Impact of decentralization of Antiretroviral Therapy services on HIV testing and care at population level in Agago District in rural Northern Uganda: Results from the Lablite population surveys

BACKGROUND: We conducted unlinked cross-sectional population-based surveys in Northern Uganda before and after ART provision (including Option B+ (lifelong ART for pregnant/breast-feeding women)) at a local primary care facility (Lira Kato Health Centre (HC)).Prior to decentralization, people travelled 56-76km round-trip for ART; we aimed to evaluate changes in uptake of HIV-testing, ART coverage and access to ART following decentralization. / METHODS: 2124 adults in 1351 households in 2 parishes closest to Lira Kato HC were interviewed using questionnaires between March-April/2013; 2123 adults in 1229 households between January-March/2015. / RESULTS: Adults reporting HIV-testing in the last year increased from 1077/2124 (51%) to 1298/2123 (61%) between surveys (p<0.001). ART coverage increased from 74/136(54%) self-reported HIV-positive adults in 2013 to 108/133 (81%) in 2015 (p<0.001). Post-decentralization, 47/108(44%) of those on ART were in care at Lira Kato HC (including 37 new initiations). Most of the remainder (47/61) started ART prior to any ART provision at Lira Kato HC; the most common reason given for not accessing ART locally was concern about drug-stock-outs (30 (51%)). / CONCLUSIONS: HIV-testing and ART coverage increased after decentralization combined with Option B+ roll-out. However, patients on ART before decentralisation were reluctant to transfer to their local facility

Developmental white matter microstructure in autism phenotype and corresponding endophenotype during adolescence.

During adolescence, white matter microstructure undergoes an important stage of development. It is hypothesized that the alterations of brain connectivity that have a key role in autism spectrum conditions (ASCs) may interact with the development of white matter microstructure. This interaction may be present beyond the phenotype of autism in siblings of individuals with ASC, who are 10 to 20 times more likely to develop certain forms of ASC. We use diffusion tensor imaging to examine how white matter microstructure measurements correlate with age in typically developing individuals, and how this correlation differs in n=43 adolescents with ASC and their n=38 siblings. Correlations observed in n=40 typically developing individuals match developmental changes noted in previous longitudinal studies. In comparison, individuals with ASC display weaker negative correlation between age and mean diffusivity in a broad area centred in the right superior longitudinal fasciculus. These differences may be caused either by increased heterogeneity in ASC or by temporal alterations in the group's developmental pattern. Siblings of individuals with ASC also show diminished negative correlation between age and one component of mean diffusivity-second diffusion eigenvalue-in the right superior longitudinal fasciculus. As the observed differences match for location and correlation directionality in our comparison of typically developing individuals to those with ASC and their siblings, we propose that these alterations constitute a part of the endophenotype of autism.This research was funded by an MRC Clinician Scientist Fellowship to MDS from the UK Medical Research Council (G0701919). LRC was supported by the Gates Cambridge Scholarship Trust. SB-C was supported by the Wellcome Trust, the MRC and the Autism Research Trust, during the period of this work.This is the final published version. It first appeared at http://www.nature.com/tp/journal/v5/n3/full/tp201523a.html

Bayesian Methods for Exoplanet Science

Exoplanet research is carried out at the limits of the capabilities of current telescopes and instruments. The studied signals are weak, and often embedded in complex systematics from instrumental, telluric, and astrophysical sources. Combining repeated observations of periodic events, simultaneous observations with multiple telescopes, different observation techniques, and existing information from theory and prior research can help to disentangle the systematics from the planetary signals, and offers synergistic advantages over analysing observations separately. Bayesian inference provides a self-consistent statistical framework that addresses both the necessity for complex systematics models, and the need to combine prior information and heterogeneous observations. This chapter offers a brief introduction to Bayesian inference in the context of exoplanet research, with focus on time series analysis, and finishes with an overview of a set of freely available programming libraries.Comment: Invited revie

Voice-selective prediction alterations in nonclinical voice hearers

Auditory verbal hallucinations (AVH) are a cardinal symptom of psychosis but also occur in 6-13% of the general population. Voice perception is thought to engage an internal forward model that generates predictions, preparing the auditory cortex for upcoming sensory feedback. Impaired processing of sensory feedback in vocalization seems to underlie the experience of AVH in psychosis, but whether this is the case in nonclinical voice hearers remains unclear. The current study used electroencephalography (EEG) to investigate whether and how hallucination predisposition (HP) modulates the internal forward model in response to self-initiated tones and self-voices. Participants varying in HP (based on the Launay-Slade Hallucination Scale) listened to self-generated and externally generated tones or self-voices. HP did not affect responses to self vs. externally generated tones. However, HP altered the processing of the self-generated voice: increased HP was associated with increased pre-stimulus alpha power and increased N1 response to the self-generated voice. HP did not affect the P2 response to voices. These findings confirm that both prediction and comparison of predicted and perceived feedback to a self-generated voice are altered in individuals with AVH predisposition. Specific alterations in the processing of self-generated vocalizations may establish a core feature of the psychosis continuum.The Authors gratefully acknowledge all the participants who collaborated in the study, and particularly Dr. Franziska Knolle for feedback on stimulus generation, Carla Barros for help with scripts for EEG time-frequency analysis, and Dr. Celia Moreira for her advice on mixed linear models. This work was supported by the Portuguese Science National Foundation (FCT; grant numbers PTDC/PSI-PCL/116626/2010, IF/00334/2012, PTDC/MHCPCN/0101/2014) awarded to APP

The Cost of Simplifying Air Travel When Modeling Disease Spread

BACKGROUND: Air travel plays a key role in the spread of many pathogens. Modeling the long distance spread of infectious disease in these cases requires an air travel model. Highly detailed air transportation models can be over determined and computationally problematic. We compared the predictions of a simplified air transport model with those of a model of all routes and assessed the impact of differences on models of infectious disease. METHODOLOGY/PRINCIPAL FINDINGS: Using U.S. ticket data from 2007, we compared a simplified "pipe" model, in which individuals flow in and out of the air transport system based on the number of arrivals and departures from a given airport, to a fully saturated model where all routes are modeled individually. We also compared the pipe model to a "gravity" model where the probability of travel is scaled by physical distance; the gravity model did not differ significantly from the pipe model. The pipe model roughly approximated actual air travel, but tended to overestimate the number of trips between small airports and underestimate travel between major east and west coast airports. For most routes, the maximum number of false (or missed) introductions of disease is small (<1 per day) but for a few routes this rate is greatly underestimated by the pipe model. CONCLUSIONS/SIGNIFICANCE: If our interest is in large scale regional and national effects of disease, the simplified pipe model may be adequate. If we are interested in specific effects of interventions on particular air routes or the time for the disease to reach a particular location, a more complex point-to-point model will be more accurate. For many problems a hybrid model that independently models some frequently traveled routes may be the best choice. Regardless of the model used, the effect of simplifications and sensitivity to errors in parameter estimation should be analyzed

A family history of breast cancer will not predict female early onset breast cancer in a population-based setting

ABSTRACT: BACKGROUND: An increased risk of breast cancer for relatives of breast cancer patients has been demonstrated in many studies, and having a relative diagnosed with breast cancer at an early age is an indication for breast cancer screening. This indication has been derived from estimates based on data from cancer-prone families or from BRCA1/2 mutation families, and might be biased because BRCA1/2 mutations explain only a small proportion of the familial clustering of breast cancer. The aim of the current study was to determine the predictive value of a family history of cancer with regard to early onset of female breast cancer in a population based setting. METHODS: An unselected sample of 1,987 women with and without breast cancer was studied with regard to the age of diagnosis of breast cancer. RESULTS: The risk of early-onset breast cancer was increased when there were: (1) at least 2 cases of female breast cancer in first-degree relatives (yes/no; HR at age 30: 3.09; 95% CI: 128-7.44), (2) at least 2 cases of female breast cancer in first or second-degree relatives under the age of 50 (yes/no; HR at age 30: 3.36; 95% CI: 1.12-10.08), (3) at least 1 case of female breast cancer under the age of 40 in a first- or second-degree relative (yes/no; HR at age 30: 2.06; 95% CI: 0.83-5.12) and (4) any case of bilateral breast cancer (yes/no; HR at age 30: 3.47; 95%: 1.33-9.05). The positive predictive value of having 2 or more of these characteristics was 13% for breast cancer before the age of 70, 11% for breast cancer before the age of 50, and 1% for breast cancer before the age of 30. CONCLUSION: Applying family history related criteria in an unselected population could result in the screening of many women who will not develop breast cancer at an early age

Replication of LDL SWAs hits in PROSPER/PHASE as validation for future (pharmaco)genetic analyses

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; The PHArmacogenetic study of Statins in the Elderly at risk (PHASE) is a genome wide association study in the PROspective Study of Pravastatin in the Elderly at risk for vascular disease (PROSPER) that investigates the genetic variation responsible for the individual variation in drug response to pravastatin. Statins lower LDL-cholesterol in general by 30%, however not in all subjects. Moreover, clinical response is highly variable and adverse effects occur in a minority of patients. In this report we first describe the rationale of the PROSPER/PHASE project and second show that the PROSPER/PHASE study can be used to study pharmacogenetics in the elderly.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; The genome wide association study (GWAS) was conducted using the Illumina 660K-Quad beadchips following manufacturer's instructions. After a stringent quality control 557,192 SNPs in 5,244 subjects were available for analysis. To maximize the availability of genetic data and coverage of the genome, imputation up to 2.5 million autosomal CEPH HapMap SNPs was performed with MACH imputation software. The GWAS for LDL-cholesterol is assessed with an additive linear regression model in PROBABEL software, adjusted for age, sex, and country of origin to account for population stratification.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Forty-two SNPs reached the GWAS significant threshold of p = 5.0e-08 in 5 genomic loci (APOE/APOC1; LDLR; FADS2/FEN1; HMGCR; PSRC1/CELSR5). The top SNP (rs445925, chromosome 19) with a p-value of p = 2.8e-30 is located within the APOC1 gene and near the APOE gene. The second top SNP (rs6511720, chromosome 19) with a p-value of p = 5.22e-15 is located within the LDLR gene. All 5 genomic loci were previously associated with LDL-cholesterol levels, no novel loci were identified. Replication in WOSCOPS and CARE confirmed our results.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusion:&lt;/b&gt; With the GWAS in the PROSPER/PHASE study we confirm the previously found genetic associations with LDL-cholesterol levels. With this proof-of-principle study we show that the PROSPER/PHASE study can be used to investigate genetic associations in a similar way to population based studies. The next step of the PROSPER/PHASE study is to identify the genetic variation responsible for the variation in LDL-cholesterol lowering in response to statin treatment in collaboration with other large trials.&lt;/p&gt

Cardiac Procedures among American Indians and Alaska Natives compared to Non-Hispanic Whites Hospitalized with Ischemic Heart Disease in California

BackgroundAmerican Indians/Alaska Natives (AIAN) experience a high burden of cardiovascular disease with rates for fatal and nonfatal heart disease approximately twofold higher than the U.S. population.ObjectiveTo determine if disparities exist in cardiac procedure rates among AIAN compared to non-Hispanic whites hospitalized in California for ischemic heart disease defined as acute myocardial infarction or unstable angina.DesignCross-sectional study. EVENTS: A total of 796 ischemic heart disease hospitalizations among AIAN and 90971 among non-Hispanic whites in 37 of 58 counties in California from 1998-2002.MeasurementsCardiac catheterization, percutaneous cardiac intervention, and coronary artery bypass graft surgery procedure rates from hospitalization administrative data.Main resultsAIAN did not have lower cardiac procedure rates for cardiac catheterization and percutaneous cardiac intervention compared to non-Hispanic whites (unadjusted OR 1.00, 95% CI 0.87-1.16 and OR 1.04, 95% CI 0.90-1.20, respectively). Adjustment for age, sex, comorbidities, and payer source did not alter the results (adjusted OR 0.95, 95% CI 0.82-1.10 and OR 0.98, 95% CI 0.85-1.14, respectively). We found higher odds (unadjusted OR 1.36, 95% CI 1.09-1.70) for receipt of coronary artery bypass graft surgery among AIAN hospitalized for ischemic heart disease compared to non-Hispanic whites which after adjustment attenuated some and was no longer statistically significant (adjusted OR 1.26, 95% CI 1.00-1.58).ConclusionAIAN were not less likely to receive cardiac procedures as non-Hispanic whites during hospitalizations for ischemic heart disease. Additional research is needed to determine whether differences in specialty referral patterns, patients' treatment preferences, or outpatient management may explain some of the health disparities due to cardiovascular disease that is found among AIAN

Cambodian Higher Education Governance: The Politics of Global Summitry and Clientelism

This chapter uses the concepts of “global summitry” and “clientelism” to theorize higher education governance in Cambodia. After reviewing the history of higher education since the 1960s, the chapter analyzes the country’s experiences amid regional attempts to harmonize standards, degree structures, quality assurance systems, and credit systems in Southeast Asia. Rather than explicit intervention into Cambodia’s higher education sector as has been historically common, the contemporary order transmits policy and governance practices through various regional and international forums, creating a seemingly homogenous system of higher education. External influence through global summitry, however, must be paired with a recognition of the prevalence of clientelism. By exploring the case of the Accreditation Council of Cambodia, higher education governance is shown to reproduce the engrained system of clientelism, empowering elites and contributing further to systems of informal patronage. The chapter concludes with recent (up to April 2016) developments in higher education governance, offering some observations and obstacles for future development in the sector

A systematic review of strategies to recruit and retain primary care doctors

Background There is a workforce crisis in primary care. Previous research has looked at the reasons underlying recruitment and retention problems, but little research has looked at what works to improve recruitment and retention. The aim of this systematic review is to evaluate interventions and strategies used to recruit and retain primary care doctors internationally. Methods A systematic review was undertaken. MEDLINE, EMBASE, CENTRAL and grey literature were searched from inception to January 2015.Articles assessing interventions aimed at recruiting or retaining doctors in high income countries, applicable to primary care doctors were included. No restrictions on language or year of publication. The first author screened all titles and abstracts and a second author screened 20%. Data extraction was carried out by one author and checked by a second. Meta-analysis was not possible due to heterogeneity. Results 51 studies assessing 42 interventions were retrieved. Interventions were categorised into thirteen groups: financial incentives (n=11), recruiting rural students (n=6), international recruitment (n=4), rural or primary care focused undergraduate placements (n=3), rural or underserved postgraduate training (n=3), well-being or peer support initiatives (n=3), marketing (n=2), mixed interventions (n=5), support for professional development or research (n=5), retainer schemes (n=4), re-entry schemes (n=1), specialised recruiters or case managers (n=2) and delayed partnerships (n=2). Studies were of low methodological quality with no RCTs and only 15 studies with a comparison group. Weak evidence supported the use of postgraduate placements in underserved areas, undergraduate rural placements and recruiting students to medical school from rural areas. There was mixed evidence about financial incentives. A marketing campaign was associated with lower recruitment. Conclusions This is the first systematic review of interventions to improve recruitment and retention of primary care doctors. Although the evidence base for recruiting and care doctors is weak and more high quality research is needed, this review found evidence to support undergraduate and postgraduate placements in underserved areas, and selective recruitment of medical students. Other initiatives covered may have potential to improve recruitment and retention of primary care practitioners, but their effectiveness has not been established