Although anthropogenic climate change is expected to have caused large shifts in temperature and rainfall, the detection of human influence on global drought has been complicated by large internal ...variability and the brevity of observational records. Here we address these challenges using reconstructions of the Palmer drought severity index obtained with data from tree rings that span the past millennium. We show that three distinct periods are identifiable in climate models, observations and reconstructions during the twentieth century. In recent decades (1981 to present), the signal of greenhouse gas forcing is present but not yet detectable at high confidence. Observations and reconstructions differ significantly from an expected pattern of greenhouse gas forcing around mid-century (1950-1975), coinciding with a global increase in aerosol forcing. In the first half of the century (1900-1949), however, a signal of greenhouse-gas-forced change is robustly detectable. Multiple observational datasets and reconstructions using data from tree rings confirm that human activities were probably affecting the worldwide risk of droughts as early as the beginning of the twentieth century.
Peripheral administration of lipopolysaccharide (LPS), a potent activator of the immune system, induces symptoms of behavioral depression, such as social withdrawal, concommitant with increases in ...c-Fos expression in central autonomic network nuclei. Previous studies implicated vagal visceral sensory nerves in transduction of immune-related signals relevant to for the induction of social withdrawal, a symptom of behavioral depression. Vagal sensory nerves terminate in the dorsal vagal complex (DVC) of the brainstem, a region that functions to integrate visceral signals and may also play a role in modulating arousal and affect. The objective of the current study was to determine whether the DVC contributes to immunosensory pathways driving symptoms of social withdrawal associated with LPS-induced behavioral depression, using a reversible lesion technique to temporarily inactivate the DVC. To assess the effects of DVC inactivation on LPS-induced social withdrawal and the subsequent changes in brain activation, we used behavioral assessment of social withdrawal, and analyzed c-Fos expression, a marker of neuronal activation, in the central nucleus of the amygdala (CEA), bed nucleus of the stria terminalis (BST), hypothalamic paraventricular nucleus (PVN), and ventromendial preoptic area (VMPO). Two hours following intraperitoneal LPS injection, there was a significant increase in c-Fos immunoreactivity in forebrain regions in animals treated with LPS. DVC inactivation completely blocked LPS-induced social withdrawal and dramatically reduced LPS-induced Fos expression in all four forebrain regions assessed. Collectively, these findings support the idea that the DVC acts as an immune-behavior interface between the peripheral stimuli and brain areas involved in modulating social behavior.
Children exposed to maternal smoking during pregnancy exhibit increased risk for many adverse health effects. Maternal smoking influences methylation in newborns at specific CpG sites (CpGs). Here, ...we extend evaluation of individual CpGs to gene-level and pathway-level analyses among 1062 participants in the Norwegian Mother and Child Cohort Study (MoBa) using the Illumina 450 K platform to measure methylation in newborn DNA and maternal smoking in pregnancy, assessed using the biomarker, plasma cotinine. We used novel implementations of bioinformatics tools to collapse epigenome-wide methylation data into gene- and pathway-level effects to test whether exposure to maternal smoking in utero differentially methylated CpGs in genes enriched in biologic pathways. Unlike most pathway analysis applications, our approach allows replication in an independent cohort.
Data on 485,577 CpGs, mapping to a total of 20,199 genes, were used to create gene scores that were tested for association with maternal plasma cotinine levels using Sequence Kernel Association Test (SKAT), and 15 genes were found to be associated (q < 0.25). Six of these 15 genes (GFI1, MYO1G, CYP1A1, RUNX1, LCTL, and AHRR) contained individual CpGs that were differentially methylated with regards to cotinine levels (p < 1.06 × 10
). Nine of the 15 genes (FCRLA, MIR641, SLC25A24, TRAK1, C1orf180, ITLN2, GLIS1, LRFN1, and MIR451) were associated with cotinine at the gene-level (q < 0.25) but had no genome-wide significant individual CpGs (p > 1.06 × 10
). Pathway analyses using gene scores resulted in 51 significantly associated pathways, which we tested for replication in an independent cohort (q < 0.05). Of those 32 replicated in an independent cohort, which clustered into six groups. The largest cluster consisted of pathways related to cancer, cell cycle, ERα receptor signaling, and angiogenesis. The second cluster, organized into five smaller pathway groups, related to immune system function, such as T-cell regulation and other white blood cell related pathways.
Here we use novel implementations of bioinformatics tools to determine biological pathways impacted through epigenetic changes in utero by maternal smoking in 1062 participants in the MoBa, and successfully replicate these findings in an independent cohort. The results provide new insight into biological mechanisms that may contribute to adverse health effects from exposure to tobacco smoke in utero.
Machine learning (ML) refers to computational algorithms that iteratively improve their ability to recognize patterns in data. The digitization of our healthcare infrastructure is generating an ...abundance of data from electronic health records, imaging, wearables, and sensors that can be analyzed by ML algorithms to generate personalized risk assessments and promote guideline-directed medical management. ML's strength in generating insights from complex medical data to guide clinical decisions must be balanced with the potential to adversely affect patient privacy, safety, health equity, and clinical interpretability. This review provides a primer on key advances in ML for cardiovascular disease prevention and how they may impact clinical practice.
Cardiovascular disease prevention with machine learning (ML) and digital health technology. Silent cardiovascular sensors will automatically record biometric data in a personal electronic health record (EHR) which also contains long-term health information like past medical history, demographics, polygenic sequencing, laboratory values, and imaging results. These will feed into ML models that analyze data, risk stratify, and complete appropriate actions in real-time, such as adjusting the temperature of the bedroom during sleep, delivering real-time feedback during exercise, scheduling lab and telehealth appointments, or contacting emergency medical services. EKG = electrocardiogram, PPG = photoplethysmography, CAC = coronary artery calcium, US = ultrasound. Display omitted
Objective
To determine signalment, injury type, trauma severity score, and outcome of canine trauma patients undergoing surgical (emergency room ER or operating room OR) and nonsurgical treatment in ...addition to time to surgery, specialty services involved, and cost in the OR surgery population.
Design
Retrospective evaluation of medical record and hospital trauma registry data on canine trauma cases.
Setting
University teaching hospital.
Animals
One thousand six hundred and thirty dogs presenting for traumatic injury between May 2017 and July 2020.
Interventions
None.
Measurements and Main Results
Demographics and outcome were compared for canine trauma patients undergoing OR surgery (12.8%, 208/1630), ER surgery (39.1%, 637/1630), or no surgical intervention (48.2%, 785/1630). Among the 2 surgical groups, 98.9% (836/845) survived to discharge compared with 92.2% (724/785) of the nonsurgical group (P < 0.0001). The OR surgical group had significantly higher median Animal Trauma Triage scores (2 vs 1, P < 0.0001) and median days in hospital (2 vs < 1, P < 0.0001) compared with the other groups. For the OR surgical cohort, electronic medical records were reviewed to determine the specialty surgery service involved, time to and duration of anesthesia and surgery, and visit cost. The most common surgery services involved were orthopedics (45.2%, 94/208) and general surgery (26.9%, 56/208). Neurology and general surgery cases required the longest median length of stay in hospital, and ophthalmology and dentistry cases required the shortest. The median cost of visit was highest in neurology ($10,032) and lowest in ophthalmology ($2305) and dentistry ($2404).
Conclusions
Surgical intervention in canine trauma patients appears to be associated with higher survival rates, and among the surgery groups, mortality was highest in the ER and general surgery groups. OR surgical intervention, in particular general surgery and neurology, was associated with increased length of hospitalization, increased cost, and higher Animal Trauma Triage scores.
We demonstrate photothermally induced optical switching of ultra-compact hybrid Si-VO₂ ring resonators. The devices consist of a sub-micron length ~70 nm thick patch of phase-changing VO₂ integrated ...onto silicon ring resonators as small as 1.5 μm in radius. The semiconductor-to-metal transition (SMT) of VO₂ is triggered using a 532 nm pump laser, while optical transmission is probed using a tunable cw laser near 1550 nm. We observe optical modulation greater than 10dB from modest quality-factor (~10³) resonances, as well as a large -1.26 nm change in resonant wavelength Δλ, resulting from the large change in the dielectric function of VO₂ in the insulator-to-metal transition achieved by optical pumping.
We demonstrate dynamic reversible switching of VO2 insulator-to-metal transition (IMT) locally on the scale of 15 nm or less and control of nanoantennas, observed for the first time in the ...near-field. Using polarization-selective near-field imaging techniques, we simultaneously monitor the IMT in VO2 and the change of plasmons on gold infrared nanoantennas. Structured nanodomains of the metallic VO2 locally and reversibly transform infrared plasmonic dipole nanoantennas to monopole nanoantennas. Fundamentally, the IMT in VO2 can be triggered on femtosecond timescale to allow ultrafast nanoscale control of optical phenomena. These unique features open up promising novel applications in active nanophotonics.
Transcription factor Sp1 has recently been shown to be overexpressed in a number of human cancers and its overexpression contributes to malignant transformation. Sp1 regulates the expression of a ...number of genes participating in multiple aspects of tumorigenesis such as angiogenesis, cell growth and apoptosis resistance. To better understand the role of increased Sp1 levels on apoptosis regulation we have used retroviruses to overexpress this protein in haematopoietic Baf-3 cells and in 3T3 fibroblasts. We have also used inducible expression systems to control ectopic Sp1 levels in different cell types. Surprisingly, Sp1 overexpression on its own induces apoptosis in all the cellular models tested. The apoptotic pathways induced by Sp1 overexpression are cell type specific. Finally, using a truncated form of Sp1, we show that Sp1-induced apoptosis requires its DNA-binding domain. Our results highlight that Sp1 levels in untransformed cells must be tightly regulated as Sp1 overexpression leads to the induction of apoptosis. Our results also suggest that cancer cells overexpressing Sp1 can avoid Sp1-induced apoptosis.
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