Whispered voice test for screening for hearing impairment in adults and children: systematic review

Objective To determine the accuracy of the whispered voice test in detecting hearing impairment in adults and children. Design Systematic review of studies of test accuracy. Data sources Medline, Embase, Science Citation Index, unpublished theses, manual searching of bibliographies of known primary and review articles, and contact with authors. Study selection Two reviewers independently selected and extracted data on study characteristics, quality, and accuracy of studies. Studies were included if they had cross sectional designs, at least one of the index tests was the whispered voice test, and the reference test (audiometry) was performed on at least 80% of the participants. Data extraction Data were used to form 2x2 contingency tables with hearing impairment by audiometry as the reference standard. Data synthesis The eight studies that were found used six different techniques. The sensitivity in the four adult studies was 90% or 100% and the specificity was 70% to 87%. The sensitivity in the four childhood studies ranged from 80% to 96% and specificity ranged from 90% to 98%. Conclusion The whispered voice test is a simple and accurate test for detecting hearing impairment. There is some concern regarding the lower sensitivity in children and the overall reproducibility of the test, particularly in primary care settings. Further studies should be conducted in primary care settings to explore the influence of components of the testing procedure to optimise test sensitivity and to promote standardisation of the testing procedure.

A medial to lateral shift in premovement cortical activity in hemi-Parkinson's disease: Studies of event-related potentials and whole-scalp magneto encephalography

Cortical activity associated with voluntary movement is shifted from medial to lateral premotor areas in Parkinson's disease. This occurs bilaterally, even for unilateral movements. We have used both EEG and MEG to further investigate medial and lateral premotor activity in patients with hemi-Parkinson's disease, in whom basal ganglia impairment is most pronounced in one hemisphere. The CNV, recorded from 21 scalp positions in a Go/NoGo task, was maximal over central medial regions in control subjects. For hemi-Parkinson's disease subjects, activity was shifted more frontally, reduced in the midline and lateralised towards the side of greatest basal ganglia impairment. With 143 channel whole-scalp magneto encephalography (MEG) we are further examining asymmetries in supplementary motor/premotor cortical activity prior to self-paced voluntary movement. In preliminary results, one hemi-Parkinson's disease patient with predominantly left-side symptoms showed strong medial activity consistent with a dominant source in the left supplementary motor area (SMA). Three patients showed little medial activity, but early bilateral sources within lateral premotor cortex. Results suggest greater involvement of lateral premotor rather than the SMA prior to movement in Parkinson's disease and provide evidence for asymmetric function of the SMA in hemi- Parkinson's disease, with reduced activity on the side of greatest basal ganglia deficit.

Constitutive mutants of the GM-CSF receptor reveal multiple pathways leading to myeloid cell survival, proliferation, and granulocyte-macrophage differentiation

Activation of the granulocyte-macrophage colony-stimulating factor (GM-CSF) family of receptors promotes the survival, proliferation, and differentiation of cells of the myeloid compartment. Several signaling pathways are activated downstream of the receptor, however it is not clear how these induce specific biologic outcomes. We have previously identified 2 classes of constitutively active mutants of the shared signaling subunit, human (h) betac, of the human GM-CSF/interieukin-3 (IL-3)/IL-5 receptors that exhibit different modes of signaling. In a factor-dependent bipotential myeloid cell line, FDB1, an activated mutant containing a substitution in the transmembrane domain (V449E) induces factor-independent proliferation and survival, while mutants in the extracellular domain induce factor-independent granulocyte-macrophage differentiation. Here we have used further mutational analysis to demonstrate that there are nonredundant functions for several regions of the cytoplasmic domain with regard to mediating proliferation, viability, and differentiation, which have not been revealed by previous studies with the wild-type GM-CSF receptor. This unique lack of redundancy has revealed an association of a conserved membrane-proximal region with viability signaling and a critical but distinct role for tyrosine 577 in the activities of each class of mutant.

Expression, purification, crystallization, and NMR studies of the helicase interaction domain of Escherichia coli DnaG primase

in Escherichia coli, the DnaG primase is the RNA polymerase that synthesizes RNA primers at replication forks. It is composed of three domains, a small N-terminal zinc-binding domain, a larger central domain responsible for RNA synthesis, and a C-terminal domain comprising residues 434-581 [DnaG(434-581)] that interact with the hexameric DnaB helicase. Presumably because of this interaction, it had not been possible previously to express the C-terminal domain in a stably transformed E coli strain. This problem was overcome by expression of DnaG(434-581) under control of tandem bacteriophage gimel-promoters, and the protein was purified in yields of 4-6 mg/L of culture and studied by NMR. A TOCSY spectrum of a 2 mM solution of the protein at pH 7.0, indicated that its structured core comprises residues 444-579. This was consistent with sequence conservation among most-closely related primases. Linewidths in a NOESY spectrum of a 0.5 mM sample in 10 mM phosphate, pH 6.05, 0.1 M NaCl, recorded at 36 degreesC, indicated the protein to be monomeric. Crystals of selenomethionine-substituted DnaG(434-581) obtained by the hanging-drop vapor-diffusion method were body-centered tetragonal, space group I4(1)22, with unit cell parameters a = b 142.2 Angstrom, c = 192.1 Angstrom, and diffracted beyond 2.7 Angstrom resolution with synchrotron radiation. (C) 2003 Elsevier Inc. All rights reserved.

Assessing cost-effectiveness in mental health: family interventions for schizophrenia and related conditions

Objective: Existing evidence suggests that family interventions can be effective in reducing relapse rates in schizophrenia and related conditions. Despite this, such interventions are not routinely delivered in Australian mental health services. The objective of the current study is to investigate the incremental cost-effectiveness ratios (ICERs) of introducing three types of family interventions, namely: behavioural family management (BFM); behavioural intervention for families (BIF); and multiple family groups (MFG) into current mental health services in Australia. Method: The ICER of each of the family interventions is assessed from a health sector perspective, including the government, persons with schizophrenia and their families/carers using a standardized methodology. A two-stage approach is taken to the assessment of benefit. The first stage involves a quantitative analysis based on disability-adjusted life years (DALYs) averted. The second stage involves application of 'second filter' criteria (including equity, strength of evidence, feasibility and acceptability to stakeholders) to results. The robustness of results is tested using multivariate probabilistic sensitivity analysis. Results: The most cost-effective intervention, in order of magnitude, is BIF (A$8000 per DALY averted), followed by MFG (A$21 000 per DALY averted) and lastly BFM (A$28 000 per DALY averted). The inclusion of time costs makes BFM more cost-effective than MFG. Variation of discount rate has no effect on conclusions. Conclusions: All three interventions are considered 'value-for-money' within an Australian context. This conclusion needs to be tempered against the methodological challenge of converting clinical outcomes into a generic economic outcome measure (DALY). Issues surrounding the feasibility of routinely implementing such interventions need to be addressed.

A long-term study in Merino sheep experimentally infected with Mycobacterium avium subsp paratuberculosis: clinical disease, faecal culture and immunological studies

Two longitudinal experiments involving Merino sheep challenged with either bovine or ovine strains of Mycobacterium avium subsp. paratuberculosis (Map) have been conducted over a period of 54 and 35 months, respectively. Blood samples for the interferon-gamma test, the absorbed ELISA and faecal samples for bacteriological culture were taken pre-challenge and monthly post-challenge. Infections were induced with either a bovine or ovine strain of Map in separate experiments with infections being more easily established, in terms of faecal bacterial shedding and clinical disease when the challenge inoculum was prepared from gut mucosal tissue than cultured bacteria. The patterns of response for shedding and clinical disease were similar. Cell-mediated immune responses were proportionally elevated by at least an order of magnitude in all sheep dosed with either a bovine or ovine strain of Map. Conversely, antibody responses were only elevated in a relatively small proportion of infected sheep. Neither of the clinically affected tissue challenged sheep developed an antibody response despite the presence of persistent shedding and the development and decline in cell-mediated immunity. The results indicated that for sheep the interferon-gamma test may be useful for determining if a flock has been exposed to ovine Johne's disease. (C) 2004 Elsevier B.V. All rights reserved.

The effects of predator odors in mammalian prey species: A review of field and laboratory studies

wPrey species show specific adaptations that allow recognition, avoidance and defense against predators. For many mammalian species this includes sensitivity towards predator-derived odors. The typical sources of such odors include predator skin and fur, urine, feces and anal gland secretions. Avoidance of predator odors has been observed in many mammalian prey species including rats, mice, voles, deer, rabbits, gophers, hedgehogs, possums and sheep. Field and laboratory studies show that predator odors have distinctive behavioral effects which include (1) inhibition of activity, (2) suppression of non-defensive behaviors such as foraging, feeding and grooming, and (3) shifts to habitats or secure locations where such odors are not present. The repellent effect of predator odors in the field may sometimes be of practical use in the protection of crops and natural resources, although not all attempts at this have been successful. The failure of some studies to obtain repellent effects with predator odors may relate to (1) mismatches between the predator odors and prey species employed, (2) strain and individual differences in sensitivity to predator odors, and (3) the use of predator odors that have low efficacy. In this regard, a small number of recent studies have suggested that skin and fur-derived predator odors may have a more profound lasting effect on prey species than those derived from urine or feces. Predator odors can have powerful effects on the endocrine system including a suppression of testosterone and increased levels of stress hormones such as corticosterone and ACTH. Inhibitory effects of predator odors on reproductive behavior have been demonstrated, and these are particularly prevalent in female rodent species. Pregnant female rodents exposed to predator odors may give birth to smaller litters while exposure to predator odors during early life can hinder normal development. Recent research is starting to uncover the neural circuitry activated by predator odors, leading to hypotheses about how such activation leads to observable effects on reproduction, foraging and feeding. (c) 2005 Elsevier Ltd. All rights reserved.

Premovement activity of the pre-supplementary motor area and the readiness for action: Studies of time-resolved event-related functional MRI

The supplementary motor area (SMA) is thought to play in important role in the preparation and organisation of voluntary movement. It has long been known that cortical activity begins to increase up to 2 s prior to voluntary self-initiated movement. This increasing premovement activity measured in EEG is known as the Bereitschaftspotential or readiness potential. Modern functional brain imaging methods, using event-related and time-resolved functional MRI techniques, are beginning to reveal the role of the SMA, and in particular the more anterior pre-SMA, in premovement activity associated with the readiness for action. In this paper we review recent studies using event-related time-resolved fMRI methods to examine the time-course of activation changes within the SMA throughout the preparation, readiness and execution of action. These studies suggest that the preSMA plays a common role in encoding or representing actions prior to our own voluntary self-initiated movements, during motor imagery, and from the observation of others' actions. We suggest that the pre-SMA generates and encodes motor representations which are then maintained in readiness for action. (c) 2005 Elsevier B.V. All rights reserved.