Temporal trends in mode, site and stage of presentation with the introduction of colorectal cancer screening: a decade of experience from the West of Scotland

background:  Population colorectal cancer screening programmes have been introduced to reduce cancer-specific mortality through the detection of early-stage disease. The present study aimed to examine the impact of screening introduction in the West of Scotland. methods:  Data on all patients with a diagnosis of colorectal cancer between January 2003 and December 2012 were extracted from a prospectively maintained regional audit database. Changes in mode, site and stage of presentation before, during and after screening introduction were examined. results:  In a population of 2.4 million, over a 10-year period, 14 487 incident cases of colorectal cancer were noted. Of these, 7827 (54%) were males and 7727 (53%) were socioeconomically deprived. In the postscreening era, 18% were diagnosed via the screening programme. There was a reduction in both emergency presentation (20% prescreening vs 13% postscreening, P0.001) and the proportion of rectal cancers (34% prescreening vs 31% pos-screening, P0.001) over the timeframe. Within non-metastatic disease, an increase in the proportion of stage I tumours at diagnosis was noted (17% prescreening vs 28% postscreening, P0.001). conclusions:  Within non-metastatic disease, a shift towards earlier stage at diagnosis has accompanied the introduction of a national screening programme. Such a change should lead to improved outcomes in patients with colorectal cancer

The potential for climate-driven bathymetric range shifts: sustained temperature and pressure exposures on a marine ectotherm, Palaemonetes varians

Range shifts are of great importance as a response for species facing climate change. In the light of current ocean-surface warming, many studies have focused on the capacity of marine ectotherms to shift their ranges latitudinally. Bathymetric range shifts offer an important alternative, and may be the sole option for species already at high latitudes or those within enclosed seas; yet relevant data are scant. Hydrostatic pressure (HP) and temperature have wide ranging effects on physiology, importantly acting in synergy thermodynamically, and therefore represent key environmental constraints to bathymetric migration. We present data on transcriptional regulation in a shallow-water marine crustacean (Palaemonetes varians) at atmospheric and high HP following 168-h exposures at three temperatures across the organisms' thermal scope, to establish the potential physiological limit to bathymetric migration by neritic fauna. We observe changes in gene expression indicative of cellular macromolecular damage, disturbances in metabolic pathways and a lack of acclimation after prolonged exposure to high HP. Importantly, these effects are ameliorated (less deleterious) at higher temperatures, and exacerbated at lower temperatures. These data, alongside previously published behavioural and heat-shock analyses, have important implications for our understanding of the potential for climate-driven bathymetric range shift

Full sphere hydrodynamic and dynamo benchmarks

Convection in planetary cores can generate fluid flow and magnetic fields, and a number of sophisticated codes exist to simulate the dynamic behaviour of such systems. We report on the first community activity to compare numerical results of computer codes designed to calculate fluid flow within a whole sphere. The flows are incompressible and rapidly rotating and the forcing of the flow is either due to thermal convection or due to moving boundaries. All problems defined have solutions that allow easy comparison, since they are either steady, slowly drifting or perfectly periodic. The first two benchmarks are defined based on uniform internal heating within the sphere under the Boussinesq approximation with boundary conditions that are uniform in temperature and stress-free for the flow. Benchmark 1 is purely hydrodynamic, and has a drifting solution. Benchmark 2 is a magnetohydrodynamic benchmark that can generate oscillatory, purely periodic, flows and magnetic fields. In contrast, Benchmark 3 is a hydrodynamic rotating bubble benchmark using no slip boundary conditions that has a stationary solution. Results from a variety of types of code are reported, including codes that are fully spectral (based on spherical harmonic expansions in angular coordinates and polynomial expansions in radius), mixed spectral and finite difference, finite volume, finite element and also a mixed Fourier–finite element code. There is good agreement between codes. It is found that in Benchmarks 1 and 2, the approximation of a whole sphere problem by a domain that is a spherical shell (a sphere possessing an inner core) does not represent an adequate approximation to the system, since the results differ from whole sphere results

The Impact of Generational Intelligence and Its Relationship With Team Cohesion and Team Performance in a Jamaican Multi-Generational Workforce

Problem The Jamaica Union Conference (JAMU) currently faces a phenomenon of having a multi-generational workforce that includes four generations working alongside each other across its five fields for the first time in its history. This intersection of generations brings challenges concerning the adequacy of leaders’ generational intelligence and its relationship to team outcomes and perceptions of performance. The potential concerns for leaders center around employee recruitment, retention and engagement, conflict resolution, workplace culture, and productivity, among others (Tapscott, 2009). Any potential misunderstanding resulting from inadequate cross-generational intelligence among members of the generations currently represented may result in these Jamaican generationally diverse groups of workers falling short of effective relationship-building because these differences may have led to relationships and environments that are not conducive to productive positive outcomes. Most relevant studies direct attention to non-religious companies when conducting large scale research to understand multi-generational workforce challenges and associated shifting needs. Unfortunately, few pertinent studies and related data on the Seventh-day Adventist Church’s contemporary workforce exist. Any lack of understanding of generational intelligence to inform leaders on how best to move forward creatively and innovatively to ensure that teams are empowered to achieve common goals might significantly impact the quality of church life, leadership, and retention of workers. Method The methodology involved an explanatory sequential mixed-methods investigative study encompassing a group of four generations of individuals in workplaces within the Jamaican Union Conference (JAMU) of Seventh-day Adventists, using individuals and cases. The qualitative focus relied on first-hand observations. Attention was directed to the central question: What is the impact of the multigenerational phenomenon on the experiences of workers in regards to generational intelligence, team cohesion, and perceptions of performance in the JAMU? The mixed-method study also used quantitative data, focusing on inferential analysis to address the research hypotheses derived from the literature review. The deductive approach explored any possible connection between the perspectives of digital natives and prior generations. This correlational descriptive research sought to describe the current status of relevant variables and their relationships by systematically gathering information about the phenomenon from members of the four generations. The identification of relationships among generational intelligence, team cohesion, and team performance was studied, measuring each core variable thoroughly. The participants came from all the generational cohorts, sectors, ranks, and Conferences within the JAMU. The JAMU employs over 1300 employees across five Conferences (or administrative divisions), one university, one hospital, schools, and clinics. The demographic data currently available indicate that the age span of the employees ranges from 18 to 79; this covers four generational cohorts. The participants were included in the study if they were current employees of the JAMU and over the age of eighteen. Results This study’s results give insights and hopefully increased understanding about the phenomenon of a contemporary intergenerational workforce within the JAMU. Answers from both the quantitative and qualitative portions of this mixed-method study reveal some potentially relevant and useful differences in the perceptions from the participants. The study shows that there is a significant correlation between generational intelligence and team cohesion (R2 = 0.12) and also a significant relationship between generational intelligence and team performance (R2 = 0.17). These results suggest that generational intelligence can estimate team cohesion, and generational intelligence also can estimate team performance. Thus, these empirical findings in other contexts may also hold within the JAMU workforce. Furthermore, the results also include findings about possible concerns centered around the quality of inclusion in church life, leadership, and the job satisfaction of workers – particularly among younger employees. Conclusions This explanatory sequential mixed-methods investigative study has yielded some insights that are potentially relevant for leaders faced with the challenges associated with JAMU’s currently generationally diverse workforce. Foremost among these insights is the significant relationship generational intelligence has with team cohesion and team performance. To maximize this advantage, there needs to be effective, multi-faceted approaches to understanding, building and sustaining teams in this new environment. This will impact the way in which leadership supports, empowers and collaborates with employees to embrace a shifting culture and work environment. To this end, the issue of inclusion, empowerment and innovation are key to unlock the potential and growing expectation of an intelligent and educated workforce. The study also highlights the need for carefully examining the systems, structures and manner of work best suited to respond to the new workforce of JAMU. This mixed-method research provides useful, convergent insights for addressing any misunderstandings arising from the various perspectives and priorities of members of different generations working for JAMU

A Crystal Structure of the Bifunctional Antibiotic Simocyclinone D8, Bound to DNA Gyrase

Simocyclinones are bifunctional antibiotics that inhibit bacterial DNA gyrase by preventing DNA binding to the enzyme. We report the crystal structure of the complex formed between the N-terminal domain of the Escherichia coli gyrase A subunit and simocyclinone D8, revealing two binding pockets that separately accommodate the aminocoumarin and polyketide moieties of the antibiotic. These are close to, but distinct from, the quinolone-binding site, consistent with our observations that several mutations in this region confer resistance to both agents. Biochemical studies show that the individual moieties of simocyclinone D8 are comparatively weak inhibitors of gyrase relative to the parent compound, but their combination generates a more potent inhibitor. Our results should facilitate the design of drug molecules that target these unexploited binding pockets

Calibration of optimal execution of financial transactions in the presence of transient market impact

Trading large volumes of a financial asset in order driven markets requires the use of algorithmic execution dividing the volume in many transactions in order to minimize costs due to market impact. A proper design of an optimal execution strategy strongly depends on a careful modeling of market impact, i.e. how the price reacts to trades. In this paper we consider a recently introduced market impact model (Bouchaud et al., 2004), which has the property of describing both the volume and the temporal dependence of price change due to trading. We show how this model can be used to describe price impact also in aggregated trade time or in real time. We then solve analytically and calibrate with real data the optimal execution problem both for risk neutral and for risk averse investors and we derive an efficient frontier of optimal execution. When we include spread costs the problem must be solved numerically and we show that the introduction of such costs regularizes the solution.Comment: 31 pages, 8 figure

Book Reviews

The British Year Book of International Law, 1920-1921. Editor, Cyril M. Picciotto. Editorial Committee, Sir Erle Richards, Prof. A. Pearce Higgins, Sir John Macdonell, Sir Cecil Hurst, and, E. A. Whittuck. London: Henry Fioude and Hodder & Stoughton, x92o. Pp. viii, 292

Neurovasculature of high and low tie ligation of the inferior mesenteric artery

PURPOSE: Controversy exists as to whether a high or low tie ligation of the inferior mesenteric artery (IMA) is the preferred technique in surgeries of the left colon and rectum. This study aims to contribute to the discussion as to which is the more beneficial technique by investigating the neurovasculature at each site. METHODS: Ten embalmed cadaveric donors underwent division of the inferior mesenteric artery at the level of the low tie. The artery was subsequently ligated at the root to render a section of tissue for histological analysis of the proximal (high tie), mid and distal (low tie) segments. RESULTS: Ganglia observed in the proximal end of seven specimens in the sample imply that there would be disruption to the innervation in a high tie procedure. CONCLUSION: This study suggests that a high tie should be avoided if the low tie is oncologically viable

A Comprehensive Workflow for General-Purpose Neural Modeling with Highly Configurable Neuromorphic Hardware Systems

In this paper we present a methodological framework that meets novel requirements emerging from upcoming types of accelerated and highly configurable neuromorphic hardware systems. We describe in detail a device with 45 million programmable and dynamic synapses that is currently under development, and we sketch the conceptual challenges that arise from taking this platform into operation. More specifically, we aim at the establishment of this neuromorphic system as a flexible and neuroscientifically valuable modeling tool that can be used by non-hardware-experts. We consider various functional aspects to be crucial for this purpose, and we introduce a consistent workflow with detailed descriptions of all involved modules that implement the suggested steps: The integration of the hardware interface into the simulator-independent model description language PyNN; a fully automated translation between the PyNN domain and appropriate hardware configurations; an executable specification of the future neuromorphic system that can be seamlessly integrated into this biology-to-hardware mapping process as a test bench for all software layers and possible hardware design modifications; an evaluation scheme that deploys models from a dedicated benchmark library, compares the results generated by virtual or prototype hardware devices with reference software simulations and analyzes the differences. The integration of these components into one hardware-software workflow provides an ecosystem for ongoing preparative studies that support the hardware design process and represents the basis for the maturity of the model-to-hardware mapping software. The functionality and flexibility of the latter is proven with a variety of experimental results

Recombination rate and selection strength in HIV intra-patient evolution

The evolutionary dynamics of HIV during the chronic phase of infection is driven by the host immune response and by selective pressures exerted through drug treatment. To understand and model the evolution of HIV quantitatively, the parameters governing genetic diversification and the strength of selection need to be known. While mutation rates can be measured in single replication cycles, the relevant effective recombination rate depends on the probability of coinfection of a cell with more than one virus and can only be inferred from population data. However, most population genetic estimators for recombination rates assume absence of selection and are hence of limited applicability to HIV, since positive and purifying selection are important in HIV evolution. Here, we estimate the rate of recombination and the distribution of selection coefficients from time-resolved sequence data tracking the evolution of HIV within single patients. By examining temporal changes in the genetic composition of the population, we estimate the effective recombination to be r=1.4e-5 recombinations per site and generation. Furthermore, we provide evidence that selection coefficients of at least 15% of the observed non-synonymous polymorphisms exceed 0.8% per generation. These results provide a basis for a more detailed understanding of the evolution of HIV. A particularly interesting case is evolution in response to drug treatment, where recombination can facilitate the rapid acquisition of multiple resistance mutations. With the methods developed here, more precise and more detailed studies will be possible, as soon as data with higher time resolution and greater sample sizes is available.Comment: to appear in PLoS Computational Biolog