Future treatment strategies of aggressive pituitary tumors

While surgery remains the first-line treatment of most aggressive pituitary adenomas, medical therapy is important as second-line or adjunctive therapy in a large proportion of patients. Dopamine agonists (DAs) are the best treatment for prolactinomas, but when DAs are not tolerated, new somatostatin receptor subtype 5 (SSTR5) inhibitors may offer an alternative in the future. Unfortunately, these are unlikely to be effective in DA-resistant prolactinomas. In acromegaly, the existing somatostatin analogs, octreotide and lanreotide, will remain the medical treatment of choice for the foreseeable future. There is an urgent need for medical therapies in Cushing’s disease, and the SSTR5 analogs could offer an effective treatment in a proportion of patients within the next few years. Finally, the medical management options for non-functioning pituitary adenomas are also very limited, and a new chimeric agent with activity towards dopamine receptors, SSTR5 and SSTR2 may help reduce adenoma recurrence in the future

Healthcare workers' attitudes towards working during pandemic influenza: A multi method study

Background: Healthcare workers (HCWs) will be key players in any response to pandemic influenza, and will be in the front line of exposure to infection. Responding effectively to a pandemic relies on the majority of medical, nursing, laboratory and hotel services staff continuing to work normally. Planning assumes that during a pandemic normal healthcare service levels will be provided, although it anticipates that as caseloads increase only essential care will be provided. The ability of the NHS to provide expected service levels is entirely dependent upon HCWs continuing to work as normal. Methods/design: This study is designed as a two-phase multi-method study, incorporating focus groups and a questionnaire survey. In phase one, qualitative methods will be used to collect the views of a purposive sample of HCWs, to determine the range of factors associated with their responses to the prospect of working through pandemic influenza. In phase two, the findings from the focus groups, combined with the available literature, will be used to inform the design of a survey to determine the generalisability of these factors, enabling the estimation of the likely proportion of HCWs affected by each factor, and how likely it is that they would be willing and/or able to continue to work during an influenza pandemic. Discussion: There are potentially greater than normal health risks for some healthcare workers working during a pandemic, and these workers may be concerned about infecting family members/ friends. HCWs will be as liable as other workers to care for sick family members and friends. It is vital to have information about how motivated HCWs will be to continue to work during such a crisis, and what factors might influence their decision to work/not to work. Through the identification and subsequent management of these factors it may be possible to implement strategies that will alleviate the concerns and fears of HCWs and remove potential barriers to working

A CD8+ T cell transcription signature predicts prognosis in autoimmune disease.

Autoimmune diseases are common and debilitating, but their severe manifestations could be reduced if biomarkers were available to allow individual tailoring of potentially toxic immunosuppressive therapy. Gene expression-based biomarkers facilitating such tailoring of chemotherapy in cancer, but not autoimmunity, have been identified and translated into clinical practice. We show that transcriptional profiling of purified CD8(+) T cells, which avoids the confounding influences of unseparated cells, identifies two distinct subject subgroups predicting long-term prognosis in two autoimmune diseases, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), a chronic, severe disease characterized by inflammation of medium-sized and small blood vessels, and systemic lupus erythematosus (SLE), characterized by autoantibodies, immune complex deposition and diverse clinical manifestations ranging from glomerulonephritis to neurological dysfunction. We show that the subset of genes defining the poor prognostic group is enriched for genes involved in the interleukin-7 receptor (IL-7R) pathway and T cell receptor (TCR) signaling and those expressed by memory T cells. Furthermore, the poor prognostic group is associated with an expanded CD8(+) T cell memory population. These subgroups, which are also found in the normal population and can be identified by measuring expression of only three genes, raise the prospect of individualized therapy and suggest new potential therapeutic targets in autoimmunity

"I could cry, the amount of shoes I can't get into": A qualitative exploration of the factors that influence retail footwear selection in women with rheumatoid arthritis

<p>Abstract</p> <p>Background</p> <p>Studies have reported that women with rheumatoid arthritis (RA) are not wearing NHS supplied therapeutic footwear; therefore it is likely they are wearing footwear sourced through retailers. Previous research gives limited information (largely associated with cosmesis) on people's perceptions on the relationships that exist between retail footwear, well-being and quality of life. This study aimed to explore the perceptions of women with RA regarding their choice of retail footwear and identify the factors influencing retail footwear selection.</p> <p>Methods</p> <p>Eleven women with RA wearing normal retail footwear were recruited from an out-patient podiatry clinic in the south east of England. Semi-structured interviews were carried out and an interpretative phenomenological approach was adopted for data collection and transcript analysis.</p> <p>Results</p> <p>Six key themes were revealed from the analysis: (1) the nature of foot complaints and deformities, (2) aesthetic appearance and design of footwear, (3) body image, (4) psychosocial aspects, (5) Perceptions of footwear and (6) the therapeutic value of retail shoes. These contributed to an overarching concept of loss of choice associated with retail footwear. In particular, the areas discussed most frequently throughout were themes (2), (3) and (4), which were notably more 'emotional' in nature.</p> <p>Conclusions</p> <p>Limitations in retail footwear for these women have impacted on their individuality, linking significantly with their body image. The loss of choice in footwear as a consequence of the disease impacts negatively on emotions, wellbeing and was identified in reduced self-perceived quality of life.</p

Dissociating Markers of Senescence and Protective Ability in Memory T Cells

No unique transcription factor or biomarker has been identified to reliably distinguish effector from memory T cells. Instead a set of surface markers including IL-7Rα and KLRG1 is commonly used to predict the potential of CD8 effector T cells to differentiate into memory cells. Similarly, these surface markers together with the tumor necrosis factor family member CD27 are frequently used to predict a memory T cell's ability to mount a recall response. Expression of these markers changes every time a memory cell is stimulated and repeated stimulation can lead to T cell senescence and loss of memory T cell responsiveness. This is a concern for prime–boost vaccine strategies which repeatedly stimulate T cells with the aim of increasing memory T cell frequency. The molecular cues that cause senescence are still unknown, but cell division history is likely to play a major role. We sought to dissect the roles of inflammation and cell division history in developing T cell senescence and their impact on the expression pattern of commonly used markers of senescence. We developed a system that allows priming of CD8 T cells with minimal inflammation and without acquisition of maximal effector function, such as granzyme expression, but a cell division history similar to priming with systemic inflammation. Memory cells derived from minimal effector T cells are fully functional upon rechallenge, have full access to non-lymphoid tissue and appear to be less senescent by phenotype upon rechallenge. However, we report here that these currently used biomarkers to measure senescence do not predict proliferative potential or protective ability, but merely reflect initial priming conditions

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Search for squarks and gluinos in events with isolated leptons, jets and missing transverse momentum at s√=8 TeV with the ATLAS detector

The results of a search for supersymmetry in final states containing at least one isolated lepton (electron or muon), jets and large missing transverse momentum with the ATLAS detector at the Large Hadron Collider are reported. The search is based on proton-proton collision data at a centre-of-mass energy s√=8 TeV collected in 2012, corresponding to an integrated luminosity of 20 fb−1. No significant excess above the Standard Model expectation is observed. Limits are set on supersymmetric particle masses for various supersymmetric models. Depending on the model, the search excludes gluino masses up to 1.32 TeV and squark masses up to 840 GeV. Limits are also set on the parameters of a minimal universal extra dimension model, excluding a compactification radius of 1/R c = 950 GeV for a cut-off scale times radius (ΛR c) of approximately 30

Evidence for the Higgs-boson Yukawa coupling to tau leptons with the ATLAS detector

Results of a search for H → τ τ decays are presented, based on the full set of proton-proton collision data recorded by the ATLAS experiment at the LHC during 2011 and 2012. The data correspond to integrated luminosities of 4.5 fb−1 and 20.3 fb−1 at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV respectively. All combinations of leptonic (τ → `νν¯ with ` = e, µ) and hadronic (τ → hadrons ν) tau decays are considered. An excess of events over the expected background from other Standard Model processes is found with an observed (expected) significance of 4.5 (3.4) standard deviations. This excess provides evidence for the direct coupling of the recently discovered Higgs boson to fermions. The measured signal strength, normalised to the Standard Model expectation, of µ = 1.43 +0.43 −0.37 is consistent with the predicted Yukawa coupling strength in the Standard Model