Parameterized Inapproximability of Target Set Selection and Generalizations

In this paper, we consider the Target Set Selection problem: given a graph and a threshold value $thr(v)$ for any vertex $v$ of the graph, find a minimum size vertex-subset to "activate" s.t. all the vertices of the graph are activated at the end of the propagation process. A vertex $v$ is activated during the propagation process if at least $thr(v)$ of its neighbors are activated. This problem models several practical issues like faults in distributed networks or word-to-mouth recommendations in social networks. We show that for any functions $f$ and $\rho$ this problem cannot be approximated within a factor of $\rho(k)$ in $f(k) \cdot n^{O(1)}$ time, unless FPT = W[P], even for restricted thresholds (namely constant and majority thresholds). We also study the cardinality constraint maximization and minimization versions of the problem for which we prove similar hardness results

World report on violence and health

This report examines the types of violence that are present worldwide, in the everyday lives of people, and that constitute the bulk of the health burden imposed by violence. Accordingly, the information has been arranged in nine chapters, covering the following topics: 1. Violence – a global public health problem 2. Youth violence 3. Child abuse and neglect by parents and other caregivers 4. Violence by intimate partners 5. Abuse of the elderly 6. Sexual violence 7. Self-directed violence 8. Collective violence 9. The way forward: recommendations for action; Because it is impossible to cover all types of violence fully and adequately in a single document, each chapter has a specific focus. For example, the chapter on youth violence examines interpersonal violence among adolescents and young adults in the community. The chapter on child abuse discusses physical, sexual and psychological abuse, as well as neglect by parents and other caregivers; other forms of maltreatment of children, such as child prostitution and the use of children as soldiers, are covered in other parts of the report. The chapter on abuse of the elderly focuses on abuse by caregivers in domestic and institutional settings, while that on collective violence discusses violent conflict. The chapters on intimate partner violence and sexual violence focus primarily on violence against women, though some discussion of violence directed at men and boys is included in the chapter on sexual violence. The chapter on self-directed violence focuses primarily on suicidal behaviour. The chapter is included in the report because suicidal behaviour is one of the external causes of injury and is often the product of many of the same underlying social, psychological and environmental factors as other types of violence. The chapters follow a similar structure. Each begins with a brief discussion of definitions for the specific type of violence covered in the chapter, followed by a summary of current knowledge about the extent of the problem in different regions of the world. Where possible, country-level data are presented, as well as findings from a range of research studies. The chapters then describe the causes and consequences of violence, provide summaries of the interventions and policy responses that have been tried, and make recommendations for future research and action. Tables, figures and boxes are included to highlight specific epidemiological patterns and findings, illustrate examples of prevention activities, and draw attention to specific issues. The report concludes with two additional sections: a statistical annex and a list of Internet resources. The statistical annex contains global, regional and country data derived from the WHO mortality and morbidity database and from Version 1 of the WHO Global Burden of Disease project for 2000. A description of data sources and methods is provided in the annex to explain how these data were collected and analysed. The list of Internet resources includes web site addresses for organizations involved in violence research, prevention and advocacy. The list includes metasites (each site offers access to hundreds of organizations involved in violence research, prevention and advocacy), web sites that focus on specific types of violence, web sites that address broader contextual issues related to violence, and web sites that offer surveillance tools for improving the understanding of violence

Bile Nephropathy in Flucloxacillin-Induced Cholestatic Liver Dysfunction

Kidney injury in the context of cholestatic liver dysfunction is not uncommon; this has been historically referred to as cholemic nephrosis implying a direct deleterious renal effect of cholemia. However, scepticism about the exact role that bile and its constituents play in this injury has led to the disappearance of the term. We describe a case of severe AKI due to bile nephropathy with bile casts in flucloxacillin-induced liver dysfunction. We also discuss the recent literature reviving the concept of bile nephropathy

Malignancy in Membranous Nephropathy: Evaluation of Incidence

Background. Membranous nephropathy (MN) can be associated with malignancy. However, the relative risk for malignancy remains unclear. It has been reported that higher numbers of inflammatory cells seen in the glomeruli at biopsy correlate with the occurrence of malignancy in patients with MN and might be used to direct screening. Methods. We examined the occurrence of malignancy in 201 MN patients in Auckland, New Zealand. We also examined the pathology of renal biopsies from 17 MN patients with malignancies and compared the number of inflammatory cells per glomerulus with matched control patients with MN but no malignancy. Results. 40 malignancies were identified in 37 patients, 28 of which occurred after the MN diagnosis. The standardized incidence ratio (SIR) was 2.1 (95% CI, 1.3–2.85) which was similar between patients ≥ 60 years and those <60 years. The median number of inflammatory cells per glomerulus did not differ between MN patients with and without malignancy at 1.86 (IQR, 1.17–2.7) and 2.07 (IQR, 1.17–3.65), respectively (p value 0.56). Conclusions. The relative risk of malignancy in MN patients was similar across different age groups. The number of inflammatory cells per glomerulus did not differentiate between MN patients with and without malignancies

Intersectionality: Social Marginalisation and Self-Reported Health Status in Young People.

BACKGROUND:The aim of this study was to measure young people's health status and explore associations between health status and belonging to one or more socio-culturally marginalised group. METHODS:part of the Access 3 project, this cross-sectional survey of young people aged 12-24 years living in New South Wales, Australia, oversampled young people from one or more of the following groups: Aboriginal and or Torres Strait Islander; living in rural and remote areas; homeless; refugee; and/or, sexuality and/or gender diverse. This paper reports on findings pertaining to health status, presence of chronic health conditions, psychological distress, and wellbeing measures. RESULTS:1416 participants completed the survey; 897 (63.3%) belonged to at least one marginalised group; 574 (40.5%) to one, 281 (19.8%) to two and 42 (3.0%) to three or four groups. Belonging to more marginalised groups was significantly associated with having more chronic health conditions (p = 0.001), a greater likelihood of high psychological distress (p = 0.001) and of illness or injury related absence from school or work (p < 0.05). CONCLUSIONS:increasing marginalisation is associated with decreasing health status. Using an intersectional lens can to be a useful way to understand disadvantage for young people belonging to multiple marginalised groups

Highly purified extracellular vesicles from human cardiomyocytes demonstrate preferential uptake by human endothelial cells

Extracellular vesicles (EVs) represent a promising cell-free alternative for treatment of cardiovascular diseases. Nevertheless, the lack of standardised and reproducible isolation methods capable of recovering pure, intact EVs presents a significant obstacle. Additionally, there is significant interest in investigating the interactions of EVs with different cardiac cell types. Here we established a robust technique for the production and isolation of EVs harvested from an enriched (>97% purity) population of human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) with size exclusion chromatography. Utilizing an advanced fluorescence labelling strategy, we then investigated the interplay of the CM-EVs with the three major cellular components of the myocardium (fibroblasts, cardiomyocytes and endothelial cells) and identified that cardiac endothelial cells show preferential uptake of these EVs. Overall, our findings provide a great opportunity to overcome the translational hurdles associated with the isolation of intact, non-aggregated human iPSC-CM EVs at high purity. Furthermore, understanding in detail the interaction of the secreted EVs with their surrounding cells in the heart may open promising new avenues in the field of EV engineering for targeted delivery in cardiac regeneration

Highly purified extracellular vesicles from human cardiomyocytes demonstrate preferential uptake by human endothelial cells

Extracellular vesicles (EVs) represent a promising cell-free alternative for treatment of cardiovascular diseases. Nevertheless, the lack of standardised and reproducible isolation methods capable of recovering pure, intact EVs presents a significant obstacle. Additionally, there is significant interest in investigating the interactions of EVs with different cardiac cell types. Here we established a robust technique for the production and isolation of EVs harvested from an enriched (>97% purity) population of human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) with size exclusion chromatography. Utilizing an advanced fluorescence labelling strategy, we then investigated the interplay of the CM-EVs with the three major cellular components of the myocardium (fibroblasts, cardiomyocytes and endothelial cells) and identified that cardiac endothelial cells show preferential uptake of these EVs. Overall, our findings provide a great opportunity to overcome the translational hurdles associated with the isolation of intact, non-aggregated human iPSC-CM EVs at high purity. Furthermore, understanding in detail the interaction of the secreted EVs with their surrounding cells in the heart may open promising new avenues in the field of EV engineering for targeted delivery in cardiac regeneration