolescence, young adulthood and into parenthood. Data will be used to map preconception determinants of emotional health, and enhance approa

BACKGROUND: Young people's gambling behaviours are associated with a range of individual, interpersonal and community factors. This study explored the association between exposure to types of gambling advertising and promotions and adolescent gambling behaviours. METHODS: Students from two states answered gambling questions as part of the 2017 Australian Secondary Students' Alcohol and Drug (ASSAD) Survey. Students reported gambling behaviours (gambling in the last month, types of gambling activities), exposure to gambling promotions during the last 30 days (e.g. ads for gambling on TV, online, live studio crosses), and were assessed for problem gambling. Principal Component Analysis suggested four groups of gambling promotion exposure. Logistic regression analyses examined the association between gambling promotion exposure and student gambling, engagement in hard gambling activities in the last month, and problem or at risk gambling, controlling for a range of student characteristics. RESULTS: Most students (81%) had been exposed to some form of gambling promotion or advertisement in the last month, most commonly TV, social media and sporting event advertisements. Exposure to online gambling ads (including websites, pop-ups on websites, and social media) in the last month was significantly associated with gambling in the last month, and being classified as an at risk or problem gambler; but not with participating in hard gambling activities. After adjusting for exposure to gambling advertising across categories, no other advertising exposure types were associated with adolescent gambling behaviours. CONCLUSIONS: Study findings point to the need to impose restrictions on gambling advertisements and promotions, particularly those presented online.

No previous generation of children has grown up in the context of an existential threat comparable to the climate crisis. This Special Issue examines the implications of the climate crisis for children and young people in relation to their mental health and well-being, and, as a corollary, the implications for mental health professionals. Evidence is accumulating on the prevalence of worry among children world-wide, as well as on the direct impacts of the climate crisis on mental health. Despite the huge threat that this crisis poses for the next generation's mental health and well-being, and the recognition that this is now a global mental health emergency, there has been surprisingly little research on the topic. We therefore saw the urgent need to draw together a wide range of original research and perspectives and to consider what this mean for professionals who have dedicated themselves to improving the well-being of children and young people.

Futibatinib, a highly selective, irreversible FGFR1-4 inhibitor, was evaluated in a large multihistology phase I dose-expansion trial that enrolled 197 patients with advanced solid tumors. Futibatinib demonstrated an objective response rate (ORR) of 13.7%, with responses in a broad spectrum of tumors (cholangiocarcinoma and gastric, urothelial, central nervous system, head and neck, and breast cancer) bearing both known and previously uncharacterized FGFR1-3 aberrations. The greatest activity was observed in FGFR2 fusion/rearrangement-positive intrahepatic cholangiocarcinoma (ORR, 25.4%). Some patients with acquired resistance to a prior FGFR inhibitor also experienced responses with futibatinib. Futibatinib demonstrated a manageable safety profile. The most common treatment-emergent adverse events were hyperphosphatemia (81.2%), diarrhea (33.5%), and nausea (30.4%). These results formed the basis for ongoing futibatinib phase II/III trials and demonstrate the potential of genomically selected early-phase trials to help identify molecular subsets likely to benefit from targeted therapy. SIGNIFICANCE: This phase I dose-expansion trial demonstrated clinical activity and tolerability of the irreversible FGFR1-4 inhibitor futibatinib across a broad spectrum of FGFR-aberrant tumors. These results formed the rationale for ongoing phase II/III futibatinib trials in cholangiocarcinoma, breast cancer, gastroesophageal cancer, and a genomically selected disease-agnostic population.This article is highlighted in the In This Issue feature, p. 275.

This article aims to apprehend the present elements in the social representation of faculty development (FD) in higher education in health areas. FD is understood as a set of institutional tools that enable teachers to carry out a multiplicity of action to support their pedagogical practice. Social representation research with a qualitative approach. The research took place at three higher education institutions on southern Brazil, with faculty members from the undergraduate courses in Nursing (10) and Medicine (11), totaling 21. The production of data took place through in-person and online semi-structured interviews (COVID-19). The analysis technique followed Moscovici’s metodological steps, through two processes of Social Representation formation: objectification and anchoring. It is concluded that the FD process is shown to the personal and professional growth of those who commit to it, providing the development of critical-reflective thinking., Este artigo tem por objetivo apreender os elementos presentes nas representações sociais de docentes sobre o processo de desenvolvimento docente (DD) no ensino superior da área de saúde. Entende-se DD como um conjunto de ferramentas institucionais que viabilizam ao docente uma multiplicidade de ações para suporte a sua prática pedagógica. Pesquisa de representação social com abordagem qualitativa, realizou-se em três instituições de ensino superior no sul do Brasil, tendo como participantes docentes dos cursos de graduação em Enfermagem (10) e Medicina (11), totalizando 21. A produção de dados deu-se por entrevista semiestruturada presencial e online (Pandemia COVID-19). A técnica de análise seguiu os passos metodológicos de Moscovici, por meio de dois processos de formação das Representações Sociais: objetivação e ancoragem. Conclui-se que o processo de DD se mostra legítimo no que tange ao crescimento pessoal e profissional daqueles que se comprometem com o processo, proporcionando o desenvolvimento do pensamento crítico-reflexivo., Este artículo tiene como objetivo aprehender los elementos presentes en las representaciones sociales de los docentes sobre el proceso de desarrollo docente (DD) en la educación superior en el área de la salud. El DD se entiende como un conjunto de herramientas institucionales que permiten al docente realizar una multiplicidad de acciones para apoyar su práctica pedagógica. Se realizó una investigación de la representación social con enfoque cualitativo en tres instituciones de educación superior en el sur de Brasil, con docentes de las carreras en Enfermería (10) y Medicina (11), totalizando 21. La producción de datos se ha hecho a través de entrevistas semiestructuradas presenciales y en línea (COVID-19). La técnica de análisis siguió los pasos metodológicos de Moscovici, a través de los procesos de formación de Representaciones Sociales: objetivación y anclaje. Se concluye que el proceso de DD se muestra legítimo en cuanto al crecimiento personal y profesional de quienes están comprometidos con el proceso, proporcionando el desarrollo del pensamiento crítico-reflexivo.

There is already a time when fashion has been rethought in terms of issues of its existential cycle, of a piece, for example. The construction of an identity from DIY fashion resignifies thrift stores as an object of growing consumption in societies, where consumers/ public can express themselves from a unique identity, using a mixture of styles, where the pieces mined in thrift stores take scene in the daily life of his clothing, enabling a culture of “resistance” to the common trend, to the mainstream, that many seek when using second-hand or handmade pieces, thus seeking their own style as a way of differentiating themselves in terms of their visual communication. This text problematizes the construction of an identity from DIY fashion and its relationship with consumption in thrift stores, specifically in Bendita Traça. A bibliographic review was carried out on the subject. It is noticed that thrift stores are attentive to the choices of pieces that are true memorial vestiges, and those who acquire these pieces are even more attentive, as they represent one of the bases of DIY. The work from the researched thrift store Bendita Traça, reveals a connection between the past and the present, through the traces and, in this way, it was possible to reflect on the relationship of the consumer public with this type of establishment, in order to establish a differentiated visual communication., Já existe um tempo em que a moda está sendo repensada no que tange às questões do seu ciclo existencial, o de uma peça, por exemplo. A construção de uma identidade com base na moda DIY ressignifica os brechós como objeto de consumo crescente nas sociedades. Assim, o público pode se expressar com uma identidade única, uma mistura de estilos em que as peças garimpadas em brechós tomam cena no cotidiano do vestuário e possibilitam uma cultura de “resistência” à tendência comum, ao mainstream, que muitos buscam ao vestir peças de segunda mão ou feitas de forma artesanal, criando, assim, um estilo próprio como forma de se diferenciar no que tange sua comunicação visual. Este texto problematiza a construção de uma identidade a partir da moda DIY e sua relação com o consumo em brechós, especificamente no Bendita Traça. Fez-se uma revisão bibliográfica sobre o tema. Percebe-se que os donos de brechós estão atentos à escolha de peças que são verdadeiros vestígios memoriais, e aqueles que as adquirem mais atentos ainda, pois elas representam uma das bases do DIY. O trabalho oriundo do brechó pesquisado (Bendita Traça) revela uma conexão do passado com o presente por meio dos vestígios e, dessa forma, foi possível refletir sobre a relação do público consumidor com esse tipo de estabelecimento, de forma a estabelecer uma comunicação visual diferenciada.

The investigation of spatio-temporal couplings (STCs) of broadband light beams is becoming a key topic for the optimization as well as applications of ultrashort laser systems. This calls for accurate measurements of STCs. Yet, it is only recently that such complete spatio-temporal or spatio-spectral characterization has become possible, and it has so far mostly been implemented at the output of the laser systems, where experiments take place. In this survey, we present for the first time STC measurements at different stages of a collection of high-power ultrashort laser systems, all based on the chirped-pulse amplification (CPA) technique, but with very different output characteristics. This measurement campaign reveals spatio-temporal effects with various sources, and motivates the expanded use of STC characterization throughout CPA laser chains, as well as in a wider range of types of ultrafast laser systems. In this way knowledge will be gained not only about potential defects, but also about the fundamental dynamics and operating regimes of advanced ultrashort laser systems., info:eu-repo/semantics/published

The investigation of spatio-temporal couplings (STCs) of broadband light beams is becoming a key topic for the optimization as well as applications of ultrashort laser systems. This calls for accurate measurements of STCs. Yet, it is only recently that such complete spatio-temporal or spatio-spectral characterization has become possible, and it has so far mostly been implemented at the output of the laser systems, where experiments take place. In this survey, we present for the first time STC measurements at different stages of a collection of high-power ultrashort laser systems, all based on the chirped-pulse amplification (CPA) technique, but with very different output characteristics. This measurement campaign reveals spatio-temporal effects with various sources, and motivates the expanded use of STC characterization throughout CPA laser chains, as well as in a wider range of types of ultrafast laser systems. In this way knowledge will be gained not only about potential defects, but also about the fundamental dynamics and operating regimes of advanced ultrashort laser systems.

In this work, we reflect on the questions about tradition and modernity in the artistic and cultural perceptions of the bell’s tradition in the city of São João del Rei in the state of Minas Gerais. We bring as material for analysis the visual EP entitled “Sinógeno”, which, when published in March 2021, brought a series of repercussions, among them some controversies, around the possible artistic or sacrilege contained in the work. Here, we will discuss, through this object, themes about the Minas Gerais perception about cosmopolitanism and artistic experimentation, relating the message concepts of José Miguel Wisnik, as well as the in-between of the local and global conceptions. Passing briefly through the historical context of Minas, from the land exploration process, through the influence of Churches and the Catholic religion in the process of building the region, to contemporary sound, visual and performance experiments, this work addresses the idea of movements and narratives. artistic works in São João del Rei and other bell cities. The sociability inherent in the language of the bells, which crosses the place, the soundscape (SCHAFER, 2001) of the ringtones, as well as the imagination of the listeners, bring up reflections on the various artistic practices and knowledge involved in this tradition. We defend that the culture and bells’s tradition and Minas are being negotiated daily by the people who invent and move them through the mediations that operate in their relationships. In this sense, the controversy around the Sinógeno expresses this relational aspect in the production of assemblages and meanings from works of art, whether through the attempt, by some, to accuse it of sacrilege, or through the attempt of others, to affirm and claim the expression of belongings and contributions of African sounds and rhythms in Brazilian territory as bases for nation building. Let us therefore analyze the way in which the Sineira culture manifests itself in São João, Neste trabalho, refletimos acerca das questões sobre tradição e modernidade nas percepções artísticas e culturais da tradição sineira na cidade de São João del Rei no estado de Minas Gerais. Trazemos como material de análise o EP visual intitulado “Sinógeno”, que, ao ser publicado em março de 2021, trouxe uma série de repercussões, dentre elas algumas controvérsias, em torno do possível caráter artístico ou sacrilégio contido na obra. Aqui, discutiremos através deste objeto, temáticas acerca da percepção mineira a respeito do cosmopolitismo e da experimentação artística, relacionando os conceitos de recado de José Miguel Wisnik, como também o entre-lugar das concepções de local e global. Passando brevemente pelo contexto histórico de Minas desde o processo de exploração das terras, pela influência das Igrejas e da religião católica no processo de construção da região, até experimen-tações sonoras, visuais e performáticas contemporâneas, aborda-se neste trabalho a ideia de movimentos e narrativas artísticas em São João del Rei e outras cidades sineiras. A sociabilidade inerente à linguagem dos sinos, que atravessa o local, a paisagem sonora (SCHAFER, 2001) dos toques, assim como a imaginação dos ouvintes, trazem à tona reflexões sobre os diversos fazeres e saberes artísticos envolvidos nessa tradição. Argumenta-se que a cultura e a tradição sineira e mineira estão sendo negociadas cotidianamente pelas pessoas que as inventam e movimentam por meio das mediações que operadas em suas relações. Nesse sentido, a polêmica em torno do Sinógeno expressa esse aspecto relacional na produção de agenciamentos e significados a partir das obras de arte, seja por meio da tentativa, de alguns, de acusá-lo de sacrilégio, seja pela de outros, de afirmar e reivindicar a expressão dos pertencimentos e contribuições de sons e ritmos africanos em território brasileiro como bases da construção da nação. Analisemos, portanto, a forma como a cultura sineira se manifesta em São João Del Rei

Background: No systemic treatment has been established for meningioma progressing after local therapies. Methods: This randomized, multicenter, open-label, phase II study included adult patients with recurrent WHO grade 2 or 3 meningioma. Patients were 2:1 randomly assigned to intravenous trabectedin (1.5 mg/m2 every 3 weeks) or local standard of care (LOC). The primary endpoint was progression-free survival (PFS). Secondary endpoints comprised overall survival (OS), objective radiological response, safety, quality of life (QoL) assessment using the QLQ-C30 and QLQ-BN20 questionnaires, and we performed tissue-based exploratory molecular analyses. Results: Ninety patients were randomized (n = 29 in LOC, n = 61 in trabectedin arm). With 71 events, median PFS was 4.17 months in the LOC and 2.43 months in the trabectedin arm (hazard ratio [HR] = 1.42; 80% CI, 1.00-2.03; P =. 294) with a PFS-6 rate of 29.1% (95% CI, 11.9%-48.8%) and 21.1% (95% CI, 11.3%-32.9%), respectively. Median OS was 10.61 months in the LOC and 11.37 months in the trabectedin arm (HR = 0.98; 95% CI, 0.54-1.76; P =. 94). Grade ≥3 adverse events occurred in 44.4% of patients in the LOC and 59% of patients in the trabectedin arm. Enrolled patients had impeded global QoL and overall functionality and high fatigue before initiation of systemic therapy. DNA methylation class, performance status, presence of a relevant co-morbidity, steroid use, and right hemisphere involvement at baseline were independently associated with OS. Conclusions: Trabectedin did not improve PFS and OS and was associated with higher toxicity than LOC treatment in patients with non-benign meningioma. Tumor DNA methylation class is an independent prognostic factor for OS.

This work investigates, for the first time, the hydrogen permeation of BaCeZrYO-CeGdO (BCZY-GDC) asymmetric membranes for 100 h, using wet 15% CO in Ar as sweep gas. In the same frame, ex-situ aging tests were performed for 100 h exposure at 750 °C in different atmospheres (H, CO, H + CO), to evaluate the phase, microstructure, and mechanical long-term stability of this system. The thermal aging in H-atmosphere leads to lower flexural strength caused by a microstructure embrittlement of the BCZY-GDC asymmetric membrane, due to chemical expansion/contraction of the GDC cell after the aging cycle. Indeed, micro-cracking of GDC grains, that decreases the composite hardness, is observed in symmetric (pressed pellet) membranes. The aging in CO causes a slightly increase in flexural strength values due to the formation of sub-micrometric Zr-doped ceria-BaCO phases at the expense of the perovskite. Higher hardness values related to the emerging of BaCO islands on the symmetric membrane surface were also recorded. In H + CO atmosphere (real testing condition), the membrane shows a slight decrease in flexural strength and hardness while no evident morphological or structural changes (except the BaCO formation in traces) were observed. This study highlights that promising and stable hydrogen permeation flux values can be recorded using the asymmetric configuration for 100 h, using wet 15% CO in Ar as sweep gas. Neither structural nor morphological modification of the membrane were detected after the testing.

Anthelmintic resistance (AR) is a growing concern for effective parasite control in farmed ruminants globally. Combatting AR will require intensified and integrated research efforts in the development of innovative diagnostic tests to detect helminth infections and AR, sustainable anthelmintic treatment strategies and the development of complementary control approaches such as vaccination and plant-based control. It will also require a better understanding of socio-economic drivers of anthelmintic treatment decisions, in order to support a behavioural shift and develop targeted communication strategies that promote the uptake of evidence-based sustainable solutions. Here, we review the state-of-the-art in these different fields of research activity related to AR in helminths of livestock ruminants in Europe and beyond. We conclude that in the advent of new challenges and solutions emerging from continuing spread of AR and intensified research efforts, respectively, there is a strong need for transnational multi-actor initiatives. These should involve all key stakeholders to develop indicators of infection and sustainable control, set targets and promote good practices to achieve them.

Spontaneous pneumomediastinum is characterized by the accumulation of air in the mediastinum with no identified cause. It is a rare and self-limiting condition. We report the case of a 32-year-old female patient with controlled bronchial asthma, who presented with spontaneous pneumomediastinum, with no precipitating event. The evolution is generally benign and the treatment is conservative. Symptomatic medication may be instituted.

Introduction High quality research involving Indigenous people with cognitive impairment and dementia is critical for informing evidence-based policy and practice. We examined the volume, scope and ethical considerations of research related to dementia with Indigenous populations globally from January 2000–December 2021. Methods Studies were included if they were published in English from 2000 to 2021 and provided original data that focused on cognitive impairment or dementia in any Indigenous population. Results The search yielded 13,009 papers of which, 76 met inclusion criteria. The overall number of papers increased over time. Studies were mostly conducted in Australia with Aboriginal and Torres Strait Islander people (n = 30; 39%). Twenty-six papers directly involved Indigenous participants with cognitive impairment or dementia. Of these studies, ethics approval was commonly required from two or more committees (n = 23, 88.5%). Ethical and legal governance frameworks were rarely discussed. Discussion There is a clear need for further robust studies examining cognitive impairment and dementia with Indigenous populations. Future research should consider the ethical aspects of involving Indigenous participants with cognitive impairment in research.

[Purpose] Heart failure is a highly prevalent chronic health problem associated with poor quality-of-life and negative outcomes. Self-care is a cornerstone in patients suffering from heart failure. Nurses are commonly engaged in enhancing patients’ self-care behaviors, but the specific condition of deficit on self-care is not clearly identified by nurses. No nursing diagnoses focused on self-care of heart failure patients is currently available. This study aimed to develop a new nursing diagnosis that focuses on self-care in heart failure patients., [Data sources] A concept and content analysis were used. Some steps of the concept analysis were performed through an integrative literature review conducted searching in PUBMED and CINAHL databases to identify attributes, antecedents, and consequences of the diagnosis. Forty-five articles were selected from the 1450 studies found. Then, the content analysis was performed by an international panel of 29 experts. Two Delphi rounds were used to achieve consensus and an item content validity index was calculated for each diagnostic element., [Data synthesis] Integrative review proposed four diagnostic labels, two definitions, 15 defining characteristics, and 44 related factors. After the two Delphi rounds a consensus was reached for each diagnostic indicator with a content validity index ranging from 82.8% to 100%. The nursing diagnosis—labeled heart failure self-care deficit—was validated with a definition, eight defining characteristics, 15 related factors, and five at-risk populations., [Conclusions] This diagnosis allows nurses to document patients’ self-care in daily clinical practice through a standard nursing terminology, by naming this health problem, describing its etiology, and clinical manifestations., [Implications for nursing practice] This new diagnosis is expected to assist nursing clinicians, educators, and students in clinical reasoning with the aim to improve diagnostic accuracy in identifying patients with a heart failure self-care deficit, to select the most appropriate interventions and pursue better outcomes.

Purpose: In a post hoc analysis of the CATNON trial (NCT00626990), we explored whether adding temozolomide to radiotherapy improves outcome in patients with IDH1/2 wildtype (wt) anaplastic astrocytomas with molecular features of glioblastoma [redesignated as glioblastoma, isocitrate dehydrogenase- wildtype (IDH-wt) in the 2021 World Health Organization (WHO) classification of central nervous system tumors]. Patients and Methods: From the randomized phase III CATNON study examining the addition of adjuvant and concurrent temozolomide to radiotherapy in anaplastic astrocytomas, we selected a subgroup of IDH1/2wt and H3F3Awt tumors with presence of TERT promoter mutations and/or EGFR amplifications and/or combined gain of chromosome 7 and loss of chromosome 10. Molecular abnormalities including MGMT promoter methylation status were determined by next-generation sequencing, DNA methylation profiling, and SNaPshot analysis. Results: Of the 751 patients entered in the CATNON study, 670 had fully molecularly characterized tumors. A total of 159 of these tumors met the WHO 2021 molecular criteria for glioblastoma, IDH-wt. Of these patients, 47 received radiotherapy only and 112 received a combination of radiotherapy and temozolomide. There was no added effect of temozolomide on either overall survival [HR, 1.19; 95% confidence interval (CI), 0.82-1.71] or progression-free survival (HR, 0.87; 95% CI, 0.61-1.24). MGMT promoter methylation was prognostic for overall survival, but was not predictive for outcome to temozolomide treatment either with respect to overall survival or progression-free survival. Conclusions: In this cohort of patients with glioblastoma, IDH-wt temozolomide treatment did not add benefit beyond that observed from radiotherapy, regardless of MGMT promoter status. These findings require a new well-powered prospective clinical study to explore the efficacy of temozolomide treatment in this patient population.

PURPOSE: In a post-hoc analysis of the CATNON trial (NCT00626990), we explored whether adding temozolomide to radiotherapy improves outcome in patients with IDH1/2wt anaplastic astrocytomas with molecular features of glioblastoma (redesignated as glioblastoma, IDH-wildtype in the 2021 WHO classification of CNS tumors). EXPERIMENTAL DESIGN: From the randomized phase 3 CATNON study examining the addition of adjuvant and concurrent temozolomide to radiotherapy in anaplastic astrocytomas, we selected a subgroup of IDH1/2wt and H3F3Awt tumors with presence of TERT promoter mutations and/or EGFR amplifications and/or combined gain of chromosome 7 and loss of chromosome 10. Molecular abnormalities including MGMT promoter methylation status were determined by next-generation sequencing, DNA methylation profiling, and SNaPshot analysis. RESULTS: Of the 751 patients entered in the CATNON study, 670 had fully molecularly characterized tumors. 159 of these tumors met the WHO 2021 molecular criteria for glioblastoma, IDH-wildtype. Of these patients, 47 received radiotherapy only and 112 received a combination of radiotherapy and temozolomide. There was no added effect of temozolomide on either overall survival (HR 1.19, 95%CI 0.82-1.71) or progression-free survival (HR 0.87, 95%CI 0.61-1.24). MGMT promoter methylation was prognostic for overall survival, but was not predictive for outcome to temozolomide treatment either with respect to overall survival or progression-free survival. CONCLUSIONS: In this cohort of patients with glioblastoma, IDH-wildtype temozolomide treatment did not add benefit beyond that observed from radiotherapy, regardless of MGMT promoter status. These findings require a new well-powered prospective clinical study to explore the efficacy of temozolomide treatment in this patient population.

Découvrez le testament littéraire des bourreaux Sanson, les exécuteurs de Louis XVI, de Robespierre et d'autres personnalités de l'histoire de France. Originaire de Normandie, la famille Sanson a la particularité de compter parmi ses membres sept générations d’exécuteurs au service de la France, de 1688 à 1847.Testament littéraire des bourreaux Sanson, ce texte dépeint la mise à mort du point de vue des exécuteurs. Les exécutions qui s’y succèdent, de Charlotte Corday à Louis XVI, en passant par Cartouche, Damiens, Danton, Robespierre ou encore Lacenaire, sont ici perçues dans un contexte intime et empreint de compassion. Publié en 1862 par Henri-Clément Sanson, dernier représentant de la lignée, cet ouvrage, alors sulfureux, fut un temps célèbre avant de sombrer dans l’oubli.Henri-Clément Sanson, le dernier bourreau de France, nous offre un témoignage poignant sur la peine de mort, un supplice qu'il considérait comme étant un dernier vestige des sacrifices humains de la barbarie.EXTRAITJe reconnus de suite ce large pli et ce large sceau dont l’aspect m’avait toujours fait frissonner d’épouvante et de douleur. Je pris en tremblant le message, et, m’attendant à y trouver un de ces ordres funèbres auxquels ma terrible consigne me faisait un devoir d’obéir, je montai péniblement les marches du perron de mon hôtel.Arrivé dans mon cabinet, je rompis avec désespoir ce pli fatal qui devait renfermer quelque mission de mort à remplir. J’ouvris la lettre : C’ÉTAIT MA RÉVOCATION !Un sentiment étrange et indéfinissable s’empara de moi. Je relevai les yeux sur les portraits de mes ancêtres. Je parcourus toutes ces figures sombres, méditatives, sur lesquelles se lisait cette même pensée qui avait jusque-là flétri mon existence. Je regardai mon grand-père, en costume de chasse, mélancoliquement appuyé sur le canon de son fusil, et flattant de la main son chien, le seul ami peut-être qu’il lui eût été donné d’avoir.Je regardai mon père, grave, tenant son chapeau à la main et couve

Background: Survival in patients with IDH1/2-mutant (mt) anaplastic astrocytomas is highly variable. We have used the prospective phase 3 CATNON trial to identify molecular factors related to outcome in IDH1/2mt anaplastic astrocytoma patients. Methods: The CATNON trial randomized 751 adult patients with newly diagnosed 1p/19q non-codeleted anaplastic glioma to 59.4 Gy radiotherapy +/- concurrent and/or adjuvant temozolomide. The presence of necrosis and/or microvascular proliferation was scored at central pathology review. Infinium MethylationEPIC BeadChip arrays were used for genome-wide DNA methylation analysis and the determination of copy number variations (CNV). Two DNA methylation-based tumor classifiers were used for risk stratification. Next-generation sequencing (NGS) was performed using 1 of the 2 glioma-tailored NGS panels. The primary endpoint was overall survival measured from the date of randomization. Results: Full analysis (genome-wide DNA methylation and NGS) was successfully performed on 654 tumors. Of these, 432 tumors were IDH1/2mt anaplastic astrocytomas. Both epigenetic classifiers identified poor prognosis patients that partially overlapped. A predictive prognostic Cox proportional hazard model identified that independent prognostic factors for IDH1/2mt anaplastic astrocytoma patients included; age, mini-mental state examination score, treatment with concurrent and/or adjuvant temozolomide, the epigenetic classifiers, PDGFRA amplification, CDKN2A/B homozygous deletion, PI3K mutations, and total CNV load. Independent recursive partitioning analysis highlights the importance of these factors for patient prognostication. Conclusion: Both clinical and molecular factors identify IDH1/2mt anaplastic astrocytoma patients with worse outcome. These results will further refine the current WHO criteria for glioma classification.

Item does not contain fulltext, BACKGROUND: The CATNON trial investigated the addition of concurrent, adjuvant, and both current and adjuvant temozolomide to radiotherapy in adults with newly diagnosed 1p/19q non-co-deleted anaplastic gliomas. The benefit of concurrent temozolomide chemotherapy and relevance of mutations in the IDH1 and IDH2 genes remain unclear. METHODS: This randomised, open-label, phase 3 study done in 137 institutions across Australia, Europe, and North America included patients aged 18 years or older with newly diagnosed 1p/19q non-co-deleted anaplastic gliomas and a WHO performance status of 0-2. Patients were randomly assigned (1:1:1:1) centrally using a minimisation technique to radiotherapy alone (59·4 Gy in 33 fractions; three-dimensional conformal radiotherapy or intensity-modulated radiotherapy), radiotherapy with concurrent oral temozolomide (75 mg/m(2) per day), radiotherapy with adjuvant oral temozolomide (12 4-week cycles of 150-200 mg/m(2) temozolomide given on days 1-5), or radiotherapy with both concurrent and adjuvant temozolomide. Patients were stratified by institution, WHO performance status score, age, 1p loss of heterozygosity, the presence of oligodendroglial elements on microscopy, and MGMT promoter methylation status. The primary endpoint was overall survival adjusted by stratification factors at randomisation in the intention-to-treat population. A second interim analysis requested by the independent data monitoring committee was planned when two-thirds of total required events were observed to test superiority or futility of concurrent temozolomide. This study is registered with ClinicalTrials.gov, NCT00626990. FINDINGS: Between Dec 4, 2007, and Sept 11, 2015, 751 patients were randomly assigned (189 to radiotherapy alone, 188 to radiotherapy with concurrent temozolomide, 186 to radiotherapy and adjuvant temozolomide, and 188 to radiotherapy with concurrent and adjuvant temozolomide). Median follow-up was 55·7 months (IQR 41·0-77·3). The second interi

Contains fulltext : 235663.pdf (Publisher’s version ) (Open Access), Somatic mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 occur at high frequency in several tumour types. Even though these mutations are confined to distinct hotspots, we show that gliomas are the only tumour type with an exceptionally high percentage of IDH1(R132H) mutations. Patients harbouring IDH1(R132H) mutated tumours have lower levels of genome-wide DNA-methylation, and an associated increased gene expression, compared to tumours with other IDH1/2 mutations ("non-R132H IDH1/2 mutations"). This reduced methylation is seen in multiple tumour types and thus appears independent of the site of origin. For 1p/19q non-codeleted glioma (astrocytoma) patients, we show that this difference is clinically relevant: in samples of the randomised phase III CATNON trial, patients harbouring tumours with IDH mutations other than IDH1(R132H) have a better outcome (hazard ratio 0.41, 95% CI [0.24, 0.71], p = 0.0013). Such non-R132H IDH1/2-mutated tumours also had a significantly lower proportion of tumours assigned to prognostically poor DNA-methylation classes (p < 0.001). IDH mutation-type was independent in a multivariable model containing known clinical and molecular prognostic factors. To confirm these observations, we validated the prognostic effect of IDH mutation type on a large independent dataset. The observation that non-R132H IDH1/2-mutated astrocytomas have a more favourable prognosis than their IDH1(R132H) mutated counterpart indicates that not all IDH-mutations are identical. This difference is clinically relevant and should be taken into account for patient prognostication.

Biomimetic exploration of stimuli-responsive and crack-resistant hydrogels is of great academic and practical significance, although the rational design of tough hydrogels is limited by insufficient mechanism study due to the lack of imaging techniques to “see” hydrogels at mesoscale level. A series of composite hydrogels with compartmentalized thermal response is designed by incorporating aggregation- and polarity-sensitive fluorescent probes in a poly(N-isopropylacrylamide) (PNIPAM) network grafted with poly(N,N-dimethylacrylamide) side-chains. The fluorescence technique is explored as a powerful tool to directly visualize their hydrophilicity-hydrophobicity transformation and the composition-dependent microphase separation. Based on the morphological observation and mechanical measurements, the concept of morphomechanics with a comprehensive mechanism clarification is proposed. In this regard, the thermoresponsive toughening is attributed to the formation of multiple noncovalent interactions and the conformational changes of PNIPAM chains. The enhanced fracture energy by crack multifurcation is related to the tearing-like disruption of weak interfaces between the separated phases. © 2021 Wiley-VCH GmbH