Living with multimorbidity: medical and lay healthcare approaches

Multimorbidity is rapidly becoming the norm rather than the exception in healthcare. Research on this issue is increasing and this review discusses a selection of clinical and social science literature. The focus is on understanding the complexity of the lived experience of multimorbidity and how this is presented in clinical encounters, drawing on examples of arthritis within a multimorbidity context. Taking into account the biophysical, psychological, social and cultural factors that shape multimorbidity this paper calls for a re-conceptualization of the concept, allowing a more dynamic and holistic approach

The Effect of Pre-Injury Anti-Platelet Therapy on the Development of Complications in Isolated Blunt Chest Wall Trauma: A Retrospective Study

INTRODUCTION: The difficulties in the management of the blunt chest wall trauma patient in the Emergency Department due to the development of late complications are well recognised in the literature. Pre-injury anti-platelet therapy has been previously investigated as a risk factor for poor outcomes following traumatic head injury, but not in the blunt chest wall trauma patient cohort. The aim of this study was to investigate pre-injury anti-platelet therapy as a risk factor for the development of complications in the recovery phase following blunt chest wall trauma. METHODS: A retrospective study was completed in which the medical notes were analysed of all blunt chest wall trauma patients presenting to a large trauma centre in Wales in 2012 and 2013. Using univariate and multivariable logistic regression analysis, pre-injury platelet therapy was investigated as a risk factor for the development of complications following blunt chest wall trauma. Previously identified risk factors were included in the analysis to address the influence of confounding. RESULTS: A total of 1303 isolated blunt chest wall trauma patients presented to the ED in Morriston Hospital in 2012 and 2013 with complications recorded in 144 patients (11%). On multi-variable analysis, pre-injury anti-platelet therapy was found to be a significant risk factor for the development of complications following isolated blunt chest wall trauma (odds ratio: 16.9; 95% confidence intervals: 8.2-35.2). As in previous studies patient age, number of rib fractures, chronic lung disease and pre-injury anti-coagulant use were also found to be significant risk factors. CONCLUSIONS: Pre-injury anti-platelet therapy is being increasingly used as a first line treatment for a number of conditions and there is a concurrent increase in trauma in the elderly population. Pre-injury anti-platelet therapy should be considered as a risk factor for the development of complications by clinicians managing blunt chest wall trauma

A Latent Pro-survival Function for the Mir-290-295 Cluster in Mouse Embryonic Stem Cells

MicroRNAs (miRNAs) post-transcriptionally regulate the expression of thousands of distinct mRNAs. While some regulatory interactions help to maintain basal cellular functions, others are likely relevant in more specific settings, such as response to stress. Here we describe such a role for the mir-290-295 cluster, the dominant miRNA cluster in mouse embryonic stem cells (mESCs). Examination of a target list generated from bioinformatic prediction, as well as expression data following miRNA loss, revealed strong enrichment for apoptotic regulators, two of which we validated directly: Caspase 2, the most highly conserved mammalian caspase, and Ei24, a p53 transcriptional target. Consistent with these predictions, mESCs lacking miRNAs were more likely to initiate apoptosis following genotoxic exposure to gamma irradiation or doxorubicin. Knockdown of either candidate partially rescued this pro-apoptotic phenotype, as did transfection of members of the mir-290-295 cluster. These findings were recapitulated in a specific mir-290-295 deletion line, confirming that they reflect miRNA functions at physiological levels. In contrast to the basal regulatory roles previously identified, the pro-survival phenotype shown here may be most relevant to stressful gestations, where pro-oxidant metabolic states induce DNA damage. Similarly, this cluster may mediate chemotherapeutic resistance in a neoplastic context, making it a useful clinical target.National Institutes of Health (U.S.) (NIH grant RO1-GM34277)National Cancer Institute (U.S.) (NCI grant PO1-CA42063)National Cancer Institute (U.S.) (NCI Cancer Center Support (core) grant P30-CA14051

Evolutionary and pulsational properties of white dwarf stars

Abridged. White dwarf stars are the final evolutionary stage of the vast majority of stars, including our Sun. The study of white dwarfs has potential applications to different fields of astrophysics. In particular, they can be used as independent reliable cosmic clocks, and can also provide valuable information about the fundamental parameters of a wide variety of stellar populations, like our Galaxy and open and globular clusters. In addition, the high densities and temperatures characterizing white dwarfs allow to use these stars as cosmic laboratories for studying physical processes under extreme conditions that cannot be achieved in terrestrial laboratories. They can be used to constrain fundamental properties of elementary particles such as axions and neutrinos, and to study problems related to the variation of fundamental constants. In this work, we review the essentials of the physics of white dwarf stars. Special emphasis is placed on the physical processes that lead to the formation of white dwarfs as well as on the different energy sources and processes responsible for chemical abundance changes that occur along their evolution. Moreover, in the course of their lives, white dwarfs cross different pulsational instability strips. The existence of these instability strips provides astronomers with an unique opportunity to peer into their internal structure that would otherwise remain hidden from observers. We will show that this allows to measure with unprecedented precision the stellar masses and to infer their envelope thicknesses, to probe the core chemical stratification, and to detect rotation rates and magnetic fields. Consequently, in this work, we also review the pulsational properties of white dwarfs and the most recent applications of white dwarf asteroseismology.Comment: 85 pages, 28 figures. To be published in The Astronomy and Astrophysics Revie

Methods for peptide identification by spectral comparison

BACKGROUND: Tandem mass spectrometry followed by database search is currently the predominant technology for peptide sequencing in shotgun proteomics experiments. Most methods compare experimentally observed spectra to the theoretical spectra predicted from the sequences in protein databases. There is a growing interest, however, in comparing unknown experimental spectra to a library of previously identified spectra. This approach has the advantage of taking into account instrument-dependent factors and peptide-specific differences in fragmentation probabilities. It is also computationally more efficient for high-throughput proteomics studies. RESULTS: This paper investigates computational issues related to this spectral comparison approach. Different methods have been empirically evaluated over several large sets of spectra. First, we illustrate that the peak intensities follow a Poisson distribution. This implies that applying a square root transform will optimally stabilize the peak intensity variance. Our results show that the square root did indeed outperform other transforms, resulting in improved accuracy of spectral matching. Second, different measures of spectral similarity were compared, and the results illustrated that the correlation coefficient was most robust. Finally, we examine how to assemble multiple spectra associated with the same peptide to generate a synthetic reference spectrum. Ensemble averaging is shown to provide the best combination of accuracy and efficiency. CONCLUSION: Our results demonstrate that when combined, these methods can boost the sensitivity and specificity of spectral comparison. Therefore they are capable of enhancing and complementing existing tools for consistent and accurate peptide identification

A competitive integration model of exogenous and endogenous eye movements

We present a model of the eye movement system in which the programming of an eye movement is the result of the competitive integration of information in the superior colliculi (SC). This brain area receives input from occipital cortex, the frontal eye fields, and the dorsolateral prefrontal cortex, on the basis of which it computes the location of the next saccadic target. Two critical assumptions in the model are that cortical inputs are not only excitatory, but can also inhibit saccades to specific locations, and that the SC continue to influence the trajectory of a saccade while it is being executed. With these assumptions, we account for many neurophysiological and behavioral findings from eye movement research. Interactions within the saccade map are shown to account for effects of distractors on saccadic reaction time (SRT) and saccade trajectory, including the global effect and oculomotor capture. In addition, the model accounts for express saccades, the gap effect, saccadic reaction times for antisaccades, and recorded responses from neurons in the SC and frontal eye fields in these tasks. © The Author(s) 2010

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Influenza vaccination for immunocompromised patients: systematic review and meta-analysis from a public health policy perspective.

Immunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events

Does maternal exposure to an environmental stressor affect offspring response to predators?

There is growing recognition of the ways in which maternal effects can influence offspring size, physiological performance, and survival. Additionally, environmental contaminants increasingly act as stressors in maternal environments, possibly leading to maternal effects on subsequent offspring. Thus, it is important to determine whether contaminants and other stressors can contribute to maternal effects, particularly under varied ecological conditions that encompass the range under which offspring develop. We used aquatic mesocosms to determine whether maternal effects of mercury (Hg) exposure shape offspring phenotype in the American toad (Bufo americanus) in the presence or absence of larval predators (dragonfly naiads). We found significant maternal effects of Hg exposure and significant effects of predators on several offspring traits, but there was little evidence that maternal effects altered offspring interactions with predators. Offspring from Hg-exposed mothers were 18% smaller than those of reference mothers. Offspring reared with predators were 23% smaller at metamorphosis than those reared without predators. There was also evidence of reduced larval survival when larvae were reared with predators, but this was independent of maternal effects. Additionally, 5 times more larvae had spinal malformations when reared without predators, suggesting selective predation of malformed larvae by predators. Lastly, we found a significant negative correlation between offspring survival and algal density in mesocosms, indicating a role for top-down effects of predators on periphyton communities. Our results demonstrate that maternal exposure to an environmental stressor can induce phenotypic responses in offspring in a direction similar to that produced by direct exposure of offspring to predators