Clinical field study to evaluate the efficacy and safety of the amino-acetonitrile derivative, monepantel, compared with registered anthelmintics against gastrointestinal nematodes of sheep in Australia

Objective   To determine the efficacy of monepantel, a developmental compound from the amino-acetonitrile derivative class of anthelmintics, against field infections of gastrointestinal nematodes in sheep.
Procedures   Comparisons of efficacy (using standard faecal worm egg count reduction tests) and safety (on the basis of visual observations) were made in a large-scale field study in Australia, between groups of sheep treated with either an oral solution of monepantel or a registered anthelmintic. The sheep were naturally infected with the major gastrointestinal nematode genera present in Australia.
Results   The post-treatment efficacy results for monepantel were: at 7 days (±1 day) efficacy was >98%; at 14 days (±1 day) it was generally close to or >99%; and at 21 days (±1 day) efficacy was consistently >99%. A high proportion of the targeted nematode populations were confirmed as being resistant to one or more of the currently available anthelmintic classes.
Conclusions   Monepantel when used under field conditions at a minimum dose rate of 2.5 mg/kg was highly effective against mixed-genus natural field infections of the major gastrointestinal nematode genera including Haemonchus , Teladorsagia ( Ostertagia ), Trichostrongylus , Nematodirus , Chabertia and Oesophagostomum . This result included efficacy against some populations resistant to the currently available broad-spectrum anthelmintics. Few Cooperia spp. were present to allow confirmation of efficacy against this genus. On no occasion after treatment did any commercial anthelmintic-treated groups have significantly lower faecal egg counts than the monepantel-treated groups. Monepantel was safe for the target animals and human operators when used in a field situation.     

Genes controlling vaccine responses and disease resistance to respiratory viral pathogens in cattle

Farm animals remain at risk of endemic, exotic and newly emerging viruses. Vaccination is often promoted as the best possible solution, and yet for many pathogens, either there are no appropriate vaccines or those that are available are far from ideal. A complementary approach to disease control may be to identify genes and chromosomal regions that underlie genetic variation in disease resistance and response to vaccination. However, identification of the causal polymorphisms is not straightforward as it generally requires large numbers of animals with linked phenotypes and genotypes. Investigation of genes underlying complex traits such as resistance or response to viral pathogens requires several genetic approaches including candidate genes deduced from knowledge about the cellular pathways leading to protection or pathology, or unbiased whole genome scans using markers spread across the genome. Evidence for host genetic variation exists for a number of viral diseases in cattle including bovine respiratory disease and anecdotally, foot and mouth disease virus (FMDV). We immunised and vaccinated a cattle cross herd with a 40-mer peptide derived from FMDV and a vaccine against bovine respiratory syncytial virus (BRSV). Genetic variation has been quantified. A candidate gene approach has grouped high and low antibody and T cell responders by common motifs in the peptide binding pockets of the bovine major histocompatibility complex (BoLA) DRB3 gene. This suggests that vaccines with a minimal number of epitopes that are recognised by most cattle could be designed. Whole genome scans using microsatellite and single nucleotide polymorphism (SNP) markers has revealed many novel quantitative trait loci (QTL) and SNP markers controlling both humoral and cell-mediated immunity, some of which are in genes of known immunological relevance including the toll-like receptors (TLRs). The sequencing, assembly and annotation of livestock genomes and is continuing apace. In addition, provision of high-density SNP chips should make it possible to link phenotypes with genotypes in field populations without the need for structured populations or pedigree information. This will hopefully enable fine mapping of QTL and ultimate identification of the causal gene(s). The research could lead to selection of animals that are more resistant to disease and new ways to improve vaccine efficacy.     

Stratospheric Mean Ages and Transport Rates from Observations of Carbon Dioxide and Nitrous Oxide

Measurements of stratospheric carbon dioxide (CO2) and nitrous oxide (N2O) concentrations were analyzed to investigate stratospheric transport rates. Temporal variations in tropospheric CO2 were observed to propagate into the stratosphere, showing that tropospheric air enters the lower tropical stratosphere continuously, ascends, and is transported rapidly (in less than 1 month) to both hemispheres. The mean age A of stratospheric air determined from CO2 data is approximately 5 years in the mid-stratosphere. The mean age is mathematically equivalent to a conserved tracer analogous to exhaust from stratospheric aircraft. Comparison of values for A from models and observations indicates that current model simulations likely underestimate pollutant concentrations from proposed stratospheric aircraft by 25 to 100 percent.     

Brain abscess in seven cats due to a bite wound: MRI findings, surgical management and outcome

PRESENTATION AND LESION LOCALISATION: Seven adult domestic shorthair cats were presented with a 1- to 6-day history of progressive neurological signs. A focal skin puncture and subcutaneous swelling over the dorsal part of the head were detected on physical examination. Neurological examination indicated lesion(s) in the right forebrain in four cats, multifocal forebrain in one cat, left forebrain in one cat, and multifocal forebrain and brainstem in the remaining cat. In all cats, magnetic resonance imaging revealed a space-occupying forebrain lesion causing a severe mass effect on adjacent brain parenchyma. CLINICAL APPROACH AND OUTCOME: All cats were managed with a combination of medical and surgical treatment. At surgery a small penetrating calvarial fracture was detected in all cats, and a tooth fragment was found within the content of the abscess in two cats. The combination of surgical intervention, intensive care and intravenous antimicrobials led to a return to normal neurological function in five cats. PRACTICAL RELEVANCE: As this series of cases indicates, successful resolution of a brain abscess due to a bite injury depends on early recognition and combined used of antimicrobials and surgical intervention. A particular aim of surgery is to remove any skull and foreign body (tooth) fragments that may represent a continuing focus of infection.     

Short hold times in dynamic vapor sorption measurements mischaracterize the equilibrium moisture content of wood

Recently, the dynamic vapor sorption (DVS) technique has been used to measure sorption isotherms and develop moisture-mechanics models for wood and cellulosic materials. This method typically involves measuring the time-dependent mass response of a sample following step changes in relative humidity (RH), fitting a kinetic model to the data, and extrapolating the asymptotic mass. A series of steps covering the full RH range is used to generate the sorption isotherm. The majority of prior DVS data were taken with hold times of either 60 min or until the change in moisture content was <0.002% per minute over a 10-min period. Here, DVS measurements on wood and isolated wood polymers are presented where the hold times at certain relative humidity steps were much longer, ranging between 24 and 50 h. The data clearly show that the criteria for hold time in previous DVS measurements result in significant errors in prediction of the asymptotic mass. Although the data at short times are consistent with previous measurements, the data exhibit slow sorption behavior with characteristic times on the order of 500–2000 min that cannot be identified with shorter hold times. The results suggest that new hold time criteria need to be developed for dynamic vapor sorption measurements in wood.     

Recombinant expression of porcine spermadhesin AWN and its phospholipid interaction: Indication for a novel lipid binding property

AWN is a porcine (Sus scrofa domestica) seminal plasma protein and has been linked to a variety of processes related to fertilization. To acquire the protein in sufficient amount and purity for functional studies, we established its recombinant expression in E. coli and a three‐step purification protocol based on different chromatographies. The test for AWN–phospholipid interaction revealed phosphatidic acid and cardiolipin as potential binding partners. As phosphatidic acid is surmised to play a role in cation‐induced membrane destabilization and fusion events, we propose a membrane protective function of the presented binding affinity. Further studies with recombinant AWN will allow new insights into the mechanism of sperm–spermadhesin interaction and might provide new approaches for artificial reproduction techniques.     

The Japanese science education centers

These six Japanese science education centers signify a sweeping reform of elementary and secondary school science teaching. They achieve their striking results because they are established on a permanent, local basis and are supported mainly by the local boards of education. They have avoided control by pedagogues and specialists in "education." Instead, they are operated by trained scientists and experienced school teachers who work together to devise programs specially suited to the needs of their teachers. With small and practicable steps, the teachers improve their understanding of methods which they can readily test in their own classrooms rooms and laboratories. The laboratory equipment in the science education centers is only slightly superior to that which the teachers have in their own schools, but superior enough to make them desire to improve their own facilities. Major facilities, such as x-ray machines, electron microscopes, telescopes (15-cm), and machine shops, as well as good working collections of minerals and fossils, and adequate greenhouses, permit the teachers to work with more expensive equipment, to gain a firsthand knowledge of its operation, and to bring groups of students to the center to observe what such instruments make possible. The use of American experimental course content improvement programs is widespread. Every science education center I visited is using PSSC, CHEMS, CBA, BSCS, or ESCP materials and studying the philosophy of these programs. Yet no center is entirely dependent on these programs, but uses them critically to supplement and improve its own courses. The emphasis is on good laboratory and field teaching as a basis for understanding scientific methods and concepts. Science as investigation and inquiry, instead of treatment solely as an authoritative body of facts, is coming into its own. The few defects of the science education centers of Japan inhere in the educational situation itself. The centers are at present inadequate to reach even a reasonable proportion of the science teachers within a 5-year, or even a 10-year cycle. The shortage of substitute teachers causes most of the courses to be far too brief for maximum effectiveness. Staff programming tends to be rather spotty instead of comprehensive. A major difficulty, frequently expressed, lies in the grim hold of the university entrance examination system over the science curricula of the lower schools. The university is the goal of every able student, for economic as well as intellectual reasons. To enter a university he must pass the examinations, which are established separately by each institution. The professor who makes out the examination questions therefore controls what must be taught and learned in the lower schools. This same rigorous control is in part reflected in the Ministry of Education syllabi, which must be followed by the teachers. Nevertheless, I found the men in the biological section of the Ministry of Education very enlightened and pressing for change. Many professors in the universities are also in the full current of modern biological thought, participate gladly in the programs of the science education centers, and would write examinations that emphasize interpreting data, applying tests to hypotheses, and drawing valid conclusions instead of merely memorizing and regurgitating facts. On the other hand, in many universities the upper positions are still filled by men to whom biology means classification rather than experimentation, morphology rather than biochemistry, organ physiology rather than cell biology. We cannot afford to discard taxonomy, morphology, or gross physiology-they are important parts of biology and will remain so. But they do not comprise all of biology-they are only a diminishing proportion of it. In Japan, as in the United States, the examination system must become more flexible. It must change with the development of science itself, must encourage scientific attitudes and cease defeating the introduction of new disciplines, new outlooks, new subject matter. The university and the examining boards in some educational systems indeed exhibit a rigor mortis. On balance, the science education centers in Japan may well represent the most significant educational experiment of our time. Their vitality, which springs from their local relationship to the prefectural schools and their permenent staffs, far exceeds in my own estimation that of most of the summer science institutes held in the United States, which lack that close relation to the local schools and which by their impermanency countenance ill-planned and ill-taught programs that are often little different from the usual summer school sessions. The best summer institutes in the United States are indeed very good, but far too few of them reach a passable standard. That is because, for the most part, their staffs are recruited quickly, teach their favorite subjects without much consideration of their appropriateness or suitability for improving science education in the lower schools, and depart without much contact with other members of the staff. What is needed is serious, continuous, prolonged, hard work devoted to the development of the right sorts of courses for renewing the training of science teachers. The Japanese seem to be achieving just that. We would do well, with our vast resources for the improvement of education, to emulate them. As they have profited by employing and improving upon our NSF supported programs in science education, we may likewise profit through the establishment of science education centers modeled on theirs.