An isotope dilution model for partitioning of phenylalanine and tyrosine uptake by the liver of lactating dairy cows.

An isotope dilution model to describe the partitioning of phenylalanine and tyrosine in the bovine liver was developed. The model comprises four intracellular and six extracellular pools and various flows connecting these pools and external blood. Conservation of mass principles were applied to generate the fundamental equations describing the behaviour of the system in the steady state. The model was applied to datasets from multi-catheterised dairy cattle during a constant infusion of [1-13C]phenylalanine and [2,3,5,6-2H]tyrosine tracers. Model solutions described the extraction of phenylalanine and tyrosine from the liver via the portal vein and hepatic artery. In addition, the exchange of free phenylalanine and tyrosine between extracellular and intracellular pools was explained and the hydroxylation of phenylalanine to tyrosine was estimated. The model was effective in providing information about the fates of phenylalanine and tyrosine in the liver and could be used as part of a more complex system describing amino acid metabolism in the whole animal.

The Fellowship of the Royal College of Radiologists (FRCR) examination: a review of the evidence.

The Fellowship of the Royal College of Radiologists (FRCR) examination is the professional qualification that is essential for career progression in clinical radiology within the UK. It is also important for career progression in many countries internationally. The FRCR has evolved and changed over the last decade. In this systematic review we appraise and summarise the available data relating to the FRCR emphasising the published evidence regarding the validity, reliability, and acceptability of this examination. Comparison is made to other equivalent medical examinations, as well as a more recently published commissioned external review of the FRCR examinations. The Clinical Radiology Part 2B (CR2B) examination in its pre-existing format is reliable, valid, and acceptable. Recommendations from the commissioned external review are based primarily on expert opinion, with a limited evidence base comprising data from a small sample acquired during a single examination sitting and without peer review. Unlike the CR2B examination, there is little evidence regarding assessment of the CR1 and CR2 examinations. Both the CR1 and CR2 examinations are currently in the process of undergoing major changes to their formats. Blueprinting items to the curriculum might improve acceptability. Other changes may improve transparency and reliability of these assessments. Our analysis and many aspects of the external review may provide pointers regarding how the upcoming data produced by the "automated" FRCR examinations can be further analysed to provide a more robust evaluation.

Dietary mannoheptulose does not alter glucose or lipid metabolism in adult Labrador Retrievers.

Mannoheptulose (MH), a glycolytic inhibitor, has been preliminarily investigated as a novel functional food ingredient for dogs. This study aimed to determine the effects of dietary MH, delivered as an extract of un-ripened avocados, on fatty acid and glucose kinetics in healthy adult Labrador Retriever dogs (n = 12 dogs). The study was a double-blindcrossover with each dog receiving both dietary treatments, control (CON) and MH (400 mg/kg of diet), in random order. Glucose and glycerol plasma turnover (Ra) and oxidation (Ox) were measured in fasting and in response to repeated meal feeding ("fed") with stable isotope tracers (U-13 C-glucose, 1,1,2,3,3-D5 -glycerol) and indirect calorimetry. Palmitate Ra and Ox were examined during repeated meal feeding only using an oral bolus of U-13 C-K2 -palmitate and indirect calorimetry. MH had no discernible effect on fasting glucose Ra (677, 722 SEM 36 µmol/min, CON, MH) or Ox (107, 109 µmol/min, CON, MH SEM 10 µmol/min) or fed glucose Ra (2913, 3626 SEM 644 µmol/min, CON, MH) or Ox (951, 936 SEM 174 µmol/min, CON, MH). Glycerol Ra, an index of the rate of lipolysis, was not different between dietary treatments (Fast 162, 113 SEM 35 µmol/min CON, MH; Fed 172, 135 SEM 21 µmol/min, CON, MH). Similarly, palmitate oxidation was not impacted by MH feeding (1966, 2276 SEM 79 µmol/min, CON, MH). Together, these findings do not support MH as a novel functional food ingredient at least at the dietary dose tested.

Is the follow-up of small renal angiomyolipomas a necessary precaution?

AIM: To investigate the natural history and rationalize follow-up of renal angiomyolipomas (AMLs). MATERIALS AND METHODS: A prospectively gathered radiology database was scrutinized to identify patients with renal AMLs over a 3 year period (January 2006 to December 2008). Radiological investigations were examined to identify those AMLs exhibiting change during surveillance. RESULTS: A total of 135 patients were identified. Mean age at first detection was 49.6 years and patients were followed up for a median 21.8 months (6-85.3 months). Small AMLs (≤20 mm) were less likely to grow than their larger counterparts [odds ratio 13.3, confidence interval (95% CI) 1.4-123.9, p = 0.02] and exhibited a slower growth rate (0.7 versus 9.2 mm/year). Patients with AMLs that increased in size were significantly younger (median age 43 versus 52 years, p < 0.001). Multiple AMLs or those associated with genetic conditions grew at a significantly greater rate (3 versus 0.1 mm/year, p < 0.001). AMLs with a large extra-renal component are less reliably measured on ultrasound (median error 7 versus 1 mm, p < 0.001). CONCLUSION: This is the first study with the primary purpose to investigate growth of small AMLs (≤20 mm). Small, solitary AMLs (≤20 mm) do not require follow-up due to their low probability of growth. Patients with multiple AMLs and younger patients require closer monitoring due to their comparatively greater AML growth rate. Ultrasound-detected AMLs with an extra-renal component may require computed tomography (CT) to confirm their size.

Performance in the FRCR (UK) Part 2B examination: analysis of factors associated with success.

AIM: To assess factors that influence pass rates and examination scores in the Fellowship of the Royal College of Radiologists (FRCR) 2B examination. MATERIALS AND METHODS: 2238 attempts at the FRCR 2B examination were evaluated between Spring 2006 and Spring 2010. Pass rates and examination scores were analysed by gender and ethnicity, and the influence of factors such as radiology training (UK versus non-UK), sitting (Spring versus Autumn), and the presence of an undergraduate or postgraduate degree were examined. RESULTS: 1571 candidates made 2238 examination attempts, with an overall pass rate of 59.4% (63.1% at first attempt). 66.2% entrants were male; 48.8% attempts were by candidates from a UK radiology training scheme. UK candidates were significantly more likely to pass than non-UK candidates (p < 0.0001). White candidates were more likely to pass at first or second attempt than non-white candidates (p < 0.0001), but when restricted to UK entrants ethnicity did not influence success at first attempt. Overall, females were more successful than males (p < 0.001). Presence of an undergraduate (p = 0.19) or postgraduate (p = 0.80) degree did not affect pass rate at first attempt for UK candidates. However, logistic regression demonstrated that the only significant factor influencing pass rates at first attempt was whether radiology training was undertaken in the UK (p < 0.0001). A trend towards increased pass rates in autumn sittings was seen (p = 0.06), but ethnicity (p = 0.99) and gender (p = 0.41) were not significant factors. CONCLUSION: The FRCR 2B examination is non-discriminatory for UK candidates with respect to gender and ethnicity. Poorer performance of non-UK trained candidates is a consistent outcome in the literature.

The FRCR 2B oral examination: is it reliable?

AIM: To investigate the reliability of the oral component of the Fellowship of the Royal College of Radiologists (FRCR) 2B examination. MATERIALS AND METHODS: Anonymized candidate test scores were analysed from nine consecutive sittings of the FRCR 2B oral examination covering the period from spring 2006 to spring 2010. Interobserver reliability was assessed using weighted Kappa coefficient, intraclass correlation coefficient, and a modified Bland-Altman plot. RESULTS: During the study period, 2235 candidates sat the FRCR 2B examination. Eighty-five point one percent of candidates obtained paired oral assessment scores within one mark of each other. This figure rises to 95.7% for paired scores within 1.5 marks of each other. Mean difference in scores was 0.67 (95% CI: 0.65-0.70). Agreement rises at the extremities of mean score. Reliability coefficients for the FRCR 2B oral examination were calculated as 0.27 (weighted Kappa) and 0.44 (intraclass correlation coefficient). CONCLUSION: The calculated reliability coefficients indicate fair to, at best, moderate interobserver reliability in the FRCR 2B oral examination. These findings are disappointing but are comparable with other oral assessment reliability studies. There is scope for improvement, although further work to measure the combined reliability of all the components of the FRCR 2B examination is desirable. Measures that could potentially increase reliability must be carefully considered against any negative impact on test validity, acceptability, and cost.

Tuberculous pancreatitis complicated by ruptured splenic artery pseudoaneurysm.

Tuberculosis involving the pancreas is rare. We report a patient with pancreatic tuberculosis complicated by haemorrhage from a splenic artery pseudoaneurysm. As far as we are aware, the development of a splenic artery pseudoaneurysm in association with a large caseating mass of tuberculous pancreatic lymph nodes has not been reported previously. We review the literature and discuss the varied presentations of tuberculosis involving the pancreas or the pancreatic bed and its draining lymph nodes.

The FRCR 2B examination: a survey of candidate perceptions and experiences.

AIM: To survey the views of recent candidates of the Fellowship of the Royal College of Radiologists (FRCR) 2B examination with reference to assessment validity, reliability, and acceptability. MATERIALS AND METHODS: One thousand, two hundred and four UK radiology trainees and consultants were invited to complete an automated internet questionnaire regarding their experiences and perceptions of the FRCR 2B examination. The questionnaire was informed by a review of the literature. Eligible participants were candidates who had taken the examination within the previous 3 years. RESULTS: Four hundred and ninety-seven out of 1204 (41%) responses were received; of which 258/497 (52% of respondents) were eligible for inclusion into the study. The rapid reporting component is perceived to be significantly fairer than the oral section (82 versus 70% agree; p<0.001). The oral component fared poorly in perceived performance-reducing anxiety levels but well in questions relating to validity and reliability. Female candidates are more likely to find the FRCR 2B unfair (p=0.01) and experience performance-reducing anxiety (p<0.001) than males. No gender differences were observed in first-time pass rates (p=0.6). Candidate first language did not affect anxiety levels (p=0.9) or first-time pass rates (p=0.06). Only 12% of candidates agreed that the oral examination should move to an objective structured clinical format. CONCLUSION: Candidates score the FRCR 2B examination well in test validity with little desire for change to the oral examination format. Efforts to help reduce anxiety levels in the oral component would improve perceived fairness.

Workplace-based assessment in radiology-where to now?

Assessment of doctors is in a state of flux. Traditional methods of assessment have been critically examined and found inherently limited. The wholesale shift towards outcome-orientated education in the last 10 years has led to the relatively rapid development of a radically different method of assessment. This method focuses on assessing what doctors do in everyday practice rather than written or practical simulations. Known collectively as "workplace-based assessment" tools, these have been embraced in North America, whereas they have been more cautiously adopted in the UK. However, many of these assessment tools have not been rigorously studied and, moreover, few have been specifically developed for assessing radiologists. However, they are likely to be incorporated into radiology training in the near future. This paper critically analyses both the underpinning assumptions behind this method and the evidence behind existing tools, and looks at the work that is required to develop, adopt or adapt such tools for use in radiology.

Survey of Occupational and Environmental Exposure Monitoring Solutions.

INTRODUCTION: Service members are exposed to ambient airborne pollutants that have been linked to adverse health effects; however, capabilities to identify and characterize exposures across multi-domain operations are currently lacking. Occupational and environmental exposure monitoring is problematic because there is not a single simple solution, and current technological limitations suggest that simultaneous deployment of multiple devices may be the most effective near-term strategy. MATERIALS AND METHODS: A broad industry scan of wearable, handheld, or portable occupational and environmental exposure monitoring devices was conducted, and subject matter experts were interviewed about the state of the field. RESULTS: This survey identified limitations including the inability to detect multiple analytes or analyte classes, size and weight, and detection limits, but multiple implementation strategies could be employed to meet a variety of combat needs. Device types could be layered, or specific device types could be deployed in acute toxic exposure environments such as dense urban population centers or subterranean spaces. CONCLUSIONS: Evolving technologies and data management strategies may advance personal exposure monitoring in the future. These new devices and methods will likely supplant current technologies, while still using the programmatic and data framework established with early implementation of current commercial off the shelf devices.

Hit-and-run programming of therapeutic cytoreagents using mRNA nanocarriers.

Therapies based on immune cells have been applied for diseases ranging from cancer to diabetes. However, the viral and electroporation methods used to create cytoreagents are complex and expensive. Consequently, we develop targeted mRNA nanocarriers that are simply mixed with cells to reprogram them via transient expression. Here, we describe three examples to establish that the approach is simple and generalizable. First, we demonstrate that nanocarriers delivering mRNA encoding a genome-editing agent can efficiently knock-out selected genes in anti-cancer T-cells. Second, we imprint a long-lived phenotype exhibiting improved antitumor activities into T-cells by transfecting them with mRNAs that encode a key transcription factor of memory formation. Third, we show how mRNA nanocarriers can program hematopoietic stem cells with improved self-renewal properties. The simplicity of the approach contrasts with the complex protocols currently used to program therapeutic cells, so our methods will likely facilitate manufacturing of cytoreagents.Current widely used viral and electroporation methods for creating therapeutic cell-based products are complex and expensive. Here, the authors develop targeted mRNA nanocarriers that can transiently program gene expression by simply mixing them with cells, to improve their therapeutic potential.

The importance of appropriate frequency selection in sonographic gallstone detection.

A prospective study was performed on 161 patients referred for gallbladder ultrasound to determine whether routine use of a 5 MHz probe in addition to a standard 3.5 MHz probe provided useful additional information. Seventy-two patients were found to have gallstones. In 26.4% of these patients (19 cases) a confident diagnosis of gallstones was possible only when the 5 MHz probe was used. These results confirm theoretical assertions on the value of high-frequency probes in the evaluation of superficially located organs such as the gallbladder. Our findings lend support to their routine use in cholecystosonography.

The importance of pubic pain following childbirth: a clinical and ultrasonographic study of diastasis of the pubic symphysis.

This study aimed to investigate the diagnosis and consequences of pubic symphysis diastasis postpartum, in particular the use of ultrasonography to measure interpubic gap. It was a prospective follow-up study, which included an ultrasonographic comparison between symptomatic mothers and controls, set in Morriston Hospital, Swansea. Nine women presenting with unusual pubic pain post-partum were included: there were no exclusion criteria. Forty-two controls were also studied: the only exclusion criterion was unusual pubic pain. Interpubic gap was measured with ultrasonography. Follow up was undertaken for a median of 37 months (range 2-57). An abnormal interpubic gap was found in all symptomatic women. The incidence of diastasis was found to be at least one in 800 deliveries and significant long-term disability was found in three women. Diastasis is commoner than generally acknowledged and its consequences may be severe. Interpubic gap confirms diagnosis but does not appear to predict outcome. Ultrasonography aids diagnosis and follow up.

Single best answer MCQs: a new format for the FRCR part 2a exam.

The single best answer multiple-choice question (MCQ) format has many advantages over traditional true/false format MCQs. From 2009, the Royal College of Radiologists will be adopting this format for written examinations. This article describes the background of this decision and the evidence behind it. There are numerous benefits to examiners and candidates alike from adopting this format. Using examples, the usual structure of the format of this type of questions is explained, how they are written, and tips provided on how to prepare for and answer them.

Occurrence of antibodies against insect virus proteins in mammals: simple model to differentiate between passive exposure and active virus growth.

Antibodies against an "enterovirus-like" virus of insects, cricket paralysis virus, occur in the sera of domestic animals. When these antibodies were used in combination with the immunoprecipitation of radiolabeled virus proteins from infected Drosophila cells in culture, it could be demonstrated that the animals were exposed to preformed virus.

Perceived information needs and communication difficulties of inpatient physicians and nurses.

In order to understand the differing perceptions of information needs and communication patterns of healthcare professionals as they relate to medical errors, we conducted a survey and 5 focus group sessions of inpatient physicians and nurses. Although nurses and physicians stated differing information needs, both groups expressed significant problems with obtaining patient, domain and institution-specific information in a timely manner. Identification of appropriate providers and establishing contact with those people was perceived as the most pressing communication need. All focus group participants felt that communication difficulties were common and could give examples in which such difficulties led to adverse events. Our studies suggest that information needs and communication difficulties are common and can lead to medical errors or near misses. Many of these problems may be amenable to information technology solutions.