Neurology and psychiatry: waking up to opportunities of sleep. State of the art and clinical/research priorities for the next decade.

In recent years, evidence has emerged for a bidirectional relationship between sleep and neurological and psychiatric disorders. First, sleep-wake disorders (SWDs) are very common and may be the first/main manifestation of underlying neurological and psychiatric disorders. Secondly, SWDs may represent an independent risk factor for neuropsychiatric morbidities. Thirdly, sleep-wake function (SWF) may influence the course and outcome of neurological and psychiatric disorders. This review summarizes the most important research and clinical findings in the fields of neuropsychiatric sleep and circadian research and medicine, and discusses the promise they bear for the next decade. The findings herein summarize discussions conducted in a workshop with 26 European experts in these fields, and formulate specific future priorities for clinical practice and translational research. More generally, the conclusion emerging from this workshop is the recognition of a tremendous opportunity offered by our knowledge of SWF and SWDs that has unfortunately not yet entered as an important key factor in clinical practice, particularly in Europe. Strengthening pre-graduate and postgraduate teaching, creating academic multidisciplinary sleep-wake centres and simplifying diagnostic approaches of SWDs coupled with targeted treatment strategies yield enormous clinical benefits for these diseases.

A phase 1-2 clinical trial of gene therapy for recurrent glioblastoma multiforme by tumor transduction with the herpes simplex thymidine kinase gene followed by ganciclovir.

This study has investigated the effects of herpes simplex thymidine kinase gene (HSV-tk) transfer followed by ganciclovir treatment as adjuvant gene therapy to surgical resection in patients with recurrent glioblastoma multiforme (GBM). The study was open and single-arm, and aimed at assessing the feasibility and safety of the technique and indications of antitumor activity. In 48 patients a suspension of retroviral vector-producing cells (VPCs) was administered by intracerebral injection immediately after tumor resection. Intravenous ganciclovir was infused daily 14 to 27 days after surgery. Patients were monitored for adverse events and for life by regular biosafety assaying. Tumor changes were monitored by magnetic resonance imaging (MRI). Reflux during injection was a frequent occurrence but serious adverse events during the treatment period (days 1-27) were few and of a nature not unexpected in this population. One patient experienced transient neurological disorders associated with postganciclovir MRI enhancement. There was no evidence of replication-competent retrovirus in peripheral blood leukocytes or in tissue samples of reresection or autopsy. Vector DNA was shown in the leukocytes of some patients but not in autopsy gonadal samples. The median survival time was 8.6 months, and the 12-month survival rate was 13 of 48 (27%). On MRI studies, tumor recurrence was absent in seven patients for at least 6 months and for at least 12 months in two patients, one of whom remains recurrence free at more than 24 months. Treatment-characteristic images of injection tracks and intracavity hemoglobin were apparent. In conclusion, the gene therapy is feasible and appears to be satisfactorily safe as an adjuvant to the surgical resection of recurrent GBM, but any benefit appears to be marginal. Investigation of the precise effectiveness of this gene therapy requires prospective, controlled studies.

Cross-sectional study of 168 patients with hepatorenal tyrosinaemia and implications for clinical practice

Background: Hepatorenal tyrosinaemia (Tyr 1) is a rare inborn error of tyrosine metabolism. Without treatment, patients are at high risk of developing acute liver failure, renal dysfunction and in the long run hepatocellular carcinoma. The aim of our study was to collect cross-sectional data. Methods. Via questionnaires we collected retrospective data of 168 patients with Tyr 1 from 21 centres (Europe, Turkey and Israel) about diagnosis, treatment, monitoring and outcome. In a subsequent consensus workshop, we discussed data and clinical implications. Results: Early treatment by NTBC accompanied by diet is essential to prevent serious complications such as liver failure, hepatocellular carcinoma and renal disease. As patients may remain initially asymptomatic or develop uncharacteristic clinical symptoms in the first months of life newborn mass screening using succinylacetone (SA) as a screening parameter in dried blood is mandatory for early diagnosis. NTBC-treatment has to be combined with natural protein restriction supplemented with essential amino acids. NTBC dosage should be reduced to the minimal dose allowing metabolic control, once daily dosing may be an option in older children and adults in order to increase compliance. Metabolic control is judged by SA (below detection limit) in dried blood or urine, plasma tyrosine (<400 μM) and NTBC-levels in the therapeutic range (20-40 μM). Side effects of NTBC are mild and often transient. Indications for liver transplantation are hepatocellular carcinoma or failure to respond to NTBC. Follow-up procedures should include liver and kidney function tests, tumor markers and imaging, ophthalmological examination, blood count, psychomotor and intelligence testing as well as therapeutic monitoring (SA, tyrosine, NTBC in blood). Conclusion: Based on the data from 21 centres treating 168 patients we were able to characterize current practice and clinical experience in Tyr 1. This information could form the basis for clinical practice recommendations, however further prospective data are required to underpin some of the recommendations.

The importance of operating costs about making decisions in farm machine labor contractors services : the case of Cordoba province

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Association of fever and severe clinical course in bronchiolitis

Little attention has been given to the relation between fever and the severity of bronchiolitis. Therefore, the relation between fever and the clinical course of 90 infants (59 boys, 31 girls) hospitalised during one season with bronchiolitis was studied prospectively. Fever (defined as a single recording > 38.0°C or two successive recording > 37.8°C) was present in 28 infants. These infants were older (mean age, 5.3 v 4.0 months), had a longer mean hospital stay (4.2 v2.7 days), and a more severe clinical course (71.0%v 29.0%) than those infants without fever. Radiological abnormalities (collapse/consolidation) were found in 60.7% of the febrile group compared with 14.8% of the afebrile infants. These results suggest that monitoring of body temperature is important in bronchiolitis and that fever is likely to be associated with a more severe clinical course and radiological abnormalities.

Batching decisions for assembly production systems

The two-stage assembly scheduling problem is a model for production processes that involve the assembly of final or intermediate products from basic components. In our model, there are m machines at the first stage that work in parallel, and each produces a component of a job. When all components of a job are ready, an assembly machine at the second stage completes the job by assembling the components. We study problems with the objective of minimizing the makespan, under two different types of batching that occur in some manufacturing environments. For one type, the time to process a batch on a machine is equal to the maximum of the processing times of its operations. For the other type, the batch processing time is defined as the sum of the processing times of its operations, and a setup time is required on a machine before each batch. For both models, we assume a batch availability policy, i.e., the completion times of the operations in a batch are defined to be equal to the batch completion time. We provide a fairly comprehensive complexity classification of the problems under the first type of batching, and we present a heuristic and its worst-case analysis under the second type of batching.

An investigation of passenger exit selection decisions in aircraft evacuation situations

This paper presents results from a questionnaire study of participant exit awareness and suggested exit selection in the event of emergency evacuations involving narrow body aircraft. The study involved 459 participants with varying flight experience. The results of this study supports the hypothesis that poor understanding by passengers of aircraft exit location and configuration may be a contributory factor in the resulting poor exit selection decisions made by passengers in emergency situations. These results have important safety implications for airlines and also provide important insight to evacuation model developers regarding the decision making process in agent exit selection.

Workplace violence and intentions to quit: results from a survey of London nurses

Study Objective: Work-place violence, harassment and abuse is an increasing feature of nurses’ experience of work in many countries. There is some evidence that the experience of workplace violence affects levels of job satisfaction (Hesketh et al 2003) and career decisions (e.g. Mayer et al 1999, Fernandes et al 1999). This paper reports on verbal and physical abuse by patients, relatives and carers, as well as racial and sexual harassment in Acute Hospitals in London and investigates whether workplace violence affects nurses’ intentions to leave either their current job or the nursing profession, controlling for a number of other factors that are known to affect career decisions, such as workload, pay and own health. Method: A questionnaire designed by two of the authors (Reeves and West) to assess many different aspects of nurses work life was used in a postal survey of nurses grades A to I practising in twenty London acute trusts in 2002. A total of 6,160 clinical nurses were mailed the questionnaires and 2,880 returned completed questionnaires, resulting in an overall response rate of 47%, discounting undelivered questionnaires. Respondents worked in a wide variety of clinical settings but mainly in acute medical and surgical wards. In addition to descriptive statistics, results were analysed using logistic regression with robust standard errors: the appropriate test when the dependent variable is dichotomous and the individual respondents clustered within units (nurses working within hospitals are not statistically independent). Results: Our results show high levels of racial (%), sexual (%) and other, unspecified forms of harassment (%), as well as verbal and physical abuse (14% had been physically assaulted with 5% being assaulted more than once), over the previous 6 months. A very small number (1%) reported experiencing all three forms of harassment; 12% two forms and 29% one form. Only 45% of this sample intended to stay in nursing for at least 3 years; 40% were undecided and 15% intended to leave. Logistic regression estimates showed that reported levels of abuse and harassment had a significant impact on respondents’ career intentions, even in models that controlled for known factors affecting career decisions. About 70% of our respondents reported that they had had too little training in dealing with aggressive behaviour—or none at all—but there was no statistical relationship between lack of training and reported assaults. Conclusions: The international shortage of health care workers is due at least in part to low retention rates. It is crucial to investigate nurses’ experiences of work to identify the factors that shape their career decisions. Workplace violence is increasingly acknowledged as an international, service-wide, health care problem. This paper adds to the literature that shows that workplace violence has an impact on nurses’ career decisions. The implications for managers and policy makers are that strengthening systems of security and providing nurses with training in interpersonal relationships including dealing with aggressive patients could slow nurse turnover.

Polyacid-modified composite resins ("compomers") and their use in clinical dentistry

OBJECTIVES: This paper describes the chemistry and properties of polyacid-modified composite resins ("compomers") designed for use in clinical dentistry, and reviews the literature in this area. METHODS: Information has been obtained from over 50 published articles appearing in the dental and biomaterials literature, with studies being principally identified through MedLine. RESULTS: Published work shows that polyacid-modified composite resins constitute a discrete class of polymeric repair material for use in dentistry. Their distinction is that they contain hydrophilic components, and these cause water to be drawn into the material following cure. This triggers an acid-base reaction, and gives the materials certain clinically-desirable properties (fluoride release, buffering capability) that are also associated with glass-ionomer cements. The water uptake leads to a decline in certain, though not all, physical properties. However, clinical studies have shown these materials to perform acceptably in a variety of applications (Class I, Class II and Class V cavities, as fissure sealants and as orthodontic band cements), especially in children's teeth. CONCLUSIONS/SIGNIFICANCE: Polyacid-modified composite resins constitute a versatile class of dental repair material, whose bioactivity confers clinical advantages, and which are particularly useful in children's dentistry.

Characteristics of people who assault nurses in clinical practice

This article discusses certain variables relating to the characteristics of people who assault nurses, including patients, relatives and friends. The author suggests that the nature of nurses' occupational roles and responsibilities puts them at risk in their work but that individual or organisational strategies can be developed to minimise this risk.

Challenges to Slovakia and Poland health policy decisions: use of investment treaties to claim compensation for reversal of privatisation/liberalisation policies

Investment treaties, and possibly the EU Treaty itself, are being used by multinational companies Penta and Eureko to try and force the Slovak government to pay compensation for reversing health privatisation and liberalisation policies. Similar action has been used against the Polish government by Eureko to win compensation worth nearly 2 billion Euros and a policy commitment to further privatisation.

Pathophysiology of feline hyperadrenocorticism clinical. Case presentation

Hyperadrenocorticism is a rare endocrine disease in the cat; it is characterized by elevated blood cortisol level that generates numerous clinical signs including hyperglycemia, polyuria, polydipsia, polyphagia and skin diseases. The average age of onset is around 10 years. This disease usually occurs link with other endocrine disorders such as diabetes mellitus.The disease can be produced by functional alteration of the pituitary gland or the adrenal. A case report, with differential diagnosis and review of the literature, is presented.

The clinical significance of cathepsin S expression in human astrocytomas

Early local invasion by astrocytoma. cells results in tumor recurrence even after apparent total surgical resection, leading to the poor prognosis associated with malignant astrocytomas. Proteolytic enzymes have been implicated in facilitating tumor cell invasion and the current study was designed to characterize the expression of the cysteine proteinase cathepsin S (CatS) in astrocytomas and examine its potential role in invasion. Immunohistochemical analysis of biopsies demonstrated that CatS was expressed in astrocytoma cells but absent from normal astrocytes, oligodendrocytes, neurones and endothelial cells. Microglial cells and macrophages were also positive. Assays of specific activity in 59 astrocytoma biopsies confirmed CatS expression and in addition demonstrated that the highest levels of activity were expressed in grade IV tumors. CatS activity was also present in astrocytoma cells in vitro and the extracellular levels of activity were highest in cultures derived from grade IV tumors. In vitro invasion assays were carried out using the U251MG cell line and the invasion rate was reduced by up to 61% in the presence of the selective CatS inhibitor 4-Morpholineurea-LeuHomoPhe-vinylsulphone. We conclude that CatS expression is up-regulated in astrocytoma. cells and provide evidence for a potential role for CatS in invasion.