A low cost virtual reality system for home based rehabilitation of the arm following stroke: a randomised controlled feasibility trial.

OBJECTIVE: To assess the feasibility of conducting a randomised controlled trial of a home-based virtual reality system for rehabilitation of the arm following stroke. DESIGN: Two group feasibility randomised controlled trial of intervention versus usual care. SETTING: Patients' homes. PARTICIPANTS: Patients aged 18 or over, with residual arm dysfunction following stroke and no longer receiving any other intensive rehabilitation. INTERVENTIONS: Eight weeks' use of a low cost home-based virtual reality system employing infra-red capture to translate the position of the hand into game play or usual care. MAIN MEASURES: The primary objective was to collect information on the feasibility of a trial, including recruitment, collection of outcome measures and staff support required. Patients were assessed at three time points using the Wolf Motor Function Test, Nine-Hole Peg Test, Motor Activity Log and Nottingham Extended Activities of Daily Living. RESULTS: Over 15 months only 47 people were referred to the team. Twenty seven were randomised and 18 (67%) of those completed final outcome measures. Sample size calculation based on data from the Wolf Motor Function Test indicated a requirement for 38 per group. There was a significantly greater change from baseline in the intervention group on midpoint Wolf Grip strength and two subscales of the final Motor Activity Log. Training in the use of the equipment took a median of 230 minutes per patient. CONCLUSIONS: To achieve the required sample size, a definitive home-based trial would require additional strategies to boost recruitment rates and adequate resources for patient support.

Systematic evaluation of current control devices used by people with intellectual disabilities in non-immersive virtual environments.

Virtual environments have a role to play in facilitating the acquisition of living skills in people with intellectual disabilities, improving their cognitive skills and providing them with entertainment. However, the currently recommended devices to allow navigation in and interaction with the environments are difficult to use. Using a methodology established in an earlier study, the study aims to systematically document the performance of users with the currently recommended devices in order to (i) inform the design of a usable control device or devices and (ii) act as a baseline against which they can be evaluated. 40 people with severe intellectual disabilities aged 21-67 years used four environments with an equal number of sessions with the different devices being evaluated. Results indicate that when forward movement is provided by the software using the mouse for both navigation and interaction allows better performance both initially and after exposure than using the fire button on the joystick. When the user had to initiate forward movement with the navigation device, the joystick allowed better performance than the arrows on the keyboard. Preventing slippage of the joystick base would make its use much easier and it is suggested that separate devices are retained for navigation and interaction.

Exposure of Sprague-Dawley rats to a 50-Hertz, 100-microTesla magnetic field for 27 weeks facilitates mammary tumorigenesis in the 7,12-dimethylbenz[a]-anthracene model of breast cancer.

We have shown previously (W. Löscher et al., Cancer Lett., 71: 75-81, 1993; M. Mevissen et al., Carcinogenesis (Lond.), 17: 903-910, 1996) that 50-Hz magnetic fields (MFs) of low [50 or 100 microTesla (T)] flux density enhance mammary gland tumor development and growth in the 7,12-dimethylbenz[a]anthracene (DMBA) model of breast cancer in female Sprague Dawley rats. In these previous experiments, groups of rats were given 20 mg of DMBA (four weekly gavage doses of 5 mg each) and were MF- or sham-exposed for 13 weeks. The objective of the present study was to examine whether the use of a lower dose of DMBA (10 instead of 20 mg per rat), MF exposure of the rats before DMBA injection, and the increase of the MF exposure period after DMBA application to 26 weeks enhance the effect of MF on tumor development and growth. A group 99 rats was exposed to a homogeneous, horizontally polarized 100-microT MF of 50-Hz for 24 h/day for 7 days/week; another group of 99 rats was sham-exposed under the same environmental conditions as the MF-exposed rats. The exposure chambers were identical for MF-exposed and sham-exposed animals. The age of the rats was 45-49 days at the onset of exposure; duration of MF or sham exposure was 27 weeks. DMBA was administered p.o. at a dose of 10 mg/rat after 1 week of MF or sham exposure. The animals were palpated once weekly from week 6 onwards to assess the development of mammary tumors. At the end of the exposure period, the animals were killed for the determination of number and volume and histological verification of mammary tumors. All of the recordings were done in a blinded fashion; i.e., the investigators were not aware which animals were MF- or sham-exposed. Mammary tumor development and growth was significantly enhanced by MF exposure, the most marked effect on tumor incidence (190% above sham control) being observed 13 weeks after DMBA administration. At the time of necropsy, i.e., 26 weeks after DMBA administration, the incidence of histologically verified mammary tumors was 50.5% in controls and 64.7% in MF-exposed rats, the difference being statistically significant. More marked intergroup differences were recorded when tumor incidence was separately evaluated for each of the six mammary complexes, the most pronounced MF effect on tumor incidence being seen in the cranial thoracic complex. The data substantiate that, at least under the experimental conditions used in our laboratory, 50-Hz, 100-microT MF exposure significantly facilitates the development and growth of mammary tumors in the DMBA rat model of breast cancer.

Expression and regulation of the prokineticins (endocrine gland-derived vascular endothelial growth factor and Bv8) and their receptors in the human endometrium across the menstrual cycle.

This study investigated the possible role of the newly discovered endocrine gland-derived vascular endothelial growth factors and their cognate receptors in the human endometrium during the menstrual cycle. Endocrine gland-derived vascular endothelial growth factors are also known as prokineticin (PK) 1 and PK2 and their receptors as PKR1 and PKR2. Expression of PK1 was elevated in the secretory compared with the proliferative phase of the menstrual cycle (P < 0.05). There was no temporal variation in expression of PK2, PKR1, or PKR2. PK1 and PK2 and their receptors were localized to multiple cellular compartments, including glandular epithelial, stromal, and endothelial cells in the endometrium and endothelial and smooth muscle cells in the myometrium. The elevation in PK1 expression in the secretory phase of the menstrual cycle indicated potential regulation of PK1 by progesterone. To investigate this, endometrial tissue was treated with 1 microM (micromol/liter(-1)) progesterone for 24 h, and PK1 expression was assessed by quantitative RT-PCR. Treatment with 1 microM ( micromol/liter(-1)) progesterone resulted in 2.91 +/- 0.75-fold elevation in PK1 expression, compared with controls (P < 0.05). These data identify a paracrine role for the PKs and their receptors in endometrial vascular function.

Refined mapping of the human serotonin transporter (SLC6A4) gene within 17q11 adjacent to the CPD and NF1 genes.

The SLC6A4 gene encodes the serotonin transporter, the target of an important class of antidepressant drugs (serotonin selective reuptake inhibitors). Polymorphisms in the SLC6A4 gene have been reported to be associated with susceptibility to depression and other psychiatric disorders. We have constructed a 1 Mb YAC and PAC contig which harbours both the SLC6A4 and the carboxypeptidase D (CPD) genes. The order of loci within the contig was cen-D17S975-D17S1549-24R-D17S1294-SLC6A4-28L+ ++-(CPD, D17S2009, D17S2004)-D17S2120-ter. Both genes were deleted in one of 17 neurofibromatosis type 1 (NF1) patients carrying submicroscopic NF1 contiguous gene deletions.

Association of short alleles of a VNTR of the serotonin transporter gene with anxiety symptoms in patients presenting after deliberate self harm.

The polymorphism of a variable number tandem repeat (VNTR) region of the serotonin transporter gene consists of three alleles containing, respectively, 9 (STin2.9), 10 (STin2.10) and 12 (STin2.12) copies of a repetitive element. The frequencies of the three alleles in 384 individuals presenting after deliberate self harm were the same as a group of 346 controls. However, ratings of anxiety (and state anger) were higher in those patients with genotypes including the shorter repetitive elements. The findings support the hypothesis that, in this group of patients with low rates of severe psychiatric disorder, allelic variation in the serotonin transporter gene may contribute to the expression of anxiety symptoms.

X-ray microanalysis of zinc and calcium in ultrathin sections of human sperm cells using the pyroantimonate technique.

X-ray microanalysis of pyroantimonate-fixed sperm cells indicates the retention of calcium and zinc subcellularly in similar proportions to air dried cells. The ultrastructure is well preserved and is corelated with the analysis. Sodium, potassium and chlorine are all removed during the fixation. CAlcium and zinc are found present intracellularly both in association with and independent of antimonate precipitation. There thus appears to be a varying degree of binding of those elements subcellularly, precipitation occurring where binding is reduced.

Oral contraceptive use influences resting breast proliferation.

The controversy that surrounds oral contraceptive use and breast cancer risk has arisen from epidemiologic studies, yet the direct effect of such use on breast tissue remains undefined. Breast epithelial proliferation was assessed by 3H-thymidine labeling of normal lobular units dissected from benign biopsies of 347 females aged 14 to 48 years. Factors shown to influence this response included cycle phase, time since menarche (breast age), and parity status. Multivariate analysis allowing for these influences was used to compare activity of natural cycles and those artificially regulated by oral contraceptives (OC). The increased activity in nulliparous OC users was highly significant (P less than .005). Comparing the effect of differences in OC type, whether combined, triphasic, progestin only, or according to estrogen or progestin content, showed a heterogeneity in response that was significant (P less than .01). Examined specifically, the formulation of OC according to progestin content did not have a significant influence, although progestin-only OC was most active, while the influence of increasing estrogen content was significant (P less than .05). However, emphasis is given to acknowledging the multiple factors and interactive processes responsible for breast epithelial stimulation when considering strategies of intervention.

Lymphocyte subset analyses in blood, spleen and lymph nodes of female Sprague-Dawley rats after short or prolonged exposure to a 50 Hz 100-microT magnetic field.

Based primarily on the results of in vitro studies, it has been suggested that power-line (50 or 60 Hz) magnetic fields (MFs) may reduce immune function, which could lower resistance to infection or cancer. This study was conducted to evaluate the influence of acute and chronic in vivo exposure to a linearly polarized 50 Hz MF on immune function in female Sprague-Dawley rats. Groups of rats were exposed continuously to the MF at a flux density of 100 microT for periods of 3 days, 14 days or 13 weeks. For each exposure period, one control group of rats was sham-exposed together with each MF-exposed group. Experimental end points included analyses of T-lymphocyte subsets as well as other immune cells involved in cell-mediated immune responses, i.e. natural killer (NK) cells, B lymphocytes, macrophages, and granulocytes in blood, spleen and mesenteric lymph nodes. In addition, immunohistochemical methods were used to detect proliferating and apoptotic cells in the various compartments of spleen tissue. The results obtained failed to demonstrate a significant effect of short or prolonged MF exposure on different types of leukocytes, including lymphocyte subsets. Furthermore, the experiments on the in vivo proliferation activity of lymphocytes and the extent of apoptosis in spleen samples did not indicate a difference between the MF-exposed and sham-exposed groups, indicating that MF exposure does not affect the mechanisms involved in the control of lymphocyte homeostasis. The lack of MF effects in the immune tests used in the present in vivo study makes it highly unlikely that MF exposure induces immunotoxicity, at least under the experimental conditions used. However, the data do not exclude the possibility that functional alterations in T-cell responses to mitogens and in NK cell activity as recently described for MF-exposed rodents may be one mechanism involved in the carcinogenic effects of MF exposure observed in some models of co-carcinogenesis.

Structure of a variable number tandem repeat of the serotonin transporter gene and association with affective disorder.

We have recently reported an association between a polymorphism of a variable number tandem repeat (VNTR) region of the serotonin transporter gene and susceptibility to major depressive disorder. We identified three alleles containing respectively 9 (STin2.9), 10 (STin2.10) and 12 (STin2.12) copies of a repetitive element. We report here the sequences of the three alleles. The repetitive element conformed to the consensus sequence, GGCTGYGACCY(R)GRRTG, where Y = T/C, R = G/A, with loss of the 12th base pair in one of the repeating elements. We have also extended the numbers of cases and controls in the study. The frequencies of the three alleles in 119 individuals with single or recurrent major depressive episodes, 128 individuals with bipolar disorder and a group of 346 controls were compared. There was a significant difference between patients with affective disorder and controls in the proportion of individuals carrying the STin2.9 allele. For the risk of unipolar disorder given a single STin2.9 allele, the odds ratio was 4.44 (95% Cl, 1.65-11.95) and for bipolar disorder 3.22 (95% Cl, 1.15-9.09). The findings support the hypothesis that allelic variation in the serotonin transporter gene may contribute to susceptibility for both major depression and bipolar disorder.

Allelic variation in the serotonin 5-HT2C receptor gene and migraine.

The 5-HT2C (serotonin-2C) receptor has been implicated along with other components of the 5-HT system in the pathophysiology and pharmacotherapy of migraine. To investigate whether the 5-HT2C receptor gene contributes to the risk of migraine we performed an association study of allelic variation at codon 23 (Cys or Ser) of the gene in 242 migraineurs, including 73 with aura, and 129 controls. No differences nor trends in allele or genotype frequencies were seen in the migraineurs compared to the controls. Neither did the frequencies vary significantly in migraineurs with and without aura, or if men and women were analysed separately. In conjunction with an earlier negative linkage study, these data indicate that the 5-HT2C receptor gene does not contribute to the genetic predisposition to migraine.

The serotonin transporter is a potential susceptibility factor for bipolar affective disorder.

The serotonin transporter is a strong candidate for aetiological involvement in affective disorders and psychosis. We analysed a VNTR in intron 2 of the human serotonin transporter gene (hSERT) for allelic association with bipolar affective disorder, unipolar depression and schizophrenia. An increased frequency of allele 12 of the VNTR was observed in subjects with bipolar affective disorder (n = 191; chi 2 p = 0.00048 by allele) but not unipolar depression (n = 86; chi 2 p = 0.18, ns) or schizophrenia (n = 129; chi 2 p = 0.08, ns), although a trend towards an excess of allele 12 was observed for the latter. There was also a significant difference in the frequency of allele 12 between bipolar affective disorder and unipolar depression (p = 0.0087). The relative risk for bipolar affective disorder with respect to allele 12 was 1.84 (95% CI 0.97-3.56) for heterozygotes, and 3.10 (95% CI 1.60-6.07) for homozygotes, with evidence for a gene-dosage effect. Because allele 12 is common in the population, the attributable risk is 50.8% (95% CI 14.5%-73.3%). We hypothesize that either the VNTR affects regulation of expression of hSERT at the transcriptional level or it is in linkage disequilibrium with another functional polymorphism in the gene, and this results in an increased risk for the development of bipolar affective disorder.

Effect of low-intensity 50-Hz magnetic fields on kindling acquisition and fully kindled seizures in rats.

The possibility that chronic exposure to power-line frequency (50 Hz) magnetic fields (MFs) might affect the acquisition or characteristics of focal and generalized seizures in amygdala kindled rats was studied. Acute, short-lasting 50-Hz MF exposure of fully kindled rats at either 1 or 100 microT had no effect on afterdischarge threshold (ADT) or seizure parameters recorded at ADT. In the chronic experiments, rats with electrodes implanted in the basolateral amygdala were exposed to a 50-Hz, 100-microT (1 Gauss) MF or to a sham field condition before and after onset of daily electrical stimulations over the whole period of kindling development. The focal seizure threshold (ADT) was determined before and after kindling development in MF exposed and sham exposed rats. Pre-kindling ADT was significantly increased by MF exposure. Exposed rats needed about the same number of stimulations to kindle than sham exposed rats, but the cumulative afterdischarge duration to reach criterion (i.e., a stage 5 seizure) was significantly reduced in MF exposed animals. Post-kindling ADT was similar in the two groups, but MF exposed rats showed a significantly higher threshold for generalized seizures. The data indicate that chronic exposure of rats to a 50-Hz, 100-microT MF exerts weak inhibitory effects on some seizure parameters of the kindling model.

Correlation between elemental composition and motility of human spermatozoa.

X-ray microanalysis of human sperm cells in donor semen having a range of motilities from 0% to 85% showed that elemental composition is not strongly correlated with spermatozoal motility. Only copper in the midpiece was positively correlated with motility when high- and low-fertility groups were compared. Aging of cells in semen caused large changes in subcellular elemental concentrations as motility decreased, notably with uptake of zinc, but these changes were not reflected in the range of motilities in the clinical samples. Electrolyte balance as measured by sodium to potassium ratios also appeared not to be correlated with motility. Subcellular elemental distribution is not a major factor in determining sperm motility in normal human semen.

PIP: A possible correlation between the elemental composition of human spermatozoa and sperm motility was investigated. X-ray microanalysis did not reveal any strong correlation between sperm motilities of C-85% and elemental composition. However, when high- and low-fertility samples were compared, a significant (p less than .025) correlation was found between copper in the midpiece region and motility. As cells aged and motility decreased, there were considerable changes in subcellular elemental concentrations, particularly with regard to zinc uptake. However, these changes were not correlated with the range of motilities. No apparent correlation was found between electrolyte balance, as determined by sodium to potassium ratios, and motility. It is concluded that the subcellular distribution of elements in semen is not a determining factor in sperm motility.

Toxicity and uptake of heavy metals by human spermatozoa.

The effects of metallic copper on human spermatozoa are described. Incubation with the metal caused a fall on the percentage of motile sperm, which was directly related to the surface area of copper employed and to the copper content of whole semen. These changes were accompanied by a decrease in semen zinc levels and an uptake of copper by individual sperm cells, as determined by X-ray microanalysis. Low concentrations of ionic copper caused a less marked fall in sperm motility, although the metal was generally more toxic than zinc or cadmium ions. All three metals were accumulated by spermatozoa on incubation, with cadmium causing a decrease in sperm nuclear zinc concentrations.

Community midwives' and general practitioners' perspectives, of antenatal care in the community.

OBJECTIVE: to ascertain who was providing antenatal care in the community in a defined geographical area in the north of England, and whether the care could achieve the government objectives presented in Changing Childbirth (DoH 1993). DESIGN: a questionnaire was used to obtain demographic information and semi-structured interviews were held with care providers in order to assess the perspective of those providing care. PARTICIPANTS: a purposive sample of nine community midwives and six general practitioners (GPs). FINDINGS: the midwife was the professional undertaking most of the antenatal care although in most instances there was a GP available on site if required. GPs saw the midwife as the main provider of care with themselves as 'back up'. Conflict over responsibility for care was an issue in some instances. Whilst changes in antenatal care provision had been, or were about to be made, only one midwife expressed a clear positive feeling towards midwife-led care. Giving women the opportunity for choice provoked an overwhelming feeling of helplessness for midwives. Midwives and GPs believed their education adequately prepared them to provide antenatal care in the community, however, GPs did not attend regular updating sessions. IMPLICATIONS FOR PRACTICE: whilst it was recognised that midwives are taking increasing responsibility for antenatal care, GPs still believe that overall responsibility lies with them; therefore, there is a need to clarify roles. The majority of midwives expressed reservations about midwife-led care.

Design guidelines for interactive multimedia learning environments to promote social inclusion.

PURPOSE: There is a continuing need for guidelines to aid in the design of Interactive Multimedia Learning Environments (IMLE) to promote effective learning. The project introduced in this paper looks at an important subset of this problem, the design of interactive learning environments to promote social inclusion. METHOD: A consortium of six partners contributed toward defining learning material to develop a range of work based skills, including horticulture, IT and catering. These were then developed into IMLE prototypes. Formative evaluation of these prototypes then revealed a range of usability problems, which were grouped into generic types and frequency of occurrence. RESULTS: The most important and frequently occurring problems were used to distil a set of design guidelines for the development of effective IMLE. The results from this usability content analysis were also used to refine the initial prototypes to improve their usability and effectiveness. CONCLUSIONS: These guidelines, termed the Greenhat Design Guidelines, can be adopted for use by all multimedia developers aiming to promote the social inclusion of vulnerable or socially disadvantaged groups of people. The refined IMLE can be accessed via the Greenhat Server to improve the employment-related skills of socially excluded people.