Effect of Integrase Strand Transfer Inhibitor Use on Time to HIV Viral Suppression before Delivery.

OBJECTIVES: We sought to determine whether pregnant individuals with human immunodeficiency virus (HIV) prescribed integrase strand transfer inhibitor (INSTI) antiretrovirals (ARVs) achieve viral suppression faster than individuals taking non-INSTI regimens and to determine whether there were differences in viral suppression at delivery among INSTI ARVs. METHODS: This is a retrospective cohort study of pregnant individuals with HIV who delivered a live infant during the study period (January 1, 2009-December 31, 2020). Patients' ARV therapy (ART) was classified as including INSTI or non-INSTI. We compared the proportion of individuals with viral suppression at delivery by group and individual INSTI ARVs using χ2 and Fisher exact tests. A log rank test was used to compare time to viral suppression on ARVs. RESULTS: During the study period, 168 individuals delivered a live infant. Most of the patients were diagnosed as having HIV before pregnancy and had taken ARVs before conception (76%), but fewer than half had an undetectable viral load at the first antenatal visit (45%). During pregnancy, 46% were prescribed INSTI and 54% were prescribed non-INSTI ARVs. Most had an undetectable HIV RNA viral load at delivery (75% INSTI and 72% non-INSTI, P = 0.7). The time to viral suppression was similar between groups (log rank test P = 0.43). Viral suppression at delivery was similar among INSTI ARVs: raltegravir (53%), elvitegravir (88%), dolutegravir (73%), and bictegravir (88%) (P = 0.13). CONCLUSIONS: Despite recommendations to prescribe INSTI in pregnancy for rapid viral suppression, we did not find a significant difference in time to viral suppression when pregnant individuals were taking non-INSTI ARVs. We did not find that one INSTI ARV was superior for viral suppression.

A novel visual illusion paradigm provides evidence for a general factor of illusion sensitivity and personality correlates.

Visual illusions are a gateway to understand how we construct our experience of reality. Unfortunately, important questions remain open, such as the hypothesis of a common factor underlying the sensitivity to different types of illusions, as well as of personality correlates of illusion sensitivity. In this study, we used a novel parametric framework for visual illusions to generate 10 different classic illusions (Delboeuf, Ebbinghaus, Rod and Frame, Vertical-Horizontal, Zöllner, White, Müller-Lyer, Ponzo, Poggendorff, Contrast) varying in strength, embedded in a perceptual discrimination task. We tested the objective effect of the illusions on errors and response times, and extracted participant-level performance scores (n=250) for each illusion. Our results provide evidence in favour of a general factor underlying the sensitivity to different illusions (labelled Factor i). Moreover, we report a positive link between illusion sensitivity and personality traits such as Agreeableness, Honesty-Humility, and negative relationships with Psychoticism, Antagonism, Disinhibition, and Negative Affect.

Impact of Integrase Strand Transfer Inhibitor Use During Pregnancy on Viral Suppression at Delivery and Infant Outcomes: A Statewide Retrospective Cohort Study.

BACKGROUND: We sought to determine whether pregnant women with HIV prescribed integrase strand transfer inhibitor (INSTI) were more likely to have viral suppression at delivery and any increased risk of adverse infant outcomes. METHODS: This was a retrospective, statewide cohort study of women with HIV and their HIV-exposed infants who delivered in South Carolina from 2008 to 2019. Women's antenatal AVRs were classified as INSTI or non-INSTI. We compared the percentage of women with undetectable HIV RNA viral load (<40 copies/mL) at delivery between groups. We compared the percentage of HIV-exposed singleton infants who were born preterm delivery, low birth weight, and small for gestational age and had confirmed perinatal HIV infection. Categorical outcomes were compared using the χ2 test or Fischer exact test. RESULTS: A total of 832 infants, including 11 sets of twins, were exposed to maternal HIV. Detailed antiretroviral regimens were available for analysis in a third of mother-infant pairs (n = 315). Half of the infants were exposed to INSTI (159) and half to non-INSTI antiretrovirals (156). Most women had an undetectable viral load at delivery (80% INSTI and 73% non-INSTI, P= 0.11). The percentage of singleton infants with adverse outcomes was similar between INSTI and non-INSTI groups: preterm delivery (21% and 16%, P = 0.3), low birth weight (19% and 21%, P = 0.7), small for gestational age (11% vs 9%, P = 0.5), and perinatal HIV infection (2.5% and 1.3%, P = 0.7). CONCLUSIONS: We observed that viral suppression before delivery was similar between pregnant women prescribed INSTI and non-INSTI antiretroviral therapy. The percentage of infants with adverse outcomes was similar when exposed to INSTI and non-INSTI antiretroviral therapy.

Contemporary Issues in Pregnancy (and Offspring) in the Current HIV Era.

PURPOSE OF REVIEW: Although antiretroviral therapy (ART) has dramatically reduced mother to child transmission of HIV, data continue to mount that infants exposed to HIV in utero but are not infected (HEU) have serious negative health consequences compared to unexposed infants. This review evaluates recent literature on contemporary issues related to complications seen in pregnant women with HIV and their offspring. RECENT FINDINGS: Current studies show that HEU infants are at a high risk of adverse outcomes, including premature birth, poor growth, neurodevelopmental impairment, immune dysfunction, infectious morbidity, and death. Etiologies for the observed clinical events and subclinical alterations are complex and multifactorial, and the long-term consequences of many findings are yet unknown. HEU infants have an unacceptable rate of morbidity and mortality from perinatal HIV and ART exposure, even in the modern ART era. Continual monitoring and reporting is imperative to protect this vulnerable population in our everchanging landscape of HIV treatment and prevention.

Individualized 131I-mIBG therapy in the management of refractory and relapsed neuroblastoma.

OBJECTIVE: Iodine-131-labelled meta-iodobenzylguanidine (I-mIBG) therapy is an established treatment modality for relapsed/refractory neuroblastoma, most frequently administered according to fixed or weight-based criteria. We evaluate response and toxicity following a dosimetry-based, individualized approach. MATERIALS AND METHODS: A review of 44 treatments in 25 patients treated with I-mIBG therapy was performed. Patients received I-mIBG therapy following relapse (n=9), in refractory disease (n=12), or with surgically unresectable disease despite conventional treatment (n=4). Treatment schedule (including mIBG dose and number of administrations) was individualized according to the clinical status of the patient and dosimetry data from either a tracer study or previous administrations. Three-dimensional tumour dosimetry was also performed for eight patients. RESULTS: The mean administered activity was 11089±7222 MBq and the mean whole-body dose for a single administration was 1.79±0.57 Gy. Tumour-absorbed doses varied considerably (3.70±3.37 mGy/MBq). CTCAE grade 3/4 neutropenia was documented following 82% treatments and grade 3/4 thrombocytopenia following 71% treatments. Further acute toxicity was found in 49% of patients. All acute toxicities resolved with appropriate therapy. The overall response rate was 58% (complete or partial response), with a further 29% of patients having stable disease. CONCLUSION: A highly personalized approach combining patient-specific dosimetry and clinical judgement enables delivery of high activities that can be tolerated by patients, particularly with stem cell support. We report excellent response rates and acceptable toxicity following individualized I-mIBG therapy.

Calibration and validation of the 2WIN photoscreener compared to the PlusoptiX S12 and the SPOT.

PURPOSE: Pediatricians are interested in the amblyopia detection ability of photoscreeners, whereas ophthalmologists ponder their value as autorefractors. The 2WIN (Adaptica, Padova, Italy) is a new device capable of estimating refractive error and ocular alignment by infrared photoscreening. METHODS: Sequential pediatric eye patients with a high (56% to 60%) prescreening prevalence of amblyopia risk factors were screened with the PlusoptiX S12 (PlusoptiX, Inc., Atlanta, GA), SPOT (PediaVision, Lake Mary, FL), and 2WIN photoscreeners before confirmatory examination adhering to American Association for Pediatric Ophthalmology and Strabismus guidelines and Alaska Blind Child Discovery institutional review board protocol. Instrument referral guidelines determined through phase 1 comparison was then applied on additional patients for validation in phase 2. RESULTS: Sixty-two children (age: 1 to 10 years, mean: 5.2 years) were screened with all three devices before cycloplegic examination. Refractive results were inconclusive due to pupil size, cooperation, and out-of-range values. Values for sensitivity (91% and 78%), specificity (71% and 59%), and inconclusive rate (10% and 13%) were found for PlusoptiX and SPOT. The 2WIN was calibrated for this age range (phase 1), yielding 71% sensitivity, 67% specificity, and a 5% inconclusive rate. Regression compared to examination for the PlusoptiX, SPOT, and 2WIN, respectively, were sphere (r(2): 0.76, 0.87, and 0.58), cylinder power (r(2): 0.67, 0.56, and 0.50), and cylinder axis (r(2): 0.71, 0.41, and 0.40). A preferred 2WIN instrument criteria set was determined from the receiver operating characteristic curve. In phase 2, with 117 patients comparing 2WIN to PlusoptiX A-09, sensitivity was 73% and 85%, specificity was 76% and 73%, and inconclusive rate was 8% and 12%, respectively. The three instant-interpreting photorefractors performed well on amblyopic children, with the 2WIN having low inconclusive results. The PlusoptiX outperformed the SPOT and 2WIN as an autorefractor, particularly with respect to astigmatism power and axis. CONCLUSIONS: The new 2WIN is a promising addition to portable photoscreeners for amblyopia detection and estimating refractive error.

Detection of outlier loci and their utility for fisheries management.

Genetics-based approaches have informed fisheries management for decades, yet remain challenging to implement within systems involving recently diverged stocks or where gene flow persists. In such cases, genetic markers exhibiting locus-specific ('outlier') effects associated with divergent selection may provide promising alternatives to loci that reflect genome-wide ('neutral') effects for guiding fisheries management. Okanagan Lake kokanee (Oncorhynchus nerka), a fishery of conservation concern, exhibits two sympatric ecotypes adapted to different reproductive environments; however, previous research demonstrated the limited utility of neutral microsatellites for assigning individuals. Here, we investigated the efficacy of an outlier-based approach to fisheries management by screening >11 000 expressed sequence tags for linked microsatellites and conducting genomic scans for kokanee sampled across seven spawning sites. We identified eight outliers among 52 polymorphic loci that detected ecotype-level divergence, whereas there was no evidence of divergence at neutral loci. Outlier loci exhibited the highest self-assignment accuracy to ecotype (92.1%), substantially outperforming 44 neutral loci (71.8%). Results were robust among-sampling years, with assignment and mixed composition estimates for individuals sampled in 2010 mirroring baseline results. Overall, outlier loci constitute promising alternatives for informing fisheries management involving recently diverged stocks, with potential applications for designating management units across a broad range of taxa.

Critical factors for assembling a high volume of DNA barcodes.

Large-scale DNA barcoding projects are now moving toward activation while the creation of a comprehensive barcode library for eukaryotes will ultimately require the acquisition of some 100 million barcodes. To satisfy this need, analytical facilities must adopt protocols that can support the rapid, cost-effective assembly of barcodes. In this paper we discuss the prospects for establishing high volume DNA barcoding facilities by evaluating key steps in the analytical chain from specimens to barcodes. Alliances with members of the taxonomic community represent the most effective strategy for provisioning the analytical chain with specimens. The optimal protocols for DNA extraction and subsequent PCR amplification of the barcode region depend strongly on their condition, but production targets of 100K barcode records per year are now feasible for facilities working with compliant specimens. The analysis of museum collections is currently challenging, but PCR cocktails that combine polymerases with repair enzyme(s) promise future success. Barcode analysis is already a cost-effective option for species identification in some situations and this will increasingly be the case as reference libraries are assembled and analytical protocols are simplified.