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HIV-1 Subtype C Phylodynamics in the Global Epidemic
Vlad Novitsky,Rui Wang,Stephen Lagakos,Max Essex
Viruses , 2010, DOI: 10.3390/v2010033
Abstract: The diversity of HIV-1 and its propensity to generate escape mutants present fundamental challenges to control efforts, including HIV vaccine design. Intra-host diversification of HIV is determined by immune responses elicited by an HIV-infected individual over the course of the infection. Complex and dynamic patterns of transmission of HIV lead to an even more complex population viral diversity over time, thus presenting enormous challenges to vaccine development. To address inter-patient viral evolution over time, a set of 653 unique HIV-1 subtype C gag sequences were retrieved from the LANL HIV Database, grouped by sampling year as <2000, 2000, 2001–2002, 2003, and 2004–2006, and analyzed for the site-specific frequency of translated amino acid residues. Phylogenetic analysis revealed that a total of 289 out of 653 (44.3%) analyzed sequences were found within 16 clusters defined by aLRT of more than 0.90. Median (IQR) inter-sample diversity of analyzed gag sequences was 8.7% (7.7%; 9.8%). Despite the heterogeneous origins of analyzed sequences, the gamut and frequency of amino acid residues in wild-type Gag were remarkably stable over the last decade of the HIV-1 subtype C epidemic. The vast majority of amino acid residues demonstrated minor frequency fluctuation over time, consistent with the conservative nature of the HIV-1 Gag protein. Only 4.0% (20 out of 500; HXB2 numbering) amino acid residues across Gag displayed both statistically significant (p<0.05 by both a trend test and heterogeneity test) changes in amino acid frequency over time as well as a range of at least 10% in the frequency of the major amino acid. A total of 59.2% of amino acid residues with changing frequency of 10%+ were found within previously identified CTL epitopes. The time of the most recent common ancestor of the HIV-1 subtype C was dated to around 1950 (95% HPD from 1928 to 1962). This study provides evidence for the overall stability of HIV-1 subtype C Gag among viruses circulating in the epidemic over the last decade. However selected sites across HIV-1C Gag with changing amino acid frequency are likely to be under selection pressure at the population level.
Sustainability, Food Security, and Development Aid after the Food Crisis: Assessing Aid Strategies across Donor Contexts
Jamey Essex
Sustainability , 2010, DOI: 10.3390/su2113354
Abstract: The most recent global food crisis has forced development agencies in the global North to rethink the nexus between agricultural development, food aid, and food security, and how development assistance strategies can enhance food security to more effectively respond to or prevent such crises in the future. Central to this rethinking is the concept of sustainability, though the term has shifting and imprecise meanings across different institutional and strategic contexts. Analyzing the strategic response of major state and multilateral development agencies to the global food crisis, this paper examines the diverse and slippery meanings and uses of sustainability in the post-crisis development assistance architecture.
The Work of Hunger: Security, Development and Food-for-Work in Post-crisis Jakarta
Jamey Essex
Studies in Social Justice , 2009,
Abstract: Food-for-work programs distribute food aid to recipients in exchange for labor, and are an important mode of aid delivery for both public and private aid providers. While debate continues as to whether food-for-work programs are socially just and economically sensible, governments, international institutions, and NGOs continue to tout them as a flexible and cost-effective way to deliver targeted aid and promote community development. This paper critiques the underlying logic of food-for-work, focusing on how this approach to food aid and food security promote labor force participation by leveraging hunger against poverty, and how the ideological and practical assumptions of food-for-work become enmeshed within discourses of geopolitical security. I rely on a case study examination of US-funded food-for-work programs implemented in Jakarta, Indonesia following the 1997 financial crisis. The crisis produced acute food insecurity and poverty in Indonesia, provoking fears of mob violence by the hungry poor and the spread of radical Islamism in the post-crisis political vacuum. Food-for-work programs were, in this context, meant to resolve the problems of both food insecurity and geopolitical insecurity by providing food to targeted populations, employment to those otherwise thrown out of work, and resituating the hungry poor in relation to broader scales of local, national, and global power.
Birth weight for gestational age norms for a large cohort of infants born to HIV-negative women in Botswana compared with norms for U.S.-born black infants
Lynn T Matthews, Heather J Ribaudo, Natasha K Parekh, Jennifer Y Chen, Kelebogile Binda, Anthony Ogwu, Joseph Makhema, Sajini Souda, Shahin Lockman, Max Essex, Roger L Shapiro
BMC Pediatrics , 2011, DOI: 10.1186/1471-2431-11-115
Abstract: Birth weight data were collected from six hospitals in Botswana. Infants born to HIV-negative women between 26-44 weeks gestation were analyzed to construct birth weight for gestational age charts. These data were compared with published norms for black infants in the United States.During a 29 month period from 2007-2010, birth records were reviewed in real-time from 6 hospitals and clinics in Botswana. Of these, 11,753 live infants born to HIV-negative women were included in the analysis. The median gestational age at birth was 39 weeks (1st quartile 38, 3rd quartile 40 weeks), and the median birth weight was 3100 grams (1st quartile 2800, 3rd quartile 3400 grams). We constructed estimated percentile curves for birth weight by gestational age which demonstrate increasing slope during the third trimester and leveling off beyond 40 weeks. Compared with black infants in the United States, Botswana-born infants had lower median birth weight for gestational age from weeks 37 through 42 (p < .02).We present birth weight for gestational age norms for Botswana, which are lower at term than norms for black infants in the United States. These findings suggest the importance of regional birth weight norms to identify and define risk factors for higher risk births. These data serve as a reference for Botswana, may apply to southern Africa, and may help to identify infants at risk for perinatal complications and inform comparisons among infants exposed to HIV and antiretrovirals in utero.Each year over 4 million infants die in the first four weeks of life (the neonatal period). Ninety-eight percent of neonatal deaths take place in the developing world, and the highest risk is in Africa, where an average of 41 neonatal deaths occur per 1000 live births [1]. Botswana, a middle-income country in southern Africa, has a well-developed medical infrastructure where 97% of women access antenatal care, 94% of births are overseen by a skilled attendant, and 80% of women access hospital-b
Cotrimoxazole Prophylaxis and Risk of Severe Anemia or Severe Neutropenia in HAART-Exposed, HIV-Uninfected Infants
Scott Dryden-Peterson, Oluwemimo Jayeoba, Michael D. Hughes, Haruna Jibril, Kenneth McIntosh, Taolo A. Modise, Aida Asmelash, Kathleen M. Powis, Max Essex, Roger L. Shapiro, Shahin Lockman
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0074171
Abstract: Background Prophylactic cotrimoxazole is recommended for infants born to HIV-infected mothers. However, cotrimoxazole may increase the risk of severe anemia or neutropenia. Methods We compared the proportion of HIV-exposed uninfected (HIV-EU) infants experiencing incident severe anemia (and separately, severe neutropenia) between a prospective cohort receiving prophylactic cotrimoxazole from 1 to 6 months vs. infants from two prior trials who did not receive cotrimoxazole. Infants were from rural and urban communities in southern Botswana. Results A total of 1705 HIV-EU infants were included. Among these 645 (37.8%) were fed with iron-supplemented formula from birth. Severe anemia developed in 87 (5.1%) infants, and severe neutropenia in 164 (9.6%) infants. In an analysis stratified by infant feeding method, there were no significant differences in the risk of severe anemia by prophylactic cotrimoxazole exposure–risk difference, ?0.69% (95% confidence interval [CI] ?2.1 to 0.76%). Findings were similar in multivariable analysis, adjusted odds ratio (aOR) 0.35 (95% CI 0.07 to 1.65). There were also no significant differences observed for severe neutropenia by cotrimoxazole exposure, risk difference 2.0% (95% CI ?1.3 to 5.2%) and aOR 0.80 (95% CI 0.33 to 1.93). Conclusions Severe anemia and severe neutropenia were infrequent among HIV-exposed uninfected infants receiving cotrimoxazole from 1–6 months of age. Concerns regarding hematologic toxicity should not limit the use of prophylactic cotrimoxazole in HIV-exposed uninfected infants. ClinicalTrials.gov Registration Numbers NCT01086878 (http://clinicaltrials.gov/show/NCT010868?78), NCT00197587 (http://clinicaltrials.gov/show/NCT001975?87), and NCT00270296 (http://clinicaltrials.gov/show/NCT002702?96).
Immune Activation Markers in Peripartum Women in Botswana: Association with Feeding Strategy and Maternal Morbidity
Elizabeth S. Russell, Terence Mohammed, Laura Smeaton, Baitshepi Jorowe, Iain J. MacLeod, Risa M. Hoffman, Judith S. Currier, Sikhulile Moyo, Max Essex, Shahin Lockman
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0089928
Abstract: Hormone levels shift the immune state in HIV-uninfected pregnant and breastfeeding women away from Th1 responses and toward regulation to permit fetal tolerance. Limited data exist on inflammation during pregnancy or postpartum in HIV-infected women, though certain inflammatory markers are associated with adverse health outcomes among HIV-infected persons. We measured hsCRP, D-dimer, IFN-γ, IL-6, IL-10 and TNF-α at 34 weeks gestation and six months postpartum in HIV-infected women from the Botswana Mashi PMTCT trial who were randomized to breastfeeding or formula-feeding. Differences in inflammatory markers between gestation and postpartum periods, and by randomized feeding method, were estimated using generalized estimating equations, adjusting for baseline plasma HIV-1 viral load, CD4 count, calendar time, and antiretroviral treatment status. Additionally, we studied the association between marker concentrations at six months postpartum and major adverse clinical events over the following 4.5 years, using case-cohort sampling and adjusted Cox proportional hazards models. In 86 breastfeeding and 75 formula-feeding women, hsCRP and D-dimer decreased significantly between 34 weeks gestation and six months postpartum, while IFN-γ increased. There was no significant association between inflammatory marker change and randomized feeding method after adjusting for multiple comparisons and removing outliers. In univariate analysis, TNF-α, D-dimer, and IFN-γ concentrations at six months postpartum were significant predictors of subsequent clinical events, and TNF-α remained significant in multivariate analysis (HR = 4.16, p = 0.001). In young HIV-infected women in Botswana inflammatory marker concentrations did not differ significantly between women who breast- vs. formula-fed. However, postpartum TNF-α level was predictive of subsequent adverse clinical event.
Table of Contents
Essex Human Rights Review
Essex Human Rights Review , 2008,
Editor's Note
Essex Human Rights Review
Essex Human Rights Review , 2008,
Cover Page - Special Issue: 25th Anniversary of the Human Rights Centre. Human Rights Perspectives: What We Have Learnt So Far
Essex Human Rights Review
Essex Human Rights Review , 2008,
Machian space quanta
David W. Essex
Physics , 2015,
Abstract: A new model for space and matter is obtained by joining every pair of point charges in the observable universe by an ethereal string. Positive gravitational potential energy in each string gives an attractive gravitational force due to the action of an energy conservation constraint. Newton's laws of motion are derived and inertia is explained in accordance with Mach's principle. The Machian string model gives a surprisingly simple way to understand the expansion history of the Universe. The decelerating expansion in the radiation era and the matter era is explained without using General Relativity and the transition from deceleration to acceleration is explained without the need to introduce a separate 'dark energy' component. The interaction between Machian strings gives a physical model for modified Newtonian dynamics (MOND) and is therefore an alternative to 'dark matter'.
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