Bilateral lower limb examinations for deep vein thrombosis: A single-centre pilot study comparing request and report parameters for bilateral and unilateral referrals.

INTRODUCTION: Deep vein thrombosis (DVT) is a common pathology with significant morbidity and mortality, often occurring in the lower limb. Ultrasound is the modality of choice for diagnosis of DVT, but all guidance in the United Kingdom assumes a single leg referral. Few studies have addressed the question of bilateral referrals and bilateral DVTs, and it is not known how these should be included in ultrasound protocols. This study aims to compare the request and report parameters of bilateral examinations with those for single leg examinations over a six-month period. METHODS: A single-centre feasibility study collected data on all single and bilateral leg examinations performed by sonographers, over a six-month period at a small general hospital. Data collected for each examination included the referral and report findings. These were compared using basic statistical methods to compare DVT yield by laterality, referrer, DVT site, and patient factors. RESULTS: Six hundred and thirty examinations were included, eighteen of which were bilateral examinations. Although the bilateral leg cohort was small, there were significant differences in DVT yield between the groups, with single leg referrals more than eight times more likely to demonstrate a DVT at ultrasound. CONCLUSION: In a context of limited ultrasound resource, the low DVT yield of bilateral examinations has implications for service design. Further data collection will be needed to validate initial results, and to establish suitable criteria for acceptance of bilateral DVT referrals. IMPLICATIONS FOR PRACTICE: Low yield of DVTs in bilateral examinations can be validated via further research. Bilateral examinations can be explicitly included in DVT service design.

Whole-genome sequencing of bladder cancers reveals somatic CDKN1A mutations and clinicopathological associations with mutation burden.

Bladder cancers are a leading cause of death from malignancy. Molecular markers might predict disease progression and behaviour more accurately than the available prognostic factors. Here we use whole-genome sequencing to identify somatic mutations and chromosomal changes in 14 bladder cancers of different grades and stages. As well as detecting the known bladder cancer driver mutations, we report the identification of recurrent protein-inactivating mutations in CDKN1A and FAT1. The former are not mutually exclusive with TP53 mutations or MDM2 amplification, showing that CDKN1A dysfunction is not simply an alternative mechanism for p53 pathway inactivation. We find strong positive associations between higher tumour stage/grade and greater clonal diversity, the number of somatic mutations and the burden of copy number changes. In principle, the identification of sub-clones with greater diversity and/or mutation burden within early-stage or low-grade tumours could identify lesions with a high risk of invasive progression.

Characterisation of user-defined health status in older adults with intellectual disabilities.

BACKGROUND: Older adults with Intellectual Disabilities (ID) have an excess disease burden that standard health assessments are designed to detect. Older adults with ID have a broader concept of health with dimensions of well being in addition to absence of disease in line with the World Health Organization's health definition. We sought to characterise user-defined health status in a sample of older adults with ID. METHODS: We administered a user-led health assessment to 57 adults with ID aged 40 years and over. Cluster analysis on user-defined health themes of participation, nutrition and hygiene/self-care identified clear separation of participants into a healthier and a less healthy group. RESULTS: Disease burden (P = 0.002) and medication use (P = 0.003) were greater in the less healthy group. The healthier group were taller (P = 0.005), stronger (P = 0.005) and had better vision (P < 0.001) than the less healthy group. Constipation (P = 0.014), urinary incontinence (P < 0.001) and faecal incontinence (P < 0.001) were commoner in the less healthy group. There were few significant differences between health groups on the majority of standard physical-examination items. CONCLUSIONS: There is considerable overlap between user-defined health and that assessed by standard instruments. In addition, user-defined health encompasses aspects of physical fitness not captured by traditional disease-based health models.

Functional mapping of Toll/interleukin-1 signalling networks by expression cloning.

Multiple cellular proteins have been identified as participating in Toll/interleukin-1 receptor-mediated inflammatory gene expression. The continuing isolation of novel components, based on sequence similarities, protein-protein interactions and protein purification, suggests that many elements of this signalling network remain to be identified. We report here the development of a high-throughput functional screening platform and its application for the identification of components of inflammatory signalling networks. Our results enable us to estimate that 100-150 gene products are involved in controlling the transcription of the human interleukin 8 gene. The approach, which is simple and robust, constitutes a general method for mapping signal transduction systems and for rapid isolation of a large number of signalling components based on the control of pathways leading to regulation of gene expression.

Geotechnical techniques for the construction of reactive barriers

One of the newest and most promising remediation techniques for the treatment of contaminated groundwater and soil is the reactive barrier wall (commonly known as PRB for permeable reactive barrier or reactive barrier). Although a variety of treatment media and strategies are available, the most common technique is to bury granular iron in a trench so that contaminated groundwater passes through the reactive materials, the contaminants are removed and the water becomes 'clean'. The principal advantages of the technique are the elimination of pumping, mass excavation, off-site disposal, and a very significant reduction in costs. The use of this technology is now becoming better known and implemented. Special construction considerations need to be made when planning the installation of reactive barriers or PRBs to ensure the design life of the installation and to be cost-effective. Geotechnical techniques such as slurry trenching, deep soil mixing, and grouting can be used to simplify and improve the installation of reactive materials relative to conventional trench and fill methods. These techniques make it possible to reduce the hazards to workers during installation, reduce waste and reduce costs for most installations. To date, most PRBs have been installed to shallow depths using construction methods such as open trenching and/or shored excavations. While these methods are usable, they are limited to shallow depths and more disruptive to the site's normal use. Geotechnical techniques are more quickly installed and less disruptive to site activities and thus more effective. Recently, laboratory studies and pilot projects have demonstrated that geotechnical techniques can be used successfully to install reactive barriers. This paper describes the factors that are important in designing a reactive barrier or PRB installation and discusses some of the potential problems and pitfalls that can be avoided with careful planning and the use of geotechnical techniques. Copyright 1999 Elsevier Science B.V.

Validation of the Health of the Nation Outcome Scales.

BACKGROUND: The Health of the Nation Outcome Scales (HoNOS) were developed to assess the outcome of severe mental disorders in relation to the Health of the Nation Strategy for England. AIMS: To validate the HoNOS. METHOD: One hundred and fifteen patients were assessed by keyworkers using HoNOS, and by research workers using SCAN, SBS, and SRPS, and completing HoNOS in the light of this additional material. These assessments were repeated after 6 weeks. RESULTS: The performance of HoNOS in the hands of keyworkers was generally poor, in relation both to the research workers' rating of HoNOS and to the criterion instruments. Performance was particularly poor when the change in scores was used as a measure of outcome. CONCLUSIONS: There are serious problems in using HoNOS as a routine measure of clinical status in busy psychiatric services. Its performance is probably related to the training and experience of keyworkers. Sequential ratings are not a good method for assessing outcome. Managers and planners should be cautious in adopting HoNOS, but it is worthy consideration in developing a suite of locally agreed outcome measures.

The need for psychiatric treatment in the general population: the Camberwell Needs for Care Survey.

BACKGROUND: This paper presents the first results of a two-stage psychiatric population survey, which uses a new method of directly evaluating needs for specific psychiatric treatment and the extent to which they have been met. METHOD: The sample was drawn at random from the population of an area of inner south London with high levels of deprivation. Seven hundred and sixty subjects aged 18-65 completed the GHQ-28. All those scoring > 5 and half of the rest were invited to take part in the second stage, comprising measures of mental state (SCAN), social role performance (SRPS), life events and difficulties (LEDS) and a Treatment Inventory. This information was used to rate the community version of the Needs for Care Assessment (NFCAS-C). RESULTS: In all, 408 subjects were interviewed in the second stage. The weighted 1 month prevalence of hierarchically ordered ICD-10 psychiatric disorders was 9.8%, the 1 year prevalence 12.3%. The equivalent prevalences for depressive episode were 3.1% and 5.3% respectively, while those for anxiety states were both 2.8%. At interview nearly 10% of the population were identified as having a need for the treatment of a psychiatric condition. This rose to 10.4% if the whole of the preceding year was assessed. Less than half of all potentially meetable needs were met. There was only partial overlap between diagnosis and an adjudged need for treatment. CONCLUSION: A majority of people with mental health problems do not have proper treatment; given more resources and greater public and medical awareness, most could be treated by family doctors.

Measuring the need for psychiatric treatment in the general population: the community version of the MRC Needs for Care Assessment.

The community version of the MRC Needs for Care Assessment Schedule (NFCAS-C) is a new instrument designed for the psychiatric conditions seen in general populations. Its principles are based on the original Needs for Care Assessment, although that was developed for the very different population of those with long-standing mental illness (Brewin et al. 1987). The NFCAS-C is designed to reproduce, in an itemized and systematic manner, the functioning of well-organized primary care and psychiatric services. It is primarily intended for research purposes, in particular, the comparison of treatment needs and services in different populations. In this paper we describe the problems of assessing the need for psychiatric care in general populations and the rationale and development of the instrument, while in its companion we present the results of a reliability study (Lesage et al. 1995).

The use of orthotic devices to correct plantar callus in people with diabetes.

Foot problems are a major cause of morbidity in people with diabetes. Plantar callus is common and is a sign of abnormal foot pressures. Shear stresses at these areas of high foot pressures may ultimately result in ulcer formation. This study compared the effect on plantar callus of the use of rigid orthotic devices and conventional podiatric care. Twenty diabetic subjects participated in the study and were randomly allocated to conventional treatment (n = 11) or orthotic device treatment (n = 9). After 12 months the patients in the orthotic group showed a significant reduction in callus grade, whereas the conventionally treated group showed no significant change. There were no adverse effects from wearing the orthotic device. Rigid orthoses have a beneficial effect on plantar callus presumably through the lowering and redistribution of abnormal foot pressures.

Biochemical characterization of a family of serine/threonine protein kinases regulated by tyrosine and serine/threonine phosphorylations.

Mitogen-activated protein kinase (p42mapk) becomes transiently activated after treatment of serum-starved murine Swiss 3T3 cells or EL4 thymocytes with a diversity of mitogens. Similarly, a meiosis-activated protein kinase (p44mpk) becomes stimulated during maturation of sea star oocytes induced by 1-methyladenine. Both p42mapk and p44mpk have been identified as protein-serine/threonine kinases that are activated as a consequence of their phosphorylation. Because homologous protein kinases may play essential roles in both mitogenesis and oogenesis, we have compared in detail the biochemical properties of these two kinases. We find that these kinases are highly related based on their in vitro substrate specificities, sensitivity to inhibitors, and immunological cross-reactivity. However, they differ in apparent molecular weight and can be separated chromatographically, indicating that the two enzymes are distinct. Furthermore, in the course of this investigation, we have identified a 44-kDa protein kinase in mitogen-stimulated Swiss mouse 3T3 cells and EL4 thymocytes that co-purifies with p44mpk and thus appears to be a closer homolog of the sea star enzyme. Analysis of these protein kinases clarifies the relationships between a set of tyrosine-phosphorylated 41-45-kDa proteins present in mitogen-stimulated cells (Martinez, R., Nakamura., K. D., and Weber, M. J. (1982) Mol. Cell. Biol. 2, 653-655; Cooper, J. A., and Hunter, T. (1984) Mol. Cell. Biol. 4, 30-37), two myelin basic protein kinases identified in epidermal growth factor-treated Swiss mouse 3T3 cells (Ahn, N. G., Weiel, J. E., Chan, C. P., and Krebs, E. G. (1990) J. Biol. Chem. 265, 11487-11494), and p42mapk. Our work points to the existence of a group of related serine/threonine protein kinases, regulated by tyrosine phosphorylation and functioning at different stages of the cell cycle.

Raf-1 is a potential substrate for mitogen-activated protein kinase in vivo.

MAP (mitogen-activated protein) kinase is shown to phosphorylate baculovirally expressed Raf-1 in vitro, generating one major tryptic phosphopeptide which co-migrated with a peptide from Raf-1 32P-labelled in situ. This peptide also undergoes an insulin-dependent increase in labelling. Thus the serine/threonine kinase Raf-1 may be a substrate for MAP kinase in vivo.

Self-evaluation, role satisfaction and anxiety in the woman alcoholic.

Compared with a matched group of 100 controls, 100 alcoholic women were found to have a significantly poorer self-concept, to view themselves as less personally competent, to experience greater anxiety, and to be less satisfied with themselves. The alcoholic and nonalcoholic women had similar concepts of other men and women and shared similar views of the roles of women in comtemporary society. The need for research comparing alcoholic women with matched female controls was stressed.

New Salmonella serotype: Salmonella enteritidis ser. Ordonez.

The antigenic formula of a new serotype, Salmonella enteritidis serotype Ordonez, was characterized as (1),13,23,37:y:l,w.