Political and Governance Challenges to Achieving Global HIV Goals with Injecting Drug Users: The Case of Pakistan

Background The Joint United Nations Programme on HIV/AIDS (UNAIDS) has recently set the ambitious “90-90-90 target” of having 90% of people living with HIV (PLHIV) know their status, receive antiretroviral therapy (ART), and achieve viral suppression by 2020. This ambitious new goal is occurring in a context of global “scale-down” following nearly a decade of heightened investment in HIV prevention and treatment efforts. Arguably international goals spur action, however, setting unrealistic goals that do not take weak health systems and variations in the nature of the epidemic across countries into consideration may set them up for failure in unproductive ways that lead to a decline in confidence in global governance institutions. This study explores how policy actors tasked with implementing HIV programs navigate the competing demands placed upon them by development targets and national politics, particularly in the current context of waning international investments towards HIV. Methods To examine these questions, we interviewed 29 key informants comprising health experts in donor organizations and government employees in HIV programs in Pakistan, a country where HIV programs must compete with other issues for attention. Themes were identified inductively through an iterative process and findings were triangulated with various data sources and existing literature. Results We found both political and governance challenges to achieving the target, particularly in the context of the global HIV scale-down. Political challenges included, low and heterogeneous political commitment for HIV and a conservative legal environment that contributed towards a ban on opiate substitution therapy, creating low treatment coverage. Governance challenges includedstrained state and non-governmental organization (NGO) relations creating a hostile service delivery environment, weak bureaucratic and civil society capacity contributing to poor regulation of the health infrastructure, and resource mismanagement on both the part of the government and NGOs. Conclusion Our findings suggest that in a context of waning international attention to HIV, policy actors on the ground face a number of practical hurdles to achieving the ambitious targets set out by international agencies. Greater attention to the political and governance challenges of implementing HIV programs in low- and middle-income countries (LMICs) could help technical assistance agencies to develop more realistic implementation plans

How increasing administrative burdens and means testing in the US safety-net punishes the poor

Millions of Americans rely on safety-net programs such as the Temporary Assistance for Needy Families, the Supplemental Nutrition Assistance Program, and Medicaid. In recent decades, these programs have been reformed with the aim of better targeting those most in need by creating rules and eligibility assessments. In new research. Ashley Fox, Wenhui Feng and Megan Reynolds find that the introduction of these rules has created substantial barriers and often reduced the enrolment of those who need the programs’ support the most. They argue that if we want needy individuals to access benefits, then we need to make it easy for them to do so by relaxing or removing the burdensome rules that serve as barriers to access

Decentralizing for a deeper, more supple democracy

Well-designed decentralization can deepen democracy and strengthen the state in five key ways. Decentralizing below the level of social cleavages should undermine secessionism by peeling away moderates from radical leaders. The “fragmentation of authority” critique is mistaken; decentralization transforms the state from a simpler, brittler command structure to one of multilevel complementarity more robust to local failure. Decentralizing services with low economies of scale, with devolved taxation and bail-outs prohibited, should increase accountability. Lastly, the small scale of local politics allows citizens to become political actors, promoting social learning-by-doing, strengthening political legitimacy and ‘democratic suppleness’ from the grass-roots upwards

Does decentralization strengthen or weaken the state? Authority and social learning in a supple state

We examine how decentralization affects four key aspects of state strength: (i) Authority over territory and conflict prevention, (ii) Policy autonomy and the ability to uphold the law, (iii) Responsive, accountable service provision, and (iv) Social learning. We provide specific reform paths that should lead to strengthening in each. Decentralizing below the level of social cleavages should drain secessionist pressure by peeling away moderate citizens from radical leaders. The regional specificity of elite interests is key. If regional elites have more to lose than gain from national schism, they will not invest in politicians and conflicts that promote secession. Strong accountability mechanisms and national safeguards of minority rights can align local leaders’ incentives with citizens’, so promoting power-sharing and discouraging local capture or oppression. “Fragmentation of authority” is a mistaken inference; what decentralization really does is transform politics from top-down to bottom-up, embracing many localities and their concerns. The state moves from a simpler, brittler command structure to one based on overlapping authority and complex complementarity, where government is more robust to failure in any of its parts. Well-designed reform, focusing on services with low economies of scale, with devolved taxation and bail-outs prohibited, should increase public accountability. Lastly, by allowing citizens to become political actors in their own right, the small scale of local politics should promote social learning-by-doing, so strengthening political legitimacy, state-building, and ‘democratic suppleness’ from the grass-roots upwards

Islamism, Secularism and the Woman Question in the Aftermath of the Arab Spring: Evidence from the Arab Barometer

The uprisings that led to regime change during the early period of the Arab Spring were initially inclusive and pluralistic in nature, with men and women from every political and religious orientation engaging actively in political activities on the street and in virtual spaces. While there was an opening of political space for women and the inclusion of demands of marginalized groups in the activists’ agenda, the struggle to reimagine national identities that balance Islamic roots and secular yearnings is still ongoing in many countries in the region. This paper seeks to deepen understanding of the extent to which the pluralistic sentiments and openness to accepting the rights women have persisted following the uprising. We aim to examine changes in attitudes towards women’s equality in countries that underwent regime change through popular uprisings during revolutionary upheavals of the Arab Spring and in countries where regimes have remained unchanged. Using available data from consecutive rounds of the Arab Barometer survey, we examine changes in attitudes in nine countries with two rounds of Arab Barometer during and post Arab Spring (Egypt, Yemen, Tunisia, Algeria, Lebanon, Sudan, Jordan, Iraq, Palestine). We find that support for “Muslim feminism” (an interpretation of gender equality grounded in Islam) has increased over the period and particularly in Arab Spring countries, while support for “secular feminism” has declined. In most countries examined, relatively high degrees of support for gender equality co-exist with a preference for Islamic interpretations of personal status codes pertaining to women. We discuss the implications of these findings for academics and activists concerned with women’s rights in the Middle East North Africa (MENA)

The Nicotine Metabolite, Cotinine, Alters the Assembly and Trafficking of a Subset of Nicotinic Acetylcholine Receptors

Exposure to nicotine alters the trafficking and assembly of nicotinic receptors (nAChRs), leading to their up-regulation on the plasma membrane. Although the mechanism is not fully understood, nicotine-induced up-regulation is believed to contribute to nicotine addiction. The effect of cotinine, the primary metabolite of nicotine, on nAChR trafficking and assembly has not been extensively investigated. We utilize a pH-sensitive variant of GFP, super ecliptic pHluorin, to differentiate between intracellular nAChRs and those expressed on the plasma membrane to quantify changes resulting from cotinine and nicotine exposure. Similar to nicotine, exposure to cotinine increases the number of α4β2 receptors on the plasma membrane and causes a redistribution of intracellular receptors. In contrast to this, cotinine exposure down-regulates α6β2β3 receptors. We also used single molecule fluorescence studies to show that cotinine and nicotine both alter the assembly of α4β2 receptors to favor the high sensitivity (α4)2(β2)3 stoichiometry

Organelle-Specific Single-Molecule Imaging of \u3cem\u3eα\u3c/em\u3e4\u3cem\u3eβ\u3c/em\u3e2 Nicotinic Receptors Reveals the Effect of Nicotine on Receptor Assembly and Cell-Surface Trafficking

Nicotinic acetylcholine receptors (nAChRs) assemble in the endoplasmic reticulum (ER) and traffic to the cell surface as pentamers composed of α and β subunits. Many nAChR subtypes can assemble with varying subunit ratios, giving rise to multiple stoichiometries exhibiting different subcellular localization and functional properties. In addition to the endogenous neurotransmitter acetylcholine, nicotine also binds and activates nAChRs and influences their trafficking and expression on the cell surface. Currently, no available technique can specifically elucidate the stoichiometry of nAChRs in the ER versus those in the plasma membrane. Here, we report a method involving single-molecule fluorescence measurements to determine the structural properties of these membrane proteins after isolation in nanoscale vesicles derived from specific organelles. These cell-derived nanovesicles allowed us to separate single membrane receptors while maintaining them in their physiological environment. Sorting the vesicles according to the organelle of origin enabled us to determine localized differences in receptor structural properties, structural influence on transport between organelles, and changes in receptor assembly within intracellular organelles. These organelle-specific nanovesicles revealed that one structural isoform of the α4β2 nAChR was preferentially trafficked to the cell surface. Moreover, nicotine altered nAChR assembly in the ER, resulting in increased production of the receptor isoform that traffics more efficiently to the cell surface. We conclude that the combined effects of the increased assembly of one nAChR stoichiometry and its preferential trafficking likely drive the up-regulation of nAChRs on the cell surface upon nicotine exposure

Utilizing pHluorin-Tagged Receptors to Monitor Subcellular Localization and Trafficking

Understanding membrane protein trafficking, assembly, and expression requires an approach that differentiates between those residing in intracellular organelles and those localized on the plasma membrane. Traditional fluorescence-based measurements lack the capability to distinguish membrane proteins residing in different organelles. Cutting edge methodologies transcend traditional methods by coupling pH-sensitive fluorophores with total internal reflection fluorescence microscopy (TIRFM). TIRF illumination excites the sample up to approximately 150 nm from the glass-sample interface, thus decreasing background, increasing the signal to noise ratio, and enhancing resolution. The excitation volume in TIRFM encompasses the plasma membrane and nearby organelles such as the peripheral ER. Superecliptic pHluorin (SEP) is a pH sensitive version of GFP. Genetically encoding SEP into the extracellular domain of a membrane protein of interest positions the fluorophore on the luminal side of the ER and in the extracellular region of the cell. SEP is fluorescent when the pH is greater than 6, but remains in an off state at lower pH values. Therefore, receptors tagged with SEP fluoresce when residing in the endoplasmic reticulum (ER) or upon insertion in the plasma membrane (PM) but not when confined to a trafficking vesicle or other organelles such as the Golgi. The extracellular pH can be adjusted to dictate the fluorescence of receptors on the plasma membrane. The difference in fluorescence between TIRF images at neutral and acidic extracellular pH for the same cell corresponds to a relative number of receptors on the plasma membrane. This allows a simultaneous measurement of intracellular and plasma membrane resident receptors. Single vesicle insertion events can also be measured when the extracellular pH is neutral, corresponding to a low pH trafficking vesicle fusing with the plasma membrane and transitioning into a fluorescent state. This versatile technique can be exploited to study localization, expression, and trafficking of membrane proteins

Conceptual and methodological challenges to measuring political commitment to respond to HIV

Background: Researchers have long recognized the importance of a central government’s political “commitment” in order to mount an effective response to HIV. The concept of political commitment remains ill-defined, however, and little guidance has been given on how to measure this construct and its relationship with HIV-related outcomes. Several countries have experienced declines in HIV infection rates, but conceptual difficulties arise in linking these declines to political commitment as opposed to underlying social and behavioural factors. Methods: This paper first presents a critical review of the literature on existing efforts to conceptualize and measure political commitment to respond to HIV and the linkages between political commitment and HIV-related outcomes. Based on the elements identified in this review, the paper then develops and presents a framework to assist researchers in making choices about how to assess a government's level of political commitment to respond to HIV and how to link political commitment to HIV-related outcomes. Results: The review of existing studies identifies three components of commitment (expressed, institutional and budgetary commitment) as different dimensions along which commitment can be measured. The review also identifies normative and ideological aspects of commitment and a set of variables that mediate and moderate political commitment that need to be accounted for in order to draw valid inferences about the relationship between political commitment and HIV-related outcomes. The framework summarizes a set of steps that researchers can follow in order to assess a government's level of commitment to respond to HIV and suggests ways to apply the framework to country cases. Conclusions: Whereas existing studies have adopted a limited and often ambiguous conception of political commitment, we argue that conceiving of political commitment along a greater number of dimensions will allow researchers to draw a more complete picture of political commitment to respond to HIV that avoids making invalid inferences about the relationship between political commitment and HIV outcomes