The Best Laid Plans: How Administrative Burden Complicates Voting Rights Restoration Law and Policy

Despite significant literature on the electoral and democratic implications of laws that restore the right to vote to individuals with felony convictions, few scholars have explored whether these reforms result in practical changes. This Article examines the effect of administrative capacity and individual experience on policy implementation and finds that, even in the face of de jure felon rights restoration, policymakers can (knowingly or unwittingly) alter de facto restoration. Specifically, states have limited administrative capacity to absorb the costs of rights restoration. As a result, the burden of restoration falls onto citizens. Facing learning, compliance, and psychological hurdles to the right to vote, many individuals with felony convictions simply do not have the resources to restore their civil rights. Put simply, even the best laid plans often go awry when it comes to the burden of policy implementation

Early Epstein-Barr Virus Genomic Diversity and Convergence toward the B95.8 Genome in Primary Infection

Over 90% of the world\u27s population is persistently infected with Epstein-Barr virus. While EBV does not cause disease in most individuals, it is the common cause of acute infectious mononucleosis (AIM) and has been associated with several cancers and autoimmune diseases, highlighting a need for a preventive vaccine. At present, very few primary, circulating EBV genomes have been sequenced directly from infected individuals. While low levels of diversity and low viral evolution rates have been predicted for double-stranded DNA (dsDNA) viruses, recent studies have demonstrated appreciable diversity in common dsDNA pathogens (e.g., cytomegalovirus). Here, we report 40 full-length EBV genome sequences obtained from matched oral wash and B cell fractions from a cohort of 10 AIM patients. Both intra- and interpatient diversity were observed across the length of the entire viral genome. Diversity was most pronounced in viral genes required for establishing latent infection and persistence, with appreciable levels of diversity also detected in structural genes, including envelope glycoproteins. Interestingly, intrapatient diversity declined significantly over time (P \u3c 0.01), and this was particularly evident on comparison of viral genomes sequenced from B cell fractions in early primary infection and convalescence (P \u3c 0.001). B cell-associated viral genomes were observed to converge, becoming nearly identical to the B95.8 reference genome over time (Spearman rank-order correlation test; r = -0.5589, P = 0.0264). The reduction in diversity was most marked in the EBV latency genes. In summary, our data suggest independent convergence of diverse viral genome sequences toward a reference-like strain within a relatively short period following primary EBV infection. IMPORTANCE Identification of viral proteins with low variability and high immunogenicity is important for the development of a protective vaccine. Knowledge of genome diversity within circulating viral populations is a key step in this process, as is the expansion of intrahost genomic variation during infection. We report full-length EBV genomes sequenced from the blood and oral wash of 10 individuals early in primary infection and during convalescence. Our data demonstrate considerable diversity within the pool of circulating EBV strains, as well as within individual patients. Overall viral diversity decreased from early to persistent infection, particularly in latently infected B cells, which serve as the viral reservoir. Reduction in B cell-associated viral genome diversity coincided with a convergence toward a reference-like EBV genotype. Greater convergence positively correlated with time after infection, suggesting that the reference-like genome is the result of selection

High Epstein-Barr Virus Load and Genomic Diversity Are Associated with Generation of gp350-Specific Neutralizing Antibodies following Acute Infectious Mononucleosis

The Epstein-Barr virus (EBV) gp350 glycoprotein interacts with the cellular receptor to mediate viral entry and is thought to be the major target for neutralizing antibodies. To better understand the role of EBV-specific antibodies in the control of viral replication and the evolution of sequence diversity, we measured EBV gp350-specific antibody responses and sequenced the gp350 gene in samples obtained from individuals experiencing primary EBV infection (acute infectious mononucleosis [AIM]) and again 6 months later (during convalescence [CONV]). EBV gp350-specific IgG was detected in the sera of 17 (71%) of 24 individuals at the time of AIM and all 24 (100%) individuals during CONV; binding antibody titers increased from AIM through CONV, reaching levels equivalent to those in age-matched, chronically infected individuals. Antibody-dependent cell-mediated phagocytosis (ADCP) was rarely detected during AIM (4 of 24 individuals; 17%) but was commonly detected during CONV (19 of 24 individuals; 79%). The majority (83%) of samples taken during AIM neutralized infection of primary B cells; all samples obtained at 6 months postdiagnosis neutralized EBV infection of cultured and primary target cells. Deep sequencing revealed interpatient gp350 sequence variation but conservation of the CR2-binding site. The levels of gp350-specific neutralizing activity directly correlated with higher peripheral blood EBV DNA levels during AIM and a greater evolution of diversity in gp350 nucleotide sequences from AIM to CONV. In summary, we conclude that the viral load and EBV gp350 diversity during early infection are associated with the development of neutralizing antibody responses following AIM. IMPORTANCE: Antibodies against viral surface proteins can blunt the spread of viral infection by coating viral particles, mediating uptake by immune cells, or blocking interaction with host cell receptors, making them a desirable component of a sterilizing vaccine. The EBV surface protein gp350 is a major target for antibodies. We report the detection of EBV gp350-specific antibodies capable of neutralizing EBV infection in vitro The majority of gp350-directed vaccines focus on glycoproteins from lab-adapted strains, which may poorly reflect primary viral envelope diversity. We report some of the first primary gp350 sequences, noting that the gp350 host receptor binding site is remarkably stable across patients and time. However, changes in overall gene diversity were detectable during infection. Patients with higher peripheral blood viral loads in primary infection and greater changes in viral diversity generated more efficient antibodies. Our findings provide insight into the generation of functional antibodies, necessary for vaccine development

Depression and incident HIV in adolescent girls and young women in HPTN 068:Targets for prevention and mediating factors

Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US. The human immunodeficiency virus (HIV) epidemic among adolescent girls and young women (AGYW) in sub-Saharan Africa is a critical public health problem. We assessed whether depressive symptoms in AGYW were longitudinally associated with incident HIV, and identified potential social and behavioral mediators. Data came from a randomized trial of a cash transfer conditional on school attendance among AGYW (ages 13-21 years) in rural Mpumalanga Province, South Africa, during 2011-2017. We estimated the relationship between depressive symptoms and cumulative HIV incidence using a linear probability model, and we assessed mediation using inverse odds ratio weighting. Inference was calculated using the nonparametric bootstrap. AGYW with depressive symptoms had higher cumulative incidence of HIV compared with those without (risk difference = 3.5, 95% confidence interval (CI): 0.1, 7.0). The strongest individual mediators of this association were parental monitoring and involvement (indirect effect = 1.6, 95% CI: 0.0, 3.3) and reporting a partner would hit her if she asked him to wear a condom (indirect effect = 1.5, 95% CI: -0.3, 3.3). All mediators jointly explained two-thirds (indirect effect = 2.4, 95% CI: 0.2, 4.5) of the association between depressive symptoms and HIV incidence. Interventions addressing mental health might reduce risk of acquiring HIV among AGYW

Tourism Partnerships in Protected Areas: Exploring Contributions to Sustainability

Partnerships between natural-area managers and the tourism industry have been suggested to contribute to sustainability in protected areas. This article explores how important sustainability outcomes of partnerships are to their members, how well they are realised and the features of partnerships leading to their achievement. In 21 case studies in Australia, interviews (n = 97) and surveys (n = 100) showed that of 14 sustainability outcomes, improved understanding of protected areas values and improved biodiversity conservation were the most important. Other highly ranked outcomes were greater respect for culture, heritage, and/or traditions; improved quality of environmental conditions; social benefits to local communities; and improved economic viability of the protected area. Scores for satisfaction with outcomes were, like those for importance, all high but were less than those for importance for the majority, with improvement in quality of environmental conditions showing the largest gap. The satisfaction score exceeded that for importance only for increased competitiveness of the protected area as a tourist destination. “Brown” aspects of sustainability, i.e., decreased waste or energy use, were among the lowest-scoring outcomes for both importance and satisfaction. The most important factor enabling sustainability outcomes was provision of benefits to partnership members. Others were increased financial support, inclusiveness, supportive organisational and administrative arrangements, direct involvement of decision makers, partnership maturity, creation of new relationships, decreased conflict, and stimulation of innovation. Improving sustainability outcomes, therefore, requires maintaining these partnership attributes and also increasing emphasis on reducing waste and resource use

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

The Best Laid Plans: How Administrative Burden Complicates Voting Rights Restoration Law and Policy

Despite significant literature on the electoral and democratic implications of laws that restore the right to vote to individuals with felony convictions, few scholars have explored whether these reforms result in practical changes. This Article examines the effect of administrative capacity and individual experience on policy implementation and finds that, even in the face of de jure felon rights restoration, policymakers can (knowingly or unwittingly) alter de facto restoration. Specifically, states have limited administrative capacity to absorb the costs of rights restoration. As a result, the burden of restoration falls onto citizens. Facing learning, compliance, and psychological hurdles to the right to vote, many individuals with felony convictions simply do not have the resources to restore their civil rights. Put simply, even the best laid plans often go awry when it comes to the burden of policy implementation

Men\u27s perspectives on the impact of female-directed cash transfers on gender relations: Findings from the HPTN 068 qualitative study

HIV is an inherently gendered disease in eastern and southern Africa, not only because more women than men are infected, but also because socially constructed gender norms work to increase women\u27s HIV-infection risk. The provision of cash transfers to young women alone in such a context adds another dimension to already existing complex social relations where patriarchal values are entrenched, gender inequality is the norm, and violence against women and girls is pervasive. It raises concerns about complicating young women\u27s relationships with their male partners or possibly even setting them up for more violence. In our attempt to understand how cash transfers influence social relations in the context of a trial among young women in South Africa, we used qualitative data collected during the trial to explore men\u27s perceptions of the impact of cash transfers on male-female relationships, both intimate and platonic, peer relationships