Phase II evaluation of VDC-1101 in canine cutaneous T-cell lymphoma.

BackgroundCanine cutaneous T-cell lymphoma (CTCL) is an uncommon disease for which efficacious therapies are lacking. The novel anticancer nucleotide prodrug VDC-1101 (formerly known as GS-9219) has shown efficacy in dogs with multicentric lymphoma. One of the observed adverse effects with this drug was a skin change characterized by hair loss, erythema, and pruritus, implying delivery of VDC-1101 to the skin.Hypothesis/objectivesThe primary study objective was to identify the objective response rate (ORR) to VDC-1101 in canine CTCL; secondary objectives included characterization of progression-free survival (PFS) and adverse events (AEs).AnimalsTwelve dogs with chemotherapy-naïve or relapsed, histologically and immunohistochemically confirmed CTCL.MethodsDogs received VDC-1101 as a 30-minute IV infusion once every 21 days. Prednisone (1 mg/kg PO q48h) was administered concurrently.ResultsIn 11 evaluable patients, responses included 1 complete response (CR), 4 partial responses (PR), 2 stable disease (SD), and 4 progressive disease for an ORR of 45% and biologic response rate (CR/PR/SD) of 64%. The median PFS was 37.5 days (26 to >399 days), which includes 1 durable and ongoing CR (>1 year). Gastrointestinal and hematologic AEs were mild; no dogs developed grade 3 or 4 AEs. Three dogs developed dermatopathies and 1 of these dogs was removed from the study as a result of this AE.Conclusions and clinical importanceVDC-1101 has activity against canine CTCL and could provide another treatment option in a disease process with a poor prognosis

Peritoneal implantation of ureter in cadaveric renal transplant

Case reportWe report here a case of complication of peritoneal implantation of ureter in cadaveric renal transplant. The patient presented with anuria and delayed graft function. The diagnosis was suspected upon physical examination and radiological investigation. The complication was managed with reimplantation of the ureter into the bladder and the patient recovered with good graft function. We discuss this case, review the literature on this rare complication, and share our suggestions on how it can be prevented.published_or_final_versio

Recent data on the prevalence of intestinal parasites in N’Djamena, Chad Republic

This cross sectional study assessed the prevalence of intestinal protozoan and helminth infections in N’Djamena, Chad Republic, and determined the main  epidemiological transmission factors of these pathogens in order to develop efficient control strategies of intestinal parasites. Four hundred and sixty two  randomly selected persons, from eight quarters (administrative districts), of age less than one year to seventy six years old of both sexes, were examined in  N’Djamena town. Out of the 462 samples, 235 (51%) were found to harbour at least one parasite species. The prevalences of the eight (8) parasite species detected were: Entamoeba histolytica (30%), Hymenolepis nana (13%), Ascaris  lumbricoides (10%), Trichomonas hominis (6%), Giardia intestinalis (3%),  hookworm (0.5%), and Schistosoma mansoni (0.2%). These pathogens appeared mostly in single infections. The quarters with higher infection indices were those that experienced floods (Abena and Chagoua) and where people do not use latrines (Naga and Goudji). The population customs and the environmental conditions in N’Djamena still favour high faecal- oral transmission of intestinal parasites.Key words: Prevalence, Intestinal Parasites, Protozoans, Helminths, N’Djamena, Chad

Determination of Chlorinated organic compounds in aqueous matrices

Thirteen pure volatile, semi-volatile and non-volatile chlorinated organic compounds of molecular weights ranging from trichloroethylene (MW = 131.39 g mole -¹) to hexachlorobenzene (MW = 284.78 g mole-¹) were determined in aqueous matrices by GC-ECD. After 10% salt addition, different extraction tests were performed using fibres whose adsorbing phase was based on microsphere carbon particles characterized by a constant size. Five experimental parameters were optimized: extraction temperature and time, position of the fibre in the GC injector port, desorption temperature and time. The optimized analytical protocol was employed to determine the efficiency of a real activated carbon adsorption plant to remove organic chlorinated pollutants from an industrial wastewater at ng l-¹ levels

A molecular mechanism of symmetry breaking in the early chick embryo

The first obvious sign of bilateral symmetry in mammalian and avian embryos is the appearance of the primitive streak in the future posterior region of a radially symmetric disc. The primitive streak marks the midline of the future embryo. The mechanisms responsible for positioning the primitive streak remain largely unknown. Here we combine experimental embryology and mathematical modelling to analyse the role of the TGFβ-related molecules BMP4 and Vg1/GDF1 in positioning the primitive streak. Bmp4 and Vg1 are first expressed throughout the embryo, and then become localised to the future anterior and posterior regions of the embryo, where they will, respectively, inhibit or induce formation of the primitive streak. We propose a model based on paracrine signalling to account for the separation of the two domains starting from a homogeneous array of cells, and thus for the topological transformation of a radially symmetric disc to a bilaterally symmetric embryo

Cultural Adaptation and Linguistic Validation of the Beliefs about Medicines Questionnaire in Malaysia

BACKGROUND: Low rate of adherence was found strongly associated with patients' beliefs across the studies about chronic diseases with hypertension. A crucial move is needed to bridge the gap between appropriate assessment tools and local hypertensive patients' medication adherence. OBJECTIVE: To produce a translated version in Malay language of Beliefs about Medicines Questionnaire (BMQ) that was "conceptually equivalent" to the original English version for use in local clinical practice and research. METHODS: The forward translation process was conducted by two independent professional translators and back translation was done by two other independent translators. A reliability analysis was conducted on 238 conveniently selected hypertensive patients. Intraclass correlation coefficient (ICC) was used to assess test-retest reliability for the randomly selected 40 patients in a period of 2 weeks. Discriminant validity was tested through Necessity-Concerns differential, BMQ subscales, and other parameters. RESULTS: The overall Cronbach alpha for the internal consistency was good (0.860). The subscales of the BMQ demonstrated adequate internal consistency, with Cronbach alpha value of 0.759 for Specific-Necessity, 0.762 for Specific Concern, 0.624 for General-Overuse, and 0.756 for General-Harm. The ICC was excellent (0.922). Discriminant validity revealed that BMQ Specific-Necessity score was significantly inversely correlated with the systolic blood pressure level. Systolic and diastolic blood pressure levels (P = 0.038; P = 0.05) were reported to be significantly correlated with the Necessity-Concerns differential, with Necessity score equal or exceeding Concerns score. CONCLUSIONS: The Malay-translated version of BMQ is a reliable and valid tool to assess patient belief about medication, especially medication adherence among the hypertensive patients in Malaysia

Quantifying the role and value of chemical looping combustion in future electricity systems via a retrosynthetic approach

Carbon capture and sequestration of CO2 from the combustion of fossil fuels in thermal power plants is expected to be important in the mitigation of climate change. Deployment however falls far short of what is required. A key barrier is the perception by developers and investors that these technologies are too inefficient, expensive and risky. To address these issues, we have developed a novel retrosynthetic approach to evaluate technologies and their design based on the demands of the system in which they would operate. We have applied it to chemical looping combustion (CLC), a promising technology, which enables carbon dioxide emissions to be inherently captured from the combustion of fossil fuels. Our approach has provided unique insight into the potential role and value of different CLC variants in future electricity systems and the likely impact of their integration on the optimal capacity mix, the operational and system cost, and dispatch patterns. The three variants investigated could all provide significant value by reducing the total investment and operational cost of a future electricity system. The minimisation of capital cost appears to be key for the attractiveness of CLC, rather than other factors such as higher efficiency or lower oxygen carrier costs

Coupled coarse graining and Markov Chain Monte Carlo for lattice systems

We propose an efficient Markov Chain Monte Carlo method for sampling equilibrium distributions for stochastic lattice models, capable of handling correctly long and short-range particle interactions. The proposed method is a Metropolis-type algorithm with the proposal probability transition matrix based on the coarse-grained approximating measures introduced in a series of works of M. Katsoulakis, A. Majda, D. Vlachos and P. Plechac, L. Rey-Bellet and D.Tsagkarogiannis,. We prove that the proposed algorithm reduces the computational cost due to energy differences and has comparable mixing properties with the classical microscopic Metropolis algorithm, controlled by the level of coarsening and reconstruction procedure. The properties and effectiveness of the algorithm are demonstrated with an exactly solvable example of a one dimensional Ising-type model, comparing efficiency of the single spin-flip Metropolis dynamics and the proposed coupled Metropolis algorithm.Comment: 20 pages, 4 figure