Immunofluorescence pattern of antinuclear antibody and its association with autoantibody profile in systemic lupus erythematosus

Background: Antinuclear antibody (ANA) is useful in the diagnosis of systemic lupus erythematosus (SLE). Association of specific autoantibodies with the immunofluorescence pattern of ANA in SLE as noted in Western literature has been taken as reference in all over the world. However, in Bangladesh such research work or data correlating the autoantibodies and their ANA patterns is inadequate. Objective: To identify an association between immunofluorescence patterns of antinuclear antibody on HEp-2 cell and more specific antinuclear reactivities (e.g. anti-dsDNA and anti-extractable nuclear antigen) in the serum samples of SLE patients.Methods: Serum samples of 37 SLE patients who were diagnosed by ARA (American Rheumatism Association) classification criteria and laboratory tests, attending at lupus clinic of Bangabandhu Sheikh Mujib Medical University (BSMMU) during the study period of six months were subjected for ANA testing by Indirect Imrnunofluorescence (IIF) on HEp-2 cell, anti-dsDNA by ELISA and anti- extractable nuclear antigen (anti-ENA) by Dot Immunoblot. Dot blot strips were tested for anti-Sm, anti-RNP, anti-SSA/Ro, and anti-SSB/La. Results: Out of 37 SLE patients 32 (86.5%) cases were ANA positive by IIF on HEp-2 cell. ANA positive sera exhibited three fluorescence patterns such as speckled (43.7%), peripheral (34.3%) and homogenous pattern (21.8%). Peripheral pattern (100%) was strongly associated with anti-dsDNA (p<0.05) and homogenous pattern (85.7%) was also predominantly associated with anti-dsDNA (p<0.05). Speckled pattern (85.6%) was significantly associated with anti-ENA (p<0.05). Anti-dsDNA was positive in 75% of SLE cases and majority (45.8%) of which showed peripheral pattern whereas anti-ENA was positive in 48.6% cases and majority (70.5%) of which showed speckled pattern. The most commonly identified antinuclear autoreactivity was directed towards anti-RNP (22.2%) then anti-Sm (16.6%), anti-SSA (16.6%) and anti-SSB (11.1 %). Multiple anti-ENA reactivities were identified in 33.3% cases. Conclusion: Peripheral and homogenous pattern is strongly associated with anti-dsDNA therefore may be predicted that patients have active SLE and speckled pattern may predict anti-ENA (specially ribonucleoprotiens). Thus, ANA-IIF method may suffice and probably reduce the expense of detailed immunological work-up with minimal loss in diagnostic accuracy

Does courtesy bias affect how clients report on objective and subjective measures of family planning service quality? A comparison between facility- and home-based interviews

Purpose: Despite a general understanding that exit interviews being conducted at service providers\u27 facilities may influence clients\u27 responses favorably to health professionals, there is very little evidence available that demonstrates the extent to which this problem exists. This study aimed at assessing and comparing clients\u27 perceptions of the quality of family planning services and their satisfaction levels between facility- and home-based interviews.Methods: A cross-sectional survey was conducted among clients receiving family planning services across three service delivery channels - nongovernmental organization (NGO) clinics, social franchise (SF) centers, and outreach camps. The survey took place from December 2015 to January 2016 in 70 districts across all four provinces of Pakistan. A total of 2,807 clients were interviewed, of whom 1,404 clients were interviewed at health facilities after receiving services and 1,403 were interviewed at their homes within 3 days of method uptake.Results: Overall, we found no significant differences between the characteristics of study participants interviewed at health facilities or at home. The findings suggested that experiences reported in exit surveys at facilities were strongly biased positively. This was true for both experiential (service quality) and perception-based (satisfaction) questions in the context of SF centers, while at NGO clinics the interview location only affected clients\u27 responses regarding service quality. However, in outreach settings, clients are more likely to share bad experiences in exit interviews than in home-based interviews on objectively asked questions (service quality).Conclusion: Our study indicates signs of courtesy bias and possibly the Hawthorne effect in exit interviews. Program implementers could opt for home-based interviews for women receiving services at NGO clinics or SF center, whereas exit interviews could be used in outreach settings

Bacteremic Typhoid Fever in Children in an Urban Slum, Bangladesh

We confirmed a bacteremic typhoid fever incidence of 3.9 episodes/1,000 person-years during fever surveillance in a Dhaka urban slum. The relative risk for preschool children compared with older persons was 8.9. Our regression model showed that these children were clinically ill, which suggests a role for preschool immunization

A three-drug nanoscale drug delivery system designed for preferential lymphatic uptake for the treatment of metastatic melanoma

Metastatic melanoma has a high mortality rate due to lymphatic progression of the disease. Current treatment is surgery followed by radiation and intravenous chemotherapy. However, drawbacks for current chemotherapeutics lie in the fact that they develop resistance and do not achieve therapeutic concentrations in the lymphatic system. We hypothesize that a three-drug nanoscale drug delivery system, tailored for lymphatic uptake, administered subcutaneously, will have decreased drug resistance and therefore offer better therapeutic outcomes. We prepared and characterized nanoparticles (NPs) with docetaxel, everolimus, and LY294002 in polyethyleneglycol-block-poly(ε-caprolactone) (PEG-PCL) polymer with different charge distributions by modifying the ratio of anionic and neutral end groups on the PEG block. These NPs are similarly sized (~48nm), with neutral, partially charged, or fully charged surface. The NPs are able to load ~2mg/mL of each drug and are stable for 24h. The NPs are assessed for safety and efficacy in two transgenic metastatic melanoma mouse models. All the NPs were safe in both models based on general appearance, weight changes, death, and blood biochemical analyses. The partially charged NPs are most effective in decreasing the number of melanocytes at both the proximal (sentinel) lymph node (LN) and the distal LN from the injection site. The neutral NPs are efficacious at the proximal LN, while the fully charged NPs have no effect on either LNs. Thus, our data indicates that the NP surface charge and lymphatic efficacy are closely tied to each other and the partially charged NPs have the highest potential in treating metastatic melanoma

Influence of Differential Calcification in the Descending Thoracic Aorta on Aortic Pulse Pressure

Purpose: Multiple studies have shown pulse pressure (PP) to be a strong predictor of aortic calcification. However, no studies are available that correlate PP with aortic calcification at the segmental level. Methods: We identified 37 patients with aortic PP measured during cardiac catheterization. Their noncontrast chest computed tomography scans were evaluated for the presence of calcium in different segments (ascending aorta, arch of aorta [arch], descending aorta) and quantified. Patients with calcification (Calcified Group A) were compared against patients without calcification (Noncalcified Group B) in terms of PP, calcification and compliance. Results: The mean of the total calcium score was higher in the descending aorta than the arch or ascending aorta (691 vs 571 vs 131, respectively, P < 0.0001). PP had the strongest correlation with calcification in the descending aorta (r = 0.47, P = 0.004). Calcified Group A had a much higher PP than Noncalcified Group B, with the greatest difference in the descending aorta (20 mmHg, P < 0.0001), lesser in the ascending aorta (10 mmHg, P = 0.12) and the least in the arch (5 mmHg, P = 0.38). Calcified Group A patients also had much lower compliance than Noncalcified Group B patients, with the greatest difference among groups seen in the descending aorta (0.7 mL/mmHg, P = 0.002), followed by the ascending aorta, then arch. Conclusions: These are the first data to evaluate the relative impact of aortic segments in PP. Finding the greatest amount of calcification along with greatest change in PP and compliance in the descending aorta makes a case that the descending aorta plays a major role in PP as compared to other segments of the thoracic aorta

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

Accountability of International NGOs: Human Rights Violations in Healthcare Provision in Developing Countries and the Effectiveness of Current Measures

In recent years, the number of non-governmental organizations (NGOs) working in the international arena has vastly increased, generally making a positive impact. But, as this influence has deepened, governments in the developing world and scholars have scrutinized the work and accountability of NGOs given they are mostly independent and not subjected to international law. While NGOs must adhere to the domestic laws of the places within which they work, adherence is dependent upon the strength of enforcement of those laws. Proponents argue that this independence is essential for NGOs to effectively carry out their work. However, a review of healthcare programs funded by the Bill & Melinda Gates Foundation (Gates Foundation) calls into question current accountability measures of NGOs in the healthcare sector and can shine a light on weaknesses and potential areas of improvement in the current accountability regime for NGOs. The shortcomings of the current accountability regime for NGOs must be addressed in two critical areas: monitoring projects and monitoring potential influences and exploitation between donors and NGOs. Through the review of recent Gates-funded healthcare campaigns in Africa and India, this paper seeks to highlight and analyze these shortcomings by looking at the failures of the current accountability regime to prevent and resolve human rights abuses committed during these programs. This paper will offer recommendations to strengthen the accountability regime for NGOs through a more active role by the local governments and through community outreach and development. The findings in this paper will have implications for all NGOs working in the healthcare sector and potentially other sectors

What happens between the taq and the Old City of Srinagar in Kashmir?

This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Thesis: S.M., Massachusetts Institute of Technology, Department of Architecture, 2019Cataloged from PDF version of thesis.Includes bibliographical references (pages 93-96).This thesis explores the importance of the traditional building crafts as integral and inextricable parts of traditional architecture, known as the 'taq', in the Old City of Srinagar and delves into the question, 'How does architecture become a platform for the different building crafts and a medium to facilitate their development, and vice versa?' The study shows the interrelation of Architecture and Craft through five scales of spatial configuration in the old city: 1) the urban context of the city; 2) the streetscapes in it; 3) the Dargahs amidst neighbourhoods; 4) traditional houses in the city; and 5) finally the crafts as they have been practiced individually in incorporated within interior architecture. This approach seeks to understand the relation of Architecture and Craft in Srinagar at different levels and to explore in detail, where the two meet and where they diverge. It is important to explore the intricate interdependency of these systems of spatial expressions and building functions to study their growth and diversification that we see in the old city of Srinagar today. There is ample research on both Traditional Crafts and Architecture in Kashmir as individual and separate topics of study, but this thesis study helps to look at them as cohesive and mutually supportive elements of the traditional built environment in the urban context of the Old City of Srinagar. It explores those relationship through fieldwork and visual methods of studying and enquiring at different spatial scales (e.g. maps at the urban scale and photography and drawing at the architectural scale). The results of the study encourage a new and different way of looking at, and studying, the relationship between architecture and craft in the old city of Srinagar. It synthesizes a framework that can have a broader application to study areas with similar circumstances in other regions of India.by Sharmeen Sayed Dafedar.S.M.S.M. Massachusetts Institute of Technology, Department of Architectur

Regression analysis : effectiveness of Bangladesh's economic diplomacy with China and India

In light of the use of economic diplomacy in the 21st century, this paper seeks to examine\ud the effect of bilateral economic activities with India and China on Bangladesh???s growth.\ud Previous growth studies have used either general growth regressions or case studies for\ud evaluation. However, the dominant trend, employed here, is to use regression analysis\ud since it is more applicable for general study. The impact of the determinants of growth,\ud chosen to be aid, trade and foreign direct investment, will be evaluated from the context\ud of a Bangladesh-India and Bangladesh-China model using both an individual\ud determinant-growth regression and an adapted general growth regression. The general\ud growth regression model used in this paper has been modified by partial differentiation,\ud which allows the model to assume no linearity and removes the need for country specific\ud effects. The study concludes that free trade is favorable to regional trade for Bangladesh