Safety and efficacy of Option B+ ART in Malawi: few severe maternal toxicity events or infant HIV infections among pregnant women initiating tenofovir/lamivudine/efavirenz

Objectives: Malawi's Option B+ universal antiretroviral therapy (ART) program for pregnant and breastfeeding women does not include routine laboratory monitoring. We report safety outcomes of pregnant women who initiated ART through Option B+. Methods: We analysed 12-month data from an observational cohort study on Option B+ among women newly initiating tenofovir/lamivudine/efavirenz (TDF/3TC/EFV) at a government antenatal clinic in Lilongwe, Malawi. Proportions of women engaged in care, incidence of DAIDS grade ≥ 2 laboratory toxicity, grade ≥ 3 adverse events (AEs), viral suppression (<1000 copies/mL), birth outcomes and infant HIV infections are reported. Results: At ART initiation, participants (n = 299) had a median age of 26 years (IQR 22–30), median CD4 count of 352 cells/μl (IQR 231–520) and 94% were in WHO Stage 1. We noted 76 incident DAIDS Grade ≥ 2 laboratory results among 58 women, most commonly elevated liver function tests (n = 30 events) and low haemoglobin (n = 27). No women had elevated creatinine. Clinical AEs (n = 45) were predominantly infectious diseases and Grade 3. Five participants (2%) discontinued TDF/3TC/EFV due to virologic failure (3) or toxicity (2). Twelve months after ART initiation, most women were engaged in care (89%) and had HIV RNA < 1000 copies/ml (90%). 8% of pregnancies resulted in preterm birth, 9% were low birthweight (<2500 g), and 2% resulted in infant HIV infection at 6 weeks post-delivery. Conclusion: Most women remained on ART and were virally suppressed 12 months after starting Option B+. Few infants contracted HIV perinatally. While some women experienced adverse laboratory events, clinical symptom monitoring is likely reasonable

Freeform three-mirror anastigmatic large-aperture telescope and receiver optics for CMB-S4

CMB-S4, the next-generation ground-based cosmic microwave background (CMB) observatory, will provide detailed maps of the CMB at millimeter wavelengths to dramatically advance our understanding of the origin and evolution of the universe. CMB-S4 will deploy large and small aperture telescopes with hundreds of thousands of detectors to observe the CMB at arcminute and degree resolutions at millimeter wavelengths. Inflationary science benefits from a deep delensing survey at arcminute resolutions capable of observing a large field of view at millimeter wavelengths. This kind of survey acts as a complement to a degree angular resolution survey. The delensing survey requires a nearly uniform distribution of cameras per frequency band across the focal plane. We present a large-throughput, large-aperture (5-meter diameter) freeform three-mirror anastigmatic telescope and an array of 85 cameras for CMB observations at arcminute resolutions, which meets the needs of the delensing survey of CMB-S4. A detailed prescription of this three-mirror telescope and cameras is provided, with a series of numerical calculations that indicate expected optical performance and mechanical tolerance

Prevalence and incidence of probable perinatal depression among women enrolled in Option B+ antenatal HIV care in Malawi

Background: Perinatal depression is a common condition of pregnancy and the postpartum period. Depression negatively affects engagement in HIV care, but systematic screening for perinatal depression is not done in most sub-Saharan African countries. Estimating the burden and timing of perinatal depression can help inform medical programs with the current scale-up of HIV care for pregnant women. Methods: Women (n = 299) initiating antiretroviral therapy for HIV were recruited from a government antenatal clinic in Malawi in 2015–2016 into a cohort study. Probable perinatal depression was assessed at enrollment and at 6 weeks and 3, 6, and 12 months postpartum with the Edinburgh Postnatal Depression Scale (EPDS) and Patient Health Questionnaire-9 (PHQ-9). We estimated point prevalence and incidence of depression as well as concordance between EPDS and PHQ-9 scores. Results: One in ten women screened positive for probable antenatal depression, whereas 1–6% screened positive postpartum. Sensitivity analyses to account for loss to follow-up suggested that postpartum depression prevalence could have ranged from 1–11%. At postpartum time points, 0–3% of participants screened positive for incident probable depression. EPDS and PHQ-9 scores were concordant for 96% of assessments during antenatal and postpartum visits. Limitations: Lack of diagnostic psychiatric evaluation precludes actual diagnosis of major depression, and social desirability bias may have contributed to low postpartum scores. Conclusions: Probable depression was more common during the antenatal period than postpartum among our participants. Given the association between depression and negative HIV outcomes, screening for depression during pregnancy should be integrated into antenatal HIV care

Probable perinatal depression and social support among women enrolled in Malawi's Option B+ Program: A longitudinal analysis

Background: Malawi's PMTCT Option B+ program has expanded the reach of ART services among pregnant and breastfeeding women, but retention in lifelong HIV care remains challenging. Given that depression can undermine retention, it is important to understand how depression changes over the perinatal period, varies across treatment and retention groups, and could be buffered by social support. Methods: Data are from an observational study conducted among women enrolled in Malawi's PMTCT Option B+ program. We used multilevel generalized linear models to estimate the odds of probable depression by time, treatment and retention group, and social support. Probable depression was assessed with the Edinburgh Postnatal Depression Scale and Patient Health Questionnaire-9. Results: Of 468 women, 15% reported probable depression at antenatal enrollment and prevalence differed across newly diagnosed individuals, second line therapy users, and previous defaulters (18%, 21%, 5%, p = 0.001). Odds of probable perinatal depression decreased over time (OR per month: 0.87, 95% CI: 0.82–0.92) but were higher among those newly diagnosed (OR: 3.25, 95% CI: 1.59–6.65) and on second line therapy (OR: 3.39, 95% CI: 1.44–7.99) as compared to previous defaulters. Odds of probable postpartum depression were lower for participants with high social support (OR: 0.19, 95% CI: 0.09–0.39). Limitations: Lack of diagnostic psychiatric evaluation precludes actual diagnosis of depression. Conclusions: Probable depression varied across the perinatal period and across treatment and retention groups. Social support was protective for postpartum depression among all participants. Depression screening and provision of social support should be considered in PMTCT programs

Factors associated with a history of treatment interruption among pregnant women living with HIV in Malawi: A cross-sectional study

Long-term care engagement of women on antiretroviral therapy (ART) is essential to effective HIV public health measures. We sought to explore factors associated with a history of HIV treatment interruption among pregnant women living with HIV presenting to an antenatal clinic in Lilongwe, Malawi. Methods We performed a cross-sectional study of pregnant women living with HIV who had a history of ART interruption presenting for antenatal care. Women were categorized as either retained in HIV treatment or reinitiating care after loss-to-follow up (LTFU). To understand factors associated with treatment interruption, we surveyed socio-demographic and partner relationship characteristics. Crude and adjusted prevalence ratios (aPR) for factors associated with ART interruption were estimated using modified Poisson regression with robust variance. We additionally present patients’ reasons for ART interruption. Results We enrolled 541 pregnant women living with HIV (391 retained and 150 reinitiating). The median age was 30 years (interquartile range (IQR): 25–34). Factors associated with a history of LTFU were age <30 years (aPR 1.46; 95% CI: 1.33–1.63), less than a primary school education (aPR 1.25; CI: 1.08–1.46), initiation of ART during pregnancy or breastfeeding (aPR 1.49, CI: 1.37–1.65), nondisclosure of HIV serostatus to their partner (aPR 1.39, CI: 1.24–1.58), lack of awareness of partner’s HIV status (aPR 1.41, CI: 1.27–1.60), and no contraception use at conception (aPR 1.60, CI 1.40–1.98). Access to care challenges were the most common reasons reported by women for treatment interruption (e.g., relocation, transport costs, or misplacing health documentation). Conclusions Interventions that simplify the ART clinic transfer process, facilitate partner disclosure, and provide counseling about the importance of lifelong ART beyond pregnancy and breastfeeding should be further evaluated for improving retention in ART treatment of women living with HIV in Malawi

High-redshift post-reionization cosmology with 21cm intensity mapping

We investigate the possibility of performing cosmological studies in the redshift range 2.5<z<5 through suitable extensions of existing and upcoming radio-telescopes like CHIME, HIRAX and FAST. We use the Fisher matrix technique to forecast the bounds that those instruments can place on the growth rate, the BAO distance scale parameters, the sum of the neutrino masses and the number of relativistic degrees of freedom at decoupling, Neff. We point out that quantities that depend on the amplitude of the 21cm power spectrum, like f\u3c38, are completely degenerate with \u3a9HI and bHI, and propose several strategies to independently constrain them through cross-correlations with other probes. Assuming 5% priors on \u3a9HI and bHI, kmax=0.2 h Mpc-1 and the primary beam wedge, we find that a HIRAX extension can constrain, within bins of \u394 z=0.1: 1) the value of f\u3c38 at 4%, 2) the value of DA and H at 1%. In combination with data from Euclid-like galaxy surveys and CMB S4, the sum of the neutrino masses can be constrained with an error equal to 23 meV (1\u3c3), while Neff can be constrained within 0.02 (1\u3c3). We derive similar constraints for the extensions of the other instruments. We study in detail the dependence of our results on the instrument, amplitude of the HI bias, the foreground wedge coverage, the nonlinear scale used in the analysis, uncertainties in the theoretical modeling and the priors on bHI and \u3a9HI. We conclude that 21cm intensity mapping surveys operating in this redshift range can provide extremely competitive constraints on key cosmological parameters

The ARIA score of allergic rhinitis using mobile technology correlates with quality-of-life:The MASK study

Mobile technology has been used to appraise allergic rhinitis control but more data are needed. In order to better assess the importance of mobile technologies in rhinitis control, the ARIA (Allergic Rhinitis and its Impact on Asthma) score ranging from 0 to 4 of the Allergy Diary was compared with EQ-5D (EuroQuol) and WPAI-AS (Work Productivity and Activity Impairment in allergy) in 1,288 users in 18 countries. This study showed that quality-of-life data (EQ-5D visual analogue scale and WPA-IS Question 9) are similar in users without rhinitis and in those with mild rhinitis (scores 0-2). Users with a score of 3 or 4 had a significant impairment in quality-of-life questionnaires. This article is protected by copyright. All rights reserved.status: publishe

Mass calibration of optically selected DES clusters using a measurement of CMB-cluster lensing with SPTpol data

We use cosmic microwave background (CMB) temperature maps from the 500 deg2 SPTpol survey to measure the stacked lensing convergence of galaxy clusters from the Dark Energy Survey (DES) Year-3 redMaPPer (RM) cluster catalog. The lensing signal is extracted through a modified quadratic estimator designed to be unbiased by the thermal Sunyaev-Zel{'}dovich (tSZ) effect. The modified estimator uses a tSZ-free map, constructed from the SPTpol 95 and 150 GHz datasets, to estimate the background CMB gradient. For lensing reconstruction, we employ two versions of the RM catalog: a flux-limited sample containing 4003 clusters and a volume-limited sample with 1741 clusters. We detect lensing at a significance of 8.7 σ (6.7σ) with the flux(volume)-limited sample. By modeling the reconstructed convergence using the Navarro-Frenk-White profile, we find the average lensing masses to be M200m = (1.62 +0.32 −0.25 [stat.] ± 0.04 [sys.]) and (1.28 +0.14 −0.18 [stat.] ±0.03 [sys.])×1014 M⊙for the volume- and flux-limited samples respectively. The systematic error budget is much smaller than the statistical uncertainty and is dominated by the uncertainties in the RM cluster centroids. We use the volume-limited sample to calibrate the normalization of the mass-richness scaling relation, and find a result consistent with the galaxy weak-lensing measurements from DES (Mcclintock et al. 2018)

Immunohistochemical Method and Histopathology Judging for the Systemic Synuclein Sampling Study (S4)

Immunohistochemical (IHC) α-synuclein (Asyn) pathology in peripheral biopsies may be a biomarker of Parkinson disease (PD). The multi-center Systemic Synuclein Sampling Study (S4) is evaluating IHC Asyn pathology within skin, colon and submandibular gland biopsies from 60 PD and 20 control subjects. Asyn pathology is being evaluated by a blinded panel of specially trained neuropathologists. Preliminary work assessed 2 candidate immunoperoxidase methods using a set of PD and control autopsy-derived sections from formalin-fixed, paraffin-embedded blocks of the 3 tissues. Both methods had 100% specificity; one, utilizing the 5C12 monoclonal antibody, was more sensitive in skin (67% vs 33%), and was chosen for further use in S4. Four trainee neuropathologists were trained to perform S4 histopathology readings; in subsequent testing, their scoring was compared to that of the trainer neuropathologist on both glass slides and digital images. Specificity and sensitivity were both close to 100% with all readers in all tissue types on both glass slides and digital images except for skin, where sensitivity averaged 75% with digital images and 83.5% with glass slides. Semiquantitative (0-3) density score agreement between trainees and trainer averaged 67% for glass slides and 62% for digital images

CMB-S4: Forecasting Constraints on Primordial Gravitational Waves

CMB-S4---the next-generation ground-based cosmic microwave background (CMB) experiment---is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the Universe, from the highest energies at the dawn of time through the growth of structure to the present day. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semi-analytic projection tool, targeted explicitly towards optimizing constraints on the tensor-to-scalar ratio, $r$, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2--3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments given a desired scientific goal. To form a closed-loop process, we couple this semi-analytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for $r > 0.003$ at greater than $5\sigma$, or, in the absence of a detection, of reaching an upper limit of $r < 0.001$ at $95\%$ CL.Comment: 24 pages, 8 figures, 9 tables, submitted to ApJ. arXiv admin note: text overlap with arXiv:1907.0447