Burden And Pattern Of Cancer In Western Kenya

Background: Cancer regisries worldwide have evolved to provide useful information on the burden and diversity of the patterns of cancer, information that is vital for establishing appropriate programmes for disease management. Population based data on cancer in western Kenya as captured in the Eldoret cancer registry established in1999 is analysed and reported in this paper.Objective: To determine the burden and pattern of cancer in Western Kenya by use of data from the Eldoret cancer registry.Design: Retrospective study.Setting: The cancer registry located in the Department of Haematology at the Moi University, School of Medicine situated at the Moi Teaching and Referral Hospital, Eldoret, Kenya. The hospital has a catchment population of 13 to 15 million people forming about 40% of the Kenyan population.Results: A total of 5,366 patients were diagnosed to have cancer and attended to at the MTRH and other hospitals in Eldoret during the period between January 1999 and December 2006 giving an average of 671 cases per year. Among those treated 2,699 were males and 2,667 were females giving a M: F ratio of 1:1. About 21% of the patients had haematological malignancies with non-Hodgkins lymphoma being the most common.Another 79% of the patients had solid tumours with cancer of the oesophagus being the commonest. Cancer of the cervix and prostrate were the commonest among the females and males respectively. A general increase in the number of patients with Kaposis sarcoma associated with HIV/AIDS pandemic was observed.Conclusion: The burden of cancer is a significant health problem in western Kenya and there is need for the development of a comprehensive cancer care programme in the region to address the growing problem

Clinical impact of FDG PET-CT on management decisions for patients with primary biliary tumours

Objectives: To assess the impact on clinical management of introducing 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)-computed tomography (CT) in to the work-up of patients with primary and recurrent biliary malignancy. Methods: Consecutive patients with primary biliary tumours undergoing FDG PET-CT at a single large tertiary referral centre between November 2007 and September 2010 were retrospectively analysed. Findings on FDG PET-CT compared with CT/magnetic resonance imaging (MRI) and impact on subsequent patient management were evaluated. Impact was divided into: (1) major—detection of occult disease or characterisation of indeterminate lesion(s) on CT/MRI; (2) minor—confirmation of suspected metastases seen on CT/MRI; (3) no impact. Results: One hundred and eleven patients underwent 118 FDG PET-CT scans, including 30 with suspected gallbladder carcinoma and 81 with cholangiocarcinoma. Eighty-nine scans were performed for initial staging, five for restaging following neoadjuvant chemotherapy and 24 for suspected disease recurrence. In 33 cases (28 %), FDG PET-CT had a major impact on subsequent patient management (39 % gallbladder carcinoma, 26 % intrahepatic cholangiocarcinoma and 21 % extrahepatic cholangiocarcinoma). FDG PET-CT had a minor impact in 20 cases (17 %) and no impact in 65 cases (55 %). Conclusions: By detecting occult metastatic disease and characterising indeterminate lesions, FDG PET-CT can have a major influence on clinical decision-making in primary and recurrent biliary malignancy

Ex vivo and In vivo Evaluation of Chitosan Coated Nanostructured Lipid Carriers for Ocular Delivery of Acyclovir

Background: Herpes keratitis is the most common infectious cause of blindness in the developed world. It may be treated by acyclovir (ACV), however this antiviral drug is poorly soluble with low ocular bioavailability requiring high and frequent dosing. Nanostructured lipid carriers (NLCs) were investigated to improve the ocular bioavailability of ACV by enhancing corneal penetration as well as prolonging the exposure of infected cells to the antiviral agent. Methods: Cell uptake studies, ex vivo tolerance and cell uptake efficacy as well as in vivo corneal permeation of the developed lipid based formulations were investigated. NLCs were fabricated by the hot microemulsion technique and coated with 0.5% w/v chitosan. NLCs were capable of increasing the cell uptake of encapsulated fluorescein and ACV as examined by fluorescence microscopy and high performance liquid chromatography (HPLC) respectively. Results: When entrapped in NLCs, the antiviral efficacy of ACV was increased by 3.5 fold after 24 hrs of exposure. The in vivo corneal permeation of the formulation was studied on Albino rabbits with NLCs capable of increasing the corneal bioavailability by 4.5 fold when compared to a commercially available ACV ophthalmic ointment. Conclusion: NLCs enhanced the ocular bioavailability and antiviral properties of ACV through cell internalisation, sustained release, and increased corneal permeation

Clinical impact and diagnostic accuracy of 2-[18F]-fluoro-2-deoxy-d-glucose positron-emission tomography/computed tomography (PET/CT) brain imaging in patients with cognitive impairment: a tertiary centre experience in the UK

Aim To evaluate the clinical impact of combined 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) positron-emission tomography/computed tomography (PET/CT) brain imaging performed in selected patients with cognitive impairment at a tertiary referral centre in the UK, and to assess the accuracy of FDG PET/CT to correctly establish the diagnosis of Alzheimer's dementia (AD) in “real-world” clinical practice. Methods and materials Using an institutional radiology database, 136 patients were identified for inclusion in the study. FDG PET/CT was performed using a standard technique and interpreted by dual-trained radiologists and nuclear medicine physicians. Standardised questionnaires were sent to the referring clinicians to establish the final clinical diagnosis and to obtain information about the clinical impact of FDG PET/CT. Results There was a 72% questionnaire return (98/136), with mean patient follow-up of 471 (standard deviation 205) days. FDG PET/CT had an impact on patient management in 81%, adding confidence to the pre-test diagnosis in 43%, changing the pre-test diagnosis in 35%, reducing the need for further investigations in 42%, and resulting in a change in therapy in 32%. There was substantial correlation between the PET/CT diagnosis and final clinical diagnosis with a correlation (k) coefficient of 0.78 (p<0.0001). The accuracy of FDG PET/CT in diagnosis of AD was 94% (95% confidence interval [CI]: 87–99), with a sensitivity of 87% (95% CI: 75–92) and a specificity of 97% (95% CI: 87–99). Conclusion FDG PET/CT brain imaging has a significant clinical impact when performed selectively in patients with cognitive impairment and shows high accuracy in the diagnosis of AD in “real-world” clinical practice

EmLog:Tamper-Resistant System Logging for Constrained Devices with TEEs

Remote mobile and embedded devices are used to deliver increasingly impactful services, such as medical rehabilitation and assistive technologies. Secure system logging is beneficial in these scenarios to aid audit and forensic investigations particularly if devices bring harm to end-users. Logs should be tamper-resistant in storage, during execution, and when retrieved by a trusted remote verifier. In recent years, Trusted Execution Environments (TEEs) have emerged as the go-to root of trust on constrained devices for isolated execution of sensitive applications. Existing TEE-based logging systems, however, focus largely on protecting server-side logs and offer little protection to constrained source devices. In this paper, we introduce EmLog -- a tamper-resistant logging system for constrained devices using the GlobalPlatform TEE. EmLog provides protection against complex software adversaries and offers several additional security properties over past schemes. The system is evaluated across three log datasets using an off-the-shelf ARM development board running an open-source, GlobalPlatform-compliant TEE. On average, EmLog runs with low run-time memory overhead (1MB heap and stack), 430--625 logs/second throughput, and five-times persistent storage overhead versus unprotected logs.Comment: Accepted at the 11th IFIP International Conference on Information Security Theory and Practice (WISTP '17

Simulation method for investigating the use of transition-edge sensors as spectroscopic electron detectors

Transition-edge sensors (TESs) are capable of highly accurate single particle energy measurement. TESs have been used for a wide range of photon detection applications, particularly in astronomy, but very little consideration has been given to their capabilities as electron calorimeters. Existing electron spectrometers require electron filtering optics to achieve energy discrimination, but this step discards the vast majority of electrons entering the instrument. TESs require no such energy filtering, meaning they could provide orders of magnitude improvement in measurement rate. To investigate the capabilities of TESs in electron spectroscopy, a simulation pipeline has been devised. The pipeline allows the results of a simulated experiment to be compared with the actual spectrum of the incident beam, thereby allowing measurement accuracy and efficiency to be studied. Using Fisher information, the energy resolution of the simulated detectors was also calculated, allowing the intrinsic limitations of the detector to be separated from the specific data analysis method used. The simulation platform has been used to compare the performance of TESs with existing X-ray photoelectron spectroscopy (XPS) analysers. TESs cannot match the energy resolution of XPS analysers for high-precision measurements but have comparable or better resolutions for high count rate applications. The measurement rate of a typical XPS analyser can be matched by an array of 10 TESs with 120 microsecond response times and there is significant scope for improvement, without compromising energy resolution, by increasing array size

Feasibility of a streamlined imaging protocol in technetium-99m-Tektrotyd somatostatin receptor SPECT/CT

Aim: To assess the feasibility and efficacy of a streamlined single time-point 99m Tc-HYNIC-Tyr3-octreotide (Tektrotyd) somatostatin receptor scintigraphy (SRS) protocol to differentiate pathological uptake by neuroendocrine tumours (NETs) from physiological activity. Methods and materials: Tektrotyd imaging in 50 consecutive patients with NETs was reviewed retrospectively. Imaging was independently assessed by two experienced reporters with dual-certification in radiology and nuclear medicine and agreed in consensus. The presence of physiological bowel activity and/or further sites of equivocal uptake on 4-hour planar imaging and whether combined single-photon-emission computed tomography (SPECT)/computed tomography (CT) assessment allowed accurate diagnosis was tabulated. A judgement was also made in each case on whether 2-hour planar imaging was necessary for accurate diagnostic interpretation. Results: Thirty-six patients (72%) had positive findings on Tektrotyd SPECT/CT. Eight patients (16%) had bowel activity on 4-hour planar imaging, which could be considered to have hampered interpretation without access to SPECT/CT. Eleven studies in 10 patients (20%) demonstrated areas of indeterminate uptake on planar imaging; five in the uncinate process of the pancreas, three in the nasal cavity or paranasal sinuses, one in the adrenal glands, one in a focus of inflammation on the posterior abdominal wall, and one at the tip of a central venous line. In all cases, accurate interpretation of findings was possible with SPECT/CT, without the 2-hour planar image. Conclusion: Two-hour planar imaging could be safely omitted from Tektrotyd SRS incorporating SPECT/CT imaging without reducing the accuracy of diagnostic interpretation. Streamlined imaging has the potential to reduce patient inconvenience and improve scanner and staff efficiency

The extraordinary evolutionary history of the reticuloendotheliosis viruses

The reticuloendotheliosis viruses (REVs) comprise several closely related amphotropic retroviruses isolated from birds. These viruses exhibit several highly unusual characteristics that have not so far been adequately explained, including their extremely close relationship to mammalian retroviruses, and their presence as endogenous sequences within the genomes of certain large DNA viruses. We present evidence for an iatrogenic origin of REVs that accounts for these phenomena. Firstly, we identify endogenous retroviral fossils in mammalian genomes that share a unique recombinant structure with REVs—unequivocally demonstrating that REVs derive directly from mammalian retroviruses. Secondly, through sequencing of archived REV isolates, we confirm that contaminated Plasmodium lophurae stocks have been the source of multiple REV outbreaks in experimentally infected birds. Finally, we show that both phylogenetic and historical evidence support a scenario wherein REVs originated as mammalian retroviruses that were accidentally introduced into avian hosts in the late 1930s, during experimental studies of P. lophurae, and subsequently integrated into the fowlpox virus (FWPV) and gallid herpesvirus type 2 (GHV-2) genomes, generating recombinant DNA viruses that now circulate in wild birds and poultry. Our findings provide a novel perspective on the origin and evolution of REV, and indicate that horizontal gene transfer between virus families can expand the impact of iatrogenic transmission events

Metabolic acetate therapy improves phenotype in the tremor rat model of Canavan disease

Genetic mutations that severely diminish the activity of aspartoacylase (ASPA) result in the fatal brain dysmyelinating disorder, Canavan disease. There is no effective treatment. ASPA produces free acetate from the concentrated brain metabolite, N-acetylaspartate (NAA). Because acetyl coenzyme A is a key building block for lipid synthesis, we postulated that the inability to catabolize NAA leads to a brain acetate deficiency during a critical period of CNS development, impairing myelination and possibly other aspects of brain development. We tested the hypothesis that acetate supplementation during postnatal myelination would ameliorate the severe phenotype associated with ASPA deficiency using the tremor rat model of Canavan disease. Glyceryltriacetate (GTA) was administered orally to tremor rats starting 7 days after birth, and was continued in food and water after weaning. Motor function, myelin lipids, and brain vacuolation were analyzed in GTA-treated and untreated tremor rats. Significant improvements were observed in motor performance and myelin galactocerebroside content in tremor rats treated with GTA. Further, brain vacuolation was modestly reduced, and these reductions were positively correlated with improved motor performance. We also examined the expression of the acetyl coenzyme A synthesizing enzyme acetyl coenzyme A synthase 1 and found upregulation of expression in tremor rats, with a return to near normal expression levels in GTA-treated tremor rats. These results confirm the critical role played by NAA-derived acetate in brain myelination and development, and demonstrate the potential usefulness of acetate therapy for the treatment of Canavan disease