Outcomes of Patients Lost to Follow-up in African Antiretroviral Therapy Programs: Individual Patient Data Meta-analysis.

BACKGROUND: Low retention on combination antiretroviral therapy (cART) has emerged as a threat to the Joint United Nations Programme on human immunodeficiency virus (HIV)/AIDS (UNAIDS) 90-90-90 targets. We examined outcomes of patients who started cART but were subsequently lost to follow-up (LTFU) in African treatment programs. METHODS: This was a systematic review and individual patient data meta-analysis of studies that traced patients who were LTFU. Outcomes were analyzed using cumulative incidence functions and proportional hazards models for the competing risks of (i) death, (ii) alive but stopped cART, (iii) silent transfer to other clinics, and (iv) retention on cART. RESULTS: Nine studies contributed data on 7377 patients who started cART and were subsequently LTFU in sub-Saharan Africa. The median CD4 count at the start of cART was 129 cells/μL. At 4 years after the last clinic visit, 21.8% (95% confidence interval [CI], 20.8%-22.7%) were known to have died, 22.6% (95% CI, 21.6%-23.6%) were alive but had stopped cART, 14.8% (95% CI, 14.0%-15.6%) had transferred to another clinic, 9.2% (95% CI, 8.5%-9.8%) were retained on cART, and 31.6% (95% CI, 30.6%-32.7%) could not been found. Mortality was associated with male sex, more advanced disease, and shorter cART duration; stopping cART with less advanced disease andlonger cART duration; and silent transfer with female sex and less advanced disease. CONCLUSIONS: Mortality in patients LTFU must be considered for unbiased assessments of program outcomes and UNAIDS targets in sub-Saharan Africa. Immediate start of cART and early tracing of patients LTFU should be priorities

Theoretical study of large conformational transitions in DNA: the B↔A conformational change in water and ethanol/water

We explore here the possibility of determining theoretically the free energy change associated with large conformational transitions in DNA, like the solvent-induced B⇔A conformational change. We find that a combination of targeted molecular dynamics (tMD) and the weighted histogram analysis method (WHAM) can be used to trace this transition in both water and ethanol/water mixture. The pathway of the transition in the A→B direction mirrors the B→A pathway, and is dominated by two processes that occur somewhat independently: local changes in sugar puckering and global rearrangements (particularly twist and roll) in the structure. The B→A transition is found to be a quasi-harmonic process, which follows closely the first spontaneous deformation mode of B-DNA, showing that a physiologically-relevant deformation is in coded in the flexibility pattern of DNA

The Banff 2022 Kidney Meeting Work Plan:Data-driven refinement of the Banff Classification for renal allografts

The XVIth Banff Meeting for Allograft Pathology was held in Banff, Alberta, Canada, from September 19 to 23, 2022, as a joint meeting with the Canadian Society of Transplantation. In addition to a key focus on the impact of microvascular inflammation and biopsy-based transcript analysis on the Banff Classification, further sessions were devoted to other aspects of kidney transplant pathology, in particular T cell–mediated rejection, activity and chronicity indices, digital pathology, xenotransplantation, clinical trials, and surrogate endpoints. Although the output of these sessions has not led to any changes in the classification, the key role of Banff Working Groups in phrasing unanswered questions, and coordinating and disseminating results of investigations addressing these unanswered questions was emphasized. This paper summarizes the key Banff Meeting 2022 sessions not covered in the Banff Kidney Meeting 2022 Report paper and also provides an update on other Banff Working Group activities relevant to kidney allografts.</p

The Banff 2022 Kidney Meeting Work Plan:Data-driven refinement of the Banff Classification for renal allografts

The XVIth Banff Meeting for Allograft Pathology was held in Banff, Alberta, Canada, from September 19 to 23, 2022, as a joint meeting with the Canadian Society of Transplantation. In addition to a key focus on the impact of microvascular inflammation and biopsy-based transcript analysis on the Banff Classification, further sessions were devoted to other aspects of kidney transplant pathology, in particular T cell–mediated rejection, activity and chronicity indices, digital pathology, xenotransplantation, clinical trials, and surrogate endpoints. Although the output of these sessions has not led to any changes in the classification, the key role of Banff Working Groups in phrasing unanswered questions, and coordinating and disseminating results of investigations addressing these unanswered questions was emphasized. This paper summarizes the key Banff Meeting 2022 sessions not covered in the Banff Kidney Meeting 2022 Report paper and also provides an update on other Banff Working Group activities relevant to kidney allografts.</p

The Banff 2019 Kidney Meeting Report (I): Updates on and clarification of criteria for T cell– and antibody-mediated rejection

The XV. Banff conference for allograft pathology was held in conjunction with the annual meeting of the American Society for Histocompatibility and Immunogenetics in Pittsburgh, PA (USA) and focused on refining recent updates to the classification, advances from the Banff working groups, and standardization of molecular diagnostics. This report on kidney transplant pathology details clarifications and refinements to the criteria for chronic active (CA) T cell–mediated rejection (TCMR), borderline, and antibody-mediated rejection (ABMR). The main focus of kidney sessions was on how to address biopsies meeting criteria for CA TCMR plus borderline or acute TCMR. Recent studies on the clinical impact of borderline infiltrates were also presented to clarify whether the threshold for interstitial inflammation in diagnosis of borderline should be i0 or i1. Sessions on ABMR focused on biopsies showing microvascular inflammation in the absence of C4d staining or detectable donor-specific antibodies; the potential value of molecular diagnostics in such cases and recommendations for use of the latter in the setting of solid organ transplantation are presented in the accompanying meeting report. Finally, several speakers discussed the capabilities of artificial intelligence and the potential for use of machine learning algorithms in diagnosis and personalized therapeutics in solid organ transplantation

Institutional Impediments and Reluctant Actors – The Limited Role of Democracy Aid in Democratic Development.

Poverty reduction and societal modernization have traditionally been the main goals for development aid but increasingly, since the early 1990s, democracy and human rights have ascended in importance and democracy aid has been growing steadily, both in total amounts and as a share of the total aid package. This dissertation contributes to the understanding of the role of democracy aid in democratic development. It includes four papers, three of which analyze the role of democracy aid in democratic development and a fourth one which develops why, and tests whether, a meritocratic-based administrative structure is important for democratic survival and therefore a key aspect to take into consideration for future efforts of promoting democracy. The first two papers of this dissertation show that democracy aid may have positive effects on democracy levels and regime change but that the effects are limited to certain contexts: when recipient rulers perceive that they have more to gain than to lose from implementing democracy aid activities. Democracy aid only has a positive effect on democracy levels in one-party regimes and in preventing democratic breakdown in existing democracies. Democracy aid does not contribute to democratization in authoritarian regimes. The third paper develops a theoretical framework for understanding why democracy aid could be difficult to implement in democracies with unstable bureaucracies and, in particular, in bureaucracies where this instability is due to a high rate of turnover caused by political appointments. The fourth paper shows that democracies with meritocratic types of bureaucracies survive longer than democracies with patronage-based administrations. The main joint conclusion is that democracy aid may alter things on the margin but only under some fruitful conditions when donors’ and recipients’ interests coincide. In other circumstances institutional impediments and reluctant actors are likely to limit the role of democracy aid in democratic development. Moreover, the fruitful conditions imply political stability; therefore the prospects of radical change, as a result of aid projects, are small. This is a paradoxical conclusion given that the very aim of democracy aid is rather to promote political change than the status quo. The research design is mainly oriented towards performing large N-empirical tests of hypotheses (Papers I, II, and IV) but it also includes more qualitative accounts on how theoretical mechanisms play out in practice, both based on field interviews (Paper III) and historical examples (Paper IV). This empirical contribution, in comparison to previous research on democracy aid, broadens the analytical scope in terms of time frame, and the recipients and donors included. The qualitative accounts, on the other hand, explore mechanisms not studied previously in relation to the novel hypotheses developed in this dissertation

Disruptive Protests and Bureaucratic Structures in Latin America and the Caribbean

The paper examines why citizens in some democracies engage in disruptive political actions to a larger extent than in other countries. Our hypothesis adds to previous research that focuses on individual factors, representational issues or discontent with public sector performance to explain the occurrence of disruptive protests. We hypothesize that a more politically controlled administration introduces turbulence in democracies, especially where civil society is strong. A public administration heavily controlled by politicians, and staffed to a large extent with politically appointed individuals, allows politicians to intervene in policy implementation and favor some groups over others in terms of access to public services and employment. Such a system may induce citizens to resort to disruptive actions to express demands and grievances, and secure access to public goods. We test this argument empirically on data from 19 countries in Latin America and the Caribbean. The findings are consistent with the hypothesis

The Ambiguous Effects of Democracy on Bureaucratic Quality

Recent studies find that higher degrees of democracy are related to higher levels of bureaucratic quality. However, they only offer limited explanations for this pattern based on a unidimensional understanding of democracy. We argue that future uncertainties as perceived by the incumbent, the opposition, and voters are important for why bureaucratic reform takes place. Therefore, we expect no uniform effects of democracy but that the effect depends on the socioeconomic status of the median voter. Empirically, we examine the separate effects of three dimensions of democracy – competitive elections, legislative constraints on the executive, and suffrage. Based on a global sample of countries from 1790 to 2016 that adds historical depth and variation on bureaucratic quality and the dimensions of democracy, the results show that competitive elections and legislative constraints are connected with higher levels of bureaucratic quality. However, the third dimension of suffrage is not related to bureaucratic quality. Rather, the positive effects of competitive elections and legislative constraints seem to decrease in times of large suffrage extensions