Clinical presentation of simple and combined or syndromic arteriovenous malformations.

OBJECTIVES Arteriovenous malformations of the lower extremities (AVMLE) can present as simple or complex combined or syndromic forms (e.g. Parkes Weber Syndrome). We aimed to characterize the differences in clinical presentation and natural history of these potentially life and limb threatening congenital vascular malformations. METHODS We conducted a retrospective analysis of a consecutive series of patients with AVMLE, who presented to a tertiary referral center in Switzerland between 2008 and 2018. Clinical baseline characteristics, D-dimer level and course were summarized and differences between simple, non-syndromic and combined or syndromic AVMLE determined. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models. RESULTS Overall, 506 patients were prospectively enrolled in the Bernese Congenital Vascular Malformation Registry, 31 (6%) with AVMLE. There were 16 women and 15 men with a mean age of 18 years at first diagnosis (1 month - 72 years). Simple AVMLE was present in 22 (71%), combined or syndromic AVMLE with limb overgrowth in 9 patients (29%), respectively. Common symptoms and signs were pain 25 (81%), swelling 21 (68%) and soft tissue hypertrophy 13 (42%). Among combined or syndromic patients, 3 patients died from wound infection with sepsis or disseminated intravascular coagulation with bleeding complications (intracranial hemorrhage and bleeding from extensive leg ulcers). Combined or syndromic patients presented more often with bleeding (67% vs. 5%; p<0.001), malformation related infection (44% vs. 5%; p=0,017) and leg length difference (56% vs. 14%; p=0.049). D-dimer levels were elevated (mean 17256 μg/L, range 1557 μg/L to 80000 μg/L) and angiographic appearance showed complex, mixed type of AVMs, including interstitial type IV, in all patients with combined or syndromic AVMLE. CONCLUSION Patients with congenital simple AVMLE most often present with benign clinical features and rarely complications related to hemodynamic changes. Patients with combined or syndromic AVMLE often face serious outcomesdominated by complications other than direct high flow related heart failure

Calibration trending in the Spitzer beyond era

The Spitzer Space Telescope currently operates in the "Beyond Era", over nine years past an original cryogenic mission. As the astronomy community continues to advance scientific boundaries and push beyond original specifications, the stability of the Infrared Array Camera (IRAC) instrument is paramount. The Instrument Team (IST) monitors the pointing accuracy, temperature, and calibration and provides the information in a timely manner to observers. The IRAC IST created a calibration trending web page, available to the general astronomy community, where the team posts updates of three most pertinent scientific stability measures of the IRAC data: calibration, bias, and bad pixels. In addition, photometry and telescope properties from all the staring observations (>1500 as of April 2018) are trended to examine correlations with changes in the age or thermal properties of the telescope. A long, well-sampled baseline established by consistent monitoring outside anomalies and space weather events allows even the smallest changes to be detected

Spitzer/IRAC precision photometry: a machine learning approach

The largest source of noise in exoplanet and brown dwarf photometric time series made with Spitzer/IRAC is the coupling between intra-pixel gain variations and spacecraft pointing fluctuations. Observers typically correct for this systematic in science data by deriving an instrumental noise model simultaneously with the astrophysical light curve and removing the noise model. Such techniques for self-calibrating Spitzer photometric datasets have been extremely successful, and in many cases enabled near-photon-limited precision on exoplanet transit and eclipse depths. Self-calibration, however, can suffer from certain limitations: (1) temporal astrophysical signals can become aliased as part of the instrument model; (2) for some techniques adequate model estimation often requires a high degree of intra-pixel positional redundancy (multiple samples with nearby centroids) over long time spans; (3) many techniques do not account for sporadic high frequency telescope vibrations that smear out the point spread function. We have begun to build independent general-purpose intra-pixel systematics removal algorithms using three machine learning techniques: K-Nearest Neighbors (with kernel regression), Random Decision Forests, and Artificial Neural Networks. These methods remove many of the limitations of self-calibration: (1) they operate on a dedicated calibration database of approximately one million measurements per IRAC waveband (3.6 and 4.5 microns) of non-variable stars, and thus are independent of the time series science data to be corrected; (2) the database covers a large area of the "Sweet Spot, so the methods do not require positional redundancy in the science data; (3) machine learning techniques in general allow for flexibility in training with multiple, sometimes unorthodox, variables, including those that trace PSF smear. We focus in this report on the K-Nearest Neighbors with Kernel Regression technique. (Additional communications are in preparation describing Decision Forests and Neural Networks.

Intra-pixel gain variations and high-precision photometry with the Infrared Array Camera (IRAC)

The Infrared Array Camera (IRAC) on the Spitzer Space Telescope has been used to measure < 10^(-4) temporal variations in point sources (such as transiting extrasolar planets) at 3.6 and 4.5 μm. Due to the under-sampled nature of the PSF, the warm IRAC arrays show variations of as much as 8% in sensitivity as the center of the PSF moves across a pixel due to normal spacecraft pointing wobble and drift. These intra-pixel gain variations are the largest source of correlated noise in IRAC photometry. Usually this effect is removed by fitting a model to the science data themselves (self-calibration), which could result in the removal of astrophysically interesting signals. We describe a new technique for significantly reducing the gain variations and improving photometric precision in a given observation, without using the data to be corrected. This comprises: (1) an adaptive centroiding and repositioning method ("Peak-Up") that uses the Spitzer Pointing Control Reference Sensor (PCRS) to repeatedly position a target to within 0.1 IRAC pixels of an area of minimal gain variation; and (2) the high-precision, high-resolution measurement of the pixel gain structure using non-variable stars. We show that the technique currently allows the reduction of correlated noise by almost an order of magnitude over raw data, which is comparable to the improvement due to self-calibration. We discuss other possible sources of correlated noise, and proposals for reducing their impact on photometric precision

Modifications to the warm Spitzer data reduction pipeline

The Spitzer Space Telescope Infrared Array Camera (IRAC) basic calibrated data reduction pipeline is designed to take a single raw frame from a single IRAC detector and produce a flux-calibrated image that has had all well-understood instrumental signatures removed. We discuss several modifications to the pipeline developed in the last two years in response to the Spitzer warm mission. Due to the different instrument characteristics in the warm mission, we have significantly changed pipeline procedures for masking residual images and mitigating column pulldown. In addition, the muxbleed correction was turned off, because it is not present in the warm data. Parameters relevant to linearity correction, bad pixels, and the photometric calibration have been updated and are continually monitored

A systematic review of the safety and efficacy of currently used treatment modalities in the treatment of patients with PIK3CA-related overgrowth spectrum.

BACKGROUND PIK3CA-related overgrowth syndromes (PROS) include a variety of clinical presentations that are associated with hypertrophy of different parts of the body. AIM Perform a systematic literature review to assess the current treatment options and their efficacy and safety in PROS. METHODS A literature search was performed in EMBASE, MEDLINE (Ovid), Web of Science Core Collection, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and Google Scholar to retrieve publications on the treatment for hypertrophy in PROS and randomized controlled trials, cohort studies or case series including ≥10 patients reporting were included in the review. Titles, abstracts and full texts were assessed by two reviewers independently. The Risk of Bias (RoB) was assessed using the Newcastle Ottawa Scale. RESULTS 16 articles for the treatment of hypertrophy in PROS patients were included, 13 (81.3%) from clinical retrospective studies and 3 (13.7%) from prospective cohort studies. The ROB grade was low for 2, medium for 12 and high for 2 studies. 13 articles reported surgical treatment, while 3 reported pharmacological treatment using PIK3/mTOR pathway inhibitors in PROS patients. In 3 studies, PROS was defined by a mutation in the PIK3CA gene, while the other studies relied on a clinical definition of PROS. Surgical therapy was beneficial for a specific subgroup of PROS (macrodactyly), but little was reported concerning surgery and potential benefits in other PROS entities. Reported side effects in surgical therapy were mostly prolonged wound healing or scarring. PIK3/mTOR pathway inhibition was beneficial in patients with PROS reducing hypertrophy as well as systemic symptoms. Adverse effects reported included infection, changes in blood count, liver enzymes and metabolic measures. CONCLUSION Surgery is a locally limited treatment option in specific types of PROS. A promising treatment option in PROS is the pharmacological PIK3CA inhibition. However, the level of evidence on treatment of overgrowth in PROS patients is limited

Pointing effects and their consequences for Spitzer IRAC exoplanet observations

Spitzer observations of exoplanets routinely yield accuracies of better than one part in 10,000. However, there remain a number of issues that limit the attainable precision, particularly for long duration observations. These include initial pointing inaccuracies, pointing wobble, initial target drift, long-term pointing drifts, and low and high frequency jitter. Coupled with small scale, intrapixel sensitivity variations, all of these pointing issues have the potential to produce significant, correlated photometric noise. We examine each of these issues in turn, discussing their suspected causes and consequences, and describing possible and planned mitigation techniques

Neonatal Metabolomic Profiles Related to Prenatal Arsenic Exposure

Prenatal inorganic arsenic (iAs) exposure is associated with health effects evident at birth and later in life. An understanding of the relationship between prenatal iAs exposure and alterations in the neonatal metabolome could reveal critical molecular modifications, potentially underpinning disease etiologies. In this study, nuclear magnetic resonance (NMR) spectroscopy-based metabolomic analysis was used to identify metabolites in neonate cord serum associated with prenatal iAs exposure in participants from the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort, in GoÌmez Palacio, Mexico. Through multivariable linear regression, ten cord serum metabolites were identified as significantly associated with total urinary iAs and/or iAs metabolites, measured as %iAs, %monomethylated arsenicals (MMAs), and %dimethylated arsenicals (DMAs). A total of 17 metabolites were identified as significantly associated with total iAs and/or iAs metabolites in cord serum. These metabolites are indicative of changes in important biochemical pathways such as vitamin metabolism, the citric acid (TCA) cycle, and amino acid metabolism. These data highlight that maternal biotransformation of iAs and neonatal levels of iAs and its metabolites are associated with differences in neonate cord metabolomic profiles. The results demonstrate the potential utility of metabolites as biomarkers/indicators of in utero environmental exposure

Calibration trending in the Spitzer beyond era

The Spitzer Space Telescope currently operates in the "Beyond Era", over nine years past an original cryogenic mission. As the astronomy community continues to advance scientific boundaries and push beyond original specifications, the stability of the Infrared Array Camera (IRAC) instrument is paramount. The Instrument Team (IST) monitors the pointing accuracy, temperature, and calibration and provides the information in a timely manner to observers. The IRAC IST created a calibration trending web page, available to the general astronomy community, where the team posts updates of three most pertinent scientific stability measures of the IRAC data: calibration, bias, and bad pixels. In addition, photometry and telescope properties from all the staring observations (>1500 as of April 2018) are trended to examine correlations with changes in the age or thermal properties of the telescope. A long, well-sampled baseline established by consistent monitoring outside anomalies and space weather events allows even the smallest changes to be detected