GridPP: the UK grid for particle physics.

The start-up of the Large Hadron Collider (LHC) at CERN, Geneva, presents a huge challenge in processing and analysing the vast amounts of scientific data that will be produced. The architecture of the worldwide grid that will handle 15 PB of particle physics data annually from this machine is based on a hierarchical tiered structure. We describe the development of the UK component (GridPP) of this grid from a prototype system to a full exploitation grid for real data analysis. This includes the physical infrastructure, the deployment of middleware, operational experience and the initial exploitation by the major LHC experiments.

Pregnancy registries in epilepsy: a consensus statement on health outcomes.

Most pregnant women with epilepsy require antiepileptic drug (AED) therapy. Present guidelines recommend optimizing treatment prior to conception, choosing the most effective AED for seizure type and syndrome, using monotherapy and lowest effective dose, and supplementing with folate. The Epilepsy Therapy Project established the international Health Outcomes in Pregnancy and Epilepsy (HOPE) forum to learn more about the impact of AEDs on the developing fetus, particularly the role of pregnancy registries in studying AED teratogenicity. The primary outcome of interest in these registries is the occurrence of major congenital malformations, with some data collected on minor malformations. Cognitive and behavioral outcomes are often beyond the timeframe for follow-up of these registries and require independent study. The HOPE consensus report describes the current state of knowledge and the limitations to interpretations of information from the various sources. Data regarding specific risks for both older and newer AEDs need to be analyzed carefully, considering study designs and confounding factors. There is a critical need for investigations to delineate the underlying mechanisms and explain the variance seen in outcomes across AEDs and within a single AED.

Recruitment bias resulted in poorer overall health status in a community-based control group.

OBJECTIVE: During a prospective community-based incidence study of parkinsonism, a control group was recruited for comparison with the incident patients. This study compared the demographic and health status of recruited vs. nonrecruited controls. STUDY DESIGN AND SETTING: For each incident patient, attempts were made to recruit an age-gender matched control from the same general practice or, failing that, from a previously identified community cohort of people aged over 64 years who had expressed an interest in taking part in future research. Recruited controls were compared with those who were approached but not recruited in terms of age, socioeconomic status, gender, several measures of health status, and survival. RESULTS: A total of 74 controls (40%) were recruited out of 186 potential controls who were approached. Recruited controls scored slightly worse than nonrecruited controls on every measure of health status, which reached statistical significance for numbers of acute prescriptions and major surgical procedures. There were no significant differences in age, gender, socioeconomic status, or survival. CONCLUSION: The control cohort was affected by recruitment bias, which suggested that recruited controls had slightly poorer health compared to nonrecruited controls. This bias may reduce differences in health when comparisons are made between the controls and the parkinsonian patients.

Changes in diagnosis with follow-up in an incident cohort of patients with parkinsonism.

BACKGROUND: Accurate diagnosis of the cause of parkinsonism during life can be difficult, particularly at presentation, but few studies have described changes in clinical diagnosis over time and the effect of applying strict research criteria. METHODS: Incident patients with a possible/probable diagnosis of degenerative or vascular parkinsonism had a standardised assessment at diagnosis and at yearly intervals thereafter at which the most likely clinical diagnosis was recorded without strict application of research criteria. Four years after the beginning of the incident period, formal research criteria were applied retrospectively using patient records at baseline and the latest yearly follow-up. RESULTS: Of 82 incident patients, 66 underwent at least 1 year of follow-up. After a median follow-up of 29 months, clinical diagnosis had changed in 22 (33%). Most (82%) changes occurred in the first year and were due to the development of atypical clinical features, particularly early cognitive impairment; the results of brain imaging; responsiveness to levodopa; and the rate of disease progression. Diagnosis on research criteria differed from latest clinical diagnosis in eight participants (12%). Research criteria gave a "probable" diagnosis in 71% of parkinsonian patients at follow-up but in only 15% at the initial assessment. DISCUSSION: The clinical diagnosis of the cause of parkinsonism at presentation was often incorrect, even when made by those with a special interest. In particular, Parkinson's disease was overdiagnosed. Research criteria were often unhelpful in clarifying the diagnosis, even after a median of 29 months of follow-up. Further research is required to identify factors that may be used to improve the accuracy of diagnosis at initial assessment.

Changes in quality of life in people with Parkinson's disease left untreated at diagnosis.

BACKGROUND: The issue of whether to adopt a "wait and watch" strategy or to initiate drug therapy soon after diagnosis in Parkinson's disease (PD) has been the subject of some debate. A recent observational study supported early treatment by demonstrating deterioration in self-reported health status in those left untreated, but not those who received therapy. We aimed to replicate this observation. METHODS: People with PD from a prospective incidence study underwent follow-up with yearly clinical assessment of parkinsonian impairment (Unified Parkinson's Disease Rating Scale (UPDRS)) and self-reported health status (Parkinson's Disease Questionnaire (PDQ-39)). Two year outcomes were compared with those who started treatment within 1 year of diagnosis and those left untreated. RESULTS: 42 patients with PD were followed-up for 2 years, of whom 26 started treatment during the first year and 16 remained untreated. Those receiving treatment had significantly higher UPDRS and PDQ-39 scores at baseline. There was no significant deterioration in PDQ-39 score in either group (median change untreated 0.8 vs treated 4.0; p = 0.47), despite a significant difference in the change in motor UPDRS scores (untreated 6.0 vs treated -6.0; p = 0.03). CONCLUSION: Given the lack of significant deterioration in the PDQ-39 in untreated patients, we believe a "wait and watch" strategy for the treatment of newly diagnosed PD remains a credible approach unless randomised trials prove otherwise.

LiNaSiB3O7(OH)--novel structure of the new borosilicate mineral jadarite determined from laboratory powder diffraction data.

The structure of a new mineral jadarite, LiNaSiB(3)O(7)(OH) (IMA mineral 2006-36), has been determined by simulated annealing and Rietveld refinement of laboratory X-ray powder diffraction data. The structure contains a layer of corner-sharing, tetrahedrally coordinated Li, Si and B forming an unbranched vierer single layer, which is decorated with triangular BO(3) groups. The Na ion is situated between the tetrahedral layers in a distorted octahedral site. As the very high boron content in this mineral makes obtaining neutron diffraction data very problematic, ab initio optimization using VASP was used to validate the structure and to better localize the H atom. The H atom is located on the apex of the triangular BO(3) group and is involved in a weak intralayer hydrogen bond. The final Rietveld refinement agrees with the ab initio optimization with regard to a hydrogen bond between the H atom and one of the tetrahedral corner O atoms. The refined structure seems to be of a remarkably high quality given the complexity of the structure, the high proportion of very light elements and the fact that it was determined from relatively low-resolution laboratory data over a limited 2theta range (10-90 degrees 2theta).

Screening for undiagnosed parkinsonism in people aged 65 years and over in the community.

We screened a random sample of 2449 people aged 65 years and over for undiagnosed parkinsonism, using a postal screening questionnaire followed by clinical neurological assessment. Amongst the 1556 (63.5%) patients who responded, four patients with previously undiagnosed parkinsonism were identified, suggesting a prevalence of 257 per 100,000 (95% CI 70, 658) in this age-group. Although only small, the numbers were sufficient to significantly increase the incidence of parkinsonism in an incidence study. Two simple screening questions achieved a high sensitivity for newly diagnosed parkinsonism of 95%, but a low specificity of 28%.

Experimental induction of equine protozoan myeloencephalitis (EPM) in the horse: effect of Sarcocystis neurona sporocyst inoculation dose on the development of clinical neurologic disease.

The effect of inoculation dose of Sarcocystis neurona sporocysts on the development of clinical neurologic disease in horses was investigated. Twenty-four seronegative weanling horses were subjected to the natural stress of transport and then randomly assigned to 6 treatment groups of 4 horses each. Horses were then immediately inoculated with either 10(2), 10(3), 10(4), 10(5), or 10(6) S. neurona sporocysts or placebo using nasogastric tube and housed indoors. Weekly neurologic examinations were performed by a blinded observer. Blood was collected weekly for antibody determination by Western blot analysis. Cerebrospinal fluid was collected before inoculation and before euthanasia for S. neurona antibody determination. Horses were killed and necropsied between 4 and 5 wk after inoculation. Differences were detected among dose groups based on seroconversion times, severity of clinical neurologic signs, and presence of microscopic lesions. Seroconversion of challenged horses was observed as early as 14 days postinfection in the 10(6) sporocyst dose group. Mild to moderate clinical signs of neurologic disease were produced in challenged horses from all groups, with the most consistent signs seen in the 10(6) sporocyst dose group. Histologic lesions suggestive of S. neurona infection were detected in 4 of the 20 horses fed sporocysts. Parasites were not detected in equine tissues by light microscopy, immunohistochemistry, or bioassay in gamma-interferon gene knockout mice. Control horses remained seronegative for the duration of the study and had no histologic evidence of protozoal infection.

The 5-HT3 antagonist tropisetron (ICS 205-930) is a potent and selective alpha7 nicotinic receptor partial agonist.

The 5-HT3 receptor antagonist tropisetron (ICS 205-930) was found to be a potent and selective partial agonist at alpha7 nicotinic receptors. Two other 5-HT3 receptor antagonists, ondansetron and LY-278,584, were found to lack high affinity at the alpha7 nicotinic receptor. Quinuclidine analogues (1 and 2) of tropisetron were also found to be potent and selective partial agonists at alpha7 nicotinic receptors.

Performance of female Rhipicephalus sanguineus (Acari: Ixodidae) fed on dogs exposed to multiple infestations or immunization with tick salivary gland or midgut tissues.

This investigation compared the effects of repeated infestations to immunization of dogs with tick salivary gland or midgut extracts on the feeding and fecundity performances of female Rhipicephalus sanguineus (Latrielle). In each immunized group, three tick-naive dogs were immunized three times with tick salivary gland or midgut extracts, and twice challenged at 21-d intervals by allowing 80 female and 40 male adult ticks to feed on each host. The repeated infestation group of three naive dogs was infested five times at 21-d intervals by the same numbers of ticks. The repeated infestation group showed a trend of reduced tick performance after the third infestation, but some of the tick performance parameters had recovered by the fifth infestation. Tick attachment was reduced by immunization with either tick salivary gland or midgut extract. Immunization with tick salivary gland extract had the greatest impact on the feeding period and engorgement weight of the female ticks. Immunization with tick midgut extract resulted in the greatest reduction of tick fecundity parameters, which included preoviposition, oviposition, and egg-incubation periods in addition to reduced egg production and egg viability. These results confirm that dogs can become resistant to R. sanguineus, and demonstrate that immunization with tick salivary gland or midgut extract has different effects on tick feeding and fecundity.

Congenital pseudoarthrosis of the tibia.

Congenital pseudoarthrosis of the tibia remains one of the most difficult conditions to treat in orthopedic surgery. Seven cases were treated in our hospital by different methods. Three out of seven patients were healed, two of these refractured. At follow-up, the success rate was 14% (one out of seven cases). It is our recommendation that early primary amputation with an appropriate prosthesis should be considered, and that the final evaluation should not be based on obtaining bone union, but on the level of function of the lower extremity.

Humoral immune response of dogs immunized with salivary gland, midgut, or repeated infestations with Rhipicephalus sanguineus.

The antibody (Ab) responses of dogs immunized with adult tick salivary gland (TSG), midgut (TMG), or repeated infestations of Rhipicephalus sanguineus were monitored to determine if there is an association between Ab production and R. sanguineus performance. Tick-naïve dogs were immunized with TSG or TMG and subjected to two challenge infestations. The control group was infested five times at 21-day intervals. The ELISA technique was used to measure Ab levels in sera from these dogs, which expressed different forms of resistance against R. sanguineus. In dogs immunized with TSG or TMG, similar Ab levels were detected against TMG, TSG, muscle, synganglion, and reproductive organs. However, these sera had different Ab levels against egg mass, unfed larvae, fed larvae, and nymph antigens. Ab levels to muscle, nerve, and reproductive antigens were lower than those observed when TMG or TSG antigens were used. Sera from dogs immunized with TMG or TSG responded to most tick stages or tissue antigens, whereas repeated infestation sera showed the lowest response among the three groups.

Demographic and needs assessment survey of animal care and control agencies.

OBJECTIVE: To characterize demographic and needs assessment information for animal care and control agencies in Ohio. DESIGN: Mail survey. SAMPLE POPULATION: 222 animal care and control agencies. PROCEDURE: A questionnaire was mailed to animal care and control agencies in Ohio. Data were collected for 1996. RESULTS: Of 222 agencies contacted, 180 (81%) responded. Agencies estimated that they spent $28.4 million ($2.47/person). Approximately 339,207 animals were taken in, comprising 214,143 (63%) dogs, 114,877 (34%) cats, and 10,187 (3%) wildlife or other species. Of these animals, a fourth were adopted, about a tenth were reclaimed by their owners, and two thirds were euthanatized. Approximately 302,589 animal control complaints were received, and 22,053 (7%) citations were issued. One hundred three (57%) agencies reported 25,564 cruelty complaints; criminal charges were filed for 543 (2%) cases, with 445 (82%) resulting in guilty verdicts. Among 155 agencies that provided information, 87 (56%) had spay/neuter policies. Only 69 of 178 (39%) agencies reported an association with a veterinarian. Less than half (64/150; 43%) of the agencies administered vaccinations, and 69 of 152 (45%) treated animals for intestinal parasites. The top 5 things needed by agencies were capital/facility improvements, increased funding, improved legislation for animals, educational needs, and veterinary services. CLINICAL IMPLICATIONS: In Ohio in 1996, 9.9% of dogs and 4.5% of cats received care or assistance from animal care and control agencies. Only 39% of animal care and control agencies have an association with a veterinarian.

Serological titers of equine monocytic ehrlichiosis associated with gastro-intestinal disorders and serological follow-up on two endemic farms.

The purpose of this work was to study the association of positive serological titers to Ehrlichia risticii, the causative agent of equine monocytic ehrlichiosis (EME) with gastro-intestinal disorders in hospitalized horses referred to The Ohio State University College of Veterinary Medicine Teaching Hospital (OSU VMTH). In addition, serological titers for E. risticii were monitored in two horse populations with endemic EME for one season to monitor temporal changes in titers. A statistically significant difference was found between the proportion of the total hospitalized horse population presented with a gastro-intestinal disorder during the study period, and study horses with IFA titers > or = 1:80 with these signs (P < 0.05). No such difference was found between the proportion of the total hospital horse population presented with signs of gastro-intestinal disorder, and the study horses with IFA titers of 1:20-1:40 with these signs, suggesting that these titers may not have any clinical significance for EME (P > 0.05). Thirty-eight horses on two farms endemic for EME were tested approximately every 3 weeks, 33 of which were tested serially at least two times. Five of the 38 horses (13.2%) had IFA titers > or = 1:80--two that were positive initially and three that seroconverted during the study; 15 horses' titers fluctuated between negative (IFA titers < 1:20) and exposed titers (1:20 through 1:40); and 18 horses remained negative throughout the study.

IgG response in guinea pigs to Trichinella spiralis infection.

An enzyme-linked immunosorbent assay (ELISA) using excretory-secretory antigens was developed to study the dynamics of the IgG antibody response to varying levels of Trichinella spiralis infection in the guinea pig. Four groups of four Hartley guinea pigs each were infected with 1250, 250, 50 or 10 T. spiralis infective muscle larvae. They were bled every 15 days for 6 months and the IgG antibody response determined by ELISA. The time of seroconversion was dose dependent as the larger the dose, the earlier the response occurred. Significant differences in antibody response between the dose groups were evident at 30 days post-infection (P less than 0.05). Beyond 60 days post-infection, the response was similar in the four groups. The antibody response in the groups infected with 250 and 50 infective larvae was similar, but was significantly different from that of the high (1250) and low (10) dose groups from 30 days post-infection (P less than 0.01). Once seroconversion occurred, the antibody titer rose to the same level, irrespective of the initial dose. To compare the antibody response according to muscle larvae recovered, the guinea pigs were grouped into four categories: less than 10 larvae; 10-25 larvae, 50-80 larvae, greater than 100 larvae. A significant positive correlation (P less than 0.05) was observed at 60 days post-infection when these groups were compared.

Serosurvey of horses with evidence of equine monocytic ehrlichiosis.

In August 1986, an extensive serosurvey for prevalence of IgG and IgM antibodies against Ehrlichia risticii, the causative agent of equine monocytic ehrlichiosis (EME), was performed at 2 Ohio racetracks, River Downs (RD) and Beulah Park (BP). Of 840 horses at RD and 574 at BP, 13 and 20%, respectively, were IgG antibody-positive (by indirect fluorescent antibody test results), with antibody titer ranging from 1:20 to 1:10,240. The titer observed at highest frequency at both racetracks was 1:80. A higher proportion of horses was ill at RD (operating during the summer months) than at BP (winter track). Of ill horses, 41% (24/58) at RD and 58% (11/19) at BP were seropositive. At RD, 70% (589/840) of all horses and 95% (102/107) of IgG seropositive horses had been stabled only at RD during the month prior to testing. Analysis of these sera by use of an ELISA to detect IgM antibody against E risticii antigen indicated that at RD, 42% (57/137) of the seropositive horses were IgM seropositive. At BP, 17% (20/120) of seropositive horses were IgM seropositive. The larger number of IgM seropositive horses at RD indicates that more horses were recently infected at RD than at BP (P = 0.0001). Therefore, at least half the seropositive horses at RD seemed to have acquired the infection at RD. These serosurvey data also indicate that at BP and RD, 78% (85/109) and 91% (111/122) of IgG seropositive horses, respectively, had subclinical infection. At less than or equal to 1:40 titer, there was no difference in seropositive rates between healthy and ill horses.(ABSTRACT TRUNCATED AT 250 WORDS)

Solubilization of a 5-HT3 binding site from rabbit small bowel muscularis membranes.

A 5-HT3 binding site, with high affinity for (S-)[3H]zacopride, was solubilized from rabbit small bowel muscularis membranes utilizing 0.5% sodium cholate and 400 mM (NH4)2SO4. Approximately 72% of the (S-)[3H]zacopride binding activity was recovered in a form that retained the high affinity (Kd = 0.7 nM) and specificity for this radioligand that is characteristic of the membrane-bound receptor. ICS 205-930 and other 5-HT3 compounds were effective inhibitors and exhibited the same rank order of potency in the solubilized and membrane-bound preparations. The receptor-detergent complex did not sediment after centrifugation for 1 h at 150,000 x g and eluted between thyroglobulin (MW = 669,000) and apoferritin (MW = 443,000) when fractionated by high-performance liquid chromatography gel filtration. This is the first report of the solubilization of a 5-HT3 binding site.