In Vitro Clot Trapping Efficiency of the FDA Generic Inferior Vena Cava Filter in an Anatomical Model: An Experimental Fluid-Structure Interaction Benchmark.

PURPOSE: Robust experimental data for performing validation of fluid-structure interaction (FSI) simulations of the transport of deformable solid bodies in internal flow are currently lacking. This in vitro experimental study characterizes the clot trapping efficiency of a new generic conical-type inferior vena cava (IVC) filter in a rigid anatomical model of the IVC with carefully characterized test conditions, fluid rheological properties, and clot mechanical properties. METHODS: Various sizes of spherical and cylindrical clots made of synthetic materials (nylon and polyacrylamide gel) and bovine blood are serially injected into the anatomical IVC model under worst-case exercise flow conditions. Clot trapping efficiencies and their uncertainties are then quantified for each combination of clot shape, size, and material. RESULTS: Experiments reveal the clot trapping efficiency increases with increasing clot diameter and length, with trapping efficiencies ranging from as low as approximately 42% for small 3.2 mm diameter spherical clots up to 100% for larger clot sizes. Because of the asymmetry of the anatomical IVC model, the data also reveal the iliac vein of clot origin influences the clot trapping efficiency, with the trapping efficiency for clots injected into the left iliac vein up to a factor of 7.5 times greater than that for clots injected into the right iliac (trapping efficiencies of approximately 10% versus 75%, respectively). CONCLUSION: Overall, this data set provides a benchmark for validating simulations predicting IVC filter clot trapping efficiency and, more generally, low-Reynolds number FSI modeling.

An independent validation study of loci associated with nematode resistance in sheep.

Gastrointestinal nematode infection is a constraint on sheep production worldwide. Selective breeding programmes to enhance resistance to nematode infection are currently being implemented in a number of countries. Identification of loci associated with resistance to infection or causative mutations for resistance would enable more effective selection. Loci associated with indicator traits for nematode resistance has been identified in previous studies. In this study, Scottish Blackface, Texel and Suffolk lambs were used to validate the effects at eight genomic regions previously associated with nematode resistance (OAR3, 4, 5, 7, 12, 13, 14, 21). No SNP was significantly associated with nematode resistance at the region-wide level but seven SNPs in three of the regions (OAR4, 12, 14) were nominally associated with trichostrongyle egg count in this study and six of these were also significant when fitted as single SNP effects. Nematodirus egg count was nominally associated with SNPs on OAR3, 4, 7 and 12.

Immunogenomics of gastrointestinal nematode infection in ruminants - breeding for resistance to produce food sustainably and safely.

Gastrointestinal nematode (GIN) infection of ruminants represents a major health and welfare challenge for livestock producers worldwide. The emergence of anthelmintic resistance in important GIN species and the associated animal welfare concerns have stimulated interest in the development of alternative and more sustainable strategies aimed at the effective management of the impact of GINs. These integrative strategies include selective breeding using genetic/genomic tools, grazing management, biological control, nutritional supplementation, vaccination and targeted selective treatment. In this review, the logic of selecting for "resistance" to GIN infection as opposed to "resilience" or "tolerance" is discussed. This is followed by a review of the potential application of immunogenomics to genetic selection for animals that have the capacity to withstand the impact of GIN infection. Advances in relevant genomic technologies are highlighted together with how these tools can be advanced to support the integration of immunogenomic information into ruminant breeding programmes.

The host immune response to gastrointestinal nematode infection in sheep.

Gastrointestinal nematode infection represents a major threat to the health, welfare and productivity of sheep populations worldwide. Infected lambs have a reduced ability to absorb nutrients from the gastrointestinal tract, resulting in morbidity and occasional mortality. The current chemo-dominant approach to nematode control is considered unsustainable due to the increasing incidence of anthelmintic resistance. In addition, there is growing consumer demand for food products from animals not subjected to chemical treatment. Future mechanisms of nematode control must rely on alternative, sustainable strategies such as vaccination or selective breeding of resistant animals. Such strategies take advantage of the host's natural immune response to nematodes. The ability to resist gastrointestinal nematode infection is considered to be dependent on the development of a protective acquired immune response, although the precise immune mechanisms involved in initiating this process remain to be fully elucidated. In this study, current knowledge on the innate and acquired host immune response to gastrointestinal nematode infection in sheep and the development of immunity is reviewed.

Temporal studies on Fasciola hepatica in Galba truncatula in the west of Ireland.

The population dynamics and prevalence of Fasciola hepatica in Galba truncatula were investigated on the Teagasc hill sheep farm in Country Mayo, Ireland from August 2006 until March 2008. Galba truncatula (n=974) were collected at fortnightly intervals in 4 snail habitats on the farm, their relative density and mean monthly rainfall and temperature were recorded. Snail abundance was associated with rainfall and temperature. G. truncatula abundance was generally low during winter 2006/2007 (December 2006-February 2007), mid spring and summer 2007 (April-July) and late autumn and winter 2007/2008 (October 2007-February 2008). Overall, two peaks in G. truncatula abundance were evident during the study period, an early spring (March) and late summer/autumn (late August-October) peak. Seasonal differences were observed in the prevalence of F. hepatica in G. truncatula, the greatest prevalence was evident in 2007 during the summer (25%) and autumn (16%). Two seasonal transmission peaks, as evident by the presence of mature infections in snails, one in summer/autumn and the other in late winter/early spring. Not unsurprising, cercariae (28%) and rediae (29%) were the predominant developmental stages observed in mature and pre-adult snails respectively. Worthy of note in this study, cercariae were also evident in pre-adult snails. The present study highlights the influence of milder temperatures and wetter conditions on both snail and fluke development. If the trend in mild and wet weather conditions continues, there is the potential for an increase in the number of G. truncatula habitats and ultimately the prevalence of fasciolosis in grazing livestock in Ireland.

First principles calculations for defects in U.

Uranium (U) exhibits a high temperature body-centered cubic (bcc) allotrope that is often stabilized by alloying with transition metals such as Zr, Mo, and Nb for technological applications. One such application involves U-Zr as nuclear fuel, where radiation damage and diffusion (processes heavily dependent on point defects) are of vital importance. Several systems of U are examined within a density functional theory framework utilizing projector augmented wave pseudopotentials. Two separate generalized gradient approximations of the exchange-correlation are used to calculate defect properties and are compared. The bulk modulus, the lattice constant, and the Birch-Murnaghan equation of state for the defect free bcc uranium allotrope are calculated. Defect parameters calculated include energies of formation of vacancies in the α and γ allotropes, as well as self-interstitials, Zr interstitials, and Zr substitutional defects for the γ allotrope. The results for vacancies agree very well with experimental and previous computational studies. The most probable self-interstitial site in γ-U is the (110) dumbbell, and the most probable defect location for dilute Zr in γ-U is the substitutional site. This is the first detailed study of self-defects in the bcc allotrope of U and also the first comprehensive study of dilute Zr defects in γ-U.

The comparative efficacy of four anthelmintics against a natural acquired Fasciola hepatica infection in hill sheep flock in the west of Ireland.

The aim of this study was to evaluate the efficacy of four different anthelmintics against F. hepatica in a naturally infected hill sheep flock in the west of Ireland. In a randomised trial, 138 ewes were divided into four groups. On day 0 each group was dosed with one of four anthelmintics: triclabendazole, closantel, oxyclozanide or nitroxynil. Faecal samples were obtained from each animal per rectum on the day of treatment and again at 7, 14, 21 and 56 days post-treatment. The number of F. hepatica eggs per gram of faeces was determined using the sedimentation technique and the efficacy of each anthelmintic was calculated in terms of the percentage reduction in egg count at each time point. The results for closantel, oxyclozanide and nitroxynil indicate that these drugs are effective with faecal egg count being reduced by 100% by day 14 post-treatment. However, the results for triclabendazole group yielded lower efficacy levels, with faecal egg count reductions of between 49% and 66% based on arithmetic means, over the period 7-56 days post-treatment. These results are highly indicative of triclabendazole resistant F. hepatica in sheep on this farm.

Evidence of Fasciola hepatica infection in Radix peregra and a mollusc of the family Succineidae in Ireland.

Worldwide molluscs of the genera Lymnaea, Pseudosuccinea, Galba and Stagnicola act as intermediate hosts of the common liver fluke, Fasciola hepatica. Galba truncatula is the only recorded intermediate host of F. hepatica within Ireland and is the principle intermediate host within Europe. To investigate the transmission of liver fluke on the Teagasc hill sheep farm, Co. Mayo, Ireland, snail species other than G. truncatula, were collected from the lowland pasture (snail sp. 'A') in May (n=23) and from the hill area (snail sp. 'B') in March, April and May 2008 (n=78, 53 and 36 respectively). Morphological characteristics identified snail sp. 'A' as a Succinea sp. and snail sp. 'B' as Radix peregra. PCR and subsequent sequencing of the 18S gene and internal transcribed spacer 2 (ITS-2) region of the snail rDNA were used for molecular identification. The 18S ribosomal DNA (rDNA) sequences revealed a 99% similarity with Omalonyx matheroni (Succineidae) for snail sp. 'A', and for snail sp. 'B' a 99% and 98% similarity with Radix auricularia and R. peregra, respectively. The ITS-2 sequences of snail sp. 'B' revealed a 100% similarity with R. peregra. Using PCR F. hepatica DNA was identified in 73.9% (n=17) of snail sp. 'A' collected during May and 10.3% (n=8), 60.4% (n=32) and 61.1% (n=22) of snail sp. 'B' collected during March, April and May, respectively. A priori knowledge of habitat preference and environmental tolerances of G. truncatula has failed to explain the prevalence of infection recorded in the hill sheep flock on Teagasc hill sheep farm. These findings may explain the presence of infection in sheep populations grazing hill habitats considered too acidic to maintain G. truncatula populations.

Breed differences in mucosal and systemic antibody response to nematode infection in sheep: an important role for IgE?

This study compared the immunological and biochemical responses of co-grazed Suffolk and Texel lambs to a natural gastrointestinal nematode infection. Variables analysed included serum pepsinogen, total protein, albumin, haematological variables and nematode-specific serum immunoglobulin activity, at 11, 14 and 17 weeks of age. At 17 weeks, randomly selected lambs were necropsied to determine worm burdens, nematode-specific mucosal abomasal and intestinal immunoglobulin activity. Nematode burden, faecal egg count and pepsinogen concentrations were significantly higher in Suffolks relative to Texels, at all 3 time-points investigated. Suffolks displayed significantly higher erythrocyte, total leukocyte, lymphocyte and neutrophil counts, mean cell volume and packed cell volume, than Texels (P<0.01). However, breed differences in eosinophil counts were not significant. While serum nematode-specific antibody activity levels were significantly higher (P<0.001) in Texels for all isotypes measured, antibody activity levels at a mucosal level were equivalent in both breeds. Correlation analysis of mucosal antibody levels and nematode variables highlighted a more consistent pattern of events in Texels, with more mucosal antibodies negatively correlated with FEC and worm burden, in comparison to Suffolks. In particular, an important role for mucosal IgE is proposed. In Texels, a significant and negative correlation was identified between IgE and faecal egg counts and worm burden (FEC: -0.48, P<0.005). This was not observed in Suffolks. The evidence suggests that susceptibility in Suffolks may be mediated through poor IgE affinity/avidity and/or through deficiencies in related mechanisms such as mast cell production, recruitment or activation.

Phase-specific gene expression underlying morphological adaptations of the dimorphic human pathogenic fungus, Coccidioides posadasii.

Coccidioides posadasii is a dimorphic fungal pathogen that grows as a filamentous saprobe in the soil and as endosporulating spherules within the host. To identify genes specific to the pathogenic phase of Co. posadasii, we carried out a large-scale study of gene expression in two isolates of the species. From the sequenced Co. posadasii genome, we chose 1,000 open reading frames to construct a 70-mer microarray. RNA was recovered from both isolates at three life-cycle phases: hyphae, presegmented spherules, and spherules releasing endospores. Comparative hybridizations were conducted in a circuit design, permitting comparison between both isolates at all three life-cycle phases, and among all life-cycle phases for each isolate. By using this approach, we identified 92 genes that were differentially expressed between pathogenic and saprobic phases in both fungal isolates, and 43 genes with consistent differential expression between the two parasitic developmental phases. Genes with elevated expression in the pathogenic phases of both isolates included a number of genes that were involved in the response to environmental stress as well as in the metabolism of lipids. The latter observation is in agreement with previous studies demonstrating that spherules contain a higher proportion of lipids than saprobic phase tissue. Intriguingly, we discovered statistically significant and divergent levels of gene expression between the two isolates profiled for 64 genes. The results suggest that incorporating more than one isolate in the experimental design offers a means of categorizing the large collection of candidate genes that transcriptional profiling typically identifies into those that are strain-specific and those that characterize the entire species.

Texel sheep are more resistant to natural nematode challenge than Suffolk sheep based on faecal egg count and nematode burden.

Limited information is available on differences between sheep breeds with respect to helminth resistance under temperate conditions. The present study was designed to confirm and extend preliminary findings on observed breed differences in resistance to naturally acquired gastrointestinal nematodes in Suffolk and Texel sheep. Three trials were carried out. In trial 1 (1999-2003) lambs co-grazed from birth were faecal sampled at various time points up to 17 weeks of age. Worm burden was assessed at 17 weeks of age from a minimum of six lambs per breed in each of the 3 years. In trial 2, faecal egg count (FEC) was determined on six farms with co-grazed Suffolk and Texel purebred lambs. In trial 3 (2001-2003), ewes were faecal sampled at winter housing. In all three trials, an influence of breed on resistance to naturally acquired trichostrongyle infection was demonstrated. In trial 1, significantly higher FEC and worm burden was observed in Suffolk compared with Texel lambs following natural challenge. In trial 2, FEC recorded in lambs from six farms confirmed the breed differences previously observed. A breed difference in resistance to GI parasites was also observed in older ewes. In both breeds, an age effect on the FEC was observed with younger ewes having greater FEC than older ewes.

Major histocompatibility complex DRB1 gene: its role in nematode resistance in Suffolk and Texel sheep breeds.

A potential control strategy for nematode infection in sheep is the implementation of a breeding programme to select for genes associated with resistance. The Texel breed is more resistant to gastrointestinal nematode infection than the Suffolk breed, based on faecal egg count, and this difference should enable the identification of some of the genes responsible for resistance. The objective of this study was to determine if variation at the ovine MHC-DRB1 locus was associated with variation in faecal egg count in Suffolk and Texel sheep. Ovar-DRB1 alleles and faecal egg count were determined for Texel (n = 105) and Suffolk (n = 71) lambs. Eight Ovar-DRB1 alleles, including 1 previously unknown allele, were identified in the Texel breed by sequence-base-typing. Seven Ovar-DRB1 alleles were identified in the Suffolk breed. Two Ovar-DRB1 alleles were common to both breeds, but were among the least frequent in the Suffolk population. In the Suffolk breed 1 Ovar-DRB1 allele was associated with a decrease in faecal egg count and 2 alleles with an increase in faecal egg count. This locus accounted for 14% of the natural variation in faecal egg count in Suffolks. There was no evidence for an association between Ovar-DRB1 alleles and faecal egg count in the Texel breed and the Ovar-DRB1 locus accounted for only 3% of the phenotypic variation in faecal egg count. These results suggest that the Ovar-DRB1 gene plays an important role in resistance to nematode infection in the Suffolk breed. The difference in faecal egg counts between these breeds may be attributable in part to the different allele profile at the Ovar-DRB1 locus.

Intron 1 of the interferon gamma gene: Its role in nematode resistance in Suffolk and Texel sheep breeds.

Genetic variation at intron 1 of the interferon gamma gene has recently been associated with variation in faecal egg count in Romney, Merino and Soay breeds of sheep. The Texel breed is more resistant to gastrointestinal nematode infection than the Suffolk breed, based on faecal egg count. Hence, the objective of this experiment was to characterise the polymorphisms of intron 1 of the interferon gammagene in Suffolk and Texel sheep, and to determine if the characterised haplotype variants were associated with faecal egg count variation in these breeds. Intron 1 haplotypes and faecal egg measurements were determined for Suffolks (n=113) and Texels (n=135). Four haplotypes were identified in Suffolks (A, B, C and D), two haplotypes as previously described, and two previously unknown haplotypes. However, there was no association between interferon gamma intron 1 haplotype and faecal egg count in Suffolks. In contrast, two previously identified haplotypes (A and B) were present in the Texel breed, and the B haplotype was associated with resistance to nematode infection (P=0.02). These results suggest that intron 1 of the interferon gamma gene has an important role in resistance to nematode infection in the Texel breed.

Genetic composition of human immunodeficiency virus type 1 in cerebrospinal fluid and blood without treatment and during failing antiretroviral therapy.

Human immunodeficiency virus (HIV) infection of the central nervous system (CNS) is a significant cause of morbidity. The requirements for HIV adaptation to the CNS for neuropathogenesis and the value of CSF virus as a surrogate for virus activity in brain parenchyma are not well established. We studied 18 HIV-infected subjects, most with advanced immunodeficiency and some neurocognitive impairment but none with evidence of opportunistic infection or malignancy of the CNS. Clonal sequences of C2-V3 env and population sequences of pol from HIV RNA in cerebrospinal fluid (CSF) and plasma were correlated with clinical and virologic variables. Most (14 of 18) subjects had partitioning of C2-V3 sequences according to compartment, and 9 of 13 subjects with drug resistance exhibited discordant resistance patterns between the two compartments. Regression analyses identified three to seven positions in C2-V3 that discriminated CSF from plasma HIV. The presence of compartmental differences at one or more of the identified positions in C2-V3 was highly associated with the presence of discordant resistance (P = 0.007), reflecting the autonomous replication of HIV and the independent evolution of drug resistance in the CNS. Discordance of resistance was associated with severity of neurocognitive deficits (P = 0.07), while low nadir CD4 counts were linked both to the severity of neurocognitive deficits and to discordant resistance patterns (P = 0.05 and 0.09, respectively). These observations support the study of CSF HIV as an accessible surrogate for HIV virions in the brain, confirm the high frequency of discordant resistance in subjects with advanced disease in the absence of opportunistic infection or malignancy of the CNS, and begin to identify genetic patterns in HIV env associated with adaptation to the CNS.

Ocular toxocariasis in schoolchildren.

Ocular toxocariasis in humans is typically a unilateral disease caused by second-stage larvae of the Toxocara species. Serological evidence of widespread infection in humans provides little information on clinical disease. There is only a single previous estimate of the prevalence of ocular toxocariasis (from Alabama). The present survey examined the extent of consultant-diagnosed toxocaral eye disease among a population of schoolchildren. More than 120,000 participants were surveyed by questionnaire and follow-up. Two sets of control subjects from the same school and from the same county were compared with persons who had ocular toxocariasis. The prevalence of consultant-diagnosed toxocaral eye disease was 6.6 cases per 100,000 persons when only cases regarded as definite by the consultant ophthalmologist were included. This increased to 9.7 cases per 100,000 persons when both definite and strongly suspected cases were included. Geophagia and a history of convulsion were associated with toxocaral eye disease in both of the case-control studies.

Chemoprevention of breast cancer and the trials of the National Surgical Adjuvant Breast and Bowel Project and others.

The idea of breast cancer prevention by hormonal means stemmed from the results of treatment trials, many of them carried out by the National Surgical Adjuvant Breast and Bowel Project (NSABP). Over the years, a number of NSABP treatment studies demonstrated that breast cancer recurrence was reduced in women with the disease who were given tamoxifen, a selective estrogen receptor (ER) modulator (SERM). Five subsequent tamoxifen prevention trials with this agent have shown a 48% reduction in ER-positive cancers, but no effect for ER-negative cancers, and an increase in endometrial cancer and thromboembolic events. The drug raloxifene, another SERM, originally examined as an osteoporosis agent, has also shown promise for the prevention of breast cancer, although, as with tamoxifen, the drug carries a risk for thromboembolic events. There is recent evidence in a large treatment trial that the aromastase inhibitor anastrazole, a 'pure anti-estrogen', holds promise as a breast cancer preventive agent. Longer follow-up and the testing of additional agents is required before these drugs can be used widely for prevention. In addition, future research should focus on the identification of at-risk women who can perhaps be targeted for specific prevention agents.

The influence of inoculum size and time post-infection on the number and position of Toxocara canis larvae recovered from the brains of outbred CD1 mice.

Outbred CD1 mice were administered doses of 1000 and 3000 Toxocara canis eggs and postmortem took place on days 7, 42 and 120 post-infection. Mice were killed by cervical dislocation and brains were sagitally bisected and fixed in 10% neutral buffered formalin prior to histological preparation and examination. The number of T. canis larvae were counted per brain and per section and the number of larvae cited for the first time per section were also recorded. These observations were compared by dose administered and by day of postmortem. The total number of larvae per brain and per section was higher for the 3000 dose compared to the 1000 dose. A different pattern emerged for the number of larvae observed in the brain over the three postmortem days depending upon the dose received. For the 1000 dose larval numbers increase from day 7 to day 120 whereas for the 3000 dose the opposite trend occurs. Larvae were assigned to one of five regions in the brain - the telencephalon, diencephalon, cerebellum, medulla, pons and brain stem and the olfactory bulb. Larvae did not show a random distribution in the brain. The majority of larvae were recorded from the telencephalon and the cerebellum. The percentage of sections with larvae in them is higher for the 3000 dose compared to the 1000 dose for all regions of the brain. For the majority of regions, the percentage of sections with larvae in them increases between day 7 and 42 and then decreases by day 120 and this is most pronounced for the cerebellum. For the telencephalon and diencephalon only, more larvae were detected on the right hand side of the brain compared to the left hand side. Statistical analysis revealed that dose and brain region are significant factors which influence the number of larvae observed in histological sections of the brain but day post-infection is not.

Improving access to mammograms through community-based influenza clinics. A quasi-experimental study.

BACKGROUND: It is a national priority to increase breast-cancer screening among women aged > or = 50. Annual influenza clinics may represent an efficient setting in which to promote breast-cancer screening among older women. To our knowledge, this possibility has not previously been explored. OBJECTIVE: To examine whether offering women attending community-based influenza clinics the opportunity to receive a scheduling telephone call from a mammography facility will result in an increase in the number of mammograms performed over a 6-month period. METHODS: We used a quasi-experimental design with 6-month follow-up. A contemporaneous population-based survey provided a further control group for comparison. The sample group consisted of a total of 284 women attending nine community-based influenza clinics in a semirural county in Connecticut. All women were aged > or = 50 and reported no mammogram in the preceding 12 months. All women received informational literature on mammography. Experimental subjects were each asked if a radiology facility chosen by the subject could call her at home to schedule a mammogram. Mammograms performed were determined by hospital record for participants who received a scheduling call from a radiology facility, and by self-report for all other participants. RESULTS: Mammography use following access through influenza clinics was approximately twice that of women attending influenza clinics where access to mammography was not offered. Using three different assumptions regarding participants whose mammography status was unknown, the relative risks ranged between 1.6 and 2.1. For each assumption the results were statistically significant (chi(2)=8.51-12.2; p<0.001). CONCLUSIONS: Linking access to mammography at community-based influenza clinics can significantly increase the use of mammograms among women aged > or = 50. Further studies should seek to confirm these findings and determine the degree to which they can be replicated in a variety of communities. Enhancing preventive health practice through the bundling of services suggests a new strategy to exploit available interventions to improve health.

Clinician experiences of managed mental health care: a rereading of the threat.

The threat mental health professionals perceive in managed care, as indicated by their writings on the subject, is re-examined in light of evidence from an ethnographic study. Fieldwork focusing on clinician experiences of managed care was carried out at an urban community mental health center. Existing explanations of "the threat"--the possibility of deprofessionalization and the potential for deterioration in the quality of care--proved inadequate to account for the power it wielded at this site, perhaps because its full impact had yet to be felt at the time of data collection. A "rereading" suggests the meaning of managed care for this group of clinicians lies in the prospect of being gradually, unknowingly, and unwillingly reprofessionalized from critics into proponents simply by virtue of continuing to practice in a managed care context, and in losing a moral vision of good mental health treatment in the process.