Neurocognitive function in HIV infected patients on antiretroviral therapy

OBJECTIVE To describe factors associated with neurocognitive (NC) function in HIV-positive patients on stable combination antiretroviral therapy. DESIGN We undertook a cross-sectional analysis assessing NC data obtained at baseline in patients entering the Protease-Inhibitor-Monotherapy-Versus-Ongoing-Triple therapy (PIVOT) trial. MAIN OUTCOME MEASURE NC testing comprised of 5 domains. Raw results were z-transformed using standard and demographically adjusted normative datasets (ND). Global z-scores (NPZ-5) were derived from averaging the 5 domains and percentage of subjects with test scores >1 standard deviation (SD) below population means in at least two domains (abnormal Frascati score) calculated. Patient characteristics associated with NC results were assessed using multivariable linear regression. RESULTS Of the 587 patients in PIVOT, 557 had full NC results and were included. 77% were male, 68% Caucasian and 28% of Black ethnicity. Mean (SD) baseline and nadir CD4+ lymphocyte counts were 553(217) and 177(117) cells/µL, respectively, and HIV RNA was <50 copies/mL in all. Median (IQR) NPZ-5 score was -0.5 (-1.2/-0) overall, and -0.3 (-0.7/0.1) and -1.4 (-2/-0.8) in subjects of Caucasian and Black ethnicity, respectively. Abnormal Frascati scores using the standard-ND were observed in 51%, 38%, and 81%, respectively, of subjects overall, Caucasian and Black ethnicity (p<0.001), but in 62% and 69% of Caucasian and Black subjects using demographically adjusted-ND (p = 0.20). In the multivariate analysis, only Black ethnicity was associated with poorer NPZ-5 scores (P<0.001). CONCLUSIONS In this large group of HIV-infected subjects with viral load suppression, ethnicity but not HIV-disease factors is closely associated with NC results. The prevalence of abnormal results is highly dependent on control datasets utilised. TRIAL REGISTRY ClinicalTrials.gov, NCT01230580

Quantum systems in weak gravitational fields

Fully covariant wave equations predict the existence of a class of inertial-gravitational effects that can be tested experimentally. In these equations inertia and gravity appear as external classical fields, but, by conforming to general relativity, provide very valuable information on how Einstein's views carry through in the world of the quantum.Comment: 22 pages. To be published in Proceedings of the 17th Course of the International School of Cosmology and Gravitation "Advances in the interplay between quantum and gravity physics" edited by V. De Sabbata and A. Zheltukhin, Kluwer Academic Publishers, Dordrech

Trends in the prevalence and management of diagnosed type 2 diabetes 1994–2001 in England and Wales

BACKGROUND: Type 2 diabetes is an important cause of morbidity and mortality. Its prevalence appears to be increasing. Guidelines exist regarding its management. Recommendations regarding drug therapy have changed. Little is known about the influence of these guidelines and changed recommendations on the actual management of patients with type 2 diabetes. This study aims to document trends in the prevalence, drug treatment and recording of measures related to the management of type 2 diabetes; and to assess whether recommended targets can be met. METHODS: The population comprised subjects registered between 1994 and 2001 with 74 general practices in England and Wales which routinely contribute to the Doctors' Independent Network database. Approximately 500,000 patients and 10,000 type 2 diabetics were registered in each year. RESULTS: Type 2 diabetes prevalence rose from 17/1000 in 1994 to 25/1000 in 2001. Drug therapy has changed: use of long acting sulphonylureas is falling while that of short acting sulphonylureas, metformin and newer therapies including glitazones is increasing. Electronic recording of HbA1c, blood pressure, cholesterol and weight have risen steadily, and improvements in control of blood pressure and cholesterol levels have occurred. However, glycaemic control has not improved, and obesity has increased. The percentage with a BMI under 25 kg/m(2 )fell from 27.0% in 1994 to 19.4% in 2001 (p < 0.001). CONCLUSION: Prevalence of type 2 diabetes is increasing. Its primary care management has changed in accordance with best evidence. Monitoring has improved, but further improvement is possible. Despite this, glycaemic control has not improved, while the prevalence of obesity in the diabetic population is rising

The impact of low erythrocyte density in human blood on the fitness and energetic reserves of the African malaria vector Anopheles gambiae

Background Anaemia is a common health problem in the developing world. This condition is characterized by a reduction in erythrocyte density, primarily from malnutrition and/or infectious diseases such as malaria. As red blood cells are the primary source of protein for haematophagous mosquitoes, any reduction could impede the ability of mosquito vectors to transmit malaria by influencing their fitness or that of the parasites they transmit. The aim of this study was to determine the impact of differences in the density of red blood cells in human blood on malaria vector (Anopheles gambiae sensu stricto) fitness. The hypotheses tested are that mosquito vector energetic reserves and fitness are negatively influenced by reductions in the red cell density of host human blood meals commensurate with those expected from severe anaemia. Methods Mosquitoes (An. gambiae s.s.) were offered blood meals of different packed cell volume(PCV) of human blood consistent with those arising from severe anaemia (15%) and normalPCV (50%). Associations between mosquito energetic reserves (lipid, glucose and glycogen)and fitness measures (reproduction and survival) and blood meal PCV were investigated. Results The amount of protein that malaria vectors acquired from blood feeding (indexed by haematin excretion) was significantly reduced at low blood PCV. However, mosquitoes feeding on blood of low PCV had the same oviposition rates as those feeding on blood of normal PCV, and showed an increase in egg production of around 15%. The long-term survival of An. gambiae s.s was reduced after feeding on low PCV blood, but PCV had no significant impact on the proportion of mosquitoes surviving through the minimal period required to develop and transmit malaria parasites (estimated as 14 days post-blood feeding). The impact of blood PCV on the energetic reserves of mosquitoes was relatively minor. Conclusions These results suggest that feeding on human hosts whose PCV has been depleted due to severe anaemia does not significantly reduce the fitness or transmission potential of malaria vectors, and indicates that mosquitoes may be able exploit resources for reproduction more efficiently from blood of low rather than normal PCV

Identifying sources, pathways and risk drivers in ecosystems of Japanese Encephalitis in an epidemic-prone north Indian district

Japanese Encephalitis (JE) has caused repeated outbreaks in endemic pockets of India. This study was conducted in Kushinagar, a highly endemic district, to understand the human-animal-ecosystem interactions, and the drivers that influence disease transmission. Utilizing the ecosystems approach, a cross-sectional, descriptive study, employing mixed methods design was employed. Four villages (two with pig-rearing and two without) were randomly selected from a high, a medium and a low burden (based on case counts) block of Kushinagar. Children, pigs and vectors were sampled from these villages. A qualitative arm was incorporated to explain the findings from the quantitative surveys. All human serum samples were screened for JE-specific IgM using MAC ELISA and negative samples for JE RNA by rRT-PCR in peripheral blood mononuclear cells. In pigs, IgG ELISA and rRT-PCR for viral RNA were used. Of the 242 children tested, 24 tested positive by either rRT-PCR or MAC ELISA; in pigs, 38 out of the 51 pigs were positive. Of the known vectors, Culex vishnui was most commonly isolated across all biotopes. Analysis of 15 blood meals revealed human blood in 10 samples. Univariable analysis showed that gender, religion, lack of indoor residual spraying of insecticides in the past year, indoor vector density (all species), and not being vaccinated against JE in children were significantly associated with JE positivity. In multivariate analysis, only male gender remained as a significant risk factor. Based on previous estimates of symptomatic: asymptomatic cases of JE, we estimate that there should have been 618 cases from Kushinagar, although only 139 were reported. Vaccination of children and vector control measures emerged as major control activities; they had very poor coverage in the studied villages. In addition, lack of awareness about the cause of JE, lack of faith in the conventional medical healthcare system and multiple referral levels causing delay in diagnosis and treatment emerged as factors likely to result in adverse clinical outcomes

Surgical management of mesh-related complications after prior pelvic floor reconstructive surgery with mesh

Contains fulltext : 96379.pdf (publisher's version ) (Closed access)INTRODUCTION AND HYPOTHESIS: The objective of this study is to evaluate the complications and anatomical and functional outcomes of the surgical treatment of mesh-related complications. METHODS: A retrospective cohort study of patients who underwent complete or partial mesh excision to treat complications after prior mesh-augmented pelvic floor reconstructive surgery was conducted. RESULTS: Seventy-three patients underwent 30 complete and 51 partial mesh excisions. Intraoperative complications occurred in 4 cases, postoperative complications in 13. Symptom relief was achieved in 92% of patients. Recurrence of pelvic organ prolapse (POP) occurred in 29% of complete and 5% of partial excisions of mesh used in POP surgery. De novo stress urinary incontinence (SUI) occurred in 36% of patients who underwent excision of a suburethral sling. CONCLUSIONS: Mesh excision relieves mesh-related complications effectively, although with a substantial risk of serious complications and recurrence of POP or SUI. More complex excisions should be performed in skilled centers

A Multispecialty Evaluation of Thiel Cadavers for Surgical Training

Background: Changes in UK legislation allow for surgical procedures to be performed on cadavers. The aim of this study was to assess Thiel cadavers as high-fidelity simulators and to examine their suitability for surgical training. Methods: Surgeons from various specialties were invited to attend a 1 day dissection workshop using Thiel cadavers. The surgeons completed a baseline questionnaire on cadaveric simulation. At the end of the workshop, they completed a similar questionnaire based on their experience with Thiel cadavers. Comparing the answers in the pre- and post-workshop questionnaires assessed whether using Thiel cadavers had changed the surgeons’ opinions of cadaveric simulation. Results: According to the 27 participants, simulation is important for surgical training and a full-procedure model is beneficial for all levels of training. Currently, there is dissatisfaction with existing models and a need for high-fidelity alternatives. After the workshop, surgeons concluded that Thiel cadavers are suitable for surgical simulation (p = 0.015). Thiel were found to be realistic (p < 0.001) to have reduced odour (p = 0.002) and be more cost-effective (p = 0.003). Ethical constraints were considered to be small. Conclusion: Thiel cadavers are suitable for training in most surgical specialties

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

Distinct Visual Working Memory Systems for View-Dependent and View-Invariant Representation

Background: How do people sustain a visual representation of the environment? Currently, many researchers argue that a single visual working memory system sustains non-spatial object information such as colors and shapes. However, previous studies tested visual working memory for two-dimensional objects only. In consequence, the nature of visual working memory for three-dimensional (3D) object representation remains unknown. Methodology/Principal Findings: Here, I show that when sustaining information about 3D objects, visual working memory clearly divides into two separate, specialized memory systems, rather than one system, as was previously thought. One memory system gradually accumulates sensory information, forming an increasingly precise view-dependent representation of the scene over the course of several seconds. A second memory system sustains view-invariant representations of 3D objects. The view-dependent memory system has a storage capacity of 3–4 representations and the view-invariant memory system has a storage capacity of 1–2 representations. These systems can operate independently from one another and do not compete for working memory storage resources. Conclusions/Significance: These results provide evidence that visual working memory sustains object information in two separate, specialized memory systems. One memory system sustains view-dependent representations of the scene, akin to the view-specific representations that guide place recognition during navigation in humans, rodents and insects. Th