Analytical setup margin for spinal stereotactic body radiotherapy based on measured errors.

BACKGROUND: No consensus currently exists about the correct margin size to use for spinal SBRT. Margins have been proposed to account for various errors individually, but not with all errors combined to result in a single margin value. The purpose of this work was to determine a setup margin for five-fraction spinal SBRT based on known errors during radiotherapy to achieve at least 90% coverage of the clinical target volume with the prescription dose for at least 90% of patients and not exceed a 30 Gy point dose or 23 Gy to 10% of the spinal cord subvolume. METHODS: The random and systematic error components of intrafraction motion, residual setup error, and end-to-end system accuracy were measured. The patient's surface displacement was measured to quantify intrafraction motion, the residual setup error was quantified by re-registering accepted daily cone beam computed tomography setup images, and the displacement between measured and planned dose profiles in a phantom quantified the end-to-end system accuracy. These errors and parameters were used to identify the minimum acceptable margin size. The margin recommendation was validated by assessing dose delivery across 140 simulated patient plans suffering from various random shifts representative of the measured errors. RESULTS: The errors were quantified in three dimensions and the analytical margin generated was 2.4 mm. With this margin applied in the superior/inferior direction only, at least 90% of the CTV was covered with the prescription dose for 96% of the 140 patients simulated with minimal negative effect on the spinal cord dose levels. CONCLUSIONS: The findings of this work support that a 2.4 mm margin applied in the superior/inferior direction can achieve at least 90% coverage of the CTV for at least 90% of dual-arc volumetric modulated arc therapy spinal SBRT patients in the presence of errors when immobilized with vacuum bags.

Brief Report: High Programmatic Isoniazid Preventive Therapy (IPT) Use in Pregnancy Among HIV-Infected Women.

BACKGROUND: The World Health Organization recommends isoniazid preventive therapy (IPT) for people living with HIV (PLHIV) to prevent tuberculosis (TB), including pregnant women. Recent trial results suggest increased adverse pregnancy outcomes associated with IPT during pregnancy. Data are limited regarding programmatic IPT use in pregnant PLHIV. METHODS: We assessed previous programmatic IPT during pregnancy among HIV-infected mothers on enrollment to an infant TB prevention trial in Kenya. Pregnancy IPT use was assessed by the estimated conception date assuming 38 weeks of gestation. Correlates of initiation and completion were analyzed by relative risk regression, using generalized linear models with log link and Poisson family adjusted for IPT initiation year. RESULTS: Between August 15, 2016, to June 6, 2018, 300 HIV-infected women enrolled at 6 weeks postpartum. Two hundred twenty-four (74.7%) women reported previous IPT, of whom 155/224 (69.2%) had any pregnancy IPT use. Forty-five (29.0%) initiated preconception extending into early pregnancy, 41 (26.5%) initiated and completed during pregnancy, and 69 (44.5%) initiated in pregnancy and extended into early postpartum. The median gestational age at IPT pregnancy initiation was 15.1 weeks (interquartile range 8.3-28.4). Pregnancy/early postpartum IPT initiation was associated with new pregnancy HIV diagnosis [adjusted relative risk 1.9 95% confidence interval (CI): 1.6 to 2.2, P < 0.001]. Six-month IPT completion rates were high [147/160 (91.9%)] among women with sufficient time to complete before trial enrollment and similar among preconception or during pregnancy initiators [adjusted relative risk 0.93 (95% confidence interval: 0.83 to 1.04, P = 0.19)]. CONCLUSIONS: Programmatic IPT use was high in pregnant PLHIV, with frequent periconception and early pregnancy initiation. Programmatic surveillance could provide further insights on pregnancy IPT implementation and maternal and infant safety outcomes.

Significant Impacts of Increasing Aridity on the Arid Soil Microbiome.

Global deserts occupy one-third of the Earth's surface and contribute significantly to organic carbon storage, a process at risk in dryland ecosystems that are highly vulnerable to climate-driven ecosystem degradation. The forces controlling desert ecosystem degradation rates are poorly understood, particularly with respect to the relevance of the arid-soil microbiome. Here we document correlations between increasing aridity and soil bacterial and archaeal microbiome composition along arid to hyperarid transects traversing the Atacama Desert, Chile. A meta-analysis reveals that Atacama soil microbiomes exhibit a gradient in composition, are distinct from a broad cross-section of nondesert soils, and yet are similar to three deserts from different continents. Community richness and diversity were significantly positively correlated with soil relative humidity (SoilRH). Phylogenetic composition was strongly correlated with SoilRH, temperature, and electrical conductivity. The strongest and most significant correlations between SoilRH and phylum relative abundance were observed for Acidobacteria, Proteobacteria, Planctomycetes, Verrucomicrobia, and Euryarchaeota (Spearman's rank correlation [rs] = >0.81; false-discovery rate [q] = ≤0.005), characterized by 10- to 300-fold decreases in the relative abundance of each taxon. In addition, network analysis revealed a deterioration in the density of significant associations between taxa along the arid to hyperarid gradient, a pattern that may compromise the resilience of hyperarid communities because they lack properties associated with communities that are more integrated. In summary, results suggest that arid-soil microbiome stability is sensitive to aridity as demonstrated by decreased community connectivity associated with the transition from the arid class to the hyperarid class and the significant correlations observed between soilRH and both diversity and the relative abundances of key microbial phyla typically dominant in global soils. IMPORTANCE We identify key environmental and geochemical factors that shape the arid soil microbiome along aridity and vegetation gradients spanning over 300 km of the Atacama Desert, Chile. Decreasing average soil relative humidity and increasing temperature explain significant reductions in the diversity and connectivity of these desert soil microbial communities and lead to significant reductions in the abundance of key taxa typically associated with fertile soils. This finding is important because it suggests that predicted climate change-driven increases in aridity may compromise the capacity of the arid-soil microbiome to sustain necessary nutrient cycling and carbon sequestration functions as well as vegetative cover in desert ecosystems, which comprise one-third of the terrestrial biomes on Earth.