Long-term use of cyclosporine in liver recipients: Reduction of dosages in the first year to avoid nephrotoxicity

Cyclosporine is a potent immunosuppressive drug, which has dose-related nephrotoxicity. In renal transplantation, the differentiation between rejection and toxicity is difficult and even with the aid of blood levels of the drug, it may be difficult to establish a chronic maintenance dose. Long-term survivors after liver transplantation can provide modes with which to establish maintenance doses, as these are dictated by nephrotoxicity in these patients. Twenty-nine liver transplant patients who survived one year or more were followed for changes in their cyclosporine doses. Daily oral cyclosporine dose, BUN, serum creatinine and bilirubin were monitored. The reductions in cyclosporine were dictated almost entirely by the findings of nephrotoxicity. © 1983 by The Williams and Wilkins Co

Detection of the gas–liquid two-phase flow regimes using non-intrusive microwave cylindrical cavity sensor

Gas–liquid two-phase flow phenomenon occurs in various engineering applications and the measurement of it is important. A microwave sensor in the form of a cylindrical cavity has been designed to operate between 5 and 5.7 GHz. The aim is to analyse a two phase gas–liquid flow regime in a pipeline. LabVIEW software is utilised to capture the data, process them and display the results in real time. The results have shown that the microwave sensor has successfully detected the two-phase flow regimes in both the static and dynamic flow environments with reasonable accuracy. The study has also shown the independence of the technique and its accuracy to the temperature change (28–83 °C). Several flow regimes of the gas–liquid two-phase flow have been discussed. The system is also able to detect the stratified, wavy, elongated bubbles and homogeneous flow regimes

Concealed concern: Fathers' experience of having a child with Juvenile Idiopathic Arthritis

Despite increased research into families of chronically ill children, more needs to be known about the father’s experience. We address this issue through asking: ‘What is it like to be the father of a child with juvenile idiopathic arthritis?’ (JIA). Four members of eight families with an adolescent diagnosed with JIA, including seven fathers, were interviewed and transcripts analyzed using grounded theory. This study suggests that fathers of children with JIA experience several severe losses which are exacerbated through comparisons they make between their own situation and that of fathers of healthy children. In addition, the fathers faced several constraints which reduced their opportunities to communicate with their ill child through shared activities. Fathers appeared to conceal their distress by adopting strategies of denial and distraction however their adjustment was facilitated, to some extent, by social support. They could also develop greater acceptance of their situation over time as the care of their ill child became assimilated into family life and constraints upon their life gradually reduced through the increased maturity of their son or daughter with JIA. These findings have implications for healthcare professionals and voluntary organizations

Functional significance may underlie the taxonomic utility of single amino acid substitutions in conserved proteins

We hypothesized that some amino acid substitutions in conserved proteins that are strongly fixed by critical functional roles would show lineage-specific distributions. As an example of an archetypal conserved eukaryotic protein we considered the active site of ß-tubulin. Our analysis identified one amino acid substitution—ß-tubulin F224—which was highly lineage specific. Investigation of ß-tubulin for other phylogenetically restricted amino acids identified several with apparent specificity for well-defined phylogenetic groups. Intriguingly, none showed specificity for “supergroups” other than the unikonts. To understand why, we analysed the ß-tubulin Neighbor-Net and demonstrated a fundamental division between core ß-tubulins (plant-like) and divergent ß-tubulins (animal and fungal). F224 was almost completely restricted to the core ß-tubulins, while divergent ß-tubulins possessed Y224. Thus, our specific example offers insight into the restrictions associated with the co-evolution of ß-tubulin during the radiation of eukaryotes, underlining a fundamental dichotomy between F-type, core ß-tubulins and Y-type, divergent ß-tubulins. More broadly our study provides proof of principle for the taxonomic utility of critical amino acids in the active sites of conserved proteins

Successful Internalization of a Chronic Biliary Cutaneous Fistula After Liver Transplantation: Deepithelializing the Fistula Tract

Biliary cutaneous fistulas are uncommon sequelae after biliary surgery and can be a source of significant morbidity. We describe a liver recipient who developed a biliary cutaneous fistula secondary to hepatic artery thrombosis; this subsequently drained for over 7 years. Through a novel approach, using the transabdominal fistula tract as a conduit, the fistula skin opening was deepithelialized and anastomosed to a jejunal loop, internally draining the tract. For over 7 years postoperatively, this internal drainage procedure has continued to function effectively. This approach may have value in internalizing longstanding biliary cutaneous fistulas in well-selected patients in whom there is no existing biliary ductal system or the existing system anatomically does not lend itself to restoration of functional internal drainage through conventional approaches

Gac two-component system in Pseudomonas syringae pv. tabaci is required for virulence but not for hypersensitive reaction

Pseudomonas syringae pv. tabaci 6605 causes wildfire disease on host tobacco plants. To investigate the regulatory mechanism of the expression of virulence, Gac two-Component system-defective mutants, Delta gacA and Delta gacS, and a double mutant, Delta gacA Delta gacS, were generated. These mutants produced smaller amounts of N-acyl homoserine lactones required for quorum sensing, had lost swarming motility, and had reduced expression of virulence-related hrp genes and the algT gene required for exopolysaccharide production. The ability of the mutants to cause disease symptoms in their host tobacco plant was remarkably reduced, while they retained the ability to induce hypersensitive reaction (HR) in the nonhost plants. These results indicated that the Gac two-component system of P. syringae pv. tabaci 6605 is indispensable for virulence on the host plant, but not for HR induction in the nonhost plants.</p

An empirical analysis of supply and manufacturing risk and business performance: A Chinese manufacturing supply chain perspective

Purpose – This study explores the importance and impact of supply and manufacturing risk management upon business performance within the context of Chinese manufacturing supply chains. Design/Methodology/Approach – A two phased multi-method approach was adopted, which included a survey questionnaire to practitioners in Chinese manufacturing supply chains followed by semi-structured interviews. The findings included 103 valid survey responses complemented by six semi-structured interviews. Findings – The results indicate that in Chinese manufacturing context supply risk and manufacturing risk management are both vital for business performance. A high correlation between business and manufacturing risk management performance exists, however no significant impact of supplier dependency, systematic purchasing, maturity of production and supply chain, and human resources was found despite previously these elements being regarded as key influencers for supply and manufacturing risk management performance. The Chinese manufacturing supply chain indicated that elements such as the supplier and customer orientation, flexibility, manufacturing and supply risk highly connotes with business performance. Theoretical/Practical implications – In the current unpredictable and volatile business environment the competitiveness of manufacturing supply chains to a large extent depend on their ability to identify, assess and manage the manufacturing and supply risks. The findings of this study will assist supply chain managers in taking decision on manufacturing and supply risk management and reducing the uncertainty upon their business performance. Originality/value – The supply chain risk has been widely explored within the context of individual case studies, or standalone models focusing on either supply or manufacturing risk in supply chains, however to what extent this has been applicable to a wider context and its impact upon business process has not been explored. Hence, this study simultaneously has analysed manufacturing risk and supply risk and its impact upon Chinese manufacturing supply chains business performance. Moreover, this study uses a combination of quantitative and qualitative methods, which is often limited in this area. Finally, the institutional theory lens offers novel insights in better understanding the factors that can affect the impact of supply and manufacturing risk management upon business performance in those contexts, such as China, where the institutional aspect presents specific features

A bi-directional relationship between obesity and health-related quality of life : evidence from the longitudinal AusDiab study

Objective: To assess the prospective relationship between obesity and health-related quality of life, including a novel assessment of the impact of health-related quality of life on weight gain.Design and setting: Longitudinal, national, population-based Australian Diabetes, Obesity and Lifestyle (AusDiab) study, with surveys conducted in 1999/2000 and 2004/2005.Participants: A total of 5985 men and women aged 25 years at study entry.Main outcome measure(s): At both time points, height, weight and waist circumference were measured and self-report data on health-related quality of life from the SF-36 questionnaire were obtained. Cross-sectional and bi-directional, prospective associations between obesity categories and health-related quality of life were assessed.Results: Higher body mass index (BMI) at baseline was associated with deterioration in health-related quality of life over 5 years for seven of the eight health-related quality of life domains in women (all P0.01, with the exception of mental health, P&gt;0.05), and six out of eight in men (all P&lt;0.05, with the exception of role-emotional, P=0.055, and mental health, P&gt;0.05). Each of the quality-of-life domains related to mental health as well as the mental component summary were inversely associated with BMI change (all P&lt;0.0001 for women and P0.01 for men), with the exception of vitality, which was significant in women only (P=0.008). For the physical domains, change in BMI was inversely associated with baseline general health in women only (P=0.023).Conclusions: Obesity was associated with a deterioration in health-related quality of life (including both physical and mental health domains) in this cohort of Australian adults followed over 5 years. Health-related quality of life was also a predictor of weight gain over 5 years, indicating a bi-directional association between obesity and health-related quality of life. The identification of those with poor health-related quality of life may be important in assessing the risk of future weight gain, and a focus on health-related quality of life may be beneficial in weight management strategies.<br /

Optimizing administrative datasets to examine acute kidney injury in the era of big data: Workgroup statement from the 15^th ADQI Consensus Conference

Purpose of review: The purpose of this review is to report how administrative data have been used to study AKI, identify current limitations, and suggest how these data sources might be enhanced to address knowledge gaps in the field. Objectives: 1) To review the existing evidence-base on how AKI is coded across administrative datasets, 2) To identify limitations, gaps in knowledge, and major barriers to scientific progress in AKI related to coding in administrative data, 3) To discuss how administrative data for AKI might be enhanced to enable "communication" and "translation" within and across administrative jurisdictions, and 4) To suggest how administrative databases might be configured to inform 'registry-based' pragmatic studies. Source of information: Literature review of English language articles through PubMed search for relevant AKI literature focusing on the validation of AKI in administrative data or used administrative data to describe the epidemiology of AKI. Setting: Acute Dialysis Quality Initiative (ADQI) Consensus Conference September 6-7th, 2015, Banff, Canada Patients: Hospitalized patients with AKI Key messages: The coding structure for AKI in many administrative datasets limits understanding of true disease burden (especially less severe AKI), its temporal trends, and clinical phenotyping. Important opportunities exist to improve the quality and coding of AKI data to better address critical knowledge gaps in AKI and improve care. Methods: A modified Delphi consensus building process consisting of review of the literature and summary statements were developed through a series of alternating breakout and plenary sessions. Results: Administrative codes for AKI are limited by poor sensitivity, lack of standardization to classify severity, and poor contextual phenotyping. These limitations are further hampered by reduced awareness of AKI among providers and the subjective nature of reporting. While an idealized definition of AKI may be difficult to implement, improving standardization of reporting by using laboratory-based definitions and providing complementary information on the context in which AKI occurs are possible. Administrative databases may also help enhance the conduct of and inform clinical or registry-based pragmatic studies. Limitations: Data sources largely restricted to North American and Europe Implications: Administrative data are rapidly growing and evolving, and represent an unprecedented opportunity to address knowledge gaps in AKI. Progress will require continued efforts to improve awareness of the impact of AKI on public health, engage key stakeholders, and develop tangible strategies to reconfigure infrastructure to improve the reporting and phenotyping of AKI. Why is this review important?: Rapid growth in the size and availability of administrative data has enhanced the clinical study of acute kidney injury (AKI). However, significant limitations exist in coding that hinder our ability to better understand its epidemiology and address knowledge gaps. The following consensus-based review discusses how administrative data have been used to study AKI, identify current limitations, and suggest how these data sources might be enhanced to improve the future study of this disease. What are the key messages?: The current coding structure of administrative data is hindered by a lack of sensitivity, standardization to properly classify severity, and limited clinical phenotyping. These limitations combined with reduced awareness of AKI and the subjective nature of reporting limit understanding of disease burden across settings and time periods. As administrative data become more sophisticated and complex, important opportunities to employ more objective criteria to diagnose and stage AKI as well as improve contextual phenotyping exist that can help address knowledge gaps and improve care

Medical students' personal experience of high-stakes failure:case studies using interpretative phenomenological analysis

Abstract (provisional): Background Failing a high-stakes assessment at medical school is a major event for those who go through the experience. Students who fail at medical school may be more likely to struggle in professional practice, therefore helping individuals overcome problems and respond appropriately is important. There is little understanding about what factors influence how individuals experience failure or make sense of the failing experience in remediation. The aim of this study was to investigate the complexity surrounding the failure experience from the student’s perspective using interpretative phenomenological analysis (IPA). Methods The accounts of 3 medical students who had failed final re-sit exams, were subjected to in-depth analysis using IPA methodology. IPA was used to analyse each transcript case-by-case allowing the researcher to make sense of the participant’s subjective world. The analysis process allowed the complexity surrounding the failure to be highlighted, alongside a narrative describing how students made sense of the experience. Results The circumstances surrounding students as they approached assessment and experienced failure at finals were a complex interaction between academic problems, personal problems (specifically finance and relationships), strained relationships with friends, family or faculty, and various mental health problems. Each student experienced multi-dimensional issues, each with their own individual combination of problems, but experienced remediation as a one-dimensional intervention with focus only on improving performance in written exams. What these students needed to be included was help with clinical skills, plus social and emotional support. Fear of termination of the their course was a barrier to open communication with staff. Conclusions These students’ experience of failure was complex. The experience of remediation is influenced by the way in which students make sense of failing. Generic remediation programmes may fail to meet the needs of students for whom personal, social and mental health issues are a part of the picture