Malignant and noninvasive skin tumours in renal transplant recipients.

Background. Transplant recipients require immunosuppression to prevent graft rejection. This conveys an increased risk of malignancy, particularly skin tumours. There is a need for up-to-date data for the South of England. Method. Pathology records were reviewed for 709 kidney transplant recipients on immunosuppression at our hospital from 1995 to 2008. Skin tumours were recorded/analysed. Results. Mean age at transplant was 46 years. Mean length of follow-up was 7.2 years and total follow-up was 4926 person-years. 53 (7.5%) patients (39/458 (8.5%) males and 14/251 (5.6%) females) developed ≥1 skin malignancy. Cumulative incidences of 4.0%, 7.5%, and 12.2% were observed for those with <5, <10, and ≥10 years follow-up, respectively. The rate was 45 tumours per 1000 person-years at risk. Additionally, 21 patients (3.0%) only had noninvasive tumours. 221 malignant skin tumours were found: 50.2% were SCCs, 47.1% BCCs, and 2.7% malignant melanomas. Mean years to first tumour were 5.8. Mean number of tumours per patient was 4, with mean interval of 12 months. Conclusions. Despite changes in transplantation practice during the time since the last data were published in this region, these findings are similar to previous studies. This adds to the evidence allowing clinicians to inform patients in this region of their risk

Changes in life-style after liver transplantation

Sixty-five pediatric patients who received liver transplants between May 1981 and May 1984 were observed for as many as 5 years and examined for changes in life-style. Children were less frequently hospitalized, spent less time hospitalized, required fewer medications, and generally had excellent liver and renal function after hepatic transplantation as compared with their pretransplantation status. Most children were in age-appropriate and standard school classes or were only 1 year behind. Cognitive abilities remained unchanged. Children improved in gross motor function and patients' behavior significantly improved according to parents' perceptions. Enuresis was more prevalent, however, than in the population of children who had not received liver transplants. Parental divorce rates were no greater than those reported for other families with chronically ill children. Overall, objective changes in life-style as well as parents' perceptions of behavior of children appear to be improved after liver transplantation

Experience in hepatic resection for metastatic colorectal cancer: Analysis of clinical and pathologic risk factors

Background. The selection of patients for resective therapy of hepatic colorectal metastases remains controversial. A number of clinical and pathologic prognostic risk factors have been variably reported to influence survival. Methods. Between January 1981 and December 1991, 204 patients underwent curative hepatic resection for metastatic colorectal cancer. Fourteen clinical and pathologic determinants previously reported to influence outcome were examined retrospectively. This led to a proposed TNM staging system for metastatic colorectal cancer (mTNM). Results. No operative deaths occurred (death within 1 month). Overall 1-, 3-, and 5-year survivals were 91%, 43%, and 32%, respectively. Gender, Dukes' classification, site of primary colorectal cancer, histologic differentiation, size of metastatic tumor, and intraoperative blood transfusion requirement were not statistically significant prognostic factors (p > 0.05). Age of 60 years or more, interval of 24 months or less between colorectal and hepatic resection, four or more gross tumors, bilobar involvement, positive resection margin, lymph node involvement, and direct invasion to adjacent organs were significant poor prognostic factors (p < 0.05). In the absence of nodal disease or direct invasion, patients with unilobar solitary tumor of any size, or unilobar multiple tumors of 2 cm or smaller (stages I and II) had the highest survival rates of 93% at 1 year, 68% at 3 years, and 61% at 5 years. Unilobar disease with multiple lesions greater than 2 cm (stage III) resulted in 1-, 3-, and 5-year survivals of 98%, 45%, and 28%, respectively. Patients with bilobar involvement (multiple tumors, any size, or a single large metastasis) (stage IVA) had survival rates of 88% at 1 year, 28% at 3 years, and 20% at 5 years (p < 0.00001). Patients with nodal involvement or extrahepatic disease (stage IVB) experienced the poorest outcome with 1-, 3- , and 5-year survivals of 80%, 12%, and 0%, respectively (p < 0.00001). Conclusions. The proposed mTNM staging system appears to be useful in predicting the outcomes after hepatic resection of metastatic colorectal tumors

Outcomes-based Contracting and Public Management Reform: Lessons from a Decade of Experimentation

A decade after the launch of the world’s first social impact bond (SIB) at Her Majesty’s Prison Peterborough in England, a further 250 SIBs have been developed in over 30 countries raising over $750 m (USD) of capital and serving some 1.7 million people. As investment-backed outcomes-based contracts (OBCs), SIBs are one of many outcomes-oriented reforms being taken up globally. In this introduction, we offer a framework for navigating the inchoate landscape of these reforms and a brief review of literature on OBCs and SIBs to frame the articles in this special issue. We then underscore the major contributions of the six included articles before offering summaries of each. In closing, we discuss the article findings and offer avenues for future research

Diffusion flame attachment and flame front propagation along mixing layers

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Deciphering the response of Mycobacterium smegmatis to nitrogen stress using bipartite active modules.

Background The ability to adapt to environments with fluctuating nutrient availability is vital for bacterial survival. Although essential for growth, few nitrogen metabolism genes have been identified or fully characterised in mycobacteria and nitrogen stress survival mechanisms are unknown. Results A global transcriptional analysis of the mycobacterial response to nitrogen stress, showed a significant change in the differential expression of 16% of the Mycobacterium smegmatis genome. Gene expression changes were mapped onto the metabolic network using Active Modules for Bipartite Networks (AMBIENT) to identify metabolic pathways showing coordinated transcriptional responses to the stress. AMBIENT revealed several key features of the metabolic response not identified by KEGG enrichment alone. Down regulated reactions were associated with the general reduction in cellular metabolism as a consequence of reduced growth rate. Up-regulated modules highlighted metabolic changes in nitrogen assimilation and scavenging, as well as reactions involved in hydrogen peroxide metabolism, carbon scavenging and energy generation. Conclusions Application of an Active Modules algorithm to transcriptomic data identified key metabolic reactions and pathways altered in response to nitrogen stress, which are central to survival under nitrogen limiting environments

Liposome-based drug delivery in breast cancer treatment

Drug delivery systems can in principle provide enhanced efficacy and/or reduced toxicity for anticancer agents. Long circulating macromolecular carriers such as liposomes can exploit the 'enhanced permeability and retention' effect for preferential extravasation from tumor vessels. Liposomal anthracyclines have achieved highly efficient drug encapsulation, resulting in significant anticancer activity with reduced cardiotoxicity, and include versions with greatly prolonged circulation such as liposomal daunorubicin and pegylated liposomal doxorubicin. Pegylated liposomal doxorubucin has shown substantial efficacy in breast cancer treatment both as monotherapy and in combination with other chemotherapeutics. Additional liposome constructs are being developed for the delivery of other drugs. The next generation of delivery systems will include true molecular targeting; immunoliposomes and other ligand-directed constructs represent an integration of biological components capable of tumor recognition with delivery technologies

Impaired health-related quality of life in children and adolescents with chronic conditions: a comparative analysis of 10 disease clusters and 33 disease categories/severities utilizing the PedsQL™ 4.0 Generic Core Scales

<p>Abstract</p> <p>Background</p> <p>Advances in biomedical science and technology have resulted in dramatic improvements in the healthcare of pediatric chronic conditions. With enhanced survival, health-related quality of life (HRQOL) issues have become more salient. The objectives of this study were to compare generic HRQOL across ten chronic disease clusters and 33 disease categories/severities from the perspectives of patients and parents. Comparisons were also benchmarked with healthy children data.</p> <p>Methods</p> <p>The analyses were based on over 2,500 pediatric patients from 10 physician-diagnosed disease clusters and 33 disease categories/severities and over 9,500 healthy children utilizing the PedsQL™ 4.0 Generic Core Scales. Patients were recruited from general pediatric clinics, subspecialty clinics, and hospitals.</p> <p>Results</p> <p>Pediatric patients with diabetes, gastrointestinal conditions, cardiac conditions, asthma, obesity, end stage renal disease, psychiatric disorders, cancer, rheumatologic conditions, and cerebral palsy self-reported progressively more impaired overall HRQOL than healthy children, respectively, with medium to large effect sizes. Patients with cerebral palsy self-reported the most impaired HRQOL, while patients with diabetes self-reported the best HRQOL. Parent proxy-reports generally paralleled patient self-report, with several notable differences.</p> <p>Conclusion</p> <p>The results demonstrate differential effects of pediatric chronic conditions on patient HRQOL across diseases clusters, categories, and severities utilizing the PedsQL™ 4.0 Generic Core Scales from the perspectives of pediatric patients and parents. The data contained within this study represents a larger and more diverse population of pediatric patients with chronic conditions than previously reported in the extant literature. The findings contribute important information on the differential effects of pediatric chronic conditions on generic HRQOL from the perspectives of children and parents utilizing the PedsQL™ 4.0 Generic Core Scales. These findings with the PedsQL™ have clinical implications for the healthcare services provided for children with chronic health conditions. Given the degree of reported impairment based on PedsQL™ scores across different pediatric chronic conditions, the need for more efficacious targeted treatments for those pediatric patients with more severely impaired HRQOL is clearly and urgently indicated.</p

Mixed pathologies including chronic traumatic encephalopathy account for dementia in retired Association football (soccer) players

In retired professional Association football (soccer) players with a past history of repetitive head impacts, chronic traumatic encephalopathy (CTE) is a potential neurodegenerative cause of dementia and motor impairments. From 1980 to 2010, 14 retired footballers with dementia were followed up regularly until death. Their clinical data, playing career and concussion history were prospectively collected. Next-of-kin consented for six to have post-mortem brain examination. Of the 14 male participants, 13 were professional and 1 was a committed amateur. All were skilled headers of the ball and had played football for an average of 26 years. Concussion rate was limited in six cases to one episode each during their careers. All cases developed progressive cognitive impairment with an average age at onset of 63.6 years and disease duration of 10 years. Neuropathological examination revealed septal abnormalities in all six post-mortem cases, supportive of a history of chronic repetitive head impacts. Four cases had pathologically confirmed CTE; concomitant pathologies included Alzheimer’s disease (N=6), TDP-43 (N=6), cerebral amyloid angiopathy (N=5), hippocampal sclerosis (N=2), corticobasal degeneration (N=1), dementia with Lewy bodies (N=1) and vascular pathology (N=1), all would have contributed synergistically to the clinical manifestations. The pathological diagnosis of CTE was established in four individuals according to the latest consensus diagnostic criteria. This finding is probably related to their past prolonged exposure to repetitive head impacts from head-to-player collisions and heading the ball thousands of time throughout their careers. Alzheimer’s disease and TDP-43 pathologies are common concomitant findings in CTE, both of which are increasingly considered as part of the CTE pathological entity in older individuals. Association Football is the most popular sport in the world and the potential link between repetitive head impacts from playing football and CTE as indicated from our findings is of considerable public health interest. Clearly a definitive link cannot be established in this clinico-pathological series, but our findings support the need for further systematic investigation including large scale case-control studies to identify at risk groups of footballers which will justify for the implementation of protective strategies