Differential Subordinations Involving Generalized Bessel Functions

In this paper our aim is to present some subordination and superordination results, by using an operator, which involves the normalized form of the generalized Bessel functions of first kind. These results are obtained by investigating some appropriate classes of admissible functions. We obtain also some sandwich-type results and we point out various known or new special cases of our main results.Comment: 15 pages, accepted in Bulletin of the Malaysian Mathematical Sciences Societ

Optimal search strategies for identifying sound clinical prediction studies in EMBASE

BACKGROUND: Clinical prediction guides assist clinicians by pointing to specific elements of the patient's clinical presentation that should be considered when forming a diagnosis, prognosis or judgment regarding treatment outcome. The numbers of validated clinical prediction guides are growing in the medical literature, but their retrieval from large biomedical databases remains problematic and this presents a barrier to their uptake in medical practice. We undertook the systematic development of search strategies ("hedges") for retrieval of empirically tested clinical prediction guides from EMBASE. METHODS: An analytic survey was conducted, testing the retrieval performance of search strategies run in EMBASE against the gold standard of hand searching, using a sample of all 27,769 articles identified in 55 journals for the 2000 publishing year. All articles were categorized as original studies, review articles, general papers, or case reports. The original and review articles were then tagged as 'pass' or 'fail' for methodologic rigor in the areas of clinical prediction guides and other clinical topics. Search terms that depicted clinical prediction guides were selected from a pool of index terms and text words gathered in house and through request to clinicians, librarians and professional searchers. A total of 36,232 search strategies composed of single and multiple term phrases were trialed for retrieval of clinical prediction studies. The sensitivity, specificity, precision, and accuracy of search strategies were calculated to identify which were the best. RESULTS: 163 clinical prediction studies were identified, of which 69 (42.3%) passed criteria for scientific merit. A 3-term strategy optimized sensitivity at 91.3% and specificity at 90.2%. Higher sensitivity (97.1%) was reached with a different 3-term strategy, but with a 16% drop in specificity. The best measure of specificity (98.8%) was found in a 2-term strategy, but with a considerable fall in sensitivity to 60.9%. All single term strategies performed less well than 2- and 3-term strategies. CONCLUSION: The retrieval of sound clinical prediction studies from EMBASE is supported by several search strategies

Significance of herpesvirus immediate early gene expression in cellular immunity to cytomegalovirus infection

Interstitial pneumonia linked with reactivation of latent human cytomegalovirus due to iatrogenic immunosuppression can be a serious complication of bone marrow transplantation therapy of aplastic anaemia and acute leukaemia1. Cellular immunity plays a critical role in the immune surveillance of inapparent cytomegalovirus infections in man and the mouse1−7. The molecular basis of latency, however, and the interaction between latently or recurrently infected cells and the immune system of the host are poorfy understood. We have detected a so far unknown antigen in the mouse model. This antigen is found in infected cells in association with the expression of the herpesvirus 'immediate early' genes and is recognized by cytolytic T lymphocytes (CTL)8. We now demonstrate that an unexpectedly high proportion of the CTL precursors generated in vivo during acute murine cytomegalovirus infection are specific for cells that selectively synthesize immediate early proteins, indicating an immunodominant role of viral non-structural proteins

The science of clinical practice: disease diagnosis or patient prognosis? Evidence about "what is likely to happen" should shape clinical practice.

BACKGROUND: Diagnosis is the traditional basis for decision-making in clinical practice. Evidence is often lacking about future benefits and harms of these decisions for patients diagnosed with and without disease. We propose that a model of clinical practice focused on patient prognosis and predicting the likelihood of future outcomes may be more useful. DISCUSSION: Disease diagnosis can provide crucial information for clinical decisions that influence outcome in serious acute illness. However, the central role of diagnosis in clinical practice is challenged by evidence that it does not always benefit patients and that factors other than disease are important in determining patient outcome. The concept of disease as a dichotomous 'yes' or 'no' is challenged by the frequent use of diagnostic indicators with continuous distributions, such as blood sugar, which are better understood as contributing information about the probability of a patient's future outcome. Moreover, many illnesses, such as chronic fatigue, cannot usefully be labelled from a disease-diagnosis perspective. In such cases, a prognostic model provides an alternative framework for clinical practice that extends beyond disease and diagnosis and incorporates a wide range of information to predict future patient outcomes and to guide decisions to improve them. Such information embraces non-disease factors and genetic and other biomarkers which influence outcome. SUMMARY: Patient prognosis can provide the framework for modern clinical practice to integrate information from the expanding biological, social, and clinical database for more effective and efficient care

The impact of point mutations in the human androgen receptor : classification of mutations on the basis of transcriptional activity

Peer reviewedPublisher PD

Celecoxib exerts protective effects in the vascular endothelium via COX-2-independent activation of AMPK-CREB-Nrf2 signalling

Although concern remains about the athero-thrombotic risk posed by cyclo-oxygenase (COX)-2-selective inhibitors, recent data implicates rofecoxib, while celecoxib appears equivalent to NSAIDs naproxen and ibuprofen. We investigated the hypothesis that celecoxib activates AMP kinase (AMPK) signalling to enhance vascular endothelial protection. In human arterial and venous endothelial cells (EC), and in contrast to ibuprofen and naproxen, celecoxib induced the protective protein heme oxygenase-1 (HO-1). Celecoxib derivative 2,5-dimethyl-celecoxib (DMC) which lacks COX-2 inhibition also upregulated HO-1, implicating a COX-2-independent mechanism. Celecoxib activated AMPKα(Thr172) and CREB-1(Ser133) phosphorylation leading to Nrf2 nuclear translocation. Importantly, these responses were not reproduced by ibuprofen or naproxen, while AMPKα silencing abrogated celecoxib-mediated CREB and Nrf2 activation. Moreover, celecoxib induced H-ferritin via the same pathway, and increased HO-1 and H-ferritin in the aortic endothelium of mice fed celecoxib (1000 ppm) or control chow. Functionally, celecoxib inhibited TNF-α-induced NF-κB p65(Ser536) phosphorylation by activating AMPK. This attenuated VCAM-1 upregulation via induction of HO-1, a response reproduced by DMC but not ibuprofen or naproxen. Similarly, celecoxib prevented IL-1β-mediated induction of IL-6. Celecoxib enhances vascular protection via AMPK-CREB-Nrf2 signalling, a mechanism which may mitigate cardiovascular risk in patients prescribed celecoxib. Understanding NSAID heterogeneity and COX-2-independent signalling will ultimately lead to safer anti-inflammatory drugs

Identification of the factors associated with outcomes in a condition management programme

<p>Background: A requirement of the Government’s Pathways to Work (PtW) agenda was to introduce a Condition Management Programme (CMP). The aim of the present study was to identify the differences between those who engaged and made progress in this telephone-based biopsychosocial intervention, in terms of their health, and those who did not and to determine the client and practitioner characteristics and programme elements associated with success in a programme aimed at improving health.</p> <p>Methods: Data were obtained from the CMP electronic spreadsheets and clients paper-based case records. CMP standard practice was that questionnaires were administered during the pre- and post-assessment phases over the telephone. Each client’s record contains their socio-demographic data, their primary health condition, as well as the pre- and post-intervention scores of the health assessment tool administered. Univariate and multivariate statistical analysis was used to investigate the relationships between the database variables. Clients were included in the study if their records were available for analysis from July 2006 to December 2007.</p> <p> Results: On average there were 112 referrals per month, totalling 2016 referrals during the evaluation period. The majority (62.8%) of clients had a mental-health condition. Successful completion of the programme was 28.5% (575 “completers”; 144 “discharges”). Several factors, such as age, health condition, mode of contact, and practitioner characteristics, were significant determinants of participation and completion of the programme. The results showed that completion of the CMP was associated with a better mental-health status, by reducing the number of clients that were either anxious, depressed or both, before undertaking the programme, from 74% to 32.5%.</p> <p>Conclusions: Our findings showed that an individual's characteristics are associated with success in the programme, defined as completing the intervention and demonstrating an improved health status. This study provides some evidence that the systematic evaluation of such programmes and interventions could identify ways in which they could be improved.</p&gt

Type D patients report poorer health status prior to and after cardiac rehabilitation compared to non-type D patients

Background: Type D personality is an emerging risk factor in coronary artery disease (CAD). Cardiac rehabilitation (CR) improves outcomes, but little is known about the effects of CR on Type D patients. Purpose: We examined (1) variability in Type D caseness following CR, (2) Type D as a determinant of health status, and (3) the clinical relevance of Type D as a determinant of health status compared to cardiac history. Methods: CAD patients (n = 368) participating in CR completed the Type D Scale, the Short-Form Health Survey 36 pre- and post-CR, and the Hospital Anxiety and Depression Scale pre-CR, to assess health status and depressive and anxious symptomatology, respectively. Results: The prevalence of Type D decreased from 26.6% to 20.7% (p = 0.012) following CR, but Type D caseness remained stable in 81% of patients. Health status significantly improved following CR [F(1,359) = 17.48, p < 0.001], adjusting for demographic and clinical factors and anxious and depressive symptoms. Type D patients reported poorer health status [F(1,359) = 10.40, p = 0.001], with the effect of Type D being stable over time [F(1,359) = 0.49, p = 0.48]. Patients with a cardiac history benefited less from CR [F(1,359) = 5.76, p = 0.02]. The influence of Type D on health status was larger compared to that for cardiac history, as indicated by Cohen's effect size index. Conclusions: Type D patients reported poorer health status compared to non-Type D patients pre- and post-CR. In the majority of patients, CR did not change Type D caseness, with Type D being associated with a stable and clinically relevant effect on outcome. These high-risk patients should

Stat3 controls cell death during mammary gland involution by regulating uptake of milk fat globules and lysosomal membrane permeabilization.

We have previously demonstrated that Stat3 regulates lysosomal-mediated programmed cell death (LM-PCD) during mouse mammary gland involution in vivo. However, the mechanism that controls the release of lysosomal cathepsins to initiate cell death in this context has not been elucidated. We show here that Stat3 regulates the formation of large lysosomal vacuoles that contain triglyceride. Furthermore, we demonstrate that milk fat globules (MFGs) are toxic to epithelial cells and that, when applied to purified lysosomes, the MFG hydrolysate oleic acid potently induces lysosomal leakiness. Additionally, uptake of secreted MFGs coated in butyrophilin 1A1 is diminished in Stat3-ablated mammary glands and loss of the phagocytosis bridging molecule MFG-E8 results in reduced leakage of cathepsins in vivo. We propose that Stat3 regulates LM-PCD in mouse mammary gland by switching cellular function from secretion to uptake of MFGs. Thereafter, perturbation of lysosomal vesicle membranes by high levels of free fatty acids results in controlled leakage of cathepsins culminating in cell death.This work was supported by a grant from the Medical Research Council programme grant no. MR/J001023/1 (T.J.S. and B. L-L.) and a Cancer Research UK Cambridge Cancer Centre PhD studentship (H.K.R.).This is the accepted manuscript. The final version is available from Nature Publishing at http://www.nature.com/ncb/journal/vaop/ncurrent/full/ncb3043.html

Proactive and politically skilled professionals: What is the relationship with affective occupational commitment?

The aim of this study is to extend research on employee affective commitment in three ways: (1) instead of organizational commitment the focus is on occupational commitment; (2) the role of proactive personality on affective occupational commitment is examined; and (3) occupational satisfaction is examined as a mediator and political skills as moderator in the relationship between proactive personality and affective occupational commitment. Two connected studies, one in a hospital located in the private sector and one in a university located in the public sector, are carried out in Pakistan, drawing on a total sample of over 400 employees. The results show that proactive personality is positively related to affective occupational commitment, and that occupational satisfaction partly mediates the relationship between proactive personality and affective occupational commitment. No effect is found for a moderator effect of political skills in the relationship between proactive personality and affective occupational commitment. Political skills however moderate the relationship between proactive personality and affective organizational commitment