Burden of Illness in UK Subjects with Reported Respiratory Infections Vaccinated or Unvaccinated against Influenza: A Retrospective Observational Study

<div><p>Objective</p><p>Detailed data are lacking on influenza burden in the United Kingdom (UK). The objective of this study was to estimate the disease burden associated with influenza-like illness (ILI) in the United Kingdom stratified by age, risk and influenza vaccination status.</p><p>Methods</p><p>This retrospective, cross-sectional, exploratory, observational study used linked data from the General Practice Research Database and the Hospital Episode Statistics databases to estimate resource use and cost associated with ILI in the UK.</p><p>Results</p><p>Data were included from 156,193 patients with ≥1 general practitioner visit with ILI. There were 21,518 high-risk patients, of whom 12,514 (58.2%) were vaccinated and 9,004 (41.8%) were not vaccinated, and 134,675 low-risk patients, of whom 17,482 (13.0%) were vaccinated and 117,193 (87.0%) were not vaccinated. High-risk vaccinated patients were older (p<0.001) and had more risk conditions (p<0.001). High-risk (odds ratio [OR] 2.16) or vaccinated (OR 1.19) patients had a higher probability of >1 general practitioner visit compared with low-risk and unvaccinated patients. Patients who were high-risk and vaccinated had a reduced risk of >1 general practitioner visit (OR 0.82; p<0.001). High-risk individuals who were also vaccinated had a lower probability of ILI-related hospitalisation than individuals who were high-risk or vaccinated alone (OR 0.59). In people aged ≥65 years, the mortality rate was lower in vaccinated than unvaccinated individuals (OR 0.75). The cost of ILI-related GP visits and hospital admissions in the UK over the study period in low-risk vaccinated patients was £27,391,142 and £141,932,471, respectively. In low-risk unvaccinated patients the corresponding values were £168,318,709 and £112,534,130, respectively.</p><p>Conclusions</p><p>Although vaccination rates in target groups have increased, many people are still not receiving influenza vaccination, and the burden of ILI in the United Kingdom remains substantial. Improving influenza vaccination uptake may have the potential to reduce this burden.</p></div

Collisional kinetics of non-uniform electric field, low-pressure, direct-current discharges in H2_{2}

A model of the collisional kinetics of energetic hydrogen atoms, molecules, and ions in pure H$_2$ discharges is used to predict H$_\alpha$ emission profiles and spatial distributions of emission from the cathode regions of low-pressure, weakly-ionized discharges for comparison with a wide variety of experiments. Positive and negative ion energy distributions are also predicted. The model developed for spatially uniform electric fields and current densities less than $10^{-3}$ A/m$^2$ is extended to non-uniform electric fields, current densities of $10^{3}$ A/m$^2$, and electric field to gas density ratios $E/N = 1.3$ MTd at 0.002 to 5 Torr pressure. (1 Td = $10^{-21}$ V m$^2$ and 1 Torr = 133 Pa) The observed far-wing Doppler broadening and spatial distribution of the H$_\alpha$ emission is consistent with reactions among H$^+$, H$_2^+$, H$_3^+$, and H$^-H$ ions, fast H atoms, and fast H$_2$ molecules, and with reflection, excitation, and attachment to fast H atoms at surfaces. The H$_\alpha$ excitation and H$^-$ formation occur principally by collisions of fast H, fast H$_2$, and H$^+$ with H$_2$. Simplifications include using a one-dimensional geometry, a multi-beam transport model, and the average cathode-fall electric field. The H$_\alpha$ emission is linear with current density over eight orders of magnitude. The calculated ion energy distributions agree satisfactorily with experiment for H$_2^+$ and H$_3^+$, but are only in qualitative agreement for H$^+$ and H$^-$. The experiments successfully modeled range from short-gap, parallel-plane glow discharges to beam-like, electrostatic-confinement discharges.Comment: Submitted to Plasmas Sources Science and Technology 8/18/201

Effect of genotypic, meteorological and agronomic factors on the gluten index of winter durum wheat

The determination of the gluten index is a widely used method for analysing the gluten strength of bread wheat and spring durum wheat genotypes. The present work was carried out to study the effect of the genotype, meteorological factors (temperature, precipitation and number of days with Tmax ≥ 30 °C) and agronomic treatments (N fertilisation and plant protection) on the gluten index of winter durum wheat varieties and breeding lines. The results indicated that the gluten index had little dependence on the environment, being determined to the greatest extent by the genotype. Compared with varieties having weak gluten, those with a strong gluten matrix responded less sensitively to changes in environmental conditions. Among the meteorological factors, high temperature at the end of the grain-filling period caused the greatest reduction in the mean gluten index of three varieties (R 2 = 0.462), while the fertiliser was found to be a significant factor affecting the gluten strength of winter durum wheat varieties. Using selection based on the gluten index, the gluten strength of winter durum wheat lines can be improved sufficiently to make them competitive with high quality spring varieties

Standing orders for influenza and pneumococcal polysaccharide vaccination: Correlates identified in a national survey of U.S. Primary care physicians

<p>Abstract</p> <p>Background</p> <p>Standing orders programs (SOPs) allow non-physician medical staff to assess eligibility and administer vaccines without a specific physician's order. SOPs increase vaccination rates but are underutilized.</p> <p>Method</p> <p>In 2009, correlates of SOPs use for influenza vaccine and pneumococcal polysaccharide vaccination (PPV) were assessed in a nationally representative, stratified random sample of U.S. physicians (n = 880) in family and internal medicine who provided office immunization. The response rate was 67%. Physicians reporting no SOPs, only influenza SOPs, and joint influenza and PPV SOPs were compared using multinomial and logistic regression models to examine individual and practice-level correlates.</p> <p>Results</p> <p>23% reported using SOPs consistently for both influenza vaccine and PPV, and 20% for influenza vaccination only, with the remainder not using SOPs. Practice-level factors that distinguished practices with joint influenza-PPV SOPs included perceived practice openness to change, strong practice teamwork, access to an electronic medical record, presence of an immunization champion in the practice, and access to nurse/physician assistant staff as opposed to medical assistants alone.</p> <p>Discussion</p> <p>Physicians in practices with SOPs for both vaccines reported greater awareness of ACIP recommendations and/or Medicare regulations and were more likely to agree that SOPs are an effective way to boost vaccination coverage. However, implementation of both influenza and PPV SOPs was also associated with a variety of practice-level factors, including teamwork, the presence of an immunization champion, and greater availability of clinical assistants with advanced training.</p> <p>Conclusions</p> <p>Practice-level factors are critical for the adoption of more complex SOPs, such as joint SOPs for influenza and PPV.</p

Oxidative Inactivation of Mitochondrial Aconitase Results in Iron and H2O2-Mediated Neurotoxicity in Rat Primary Mesencephalic Cultures

BACKGROUND:Mitochondrial oxidative stress is a contributing factor in the etiology of numerous neuronal disorders. However, the precise mechanism(s) by which mitochondrial reactive oxygen species (ROS) modify cellular targets to induce the death of neurons remains unknown. The goal of this study was to determine if oxidative inactivation of mitochondrial aconitase (m-aconitase) resulted in the release of redox-active iron (Fe2+) and hydrogen peroxide (H2O2) and whether this contributes to cell death. METHODOLOGY/PRINCIPAL FINDINGS:Incubation of rat primary mesencephalic cultures with the redox cycling herbicide paraquat (PQ2+) resulted in increased production of H2O2 and Fe2+ at times preceding cell death. To confirm the role of m-aconitase as a source of Fenton reagents and death, we overexpressed m-aconitase using an adenoviral construct thereby increasing the target available for inactivation by ROS. Co-labeling studies identified astrocytes as the predominant cell type expressing transduced m-aconitase although neurons were identified as the primary cell type dying. Oxidative inactivation of m-aconitase overexpressing cultures resulted in exacerbation of H2O2 production, Fe2+ accumulation and increased neuronal death. Increased cell death in m-aconitase overexpressing cultures was attenuated by addition of catalase and/or a cell permeable iron chelator suggesting that neuronal death occurred in part via astrocyte-derived H2O2. CONCLUSIONS:These results suggest a role of ROS-sensitive m-aconitase as a source of Fe2+ and H2O2 and as a contributing factor to neurotoxicity

The effect of the stromal component of breast tumours on prediction of clinical outcome using gene expression microarray analysis

INTRODUCTION: The aim of this study was to examine the effect of the cellular composition of biopsies on the error rates of multigene predictors of response of breast tumours to neoadjuvant adriamycin and cyclophosphamide (AC) chemotherapy. MATERIALS AND METHODS: Core biopsies were taken from primary breast tumours of 43 patients prior to AC, and subsequent clinical response was recorded. Post-chemotherapy (day 21) samples were available for 16 of these samples. Frozen sections of each core were used to estimate the proportion of invasive cancer and other tissue components at three levels. Transcriptional profiling was performed using a cDNA array containing 4,600 elements. RESULTS: Twenty-three (53%) patients demonstrated a 'good' and 20 (47%) a 'poor' clinical response. The percentage invasive tumour in core biopsies collected from these patients varied markedly. Despite this, agglomerative clustering of sample expression profiles showed that almost all biopsies from the same tumour aggregated as nearest neighbours. SAM (significance analysis of microarrays) regression analysis identified 144 genes which distinguished high- and low-percentage invasive tumour biopsies at a false discovery rate of not more than 5%. The misclassification error of prediction of clinical response using microarray data from pre-treatment biopsies (on leave-one-out cross-validation) was 28%. When prediction was performed on subsets of samples which were more homogeneous in their proportions of malignant and stromal cells, the misclassification error was considerably lower (8%–13%, p < 0.05 on permutation). CONCLUSION: The non-tumour content of breast cancer samples has a significant effect on gene expression profiles. Consideration of this factor improves accuracy of response prediction by expression array profiling. Future gene expression array prediction studies should be planned taking this into account

Promotion of prostatic metastatic migration towards human bone marrow stoma by Omega 6 and its inhibition by Omega 3 PUFAs

Epidemiological studies have shown not only a relationship between the intake of dietary lipids and an increased risk of developing metastatic prostate cancer, but also the type of lipid intake that influences the risk of metastatic prostate cancer. The Omega-6 poly-unsaturated fatty acid, Arachidonic acid, has been shown to enhance the proliferation of malignant prostate epithelial cells and increase the risk of advanced prostate cancer. However, its role in potentiating the migration of cancer cells is unknown. Here we show that arachidonic acid at concentrations ⩽5 μM is a potent stimulator of malignant epithelial cellular invasion, which is able to restore invasion toward hydrocortisone-deprived adipocyte-free human bone marrow stroma completely. This observed invasion is mediated by the arachidonic acid metabolite prostaglandin E2 and is inhibited by the Omega-3 poly-unsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid at a ratio of 1 : 2 Omega-3 : Omega-6, and by the COX-2 inhibitor NS-398. These results identify a mechanism by which arachidonic acid may potentiate the risk of metastatic migration and secondary implantation in vivo, a risk which can be reduced with the uptake of Omega-3 poly-unsaturated fatty acids

Molecular response to aromatase inhibitor treatment in primary breast cancer

BackgroundAromatase inhibitors such as anastrozole and letrozole are highly effective suppressants of estrogen synthesis in postmenopausal women and are the most effective endocrine treatments for hormone receptor positive breast cancer in such women. Little is known of the molecular effects of these agents on human breast carcinomas in vivo.MethodsWe randomly assigned primary estrogen receptor positive breast cancer patients to treatment with anastrozole or letrozole for 2 weeks before surgery. Expression profiling using cDNA arrays was conducted on pretreatment and post-treatment biopsies. Sample pairs from 34 patients provided sufficient RNA for analysis.ResultsProfound changes in gene expression were seen with both aromatase inhibitors, including many classical estrogen-dependent genes such as TFF1, CCND1, PDZK1 and AGR2, but also many other genes that are likely to represent secondary responses; decrease in the expression of proliferation-related genes were particularly prominent. Many upregulated genes are involved in extracellular matrix remodelling, including collagens and members of the small leucine-rich proteoglycan family (LUM, DCN, and ASPN). No significant differences were seen between letrozole and anastrozole in terms of molecular effects. The gene changes were integrated into a Global Index of Dependence on Estrogen (GIDE), which enumerates the genes changing by at least twofold with therapy. The GIDE varied markedly between tumours and related significantly to pretreatment levels of HER2 and changes in immunohistochemically detected Ki67.ConclusionOur findings identify the transcriptional signatures associated with aromatase inhibitor treatment of primary breast tumours. Larger datasets using this approach should enable identification of estrogen-dependent molecular changes, which are the determinants of benefit or resistance to endocrine therapy

Fussy Feeders: Phyllosoma Larvae of the Western Rocklobster (Panulirus cygnus) Demonstrate Prey Preference

The Western Rocklobster (Panulirus cygnus) is the most valuable single species fishery in Australia and the largest single country spiny lobster fishery in the world. In recent years a well-known relationship between oceanographic conditions and lobster recruitment has become uncoupled, with significantly lower recruitment than expected, generating interest in the factors influencing survival and development of the planktonic larval stages. The nutritional requirements and wild prey of the planktotrophic larval stage (phyllosoma) of P. cygnus were previously unknown, hampering both management and aquaculture efforts for this species. Ship-board feeding trials of wild-caught mid-late stage P. cygnus phyllosoma in the eastern Indian Ocean, off the coast of Western Australia, were conducted in July 2010 and August-September 2011. In a series of experiments, phyllosoma were fed single and mixed species diets of relatively abundant potential prey items (chaetognaths, salps, and krill). Chaetognaths were consumed in 2–8 times higher numbers than the other prey, and the rate of consumption of chaetognaths increased with increasing concentration of prey. The highly variable lipid content of the phyllosoma, and the fatty acid profiles of the phyllosoma and chaetognaths, indicated they were from an oligotrophic oceanic food chain where food resources for macrozooplankton were likely to be constrained. Phyllosoma fed chaetognaths over 6 days showed significant changes in some fatty acids and tended to accumulate lipid, indicating an improvement in overall nutritional condition. The discovery of a preferred prey for P. cygnus will provide a basis for future oceanographic, management and aquaculture research for this economically and ecologically valuable species