Impact and Cost of the HIV/AIDS National Strategic Plan for Mozambique, 2015-2019—Projections with the Spectrum/Goals Model

Introduction

Mozambique continues to face a severe HIV epidemic and high cost for its control, largely born by international donors. We assessed feasible targets, likely impact and costs for the 2015–2019 national strategic HIV/AIDS plan (NSP).

Methods

The HIV epidemic and response was modelled in the Spectrum/Goals/Resource Needs dynamical simulation model, separately for North/Center/South regions, fitted to antenatal clinic surveillance data, household and key risk group surveys, program statistics, and financial records. Intervention targets were defined in collaboration with the National AIDS Council, Ministry of Health, technical partners and implementing NGOs, considering existing commitments.

Results

Implementing the NSP to meet existing coverage targets would reduce annual new infections among all ages from 105,000 in 2014 to 78,000 in 2019, and reduce annual HIV/AIDS-related deaths from 80,000 to 56,000. Additional scale-up of prevention interventions targeting high-risk groups, with improved patient retention on ART, could further reduce burden to 65,000 new infections and 51,000 HIV-related deaths in 2019. Program cost would increase from US$ 273 million in 2014, to US$ 433 million in 2019 for ‘Current targets’, or US$ 495 million in 2019 for ‘Accelerated scale-up’. The ‘Accelerated scale-up’ would lower cost per infection averted, due to an enhanced focus on behavioural prevention for high-risk groups. Cost and mortality impact are driven by ART, which accounts for 53% of resource needs in 2019. Infections averted are driven by scale-up of interventions targeting sex work (North, rising epidemic) and voluntary male circumcision (Center & South, generalized epidemics).

Conclusion

The NSP could aim to reduce annual new HIV infections and deaths by 2019 by 30% and 40%, respectively, from 2014 levels. Achieving incidence and mortality reductions corresponding to UNAIDS’ ‘Fast track’ targets will require increased ART coverage and additional behavioural prevention targeting key risk groups.     

Unexpected Dual Task Benefits on Cycling in Parkinson Disease and Healthy Adults: A Neuro-Behavioral Model

BackgroundWhen performing two tasks at once, a dual task, performance on one or both tasks typically suffers. People with Parkinson’s disease (PD) usually experience larger dual task decrements on motor tasks than healthy older adults (HOA). Our objective was to investigate the decrements in cycling caused by performing cognitive tasks with a range of difficulty in people with PD and HOAs.MethodsTwenty-eight participants with Parkinson’s disease and 20 healthy older adults completed a baseline cycling task with no secondary tasks and then completed dual task cycling while performing 12 tasks from six cognitive domains representing a wide range of difficulty.ResultsCycling was faster during dual task conditions than at baseline, and was significantly faster for six tasks (all p<.02) across both groups. Cycling speed improved the most during the easiest cognitive tasks, and cognitive performance was largely unaffected. Cycling improvement was predicted by task difficulty (p<.001). People with Parkinson’s disease cycled slower (p<.03) and showed reduced dual task benefits (p<.01) than healthy older adults.ConclusionsUnexpectedly, participants’ motor performance improved during cognitive dual tasks, which cannot be explained in current models of dual task performance. To account for these findings, we propose a model integrating dual task and acute exercise approaches which posits that cognitive arousal during dual tasks increases resources to facilitate motor and cognitive performance, which is subsequently modulated by motor and cognitive task difficulty. This model can explain both the improvement observed on dual tasks in the current study and more typical dual task findings in other studies.     

Development and Validation of a Novel Platform-Independent Metastasis Signature in Human Breast Cancer

PurposeThe molecular drivers of metastasis in breast cancer are not well understood. Therefore, we sought to identify the biological processes underlying distant progression and define a prognostic signature for metastatic potential in breast cancer.ResultsWe identified a broad range of metastatic potential that was independent of intrinsic breast cancer subtypes. 146 genes were significantly associated with metastasis progression and were linked to cancer-related biological functions, including cell migration/adhesion, Jak-STAT, TGF-beta, and Wnt signaling. These genes were used to develop a platform-independent gene expression signature (M-Sig), which was trained and subsequently validated on 5 independent cohorts totaling nearly 1800 breast cancer patients with all p-values < 0.005 and hazard ratios ranging from approximately 2.5 to 3. On multivariate analysis accounting for standard clinicopathologic prognostic variables, M-Sig remained the strongest prognostic factor for metastatic progression, with p-values < 0.001 and hazard ratios > 2 in three different cohorts.ConclusionM-Sig is strongly prognostic for metastatic progression, and may provide clinical utility in combination with treatment prediction tools to better guide patient care. In addition, the platform-independent nature of the signature makes it an excellent research tool as it can be directly applied onto existing, and future, datasets.     

The discovery of carboline analogs as potent MAPKAP-K2 inhibitors

The discovery of a series of potent, carboline-based MK2 inhibitors is described. These compounds inhibit MK2 with IC50s as low as 10 nM, as measured in a DELFIA assay. An X-ray crystal structure reveals that they bind in a region near the p-loop and the hinge region of MK2a.     

Activation of endocytosis as an adaptation to the mammalian host by trypanosomes

Immune evasion in African trypanosomes is principally mediated by antigenic variation, but rapid internalization of surface-bound immune factors may contribute to survival. Endocytosis is upregulated approximately 10-fold in bloodstream compared to procyclic forms, and surface coat remodeling accompanies transition between these life stages. Here we examined expression of endocytosis markers in tsetse fly stages in vivo and monitored modulation during transition from bloodstream to procyclic forms in vitro. Among bloodstream stages nonproliferative stumpy forms have endocytic activity similar to that seen with rapidly dividing slender forms, while differentiation of stumpy forms to procyclic forms is accompanied by rapid down-regulation of Rab11 and clathrin, suggesting that modulation of endocytic and recycling systems accompanies this differentiation event. Significantly, rapid down-regulation of endocytic markers occurs upon entering the insect midgut and expression of Rab11 and clathrin remains low throughout subsequent development, which suggests that high endocytic activity is not required for remodeling the parasite surface or for survival within the fly. However, salivary gland metacyclic forms dramatically increase expression of clathrin and Rab11, indicating that emergence of mammalian infective forms is coupled to reacquisition of a high-activity endocytic-recycling system. These data suggest that high-level endocytosis in Trypanosoma brucei is an adaptation required for viability in the mammalian host.     

College and university planning for pandemic influenza: a survey of Philadelphia schools

OBJECTIVES: This study was undertaken to assess the current state of college and university planning for pandemic influenza and to inform guidance for these institutions. METHODS: The Philadelphia Department of Public Health developed an interview guide based on CDC guidance and conducted in-depth structured interviews with college and university pandemic planners in Philadelphia. RESULTS: Thirteen of 14 schools contacted participated in interviews. Six schools, or slightly fewer than half, reported having a draft pandemic influenza plan. Schools noted barriers such as insufficient information and financial resources and institutional support. They reported that they lacked concrete policy recommendations suited to different types of institutions (e.g., small colleges) and lacked the political will to tackle a hypothetical threat. Schools requested further guidance on triggers for campus closure, materials to stockpile, and policies for refunding tuition and adjusting credits for missed coursework. CONCLUSIONS: School pandemic planning is in its early stages. Local government can provide recommendations as to the appropriate level of planning detail, disseminate examples of best practices planning, and continue to emphasize the importance of all-hazards approaches to emergency planning.     

Intertooth patterns of hypoplasia expression: Implications for childhood health in the Classic Maya collapse

Enamel hypoplasias, which record interacting stresses of nutrition and illness during the period of tooth formation, are a key tool in the study of childhood health in prehistory. But interpretation of the age of peak morbidity is complicated by differences in susceptibility to stress both between tooth positions and within a single tooth. Here, hypoplasias are used to evaluate the prevailing ecological model for the collapse of Classic Period Lowland Maya civilization, circa AD 900. Hypoplasias were recorded in the full dentition of 160 adult skeletons from six archaeological sites in the Pasión River region of Guatemala. Instead of constructing a composite scale of stress experience, teeth are considered separately by position in the analysis. No statistical differences are found in the proportion of teeth affected by hypoplasia between “Early,” Late Classic, and Terminal Classic Periods for anterior teeth considered to be most susceptible to stress, indicating stability in the overall stress loads affecting children of the three chronological periods. However, hypoplasia trends in posterior teeth may imply a change in the ontogenetic timing of more severe stress episodes during the final occupation and perhaps herald a shift in child-care practices. These results provide little support for the ecological model of collapse but do call to attention the potential of posterior teeth to reveal subtle changes in childhood morbidity when considered individually. Am J Phys Anthropol 102:233–247, 1997 © 1997 Wiley-Liss, Inc.     

Lateralized behavior in two captive bottlenose dolphins (Tursiops truncatus)

The study of behavioral laterality in humans and nonhumans can contribute to our understanding of brain evolution and functional similarities across species. Few studies have focused on cetaceans. This report exams lateralized behaviors in two captive bottlenose dolphins (Tursiops truncatus). Observations were made by videotaping through a 90 × 150 cm underwater one-way Plexiglass mirror. Directional bias in swimming, “barrel-roll” maneuvers, and circular head movements was assessed for each subject. There was a strong clockwise bias in swimming direction and direction of “barrel-rolls,” but not circular head movements. The clockwise bias in swimming direction and “barrel-roll” maneuvers may be consistent with a rightward turning bias. Zoo Biol 16:173–177, 1997. © 1997 Wiley-Liss, Inc.     

Evolution of protection after maternal immunization for respiratory syncytial virus in cotton rats

Maternal anti-respiratory syncytial virus (RSV) antibodies acquired by the fetus through the placenta protect neonates from RSV disease through the first weeks of life. In the cotton rat model of RSV infections, we previously reported that immunization of dams during pregnancy with virus-like particles assembled with mutation stabilized pre-fusion F protein as well as the wild type G protein resulted in robust protection of their offspring from RSV challenge. Here we describe the durability of those protective responses in dams, the durability of protection in offspring, and the transfer of that protection to offspring of two consecutive pregnancies without a second boost immunization. We report that four weeks after birth, offspring of the first pregnancy were significantly protected from RSV replication in both lungs and nasal tissues after RSV challenge, but protection was reduced in pups at 6 weeks after birth. However, the overall protection of offspring of the second pregnancy was considerably reduced, even at four weeks of age. This drop in protection occurred even though the levels of total anti-pre-F IgG and neutralizing antibody titers in dams remained at similar, high levels before and after the second pregnancy. The results are consistent with an evolution of antibody properties in dams to populations less efficiently transferred to offspring or the less efficient transfer of antibodies in elderly dams.