657 research outputs found

    The prevalence of occult hepatitis B virus (hbv) infection in a large multi-ethnic haemodialysis cohort.

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    Haemodialysis patients are at increased risk of exposure to blood borne viruses. To reduce transmission in the UK, all haemodialysis patients are regularly screened, and if susceptible to Hepatitis B virus (HBV) infection, vaccinated

    Mixed-length SIMD code generation for VLIW architectures with multiple native vector-widths

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    The degree of DLP parallelism in applications is not fixed and varies due to different computational characteristics of applications. On the contrary, most of the processors today include single-width SIMD (vector) hardware to exploit DLP. However, single-width SIMD architectures may not be optimal to serve applications with varying DLP and they may cause performance and energy inefficiency. We propose the usage of VLIW processors with multiple native vector-widths to better serve applications with changing DLP. SHAVE is an example of such VLIW processor and provides hardware support for the native 32-bit and 128-bit wide vector operations. This paper researches and implements the mixed-length SIMD code generation support for SHAVE processor. More specifically, we target generating 32-bit and 128/64-bit SIMD code for the native 32-bit and 128-bit wide vector units of SHAVE processor. In this way, we improved the performance of compiler generated SIMD code by reducing the number of overhead operations and by increasing the SIMD hardware utilization. Experimental results demonstrated that our methodology implemented in the compiler improves the performance of synthetic benchmarks up to 47%

    Reagent free electrochemical-based detection of silver ions at interdigitated microelectrodes using in-situ pH control

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    Herein we report on the development of an electrochemical sensor for silver ions detection in tap water using anodic sweep voltammetry with in-situ pH control; enabled by closely spaced interdigitated electrode arrays. The in-situ pH control approach allowed the pH of a test solution to be tailored to pH 3 (experimentally determined as the optimal pH) by applying 1.65 V to a protonator electrode with the subsequent production of protons, arising from water electrolysis, dropping the local pH value. Using this approach, an initial proof-of-concept study for silver detection in sodium acetate was undertaken where 1.25 V was applied during deposition (to compensate for oxygen production) and 1.65 V during stripping. Using these conditions, calibration between 0.2 and 10 μM was established with the silver stripping peak ∼0.3 V. The calculated limit of detection was 13 nM. For the final application in tap water, 1.65 V was applied to a protonator electrode for both deposition and stripping of silver. The chloride ions, present in tap water (as a consequence of adding chlorine during the disinfection process) facilitated silver detection and caused the striping peak to shift catholically to ∼0.2 V. The combination of the complexation of silver ions with chloride and in-situ pH control resulted in a linear calibration range between 0.25 and 2 μM in tap water and a calculated limit of detection of 106 nM without the need to add acid or supporting electrolytes

    Effect of a grazing period prior to finishing on a high concentrate diet on meat quality from bulls and steers

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    Bulls and steers (n = 60) were assigned to a pre-finishing grazing period and subsequently finished on concentrates or offered concentrates without grazing until slaughter (19 months). Colour and pH of longissimus thoracis were measured (48 h post-slaughter), and samples collected for proximate composition, collagen, sarcomere length, muscle fibre and enzymatic profile analysis. Steaks for texture, cook loss and sensory were aged (14 days). Castration increased intramuscular fat content, cook loss and myosin isoforms IIa and I proportions, and decreased IIx proportion (P < 0.05). Steer meat was positively correlated to overall tenderness, texture and acceptability (P < 0.05). The presence of a pre-finishing grazing period decreased intramuscular fat and increased the proportion of IIa compared with animals on concentrates, while no differences were found in sensory. Muscle colour, collagen, sarcomere length and instrumental texture were not modified by diet or castration. In conclusion, beef sensory characteristics were unaffected by diet, whereas castration resulted in a small improvement; however all the treatments produced an acceptable product

    Brucella abortus Infection of Placental Trophoblasts Triggers Endoplasmic Reticulum Stress-Mediated Cell Death and Fetal Loss via Type IV Secretion System-Dependent Activation of CHOP.

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    Subversion of endoplasmic reticulum (ER) function is a feature shared by multiple intracellular bacteria and viruses, and in many cases this disruption of cellular function activates pathways of the unfolded protein response (UPR). In the case of infection with Brucella abortus, the etiologic agent of brucellosis, the unfolded protein response in the infected placenta contributes to placentitis and abortion, leading to pathogen transmission. Here we show that B. abortus infection of pregnant mice led to death of infected placental trophoblasts in a manner that depended on the VirB type IV secretion system (T4SS) and its effector VceC. The trophoblast death program required the ER stress-induced transcription factor CHOP. While NOD1/NOD2 expression in macrophages contributed to ER stress-induced inflammation, these receptors did not play a role in trophoblast death. Both placentitis and abortion were independent of apoptosis-associated Speck-like protein containing a caspase activation and recruitment domain (ASC). These studies show that B. abortus uses its T4SS to induce cell-type-specific responses to ER stress in trophoblasts that trigger placental inflammation and abortion. Our results suggest further that in B. abortus the T4SS and its effectors are under selection as bacterial transmission factors.IMPORTANCE Brucella abortus infects the placenta of pregnant cows, where it replicates to high levels and triggers abortion of the calf. The aborted material is highly infectious and transmits infection to both cows and humans, but very little is known about how B. abortus causes abortion. By studying this infection in pregnant mice, we discovered that B. abortus kills trophoblasts, which are important cells for maintaining pregnancy. This killing required an injected bacterial protein (VceC) that triggered an endoplasmic reticulum (ER) stress response in the trophoblast. By inhibiting ER stress or infecting mice that lack CHOP, a protein induced by ER stress, we could prevent death of trophoblasts, reduce inflammation, and increase the viability of the pups. Our results suggest that B. abortus injects VceC into placental trophoblasts to promote its transmission by abortion

    Recording problems and diagnoses in clinical care: developing guidance for healthcare professionals and system designers

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    BACKGROUND: Accurate recording of problems and diagnoses in health records is key to safe and effective patient care, yet it is often done poorly. Electronic health record systems vary in their functionality and ease of use, and are not optimally designed for easy recording and sharing of clinical information. There is a lack of professional consensus and guidance on how problems and diagnoses should be recorded. METHODS: The Professional Record Standards Body commissioned work led by the Royal College of Physicians Health Informatics Unit to carry out a literature review, draft guidance, carry out an online consultation and round table discussion, and produce a report including recommendations for systems. A patient workshop was held to explore patient preferences for mechanisms for sharing diagnosis information between primary and secondary care. RESULTS: Consensus was reached among medical specialties on key elements of diagnosis recording, and draft guidance was produced ready for piloting in a variety of care settings. Patients were keen for better ways for diagnosis information to be shared. DISCUSSION: Improving the recording of diagnoses and problems will require a major effort of which the new guidance is only a part. The guidance needs to be embedded in training, and clinical systems need to have improved, standardised functionality. Front-line clinicians, specialist societies, clinical informaticians and patients need to be engaged in developing information models for diagnoses to support care and research, accessible via user-friendly interfaces

    Nonclassic lipoid congenital adrenal hyperplasia masquerading as familial glucocorticoid deficiency

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    Context: Familial glucocorticoid deficiency (FGD) is an autosomal recessive disorder resulting from resistance to the action of ACTH on the adrenal cortex. Affected individuals are deficient in cortisol and, if untreated, are likely to succumb to hypoglycemia and/or overwhelming infection. Mutations of the ACTH receptor (MC2R) and the melanocortin 2 receptor accessory protein (MRAP), FGD types 1 and 2 respectively, account for approximately 45% of cases. Objective: A locus on chromosome 8 has previously been linked to the disease in three families, but no underlying gene defect has to date been identified. Design: The study design comprised single-nucleotide polymorphism genotyping and mutation detection. Setting: The study was conducted at secondary and tertiary referral centers. Patients: Eighty probands from families referred for investigation of the genetic cause of FGD participated in the study. Interventions: There were no interventions. Results: Analysis by single-nucleotide polymorphism array of the genotype of one individual with FGD previously linked to chromosome 8 revealed a large region of homozygosity encompassing the steroidogenic acute regulatory protein gene, STAR. We identified homozygous STAR mutations in this patient and his affected siblings. Screening of our total FGD patient cohort revealed homozygous STAR mutations in a further nine individuals from four other families. Conclusions: Mutations in STAR usually cause lipoid congenital adrenal hyperplasia, a disorder characterized by both gonadal and adrenal steroid deficiency. Our results demonstrate that certain mutations in STAR (R192C and the previously reported R188C) can present with a phenotype indistinguishable from that seen in FGD

    Homozygous nonsense and frameshift mutations of the ACTH receptor in children with familial glucocorticoid deficiency (FGD) are not associated with long-term mineralocorticoid deficiency

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    Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease characterized by isolated glucocorticoid deficiency with preserved mineralocorticoid secretion. Mutations in the ACTH receptor (MC2R) account for approximately 25% of all FGD cases, but since these are usually missense mutations, a degree of receptor function is frequently retained. A recent report, however, suggested that disturbances in the renin-aldosterone axis were seen in some patients with potentially more severe MC2R mutations. Furthermore, MC2R knock out mice have overt aldosterone deficiency and hyperkalaemia despite preservation of a normal zona glomerulosa. We wished to determine whether a group of patients with severe nonsense mutations of the MC2R exhibited evidence of mineralocorticoid deficiency, thereby challenging the conventional diagnostic feature of FGD which might result in diagnostic misclassification
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