Effect of MR head coil geometry on deep-learning-based MR image reconstruction.

PURPOSE: To investigate whether parallel imaging-imposed geometric coil constraints can be relaxed when using a deep learning (DL)-based image reconstruction method as opposed to a traditional non-DL method. THEORY AND METHODS: Traditional and DL-based MR image reconstruction approaches operate in fundamentally different ways: Traditional methods solve a system of equations derived from the image data whereas DL methods use data/target pairs to learn a generalizable reconstruction model. Two sets of head coil profiles were evaluated: (1) 8-channel and (2) 32-channel geometries. A DL model was compared to conjugate gradient SENSE (CG-SENSE) and L1-wavelet compressed sensing (CS) through quantitative metrics and visual assessment as coil overlap was increased. RESULTS: Results were generally consistent between experiments. As coil overlap increased, there was a significant (p < 0.001) decrease in performance in most cases for all methods. The decrease was most pronounced for CG-SENSE, and the DL models significantly outperformed (p < 0.001) their non-DL counterparts in all scenarios. CS showed improved robustness to coil overlap and signal-to-noise ratio (SNR) versus CG-SENSE, but had quantitatively and visually poorer reconstructions characterized by blurriness as compared to DL. DL showed virtually no change in performance across SNR and very small changes across coil overlap. CONCLUSION: The DL image reconstruction method produced images that were robust to coil overlap and of higher quality than CG-SENSE and CS. This suggests that geometric coil design constraints can be relaxed when using DL reconstruction methods.

Patient Perspectives of the Manifestations and Treatment of Anti-MDA5 Antibody-Positive Dermatomyositis: An Observational Survey.

Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of autoimmune disorders classically characterized by proximal skeletal muscle inflammation leading to weakness, but they often possess additional systemic manifestations such as cutaneous, pulmonary, and articular disease.1 Although originally dichotomized as either dermatomyositis (DM) or polymyositis, the discovery of new myositis-specific antibodies (MSA) and myositis-associated antibodies has led to the delineation of more refined IIM patient subgroups.

Collective acoustic modes of a bubble plume.

We derive a simple formula for the lowest natural frequencies of an infinitely long bubble plume with arbitrary cross section. Expressions are derived in terms of bubble volume fraction and equivalent radius of the plume, and a criterion for the existence of collective modes is established. For the plume with the circular cross section, our analytical approach is validated with the results of previous studies and numerical solution.

Fitting high-resolution electron density maps from atomic models to solution scattering data.

Solution scattering techniques, such as small- and wide-angle X-ray scattering (SWAXS), provide valuable insights into the structure and dynamics of biological macromolecules in solution. In this study, we present an approach to accurately predict solution X-ray scattering profiles at wide angles from atomic models by generating high-resolution electron density maps. Our method accounts for the excluded volume of bulk solvent by calculating unique adjusted atomic volumes directly from the atomic coordinates. This approach eliminates the need for one of the free fitting parameters commonly used in existing algorithms, resulting in improved accuracy of the calculated SWAXS profile. An implicit model of the hydration shell is generated that uses the form factor of water. Two parameters, namely the bulk solvent density and the mean hydration shell contrast, are adjusted to best fit the data. Results using eight publicly available SWAXS profiles show high-quality fits to the data. In each case, the optimized parameter values show small adjustments demonstrating that the default values are close to the true solution. Disabling parameter optimization produces significantly more accurate predicted scattering profiles compared to the leading software. The algorithm is computationally efficient, comparable to the leading software and up to 10 times faster for large molecules. The algorithm is encoded in a command line script called denss.pdb2mrc.py and is available open source as part of the DENSS v1.7.0 software package. In addition to improving the ability to compare atomic models to experimental SWAXS data, these developments pave the way for increasing the accuracy of modeling algorithms using SWAXS data and decreasing the risk of overfitting.

Concurrently mapping quantitative trait loci associations from multiple subspecies within hybrid populations.

Many of the world's agriculturally important plant and animal populations consist of hybrids of subspecies. Cattle in tropical and sub-tropical regions for example, originate from two subspecies, Bos taurus indicus (Bos indicus) and Bos taurus taurus (Bos taurus). Methods to derive the underlying genetic architecture for these two subspecies are essential to develop accurate genomic predictions in these hybrid populations. We propose a novel method to achieve this. First, we use haplotypes to assign SNP alleles to ancestral subspecies of origin in a multi-breed and multi-subspecies population. Then we use a BayesR framework to allow SNP alleles originating from the different subspecies differing effects. Applying this method in a composite population of B. indicus and B. taurus hybrids, our results show that there are underlying genomic differences between the two subspecies, and these effects are not identified in multi-breed genomic evaluations that do not account for subspecies of origin effects. The method slightly improved the accuracy of genomic prediction. More significantly, by allocating SNP alleles to ancestral subspecies of origin, we were able to identify four SNP with high posterior probabilities of inclusion that have not been previously associated with cattle fertility and were close to genes associated with fertility in other species. These results show that haplotypes can be used to trace subspecies of origin through the genome of this hybrid population and, in conjunction with our novel Bayesian analysis, subspecies SNP allele allocation can be used to increase the accuracy of QTL association mapping in genetically diverse populations.

Effect of selinexor on lipogenesis in virus-positive Merkel cell carcinoma cell lines.

BACKGROUND: Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine cutaneous carcinoma aetiologically linked to the Merkel cell polyomavirus (MCPyV). Immune checkpoint inhibitors are currently the first-line therapy for metastatic MCC; however, the treatment is effective in only about half of patients, highlighting the need for alternative therapies. Selinexor (KPT-330) is a selective inhibitor of nuclear exportin 1 (XPO1) and has been shown to inhibit MCC cell growth in vitro, but the pathogenesis has not been established. Decades of research have established that cancer cells significantly upregulate lipogenesis to meet an increased demand for fatty acids and cholesterol. Treatments that inhibit lipogenic pathways may halt cancer cell proliferation. AIM: To determine the effect of increasing doses of selinexor on fatty acid and cholesterol synthesis in MCPyV-positive MCC (MCCP) cell lines and aid in elucidating the mechanism by which selinexor prevents and reduces MCC growth. METHODS: MKL-1 and MS-1 cell lines were treated with increasing doses of selinexor for 72 h. Protein expression quantification was determined using chemiluminescent Western immunoblotting and densitometric analysis. Fatty acids and cholesterol were quantified using free fatty acid assay and cholesterol ester detection kits. RESULTS: Selinexor causes statistically significant reductions of the lipogenic transcription factors sterol regulatory element-binding proteins 1 and 2, and lipogenic enzymes acetyl-CoA carboxylase, fatty acid synthase, squalene synthase and 3ß-hydroxysterol Δ-24-reductase in a dose-dependent manner in two MCCP cell lines. Although inhibiting the fatty acid synthesis pathway results in meaningful decreases in fatty acids, the cellular cholesterol levels did not demonstrate such reductions. CONCLUSION: For patients with metastatic MCC refractory to immune checkpoint inhibitors, selinexor may provide clinical benefit through the inhibition of the lipogenesis pathway; however, further research and clinical trials are needed to evaluate these findings.

Cytogenetically Cryptic Acute Promyelocytic Leukemia: A Diagnostic Challenge.

Cytogenetically cryptic acute promyelocytic leukemia (APL) is rare, characterized by typical clinical and morphological features, but lacks t(15;17)(q24;q21)/PML::RARA translocation seen in conventional karyotyping or FISH. The prompt diagnosis and treatment of APL are critical due to life-threatening complications associated with this disease. However, cryptic APL cases remain a diagnostic challenge that could mislead the appropriate treatment. We describe four cryptic APL cases and review reported cases in the literature. Reverse transcriptase polymerase chain reaction (RT-PCR) is the most efficient diagnostic modality to detect these cases, and alternative methods are also discussed. This study highlights the importance of using parallel testing methods to diagnose cryptic APL cases accurately and effectively.

Trichodysplasia spinulosa polyomavirus small T antigen synergistically modulates S6 protein translation and DNA damage response pathways to shape host cell environment.

TSPyV is a viral agent linked to Trichodysplasia spinulosa, a disfiguring human skin disease which presents with hyperkeratotic spicule eruption in immunocompromised hosts. This proliferative disease state requires extensive modulation of the host cell environment. While the small T (sT) antigen of TSPyV has been postulated to cause widespread cellular perturbation, its specific substrates and their mechanistic connection are unclear. To identify the cellular substrates and pathways perturbed by TSPyV sT and propose a nuanced model that reconciles the multiple arms of TSPyV pathogenesis, changes in expression of several proteins and phospho-proteins in TSPyV sT expressing and TSPyV sT deletion mutant-expressing cell lysates were interrogated using Western blot assays. TSPyV sT expression exploits the DNA damage response pathway, by inducing hyperphosphorylation of ATM and 53BP1 and upregulation of BMI-1. Concurrently, sT dysregulates the S6 protein translation pathway via hyperphosphorylation of CDC2, p70 S6 kinase, S6, and PP1α. The S6S244/247 and p-PP1αT320 phospho-forms are points of overlap between the DDR and S6 networks. We propose a mechanistic rationale for previous reports positioning sT antigen as the key driver of TSPyV pathogenesis. We illuminate novel targets in the S6 and DDR pathways and recognize a potential synergy between these pathways. TSPyV may sensitize the cell to both unrestricted translation and genomic instability. This multi-pronged infection model may inform future therapeutic modalities against TSPyV and possibly other viruses with overlapping host substrates.

Selinexor is a novel inhibitor of DNA damage response in Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a highly lethal cutaneous carcinoma, which in ~80% of cases in the USA is aetiologically linked to Merkel cell polyomavirus (MCPyV). Immune checkpoint inhibitors (ICIs) can successfully treat ~50% of patients with metastatic MCC, but some MCCs are refractory to ICIs, possibly due to altered DNA damage response (DDR). Selinexor, an anticancer therapy that is currently approved in combination with chemotherapy for multiple myeloma, downregulates the small T and large T tumour antigens in MCC through selective inhibition of nuclear exportin 1 (XPO1). We examined the effect of varying doses of selinexor on DDR protein expression in MCPyV-positive and MCPyV-negative MCC cells. Selinexor was found to inhibit DDR protein expression in both MCPyV-positive and MCPyV-negative cells. Addition of selinexor alone or combined with ICI may be a promising treatment for MCC, but further in vivo research and clinical trials are required to validate these findings.

Targeting HIF2α-ARNT hetero-dimerisation as a novel therapeutic strategy for pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a destructive disease of the pulmonary vasculature often leading to right heart failure and death. Current therapeutic intervention strategies only slow disease progression. The role of aberrant hypoxia-inducible factor (HIF)2α stability and function in the initiation and development of pulmonary hypertension (PH) has been an area of intense interest for nearly two decades.Here we determine the effect of a novel HIF2α inhibitor (PT2567) on PH disease initiation and progression, using two pre-clinical models of PH. Haemodynamic measurements were performed, followed by collection of heart, lung and blood for pathological, gene expression and biochemical analysis. Blood outgrowth endothelial cells from idiopathic PAH patients were used to determine the impact of HIF2α-inhibition on endothelial function.Global inhibition of HIF2a reduced pulmonary vascular haemodynamics and pulmonary vascular remodelling in both su5416/hypoxia prevention and intervention models. PT2567 intervention reduced the expression of PH-associated target genes in both lung and cardiac tissues and restored plasma nitrite concentration. Treatment of monocrotaline-exposed rodents with PT2567 reduced the impact on cardiovascular haemodynamics and promoted a survival advantage. In vitro, loss of HIF2α signalling in human pulmonary arterial endothelial cells suppresses target genes associated with inflammation, and PT2567 reduced the hyperproliferative phenotype and overactive arginase activity in blood outgrowth endothelial cells from idiopathic PAH patients. These data suggest that targeting HIF2α hetero-dimerisation with an orally bioavailable compound could offer a new therapeutic approach for PAH. Future studies are required to determine the role of HIF in the heterogeneous PAH population.

Sensitivity assessment and optimal economic evaluation of a new COVID-19 compartmental epidemic model with control interventions.

Optimal economic evaluation is pivotal in prioritising the implementation of non-pharmaceutical and pharmaceutical interventions in the control of diseases. Governments, decision-makers and policy-makers broadly need information about the effectiveness of a control intervention concerning its cost-benefit to evaluate whether a control intervention offers the best value for money. The outbreak of COVID-19 in December 2019, and the eventual spread to other parts of the world, have pushed governments and health authorities to take drastic socioeconomic, sociocultural and sociopolitical measures to curb the spread of the virus, SARS-CoV-2. To help policy-makers, health authorities and governments, we propose a Susceptible, Exposed, Asymptomatic, Quarantined asymptomatic, Severely infected, Hospitalized, Recovered, Recovered asymptomatic, Deceased, and Protective susceptible (individuals who observe health protocols) compartmental structure to describe the dynamics of COVID-19. We fit the model to real data from Ghana and Egypt to estimate model parameters using standard incidence rate. Projections for disease control and sensitivity analysis are presented using MATLAB. We noticed that multiple peaks (waves) of COVID-19 for Ghana and Egypt can be prevented if stringent health protocols are implemented for a long time and/or the reluctant behaviour on the use of protective equipment by individuals are minimized. The sensitivity analysis suggests that: the rate of diagnoses and testing, the rate of quarantine through doubling enhanced contact tracing, adhering to physical distancing, adhering to wearing of nose masks, sanitizing-washing hands, media education remains the most effective measures in reducing the control reproduction number R c , to less than unity in the absence of vaccines and therapeutic drugs in Ghana and Egypt. Optimal control and cost-effectiveness analysis are rigorously studied. The main finding is that having two controls (transmission reduction and case isolation) is better than having one control, but is economically expensive. In case only one control is affordable, then transmission reduction is better than case isolation. Hopefully, the results of this research should help policy-makers when dealing with multiple waves of COVID-19.

A cost-effectiveness analysis of community water fluoridation for schoolchildren.

BACKGROUND: Community water fluoridation (CWF), the controlled addition of fluoride to the water supply for the prevention of dental caries (tooth decay), is considered a safe and effective public health intervention. The Republic of Ireland (Ireland) is the only country in Europe with a legislative mandate for the fluoridation of the public water supply, a key component of its oral health policy. However, more recently, there has been an increase in public concern around the relevance of the intervention given the current environment of multiple fluoride sources and a reported increase in the prevalence of enamel fluorosis. The aim of this economic analysis is to provide evidence to inform policy decisions on whether the continued public investment in community water fluoridation remains justified under these altered circumstances. METHODS: Following traditional methods of economic evaluation and using epidemiological data from a representative sample of 5-, 8-, and 12-year-old schoolchildren, this cost-effectiveness analysis, conducted from the health-payer perspective, compared the incremental costs and consequences associated with the CWF intervention to no intervention for schoolchildren living in Ireland in 2017. A probabilistic model was developed to simulate the potential lifetime treatment savings associated with the schoolchildren's exposure to the intervention for one year. RESULTS: In 2017, approximately 71% of people living in Ireland had access to a publicly provided fluoridated water supply at an average per capita cost to the state of €2.15. The total cost of CWF provision to 5-, 8-, and 12-year-old schoolchildren (n = 148,910) was estimated at €320,664, and the incremental cost per decayed, missing, or filled tooth (d3vcmft/D3vcMFT) prevented was calculated at €14.09. The potential annual lifetime treatment savings associated with caries prevented for this cohort was estimated at €2.95 million. When the potential treatment savings were included in the analysis, the incremental cost per d3vcmft/D3vcMFT prevented was -€115.67, representing a cost-saving to the health-payer and a positive return on investment. The results of the analysis were robust to both deterministic and probability sensitivity analyses. CONCLUSION: Despite current access to numerous fluoride sources and a reported increase in the prevalence of enamel fluorosis, CWF remains a cost-effective public health intervention for Irish schoolchildren.

Examining the impact of video-based outpatient education on patient demand for a rheumatology CNS service.

BACKGROUND: Patient demand for education and access to the clinical nurse specialists (CNSs) during the rheumatology clinic at one hospital in Ireland was increasing. Alternative methods of providing patient education had to be examined. AIMS: To explore the efficacy of video-based outpatient education, and its impact on demand for the CNSs. METHODS: A video was produced to play in a rheumatology outpatient department. A representative sample of 240 patients (120 non-exposed and 120 exposed to the video) attending the clinic was selected to complete a questionnaire exploring the effect of the video. Data were analysed using chi-square tests with Yates' continuity correction. FINDINGS: Demand for the CNSs was six times higher in the non-exposed group compared with the exposed group (non-exposed: 25%, exposed: 4.8%) (χ2=15.7, P=0.00007), representing a significant decrease in resource demand. CONCLUSION: High-quality educational videos on view in the rheumatology outpatient department provide patients with information sufficient to meet their educational needs, thus releasing CNS resources.

4PBA Restores Signaling of a Cysteine-substituted Mutant BMPR2 Receptor Found in Patients with Pulmonary Arterial Hypertension.

Mutations in the gene encoding BMPR2 (bone morphogenetic protein type 2 receptor) are the major cause of heritable pulmonary arterial hypertension (PAH). Point mutations in the BMPR2 ligand-binding domain involving cysteine residues (such as C118W) are causative of PAH and predicted to cause protein misfolding. Using heterologous overexpression systems, we showed previously that these mutations lead to retention of BMPR2 in the endoplasmic reticulum but are partially rescued by chemical chaperones. Here, we sought to determine whether the chemical chaperone 4-phenylbutyrate (4PBA) restores BMPR2 signaling in primary cells and in a knockin mouse harboring a C118W mutation. First, we confirmed dysfunctional BMP signaling in dermal fibroblasts isolated from a family with PAH segregating the BMPR2 C118W mutation. After BMP4 treatment, the induction of downstream signaling targets (Smad1/5, ID1 [inhibitor of DNA binding 1], and ID2) was significantly reduced in C118W mutant cells. Treatment with 4PBA significantly rescued Smad1/5, ID1, and ID2 expression. Pulmonary artery smooth muscle cells isolated from the lungs of heterozygous mice harboring the Bmpr2 C118W mutation exhibited significantly increased proliferation. In the presence of 4PBA, hyperproliferation was dramatically reduced. Furthermore, in vivo, 4PBA treatment of Bmpr2 C118W mice partially rescued Bmpr2 expression, restored downstream signaling, and improved vascular remodeling. These findings demonstrate in primary cells and in a knockin mouse that the repurposed small-molecule chemical chaperone 4PBA might be a promising precision medicine approach to treat PAH in patients with specific subtypes of BMPR2 mutation involving cysteine substitutions in the ligand-binding domain.

The Hitchhiker's Guide to Nucleocytoplasmic Trafficking in Neurodegeneration.

The widespread nature of nucleocytoplasmic trafficking defects and protein accumulation suggests distinct yet overlapping mechanisms in a variety of neurodegenerative diseases. Detailed understanding of the cellular pathways involved in nucleocytoplasmic transport and its dysregulation are essential for elucidating neurodegenerative pathogenesis and pinpointing potential areas for therapeutic intervention. The transport of cargos from the nucleus to the cytoplasm is generally regulated by the structure and function of the nuclear pore as well as the karyopherin α/ß, importin, exportin, and mRNA export mechanisms. The disruption of these crucial transport mechanisms has been extensively described in the context of neurodegenerative diseases. One common theme in neurodegeneration is the cytoplasmic aggregation of proteins, including nuclear RNA binding proteins, repeat expansion associated gene products, and tau. These cytoplasmic aggregations are partly a consequence of failed nucleocytoplasmic transport machinery, but can also further disrupt transport, creating cyclical feed-forward mechanisms that exacerbate neurodegeneration. Here we describe the canonical mechanisms that regulate nucleocytoplasmic trafficking as well as how these mechanisms falter in neurodegenerative diseases.

Genetic control of temperament traits across species: association of autism spectrum disorder risk genes with cattle temperament.

BACKGROUND: Temperament traits are of high importance across species. In humans, temperament or personality traits correlate with psychological traits and psychiatric disorders. In cattle, they impact animal welfare, product quality and human safety, and are therefore of direct commercial importance. We hypothesized that genetic factors that contribute to variation in temperament among individuals within a species will be shared between humans and cattle. Using imputed whole-genome sequence data from 9223 beef cattle from three cohorts, a series of genome-wide association studies was undertaken on cattle flight time, a temperament phenotype measured as the time taken for an animal to cover a short-fixed distance after release from an enclosure. We also investigated the association of cattle temperament with polymorphisms in bovine orthologs of risk genes for neuroticism, schizophrenia, autism spectrum disorders (ASD), and developmental delay disorders in humans. RESULTS: Variants with the strongest associations were located in the bovine orthologous region that is involved in several behavioural and cognitive disorders in humans. These variants were also partially validated in independent cattle cohorts. Genes in these regions (BARHL2, NDN, SNRPN, MAGEL2, ABCA12, KIFAP3, TOPAZ1, FZD3, UBE3A, and GABRA5) were enriched for the GO term neuron migration and were differentially expressed in brain and pituitary tissues in humans. Moreover, variants within 100 kb of ASD susceptibility genes were associated with cattle temperament and explained 6.5% of the total additive genetic variance in the largest cattle cohort. The ASD genes with the most significant associations were GABRB3 and CUL3. Using the same 100 kb window, a weak association was found with polymorphisms in schizophrenia risk genes and no association with polymorphisms in neuroticism and developmental delay disorders risk genes. CONCLUSIONS: Our analysis showed that genes identified in a meta-analysis of cattle temperament contribute to neuron development functions and are differentially expressed in human brain tissues. Furthermore, some ASD susceptibility genes are associated with cattle temperament. These findings provide evidence that genetic control of temperament might be shared between humans and cattle and highlight the potential for future analyses to leverage results between species.

Use of whole-genome sequence data and novel genomic selection strategies to improve selection for age at puberty in tropically-adapted beef heifers.

BACKGROUND: In tropically-adapted beef heifers, application of genomic prediction for age at puberty has been limited due to low prediction accuracies. Our aim was to investigate novel methods of pre-selecting whole-genome sequence (WGS) variants and alternative analysis methodologies; including genomic best linear unbiased prediction (GBLUP) with multiple genomic relationship matrices (MGRM) and Bayesian (BayesR) analyses, to determine if prediction accuracy for age at puberty can be improved. METHODS: Genotypes and phenotypes were obtained from two research herds. In total, 868 Brahman and 960 Tropical Composite heifers were recorded in the first population and 3695 Brahman, Santa Gertrudis and Droughtmaster heifers were recorded in the second population. Genotypes were imputed to 23 million whole-genome sequence variants. Eight strategies were used to pre-select variants from genome-wide association study (GWAS) results using conditional or joint (COJO) analyses. Pre-selected variants were included in three models, GBLUP with a single genomic relationship matrix (SGRM), GBLUP MGRM and BayesR. Five-way cross-validation was used to test the effect of marker panel density (6 K, 50 K and 800 K), analysis model, and inclusion of pre-selected WGS variants on prediction accuracy. RESULTS: In all tested scenarios, prediction accuracies for age at puberty were highest in BayesR analyses. The addition of pre-selected WGS variants had little effect on the accuracy of prediction when BayesR was used. The inclusion of WGS variants that were pre-selected using a meta-analysis with COJO analyses by chromosome, fitted in a MGRM model, had the highest prediction accuracies in the GBLUP analyses, regardless of marker density. When the low-density (6 K) panel was used, the prediction accuracy of GBLUP was equal (0.42) to that with the high-density panel when only six additional sequence variants (identified using meta-analysis COJO by chromosome) were included. CONCLUSIONS: While BayesR consistently outperforms other methods in terms of prediction accuracies, reasonable improvements in accuracy can be achieved when using GBLUP and low-density panels with the inclusion of a relatively small number of highly relevant WGS variants.

Using Contrast Motion to Generate Patient-Specific Blood Flow Simulations During Invasive Coronary Angiography.

Virtual fractional flow reserve (vFFR) is an emerging technology employing patient-specific computational fluid dynamics (CFD) simulations to infer the hemodynamic significance of a coronary stenosis. Patient-specific boundary conditions are an important aspect of this approach and while most efforts make use of lumped parameter models to capture key phenomena, they lack the ability to specify the associated parameters on a patient-specific basis. When applying vFFR in a catheter laboratory setting using X-ray angiograms as the basis for creating the simulations, there is some indirect functional information available through the observation of the radio-opaque contrast agent motion. In this work, we present a novel method for tuning the lumped parameter arterial resistances (commonly incorporated in such simulations), based on simulating the physics of the contrast motion and comparing the observed and simulated arrival times of the contrast front at key points within a coronary tree. We present proof of principle results on a synthetically generated coronary tree comprised of multiple segments, demonstrating that the method can successfully optimize the arterial resistances to reconstruct the underlying velocity and pressure fields, providing a potential new means to improve the patient specificity of simulation-based technologies in this area.

Evaluation of cervical and uterine size, at 4 weeks postpartum, as a predictor of subsequent fertility in Jersey cattle.

Uterine and cervical size of Holstein dairy cows is reported among reasons for a decline in dairy cow fertility. Therefore, the objectives of this study were to (a) determine whether size of the cervix and uterus at 4 weeks postpartum impacted subsequent fertility at first service in Jersey cattle, (b) determine whether progesterone level at 4 weeks postpartum impacted cyclicity and (c) the association of the presence of corpus luteum and uterus and cervix size. Body condition scores at calving, presence of postpartum diseases, parity number and milk weights were taken from lactating Jersey dairy cows (N = 147) for 28 days postpartum. During the fourth week postpartum, a blood sample was obtained for progesterone concentration, and transrectal ultrasonography was performed by a high-resolution ultrasound machine to determine cervical and uterine horn diameter, as well as ovarian structures measurements. Correcting for parity number, BCS at calving, presence of diseases and milk yield, cows with a cervix >2.54 ± 0.63 cm and uterine horn >2.25 ± 0.59 cm were less likely to become pregnant at first service (p = .04 and p = .003, respectively). The cows with larger cervix had a trend to be less likely to have a corpus luteum present at the 4th week of lactation (p = .067). Cows with larger uterine horn size were less likely to have a corpus luteum present at the 4th week of lactation (p = .015). It is concluded that a larger cervix and/or uterus during the postpartum was associated negatively with fertility and cyclicity in Jersey cows.

Adequate supply of dietary taurine stimulates expression of molecular markers of growth and protein turnover in juvenile barramundi (Lates calcarifer).

A trial was conducted to investigate the effect of dietary taurine (Tau) supply on the plasma amino acid composition and hepatic expression of several genes in juvenile barramundi (Lates calcarifer) after feeding. Triplicate tanks of fish (average weight, 89.3 g) were fed diets containing either a deficient (1 g kg-1), adequate (8 g kg-1) or excessive (19 g kg-1) level of dietary Tau. Liver tissues collected before feeding, and at 2- and 4-h post-feeding, were analysed for expression of genes involved in pathways of sulphur amino acid turnover, Tau biosynthesis and transport, target of rapamycin (TOR) signalling, the somatotropic axis and protein turnover. The treatment had no significant effect on the profiles of any amino acid in plasma collected over time after feeding, other than Tau and glycine. The expression profile of cystine and Tau synthetic genes suggested an effect of Tau excess on the metabolism of cystine. Markers of two pathways of Tau biosynthesis appear to be active in this species, providing proof that this species possesses the ability to synthesise Tau from SAA precursors. A marker for the regulation of Tau transport and homeostasis was shown to be directly regulated by Tau availability, whilst a link between adequate supply of Tau and TOR pathway-mediated growth stimulation was also apparent. An observed depression in expression of genes of the somatotropic axis, coupled with upregulation of the proteolytic and TOR-suppressing genes, in response to excessive Tau supply in the diet, signalled that excessive Tau may not be conducive to optimal growth in this species.