Randomised controlled trial. Comparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis:Trial design and protocol (CONSTRUCT)

Introduction: Many patients with ulcerative colitis (UC) present with acute exacerbations needing hospital admission. Treatment includes intravenous steroids but up to 40% of patients do not respond and require emergency colectomy. Mortality following emergency colectomy has fallen, but 10% of patients still die within 3 months of surgery. Infliximab and ciclosporin, both immunosuppressive drugs, offer hope for treating steroid-resistant UC as there is evidence of their short-term effectiveness. As there is little long-term evidence, this pragmatic randomised trial, known as Comparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis: a Trial (CONSTRUCT), aims to compare the clinical and cost-effectiveness of infliximab and ciclosporin for steroid-resistant UC. Methods and analysis: Between May 2010 and February 2013, 52 UK centres recruited 270 patients admitted with acute severe UC who failed to respond to intravenous steroids but did not need surgery. We allocated them at random in equal proportions between infliximab and ciclosporin.The primary clinical outcome measure is quality-adjusted survival, that is survival weighted by Crohn's and Colitis Questionnaire (CCQ) participants' scores, analysed by Cox regression. Secondary outcome measures include: the CCQ—an extension of the validated but community-focused UK Inflammatory Bowel Disease Questionnaire (IBDQ) to include patients with acute severe colitis and stoma; two general quality of life measures—EQ-5D and SF-12; mortality; survival weighted by EQ-5D; emergency and planned colectomies; readmissions; incidence of adverse events including malignancies, serious infections and renal disorders; disease activity; National Health Service (NHS) costs and patient-borne costs. Interviews investigate participants’ views on therapies for acute severe UC and healthcare professionals’ views on the two drugs and their administration. Ethics and dissemination: The Research Ethics Committee for Wales has given ethical approval (Ref. 08/MRE09/42); each participating Trust or Health Board has given NHS Reseach & Development approval. We plan to present trial findings at international and national conferences and publish in high-impact peer-reviewed journals.11 page(s

Population genomics of the Viking world.

The maritime expansion of Scandinavian populations during the Viking Age (about AD 750-1050) was a far-flung transformation in world history1,2. Here we sequenced the genomes of 442 humans from archaeological sites across Europe and Greenland (to a median depth of about 1×) to understand the global influence of this expansion. We find the Viking period involved gene flow into Scandinavia from the south and east. We observe genetic structure within Scandinavia, with diversity hotspots in the south and restricted gene flow within Scandinavia. We find evidence for a major influx of Danish ancestry into England; a Swedish influx into the Baltic; and Norwegian influx into Ireland, Iceland and Greenland. Additionally, we see substantial ancestry from elsewhere in Europe entering Scandinavia during the Viking Age. Our ancient DNA analysis also revealed that a Viking expedition included close family members. By comparing with modern populations, we find that pigmentation-associated loci have undergone strong population differentiation during the past millennium, and trace positively selected loci-including the lactase-persistence allele of LCT and alleles of ANKA that are associated with the immune response-in detail. We conclude that the Viking diaspora was characterized by substantial transregional engagement: distinct populations influenced the genomic makeup of different regions of Europe, and Scandinavia experienced increased contact with the rest of the continent

The Impacts of the Covid-19 Pandemic and Lockdown Policies on Young Fathers: Comparative Insights from the UK and Sweden

This article explores the impacts of the first wave of the COVID-19 pandemic and lockdown policies on young fathers and their families. We present analyses from a larger programme of qualitative longitudinal research examining young fatherhood in the UK and Sweden to develop a unique international comparative and empirical contribution. The views and experiences of young fathers are examined in the context of two ostensibly different policy approaches during the pandemic. Organised thematically to enable comparison, our findings demonstrate myriad impacts, illustrating heightened precarity in young fathers’ transitions into and through fatherhood linked to restrictions on their engagement and changes to their education and employment trajectories and relational contexts, especially in the UK. We observe how differences in policy approaches before and during the first wave of the pandemic shaped the experiences of young fathers in the respective countries

The impacts of the Covid-19 pandemic and lockdown policies on young fathers: comparative insights from the UK and Sweden

This article explores the impacts of the first wave of the COVID-19 pandemic and lockdown policies on young fathers and their families. We present analyses from a larger programme of qualitative longitudinal research examining young fatherhood in the UK and Sweden to develop a unique international comparative and empirical contribution. The views and experiences of young fathers are examined in context of two ostensibly different policy approaches to the pandemic. Organised thematically to enable comparison, our findings demonstrate myriad impacts, illustrating heightened precarity in young fathers’ transitions to and through fatherhood linked to restrictions on support and changes to their education and employment trajectories and relational contexts, especially in the UK. We observe how differences in policy approaches in the first wave of the pandemic shaped the experiences of young men in the respective countries

Perceptions of gender equality and engaged fatherhood among young fathers: parenthood and family policy in Sweden and the UK

This article presents analyses from an international empirical study of young fatherhood in Sweden and the UK to interrogate how welfare contexts and family policy shape young fathers’ views of parenthood. Our analyses demonstrate that despite differences in constructions of young fatherhood, whereby young parenthood is problematised in UK family policy, more so than in Sweden, young fathers in both countries express an encouraging commitment to contemporary cultural imperatives for engaged fatherhood. However, differences in welfare and parental leave systems have a clear influence on the extent to which the young men in the respective countries fulfil their parental commitments and act as local agents of change in the wider social project of gender equality. We argue that while policy processes and discourses in support of young parenthood and gender equality are currently treated as disparate concerns, their articulations with one another may instead be seen as complementary and symbiotic

Role of Intestinal Transit in the Pathogenesis of Gallbladder Stones

Increasing evidence implicates prolonged intestinal transit (slow transit constipation) in the pathogenesis of conventional gallbladder stones (GBS), and that of gallstones induced by long term octreotide (OT) treatment. Both groups of GBS patients have multiple abnormalities in the lipid composition and physical chemistry of their gallbladder bile - associated with, and possibly due to, an increased proportion of deoxycholic acid (DCA) (percentage of total bile acids). In turn, this increase in the percentage of DCA seems to be a consequence of prolonged colonic transit. Thus, in acromegalic patients OT treatment significantly prolongs large bowel transit time (LBTT) and leads to an associated increase of the percentage of DCA in fasting serum (and, by implication, in gallbladder bile). LBTT is linearly related to the percentage of DCA in fasting serum and correlates significantly with DCA input (into the enterohepatic circulation) and DCA pool size. However, these adverse effects of OT can be overcome by the concomitant use of the prokinetic drug cisapride, which normalizes LBTT and prevents the rise in the percentage of serum DCA. Therefore, in OT-treated patients and other groups at high risk of developing stones, it may be possible to prevent GBS formation with the use of intestinal prokinetic drugs