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“I love it…I love that story”:The perspectives of children with Down syndrome and their mothers on reading experiences at home
Get PDFPurpose: Home literacy practices play an important role in shaping the reading development of children with Down syndrome. However, the majority of research to date has been quantitative in nature, and very little has included children’s own perspectives and experiences. This study aimed to provide new research insights into the home literacy practices and reading experiences of children with Down syndrome, from the perspective of the children and their parents.Methods: There were 19 participants from ten families: ten mothers participated in semi-structured interviews, exploring their views of their child’s reading experiences and how they supported their child’s reading development; nine children with Down syndrome (aged 5-13 years) participated in a ‘book tour’ and conversation about reading. Reflexive thematic analysis was used to develop themes from the mothers’ data, and children’s data were categorised. Results: Mothers and children both described a diversity of reading experiences within the home. Mothers also highlighted: reading as a source of comfort and connection; the need for flexible and child-led reading routines and strategies which respond to the individual child and their developmental stage; and the complexities of navigating book choice and format. Children also shared clear and positive views about particular books and about being read to by family members.Conclusion: While some home-based reading practices and experiences share parallels with neurotypical children, many related more specifically to Down syndrome, and highlight the importance of syndrome-specific explorations of reading which focus on understanding both socio-affective and cognitive aspects of reading development and experience. <br/
ENPP1 Inhibition: A Promising Oral Therapy for Later-Onset Hypophosphatasia
Get PDFHypophosphatasia (HPP) is a rare, inherited metabolic bone disorder characterized by deficient activity of tissue-nonspecific alkaline phosphatase (TNAP), an enzyme encoded by the ALPL gene. Loss-of-function mutations in ALPL lead to reduced TNAP activity, resulting in the accumulation of extracellular inorganic pyrophosphate (PPi), a potent inhibitor of hydroxyapatite crystal formation and skeletal mineralization. Clinically, this presents as a broad spectrum of dento-osseous complications, including premature tooth loss, rickets or osteomalacia, and calcific arthropathies
Targeting DNA damage repair pathways beyond PARP inhibition
Get PDFExploiting DNA damage repair (DDR) vulnerabilities has become a major focus in cancer drug development following the clinical success of poly (ADP-ribose) polymerase (PARP) inhibitors. Beyond PARP, inhibitors of multiple other DDR proteins have progressed from pre-clinical development to early phase clinical trials. DDR inhibitors have shown promise both as a selective therapeutic strategy in genomically-selected cancers harbouring specific genetic vulnerabilities, and as a potential treatment approach to overcome innate and acquired PARP inhibitor resistance. This review summarises the most recent DDR inhibitor clinical evidence, focusing on DDR signalling targets; ATR (ataxia telangiectasia and Rad3-related protein serine/threonine kinase), ATM (ataxia telangiectasia mutated), DNA-PK (DNA-dependent protein kinase), CHK1 (checkpoint kinase 1), WEE1, and recently emerging DNA repair targets; RAD51, PolƟ (DNA polymerase theta), WRN (Werner syndrome helicase), USP1 (ubiquitin specific peptidase 1) and PARG (poly(ADP-ribose) glycohydrolase). We highlight both clinical successes and failures of DDR inhibitors as monotherapy or in combination with chemotherapy, PARP and other DDR inhibitors. The challenges that must be addressed to see the true potential of these agents are discussed. Finally, we consider future directions and the necessity for integration of biomarkers and genomic profiling in DDR inhibitor clinical trials to optimally identify patients with tumours genetically vulnerable, and so crucially, take advantage of the selective therapeutic opportunity provided by DDR inhibition
“People are afraid of getting injections”:Feasibility of community-placed atropine auto-injectors in treating organophosphate poisoning in Sri Lanka
Get PDFIntroductionOrganophosphorus insecticide poisoning remains a major problem in rural low- and middle-income communities. Atropine auto-injectors are used for organophosphorus nerve agent poisoning, but not organophosphorus insecticide poisoning. We explore the social and practical feasibility of introducing atropine auto-injectors in Sri Lankan villages to initiate first-line treatment for acute organophosphorus insecticide poisoning. We investigate how auto-injectors might be best integrated into the social and spatial context of rural communities with high levels of organophosphorus insecticide use and poisoning.MethodsWith an ethnographic approach, we combined semi-structured interviews with community members (n = 18) and healthcare workers (n = 9), focus group discussions (n = 5), participatory mapping (n = 3), oral history interviews (n = 7), and ethnographic observations in three rural villages. A collaborative thematic data analysis was performed alongside continuous discussions within the global, interdisciplinary research team.ResultsAcute organophosphorus insecticide poisoning was not perceived as a major public health concern that would demand an urgent intervention in communities. Following COVID-19 vaccination interventions, findings showed a lack of trust related to new medical injection technologies. Consequently, finding people to handle auto-injectors who had the capacity and willingness to take responsibility and were trusted by the community is a major challenge.DiscussionEthnographic research methods are important and relevant in planning and implementing community health interventions. They contribute to making health interventions more effective and sustainable by analyzing context-dependent and often intractable complex health problems.ConclusionsWhile our findings do not support introducing auto-injectors in the selected communities, it suggests placing them in the ambulances used to transport patients who have ingested pesticides. To further explore the need and feasibility of auto-injectors, similar situational, ethnographic analysis should be conducted in other parts of Sri Lanka and low- and middle-income countries with high numbers of acute organophosphorus insecticide poisoning and limited infrastructure facilities
The role of the tropical carbon balance in determining the large atmospheric CO2 growth rate in 2023
Get PDFThe global annual mean atmospheric CO2 growth rate in 2023 was one of the highest since records began in 1958, comparable to values recorded during previous major El Niño events. We do not fully understand this anomalous growth rate, although a recent study highlighted the role of boreal North American forest fires. We use a Bayesian inverse method to interpret global-scale atmospheric CO2 data from NASA's Orbiting Carbon Observatory (OCO-2). The resulting a posteriori CO2 flux estimates reveal that from 2022 to 2023, the biggest changes in CO2 fluxes of net biosphere exchange (NBE) – for which positive values denote a flux to the atmosphere – were over the land tropics. We find that the largest NBE increase is over eastern Brazil, with small increases over southern Africa and Southeast Asia. We also find significant increases over southeastern Australia, Alaska, and western Russia. A large NBE increase over boreal North America, due to fires, is driven by our a priori inventory, informed by independent data. The largest NBE reductions are over western Europe, the USA, and central Canada. Our NBE estimates are consistent with gross primary production estimates inferred from satellite observations of solar-induced fluorescence and from satellite observations of vegetation greenness. We find that warmer temperatures in 2023 explain most of the NBE change over eastern Brazil, with hydrological changes more important elsewhere across the tropics. Our results suggest that the ongoing environmental degradation of the Amazon is now playing a substantial role in increasing the global atmospheric CO2 growth rate
Late-surviving New Mexican dinosaurs illuminate high end-Cretaceous diversity and provinciality
No full textIt has long been debated whether non-avian dinosaurs went extinct abruptly or gradually at the end-Cretaceous (66 million years ago), because their fossil record at this time is mostly limited to northern North America. We constrain a dinosaur-rich unit to the south, the Naashoibito Member in New Mexico, to the very latest Cretaceous (~66.4 to 66.0 million years), preserving some of the last-known non-avian dinosaurs. Ecological modeling shows that North American terrestrial vertebrates maintained high diversity and endemism in the latest Cretaceous and early Paleogene, with bioprovinces shaped by temperature and geography. This counters the notion of a low-diversity cross-continental fauna and suggests that dinosaurs were diverse and partitioned into regionally distinct assemblages during the final few hundred thousand years before the end-Cretaceous asteroid impact
Risk management framework for competitive alpine skiing—co-developed with stakeholders
No full textPrevious research has shown that stakeholders in the competitive alpine skiing communities consider risk management to be crucial in sports injury prevention. However, to date, there is a lack of a publicly available systematic and structured risk management approach for the competitive alpine skiing context. This work describes the codevelopment process of a risk management framework with stakeholders in the field of competitive alpine skiing. A panel of international experts invited through personal requests and with expertise in health protection and performance enhancement in competitive alpine skiing convened three times through online group meetings to co-develop a risk management framework through different activities. The underlying discussions focused on the fundamental questions of ‘why’, ‘what’, ‘who’, ‘how’ and ‘for whom’ and included the debate on specific examples from sports practice. The outcome after three meetings was a risk management framework. This framework includes a competitive alpine skiing-specific prevention wheel that integrates different stakeholder views relevant to different levels, their risk priorities, the main five domains and intervention areas identified from the literature, the graded and progressive timescale to intervene and the potential targets for risk management interventions. Moreover, the framework includes a decision-making tree, which operationalises the prevention wheel into a step-by-step sequence for risk management, including risk identification, risk assessment and risk mitigation. It should help stakeholders recognise their responsibilities and the potential actions they can take. Practical examples are provided to demonstrate how to apply the framework and to illustrate the complexity and dynamic interaction of the various factors in the competitive alpine skiing setting. The risk management framework developed lays a strong foundation for creating a safer environment for alpine skiers. It likewise contributes to providing overall awareness of the complexity and inter-relations of risks and prevention measures in the sport. By doing so, this framework has the potential to initiate further processes and on-field translation to sustainably and long-term improve athlete health and safety in competitive alpine skiing.</p
Longitudinal and bidirectional relationships between sleep, emotional wellbeing and weight status in childhood and adolescence:Growing Up in Scotland cohort analysis
No full textBackground: Poor sleep and emotional wellbeing, which often decline during puberty, are associated with declines in metabolic health and are key determinants of childhood obesity. The aim of the study was to explore bidirectional associations between sleep, emotional wellbeing, and obesity from ages 8–14 using the Growing Up in Scotland cohort.Methods: Secondary analyses were conducted on data from sweeps 7–10 (ages 8–14). Sleep duration was reported by carers at age 8 and self-reported at 14. Obesity was assessed using BMI percentiles (BMIp), derived from objective height and weight at ages 8, 10, 12, and 14. Emotional wellbeing was assessed using the Strengths and Difficulties Questionnaire Emotional Symptoms Subscale via caregiver-report at ages 10 and 12, and self-report at age 14. Pearson correlations and adjusted regressions examined associations between sleep, BMIp, and emotional wellbeing from ages 8–14.Results: Analyses included 4,157 participants (50.2% male). Shorter sleep at 8 years was associated with higher BMIp at 12 years (β=–.172, CI(95%)=-.335, -.116, p<.001) and poorer emotional wellbeing at 10 (β=–.120, CI(95%)=-.179, -.034, p<.001) and 12 years (β=–.101, CI(95%)=-.164, -.026, p< .001). Poorer emotional wellbeing at 10 (β=–.116, CI(95%)=-.232, -.093, p<.001) and 12 years (β=–.194, CI(95%)=-.328, -.174, p<.001) predicted shorter sleep at 14 years. Higher BMIp at 8 years was associated with shorter sleep at 14 years (β=–.182, CI(95%)=-.359, -.111, p<.001). Poorer emotional wellbeing at 10 years was associated with higher BMIp at 14 years (β=.142, CI(95%)=.074, .629, p=.13).Discussion: Bidirectional associations emerged between short sleep and emotional wellbeing and higher BMIp. Poor emotional wellbeing was associated with subsequent obesity; but not bidirectionally. These interactions should inform the design of health interventions for 8–14-year-olds
Separate and cumulative impacts of trauma-informed practices and a housing intervention on the safety, housing stability and mental health of domestic violence survivors over two years
No full textPurpose: Trauma-informed practices (TIP) with intimate partner violence (IPV) survivors contributes to short-term improvements in their mental health. However, less is known about TIP’s long-term value for mental health and whether TIP’s value extends to other life domains, such as housing. Focused on the outcomes of housing stability, mental health, and violence experiences, this longitudinal study examined the contributions of TIP and Domestic Violence Housing First (DVHF), which is a novel intervention that engages survivors in housing-inclusive advocacy and flexible financial assistance.Methods: The community-based, quasi-experimental study included homeless and unstably housed survivors (n = 351) who sought services for IPV. Survivors were interviewed across five timepoints over two years, assessing the services they received, including experiences with TIP. Participants also reported their housing stability, violence experiences, and mental health symptoms, including depression, anxiety, and post-traumatic stress. Based on the services they received, survivors were categorized as either receiving only services-as-usual (e.g., counseling, safety planning, shelter) or DVHF (i.e., housing-inclusive advocacy, flexible financial assistance, plus usual services). Data were analyzed using conditional random intercept models.Results: Survivors who received DVHF and/or reported their services to be trauma-informed also reported greater housing stability, less violence, and better mental health over time. Those who both received DVHF and reported their services to be highly trauma-informed reported the most improvements in housing, mental health, and violence.Conclusions: Study results suggest that DVHF and TIP can work in tandem over time to produce positive outcomes for survivors seeking housing stability, improved mental health, and safety
Decadal scale fire dynamics in savannas and forests of the Nilgiri Biosphere Reserve, India
No full textBackground: The Nilgiri Biosphere Reserve (NBR) in the Western Ghats, India, contains a mosaic of savannas and forests. This landscape experiences wildfires regularly, but we lack an understanding of factors driving fire regimes in the region. Aims: To examine the effects of climate, vegetation and human activity on wildfires in the NBR. Methods: Using remotely sensed datasets, we examine how mean annual rainfall (MAR), topographic complexity and human activity influence fires in savannas and forests of the NBR across a wet (2001–2010) and dry decade (2011–2020). Key results: Across both decades, savannas burned more frequently and over larger areas than forests. Burnt area and fire frequency in both habitats were higher in the wet decade. Human modification was the major driver of fire occurrence in the wet decade, but MAR took on greater importance in the dry decade. Conclusions: Savannas and forests in the NBR have differing fire regimes. During dry periods, these systems are fuel limited and MAR best describes the occurrence of fires. During wet periods when fuel is not limiting, proxies for anthropogenic ignitions best explain fire occurrence. Implications: Climate, vegetation and humans collectively determine fire regimes in the NBR. Fire management must integrate across all these factors at the landscape scale to be effective.</p
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