Non-AIDS defining cancers in the D:A:D Study-time trends and predictors of survival : a cohort study

BACKGROUND:Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.METHODS:Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.RESULTS:Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.CONCLUSIONS:The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC

The effect of pretreatment of allogeneic bone marrow graft recipients with antilymphocytic serum on the acute graft-versus-host reaction in monkeys

Short-term pretreatment of irradiated, bone marrow-treated monkeys with horse antilymphocyte serum (ALS) roughly doubles the survival time by decreasing the severity and delaying the onset of acute secondary disease in random host-donor combinations. It was found that (1) horse anti monkey serum does not interfere with the take and proliferation of the graft, and that (2) rabbit anti monkey serum acts less selectively, as shown by a high incidence of transplant failures. The absence of signs of stem cell toxicity in monkeys treated with horse ALS cannot be attributed to a lower degree of immunosuppression, because lower doses of rabbit ALS are as toxic as larger doses. The use of ALS for pretreatment of human bone marrow recipients is recommended, but, for the time being, only horse serum should be used. The effective dose of horse ALS for monkeys is in the order of 60 mg of IgG/ kg body wt/ day. Pretreatment for 2 days seems to be adequate

Exome sequencing in patients with chronic central serous chorioretinopathy

Contains fulltext : 203997.pdf (publisher's version ) (Open Access

Properties of non-polar a-plane GaN/AlGaN quantum wells

The structural and optical properties of a series of GaN/Al0.18Ga0.82N multiple quantum well (MQW) structures, in which the well thickness was varied between 2 and 8 nm, grown on a-plane (1 1 0) GaN on r-plane (1 0 2) sapphire substrates have been investigated. High-resolution X-ray diffraction and low-angle X-ray reflectivity measurements were used to determine the well and barrier thicknesses and the barrier composition after matrix transformation of the (binary) elastic constants for the appropriate coordinates, and assuming a pseudo-morphically strained system. The microstructure of the (1 1 0) samples is dominated by I1-type basal-plane stacking faults (BSF) terminated by partial dislocations or prismatic stacking faults, as determined by conventional and high-resolution transmission electron microscopy. The low temperature photoluminescence (PL) spectra of the QW structures show two emission bands which are assigned (partly based on photoluminescence excitation (PLE) spectroscopy) to excitons that are confined solely by the quantum wells and, at lower energy, those carriers that recombine in the region where the wells are intersected by BSFs. Both bands shift to higher energy with decreasing quantum well thickness. The optical data indicate that the non-polar (1 1 0) GaN/AlGaN system is free of polarization-induced electric fields, since the QW exciton emission energy is not below the band-edge emission energy of the GaN template

Screening of nutritional status in The Netherlands

Background and Aims: In 2001, the Dutch Dietetic Association conducted a national screening on malnutrition. The goal of this screening was to determine the prevalence of disease-related malnutrition in The Netherlands in all fields of medical care and to investigate the involvement of the dietitian in the treatment of malnutrition. Methods: Eight thousand five hundred and twenty nine patients were screened of which data of 7606 patients could be analysed. Eighty one per cent (6150) of the patients were hospital patients. Eleven per cent (808) of the patients lived in a nursing home. Seven per cent (533) of the patients were home-care patients, who were measured at home or at the general practitioner's office. The origin of 115 patients (2%) was not registered. Age, height, weight, unintentional weight loss, kind of illness and intervention by a dietitian were registered. Malnutrition was defined as >10% unintentional weight loss during the past 6 months and risk of malnutrition was defined as 5-10% unintentional weight loss during the past 6 months. Results: Twelve per cent (884) of all patients appeared to be malnourished. Thirteen per cent (962) were at risk of malnutrition and 75% (5760) were well nourished. Fifty four per cent of the malnourished patients were referred to a dietitian. Oncological disease was more associated with malnutrition than non-oncological disease (in particular in the head and neck, lung and intestinal areas). Also, non-oncological gastro-intestinal and lung disease patients were often categorised as malnourished. Elderly patients (>75 years) were more at risk of malnutrition. BMI and unintentional weight loss did not correlate well. Conclusion: In this national survey conducted by dietitians, including a convenience sample of mainly institutionalised patients, approximately 25% of patients in all medical fields were categorised as moderately or severely malnourished. About half of these patients were seen by a dietitian. (C) 2003 Elsevier Science Ltd. All rights reserved

The ADAMTS18 gene is responsible for autosomal recessive early onset severe retinal dystrophy

Contains fulltext : 117740.pdf (publisher's version ) (Open Access)BACKGROUND: Inherited retinal dystrophies, including Retinitis Pigmentosa and Leber Congenital Amaurosis among others, are a group of genetically heterogeneous disorders that lead to variable degrees of visual deficits. They can be caused by mutations in over 100 genes and there is evidence for the presence of as yet unidentified genes in a significant proportion of patients. We aimed at identifying a novel gene for an autosomal recessive form of early onset severe retinal dystrophy in a patient carrying no previously described mutations in known genes. METHODS: An integrated strategy including homozygosity mapping and whole exome sequencing was used to identify the responsible mutation. Functional tests were performed in the medaka fish (Oryzias latipes) model organism to gain further insight into the pathogenic role of the ADAMTS18 gene in eye and central nervous system (CNS) dysfunction. RESULTS: This study identified, in the analyzed patient, a homozygous missense mutation in the ADAMTS18 gene, which was recently linked to Knobloch syndrome, a rare developmental disorder that affects the eye and the occipital skull. In vivo gene knockdown performed in medaka fish confirmed both that the mutation has a pathogenic role and that the inactivation of this gene has a deleterious effect on photoreceptor cell function. CONCLUSION: This study reveals that mutations in the ADAMTS18 gene can cause a broad phenotypic spectrum of eye disorders and contribute to shed further light on the complexity of retinal diseases