The use the a high intensity neutrino beam from the ESS proton linac for measurement of neutrino CP violation and mass hierarchy

It is proposed to complement the ESS proton linac with equipment that would enable the production, concurrently with the production of the planned ESS beam used for neutron production, of a 5 MW beam of 10$^{23}$ 2.5 GeV protons per year in microsecond short pulses to produce a neutrino Super Beam, and to install a megaton underground water Cherenkov detector in a mine to detect $\nu_e$ appearance in the produced $\nu_\mu$ beam. Results are presented of preliminary calculations of the sensitivity to neutrino CP violation and the mass hierarchy as a function of the neutrino baseline. The results indicate that, with 8 years of data taking with an antineutrino beam and 2 years with a neutrino beam and a baseline distance of around 400 km, CP violation could be discovered at 5 $\sigma$ (3 $\sigma$) confidence level in 48% (73%) of the total CP violation angular range. With the same baseline, the neutrino mass hierarchy could be determined at 3 $\sigma$ level over most of the total CP violation angular range. There are several underground mines with a depth of more than 1000 m, which could be used for the creation of the underground site for the neutrino detector and which are situated within or near the optimal baseline range

RELATIONSHIP BETWEEN ATOPIC DERMATITIS AND IMMUNOGLOBULIN E

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66225/1/j.1365-4362.1976.tb00705.x.pd

Implications of troponin testing in clinical medicine

During the past decade considerable research has been conducted into the use of cardiac troponins, their diagnostic capability and their potential to allow risk stratification in patients with acute chest pain. Determination of risk in patients with suspected myocardial ischaemia is known to be as important as retrospective confirmation of a diagnosis of myocardial infarction (MI). Therefore, creatine kinase (CK)-MB - the former 'gold standard' in detecting myocardial necrosis - has been supplanted by new, more accurate biomarkers.Measurement of cardiac troponin levels constitute a substantial determinant in assessment of ischaemic heart disease, the presentations of which range from silent ischaemia to acute MI. Under these conditions, troponin release is regarded as surrogate marker of thrombus formation and peripheral embolization, and therefore new therapeutic strategies are focusing on potent antithrombotic regimens to improve long-term outcomes. Although elevated troponin levels are highly sensitive and specific indicators of myocardial damage, they are not always reflective of acute ischaemic coronary artery disease; other processes have been identified that cause elevations in these biomarkers. However, because prognosis appears to be related to the presence of troponins regardless of the mechanism of myocardial damage, clinicians increasingly rely on troponin assays when formulating individual therapeutic plans

Fourteen-Year Trends in the Use of Psychotropic Medications, Opioids, and Other Sedatives Among Institutionalized Older People in Helsinki, Finland

Objectives: The use of psychotropic drugs in long-term care (LTC) is very common, despite their known adverse effects. The prevalence of opioid use is growing among older adults. This study aimed to investigate trends in the prevalence of psychotropics, opioids, and sedative load in a LTC setting over a 14-year period. We also explored the interaction of psychotropic and opioid use according to residents' dementia status in nursing home (NH) and assisted living facility (ALF) settings. Design: Four cross-sectional studies. Setting: Institutional settings in Helsinki, Finland. Participants: Older residents in NHs in 2003 (n = 1987), 2011 (n = 1576), and 2017 (n = 791) and in ALFs in 2007 (n = 1377), 2011 (n = 1586), and 2017 (n = 1624). Measures: Comparable assessments were conducted among LTC residents at 4 time points over 14 years. The prevalence of regular psychotropics, opioids, and other sedatives and data on demographics and diagnoses were collected from medical records. Results: Disabilities and severity of dementia increased in both settings over time. The prevalence of all psychotropics decreased significantly in NHs (from 81% in 2003 to 61% in 2017), whereas in ALFs there was no similar linear trend (65% in 2007 and 64% in 2017). There was a significant increase in the prevalence of opioids in both settings (30% in NHs and 22% in AFLs in 2017). Residents with dementia used less psychotropics and opioids than those without dementia in both settings and at each time point. Conclusions/Implications: NHs show a favorable trend in psychotropic drug use, but the rates of psychotropic use remain high in both NHs and ALFs. In addition, the rates of opioid use have almost tripled, leading to a high sedative load among LTC residents. Clinicians should carefully consider the risk-to-benefit ratio when prescribing in LTC. (C) 2018 AMDA - The Society for Post-Acute and Long-Term Care Medicine.Peer reviewe

Phenomenology as a resource for patients

Patient support tools have drawn on a variety of disciplines, including psychotherapy, social psychology, and social care. One discipline that has not so far been used to support patients is philosophy. This paper proposes that a particular philosophical approach, phenomenology, could prove useful for patients, giving them tools to reflect on and expand their understanding of their illness. I present a framework for a resource that could help patients to philosophically examine their illness, its impact on their life, and its meaning. I explain the need for such a resource, provide philosophical grounding for it, and outline the epistemic and existential gains philosophy offers. Illness often begins as an intrusion on one's life but with time becomes a way of being. I argue that this transition impacts on core human features such as the experience of space and time, human abilities, and adaptability. It therefore requires philosophical analysis and response. The paper uses ideas from Husserl and Merleau-Ponty to present such a response in the form of a phenomenological toolkit for patients. The toolkit includes viewing illness as a form of phenomenological reduction, thematizing illness, and examining illness as altering the ill person's being in the world. I suggest that this toolkit could be offered to patients as a workshop, using phenomenological concepts, texts, and film clips to reflect on illness. I conclude by arguing that examining illness as a limit case of embodied existence deepens our understanding of phenomenology.© The Author 2012. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved

Rate versus rhythm control and outcomes in patients with atrial fibrillation and chronic kidney disease: Data from the GUSTO-III Trial

Background: Atrial fi brillation (AF) and chronic kidney disease (CKD) have both beenshown to portend worse outcomes after acute myocardial infarction (MI); however, the benefi tof a rhythm control strategy in patients with CKD post-MI is unclear.Methods: We prospectively studied 985 patients with new-onset AF post-MI in theGUSTO-III trial, of whom 413 (42%) had CKD (creatinine clearance < 60 mL/min).A rhythm control strategy, defi ned as the use of an antiarrhythmic medication and/orelectrical cardioversion, was used in 346 (35%) of patients.Results: A rhythm control strategy was used in 34% of patients with CKD and 36% of patientswith no CKD. At hospital discharge, sinus rhythm was present in 487 (76%) of patients treatedwith a rate control strategy, vs. 276 (80%) in those treated with rhythm control (p = 0.20). CKDwas associated with a lower odds of sinus rhythm at discharge (unadjusted OR 0.56, 95% CI0.38–0.84, p < 0.001). However, in multivariable analyses, treatment with a rhythm controlstrategy was not associated with discharge rhythm (HR 1.068, 95% CI 0.69–1.66, p = 0.77),30-day mortality (HR 0.78, 95% CI 0.54–1.12, p = 0.18) or mortality from day 30 to 1 year(HR 1.00, 95% CI 0.59–1.69, p = 0.99). CKD status did not signifi cantly impact the relationshipbetween rhythm control and outcomes.Conclusions: Treatment with a rhythm or rate control strategy does not signifi cantly impactshort-term or long-term mortality in patients with post-MI AF, regardless of kidney disease status.Future studies to investigate the optimal management of AF in CKD patients are needed

A beta 2-Integrin/MRTF-A/SRF Pathway Regulates Dendritic Cell Gene Expression, Adhesion, and Traction Force Generation

beta 2-integrins are essential for immune system function because they mediate immune cell adhesion and signaling. Consequently, a loss of beta(2)-integrin expression or function causes the immunodeficiency disorders, Leukocyte Adhesion Deficiency (LAD) type I and III. LAD-III is caused by mutations in an important integrin regulator, kindlin-3, but exactly how kindlin-3 regulates leukocyte adhesion has remained incompletely understood. Here we demonstrate that mutation of the kindlin-3 binding site in the beta 2-integrin (TTT/AAA-beta 2-integrin knock-in mouse/KI) abolishes activation of the actin-regulated myocardin related transcription factor A/serum response factor (MRTF-A/SRF) signaling pathway in dendritic cells and MRTF-A/SRF-dependent gene expression. We show that Ras homolog gene family, member A (RhoA) activation and filamentous-actin (F-actin) polymerization is abolished in murine TTT/AAA-beta 2-integrin KI dendritic cells, which leads to a failure of MRTF-A to localize to the cell nucleus to coactivate genes together with SRF. In addition, we show that dendritic cell gene expression, adhesion and integrin-mediated traction forces on ligand coated surfaces is dependent on the MRTF-A/SRF signaling pathway. The participation of beta 2-integrin and kindlin-3-mediated cell adhesion in the regulation of the ubiquitous MRTF-A/SRF signaling pathway in immune cells may help explain the role of beta 2-integrin and kindlin-3 in integrin-mediated gene regulation and immune system function

Expression of UDP-glucuronosyltransferase 1A4 in human placenta at term

The placenta contains a large variety of metabolizing enzymes, among them UDP-glucuronosyltransferase (UGT). Several UGT2B isozymes have so far been detected in human placenta, but little is known on placental expression of UGT1A isozymes. The antiepileptic drug lamotrigine (LTG) is a UGT1A4-substrate, and its serum concentration falls by over 50% during pregnancy, leading to impaired seizure control. The placenta may be involved in this. Microsomes from term placentas of 4 LTG-users and 10 healthy control subjects were prepared. Western blot analysis detected UGT1A proteins in all placentas. The presence of UGT1A4 in placenta from LTG users was confirmed with UGT1A4 commercial standard and a specific UGT1A4 primary antibody. Since LTG is primarily metabolized by UGT1A4 and this isozyme is shown to be present in placenta at term, it may be hypothesized that the placenta is involved in the fall of LTG serum concentrations during pregnancy