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

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

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

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

Characteristics and trends in required home care by GPs in Austria: diseases and functional status of patients

BACKGROUND: Almost all societies carry responsibility towards patients who require continuous medical care at home. In many health systems the general practitioner cooperates with community based services of home care and coordinates all medical and non medical activities. In Austria the general practitioner together and in cooperation with relatives of the patient and professional organisations usually takes on this task by visiting his patients. This study was carried out to identify diseases that need home care and to describe the functional profile of home care patients in eastern Austria. METHODS: Cross sectional observational study with 17 GP practices participating during 2 study periods in 1997 and in 2004 in eastern Austria. Each GP identified patients requiring home care and assessed their underlying diseases and functional status by filling in a questionnaire personally after an encounter. Patients in nursing homes were excluded. Statistical tests used were t-tests, contingency tables, nonparametric Wilcoxon signed rank sum test and Fisher-combination test. RESULTS: Patients with degenerative diseases of the central nervous system (65%) caused by Alzheimer's disease and cerebrovascular occlusive disease and patients with degenerative diseases of the skeletal system (53%) were the largest groups among the 198 (1997) and 261 (2004) home care cases of the 11 (1997) and 13 (2004) practices. Malignant diseases in a terminal state constituted only 5% of the cases. More than two thirds of all cases were female with an average age of 80 years. Slightly more than 70% of the patients were at least partially mobile. CONCLUSION: Home care and home visits for patients with degenerative diseases of the central nervous and skeletal system are important elements of GP's work. Further research should therefore focus on effective methods of training and rehabilitation to better the mental and physical status of patients living in their private homes

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 comparative evaluation of the effect of internet-based CME delivery format on satisfaction, knowledge and confidence

<p>Abstract</p> <p>Background</p> <p>Internet-based instruction in continuing medical education (CME) has been associated with favorable outcomes. However, more direct comparative studies of different Internet-based interventions, instructional methods, presentation formats, and approaches to implementation are needed. The purpose of this study was to conduct a comparative evaluation of two Internet-based CME delivery formats and the effect on satisfaction, knowledge and confidence outcomes.</p> <p>Methods</p> <p>Evaluative outcomes of two differing formats of an Internet-based CME course with identical subject matter were compared. A Scheduled Group Learning format involved case-based asynchronous discussions with peers and a facilitator over a scheduled 3-week delivery period. An eCME On Demand format did not include facilitated discussion and was not based on a schedule; participants could start and finish at any time. A retrospective, pre-post evaluation study design comparing identical satisfaction, knowledge and confidence outcome measures was conducted.</p> <p>Results</p> <p>Participants in the Scheduled Group Learning format reported significantly higher mean satisfaction ratings in some areas, performed significantly higher on a post-knowledge assessment and reported significantly higher post-confidence scores than participants in the eCME On Demand format that was not scheduled and did not include facilitated discussion activity.</p> <p>Conclusions</p> <p>The findings support the instructional benefits of a scheduled delivery format and facilitated asynchronous discussion in Internet-based CME.</p

Basement membrane and vascular remodelling in smokers and chronic obstructive pulmonary disease: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Little is known about airway remodelling in bronchial biopsies (BB) in smokers and chronic obstructive pulmonary disease (COPD). We conducted an initial pilot study comparing BB from COPD patients with nonsmoking controls. This pilot study suggested the presence of reticular basement membrane (Rbm) fragmentation and altered vessel distribution in COPD.</p> <p>Methods</p> <p>To determine whether Rbm fragmentation and altered vessel distribution in BB were specific for COPD we designed a cross-sectional study and stained BB from 19 current smokers and 14 ex-smokers with mild to moderate COPD and compared these to 15 current smokers with normal lung function and 17 healthy and nonsmoking subjects.</p> <p>Results</p> <p>Thickness of the Rbm was not significantly different between groups; although in COPD this parameter was quite variable. The Rbm showed fragmentation and splitting in both current smoking groups and ex-smoker COPD compared with healthy nonsmokers (p < 0.02); smoking and COPD seemed to have additive effects. Rbm fragmentation correlated with smoking history in COPD but not with age. There were more vessels in the Rbm and fewer vessels in the lamina propria in current smokers compared to healthy nonsmokers (p < 0.05). The number of vessels staining for vascular endothelial growth factor (VEGF) in the Rbm was higher in both current smoker groups and ex-smoker COPD compared to healthy nonsmokers (p < 0.004). In current smoker COPD VEGF vessel staining correlated with FEV1% predicted (r = 0.61, p < 0.02).</p> <p>Conclusions</p> <p>Airway remodelling in smokers and mild to moderate COPD is associated with fragmentation of the Rbm and altered distribution of vessels in the airway wall. Rbm fragmentation was also present to as great an extent in ex-smokers with COPD. These characteristics may have potential physiological consequences.</p

Maximum in the Middle: Nonlinear Response of Microbial Plankton to Ultraviolet Radiation and Phosphorus

The responses of heterotrophic microbial food webs (HMFW) to the joint action of abiotic stressors related to global change have been studied in an oligotrophic high-mountain lake. A 2×5 factorial design field experiment performed with large mesocosms for >2 months was used to quantify the dynamics of the entire HMFW (bacteria, heterotrophic nanoflagellates, ciliates, and viruses) after an experimental P-enrichment gradient which approximated or surpassed current atmospheric P pulses in the presence vs. absence of ultraviolet radiation. HMFW underwent a mid-term (<20 days) acute development following a noticeable unimodal response to P enrichment, which peaked at intermediate P-enrichment levels and, unexpectedly, was more accentuated under ultraviolet radiation. However, after depletion of dissolved inorganic P, the HMFW collapsed and was outcompeted by a low-diversity autotrophic compartment, which constrained the development of HMFW and caused a significant loss of functional biodiversity. The dynamics and relationships among variables, and the response patterns found, suggest the importance of biotic interactions (predation/parasitism and competition) in restricting HMFW development, in contrast to the role of abiotic factors as main drivers of autotrophic compartment. The response of HMFW may contribute to ecosystem resilience by favoring the maintenance of the peculiar paths of energy and nutrient-mobilization in these pristine ecosystems, which are vulnerable to threats by the joint action of abiotic stressors related to global change.This research was supported by Junta de Andalucía (Excelencia P07-CVI-02598 to PC, and P09-RNM-5376 to JMMS), the Spanish Ministries of Medio Ambiente, Rural y Marino (PN2009/067 to PC) and Ciencia e Innovación (GLC2008-01127/BOS and CGL2011-23681 to PC), the ERC Advanced Grant project number 250254 “MINOS” (to GB), and two Spanish government grants (to JADM and FJB)