A systematic review of health system barriers and enablers for antiretroviral therapy (ART) for HIV-infected pregnant and postpartum women

BACKGROUND: Despite global progress in the fight to reduce maternal mortality, HIV-related maternal deaths remain persistently high, particularly in much of Africa. Lifelong antiretroviral therapy (ART) appears to be the most effective way to prevent these deaths, but the rates of three key outcomes--ART initiation, retention in care, and long-term ART adherence--remain low. This systematic review synthesized evidence on health systems factors affecting these outcomes in pregnant and postpartum women living with HIV. METHODS: Searches were conducted for studies addressing the population of interest (HIV-infected pregnant and postpartum women), the intervention of interest (ART), and the outcomes of interest (initiation, adherence, and retention). Quantitative and qualitative studies published in English since January 2008 were included. A four-stage narrative synthesis design was used to analyze findings. Review findings from 42 included studies were categorized according to five themes: 1) models of care, 2) service delivery, 3) resource constraints and governance challenges, 4) patient-health system engagement, and 5) maternal ART interventions. RESULTS: Low prioritization of maternal ART and persistent dropout along the maternal ART cascade were key findings. Service delivery barriers included poor communication and coordination among health system actors, poor clinical practices, and gaps in provider training. The few studies that assessed maternal ART interventions demonstrated the importance of multi-pronged, multi-leveled interventions. CONCLUSIONS: There has been a lack of emphasis on the experiences, needs and vulnerabilities particular to HIV-infected pregnant and postpartum women. Supporting these women to successfully traverse the maternal ART cascade requires carefully designed and targeted interventions throughout the steps. Careful design of integrated service delivery models is of critical importance in this effort. Key knowledge gaps and research priorities were also identified, including definitions and indicators of adherence rates, and the importance of cumulative measures of dropout along the maternal ART cascade

Quantum and classical localisation, the spin quantum Hall effect and generalisations

We consider network models for localisation problems belonging to symmetry class C. This symmetry class arises in a description of the dynamics of quasiparticles for disordered spin-singlet superconductors which have a Bogoliubov - de Gennes Hamiltonian that is invariant under spin rotations but not under time-reversal. Our models include but also generalise the one studied previously in the context of the spin quantum Hall effect. For these systems we express the disorder-averaged conductance and density of states in terms of sums over certain classical random walks, which are self-avoiding and have attractive interactions. A transition between localised and extended phases of the quantum system maps in this way to a similar transition for the classical walks. In the case of the spin quantum Hall effect, the classical walks are the hulls of percolation clusters, and our approach provides an alternative derivation of a mapping first established by Gruzberg, Read and Ludwig, Phys. Rev. Lett. 82, 4254 (1999).Comment: 11 pages, 5 figure

Multiple ART Programs Create a Dilemma for Providers to Monitor ARV Adherence in Uganda

Background: Increased availability and accessibility of antiretroviral therapy (ART) has improved the length and quality of life amongst people living with HIV/AIDS. This has changed the landscape for care from episodic to longterm care that requires more monitoring of adherence. This has led to increased demand on human resources, a major problem for most ART programs. This paper presents experiences and perspectives of providersin ART facilities, exploring the organizational factors affecting their capacity to monitor adherence to ARVs. Methods: From an earlier survey to test adherence indicators and rank facilities as good, medium or poor adherence performances, six facilities were randomly selected, two from each rank. Observations on facility set-up, provider-patient interactions and key informant interviews were carried out. The strengths, weaknesses, opportunities and threats identified by health workers as facilitators or barriers to their capacity to monitor adherence to ARVs were explored during group discussions. Results: Findings show that the performance levels of the facilities were characterized by four different organizational ARTprograms operating in Uganda, with apparent lack of integration and coordination at the facilities. Of the six facilities studied, the two highadherence performing facilities were Non-Governmental Organization (NGO) programs, while facilities with dual organizational programs(Governmental/NGO) performed poorly. Working conditions, record keeping and the duality of programs underscored the providers' capacity tomonitor adherence. Overall 70% of the observed provider-patient interactions were conducted in environments that ensured privacy of the patient. The mean performance for record keeping was 79% and 50% in the high and low performing facilities respectively. Providers often found it difficult to monitor adherence due to the conflicting demands from the different organizational ART programs. Conclusion: Organizational duality at facilities is a major factor in poor adherence monitoring. The different ART programs in Uganda need to be coordinated and integrated into a single well resourced program to improve ART services and adherence monitoring. The focus on long-term care of patients on ART requires that the limitations to providers' capacity for monitoring adherence become central during the planning and implementation of ART programs

Magnon Localization in Mattis Glass

We study the spectral and transport properties of magnons in a model of a disordered magnet called Mattis glass, at vanishing average magnetization. We find that in two dimensional space, the magnons are localized with the localization length which diverges as a power of frequency at small frequencies. In three dimensional space, the long wavelength magnons are delocalized. In the delocalized regime in 3d (and also in 2d in a box whose size is smaller than the relevant localization length scale) the magnons move diffusively. The diffusion constant diverges at small frequencies. However, the divergence is slow enough so that the thermal conductivity of a Mattis glass is finite, and we evaluate it in this paper. This situation can be contrasted with that of phonons in structural glasses whose contribution to thermal conductivity is known to diverge (when inelastic scattering is neglected).Comment: 11 page

Critical statistics for non-Hermitian matrices

We introduce a generalized ensemble of nonhermitian matrices interpolating between the Gaussian Unitary Ensemble, the Ginibre ensemble and the Poisson ensemble. The joint eigenvalue distribution of this model is obtained by means of an extension of the Itzykson-Zuber formula to general complex matrices. Its correlation functions are studied both in the case of weak nonhermiticity and in the case of strong nonhermiticity. In the weak nonhermiticity limit we show that the spectral correlations in the bulk of the spectrum display critical statistics: the asymptotic linear behavior of the number variance is already approached for energy differences of the order of the eigenvalue spacing. To lowest order, its slope does not depend on the degree of nonhermiticity. Close the edge, the spectral correlations are similar to the Hermitian case. In the strong nonhermiticity limit the crossover behavior from the Ginibre ensemble to the Poisson ensemble first appears close to the surface of the spectrum. Our model may be relevant for the description of the spectral correlations of an open disordered system close to an Anderson transition.Comment: 25 pages, 6 figure

Constant photocurrent method to probe the sub-bandgap absorption in wide bandgap semiconductor films : the case of α-Ga2O3

The optical absorption coefficient is one of the fundamental properties of semiconductors and is critical to the development of optical devices. Herein, a revival of the constant photocurrent method is presented to measure sub-bandgap absorption in wide bandgap semiconductor films. The method involves maintaining a constant photocurrent by continually adjusting the impinging photon flux across the energy spectrum. Under such conditions, the reciprocal of the photon flux for uniformly absorbed light is proportional to the absorption coefficient. This method is applied to α-Ga 2O 3 and reveals that it can access the absorption coefficient from 1 × 10 5 cm −1 at the band edge (5.3 eV) to 0.8 cm −1 close to mid-bandgap (2.7 eV). Changes in the steepness of the absorption curve in the sub-bandgap region are in excellent agreement with defect states of α-Ga 2O 3 reported by deep level transient spectroscopy, indicating that the technique shows promise as a probe of energetically distributed defect states in thin film wide bandgap semiconductors

Pediatric pan-central nervous system tumor analysis of immune-cell infiltration identifies correlates of antitumor immunity

Here, using methylCIBERSORT, the authors characterize the tumour-immune microenvironment of paediatric central nervous system (CNS) tumours and its association with tumour type and prognosis. These findings suggest that immuno-methylomic profiling may inform immunotherapy approaches in paediatric patients with CNS tumour

Random Matrices close to Hermitian or unitary: overview of methods and results

The paper discusses progress in understanding statistical properties of complex eigenvalues (and corresponding eigenvectors) of weakly non-unitary and non-Hermitian random matrices. Ensembles of this type emerge in various physical contexts, most importantly in random matrix description of quantum chaotic scattering as well as in the context of QCD-inspired random matrix models.Comment: Published version, with a few more misprints correcte

Measuring adherence to antiretroviral treatment in resource-poor settings: The feasibility of collecting routine data for key indicators

<p>Abstract</p> <p>Background</p> <p>An East African survey showed that among the few health facilities that measured adherence to antiretroviral therapy, practices and definitions varied widely. We evaluated the feasibility of collecting routine data to standardize adherence measurement using a draft set of indicators.</p> <p>Methods</p> <p>Targeting 20 facilities each in Ethiopia, Kenya, Rwanda, and Uganda, in each facility we interviewed up to 30 patients, examined 100 patient records, and interviewed staff.</p> <p>Results</p> <p>In 78 facilities, we interviewed a total of 1,631 patients and reviewed 8,282 records. Difficulties in retrieving records prevented data collection in two facilities. Overall, 94.2% of patients reported perfect adherence; dispensed medicine covered 91.1% of days in a six month retrospective period; 13.7% of patients had a gap of more than 30 days in their dispensed medication; 75.8% of patients attended clinic on or before the date of their next appointment; and 87.1% of patients attended within 3 days.</p> <p>In each of the four countries, the facility-specific median indicators ranged from: 97%-100% for perfect self-reported adherence, 90%-95% of days covered by dispensed medicines, 2%-19% of patients with treatment gaps of 30 days or more, and 72%-91% of appointments attended on time. Individual facilities varied considerably.</p> <p>The percentages of days covered by dispensed medicine, patients with more than 95% of days covered, and patients with a gap of 30 days or more were all significantly correlated with the percentages of patients who attended their appointments on time, within 3 days, or within 30 days of their appointment. Self reported recent adherence in exit interviews was significantly correlated only with the percentage of patients who attended within 3 days of their appointment.</p> <p>Conclusions</p> <p>Field tests showed that data to measure adherence can be collected systematically from health facilities in resource-poor settings. The clinical validity of these indicators is assessed in a companion article. Most patients and facilities showed high levels of adherence; however, poor levels of performance in some facilities provide a target for quality improvement efforts.</p

Recurrent adamantinomatous craniopharyngiomas show MAPK pathway activation, clonal evolution and rare <i>TP53 </i>-loss-mediated malignant progression

The two types of craniopharyngioma, adamantinomatous (ACP) and papillary (PCP), are clinically relevant tumours in children and adults. Although the biology of primary craniopharyngioma is starting to be unravelled, little is known about the biology of recurrence. To fill this gap in knowledge, we have analysed through methylation array, RNA sequencing and pERK1/2 immunohistochemistry a cohort of paired primary and recurrent samples (32 samples from 14 cases of ACP and 4 cases of PCP). We show the presence of copy number alterations and clonal evolution across recurrence in 6 cases of ACP, and analysis of additional whole genome sequencing data from the Children’s Brain Tumour Network confirms chromosomal arm copy number changes in at least 7/67 ACP cases. The activation of the MAPK/ERK pathway, a feature previously shown in primary ACP, is observed in all but one recurrent cases of ACP. The only ACP without MAPK activation is an aggressive case of recurrent malignant human craniopharyngioma harbouring a CTNNB1 mutation and loss of TP53. Providing support for a functional role of this TP53 mutation, we show that Trp53 loss in a murine model of ACP results in aggressive tumours and reduced mouse survival. Finally, we characterise the tumour immune infiltrate showing differences in the cellular composition and spatial distribution between ACP and PCP. Together, these analyses have revealed novel insights into recurrent craniopharyngioma and provided preclinical evidence supporting the evaluation of MAPK pathway inhibitors and immunomodulatory approaches in clinical trials in against recurrent ACP