Quality Improvement Intervention for Reduction of Redundant Testing

Laboratory data are critical to analyzing and improving clinical quality. In the setting of residual use of creatine kinase M and B isoenzyme testing for myocardial infarction, we assessed disease outcomes of discordant creatine kinase M and B isoenzyme +/troponin I (−) test pairs in order to address anticipated clinician concerns about potential loss of case-finding sensitivity following proposed discontinuation of routine creatine kinase and creatine kinase M and B isoenzyme testing. Time-sequenced interventions were introduced. The main outcome was the percentage of cardiac marker studies performed within guidelines. Nonguideline orders dominated at baseline. Creatine kinase M and B isoenzyme testing in 7496 order sets failed to detect additional myocardial infarctions but was associated with 42 potentially preventable admissions/quarter. Interruptive computerized soft stops improved guideline compliance from 32.3% to 58% (P \u3c .001) in services not receiving peer leader intervention and to \u3e80% (P \u3c .001) with peer leadership that featured dashboard feedback about test order performance. This successful experience was recapitulated in interrupted time series within 2 additional services within facility 1 and then in 2 external hospitals (including a critical access facility). Improvements have been sustained postintervention. Laboratory cost savings at the academic facility were estimated to be ≥US$635 000 per year. National collaborative data indicated that facility 1 improved its order patterns from fourth to first quartile compared to peer norms and imply that nonguideline orders persist elsewhere. This example illustrates how pathologists can provide leadership in assisting clinicians in changing laboratory ordering practices. We found that clinicians respond to local laboratory data about their own test performance and that evidence suggesting harm is more compelling to clinicians than evidence of cost savings. Our experience indicates that interventions done at an academic facility can be readily instituted by private practitioners at external facilities. The intervention data also supplement existing literature that electronic order interruptions are more successful when combined with modalities that rely on peer education combined with dashboard feedback about laboratory order performance. The findings may have implications for the role of the pathology laboratory in the ongoing pivot from quantity-based to value-based health care

Effects of Germline VHL Deficiency on Growth, Metabolism, and Mitochondria.

Mutations in VHL, which encodes von Hippel-Lindau tumor suppressor (VHL), are associated with divergent diseases. We describe a patient with marked erythrocytosis and prominent mitochondrial alterations associated with a severe germline VHL deficiency due to homozygosity for a novel synonymous mutation (c.222C→A, p.V74V). The condition is characterized by early systemic onset and differs from Chuvash polycythemia (c.598C→T) in that it is associated with a strongly reduced growth rate, persistent hypoglycemia, and limited exercise capacity. We report changes in gene expression that reprogram carbohydrate and lipid metabolism, impair muscle mitochondrial respiratory function, and uncouple oxygen consumption from ATP production. Moreover, we identified unusual intermitochondrial connecting ducts. Our findings add unexpected information on the importance of the VHL-hypoxia-inducible factor (HIF) axis to human phenotypes. (Funded by Associazione Italiana Ricerca sul Cancro and others.)

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Recessive mutations in SPTBN2 implicate β-III spectrin in both cognitive and motor development

β-III spectrin is present in the brain and is known to be important in the function of the cerebellum. Heterozygous mutations in SPTBN2, the gene encoding β-III spectrin, cause Spinocerebellar Ataxia Type 5 (SCA5), an adult-onset, slowly progressive, autosomal-dominant pure cerebellar ataxia. SCA5 is sometimes known as "Lincoln ataxia," because the largest known family is descended from relatives of the United States President Abraham Lincoln. Using targeted capture and next-generation sequencing, we identified a homozygous stop codon in SPTBN2 in a consanguineous family in which childhood developmental ataxia co-segregates with cognitive impairment. The cognitive impairment could result from mutations in a second gene, but further analysis using whole-genome sequencing combined with SNP array analysis did not reveal any evidence of other mutations. We also examined a mouse knockout of β-III spectrin in which ataxia and progressive degeneration of cerebellar Purkinje cells has been previously reported and found morphological abnormalities in neurons from prefrontal cortex and deficits in object recognition tasks, consistent with the human cognitive phenotype. These data provide the first evidence that β-III spectrin plays an important role in cortical brain development and cognition, in addition to its function in the cerebellum; and we conclude that cognitive impairment is an integral part of this novel recessive ataxic syndrome, Spectrin-associated Autosomal Recessive Cerebellar Ataxia type 1 (SPARCA1). In addition, the identification of SPARCA1 and normal heterozygous carriers of the stop codon in SPTBN2 provides insights into the mechanism of molecular dominance in SCA5 and demonstrates that the cell-specific repertoire of spectrin subunits underlies a novel group of disorders, the neuronal spectrinopathies, which includes SCA5, SPARCA1, and a form of West syndrome

Planck 2013 results. VI. High Frequency Instrument data processing

We describe the processing of the 531 billion raw data samples from the High Frequency Instrument (HFI), which we performed to produce six temperature maps from the first 473 days of Planck-HFI survey data. These maps provide an accurate rendition of the sky emission at 100, 143, 217, 353, 545, and 857GHz with an angular resolution ranging from 9.́7 to 4.́6. The detector noise per (effective) beam solid angle is respectively, 10, 6 , 12, and 39 μK in the four lowest HFI frequency channels (100−353GHz) and 13 and 14 kJy sr-1 in the 545 and 857 GHz channels. Relative to the 143 GHz channel, these two high frequency channels are calibrated to within 5% and the 353 GHz channel to the percent level. The 100 and 217 GHz channels, which together with the 143 GHz channel determine the high-multipole part of the CMB power spectrum (50 <ℓ < 2500), are calibrated relative to 143 GHz to better than 0.2%

Measurement of inclusive π0\pi^{0} production in hadronic Z0Z^{0} decays

An analysis is presented of inclusive \pi^0 production in Z^0 decays measured with the DELPHI detector. At low energies, \pi^0 decays are reconstructed by \linebreak using pairs of converted photons and combinations of converted photons and photons reconstructed in the barrel electromagnetic calorimeter (HPC). At high energies (up to x_p = 2 \cdot p_{\pi}/\sqrt{s} = 0.75) the excellent granularity of the HPC is exploited to search for two-photon substructures in single showers. The inclusive differential cross section is measured as a function of energy for {q\overline q} and {b \bar b} events. The number of \pi^0's per hadronic Z^0 event is N(\pi^0)/ Z_{had}^0 = 9.2 \pm 0.2 \mbox{(stat)} \pm 1.0 \mbox{(syst)} and for {b \bar b}~events the number of \pi^0's is {\mathrm N(\pi^0)/ b \overline b} = 10.1 \pm 0.4 \mbox{(stat)} \pm 1.1 \mbox{(syst)} . The ratio of the number of \pi^0's in b \overline b events to hadronic Z^0 events is less affected by the systematic errors and is found to be 1.09 \pm 0.05 \pm 0.01. The measured \pi^0 cross sections are compared with the predictions of different parton shower models. For hadronic events, the peak position in the \mathrm \xi_p = \ln(1/x_p) distribution is \xi_p^{\star} = 3.90^{+0.24}_{-0.14}. The average number of \pi^0's from the decay of primary \mathrm B hadrons is found to be {\mathrm N} (B \rightarrow \pi^0 \, X)/\mbox{B hadron} = 2.78 \pm 0.15 \mbox{(stat)} \pm 0.60 \mbox{(syst)}

Search for new phenomena using single photon events in the DELPHI detector at LEP

Data are presented on the reaction \epem~\into~\gamma + no other detected particle at center-of-mass energies, \sqs = 89.48 GeV, 91.26 GeV and 93.08 GeV. The cross section for this reaction is related directly to the number of light neutrino generations which couple to the \zz boson, and to several other phenomena such as excited neutrinos, the production of an invisible `X' particle, a possible magnetic moment of the tau neutrino, and neutral monojets. Based on the observed number of single photon events, the number of light neutrinos which couple to the \zz is measured to be N_\nu = 3.15 \pm 0.34. No evidence is found for anomalous production of energetic single photons, and upper limits at the 95\% confidence level are determined for excited neutrino production (BR < 4-9 \times 10^{-6}), production of an invisible `X' particle (\sigma < 0.1 pb), and the magnetic moment of the tau neutrino (< 5.2 \times 10^{-6} \mu_B). No event with the topology of a neutral monojet is found, and this corresponds to the limit \sigma < 0.044/\epsilon pb at the 95\% confidence level, where \epsilon is the unknown overall monojet detection efficiency

Energy dependence of the differences between the quark and gluon jet fragmentation

Three jet events arising from decays of the Z boson, collected by the DELPHI detector, were used to measure differences in quark and gluon fragmentation. Gluon jets were anti-tagged by identifying b quark jets. Unbiased quark jets came from events with two jets plus one photon. Quark and gluon jet properties in different energy ranges were compared for the first time within the same detector. Quark and gluon jets of nearly the same energy in symmetric three jet event topologies were also compared. Using three independent methods, the average value of the ratio of the mean charged multiplicities of gluon and quark jets is $$=1.241\pm 0.015\ (stat.) \pm 0.025\ (syst.).$$ Gluon jets are broader and produce fragments with a softer energy spectrum than quark jets of equivalent energy. The string effect has been observed in fully symmetric three jet events. The measured ratio R_{\gamma} of the charged particle flow in the q\overline{q} inter-jet region of the q\bar{q}g and q\bar{q}\gamma samples agrees with the perturbative QCD expectation. The dependence of the mean charged multiplicity on the hadronic center-of-mass energy was analysed in photon plus n-jet events. The value for \alpha_s(M_Z) determined from these data using a QCD prediction with corrections at leading and next-to-leading order is \[ \alpha_s(M_Z)=0.116 \pm 0.003\ (stat.) \pm 0.009\ (syst.). \