Cost-effectiveness of an insertable cardiac monitor in a high-risk population in the UK

Objective To evaluate the cost-effectiveness of insertable cardiac monitors (ICMs) compared with standard of care (SoC) for detecting atrial fibrillation (AF) in patients at high risk of stroke (CHADS 2 >2), using a UK National Health Service (NHS) perspective. Methods Using patient characteristics and clinical data from the REVEAL AF trial, a Markov model assessed the cost-effectiveness of detecting AF with an ICM compared with SoC. Costs and benefits were extrapolated across modelled patient lifetime. Ischaemic and haemorrhagic strokes, intracranial and extracranial haemorrhages and minor bleeds were modelled. Diagnostic and device costs were included, plus costs of treating stroke and bleeding events and costs of oral anticoagulants (OACs). Costs and health outcomes, measured as quality-adjusted life years (QALYs), were discounted at 3.5% per annum. One-way deterministic and probabilistic sensitivity analyses (PSA) were undertaken. Results The total per-patient cost for ICM was £13 360 versus £11 936 for SoC (namely, annual 24 hours Holter monitoring). ICMs generated a total of 6.50 QALYs versus 6.30 for SoC. The incremental cost-effectiveness ratio (ICER) was £7140/QALY gained, below the £20 000/QALY acceptability threshold. ICMs were cost-effective in 77.4% of PSA simulations. The number of ICMs needed to prevent one stroke was 21 and to cause a major bleed was 37. ICERs were sensitive to assumed proportions of patients initiating or discontinuing OAC after AF diagnosis, type of OAC used and how intense the traditional monitoring was assumed to be under SoC. Conclusions The use of ICMs to identify AF in a high-risk population is cost-effective for the UK NHS

No Benefit from Chronic Lithium Dosing in a Sibling-Matched, Gender Balanced, Investigator-Blinded Trial Using a Standard Mouse Model of Familial ALS

Background: In any animal model of human disease a positive control therapy that demonstrates efficacy in both the animal model and the human disease can validate the application of that animal model to the discovery of new therapeutics. Such a therapy has recently been reported by Fornai et al. using chronic lithium carbonate treatment and showing therapeutic efficacy in both the high-copy SOD1G93A mouse model of familial amyotrophic lateral sclerosis (ALS), and in human ALS patients. Methodology/Principal Findings: Seeking to verify this positive control therapy, we tested chronic lithium dosing in a sibling-matched, gender balanced, investigator-blinded trial using the high-copy (average 23 copies) SOD1G93A mouse (n = 27–28/group). Lithium-treated mice received single daily 36.9 mg/kg i.p. injections from 50 days of age through death. This dose delivered 1 mEq/kg (6.94 mg/kg/day lithium ions). Neurological disease severity score and body weight were determined daily during the dosing period. Age at onset of definitive disease and survival duration were recorded. Summary measures from individual body weight changes and neurological score progression, age at disease onset, and age at death were compared using Kaplan-Meier and Cox proportional hazards analysis. Our study did not show lithium efficacy by any measure. Conclusions/Significance: Rigorous survival study design that includes sibling matching, gender balancing, investigato

Expression of endothelia and lymphocyte adhesion molecules in bronchus-associated lymphoid tissue (BALT) in adult human lung

BACKGROUND: Bronchus-associated lymphoid tissue (BALT) is the secondary lymphoid tissue in bronchial mucosa and is involved in the development of bronchopulmonary immune responses. Although migration of lymphocytes from blood vessels into secondary lymphoid tissues is critical for the development of appropriate adaptive immunity, the endothelia and lymphocyte adhesion molecules that recruit specific subsets of lymphocytes into human BALT are not known. The aim of this study was to determine which adhesion molecules are expressed on lymphocytes and high endothelial venules (HEVs) in human BALT. METHODS: We immunostained frozen sections of BALT from lobectomy specimens from 17 patients with lung carcinoma with a panel of monoclonal antibodies to endothelia and lymphocyte adhesion molecules. RESULTS: Sections of BALT showed B cell follicles surrounded by T cells. Most BALT CD4+ T cells had a CD45RO+ memory phenotype. Almost all BALT B cells expressed alpha4 integrin and L-selectin. In contrast, 43% of BALT T cells expressed alpha4 integrin and 20% of BALT T cells expressed L-selectin. Almost all BALT lymphocytes expressed LFA-1. HEVs, which support the migration of lymphocytes from the bloodstream into secondary lymphoid tissues, were prominent in BALT. All HEVs expressed peripheral node addressin, most HEVs expressed vascular cell adhesion molecule-1, and no HEVs expressed mucosal addressin cell adhesion molecule-1. CONCLUSION: Human BALT expresses endothelia and lymphocyte adhesion molecules that may be important in recruiting naive and memory/effector lymphocytes to BALT during protective and pathologic bronchopulmonary immune responses

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Perspectives on ethnic and racial disparities in Alzheimer's disease and related dementias: Update and areas of immediate need

Alzheimer's disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART; alz.org/ISTAART) comprises a number of professional interest areas (PIAs), each focusing on a major scientific area associated with ADRDs. We leverage the expertise of the existing international cadre of ISTAART scientists and experts to synthesize a cross‐PIA white paper that provides both a concise "state-of-the-science" report of ethnoracial factors across PIA foci and updated recommendations to address immediate needs to advance ADRD science across ethnoracial populations

Differentiating criminal networks in the illegal wildlife trade: organized, corporate and disorganized crime

Historically, the poaching of wildlife was portrayed as a small-scale local activity in which only small numbers of wildlife would be smuggled illegally by collectors or opportunists. Nowadays, this image has changed: criminal networks are believed to be highly involved in wildlife trafficking, which has become a significant area of illicit activity. Even though wildlife trafficking has become accepted as a major area of crime and an important topic and criminologists have examined a variety of illegal wildlife markets, research that specifically focusses on the involvement of different criminal networks and their specific nature is lacking. The concept of a ‘criminal network’ or ‘serious organized crime’ is amorphous – getting used interchangeably and describes all crime that is structured rather than solely reflecting crime that fits within normative definitions of ‘organized’ crime. In reality, criminal networks are diverse. As such, we propose categories of criminal networks that are evidenced in the literature and within our own fieldwork: (1) organized crime groups (2) corporate crime groups and (3) disorganized criminal networks. Whereas there are instances when these groups act alone, this article will (also) discuss the overlap and interaction that occurs between our proposed categories and discuss the complicated nature of the involved criminal networks as well as predictions as to the future of these networks

Parenting Culture(s): Ideal-Parent Beliefs Across 37 Countries

What is it to be “an ideal parent”? Does the answer differ across countries and social classes? To answer these questions in a way that minimizes bias and ethnocentrism, we used open-ended questions to explore ideal-parent beliefs among 8,357 mothers and 3,517 fathers from 37 countries. Leximancer Semantic Network Analysis was utilized to first determine parenting culture zones (i.e., countries with shared ideal-parent beliefs) and then extract the predominant themes and concepts in each culture zone. The results yielded specific types of ideal-parent beliefs in five parenting culture zones: being “responsible and children/family-focused” for Asian parents, being “responsible and proper demeanor-focused” for African parents, and being “loving and responsible” for Hispanic-Italian parents. Although the most important themes and concepts were the same in the final two zones—being “loving and patient,” there were subtle differences: English-speaking, European Union, and Russian parents emphasized “being caring,” while French-speaking parents valued “listening” or being “present.” Ideal-parent beliefs also differed by education levels within culture zones, but no general pattern was discerned across culture zones. These findings suggest that the country in which parents were born cannot fully explain their differences in ideal-parent beliefs and that differences arising from social class or education level cannot be dismissed. Future research should consider how these differences affect the validity of the measurements in question and how they can be incorporated into parenting intervention research within and across cultures

Parental Burnout Around the Globe: a 42-Country Study

High levels of stress in the parenting domain can lead to parental burnout, a condition that has severe consequences for both parents and children. It is not yet clear, however, whether parental burnout varies by culture, and if so, why it might do so. In this study, we examined the prevalence of parental burnout in 42 countries (17,409 parents; 71% mothers; M_{age} = 39.20) and showed that the prevalence of parental burnout varies dramatically across countries. Analyses of cultural values revealed that individualistic cultures, in particular, displayed a noticeably higher prevalence and mean level of parental burnout. Indeed, individualism plays a larger role in parental burnout than either economic inequalities across countries, or any other individual and family characteristic examined so far, including the number and age of children and the number of hours spent with them. These results suggest that cultural values in Western countries may put parents under heightened levels of stress