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Mixed-sex survivor services, gender-neutral policies and lack of sex-disaggregated data on violence against women inconsistent with Istanbul Convention
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International Perspectives on Primary-Secondary School Transitions
No full textThis chapter focusses on primary-secondary school transitions of young people (YP), including those with additional support needs, and their transitions experiences. The chapter draws on, and presents, international perspectives and research, and sets the context for the importance of getting transitions policy and practice right for all YP. After discussing the policy and legislative context, I focus on the academic and social changes experienced by young people, and their impact on YP’s transitions experiences. I discuss the factors that have been found to facilitate and/or hinder successful primary-secondary school transitions, including the role of different educational systems internationally. These are followed by a case study of a longitudinal study which provides further insights into some trends that have not been discussed before and/or are different from previous research. Relationships of YP with significant others (e.g., peers, teachers) are very important and have been discussed in detail. Finally, I have provided recommendations for primary and secondary schools’ transitions practice and policy
The Prostitution (Offences and Support) (Scotland) Bill:Opinion on consistency with international human rights law*
Get PDFThis opinion considers the consistency of the Prostitution (Offences and Support) (Scotland) Bill (the Bill) with international human rights law applicable in Scotland and the UK. Currently in Scotland, soliciting for prostitution is a criminal offence. The Bill seeks to repeal this offence and quash historic soliciting convictions. In parallel it would establish a new criminal offence of paying for sexual acts and a right to support for individuals exiting prostitution. Based on treaties to which the UK is a party, and associated interpretive materials, this opinion considers that:1. In criminalising the sale of sexual acts by individuals engaged in prostitution, Scottish law breaches applicable human rights treaty obligations, due to the discriminatory character of this approach of regulating prostitution with regard to women and girls. To achieve offence of soliciting under section 46 Civic Government (Scotland) Act 1982, should accordingly be repealed, and historical soliciting convictions pardoned / disregarded, as the Bill proposes.2. De-regulating both the sale and purchase of sexual acts in Scotland would be inconsistent with applicable treaty obligations, given legal duties on the UK and Scottish Governments to take all reasonable measure to eliminate discrimination and prevent violence against women, to reduce demand for trafficking and for commercial sex, and to address other human rights abuses experienced by individuals in prostitution.3. Adopting demand-side or ‘Nordic’ model legislation on prostitution in Scotland, which criminalises the purchase of sexual acts, as proposed by the Bill, does not present a risk of non-compliance with the UK’s human rights obligations. In particular, any interference with the right to privacy by legislation criminalizing the purchase of sexual acts while decriminalizing their sale and supporting exit is likely to be assessed as lawful by human rights courts or other mechanisms supervising instruments to which the UK is a party.4. Overall, the measures proposed by the Bill would both resolve a matter giving rise to a persistent breach of international human rights laws in Scotland and contribute significantly to fulfilling international human rights duties owed to women in Scotland and borne by the UK and Scottish governments
Identification of important outcomes for surgical and brace treatment of adolescent idiopathic scoliosis
Get PDFAimsHigh-quality clinical trials in adolescent idiopathic scoliosis (AIS) are needed to guide decision-making but progress is hindered by suboptimal selection of outcome measures. Identifying meaningful outcomes for consistent measurement across clinical trials and routine practice is critical. However, there is currently no understanding of which treatment outcome domains are considered important by adolescents, their parents, and healthcare professionals (HCPs). This study is the first to address this gap internationally.MethodsThis study represents the first stage of core outcome set (COS) development, following gold-standard guidance. A cross-sectional qualitative interview study with 40 participants (adolescents with AIS, their parents, and HCPs) was conducted. Semi-structured interviews were analyzed to identify and categorize important AIS treatment outcomes. Analytical rigour was ensured through coder agreement and stakeholder consultation.ResultsA total of 91 important outcome domains were identified; 53 outcome domains applying to both bracing and surgery, with 15 additional outcome domains for bracing only, and 23 additional outcome domains for surgery only. Of the 91 outcome domains, more than three-quarters (71/91, 78%) related to life impact, with smaller proportions relating to physiological/clinical outcomes (13/91, 14%), resource use (4/91, 4%), and adverse events (1/91, 1%).ConclusionThe current study highlights treatment outcomes considered important by adolescents with AIS, their parents, and HCPs. These findings will inform outcome selection in clinical trials and routine practice, as well as facilitating an ongoing programme of research to develop a COS for evaluating treatment of AIS
<i>“Doctors are targeted and kidnapped”</i>:crimes and insecurity contribute to health problems and constrain the delivery of health services in urban settings in Nigeria
Get PDFBackground: Nigeria ranked third in Africa and eleventh globally in the 2024 Crime Index. Despite the country’s endemic crime level, its impact on the health sector has been under-researched. The paper presents qualitative data from a study conducted in selected urban Local Government Areas in Abia and Anambra states in the southeastern part of Nigeria.Method: Fifty-two key stakeholders in security and health sectors, comprising health policymakers (n = 8), public safety officers (n = 10), local community leaders (n = 10), frontline health managers (n = 14), and informal healthcare providers (n = 10), Eight focus group discussions were held with male and female service users.Results: Findings indicate that acquisitive offenses such as theft, robbery, kidnapping, sexual offenses, and gang-related or cultism-driven violence were frequently reported. Residents, healthcare professionals, local authorities, and policymakers noted that these crimes posed significant threats to health workers and negatively impacted the functionality of health facilities. Incidents of staff absenteeism, equipment theft, and night shift interruptions were reported. Furthermore, elevated crime rates have led service users to consider safe times when accessing healthcare facilities carefully
A transcriptomic and proteomic map of primary human cell types
No full textMolecular profiling of human primary cell types is essential for understanding human biology. We present a transcriptome and proteome map of 28 primary human cell types. Three major clusters of epithelial, endothelial, and mesenchymal cell types were observed in both the transcriptome and proteome levels along with the discovery of cell type enriched molecules including GRAP and C1orf116. The epithelial cell specific protein C1orf116 was further validated using immunohistochemistry across various human tissues. An exhaustive protein database search considering 39 post-translational modifications (PTMs) revealed novel insights into the PTM landscape including identification of understudied PTMs such as serine O-acetylation and histidine methylation. This also enabled comprehensive characterization of proteins with diverse PTMs. Interestingly, an unexpectedly higher frequency of dioxidation on tryptophan compared to methionine led to the identification of oxidative mitochondria complex subunit proteins. Further, a search strategy accounting for alternative translational start sites, splice junctions and translational readthrough refined genome annotation using proteomic evidence. For example, peptides from translational readthrough including extended sequence of LDHB and MDH1 were detected representing the first peptide-level evidence of these protein readthrough isoforms. Our comprehensive transcriptome and proteome data revealed cell type-specific molecular cues and heterogeneity, offering new insights into disease mechanisms often overlooked by tissue proteomics.</p
Aberrant NSUN1 Activity Connects m5C RNA Modification to TDP-43 Neurotoxicity in ALS/FTD
No full textIn amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), the nuclear RNA-binding protein TDP-43 mislocalises to the cytoplasm and forms insoluble aggregates, but the mechanisms controlling this remain unclear. We define a native TDP-43 interactome in human SH-SY5Y cells and identify proteins linked to the 5-methylcytosine (m5C) RNA modification as highly enriched. Using a Drosophila model of TDP-43 pathology, we show that aberrant activity of m5C-RNA methyltransferases Nsun1 drives TDP-43-induced m5C-RNA hypermethylation, whereas Nsun1 down-regulation alleviates TDP-43-induced degeneration, lifespan deficits, and cytoplasmic accumulation. In human cells, TDP-43 selectively interacts with NSUN1 isoform 3 independently of RNA. Furthermore, NSUN1 is nucleolar and TDP-43 is largely nucleoplasmic, yet they interact in both compartments, suggesting functional roles beyond their predominant localisations. In ALS/FTD postmortem frontal cortex, NSUN1 isoform 3 persists, whereas the shorter isoform is reduced, suggesting that a pool of NSUN1 capable of contributing to pathological TDP-43 interactions remains in disease. These findings suggest that TDP-43 neurotoxicity is coupled to NSUN1 activation and m5C-RNA methylation, revealing a potential therapeutic axis in ALS/FTD.</p
Recurrent hypoglycaemia promotes cardiomyopathy and cardiac vulnerability in a rodent model of type 1 diabetes
Get PDFAims/hypothesis: CVD remains the leading cause of mortality in individuals with type 1 diabetes over the age of 40 years. Although intensive insulin therapy lowers chronic hyperglycaemia and improves cardiovascular outcomes, it also increases the frequency of hypoglycaemic episodes, an emerging but poorly understood contributor to CVD risk. The mechanisms by which recurrent hypoglycaemia exacerbates cardiovascular pathology in type 1 diabetes are unknown. Methods: Using a C57BL/J streptozocin-induced male mouse model of type 1 diabetes, combined with detailed physiological and molecular assessments, we investigated the impact of recurrent hypoglycaemia (<3.0 mmol/l) on cardiovascular structure and function using laser Doppler imaging with iontophoresis and ultrasound imaging. Results: Type 1 diabetes induces significant microvascular endothelial dysfunction, which is worsened by recurrent hypoglycaemia. Chronic exposure to hypoglycaemia (60 episodes over 20 weeks) resulted in compensatory shifts in cardiac haemodynamics, which in type 1 diabetic mice but not non-diabetic mice resulted in early dilated cardiomyopathy. In both type 1 diabetic and non-diabetic mice, recurrent hypoglycaemia resulted in impaired systolic function during a subsequent hypoglycaemic challenge, indicating increased cardiac vulnerability despite any compensatory changes. Transcriptomic profiling of left ventricular tissue revealed that recurrent hypoglycaemia induces distinct gene expression changes involving ion homeostasis, repolarisation dynamics and microvascular signalling—molecular alterations characteristic of early diabetic cardiomyopathy. Conclusions/interpretation: These findings provide the first in vivo evidence that recurrent hypoglycaemia synergises with hyperglycaemia to accelerate microvascular dysfunction and adverse cardiac remodelling in type 1 diabetes. This work identifies a novel mechanistic link between hypoglycaemia and diabetic heart disease, underscoring the need for therapeutic strategies that mitigate glycaemic variability without increasing the hypoglycaemic burden. Data availability: Transcriptomic data are available as supplementary data.</p
Estimating incidence rates of primary infection and reinfection with hepatitis C virus among people who inject drugs in Scotland:a model-based analysis of repeated cross-sectional survey data
Get PDFBACKGROUND: Reducing the incidence of hepatitis C virus (HCV) infection is a World Health Organization (WHO) elimination goal, but approaches to estimate this from population-level survey data are lacking. We modelled HCV incidence among people who inject drugs (PWID) surveyed over time, to provide evidence on whether Scotland has reached the WHO elimination target of ≤2 per 100 person-years in this population.METHODS: A statistical model was fitted using HCV infection data from five sweeps (2013-14, 2015-16, 2017-18, 2019-20, and 2022-23) of a national bio-behavioural survey, involving 11,651 PWID recruited at sites providing injecting equipment. Per-sweep incidence rates of primary chronic HCV infection, reinfection, and combined primary and reinfection ('total infection') were inferred within a Bayesian framework. Incidence rates relate to the number of new infections per 100 person-years for the population at risk of (primary, reinfection and total) infection.FINDINGS: In 2022-23, the model-estimated total, re-infection and primary infection incidence rates were 3.4 per 100 person-years (95% credible interval (CrI):2.6-4.3), 1.9 (1.3-2.6), and 4.1 (3.0-5.4), respectively. For total new infections, the model-estimated incidence rate decreased by 51% from 7.0 per 100 person-years in 2015-16 to 3.4 in 2022-23 (relating to an absolute decrease of 3.6 per 100 person-years; 95% CrI: 2.0-5.3). Between 2015-16 and 2022-23, model-estimated re-infection and primary infection incidence rates decreased by 78% and 40%, respectively.INTERPRETATION: Over a period when direct-acting antiviral therapy was scaled-up in Scotland, major reductions in the incidence of primary infection, reinfection, and total HCV infection were evident, indicating that the WHO target is within reach, for a relatively high-risk population of PWID.FUNDING: Public Health Scotland (for NESI); NIHR HPRU in Behavioural Science and Evaluation; NIHR Programme Grants for Applied Research programme (reference number RP-PG-0616-20008).</p
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