Pain, quality of life and safety outcomes of kyphoplasty for vertebral compression fractures: report of a task force of the American Society for Bone and Mineral Research.

The relative efficacy and harms of balloon kyphoplasty (BK) for treating vertebral compression fractures (VCF) are uncertain. We searched multiple electronic databases to March 2016 for randomised and quasi-randomised controlled trials comparing BK with control treatment (non-surgical management [NSM], percutaneous vertebroplasty [PV], KIVA®, vertebral body stenting, or other) in adults with VCF. Outcomes included back pain, back disability, quality of life (QoL), new VCF and adverse events (AE). One reviewer extracted data, a second checked accuracy, and two rated risk of bias (ROB). Mean differences and 95% confidence intervals were calculated using inverse-variance models. Risk ratios of new VCF and AE were calculated using Mantel-Haenszel models. Ten unique trials enrolled 1,837 participants (age range: 61-76 years, 74% female), all rated as having high or uncertain ROB. Versus NSM, BK was associated with greater reductions in pain, back-related disability, and better QoL (k = 1 trial) that appeared to lessen over time, but were less than minimally clinically important differences. Risk of new VCF at 3 and 12 months was not significantly different (k = 2 trials). Risk of any AE was increased at 1 month (RR = 1.73 [1.36, 2.21]). There were no significant differences between BK and PV in back pain, back disability, QoL, risk of new VCF or any AE (k = 1 to 3 trials). Limitations included lack of a BK versus sham comparison, availability of only one RCT of BK versus NSM, and lack of study blinding. Individuals with painful VCF experienced symptomatic improvement compared with baseline with all interventions. The clinical importance of the greater improvements with BK versus NSM is unclear, may be due to placebo effect, and may not counterbalance short-term AE risks. Outcomes appeared similar between BK and other surgical interventions. Well-conducted randomized trials comparing BK with sham would help resolve remaining uncertainty about the relative benefits and harms of BK. This article is protected by copyright. All rights reserved

Selberg Supertrace Formula for Super Riemann Surfaces III: Bordered Super Riemann Surfaces

This paper is the third in a sequel to develop a super-analogue of the classical Selberg trace formula, the Selberg supertrace formula. It deals with bordered super Riemann surfaces. The theory of bordered super Riemann surfaces is outlined, and the corresponding Selberg supertrace formula is developed. The analytic properties of the Selberg super zeta-functions on bordered super Riemann surfaces are discussed, and super-determinants of Dirac-Laplace operators on bordered super Riemann surfaces are calculated in terms of Selberg super zeta-functions.Comment: 43 pages, amste

Proteome profiling outperforms transcriptome profiling for coexpression based gene function prediction

Coexpression of mRNAs under multiple conditions is commonly used to infer cofunctionality of their gene products despite well-known limitations of this "guilt-by-association" (GBA) approach. Recent advancements in mass spectrometry-based proteomic technologies have enabled global expression profiling at the protein level; however, whether proteome profiling data can outperform transcriptome profiling data for coexpression based gene function prediction has not been systematically investigated. Here, we address this question by constructing and analyzing mRNA and protein coexpression networks for three cancer types with matched mRNA and protein profiling data from The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC). Our analyses revealed a marked difference in wiring between the mRNA and protein coexpression networks. Whereas protein coexpression was driven primarily by functional similarity between coexpressed genes, mRNA coexpression was driven by both cofunction and chromosomal colocalization of the genes. Functionally coherent mRNA modules were more likely to have their edges preserved in corresponding protein networks than functionally incoherent mRNA modules. Proteomic data strengthened the link between gene expression and function for at least 75% of Gene Ontology (GO) biological processes and 90% of KEGG pathways. A web application Gene2Net (http://cptac.gene2net.org) developed based on the three protein coexpression networks revealed novel gene-function relationships, such as linking ERBB2 (HER2) to lipid biosynthetic process in breast cancer, identifying PLG as a new gene involved in complement activation, and identifying AEBP1 as a new epithelial-mesenchymal transition (EMT) marker. Our results demonstrate that proteome profiling outperforms transcriptome profiling for coexpression based gene function prediction. Proteomics should be integrated if not preferred in gene function and human disease studies

Correlations of structural, magnetic, and dielectric properties of undoped and doped CaCu3Ti4O12

The present work reports synthesis, as well as a detailed and careful characterization of structural, magnetic, and dielectric properties of differently tempered undoped and doped CaCu3Ti4O12 (CCTO) ceramics. For this purpose, neutron and x-ray powder diffraction, SQUID measurements, and dielectric spectroscopy have been performed. Mn-, Fe-, and Ni-doped CCTO ceramics were investigated in great detail to document the influence of low-level doping with 3d metals on the antiferromagnetic structure and dielectric properties. In the light of possible magnetoelectric coupling in these doped ceramics, the dielectric measurements were also carried out in external magnetic fields up to 7 T, showing a minor but significant dependence of the dielectric constant on the applied magnetic field. Undoped CCTO is well-known for its colossal dielectric constant in a broad frequency and temperature range. With the present extended characterization of doped as well as undoped CCTO, we want to address the question why doping with only 1% Mn or 0.5% Fe decreases the room-temperature dielectric constant of CCTO by a factor of ~100 with a concomitant reduction of the conductivity, whereas 0.5% Ni doping changes the dielectric properties only slightly. In addition, diffraction experiments and magnetic investigations were undertaken to check for possible correlations of the magnitude of the colossal dielectric constants with structural details or with magnetic properties like the magnetic ordering, the Curie-Weiss temperatures, or the paramagnetic moment. It is revealed, that while the magnetic ordering temperature and the effective moment of all investigated CCTO ceramics are rather similar, there is a dramatic influence of doping and tempering time on the Curie-Weiss constant.Comment: 10 pages, 11 figure

HER2-HER3 heterodimer quantification by FRET-FILM and patient subclass analysis of the COIN colorectal trial

BACKGROUND: The phase 3 MRC COIN trial showed no statistically significant benefit from adding the EGFR-target cetuximab to oxaliplatin-based chemotherapy in first-line treatment of advanced colorectal cancer. This study exploits additional information on HER2-HER3 dimerization to achieve patient stratification and reveal previously hidden subgroups of patients who had differing disease progression and treatment response. METHODS: HER2-HER3 dimerization was quantified by 'FLIM Histology' in primary tumor samples from 550 COIN trial patients receiving oxaliplatin and fluoropyrimidine chemotherapy +/-cetuximab. Bayesian latent class analysis (LCA) and covariate reduction was performed to analyze the effects of HER2-HER3 dimer, RAS mutation and cetuximab on progression-free survival (PFS) and overall survival (OS). All statistical tests were two-sided. RESULTS: LCA on a cohort of 398 patients revealed two patient subclasses with differing prognoses (median OS: 1624 days [95%CI=1466-1816] vs 461 [95%CI=431-504]): Class 1 (15.6%) showed a benefit from cetuximab in OS (HR = 0.43 [95%CI=0.25-0.76]; p = 0.004). Class 2 showed an association of increased HER2-HER3 with better OS (HR = 0.64 [95%CI=0.44-0.94]; p = 0.02). A class prediction signature was formed and tested on an independent validation cohort (N = 152) validating the prognostic utility of the dimer assay. Similar subclasses were also discovered in full trial dataset (N = 1,630) based on 10 baseline clinicopathological and genetic covariates. CONCLUSIONS: Our work suggests that the combined use of HER dimer imaging and conventional mutation analyses will be able to identify a small subclass of patients (>10%) who will have better prognosis following chemotherapy. A larger prospective cohort will be required to confirm its utility in predicting the outcome of anti-EGFR treatment

Astroparticle Physics with a Customized Low-Background Broad Energy Germanium Detector

The MAJORANA Collaboration is building the MAJORANA DEMONSTRATOR, a 60 kg array of high purity germanium detectors housed in an ultra-low background shield at the Sanford Underground Laboratory in Lead, SD. The MAJORANA DEMONSTRATOR will search for neutrinoless double-beta decay of 76Ge while demonstrating the feasibility of a tonne-scale experiment. It may also carry out a dark matter search in the 1-10 GeV/c^2 mass range. We have found that customized Broad Energy Germanium (BEGe) detectors produced by Canberra have several desirable features for a neutrinoless double-beta decay experiment, including low electronic noise, excellent pulse shape analysis capabilities, and simple fabrication. We have deployed a customized BEGe, the MAJORANA Low-Background BEGe at Kimballton (MALBEK), in a low-background cryostat and shield at the Kimballton Underground Research Facility in Virginia. This paper will focus on the detector characteristics and measurements that can be performed with such a radiation detector in a low-background environment.Comment: Submitted to NIMA Proceedings, SORMA XII. 9 pages, 4 figure

Subclone eradication analysis identifies targets for enhanced cancer therapy and reveals L1 retrotransposition as a dynamic source of cancer heterogeneity

Treatment-eradicated cancer subclones have been reported in leukemia and have recently been detected in solid tumors. Here we introduce Differential Subclone Eradication and Resistance Analysis (DSER), a method developed to identify molecular targets for improved therapy by direct comparison of genomic features of eradicated and resistant subclones in pre- and post-treatment samples from a patient with BRCA2-deficient metastatic prostate cancer. FANCI and EYA4 were identified as candidate DNA repair-related targets for converting subclones from resistant to eradicable, and RNAi-mediated depletion of FANCI confirmed it as a potential target. The EYA4 alteration was associated with adjacent L1 transposon insertion during cancer evolution upon treatment, raising questions surrounding the role of therapy in L1 activation. Both carboplatin and enzalutamide turned on L1 transposon machinery in LNCaP and VCaP but not in PC-3 and 22Rv1 prostate cancer cell lines. L1 activation in LNCaP and VCaP was inhibited by the antiretroviral drug azidothymidine. L1 activation was also detected post-castration in LuCaP 77 and LuCaP 105 xenograft models and post-chemotherapy in previously published time-series transcriptomic data from SCC25 head and neck cancer cells. In conclusion DSER provides an informative intermediate step toward effective precision cancer medicine and should be tested in future studies, especially those including dramatic but temporary metastatic tumor regression. L1 transposon activation may be a modifiable source of cancer genomic heterogeneity, suggesting the potential of leveraging newly discovered triggers and blockers of L1 activity to overcome therapy resistance