Epidemiology and Immune Pathogenesis of Viral Sepsis

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis can be caused by a broad range of pathogens; however, bacterial infections represent the majority of sepsis cases. Up to 42% of sepsis presentations are culture negative, suggesting a non-bacterial cause. Despite this, diagnosis of viral sepsis remains very rare. Almost any virus can cause sepsis in vulnerable patients (e.g., neonates, infants, and other immunosuppressed groups). The prevalence of viral sepsis is not known, nor is there enough information to make an accurate estimate. The initial standard of care for all cases of sepsis, even those that are subsequently proven to be culture negative, is the immediate use of broad-spectrum antibiotics. In the absence of definite diagnostic criteria for viral sepsis, or at least to exclude bacterial sepsis, this inevitably leads to unnecessary antimicrobial use, with associated consequences for antimicrobial resistance, effects on the host microbiome and excess healthcare costs. It is important to understand non-bacterial causes of sepsis so that inappropriate treatment can be minimised, and appropriate treatments can be developed to improve outcomes. In this review, we summarise what is known about viral sepsis, its most common causes, and how the immune responses to severe viral infections can contribute to sepsis. We also discuss strategies to improve our understanding of viral sepsis, and ways we can integrate this new information into effective treatment

An O(n^{5/2} log n) Algorithm for the Rectilinear Minimum Link-Distance Problem in Three Dimensions (Extended Abstract)

In this paper we consider the Rectilinear Minimum Link-Distance Problem in Three Dimensions. The problem is well studied in two dimensions, but is relatively unexplored in higher dimensions. We solve the problem in O(B n log n) time, where n is the number of corners among all obstacles, and B is the size of a BSP decomposition of the space containing the obstacles. It has been shown that in the worst case B = Theta(n^{3/2}), giving us an overall worst case time of O(n^{5/2} log n). Previously known algorithms have had worst-case running times of Omega(n^3)

Evolutionary history of the ADRB2 gene in humans

No abstract available

Self-sampling for cervical screening offered at the point of invitation: A cross-sectional study of preferences in England

OBJECTIVES: This study assessed preferences for human papillomavirus (HPV) self-sampling if offered as an alternative to clinician-based screening at the point of invitation for cervical screening. SETTING AND METHODS: An online questionnaire was completed by screening-eligible women living in England (n = 3672). Logistic regressions explored associations between demographic characteristics and screening preferences, stratified by previous screening attendance. Reasons for preferences were also assessed. RESULTS: Half of participants (51.4%) intended to choose self-sampling, 36.5% preferred clinician screening, 10.5% were unsure, and <2% preferred no screening. More irregular and never attenders chose self-sampling, compared with regular attenders (71.1% and 70.1% vs. 41.0% respectively). Among regular attenders, self-sampling was preferred more frequently by the highest occupational grade, older and lesbian, gay and bisexual women, and those with experience of blood self-tests. In the irregular attender group, older women and those with experience of blood self-tests were more likely to choose self-sampling. In ‘never attenders’, self-sampling was less popular in ethnic minority groups. CONCLUSIONS: If offered a choice of screening, around half of women in England may choose self-sampling, but a substantial proportion would still opt for clinician screening. Screening providers will need to manage a high take-up of self-sampling if many regular attenders switch to self-sampling

Stimulation of the noradrenergic system enhances and blockade reduces memory for emotional material in man

Background. It is clearly established that emotional events tend to be remembered particularly vividly. The neurobiological substrates of this phenomenon are poorly understood. Recently, the noradrenergic system has been implicated in that beta blockade has been shown to reduce significantly the delayed recall of emotional material with matched neutral material being unaffected. Methods. In the present study, 36 healthy young adults were randomly allocated to receive either yohimbine, which stimulates central noradrenergic activity, metoprolol which blocks noradrenergic activity, or matched placebo. The three groups were well matched. All capsules were taken orally, prior to viewing a narrated 11 slide show described a boy being involved in an accident. Results. Yohimbine significantly elevated, and metoprolol reduced mean heart rate during the slide show relative to placebo, thus confirming the efficacy of the pharmacological manipulation. One week later, in a ‘surprise’ test, memory for the slide show was tested. As predicted, yohimbine-treated subjects recalled significantly more and metoprolol subjects fewer slides relative to placebo. This result was confirmed via analysis of multiple-choice recognition memory scores. Conclusions. We conclude that stimulation of the noradrenergic system results in the enhancement and blockade in a reduction of recall and recognition of emotional material in man

"It's a revolving door": Ego-depletion among prisoners with injecting drug use histories as a barrier to post-release success

Background: People who inject drugs (PWID) are overrepresented among prisoner populations worldwide. This qualitative study used the psychological concept of “ego-depletion” as an exploratory framework to better understand the disproportionate rates of reincarceration among people with injecting drug use histories. The aim was to illuminate mechanisms by which prospects for positive post-release outcomes for PWID are enhanced or constricted. Methods: Participants were recruited from a longitudinal cohort study, SuperMIX, in Victoria, Australia. Eligible participants were invited to participate in an in-depth interview. Inclusion criteria were: aged 18+; lifetime history of injecting drug use; incarcerated for >three months and released from custody <12 months previously. Analysis of 48 interviews examined how concepts relevant to the ego-depletion framework (self-regulation; standards; consequences and mitigators of ego-depletion) manifested in participants’ narratives. Results: Predominantly, participants aimed to avoid a return to problematic drug use and recidivism, and engaged in effortful self-regulation to pursue their post-release goals. Post-release environments were found to diminish self-regulation resources, leading to states of ego-depletion and compromising the capacity to self-regulate according to their ideals. Fatalism, stress, and fatigue associated with the transition period exacerbated ego-depletion. Strategies that mitigated ego-depletion included avoidance of triggering environments; reducing stress through opioid agonist therapy; and fostering positive affect through supportive relationships. Conclusions: Post-release environments are ego-depleting and inconducive to sustaining behavioural changes for PWID leaving prison. Corrections’ behaviourist paradigms take insufficient account of the socio-structural factors impacting on an individual's self-regulation capacities in the context of drug dependence and desistance processes. Breaking the cycles of reincarceration among PWID requires new approaches that moderate ego-depletion and facilitate long-term goal-pursuit

The Suaineadh Project : a stepping stone towards the deployment of large flexible structures in space

The Suaineadh project aims at testing the controlled deployment and stabilization of space web. The deployment system is based on a simple yet ingenious control of the centrifugal force that will pull each of the four daughters sections apart. The four daughters are attached onto the four corners of a square web, and will be released from their initial stowed configuration attached to a central hub. Enclosed in the central hub is a specifically designed spinning reaction wheel that controls the rotational speed with a closed loop control fed by measurements from an onboard inertial measurement sensor. Five other such sensors located within the web and central hub provide information on the surface curvature of the web, and progression of the deployment. Suaineadh is currently at an advanced stage of development: all the components are manufactured with the subsystems integrated and are presently awaiting full integration and testing. This paper will present the current status of the Suaineadh project and the results of the most recent set of tests. In particular, the paper will cover the overall mechanical design of the system, the electrical and sensor assemblies, the communication and power systems and the spinning wheel with its control system