A clinical risk score to predict 3-, 5- and 10-year survival in patients undergoing surgery for Dukes B colorectal cancer

<p>Background: The prognosis of patients with Dukes stage B colorectal cancer is unpredictable and there is continuing interest in simply and reliably identifying patients at high risk of developing recurrence and dying of their disease. The aim of this study was to devise a clinical risk score to predict 3-, 5- and 10-year survival in patients undergoing surgery for Dukes stage B colorectal cancer.</p> <p>Methods: A total of 1350 patients who underwent surgery for Dukes stage B colorectal cancer between 1991 and 1994 in 11 hospitals in Scotland were included in the analysis.</p> <p>Results: On follow-up, 926 patients died of whom 479 died of their cancer. At 10 years, cancer-specific survival was 61% and overall survival was 38%. On multivariate analysis, age ≥75 (hazard ratio (HR) 1.45, 95% confidence interval (CI) 1.15-1.82, P=0.001), emergency presentation (HR 1.59, 95% CI 1.27-1.99, P<0.001) and anastomotic leak (HR 2.17, 95% CI 1.24-3.78, P<0.01) were independently associated with cancer-specific survival in colon cancer. On multivariate analysis, only age ≥75 (HR 1.58, 95% CI 1.14-2.18, P<0.01) was associated with cancer-specific survival in rectal cancer. Age, presentation and anastomotic leak hazards could be simply added to form a clinical risk score from 0 to 2 in colon cancer. In patients with Dukes B stage colon cancer, the cancer-specific survival at 5 years for patients with a cumulative score 0 was 81%, 1 was 67% and 2 was 63%. The cancer-specific survival rate at 10 years for patients with a clinical risk score of 0 was 72%, 1 was 58% and 2 was 53%.</p> <p>Conclusion: The results of this study, in a mature cohort, introduce a new simple clinical risk score for patients undergoing surgery for Dukes B colon cancer. This provides a solid foundation for the examination of the impact of additional factors and treatment on prediction of 3-, 5- and 10-year cancer-specific survival.</p&gt

Nonlinear instability and chaos in plasma wave-wave interactions. II. Numerical methods and results

In Part I of this work and Physics of Plasmas, June 1995, the behavior of linearly stable, integrable systems of waves in a simple plasma model was described using a Hamiltonian formulation. It was shown that explosive instability arises from nonlinear coupling between modes of positive and negative energy, with well-defined threshold amplitudes depending on the physical parameters. In this concluding paper, the nonintegrable case is treated numerically. Several sets of waves are considered, comprising systems of two and three degrees of freedom. The time evolution is modelled with an explicit symplectic integration algorithm derived using Lie algebraic methods. When initial wave amplitudes are large enough to support two-wave decay interactions, strongly chaotic motion destroys the separatrix bounding the stable region for explosive triplets. Phase space orbits then experience diffusive growth to amplitudes that are sufficient for explosive instability, thus effectively reducing the threshold amplitude. For initial amplitudes too small to drive decay instability, small perturbations might still grow to arbitrary size via Arnold diffusion. Numerical experiments do not show diffusion in this case, although the actual diffusion rate is probably underestimated due to the simplicity of the model

The effects of dietary supplementation with inulin and inulin-propionate ester on hepatic steatosis in adults with non-alcoholic fatty liver disease

The short chain fatty acid (SCFA) propionate, produced through fermentation of dietary fibre by the gut microbiota, has been shown to alter hepatic metabolic processes that reduce lipid storage. We aimed to investigate the impact of raising colonic propionate production on hepatic steatosis in adults with non-alcoholic fatty liver disease (NAFLD). Eighteen adults were randomised to receive 20g/day of an inulin-propionate ester (IPE), designed to deliver propionate to the colon, or an inulin-control for 42-days in a parallel design. The change in intrahepatocellular lipid (IHCL) following the supplementation period was not different between groups (P=0.082), however IHCL significantly increased within the inulin-control group (20.9±2.9 to 26.8±3.9%; P=0.012; n=9), which was not observed within the IPE group (22.6±6.9 to 23.5±6.8%; P=0.635; n=9). The predominant SCFA from colonic fermentation of inulin is acetate, which in a background of NAFLD and a hepatic metabolic profile that promotes fat accretion, may provide surplus lipogenic substrate to the liver. The increased colonic delivery of propionate from IPE appears to attenuate this acetate- mediated increase in IHC

Spin-orbit interaction in InAs/GaSb heterostructures quantified by weak antilocalization

We study the spin-orbit interaction (SOI) in InAs/GaSb and InAs quantum wells. We show through temperature- and gate-dependent magnetotransport measurements of weak antilocalization that the dominant spin-orbit relaxation mechanism in our low-mobility heterostructures is Elliott-Yafet and not Dyakonov-Perel in the form of the Rashba or Dresselhaus SOI as previously suggested. We compare our findings with recent work on this material system and show that the SOI length lies within the same range. The SOI length may be controlled using an electrostatic gate, opening up prospects for developing spintronic applications

Flux Compactifications on Calabi-Yau Threefolds

The presence of RR and NS three-form fluxes in type IIB string compactification on a Calabi-Yau orientifold gives rise to a nontrivial superpotential W for the dilaton and complex structure moduli. This superpotential is computable in terms of the period integrals of the Calabi-Yau manifold. In this paper, we present explicit examples of both supersymmetric and nonsupersymmetric solutions to the resulting 4d N=1 supersymmetric no-scale supergravity, including some nonsupersymmetric solutions with relatively small values of W. Our examples arise on orientifolds of the hypersurfaces in $WP^{4}_{1,1,1,1,4}$ and $WP^{4}_{1,1,2,2,6}$. They serve as explicit illustrations of several of the ingredients which have played a role in the recent proposals for constructing de Sitter vacua of string theory.Comment: 30 pages, harvmac big; refs and minor comments adde

Hierarchies from Fluxes in String Compactifications

Warped compactifications with significant warping provide one of the few known mechanisms for naturally generating large hierarchies of physical scales. We demonstrate that this mechanism is realizable in string theory, and give examples involving orientifold compactifications of IIB string theory and F-theory compactifications on Calabi-Yau four-folds. In each case, the hierarchy of scales is fixed by a choice of RR and NS fluxes in the compact manifold. Our solutions involve compactifications of the Klebanov-Strassler gravity dual to a confining N=1 supersymmetric gauge theory,and the hierarchy reflects the small scale of chiral symmetry breaking in the dual gauge theory.Comment: 35 pages. v2: minor eqn. and reference change

Making things happen : a model of proactive motivation

Being proactive is about making things happen, anticipating and preventing problems, and seizing opportunities. It involves self-initiated efforts to bring about change in the work environment and/or oneself to achieve a different future. The authors develop existing perspectives on this topic by identifying proactivity as a goal-driven process involving both the setting of a proactive goal (proactive goal generation) and striving to achieve that proactive goal (proactive goal striving). The authors identify a range of proactive goals that individuals can pursue in organizations. These vary on two dimensions: the future they aim to bring about (achieving a better personal fit within one’s work environment, improving the organization’s internal functioning, or enhancing the organization’s strategic fit with its environment) and whether the self or situation is being changed. The authors then identify “can do,” “reason to,” and “energized to” motivational states that prompt proactive goal generation and sustain goal striving. Can do motivation arises from perceptions of self-efficacy, control, and (low) cost. Reason to motivation relates to why someone is proactive, including reasons flowing from intrinsic, integrated, and identified motivation. Energized to motivation refers to activated positive affective states that prompt proactive goal processes. The authors suggest more distal antecedents, including individual differences (e.g., personality, values, knowledge and ability) as well as contextual variations in leadership, work design, and interpersonal climate, that influence the proactive motivational states and thereby boost or inhibit proactive goal processes. Finally, the authors summarize priorities for future researc

Large-scale whole-exome sequencing association studies identify rare functional variants influencing serum urate levels.

Elevated serum urate levels can cause gout, an excruciating disease with suboptimal treatment. Previous GWAS identified common variants with modest effects on serum urate. Here we report large-scale whole-exome sequencing association studies of serum urate and kidney function among ≤19,517 European ancestry and African-American individuals. We identify aggregate associations of low-frequency damaging variants in the urate transporters SLC22A12 (URAT1; p = 1.3 × 10 <sup>-56</sup> ) and SLC2A9 (p = 4.5 × 10 <sup>-7</sup> ). Gout risk in rare SLC22A12 variant carriers is halved (OR = 0.5, p = 4.9 × 10 <sup>-3</sup> ). Selected rare variants in SLC22A12 are validated in transport studies, confirming three as loss-of-function (R325W, R405C, and T467M) and illustrating the therapeutic potential of the new URAT1-blocker lesinurad. In SLC2A9, mapping of rare variants of large effects onto the predicted protein structure reveals new residues that may affect urate binding. These findings provide new insights into the genetic architecture of serum urate, and highlight molecular targets in SLC22A12 and SLC2A9 for lowering serum urate and preventing gout

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types