Search

Along the river–ocean transition, few freshwater species persist into polyhaline zones. Among those insect species capable of living in estuaries, it is unclear which Odonata, Trichoptera, and Coleoptera species can occur at intermittent or average salinities above 18 PSU. During surveys of fish and crustaceans in Prince Edward Island (PEI), we noted 3 unexpected insect species from within subtidal-channels. Multiple instars of Coenagrionidae n. det. and Enallagma civile (Familiar Bluet) were collected around marine macroalgae at 5 localities with 6-26 PSU salinities and observed emerging atop macroalgae. Also, collections of the larvae of the caddisfly Limnephilus externus (Limniphilidae), and adult Haliplus cribrarius (Haliplidae) beetles at sites with maxima of 23 and 20 PSU, respectively, suggest rare occurrences of these species within estuarine ecotones. [ABSTRACT FROM AUTHOR]

Objectives: Human populations exhibit substantial geographical variability in body size and shape. However, the ecological stresses underlying this morphological variability remain poorly understood. The prevailing evolutionary explanation, "Bergmann's rule" assumes that morphological variability represents an adaptive response to average thermal conditions. We hypothesized that other climate factors—annual average precipitation, a marker of ecological productivity and inter‐annual temperature volatility, a marker of infectious disease spikes—may also contribute to variability in body composition. Materials and Methods: We explored this hypothesis by examining associations between these climate factors and geographic variability in body composition across 133 male and 105 female populations from nonindustrialized settings. We used monthly climate data over 113 years (1901–2013) to develop new climate indices for all worldwide land areas. We stratified our analyses by hot/cold setting (>/<20°C). Results: In hot environments, lean mass increased as predicted in association with ecological productivity, and decreased in association with ecological volatility. Conversely, levels of body fat increased in association with temperature volatility and precipitation. However, in cold settings, equivalent associations were only partially consistent with our hypotheses, and there was suggestive evidence of sex differences in these associations. Discussion: Beyond associations with mean annual temperature predicted by Bergmann's rule, variability in human body composition is also associated with mean annual temperature and inter‐annual temperature volatility, with these associations further differing between hot and cold settings. Collectively, our results suggest that associations of human body composition with climate are complex for both physique (fat‐free mass) and energy stores (adiposity). [ABSTRACT FROM AUTHOR]

• This Phase Ib trial found that oral administration of AN0025 in combination with preoperative treatment of rectal cancer was well tolerated and shows promising activity. • Overall, 36% of subjects (9 of 25) achieved a complete clinical or pathological response. • AN0025 showed improved response in subjects with more immunogenic tumors at baseline and induced an immune response, in the both the tumor and peripheral samples. • AN0025 should be evaluated in further trials. To assess the safety and efficacy of AN0025 in combination with preoperative radiotherapy and chemotherapy in either short course (SCRT) or long course radiotherapy (LCRT) settings for those with locally advanced rectal cancer. Twenty-eight subjects with locally advanced rectal cancer participated in this multicenter, open-label, Phase Ib trial. Enrolled subjects received either 250 mg or 500 mg of AN0025 once daily for 10 weeks with either LCRT or SCRT with chemotherapy (7 subjects/group). Participants were assessed for safety/efficacy starting from the first dose of study drug administration and were followed for 2 years. No treatment-emergent adverse or serious adverse events meeting dose-limiting criteria were observed, with only 3 subjects discontinuing AN0025 treatment due to adverse events. Twenty-five of 28 subjects completed 10 weeks of AN0025 and adjuvant therapy and were evaluated for efficacy. Overall, 36.0% of subjects (9/25 subjects) achieved a pathological complete response or a complete clinical response, including 26.7% of subjects (4/15 subjects who underwent surgery) who achieved a pathological complete response. A total of 65.4% of subjects had magnetic resonance imaging-confirmed down-staging ≤ stage 3 following completion of treatment. With a median follow-up of 30 months. The 12-month disease-free survival and overall survival were 77.5% (95% confidence interval [CI]: 56.6, 89.2) and 96.3% (95% CI: 76.5, 99.5), respectively. Treatment with AN0025 administered for 10 weeks along with preoperative SCRT or LCRT did not appear to worsen the toxicity in subjects with locally advanced rectal cancer, was well-tolerated and showed promise in inducing both a pathological and complete clinical response. These findings suggest its activity deserves further investigation in larger clinical trials. [ABSTRACT FROM AUTHOR]

Background: Pharmacokinetic guided dosing of 5-fluorouracil chemotherapies to bring plasma 5-fluorouracil into a desired therapeutic range may lead to fewer side effects and better patient outcomes. High performance liquid chromatography and a high throughput nanoparticle immunoassay (My5-FU) have been used in conjunction with treatment algorithms to guide dosing. The objective of this study was to assess accuracy, clinical effectiveness and safety of plasma 5-fluorouracil guided dose regimen(s) versus standard regimens based on body surface area in colorectal cancer.Methods: We undertook a systematic review. MEDLINE; MEDLINE In-Process & Other Non-Indexed Citations; EMBASE; Cochrane Library; Science Citation Index and Conference Proceedings (Web of Science); and NIHR Health Technology Assessment Programme were searched from inception to January 2014. We reviewed evidence on accuracy of My5-FU for estimating plasma 5-fluorouracil and on the clinical effectiveness of pharmacokinetic dosing compared to body surface area dosing. Estimates of individual patient data for overall survival and progression-free survival were reconstructed from published studies. Survival and adverse events data were synthesised and examined for consistency across studies.Results: My5-FU assays were found to be consistent with reference liquid chromatography tandem mass spectrometry. Comparative studies pointed to gains in overall survival and in progression-free survival with pharmacokinetic dosing, and were consistent across multiple studies.Conclusions: Although our analyses are encouraging, uncertainties remain because evidence is mainly from outmoded 5-fluorouracil regimens; a randomised controlled trial is urgently needed to investigate new dose adjustment methods in modern treatment regimens. [ABSTRACT FROM AUTHOR]

This article focuses on the challenges for authors of dealing with an editor’s and reviewers’ comments within the manuscript publication process. The paper commences with an overview of the peer review process. The nature and style of comments from editors and reviewers is outlined and the inherent meaning demystified. Using a wide range of anonymised examples, sample comments are categorised according to their ease of being addressed and whether or not the author agrees with them and the need to respond highlighted. Advice is offered regarding the construction of a response document, outlining how editor and reviewer comments have been addressed in the revised manuscript and an example comprising both editor and reviewer comments and author responses provided. The importance of this document in providing a clear audit trail of associated amendments to the manuscript and their justifications in response to the editor’s and reviewers’ comments is emphasised. [ABSTRACT FROM PUBLISHER]

Background The oral multikinase inhibitor regorafenib improves overall survival (OS) in patients with metastatic colorectal cancer (CRC) for which all standard treatments have failed. This study investigated regorafenib plus modified FOLFOX (mFOLFOX6) as first-line treatment of metastatic CRC. Methods In this single-arm, open-label, multicentre, phase II study, patients received mFOLFOX6 on days 1 and 15, and regorafenib 160 mg orally once daily on days 4–10 and 18–24 of each 28-day cycle. The primary end-point was centrally assessed objective response rate (ORR). Secondary end-points included disease control rate (DCR), OS, progression-free survival (PFS) and safety. Results Median overall treatment duration with any study drug was 9.9 months (range 0.6–19.6); median treatment duration with regorafenib was 7.7 months (range 0.1–19.5); six patients remained on regorafenib for more than 1 year. Fifty-three patients received at least one dose of regorafenib. ORR was 43.9% (all partial responses); DCR was 85.4%; median OS was not reached; median PFS was 8.5 months. Treatment-emergent adverse events were experienced by all patients but were manageable with dose modifications. Conclusion Regorafenib + mFOLFOX6 as first-line treatment in patients with metastatic CRC did not improve ORR over historical controls. Regorafenib plus mFOLFOX6 did not appear to be associated with a markedly worse tolerability profile versus mFOLFOX6 alone. ClinicalTrials.gov identifier: NCT01289821. [ABSTRACT FROM AUTHOR]

Background: Epidermal growth factor receptor (EGFR) is a therapeutic target to which HER2/HER3 activation may contribute resistance. This Phase I/II study examined the toxicity and efficacy of high-dose pulsed AZD8931, an EGFR/HER2/HER3 inhibitor, combined with chemotherapy, in metastatic colorectal cancer (CRC).Methods: Treatment-naive patients received 4-day pulses of AZD8931 with irinotecan/5-FU (FOLFIRI) in a Phase I/II single-arm trial. Primary endpoint for Phase I was dose limiting toxicity (DLT); for Phase II best overall response. Samples were analysed for pharmacokinetics, EGFR dimers in circulating exosomes and Comet assay quantitating DNA damage.Results: Eighteen patients received FOLFIRI and AZD8931. At 160 mg bd, 1 patient experienced G3 DLT; 160 mg bd was used for cohort expansion. No grade 5 adverse events (AE) reported. Seven (39%) and 1 (6%) patients experienced grade 3 and grade 4 AEs, respectively. Of 12 patients receiving 160 mg bd, best overall response rate was 25%, median PFS and OS were 8.7 and 21.2 months, respectively. A reduction in circulating HER2/3 dimer in the two responding patients after 12 weeks treatment was observed.Conclusions: The combination of pulsed high-dose AZD8931 with FOLFIRI has acceptable toxicity. Further studies of TKI sequencing may establish a role for pulsed use of such agents rather than continuous exposure.Trial Registration Number: ClinicalTrials.gov number: NCT01862003. [ABSTRACT FROM AUTHOR]

When writing about research, explaining the method can appear as an afterthought or even madness: wasting precious words that could be better used in discussing the findings. Yet, a section explicitly explaining and justifying the method is crucial to any research report or academic paper, in coaching or other disciplines. In fact, we would argue that a well-articulated method section is particularly important in coaching research, as the setting up of studies can be complex, highlighting a necessity to be very clear about data collection techniques and analysis procedures used. We offer here the analogy of your research as a building with firm foundations – for a building to be safe, it needs to be built on firm foundations. Similarly, you need to show that your research is well founded. A clear concise explanation of your research method provides the foundation allowing your readers to know your research findings can be trusted. [ABSTRACT FROM PUBLISHER]

Abstract: This research explores how elective surgical patients make sense of their hospitalization experiences. We explore sensemaking using longitudinal narrative interviews (n =72) with 38 patients undergoing elective surgical procedures between June 2010 and February 2011. We consider patients' narratives, the stories they tell of their prior expectations, and subsequent post-surgery experiences of their care in a United Kingdom (UK) hospital. An emergent pre-surgery theme is that of a paradoxical position in which they choose to make themselves vulnerable by agreeing to surgery to enhance their health, this necessitating trust of clinicians (doctors and nurses). To make sense of their situation, patients draw on technical (doctors' expert knowledge and skills), bureaucratic (National Health Service as a revered institution) and ideological (hospitals as places of safety), discourses. Post-operatively, themes of ‘chaos’ and ‘suffering’ emerge from the narratives of patients whose pre-surgery expectations (and trust) have been violated. Their stories tell of unmet expectations and of inability to make shared sense of experiences with clinicians who are responsible for their care. We add to knowledge of how patients play a critical part in the co-construction of safety by demonstrating how patient–clinician intersubjectivity contributes to the type of harm that patients describe. Our results suggest that approaches to enhancing patients' safety will be limited if they fail to reflect patients' involvement in the negotiated process of healthcare. We also provide further evidence of the contribution narrative inquiry can make to patient safety. [Copyright &y& Elsevier]

Explaining the purpose of a research study and providing a compelling rationale is an important part of any coaching research project, enabling the work to be set in the context of both existing evidence (and theory) and its practical applications. This necessitates formulating a clear research question and deriving specific research objectives, thereby justifying and contextualising the study. In this research note we consider the characteristics of good research questions and research objectives and the role of theory in developing these. We conclude with a summary and a checklist to help ensure the rationale for a coaching research study is convincing. [ABSTRACT FROM PUBLISHER]

Despite organizations’ widespread Internet use and ready availability of Web survey software, few studies have examined explicitly the impact on employees’ responses of using the Web as opposed to mail-based surveys (MBS). This article addresses this gap using an employee attitude survey distributed to a 50% systematic sample of 3,338 employees by mail, the remaining employees receiving the survey via a Web link. Although the return rate for the Web (49.1%) was higher than for mail (33.5%), the quality of Web returns was reduced by a higher number of partial responses and abandonments. Taking into account effect size, significant differences in response were small other than for open question content. Recommendations regarding use of Web-based surveys (WBS) are offered and areas for future research suggested. [ABSTRACT FROM PUBLISHER]

Abstract: Lumpectomy followed by whole breast radiation therapy (i.e. breast conservation therapy (BCT)) is the standard of care for management of early stage breast cancer. However, its utilization has not been maximized because of a number of reasons including the logistic issues associated with the 5–6weeks of radiation treatment. Also, pathological and clinical data suggest that most ipsilateral breast cancer recurrences are in the vicinity of the lumpectomy. Accelerated partial breast irradiation (APBI) is an approach that treats only the lumpectomy bed plus a 1–2cm margin, rather than the whole breast with higher doses of radiation in a shorter period of time. There has been growing interest for APBI and various approaches have been developed and are under phase I–III clinical studies. This paper reviews external beam conformal radiation therapy (EBCRT) as a possible technique to APBI. The various EBCRT approaches such as 3D conformal radiation therapy, IMRT, proton therapy, tomotherapy, and volumetric arc therapy are discussed. Issues with the implementation of these techniques such as target volume delineation and organ motion are also presented. It is evident that EBCRT has potential for APBI of a selected group of early breast cancer patient. However, issues with setup errors and breathing motions need to be adequately addressed. [Copyright &y& Elsevier]

Purpose: To evaluate the use of thermal ink-jetting as a method for dosing drugs onto oral films. Methods: A Hewlett-Packard printer cartridge was modified so that aqueous drug solutions replaced the ink. The performance of the printer as a function of print solution viscosity and surface tension was determined; viscosities between 1.1 and 1.5 mm s were found to be optimal, while surface tension did not affect deposition. A calibration curve for salbutamol sulphate was prepared, which demonstrated drug deposition onto an acetate film varied linearly with concentration (r = 0.9992). The printer was then used to deposit salbutamol sulphate onto an oral film made of potato starch. Results: It was found that when doses were deposited in a single pass under the print head, then the measured dose was in good agreement with the theoretical dose. With multiple passes the measured dose was always significantly less than the theoretical dose. It is proposed that the losses arise from erosion of the printed layer by shearing forces during paper handling. The losses were predictable, and the variance in dose deposited was always less than the BP limits for tablet and oral syrup salbutamol sulphate preparations. Conclusions: TIJ printing offers a rapid method for extemporaneous preparation of personalized-dose medicines. [ABSTRACT FROM AUTHOR]

Exploring and evaluating findings from previous research is an essential aspect of all research projects enabling the work to be set in the context of what is known and what is not known. This necessitates a critical review of the literature in which existing research is discussed and evaluated, thereby contextualising and justifying the project. In this research note we consider what is understood by being critical when reviewing prior to outlining the key attributes of a critical literature review. We conclude with a summary checklist to help ensure a literature review is critical. [ABSTRACT FROM AUTHOR]

Breast conservation therapy (BCT) is the procedure of choice for the management of the early stage breast cancer. However, its utilization has not been maximized because of logistics issues associated with the protracted treatment involved with the radiation treatment. Accelerated Partial Breast Irradiation (APBI) is an approach that treats only the lumpectomy bed plus a 1-2 cm margin, rather than the whole breast. Hence because of the small volume of irradiation a higher dose can be delivered in a shorter period of time. There has been growing interest for APBI and various approaches have been developed under phase I-III clinical studies; these include multicatheter interstitial brachytherapy, balloon catheter brachytherapy, conformal external beam radiation therapy and intraoperative radiation therapy (IORT). Balloon-based brachytherapy approaches include Mammosite, Axxent electronic brachytherapy and Contura, Hybrid brachytherapy devices include SAVI and ClearPath. This paper reviews the different techniques, identifying the weaknesses and strength of each approach and proposes a direction for future research and development. It is evident that APBI will play a role in the management of a selected group of early breast cancer. However, the relative role of the different techniques is yet to be clearly identified. [ABSTRACT FROM AUTHOR]

The safety and tolerability of vandetanib (ZACTIMA™; ZD6474) plus FOLFIRI was investigated in patients with advanced colorectal cancer (CRC). Patients eligible for first- or second-line chemotherapy received once-daily oral doses of vandetanib (100 or 300 mg) plus 14-day treatment cycles of FOLFIRI. A total of 21 patients received vandetanib 100 mg ( n = 11) or 300 mg ( n = 10) + FOLFIRI. Combination therapy was well tolerated at both vandetanib dose levels. There were no DLTs in the vandetanib 100 mg cohort and one DLT of hypertension (CTCAE grade 3) in the 300 mg cohort. The most common adverse events were diarrhoea ( n = 20), nausea ( n = 12) and fatigue ( n = 10). Two patients (one in each cohort) discontinued vandetanib due to adverse events (rash, 100 mg cohort; hypertension, 300 mg cohort). There was no apparent pharmacokinetic interaction between vandetanib and FOLFIRI. Preliminary efficacy results included two confirmed partial responses in the 100 mg cohort and 9 patients with stable disease ≥8 weeks (100 mg, n = 7; 300 mg, n = 2). Once-daily vandetanib (100 or 300 mg) in combination with a standard FOLFIRI regimen was generally well tolerated in patients with advanced CRC. [ABSTRACT FROM AUTHOR]

5-Fluorouracil (5-FU) has been the most widely used chemotherapeutic agent for metastatic colorectal cancer (mCRC) and 5-FU combination therapy improves efficacy compared with monotherapy. The oral fluoropyrimidine UFT (tegafur-uracil) with leucovorin (LV) improves tolerability and has replaced 5-FU in many regimens. The efficacy and tolerability of UFT with LV in the first-line treatment of mCRC has been demonstrated in a number of phase II studies. In two phase III studies, UFT with LV has been shown to have comparable efficacy and improved tolerability versus intravenous bolus 5-FU, with very few cases of hand-foot syndrome (HFS). Indirect comparisons of UFT and capecitabine suggest that they are comparable in terms of survival. In first-line treatment, UFT in combination with oxaliplatin (TEGAFOX) or irinotecan (TEGAFIRI) is effective and well tolerated, with similar efficacy and tolerability to the corresponding 5-FU- and capecitabine-based combinations, but with a lower incidence of HFS. Alternating cycles of TEGAFOX and TEGAFIRI are effective and well tolerated, and the combination of TEGAFIRI and the targeted monoclonal antibody cetuximab has shown promising activity, similar to that of FOLFIRI plus cetuximab. UFT can be considered a rational replacement for intravenous 5-FU in the first- and second-line treatment of patients with mCRC. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Elevated nitrogen (N) deposition can affect litter decomposition directly, by raising soil N availability and the quantity and quality of litter inputs, and indirectly by altering plant community composition. We investigated the importance of these controls on litter decomposition using litter bags placed in annual herb based microcosm ecosystems that had been subject to two rates of N deposition (which raised soil inorganic N availability and stimulated litter inputs) and two planting regimes, namely the plant species compositions of low and high N deposition environments. In each microcosm, we harvested litter bags of 10 annual plant species, over an 8-week period, to determine mass loss from decomposition. Our data showed that species differed greatly in their decomposability, but that these differences were unlikely to affect decomposition at the ecosystem level because there was no correlation between a species’ decomposability and its response to N deposition (measured as population seed production under high N, relative to low N, deposition). Litter mass loss was ∼2% greater in high N deposition microcosms. Using a comprehensive set of measurements of the microcosm soil environments, we found that the most statistically likely explanation for this effect was increased soil enzyme activity (cellobiosidase, β-glucosidase and β-xylosidase), which appears to have occurred in response to a combination of raised soil inorganic N availability and stimulated litter inputs. Our data indicate that direct effects of N deposition on litter input and soil N availability significantly affected decomposition but indirect effects did not. We argue that indirect effects of changes to plant species composition could be stronger in natural ecosystems, which often contain a greater diversity of plant functional types than those considered here. [Copyright &y& Elsevier]

Atlantic hurricane activity has increased significantly since 1995 (refs 1–4), but the underlying causes of this increase remain uncertain. It is widely thought that rising Atlantic sea surface temperatures have had a role in this, but the magnitude of this contribution is not known. Here we quantify this contribution for storms that formed in the tropical North Atlantic, Caribbean Sea and Gulf of Mexico; these regions together account for most of the hurricanes that make landfall in the United States. We show that a statistical model based on two environmental variables—local sea surface temperature and an atmospheric wind field—can replicate a large proportion of the variance in tropical Atlantic hurricane frequency and activity between 1965 and 2005. We then remove the influence of the atmospheric wind field to assess the contribution of sea surface temperature. Our results indicate that the sensitivity of tropical Atlantic hurricane activity to August–September sea surface temperature over the period we consider is such that a 0.5 °C increase in sea surface temperature is associated with a ∼40% increase in hurricane frequency and activity. The results also indicate that local sea surface warming was responsible for ∼40% of the increase in hurricane activity relative to the 1950–2000 average between 1996 and 2005. Our analysis does not identify whether warming induced by greenhouse gases contributed to the increase in hurricane activity, but the ability of climate models to reproduce the observed relationship between hurricanes and sea surface temperature will serve as a useful means of assessing whether they are likely to provide reliable projections of future changes in Atlantic hurricane activity. [ABSTRACT FROM AUTHOR]

Purpose: Postoperative chemoradiotherapy in gastric cancer improves locoregional control and survival. Reports on late toxicity, however, have been scarce thus far. Because renal toxicity is one of the most serious late complications in upper abdominal radiotherapy, we prospectively analyzed kidney function in patients who underwent postoperative chemoradiotherapy for gastric cancer. Patients and Methods: In 44 patients, Tc99m-thiatide renography was performed before and at regular intervals after postoperative chemoradiotherapy. The left-to-right (L/R) ratio was used as an index of the relative kidney function. Mean L/R values were calculated for four follow-up time intervals. For all patients, kidney V20 (percentage of the volume of the kidney that received more than 20 Gy) and mean dose of both kidneys were retrieved from the three-dimensional dose–volume histograms. Results: We observed a progressive decrease in left renal function of 11% (p = 0.012) after 6 months, up to 52% (p < 0.001) after >18 months. The V20 (left kidney) and mean left kidney dose were identified as parameters associated with decreased kidney function. Mean serum creatinine was increased from 74.6 μmol/L before treatment to 86.1 μmol/L at 1 year after chemoradiotherapy (p < 0.001). In patients with a follow-up of 18–28 months, one case of severe renovascular hypertension was observed. Conclusion: A progressive relative functional impairment of the left kidney in patients after postoperative chemoradiotherapy for gastric cancer is demonstrated. To optimize the survival benefit that can be established with adjuvant regimens, strategies to minimize the dose to the kidneys and other critical organs should be explored. [Copyright &y& Elsevier]

Recent proposed seasonal hindcast skill estimates for the winter North Atlantic Oscillation (NAO) are derived from different lagged predictors, NAO indices, skill assessment periods, and skill validation methodologies. This creates confusion concerning what is the best-lagged predictor of the winter NAO. To rectify this situation, a standardized comparison of NAO cross-validated hindcast skill is performed against three NAO indices over three extended periods (1900–2001, 1950–2001, and 1972–2001). The lagged predictors comprise four previously published predictors involving anomalies in North Atlantic sea surface temperature (SST), Northern Hemisphere (NH) snow cover, and an additional predictor, an index of NH subpolar summer air temperature (TSP). Significant (p < 0.05) NAO hindcast skill is found with May SST 1900–2001, summer/autumn SST 1950–2001, and warm season snow cover 1972–2001. However, the highest and most significant hindcast skill for all periods and all NAO indices is achieved with TSP. Hindcast skill is nonstationary using all predictors and is highest during 1972–2001 with a TSP correlation skill of 0.59 and a mean-squared skill score of 35%. Observational evidence is presented to support a dynamical link between summer TSP and the winter NAO. Summer TSP is associated with a contemporaneous midlatitude zonal wind anomaly. This leads a pattern of North Atlantic SST that persists through autumn. Autumn SSTs may force a direct thermal NAO response or initiate a response via a third variable. These findings suggest that the NH subpolar regions may provide additional winter NAO lagged predictability alongside the midlatitudes and the Tropics. [ABSTRACT FROM AUTHOR]

Abstract: A 38-year-old man experienced double vision with pupillary abnormalities and convergence retraction nystagmus. A mass, which responded to radiation therapy, was seen as the cause of his dorsal midbrain syndrome. The neural control of vertical eye movements is reviewed and the management of a third ventricular-pineal region mass discussed. [Copyright &y& Elsevier]

This article examines the key to a successful author-publisher relationship. Authors are often identified as suppliers to publishing houses as the author supplies the raw material to the publisher. However, the author's relationship with the publisher does not end with supplying the raw material. The publisher is offering services to the author to edit, design, print, promote and sell the work on the author's behalf. The publisher supplies a service to the author, since the publishing profession is inextricably linked to authorship and the market of readers and users. According to a research undertaken in the English Language Teaching (ELT) division of an educational publishing house, authors expected publishers to provide enthusiasm, excitement, support, encouragement and a gate-keeping role. Professionalism and publishing expertise, including appropriate feedback skills, were expected from publishers. Authors assumed that publishers would respect their sense of ownership, and communicate clearly to them opinions about their work. In particular the research highlighted that authors perceived that the publishers were providing a service.

Much of the property damage from natural hazards in the United States is caused by landfalling hurricanes-strong tropical cyclones that reach the coast. For the southeastern Atlantic coast of the US, a statistical method for forecasting the occurrence of landfalling hurricanes for the season ahead has been reported, but the physical mechanisms linking the predictor variables to the frequency of hurricanes remain unclear. Here we present a statistical model that uses July wind anomalies between 1950 and 2003 to predict with significant and useful skill the wind energy of US landfalling hurricanes for the following main hurricane season (August to October). We have identified six regions over North America and over the east Pacific and North Atlantic oceans where July wind anomalies, averaged between heights of 925 and 400?mbar, exhibit a stationary and significant link to the energy of landfalling hurricanes during the subsequent hurricane season. The wind anomalies in these regions are indicative of atmospheric circulation patterns that either favour or hinder evolving hurricanes from reaching US shores. [ABSTRACT FROM AUTHOR]

For many students and lecturers evaluation is confined to some form of survey. Whilst these can provide useful feedback, their focus is likely to reflect the values and norms of those commissioning and undertaking the evaluation. For real improvements in quality to occur both lecturers' and students' perspectives of factors that are important need to be made explicit and understood. Drawing upon literature relating to service quality and in particular the Service Template, this article outlines and evaluates an alternative approach for establishing students' and lecturers' perspectives, obtaining feedback and developing an agenda for improvement. Using the example of dissertation supervision, it is argued that a revised Template Process operating within a process consultation framework can meet these concerns. The article concludes with a discussion of the applicability of the Template Process to evaluating teaching and learning. [ABSTRACT FROM AUTHOR]

A prime challenge for ENSO seasonal forecast models is to predict boreal summer ENSO conditions at lead. August–September ENSO has a strong influence on Atlantic hurricane activity, Northwest Pacific typhoon activity, and tropical precipitation. However, summer ENSO skill is low due to the spring predictability barrier between March and May. A “consolidated” ENSO–climatology and persistence (CLIPER) seasonal prediction model is presented to address this issue with promising initial results. Consolidated CLIPER comprises the ensemble of 18 model variants of the statistical ENSO–CLIPER prediction model. Assessing August–September ENSO skill using deterministic and probabilistic skill measures applied to cross-validated hindcasts from 1952 to 2002, and using deterministic skill measures applied to replicated real-time forecasts from 1900 to 1950, shows that the consolidated CLIPER model consistently outperforms the standard CLIPER model at leads from 2 to 6 months for all the main ENSO indices (3, 3.4, and 4). The consolidated CLIPER August–September 1952–2002 hindcast skill is also positive to 97.5% confidence at leads out to 4 months (early April) for all ENSO indices. Optimization of the consolidated CLIPER model may lead to further skill improvements. [ABSTRACT FROM AUTHOR]

The thermal properties of two polymorphs of the drug carbamazepine, Forms I and III, were studied using high-speed differential scanning calorimetry (DSC). Previously, accurate determination of the heat enthalpy of fusion of Form III has not been possible using DSC at typical heating rates, due to concurrent exothermic recrystallisation to the higher-melting Form I. Here, it is demonstrated that heating rates of 250° C/min altered the kinetics of the melting transition of Form III such that this concurrent exothermic recrystallisation was inhibited. This allowed direct measurement of the enthalpy of the melting endotherm for Form III from a single transition. The enthalpy of this transition was found to be 109.5 J/g. Further investigations were then performed to test the utility of this technique in quantifying relative amounts of Forms I and III in mixtures of the two polymorphs. It was demonstrated that a limit of detection of 1% (w/w) was possible in this system. However, accurate quantification was not possible due to seeding effects initiating recrystallisation to Form I in these mixtures, even at these elevated heating rates. The utility of this novel technique as a fast analytical tool for studying the polymorphic behaviour of metastable polymorphs has been successfully demonstrated. [Copyright &y& Elsevier]

The purpose of this study was to explore whether it is possible to use hyper differential scanning calorimetry (HDSC) to detect and quantify low levels of amorphous content in samples that are mostly crystalline. HDSC uses scan rates that are much faster than conventional DSC, and consequently results in greater sensitivity. It was found that with every increase in scan rate it became easier to detect the glass transition (Tg) response. Scanning at 500 °C/min was possible and this gave such great sensitivity that very low sample mass (ca. 1 mg) could be used without any loss in detection of Tg. Mixtures of crystalline and amorphous (spray dried) lactose were prepared and scanned at 500 °C/min. It was observed that the Tg response was easily detected even for samples that contained 1.5% amorphous content when using very low samples mass. The view held at present is that DSC is not well suited to studies of amorphous content if the sample contains 10% or less of the amorphous material. The data generated here show that much better detection sensitivity is possible when using the rapid scan rates. As well as being able to detect the presence of very low amorphous contents it was also possible to obtain a quantification, as a linear response was obtained for the step height change in heat flow as a function of amorphous content. It was concluded that HDSC provides a method of obtaining a very fast assessment of the presence of amorphous form, the possibility to quantify this and the need to use a very low sample mass. The combination of speed, low sample mass and sensitivity makes this a very valuable technique for studies on partially amorphous samples. [Copyright &y& Elsevier]

Motivated by an attempt to predict summer (June–August) U.K. temperatures, the time-lagged correlations between summer U.K. and European temperatures and prior snow cover, North Atlantic sea surface temperatures (SSTs), and the North Atlantic Oscillation (NAO) are examined. The analysis centers on the 30-yr period 1972–2001 corresponding to the interval of reliable satellite-derived land snow cover data. A significant association is found between late winter Eurasian snow cover and upcoming summer temperatures over the British Isles and adjacent areas, this link being strongest with January–March snow cover. Significant links are also observed between summer temperatures and the preceding late winter NAO index and with a leading principal component of North Atlantic SST variability. The physical mechanisms underlying these time-lagged correlations are investigated by studying the associated variability in large-scale atmospheric circulation over the Euro–Atlantic sector. Seasonal expansion in the Azores high pressure system may play an important role in the time-lagged relationships. The potential seasonal predictability of summer U.K. temperatures during the period 1972–2001 is assessed by cross-validated hindcasts and usable predictive skill is found. However, the presence and cause of temporal instability in the time-lagged relationships over longer periods of time requires further investigation. [ABSTRACT FROM AUTHOR]

Gene therapy is a modality for the treatment of solid tumors that involves the introduction of a suicide gene into the tumor cells. Genetic radiotherapy involves the placement of a radiation-sensitive promoter upstream from a suicide gene. Because of their irregular vasculature some solid tumors are chronically hypoxic and hence are resistant to conventional treatment with chemotherapy and ionizing radiation (IR). The purpose of this study was to demonstrate that regional tumor hypoxia could be exploited to improve local tumor control. The cDNA coding the erythropoietin hypoxia-responsive element (EPO) was placed upstream from the Egr-TNF-alpha construct. WIDR human colon adenocarcinoma cells were injected into the right hind limb of nude mice and treated with Epo-Egr-TNF-alpha plasmid with or without IR. Tumor volumes were measured by calipers and tumor necrosis factor (TNF)-alpha content of the tumor was determined by enzyme-linked immunosorbent assay. Treatment with the combined regimen of Epo-Egr-TNF-alpha plasmid + IR resulted in significant tumor growth delay. Tumor TNF-alpha content was increased by 30 per cent in the combined treatment group compared with each treatment alone. Regional tumor hypoxia can be exploited successfully to induce tumor growth delay, enhance local control, and enhance the therapeutic ratio. [ABSTRACT FROM AUTHOR]

Background: There is uncertainty in the relative benefits and harms of hyperthermic intraoperative peritoneal chemotherapy (HIPEC) when added to cytoreductive surgery (CRS) +/− systemic chemotherapy or systemic chemotherapy alone in people with peritoneal metastases from colorectal, gastric, or ovarian cancers. Methods: We searched randomized controlled trials (RCTs) in the medical literature until April 14, 2022 and applied methods used for high‐quality systematic reviews. Findings: We included a total of eight RCTs (seven RCTs included in quantitative analysis as one RCT did not provide data in an analyzable format). All comparisons other than ovarian cancer contained only one trial. For gastric cancer, there is high uncertainty about the effect of CRS + HIPEC + systemic chemotherapy. For stage III or greater epithelial ovarian cancer undergoing interval cytoreductive surgery, CRS + HIPEC + systemic chemotherapy probably decreases all‐cause mortality compared to CRS + systemic chemotherapy. For colorectal cancer, CRS + HIPEC + systemic chemotherapy probably results in little to no difference in all‐cause mortality and may increase the serious adverse events proportions compared to CRS +/− systemic chemotherapy, but probably decreases all‐cause mortality compared to fluorouracil‐based systemic chemotherapy alone. Interpretation: The role of CRS + HIPEC in gastric peritoneal metastases is uncertain. CRS + HIPEC should be standard of care in women with stage III or greater epithelial ovarian cancer undergoing interval CRS. CRS + systemic chemotherapy should be standard of care for people with colorectal peritoneal metastases, with HIPEC given only as part of a RCT focusing on subgroups and regimes. PROSPERO Registration: CRD42019130504. [ABSTRACT FROM AUTHOR]

The presence of stratospheric aerosol can bias the results of infrared satellite retrievals of sea surface temperature (SST) and total precipitable water (TPW). In the case of linear SST retrieval using the Along Track Scanning Radiometer (ATSR), on the ESA European remote-sensing satellites, constant coefficients can be found that give negligible bias (less than 0.1 K) over a wide range of aerosol amount (11- microm optical thickness from 0.0 to 0.022). For TPW retrieval, in contrast, the biases associated with stratospheric aerosol are less satisfactory (2 kg m[sup-2] or greater across a range of 11- microm optical thickness of 0.0--0.01). However, the authors show how to find optimal aerosol-dependent retrieval coefficients for any stratospheric aerosol distribution from knowledge of the mean and variance of that aerosol distribution. Examples of SST and TPW retrieval using simulated ATSR brightness temperature data are given. [ABSTRACT FROM AUTHOR]

Tumour-infiltrating CD8+ cytotoxic T cells confer favourable prognosis in colorectal cancer. The added prognostic value of other infiltrating immune cells is unclear and so we sought to investigate their prognostic value in two large clinical trial cohorts. We used multiplex immunofluorescent staining of tissue microarrays to assess the densities of CD8+, CD20+, FoxP3+, and CD68+ cells in the intraepithelial and intrastromal compartments from tumour samples of patients with stage II–III colorectal cancer from the SCOT trial (ISRCTN59757862), which examined 3 months versus 6 months of adjuvant oxaliplatin-based chemotherapy, and from the QUASAR 2 trial (ISRCTN45133151), which compared adjuvant capecitabine with or without bevacizumab. Both trials included patients aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0–1. Immune marker predictors were analysed by multiple regression, and the prognostic and predictive values of markers for colorectal cancer recurrence-free interval by Cox regression were assessed using the SCOT cohort for discovery and QUASAR 2 cohort for validation. After exclusion of cases without tissue microarrays and with technical failures, and following quality control, we included 2340 cases from the SCOT trial and 1069 from the QUASAR 2 trial in our analysis. Univariable analysis of associations with recurrence-free interval in cases from the SCOT trial showed a strong prognostic value of intraepithelial CD8 (CD8IE) as a continuous variable (hazard ratio [HR] for 75th vs 25th percentile [75 vs 25] 0·73 [95% CI 0·68–0·79], p=2·5 × 10−16), and of intrastromal FoxP3 (FoxP3IS; 0·71 [0·64–0·78], p=1·5 × 10−13) but not as strongly in the epithelium (FoxP3IE; 0·89 [0·84–0·96], p=1·5 × 10−4). Associations of other markers with recurrence-free interval were moderate. CD8IE and FoxP3IS retained independent prognostic value in bivariable and multivariable analysis, and, compared with either marker alone, a composite marker including both markers (CD8IE-FoxP3IS) was superior when assessed as a continuous variable (adjusted [a]HR75 vs 25 0·70 [95% CI 0·63–0·78], p=5·1 × 10−11) and when categorised into low, intermediate, and high density groups using previously published cutpoints (aHR for intermediate vs high 1·68 [95% CI 1·29–2·20], p=1·3 × 10−4; low vs high 2·58 [1·91–3·49], p=7·9 × 10−10), with performance similar to the gold-standard Immunoscore. The prognostic value of CD8IE-FoxP3IS was confirmed in cases from the QUASAR 2 trial, both as a continuous variable (aHR75 vs 25 0·84 [95% CI 0·73–0·96], p=0·012) and as a categorical variable for low versus high density (aHR 1·80 [95% CI 1·17–2·75], p=0·0071) but not for intermediate versus high (1·30 [0·89–1·88], p=0·17). Combined evaluation of CD8IE and FoxP3IS could help to refine risk stratification in colorectal cancer. Investigation of FoxP3IS cells as an immunotherapy target in colorectal cancer might be merited. Medical Research Council, National Institute for Health Research, Cancer Research UK, Swedish Cancer Society, Roche, and Promedica Foundation. [ABSTRACT FROM AUTHOR]

In this article, the author discusses the ruling regarding treatment in Great Britain. It mentions that the ruling is for medico-legal practice and proposed treatment, and states that ruling emphasizes the importance of patient autonomy. It also mentions that the ruling is centered on a woman with diabetes and have complications during delivery.

Using an online sample of participants that reported using pornography in the last six months and being in a committed relationship, support was found for a moderated mediation model in which sexual shame and sexual satisfaction mediated the relationship between pornography use and couple satisfaction; this indirect effect was moderated by participants' level of moral disapproval of pornography. Findings suggest that pornography use amongst those who morally disapprove of its use is associated with increased sexual shame, which is associated with decreased sexual satisfaction, leading to subsequent reductions in couple satisfaction. Results expand upon the branch of pornography literature suggesting that the association between pornography use and adverse intra- and interpersonal consequences are conditioned on the degree to which users morally disapprove of their use. [ABSTRACT FROM AUTHOR]

Accurate assessment of record extreme wind gusts is important for building design standards and for industries such as insurance and forestry. Here, we show that the current record wind gust for Northern Ireland – 108kn (56ms−1) recorded at Kilkeel on 12 January 1974 – is almost certainly incorrect and may have arisen from an instrumental error or a power surge. We deduce this from direct anemograph inspection and from a variety of indirect supporting evidence. We recommend that other longstanding UK record wind gusts should also be independently re‐examined to assess their veracity. [ABSTRACT FROM AUTHOR]

Objectives: Cetuximab dosing is based on body surface area (BSA), an approach that is associated with significant wastage due to available vial sizes. NHS England recently introduced an alternative strategy for cetuximab dosing based on dose banding. The aim of this work was to investigate approaches to cetuximab dosing to improve its cost‐effectiveness. Methods: A simulation study using a population pharmacokinetic model was used to assess the performance of dosing strategies using exposure, probability of target attainment and cost. Two dosage regimens (500 and 400/250 mg/m2) were investigated; 5% and 10% dose banding, fixed and optimised dosing strategies were evaluated and compared to BSA strategy. Key findings: The percentage of the total cost associated with wastage for the 400/250 mg/m2 regimen were 8.75%, 5.13%, 3.61%, 9.2% and 0% for BSA; 5 and 10% bands; fixed and optimal strategies, respectively. Similar results were obtained for 500 mg/m2 regimen. In comparison with BSA strategy, other strategies have comparable or improved performance. Optimised strategy showed consistent performance and ensures equal exposure and probability of target attainment. Conclusions: Cost‐effectiveness of cetuximab treatment can be improved with alternative strategies by reducing wastage without compromising exposure. [ABSTRACT FROM AUTHOR]

This article examines and appraises a novel approach for generating shared group constructs through aggregative analysis: the application of Honey's aggregation procedure to repertory grid technique (RGT) data. Revisiting personal construct theory's underlying premises and adopting a social constructivist epistemology, we argue that, while "implicit theories" of the world, elicited via RGT, are unique to individuals, the constructs on which they are founded may be shared collectively. Drawing on a study of workplace performance, we outline a protocol for this novel use of Honey's approach, demonstrating how it can be utilized to generate shared constructs inductively to facilitate theory building. We argue that, unlike other grid aggregation processes, the approach does not compromise data granularity, offering a useful augmentation to traditional idiographic approaches examining individual-level constructs only. This approach appears especially suited to addressing complex and implicit topics, where individuals struggle to convey thoughts and ideas. [ABSTRACT FROM AUTHOR]

Background: 6 months of oxaliplatin-containing chemotherapy is usually given as adjuvant treatment for stage 3 colorectal cancer. We investigated whether 3 months of oxaliplatin-containing chemotherapy would be non-inferior to the usual 6 months of treatment.Methods: The SCOT study was an international, randomised, phase 3, non-inferiority trial done at 244 centres. Patients aged 18 years or older with high-risk stage II and stage III colorectal cancer underwent central randomisation with minimisation for centre, choice of regimen, sex, disease site, N stage, T stage, and the starting dose of capecitabine. Patients were assigned (1:1) to receive 3 months or 6 months of adjuvant oxaliplatin-containing chemotherapy. The chemotherapy regimens could consist of CAPOX (capecitabine and oxaliplatin) or FOLFOX (bolus and infused fluorouracil with oxaliplatin). The regimen was selected before randomisation in accordance with choices of the patient and treating physician. The primary study endpoint was disease-free survival and the non-inferiority margin was a hazard ratio of 1·13. The primary analysis was done in the intention-to-treat population and safety was assessed in patients who started study treatment. This trial is registered with ISRCTN, number ISRCTN59757862, and follow-up is continuing.Findings: 6088 patients underwent randomisation between March 27, 2008, and Nov 29, 2013. The intended treatment was FOLFOX in 1981 patients and CAPOX in 4107 patients. 3044 patients were assigned to 3 month group and 3044 were assigned to 6 month group. Nine patients in the 3 month group and 14 patients in the 6 month group did not consent for their data to be used, leaving 3035 patients in the 3 month group and 3030 patients in the 6 month group for the intention-to-treat analyses. At the cutoff date for analysis, there had been 1482 disease-free survival events, with 740 in the 3 month group and 742 in the 6 month group. 3 year disease-free survival was 76·7% (95% CI 75·1-78·2) for the 3 month group and 77·1% (75·6-78·6) for the 6 month group, giving a hazard ratio of 1·006 (0·909-1·114, test for non-inferiority p=0·012), significantly below the non-inferiority margin. Peripheral neuropathy of grade 2 or worse was more common in the 6 month group (237 [58%] of 409 patients for the subset with safety data) than in the 3 month group (103 [25%] of 420) and was long-lasting and associated with worse quality of life. 1098 serious adverse events were reported (492 reports in the 3 month group and 606 reports in the 6 month group) and 32 treatment-related deaths occurred (16 in each group).Interpretation: In the whole study population, 3 months of oxaliplatin-containing adjuvant chemotherapy was non-inferior to 6 months of the same therapy for patients with high-risk stage II and stage III colorectal cancer and was associated with reduced toxicity and improved quality of life. Despite the fact the study was underpowered, these data suggest that a shorter duration leads to similar survival outcomes with better quality of life and thus might represent a new standard of care.Funding: Medical Research Council, Swedish Cancer Society, NETSCC, and Cancer Research UK. [ABSTRACT FROM AUTHOR]

Purpose: Etirinotecan pegol (EP) is a long-acting topoisomerase-I inhibitor designed to provide sustained exposure to SN-38 (active metabolite of irinotecan). This phase II study compared EP versus irinotecan as second-line treatment for KRAS-mutant, irinotecan-naïve, metastatic colorectal cancer (mCRC).Methods: Patients were randomized to EP 145 mg/m2 or irinotecan 350 mg/m2 Q21d until disease progression/unacceptable toxicity. The primary endpoint was progression-free survival (PFS) with response determined by central radiologic review (RECIST version 1.1).Results: The study was terminated before completing accrual due to evolving standards of care. Eighty-three patients were randomized. Median PFS was longer with EP versus irinotecan (4.0 versus 2.8 months, respectively; HR 0.65; 95% CI 0.40-1.04; P = 0.07). Six-month PFS rates were 32.8 and 15.4%, respectively. Median OS was 9.6 and 8.4 months in EP and irinotecan arms, respectively (HR 0.91; 95% CI 0.56-1.49). ORRs were 10 and 5%, respectively (P = 0.676); median DOR was significantly longer in EP arm (7.9 versus 1.4 months; P = 0.018). The most common grade-3/4 adverse events for EP and irinotecan were diarrhea (21 vs 20%), neutropenia (10 vs 22%), abdominal pain (14 vs 5%), nausea (14 vs 2%), and vomiting (12 vs 7%), respectively.Conclusion: EP is active and safe for second-line treatment of KRAS-mutant, irinotecan-naïve mCRC. [ABSTRACT FROM AUTHOR]

The article offers information on the disastrous condition of flood in Thailand that took place in 2011, its causes and possibility of returning. It discusses several facts which include highest annual rainfall recorded in 2011 was the maximum in the country's precipitation record, nature, impacts and historical ranking of the floods and heavy rainfall from four tropical storms crossing the north of the country.

Simple Summary: The COVID-19 pandemic has resulted in unprecedented changes to the life of patients with cancer. In this study, we aim to evaluate the impact of the COVID-19 pandemic on the mental health and general well-being of patients with colorectal cancer by carrying out a prospective longitudinal questionnaire. We found that around one in four participants reported symptoms of anxiety and poor well-being, with 15% at risk of moderate to severe depression. Amongst others, those who were worried that the COVID-19 pandemic would have an effect on their mental health were most at risk of anxiety, depression, and poor well-being. Screening for the mental health impact of the COVID-19 pandemic on patients is essential to allow timely action from all key stakeholders in order to avoid potentially longer-term detrimental consequences. The COVID-19 pandemic has resulted in unprecedented changes to the lives of patients with cancer. To evaluate the impact of the COVID-19 pandemic on the mental health and well-being of patients with colorectal cancer, we conducted a prospective longitudinal questionnaire study at a UK tertiary cancer centre. In total, 216 participants were included: mean age 65 years, 57% (n = 122) male, 92% (n = 198) of white ethnicity. Amongst participants who completed the screening psychometric questionnaire, 24% (n = 48/203) reported anxiety (GAD-7 ≥ 5), 15% (n = 31/204) depressive symptoms (PHQ-9 ≥ 10), 3% (n = 5/190) probable post-traumatic stress disorder (PC-PTSD-5 ≥ 4), and 31% (n = 66/213) poor well-being (WHO-5 < 50). In the subgroup (n = 95/216, 44%) who consented to and completed a follow-up survey 6 months later, there was a significant increase in the number of participants at risk of depression (4% vs. 13%, p = 0.021). Self-reported concern about the COVID-19 pandemic impacting one's mental health is associated with increased likelihood of anxiety, depression, and poor well-being, in respective multivariate analyses. In conclusion, screening for the mental health impact of the COVID-19 pandemic is essential to ensure timely action from all key stakeholders and to avoid potentially longer-term detrimental consequences. [ABSTRACT FROM AUTHOR]