Evaluation of chlorhexidine sensitization amongst healthcare workers.

BACKGROUND: Chlorhexidine is an antiseptic widely used in healthcare settings. There are increasing reports of significant hypersensitivity reactions associated with its use. Development of chlorhexidine allergy has been identified as an important occupational risk to healthcare workers (HCWs). AIMS: To evaluate the prevalence of sensitization to chlorhexidine amongst HCWs at a large tertiary hospital to assess the potential allergic safety risks associated with chlorhexidine exposure to staff. METHODS: Sensitization to chlorhexidine was evaluated by measurement of serum-specific immunoglobulin E (IgE) in samples collected from staff assessed after a sharps-injury incident and laboratory staff collected for quality assurance procedures. This test method has been shown to have high sensitivity and specificity in the diagnosis of chlorhexidine allergy. Prevalence of sensitization was additionally evaluated with reference to changes in exposure to chlorhexidine-based hand hygiene products because of infection control procedures and the coronavirus disease 2019 pandemic. RESULTS: A total of 320 samples were examined. The prevalence of positive chlorhexidine-specific IgE was 2%. Prevalence of sensitization in samples collected before and after increased chlorhexidine exposure was 1% and 3%. This did not represent a statistically significant difference. CONCLUSIONS: The prevalence figures for chlorhexidine sensitization in this study are higher than have been estimated previously for similar HCW cohorts. Increased exposure to chlorhexidine-based hand hygiene products was not demonstrated to increase sensitization in this group. Given the risk of severe reactions in sensitized individuals, this study indicates that evaluation of chlorhexidine allergy is important when investigating occupational allergy in HCWs.

Common Diseases of Michigan Gamebirds: A Retrospective Study.

Michigan has abundant resources for outdoor activity including upland gamebird hunting in the wild and on licensed hunting preserves. Due to the popularity of hunting, Michigan had a thriving gamebird industry before the economic downturn of 2008/2009. After the economic downturn, the number of gamebird preserves decreased. To understand the health issues faced by captive gamebird raisers while the industry was thriving, a 25-year retrospective study of gamebird submissions to the Michigan State University Veterinary Diagnostic Laboratory from 1983 through 2008 was undertaken. Although pheasants, quail, partridges, grouse, and mallard ducks were raised, pheasants greatly outnumbered all other gamebird species, both in numbers and submissions, and quail were the next most predominant species. Causes for submission included parasitic, bacterial, viral, and miscellaneous causes. Parasitic diseases were predominant, with coccidiosis being the leading diagnosis in pheasants and partridges and Capillaria spp. infestation of the crop prevailing in quail. Bacterial diseases were the next most predominant affliction, with clostridial enteritis, both necrotic and ulcerative, in quail, and a variety of bacterial diseases were found in pheasants and partridges. Rotaviral enteritis and adenovirus were the most prevalent viral diseases in pheasants, with adenovirus being the predominant viral disease in quail and paramyxovirus the most prevalent in partridges. From these findings, we conclude that gamebird submissions should be closely screened for parasitic diseases and the diagnosis confirmed at necropsy through scraping and examination of affected tissues.

Reporte de caso­Enfermedades comunes de aves de caza en Michigan: Un estudio retrospectivo. Michigan tiene abundantes recursos para la actividad al aire libre, incluida la caza de aves silvestres en tierras altas silvestres y en cotos de caza autorizados. Debido a la popularidad de la caza, Michigan tenía una próspera industria de aves de caza antes de la recesión económica de los años 2008/2009. Después de la recesión económica, el número de reservas de aves de caza disminuyó. Para comprender los problemas de salud que enfrentan los criadores de aves de caza en cautiverio mientras la industria prosperaba, se realizó un estudio retrospectivo de 25 años de los casos de diagnóstico de aves de cacería remitidos al Laboratorio de Diagnóstico Veterinario de la Universidad Estatal de Michigan desde el año 1983 hasta el 2008. Aunque se criaron faisanes, codornices, perdices, urogallos y ánades reales, los faisanes superaron en gran medida a todas las demás especies de aves de caza, tanto en número como en casos clínicos y la codorniz fue la segunda especie más predominante. Las causas de envío de casos clínicos incluyeron infecciones parasitarias, bacterianas, virales y diversas. Predominaron las enfermedades parasitarias, siendo la coccidiosis el principal diagnóstico en faisanes y perdices y la infestación en el buche por Capillaria spp. fue predominante en codornices. Las enfermedades bacterianas fueron el segundo problema más predominante, con enteritis por clostridios, tanto necrótica como ulcerativa, en codornices, y una variedad de enfermedades bacterianas se encontraron en faisanes y perdices. La enteritis por rotavirus y los adenovirus fueron las enfermedades virales más prevalentes en los faisanes, siendo el adenovirus la enfermedad viral predominante en la codorniz y el paramixovirus la más prevalente en las perdices. A partir de estos hallazgos, concluimos que las presentaciones de aves de caza deben ser examinadas de cerca para detectar enfermedades parasitarias y el diagnóstico debe confirmarse en la necropsia mediante de raspados y examen de los tejidos afectados.

Diagnostic performance of whole-body SPECT/CT in bone metastasis detection using 99mTc-labelled diphosphate: a systematic review and meta-analysis.

AIM: To evaluate the diagnostic performance of whole-body (WB) integrated single photon emission tomography (SPECT)/computed tomography (CT) in detecting bone metastasis (BM) and to investigate whether WB-SPECT/CT offered any additional benefit value compared to planar bone scintigraphy (PBS) with 99mTc-hydroxy-methylene diphosphonate or 99mTc methylene diphosphonate. MATERIALS AND METHODS: Medline, EMBASE, SCOPUS, Web of Science, and CINAHL were searched systematically up to 28 August 2019. All studies using histopathological analysis and/or follow-up imaging and clinical data as the reference standard were eligible for inclusion. RESULTS: Eleven studies (1,611 patients) were analysed. Based on patient analysis, the sensitivity, specificity, and area under the curve (AUC) of WB-SPECT/CT were 92% (92% confidence interval [CI], 89-95%), 95% (95% CI, 94-96%), and 0.9835, respectively, in the case of negative equivocal findings for BM, and 94% (95% CI, 91-96%), 94% (95% CI, 92-95%), and 0.9790, respectively, when regarded positive. On a lesion basis, these parameters were 91% (95% CI, 89-94%), 96% (95% CI, 94-97%), and 0.9906, respectively, in the case negative equivocal findings, and 92% (95% CI, 89-94%), 95% (95% CI, 94-97%), and 0.9898, respectively, when regarded positive. Comparing 1,265 patients from eight studies, higher sensitivity (92% versus 74%, p=0.04) and specificity for WB-SPECT/CT against PBS (93% versus 80%, p=0.01) in the case of positive equivocal findings; however, when regarded negative, WB-SPECT/CT demonstrated higher sensitivity (91% versus 70%, p=0.01), but no significant difference was apparent in specificity (94% versus 89%, p=0.07). CONCLUSION: Compared to PBS, WB-SPECT/CT had superior diagnostic accuracy in BM detection and exhibited a more reliable performance with less equivocal results.

A novel multiplex polymerase chain reaction assay for detection of both HLA-A*31:01/HLA-B*15:02 alleles, which confer susceptibility to carbamazepine-induced severe cutaneous adverse reactions.

HLA-A*31:01 and HLA-B*15:02 have been widely reported to confer genetic susceptibility to carbamazepine (CBZ)-induced severe cutaneous adverse reactions (SCARs). Accordingly, the screening for these alleles has been highly recommended to prevent SCAR prior to introducing CBZ therapy. Although a number of methods are available for screening of HLA-A*31:01 or HLA-B*15:02 alleles separately, developing an assay that can detect both these alleles would be more clinically practical, cost-effective and less time-consuming. Therefore, in this study, a multiplex polymerase chain reaction (PCR) using TaqMan Probe was designed and validated to be able to detect HLA-A*31:01 and HLA-B*15:02. In comparison with Luminex-SSO/SBT/SSB, the multiplex PCR assay for detection of HLA-A*31:01 and HLA-B*15:02 had a perfect agreement in the validation group of 125 samples. The method was able to detect the target genes at the DNA concentration of 0.037 ng/µL. The unit cost of this assay is less than $5 USD with total time of 110 minutes.

Genomic and antigenic characterization of bovine parainfluenza-3 viruses in the United States including modified live virus vaccine (MLV) strains and field strains from cattle.

This study investigated the genetic and antigenic characterization of parainfluenza-3 virus (PI3V) of cattle. Using molecular tests including real time PCR and viral genome sequencing, PI3V strains could be separated into PI3V types, including PI3V A, PI3V B, and PI3V C. Isolates from cattle with bovine respiratory disease clinical signs and commercial vaccines in the U.S. with MLV PI3V were typed using these molecular tests. All the MLV vaccine strains tested were PI3V A. In most cases PI3V field strains from calves receiving MLV vaccines were types heterologous to the vaccine type A. Also antigenic differences were noted as PI3V C strains had lower antibody levels than PI3V A in serums from cattle receiving MLV PI3V A vaccines. This study further demonstrates there is genetic variability of U.S. PI3V strains and also antigenic variability. In addition, isolates from cattle with BRD signs and receiving MLV vaccines may have heterologous types to the vaccines, and molecular tests should be performed to differentiate field from vaccine strains. Potentially the efficacy of current PI3V A vaccines should be evaluated with other types such a PI3V B and PI3V C.

Rigid motion correction of dual opposed planar projections in single photon imaging.

Awake and/or freely moving small animal single photon emission imaging allows the continuous study of molecules exhibiting slow kinetics without the need to restrain or anaesthetise the animals. Estimating motion free projections in freely moving small animal planar imaging can be considered as a limited angle tomography problem, except that we wish to estimate the 2D planar projections rather than the 3D volume, where the angular sampling in all three axes depends on the rotational motion of the animal. In this study, we hypothesise that the motion corrected planar projections estimated by reconstructing an estimate of the 3D volume using an iterative motion compensating reconstruction algorithm and integrating it along the projection path, will closely match the true, motion-less, planar distribution regardless of the object motion. We tested this hypothesis for the case of rigid motion using Monte-Carlo simulations and experimental phantom data based on a dual opposed detector system, where object motion was modelled with 6 degrees of freedom. In addition, we investigated the quantitative accuracy of the regional activity extracted from the geometric mean of opposing motion corrected planar projections. Results showed that it is feasible to estimate qualitatively accurate motion-corrected projections for a wide range of motions around all 3 axes. Errors in the geometric mean estimates of regional activity were relatively small and within 10% of expected true values. In addition, quantitative regional errors were dependent on the observed motion, as well as on the surrounding activity of overlapping organs. We conclude that both qualitatively and quantitatively accurate motion-free projections of the tracer distribution in a rigidly moving object can be estimated from dual opposed detectors using a correction approach within an iterative reconstruction framework and we expect this approach can be extended to the case of non-rigid motion.

Dynamic changes in the clonal structure of MDS and AML in response to epigenetic therapy.

Traditional response criteria in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are based on bone marrow morphology and may not accurately reflect clonal tumor burden in patients treated with non-cytotoxic chemotherapy. We used next-generation sequencing of serial bone marrow samples to monitor MDS and AML tumor burden during treatment with epigenetic therapy (decitabine and panobinostat). Serial bone marrow samples (and skin as a source of normal DNA) from 25 MDS and AML patients were sequenced (exome or 285 gene panel). We observed that responders, including those in complete remission (CR), can have persistent measurable tumor burden (that is, mutations) for at least 1 year without disease progression. Using an ultrasensitive sequencing approach, we detected extremely rare mutations (equivalent to 1 heterozygous mutant cell in 2000 non-mutant cells) months to years before their expansion at disease relapse. While patients can live with persistent clonal hematopoiesis in a CR or stable disease, ultimately we find evidence that expansion of a rare subclone occurs at relapse or progression. Here we demonstrate that sequencing of serial samples provides an alternative measure of tumor burden in MDS or AML patients and augments traditional response criteria that rely on bone marrow blast percentage.

Effect of timing of challenge following short-term natural exposure to bovine viral diarrhea virus type 1b on animal performance and immune response in beef steers.

Bovine respiratory disease (BRD) is the most common and economically detrimental disease of beef cattle during the postweaning period, causing the majority of morbidity and mortality in feedlots. The pathogenesis of this disease often includes an initial viral infection, which can predispose cattle to a secondary bacterial infection. The objective of this experiment was to determine the effects of timing of an intratracheal (MH) challenge relative to 72 h of natural exposure to bovine viral diarrhea virus (BVDV) type 1b persistently infected (PI) calves on performance, serum antibody production, total and differential white blood cell (WBC) count, rectal temperature, clinical severity score (CS), and haptoglobin (Hp). Steers ( = 24; 276 ± 31 kg initial BW) were randomly allocated to 1 of 3 treatments (8 steers/treatment) in a randomized complete block design. Treatments were steers not exposed to calves PI with BVDV 1b and not challenged with MH (CON), steers intratracheally challenged with MH 84 h after being exposed to calves PI with BVDV 1b for 72 h (LateCh), and steers intratracheally challenged with MH 12 h after being exposed to calves PI with BVDV 1b for 72 h (EarlyCh). Performance (ADG, DMI, and G:F) was decreased ( < 0.001) for both EarlyCh and LateCh from d 0 to 4. From d 5 to 17, LateCh appeared to compensate for this lost performance and demonstrated increased ADG ( = 0.01) and G:F ( = 0.01) compared with EarlyCh. Both EarlyCh and LateCh had decreased platelet counts ( < 0.001) compared with CON. Antibody concentrations of BVDV and MH were higher ( < 0.05) for both EarlyCh and LateCh compared with CON. Rectal temperature, CS, and Hp increased ( < 0.001) across time from h 4 to 48, h 4 to 36, and h 8 to 168, respectively. Within 24 h of MH challenge, WBC and neutrophil concentrations within the blood increased whereas lymphocyte concentrations decreased. The timing of BVDV exposure relative to a MH challenge appears to influence the CS and acute phase response associated with BRD. As typical beef cattle marketing channels allow for variation in the timing of respiratory pathogen exposure, understanding the physiological changes in morbid cattle will lead to improved management of BRD.

Bovine herpesvirus-1: Genetic diversity of field strains from cattle with respiratory disease, genital, fetal disease and systemic neonatal disease and their relationship to vaccine strains.

Bovine herpesvirus-1 (BoHV-1) causes disease in cattle with varied clinical forms. In the U.S. there are two BoHV1 subtypes, BoHV-1.1 and BoHV-1.2b. Control programs in North America incorporate modified live (MLV) or killed (KV) viral vaccines. However, BoHV-1 strains continue to be isolated from diseased animals or fetuses after vaccination. It is possible to differentiate BoHV-1 wild-type from MLV vaccine strains by determining their single nucleotide polymorphism (SNP) patterns through either whole-genome sequencing or PCR sequencing of genomic regions containing vaccine-defining SNPs. To determine the BoHV-1 subtype in clinical isolates and their relationship to MLV strains, 8 isolates from varied clinical disease at three different laboratories in the U.S. were sequenced and phylogenetically analyzed. Five samples were isolated within the past 5 years from New York and 3 were archived samples recovered 35 years prior from Oklahoma and Louisiana. Based on phylogenetic analysis, four of the cases appeared to be due to an MLV vaccine: 3 cases of aborted fetuses and one neonate with systemic BoHV-1 disease. One aborted fetus was from a herd with no reported history of MLV vaccination in two years. The remaining four isolates did not group with any MLV vaccines: two were associated with bovine respiratory disease, one with vulvovaginitis, and a fourth was determined to be a BoHV-1.2b respiratory isolate. Recovery of BoHV-1.1 that is very closely related to an MLV vaccine virus from a herd not receiving vaccines in an extended period prior to its isolation suggests that MLV viruses may remain latent or circulate within herds for long periods.

Detection and characterization of viruses as field and vaccine strains in feedlot cattle with bovine respiratory disease.

This study investigated viruses in bovine respiratory disease (BRD) cases in feedlots, including bovine herpesvirus-1 (BoHV-1), bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus (BRSV), bovine coronaviruses (BoCV) and parainfluenza-3 virus (PI3V). Nasal swabs were collected from 114 cattle on initial BRD treatment. Processing included modified live virus (MLV) vaccination. Seven BRD necropsy cases were included for 121 total cases. Mean number of days on feed before first sample was 14.9 days. Swabs and tissue homogenates were tested by gel based PCR (G-PCR), quantitative-PCR (qPCR) and quantitative real time reverse transcriptase PCR (qRT-PCR) and viral culture. There were 87/114 (76.3%) swabs positive for at least one virus by at least one test. All necropsy cases were positive for at least one virus. Of 121 cases, positives included 18/121 (14.9%) BoHV-1; 19/121 (15.7%) BVDV; 76/121 (62.8%) BoCV; 11/121 (9.1%) BRSV; and 10/121 (8.3%) PI3V. For nasal swabs, G-PCR (5 viruses) detected 44/114 (38.6%); q-PCR and qRT-PCR (4 viruses) detected 81/114 (71.6%); and virus isolation detected 40/114 (35.1%). Most were positive for only one or two tests, but not all three tests. Necropsy cases had positives: 5/7 G-PCR, 5/7 q-PCR and qRT-PCR, and all were positive by cell culture. In some cases, G-PCR and both real time PCR were negative for BoHV-1, BVDV, and PI3V in samples positive by culture. PCR did not differentiate field from vaccines strains of BoHV-1, BVDV, and PI3V. However based on sequencing and analysis, field and vaccine strains of culture positive BoHV-1, BoCV, BVDV, and PI3V, 11/18 (61.1%) of BoHV-1 isolates, 6/17 (35.3%) BVDV isolates, and 1/10 (10.0%) PI3V identified as vaccine. BRSV was only identified by PCR testing. Interpretation of laboratory tests is appropriate as molecular based tests and virus isolation cannot separate field from vaccine strains. Additional testing using sequencing appears appropriate for identifying vaccine strains.

Effect of Vitamin K on Vascular Health and Physical Function in Older People with Vascular Disease--A Randomised Controlled Trial.

BACKGROUND AND AIMS: Vitamin K insufficiency is common and linked to an increased risk of cardiovascular disease and osteoporotic fractures. The aim of this study was to examine whether daily supplementation with oral vitamin K could improve vascular health and physical function in older people with established vascular disease. METHODS AND RESULTS: A double blind, randomised, placebo-controlled trial. Participants aged ≤ 70 years with a history of vascular disease were randomised to receive 6 months of daily oral 100mcg vitamin K2 (MK7 subtype) or matching placebo with outcomes measured at 0, 3 and 6 months. The primary outcome was between-group difference in endothelial function assessed using flow-mediated dilatation of the brachial artery at 6 months. Secondary outcomes included carotid-radial pulse wave velocity, augmentation index, blood pressure, carotid intima-media thickness, C-reactive protein, B-type natriuretic peptide, cholesterol and desphospho-uncarboxylated matrix Gla protein levels. Handgrip strength and the Short Physical Performance Battery assessed physical function, while postural sway was measured using a 3-dimensional force platform. RESULTS: 80 participants were randomised, mean age 77 (SD 5) years; 44/80 were male. Vitamin K levels rose in the intervention arm compared to placebo (+48 pg/ml vs -6 pg/ml, p=0.03) at 6 months. Desphospho-uncarboxylated Matrix Gla protein levels fell in the intervention group compared to placebo at 6 months (-130 [SD 117] pmol/L vs +13 [SD 180] pmol/L, p<0.001). No change was seen in endothelial function (between group difference -0.3% [95%CI -1.3 to 0.8], p=0.62). A modest, non-significant improvement in pulse wave velocity was seen in the vitamin K group (-0.8m/s [95%CI -1.8 to 0.3], p=0.15) while all other vascular and physical function outcomes unchanged. CONCLUSIONS: Six months of vitamin K2 supplementation did not improve markers of vascular health or physical function in older patients with vascular disease.

Correction for human head motion in helical x-ray CT.

Correction for rigid object motion in helical CT can be achieved by reconstructing from a modified source-detector orbit, determined by the object motion during the scan. This ensures that all projections are consistent, but it does not guarantee that the projections are complete in the sense of being sufficient for exact reconstruction. We have previously shown with phantom measurements that motion-corrected helical CT scans can suffer from data-insufficiency, in particular for severe motions and at high pitch. To study whether such data-insufficiency artefacts could also affect the motion-corrected CT images of patients undergoing head CT scans, we used an optical motion tracking system to record the head movements of 10 healthy volunteers while they executed each of the 4 different types of motion ('no', slight, moderate and severe) for 60 s. From these data we simulated 354 motion-affected CT scans of a voxelized human head phantom and reconstructed them with and without motion correction. For each simulation, motion-corrected (MC) images were compared with the motion-free reference, by visual inspection and with quantitative similarity metrics. Motion correction improved similarity metrics in all simulations. Of the 270 simulations performed with moderate or less motion, only 2 resulted in visible residual artefacts in the MC images. The maximum range of motion in these simulations would encompass that encountered in the vast majority of clinical scans. With severe motion, residual artefacts were observed in about 60% of the simulations. We also evaluated a new method of mapping local data sufficiency based on the degree to which Tuy's condition is locally satisfied, and observed that areas with high Tuy values corresponded to the locations of residual artefacts in the MC images. We conclude that our method can provide accurate and artefact-free MC images with most types of head motion likely to be encountered in CT imaging, provided that the motion can be accurately determined.

IRF6 mutation screening in non-syndromic orofacial clefting: analysis of 1521 families.

Van der Woude syndrome (VWS) is an autosomal dominant malformation syndrome characterized by orofacial clefting (OFC) and lower lip pits. The clinical presentation of VWS is variable and can present as an isolated OFC, making it difficult to distinguish VWS cases from individuals with non-syndromic OFCs. About 70% of causal VWS mutations occur in IRF6, a gene that is also associated with non-syndromic OFCs. Screening for IRF6 mutations in apparently non-syndromic cases has been performed in several modestly sized cohorts with mixed results. In this study, we screened 1521 trios with presumed non-syndromic OFCs to determine the frequency of causal IRF6 mutations. We identified seven likely causal IRF6 mutations, although a posteriori review identified two misdiagnosed VWS families based on the presence of lip pits. We found no evidence for association between rare IRF6 polymorphisms and non-syndromic OFCs. We combined our results with other similar studies (totaling 2472 families) and conclude that causal IRF6 mutations are found in 0.24-0.44% of apparently non-syndromic OFC families. We suggest that clinical mutation screening for IRF6 be considered for certain family patterns such as families with mixed types of OFCs and/or autosomal dominant transmission.

A polymorphism within the psoriasis susceptibility 1 candidate 1 (PSORS1C1) gene is not linked to HLA-B*58:01 in an Australian cohort.

Association exists between HLA-B*58:01 allele and allopurinol Stevens-Johnson syndrome (SJS), especially those of an Asian heritage but associations have been also described in Caucasian populations. This creates the need to develop a rapid, robust and inexpensive assay for pre-screening of HLA-B*58:01. A polymorphism within PSORS1C1 gene was recently found in linkage disequilibrium (LD) with HLA-B*58:01 allele in the Japanese population. The aim of this study is to confirm whether this polymorphism can be used as a surrogate biomarker to identify carriers for HLA-B*58:01. No linkage was found between the two in the Australian cohort.

The utilization of the Welfare Quality® assessment for determining laying hen condition across three housing systems.

The Welfare Quality(®) Assessment protocol for poultry ( WQA: ) provides animal-based measures allowing welfare comparisons across farms and housing systems. It was used to compare Lohmann LSL Classic White hens housed in an enriched colony ( EC: ), aviary ( AV: ), and conventional cage system ( CC: ) on a commercial farm over 2 flock cycles. Hens (n = 100/system) were scored on a variety of measures. A baseline measurement was made at placement at 19 wk of age for 1 flock, since AV hens had been reared in an aviary pullet facility ( AVP: while EC and CC hens were reared in a conventional pullet facility ( CCP: ). Hens in all systems were then assessed at 52 and 72 wk of age. Necropsies were performed on all mortalities 1 wk before and after the WQA sampling. WQAs were analyzed using Mann-Whitney U and Kruskal-Wallis tests for prevalence and Fisher's exact tests for severity. There was an effect of rearing, with AVP having shorter claws (P = 0.01), dirtier feathers (P = 0.03), and more keel abnormalities (P < 0.0001) than CCP at placement. For the hens, there were several significant housing system effects across flocks and age periods (all P ≤ 0.05). AV and EC hens had more keel abnormalities than CC hens. They also had fewer foot abnormalities than CC hens, although those in AV hens were more severe. AV hens had consistently dirtier feathers than EC and CC hens. While AV hens had the best overall feather cover, feather loss patterns suggested that loss was due to head pecking for AV, whereas in EC and CC it was due to cage abrasion. The necropsy findings and the WQA results were similar, except that the WQA failed to find enteritis at 19 wk, although it was detected in the necropsies during this sampling period. These results show that the WQA is a useful tool for detecting hen condition differences across housing systems.

Stochastic simulation of radium-223 dichloride therapy at the sub-cellular level.

Radium-223 dichloride ((223)Ra) is an alpha particle emitter and a natural bone-seeking radionuclide that is currently used for treating osteoblastic bone metastases associated with prostate cancer. The stochastic nature of alpha emission, hits and energy deposition poses some challenges for estimating radiation damage. In this paper we investigate the distribution of hits to cells by multiple alpha particles corresponding to a typical clinically delivered dose using a Monte Carlo model to simulate the stochastic effects. The number of hits and dose deposition were recorded in the cytoplasm and nucleus of each cell. Alpha particle tracks were also visualized. We found that the stochastic variation in dose deposited in cell nuclei ([Formula: see text]40%) can be attributed in part to the variation in LET with pathlength. We also found that [Formula: see text]18% of cell nuclei receive less than one sigma below the average dose per cell ([Formula: see text]15.4 Gy). One possible implication of this is that the efficacy of cell kill in alpha particle therapy need not rely solely on ionization clustering on DNA but possibly also on indirect DNA damage through the production of free radicals and ensuing intracellular signaling.

A rigid motion correction method for helical computed tomography (CT).

We propose a method to compensate for six degree-of-freedom rigid motion in helical CT of the head. The method is demonstrated in simulations and in helical scans performed on a 16-slice CT scanner. Scans of a Hoffman brain phantom were acquired while an optical motion tracking system recorded the motion of the bed and the phantom. Motion correction was performed by restoring projection consistency using data from the motion tracking system, and reconstructing with an iterative fully 3D algorithm. Motion correction accuracy was evaluated by comparing reconstructed images with a stationary reference scan. We also investigated the effects on accuracy of tracker sampling rate, measurement jitter, interpolation of tracker measurements, and the synchronization of motion data and CT projections. After optimization of these aspects, motion corrected images corresponded remarkably closely to images of the stationary phantom with correlation and similarity coefficients both above 0.9. We performed a simulation study using volunteer head motion and found similarly that our method is capable of compensating effectively for realistic human head movements. To the best of our knowledge, this is the first practical demonstration of generalized rigid motion correction in helical CT. Its clinical value, which we have yet to explore, may be significant. For example it could reduce the necessity for repeat scans and resource-intensive anesthetic and sedation procedures in patient groups prone to motion, such as young children. It is not only applicable to dedicated CT imaging, but also to hybrid PET/CT and SPECT/CT, where it could also ensure an accurate CT image for lesion localization and attenuation correction of the functional image data.

Epigenomic analysis of the HOX gene loci reveals mechanisms that may control canonical expression patterns in AML and normal hematopoietic cells.

HOX genes are highly expressed in many acute myeloid leukemia (AML) samples, but the patterns of expression and associated regulatory mechanisms are not clearly understood. We analyzed RNA sequencing data from 179 primary AML samples and normal hematopoietic cells to understand the range of expression patterns in normal versus leukemic cells. HOX expression in AML was restricted to specific genes in the HOXA or HOXB loci, and was highly correlated with recurrent cytogenetic abnormalities. However, the majority of samples expressed a canonical set of HOXA and HOXB genes that was nearly identical to the expression signature of normal hematopoietic stem/progenitor cells. Transcriptional profiles at the HOX loci were similar between normal cells and AML samples, and involved bidirectional transcription at the center of each gene cluster. Epigenetic analysis of a subset of AML samples also identified common regions of chromatin accessibility in AML samples and normal CD34(+) cells that displayed differences in methylation depending on HOX expression patterns. These data provide an integrated epigenetic view of the HOX gene loci in primary AML samples, and suggest that HOX expression in most AML samples represents a normal stem cell program that is controlled by epigenetic mechanisms at specific regulatory elements.

Bovine herpesvirus-1: evaluation of genetic diversity of subtypes derived from field strains of varied clinical syndromes and their relationship to vaccine strains.

Bovine herpesvirus-1 (BoHV-1) causes significant disease in cattle. Control programs in North America incorporate vaccination with modified live viral (MLV) or killed (KV) vaccine. BoHV-1 strains are isolated from diseased animals or fetuses after vaccination. There are markers for differentiating MLV from field strains using whole-genome sequencing and analysis identifying single nucleotide polymorphisms (SNPs). Using multiple primer sets and sequencing of products permits association of BoHV-1 isolates with vaccines. To determine association between vaccine virus and strains isolated from clinical cases following vaccination, we analyzed 12 BoHV-1 isolates from animals with various clinical syndromes; 9 corresponded to BoHV-1.1 respiratory group. The remaining three corresponded to BoHV-1.2b, typically found in genital tracts of cattle. Four BoHV-1 isolates were identical to a vaccine strain; three were from post-vaccination abortion episodes with typical herpetic lesions whose dams had received MLV vaccine during pregnancy, and one from a heifer given a related MLV vaccine; Sequences of two respiratory isolates perfectly matched mutations characterizing RLB106 strain, a temperature sensitive mutant used in intranasal and parenteral vaccines. The last three respiratory strains clearly appeared related to a group of MLV vaccines. Previously the MLV vaccines were grouped into four groups based on SNPs patterns. In contrast with above-mentioned isolates that closely matched SNP patterns of their respective MLV vaccine virus, these 3 strains both lacked some and possessed a number of additional mutations compared to a group of MLV vaccine viral genome. Finding BoHV-1.2b in respiratory cases indicates focus should be given BoHV-1.2b as an emerging virus or a virus not recognized nor fully characterized in BRD.