A single, one-off measure of depression and anxiety predicts future symptoms, higher healthcare costs, and lower quality of life in coronary heart disease patients: Analysis from a multi-wave, primary care cohort study

To determine whether a one-off, baseline measure of depression and anxiety in a primary care, coronary heart disease (CHD) population predicts ongoing symptoms, costs, and quality of life across a 3-year follow-up.Longitudinal cohort study.16 General Practice surgeries across South-East London.803 adults (70% male, mean age 71 years) contributing up to 7 follow-up points.Ongoing reporting of symptoms, health care costs, and quality of life.At baseline, 27% of the sample screened positive for symptoms of depression and anxiety, as measured by the Hospital Anxiety and Depression Scale (HADS). The probability of scoring above the cut-off throughout the follow-up was 71.5% (p<0.001) for those screening positive at baseline, and for those screening negative, the probability of scoring below the cut-off throughout the follow-up was 97.6% (p<0.001). Total health care costs were 39% higher during follow-up for those screening positive (p<0.05). Quality of life as measured by the SF-12 was lower on the mental component during follow-up for those screening positive (-0.75, CI -1.53 to 0.03, p = 0.059), and significantly lower on the physical component (-4.99, CI -6.23 to -.376, p<0.001).A one-off measure for depression and anxiety symptoms in CHD predicts future symptoms, costs, and quality of life over the subsequent three-years. These findings suggest symptoms of depression and anxiety in CHD persist throughout long periods and are detrimental to a patient's quality of life, whilst incurring higher health care costs for primary and secondary care services. Screening for these symptoms at the primary care level is important to identify and manage patients at risk of the negative effects of this comorbidity. Implementation of screening, and possible collaborative care strategies and interventions that help mitigate this risk should be the ongoing focus of researchers and policy-makers

Absence of Inhibin Alpha and Retinoblastoma Protein Leads to Early Sertoli Cell Dysfunction

Sertoli cells, the support cells of mammalian spermatogenesis, are regulated by a number of nuclear factors and express retinoblastoma (RB) tumor suppressor protein. We hypothesized that RB is an important mediator of Sertoli cell tumorigenesis in inhibin α knockout (Inha KO) mice. In our previous mouse studies, we found that conditional knockout (cKO) of Rb in Sertoli cells caused progressive Sertoli cell dysfunction. Initially, loss of RB had no gross effect on Sertoli cell function as the mice were fertile with normal testis weights at 6 weeks of age, but by 10–14 weeks of age, mutant mice demonstrated severe Sertoli cell dysfunction and infertility. Although double knockout (dKO) of Rb and Inha did not result in exacerbation of the tumorigenic phenotype of Inha-null mice, we found that the dKO mice demonstrate an acceleration of Sertoli cell dysfunction compared to Rb cKO mice. Specifically, in contrast to Rb cKO mice, Inha/Rb dKO mice showed signs of Sertoli cell dysfunction as early as 4 weeks of age. These results demonstrate that RB is not essential for Sertoli cell tumorigenesis in Inha KO mice but that loss of Inha accelerates the infertility phenotype of Rb cKO mice

Cyber-risk in Healthcare: Exploring Facilitators and Barriers to Secure Behaviour

There are increasing concerns relating to cybersecurity of healthcare data and medical devices. Cybersecurity in this sector is particularly important given the criticality of healthcare systems, the impacts of a breach or cyberattack (including in the worst instance, potential physical harm to patients) and the value of healthcare data to criminals. Technology design is important for cybersecurity, but it is also necessary to understand the insecure behaviours prevalent within healthcare. It is vital to identify the drivers behind these behaviours, i.e., why staff may engage in insecure behaviour including their goals and motivations and/or perceived barriers preventing secure behaviour. To achieve this, in-depth interviews with 50 staff were conducted at three healthcare sites, across three countries (Ireland, Italy and Greece). A range of seven insecure behaviours were reported: Poor computer and user account security; Unsafe e-mail use; Use of USBs and personal devices; Remote access and home working; Lack of encryption, backups and updates; Use of connected medical devices; and poor physical security. Thematic analysis revealed four key facilitators of insecure behaviour: Lack of awareness and experience, Shadow working processes, Behaviour prioritisation and Environmental appropriateness. The findings suggest three key barriers to security: i) Security perceived as a barrier to productivity and/or patient care; ii) Poor awareness of consequences of behaviour; and iii) a lack of policies and reinforcement of secure behaviour. Implications for future research are presented

IL-2 Regulates SEB Induced Toxic Shock Syndrome in BALB/c Mice

BACKGROUND:Toxic Shock Syndrome (TSS) is characterized by fever, rash, hypotension, constitutional symptoms, and multi-organ involvement and is caused by Staphylococcus aureus enterotoxins such as Staphylococcal Enterotoxin B (SEB). SEB binds to the MHC-IIalpha chain and is recognized by the TCRbeta chain of the Vbeta8 TCR(+) T cells. The binding of SEB to Vbeta chain results in rapid activation of T cells and production of inflammatory cytokines, such as Interleukin-2 (IL-2), Interferon-gamma and Tumor Necrosis Factor-alpha which mediate TSS. Although IL2 was originally identified as the T cell growth factor and was proposed to contribute to T cell differentiation, its role in TSS remains unexplored. METHODOLOGY/PRINCIPAL FINDINGS:Mice were injected with D-Gal (25 mg/mouse). One hour after D-Galactosamine (D-Gal) injection each mouse was injected with SEB (20 microg/mouse. Mice were then observed for 72 hrs and death was recorded at different times. We tested Interleukin-12, IFNgamma, and IL-2 deficient mice (IL-2(-/-)), but only the IL-2 deficient mice were resistant to SEB induced toxic shock syndrome. More importantly reconstitution of IL-2 in IL-2 deficient mice restored the shock. Interestingly, SEB induced IL-2 production from T cells was dependent on p38MAPK activation in macrophages as inhibition of it in macrophages significantly inhibited IL-2 production from T cells. CONCLUSION:This study shows the importance of IL -2 in TSS which has not been previously explored and it also shows that regulating macrophages function can regulate T cells and TSS

Approach to the Immunosuppressed Patient with Pulmonary Infiltrates

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65614/1/j.1365-4362.1980.tb00811.x.pd

Anti-ischemic therapy and stress testing: pathophysiologic, diagnostic and prognostic implications

Anti-ischemic therapy, in particular beta-blockers, is the most commonly employed drug for the control of myocardial ischemia in patients with stable coronary artery disease. Its widespread use also in patients with suspected coronary artery disease has important practical, clinical diagnostic and prognostic implications because diagnostic tests are heavily influenced by its effects. In the present review, the pathophysiological mechanisms of ischemia protection by antianginal therapy are described. Not all stressors are created equal in front of the different classes of antianginal drugs and on their turn the different classes of drugs exert different levels of protection on inducible ischemia. Several clinical implications can be drawn: From the diagnostic viewpoint antianginal therapy decreases test sensitivity, offsetting the real ischemic burden for a too high percentage of false negative tests. From the prognostic viewpoint test positivity in medical therapy identifies a group of subjects at higher risk of experiencing cardiac death and positivity on medical therapy can be considered a parameter of ischemia severity. Nonetheless in patients with known coronary artery disease the ability of antianginal therapy to modify the ischemic threshold at stress testing represent a powerful means to assess therapy efficacy. From a practical viewpoint, the use of antianginal therapy at time of testing has advantages and disadvantages which are largely dependent on the purpose a test is performed: if the purpose of testing is to diagnose ischemia, it should be performed in the absence of antianginal medications. If the purpose of testing is to assess the protective effects of antianginal therapy, the test should be performed on medications

“Hot Hand” on Strike: Bowling Data Indicates Correlation to Recent Past Results, Not Causality

Recently, the “hot hand” phenomenon regained interest due to the availability and accessibility of large scale data sets from the world of sports. In support of common wisdom and in contrast to the original conclusions of the seminal paper about this phenomenon by Gilovich, Vallone and Tversky in 1985, solid evidences were supplied in favor of the existence of this phenomenon in different kinds of data. This came after almost three decades of ongoing debates whether the “hot hand” phenomenon in sport is real or just a mis-perception of human subjects of completely random patterns present in reality. However, although this phenomenon was shown to exist in different sports data including basketball free throws and bowling strike rates, a somehow deeper question remained unanswered: are these non random patterns results of causal, short term, feedback mechanisms or simply time fluctuations of athletes performance. In this paper, we analyze large amounts of data from the Professional Bowling Association(PBA). We studied the results of the top 100 players in terms of the number of available records (summed into more than 450,000 frames). By using permutation approach and dividing the analysis into different aggregation levels we were able to supply evidence for the existence of the “hot hand” phenomenon in the data, in agreement with previous studies. Moreover, by using this approach, we were able to demonstrate that there are, indeed, significant fluctuations from game to game for the same player but there is no clustering of successes (strikes) and failures (non strikes) within each game. Thus we were lead to the conclusion that bowling results show correlation to recent past results but they are not influenced by them in a causal manner

Resveratrol increases BRCA1 and BRCA2 mRNA expression in breast tumour cell lines

International audienceThe phytochemical resveratrol, found in grapes, berries and peanuts, has been found to possess cancer chemopreventive effects by inhibiting diverse cellular events associated with tumour initiation, promotion and progression. Resveratrol is also a phyto-oestrogen, binds to and activates oestrogen receptors that regulate the transcription of oestrogen-responsive target genes such as the breast cancer susceptibility genes BRCA1 and BRCA2. We investigated the effects of resveratrol on BRCA1 and BRCA2 expression in human breast cancer cell lines (MCF7, HBL 100 and MDA-MB 231) using quantitative real-time RT-PCR, and by perfusion chromatography of the proteins. All cell lines were treated with 30 microM resveratrol. The expressions of BRCA1 and BRCA2 mRNAs were increased although no change in the expression of the proteins were found. These data indicate that resveratrol at 30 micro M can increase expression of genes involved in the aggressiveness of human breast tumour cell lines

Assessing an organizational culture instrument based on the Competing Values Framework: Exploratory and confirmatory factor analyses

BACKGROUND: The Competing Values Framework (CVF) has been widely used in health services research to assess organizational culture as a predictor of quality improvement implementation, employee and patient satisfaction, and team functioning, among other outcomes. CVF instruments generally are presented as well-validated with reliable aggregated subscales. However, only one study in the health sector has been conducted for the express purpose of validation, and that study population was limited to hospital managers from a single geographic locale. METHODS: We used exploratory and confirmatory factor analyses to examine the underlying structure of data from a CVF instrument. We analyzed cross-sectional data from a work environment survey conducted in the Veterans Health Administration (VHA). The study population comprised all staff in non-supervisory positions. The survey included 14 items adapted from a popular CVF instrument, which measures organizational culture according to four subscales: hierarchical, entrepreneurial, team, and rational. RESULTS: Data from 71,776 non-supervisory employees (approximate response rate 51%) from 168 VHA facilities were used in this analysis. Internal consistency of the subscales was moderate to strong (α = 0.68 to 0.85). However, the entrepreneurial, team, and rational subscales had higher correlations across subscales than within, indicating poor divergent properties. Exploratory factor analysis revealed two factors, comprising the ten items from the entrepreneurial, team, and rational subscales loading on the first factor, and two items from the hierarchical subscale loading on the second factor, along with one item from the rational subscale that cross-loaded on both factors. Results from confirmatory factor analysis suggested that the two-subscale solution provides a more parsimonious fit to the data as compared to the original four-subscale model. CONCLUSION: This study suggests that there may be problems applying conventional CVF subscales to non-supervisors, and underscores the importance of assessing psychometric properties of instruments in each new context and population to which they are applied. It also further highlights the challenges management scholars face in assessing organizational culture in a reliable and comparable way. More research is needed to determine if the emergent two-subscale solution is a valid or meaningful alternative and whether these findings generalize beyond VHA

Avalanches in a Stochastic Model of Spiking Neurons

Neuronal avalanches are a form of spontaneous activity widely observed in cortical slices and other types of nervous tissue, both in vivo and in vitro. They are characterized by irregular, isolated population bursts when many neurons fire together, where the number of spikes per burst obeys a power law distribution. We simulate, using the Gillespie algorithm, a model of neuronal avalanches based on stochastic single neurons. The network consists of excitatory and inhibitory neurons, first with all-to-all connectivity and later with random sparse connectivity. Analyzing our model using the system size expansion, we show that the model obeys the standard Wilson-Cowan equations for large network sizes ( neurons). When excitation and inhibition are closely balanced, networks of thousands of neurons exhibit irregular synchronous activity, including the characteristic power law distribution of avalanche size. We show that these avalanches are due to the balanced network having weakly stable functionally feedforward dynamics, which amplifies some small fluctuations into the large population bursts. Balanced networks are thought to underlie a variety of observed network behaviours and have useful computational properties, such as responding quickly to changes in input. Thus, the appearance of avalanches in such functionally feedforward networks indicates that avalanches may be a simple consequence of a widely present network structure, when neuron dynamics are noisy. An important implication is that a network need not be “critical” for the production of avalanches, so experimentally observed power laws in burst size may be a signature of noisy functionally feedforward structure rather than of, for example, self-organized criticality