Multiblock polymers: panacea or Pandora's box?

Advances in synthetic polymer chemistry have unleashed seemingly unlimited strategies for producing block polymers with arbitrary numbers (n) and types (k) of unique sequences of repeating units. Increasing (k,n) leads to a geometric expansion of possible molecular architectures, beyond conventional ABA-type triblock copolymers (k = 2, n = 3), offering alluring opportunities to generate exquisitely tailored materials with unparalleled control over nanoscale-domain geometry, packing symmetry, and chemical composition. Transforming this potential into targeted structures endowed with useful properties hinges on imaginative molecular designs guided by predictive theory and computer simulation. Here, we review recent developments in the field of block polymers.     

Managing anthelmintic resistance: Modelling strategic use of a new anthelmintic class to slow the development of resistance to existing classes

AIM: To test the hypothesis that a single strategic treatment with a new class of anthelmintic could slow the development of resistance to existing classes of anthelmintic.

METHODS: An existing model was used to simulate nematode parasite dynamics and the development of anthelmintic resistance. Variations on a five-drench preventive programme of treatments for lambs, in which either zero, the first, third or fifth treatment was substituted with a different class of drug, were compared for the time to reach treatment failure (defined as efficacy <95%). The sensitivity to variations in the death rate of adult worms, that varied from 1 to 5%, and the dominance of resistance genes were also assessed.

RESULTS: Replacing one of the five treatments with a different class of anthelmintic almost always slowed the development of resistance, and was never worse than using the same drug for all treatments. Further, there were large differences in the relative time to treatment failure depending on which treatment was substituted. Changing the first treatment always had the least benefit, whereas changing the fifth treatment always had the greatest. This pattern was independent of the daily death rate of adult worms, and was not influenced by the dominance of resistance under treatment.

CONCLUSIONS: The results indicated that strategic substitution of a single treatment with a new class of anthelmintic, at the end of a series of preventive treatments to lambs using an existing class, could slow the further development of resistance to the latter. This strategic use of a new anthelmintic class has the potential to greatly extend the life of existing anthelmintics if these are still effective.     

Carbendazim,at concentrations used on pasture for facial eczema control,reduces development of Trichostrongylus colubriformis when sprayed onto infected sheep faeces

Abstract

AIM: To determine whether the fungicide, carbendazim, as applied to pastures for controlling facial eczema (FE), would inhibit development of the free-living stages of the gastrointestinal nematode parasite Trichostrongylus colubriformis.

METHODS: Two studies were conducted, using sheep faeces containing eggs of T. colubriformis. In the first, the faeces were either exposed or not to an application of carbendazim sprayed at the recommended rate for FE control. After spraying, dishes containing the faeces were incubated at 20°C for 14 days, and the resulting third-stage infective larvae (L3) extracted by baermannisation and counted. In addition, naturally infested pasture was also sprayed, and the number of L3 present 7 days later was assessed by cutting herbage samples and extracting larvae by soaking in water and baermannisation. In the second, the faeces were incubated at 20°C for 0, 3 or 7 days before being exposed to no, one or two applications of carbendazim. After further incubation for 14, 11 or 7 days, L3 were similarly extracted by baermannisation and counted.

RESULTS: In the first study, there was a 74% reduction in the number of T. colubriformis larvae recovered from faeces exposed to carbendazim compared with faeces not exposed, but there was no reduction in the number of L3 recovered from herbage. In the second study, faeces incubated for 0 or 3 days prior to exposure to a single application of carbendazim yielded 98% or 89% fewer larvae, respectively, than faeces not exposed. Faeces incubated for 7 days prior to exposure yielded similar numbers of larvae to faeces not exposed.

CONCLUSION: Treatment of pastures with carbendazim for FE control is likely to result in reduced development of the larvae of T. colubriformis, and by inference those of other species, where the application coincides with the presence of freshly deposited faeces containing eggs and developing larvae. However, no effect of treatment on L3 was indicated. The significance of this for on-farm nematode parasite control remains to be determined, as does any potential for strategic applications of carbendazim to pasture aimed at reducing numbers of parasite larvae on pasture. The latter should not be contemplated without due consideration of the implications for the development of anthelmintic resistance.     

Drench-and-shift is a high-risk practice in the absence of refugia

Abstract

AIM: To examine the effect of an anthelmintic treatment to lambs, followed immediately by a shift onto pastures with differing levels of larval contamination, on the development of anthelmintic resistance, in order to support recommendations to farmers regarding drench-and-shift practices for sustainable worm control.

METHODS: Newly weaned Romney lambs (n=72) were dosed with third-stage infective larvae (L3) of two nematode parasite species, Teladorsagia (=Ostertagia) circumcincta and Trichostrongylus colubriformis, comprising benzimidazole-resistant and -susceptible isolates, calculated to yield, after treatment with albendazole, a 95% reduction in faecal nematode egg count (FEC). Once infections became patent (Day 0), lambs were randomised into nine groups of eight animals, treated with albendazole at the manufacturer's recommended dose rate, and moved to individual pastures each previously prepared to have one of three different levels of parasite larval infestation (Treatment 1 = low contamination, Treatment 2 = medium contamination, and Treatment 3 = high contamination), and grazed on those pastures before receiving a second treatment with albendazole at Day 47. Anthelmintic resistance status in each group of lambs was measured using FEC reduction (FECR) and egghatch assays (EHA) after the first anthelmintic treatment, and FECR after the second treatment.

RESULTS: Egg-hatch assays demonstrated significant differences between treatments. The concentration of anthelmintic required to kill 50% of the eggs (LC₅₀) for Treatment 1, comprising the least contaminated pastures, was significantly higher than for Treatments 2 and 3 on Days 33 and 40. Treatment 1 also had a significantly lower FECR at the final anthelmintic treatment, and significantly lower FEC than the other two treatments from Days 26 to 47.

CONCLUSIONS: The results demonstrated that the populations of T. circumcincta and T. colubriformis in lambs treated with anthelmintic had significantly higher levels of albendazole resistance at the end of the grazing period in lambs moved onto pastures with relatively low levels of parasite contamination than those moved onto pastures with relatively higher contamination, confirming drench-and-shift onto ‘clean’ pasture as a high-risk practice for the selection for anthelmintic resistance. While this does not necessarily preclude the use of this practice it does emphasise the importance of taking appropriate remedial action to minimise the risk.     

Multiple resistance in Trichostrongylus and Teladorsagia (Ostertagia) in goats to oxfendazole,levamisole and moxidectin,and ineffi cacy of trichlorphon

Extract

We wish to report the identification, from a flock of commercially-traded goats, of nematode worms that we have been unable to kill using the anthelmintic groups currently registered for use in sheep in New Zealand.     

The impact of highly concentrated Mo and Cu dietary supplements,fed as a bolus,on the efficacy of chelated versus inorganic Cu in cattle on a low-Cu diet

AIM: To compare the efficacy of chelated versus inorganic forms of dietary Cu supplements, fed as a bolus, when challenged by a daily bolus of dietary Mo in cattle on a low-Cu diet.

METHODS: Forty non-lactating, Friesian dairy cows of adequate Cu status were assigned to four groups and fed a basal diet of baled silage containing 5.3 mg Cu and 0.4 mg Mo/kg DM. The experimental design was a factorial of two chemical forms of supplemental Cu and two levels of Mo intake, provided as pelleted grain supplements made from crushed barley/molasses plus Cu and Mo. The supplements contained 140 mg Cu/kg as Cu sulphate pentahydrate (CS), 140 mg Cu/kg as Cu glycinate (CG), CS plus 38 mg Mo/kg as sodium molybdate (CS+Mo), or CG plus 38 mg Mo/kg (CG+Mo). Commencing on Day 0, supplements were fed once daily (offered 1–1.2 kg/cow) and were completely consumed within 5–10 minutes, which constitutes a bolus type of administration. Liver samples were collected by biopsy at Days ?24, 13, 41 or 47, and 69 for Cu determinations.

RESULTS: The diets fed to the Cu+Mo groups were roughly equivalent to 25 mg Cu and 5.7 mg Mo/kg DM. Mean initial concentration of Cu in liver for all groups was 516 (SE 54) μmol Cu/kg fresh tissue. In cows supplemented with CS and CG, the final (Day 69) concentrations increased (p<0.01) to 939 (SE 166) and 853 (SE 163) μmol Cu/kg, respectively. These values were not different (p=0.72). For groups CS+Mo and CG+Mo, the final concentrations of 535 (SE 122) and 453 (SE 102) μmol Cu/kg were not different from initial values or from each other (p>0.25). The rate of accumulation of Cu in liver following bolus Cu and Mo intake was highly variable but was not affected by initial concentration of Cu in liver (p>0.9) or by the form of Cu (p>0.6). Mean rates of accumulation of Cu in liver were 4.0 (SD 3.8) and 0.65 (SD 2.0) μmol Cu/kg fresh tissue/day for the Cu-only treatments and the Cu+Mo treatments, respectively.

CONCLUSIONS: When fed together as a bolus, high Mo intake negated the effect of supplemental Cu but it did not reduce liver Cu stores. There was no difference in the reaction of dietary Mo with chelated Cu (as glycinate) versus inorganic Cu (as sulphate) dietary supplements.     

Anthelmintic resistance and management of nematode parasites on beef cattle-rearing farms in the North Island of New Zealand

AIM: To provide information on current farmers’ opinions and farming practices thought to be related to anthelmintic resistance, and to test for associations between the presence of anthelmintic resistance and management practices on beef cattle- rearing farms in the North Island of New Zealand.

METHODS: A study using an interview-based questionnaire about management of internal parasites was conducted on 62 beef cattle-rearing farms in the North Island of New Zealand, using case-control analyses to test for associations between management practices and the presence or absence of resistance to ivermectin or albendazole. Resistance was inferred from faecal nematode egg count (FEC) reduction (FECR) tests (FECRTs) when there was <90% reduction in FEC 7-10 days after treatment of calves <12 months of age.

RESULTS: Of the 59 farmers who completed the questionnaire, most (n=40) ranked parasites highly, and at about the same level as quality and quantity of feed, as important production-limiting factors for their enterprises. In contrast, anthelmintic resistance was not perceived to be a problem on 13 farms, and its importance was rated low on 24, moderate on 15, and high on only six farms. Despite all farms having planned parasite control programmes, there was heavy reliance on clinical signs of parasitism to determine frequency of treatments. About one in three farmers with beef breeder cows routinely treated their calves at marking, one in five treated mixed-age cows, and almost half treated rising 2-year-old cows before calving. One in four farmers used anthelmintics on calves on 8–12 occasions in their first year of life. Co-grazing with other species was rare, but follow-on grazing within 3 months after older cattle or sheep was common. On most farms, grazing cattle was restricted to part of the farm, a finding with implications for parasite control and persistence of larvae in refugia. Macrocyclic lactone (ML) anthelmintics or their combinations with other action families were currently, and for the past 5 years, used more frequently than benzimidazoles and levamisole, and benzimidazole-levami- sole combinations. The prevalence of resistance to ivermectin was high (82%) and no plausible model of associations could be constructed from the data. The prevalence of resistance to albendazole was 60%, and the risk of resistance increased as the number of rising 1-year-old cattle present mid-winter increased, and decreased as the number of breeding cows >2 years old present mid-winter increased.

CONCLUSION: It is clear that in practice anthelmintic resistance is a secondary consideration to obtaining productivity advantages from the use of anthelmintics in beef cattle. Farmers’ opinions were divided on many issues and the overall impres- sion was of confused and diverse thinking regarding the principles of the use of anthelmintics. The overall outlook regarding anthelmintic resistance in cattle is bleak unless the need for integrated and long-term research activities is acted upon soon.     

Selective and on-demand drenching of lambs: Impact on parasite populations and performance of lambs

AIM: To determine whether drenching regimes for lambs by which a proportion (10%) of the heaviest animals was selectively left untreated, or animals are only drenched ‘on demand’ when faecal nematode egg counts (FEC) exceeded a threshold level, would result in measurable increases in parasite larval challenge in the autumn and/or decreases in the performance of lambs.

METHODS: A replicated study compared three drenching strategies in which mobs of lambs (n=360 in total) received either: a five-drench preventive programme, administered to all animals (Treatment 1); a five-drench preventive programme, but the 10% heaviest animals left untreated each time (Treatment 2); or drench treatments administered only when FEC exceeded 500 eggs per gram of faeces (epg) (Treatment 3). After the five-drench programme, animals in Treatments 1 and 2 were treated according to FEC as for Treatment 3. A triple-combination drench containing ivermectin, oxfendazole and levamisole, administered orally, was used for all treatments. There were nine farmlets, allowing three replicates of each treatment, in a completely randomised design. Parasite infestations on pasture were measured in autumn by pasture plucks, and worm burdens were monitored in tracer lambs, while the performance of lambs was assessed by liveweight gains, fleece weights, and body condition and dag scores.

RESULTS: Increased numbers of Haemonchus contortus and Trichostrongylus colubriformis larvae on pasture were found in the autumn on farmlets treating selectively or on-demand (Treatments 2 and 3). No differences were detected in other parasite species. Mean liveweight gains did not differ between treatments but some differences were detected between drenched and undrenched lambs in Treatment 2. Mean body condition and mean dag scores of lambs in Treatment 3 tended to be lower and higher, respectively, than those of lambs in Treatment 1; Treatment 2 was generally intermediate.

CONCLUSIONS: Drenching strategies for lambs designed to slow the development of anthelmintic resistance, by increasing the pool of susceptible worms available to dilute resistant survivors after treatment, resulted in increased numbers of H. contortus and T. colubriformis but not other species of parasite on pasture. The increased parasite challenge to lambs in the autumn was associated with small production losses, which may be acceptable to farmers wishing to implement such strategies. It is clear that further work is required on the interaction between management practices and the population dynamics of parasites, especially with regard to creating pools of susceptible genotypes to slow the development of drench resistance.     

Measurements of the equation of state of deuterium at the fluid insulator-metal transition

A high-intensity laser was used to shock-compress liquid deuterium to pressures from 22 to 340 gigapascals. In this regime deuterium is predicted to transform from an insulating molecular fluid to an atomic metallic fluid. Shock densities and pressures, determined by radiography, revealed an increase in compressibility near 100 gigapascals indicative of such a transition. Velocity interferometry measurements, obtained by reflecting a laser probe directly off the shock front in flight, demonstrated that deuterium shocked above 55 gigapascals has an electrical conductivity characteristic of a liquid metal and independently confirmed the radiography.