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

Nishimori point in random-bond Ising and Potts models in 2D

We study the universality class of the fixed points of the 2D random bond q-state Potts model by means of numerical transfer matrix methods. In particular, we determine the critical exponents associated with the fixed point on the Nishimori line. Precise measurements show that the universality class of this fixed point is inconsistent with percolation on Potts clusters for q=2, corresponding to the Ising model, and q=3Comment: 11 pages, 3 figures. Contribution to the proceedings of the NATO Advanced Research Workshop on Statistical Field Theories, Como 18-23 June 200

The effect of the systemic inflammatory response on plasma vitamin 25 (OH) D concentrations adjusted for albumin

<b>Aim</b><p></p> To examine the relationship between plasma 25(OH)D, CRP and albumin concentrations in two patient cohorts.<p></p> <b>Methods</b><p></p> 5327 patients referred for nutritional assessment and 117 patients with critical illness were examined. Plasma 25 (OH) D concentrations were measured using standard methods. Intra and between assay imprecision was <10%.<p></p> <b>Result</b><p></p> In the large cohort, plasma 25 (OH) D was significantly associated with CRP (rs = −0.113, p<0.001) and albumin (rs = 0.192, p<0.001). 3711 patients had CRP concentrations ≤10 mg/L; with decreasing albumin concentrations ≥35, 25–34 and <25 g/l, median concentrations of 25 (OH) D were significantly lower from 35 to 28 to 14 nmol/l (p<0.001). This decrease was significant when albumin concentrations were reduced between 25–34 g/L (p<0.001) and when albumin <25 g/L (p<0.001). 1271 patients had CRP concentrations between 11–80 mg/L; with decreasing albumin concentrations ≥35, 25–34 and <25 g/l, median concentrations of 25 (OH) D were significantly lower from 31 to 24 to 19 nmol/l (p<0.001). This decrease was significant when albumin concentration were 25–34 g/L (p<0.001) and when albumin <25 g/L (p<0.001). 345 patients had CRP concentrations >80 mg/L; with decreasing albumin concentrations ≥35, 25–34 and <25 g/l, median concentrations of 25 (OH) D were not significantly altered varying from 19 to 23 to 23 nmol/l. Similar relationships were also obtained in the cohort of patients with critical illness.<p></p> <b>Conclusion</b><p></p> Plasma concentrations of 25(OH) D were independently associated with both CRP and albumin and consistent with the systemic inflammatory response as a major confounding factor in determining vitamin D status.<p></p&gt

Platinum deposition on functionalised graphene for corrosion resistant oxygen reduction electrodes

Graphene-related materials are promising supports for electrocatalysts due to their stability and high surface area. Their innate surface chemistries can be controlled and tuned via functionalisation to improve the stability of both the carbon support and the metal catalyst. Functionalised graphenes were prepared using either aryl diazonium functionalisation or non-destructive chemical reduction, to provide groups adapted for platinum deposition. XPS and TGA-MS measurements confirmed the presence of polyethyleneglycol and sulfur-containing functional groups, and provided consistent values for the extent of the reactions. The deposited platinum nanoparticles obtained were consistently around 2 nm via reductive chemistry and around 4 nm via the diazonium route. Although these graphene-supported electrocatalysts provided a lower electrochemical surface area (ECSA), functionalised samples showed enhanced specific activity compared to a commercial platinum/carbon black system. Accelerated stress testing (AST) showed improved durability for the functionalised graphenes compared to the non-functionalised materials, attributed to edge passivation and catalyst particle anchoring

Knockout studies reveal an important role of <i>plasmodium</i> lipoic acid protein ligase a1 for asexual blood stage parasite survival

Lipoic acid (LA) is a dithiol-containing cofactor that is essential for the function of a-keto acid dehydrogenase complexes. LA acts as a reversible acyl group acceptor and 'swinging arm' during acyl-coenzyme A formation. The cofactor is post-translationally attached to the acyl-transferase subunits of the multienzyme complexes through the action of octanoyl (lipoyl): &lt;i&gt;N&lt;/i&gt;-octanoyl (lipoyl) transferase (LipB) or lipoic acid protein ligases (LplA). Remarkably, apicomplexan parasites possess LA biosynthesis as well as scavenging pathways and the two pathways are distributed between mitochondrion and a vestigial organelle, the apicoplast. The apicoplast-specific LipB is dispensable for parasite growth due to functional redundancy of the parasite's lipoic acid/octanoic acid ligases/transferases. In this study, we show that &lt;i&gt;LplA1&lt;/i&gt; plays a pivotal role during the development of the erythrocytic stages of the malaria parasite. Gene disruptions in the human malaria parasite &lt;i&gt;P.falciparum&lt;/i&gt; consistently were unsuccessful while in the rodent malaria model parasite &lt;i&gt;P. berghei&lt;/i&gt; the &lt;i&gt;LplA1&lt;/i&gt; gene locus was targeted by knock-in and knockout constructs. However, the &lt;i&gt;LplA1&lt;/i&gt; &lt;sup&gt;(-)&lt;/sup&gt; mutant could not be cloned suggesting a critical role of LplA1 for asexual parasite growth &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt;. These experimental genetics data suggest that lipoylation during expansion in red blood cells largely occurs through salvage from the host erythrocytes and subsequent ligation of LA to the target proteins of the malaria parasite

Disentangling water, ion and polymer dynamics in an anion exchange membrane

Semipermeable polymeric anion exchange membranes are essential for separation, filtration and energy conversion technologies including reverse electrodialysis systems that produce energy from salinity gradients, fuel cells to generate electrical power from the electrochemical reaction between hydrogen and oxygen, and water electrolyser systems that provide H2 fuel. Anion exchange membrane fuel cells and anion exchange membrane water electrolysers rely on the membrane to transport OH− ions between the cathode and anode in a process that involves cooperative interactions with H2O molecules and polymer dynamics. Understanding and controlling the interactions between the relaxation and diffusional processes pose a main scientific and critical membrane design challenge. Here quasi-elastic neutron scattering is applied over a wide range of timescales (100–103 ps) to disentangle the water, polymer relaxation and OH− diffusional dynamics in commercially available anion exchange membranes (Fumatech FAD-55) designed for selective anion transport across different technology platforms, using the concept of serial decoupling of relaxation and diffusional processes to analyse the data. Preliminary data are also reported for a laboratory-prepared anion exchange membrane especially designed for fuel cell applications

Toothache and associated factors in Brazilian adults: a cross-sectional population-based study

Extent: 8p.Background: Toothache is a dental public health problem and one of the predictors of dental attendance and it is strongly associated with the life quality of individuals. In spite of this, there are few population-based epidemiological studies on this theme. Objective: To estimate the prevalence of toothache and associated factors in adults of Lages, Southern Brazil. Methods: A cross-sectional population-based study was carried out in a sample of 2,022 adults aged 20 to 59 years living in the urban area of a medium sized city in Southern Brazil. A questionnaire including socioeconomic, demographic, smoking, alcohol, and use of dental service variables was applied at adults household. Toothache occurred six months previous of the interview was considered the outcome. Poisson regression analyses were performed following a theoretical hierarchical framework. All analysis was adjusted by the sample design effect. Results: The response rate was 98.6%. The prevalence of toothache was 18.0% (95% CI 16.0; 20.1). The following variables were associated with toothache after adjustment: female (PR = 1.3 95% CI 1.3; 2.0), black skin colour vs. whites (PR = 1.5 95% CI 1.1, 1.9), low per capita income (PR = 1.7 95% CI 1.2, 2.3), smokers (PR = 1.5 95% CI 1.2, 1.9) and those who reported alcohol problems (PR = 1.4 95% CI 1.1; 1.9). To be 40 years of age (PR = 0.5 95% CI 0.4, 0.7) and use dental service in the last year (RR = 0.5 95% CI 0.4, 0.6) were protective factors for toothache. Conclusion: The prevalence of toothache in adults of Lages can be considered a major problem of dental public health.Mirian Kuhnen, Marco A Peres, Anelise V Masiero and Karen G Pere

From START to FINISH : the influence of osmotic stress on the cell cycle

Peer reviewedPublisher PD

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

ICIRAS: Research and reconciliation with indigenous peoples in rural health journals.

AIM: We aim to promote discussion about an Indigenous Cultural Identity of Research Authors Standard (ICIRAS) for academic journal publications. CONTEXT: This is based on a gap in research publishing practice where Indigenous peoples' identity is not systematically and rigorously flagged in rural health research publications. There are widespread reforms, in different research areas, to counter the reputation of scientific research as a vehicle of racism and discrimination against the world's Indigenous peoples. Reflecting on these broader movements, the editorial teams of three rural health journals-the Australian Journal of Rural Health, the Canadian Journal of Rural Medicine, and Rural and Remote Health-recognised that Indigenous peoples' identity could be embedded in authorship details. APPROACH: An environmental scan (through a cultural safety lens where Indigenous cultural authority is respected, valued, and empowered) of literature was undertaken to detect the signs of inclusion of Indigenous peoples in research. This revealed many ways in which editorial boards of Journals could systematically improve their process so that there is 'nothing about Indigenous people, without Indigenous people' in rural health research publications. CONCLUSION: Improving the health and wellbeing of Indigenous peoples worldwide requires high quality research evidence. The philosophy of cultural safety supports the purposeful positioning of Indigenous peoples within the kaleidoscope of cultural knowledges as identified contributors and authors of research evidence. The ICIRAS is a call-to-action for research journals and institutions to rigorously improve publication governance that signals "Editing with IndigenUs and for IndigenUs"