Chromosome 9p deletion in clear cell renal cell carcinoma predicts recurrence and survival following surgery

BACKGROUND: Wider clinical applications of 9p status in clear cell renal cell carcinoma (ccRCC) are limited owing to the lack of validation and consensus for interphase fluorescent in situ hybridisation (I-FISH) scoring technique. The aim of this study was to analytically validate the applicability of I-FISH in assessing 9p deletion in ccRCC and to clinically assess its long-term prognostic impact following surgical excision of ccRCC. METHODS: Tissue microarrays were constructed from 108 renal cell carcinoma (RCC) tumour paraffin blocks. Interphase fluorescent in situ hybridisation analysis was undertaken based on preset criteria by two independent observers to assess interobserver variability. 9p status in ccRCC tumours was determined and correlated to clinicopathological variables, recurrence-free survival and disease-specific survival. RESULTS: There were 80 ccRCCs with valid 9p scoring and a median follow-up of 95 months. Kappa statistic for interobserver variability was 0.71 (good agreement). 9p deletion was detected in 44% of ccRCCs. 9p loss was associated with higher stage, larger tumours, necrosis, microvascular and renal vein invasion, and higher SSIGN (stage, size, grade and necrosis) score. Patients with 9p-deleted ccRCC were at a higher risk of recurrence (P=0.008) and RCC-specific mortality (P=0.001). On multivariate analysis, 9p deletion was an independent predictor of recurrence (hazard ratio 4.323; P=0.021) and RCC-specific mortality (hazard ratio 4.603; P=0.007). The predictive accuracy of SSIGN score improved from 87.7% to 93.1% by integrating 9p status to the model (P=0.001). CONCLUSIONS: Loss of 9p is associated with aggressive ccRCC and worse prognosis in patients following surgery. Our findings independently confirm the findings of previous reports relying on I-FISH to detect 9p (CDKN2A) deletion

Evaluating New Interactions in Healthcare: Challenges and Approaches

New technologies for supporting the provision of healthcare are increasingly pervasive. While healthcare computing previously referred to a desktop computer within the consulting room, we are now seeing an ever broader range of software, hardware and settings. This workshop is concerned with how to conduct evaluations which allow assessment of the overall impact of technology. The workshop will explore challenges and approaches for evaluating new interactions in healthcare. In this paper we outline the goals for this workshop and summarize the issues and questions it intends to explore

After the Standard Model: New Resonances at the LHC

Experiments will soon start taking data at CERN's Large Hadron Collider (LHC) with high expectations for discovery of new physics phenomena. Indeed, the LHC's unprecedented center-of-mass energy will allow the experiments to probe an energy regime where the standard model is known to break down. In this article, the experiments' capability to observe new resonances in various channels is reviewed.Comment: Preprint version of a Brief Review for Modern Physics Letters A. Changes w.r.t. the fully corrected version are smal

RNA-seq reveals the pan-transcriptomic impact of attenuating the gliotoxin self-protection mechanism in Aspergillus fumigatus.

BACKGROUND: Aspergillus fumigatus produces a number of secondary metabolites, one of which, gliotoxin, has been shown to exhibit anti-fungal activity. Thus, A. fumigatus must be able to protect itself against gliotoxin. Indeed one of the genes in the gliotoxin biosynthetic gene cluster in A. fumigatus, gliT, is required for self-protection against the toxin- however the global self-protection mechanism deployed is unclear. RNA-seq was employed to identify genes differentially regulated upon exposure to gliotoxin in A. fumigatus wild-type and A. fumigatus ∆gliT, a strain that is hypersensitive to gliotoxin. RESULTS: Deletion of A. fumigatus gliT resulted in altered expression of 208 genes (log2 fold change of 1.5) when compared to A. fumigatus wild-type, of which 175 genes were up-regulated and 33 genes were down-regulated. Expression of 164 genes was differentially regulated (log2 fold change of 1.5) in A. fumigatus wild-type when exposed to gliotoxin, consisting of 101 genes with up-regulated expression and 63 genes with down-regulated expression. Interestingly, a much larger number of genes, 1700, were found to be differentially regulated (log2 fold change of 1.5) in A. fumigatus ∆gliT when challenged with gliotoxin. These consisted of 508 genes with up-regulated expression, and 1192 genes with down-regulated expression. Functional Catalogue (FunCat) classification of differentially regulated genes revealed an enrichment of genes involved in both primary metabolic functions and secondary metabolism. Specifically, genes involved in gliotoxin biosynthesis, helvolic acid biosynthesis, siderophore-iron transport genes and also nitrogen metabolism genes and ribosome biogenesis genes underwent altered expression. It was confirmed that gliotoxin biosynthesis is induced upon exposure to exogenous gliotoxin, production of unrelated secondary metabolites is attenuated in A. fumigatus ∆gliT, while quantitative proteomic analysis confirmed disrupted translation in A. fumigatus ∆gliT challenged with exogenous gliotoxin. CONCLUSIONS: This study presents the first global investigation of the transcriptional response to exogenous gliotoxin in A. fumigatus wild-type and the hyper-sensitive strain, ∆gliT. Our data highlight the global and extensive affects of exogenous gliotoxin on a sensitive strain devoid of a self-protection mechanism and infer that GliT functionality is required for the optimal biosynthesis of selected secondary metabolites in A. fumigatus

Global bifurcation of homoclinic trajectories of discrete dynamical systems

We prove the existence of an unbounded connected branch of nontrivial homoclinic trajectories of a family of discrete nonautonomous asymptotically hyperbolic systems parametrized by a circle under assumptions involving the topological properties of the asymptotic stable bundles.Comment: 28 pages. arXiv admin note: text overlap with arXiv:1111.140

AdS Field Theory from Conformal Field Theory

We provide necessary and sufficient conditions for a Conformal Field Theory to have a description in terms of a perturbative Effective Field Theory in AdS. The first two conditions are well-known: the existence of a perturbative `1/N' expansion and an approximate Fock space of states generated by a finite number of low-dimension operators. We add a third condition, that the Mellin amplitudes of the CFT correlators must be well-approximated by functions that are bounded by a polynomial at infinity in Mellin space, or in other words, that the Mellin amplitudes have an effective theory-type expansion. We explain the relationship between our conditions and unitarity, and provide an analogy with scattering amplitudes that becomes exact in the flat space limit of AdS. The analysis also yields a simple connection between conformal blocks and AdS diagrams, providing a new calculational tool very much in the spirit of the S-Matrix program. We also begin to explore the potential pathologies associated with higher spin fields in AdS by generalizing Weinberg's soft theorems to AdS/CFT. The AdS analog of Weinberg's argument constrains the interactions of conserved currents in CFTs, but there are potential loopholes that are unavailable to theories of massless higher spin particles in flat spacetime.Comment: 31+7 pages, 5 figure

Mineral rich algae with pine bark improved pain, physical function and analgesic use in mild-knee joint osteoarthritis, compared to Glucosamine: a randomized controlled pilot trial

IntroductionOsteoarthritis (OA) is characterised by synovial joint pain, functional disability and affects ∼13% of people worldwide, of which ∼16-27% report Knee-OA (KOA). Glucosamine (Glu) is the most widely used nutraceutical treatment for OA despite a lack of scientific consensus, therefore alternative nutraceutical treatments are required. The aim of this study was to investigate the effect of Lithothamnion species, seawater-derived magnesium and pine bark (Aq+) on pain, symptoms and improve physical function in symptomatic (sKOA), compared to Glu.Methods358 participants were screened. In a double-blinded crossover pilot-trial, sKOA participant (n = 30) were randomly assigned to either the Glu group (2000 mg day-1) or Aq+ (3056 mg day-1) for 12 weeks (clinicaltrials.gov:NCT03106584). The Knee Injury and Osteoarthritis Outcome Score was used to assess subjective pain and symptoms. Timed-up-and-Go (TuG) and Six minute walking distance were used to assess functional change and analgesic use was recorded.ResultsAq+ improved pain, with a large effect (P < 0.01, d’ = 0.73, 95%CI 0.201-1.265) and no change for Glu (d’ = 0.38, P = 0.06). Only Aq+ improved pain (P < 0.05) for males (d’ = 0.91, 95%CI 0.162-1.667) and females (d’ = 0.55, 95%CI 0.210-1.299). In females, Aq+ improved TuG by -7.02% (d’ = 0.92, 95%CI 1.699-0.141) while Glu worsened performance by 4.18% (P = 0.04). Aq+ reduced analgesia by 71.6%, compared to Glu (P = 0.02; d’ = 0.82, 95%CI 1.524-0.123). Aq+ was superior to Glu at improving pain, KOOS subscales, physical function and analgesia use in mild-sKOA. Given these data, Aq+ should be considered as a supplementary treatment for early-stage-KOA and may have the potential to reduce use of pain medication, although larger replication studies are required

The optical counterpart of IGR J00291+5934 in quiescence

The recent (December 2004) discovery of the sixth accretion-powered millisecond X-ray pulsar IGR J00291+5934 provides a very good chance to deepen our knowledge of such systems. Although these systems are well studied at high energies, poor informations are available for their optical/NIR counterparts during quiescence. Up to now, only for SAX J1808.4-3658, the first discovered system of this type, we have a secure multiband detection of its optical counterpart in quiescence. Among the seven known system IGR J00291+5934 is the one that resembles SAX J1808.4-3658 more closely. With the Italian 3.6 m TNG telescope, we have performed deep optical and NIR photometry of the field of IGR J00291+5934 during quiescence in order to look for the presence of a variable counterpart. We present here the first multiband ($VRIJH$) detection of the optical and NIR counterpart of IGR J00291+5934 in quiescence as well as a deep upper limit in the $K-$band. We obtain an optical light curve that shows variability consistent with a sinusoidal modulation at the known 2.46 hr orbital period and present evidence for a strongly irradiated companion.Comment: 6 pages, 5 figures. Accepted for publication in Astronomy and Astrophysic

Ecosystem Modeling of College Drinking: Parameter Estimation and Comparing Models to Data

Recently we developed a model composed of five impulsive differential equations that describes the changes in drinking patterns (that persist at epidemic level) amongst college students. Many of the model parameters cannot be measured directly from data; thus, an inverse problem approach, which chooses the set of parameters that results in the “best” model to data fit, is crucial for using this model as a predictive tool. The purpose of this paper is to present the procedure and results of an unconventional approach to parameter estimation that we developed after more common approaches were unsuccessful for our specific problem. The results show that our model provides a good fit to survey data for 32 campuses. Using these parameter estimates, we examined the effect of two hypothetical intervention policies: 1) reducing environmental wetness, and 2) penalizing students who are caught drinking. The results suggest that reducing campus wetness may be a very effective way of reducing heavy episodic (binge) drinking on a college campus, while a policy that penalizes students who drink is not nearly as effective