A Case Fore Buffer Zones

Golf tournaments are fun and exciting events because they allow for up-close interaction with players, but they also present a risk management concern. Professional golfers are not immune to hitting errant golf shots and a lack of buffer zones often results in spectator injury. The purpose of this paper is to examine how buffer zones can be enhanced or developed to protect patrons. Utilizing data from the PGA Tour, a model was developed to aid in predicting errant tee shots to enhance buffer zones

Sources of Funding and Factors Influencing Choice of Journal

Open access (OA) journals distribute their content at no charge and use other means of funding the publication process. Publication fees or article processing charges (APC)s have become the predominant means for funding professional OA publishing. We surveyed 1,038 authors who recently published articles in 74 OA journals that charge APCs stratified into seven discipline categories. Authors were asked about the source of funding for the APC, factors influencing their choice of a journal and past history publishing in OA and subscription journals. Additional information about the journal and the authors’ country were obtained from the journal website. A total of 429 (41%) authors from 69 journals completed the survey. There were large differences in the source of funding among disciplines. Journals with impact factors charged higher APCs as did journals from disciplines where grant funding is plentiful. Fit, quality, and speed of publication where the most important factors in the authors’ choice of a journal. Open access was less important but a significant factor for many authors in their choice of a journal to publish. These findings are consistent with other research on OA publishing and suggest OA publishing funded through APCs is likely to continue to grow.nonPeerReviewe

Cholangiocarcinoma: Validation of Surgical Selection and Prognostic Methodologies

Background: Cholangiocarcinoma is a rare cancer with a poor prognosis. Radical surgical resection is the only option for curative treatment. Optimal determination of resectability is required so that patients can be stratified into operative or chemotherapeutic treatment cohorts. This thesis sought to validate and augment contemporaneous resectability systems in a large independent European validation cohort. Numerous putative prognostic histo-pathological and demographic characteristics have been reported to effect Overall Survival (OS). This thesis sought to validate a variety of histopathological, clinical and radiological systems and to determine the clinical prognostic utility of these systems. Improved prognostication through biomarkers has been suggested, and direct analysis of tumour may allow the development of a more personalised therapeutic approach. This thesis sought to define the utility of 2 potential prognostic biomarkers, hENT1 and Ki67, via direct immunohistochemical analysis of resected and biopsied patient specimens. Methods: Standardised meta-analytical methods were utilised to stratify clinical and biomarker prognostic co-variates. These clinical and biomarker co-variates were then assessed and validated within the context of a large, noncontinuous, European, contemporaneous registry of surgically resected cholangiocarcinoma patients at Aintree University Hospital between June 2006 – February 2017. Forty-four resected patient’s specimens and 58 non-matched biopsy specimens were acquired from CellNass. Two Tissue Matched Array’s (TMA’s) were constructed and immunohistochemical assessment of hENT1 and Ki67 abundance was undertaken. Results: Regression analyses identified that BC score, MSKCC score, age at diagnosis and left artery involvement were all significant independent predictor’s of resectability. The meta-analysis highlighted the significance of clinical prognostic variables affecting OS. The significant prognostic factors which had an effect upon OS were; ‘T’ status, lymph node involvement, microvascular invasion, peri-neural invasion, tumour differentiation and age. Numerous pre and post-operative co-variates retained prognostic utility when assessed within the validation cohort. Meta-analytical methods demonstrated that Ki67 and hENT1 biomarkers had significant prognostic effects for immunohistochemically assessed patients. Immunohistochemical assessment of the TMA specimens was undertaken. hENT1 and Ki67 abundance did not demonstrate significant survival correlates. However, an alternative commercially available hENT1 antibody was determined to demonstrate selectivity and utility in accurately assessing hENT1 abundance in resected peri-hilar cholangiocarcinoma specimens. 17 Conclusion: This thesis externally validated the utility of standardised scoring systems for pre-operatively stratifying patients for potential resection. It has also provided a potential novel anatomical co-variate which could be used to augment scoring systems to increase predictive accuracy. This thesis validated standardised clinical prognostic systems and provided novel and augmented alternative systems which explained variability in OS in the validation cohort. This thesis has validated an alternative commercially available hENT1 antibody which can accurately determine hENT1 abundance in resected peri-hilar cholangiocarcinoma specimens

Combination Early-Phase Trials of Anticancer Agents in Children and Adolescents

Trials; Anticancer agents; ChildrenEnsayos; Agentes anticancerígenos; NiñosAssajos; Agents anticancerígens; NensPURPOSE There is an increasing need to evaluate innovative drugs for childhood cancer using combination strategies. Strong biological rationale and clinical experience suggest that multiple agents will be more efficacious than monotherapy for most diseases and may overcome resistance mechanisms and increase synergy. The process to evaluate these combination trials needs to maximize efficiency and should be agreed by all stakeholders. METHODS After a review of existing combination trial methodologies, regulatory requirements, and current results, a consensus among stakeholders was achieved. RESULTS Combinations of anticancer therapies should be developed on the basis of mechanism of action and robust preclinical evaluation, and may include data from adult clinical trials. The general principle for combination early-phase studies is that, when possible, clinical trials should be dose- and schedule-confirmatory rather than dose-exploratory, and every effort should be made to optimize doses early. Efficient early-phase combination trials should be seamless, including dose confirmation and randomized expansion. Dose evaluation designs for combinations depend on the extent of previous knowledge. If not previously evaluated, limited evaluation of monotherapy should be included in the same clinical trial as the combination. Randomized evaluation of a new agent plus standard therapy versus standard therapy is the most effective approach to isolate the effect and toxicity of the novel agent. Platform trials may be valuable in the evaluation of combination studies. Patient advocates and regulators should be engaged with investigators early in a proposed clinical development pathway and trial design must consider regulatory requirements. CONCLUSION An optimized, agreed approach to the design and evaluation of early-phase pediatric combination trials will accelerate drug development and benefit all stakeholders, most importantly children and adolescents with cancer

Turnover in floral composition explains species diversity and temporal stability in the nectar supply of urban residential gardens

Residential gardens are a valuable habitat for insect pollinators worldwide, but differences in individual gardening practices substantially affect their floral composition. It is important to understand how the floral resource supply of gardens varies in both space and time so we can develop evidence‐based management recommendations to support pollinator conservation in towns and cities. We surveyed 59 residential gardens in the city of Bristol, UK, at monthly intervals from March to October. For each of 472 garden surveys, we combined floral abundances with nectar sugar data to quantify the nectar production of each garden, investigating the magnitude, temporal stability, and diversity and composition of garden nectar supplies. We found that individual gardens differ markedly in the quantity of nectar sugar they supply (from 2 to 1,662 g), and nectar production is higher in more affluent neighbourhoods, but not in larger gardens. Nectar supply peaks in July (mid‐summer), when more plant taxa are in flower, but temporal patterns vary among individual gardens. At larger spatial scales, temporal variability averages out through the portfolio effect, meaning insect pollinators foraging across many gardens in urban landscapes have access to a relatively stable and continuous supply of nectar through the year. Turnover in species composition among gardens leads to an extremely high overall plant richness, with 636 taxa recorded flowering. The nectar supply is dominated by non‐natives, which provide 91% of all nectar sugar, while shrubs are the main plant life form contributing to nectar production (58%). Two‐thirds of nectar sugar is only available to relatively specialised pollinators, leaving just one‐third that is accessible to all. Synthesis and applications. By measuring nectar supply in residential gardens, our study demonstrates that pollinator‐friendly management, affecting garden quality, is more important than the size of a garden, giving every gardener an opportunity to contribute to pollinator conservation in urban areas. For gardeners interested in increasing the value of their land to foraging pollinators, we recommend planting nectar‐rich shrubs with complementary flowering periods and prioritising flowers with an open structure in late summer and autumn

Closing the gap: human factors in cross-device media synchronization

The continuing growth in the mobile phone arena, particularly in terms of device capabilities and ownership is having a transformational impact on media consumption. It is now possible to consider orchestrated multi-stream experiences delivered across many devices, rather than the playback of content from a single device. However, there are significant challenges in realising such a vision, particularly around the management of synchronicity between associated media streams. This is compounded by the heterogeneous nature of user devices, the networks upon which they operate, and the perceptions of users. This paper describes IMSync, an open inter-stream synchronisation framework that is QoE-aware. IMSync adopts efficient monitoring and control mechanisms, alongside a QoE perception model that has been derived from a series of subjective user experiments. Based on an observation of lag, IMSync is able to use this model of impact to determine an appropriate strategy to catch-up with playback whilst minimising the potential detrimental impacts on a users QoE. The impact model adopts a balanced approach: trading off the potential impact on QoE of initiating a re-synchronisation process compared with retaining the current levels of non-synchronicity, in order to maintain high levels of QoE. A series of experiments demonstrate the potential of the framework as a basis for enabling new, immersive media experiences

Radionuclide method for evaluating the performance of hemodialysis in vivo

Radionuclide method for evaluating the performance of hemodialysis in vivo.BackgroundSpecifications of dialyzer performance are generally based on in vitro measurements. There is, however, a shortage of data on dialyzer performance in vivo. The aim of this study was to use continuous measurement of technetium-99m-diethyltriaminepentaacetic acid (Tc-99m-DTPA) blood concentration as a means of continuously monitoring dialyzer function in vivo in patients undergoing routine hemodialysis.MethodsThe study population comprised 15 patients (45 to 80 years old; 13 males). Tc-99m-DTPA was administered intravenously 90 minutes before obtaining a blood sample and starting dialysis. Blood Tc-99m-DTPA activity was continuously monitored by passing the line carrying blood from the patient to the dialyzer close to a scintillation probe mounted in a shielded housing. At the end of hemodialysis, lasting 180 to 300 minutes, chromium-51-ethylenediaminetetraacetic acid (Cr-51-EDTA) was given intravenously and a blood sample taken 90 minutes later. Baseline dialyzer blood flow (Qb) and dialysate flow (Qd) were 250 to 350mL/min and 500mL/min, respectively. The rate constant, α, of the decrease in blood Tc-99m-DTPA activity was used as the measure of moment-to-moment dialyzer function. Pre- and postdialysis extracellular fluid volumes were calculated from the blood Tc-99m-DTPA and Cr-51-EDTA concentrations (VDTPA and VEDTA) before and after dialysis. Tc-99m-DTPA clearance was measured as the product of α and VDTPA. Dialyzer urea clearance was calculated from pre- and postdialysis urea nitrogen concentrations and the time of dialysis. The effects of brief changes in Qb and Qd on dialyzer function were assessed from the associated changes in α.ResultsThe Tc-99m-DTPA clearance profile was biexponential, becoming monoexponential about 1 hour after starting hemodialysis, with α remaining constant for as long as dialysis continued in five patients in whom Qb and Qd were left unaltered. Mean (SEM) plasma Tc-99m-DTPA clearance averaged over the entire period of dialysis in all 15 patients was 110 (3.1)mL/min. It correlated with urea clearance (r = 0.71) (P < 0.01) which was 225 (9.5)mL/min based on a total body water of 2.5 that of VDTPA and 212 (13)mL/min scaled to 40 L/1.73m2. Extracellular fluid volume decreased by 1.73 (0.74) l over dialysis, which was comparable to the change in weight [1.48 (0.57) kg]. The extraction fraction of Tc-99m-DTPA across the artificial kidney, directly measured from afferent and efferent blood samples under baseline Qb and Qd, was 0.5 (0.013). Average extraction fraction indirectly estimated from Tc-99m-DTPA blood clearance and Qb was 0.54 (0.019). These two measurements of extraction fraction correlated with each other under conditions of varying Qb and Qd (r = 0.74) (N = 27) (P < 0.001). Changes in α resulting from changes in Qb and Qd were similar to changes predicted from computerized modeling. The ratio of mass transfer coefficients of urea and Tc-99m-DTPA with respect to the dialyzer, calculated as if they were permeability-surface area products, was 3.3, similar to the ratio, obtained from the literature, in continuous capillary endothelium.ConclusionTc-99m-DTPA is a useful agent for continuously monitoring dialyzer function in vivo and provides a platform for the use of other radio-pharmaceuticals of different molecular sizes that could be used in an analogous fashion

The formation of milky way-mass disk galaxies in the first 500 million years of a cold dark matter universe

Whether or not among the myriad tiny protogalaxies there exists a population with similarities to present-day galaxies is an open question. We show, using BlueTides, the first hydrodynamic simulation large enough to resolve the relevant scales, that the first massive galaxies to form are predicted to have extensive rotationally supported disks. Although their morphology resembles in some ways Milky Way types seen at much lower redshifts, these high-redshift galaxies are smaller, denser, and richer in gas than their low-redshift counterparts. From a kinematic analysis of a statistical sample of 216 galaxies at redshift z = 8–10, we have found that disk galaxies make up 70% of the population of galaxies with stellar mass ${10}^{10}{M}_{\odot }$ or greater. Cold dark matter cosmology therefore makes specific predictions for the population of large galaxies 500 million years after the Big Bang. We argue that wide-field satellite telescopes (e.g., WFIRST) will in the near future discover these first massive disk galaxies. The simplicity of their structure and formation history should make new tests of cosmology possible

Baguette:towards end-to-end service orchestration in heterogeneous networks

Network services are the key mechanism for operators to introduce intelligence and generate profit from their infrastructures. The growth of the number of network users and the stricter application network requirements have highlighted a number of challenges in orchestrating services using existing production management and configuration protocols and mechanisms. Recent networking paradigms like Software Defined Networking (SDN) and Network Function Virtualization (NFV), provide a set of novel control and management interfaces that enable unprecedented automation, flexibility and openness capabilities in operator infrastructure management. This paper presents Baguette, a novel and open service orchestration framework for operators. Baguette supports a wide range of network technologies, namely optical and wired Ethernet technologies, and allows service providers to automate the deployment and dynamic re-optimization of network services. We present the design of the orchestrator and elaborate on the integration of Baguette with existing low-level network and cloud management frameworks