The relationship between the systemic inflammatory response, tumour proliferative activity, T-lymphocytic and macrophage infiltration, microvessel density and survival in patients with primary operable breast cancer

The significance of the inter-relationship between tumour and host local/systemic inflammatory responses in primary operable invasive breast cancer is limited. The inter-relationship between the systemic inflammatory response (pre-operative white cell count, C-reactive protein and albumin concentrations), standard clinicopathological factors, tumour T-lymphocytic (CD4+ and CD8+) and macrophage (CD68+) infiltration, proliferative (Ki-67) index and microvessel density (CD34+) was examined using immunohistochemistry and slide-counting techniques, and their prognostic values were examined in 168 patients with potentially curative resection of early-stage invasive breast cancer. Increased tumour grade and proliferative activity were associated with greater tumour T-lymphocyte (P<0.05) and macrophage (P<0.05) infiltration and microvessel density (P<0.01). The median follow-up of survivors was 72 months. During this period, 31 patients died; 18 died of their cancer. On univariate analysis, increased lymph-node involvement (P<0.01), negative hormonal receptor (P<0.10), lower albumin concentrations (P<0.01), increased tumour proliferation (P<0.05), increased tumour microvessel density (P<0.05), the extent of locoregional control (P<0.0001) and limited systemic treatment (Pless than or equal to0.01) were associated with cancer-specific survival. On multivariate analysis of these significant covariates, albumin (HR 4.77, 95% CI 1.35–16.85, P=0.015), locoregional treatment (HR 3.64, 95% CI 1.04–12.72, P=0.043) and systemic treatment (HR 2.29, 95% CI 1.23–4.27, P=0.009) were significant independent predictors of cancer-specific survival. Among tumour-based inflammatory factors, only tumour microvessel density (P<0.05) was independently associated with poorer cancer-specific survival. The host inflammatory responses are closely associated with poor tumour differentiation, proliferation and malignant disease progression in breast cancer

Automatically extracting functionally equivalent proteins from SwissProt

In summary, FOSTA provides an automated analysis of annotations in UniProtKB/Swiss-Prot to enable groups of proteins already annotated as functionally equivalent, to be extracted. Our results demonstrate that the vast majority of UniProtKB/Swiss-Prot functional annotations are of high quality, and that FOSTA can interpret annotations successfully. Where FOSTA is not successful, we are able to highlight inconsistencies in UniProtKB/Swiss-Prot annotation. Most of these would have presented equal difficulties for manual interpretation of annotations. We discuss limitations and possible future extensions to FOSTA, and recommend changes to the UniProtKB/Swiss-Prot format, which would facilitate text-mining of UniProtKB/Swiss-Prot

The incidence of scarring on the dorsum of the hand

When undertaking image comparison of the hand between accused and perpetrator, it is not unusual for scars to be identified on the back of the hand. To investigate the occurrence of scarring in a discreet sample, a database of 238 individuals was examined, and the dorsum of the right and left hands was gridded for each individual. The position, size and type of scar were recorded within each grid. It was found that, in general, males exhibited a higher incidence of scarring than females. However, males were more likely to show scarring on their left hand whereas females were more likely to exhibit scarring on their right hand. Contrary to the literature, scarring was not most prevalent along the borders of the hand but occurred more frequently in association with the index and middle finger corridor regions. Surgical scars were rare as were large scars whereas linear scars smaller than 6 mm were the most frequently identified. Close to half of the sample did not exhibit scarring on one hand. The importance of understanding the pattern of scarring on the back of the hand is discussed in the light of forensic image comparison analysis

Cloned cattle derived from a novel zona-free embryo reconstruction system

As the demand for cloned embryos and offspring increases, the need arises for the development of nuclear transfer procedures that are improved in both efficiency and ease of operation. Here, we describe a novel zona-free cloning method that doubles the throughput in cloned bovine embryo production over current procedures and generates viable offspring with the same efficiency. Elements of the procedure include zona-free enucleation without a holding pipette, automated fusion of 5-10 oocyte-donor cell pairs and microdrop in vitro culture. Using this system, zona-free embryos were reconstructed from five independent primary cell lines and cultured either singularly (single-IVC) or as aggregates of three (triple-IVC). Blastocysts of transferable quality were obtained at similar rates from zona-free single-IVC, triple-IVC, and control zona-intact embryos (33%, 25%, and 29%, respectively). In a direct comparison, there was no significant difference in development to live calves at term between single-IVC, triple-IVC, and zona-intact embryos derived from the same adult fibroblast line (10%, 13%, and 15%, respectively). This zona-free cloning method could be straightforward for users of conventional cloning procedures to adopt and may prove a simple, fast, and efficient alternative for nuclear cloning of other species as well

Formation of an ion-free crystalline carbon nitride and its reversible intercalation with ionic species and molecular water

The development of processes to tune the properties of materials is essential for the progression of nextgeneration technologies for catalysis, optoelectronics and sustainability including energy harvesting and conversion. Layered carbon nitrides have also been identified as of significant interest within these fields of application. However, most carbon nitride materials studied to date have poor crystallinity and therefore their properties cannot be readily controlled or easily related to their molecular level or nanoscale structures. Here we report a process for forming a range of crystalline layered carbon nitrides with polytriazine imide (PTI) structures that can be interconverted by simple ion exchange processes, permitting the tunability of their optoelectronic and chemical properties. Notable outcomes of our work are (a) the creation of a crystalline, guest-ion-free PTI compound that (b) can be re-intercalated with ions or molecules using “soft chemistry” approaches. This includes the intercalation of HCl, demonstrating a new ambient pressure route to the layered PTI$xHCl material that was previously only available by a high-pressure-high-temperature route (c). Our work also shows (d) that the intercalantfree (IF-) PTI material spontaneously absorbs up to 10 weight% H2O from the ambient atmosphere and that this process is reversible, leading to potential applications for membranes and water capture in dry environment

Development and validation of a questionnaire to measure moral distress in community pharmacists

The Author(s) 2016. . This article is published with open access at Springerlink.com This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Jayne L. Astbury, and Cathal T. Gallagher, 'Development and validation of a questionnaire to measure moral distress in community pharmacists', International Journal of Clinical Pharmacy (2017) Vol 39(1): 156-164, first published online on 22 December 2016, the version of record is available on line via doi: 10.1007/s11096-016-0413-3 Funding for this work was provided by Pharmacy Research UK (PRUK).Background Pharmacists work within a highly-regulated occupational sphere, and are bound by strict legal frameworks and codes of professional conduct. This regulatory environment creates the potential for moral distress to occur due to the limitations it places on acting in congruence with moral judgements. Very little research regarding this phenomenon has been undertaken in pharmacy: thus, prominent research gaps have arisen for the development of a robust tool to measure and quantify moral distress experienced in the profession. Objective The aim of this study was to develop an instrument to measure moral distress in community pharmacists. Setting Community pharmacies in the United Kingdom. Method This study adopted a three-phase exploratory sequential mixed-method design. Three semi-structured focus groups were then conducted to allow pharmacists to identify and explore scenarios that cause moral distress. Each of the identified scenarios were developed into a statement, which was paired with twin seven-point Likert scales to measure the frequency and intensity of the distress, respectively. Content validity, reliability, and construct validity were all tested, and the questionnaire was refined. Main outcome measure The successful development of the valid instrument for use in the United Kingdom. Results This research has led to the development of a valid and reliable instrument to measure moral distress in community pharmacists in the UK. The questionnaire has already been distributed to a large sample of community pharmacists. Conclusion Results from this distribution will be used to inform the formulation of coping strategies for dealing with moral distress.Peer reviewedFinal Published versio

The Ecological Impacts of Contaminated Sediment from Abandoned Metal Mines

Contains public sector information licensed under the Open Government Licence v3.0. The OGL requires that users acknowledge the information provider and/or source of the information with an attribution statement.Pollution from abandoned non-coal (i.e. metal) mines is a serious impediment to rivers meeting the water quality targets set out in River Basin Management Plans. Recent work has identified the mines most likely to be causing a significant environmental impact and hence where efforts to prevent pollution need to be focussed. Yet, it is not clear to what extent rivers, and the animal and plant life they support, are impacted by the legacy of past pollution still bound up in river sediments. Work will be undertaken to reduce toxic metals in mine waters before they enter the river. However, if riverbed sediments are already contaminated and affecting life in rivers, the planned clean-up of mine water sources may not result in recovery of ecological condition. A controlled laboratory experiment was undertaken where river invertebrates (mayfly larvae) from an uncontaminated site were incubated with contaminated riverbed sediment collected downstream of an abandoned metal mine. Concentrations of metals in the tissues of the mayflies increased over the duration of the incubation, particularly those metals that were in high concentrations in the sediment, i.e. cadmium, copper and zinc. As the sediment was the only substantial source of metals in the experiment, it is apparent that the contaminated riverbed sediment was acting as a source of bioavailable metals. It is likely that contaminated sediments, including riverbed sediment, will act as a source of bioavailable metals, at least to benthic organisms, even where mine drainage water is treated to reduce metal concentrations. Metal toxicity occurs when the rate of metal uptake into an organism exceeds the combined rates of excretion and physiological detoxification. Current tests of metal toxicity on biota typically do not match in scale (temporal, spatial and taxonomic range) with assessments of ecological quality undertaken for management, which raises questions regarding the adequacy of environmental limits based on laboratory testing. Existing data were compiled describing geochemistry of riverbed sediment and the Biological Quality Elements invertebrates, diatoms, macrophytes and fish, collected by the regulatory authorities to assess the condition of rivers. As toxic effects of trace metals were not expected at low concentrations, the biological response to sediment metal concentration was determined using a threshold model. Thresholds were found for biotic metrics based on species richness, but other metrics (diatom EQR, macrophyte EQR and invertebrate ASPT) displayed implausible positive relationships with sediment metal concentrations and should not be relied upon for classification of ecological status in waterbodies affected by mining. New data were collected from 20 spatially-independent river catchments in areas affected by metal mine facilities, including samples of the macroinvertebrate community, bioavailability of metals (assessed as metal concentrations in the body tissue of tolerant taxa), and sediment metal concentrations. There were strong correlations between sediment metal concentrations and measured bioavailability, particularly for copper and lead. Measurements of bioavailable metals were related to changes in taxon richness in the invertebrate samples. The data were used to develop a new biotic index (MetTol), which can be used to assess the extent of ecological damage from metal contamination using standard invertebrate monitoring data, and to construct dose response curves based on species sensitivities. A number of approaches were used to establish tolerable limits for sediment metal concentrations based on ecological data, and the results compared with existing Canadian sediment quality guidelines. The limits for copper derived from ecological data were most consistent with existing sediment guidelines. The limits for other metals (silver, arsenic, cadmium, nickel, lead and zinc) derived from ecological data were up to an order of magnitude above the Canadian interim sediment quality guidelines. These existing guidelines, based on toxicological data, may be too precautionary, and we suggest that guideline sediment concentrations based on ecological data may provide a more appropriate level of protection for the environment

Concurrent Validity of the Child Behavior Checklist DSM-Oriented Scales: Correspondence with DSM Diagnoses and Comparison to Syndrome Scales

This study used receiver operating characteristic (ROC) methodology and discriminative analyses to examine the correspondence of the Child Behavior Checklist (CBCL) rationally-derived DSM-oriented scales and empirically-derived syndrome scales with clinical diagnoses in a clinic-referred sample of children and adolescents (N = 476). Although results demonstrated that the CBCL Anxiety, Affective, Attention Deficit/Hyperactivity, Oppositional and Conduct Problems DSM-oriented scales corresponded significantly with related clinical diagnoses derived from parent-based structured interviews, these DSM-oriented scales did not evidence significantly greater correspondence with clinical diagnoses than the syndrome scales in all cases but one. The DSM-oriented Anxiety Problems scale was the only scale that evidenced significantly greater correspondence with diagnoses above its syndrome scale counterpart —the Anxious/Depressed scale. The recently developed and rationally-derived DSM-oriented scales thus generally do not add incremental clinical utility above that already afforded by the syndrome scales with respect to corresponding with diagnoses. Implications of these findings are discussed

Effect of eicosapentaenoic acid, protein and amino acids on protein synthesis and degradation in skeletal muscle of cachectic mice

Atrophy of skeletal muscle reduces both the quality and quantity of life of patients with cancer cachexia. Loss of muscle mass is thought to arise from a reduction in protein synthesis combined with an enhanced rate of protein degradation, and few treatments are available to counteract this process. Eicosapentaenoic acid (EPA) has been shown to attenuate the enhanced protein degradation, but to have no effect on protein synthesis. This study examines the effect of EPA combined with a protein and amino-acid supplementation on protein synthesis and degradation in gastrocnemius muscle of mice bearing the cachexia-inducing MAC16 tumour. Muscles from cachectic mice showed an 80% reduction in protein synthesis and about a 50-fold increase in protein degradation compared with muscles from nontumour-bearing mice of the same age and weight. Treatment with EPA (1 g kg-1) daily reduced protein degradation by 88%, but had no effect on protein synthesis. Combination of EPA with casein (5.35 g kg-1) also had no effect on protein synthesis, but when combined with the amino acids leucine, arginine and methionine there was almost a doubling of protein synthesis. The addition of carbohydrate (10.7 g kg-1) to stimulate insulin release had no additional effect. The combination involving the amino acids produced almost a doubling of the ratio of protein synthesis to protein degradation in gastrocnemius muscle over that of EPA alone. No treatment had a significant effect on tumour growth rate, but the inclusion of amino acids had a more significant effect on weight loss induced by the MAC16 tumour than that of EPA alone. The results suggest that combination therapy of cancer cachexia involving both inhibition of the enhanced protein degradation and stimulation of the reduced protein synthesis may be more effective than either treatment alone. © 2004 Cancer Research UK