Calumet and Fleur-De-Lys: Archaeology of Indian and French Contact in the Midcontinent

Review of: Calumet and Fleur-de-Lys: Archaeology of Indian and French Contact in the Midcontinent. Walthall, John A. and Emerson, Thomas E., ed

"Some of us need to be taken care of": young adults' perspectives on support and help in drug reducing interventions in coercive contexts in Denmark and the UK

This paper provides an account of young people’s experiences of and perspectives on help and support in drug reducing interventions. It is based on interviews with young people age 14–25 who were in contact with the Criminal Justice System (CJS) and, at the same time, participated in a drug reducing intervention. The interview data forms part of the EU funded EPPIC project. Two main themes emerged from the young peoples’ accounts that cut across different types of interventions and social systems in both countries. The first revolves around the ‘system’ of welfare, criminal justice, health and educational services and the barriers young people encountered in navigating the system to find help. The second revolves around the young people’s experiences with professionals, including what they appreciated and what they found problematic in professionals’ approach to them. Basing our analysis on data from two different countries, we are able to emphasize similarities in the young peoples’ perspectives, despite being enrolled in different drug reducing and CJS interventions. The insights gained indicate a need for systems and service changes that can facilitate a better balance between building individual resilience and providing appropriate, timely and adequate support within a ‘resilience-building environmen

Clinical and functional characterisation of a novel TNFRSF1A c.605T > A/V173D cleavage site mutation associated with tumour necrosis factor receptor-associated periodic fever syndrome (TRAPS), cardiovascular complications and excellent response to etanercept treatment.

Objectives: To study the clinical outcome, treatment response, T-cell subsets and functional consequences of a novel tumour necrosis factor (TNF) receptor type 1 (TNFRSF1A) mutation affecting the receptor cleavage site. Methods: Patients with symptoms suggestive of tumour necrosis factor receptor-associated periodic syndrome (TRAPS) and 22 healthy controls (HC) were screened for mutations in the TNFRSF1A gene. Soluble TNFRSF1A and inflammatory cytokines were measured by ELISAs. TNFRSF1A shedding was examined by stimulation of peripheral blood mononuclear cells (PBMCs) with phorbol 12-myristate 13-acetate followed by flow cytometric analysis (FACS). Apoptosis of PBMCs was studied by stimulation with TNFa in the presence of cycloheximide and annexin V staining. T cell phenotypes were monitored by FACS. Results: TNFRSF1A sequencing disclosed a novel V173D/ p.Val202Asp substitution encoded by exon 6 in one family, the c.194–14G.A splice variant in another and the R92Q/p.Arg121Gln substitution in two families. Cardiovascular complications (lethal heart attack and peripheral arterial thrombosis) developed in two V173D patients. Subsequent etanercept treatment of the V173D carriers was highly effective over an 18-month follow-up period. Serum TNFRSF1A levels did not differ between TRAPS patients and HC, while TNFRSF1A cleavage from monocytes was significantly reduced in V173D and R92Q patients. TNFa-induced apoptosis of PBMCs and T-cell senescence were comparable between V173D patients and HC. Conclusions: The TNFRSF1A V173D cleavage site mutation may be associated with an increased risk for cardiovascular complications and shows a strong response to etanercept. T-cell senescence does not seem to have a pathogenetic role in affected patients

Electron-positron bremsstrahlung and pair creation in very high magnetic fields

Cross-sections for Rutherford scattering, Coulomb bremsstrahlung and pair creation, have been calculated at very high magnetic fields in order to investigate the photo-production of protons at the polar caps of pulsars whose spin is antiparallel with the polar magnetic flux density. The Landau-Pomeranchuk-Migdal effect at very high magnetic fields is included in a simple electron Green function.Comment: 10 pages; to be published in Monthly Notices of the Royal Astronomical Societ

STS-2 sail non-avionics subsystems math model requirements

Using a mathematical model, requirements for each of the nonavionic subsystems that interface with the shuttle avionics system are given

Building cultures of participation: involving young people in contact with the criminal justice system in the development of drug interventions in the United Kingdom, Denmark, Italy and Poland

This paper explores the participation of young people in contact with criminal justice systems in the development of drugs interventions. Interviews were undertaken with 160 young people (aged 15-25) and 66 practitioners involved in the design, delivery and commissioning of drug interventions. We analyse the key challenges in involving young people in the development of interventions including structural, organisational and individual factors. We argue that these barriers can be overcome by fostering flexible models of participation and identifying the most meaningful and appropriate approaches for involving young people at different stages and in different initiatives which consider socio-cultural contexts

Immunomodulatory activity of humanized anti-IL-7R monoclonal antibody RN168 in subjects with type 1 diabetes

BACKGROUND: The cytokine IL-7 is critical for T cell development and function. We performed a Phase Ib study in patients with type 1 diabetes (T1D) to evaluate how blockade of IL-7 would affect immune cells and relevant clinical responses. METHODS: Thirty-seven subjects with T1D received s.c. RN168, a monoclonal antibody that blocks the IL -7 receptor α (IL7Rα) in a dose-escalating study. RESULTS: Between 90% and 100% IL-7R occupancy and near-complete inhibition of pSTAT5 was observed at doses of RN168 1 mg/kg every other week (Q2wk) and greater. There was a significant decline in CD4+ and CD8+ effector and central memory T cells and CD4+ naive cells, but there were fewer effects on CD8+ naive T cells. The ratios of Tregs to CD4+ or CD8+ effector and central memory T cells versus baseline were increased. RNA sequencing analysis showed downmodulation of genes associated with activation, survival, and differentiation of T cells. Expression of the antiapoptotic protein Bcl-2 was reduced. The majority of treatment-emergent adverse events (TEAEs) were mild and not treatment related. Four subjects became anti-EBV IgG+ after RN168, and 2 had symptoms of active infection. The immunologic response to tetanus toxoid was preserved at doses of 1 and 3 mg/kg Q2wk but reduced at higher doses. CONCLUSIONS: This trial shows that, at dosages of 1-3 mg/kg, RN168 selectively inhibits the survival and activity of memory T cells while preserving naive T cells and Tregs. These immunologic effects may serve to eliminate pathologic T cells in autoimmune diseases. TRIAL REGISTRATION: NCT02038764. FUNDING: Pfizer Inc

Editorial DEPP: drug experienced young people in contact with the criminal justice system. Understanding the challenges and working towards solutions

The focus of this collection of papers is on young people (age 14–25) who are drug experienced and are in contact with the Criminal Justice System (CJS). In general, research tends to focus on either young people’s drug use or offending; equally, we see a tendency within policy and service responses to focus on interventions aimed either at drug use or at offending but rarely addressing complex problems that may include drug use and offending (Herold et al., 2019). By drawing on young peoples’ own perspectives and experiences and focusing on multiple problem areas at the same time, this collection presents findings that complement and augment the existing literature, and are highly relevant to policy development and service provision by: providing an account of young people’s own perspectives and experiences of their drug use and offending trajectories and the experienced relationship between these trajectories; describing young people’s own perspectives and experiences of different kinds of drug and/or offending reducing initiatives they have participated in and what they appreciate and/or find difficult in these institutional arrangements; showing how professionals engage with this group of young people, and how young people themselves consider engagement in services offered to them; and finally, highlighting the unintended consequences for and experienced by young people of the application of prohibitive drug policies and of involvement in the criminal justice system