Genome-wide association study to identify genetic loci associated with gastrointestinal nematode resistance in Katahdin sheep.

Resistance to gastrointestinal nematodes has previously been shown to be a moderately heritable trait in some breeds of sheep, but the mechanisms of resistance are not well understood. Selection for resistance currently relies upon faecal egg counts (FEC), blood packed cell volumes and FAMACHA visual indicator scores of anaemia. Identifying genomic markers associated with disease resistance would potentially improve the selection process and provide a more reliable means of classifying and understanding the biology behind resistant and susceptible sheep. A GWAS was conducted to identify possible genetic loci associated with resistance to Haemonchus contortus in Katahdin sheep. Forty animals were selected from the top and bottom 10% of estimated breeding values for FEC from a total pool of 641 sires and ram lambs. Samples were genotyped using Applied Biosystems™ Axiom™ Ovine Genotyping Array (50K) consisting of 51 572 SNPs. Following quality control, 46 268 SNPs were included in subsequent analyses. Analyses were conducted using a linear regression model in plink v1.90 and a single-locus mixed model in snp and variation suite. Genome-wide significance was determined by a Bonferroni correction for multiple testing. Using linear regression, loci on chromosomes 2, 3, 16, 23 and 24 were significantly associated at the genome level with FEC estimated breeding values, and we identified a region on chromosome 2 that was significant using both statistical analyses. We suggest a potential role for the gene DIS3L2 for gastrointestinal nematode resistance in Katahdin sheep, although further research is needed to validate these findings.

Randomized phase II trial of docetaxel plus prednisone in combination with placebo or AT-101, an oral small molecule Bcl-2 family antagonist, as first-line therapy for metastatic castration-resistant prostate cancer.

BACKGROUND: AT-101 (A), a small molecule oral inhibitor of the Bcl-2 family, has activity alone and in combination with docetaxel (Taxotere) and prednisone (DP) in metastatic castration-resistant prostate cancer (mCRPC). A randomized, double-blind, placebo-controlled phase II trial compared DP combined with either AT-101 (A) or placebo in chemonaive mCRPC. PATIENTS AND METHODS: Men with progressive mCRPC despite androgen deprivation were eligible and randomized 1:1. Patients received docetaxel (75 mg/m2 day 1) and prednisone 5 mg orally twice daily every 21 days with either AT-101 (40 mg) or placebo twice daily orally on days 1-3. The primary end point was overall survival (OS). RESULTS: Two hundred and twenty-one patients were randomly assigned. Median OS for AT-101 plus docetaxel-prednisone (ADP) and placebo-DP was 18.1 versus 17.8 months [hazard ratio (HR) 1.07, 95% confidence interval 0.72-1.55, P=0.63]. Secondary end points were also not statistically different. Grade 3/4 toxic effects for ADP versus placebo-DP were cardiac events (5% versus 2%), lymphopenia (23% versus 16%), neutropenia (47% versus 40%), ileus (2% versus 0%) and pulmonary embolism (6% versus 2%). In a subgroup of high-risk mCRPC (n=34), outcomes appeared to favor ADP (median OS 19 versus 14 months). CONCLUSIONS: AT-101 was tolerable but did not extend OS when combined with DP in mCRPC; a potential benefit was observed in high-risk patients.

Genetic diversity and population structure in cultivated sunflower and a comparison to its wild progenitor, Helianthus annuus L.

Crop germplasm collections are valuable resources for ongoing plant breeding efforts. To fully utilize such collections, however, researchers need detailed information about the amount and distribution of genetic diversity present within collections. Here, we report the results of a population genetic analysis of the primary gene pool of sunflower (Helianthus annuus L.) based on a broad sampling of 433 cultivated accessions from North America and Europe, as well as a range-wide collection of 24 wild sunflower populations. Gene diversity across the cultivars was 0.47, as compared with 0.70 in the wilds, indicating that cultivated sunflower harbors roughly two-thirds of the total genetic diversity present in wild sunflower. Population structure analyses revealed that wild sunflower can be subdivided into four genetically distinct population clusters throughout its North American range, whereas the cultivated sunflower gene pool could be split into two main clusters separating restorer lines from the balance of the gene pool. Use of a maximum likelihood method to estimate the contribution of the wild gene pool to the cultivated sunflower germplasm revealed that the bulk of the cultivar diversity is derived from two wild sunflower population genetic clusters that are primarily composed of individuals from the east-central United States, the same general region in which sunflower domestication is believed to have occurred. We also identified a nested subset of accessions that capture as much of the allelic diversity present within the sampled cultivated sunflower germplasm collection as possible. At the high end, a core set of 288 captured nearly 90% of the alleles present in the full set of 433, whereas a core set of just 12 accessions was sufficient to capture nearly 50% of the total allelic diversity present within this sample of cultivated sunflower.

Antibody-drug conjugates for previously treated aggressive lymphomas: focus on polatuzumab vedotin.

INTRODUCTION: Antibody-drug conjugates (ADCs) are immunoconjugates and comprise a monoclonal antibody that is chemically attached to a cytotoxic drug (or payload) via a stable chemical linker. Since the approval of the first ADC in 2000, there are now nine different approved agents and over 100 ADCs in the drug-development pipeline. AREAS COVERED: This review briefly describes the ADCs approved for treatment of lymphoma and their distinguishing factors in terms of target, linker and payload. The clinical implications of the use of ADCs are also considered. Here, we focus on polatuzumab vedotin, an ADC targeted to CD79b, which is approved for the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) who have received at least one (EU approval) or two (US approval) prior therapies and are not eligible for bone marrow transplantation. The characteristics of polatuzumab vedotin are discussed and clinical data are presented. The future of polatuzumab vedotin clinical development, and ADCs in general, are also considered. EXPERT OPINION: ADCs represent a significant advance in the treatment of lymphoma. Polatuzumab vedotin has shown clinical efficacy and a tolerable safety profile in both first-line and R/R DLBCL; future studies are planned to further investigate this ADC.

Garlic and papaya lack control over gastrointestinal nematodes in goats and lambs.

Gastrointestinal nematodes (GIN) continue to hinder small ruminant production because of anthelmintic resistance and lack of effective products for GIN control in organic production. The objective of this study was to examine the effectiveness of a commercially available certified organic garlic product, fresh garlic juice, or garlic bulbs as an anthelmintic to control GIN in goats and papaya seeds for GIN control in lambs. In the first experiment, weaned meat goat kids were administered water or a commercial garlic juice product (n=7/treatment). In the second experiment, kids were administered water, fresh garlic juice, or fed garlic bulbs (n=9 or 10/treatment). In a third experiment, lambs were administered nothing or papaya seed in water (n=12/treatment). Naturally infected goats were supplemented with bermudagrass hay and corn/soybean supplement in the first experiment or maintained on bermudagrass pasture in the second experiment or lambs grazed mixed grasses in the third. Blood and fecal samples were collected on Days 0, 7, and 14 after administration of treatment to examine changes in blood packed cell volume (PCV) and fecal egg counts (FEC). PCV and FEC were similar by Day 14 between kids treated with a commercial garlic juice and water in the first experiment. Similarly, PCV was not different among treatment groups in the second experiment. FEC of the garlic juice group was lower than the other two groups on Day 0, but was similar among groups by Day 14. Deworming was required in one goat within each treatment group by Day 7 and in three kids in the garlic juice group and two in the garlic bulb group by Day 14. No changes in PCV or FEC were apparent in response to papaya seed compared with untreated lambs. Based on the alternative plant products used in this study, garlic or papaya seed is not recommended as an aid to control GIN in goats or lambs.

Herbal dewormer fails to control gastrointestinal nematodes in goats.

Gastrointestinal nematode (GIN) parasitism is the most important disease of small ruminants. Control is usually based on the use of chemical anthelmintics (dewormers); but these are prohibited from use in organic livestock, and the effectiveness of chemical anthelmintics in conventional operations is limited by high levels of anthelmintic resistance. Consequently, herbal dewormers are increasing in popularity as an alternative to chemical dewormers for GIN control. However, the effectiveness of herbal dewormers remains unproven. The objective of this study was to examine the effectiveness of a commercially available herbal dewormer to control GIN in goats. Lactating (n=16) and young (n=8) dairy goats grazed poor quality mixed grass pastures between March and July 2006 at the Heifer International Ranch in Perryville, AR. Goats were supplemented with grass hay and concentrate. Goats were untreated or administered herbal dewormer (n=12/treatment) according to manufacturer recommendations. FAMACHA scores (1=red or healthy; 5=severely anemic) were determined and fecal samples collected for fecal egg count (FEC) determination every 14 days between Days 0 (day of first herbal treatment) and 112. FAMACHA scores in the herbal treated group were greater than in the untreated control group (P<0.005), indicating a higher level of anemia. FEC were greater for herbal treated goats on Pasture A compared with B by Day 42, but similar among groups thereafter. FEC (P<0.03) and FAMACHA scores (P<0.001) were greater in lactating than in non-lactating goats. Herbal dewormer treatment yielded no measurable health benefits indicating that the herbal dewormer failed to control GIN in these goats.

Impact of rotational grazing on management of gastrointestinal nematodes in weaned lambs.

Gastrointestinal nematode (GIN) control for 'natural' or organic lamb production is needed, especially where Haemonchus contortus is prevalent. The objective was to determine the impact of rotational grazing on GIN infection of weaned lambs. In year 1, naturally infected Katahdin lambs (120 days of age) were randomly assigned to graze (1) continuous bermudagrass (CB; n=14), (2) rotational bermudagrass moved every 3.5 days and returned to original plot 35 days later for three rotations (RB; n=14), or (3) rotational bermudagrass rotated when forage height fell below 10 cm (RBH; n=7) where first day of grazing=Day 0. In late summer, all lambs were supplemented with 500 g corn/SBM because of poor condition. The following year, similar animals were used and included the CB (n=18) and the RB (n=36) groups only. In both years, fecal egg counts (FECs) and blood packed cell volume (PCV) were determined every 7-14 days and body weight every 28 days. Individuals were dewormed with 0.5 g copper oxide wire particles (COWP) when FAMACHA score increased to 3 or more. Between 0 and 3 deworming treatments per lamb were necessary and there tended to be fewer RB than CB lambs dewormed by Day 84 for both years combined (P<0.001). Worm free tracer lambs were introduced to CB (n=6) and RB (n=8) plots following the last rotation during the first year to determine worm burdens after 20 days of grazing. Abomasal worm burden tended to be greater in RB than CB or RBH tracer lambs (P<0.10), but intestinal worm numbers were similar. Differences may be due to differences in grazing patterns among groups. Body weight gains were similar between CB and RB groups. Economic value between the CB and RB lambs was similar based on number of lambs that could have been marketed as organic. For both years, lambs relied exclusively on COWP for GIN control with the exception of one lamb. In summary, while there was a reduced incidence of deworming in the RB compared with the CB group of lambs, estimated economic value of these systems was similar.

Efficacy of sericea lespedeza hay as a natural dewormer in goats: dose titration study.

Gastrointestinal nematodes (GIN) parasitism is the greatest threat to economic sheep and goat production in the southern USA, and there is widespread prevalence of GIN resistance to broad-spectrum anthelmintics in this region. A natural alternative for controlling GIN in small ruminants is feeding hay of sericea lespedeza [SL, Lespedeza cuneata (Dum.-Cours., G. Don)], a perennial warm-season legume high in condensed tannins. To determine the level of SL needed to reduce GIN infection, a confinement study was completed with 32 Spanish/Boer/Kiko cross yearling bucks offered one of four diets with 75% hay and 25% concentrate (n=8, 2 pens/treatment, 4 goats/pen). The hay portion of each diet consisted of a combination of ground SL (0%, 25%, 50%, and 75% of the diet) and bermudagrass [BG, Cynodon dactylon (L.) Pers.; 75%, 50%, 25%, and 0% of the diet]. The bucks were allowed to acquire a natural GIN infection on pasture prior to moving to the pens. After a 3-week adjustment period in the pens, the goats were stratified by fecal egg count (FEC) and packed cell volume (PCV), randomly assigned to treatments and pens, and then fed the treatment diets for six weeks. During the experimental period, fecal and blood samples were collected from individual animals weekly to determine FEC and PCV, respectively. Adult worms from abomasum and small intestines were collected for counting and identification of species at slaughter. Goats fed SL hay at 25%, 50%, and 75% of the diet had 45.3% (P=0.2048), 66.3% (P=0.0134), and 74.5% (P=0.0077) lower FEC than control animals (75% BG hay) after 21 days. The 50% and 75% SL goats had 84.6% (P=0.0625) and 91.9% (P=0.0340) lower FEC than controls by day 42. The 75% SL-fed goats tended to have higher (P=0.0624) PCV and had fewer (P=0.035) abomasal worms than control animals, while PCV and adult worm numbers of the 50% and 25% SL goats were not different from controls. The optimum level of SL hay in the diet for reducing worm numbers of small ruminants appears to be 75%, whereas 50-75% SL reduces FEC, which could lead to reduced larval infection on pasture.

Vaccinia-based oncolytic immunotherapy Pexastimogene Devacirepvec in patients with advanced hepatocellular carcinoma after sorafenib failure: a randomized multicenter Phase IIb trial (TRAVERSE).

Pexastimogene devacirepvec (Pexa-Vec) is a vaccinia virus-based oncolytic immunotherapy designed to preferentially replicate in and destroy tumor cells while stimulating anti-tumor immunity by expressing GM-CSF. An earlier randomized Phase IIa trial in predominantly sorafenib-naïve hepatocellular carcinoma (HCC) demonstrated an overall survival (OS) benefit. This randomized, open-label Phase IIb trial investigated whether Pexa-Vec plus Best Supportive Care (BSC) improved OS over BSC alone in HCC patients who failed sorafenib therapy (TRAVERSE). 129 patients were randomly assigned 2:1 to Pexa-Vec plus BSC vs. BSC alone. Pexa-Vec was given as a single intravenous (IV) infusion followed by up to 5 IT injections. The primary endpoint was OS. Secondary endpoints included overall response rate (RR), time to progression (TTP) and safety. A high drop-out rate in the control arm (63%) confounded assessment of response-based endpoints. Median OS (ITT) for Pexa-Vec plus BSC vs. BSC alone was 4.2 and 4.4 months, respectively (HR, 1.19, 95% CI: 0.78-1.80; p = .428). There was no difference between the two treatment arms in RR or TTP. Pexa-Vec was generally well-tolerated. The most frequent Grade 3 included pyrexia (8%) and hypotension (8%). Induction of immune responses to vaccinia antigens and HCC associated antigens were observed. Despite a tolerable safety profile and induction of T cell responses, Pexa-Vec did not improve OS as second-line therapy after sorafenib failure. The true potential of oncolytic viruses may lie in the treatment of patients with earlier disease stages which should be addressed in future studies. ClinicalTrials.gov: NCT01387555.

Undergraduate rheumatology: can peer-assisted learning by medical students deliver equivalent training to that provided by specialist staff?

OBJECTIVE: This study addressed whether medical students using peer-assisted learning (PAL) can deliver training comparable with didactic teaching provided by a specialist. METHODS: Twelve senior students were trained in PAL and the gait, arms, legs, spine (GALS) screening technique for musculoskeletal system (MSS) examination. The students recruited and trained 45 year-2 students in the use of GALS. Nineteen students were recruited by a physiotherapist for GALS training tutorials. Trainee responses were compared by analysis of pre/post training confidence (using 100 mm visual analogue scale), course experience questionnaires (using a 5-point Likert scale) including free text comments, and in end of year examinations. RESULTS: Trainee confidence increased after PAL training from 3.7 to 89.9 (P < 0.0001). There were no significant differences in confidence levels from student trainees after PAL when compared with expert-led teaching. Results from course experience questionnaires demonstrated benefits in all parameters investigated with all students recommending PAL training. No differences between PAL and expert-led training were observed. Free-text comments showed that PAL-trained students perceived that this learning technique has potential to be applied to other areas of training, an observation not raised by expert-trained students. Examination results revealed that PAL-trained and expert-tutored students were respectively, 1.4 and 1.3 times more likely to pass the MSS examination, when compared with students undertaking standard training (P < 0.002 and P = 0.0001, respectively). CONCLUSION: PAL is a useful adjunct to musculoskeletal clinical skills training. Students using PAL techniques offered a comparable level of training with that provided by an expert.

Use of FAMACHA system to evaluate gastrointestinal nematode resistance/resilience in offspring of stud rams.

High levels of anthelmintic resistance in gastrointestinal nematodes (GIN) of small ruminants have created the need for animals with greater resistance to these parasites. The objective of this experiment was to evaluate the effectiveness of the FAMACHA system in identification of parasite resilient/resistant offspring, and thus identification of stud rams with greater resilience/resistance. Katahdin ewes bred in separate groups to two sires to lamb in spring (2004, 2005: Ram A and Ram B; 2006, 2007: Ram C and Ram D) at the USDA, Agricultural Research Station in Booneville, Arkansas produced 20-40 offspring/sire each year. Ewes and lambs grazed mixed grass (predominantly bermudagrass and ryegrass) pastures and were supplemented with corn/soybean meal between 30 days pre- and 60 days post-lambing (ewes) and starting 45 days of age until weaning (lambs; 95.0+/-0.6 days of age). Blood samples and feces were collected from the lambs to determine blood packed cell volume (PCV) and fecal egg counts (FEC) and FAMACHA scores were determined at 90, 120, and 150 days of age. Lambs were dewormed if anemic (PCV<19% or FAMACHA score >2) and data removed within 30 days after deworming. Data were analyzed for the 2004/2005 and 2006/2007 groups using general linear models with year, sex of lamb, and sire nested within year as variables. Sire differences were detected (P<0.05 or less) for PCV and FAMACHA at all time points, but not FEC. There tended (P<0.10) to be sire differences for FEC at 90 and 120 days of age, but not at 150 days of age. Lambs sired by Ram D were dewormed less by 150 days of age than those sired by Ram C. The FAMACHA system can be used to identify superior sires for parasite resilience/resistance, thus increasing flock resilience, and perhaps resistance.

Dietary copper sulfate for control of gastrointestinal nematodes in goats.

Prevalence of anthelmintic resistance in gastrointestinal nematodes (GIN) of goats has necessitated studies for alternative means of control. The objective was to determine the effectiveness of dietary copper sulfate for control of GIN in meat goats. Naturally infected buck kids received 0 (LC), 78 (MC) or 158 (HC) mg copper sulfate (CS)/kid daily mixed with concentrate supplement for 63 days. After 42 days the HC group was re-randomized into either the LC or MC treatment. In another study, naturally infected yearling does were offered trace mineral mix with and without CS and intake was estimated to be 140-200mg CS/day. Goats grazed bermudagrass pastures and were rotated among two or three pastures to minimize pasture effects. Fecal egg count (FEC) and packed cell volume (PCV) were determined every 7 days in the first experiment and 14 days in the second experiment, and goats were weighed every 28 days. On Days 49 and 56 FEC were lower in the HC-treated kids (copper by day, P<0.02), but FEC were similar on all other days in the first experiment and were similar between the two groups of does in the second experiment. Blood packed cell volume was similar among treatment groups throughout both studies. Body weight was greater in LC compared with MC or HC-supplemented kids on Days 42 and 63 (copper by day, P<0.04). Body weights of does were similar on Days 0 and 56, but were reduced in those consuming trace mineral with CS on Day 28 (copper by day, P<0.03). Dietary CS failed to control GIN in this study.

Genetic parameters for fecal egg counts and their relationship with body weights in Katahdin lambs.

Reliance on anthelmintic drugs to control internal parasites in sheep is no longer sustainable because of the development of resistance to these drugs in parasite populations. Genetic selection may offer an alternative long-term solution, as differences in parasite resistance exist both within and among sheep breeds. However, selection for parasite resistance may have correlated effects on other production traits. The objectives of this study were to estimate genetic parameters for weaning (WFEC) and postweaning (PWFEC) fecal egg counts (FEC) and assess their relationship with birth (BWT), weaning (WWT), and postweaning (PWWT) BW in Katahdin lambs. The study used WFEC (n = 2,537), PWFEC (n = 3.421), BWT (n = 12,869), WWT (n = 10,961), and PWWT (n = 7,812) from 12,869 lambs measured between 2003 and 2015 in 13 flocks enrolled in the U.S. National Sheep Improvement Program. Animal and sire models were fitted to the data using the ASReml statistical package. Records were corrected for fixed effects of dam age, joint effect of type of birth and rearing, and management group (defined by joint effects of flock, sex, and birth year and season); lamb age in days at each measurement time was fitted as a covariate. Maternal additive and maternal permanent environmental effects were not significant (P > 0.05), but litter effects influenced (P < 0.01) both WFEC and PWFEC. Heritability estimates ranged from 0.18 to 0.26 for WFEC and 0.23 to 0.46 for PWFEC, depending on the model used. Heritability estimates from sire models were higher than estimates from animal models. Direct additive, litter, residual, and phenotypic correlations between WFEC and PWFEC were 0.82, 0.25, 0.15, and 0.29, respectively. Bivariate analyses revealed low to moderate correlations between BW and FEC. Moderate heritabilities for FEC in this study indicated that genetic progress for this trait can be achieved in Katahdin lambs and that selection for low FEC should have little or no effect on BW.

Control of gastrointestinal nematodes with copper oxide wire particles in a flock of lactating Polypay ewes and offspring in Iowa, USA.

Copper oxide wire particles (COWP) have been used to reduce infection of Haemonchus contortus in hair breed lambs in southeastern USA without signs of copper toxicity. However, copper sensitivity among breeds and regions varies. The objective was to determine the effectiveness and safety of COWP in lactating Polypay ewes and their offspring grazing alfalfa/bluegrass pasture in a rotational grazing system. Mature Polypay ewes were administered 0, 0.5, 1, or 2 g (n=8 or 9/dose) COWP approximately 60 days after lambing in mid-July 2005. Their offspring were administered 0 (n=6), 0.5 or 0.75 g (n=9), 1 or 2 g (n=6) COWP 2 weeks later in late July. The primary gastrointestinal nematode was H. contortus (70%). Between Days 7 and 35, FEC were greater in 0 and 0.5 g COWP groups compared with ewes administered 2 g COWP (COWP x day, P<0.004). PCV decreased in all groups of ewes between Days 0 and 21 (day, P<0.001). Aspartate aminotransferase (AST) activity, a measure of liver copper levels, and body weight was similar among groups of ewes. FEC decreased within 7 days in COWP-treated compared with untreated lambs and remained low throughout experiment (COWP x day, P<0.05). PCV increased in COWP-treated lambs between Days 7 and 35 and decreased in untreated lambs between Days 0 and 21 (COWP x day, P<0.009). AST activity was similar among groups of lambs. Administration of 2 g COWP to ewes prevented a rise in FEC, but a dose of 0.5 g was ineffective as an anthelmintic. Administration of all doses of COWP to lambs decreased FEC and increased PCV compared to untreated lambs. There were no signs of copper toxicity in ewes or lambs. Alternative suppression of H. contortus infections may be necessary in ewes, but COWP was effective in H. contortus management for lambs.

Effect of pelleting on efficacy of sericea lespedeza hay as a natural dewormer in goats.

Resistance of gastrointestinal nematodes (GIN) to anthelmintic treatment has increased pressure to find alternative, non-chemical control methods. Feeding hay of the high condensed tannin (CT) forage sericea lespedeza [SL; Lespedeza cuneata (Dum-Cours.) G. Don.] to sheep and goats has reduced GIN fecal egg count (FEC) and worm numbers in the abomasum and small intestines. This effect has been reported with both unground (long) and ground hay. Pelleting of ground hay increases ease of storage, transport, and feeding, but heating during the pelleting process could reduce biological activity of CT. Eighteen naturally GIN-infected 5-6-month-old Kiko-Spanish cross bucks were fed pelleted and ground SL hay and ground bermudagrass [BG; Cynodon dactyon (L.) Pers.] hay diets (n=6 per treatment) in a confinement trial. The bucks were fed the ground BG hay (75% of daily intake) plus a pelleted 16% CP commercial goat chow (25% of daily intake) for 3 weeks, after which they were assigned to treatment groups based upon FEC, 12 animals were switched to ground and pelleted SL hay plus goat chow for 4 weeks, and then all animals were fed the BG ration for one additional week. Throughout the trial, feces and blood were collected from individual animals weekly to determine FEC and blood packed cell volume (PCV), respectively. All goats were slaughtered at the end of the trial, with adult worms in the abomasum and small intestines recovered, counted, and identified to species. Both forms of SL hay reduced (P<0.05) FEC in goats relative to BG hay-fed animals, with a greater reduction in goats fed the SL pellets. There was no effect on PCV until the final sampling date, when the SL pellet-fed goats' PCV increased (P<0.05) compared with the other treatments. Feeding pelleted SL reduced (P<0.05) abomasal worms, primarily Haemonchus contortus, relative to the BG hay-fed goats. Worm numbers in the goats fed ground SL hay were intermediate. Pelleting SL hay enhanced its efficacy against parasitic nematodes and may facilitate the broader use of this forage in small ruminant GIN control programs.

Accuracy of the FAMACHA system for on-farm use by sheep and goat producers in the southeastern United States.

FAMACHA is a practical on-farm system designed to provide small ruminant producers a tool for improving their management of Haemonchus contortus infections. Although this system has become very popular and widely accepted by small ruminant producers in many regions of the southern United States, there is very limited data reported on the effectiveness of the FAMACHA system when performed by farmers. The objective of this study was to evaluate the accuracy of the FAMACHA system for on-farm use by small ruminant producers during the summer season. Small ruminant producers from Georgia, Louisiana, Florida, and Puerto Rico were trained to use the FAMACHA system by veterinarians and scientists experienced with this method. FAMACHA scores were assigned at least every 2 weeks by producers to weaned and mature sheep (n=552) and goats (n=676) of various breeds and ages between April and September 2004. At intervals that varied among farms from 2 to 8 weeks, researchers determined body condition scores (BCS; 1=thin and 5=fat) and collected blood and feces from a group of animals selected randomly to determine packed cell volume (PCV) and fecal egg counts (FEC). Two separate anemia thresholds were evaluated; these were defined by either FAMACHA score (>or=3 versus >or=4) or PCV (or=3 were considered anemic and PCV cutoff was or=3 were considered anemic and PCV cutoff was

Variance components for direct and maternal effects on body weights of Katahdin lambs.

The aim of this study was to estimate genetic parameters for BW in Katahdin lambs. Six animal models were used to study direct and maternal effects on birth weight (BWT), weaning weight (WWT), and postweaning weight (PWWT) using 41,066 BWT, 33,980 WWT, and 22,793 PWWT records collected over 17 yr in 100 flocks. Models included fixed effects of management group, dam age, type of birth (for BWT) or birth and rearing (for WWT and PWWT), and lamb age at weighing (fitted as a covariate for WWT and PWWT; all < 0.05). Variance components for random effects were estimated in sequentially more complex models and tested for significance with likelihood-ratio tests. A model that fitted only an additive animal effect overestimated additive variance for all BW, resulting in larger estimates of direct heritability than models that included maternal effects. Maternal effects explained variation ( < 0.05) in all BW. Heritability estimates for optimal models were 0.15 ± 0.01 for BWT, 0.18 ± 0.02 for WWT, and 0.20 ± 0.02 for PWWT. Estimates of maternal heritabilities were 0.14 for BWT, 0.10 for WWT, and 0.06 for PWWT, with SE = 0.01. Permanent environmental maternal effects explained 4 to 6% (±1%) of total phenotypic variances for these BW. Litter effects included temporary environmental effects common to littermates and a proportion of the dominance genetic variance and accounted for 16 to 19% (±1%) of phenotypic variance. Correlations between additive direct and maternal genetic effects were -0.14 for BWT, -0.23 for WWT, and -0.04 for PWWT but differed from 0 ( < 0.05) only for WWT. The total heritability predicted the total response in direct and maternal genetic effects from mass selection and was 0.23 for BWT, 0.20 for WWT, and 0.23 for PWWT. Direct and maternal additive, maternal permanent environmental, residual, and phenotypic correlations between BWT and WWT were 0.53 ± 0.05, 0.58 ± 0.06, 0.51 ± 0.06, 0.39 ± 0.01, and 0.44 ± 0.01, respectively; those between BWT and PWWT were 0.45 ± 0.06, 0.58 ± 0.08, 0.36 ± 0.08, 0.33 ± 0.01, and 0.37 ± 0.01 respectively; and those between WWT and PWWT were 0.85, 0.99, 0.92, 0.77, and 0.81, respectively, with SE ≤ 0.02. Therefore, both direct and maternal effects had an important impact on BW in Katahdin lambs. Models that included both additive and permanent environmental maternal effects as well as a temporary environmental litter effect should result in more accurate estimates of breeding values and better selection decisions.

High-resolution anorectal manometry: A comparison of solid-state and water-perfused catheters.

BACKGROUND: Anorectal manometry is the most commonly performed investigation for assessment of anorectal dysfunction. Findings from previous studies comparing water-perfused (WP) and solid-state (SS) techniques in the anorectum are conflicting. We compared anal sphincter pressure at rest and during dynamic maneuvers (squeezing and coughing) in healthy volunteers using SS and WP high-resolution anorectal manometry (HR-ARM) employing equivalent catheter configurations, a standardized protocol, and identical data acquisition and analysis software. METHODS: Sixty healthy volunteers (40F; median age: 40; range: 18-74) underwent WP and SS HR-ARM in randomized order. Anal resting pressure, and squeeze and cough increments were measured. Median pressure and 5th and 95th percentiles were calculated for each maneuver and compared using Wilcoxon signed-rank test. Bland and Altman plots were used to assess agreement between the systems. The impact of gender and parity was also explored. KEY RESULTS: Anal sphincter pressure measurements during squeeze (P<.001) and cough (P<.001) were significantly higher using SS HR-ARM than WP HR-ARM. No differences were seen at rest between the two types of catheter (nulliparous: P=.304; parous: P=.390; males: P=.167). Normal ranges for SS and WP manometry from this small group of healthy volunteers are presented. CONCLUSIONS & INFERENCES: Greater sensitivity to rapid pressure change is one of the advantages associated with SS HR-ARM. This is reflected in the differences observed during dynamic maneuvers performed during this study. Catheter type should be taken into consideration when selecting normal ranges for comparison to disease states.

Association between FAMACHA scores and fecal egg counts in Katahdin lambs.

The FAMACHA system was introduced to the U.S. just over 10 yr ago to allow selective deworming of lambs with anemia associated with and retard the development of anthelmintic resistance. The FAMACHA system was initially developed as a predictor of packed cell volume (PCV), but correlations between FAMACHA and fecal egg counts (FEC) have also been reported. It is important to understand factors that influence FAMACHA scores among farms to improve management of gastrointestinal nematodes. The objectives of this study were therefore to quantify associations between FAMACHA scores, FEC, BW, and age in Katahdin lambs at 2 different measurement times in 8 flocks in the eastern U.S., and to assess consistency of relationships between FAMACHA and FEC among flocks. Data came from 1,644 Katahdin lambs from 7 flocks sampled at approximately 90 d of age, and 1,295 lambs from 6 flocks sampled at approximately 120 d of age over a 5 yr period. Residual correlations among log-transformed FEC (LFEC), FAMACHA scores, BW, and lamb ages at each measurement time were determined. Repeatability of each variable was also determined as residual correlations among repeated measures. At both 90 and 120 d of age, correlations of FAMACHA scores with LFEC and BW were significant ( < 0.001), but numerically modest (0.25 and -0.16, respectively at 90 d; 0.31 and -0.16, respectively at 120 d), demonstrating that higher FAMACHA scores were associated with higher FEC and more likely to be observed in lighter lambs. A small negative correlation was observed between FAMACHA score and lamb age ( = -0.05, = 0.05, 90 d; = -0.11, < 0.001, 120 d) indicating that younger lambs were more likely to have elevated FAMACHA scores. Thus, younger and lighter lambs will likely be more susceptible to parasitism and may need to be managed more diligently than older or heavier lambs. In addition, FAMACHA scores have potential to improve breeding value estimates in programs designed to genetically improve parasite resistance.

Factors affecting fecal egg counts in periparturient Katahdin ewes and their lambs.

Selection for low fecal egg counts (FEC) can be used to genetically enhance resistance to gastrointestinal nematode parasites in growing lambs, thereby reducing the frequency of use of anthelmintics, facilitating marketing of organic lamb, and reducing the risk of development of anthelmintic resistance by the parasite. Recording of FEC in lambs has, therefore, been incorporated into several national sheep genetic evaluation programs. Ewes in late gestation and early lactation are also vulnerable to parasite infection and commonly experience a periparturient rise in FEC. This study was designed to assess factors associated with the periparturient rise in FEC in Katahdin ewes and associated changes in FEC in their lambs. Data came from 1,487 lambings by 931 Katahdin ewes from 11 farms in the Eastern United States. Fecal egg counts were measured in ewes at approximately 0, 30, and 60 d postpartum and in their lambs at approximately 60, 90, and 120 d of age. Approximately 1,400 lambs were evaluated at each measurement age. Data were analyzed separately for ewes and lambs and also initially analyzed separately for each measurement time. Repeated-measures analyses were then used to evaluate responses across measurement times. In ewes, FEC peaked at approximately 28 d postpartum, and we concluded that informative periparturient FEC could be obtained from 1 wk before until approximately 5 wk after lambing. Yearling ewes had higher FEC than adult ewes ( < 0.01), and ewes that nursed twin or triplet lambs had higher FEC than ewes that nursed single lambs ( < 0.01). In lambs, FEC increased through approximately 120 d of age. Lambs from yearling ewes and lambs nursed in larger litters were, like their dams, at greater risk of parasitism ( < 0.05). Ewes and lambs in these groups would benefit from enhanced monitoring of parasite loads at lambing and in early lactation. Correlations () between FEC in lambs at 90 d of age and FEC in ewes at 0, 30, and 60 d postpartum of 0.05 to 0.09 ( ≤ 0.05) support the presence of a genetic relationship between these 2 indicators of parasite resistance.