Increased cardiovascular risk following preeclampsia is well established and there are signs of early cardiovascular aging 6 months postpartum. This study assessed whether blood pressure (BP) and ...other cardiovascular measures are abnormal 2 years postpartum in the same cohort to determine ongoing risk markers.
Six months and 2 years postpartum, BP was measured using sphygmomanometry, 24-hour ambulatory BP monitoring, and noninvasive central BP. Anthropometric measures, blood, and urine biochemistry were performed. Cross-sectional comparisons between preeclampsia and normotensive pregnancy (NP) groups and longitudinal comparisons within each group were made at 6 months and 2 years.
Two years postpartum, 129 NP, and 52 preeclampsia women were studied who also had 6 months measures. At both time points, preeclampsia group had significantly higher BP (office BP 2 years, 112±12/72±8 versus 104±9/67±7 mm Hg NP;
<0.001; mean ambulatory BP monitoring 116±9/73±8 versus 106±8/67±6 mm Hg NP;
<0.001). No significant BP changes noted 6 months to 2 years within either group. Office BP thresholds of 140 mm Hg systolic and 90 mm Hg diastolic classified 2% preeclampsia and 0% NP at 2 years. American Heart Association 2017 criteria (above normal, >120/80 mm Hg) classified 25% versus 8% (
<0.002), as did our reference range threshold of 122/79 mm Hg. American Heart Association criteria classified 60% post-preeclampsia versus 16% after NP with above-normal ambulatory BP monitoring (
<0.001). Other cardiovascular risk markers more common 2 years post-preeclampsia included higher body mass index (median 26.6 versus 23.1,
=0.003) and insulin resistance.
After preeclampsia, women have significantly higher BP 6 months and 2 years postpartum, and have higher body mass index and insulin-resistance scores, increasing their future cardiovascular risk. Regular cardiovascular risk screening should be implemented for all who have experienced preeclampsia.
Mass spectra are an important signature by which compounds can be identified. We recently formulated a mathematical approach for incorporating measurement variability when comparing sets of ...high-resolution mass spectra. Leveraging replicate mass spectra, we construct high-dimensional consensus mass spectra—representing each of the compared analytes—and compute the similarity between these data structures. In this paper, we present this approach and discuss its applications and limitations when trying to discriminate methamphetamine and phentermine using in-source collision induced dissociation mass spectra collected with direct analysis in real time mass spectrometry.
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•High dimensional consensus (HDC) mass spectra: a novel formulation for describing mass spectra as probability distributions.•Mathematical framework for comparing HDC mass spectra: after embedding mass spectra into an infinite dimensional Hilbert space, establish affordable analog of commonly employed similarity measure.•Performance: structurally similar compounds not differentiable with standard similarity are distinguishable by HDC if measurements collected under similar conditions.
We provide timing solutions for 45 radio pulsars discovered by the Robert C. Byrd Green Bank Telescope. These pulsars were found in the Green Bank North Celestial Cap pulsar survey, an all-GBT-sky ...survey being carried out at a frequency of . We include pulsar timing data from the Green Bank Telescope and Low Frequency Array. Our sample includes five fully recycled millisecond pulsars (MSPs, three of which are in a binary system), a new relativistic double neutron star system, an intermediate-mass binary pulsar, a mode-changing pulsar, a 138 ms pulsar with a very low magnetic field, and several nulling pulsars. We have measured two post-Keplerian parameters and thus the masses of both objects in the double neutron star system. We also report a tentative companion mass measurement via Shapiro delay in a binary MSP. Two of the MSPs can be timed with high precision and have been included in pulsar timing arrays being used to search for low-frequency gravitational waves, while a third MSP is a member of the black widow class of binaries. Proper motion is measurable in five pulsars, and we provide an estimate of their space velocity. We report on an optical counterpart to a new black widow system and provide constraints on the optical counterparts to other binary MSPs. We also present a preliminary analysis of nulling pulsars in our sample. These results demonstrate the scientific return of long timing campaigns on pulsars of all types.
Plasmodium species cause malaria and kill hundreds of thousands annually. The microtubule-based motor kinesin-8B is required for development of the flagellated Plasmodium male gamete, and its absence ...completely blocks parasite transmission. To understand the molecular basis of kinesin-8B's essential role, we characterised the in vitro properties of kinesin-8B motor domains from P. berghei and P. falciparum. Both motors drive ATP-dependent microtubule gliding, but also catalyse ATP-dependent microtubule depolymerisation. We determined these motors' microtubule-bound structures using cryo-electron microscopy, which showed very similar modes of microtubule interaction in which Plasmodium-distinct sequences at the microtubule-kinesin interface influence motor function. Intriguingly however, P. berghei kinesin-8B exhibits a non-canonical structural response to ATP analogue binding such that neck linker docking is not induced. Nevertheless, the neck linker region is required for motility and depolymerisation activities of these motors. These data suggest that the mechanochemistry of Plasmodium kinesin-8Bs is functionally tuned to support flagella formation.
Methane emissions associated with the production, transport, and
use of oil and natural gas increase the climatic impacts of energy use;
however, little is known about how emissions vary temporally ...and with
commodity prices. We present airborne and ground-based data, supported by
satellite observations, to measure weekly to monthly changes in total
methane emissions in the United States' Permian Basin during a period of
volatile oil prices associated with the COVID-19 pandemic. As oil prices
declined from ∼ USD 60 to USD 20 per barrel, emissions changed
concurrently from 3.3 % to 1.9 % of natural gas production; as prices
partially recovered, emissions increased back to near initial values.
Concurrently, total oil and natural gas production only declined by
∼ 10 % from the peak values seen in the months prior to the
crash. Activity data indicate that a rapid decline in well development and
subsequent effects on associated gas flaring and midstream infrastructure
throughput are the likely drivers of temporary emission reductions. Our
results, along with past satellite observations, suggest that under more
typical price conditions, the Permian Basin is in a state of overcapacity in
which rapidly growing associated gas production exceeds midstream capacity
and leads to high methane emissions.
Radiation therapy following resection of a brain metastasis increases the probability of disease control at the surgical site. We analyzed our experience with postoperative stereotactic radiosurgery ...(SRS) as an alternative to whole-brain radiotherapy (WBRT), with an emphasis on identifying factors that might predict intracranial disease control and overall survival (OS).
We retrospectively reviewed all patients through December 2008, who, after surgical resection, underwent SRS to the tumor bed, deferring WBRT. Multiple factors were analyzed for time to intracranial recurrence (ICR), whether local recurrence (LR) at the surgical bed or "distant" recurrence (DR) in the brain, for time to WBRT, and for OS.
A total of 49 lesions in 47 patients were treated with postoperative SRS. With median follow-up of 9.3 months (range, 1.1-61.4 months), local control rates at the resection cavity were 85.5% at 1 year and 66.9% at 2 years. OS rates at 1 and 2 years were 52.5% and 31.7%, respectively. On univariate analysis (preoperative) tumors larger than 3.0 cm exhibited a significantly shorter time to LR. At a cutoff of 2.0 cm, larger tumors resulted in significantly shorter times not only for LR but also for DR, ICR, and salvage WBRT. While multivariate Cox regressions showed preoperative size to be significant for times to DR, ICR, and WBRT, in similar multivariate analysis for OS, only the graded prognostic assessment proved to be significant. However, the number of intracranial metastases at presentation was not significantly associated with OS nor with other outcome variables.
Larger tumor size was associated with shorter time to recurrence and with shorter time to salvage WBRT; however, larger tumors were not associated with decrements in OS, suggesting successful salvage. SRS to the tumor bed without WBRT is an effective treatment for resected brain metastases, achieving local control particularly for tumors up to 3.0 cm diameter.
Mutations in parkin, an E3 ubiquitin ligase, are the most common cause of autosomal-recessive Parkinson's disease (PD). Here, we show that the stress-signaling non-receptor tyrosine kinase c-Abl ...links parkin to sporadic forms of PD via tyrosine phosphorylation. Under oxidative and dopaminergic stress, c-Abl was activated in cultured neuronal cells and in striatum of adult C57BL/6 mice. Activated c-Abl was found in the striatum of PD patients. Concomitantly, parkin was tyrosine-phosphorylated, causing loss of its ubiquitin ligase and cytoprotective activities, and the accumulation of parkin substrates, AIMP2 (aminoacyl tRNA synthetase complex-interacting multifunctional protein 2) (p38/JTV-1) and FBP-1.STI-571, a selective c-Abl inhibitor, prevented tyrosine phosphorylation of parkin and restored its E3 ligase activity and cytoprotective function both in vitro and in vivo. Our results suggest that tyrosine phosphorylation of parkin by c-Abl is a major post-translational modification that leads to loss of parkin function and disease progression in sporadic PD. Moreover, inhibition of c-Abl offers new therapeutic opportunities for blocking PD progression.
The variability in the prognosis of individuals with hepatocellular carcinoma (HCC) suggests that HCC may comprise several distinct biological phenotypes. These phenotypes may result from activation ...of different oncogenic pathways during tumorigenesis and/or from a different cell of origin. Here we address whether the transcriptional characteristics of HCC can provide insight into the cellular origin of the tumor. We integrated gene expression data from rat fetal hepatoblasts and adult hepatocytes with HCC from human and mouse models. Individuals with HCC who shared a gene expression pattern with fetal hepatoblasts had a poor prognosis. The gene expression program that distinguished this subtype from other types of HCC included markers of hepatic oval cells, suggesting that HCC of this subtype may arise from hepatic progenitor cells. Analyses of gene networks showed that activation of AP-1 transcription factors in this newly identified HCC subtype might have key roles in tumor development.
The data-driven discovery of partial differential equations (PDEs) consistent with spatiotemporal data is experiencing a rebirth in machine learning research. Training deep neural networks to learn ...such data-driven partial differential operators requires extensive spatiotemporal data. For learning coarse-scale PDEs from computational fine-scale simulation data, the training data collection process can be prohibitively expensive. We propose to transformatively facilitate this training data collection process by linking machine learning (here, neural networks) with modern multiscale scientific computation (here, equation-free numerics). These equation-free techniques operate over sparse collections of small, appropriately coupled, space-time subdomains (“patches”), parsimoniously producing the required macro-scale training data. Our illustrative example involves the discovery of effective homogenized equations in one and two dimensions, for problems with fine-scale material property variations. The approach holds promise towards making the discovery of accurate, macro-scale effective materials PDE models possible by efficiently summarizing the physics embodied in “the best” fine-scale simulation models available.
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