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Summary: To systematically explore the genes mediating functional crosstalk between metazoan biological processes, we apply comparative genetic interaction (GI) mapping in Saccharomyces cerevisiae and Caenorhabditis elegans to generate an inter-bioprocess network consisting of 178 C. elegans GIs. The GI network spans six annotated biological processes including aging, intracellular transport, microtubule-based processes, cytokinesis, lipid metabolic processes, and anatomical structure development. By proposing a strategy called “reciprocal functional test” for interacting gene pairs, we discover a group of genes that mediate crosstalk between distinct biological processes. In particular, we identify the ribosomal S6 Kinase/RSKS-1, previously characterized as an mTOR (mechanistic target of rapamycin) effector, as a regulator of DAF-2 endosomal recycling transport, which traces a functional correlation between endocytic recycling and aging processes. Together, our results provide an alternative and effective strategy for identifying genes and pathways that mediate crosstalk between bioprocesses with little prior knowledge. : Chen et al. develop a “reciprocal functional test” to identify genes mediating crosstalk between different bioprocesses with little prior knowledge. With this method, ribosomal S6 Kinase/RSKS-1 is identified as a potential regulator of DAF-2 recycling. This finding traces a functional link between endocytic recycling and aging processes. Keywords: genetic interaction, bioprocess crosstalk, comparative mapping, endocytic recycling, RSKS-1/S6 Kinase, Caenorhabditis elegans, Saccharomyces cerevisiae, RAB-10/Rab10, recycling endosomes, mTOR

Background: Our program uses a desensitization protocol that includes intraoperative therapeutic plasma exchange (iTPE) for crossmatch-positive lung transplants, which improves access to lung transplant for sensitized candidates while mitigating immunologic risk. Although we have reported excellent outcomes for sensitized patients with the use of this protocol, concern for perioperative bleeding appears to have hindered broader adoption of it at other programs. We conducted a retrospective cohort study to quantify the impact of iTPE on perioperative bleeding in lung transplantation., Methods: All first-time lung transplant recipients from 2014 to 2019 who received iTPE were compared to those who did not. Multivariable logistic regression was used to determine the association between iTPE and large-volume perioperative transfusion requirements (≥5 packed red blood cell units within 24 hours of transplant start), adjusted for disease type, transplant type, and extracorporeal membrane oxygenation or cardiopulmonary bypass use. The incidence of hemothorax (requiring reoperation within 7 days of lung transplant) and 30-day posttransplant mortality were compared between the 2 groups using chi-square test., Results: One hundred forty-two patients (16%) received iTPE, and 755 patients (84%) did not. The mean number of perioperative pRBC transfusions was 4.2 among patients who received iTPE and 2.9 among patients who did not. iTPE was associated with increased odds of requiring large-volume perioperative transfusion (odds ratio 1.9; 95% confidence interval: 1.2-2.9, p-value = 0.007) but was not associated with an increased incidence of hemothorax (5% in both groups, p = 0.99) or 30-day posttransplant mortality (3.5% among patients who received iTPE vs 2.1% among patients who did not, p = 0.31)., Conclusions: This study demonstrates that the use of iTPE in lung transplantation may increase perioperative bleeding but not to a degree that impacts important posttransplant outcomes., (Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Our program previously reported successful outcomes following virtual crossmatch (VXM)-positive lung transplants managed with perioperative desensitization, but our ability to stratify their immunologic risk was limited without flow cytometry crossmatch (FCXM) data before 2014. The aim of this study was to determine allograft and chronic lung allograft dysfunction (CLAD)-free survival following VXM-positive/FCXM-positive lung transplants, which are performed at a minority of programs due to the high immunologic risk and lack of data on outcomes. All first-time lung transplant recipients between January 2014 and December 2019 were divided into 3 cohorts: VXM-negative (n = 764), VXM-positive/FCXM-negative (n = 64), and VXM-positive/FCXM-positive (n = 74). Allograft and CLAD-free survival were compared using Kaplan-Meier and multivariable Cox proportional hazards models. Five-year allograft survival was 53% in the VXM-negative cohort, 64% in the VXM-positive/FCXM-negative cohort, and 57% in the VXM-positive/FCXM-positive cohort (P = .7171). Five-year CLAD-free survival was 53% in the VXM-negative cohort, 60% in the VXM-positive/FCXM-negative cohort, and 63% in the VXM-positive/FCXM-positive cohort (P = .8509). This study confirms that allograft and CLAD-free survival of patients who undergo VXM-positive/FCXM-positive lung transplants with the use of our protocol does not differ from those of other lung transplant recipients. Our protocol for VXM-positive lung transplants improves access to transplant for sensitized candidates and mitigates even high immunologic risk., (Copyright © 2023 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Asymptomatic carotid atherosclerotic stenosis (ACAS) is associated with cognitive impairment. Systemic inflammation occurs in patients with systemic atherosclerosis and is also associated with cognitive impairment. The goal of this study was to determine if cognitive impairment in patients with ACAS is the result of systemic inflammation., Methods: A cross-sectional analysis of 104 patients (63 patients with ACAS, 41 controls) with cognitive function and inflammatory biomarker assessments was performed. Venous blood was assayed for proinflammatory biomarkers (IL-1β, IL-6, IL-6R, IL-8, IL-17, tumor necrosis factor-α, matrix metalloproteinase [MMP]-1, MMP-2, MMP-7, MMP-9, vascular cell adhesion molecule, and high-sensitivity C-reactive protein). The patients also underwent comprehensive cognitive testing to compute five domain-specific cognitive scores per patient. We first assessed the associations between carotid stenosis and cognitive function, and between carotid stenosis and systemic inflammation in separate regression models. We then determined whether cognitive impairments persisted in patients with carotid stenosis after accounting for inflammation by adjusting for inflammatory biomarker levels in a combined model., Results: Patients with ACAS and control patients differed in age, race, coronary artery disease prevalence, and education. Stenosis patients had worse cognitive scores in two domains: learning and memory (P = .05) and motor and processing speed (P = .002). Despite adjusting for inflammatory biomarker levels, patients with ACAS still demonstrated deficits in the domains of learning and memory and motor and processing speed., Conclusions: Although systemic atherosclerosis-induced inflammation is a well-recognized cause for cognitive impairment, our data suggest that it is not the primary underlying mechanism behind cognitive impairments seen in ACAS. Cognitive impairments in learning and memory and motor and processing speed seen in patients with ACAS persist after adjusting for systemic inflammation. Thus, alternative mechanisms should be explored to account for the observed functional impairments., (Copyright © 2021 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Balance and mobility function worsen with age, more so for those with underlying chronic diseases. We recently found that asymptomatic carotid artery stenosis (ACAS) restricts blood flow to the brain and might also contribute to balance and mobility impairment. In the present study, we tested the hypothesis that ACAS is a modifiable risk factor for balance and mobility impairment. Our goal was to assess the effect of restoring blood flow to the brain by carotid revascularization on the balance and mobility of patients with high-grade ACAS (≥70% diameter-reducing stenosis)., Methods: Twenty adults (age, 67.0 ± 9.4 years) undergoing carotid endarterectomy for high-grade stenosis were enrolled. Balance and mobility assessments were performed before and 6 weeks after revascularization. These included the Short Physical Performance Battery, the Berg Balance Scale, the Four Square Step Test, the Dynamic Gait Index (DGI), the Timed Up and Go test, gait speed, the Mini-Balance Evaluation Systems Test (Mini-BESTest), and the Walking While Talking complex test., Results: Consistent with our previous findings, patients demonstrated reduced scores on the Short Physical Performance Battery, Berg Balance Scale, DGI, and Timed Up and Go test and in gait speed. Depending on the outcome measure, 25% to 90% of the patients had scored in the impaired range at baseline. After surgery, significant improvements were observed in the outcome measures that combined walking with dynamic movements, including the DGI (P = .02) and Mini-BESTest (P = .002). The proportion of patients with Mini-BESTest scores indicating a high fall risk had decreased significantly from 90% (n = 18) at baseline to 40% (n = 8) after surgery (P = .02). We used Pearson's correlations to examine the relationship between balance and mobility before surgery and the change after surgery. Patients with lower baseline DGI and Mini-BESTest scores demonstrated the most improvement after surgery (r = -0.59, P = .006; and r = -0.70, P = .001, respectively)., Conclusions: Carotid revascularization improved patients' balance and mobility, especially for measures that combine walking and dynamic movements. The greatest improvements were observed for the patients who had been most impaired at baseline., (Copyright © 2021 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

The Toronto Lung Transplant Program has been using a peri-operative desensitization regimen of plasma exchange, intravenous immune globulin, and antithymocyte globulin in order to accept donor-specific antibody (DSA)-positive lung transplants safely since 2008. There are no long-term data on the impact of this practice on allograft survival or the development of chronic lung allograft dysfunction (CLAD). We extended our prior study to include long-term follow-up of 340 patients who received lung transplants between January 1, 2008 and December 31, 2011. We compared allograft survival and CLAD-free survival among patients in three cohorts: DSA-positive, panel reactive antibody (PRA)-positive/DSA-negative, and unsensitized at the time of transplant. The median follow-up time in this extension study was 6.7 years. Among DSA-positive, PRA-positive/DSA-negative, and unsensitized patients, the median allograft survival was 8.4, 7.9, and 5.8 years, respectively (p = .5908), and the median CLAD-free survival was 6.8, 7.3, and 5.7 years, respectively (p = .5448). This follow-up study confirms that long-term allograft survival and CLAD-free survival of patients who undergo DSA-positive lung transplants with the use of our protocol do not differ from other lung transplant recipients. Use of protocols such as ours, therefore, may improve access to transplant for sensitized candidates., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Pulmonary endarterectomy is the treatment of choice for chronic thromboembolic pulmonary hypertension. This case report outlines the importance of venoarterial extracorporeal membrane oxygenation and plasmapheresis as two important options in the management of heparin-induced thrombocytopenia-positive patients requiring urgent pulmonary endarterectomy., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

It is widely recognized that after endocytosis, internalized cargo is delivered to endosomes that act as sorting stations. The limiting membrane of endosomes contain specialized subregions, or microdomains, that represent distinct functions of the endosome, including regions competing for cargo capture leading to degradation or recycling. Great progress has been made in defining the endosomal protein coats that sort cargo in these domains, including Retromer that recycles transmembrane cargo, and ESCRT (endosomal sorting complex required for transport) that degrades transmembrane cargo. In this review, we discuss recent work that is beginning to unravel how such coat complexes contribute to the creation and maintenance of endosomal microdomains. We highlight data that indicates that adjacent microdomains do not act independently but rather interact to cross-regulate. We posit that these interactions provide an agile means for the cell to adjust sorting in response to extracellular signals and intracellular metabolic cues., Competing Interests: Conflict of interest statement Nothing declared., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

In this contribution, we have explored the potential and strength of one-dimensional (1D) (29)Si and two-dimensional (2D) (29)S-(29)Si and (29)Si-(17)O NMR as invariants of non-oriented graph for fingerprinting zeolite frameworks. 1D and 2D (29)Si NMR can indeed provide indications on the graph vertices, edges and allow the construction of the adjacency matrix, i.e. the set of connections between the graph vertices. From the structural data, hypothetical 1D (29)Si and 2D (29)Si-(29)Si NMR signatures for 193 of the zeolite frameworks reported in the Atlas of Zeolite Structures have been generated. Comparison between all signatures shows that thanks to the 1D (29)Si NMR data only, almost 20% of the known zeolite frameworks could be distinguished. Further NMR signatures were generated by taking into account 2D (29)Si-(29)Si and (29)Si-(17)O correlations. By sorting and comparison of all the NMR data, up to 80% of the listed zeolites could be unambiguously discriminated. This work indicates that (i) solid-state NMR data indeed represent a rather strong graph invariant for zeolite framework, (ii) despite their difficulties and costs (isotopic labeling is often required, the NMR measurements can be long), (29)Si and (17)O NMR measurements are worth being investigated in the frame of zeolites structure resolution. This approach could also be generalized to other zeolite-related materials containing NMR-measurable nuclides., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Donor-specific HLA antibodies (DSA) have an adverse effect on short-term and long-term lung transplant outcomes. We implemented a perioperative strategy to treat DSA-positive recipients, leading to equivalent rejection and graft survival outcomes. Pretransplant DSA were identified to HLA-A, B, C, DR and DQ antigens. DSA-positive patients were transplanted if panel reactive antibody (PRA) ≥30% or medically urgent and desensitized with perioperative plasma exchange, intravenous immune globulin, antithymocyte globulin (ATG), and mycophenolic acid (MPA). PRA-positive/DSA-negative recipients received MPA. Unsensitized patients received routine cyclosporine, azathioprine and prednisone without ATG. From 2008-2011, 340 lung-only first transplants were performed: 53 DSA-positive, 93 PRA-positive/DSA-negative and 194 unsensitized. Thirty-day survival was 96 %/99%/96% in the three groups, respectively. One-year graft survival was 89%/88%/86% (p = 0.47). DSA-positive and PRA-positive/DSA-negative patients were less likely to experience any ≥ grade 2 acute rejection (9% and 9% vs. 18% unsensitized p = 0.04). Maximum predicted forced expiratory volume (1 s) (81%/74%/76%, p = NS) and predicted forced vital capacity (81%/77%/78%, respectively, p = NS) were equivalent between groups. With the application of this perioperative treatment protocol, lung transplantation can be safely performed in DSA/PRA-positive patients, with similar outcomes to unsensitized recipients., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)

We present an algorithm for automatically predicting the topological family of any RNA three-way junction, given only the information from the secondary structure: the sequence and the Watson-Crick pairings. The parameters of the algorithm have been determined on a data set of 33 three-way junctions whose 3D conformation is known. We applied the algorithm on 53 other junctions and compared the predictions to the real shape of those junctions. We show that the correct answer is selected out of nine possible configurations 64% of the time. Additionally, these results are noticeably improved if homology information is used. The resulting software, Cartaj, is available online and downloadable (with source) at: http://cartaj.lri.fr., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

SNARE domain proteins are key molecules mediating intracellular fusion events. SNAP25 family proteins are unique target-SNAREs possessing two SNARE domains. Here we report the genetic, molecular, and cell biological characterization of C. elegans SNAP-29. We found that snap-29 is an essential gene required throughout the life-cycle. Depletion of snap-29 by RNAi in adults results in sterility associated with endomitotic oocytes and pre-meiotic maturation of the oocytes. Many of the embryos that are produced are multinucleated, indicating a defect in embryonic cytokinesis. A profound defect in secretion by oocytes and early embryos in animals lacking SNAP-29 appears to be the underlying defect connecting these phenotypes. Further analysis revealed defects in basolateral and apical secretion by intestinal epithelial cells in animals lacking SNAP-29, indicating a broad requirement for this protein in the secretory pathway. A SNAP-29-GFP fusion protein was enriched on recycling endosomes, and loss of SNAP-29 disrupted recycling endosome morphology. Taken together these results suggest a requirement for SNAP-29 in the fusion of post-Golgi vesicles with the recycling endosome for cargo to reach the cell surface., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Patients with cleidocranial dysplasia, a rare autosomal dominant genetic syndrome, possess abnormal anatomical features of the head, mouth, neck and spinal column. These features may result in perioperative problems such as difficult airway and complicated regional anesthesia. We report the anesthetic management of a young woman with cleidocranial dysplasia undergoing four caesarean sections, one vaginal delivery and a dilatation and curettage, employing different modes of anesthesia. Anesthetic management in this disorder presents challenges for both general and neuraxial anesthesia., (Copyright 2009 Elsevier Ltd. All rights reserved.)

The completion of the Caenorhabditis elegans genome sequence was the initial step toward the use of whole-genome analysis in this model organism. Advances in C. elegans genomics include transcript profiling, gene-function screens using RNA-mediated interference, and protein-interaction mapping using the yeast two-hybrid system. Recent reports have employed these methods to gain new insights into diverse biological problems such as tissue-specific gene expression, cell-fate specification, genome organization, the DNA damage response, and early embryonic development. These studies combined genomic approaches to probe complex biological pathways on an unprecedented scale.

The "International Co-operation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH)" is an international programme of co-operation between regulatory authorities and the animal health industries of the European Union, Japan, and the United States of America which aims to harmonise the technical requirements for the registration of veterinary medicinal products. Australia and New Zealand participate as active observers. The objective of the present paper is to present the guidelines established by the working group on Anthelmintic Efficacy Guidelines: (1) efficacy of anthelmintics: general requirements (VICH GL7); (2) efficacy of anthelmintics: specific recommendations for bovines (VICH GL12); (3) efficacy of anthelmintics: specific recommendations for ovines (VICH GL13); (4) efficacy of anthelmintics: specific recommendations for caprines (VICH GL14). These guidelines do not consist of rigid stipulations, but make clear recommendations on the minimal standards needed. To the veterinary profession, livestock producers and animal owners, harmonisation should mean quicker access to safer and more effective veterinary anthelmintics. In general, products should be relatively more affordable because of the reduction in registration costs and efficient use of resources by the regulatory authorities.

To evaluate the prophylactic and therapeutic effects of an ivermectin controlled-release capsule (IVM-CRC) on the productivity of growing sheep infested with Psoroptes ovis 24 male and 24 female Merino landrace lambs, 5-6 months old and weighing 21.2-35.0 kg, were used. Sixteen replicates of three animals were formed based on sex and Day 0 body weight. Within each replicate animals were randomly allocated to one of three groups: untreated control; IVM-CRC on Day 0; IVM-CRC on Day 84. For treatment an IVM-CRC for sheep weighing 20-45 kg was used which is designed to deliver ivermectin at a minimum dose of 20 microg/kg/day for 100 days. The lambs were infested with 50-60 P. ovis mites each on days 14 and 21. The animals were shorn on Day 126. After slaughter on Day 127 the quality of the leather produced from their skins was evaluated. The IVM-CRC treatment on Day 0 prevented the establishment of P. ovis. All untreated lambs became infested. The lambs treated with an IVM-CRC on Day 84 became mite-free from Day 112 onwards. The lambs which were treated on Day 0 had significantly (p<0.05) greater clean fleece weight (1.5 kg) and fleece yield (52.1%) than the untreated controls (0.9 kg and 34.1%, respectively) or than lambs treated on Day 84 (1.0 kg and 47.8%, respectively). Clean fleece weight and fleece yield were in the tendency (p=0.055) or significantly (p<0. 001) greater, respectively, for lambs treated on Day 84 than for the untreated controls. The chrome tanned dried crust leather of all untreated controls and six of the 16 lambs treated on Day 84 showed grain surface defects such as discolourations, indurations and coarse, pitted grain. The useful (defect-free) leather size was significantly (p<0.01) higher for the lambs treated on Day 0 (100%) than for the lambs treated on Day 84 (82.7%) and the untreated controls (7.8%). The physical testing revealed that the leather of sheep treated on Day 0 had significantly (p<0.05) higher thickness, elongation break and tear resistance than the leather of both untreated controls and sheep treated on Day 84. There were no significant differences in the physical characteristics of the leather of the untreated controls and the sheep treated on Day 84.

To evaluate the prophylactic and therapeutic effects of an ivermectin controlled-release capsule (IVM-CRC) on the productivity of growing sheep infested with Psoroptes ovis 24 male and 24 female Merino landrace lambs, 5-6 months old and weighing 21.2-35.0 kg, were used. Sixteen replicates of three animals were formed based on sex and Day 0 body weight. Within each replicate animals were randomly allocated to one of three groups: untreated control; IVM-CRC on Day 0; IVM-CRC on Day 84. For treatment an IVM-CRC for sheep weighing 20-45 kg was used which is designed to deliver ivermectin at a minimum dose of 20 microg/kg per day for 100 days. The lambs were infested with 50-60 P. ovis mites each on Days 14 and 21. Mites in skin scrapings were counted on Days 70, 84, 98, 112 and 126. Body weight and feed consumption were measured every 2 weeks from Day 0 to 126. The animals were slaughtered on Day 127 and their carcasses evaluated. The IVM-CRC treatment on Day 0 prevented the establishment of P. ovis. All untreated lambs became infested. The lambs treated with an IVM-CRC on Day 84 became mite-free from Day 112 onwards. The lambs treated on Day 0 had significantly (p<0.05) greater body weight gain from Day 0 to 84 (13.9 kg) and Day 0 to 126 (20.9 kg) than the untreated controls (9.6 and 12.8 kg, respectively) and the sheep treated on Day 84 (8.4 and 14.9 kg, respectively). Feed consumption (Days 0-126) for sheep treated with the IVM-CRC on Day 0 was higher than for sheep treated on Day 84 (p<0.05) and for the untreated controls (p<0.1). The carcasses of sheep treated with the IVM-CRC on Day 0 had significantly (p<0.05) higher warm and cold weights, carcass yield, rib eye area and back fat thickness than the untreated control group and the sheep treated with the IVM-CRC on Day 84. The sheep treated with the ivermectin CRC on either Day 0 or 84 had significantly (p<0.05) better muscle scores and lower muscle pH 1h post-slaughter than the untreated controls. There was no significant (p>0.1) difference between warm and cold carcass weights, carcass yield and rib eye area between sheep treated on Day 84 and untreated controls.

A controlled trial was conducted to evaluate the efficacy of the intraruminal ivermectin controlled-release capsule (CRC) (IVOMEC Maximizer CR Capsule for Sheep, Merial Ltd.) against induced incoming third-stage larvae and established adult infections with some rarer gastrointestinal nematode parasites of sheep. Twenty-one worm-free lambs were allocated by restricted randomisation based on body weight within sex to one of the following treatments: unmedicated control, ivermectin CRC given on Day 0 prior to induced infection, and ivermectin CRC given on Day 70 after establishment of induced infection. The ivermectin CRC delivers ivermectin at a minimum dose rate of 20 microg/kg/day for 100 days. Infections were induced by daily administration of third-stage larvae for five consecutive days. Nematodes were counted on Day 84, 14 days after treatment of established infection. The treatment with the ivermectin CRC prevented the establishment of Ostertagia leptospicularis, O. ostertagi, Bunostomum trigonocephalum, Cooperia oncophora, C. punctata, C. surnabada, Nematodirus helvetianus, N. roscidus and Strongyloides papillosus by >99% as compared with the untreated controls (p < 0.01). The administration of the ivermectin CRC reduced established adult infections of O. ostertagi, B. trigonocephalum, C. oncophora, C. punctata, C. surnabada, N. roscidus and S. papillosus by >99% (p < 0.01), and reduced established adult infections of O. leptospicularis and N. helvetianus by 96.5 and 98.4% (p < 0.01), respectively.

The options for the treatment and control of sheep scab (psoroptic mange) have been increased in recent years through the introduction of the endectocides ivermectin, doramectin and moxidectin. Whilst therapeutic efficacy is good, the current injectable formulations offer limited protection against re-infestation with Psoroptes ovis. An intraruminal controlled-release formulation of ivermectin has been developed to provide therapeutic and prophylactic activity against a range of sensitive endo- and ecto-parasites of sheep for 100 days after administration. These ivermectin boluses are designed to release ivermectin at 20-40 microg/kg/day over 100 days and were developed for use in sheep of 20-90 kg bodyweight. Several controlled therapeutic and prophylactic trials against sheep scab have been conducted under a variety of protocols with such boluses in Europe and South America. The results of these studies indicate that the bolus provides 100% therapeutic efficacy against established P. ovis infestations and equivalent prophylactic efficacy against challenge infestations administered during the active life of the bolus.

Three trials including 42 sheep were conducted in Brazil or Germany to evaluate the therapeutic (two trials) and prophylactic (one trial) efficacy of an ivermectin controlled release capsule (CRC) against Psoroptes ovis infestation. In one therapeutic trial naturally infested sheep were used while in the other trials infestations were experimentally induced. In each trial half of the animals were treated on Day 0 with one ivermectin controlled release capsule that delivers ivermectin at a rate of 1.6 mg/day for approximately 100 days, that is 20 mcg/kg/day to a 80 kg animal, while the other half remained untreated. In both therapeutic trials mites were counted in skin scrapings and their presence was recorded at predilection sites one day before treatment and at weekly intervals from Day 7 to Day 56. In the trial conducted to evaluate the prophylactic efficacy the sheep were experimentally infested with P. ovis 21 and 28 days post-treatment and mites were counted and recorded at predilection sites on Days 42, 49 and 56. The ivermectin controlled release capsule was completely effective in eliminating the P. ovis mites within 28 days of administration and it prevented the establishment of an infestation of P. ovis induced 21 and 28 days after administration.

The efficacy of an in-feed formulation (IVOMEC premix) containing 0.6% ivermectin was tested against Strongyloides ransomi in swine. The efficacy of ivermectin against patent infections of S. ransomi when given via the feed at 2 ppm for 7 days (Days 0-7) to provide 100 mcg ivermectin kg-1 body weight day-1 was evaluated in a study with 16 3-month-old male castrated piglets. Seven days prior to treatment each piglet was infected subcutaneously with 2500 infective larvae of S. ransomi. Fecal egg counts were carried out on Days -7, 0, 7 and 14, and worm counts on Day 14. Efficacy was 100% in all treated piglets. Two trials involving 40 pregnant gilts were carried out to evaluate the efficacy of ivermectin against the somatic larval stages of S. ransomi when given at a daily dose of 100 mcg kg-1 body weight for 7 days starting on Days 66, 78, 92 or 103 of pregnancy. The gilts were each experimentally infected with three subcutaneous injections of 250,000 infective larvae, with the last infection given between 12 and 30 days prior to commencement of treatment. Gilts were confirmed free of pre-existing intestinal stages of S. ransomi prior to ivermectin treatment. Fecal nematode egg counts were carried out in gilts/sows and piglets subsequently born. The Strongyloides larvae present in sow milk 1, 2 and 7 days post partum were counted. Fourteen days post natum, worm counts were performed in four randomly selected piglets for each litter. IVOMEC premix given to pregnant gilts prevented shedding of larvae in sow milk, egg output in feces and the establishment of S. ransomi in piglets.

We tested the localization accuracy of magnetoencephalography (MEG) and electrocorticography (ECoG) for a current dipole in a saline filled sphere at depths ranging from 1 to 6 cm at 1 cm intervals. We used standard neuromagnetometer placements and subdural electrode grids, previously employed for patient studies, with precise measurements of sensor and electrode locations with a 3-dimensional spatial digitizer. MEG and ECoG had comparable accuracy with mean errors of 1.5 and 1.8 mm, respectively. It appears that use of the spatial digitizer increases accuracy for both MEG and EGoG localizations. The larger errors in the ECoG with increasing depths could be attributed to under-sampling of the spatial pattern of the field which spreads out with deeper sources. It should be noted that in clinical applications a grid of the dimensions used here would most typically be used for superficial sources on the cortex with depth recordings being preferred for investigations of deep epileptogenic activity. Results are encouraging for continued development of non-invasive MEG methods for further definition of epileptogenic zones in the brain.

In order to delineate the characteristics of epileptic spikes, 1946 different spikes were studied in 6 patients with complex partial epilepsy. Non-invasive MEG and EEG source analysis of interictal spikes were contrasted to ECoG localization, surgical outcome and presence of lesions on MRI. Results indicated that: (1) using the most frequent occurring spike topography patterns from a large sample of spikes improved goodness-of-fit values for both MEG and EEG localization, (2) when spike patterns could be appropriately matched on several successive MEG measurements to provide an adequate matrix (3 of 6 subjects), there was excellent agreement between MEG dipole sources and ECoG sources as well as surgical outcome and presence of MRI lesions, (3) EEG source analyses also gave good results but not as consistently as MEG.

Generally on the gas chromatogram of a volatile essential oil, terpenes, oxygenated compounds and sesquiterpenes appear. With temperature programming, it was shown that some non-volatiles are present with the volatiles. They are simple coumarin (2H-1-benzopyran-2-one) derivatives such as citropten (5,7-dimethoxycoumarin) and furocoumarins (psoralen, 7H-furo[3,2-g][1]benzopyran-7-one) such as bergapten (5-methoxypsoralen), some of which are phototoxic. Terpeneless oils are used in perfumes and cosmetics, so it is important to be able to establish rapidly if they contain phototoxic compounds.

Many factors affect dung degradation and colonization, including the location, composition, moisture content, weight, surface area and organic matter content of dung pats. Because of the number and variability of these factors, methodology plays a major role in studies using the dung pat as an experimental unit. For results of such studies to be meaningful, conditions should be standardized as much as possible and the sampling technique should be systematic and consistent. This paper reports the results of experiments or trials which pay particular attention to aspects of methodology.

Eight female calves of the Deutsches Fleckvieh breed, weighing 161-207 kg, were each treated at turnout on 16 May 1989 with one ivermectin sustained-release intraruminal bolus designed to release ivermectin at 12 mg day-1 for approximately 120 days. Eight animals remained as untreated controls. A third group of eight unmedicated tracer calves was not considered as part of this evaluation. All 24 animals grazed together on a single pasture throughout the study. On Days 21/22, 70 and 119, 15 faecal pats were selected from each treatment group and ranked according to surface area; within each group of three consecutively ranked pairs of pats, two pairs were randomly allocated as observation pats and the third as a sampling pat. The surface area of observation pats was measured, photographs taken, and dry matter, crude ash and organic matter determined at various intervals following deposition. A 1/4 sample collected from sampling pats 3, 7, 14 and 28 days after deposition was weighed and examined for Coleoptera (adults and larvae), Diptera larvae and nematodes. No differences between groups were seen in respect of organic matter content, numbers or frequency of adult Coleoptera species and soil nematodes. A decrease in numbers of Coleoptera larvae, Diptera larvae and dung-specific nematodes was observed in pats from ivermectin-treated cattle. Based on the evaluation of the surface area, a delay in the degradation rate of pats from treated compared with those from untreated animals was seen; however, the difference was statistically not significant (P > 0.05).

We investigated functional topography of human hand and lip sensorimotor cortex using somatosensory evoked potentials (SEPs) from chronically indwelling subdural grid electrodes (ECoG) in 3 epilepsy patients during stimulation of median nerve, ulnar nerve, and lower lip. We used dipole modeling to determine the cortical location of each peripheral sensory field. The cortical locations were in the postcentral gyrus and showed a clear somatotopic organization from medial superior to lateral inferior in the order: ulnar nerve, median nerve, and lip. The source localizations agreed with the results of cortical stimulations and anatomical features on intraoperative photographs. The cortical regions of median and ulnar nerve each could be modeled by sequential tangential and radial dipoles. The cortical region of lip was different and could be explained mostly by tangential dipoles. These findings suggest a difference in the cortical organization of human lip and hand sensory cortex and are consistent with a larger representation of lip in the posterior bank of central fissure in area 3b than on the gyral surface in area 1, similar to findings in macaque. Further studies in a larger population of patients with ECoG or normal subjects with scalp-EEG and MEG are warranted to test this hypothesis.

Pyrantel pamoate, formulated in a beef-based chewable tablet, was evaluated for efficacy in dogs against induced and natural infections of Toxocara canis, Toxascaris leonina, Ancylostoma caninum and Uncinaria stenocephala. Dose titration trials were conducted in Canada, the UK and Germany in dogs treated with pyrantel (as pamoate salt) at 0, 2.5, 5 or 10 mg kg-1 body weight. These studies showed that a dose rate of 2.5 mg kg-1, the efficacy of pyrantel against adult T. canis, T. leonina, U. stenocephala and A. caninum was 76.1, 85.6, 100 and 87.9%, respectively. Efficacy at 5 mg kg-1 against the same parasites was 94.2, 92.0, 93.5 and 93.8%, respectively, and at 10 mg kg-1 efficacy was 91.2, 97.6, 98.7 and 91.3%, respectively. No adverse effects due to treatment were seen in any of these trials.

We measured somatosensory evoked magnetic fields during median nerve stimulation in 6 normal subjects. We applied multiple dipole models to study the spatiotemporal structure of early somatosensory evoked magnetic fields (SEFs), as well as the number, 3-dimensional location and time activity of their underlying neuronal sources. Two dipole sources were necessary to model the first 40 msec of SEFs explaining 85% of the data variance. Source 1 was located deeper than source 2, showed primarily a tangential orientation, and accounted for a larger part of the variance; source 2 showed no consistent orientation across subjects. Both sources showed biphasic time activities corresponding to the previously described N20-P30 and P25-N35 components. Spatiotemporal modeling could identify sources which could not be modeled consistently above noise by single moving dipoles (P25 component), revealed small latency differences of the two sources in some subjects suggesting parallel activation of these sources, and allowed separation of sources overlapping considerably both in space and time. We conclude that spatiotemporal modeling of SEFs may be useful to study functional anatomy of human sensorimotor cortex non-invasively.

We measured chronic electrocorticography (ECoG) of sensorimotor cortex during contralateral median nerve stimulation in 6 patients with partial seizures evaluated for surgery. We analyzed the spatiotemporal structure of the somatosensory evoked response (SER) using multiple source modeling to investigate functional anatomy of its neuronal sources. Two dipole sources in postcentral gyrus explained the large majority of the first 60 msec of the SER, indicating a subregion of hand somatosensory cortex generating this activity. The source locations agreed with normal functional anatomy from cortical stimulations, intraoperative photographs, and postoperative neurological examinations after focal excisions. The time patterns of both sources were biphasic like the previously described N20-P30 and P25-N35 peaks. The spatiotemporal patterns of both sources overlapped. Spatiotemporal analysis with multiple dipole sources appears useful to determine the number, locations, and spatiotemporal field patterns of cortical regions active during peripheral somatosensory stimulation and reveals simplicity in the macroscopic functional anatomy of dynamic human sensorimotor cortex.

Worm counts were done in 49 gastro-intestinal tracts of fallow deer from two German enclosures. The mean worm burden was 592 worms. It was significantly higher in calves than in older animals. Sixteen different nematode species were identified. Spiculopteragia asymmetrica, Ostertagia leptospicularis, O. ostertagi, Rinadia mathevossiani, Oesophagostomum radiatum and O. venulosum were the most frequently occurring species.

As a follow-up to a previous guideline publication on efficacy evaluation of anthelmintics in ruminants, an expert group of the World Association for the Advancement of Veterinary Parasitology presents similar guidelines for the testing of anthelmintics in swine. The goal of the guidelines is to develop uniform testing standards and registration requirements. Data obtained from investigations according to the guidelines should be internationally accepted in the registering of drugs. Further, the use of the guidelines may contribute towards reducing costs, labor and the number of experimental animals used for drug testing.

Fifteen calves, each infected with approximately 3000 third stage larvae, were used to compare the tendencies of two strains of Dictyocaulus viviparus to inhibit at the fifth larval stage and to evaluate the efficacy of ivermectin. There were notable differences between the strains. While greater than 99% of worms developing from infection with an Alpine strain remained inhibited 42 days after infection, only 0-26% of those recovered following infection with a U.K. laboratory strain were arrested. Neither adult nor immature D. viviparus were present in the lungs of animals treated with ivermectin subcutaneously at 200 micrograms/kg body weight 28 days after infection with the Alpine larvae.

Magnetic fields produced by a dipolar source implanted in a spherical conductor and a human cranial specimen were measured in the magnetoencephalogram (MEG). The location of the source was accurately computed in the spherical conductor from the identified magnetic field extrema using equations for a current dipole in a sphere. This same method was insufficient for localizing the source in a human cranium, where magnetic field maps appeared as distortions from the classical dipolar pattern. A more complete computer modeling procedure was used, adjusting for the non-spherical dimensions of the recording matrix on the cranium. By fitting the gradient of computer simulated fields to those measured outside the cranium, the accuracy of source localization was substantially improved. The greatest distortion of the extracranial magnetic field was an inequality in the measured amplitude of the two extrema, produced by an increased distance and angle of the MEG probe when recording over the lower face and ear. However, gross heterogeneities in the resistance of the skull due to a craniectomy and an implanted insulating balloon had a negligible effect on the extracranial magnetic field pattern.

A method of spatiotemporal analysis, using multiple current dipoles to represent activity in multiple brain regions, was applied to the interpretation of extracranial neuromagnetic fields generated by epileptic spikes in patients with focal seizure disorders. This method permitted the identification and approximate localization of cellular currents within single and multiple brain regions engaged over the entire duration of the human epileptic spike complex. These results suggest that spatially and temporally overlapping electrical currents in human epileptic cortex may be investigated non-invasively in the magnetoencephalogram if appropriate physical models are applied.