On the Algebraic Structure of Gravitational Descendants in CP(n-1) Coset Models

We investigate how specific free-field realizations of twisted N=2 supersymmetric coset models give rise to natural extensions of the ``matter'' Hilbert spaces in such a manner as to incorporate the various gravitational excitations. In particular, we show that adopting a particular screening prescription is equivalent to imposing the requisite equivariance condition on cohomology. We find a simple algebraic characterization of the $W_n$-gravitational ground ring spectra of these theories in terms of affine-$SU(n)$ highest weights..Comment: 12p, harvmac/lanlmac with hyperlinks, 1 uuencoded PostScript figure, CERN-TH.7442/94, USC-94/01

Practicalities of using non-local or non-recent multilocus sequence typing data for source attribution in space and time of human campylobacteriosis

In this study, 1208 Campylobacter jejuni and C. coli isolates from humans and 400 isolates from chicken, collected in two separate periods over 12 years in The Netherlands, were typed using multilocus sequence typing (MLST). Statistical evidence was found for a shift of ST frequencies in human isolates over time. The human MLST data were also compared to published data from other countries to determine geographical variation. Because only MLST typed data from chicken, taken from the same time point and spatial location, were available in addition to the human data, MLST datasets for other Campylobacter reservoirs from selected countries were used. The selection was based on the degree of similarity of the human isolates between countries. The main aim of this study was to better understand the consequences of using non-local or non-recent MLST data for attributing domestically acquired human Campylobacter infections to specific sources of origin when applying the asymmetric island model for source attribution. In addition, a power-analysis was done to find the minimum number of source isolates needed to perform source attribution using an asymmetric island model. This study showed that using source data from other countries can have a significant biasing effect on the attribution results so it is important to carefully select data if the available local data lack in quality and/or quantity. Methods aimed at reducing this bias were proposed

A prediction model for recurrence after translabyrinthine surgery for vestibular schwannoma: toward personalized postoperative surveillance

Purpose The aim of this study is to compute and validate a statistical predictive model for the risk of recurrence, defined as regrowth of tumor necessitating salvage treatment, after translabyrinthine removal of vestibular schwannomas to individualize postoperative surveillance. Methods The multivariable predictive model for risk of recurrence was based on retrospectively collected patient data between 1995 and 2017 at a tertiary referral center. To assess for internal validity of the prediction model tenfold cross-validation was performed. A 'low' calculated risk of recurrence in this study was set at < 1%, based on clinical criteria and expert opinion. Results A total of 596 patients with 33 recurrences (5.5%) were included for analysis. The final prediction model consisted of the predictors 'age at time of surgery', 'preoperative tumor growth' and 'first postoperative MRI outcome'. The area under the receiver operating curve of the prediction model was 89%, with a C-index of 0.686 (95% CI 0.614-0.796) after cross-validation. The predicted probability for risk of recurrence was low (< 1%) in 373 patients (63%). The earliest recurrence in these low-risk patients was detected at 46 months after surgery. Conclusion This study presents a well-performing prediction model for the risk of recurrence after translabyrinthine surgery for vestibular schwannoma. The prediction model can be used to tailor the postoperative surveillance to the estimated risk of recurrence of individual patients. It seems that especially in patients with an estimated low risk of recurrence, the interval between the first and second postoperative MRI can be safely prolonged.Otorhinolaryngolog

Prognostic factors for the outcome of translabyrinthine surgery for vestibular schwannomas

Objective: To identify predictors of tumor recurrence and postoperative facial nerve function after translabyrinthine surgery for unilateral vestibular schwannomas. Study Design: Retrospective study. Setting: Tertiary referral center. Patients: Between 1996 and 2017 a total of 596 patients with unilateral vestibular schwannoma underwent translabyrinthine surgery. Pre- and postoperative clinical status, radiological, and surgical findings were evaluated. Intervention(s): Translabyrinthine surgery. Main Outcome Measure(s): Potential predictors for tumor recurrence and facial nerve outcome were analyzed using Cox regression and ordinal logistic regression, respectively. Results: The extent of tumor removal was total in 32%, near-total in 58%, and subtotal in 10%. In 5.5% (33/596) of patients the tumor recurred. Subtotal tumor resection (p = 0.004, hazard ratios [HR] = 10.66), a young age (p = 0.008, HR = 0.96), and tumor progression preoperatively (p = 0.042, HR = 2.32) significantly increased the risk of recurrence, whereas tumor size or histologic composition did not. A good postoperative facial nerve function (House-Brackmann grade 1-2) was achieved in 85%. The risk of postoperative facial nerve paresis or paralysis increased with tumor size (p < 0.001, OR = 1.52), but was not associated with the extent of tumor removal, histologic composition, or patient demographics. Conclusions: Translabyrinthine surgery is an effective treatment for vestibular schwannoma, with a good local control rate and facial nerve outcome. The extent of tumor removal is a clinically relevant predictor for tumor recurrence, as are young patient age and preoperative tumor progression. A large preoperative tumor size is associated with a higher risk of postoperative facial nerve paresis or paralysis.Development and application of statistical models for medical scientific researc

Risk Factors for Campylobacteriosis of Chicken, Ruminant, and Environmental Origin: A Combined Case-Control and Source Attribution Analysis

Background: Campylobacteriosis contributes strongly to the disease burden of food-borne pathogens. Case-control studies are limited in attributing human infections to the different reservoirs because they can only trace back to the points of exposure, which may not point to the original reservoirs because of cross-contamination. Human Campylobacter infections can be attributed to specific reservoirs by estimating the extent of subtype sharing between strains from humans and reservoirs using multilocus sequence typing (MLST). Methodology/Principal Findings: We investigated risk factors for human campylobacteriosis caused by Campylobacter strains attributed to different reservoirs. Sequence types (STs) were determined for 696 C. jejuni and 41 C. coli strains from endemic human cases included in a case-control study. The asymmetric island model, a population genetics approach for modeling Campylobacter evolution and transmission, attributed these cases to four putative animal reservoirs (chicken, cattle, sheep, pig) and to the environment (water, sand, wild birds) considered as a proxy for other unidentified reservoirs. Most cases were attributed to chicken (66%) and cattle (21%), identified as the main reservoirs in The Netherlands. Consuming chicken was a risk factor for campylobacteriosis caused by chicken-associated STs, whereas consuming beef and pork were protective. Risk factors for campylobacteriosis caused by ruminant-associated STs were contact with animals, barbecuing in non-urban areas, consumption of tripe, and never/seldom chicken consumption. Consuming game and swimming in a domestic swimming pool during springtime were risk factors for campylobacteriosis caused by environment-associated STs. Infections with chicken-and ruminant-associated STs were only partially explained by food-borne transmission; direct contact and environmental pathways were also important. Conclusion/Significance: This is the first case-control study in which risk factors for campylobacteriosis are investigated in relation to the attributed reservoirs based on MLST profiles. Combining epidemiological and source attribution data improved campylobacteriosis risk factor identification and characterization, generated hypotheses, and showed that genotype-based source attribution is epidemiologically sensible

Lentiviral Hematopoietic Stem Cell Gene Therapy Corrects Murine Pompe Disease

Pompe disease is an autosomal recessive lysosomal storage disorder characterized by progressive muscle weakness. The disease is caused by mutations in the acid α-glucosidase (GAA) gene. Despite the currently available enzyme replacement therapy (ERT), roughly half of the infants with Pompe disease die before the age of 3 years. Limitations of ERT are immune responses to the recombinant enzyme, incomplete correction of the disease phenotype, lifelong administration, and inability of the enzyme to cross the blood-brain barrier. We previously reported normalization of glycogen in heart tissue and partial correction of the skeletal muscle phenotype by ex vivo hematopoietic stem cell gene therapy. In the present study, using a codon-optimized GAA (GAAco), the enzyme levels resulted in close to normalization of glycogen in heart, muscles, and brain, and in complete normalization of motor function. A large proportion of microglia in the brain was shown to be GAA positive. All astrocytes contained the enzyme, which is in line with mannose-6-phosphate receptor expression and the key role in glycogen storage and glucose metabolism. The lentiviral vector insertion site analysis confirmed no preference for integration near proto-oncogenes. This correction of murine Pompe disease warrants further development toward a cure of the human condition.This publication reports that stem cell gene therapy using a codon-optimized gene encoding acid α-glucosidase (GAA) cures the mouse model of Pompe disease, a lysosomal storage disorder

Everolimus Exposure and Early Metabolic Response as Predictors of Treatment Outcomes in Breast Cancer Patients Treated with Everolimus and Exemestane

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Avalanche Dynamics in Evolution, Growth, and Depinning Models

The dynamics of complex systems in nature often occurs in terms of punctuations, or avalanches, rather than following a smooth, gradual path. A comprehensive theory of avalanche dynamics in models of growth, interface depinning, and evolution is presented. Specifically, we include the Bak-Sneppen evolution model, the Sneppen interface depinning model, the Zaitsev flux creep model, invasion percolation, and several other depinning models into a unified treatment encompassing a large class of far from equilibrium processes. The formation of fractal structures, the appearance of $1/f$ noise, diffusion with anomalous Hurst exponents, Levy flights, and punctuated equilibria can all be related to the same underlying avalanche dynamics. This dynamics can be represented as a fractal in $d$ spatial plus one temporal dimension. We develop a scaling theory that relates many of the critical exponents in this broad category of extremal models, representing different universality classes, to two basic exponents characterizing the fractal attractor. The exact equations and the derived set of scaling relations are consistent with numerical simulations of the above mentioned models.Comment: 27 pages in revtex, no figures included. Figures or hard copy of the manuscript supplied on reques

Moduli flow and non-supersymmetric AdS attractors

We investigate the attractor mechanism in gauged supergravity in the presence of higher derivatives terms. In particular, we discuss the attractor behaviour of static black hole horizons in anti-de Sitter spacetime by using the effective potential approach as well as Sen's entropy function formalism. We use the holographic techniques to interpret the moduli flow as an RG flow towards the IR attractor horizon. We find that the holographic c-function obeys the expected properties and point out some subtleties in understanding attractors in AdS.Comment: 41 pages, 3 figures, JHEP style; V2: misprints corrected, expanded references; V3: few typo's fixed in section

A new measurement of the Collins and Sivers asymmetries on a transversely polarised deuteron target

New high precision measurements of the Collins and Sivers asymmetries of charged hadrons produced in deep-inelastic scattering of muons on a transversely polarised 6LiD target are presented. The data were taken in 2003 and 2004 with the COMPASS spectrometer using the muon beam of the CERN SPS at 160 GeV/c. Both the Collins and Sivers asymmetries turn out to be compatible with zero, within the present statistical errors, which are more than a factor of 2 smaller than those of the published COMPASS results from the 2002 data. The final results from the 2002, 2003 and 2004 runs are compared with naive expectations and with existing model calculations.Comment: 40 pages, 28 figure