Affective Engagement with Research Evidence about Young People’s Sex Education in Kenya

Sex and relationships have a big impact on young people’s lives. For most young people in the world getting information about sexual pleasure, apart from pornography, can be difficult. And it’s even harder if you live in parts of the world where you often aren’t able to decide who to date or marry, or how many children you want to have. For this reason online information on sexuality is hugely popular. Research suggests that young people are arriving at sex education sites mostly through campaigns on social media. As not all young people are using these sites it is essential to find creative ways to engage with them in a way that strengthens and builds on existing online sex education. Our recent study used affective engagement as part of a multi-layered and multi-me- thod participatory action research process on online sex education for young Kenyans online. We worked with a group of students from the Sauti music academy, to explore the meaning and relevance of themes that emerged from analysis of online behaviour on the Love Matters sex education platform and off-line research on gender roles and sexuality by young people. Young musicians wrote songs based on the research analysis and recorded these on YouTube. We found that the issues raised by young people using online platforms were also relevant to Kenyan offline non-users. Interpersonal exchange between the young people directly involved in the study, the sexual health experts and international creative team were key to stimulating critical reflection on meanings of sex and love, and creativity in the production of the 15 original songs that were produced during the project. The musicians involved said they had learned how to communicate effectively about sexuality, expectations and affection. Participants also learned how to use their own experiences to connect with people, and most said they realized their responsibility and potential as artists to make progressive social change. Learning on reaching audiences was one of the main unintended benefits for the artists of this project

The Impact of Perceived Expectations and Uncertainty on Firm Investment

This paper analyses the (differential) impact of perceived expectations and uncertainty on investment spending in small and large firms. We analyse two types of investment, viz. aggregate investment and investment in energy-saving technologies, using Dutch firm level data. The results show that expectations and uncertainty about input- and output prices and domestic demand have substantial but different effects on investment spending in firms of different sizes. Furthermore, we find evidence, at least for small firms, that there are important differences between the effects of uncertainty about input and output variable

Natalizumab treatment shows low cumulative probabilities of confirmed disability worsening to EDSS milestones in the long-term setting.

Abstract Background Though the Expanded Disability Status Scale (EDSS) is commonly used to assess disability level in relapsing-remitting multiple sclerosis (RRMS), the criteria defining disability progression are used for patients with a wide range of baseline levels of disability in relatively short-term trials. As a result, not all EDSS changes carry the same weight in terms of future disability, and treatment benefits such as decreased risk of reaching particular disability milestones may not be reliably captured. The objectives of this analysis are to assess the probability of confirmed disability worsening to specific EDSS milestones (i.e., EDSS scores ≥3.0, ≥4.0, or ≥6.0) at 288 weeks in the Tysabri Observational Program (TOP) and to examine the impact of relapses occurring during natalizumab therapy in TOP patients who had received natalizumab for ≥24 months. Methods TOP is an ongoing, open-label, observational, prospective study of patients with RRMS in clinical practice. Enrolled patients were naive to natalizumab at treatment initiation or had received ≤3 doses at the time of enrollment. Intravenous natalizumab (300 mg) infusions were given every 4 weeks, and the EDSS was assessed at baseline and every 24 weeks during treatment. Results Of the 4161 patients enrolled in TOP with follow-up of at least 24 months, 3253 patients with available baseline EDSS scores had continued natalizumab treatment and 908 had discontinued (5.4% due to a reported lack of efficacy and 16.4% for other reasons) at the 24-month time point. Those who discontinued due to lack of efficacy had higher baseline EDSS scores (median 4.5 vs. 3.5), higher on-treatment relapse rates (0.82 vs. 0.23), and higher cumulative probabilities of EDSS worsening (16% vs. 9%) at 24 months than those completing therapy. Among 24-month completers, after approximately 5.5 years of natalizumab treatment, the cumulative probabilities of confirmed EDSS worsening by 1.0 and 2.0 points were 18.5% and 7.9%, respectively (24-week confirmation), and 13.5% and 5.3%, respectively (48-week confirmation). The risks of 24- and 48-week confirmed EDSS worsening were significantly higher in patients with on-treatment relapses than in those without relapses. An analysis of time to specific EDSS milestones showed that the probabilities of 48-week confirmed transition from EDSS scores of 0.0–2.0 to ≥3.0, 2.0–3.0 to ≥4.0, and 4.0–5.0 to ≥6.0 at week 288 in TOP were 11.1%, 11.8%, and 9.5%, respectively, with lower probabilities observed among patients without on-treatment relapses (8.1%, 8.4%, and 5.7%, respectively). Conclusions In TOP patients with a median (range) baseline EDSS score of 3.5 (0.0–9.5) who completed 24 months of natalizumab treatment, the rate of 48-week confirmed disability worsening events was below 15%; after approximately 5.5 years of natalizumab treatment, 86.5% and 94.7% of patients did not have EDSS score increases of ≥1.0 or ≥2.0 points, respectively. The presence of relapses was associated with higher rates of overall disability worsening. These results were confirmed by assessing transition to EDSS milestones. Lower rates of overall 48-week confirmed EDSS worsening and of transitioning from EDSS score 4.0–5.0 to ≥6.0 in the absence of relapses suggest that relapses remain a significant driver of disability worsening and that on-treatment relapses in natalizumab-treated patients are of prognostic importance

Adrenal function and dysfunction in critically ill patients

Critical illnesses are characterized by increased systemic cortisol availability, which is a vital part of the stress response. Relative adrenal failure (later termed critical-illness-related corticosteroid insufficiency (CIRCI)) is a condition in which the systemic availability of cortisol is assumed to be insufficiently high to face the stress of the illness and is most typically thought to occur in the acute phase of septic shock. Researchers suggested that CIRCI could be diagnosed by a suppressed incremental cortisol response to an injection of adrenocorticotropic hormone, irrespective of the baseline plasma cortisol. This concept triggered several randomized clinical trials on the impact of large stress doses of hydrocortisone to treat CIRCI, which gave conflicting results. Recent novel insights into the response of the hypothalamic-pituitary-adrenal axis to acute and prolonged critical illnesses challenge the concept of CIRCI, as currently defined, as well as the current practice guidelines for diagnosis and treatment. In this Review, these novel insights are integrated within a novel conceptual framework that can be used to re-appreciate adrenocortical function and dysfunction in the context of critical illness. This framework opens new avenues for further research and for preventive and/or therapeutic innovations.status: Published onlin

So Happy Together: A Review of the Literature on the Determinants of Effectiveness of Purpose-Oriented Networks in Health Care

While purpose-oriented networks are widely recognized as organizational forms to address wicked problems in health care such as increasing demands and expenditure, the associated literature is fragmented. We therefore reviewed empirical studies to identify the determinants of the effectiveness of these networks. Our search yielded 3,657 unique articles, of which 19 met our eligibility criteria. After backward snowballing and expert consultation, 33 articles were included. Results reveal no less than 283 determinants of effective health care networks. The majority of these determinants are processual and involving professionals from the operational level is particularly salient. In addition, most studies relate determinants to process outcomes (e.g., improved collaboration or sustainability of the network) and only a few to members' perception of whether the network attains its goals. We urge future research to adopt configurational approaches to identify which sets of determinants are associated with networks' ability to attain their goal of addressing wicked problems

Rescue of Newcastle Disease Virus from Cloned cDNA: Evidence that Cleavability of the Fusion Protein Is a Major Determinant for Virulence

A full-length cDNA clone of Newcastle disease virus (NDV) vaccine strain LaSota was assembled from subgenomic overlapping cDNA fragments and cloned in a transcription plasmid between the T7 RNA polymerase promoter and the autocatalytic hepatitis delta virus ribozyme. Transfection of this plasmid into cells that were infected with a recombinant fowlpoxvirus that expressed T7 RNA polymerase, resulted in the synthesis of antigenomic NDV RNA. This RNA was replicated and transcribed by the viral NP, P, and L proteins, which were expressed from cotransfected plasmids. After inoculation of the transfection supernatant into embryonated specific-pathogen-free eggs, infectious virus derived from the cloned cDNA was recovered. By introducing three nucleotide changes in the cDNA, we generated a genetically tagged derivative of the LaSota strain in which the amino acid sequence of the protease cleavage site (GGRQGR↓L) of the fusion protein F0 was changed to the consensus cleavage site of virulent NDV strains (GRRQRR↓F). Pathogenicity tests in day-old chickens showed that the strain derived from the unmodified cDNA was completely nonvirulent (intracerebral pathogenicity index [ICPI] = 0.00). However, the strain derived from the cDNA in which the protease cleavage site was modified showed a dramatic increase in virulence (ICPI = 1.28 out of a possible maximum of 2.0). Pulse-chase labeling of cells infected with the different strains followed by radioimmunoprecipitation of the F protein showed that the efficiency of cleavage of the F0 protein was greatly enhanced by the amino acid replacements. These results demonstrate that genetically modified NDV can be recovered from cloned cDNA and confirm the supposition that cleavage of the F0 protein is a key determinant in virulence of NDV