Beam-Gas Imaging at the LHCb experiment

This thesis presents a new absolute luminosity calibration measurement at the LHCb experiment for pp collsions at √s = 13 TeV measured via the beam-gas imaging (BGI) technique with data acquired in the 2016 luminosity calibration session. The measured reference cross- sections under these conditions for the Track and Vertex counters are σTrack = 65.82 ± 1.14mb and σVertex = 60.00 ± 0.98 mb, respectively. The principle of the BGI technique is set out and the BGI measurements from 2016 are presented alongside beam imaging results from a broader set of run 2 calibration data. The procedure for determining the vertex position resolution from collision data via the split vertex method, a crucial element of a precise BGI measurement, is described and measurements of this resolution are reported. With a precise knowledge of the detector resolution it is possible to accurately measure the LHC beam profiles and parameters on a bunch-by-bunch level from their interactions with gas molecules in the LHCb beam pipe and with each other. This allows for a precise evaluation of the overlap integral, a quantity that is directly proportional to the luminosity produced at a collider. The circulating bunch populations are measured by LHC instrumentation and the results relevant for the calibration measurement are presented. Ghost charge results measured via the BGI technique are reported, including the first such measurements made with the VELO subdetector in its open position and with the first xenon beams circulating in the LHC. The utility of the LHCb measurement as a cross-check on measurements from LHC instrumentation is demonstrated and a novel timing technique making use of the LHCb Outer Tracker is set out. The additional timing information from this subdetector permits the first LHCb measurement of the longitudinal LHC beam profile with a time granularity less than 25 ns. The luminosity calibration cross-section results are then reported and the full range of systematic uncertainties affecting this measurement are evaluated. The reference cross-section for the Track counter, used for the luminosity determination in LHCb physics data, is determined to a precision of 1.73%. Two additional studies that make use of beam-gas interactions at LHCb are also included. The first is a collaborative effort in which a cross-calibration of all existing bunch profile measurement techniques at the LHC was performed. The second looks at possible dynamic vacuum effects due to the movement of the VELO subdetector and relies on a novel vertexing approach making use of the LHCb experiment’s downstream tracking stations. This approach demonstrates a statistically significant pressure increase within the VELO volume due to its movement, at 2.6 standard deviations

A theorem on single-peaked preference functions in one dimension

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22790/1/0000346.pd

A factorial approach to job families

This is an experimental study of the application of factor analysis to a new domain—the formation of job families. Correlations between jobs are computed from the formula based on the number of common elements between two variables and the job analyses provide the basic data on the presence or absence of the elements. A first-order general factor and four common factors are obtained in a small sample of twenty occupations. Tentative interpretations are made and implications for job analysis and the formation of job families are pointed out.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45685/1/11336_2005_Article_BF02290138.pd

Australian Group on Antimicrobial Resistance Australian Enterobacteriaceae Sepsis Outcome Programme annual report, 2014

The Australian Group on Antimicrobial Resistance performs regular period-prevalence studies to monitor changes in antimicrobial resistance in selected enteric Gram-negative pathogens. The 2014 survey was the second year to focus on blood stream infections. During 2014, 5,798 Enterobacteriaceae species isolates were tested using commercial automated methods (Vitek 2, BioMérieux; Phoenix, BD) and results were analysed using the Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints (January 2015). Of the key resistances, non-susceptibility to the third-generation cephalosporin, ceftriaxone, was found in 9.0%/9.0% of Escherichia coli (CLSI/EUCAST criteria) and 7.8%/7.8% of Klebsiella pneumoniae, and 8.0%/8.0% K. oxytoca. Non-susceptibility rates to ciprofloxacin were 10.4%/11.6% for E. coli, 5.0%/7.7% for K. pneumoniae, 0.4%/0.4% for K. oxytoca, and 3.5%/6.5% in Enterobacter cloacae. Resistance rates to piperacillin-tazobactam were 3.2%/6.8%, 4.8%/7.2%, 11.1%/11.5%, and 19.0%/24.7% for the same 4 species respectively. Fourteen isolates were shown to harbour a carbapenemase gene, 7 blaIMP-4, 3 blaKPC-2, 3 blaVIM-1, 1 blaNDM-4, and 1 blaOXA-181-lke

Distinct emphysema subtypes defined by quantitative CT analysis are associated with specific pulmonary matrix metalloproteinases

BACKGROUND: Emphysema is characterised by distinct pathological sub-types, but little is known about the divergent underlying aetiology. Matrix-metalloproteinases (MMPs) are proteolytic enzymes that can degrade the extracellular matrix and have been identified as potentially important in the development of emphysema. However, the relationship between MMPs and emphysema sub-type is unknown. We investigated the role of MMPs and their inhibitors in the development of emphysema sub-types by quantifying levels and determining relationships with these sub-types in mild-moderate COPD patients and ex/current smokers with preserved lung function.METHODS: Twenty-four mild-moderate COPD and 8 ex/current smokers with preserved lung function underwent high resolution CT and distinct emphysema sub-types were quantified using novel local histogram-based assessment of lung density. We analysed levels of MMPs and tissue inhibitors of MMPs (TIMPs) in bronchoalveolar lavage (BAL) and assessed their relationship with these emphysema sub-types.RESULTS: The most prevalent emphysema subtypes in COPD subjects were mild and moderate centrilobular (CLE) emphysema, while only small amounts of severe centrilobular emphysema, paraseptal emphysema (PSE) and panlobular emphysema (PLE) were present. MMP-3, and -10 associated with all emphysema sub-types other than mild CLE, while MMP-7 and -8 had associations with moderate and severe CLE and PSE. MMP-9 also had associations with moderate CLE and paraseptal emphysema. Mild CLE occurred in substantial quantities irrespective of whether airflow obstruction was present and did not show any associations with MMPs.CONCLUSION: Multiple MMPs are directly associated with emphysema sub-types identified by CT imaging, apart from mild CLE. This suggests that MMPs play a significant role in the tissue destruction seen in the more severe sub-types of emphysema, whereas early emphysematous change may be driven by a different mechanism.TRIAL REGISTRATION: Trial registration number NCT01701869

Isolation and Characterization of Polymorphic Microsatellite Loci from Metapenaeopsis barbata Using PCR-Based Isolation of Microsatellite Arrays (PIMA)

The red-spot prawn, Metapenaeopsis barbata, is a commercially important, widely distributed demersal species in the Indo-West Pacific Ocean. Overfishing has made its populations decline in the past decade. To study conservation genetics, eight polymorphic microsatellite loci were isolated. Genetic characteristics of the SSR (simple sequence repeat) fingerprints were estimated in 61 individuals from adjacent seas of Taiwan and China. The number of alleles, ranging from 2 to 4, as well as observed and expected heterozygosities in populations, ranging from 0.048 to 0.538, and 0.048 and 0.654, respectively, were detected. No deviation from Hardy–Weinberg expectations was detected at either locus. No significant linkage disequilibrium was detected in locus pairs. The polymorphic microsatellite loci will be useful for investigations of the genetic variation, population structure, and conservation genetics of this species

Allogeneic stem cell transplantation for chronic lymphocytic leukemia in the era of novel agents.

Although novel agents (NAs) have improved outcomes for patients with chronic lymphocytic leukemia (CLL), a subset will progress through all available NAs. Understanding outcomes for potentially curative modalities including allogeneic hematopoietic stem cell transplantation (alloHCT) following NA therapy is critical while devising treatment sequences aimed at long-term disease control. In this multicenter, retrospective cohort study, we examined 65 patients with CLL who underwent alloHCT following exposure to ≥1 NA, including baseline disease and transplant characteristics, treatment preceding alloHCT, transplant outcomes, treatment following alloHCT, and survival outcomes. Univariable and multivariable analyses evaluated associations between pre-alloHCT factors and progression-free survival (PFS). Twenty-four-month PFS, overall survival (OS), nonrelapse mortality, and relapse incidence were 63%, 81%, 13%, and 27% among patients transplanted for CLL. Day +100 cumulative incidence of grade III-IV acute graft-vs-host disease (GVHD) was 24%; moderate-severe GVHD developed in 27%. Poor-risk disease characteristics, prior NA exposure, complete vs partial remission, and transplant characteristics were not independently associated with PFS. Hematopoietic cell transplantation-specific comorbidity index independently predicts PFS. PFS and OS were not impacted by having received NAs vs both NAs and chemoimmunotherapy, 1 vs ≥2 NAs, or ibrutinib vs venetoclax as the line of therapy immediately pre-alloHCT. AlloHCT remains a viable long-term disease control strategy that overcomes adverse CLL characteristics. Prior NAs do not appear to impact the safety of alloHCT, and survival outcomes are similar regardless of number of NAs received, prior chemoimmunotherapy exposure, or NA immediately preceding alloHCT. Decisions about proceeding to alloHCT should consider comorbidities and anticipated response to remaining therapeutic options

COBALT: A Confirmatory Trial of Obeticholic Acid in Primary Biliary Cholangitis With Placebo and External Controls.

ObjectivesObeticholic acid (OCA) treatment for primary biliary cholangitis (PBC) was conditionally approved in the phase 3 POISE trial. The COBALT confirmatory trial assessed whether clinical outcomes in PBC patients improve with OCA therapy.MethodsPatients randomized to OCA (5-10 mg) were compared with placebo (randomized controlled trial [RCT]) or external control (EC). The primary composite endpoint was time to death, liver transplant, model for end-stage liver disease score ≥15, uncontrolled ascites, or hospitalization for hepatic decompensation. A prespecified propensity score-weighted EC group was derived from a US healthcare claims database.ResultsIn the RCT, the primary endpoint occurred in 28.6% of OCA (n=168) and 28.9% of placebo patients (n=166; intent-to-treat [ITT] analysis hazard ratio [HR]=1.01, 95% CI=0.68-1.51), but functional unblinding and crossover to commercial therapy occurred, especially in the placebo arm. Correcting for these using inverse probability of censoring weighting (IPCW) and as-treated analyses shifted the HR to favor OCA. In the EC (n=1051), the weighted primary endpoint occurred in 10.1% of OCA and 21.5% of non-OCA patients (HR=0.39; 95% CI=0.22-0.69; P=0.001). No new safety signals were identified in the RCT.ConclusionsFunctional unblinding and treatment crossover, particularly in the placebo arm, confounded the ITT estimate of outcomes associated with OCA in the RCT. Comparison with the real-world EC showed that OCA treatment significantly reduced the risk of negative clinical outcomes. These analyses demonstrate the value of EC data in confirmatory trials and suggest that treatment with OCA improves clinical outcomes in patients with PBC

New Forearm Elements Discovered of Holotype Specimen Australovenator wintonensis from Winton, Queensland, Australia

New skeletal elements are reported of the holotype specimen Australovenator wintonensis, from the type locality, near Winton, central western Queensland. New elements include left and right humeri, right radius, right radiale, right distal carpal 1, near complete right metacarpal I, left manual phalanx II-1, left manual phalanx II-2, near complete left manual phalanx II-3 and a left manual phalanx III-3. These new elements combined with those previously described are compared against other neovenatorids

Reactivation of tectonics, crustal underplating, and uplift after 60 Myr of passive subsidence, Raukumara Basin, Hikurangi-Kermadec fore arc, New Zealand: implications for global growth and recycling of continents

We use seismic reflection and refraction data to determine crustal structure, to map a fore-arc basin containing 12 km of sediment, and to image the subduction thrust at 35 km depth. Seismic reflection megasequences within the basin are correlated with onshore geology: megasequence X, Late Cretaceous and Paleogene marine passive margin sediments; megasequence Y, a similar to 10,000 km(3) submarine landslide emplaced during subduction initiation at 22 Ma; and megasequence Z, a Neogene subduction margin megasequence. The Moho lies at 17 km beneath the basin center and at 35 km at the southern margin. Beneath the western basin margin, we interpret reflective units as deformed Gondwana fore-arc sediment that was thrust in Cretaceous time over oceanic crust 7 km thick. Raukumara Basin has normal faults at its western margin and is uplifted along its eastern and southern margins. Raukumara Basin represents a rigid fore-arc block > 150 km long, which contrasts with widespread faulting and large Neogene vertical axis rotations farther south. Taper of the western edge of allochthonous unit Y and westward thickening and downlap of immediately overlying strata suggest westward or northwestward paleoslope and emplacement direction rather than southwestward, as proposed for the correlative onshore allochthon. Spatial correlation between rock uplift of the eastern and southern basin margins with the intersection between Moho and subduction thrust leads us to suggest that crustal underplating is modulated by fore-arc crustal thickness. The trench slope has many small extensional faults and lacks coherent internal reflections, suggesting collapse of indurated rock, rather than accretion of > 1 km of sediment from the downgoing plate. The lack of volcanic intrusion east of the active arc, and stratigraphic evidence for the broadening of East Cape Ridge with time, suggests net fore-arc accretion since 22 Ma. We propose a cyclical fore-arc kinematic: rock moves down a subduction channel to near the base of the crust, where underplating drives rock uplift, oversteepens the trench slope, and causes collapse toward the trench and subduction channel. Cyclical rock particle paths led to persistent trench slope subsidence during net accretion. Existing global estimates of fore-arc loss are systematically too high because they assume vertical particle paths. Citation: Sutherland, R., et al. (2009), Reactivation of tectonics, crustal underplating, and uplift after 60 Myr of passive subsidence, Raukumara Basin, Hikurangi-Kermadec fore arc, New Zealand: Implications for global growth and recycling of continents, Tectonics, 28, TC5017, doi: 10.1029/2008TC002356