Distinguishing Asthma Phenotypes Using Machine Learning Approaches.

Asthma is not a single disease, but an umbrella term for a number of distinct diseases, each of which are caused by a distinct underlying pathophysiological mechanism. These discrete disease entities are often labelled as asthma endotypes. The discovery of different asthma subtypes has moved from subjective approaches in which putative phenotypes are assigned by experts to data-driven ones which incorporate machine learning. This review focuses on the methodological developments of one such machine learning technique-latent class analysis-and how it has contributed to distinguishing asthma and wheezing subtypes in childhood. It also gives a clinical perspective, presenting the findings of studies from the past 5 years that used this approach. The identification of true asthma endotypes may be a crucial step towards understanding their distinct pathophysiological mechanisms, which could ultimately lead to more precise prevention strategies, identification of novel therapeutic targets and the development of effective personalized therapies

A cost and performance comparison of Public Private Partnership and public hospitals in Spain

© 2016 Caballer-Tarazona and Vivas-Consuelo. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The Erratum to this article has been published in Health Economics Review 2016 6:20[EN] Public-private partnership (PPP) initiatives are extending around the world, especially in Europe, as an innovation to traditional public health systems, with the intention of making them more efficient. There is a varied range of PPP models with different degrees of responsibility from simple public sector contracts with the private, up to the complete privatisation of the service. As such, we may say the involvement of the private sector embraces the development, financing and provision of public infrastructures and delivery services. In this paper, one of the oldest PPP initiatives developed in Spain and transferred to other European and Latin American countries is evaluated for first time: the integrated healthcare delivery Alzira model. Through a comparison of public and PPP hospital performance, cost and quality indicators, the efficiency of the PPP experience in five hospitals is evaluated to identify the influence of private management in the results. Regarding the performance and efficiency analysis, it is seen that the PPP group obtains good results, above the average, but not always better than those directly managed. It is necessary to conduct studies with a greater number of PPP hospitals to obtain conclusive results.Caballer Tarazona, M.; Vivas Consuelo, DJJ. (2016). A cost and performance comparison of Public Private Partnership and public hospitals in Spain. Health Economics Review. 6(17):1-7. doi:10.1186/s13561-016-0095-5S17617La Forgia GM, Harding A. Public-Private Partnerships and Public Hospital Performance in Sao Paulo, Brazil. Health Aff. 2009;28(4):1114–26.Vecchi V, Hellowell M, Longo F. Are Italian healthcare organizations paying too much for their public-private partnerships? Public Money Manage. 2010;30(2):125–32.Hellowell M, Pollock AM. The private financing of NHS hospitals: politics, policy and practice. Econ Aff. 2009;29(1):13–9.McIntosh N, Grabowski A, Jack B, Nkabane-Nkholongo EL, Vian T. A public-private partnership improves clinical performance in a hospital network in Lesotho. Health Aff. 2015;34(6):954–62.Roehrich JK, Lewis MA, George G. Are public–private partnerships a healthy option? A systematic literature review. Soc Sci Med. 2014;113:110–9.Barlow J, Roehrich J, Wright S. Europe sees mixed results from public-private partnerships for building and managing health care facilities and services. Health Aff. 2013;32(1):146–54.Hoppe EI, Kusterer DJ, Schmitz PW. Public-private partnerships versus traditional procurement: an experimental investigation. J Econ Behav Organ. 2013;89:145–66.Vivas-Consuelo D, Uso-Talamantes R, Trillo-Mata JL, Caballer-Tarazona M, Barrachina-Martinez I, Buigues-Pastor L. Predictability of pharmaceutical spending in primary health services using Clinical Risk Groups. Health Policy. 2014;116(2-3):188–95.Lopez-Casasnovas G, Costa-Font J, Planas I. Diversity and regional inequalities in the Spanish ‘system of health care services’. Health Econ. 2005;14 Suppl 1:S221–S35.Spain NHSo. National Health System of Spain. National Health System of Spain; 2010.McKee M, Edwards N, Atun R. Public-private partnerships for hospitals. Bull World Health Organ. 2006;84(11):890–6.Caballer-Tarazona M, Moya-Clemente I, Vivas-Consuelo D, Barrachina-Martínez I. A model to measure the efficiency of hospital performance. Math Comput Model. 2010;52(7-8):1095–102.Barlow J, Roehrich JK, Wright S. De facto privatization or a renewed role for the EU? Paying for Europe’s healthcare infrastructure in a recession. J R Soc Med. 2010;103(2):51–5.Herr A, Schmitz H, Augurzky B. Profit efficiency and ownership of German hospitals. Health Econ. 2011;20(6):660–74.Alonso JM, Clifton J, Díaz-Fuentes D. The impact of New Public Management on efficiency: an analysis of Madrid’s hospitals. Health Policy. 2015;119(3):333–40.IASIST. Desarrollo metodológico de los indicadores ajustados 2009 [cited 2015 July 26]. Available from: ( http://www.iasist.com/archivos/top20-2009-metodologia_161215235006.pdf ). Accessed Sept 2015.Hollingsworth B. The measurement of efficiency and productivity of health care delivery. Health Econ. 2008;17(10):1107–28.Ozgen H, Ozcan YA. A national study of efficiency for dialysis centers: an examination of market competition and facility characteristics for production of multiple dialysis outputs. Health Serv Res. 2002;37(3):711–32.Valdmanis VG, Rosko MD, Mutter RL. Hospital quality, efficiency, and input slack differentials. Health Serv Res. 2008;43(5):1830–48.Acerete B, Stafford A, Stapleton P. Spanish healthcare public private partnerships: The ‘Alzira model’. Crit Perspect Account. 2011;22(6):533–49.Allard G, Trabant A. Public-private partnerships in Spain: lessons and opportunities. Int Business Econ Res J. 2008;7(2):1–24.Shaoul J, Stafford A, Stapleton P. The cost of using private finance to build, finance and operate hospitals. Public Money Manage. 2008;28(2):101–8

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

Epigenetic Regulation of Histone H3 Serine 10 Phosphorylation Status by HCF-1 Proteins in C. elegans and Mammalian Cells

BACKGROUND: The human herpes simplex virus (HSV) host cell factor HCF-1 is a transcriptional coregulator that associates with both histone methyl- and acetyltransferases, and a histone deacetylase and regulates cell proliferation and division. In HSV-infected cells, HCF-1 associates with the viral protein VP16 to promote formation of a multiprotein-DNA transcriptional activator complex. The ability of HCF proteins to stabilize this VP16-induced complex has been conserved in diverse animal species including Drosophila melanogaster and Caenorhabditis elegans suggesting that VP16 targets a conserved cellular function of HCF-1. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the role of HCF proteins in animal development, we have characterized the effects of loss of the HCF-1 homolog in C. elegans, called Ce HCF-1. Two large hcf-1 deletion mutants (pk924 and ok559) are viable but display reduced fertility. Loss of Ce HCF-1 protein at reduced temperatures (e.g., 12 degrees C), however, leads to a high incidence of embryonic lethality and early embryonic mitotic and cytokinetic defects reminiscent of mammalian cell-division defects upon loss of HCF-1 function. Even when viable, however, at normal temperature, mutant embryos display reduced levels of phospho-histone H3 serine 10 (H3S10P), a modification implicated in both transcriptional and mitotic regulation. Mammalian cells with defective HCF-1 also display defects in mitotic H3S10P status. CONCLUSIONS/SIGNIFICANCE: These results suggest that HCF-1 proteins possess conserved roles in the regulation of cell division and mitotic histone phosphorylation

The effectiveness and cost-evaluation of manual therapy and physical therapy in patients with sub-acute and chronic non specific neck pain. Rationale and design of a Randomized Controlled Trial (RCT)

Contains fulltext : 88910.pdf (publisher's version ) (Open Access)BACKGROUND: Manual Therapy applied to patients with non specific neck pain has been investigated several times. In the Netherlands, manual therapy as applied according to the Utrecht School of Manual Therapy (MTU) has not been the subject of a randomized controlled trial. MTU differs in diagnoses and treatment from other forms of manual therapy. METHODS/DESIGN: This is a single blind randomized controlled trial in patients with sub-acute and chronic non specific neck pain. Patients with neck complaints existing for two weeks (minimum) till one year (maximum) will participate in the trial. 180 participants will be recruited in thirteen primary health care centres in the Netherlands.The experimental group will be treated with MTU during a six week period. The control group will be treated with physical therapy (standard care, mainly active exercise therapy), also for a period of six weeks.Primary outcomes are Global Perceived Effect (GPE) and functional status (Neck Disability Index (NDI-DV)). Secondary outcomes are neck pain (Numeric Rating Scale (NRS)), Eurocol, costs and quality of life (SF36). DISCUSSION: This paper presents details on the rationale of MTU, design, methods and operational aspects of the trial. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00713843

The stranding anomaly as population indicator: the case of Harbour Porpoise <i>Phocoena phocoena</i> in North-Western Europe

Ecological indicators for monitoring strategies are expected to combine three major characteristics: ecological significance, statistical credibility, and cost-effectiveness. Strategies based on stranding networks rank highly in cost-effectiveness, but their ecological significance and statistical credibility are disputed. Our present goal is to improve the value of stranding data as population indicator as part of monitoring strategies by constructing the spatial and temporal null hypothesis for strandings. The null hypothesis is defined as: small cetacean distribution and mortality are uniform in space and constant in time. We used a drift model to map stranding probabilities and predict stranding patterns of cetacean carcasses under H-0 across the North Sea, the Channel and the Bay of Biscay, for the period 1990-2009. As the most common cetacean occurring in this area, we chose the harbour porpoise <i>Phocoena phocoena</i> for our modelling. The difference between these strandings expected under H-0 and observed strandings is defined as the stranding anomaly. It constituted the stranding data series corrected for drift conditions. Seasonal decomposition of stranding anomaly suggested that drift conditions did not explain observed seasonal variations of porpoise strandings. Long-term stranding anomalies increased first in the southern North Sea, the Channel and Bay of Biscay coasts, and finally the eastern North Sea. The hypothesis of changes in porpoise distribution was consistent with local visual surveys, mostly SCANS surveys (1994 and 2005). This new indicator could be applied to cetacean populations across the world and more widely to marine megafauna

MRI of the kidney—state of the art

Ultrasound and computed tomography (CT) are modalities of first choice in renal imaging. Until now, magnetic resonance imaging (MRI) has mainly been used as a problem-solving technique. MRI has the advantage of superior soft-tissue contrast, which provides a powerful tool in the detection and characterization of renal lesions. The MRI features of common and less common renal lesions are discussed as well as the evaluation of the spread of malignant lesions and preoperative assessment. MR urography technique and applications are discussed as well as the role of MRI in the evaluation of potential kidney donors. Furthermore the advances in functional MRI of the kidney are highlighted

Towards a Physiology-Based Measure of Pain: Patterns of Human Brain Activity Distinguish Painful from Non-Painful Thermal Stimulation

Pain often exists in the absence of observable injury; therefore, the gold standard for pain assessment has long been self-report. Because the inability to verbally communicate can prevent effective pain management, research efforts have focused on the development of a tool that accurately assesses pain without depending on self-report. Those previous efforts have not proven successful at substituting self-report with a clinically valid, physiology-based measure of pain. Recent neuroimaging data suggest that functional magnetic resonance imaging (fMRI) and support vector machine (SVM) learning can be jointly used to accurately assess cognitive states. Therefore, we hypothesized that an SVM trained on fMRI data can assess pain in the absence of self-report. In fMRI experiments, 24 individuals were presented painful and nonpainful thermal stimuli. Using eight individuals, we trained a linear SVM to distinguish these stimuli using whole-brain patterns of activity. We assessed the performance of this trained SVM model by testing it on 16 individuals whose data were not used for training. The whole-brain SVM was 81% accurate at distinguishing painful from non-painful stimuli (p<0.0000001). Using distance from the SVM hyperplane as a confidence measure, accuracy was further increased to 84%, albeit at the expense of excluding 15% of the stimuli that were the most difficult to classify. Overall performance of the SVM was primarily affected by activity in pain-processing regions of the brain including the primary somatosensory cortex, secondary somatosensory cortex, insular cortex, primary motor cortex, and cingulate cortex. Region of interest (ROI) analyses revealed that whole-brain patterns of activity led to more accurate classification than localized activity from individual brain regions. Our findings demonstrate that fMRI with SVM learning can assess pain without requiring any communication from the person being tested. We outline tasks that should be completed to advance this approach toward use in clinical settings