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

Understanding psychiatric institutionalization: a conceptual review

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Admission decisions following contact with an emergency mental health assessment and intervention service.

AIMS: To define the demographic and clinical profile of individuals referred to an emergency mental health assessment team. To identify factors associated with being admitted to inpatient psychiatric services or not admitted following an emergency assessment. BACKGROUND: Crisis resolution and home treatment services are being developed across the UK, targeted towards people with severe mental health problems, who would otherwise require hospitalization. Further information about people presenting to an emergency mental health assessment service may clarify the skills that are required to deliver effective crisis resolution and home treatment services. METHOD: Over a six-month period referrals to, and admission decisions by, an emergency mental health assessment team were recorded. Measures used were the Health of the Nation Outcome Scale and the Crisis Triage Rating Scale. Age, sex and postcode data were recorded. Postcode data were used to identify the Townsend Deprivation Index for each individual. Reasons given for the referral were categorized. A preliminary descriptive analysis was performed for all people referred. The Demographic and clinical characteristics of referrals admitted and not admitted were then compared. A multivariate logistic regression was performed in order to investigate the possible impact of demographic and clinical characteristics on admission status. RESULTS: A total of 375 individuals were referred. Forty-eight (12.8%) were admitted. Higher referral rates were significantly associated with more deprived areas of the city. Referrers most frequently identified suicide risk as the reason for referral, followed by deterioration of an existing serious mental health problem. The mean Health of the Nation Outcome Scale score of all people referred was 10.5. Those admitted had a significantly greater mean Health of the Nation Outcome Scale score than those not admitted. The mean Crisis Triage Rating Scale score of all people referred was 11.0. Those admitted had a significantly lower (worse) mean Crisis Triage Rating Scale score than those not admitted. Individuals with lower Crisis Triage Rating Scale scores tended to have a higher (more deprived) Townsend index scores. Crisis Triage Rating Scale and Health of the Nation Outcome Scale scores were significantly negatively correlated. Conclusions. Crisis resolution and home treatments need to target areas of greatest deprivation. Social interventions will be important. Presentations related to suicide risk are likely to be common. The Crisis Triage Rating Scale may be a useful brief alternative to Health of the Nation Outcome Scale. RELEVANCE TO CLINICAL PRACTICE: This study highlights the valuable role of mental health nurses in frontline emergency mental health care in particular mental health nurses skills in conducting a risk assessment in an emergency

Highly Pathogenic H5N1 Avian Influenza: Entry Pathways into North America via Bird Migration

Given the possibility of highly pathogenic H5N1 avian influenza arriving in North America and monitoring programs that have been established to detect and track it, we review intercontinental movements of birds. We divided 157 bird species showing regular intercontinental movements into four groups based on patterns of movement—one of these groups (breed Holarctic, winter Eurasia) fits well with the design of the monitoring programs (i.e., western Alaska), but the other groups have quite different movement patterns, which would suggest the importance of H5N1 monitoring along the Pacific, Atlantic, and Gulf coasts of North America

Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

Gaze following is modulated by expectations regarding others’ action goals

Humans attend to social cues in order to understand and predict others' behavior. Facial expressions and gaze direction provide valuable information to infer others' mental states and intentions. The present study examined the mechanism of gaze following in the context of participants' expectations about successive action steps of an observed actor. We embedded a gaze-cueing manipulation within an action scenario consisting of a sequence of naturalistic photographs. Gaze-induced orienting of attention (gaze following) was analyzed with respect to whether the gaze behavior of the observed actor was in line or not with the action-related expectations of participants (i.e., whether the actor gazed at an object that was congruent or incongruent with an overarching action goal). In Experiment 1, participants followed the gaze of the observed agent, though the gaze-cueing effect was larger when the actor looked at an action-congruent object relative to an incongruent object. Experiment 2 examined whether the pattern of effects observed in Experiment 1 was due to covert, rather than overt, attentional orienting, by requiring participants to maintain eye fixation throughout the sequence of critical photographs (corroborated by monitoring eye movements). The essential pattern of results of Experiment 1 was replicated, with the gaze-cueing effect being completely eliminated when the observed agent gazed at an action-incongruent object. Thus, our findings show that covert gaze following can be modulated by expectations that humans hold regarding successive steps of the action performed by an observed agent

Validation of non-invasive central blood pressure devices: ARTERY Society task force consensus statement on protocol standardization

The original Riva-Rocci method to measure blood pressure (BP) using a cuff at the upper arm assumed the pressure obtained by this technique was a good proxy for central aortic BP.1,2 The clinical (prognostic) importance of brachial cuff BP is undeniable for both the assessment of cardiovascular risk associated with elevated BP and the benefits of treatment-induced BP reduction.3 However, it is also generally appreciated that peripheral artery systolic BP (SBP; brachial or radial artery) may be an inaccurate substitute for central SBP.4 This has been reported in human studies using intra-arterial catheterization of peripheral and central arteries.5–8 There may also be a discrepancy between peripheral and central BP responses to vasoactive drugs.9 These findings are corroborated in larger studies using non-invasive central aortic BP methods,10–13 and, while yet to be fully adopted in clinical practice, an independent prognostic value of central BP has been demonstrated.14–16 Altogether, there is a growing interest among clinicians towards improving risk estimates by using devices that provide more accurate measures of central aortic BP than those provided by current brachial cuff BP methods. Many non-invasive devices have been developed that purport to estimate central BP from different peripheral artery sites (e.g. radial, brachial, carotid arteries) using different principles of recording the pressure or surrogate signals (e.g. applanation tonometry, oscillometry, ultrasound, or magnetic resonance imaging) and different calibration methods to derive central BP. Since upper arm cuff-based devices to estimate central BP are more clinically appealing, in recent years several companies have developed such devices using a variety of techniques (e.g. oscillometric sub-diastolic or supra-systolic waveform analysis with generalized transfer functions), which employ a variety of signal processing steps to estimate central BP from peripheral signals.17,18 Yet, with no standardized guidelines,17 the accuracy testing of these new devices (as well as the preceding devices) has not been undertaken in a uniform fashion with comparable protocols, emphasizing the need for guidance in this field.19–22 An international task force was convened to address this situation

Multilevel latent class casemix modelling: a novel approach to accommodate patient casemix

<p>Abstract</p> <p>Background</p> <p>Using routinely collected patient data we explore the utility of multilevel latent class (MLLC) models to adjust for patient casemix and rank Trust performance. We contrast this with ranks derived from Trust standardised mortality ratios (SMRs).</p> <p>Methods</p> <p>Patients with colorectal cancer diagnosed between 1998 and 2004 and resident in Northern and Yorkshire regions were identified from the cancer registry database (n = 24,640). Patient age, sex, stage-at-diagnosis (Dukes), and Trust of diagnosis/treatment were extracted. Socioeconomic background was derived using the Townsend Index. Outcome was survival at 3 years after diagnosis. MLLC-modelled and SMR-generated Trust ranks were compared.</p> <p>Results</p> <p>Patients were assigned to two classes of similar size: one with reasonable prognosis (63.0% died within 3 years), and one with better prognosis (39.3% died within 3 years). In patient class one, all patients diagnosed at stage B or C died within 3 years; in patient class two, all patients diagnosed at stage A, B or C survived. Trusts were assigned two classes with 51.3% and 53.2% of patients respectively dying within 3 years. Differences in the ranked Trust performance between the MLLC model and SMRs were all within estimated 95% CIs.</p> <p>Conclusions</p> <p>A novel approach to casemix adjustment is illustrated, ranking Trust performance whilst facilitating the evaluation of factors associated with the patient journey (e.g. treatments) and factors associated with the processes of healthcare delivery (e.g. delays). Further research can demonstrate the value of modelling patient pathways and evaluating healthcare processes across provider institutions.</p

Parallel Mechanisms for Visual Search in Zebrafish

This research was funded by project grant G1000053 from the National Centre for the Replacement, Reduction and Refinement of animals in research (NC3Rs; UK) and by the Medical Research Council (MRC; UK). CHB is a Royal Society (UK) Research Fellow

Abdominal ultrasonography in HIV/AIDS patients in southwestern Nigeria

<p>Abstract</p> <p>Background</p> <p>Though the major target of the HIV-virus is the immune system, the frequency of abdominal disorders in HIV/AIDS patients has been reported to be second only to pulmonary disease. These abdominal manifestations may be on the increase as the use of antiretroviral therapy has increased life expectancy and improved quality of life. Ultrasonography is an easy to perform, non invasive, inexpensive and safe imaging technique that is invaluable in Africa where AIDS is most prevalent and where sophisticated diagnostic tools are not readily available. Purpose: To describe the findings and evaluate the clinical utility of abdominal ultrasonography in HIV/AIDS patients in Ibadan, Nigeria</p> <p>Methods</p> <p>A Prospective evaluation of the abdominal ultrasonography of 391 HIV-positive patients as well as 391 age and sex-matched HIV-negative patients were carried out at the University College Hospital, Ibadan.</p> <p>Results</p> <p>Of the 391 cases studied, 260 (66.5%) were females; the mean age was 38.02 years, (range 15–66 years). The disease was most prevalent in the 4th decade with an incidence of 40.4%. Compared with the HIV-negative individuals, the HIV+ group of patients had a significantly higher proportion of splenomegaly (13.5% vs. 7.7%; p < 0.01), lymphadenopathy (2.0% vs. 1.3%; p < 0.70), and renal abnormalities (8.4% vs. 3.8%; p < 0.02). There were no differences in hepatic and pancreatic abnormalities between the HIV+ and HIV- groups. There were significantly fewer gallstones in the HIV+ group (1.4% vs. 5.1%; p < 0.01).</p> <p>Conclusion</p> <p>AIDS is a multi-systemic disease and its demographic and clinical pattern remains the same globally. Ultrasonography is optimally suited for its clinical management especially in Africa. Its accuracy and sensitivity may be much improved with clinico-pathologic correlation which may not be readily available in developing countries; further studies may provide this much needed diagnostic algorithms.</p