Variability of the Spectral Energy Distribution of the Blazar S5 0716+714

The emission from blazars is known to be variable at all wavelengths. The flux variability is often accompanied by spectral changes. Spectral energy distribution (SED) changes must be associated with changes in the spectra of emitting electrons and/or the physical parameters of the jet. Meaningful modeling of blazar broadband spectra is required to understand the extreme conditions within the emission region. Not only is the broadband SED crucial, but also information about its variability is needed to understand how the highest states of emission occur and how they differ from the low states. This may help in discriminating between models. Here we present the results of our SED modeling of the blazar S5 0716+714 during various phases of its activity. The SEDs are classified into different bins depending on the optical brightness state of the source.Comment: 4 pages, 3 figures, contributed talk presented at the conference Multifrequency Variability of Blazars, Guangzhou, China, September 22-24, 2010. To appear in Journal of Astrophysics and Astronomy (JAA

Role of geometrical cues in bone marrow-derived mesenchymal stem cell survival, growth and osteogenic differentiation

Mesenchymal stem cells play a vital role in bone formation process by differentiating into osteoblasts, in a tissue that offers not a flat but a discontinuous three-dimensional (3D) topography in vivo. In order to understand how geometry may be affecting mesenchymal stem cells, this study explored the influence of 3D geometry on mesenchymal stem cell-fate by comparing cell growth, viability and osteogenic potential using monolayer (two-dimensional, 2D) with microsphere (3D) culture systems normalised to surface area. The results suggested lower cell viability and reduced cell growth in 3D. Alkaline phosphatase activity was higher in 3D; however, both collagen and mineral deposition appeared significantly lower in 3D, even after osteogenic supplementation. Also, there were signs of patchy mineralisation in 3D with or without osteogenic supplementation as early as day 7. These results suggest that the convex surfaces on microspheres and inter-particulate porosity may have led to variable cell morphology and fate within the 3D culture. This study provides deeper insights into geometrical regulation of mesenchymal stem cell responses applicable for bone tissue engineering

Laser treatment in diabetic retinopathy

Diabetic retinopathy is a leading cause of visual impairment and blindness in developed countries due to macular edema and proliferative diabetic retinopathy (PDR). For both complications laser treatment may offer proven therapy: the Diabetic Retinopathy Study demonstrated that panretinal scatter photocoagulation reduces the risk of severe visual loss by >= 50% in eyes with high-risk characteristics. Pan-retinal scatter coagulation may also be beneficial in other PDR and severe nonproliferative diabetic retinopathy (NPDR) under certain conditions. For clinically significant macular edema the Early Treatment of Diabetic Retinopathy Study could show that immediate focal laser photocoagulation reduces the risk of moderate visual loss by at least 50%. When and how to perform laser treatment is described in detail, offering a proven treatment for many problems associated with diabetic retinopathy based on a high evidence level. Copyright (c) 2007 S. Karger AG, Basel

Metabonomics and Intensive Care

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency medicine 2016. Other selected articles can be found online at http://www.biomedcentral.com/collections/annualupdate2016. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901

A ‘quiet revolution’? The impact of Training Schools on initial teacher training partnerships

This paper discusses the impact on initial teacher training of a new policy initiative in England: the introduction of Training Schools. First, the Training School project is set in context by exploring the evolution of a partnership approach to initial teacher training in England. Ways in which Training Schools represent a break with established practice are considered together with their implications for the dominant mode of partnership led by higher education institutions (HEIs). The capacity of Training Schools to achieve their own policy objectives is examined, especially their efficacy as a strategy for managing innovation and the dissemination of innovation. The paper ends by focusing on a particular Training School project which has adopted an unusual approach to its work and enquires whether this alternative approach could offer a more profitable way forward. During the course of the paper, five different models of partnership are considered: collaborative, complementary, HEI-led, school-led and partnership within a partnership

Evidence for Reduced Drug Susceptibility without Emergence of Major Protease Mutations following Protease Inhibitor Monotherapy Failure in the SARA Trial

BACKGROUND: Major protease mutations are rarely observed following failure with protease inhibitors (PI), and other viral determinants of failure to PI are poorly understood. We therefore characterized Gag-Protease phenotypic susceptibility in subtype A and D viruses circulating in East Africa following viral rebound on PIs. METHODS: Samples from baseline and treatment failure in patients enrolled in the second line LPV/r trial SARA underwent phenotypic susceptibility testing. Data were expressed as fold-change in susceptibility relative to a LPV-susceptible reference strain. RESULTS: We cloned 48 Gag-Protease containing sequences from seven individuals and performed drug resistance phenotyping from pre-PI and treatment failure timepoints in seven patients. For the six patients where major protease inhibitor resistance mutations did not emerge, mean fold-change EC50 to LPV was 4.07 fold (95% CI, 2.08-6.07) at the pre-PI timepoint. Following viral failure the mean fold-change in EC50 to LPV was 4.25 fold (95% CI, 1.39-7.11, p = 0.91). All viruses remained susceptible to DRV. In our assay system, the major PI resistance mutation I84V, which emerged in one individual, conferred a 10.5-fold reduction in LPV susceptibility. One of the six patients exhibited a significant reduction in susceptibility between pre-PI and failure timepoints (from 4.7 fold to 9.6 fold) in the absence of known major mutations in protease, but associated with changes in Gag: V7I, G49D, R69Q, A120D, Q127K, N375S and I462S. Phylogenetic analysis provided evidence of the emergence of genetically distinct viruses at the time of treatment failure, indicating ongoing viral evolution in Gag-protease under PI pressure. CONCLUSIONS: Here we observe in one patient the development of significantly reduced susceptibility conferred by changes in Gag which may have contributed to treatment failure on a protease inhibitor containing regimen. Further phenotype-genotype studies are required to elucidate genetic determinants of protease inhibitor failure in those who fail without traditional resistance mutations whilst PI use is being scaled up globally

Cell-free (RNA) and cell-associated (DNA) HIV-1 and postnatal transmission through breastfeeding

<p>Introduction - Transmission through breastfeeding remains important for mother-to-child transmission (MTCT) in resource-limited settings. We quantify the relationship between cell-free (RNA) and cell-associated (DNA) shedding of HIV-1 virus in breastmilk and the risk of postnatal HIV-1 transmission in the first 6 months postpartum.</p> <p>Materials and Methods - Thirty-six HIV-positive mothers who transmitted HIV-1 by breastfeeding were matched to 36 non-transmitting HIV-1 infected mothers in a case-control study nested in a cohort of HIV-infected women. RNA and DNA were quantified in the same breastmilk sample taken at 6 weeks and 6 months. Cox regression analysis assessed the association between cell-free and cell-associated virus levels and risk of postnatal HIV-1 transmission.</p> <p>Results - There were higher median levels of cell-free than cell-associated HIV-1 virus (per ml) in breastmilk at 6 weeks and 6 months. Multivariably, adjusting for antenatal CD4 count and maternal plasma viral load, at 6 weeks, each 10-fold increase in cell-free or cell-associated levels (per ml) was significantly associated with HIV-1 transmission but stronger for cell-associated than cell-free levels [2.47 (95% CI 1.33–4.59) vs. aHR 1.52 (95% CI, 1.17–1.96), respectively]. At 6 months, cell-free and cell-associated levels (per ml) in breastmilk remained significantly associated with HIV-1 transmission but was stronger for cell-free than cell-associated levels [aHR 2.53 (95% CI 1.64–3.92) vs. 1.73 (95% CI 0.94–3.19), respectively].</p> <p>Conclusions - The findings suggest that cell-associated virus level (per ml) is more important for early postpartum HIV-1 transmission (at 6 weeks) than cell-free virus. As cell-associated virus levels have been consistently detected in breastmilk despite antiretroviral therapy, this highlights a potential challenge for resource-limited settings to achieve the UNAIDS goal for 2015 of eliminating vertical transmission. More studies would further knowledge on mechanisms of HIV-1 transmission and help develop more effective drugs during lactation.</p&gt

Arterial oxygen content is precisely maintained by graded erythrocytotic responses in settings of high/normal serum iron levels, and predicts exercise capacity: an observational study of hypoxaemic patients with pulmonary arteriovenous malformations.

Oxygen, haemoglobin and cardiac output are integrated components of oxygen transport: each gram of haemoglobin transports 1.34 mls of oxygen in the blood. Low arterial partial pressure of oxygen (PaO2), and haemoglobin saturation (SaO2), are the indices used in clinical assessments, and usually result from low inspired oxygen concentrations, or alveolar/airways disease. Our objective was to examine low blood oxygen/haemoglobin relationships in chronically compensated states without concurrent hypoxic pulmonary vasoreactivity.165 consecutive unselected patients with pulmonary arteriovenous malformations were studied, in 98 cases, pre/post embolisation treatment. 159 (96%) had hereditary haemorrhagic telangiectasia. Arterial oxygen content was calculated by SaO2 x haemoglobin x 1.34/100.There was wide variation in SaO2 on air (78.5-99, median 95)% but due to secondary erythrocytosis and resultant polycythaemia, SaO2 explained only 0.1% of the variance in arterial oxygen content per unit blood volume. Secondary erythrocytosis was achievable with low iron stores, but only if serum iron was high-normal: Low serum iron levels were associated with reduced haemoglobin per erythrocyte, and overall arterial oxygen content was lower in iron deficient patients (median 16.0 [IQR 14.9, 17.4]mls/dL compared to 18.8 [IQR 17.4, 20.1]mls/dL, p<0.0001). Exercise tolerance appeared unrelated to SaO2 but was significantly worse in patients with lower oxygen content (p<0.0001). A pre-defined athletic group had higher Hb:SaO2 and serum iron:ferritin ratios than non-athletes with normal exercise capacity. PAVM embolisation increased SaO2, but arterial oxygen content was precisely restored by a subsequent fall in haemoglobin: 86 (87.8%) patients reported no change in exercise tolerance at post-embolisation follow-up.Haemoglobin and oxygen measurements in isolation do not indicate the more physiologically relevant oxygen content per unit blood volume. This can be maintained for SaO2 ≥78.5%, and resets to the same arterial oxygen content after correction of hypoxaemia. Serum iron concentrations, not ferritin, seem to predict more successful polycythaemic responses

Etiological Profile and Treatment Outcome of Epistaxis at a Tertiary Care Hospital in Northwestern Tanzania: A Prospective Review of 104 Cases.

Epistaxis is the commonest otolaryngological emergency affecting up to 60% of the population in their lifetime, with 6% requiring medical attention. There is paucity of published data regarding the management of epistaxis in Tanzania, especially the study area. This study was conducted to describe the etiological profile and treatment outcome of epistaxis at Bugando Medical Centre, a tertiary care hospital in Northwestern Tanzania. This was a prospective descriptive study of the cases of epistaxis managed at Bugando Medical Centre from January 2008 to December 2010. Data collected were analyzed using SPSS computer software version 15. A total of 104 patients with epistaxis were studied. Males were affected twice more than the females (2.7:1). Their mean age was 32.24 ± 12.54 years (range 4 to 82 years). The modal age group was 31-40 years. The commonest cause of epistaxis was trauma (30.8%) followed by idiopathic (26.9%) and hypertension (17.3%). Anterior nasal bleeding was noted in majority of the patients (88.7%). Non surgical measures such as observation alone (40.4%) and anterior nasal packing (38.5%) were the main intervention methods in 98.1% of cases. Surgical measures mainly intranasal tumor resection was carried out in 1.9% of cases. Arterial ligation and endovascular embolization were not performed. Complication rate was 3.8%. The overall mean of hospital stay was 7.2 ± 1.6 days (range 1 to 24 days). Five patients died giving a mortality rate of 4.8%. Trauma resulting from road traffic crush (RTC) remains the most common etiological factor for epistaxis in our setting. Most cases were successfully managed with conservative (non-surgical) treatment alone and surgical intervention with its potential complications may not be necessary in most cases and should be the last resort. Reducing the incidence of trauma from RTC will reduce the incidence of emergency epistaxis in our centre

Evidence for Reduced Drug Susceptibility without Emergence of Major Protease Mutations following Protease Inhibitor Monotherapy Failure in the SARA Trial

Background Major protease mutations are rarely observed following failure with protease inhibitors (PI), and other viral determinants of failure to PI are poorly understood. We therefore characterized Gag-Protease phenotypic susceptibility in subtype A and D viruses circulating in East Africa following viral rebound on PIs. Methods Samples from baseline and treatment failure in patients enrolled in the second line LPV/r trial SARA underwent phenotypic susceptibility testing. Data were expressed as fold-change in susceptibility relative to a LPV-susceptible reference strain. Results We cloned 48 Gag-Protease containing sequences from seven individuals and performed drug resistance phenotyping from pre-PI and treatment failure timepoints in seven patients. For the six patients where major protease inhibitor resistance mutations did not emerge, mean fold-change EC50 to LPV was 4.07 fold (95% CI, 2.08–6.07) at the pre-PI timepoint. Following viral failure the mean fold-change in EC50 to LPV was 4.25 fold (95% CI, 1.39–7.11, p = 0.91). All viruses remained susceptible to DRV. In our assay system, the major PI resistance mutation I84V, which emerged in one individual, conferred a 10.5-fold reduction in LPV susceptibility. One of the six patients exhibited a significant reduction in susceptibility between pre-PI and failure timepoints (from 4.7 fold to 9.6 fold) in the absence of known major mutations in protease, but associated with changes in Gag: V7I, G49D, R69Q, A120D, Q127K, N375S and I462S. Phylogenetic analysis provided evidence of the emergence of genetically distinct viruses at the time of treatment failure, indicating ongoing viral evolution in Gag-protease under PI pressure. Conclusions Here we observe in one patient the development of significantly reduced susceptibility conferred by changes in Gag which may have contributed to treatment failure on a protease inhibitor containing regimen. Further phenotype-genotype studies are required to elucidate genetic determinants of protease inhibitor failure in those who fail without traditional resistance mutations whilst PI use is being scaled up globally