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Abstract Background Human T cell lymphotropic virus type 1 (HTLV-1) infection remains a largely neglected public health problem, particularly in resource-poor areas with high burden of communicable and non-communicable diseases, such as some remote populations in Central Australia where an estimated 37% of adults are infected with HTLV-1. Most of our understanding of HTLV-1 infection comes from studies of the globally spread subtype-A (HTLV-1a), with few molecular studies reported with the Austral-Melanesian subtype-C (HTLV-1c) predominant in the Indo-Pacific and Oceania regions. Results Using a primer walking strategy and direct sequencing, we constructed HTLV-1c genomic consensus sequences from 22 First Nations participants living with HTLV-1c in Central Australia. Phylogenetic and pairwise analysis of this subtype-C proviral gDNA showed higher levels of genomic divergence in comparison to previously published HTLV-1a genomes. While the overall genomic homology between subtypes was 92.5%, the lowest nucleotide and amino acid sequence identity occurred near the 3′ end of the proviral genome coding regulatory genes, especially overlapping hbz (85.37%, 77.46%, respectively) and orf-I product p12 (82.00%, 70.30%, respectively). Strikingly, the HTLV-1c genomic consensus sequences uniformly showed a defective translation start codon for the immune regulatory proteins p12/p8 encoded by the HTLV-1A orf-I. Deletions in the proviral genome were detected in many subjects, particularly in the structural gag, pol and env genes. Similarly, using a droplet digital PCR assay measuring the copies of gag and tax per reference host genome, we quantitatively confirmed that provirus retains the tax gene region at higher levels than gag. Conclusions Our genomic analysis of HTLV-1c in Central Australia in conjunction with earlier Melanesian HTLV-1c sequences, elucidate substantial differences with respect to the globally spread HTLV-1a. Future studies should address the impact these genomic differences have on infection and the regionally distinctive frequency of associated pulmonary disease. Understanding the host and virus subtype factors which contribute to the differential morbidity observed, is crucial for the development of much needed therapeutics and vaccine strategies against this highly endemic infection in remote First Nations communities in Central Australia.

Climate change is one of the most critical challenges facing Australia and the global community today. Data from the Australian Bureau of Meteorology (BoM) indicates that Australia has been experiencing rising temperatures, particularly since the late 20th century. The frequency, duration, and intensity of heatwaves are projected to continue increasing . Since national records began in 1910, Australia has warmed by an average of 1.47°C (±0.24°C), with the highest official temperature recorded at 50.7 degrees Celsius in Onslow, Western Australia (WA), on January 13, 2022. Furthermore, a recent unprecedented high temperature of +41.6°C was recorded during winter on August 26, 2024, in Yampi Sound, WA. Among all natural disasters in Australia, heatwave (HW) represents a leading silent killer and pose a significant public health threat. However, innovative methods for assessing vulnerability for HW-related health services remain limited.

Prior to, and since the passage of the Corporate Manslaughter and Corporate Homicide Act 2008 (CMCHA) in the United Kingdom (UK), prosecutions for serious workplace health and safety offences have been mostly underwhelming. Australia has now followed the UK in legislating for industrial manslaughter within the various workplace health and safety laws across many of its states and territories. The aim of this paper is to explore the industrial manslaughter legislation across Australia and discusses the lessons which may be learned from the UK. An analysis of the CMCHA was undertaken to determine whether it has lived up to expectations and if there may be lessons to be learned for Australia as it embarks on its post-harmonization journey. A review of publications found that the CMCHA had fallen short of expectations within its first decade of existence in the UK in both the number of successful prosecutions and in the severity of the punishments handed down. The purported deficiencies in the prosecutorial success of the United Kingdom's CMCHA provides an opportunity for Australia to heed and avoid these deficiencies.

This paper presents the results of a systematic literature review of academic publications about digital literacy games. We have analyzed a total of 30 papers and book chapters published in English, Spanish, Portuguese and Dutch between 2005 and 2021 and stored in Scopus. The results of this literature review report on: (1) the topics of the games discussed in the publications; (2) the digital literacy competencies supported by the games studied in the publications; (3) the effects of these games; and (4) ten game design considerations for digital literacy games collected from the results of the publications. This paper also provides detailed access to the original sources by reporting on which paper addressed what.

Abstract The interplay between 3D chromatin architecture and gene silencing is incompletely understood. Here, we report a novel point mutation in the non-canonical SMC protein SMCHD1 that enhances its silencing capacity at endogenous developmental targets. Moreover, it also results in enhanced silencing at the facioscapulohumeral muscular dystrophy associated macrosatellite-array, D4Z4, resulting in enhanced repression of DUX4 encoded by this repeat. Heightened SMCHD1 silencing perturbs developmental Hox gene activation, causing a homeotic transformation in mice. Paradoxically, the mutant SMCHD1 appears to enhance insulation against other epigenetic regulators, including PRC2 and CTCF, while depleting long range chromatin interactions akin to what is observed in the absence of SMCHD1. These data suggest that SMCHD1’s role in long range chromatin interactions is not directly linked to gene silencing or insulating the chromatin, refining the model for how the different levels of SMCHD1-mediated chromatin regulation interact to bring about gene silencing in normal development and disease.

Objectives: This study aimed to simulate blood flow stagnation using computational fluid dynamics and to clarify the optimal design of segmental artery reattachment for thoracoabdominal aortic repair. Methods: Blood flow stagnation, defined by low-velocity volume or area of the segmental artery, was simulated by a 3-dimensional model emulating the systolic phase. Four groups were evaluated: direct anastomosis, graft interposition, loop-graft, and end graft. Based on contemporary clinical studies, direct anastomosis can provide a superior patency rate than other reattachment methods. We hypothesized that stagnation of the blood flow is negatively associated with patency rates. Over time, velocity changes were evaluated. Results: The direct anastomosis method led to the least blood flow stagnation, whilst the end-graft reattachment method resulted in worse blood flow stagnation. The loop-graft method was comparatively during late systole, which was also influenced by configuration of the side branch. Graft interposition using 20 mm showed a low-velocity area in the distal part of the side graft. When comparing length and diameter of an interposed graft, shorter and smaller branches resulted in less blood flow stagnation. Conclusions: In our simulation, direct anastomosis of the segmental artery resulted in the most efficient design in terms of blood flow stagnation. A shorter (

The role of immunity in the pathogenesis of various pulmonary diseases, particularly interstitial lung diseases (ILDs), is being increasingly appreciated as mechanistic discoveries advance our knowledge in the field. Immune-mediated lung diseases demonstrate clinical and immunological heterogeneity and can be etiologically categorized into connective tissue disease (CTD)-associated, exposure-related, idiopathic, and other miscellaneous lung diseases including sarcoidosis, and post-lung transplant ILD. The immunopathogenesis of many of these diseases remains poorly defined and possibly involves either immune dysregulation, abnormal healing, chronic inflammation, or a combination of these, often in a background of genetic susceptibility. The heterogeneity and complex immunopathogenesis of ILDs complicate management, and thus a collaborative treatment team should work toward an individualized approach to address the unique needs of each patient. Current management of immune-mediated lung diseases is challenging; the choice of therapy is etiology-driven and includes corticosteroids, immunomodulatory drugs such as methotrexate, cyclophosphamide and mycophenolate mofetil, rituximab, or other measures such as discontinuation or avoidance of the inciting agent in exposure-related ILDs. Antifibrotic therapy is approved for some of the ILDs (e.g., idiopathic pulmonary fibrosis) and is being investigated for many others and has shown promising preliminary results. A dire need for advances in the management of immune-mediated lung disease persists in the absence of standardized management guidelines.

Female embryonic stem cells (ESCs) are the ideal model to study X chromosome inactivation (XCI) establishment; however, these cells are challenging to keep in culture. Here the authors create fluorescent ‘Xmas’ reporter mice as a renewable source of ESCs and show nucleosome remodelers Smarcc1 and Smarca4 create a nucleosome-free promoter region prior to the establishment of silencing.

BackgroundDuring respiratory infection pandemics, masks and respirators are highly sought after, especially for frontline healthcare workers and patients carrying respiratory viruses. The objective of this study was to systematically review fit test pass rates and identify factors influencing the fitting characteristics.MethodsPotentially relevant studies were identified using PubMed, Scopus, Web of Science, and Science Direct during the COVID-19 pandemic from February 5, 2020, to March 21, 2023. The search strategy using the following keywords was conducted: Quantitative Fit Test, Condensation Nuclei Counter, Controlled Negative Pressure, PortaCount, Sibata, Accufit, Fit, Seal, Mask, Respirator, Respiratory Protective Device, Respiratory Protective Equipment, Protective Device, Personal Protective Equipment, COVID-19, Coronavirus, and SARS-CoV-2. The quality of the included studies was also assessed using the Newcastle-Ottawa scale.ResultsA total of 137 articles met the eligibility criteria. Fifty articles had a quality score of less than 7 (good quality). A total of 21 studies had a fit test pass rate of less than 50%. 26 studies on disposable respirators and 11 studies on reusable respirators had an FF of less than 50 and less than 200, respectively. The most influential factors include respirator brand/model, style, gender, ethnicity, facial dimensions, facial hair, age, reuse, extensive movement, seal check, comfort and usability assessment, and training.Conclusion37.36% of the disposable respirator studies and 43% of the reusable respirator studies did not report fit test results. 67.86% of the disposable respirator studies had a fit test pass rate greater than 50%, and 35.84% of these studies had an FF greater than 100. Also, 85.71% of the reusable respirator studies had a fit test pass rate greater than 50%, and 52.77% of these studies had an FF greater than 1000. Overall, the fit test pass rate was relatively acceptable. Newly developed or modified respirators must undergo reliable testing to ensure the protection of HCWs. Subject and respirator characteristics should be considered when implementing fit testing protocols. An optimal fit test panel should be developed prior to respirator design, certification, procurement decisions, and selection procedures.

This qualitative study aimed to identify mental health hazards in the offshore oil and gas industry, as well as the role of the personality types of the Five Factor Model (FFM) in coping with these stressors. A focus group with 8 participants and a pilot study with 5 participants were conducted. Results showed that several stressors are currently present for Australian offshore oil and gas employees, in particular COVID-19 and the resulting negative effects on rosters, working hours, job security and time spent away from home. Other stressors revealed by participants were lack of space, working in a high-risk environment, stigma, helicopter travel and pressure to keep up with production. Poor safety behaviours were associated with neuroticism, extraversion and openness, while risk avoidance appear to be associated with agreeableness and conscientiousness. Tolerance to shift work was positively related to extraversion, yet negatively associated to neuroticism. Furthermore, neuroticism showed a negative association with help-seeking and productivity, as well as higher levels of concern relating to COVID-19 and job uncertainty. As personality traits are enduring throughout life, it is vital that employees are managed effectively through workplace interventions so that they are able to cope effectively, particularly during stressful events.

Patients with autoimmune inflammatory rheumatic diseases (AIIRDs) are at increased risk for severe infections. Vaccine responses and safety profiles may differ between AIIRD patients and the general population. While patients with autoimmune inflammatory rheumatic diseases (AIIRDs) often experience diminished humoral responses and reduced vaccine efficacy, factors such as the type of immunosuppressant medications used and the specific vaccine employed contribute to these outcomes. Notably, individuals undergoing B cell depletion therapy tend to have poor vaccine immunogenicity. However, despite these considerations, vaccine responses are generally considered clinically sufficient. Ideally, immunosuppressed AIIRD patients should receive vaccinations at least two weeks before commencing immunosuppressive treatment. However, it is common for many patients to already be on immunosuppressants during the immunization process. Vaccination rarely triggers flares in AIIRDs; if flares occur, they are typically mild. Despite the heightened infection risk, including COVID-19, among AIIRD patients with rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, and other diseases on immunosuppressants, the vaccination rates remain suboptimal. The future directions of vaccination in the era of immunosuppression will likely involve customized vaccines with enhanced adjuvants and alternative delivery methods. By addressing the unique challenges faced by immunosuppressed individuals, we may improve vaccine efficacy, reduce the risk of infections, and ultimately enhance the health outcomes. Additionally, clinical trials to evaluate the safety and efficacy of temporarily discontinuing immunosuppressants during vaccination in various AIIRDs are crucial.

The offshore oil and gas working environment is an inherently dangerous one, with risks posed to physical safety on a daily basis. One neglected field of research is the added psychosocial stressors present in this environment. This research examined the experiences of offshore oil and gas workers through one-on-one online interviews which were recorded and transcribed. Transcripts were analyzed through the qualitative software NVivo, which generated themes and patterns for the responses given to questions that were developed through a focus group. The results of the analysis showed that multiple psychosocial stressors are present in this population, such as fear of speaking up, unsatisfactory company-provided facilities, work–life interference, work status, micromanaging, gender harassment and bullying. In addition, interviews identified that production and time pressures, along with fatigue, can influence accidents and mistakes. Climate factors also cause discomfort. However, these are managed according to best practices by organizations. Due to the timing of the study, COVID-19 was a significant stressor for some, but not all, employees. In conclusion, offshore oil and gas workers face multiple stressors in a dangerous environment that may lead to devastating consequences.

Abstract Endogenous retroviruses (ERVs) are emerging as promising therapeutic targets in cancer. As remnants of ancient retroviral infections, ERV-derived regulatory elements coordinate expression from gene networks, including those underpinning embryogenesis and immune cell function. ERV activation can promote an interferon response, a phenomenon termed viral mimicry. Although ERV expression is associated with cancer, and provisionally with autoimmune and neurodegenerative diseases, ERV-mediated inflammation is being explored as a way to sensitize tumors to immunotherapy. Here we review ERV co-option in development and innate immunity, the aberrant contribution of ERVs to tumorigenesis, and the wider biomedical potential of therapies directed at ERVs.

While social media offer an unprecedented opportunity for orchestrating large-scale communication campaigns, it is often difficult to track audience responses on various digital platforms over time and to ascertain if their engagement is aligned with the original intention. In this article, we share a promising solution—the purposive embedding and tracking of unique content elements as “markers” using text analytics techniques. Four markers were introduced in an Indian melodramatic television serial, Main Kuch Bhi Kar Sakti Hoon ( I, A Woman, Can Achieve Anything ), which was part of a larger transmedia edutainment initiative in India to promote sanitation, family planning, and gender equality. These markers served as anchors for audience engagement with the originally intended messaging embedded in the narratives as well as for program monitoring and evaluation. We applied various web-based tools to systematically track marker-related engagement on Facebook, Twitter, and YouTube across eight months. We also conducted semantic network analysis to better understand how marker-related social media comments evolved over time. Our investigation of using markers for digital engagement and narrative exchange in MKBKSH makes an important and timely methodological contribution to the scholarship and praxis of social and behavior change communication.

Background: The relationship between risk factors and likelihood of occupational injury has been studied. However, what has been published has only provided a limited explanation of why some of the employees working in the same environment as other employees suffered a single-injury event, while other employees experienced multiple-injury events. This article reports on an investigation of whether artisanal and small-scale miners in Migori County of Kenya are susceptible to a single-injury or multiple-injury incidences, and if so, what underpinning parameters explain the differences between the single incident injured and the multiple incident injured group. Mine management commitment to safety in artisanal and small-scale mining (ASM) operations is also considered. Materials and methods: The research objectives were achieved by surveying 162 uninjured and 74 injured miners. A structured, closed-end questionnaire was administered to participants after the stratification of the study population and systematic selection of the representative samples. Results: The results showed that most injured miners suffer a single-injury incident rather than experiencing multiple-injury events, and laceration (28.40%) was the common injury suffered by the miners. The analysis showed that the risk factors for the single incident injured group were not similar to those in the multiple incident injured group. The research also found mine workers have low opinion about mine management/owners commitment to safety. Conclusion: The study concluded that mine management and miners need to be educated and sensitized on the dangers of this operation. Provision of safety gears and positive safety culture must be a top priority for management. Keywords: Incidence, Logistic model, Miners, Occupational injuries, Risk factors

Global warming has contributed to more frequent and severe extreme weather events, which has led to increased research on the health impacts of extreme heat. However, research on heatwaves, air quality, and their spatial impact on health service demand is limited. This study used machine learning (ML) approaches to obtain the optimised model to predict health service demand associated with those risk factors for an all-age model and compared it with young children (0–4 years) model in Perth. Ten years’ data (2006–2015) on emergency department attendances (EDA), socioeconomic status (SES), heatwaves, landscape fires, and gaseous and particulate air pollutants were collected. ML approaches, including decision tree, random forest (RF), and geographical random forest (GRF) models, were used to compare and select the best model for predicting EDA and identify important risk factors. Five-hundred cross validations were performed using the testing data, and a construct validation was performed by comparing actual and predicted EDA data. The results showed that the RF model outperformed other models, and SES, air quality, and heatwaves were among the important risk factors to predict EDA. The GRF model was fitted well to the data (R ^2 = 0.975) and further showed that heatwaves had significant geographic variations and a joint effect with PM _2.5 in the southern suburbs of the study area for young children. The RF and GRF models have satisfactory performance in predicting the impact of heatwaves, air quality, and SES on EDA. Heatwaves and air quality have great spatial heterogeneity. Spatial interactions between heatwaves, SES, and air quality measures were the most important predictive risk factors of EDA for young children in the Perth southern suburbs. Future studies are warranted to confirm the findings from this study on a wider scale.

This intervention study investigated how much impact a specific peer-coaching (Peer2Peer) for refugee adolescents has on different factors of well-being for both sides: refugee adolescents (peers, N = 16) and their local peer coaches (buddies, N = 16). Next to pre- and post-tests, four buddies reflected on the process via weekly media diaries. We found that higher peer-loneliness and lower self-esteem was reported for peers in the beginning but these differences disappeared. These results were confirmed by buddies’ media diaries: language and communication barriers reduced and friendships between buddies and peers grew. Buddies also reported high feelings of responsibilities in their media diaries which led to worries about their peer, but also to pride due to peers’ improvement. Online communication was used on an almost daily basis to stay in contact each other. Snapchat was found to influence emotional and affectionate support. In sum, Peer2Peer as a program showed positive effects for both sides. Future Peer2Peer programs should include trainings on social media as well, as most apps are able to be used independent of own language skills. Thus, social media can help to overcome language barriers and intensifies the feeling of being supported.

In a world of continuous migration, super-diverse cities consist of a multitude of migrants and non-migrants from a variety of cultural backgrounds. Yet one characteristic they all have in common is the place where they currently live. In addition, both groups are active users of social media, especially the young. Social media provide platforms to construct and negotiate one’s identity—particularly the identity related to where one lives: urban identity. This article presents the results of a survey study (N = 324) investigating the relationships between social media engagement and identity construction among migrant and non-migrant adolescents in the super-diverse city of Rotterdam, the Netherlands. It was found that urban identity was significantly higher for migrants than non-migrants. Certain aspects of social media engagement predicted urban identity in combination with social identity. Finally, social media engagement was found to be positively related to group self-esteem.

Background: Transapical transcatheter mitral valve implantation (TMVI) may be a therapeutic option for patients with severe mitral regurgitation (MR) excluded from cardiac surgery due to excessive risk. Exclusion criteria frequently include pulmonary hypertension and right ventricular (RV) dysfunction. The effect of TMVI on RV function has not previously been well-characterized. The aim of this study was to examine the procedural and 3-month impact of TMVI on RV hemodynamics and function. Methods: This was a multi-center, retrospective, observational cohort study of patients with >3+MR undergoing TMVI. Pre- and post-TMVI hemodynamics were assessed with right heart catheterization. RV function was assessed at baseline, pre-discharge and at 3-months by echocardiography. Results: Forty-six patients (age 72±9 years; 34 men) with ≥3+MR underwent TMVI over a 5-year period. Successful device implantation was achieved in all patients with abolition of MR (p < 0.001) and reduction in left-ventricular end-diastolic volume (p = 0.001). RV stroke work index (RVSWI) increased intra-operatively (7 ± 4 g/m/beat/m2 vs 11 ± 5 g/m/beat/m2; p < 0.001). At 3-months there were reductions in severity of tricuspid regurgitation (TR) (p < 0.001) and pulmonary artery systolic pressure (PASP) (49 ± 16 mmHg vs 36 ± 12 mmHg; p < 0.001), and improvements in RV fractional area change (28 ± 7% vs 34 ± 9%, p

Objectives This study aimed to evaluate the association between maternal ethnicity and iron deficiency (ID) in early childhood, and to evaluate whether infant feeding practices linked to ID differ between maternal ethnic groups.Methods This was a cross-sectional study of healthy children 1–3 years of age. Adjusted multivariable logistic regression analyses were used to evaluate the association between maternal ethnicity and ID (serum ferritin 2 cups; meat consumption).Results Of 1851 children included, 12.2% had ID. Compared with the European referent group, we found higher odds of ID among children of South Asian and West Asian/North African maternal ethnicities, and lower odds of ID among children of East Asian maternal ethnicity. Statistically significant covariates associated with higher odds of ID included longer breastfeeding duration and daily cow’s milk intake >2 cups. Current infant formula use was associated with lower odds of ID. Children of South Asian maternal ethnicity had higher odds of bottle use beyond 15 months of age and lower odds of meat consumption.Conclusions We found increased odds of ID among children of South Asian and West Asian/Northern African maternal ethnicities. We found a higher odds of feeding practices linked to ID in children of South Asian maternal ethnicity, but not in children of West Asian/North African maternal ethnicity. Culturally tailored approaches to providing guidance to parents on healthy infant feeding practices may be important to prevent ID in early childhood.Trial registration number NCT01869530.

The Multicultural Personality Questionnaire (MPQ) is one of the most widely used instruments for measuring individuals' intercultural competences. The original version consists of 91 items, divided into five subscales, and has been shown to predict attitudes, behavior, and outcomes in a variety of intercultural contexts. Recently, a 40-item short form of the MPQ was developed (MPQ-SF), which may be particularly useful in settings in which time or survey space are limited, or where respondent drop-out is likely to occur. For example, the MPQ-SF would be a valuable tool for assessing longitudinal development of multicultural personality traits in training or educational settings. A prerequisite for such research is to establish measurement invariance of the MPQ-SF between different respondent groups, as well as across time points. Using a sample of students in an international university program (n = 519), the present study examines how the scales perform among male and female respondents, between students of Western and Non-Western background, and across two time points, five months apart. Based on our findings, we conclude that all five subscales of the MPQ-SF display sufficient measurement invariance to be reliably used in this and similar contexts, in comparative as well as longitudinal study designs.

IntroductionCardiovascular disease is the leading cause of death in end-stage renal disease (ESRD) and is strongly associated with vascular calcification. An important driver of vascular calcification is high phosphate levels, but these become lower when patients initiate nocturnal hemodialysis or receive a kidney transplant. However, it is unknown whether nocturnal hemodialysis or kidney transplantation mitigate vascular calcification. Therefore, we compared progression of coronary artery calcification (CAC) between patients treated with conventional hemodialysis, nocturnal hemodialysis, and kidney transplant recipients.MethodsWe measured CAC annually up to 3 years in 114 patients with ESRD that were transplantation candidates: 32 that continued conventional hemodialysis, 34 that initiated nocturnal hemodialysis (≥4x 8 hours/week), and 48 that received a kidney transplant. We compared CAC progression between groups as the difference in square root transformed volume scores per year (ΔCAC SQRV) using linear mixed models. Reference category was conventional hemodialysis.ResultsThe mean age of the study population was 53 ±13 years, 75 (66%) were male, and median dialysis duration was 28 (IQR 12-56) months. Median CAC score at enrollment was 171 (IQR 10-647), which did not differ significantly between treatment groups (P = 0.83). Compared to conventional hemodialysis, CAC progression was non-significantly different in nocturnal hemodialysis -0.10 (95% CI -0.77 to 0.57) and kidney transplantation -0.33 (95% CI -0.96 to 0.29) in adjusted models.ConclusionsNocturnal hemodialysis and kidney transplantation are not associated with significantly less CAC progression compared to conventional hemodialysis during up to 3 years follow-up. Further studies are needed to confirm these findings, to determine which type of calcification is measured with CAC in end-stage renal disease, and whether that reflects cardiovascular risk.

Influencers belong to the daily media diet of many adolescents. As role models, they have the potential to play a crucial role in the identity construction of their viewers. In the age of social media, such role models may now be found more locally – in the same city – and perhaps with more diverse backgrounds. This may be particularly valuable to adolescents growing up in super-diverse cities, as they are surrounded by a multitude of groups and identities during a life phase in which they have to make sense of who they are and where they belong. Despite the heterogeneity of these identities, there is one thing all have in common: the city they live in. With the city as a common framework, local influencers may be important role models for these adolescents, particularly in negotiating their urban identity. This paper aims toward mapping the ways in which social media can play a role in the negotiation of urban identity among youngsters by investigating how YouTube influencers from a super-diverse city are related to each other online, and how their content relates to the (super-diverse) city of Rotterdam. Findings show that in their videos and on their channel pages, influencers mainly affiliate themselves with the city through having the city as the background and context of the videos, through their involvement with cultural trends (e.g., soccer, hip-hop) that link to the city, and through their affiliation with other local influencers. We argue that influencers may therefore provide their viewers with content that may potentially help their local viewers strengthen their urban identity.

Summary: Neural tube defects (NTDs) are common birth defects in humans and show an unexplained female bias. Female mice lacking the tumor suppressor p53 display NTDs with incomplete penetrance. We found that the combined loss of pro-apoptotic BIM and p53 caused 100% penetrant, female-exclusive NTDs, which allowed us to investigate the female-specific functions of p53. We report that female p53−/− embryonic neural tube samples show fewer cells with inactive X chromosome markers Xist and H3K27me3 and a concomitant increase in biallelic expression of the X-linked genes, Huwe1 and Usp9x. Decreased Xist and increased X-linked gene expression was confirmed by RNA sequencing. Moreover, we found that p53 directly bound response elements in the X chromosome inactivation center (XIC). Together, these findings suggest p53 directly activates XIC genes, without which there is stochastic failure in X chromosome inactivation, and that X chromosome inactivation failure may underlie the female bias in neural tube closure defects. : The molecular mechanisms underlying the female bias of neural tube defects are currently unclear. Delbridge et al. present evidence that p53 is required for normal Xist expression and X chromosome inactivation and show in two models that partial failure of X chromosome inactivation is associated with female-biased neural tube defects. Keywords: female-specific neural tube defects, X-chromosome inactivation, p53, Xist, Ftx, Tsix, biallelic expression, BIM, BCL2L11, SMCHD1

In recent years, vaccination rates in the Netherlands have declined slightly, but steadily. The Dutch National Institute for Public Health and the Environment (RIVM) commissioned a Committee for Vaccine Willingness (VWC) to study the societal context of the decline. One of the societal contexts is the Internet, where audiences discuss vaccination and refer to sources of health-related information of varying quality.Working for the VWC, we have explored the Dutch vaccination debate on Twitter in order to: (1) identify online communities in the vaccination debate, (2) identify vaccine-related narratives; and (3) understand how the online communities interact with each other. We identified seven different communities, including (public) health professionals, writers and journalists, anti-establishment, and international vaccination advocates.The debate is spearheaded by the writers & journalists community, while the health- and anti-establishment communities try to influence it. The health community circulates facts, figures and scientific studies, while negative messages about vaccination – either from a homeopathy or conspiracy perspective – are most prevalent in the anti-establishment. The facts and figures shared by the health community hardly reach other communities, whereas the myths introduced by the anti-establishment do spill over to other communities. Our study provides further evidence that negative perceptions about vaccination might be rooted in a wider sentiment of distrust of traditional institutions.We argue that Dutch health organizations should try to address questions, doubts, and worries among the general audience more actively, and present scientific information in a simpler and more attractive way. Keywords: Vaccine hesitancy, Health communication, Social media, Network analysis

ObjectivesOur aim was to describe the numbers and distribution of patients with different types of thalassemia and to assess the standards of care in all thalassemia treatment centers throughout Sri Lanka and the success of the ongoing prevention programme.MethodsThis cross-sectional island-wide survey was conducted by two trained medical graduates, who visited each thalassemia center to collect data from every patient, using a standardized form. Data was collected through review of patient registers and clinical records.ResultsWe collected data on 1774 patients from 23 centers. 1219 patients (68.7%) had homozygous β-thalassemia, 360 patients (20.3%) had hemoglobin E β-thalassemia, and 50 patients (2%) had sickle β-thalassemia. There were unacceptably high serum ferritin levels in almost all centers. The annual number of births of patients with β-thalassaemia varied between 45-55, with little evidence of reduction over 19 years.ConclusionsCentral coordination of the treatment and ultimately prevention of thalassemia is urgently needed in Sri Lanka. Development of expert centers with designated staff with sufficient resources will improve the quality of care and is preferred to managing patients in multiple small units.

In today’s media landscape, audiences increasingly turn to online communities for media consumption and to exchange information about specific niche interests such as health-related topics. This calls for a segmented approach in which interventions are targeted at online communities, tailored to their specific cultures and health-related perceptions, and leverage the dynamics of conversation and social influence in online networks. Strategies drawn from the field of influencer marketing provide interesting opportunities to reach and engage with audiences in a personally relevant manner, including with those who may disagree with an intervention’s message. This article reflects on what health communicators might learn from influencer strategies and proposes digital methods to target and tailor health communication in the digital era. More concretely, we present methods to: (a) identify online communities engaging on a specific health issue; (b) map community specific cultures and health-related perceptions; and (c) identify influencers as potential collaboration partners. As such, we adopt a slightly different take on tailoring by putting the creative and cultural competences of social influencers central, and by aligning our methods with a media mapping protocol to create influencer strategies that are tailored to the cultures and health-related perceptions of multiple online audience segments. We illustrate the potential of these methods with a study of how vaccination is discussed among Dutch Twitter users.

Smchd1 is an epigenetic repressor with important functions in healthy cellular processes and disease. To elucidate its role in transcriptional regulation, we performed two independent genome-wide RNA-sequencing studies comparing wild-type and Smchd1 null samples in neural stem cells and lymphoma cell lines. Using an R-based analysis pipeline that accommodates observational and sample-specific weights in the linear modeling, we identify key genes dysregulated by Smchd1 deletion such as clustered protocadherins in the neural stem cells and imprinted genes in both experiments. Here we provide a detailed description of this analysis, from quality control to read mapping and differential expression analysis. These data sets are publicly available from the Gene Expression Omnibus database (accession numbers GSE64099 and GSE65747). Keywords: RNA-sequencing, voom, Sample variability, Epigenetics

Game studies has seen an increasing interest in serious games with a persuasive goal. Yet, empirical research about the impact of these persuasive games is still limited. This paper aims to advance the field by reporting on an explorative, qualitative study, investigating player experiences in My Life as a Refugee and PeaceMaker, games that address pressing socio-political issues. Theoretically, our research was based on immersion theory and Calleja’s account of player involvement. We conducted in-depth interviews with twelve participants. Our results showed that players experienced the two games in a similar way. With respect to immersion, our results highlight its different aspects by showing that the games’ narratives had the largest impact on feeling immersed. Our participants also experienced ludic, affective, and spatial immersion, which partly deepened their narrative immersion. Finally, we found that perceived realism, narrative depth, and identification contributed to the immersive experience. The major contribution of this paper is showing that immersion heightened participants’ susceptibility to persuasion within the gaming environment, while adding that the roles of emotion and identification in immersion warrant further research.

Summary: We and others have recently reported that the SMC protein Smchd1 is a regulator of chromosome conformation. Smchd1 is critical for the structure of the inactive X chromosome and at autosomal targets such as the Hox genes. However, it is unknown how Smchd1 is recruited to these sites. Here, we report that Smchd1 localizes to the inactive X via the Xist-HnrnpK-PRC1 (polycomb repressive complex 1) pathway. Contrary to previous reports, Smchd1 does not bind Xist or other RNA molecules with any specificity. Rather, the localization of Smchd1 to the inactive X is H2AK119ub dependent. Following perturbation of this interaction, Smchd1 is destabilized, which has consequences for gene silencing genome-wide. Our work adds Smchd1 to the PRC1 silencing pathway for X chromosome inactivation. : Jansz et al. report that the chromatin protein Smchd1 depends on polycomb repressive complex 1-mediated ubiquitylation of histone H2A for its recruitment to the inactive X chromosome and for its protein stability. These data have implications for Smchd1 targeting genome-wide. Keywords: Smchd1, X inactivation, Xist, PRC1, Hnrnpk, Ring1B

BACKGROUND:Health-related quality of life (HRQOL) is an important outcome measure in patients with end-stage renal disease. HRQOL is assumed to improve with kidney transplantation and also with nocturnal hemodialysis compared to conventional hemodialysis. However, there is no evidence regarding HRQOL to support the optimal treatment choice for patients on nocturnal hemodialysis who hesitate opting for transplantation. We therefore compared HRQOL between patients who were treated with kidney transplantation or nocturnal hemodialysis for one year. METHODS:We assessed HQROL using the Kidney Disease Quality of Life-Short Form questionnaire in a cross-sectional sample of patients who were treated with kidney transplantation (n = 41) or nocturnal hemodialysis (n = 31) for one year. All patients on nocturnal hemodialysis were transplantation candidates. Using linear regression, we compared HRQOL between kidney transplantation and nocturnal hemodialysis, and adjusted for age, sex, dialysis duration, cardiovascular disease, and presence of residual urine production. RESULTS:At one year follow-up, mean age of the study population was 54 ±13 years, and median dialysis duration was 3.2 (IQR 2.1-5.0) years. Kidney transplantation was associated with significantly higher HRQOL on the domain "effects" compared to nocturnal hemodialysis (adjusted difference 12.0 points, 95% CI 3.9; 20.1). There were potentially clinically relevant differences between kidney transplantation and nocturnal hemodialysis on the domains "burden" (adjusted difference 11.1 points, 95% CI -2.6; 24.8), "social support" (adjusted difference 6.2, 95% CI -6.6; 19.1), and the physical composite score (adjusted difference 3.0, 95% CI -2.0; 8.1), but these were not significant. CONCLUSIONS:After kidney transplantation, HRQOL is especially higher on the domain "effects of kidney disease" compared to nocturnal hemodialysis. This can be useful when counseling patients on nocturnal hemodialysis who may opt for transplantation.

BACKGROUND:Cardiovascular disease is the leading cause of death in end-stage renal disease and is strongly associated with vascular calcification. Both kidney transplantation and phosphate binders may lower the risk of vascular calcification. Vascular calcification is actively inhibited by vitamin-K-dependent matrix γ-carboxyglutamic acid protein (MGP). Whether kidney transplantation or phosphate binders affect vitamin K status is unknown. Therefore, we studied the influence of kidney transplantation and phosphate binder use on vitamin K status. METHODS:We measured plasma desphospho-uncarboxylated MGP (dp-ucMGP), a marker reflecting low vitamin K status, in a cross-sectional study of patients on hemodialysis (n = 82), peritoneal dialysis (n = 31) or who recently received a kidney transplantation (n = 36). By medication inventory, we assessed phosphate binder use. With linear regression, we assessed the influence of kidney transplantation and phosphate binder use on natural-log-transformed dp-ucMGP, adjusting for potential confounders. RESULTS:Mean age of patients was 52±13 years; 102 (68%) were male. Dp-ucMGP levels were significantly lower in kidney transplant recipients (median 689 pmol/L) compared to patients on dialysis (median 1537 pmol/L, p

Background. We recently reported that frailty is independently predictive of increased mortality in patients with advanced heart failure referred for heart transplantation (HTx). The aim of this study was to assess the impact of frailty on short-term outcomes after bridge-to-transplant ventricular assist device (BTT-VAD) implantation and/or HTx and to determine if frailty is reversible after these procedures. Methods. Between August 2013 and August 2016, 100 of 126 consecutive patients underwent frailty assessment using Fried’s Frailty Phenotype before surgical intervention: 40 (21 nonfrail, 19 frail) BTT-VAD and 77 (60 nonfrail, 17 frail) HTx—including 17 of the 40 BTT-VAD supported patients. Postprocedural survival, intubation time, intensive care unit, and hospital length of stay were compared between frail and nonfrail groups. Twenty-six frail patients were reassessed at 2 months or longer postintervention. Results. Frail patients had lower survival (63 ± 10% vs 94 ± 3% at 1 year, P = 0.012) and experienced significantly longer intensive care unit (11 vs 5 days, P = 0.002) and hospital (49 vs 25 days, P = 0.003) length of stay after surgical intervention compared with nonfrail patients. Twelve of 13 frail patients improved their frailty score after VAD (4.0 ± 0.8 to 1.4 ± 1.1, P < 0.001) and 12 of 13 frail patients improved their frailty score after HTx (3.2 ± 0.4 to 0.9 ± 0.9, P < 0.001). Handgrip strength and depression improved postintervention. Only a slight improvement in cognitive function was seen postintervention. Conclusions. Frail patients with advanced heart failure experience increased mortality and morbidity after surgical intervention with BTT-VAD or HTx. Among those who survive frailty is partly or completely reversible underscoring the importance of considering this factor as a dynamic not fixed entity.

The diabetic patients in Sri Lanka use Gymnema lactiferum leaves as a treatment for diabetes. However, scientific data is not available on this plant. A clinical trial was conducted including 26, type 2 diabetic patients with hypercholesterolemia. The treatment group received a suspension of G. lactiferum leaf powder twice daily for four weeks. Blood parameters of both groups (treated and control) were determined at the beginning and the end of the study period. Study indicates significant effects on FBS (p=0.002), cholesterol (p=0.004), and LDL lowering (p=0.023) and a significant postprandial glucose lowering effect (p=0.026 for 60 min and p=0.022 for 120 min, after four weeks). In spite of the short study period, a significant reduction (p=0.012) in HbA1C levels was also observed.

Jeroen Jansz holds the Chair of Communication and Media in the Department of Media & Communication at Erasmus University Rotterdam. He was co-founder of the Special Interest Group Game Studies in the International Communication Association and the Dutch chapter of the Digital Games Research Association. Liesbet van Zoonen is professor of Sociology at Erasmus University Rotterdam, dean of the Erasmus Graduate School of Social Sciences and the Humanities and holds a chair in Media and Communication at Loughborough University (UK). This qualitative interview study explores the practices of adult female gamers who play the videogame The Sims, focusing on the motivations they have for playing and how playing a video game might influence their digital competence. We address the wider context of leisure and the household, investigating to what extent playing videogames has become domesticated in the daily life of the family. It is found that female gamers play The Sims because they enjoy the particular way it allows them to take control, fantasize, and be challenged. For some, it is clear that playing this video game has increased their digital skills. We notice that there is an interesting similarity between the pleasures of playing this videogame and more traditional ways of female media engagement such as reading women’s magazines or romance novels and watching soap operas. Our gamers similarly enjoy The Sims as leisurely moments for themselves, clearly and intentionally separated from domestic and family duties. We conclude that playing a videogame can be seen as a highly modern and liberating practice, as both playing in general and using ICT have traditionally not been a part of the female leisure domain.

Primary graft failure (PGF) is a devastating complication that occurs in the immediate postoperative period following heart transplantation. It manifests as severe ventricular dysfunction of the donor graft and carries significant mortality and morbidity. In the last decade, advances in pharmacological treatment and mechanical circulatory support have improved the outlook for heart transplant recipients who develop this complication. Despite these advances in treatment, PGF is still the leading cause of death in the first 30 days after transplantation. In today's climate of significant organ shortages and growing waiting lists, transplant units worldwide have increasingly utilised “marginal donors” to try and bridge the gap between “supply and demand.” One of the costs of this strategy has been an increased incidence of PGF. As the threat of PGF increases, the challenges of predicting and preventing its occurrence, as well as the identification of more effective treatment modalities, are vital areas of active research and development.

Gymnema lactiferum var. lactiferum is a climber distributed in many South Asian countries. It is reported that the diabetic patients in Sri Lanka use G. lactiferum leaves as a treatment for diabetes. However, scientific data is not available on this plant. A clinical trial was conducted including 26, type 2 diabetic patients with hypercholesterolemia. The treatment group received a suspension of G. lactiferum leaf powder twice daily for four weeks. Blood parameters of both groups (treated and control) were determined at the beginning and the end of the study period. Study indicates significant effects on fasting blood sugar (p=0.002), cholesterol (p=0.004), and LDL lowering (p=0.023) and a significant postprandial glucose lowering effect (p=0.026 for 60 min and p=0.022 for 120 min, after four weeks). In spite of the short study period, a significant reduction (p=0.012) in HbA1C levels was also observed.

Abstract Background We present the first phase contrast (PC) cardiovascular magnetic resonance (CMR) measurements of the distribution of blood flow in twelve late gestation human fetuses. These were obtained using a retrospective gating technique known as metric optimised gating (MOG). Methods A validation experiment was performed in five adult volunteers where conventional cardiac gating was compared with MOG. Linear regression and Bland Altman plots were used to compare MOG with the gold standard of conventional gating. Measurements using MOG were then made in twelve normal fetuses at a median gestational age of 37 weeks (range 30–39 weeks). Flow was measured in the major fetal vessels and indexed to the fetal weight. Results There was good correlation between the conventional gated and MOG measurements in the adult validation experiment (R=0.96). Mean flows in ml/min/kg with standard deviations in the major fetal vessels were as follows: combined ventricular output (CVO) 540±101, main pulmonary artery (MPA) 327±68, ascending aorta (AAo) 198±38, superior vena cava (SVC) 147±46, ductus arteriosus (DA) 220±39,pulmonary blood flow (PBF) 106±59,descending aorta (DAo) 273±85, umbilical vein (UV) 160±62, foramen ovale (FO)107±54. Results expressed as mean percentages of the CVO with standard deviations were as follows: MPA 60±4, AAo37±4, SVC 28±7, DA 41±8, PBF 19±10, DAo50±12, UV 30±9, FO 21±12. Conclusion This study demonstrates how PC CMR with MOG is a feasible technique for measuring the distribution of the normal human fetal circulation in late pregnancy. Our preliminary results are in keeping with findings from previous experimental work in fetal lambs.