A low-cost shutter driver and arbitrary waveform generator for optical switching using a programmable system-on-chip (PSoC) device.

We have developed a low-cost mechanical shutter driver with integrated arbitrary waveform generation for optical switching and control using a programmable system-on-chip device. This microcontroller-based device with configurable digital and analog blocks is readily programmed using free software, allowing for easy customization for a variety of applications. Additional digital and analog outputs with arbitrary timings can be used to control a variety of devices, such as additional shutters, acousto-optical modulators, or camera trigger pulses, for complete control and imaging of laser light. Utilizing logic-level control signals, this device can be readily integrated into existing computer control and data acquisition systems for expanded hardware capabilities.

Longitudinal analysis of the effect of water hardness on atopic eczema: evidence for gene-environment interaction.

BACKGROUND: Several studies have identified an association between water hardness and atopic eczema (AE); however, there is a paucity of longitudinal data in early life. OBJECTIVES: To examine whether water hardness is associated with an increased risk of AE and skin barrier dysfunction in infants and to assess effect modification by filaggrin (FLG) loss-of-function variants. METHODS: We performed a longitudinal analysis of data from infants in the Enquiring About Tolerance (EAT) study, who were enrolled at 3 months and followed up until 36 months of age. RESULTS: Of 1303 infants enrolled in the EAT study, 91·3% (n = 1189) attended the final clinic visit and 94·0% (n = 1225) of participants' families completed the 36-month questionnaire. In total, 761 (58·4%) developed AE by 36 months. There was no overall association between exposure to harder (> 257 mg L-1 CaCO3 ) vs. softer (≤ 257 mg L-1 CaCO3 ) water: adjusted hazard ratio (HR) 1·07, 95% confidence interval (CI) 0·92-1·24. However, there was an increased incidence of AE in infants with FLG mutations exposed to hard water (adjusted HR 2·72, 95% CI 2·03-3·66), and statistically significant interactions between hard water plus FLG and both risk of AE (HR 1·80, 95% CI 1·17-2·78) and transepidermal water loss (0·0081 g m-2 h-1 per mg L-1 CaCO3 , 95% CI 0·00028-0·016). CONCLUSIONS: There is evidence of an interaction between water hardness and FLG mutations in the development of infantile AE.

Implementation of ironXS: a study of the acceptability and feasibility of genetic screening for hereditary hemochromatosis in high schools.

Hereditary hemochromatosis (HH), most often due to HFE C282Y homozygosity, is an iron overload disorder that can result in severe morbidity including hepatic cirrhosis. Predisposition to HH is easily diagnosed and morbidity is preventable by maintaining normal body iron and thus calls have been made to introduce community screening. The current study has been designed to assess the acceptability and feasibility of HH screening in high schools. Students (mostly 15-16 years of age) watched a purpose-designed DVD for education about HH. Those with parental consent were then offered cheek-brush screening for C282Y. Students completed a questionnaire prior to screening. The program was offered to 9187 students at 32 schools and 3489 (38%) had screening. Nineteen C282Y homozygotes (1 in 183) and 376 heterozygotes (1 in 9.3) were identified. More than 90% of students answered each of five knowledge questions correctly. Eight homozygotes (42%) had elevated transferrin saturation, but only two (10.5%) had marginally elevated serum ferritin (SF). We have shown that genetic screening for HH can successfully be offered in the high school setting. Ongoing research in this study will answer questions about the impact of high school students learning that they are at risk of HH.

Waiting room oral rehydration in the paediatric emergency department.

Oral rehydration is well established in the treatment of acute gastroenteritis, however it is profoundly underutilised as a treatment in the hospital setting. We introduced a protocol of waiting room oral rehydration for children presenting to the Paediatric Emergency Department with vomiting and/or diarrhoea. These children were given oral rehydration from the time of triage prior to medical assessment. During the study period, 251 children presented 269 times with vomiting and/or diarrhoea, of which 205 (76%) were diagnosed with acute gastroenteritis. A similar period 1 year previously was used as comparison, during which 129 children were diagnosed with acute gastroenteritis. During the study period, 58 children (28%) were given intravenous fluids and 47 (23%) were admitted, compared with 72 (56%) given intravenous fluids and 42 (32%) admitted in the comparison group. This protocol is now part of our routine management of children presenting with symptoms of acute gastroenteritis. Waiting room oral rehydration is a simple yet successful intervention that can be implemented in any Emergency Department.

Matching veterinary school accreditation to the global needs of the profession and global society.

In North America, the United Kingdom and Australasia, veterinary school accreditation is an integral part of the process of registering veterinarians to practise. In these regions, the relevant accrediting authority develops a set of standards which form the basis for individual schools to prepare a self-evaluation report, in preparation for a site-visit team to spend a week validating the self assessment. Global trends in food production and animal movement increase the potential for spread of animal diseases and demands from trading partners to guarantee food quality standards. These and other trends in the practice of veterinary medicine require schools to continually review their curricula to accommodate workplace demands. Accreditation systems in the western world have been working together to improve collaboration and review standards but, to date, there has not been an international agency with responsibility for facilitating development of evolving and new systems. It is suggested that the World Organisation for Animal Health could consider whether it has a role in improving veterinary education by assisting in this area.

Does the rate of fat deposition influence the pharmacokinetic disposition of subcutaneously administered moxidectin and ivermectin in pigs?

Body condition has been shown to affect the pharmacokinetics of subcutaneously administered macrocyclic lactone anthelmintics but the underlying mechanism is unknown. This study examined the effect of different rates of fat deposition on the pharmacokinetics of moxidectin (MXD) and ivermectin (IVM). All animals initially received a diet with a high linoleic acid content for 7 weeks. One group of animals then received a normal grower diet while the other half received a maintenance ration. Within each diet group, animals were treated with either IVM (n = 4) or MXD (n = 4) or remained as untreated controls (n = 2). There was no difference in the proportion of linoleic acid between the drug treated groups and the untreated controls at any time throughout the study. At 4 and 9 weeks after treatment there was a significantly lower proportion of linoleic acid in the pigs fed the normal ration indicating a greater fat deposition in these animals compared with those that received the maintenance diet. There was an increased persistence of MXD in the plasma of pigs fed the normal ration compared with those fed the maintenance ration. No differences were seen in the kinetic disposition of IVM between pigs fed the maintenance or normal ration. Reducing the rate of fat deposition influenced the pharmacokinetic disposition of the highly lipophilic MXD but did not influence the pharmacokinetic disposition of the less lipophilic IVM.

The effects of body composition on the pharmacokinetics of subcutaneously injected ivermectin and moxidectin in pigs.

Macrocyclic lactones are characterized by their long persistence in animals because of their extensive distribution into fat. This study examined the influence of body condition on the disposition of ivermectin (IVM) and moxidectin (MXD) in blood and fat following subcutaneous (s.c.) drug administration. 'Fat' and 'thin' lines of pigs were established using two different diets. All animals were then injected with either MXD or IVM at 300 microg/kg and blood samples were taken at regular intervals until slaughter. Two IVM-treated animals from each diet group were slaughtered at either 3 days or 3 weeks posttreatment. Two MXD-treated animals from each diet group were slaughtered at 3 days, 3, 6 or 9 weeks after treatment. Samples of backfat were taken from all animals at slaughter. Fluorescence HPLC was used to determine the concentrations of MXD or IVM in the plasma and fat samples. The plasma IVM concentration peaked more rapidly in the thin IVM treated pigs compared with the fat pigs. The concentration of IVM in backfat was significantly lower in the thin animals slaughtered 3 weeks after treatment. The MXD plasma concentration peaked within the first hour in both the thin and fat groups, but from 12 h posttreatment there was a higher MXD concentration in the plasma of the fat pigs resulting in MXD being detectable in these pigs for 28 days compared with only 17 days in the thin pigs. Despite this difference in plasma persistence no differences were seen in the MXD concentration of backfat between fat and thin animals. Body condition influenced the kinetic disposition of IVM and MXD following s.c. drug administration with both drugs being less persistent in thin compared with fat animals.

Consequences of positive ions upon imaging in low vacuum scanning electron microscopy.

The effects caused by an excess quantity of ionized gas molecules within the low vacuum, variable pressure and environmental scanning electron microscope (ESEM) are described with reference to mechanisms by which they can influence imaging conditions. These effects can include specimen charging, recombination and development of space charge. They are demonstrated for three different classes of sample: (1) an electrically grounded conductor, (2) an electrically floating conductor, and (3) an electrical insulator. A new device is presented that will aid excess charge removal within the ESEM and help correct for some of these effects, thereby dramatically improving imaging over a wide range of operating conditions and samples. The mechanism of image enhancement is demonstrated with reference to the three classes of sample described above.

Topographic contrast of partially wetting water droplets in environmental scanning electron microscopy.

Partially wetting water droplets with sizes smaller than the capillary length acquire a distinct spherical cap shape controlled by the equilibrium contact angle, which is specific for different substrates and conditions. Images of such droplets in an environmental scanning electron microscope (ESEM) show strong topographic contrast. This contrast across the droplets can be analysed within a simple theoretical model, as the droplet sides are inclined smooth surfaces. Very small droplets have ESEM intensity profiles which deviate from this topographic model. Such deviations indicate that other sources of electron signal may be important for such droplets, and also demonstrate the limits of the analytical model. For droplets sufficiently large that they lie within the range of the topographic contrast model, values of contact angles on different substrates can be deduced. These are found to agree with independent direct measurements, as well as the results given in the literature. The possibilities of using this technique to analyse physical properties of different substrates are discussed.

Pharmacokinetics of moxidectin and ivermectin following intravenous injection in pigs with different body compositions.

Macrocyclic lactones (ML) are highly effective anthelmintics that provide a long protective period after administration because of their extensive distribution into fat. This study examined whether the body composition of the animal at the time of treatment had any influence on the pharmacokinetics of two MLs, moxidectin (MOX) and ivermectin (IVM). 'Fat' and 'lean' lines of pigs were established using two different diets, with weekly determination of liveweight and backfat thickness confirming the difference in body condition between the groups. Blood samples were taken at regular intervals following i.v. injection of IVM or MOX at a dose of 300 microg/kg and the plasma was analysed using fluorescence high performance liquid chromatography (HPLC) to determine the concentration of IVM or MOX in the samples. Regardless of body composition IVM and MOX kinetics were very different with MOX having a greater apparent volume of distribution, longer distribution and elimination half-lives and a slower clearance rate than IVM, which led to MOX being detectable in plasma for >40 days compared with only 8-10 days for IVM. Altering body composition had no detectable influence on the kinetic disposition of IVM in this study. In contrast, although there was no difference in AUC or the volume of distribution, MOX was distributed within and eliminated from the lean animals more rapidly than from the fat animals.

Use of a migration assay for the separation of adult pyrantel-susceptible and -resistant oesophagostomum dentatum.

A migration assay was used to separate a pyrantel-susceptible and -resistant isolate of the pig nematode, Oesophagostomum dentatum. The experiment had three steps. In the first step, LD(50) values for pyrantel of the two isolates in the assay were established. In the second step, susceptible and resistant worms were mixed in various proportions prior to exposure to a fixed concentration of pyrantel and thereafter assayed. The inhibition of migration showed to be linearly correlated with the proportion of resistant worms in a sample. In step three, this line was used as a standard curve to predict the number of resistant worms in samples from pigs infected with mixed samples of susceptible and resistant larvae.

Sample size calculation for clinical trials: the impact of clinician beliefs.

The UK Medical Research Council (MRC) randomized trial of gastric surgery, ST01, compared conventional (D1) with radical (D2) surgery. Sample size estimation was based upon the consensus opinion of the surgical members of the design team, which suggested that a change in 5-year survival from 20% (D1) to 34% (D2) could be realistic and medically important. On the basis of these survival rates, the sample size for the trial was 400 patients. However, this trial was exceptional in the way that a survey of surgeons' opinions was made at the start of the trial, in 1986, and again before results were analysed but after termination of the trial in 1994. At the initial survey, the three surgeons from the trial steering committee and 23 other surgeons experienced in treating gastric carcinoma were given detailed questionnaires. They were asked about the expected survival rate in the D1 group, anticipated difference in survival from D2 surgery, and what difference would be medically important and influence future treatment of patients. The consensus opinion of those surveyed was that there might be a survival improvement of 9.4%. In 1994, prior to closure of the trial, and before any survival information was disclosed, the survey was repeated with 21 of the original 26 surgeons. At this second survey, the opinion of the trial steering committee was that 9.5% difference was more realistic. This was in accord with the opinion of the larger group, which remained little changed since 1986. The baseline 5-year D1 survival was thought likely to be about 32%, which corresponded closely to the actual survival of recruited patients. Revised sample size calculations suggested that, on the basis of these more recent opinions, between 800 and 1200 patients would have been required. Both surveys assessed the level of treatment benefit that was deemed to be sufficient for causing surgeons to change their practice. This showed that the 13% difference in survival used as the study target was clinically relevant, but also indicated that many clinicians would remain unwilling to change their practice if the difference is only 9.5%. The experience of this carefully designed trial illustrates the problems of designing long-term, randomized trials. It raises interesting questions about the common practice of basing sample size estimates upon the beliefs of a trial design committee that may include a number of enthusiasts for the trial treatment. If their opinion of anticipated effect sizes drives the design of the trial, rather than the opinion of a larger community of experts that includes sceptics as well as enthusiasts, there is likely to be a serious miscalculation of sample size requirements.

Current role of scapulectomy.

Tumors of the scapula are an unusual clinical challenge. Partial or complete resection of the scapula, with its attached musculoaponeurotic tissue, is a seldom used technique for the treatment of primary bone and soft tissue tumors, as well as selected metastatic involvement of the scapula. Scapulectomy may allow wide margins of resection without amputation. The purpose of this study is to review our recent experience with scapulectomy. This study describes the recent experience with scapulectomy by the Section of Surgical Oncology and the Department of Orthopedics at Louisiana State Medical Center (New Orleans, LA). Between 1994 and 1998, 12 patients (between 16 and 79 years of age) underwent a resection of the scapula. Eleven of these patients had soft tissue tumors; one had a metastasis from a thyroid carcinoma. Six of these patients underwent a scapulectomy as a primary treatment, five for recurrence. Six patients also received postoperative radiation and/or chemotherapy. The follow-up ranged from 6 months to 4 years. There was no mortality or wound infection associated with scapulectomy. All patients had normal hand and wrist function after surgery. Three distant recurrences occurred, with no local or regional failures encountered during the follow-up period. Scapulectomy can result in excellent local tumor control. Whereas some loss of active shoulder motion may occur, hand, wrist and elbow function is preserved. Although maintenance of shoulder function should not take precedence over adequacy of resection, scapulectomy remains an excellent procedure for malignant disease that preserves hand, wrist, and elbow function.

A comparison of in vitro tests and a faecal egg count reduction test in detecting anthelmintic resistance in horse strongyles.

This study reports a comparison between faecal egg count reduction test (FECRT), egg hatch assay (EHA) and larval development assay (LDA) for detecting anthelmintic resistance in equine strongyles. Resistance to benzimidazoles was demonstrated in 33 of 42 (79%) farms tested by FECRT and in 32 (62%) of the 52 farms tested by EHA. As the reference strain used was not fully susceptible to benzimidazoles it was not possible to determine the level of resistance by LDA. Pyrantel resistance was indicated on three of 15 farms by faecal egg count reduction. Resistance was also indicated by LDA for one of these farms. In addition resistance was indicated by LDA on two more farms that were not tested by FECRT. Further testing is needed to confirm if these findings are truly indicative of resistance. Generally, correlations between the tests were poor and it was not possible to use the outcome of one test to predict the outcome of another.

Patient survival after D1 and D2 resections for gastric cancer: long-term results of the MRC randomized surgical trial. Surgical Co-operative Group.

Controversy still exists on the optimal surgical resection for potentially curable gastric cancer. Much better long-term survival has been reported in retrospective/non-randomized studies with D2 resections that involve a radical extended regional lymphadenectomy than with the standard D1 resections. In this paper we report the long-term survival of patients entered into a randomized study, with follow-up to death or 3 years in 96% of patients and a median follow-up of 6.5 years. In this prospective trial D1 resection (removal of regional perigastric nodes) was compared with D2 resection (extended lymphadenectomy to include level 1 and 2 regional nodes). Central randomization followed a staging laparotomy. Out of 737 patients with histologically proven gastric adenocarcinoma registered, 337 patients were ineligible by staging laparotomy because of advanced disease and 400 were randomized. The 5-year survival rates were 35% for D1 resection and 33% for D2 resection (difference -2%, 95% CI = -12%-8%). There was no difference in the overall 5-year survival between the two arms (HR = 1.10, 95% CI 0.87-1.39, where HR > 1 implies a survival benefit to D1 surgery). Survival based on death from gastric cancer as the event was similar in the D1 and D2 groups (HR = 1.05, 95% CI 0.79-1.39) as was recurrence-free survival (HR = 1.03, 95% CI 0.82-1.29). In a multivariate analysis, clinical stages II and III, old age, male sex and removal of spleen and pancreas were independently associated with poor survival. These findings indicate that the classical Japanese D2 resection offers no survival advantage over D1 surgery. However, the possibility that D2 resection without pancreatico-splenectomy may be better than standard D1 resection cannot be dismissed by the results of this trial.

A questionnaire survey on nematode control practices on horse farms in Denmark and the existence of risk factors for the development of anthelmintic resistance.

A questionnaire survey to obtain information on endoparasite control practices and management on 68 Danish horse farms was undertaken in 1995. The study revealed that foals, young horses and adults were on average, annually treated 4.3, 4.0 and 3.7 times, respectively. The most commonly used drug from 1993-1995 was ivermectin. On average 2.4 different drugs were used annually. The most used method of weight estimation was eye measure: for foals by 78%, for youngsters by 81% and adults by 82% of the herd owners. The most commonly used weight in the dosing of anthelmintics was individual weights of the horse: 72% of the herd owners dosed their foals this way. 76% their youngsters and 75% their adults. Sixty two percent of the herd owners treated at turn out, 47% at housing, 57% treated when buying new horses, 26% treated when stabling visiting horses, 78% applied pasture change and 18% performed alternate/mixed grazing. Sixty one percent of the herds had experienced problems with diarrhoea and in 18% of the cases the suspected cause was considered to be endoparasites. 33% of the farms performed disease registration and on 25% Faecal Egg Count Reduction tests had been performed before entering this study. The herd owners obtained their formation about endoparasite control from veterinarians, meetings and papers in that order of importance.