Obstetric and newborn outcomes and risk factors for low birth weight and preterm delivery among HIV-infected pregnant women at the university college hospital Ibadan

There remains uncertainty about the impact of HIV on pregnancy outcomes and effects of highly active antiretroviral therapy on fetal development. This study describes obstetric outcomes among HIV positive parturients at the University College Hospital, Ibadan. HIV positive parturients were identified in the birth register. During the 30-month period, 318 of 6203 deliveries were HIV positive (5.1%) with 97.6% record retrieval. The mean age of the HIV positive parturients was 31.66 years (± 4.66); the mean gestational age at delivery was 38.02 weeks (± 2.75) and the mean birth weight 2.85kg (±0.59). There were 35.8% (109) preterm births, 2.9% stillbirths and 21.5% low birth weights. The regimen most commonly (198, 64.5%) used was a non-nucleoside reverse transcriptase (NNRTI) based HAART. Preterm births were similar following spontaneous vaginal delivery (31.5%) and elective section (31%) but higher (41.3%) with emergency section (ñ=0.4).On univariate analysis, the preterm infants had lower mean birth weights (2.46±0.61 vs 2.96±0.44; ñ=0.000). The proportion of preterm births was higher among Low birth weight infants (71.9% vs 28.1%; ñ=0.00). Variables with more preterm births were age >35 years (51.6%), ≤6years of schooling (51.5% vs 48.4%) and being on combination ARV (PI, 37.5% or non-PI, 36.2%). However, these differences did not attain statistical significance. Low birth weight infants had mothers who had higher mean ages (33.28 years ± 4.59 vs 31.28 years ± 4.59, ñ= 0.02), lower mean gestational age at delivery (35.72 weeks ± 3.16 vs 38.49 weeks ± 2.1, ñ= 0.00). Variables with more low birth weight include <12years of schooling and being on mono/ dual therapy (31.8%). These differences were not statistically significant. On logistic regression, factors that retained an association with low birth weight were mean maternal age at delivery (ñ= 0.002; â= 0.904; 95% CI, 0.848 – 0.966) and being on mono/ dual therapy (ñ= 0.039; â= 3.042; 95% CI, 1.055 – 8.768). The only factor that retained an association with preterm birth was mean maternal age at delivery (ñ= 0.015; â= 0.935; 95% CI, 0.886 – 0.987). HIV positive (especially older) women, have high rates of preterm deliveries and low birth weights. The beneficial effects of HAART on mother-to-child transmission are indisputable but monitoring antiretroviral therapy in pregnancy remains a priority and antenatal surveillance should include fetal growth assessment.

Variation in prescribing for anxiety and depression: a reflection of health inequalities, cultural differences or variations in access to care?

BACKGROUND: There are large variations in mental health prescribing in UK populations. However the underlying reasons for these differences, which may be related to differences in prevalence, cultural expectations or practical difficulties in access to treatment, remain uncertain. METHODS: Linear modelling was used to investigate whether population characteristics or access to primary care account for variations in mental health prescribing across 39 deprived neighbourhoods. RESULTS: The proportion of sampled respondents whose first language was not English and the ratio of general practitioners to population explained 61% of variation. Deprivation and mental health status were not significant predictors of prescribing in these relatively deprived communities. CONCLUSION: These findings suggest that mental health prescribing, within deprived areas, as well as reflecting cultural and social differences in prescribing, may also be a proxy measure of access to care

Computational neuroanatomy: ontology-based representation of neural components and connectivity

Background: A critical challenge in neuroscience is organizing, managing, and accessing the explosion in neuroscientific knowledge, particularly anatomic knowledge. We believe that explicit knowledge-based approaches to make neuroscientific knowledge computationally accessible will be helpful in tackling this challenge and will enable a variety of applications exploiting this knowledge, such as surgical planning. Results: We developed ontology-based models of neuroanatomy to enable symbolic lookup, logical inference and mathematical modeling of neural systems. We built a prototype model of the motor system that integrates descriptive anatomic and qualitative functional neuroanatomical knowledge. In addition to modeling normal neuroanatomy, our approach provides an explicit representation of abnormal neural connectivity in disease states, such as common movement disorders. The ontology-based representation encodes both structural and functional aspects of neuroanatomy. The ontology-based models can be evaluated computationally, enabling development of automated computer reasoning applications. Conclusion: Neuroanatomical knowledge can be represented in machine-accessible format using ontologies. Computational neuroanatomical approaches such as described in this work could become a key tool in translational informatics, leading to decision support applications that inform and guide surgical planning and personalized care for neurological disease in the future

Generation of Functional CLL-Specific Cord Blood CTL Using CD40-Ligated CLL APC

PMCID: PMC3526610This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Physics Opportunities of e+e- Linear Colliders

We describe the anticipated experimental program of an e+e- linear collider in the energy range 500 GeV -- 1.5 TeV. We begin with a description of current collider designs and the expected experimental environment. We then discuss precision studies of the W boson and top quark. Finally, we review the range of models proposed to explain the physics of electroweak symmetry breaking and show, for each case, the central role that the linear collider experiments will play in elucidating this physics. (to appear in Annual Reviews of Nuclear and Particle Science)Comment: 93 pages, latex + 23 figures; typos corrections + 1 reference adde

Primary skin fibroblasts as a model of Parkinson's disease

Parkinson's disease is the second most frequent neurodegenerative disorder. While most cases occur sporadic mutations in a growing number of genes including Parkin (PARK2) and PINK1 (PARK6) have been associated with the disease. Different animal models and cell models like patient skin fibroblasts and recombinant cell lines can be used as model systems for Parkinson's disease. Skin fibroblasts present a system with defined mutations and the cumulative cellular damage of the patients. PINK1 and Parkin genes show relevant expression levels in human fibroblasts and since both genes participate in stress response pathways, we believe fibroblasts advantageous in order to assess, e.g. the effect of stressors. Furthermore, since a bioenergetic deficit underlies early stage Parkinson's disease, while atrophy underlies later stages, the use of primary cells seems preferable over the use of tumor cell lines. The new option to use fibroblast-derived induced pluripotent stem cells redifferentiated into dopaminergic neurons is an additional benefit. However, the use of fibroblast has also some drawbacks. We have investigated PARK6 fibroblasts and they mirror closely the respiratory alterations, the expression profiles, the mitochondrial dynamics pathology and the vulnerability to proteasomal stress that has been documented in other model systems. Fibroblasts from patients with PARK2, PARK6, idiopathic Parkinson's disease, Alzheimer's disease, and spinocerebellar ataxia type 2 demonstrated a distinct and unique mRNA expression pattern of key genes in neurodegeneration. Thus, primary skin fibroblasts are a useful Parkinson's disease model, able to serve as a complement to animal mutants, transformed cell lines and patient tissues

Proteomic identification of immunodiagnostic antigens for <i>Trypanosoma vivax </i>infections in cattle and generation of a proof-of-concept lateral flow test diagnostic device

Trypanosoma vivax is one of the causative agents of Animal African Trypanosomosis in cattle, which is endemic in sub-Saharan Africa and transmitted primarily by the bite of the tsetse fly vector. The parasite can also be mechanically transmitted, and this has allowed its spread to South America. Diagnostics are limited for this parasite and in farm settings diagnosis is mainly symptom-based. We set out to identify, using a proteomic approach, candidate diagnostic antigens to develop into an easy to use pen-side lateral flow test device. Two related members the invariant surface glycoprotein family, TvY486_0045500 and TvY486_0019690, were selected. Segments of these antigens, lacking N-terminal signal peptides and C-terminal transmembrane domains, were expressed in E. coli. Both were developed into ELISA tests and one of them, TvY486_0045500, was developed into a lateral flow test prototype. The tests were all evaluated blind with 113 randomised serum samples, taken from 37 calves before and after infection with T. vivax or T. congolense. The TvY486_0045500 and TvY486_0019690 ELISA tests gave identical sensitivity and specificity values for T. vivax infection of 94.5% (95% CI, 86.5% to 98.5%) and 88.0% (95% CI, 75.7% to 95.5%), respectively, and the TvY486_0045500 lateral flow test prototype a sensitivity and specificity of 92.0% (95% CI, 83.4% to 97.0%) and 89.8% (95% CI, 77.8% to 96.6%), respectively. These data suggest that recombinant TvY486_0045500 shows promise for the development of a pen-side lateral flow test for the diagnosis of T. vivax animal African trypanosomosis

Effect of imaging and catheter characteristics on clinical outcome for patients in the PRECISE study

The PRECISE study used convection enhanced delivery (CED) to infuse IL13-PE38QQR in patients with recurrent glioblastoma multiforme (GBM) and compared survival to Gliadel Wafers (GW). The objectives of this retrospective evaluation were to assess: (1) catheter positioning in relation to imaging features and (2) to examine the potential impact of catheter positioning, overall catheter placement and imaging features on long term clinical outcome in the PRECISE study. Catheter positioning and overall catheter placement were scored and used as a surrogate of adequate placement. Imaging studies obtained on day 43 and day 71 after resection were each retrospectively reviewed. Catheter positioning scores, catheter overall placement scores, local tumor control and imaging change scores were reviewed and correlated using Generalized Linear Mixed Models. Cox PH regression analysis was used to examine whether these imaging based variables predicted overall survival (OS) and progression free survival (PFS) after adjusting for age and KPS. Of 180 patients in the CED group, 20 patients did not undergo gross total resection. Of the remaining 160 patients only 53% of patients had fully conforming catheters in respect to overall placement and 51% had adequate catheter positioning scores. Better catheter positioning scores were not correlated with local tumor control (P = 0.61) or imaging change score (P = 0.86). OS and PFS were not correlated with catheter positioning score (OS: P = 0.53; PFS: P = 0.72 respectively), overall placement score (OS: P = 0.55; PFS: P = 0.35) or imaging changes on day 43 MRI (P = 0.88). Catheter positioning scores and overall catheter placement scores were not associated with clinical outcome in this large prospective trial

Passive Immunization Reduces Behavioral and Neuropathological Deficits in an Alpha-Synuclein Transgenic Model of Lewy Body Disease

Dementia with Lewy bodies (DLB) and Parkinson's Disease (PD) are common causes of motor and cognitive deficits and are associated with the abnormal accumulation of alpha-synuclein (α-syn). This study investigated whether passive immunization with a novel monoclonal α-syn antibody (9E4) against the C-terminus (CT) of α-syn was able to cross into the CNS and ameliorate the deficits associated with α-syn accumulation. In this study we demonstrate that 9E4 was effective at reducing behavioral deficits in the water maze, moreover, immunization with 9E4 reduced the accumulation of calpain-cleaved α-syn in axons and synapses and the associated neurodegenerative deficits. In vivo studies demonstrated that 9E4 traffics into the CNS, binds to cells that display α-syn accumulation and promotes α-syn clearance via the lysosomal pathway. These results suggest that passive immunization with monoclonal antibodies against the CT of α-syn may be of therapeutic relevance in patients with PD and DLB