Effect of solidification rate on microstructure evolution in dual phase microalloyed steel.

In steels the dependence of ambient temperature microstructure and mechanical properties on solidification rate is not well reported. In this work we investigate the microstructure and hardness evolution for a low C low Mn NbTi-microalloyed steel solidified in the cooling rate range of 1-50 Cs-1. The maximum strength was obtained at the intermediate solidification rate of 30 Cs-1. This result has been correlated to the microstructure variation with solidification rate.

Liver enzymes and clustering cardiometabolic risk factors in European adolescents: the HELENA study.

OBJECTIVES: This study aimed to explore the associations of liver biomarkers with cardiometabolic risk factors and their clustering, and to provide reference values (percentiles) and cut-off points for liver biomarkers associated with high cardiometabolic risk in European adolescents. METHODS: Alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), aspartate aminotransferase to ALT ratio (AST/ALT), waist circumference, blood pressure, triglycerides, high-density lipoprotein cholesterol and insulin were measured in 1084 adolescents. We computed a continuous cardiometabolic risk score and defined the high cardiometabolic risk. RESULTS: Higher ALT and GGT and lower AST/ALT were associated with adiposity and with the number of adverse cardiometabolic risk factors (Ps < 0.05). Higher GGT and lower AST/ALT were associated with higher cardiometabolic risk score (Ps < 0.001) in males and females, and ALT only in males (Ps < 0.001). Gender- and age-specific percentiles for liver biomarkers were provided. Receiver operating characteristic analyses showed a significant discriminatory accuracy of AST/ALT in identifying the low/high cardiometabolic risk (Ps < 0.01) and thresholds were provided. CONCLUSIONS: Higher GGT and lower AST/ALT are associated with higher cardiometabolic risk factors and their clustering in male and female European adolescents, whereas the associations of ALT were gender dependent. Our results suggest the usefulness of AST/ALT as a screening test in the assessment of adolescents with high cardiometabolic risk and provide gender- and age-specific thresholds that might be of clinical interest.

Gas formation. Formation temperatures of thermogenic and biogenic methane.

Methane is an important greenhouse gas and energy resource generated dominantly by methanogens at low temperatures and through the breakdown of organic molecules at high temperatures. However, methane-formation temperatures in nature are often poorly constrained. We measured formation temperatures of thermogenic and biogenic methane using a "clumped isotope" technique. Thermogenic gases yield formation temperatures between 157° and 221°C, within the nominal gas window, and biogenic gases yield formation temperatures consistent with their comparatively lower-temperature formational environments (<50°C). In systems where gases have migrated and other proxies for gas-generation temperature yield ambiguous results, methane clumped-isotope temperatures distinguish among and allow for independent tests of possible gas-formation models.

An eight month randomized controlled exercise intervention alters resting state synchrony in overweight children.

Children with low aerobic fitness have altered brain function compared to higher-fit children. This study examined the effect of an 8-month exercise intervention on resting state synchrony. Twenty-two sedentary, overweight (body mass index ≥85th percentile) children 8-11 years old were randomly assigned to one of two after-school programs: aerobic exercise (n=13) or sedentary attention control (n=9). Before and after the 8-month programs, all subjects participated in resting state functional magnetic resonance imaging scans. Independent components analysis identified several networks, with four chosen for between-group analysis: salience, default mode, cognitive control, and motor networks. The default mode, cognitive control, and motor networks showed more spatial refinement over time in the exercise group compared to controls. The motor network showed increased synchrony in the exercise group with the right medial frontal gyrus compared to controls. Exercise behavior may enhance brain development in children.

Measurement and compartmental modeling of the effect of CYP3A5 gene variation on systemic and intrarenal tacrolimus disposition.

We evaluated the hypothesis that cytochrome P450 3A5 (CYP3A5) expression can affect intrarenal tacrolimus accumulation. Tacrolimus was administered orally to 24 healthy volunteers who were selected on the basis of their CYP3A5 genotype. As compared with CYP3A5 nonexpressors, expressors had a 1.6-fold higher oral tacrolimus clearance and 2.0- to 2.7-fold higher metabolite/parent area under the curve (AUC) ratios for 31-desmethyl tacrolimus (31-DMT), 12-hydroxy tacrolimus, and 13-desmethyl tacrolimus (13-DMT). In addition, the apparent urinary tacrolimus clearance was 36% lower in CYP3A5 expressors as compared with nonexpressors. To explore the mechanism behind this observation, we developed a semiphysiological model of renal tacrolimus disposition and predicted that tacrolimus exposure in the renal epithelium of CYP3A5 expressors is 53% of that for CYP3A5 nonexpressors, when normalized to blood AUC. These data suggest that, at steady state, intrarenal accumulation of tacrolimus and its primary metabolites will depend on the CYP3A5 genotype of the liver and kidneys. This may contribute to interpatient differences in the risk of tacrolimus-induced nephrotoxicity.

Simultaneous liver-kidney transplantation: a survey of US transplant centers.

Consensus recommendations have been published to help better define those patients who would benefit from simultaneous liver-kidney transplantation (SLK). We conducted a survey of transplant centers that perform SLK (n = 88, 65% response rate) to determine practice patterns in the United States. The majority of centers (73%) stated that they use dialysis duration whereas only 30% of centers use acute kidney injury duration as a criterion for determining need for SLK. Dialysis duration >4 weeks was used by 32% of centers, >6 weeks by 37% and >8 weeks by 32% of centers. Glomerular filtration rate (GFR) was estimated using the modified diet in renal disease (MDRD)-4 equation in roughly half of centers whereas the MDRD-6 equation was used by only 6%. In patients with chronic kidney disease, GFR < 40 mL/min was used by 24% of centers as a criterion for SLK transplants instead of the recommended threshold of < 30 mL/min. Regional differences in practices were also observed. This survey demonstrates significant variation in the criteria used for SLK among transplant centers, with few centers following the current published recommendations, and emphasizes the need for evidence-based guidelines and uniformity in studying renal dysfunction in liver transplant candidates.

Simultaneous liver-kidney transplantation summit: current state and future directions.

Although previous consensus recommendations have helped define patients who would benefit from simultaneous liver-kidney transplantation (SLK), there is a current need to reassess published guidelines for SLK because of continuing increase in proportion of liver transplant candidates with renal dysfunction and ongoing donor organ shortage. The purpose of this consensus meeting was to critically evaluate published and registry data regarding patient and renal outcomes following liver transplantation alone or SLK in liver transplant recipients with renal dysfunction. Modifications to the current guidelines for SLK and a research agenda were proposed.

Risk factors for late-onset cytomegalovirus disease in donor seropositive/recipient seronegative kidney transplant recipients who receive antiviral prophylaxis.

BACKGROUND: Cytomegalovirus (CMV) disease occurs frequently after cessation of antiviral prophylaxis in CMV-seronegative kidney transplant recipients from seropositive donors (D+R-), and the risk factors are incompletely defined. METHOD: We retrospectively assessed the incidence, clinical features, and risk factors for CMV disease in a cohort of D+R- kidney transplant recipients who received antiviral prophylaxis at a single US transplant center using descriptive statistics and Cox proportional hazards models. RESULTS: CMV disease developed in 29 of 113 (26%) D+R- patients at a median of 185 days (interquartile range 116-231 days) post transplant, including CMV syndrome (66%) and tissue invasive disease (34%). The incidence of CMV disease was higher in patients who underwent re-transplantation (57% vs. 24%) and this factor was independently associated with a higher risk of CMV disease in multivariable analysis (hazard ratio, 4.02; 95% confidence interval, 1.3-13; P = 0.016). Other demographic and transplant variables were not independently associated with a risk of late-onset CMV disease. CONCLUSIONS: Despite a comprehensive analysis of patient and transplant variables, only re-transplantation was identified as a risk factor for CMV disease in D+R- kidney transplant recipients who received antiviral prophylaxis, but had limited clinical predictive value. The development of novel laboratory markers to identify patients at greatest risk for CMV disease should be a priority for future studies.

Adolescent Transition to Adult Care in Solid Organ Transplantation: a consensus conference report.

Transition of care from pediatric to adult-oriented health care providers is difficult for children with special health care needs. Children who have received solid organ transplants and their providers experience the same difficulties and frustrations as children with other major illnesses. A consensus conference was organized by several transplant organizations to identify major issues in this area and recommend possible approaches to easing the process of transition for solid organ transplant recipients. This report summarizes the discussions and recommendations.

Proceedings of Consensus Conference on Simultaneous Liver Kidney Transplantation (SLK).

A consensus conference sponsored by the American Society of Transplant Surgeons (ASTS), American Society of Transplantation (AST), United Network for Organ Sharing (UNOS) and American Society of Nephrology (ASN) convened to examine simultaneous liver-kidney transplantation (SLK). Directors from the 25 largest liver transplant programs along with speakers with recognized expertise attended. The purposes of this conference were to propose indications for SLK, to establish a prospective data registry and, most importantly, to recommend standard listing criteria for these patients. Scientific registry of transplant recipients data, and single center data regarding chronic kidney disease (CKD) and acute kidney injury (AKI) in conjunction with liver failure as a basis for SLK was presented and discussed. The consensus was that Regional Review Boards (RRB) should determine listing for SLK, as with other MELD exceptions, with automatic approval for: (i) End-stage renal disease with cirrhosis and symptomatic portal hypertension or hepatic vein wedge pressure gradient >/= 10 mm Hg (ii) Liver failure and CKD with GFR /= 2.0 mg/dL and dialysis >/= 8 weeks (iv) Liver failure and CKD and biopsy demonstrating > 30% glomerulosclerosis or 30% fibrosis. The RRB would evaluate all other requests to determine appropriateness.

Simultaneous liver-kidney transplantation: evaluation to decision making.

Questions about appropriate allocation of simultaneous liver and kidney transplants (SLK) are being asked because kidney dysfunction in the context of liver failure enhances access to deceased donor organs. There is specific concern that some patients who undergo combined liver and kidney transplantation may have reversible renal failure. There is also concern that liver transplants are placed prematurely in those with end-stage renal disease. Thus to assure allocation of transplants only to those truly in need, the transplant community met in March 2006 to review post-MELD (model for end-stage liver disease) data on the impact of renal function on liver waitlist and transplant outcomes and the results of SLK.

Tubular basement membrane immune deposits in association with BK polyomavirus nephropathy.

Tubular basement membrane immune deposits (TBMID) are rare in renal allografts and usually have been found in association with immune complex mediated glomerular injury. We report an association between TBMID and BK polyomavirus nephropathy (BKN). We reviewed clinical data and results of allograft biopsies of 30 patients with BKN (16 with and 14 without TBMID). TBMID were detected by immunofluorescence or electron microscopy. Initial and follow-up biopsies were assessed for degree of interstitial inflammation and fibrosis and severity of viral infection, and were correlated with patients' clinical data. Biopsies initially diagnostic for BKN with TBMID, compared to BKN biopsies without deposits, demonstrated more severe interstitial inflammation and fibrosis, and greater numbers of virally infected cells. Similar findings were present in follow-up biopsies. Utilizing three different antibodies directed against viral epitopes, viral antigens could not be detected within TBMID. Thirty percent of patients with TBMID and 70% without deposits had follow-up biopsies, in which virus could not be detected immunohistochemically. Treatment for all included decreasing immunosuppression, cidofovir and/or leflunomide. Clinical data correlated well with histological findings. We conclude that a significant proportion of patients with BKN show TBMID on kidney biopsy. The prognostic significance of this finding remains to be elucidated.

Investigation of the microstructure and mesotexture formed during thermomechanical controlled rolling in microalloyed steels.

Thermomechanical controlled rolling (TMCR) has been widely used as an effective method to improve the properties of steels. In the present paper, two commercial TMCR microalloyed steels were investigated. The grain size distributions and grain boundary misorientation angles were measured using electron backscattered diffraction patterns obtained using orientation imaging microscopy (OIM). The equivalent grain diameters were also measured using optical microscopy. Mixed coarse- and fine-grained regions were observed and the microhardness values were measured for both areas. Grain boundary misorientation angle distributions showed that the magnitude of mesotexture developed in the steel is dependent upon the rolling passes, the reduction ratio and the rolling temperatures including the finish rolling temperature. The surface layer, up to 2 mm depth, in Com-A steel had about 55% of grain boundaries with a misorientation angle below 12 degrees, much higher than in the central area ( approximately 30%), whereas Com-B steel showed similar distributions from the rolling surface to the centre. Misorientation results obtained from laboratory rolled steel plates with various TMCR procedures are also discussed as are OIM results from Charpy impact brittle fracture surfaces examining the effect of misorientation on crack propagation.

Differences in understanding of specialist palliative care amongst service providers and commissioners in South London.

This paper describes a study that sought to identify service providers' and commissioners' understanding of specialist palliative care within the context of changing service provision in one area of South London. Using a formative evaluation framework, we examined the views of 44 providers and commissioners from statutory and voluntary health and social care services about their understanding of specialist palliative care services and, in particular, the remit of current service provision delivered by a Marie Curie Centre. Face-to-face audiotaped semi-structured interviews were conducted. A qualitative thematic analysis highlighted a number of issues including a lack of consensus about definitions of palliative care, ambivalence about referral procedures, and a lack of role clarity between specialist and generalist palliative care providers. The study took place within the real world context of changing services and economic pressures. This raises methodological issues about how services are evaluated and what terminology is used to describe end-of-life care. The study findings confirm that confusion about terminology and referral criteria remain major issues for clinical workers and organizations seeking to access services.

Licensure of the cardiac sonographer: an overview of issues and activities.

The impact of echocardiography on the continuum of cardiovascular health care is well established. Ongoing concerns regarding costs, accessibility, quality, and appropriateness of services rendered by practitioners of echocardiography have prompted various legislative proposals and regulatory policies from government, medical professional groups, and health plans. Specifically, there continues to be a drive to enact law for licensure of sonographers. These activities require continuing advocacy for the profession with active leadership. As part of its mission statement, the American Society of Echocardiography (ASE) states, "ASE strives to be a leader in public policy in order to create a favorable environment for excellence in the practice of echocardiography." As such, the ASE is committed to an increase in their interaction with legislators, payers, and policy makers. This article describes the historical perspective of state, federal, and provincial sonographer licensure issues to provide an understanding of the political perspectives.

Pre-transplant cardiac testing for kidney-pancreas transplant candidates and association with cardiac outcomes.

BACKGROUND: Coronary artery disease is a major cause of mortality following renal transplantation, especially in those patients with diabetes. The accurate prediction of cardiac risk is therefore a major focus of the pre-transplant evaluation. The objective of this study was to retrospectively evaluate the ability of non-invasive cardiac testing (standard echocardiography, stress echocardiography, exercise tolerance testing, and nuclear myocardial perfusion) performed within 1 yr of kidney-pancreas transplant to predict post-transplant myocardial infarction. METHODS: Clinical history and pre-transplant cardiac testing performed within 1 yr prior to transplantation were reviewed in a non-blinded fashion for 165 kidney-pancreas transplantation patients receiving allografts between June 1990 and May 1998. The predictive values of clinical symptoms and cardiac testing for cardiac events (fatal and non-fatal myocardial infarctions) up to 1 yr post-transplant were calculated. RESULTS: Clinical history had a negative predictive value of 98% for cardiac events occurring within 1 yr following testing and 97% within 1 yr post-transplant. Collectively, non-invasive testing had a negative predictive value of 97% for 1 yr post-testing and 1 yr post-transplant. CONCLUSION: Clinical history alone is highly suggestive but not sufficient for the prediction of post-kidney-pancreas transplant myocardial infarction. Although a useful supplement, cardiac testing does not predict all cardiac events out to 1 yr post-testing. In this high-risk patient population with diabetes and renal failure, other methods of risk assessment are needed to more accurately predict long-term cardiac outcome for patients awaiting transplantation.

Receiving a diagnosis of lung cancer: patients' interpretations, perceptions and perspectives.

Lung cancer has a higher incidence than any other type of cancer and more than 80% of sufferers die within a year of diagnosis. An important aspect of caring for cancer patients is the breaking of bad news, something that most doctors admit to having difficulty with. Only a few publications on this issue adopt the patients' perspective. This study aimed to document patients' views on delivery of lung cancer diagnoses, their attitudes to methods used and ideas for improvement. Patients were selected from medical, surgical and general practitioner clinics to provide insight into patients' perceptions of care in different environments. Those who gave informed consent completed a taped semi-structured interview. Transcripts were analysed qualitatively using a phenomenological approach. Recruitment was stopped when saturation was reached: no new themes were being identified. A summary of results was sent to patients, whenever possible, for their comment. An independent researcher coded four transcripts to establish the degree of inter-rater reliability. Thirteen patients were recruited. There were five key areas: communication (including the use of words such as 'tumour' and 'growth'), family/community issues, reaction to diagnosis, views on treatment and prognosis (all of which were very variable), and suggested improvements (e.g. a clearer explanation of the experience of bronchoscopy in the patient information leaflet, PIL). Inter-rater reliability was good. The PIL is being revised. Factors including family situation and personal experience of illness vary greatly and yet they influence patients' reactions to receiving a diagnosis of lung cancer, their interpretation of this and their attitudes to the illness and treatment. These findings underline the need to continue to develop lung cancer services that can provide quality care tailored to each patient.