Key Words burden of disease, cost-effectiveness analysis, health-related quality of life s Abstract Health-adjusted life years (HALYs) are population health measures permitting morbidity and mortality to be simultaneously described within a single number. They are useful for overall estimates of burden of disease, comparisons of the relative impact of specific illnesses and conditions on communities, and in economic analyses. Quality-adjusted life years (QALYs) and disability-adjusted life years (DALYs) are types of HALYs whose original purposes were at variance. Their growing importance and the varied uptake of the methodology by different U.S. and international entities makes it useful to understand their differences as well as their similarities. A brief history of both measures is presented and methods for calculating them are reviewed. Methodological and ethical issues that have been raised in association with HALYs more generally are presented. Finally, we raise concerns about the practice of using different types of HALYs within different decision-making contexts and urge action that builds and clarifies this useful measurement field.

Control of gene expression often involves an interwoven set of regulatory processes. As information regarding regulatory pathways may be lost in ex vivo analyses, we used bioluminescence to monitor gene expression in living mammals. Viral promoters fused to firefly luciferase as transgenes in mice allowed external monitoring of gene expression both superficially and in deep tissues. In vivo bioluminescence was detectable using either intensified or cooled charge-coupled device cameras, and could be detected following both topical and systemic delivery of substrate. In vivo control of the promoter from the human immunodeficiency virus was demonstrated. As a model for DNA-based therapies and vaccines, in vivo transfection of a luciferase expression vector (SV-40 promoter and enhancer controlling expression) was detected. We conclude that gene regulation, DNA delivery and expression can now be noninvasively monitored in living mammals using a luciferase reporter. Thus, real-time, noninvasive study of gene expression in living animal models for human development and disease is possible.

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Motivation: Multiple biological clocks govern a healthy pregnancy. These biological mechanisms produce immunologic, metabolomic, proteomic, genomic and microbiomic adaptations during the course of pregnancy. Modeling the chronology of these adaptations during full-term pregnancy provides the frameworks for future studies examining deviations implicated in pregnancy-related pathologies including preterm birth and preeclampsia. Results: We performed a multiomics analysis of 51 samples from 17 pregnant women, delivering at term. The datasets included measurements from the immunome, transcriptome, microbiome, proteome and metabolome of samples obtained simultaneously from the same patients. Multivariate predictive modeling using the Elastic Net (EN) algorithm was used to measure the ability of each dataset to predict gestational age. Using stacked generalization, these datasets were combined into a single model. This model not only significantly increased predictive power by combining all datasets, but also revealed novel interactions between different biological modalities. Future work includes expansion of the cohort to preterm-enriched populations and in vivo analysis of immune-modulating interventions based on the mechanisms identified. Availability and implementation: Datasets and scripts for reproduction of results are available through: https://nalab.stanford.edu/multiomics-pregnancy/.

BACKGROUND: Extremely preterm infants are at risk for neurodevelopmental impairment (NDI). Early cranial ultrasound (CUS) is usual practice, but near-term brain MRI has been reported to better predict outcomes. We prospectively evaluated MRI white matter abnormality (WMA) and cerebellar lesions, and serial CUS adverse findings as predictors of outcomes at 18 to 22 months' corrected age.METHODS: Early and late CUS, and brain MRI were read by masked central readers, in a large cohort (n = 480) of infants ,28 weeks' gestation surviving to near term in the Neonatal Research Network. Outcomes included NDI or death after neuroimaging, and significant gross motor impairment or death, with NDI defined as cognitive composite score ,70, significant gross motor impairment, and severe hearing or visual impairment. Multivariable models evaluated the relative predictive value of neuroimaging while controlling for other factors.RESULTS: Of 480 infants, 15 died and 20 were lost. Increasing severity of WMA and significant cerebellar lesions on MRI were associated with adverse outcomes. Cerebellar lesions were rarely identified by CUS. In full multivariable models, both late CUS and MRI, but not early CUS, remained independently associated with NDI or death (MRI cerebellar lesions: odds ratio, 3.0 [95% confidence interval: 1.3-6.8]; late CUS: odds ratio, 9.8 [95% confidence interval: 2.8-35]), and significant gross motor impairment or death. In models that did not include late CUS, MRI moderate-severe WMA was independently associated with adverse outcomes.CONCLUSIONS: Both late CUS and near-term MRI abnormalities were associated with outcomes, independent of early CUS and other factors, underscoring the relative prognostic value of near-term neuroimaging.WHAT'S KNOWN ON THIS SUBJECT: White matter abnormality (WMA) on neuroimaging is considered a crucial link with adverse neurodevelopmental outcome in preterm infants. Brain MRI is more sensitive in detecting WMA than cranial ultrasound (CUS), but questions remain about timing and prognostic value of modalities.WHAT THIS STUDY ADDS: Near-term CUS and MRI abnormalities were associated with adverse 18-to 22-month outcomes, independent of early CUS and other factors, underscoring the relative prognostic value of later neuroimaging in this large, extremely preterm cohort surviving to near-term. Trained research staff at each center collected maternal, demographic, perinatal, and neonatal data by using common definitions that were developed by NICHD NRN investigators and described in previous publications. [13][14][15][16] Data were transmitted to the NRN Data Coordinating Center at RTI International, which stored, managed, and analyzed all data. Neuroimaging: CUS and Brain MRI Cranial UltrasoundAn "early" CUS at 4 to 14 days, and a "late" CUS at 35 to 42 weeks' postmenstrual age (PMA) were obtained for NEURO study participants. CUS imaging was per local center clinical protocol. Mastoid, posterior fossa, or cine views were not specifically required. Central reader interpretat...

Analysis of photon transit time for low-power light passing into the head, and through both skull and brain, of human subjects allowed for tomographic imaging of cerebral hemoglobin oxygenation based on photon diffusion theory. In healthy adults, imaging of changes in hemoglobin saturation during hand movement revealed focal, contralateral increases in motor cortex oxygenation with spatial agreement to activation maps determined by functional magnetic resonance imaging; in ill neonates, imaging of hemoglobin saturation revealed focal regions of low oxygenation after acute stroke, with spatial overlap to injury location determined by computed tomography scan. Because such slow optical changes occur over seconds and co-localize with magnetic resonance imaging vascular signals whereas fast activation-related optical changes occur over milliseconds and co-localize with EEG electrical signals, optical methods offer a single modality for exploring the spatio-temporal relationship between electrical and vascular responses in the brain in vivo, as well as for mapping cortical activation and oxygenation at the bedside in real-time for clinical monitoring.

OBJECTIVE: The current study evaluates a treatment intervention developed with the goal of reducing symptoms of posttraumatic stress, depression, and anxiety in parents of premature infants. METHODS: A total of 105 mothers of preterm infants (25–34 weeks’ gestational age; >600 g) were randomized to receive a 6-session intervention developed to target parental trauma as well as facilitate infant redefinition (n = 62) or to an active comparison group (n = 43). Mothers in the intervention group received a combination of trauma-focused treatments, including psychoeducation, cognitive restructuring, progressive muscle relaxation, and development of their trauma narrative. The intervention also incorporated material targeting infant redefinition, defined as the process of changing the mother’s negative perceptions of her infant and the parenting experience. RESULTS: Mothers in the intervention group reported a greater reduction in both trauma symptoms (Cohen’s d = 0.41, P = .023) and depression (Cohen’s d = 0.59, P < .001) compared with the comparison group. Patients under both conditions improved significantly in terms of anxiety, with no differences between groups. Results of the moderator analysis showed that mothers with higher ratings of baseline NICU stress benefited more from the intervention compared with mothers who had lower ratings (P = .036). CONCLUSIONS: This short, highly manualized intervention for mothers of preterm infants statistically significantly reduced symptoms of trauma and depression. The intervention is feasible, can be delivered with fidelity, and has high ratings of maternal satisfaction. Given that improvements in mothers’ distress may lead to improved infant outcomes, this intervention has the potential for a high public health impact.

Intramuscular administration of 5000 IU of vitamin A three times per week for four weeks reduced biochemical evidence of vitamin A deficiency and slightly decreased the risk of chronic lung disease in extremely-low-birth-weight infants.