Keratinocyte Membrane-Associated Epidermal Cell-Derived Thymocyte-Activating Factor (ETAF)

This study describes the association between secreted keratinocyte interleukin 1 (IL-1) and its presence on the keratinocyte cell surface. These properties were studied in normal and transformed human keratinocytes as well as in transformed murine keratinocytes. we will present evidence that the secretion of IL-1 by human and murine keratinocytes is associated with the presence of IL-1 on the keratinocyte membrane. In addition, although transformed murine keratinocytes secrete other cytokines, namely keratinocyte T-cell growth factor (KTGF) and IL-3, no KTGF or IL-3 activity can be demonstrated on the cell surface

Estimates of tibial shock magnitude in men and women at the start and end of a military drill training programme

This is the author accepted manuscript. The final version is available from Oxford University Press via the DOI in this record.Introduction Foot drill is a key component of military training and is characterized by frequent heel stamping, likely resulting in high tibial shock magnitudes. Higher tibial shock during running has previously been associated with risk of lower limb stress fractures, which are prevalent among military populations. Quantification of tibial shock during drill training is, therefore, warranted. This study aimed to provide estimates of tibial shock during military drill in British Army Basic training. The study also aimed to compare values between men and women, and to identify any differences between the first and final sessions of training. Materials and Methods Tibial accelerometers were secured on the right medial, distal shank of 10 British Army recruits (n = 5 men; n = 5 women) throughout a scheduled drill training session in week 1 and week 12 of basic military training. Peak positive accelerations, the average magnitude above given thresholds, and the rate at which each threshold was exceeded were quantified. Results Mean (SD) peak positive acceleration was 20.8 (2.2) g across all sessions, which is considerably higher than values typically observed during high impact physical activity. Magnitudes of tibial shock were higher in men than women, and higher in week 12 compared with week 1 of training. Conclusions This study provides the first estimates of tibial shock magnitude during military drill training in the field. The high values suggest that military drill is a demanding activity and this should be considered when developing and evaluating military training programs. Further exploration is required to understand the response of the lower limb to military drill training and the etiology of these responses in the development of lower limb stress fractures.The study was sponsored by the Headquarters Army Recruitment and Training Division, U

Diagonalization of an Integrable Discretization of the Repulsive Delta Bose Gas on the Circle

We introduce an integrable lattice discretization of the quantum system of n bosonic particles on a ring interacting pairwise via repulsive delta potentials. The corresponding (finite-dimensional) spectral problem of the integrable lattice model is solved by means of the Bethe Ansatz method. The resulting eigenfunctions turn out to be given by specializations of the Hall-Littlewood polynomials. In the continuum limit the solution of the repulsive delta Bose gas due to Lieb and Liniger is recovered, including the orthogonality of the Bethe wave functions first proved by Dorlas (extending previous work of C.N. Yang and C.P. Yang).Comment: 25 pages, LaTe

Antibodies in the Diagnosis, Prognosis, and Prediction of Psychotic Disorders.

Blood-based biomarker discovery for psychotic disorders has yet to impact upon routine clinical practice. In physical disorders antibodies have established roles as diagnostic, prognostic and predictive (theranostic) biomarkers, particularly in disorders thought to have a substantial autoimmune or infective aetiology. Two approaches to antibody biomarker identification are distinguished: a top-down approach, in which antibodies to specific antigens are sought based on the known function of the antigen and its putative role in the disorder, and emerging bottom-up or omics approaches that are agnostic as to the significance of any one antigen, using high-throughput arrays to identify distinctive components of the antibody repertoire. Here we review the evidence for antibodies (to self-antigens as well as infectious organism and dietary antigens) as biomarkers of diagnosis, prognosis, and treatment response in psychotic disorders. Neuronal autoantibodies have current, and increasing, clinical utility in the diagnosis of organic or atypical psychosis syndromes. Antibodies to selected infectious agents show some promise in predicting cognitive impairment and possibly other symptom domains (eg, suicidality) within psychotic disorders. Finally, infectious antibodies and neuronal and other autoantibodies have recently emerged as potential biomarkers of response to anti-infective therapies, immunotherapies, or other novel therapeutic strategies in psychotic disorders, and have a clear role in stratifying patients for future clinical trials. As in nonpsychiatric disorders, combining biomarkers and large-scale use of bottom-up approaches to biomarker identification are likely to maximize the eventual clinical utility of antibody biomarkers in psychotic disorders

Multifunctional cytokine production reveals functional superiority of memory CD4 T cells

T cell protective immunity is associated with multifunctional memory cells that produce several different cytokines. Currently, our understanding of when and how these cells are generated is limited. We have used an influenza virus mouse infection model to investigate whether the cytokine profile of memory T cells is reflective of primary responding cells or skewed towards a distinct profile. We found that, in comparison to primary cells, memory T cells tended to make multiple cytokines simultaneously. Analysis of the timings of release of cytokine by influenza virus‐specific T cells, demonstrated that primary responding CD4 T cells from lymphoid organs were unable to produce a sustained cytokine response. In contrast CD8 T cells, memory CD4 T cells, and primary responding CD4 T cells from the lung produced a sustained cytokine response throughout the restimulation period. Moreover, memory CD4 T cells were more resistant than primary responding CD4 T cells to inhibitors that suppress T cell receptor signalling. Together, these data suggest that memory CD4 T cells display superior cytokine responses compared to primary responding cells. These data are key to our ability to identify the cues that drive the generation of protective memory CD4 T cells following infection

Very high and low residual spenders in private health insurance markets: Germany, The Netherlands and the U.S. Marketplaces

We study the extremely high and low residual spenders in individual health insurance markets in three countries. A high (low) residual spender is someone for whom the residual—spending less payment (from premiums and risk adjustment)—is high (low), indicating that the person is highly underpaid (overpaid). We begin with descriptive analysis of the top and bottom 1% and 0.1% of residuals building to address the question of the degree of persistence in membership at the extremes. Common findings emerge among the countries. First, the diseases found among those with the highest residual spending are also disproportionately found among those with the lowest residual spending. Second, those at the top of the residual spending distribution (where spending exceeds payments the most) account for a massively high share of the unexplained variance in the predictions from the risk adjustment model. Third, in terms of persistence, we find that membership in the extremes of the residual spending distribution is highly persistent, raising concer

TCR deep sequencing of transgenic RAG-1-deficient mice reveals endogenous TCR recombination: a cause for caution

The utility of T‐cell receptor (TCR) transgenic mice in medical research has been considerable, with applications ranging from basic biology all the way to translational and clinical investigations. Crossing of TCR transgenic mice with either recombination‐activating gene (RAG)‐1 or RAG‐2 knockouts is frequently used to generate mice with a monoclonal T‐cell repertoire. However, low level productive TCR rearrangement has been reported in RAG‐deficient mice expressing transgenic TCRs. Using deep sequencing, we set out to directly examine and quantify the presence of these endogenous TCRs. Our demonstration that functional nontransgenic TCRs are present in nonmanipulated mice has wide reaching ramifications worthy of critical consideration