The Egyptian Cardiothoracic Surgeon (ECTS - E-Journal)
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A novel IL-17 signaling pathway controlling keratinocyte proliferation and tumorigenesis via the TRAF4-ERK5 axis.
No full textAlthough IL-17 is emerging as an important cytokine in cancer promotion and progression, the underlining molecular mechanism remains unclear. Previous studies suggest that IL-17 (IL-17A) sustains a chronic inflammatory microenvironment that favors tumor formation. Here we report a novel IL-17-mediated cascade via the IL-17R-Act1-TRAF4-MEKK3-ERK5 positive circuit that directly stimulates keratinocyte proliferation and tumor formation. Although this axis dictates the expression of target genes Steap4 (a metalloreductase for cell metabolism and proliferation) and p63 (a transcription factor for epidermal stem cell proliferation), Steap4 is required for the IL-17-induced sustained expansion of p63(+) basal cells in the epidermis. P63 (a positive transcription factor for the Traf4 promoter) induces TRAF4 expression in keratinocytes. Thus, IL-17-induced Steap4-p63 expression forms a positive feedback loop through p63-mediated TRAF4 expression, driving IL-17-dependent sustained activation of the TRAF4-ERK5 axis for keratinocyte proliferation and tumor formation
How important is mode of administration in treatments for rheumatic diseases and related conditions?
No full textMany new drugs do not offer clinical benefits over existing treatments but provide potentially more convenient modes of administration. These include how frequently a treatment is given, how it is delivered, who gives the treatment, and whether there are any associated local adverse reactions. We reviewed studies in rheumatology that ask patients and society the value they assign to these aspects of treatment in comparison to the benefits and side effects and costs. We find that mode of administration is generally valued by both patients and society, but the extent depends on the context of the disease and the study participants. Respondents with a more severe disease seem to assign less value to mode and frequency of administration, and prioritize improvement in pain and function. However, patients with chronic, but less severe, disease seem to place greater value on mode of administration. Furthermore, respondents with experience of the treatments perceived to be more inconvenient assigned lower value to more convenient treatments. Unfortunately, we found few examples of studies that reported values in a format that could easily be incorporated into resource allocation decisions by payers
A statistical analysis of EV charging behavior in the UK
No full textTo truly quantify the impact of electric vehicles (EVs) on the electricity network and their potential interactions in the context of Smart Grids, it is crucial to understand their charging behavior. However, as EVs are yet to be widely adopted, these data are scarce. This work presents results of a thorough statis-tical analysis of the charging behavior of 221 real residential EV users (Nissan LEAF, i.e., 24kWh, 3.6 kW) spread across the UK and monitored over one year (68,000+ samples). Probability distribution functions (PDFs) of different charging features (e.g., start charging time) are produced for both weekdays and week-ends. Crucially, these unique PDFs can be used to create sto-chastic, realistic and detailed EV profiles to carry out impact and/or Smart Grid-related studies. Finally, the effects of the EV demand on future UK distribution networks are discussed
Engendering the 'Crisis of Democracy': Institutions, Representation and Participation'
No full textMany democracies are widely perceived to be suffering a serious crisis of representation, participation and legitimacy. As part of this ‘crisis’, the male domination of democracy - both in terms of its institutions and who participates - has been identified as problematic, even emblematic, of a more generalized democratic crisis. And increasing the participation of women is advocated as one solution. Using examples drawn from both long-standing and newer democracies (parliamentary and presidential) particularly from Europe and Latin America, this article explores the gender dynamics of the ‘crisis of democracy’. Notably the ‘crisis’ has two gendered aspects. Paradoxically although democracy still privileges predominantly white, elite, heterosexual, men, more women now participate in democratic institutions, leading to claims that the ‘male monopoly’ has ended (Dahlerup and Leyenaar 2013). Second the ‘crisis of democracy’ may provide opportunities to further enhance women’s participation, as the demands of those favouring greater gender equality and those looking for solutions to the ‘crisis’ appear to coincide
A new titanosaurian braincase from the Cretaceous "Lo Hueco" locality in Spain sheds light on neuroanatomical evolution within Titanosauria
No full textGlobal, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.
No full textBACKGROUND: Up-to-date evidence about levels and trends in disease and injury incidence, prevalence, and years lived with disability (YLDs) is an essential input into global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013), we estimated these quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013. METHODS: Estimates were calculated for disease and injury incidence, prevalence, and YLDs using GBD 2010 methods with some important refinements. Results for incidence of acute disorders and prevalence of chronic disorders are new additions to the analysis. Key improvements include expansion to the cause and sequelae list, updated systematic reviews, use of detailed injury codes, improvements to the Bayesian meta-regression method (DisMod-MR), and use of severity splits for various causes. An index of data representativeness, showing data availability, was calculated for each cause and impairment during three periods globally and at the country level for 2013. In total, 35 620 distinct sources of data were used and documented to calculated estimates for 301 diseases and injuries and 2337 sequelae. The comorbidity simulation provides estimates for the number of sequelae, concurrently, by individuals by country, year, age, and sex. Disability weights were updated with the addition of new population-based survey data from four countries. FINDINGS: Disease and injury were highly prevalent; only a small fraction of individuals had no sequelae. Comorbidity rose substantially with age and in absolute terms from 1990 to 2013. Incidence of acute sequelae were predominantly infectious diseases and short-term injuries, with over 2 billion cases of upper respiratory infections and diarrhoeal disease episodes in 2013, with the notable exception of tooth pain due to permanent caries with more than 200 million incident cases in 2013. Conversely, leading chronic sequelae were largely attributable to non-communicable diseases, with prevalence estimates for asymptomatic permanent caries and tension-type headache of 2·4 billion and 1·6 billion, respectively. The distribution of the number of sequelae in populations varied widely across regions, with an expected relation between age and disease prevalence. YLDs for both sexes increased from 537·6 million in 1990 to 764·8 million in 2013 due to population growth and ageing, whereas the age-standardised rate decreased little from 114·87 per 1000 people to 110·31 per 1000 people between 1990 and 2013. Leading causes of YLDs included low back pain and major depressive disorder among the top ten causes of YLDs in every country. YLD rates per person, by major cause groups, indicated the main drivers of increases were due to musculoskeletal, mental, and substance use disorders, neurological disorders, and chronic respiratory diseases; however HIV/AIDS was a notable driver of increasing YLDs in sub-Saharan Africa. Also, the proportion of disability-adjusted life years due to YLDs increased globally from 21·1% in 1990 to 31·2% in 2013. INTERPRETATION: Ageing of the world's population is leading to a substantial increase in the numbers of individuals with sequelae of diseases and injuries. Rates of YLDs are declining much more slowly than mortality rates. The non-fatal dimensions of disease and injury will require more and more attention from health systems. The transition to non-fatal outcomes as the dominant source of burden of disease is occurring rapidly outside of sub-Saharan Africa. Our results can guide future health initiatives through examination of epidemiological trends and a better understanding of variation across countries. FUNDING: Bill & Melinda Gates Foundation
Preventing and treating foot complications associated with diabetes mellitus.
No full textDiabetes mellitus is associated with a series of macrovascular and microvascular changes that can manifest as a wide range of complications. Foot ulcerations affect ∼2-4% of patients with diabetes mellitus. Risk factors for foot lesions include peripheral and autonomic neuropathy, vascular disease and previous foot ulceration, as well as other microvascular complications, such as retinopathy and end-stage renal disease. Ulceration is the result of a combination of components that together lead to tissue breakdown. The most frequently occurring causal pathways to the development of foot ulcers include peripheral neuropathy and vascular disease, foot deformity or trauma. Peripheral vascular disease is often not diagnosed in patients with diabetes mellitus until tissue loss is evident, usually in the form of a nonhealing ulcer. Identification of patients with diabetes mellitus who are at high risk of ulceration is important and can be achieved via annual foot screening with subsequent multidisciplinary foot-care interventions. Understanding the factors that place patients with diabetes mellitus at high risk of ulceration, together with an appreciation of the links between different aspects of the disease process, is essential to the prevention and management of diabetic foot complications
Free-flow-porous-media coupling for evaporation-driven transport and precipitation of salt
No full textIllness characteristics and symptoms in an Irish early intervention for psychosis service
No full textAbstract Objectives Study of illness characteristics and symptoms in a young population with psychosis can assist for understanding of their needs, and can inform service planning strategies. The aims of the current study were to describe illness characteristics and symptoms of a first episode psychosis (FEP) sample aged 25 years and under, and compare with a sample aged over 25 years. Methods Interviews were conducted for 437 individuals aged 16–65 years presenting with suspected psychosis between 2005 and 2012 in a defined catchment area (population of 390 000) using the Structured Clinical Interview for DSM IV to determine the presence of a psychosis diagnosis. Individuals with confirmed psychosis were assessed using standardised instruments to determine illness characteristics at first presentation. Results Among the 25 years, and under FEP sample, 23.9% had their first onset of symptoms (prodromal or psychotic) before 18 years of age. After controlling for confounders, the sample aged 25 years and under had a significantly shorter log transformed duration of untreated psychosis (p=0.002), more negative symptoms (p=0.045) and greater frequency of comorbid cannabis abuse diagnosis (p=0.027). Conclusions Symptom onset in a youth FEP sample frequently occurs before age 18 years. Certain illness characteristics differed across the age categories, such as greater negative symptoms and cannabis abuse in the youth sample. Overall, the findings support the provision of adequate strategies for management of negative symptom deficits and substance abuse across all ages in FEP