External Validation Of An Electronic Phenotyping Algorithm To Detect Attention To Elevated Bmi And Weight-Related Comorbidities In Pediatric Primary Care.

Pediatric obesity is a growing national and global concern with nearly 1 in 5 children in the U.S. affected [1].The American Academy of Pediatrics endorsed expert committee recommendations in 2007 to assist clinicians in pediatric weight management; however, adherence to these recommendations among primary care providers is suboptimal, and measuring adherence in feasible and pragmatic ways is challenging[2-4]. Commonly used quality measures that rely on billing data alone are an inadequate measure of provider attention to weight status in pediatric populations as they do not capture whether providers communicate about elevated body mass index (BMI) and associated medical risks with families. Electronic phenotyping is a unique tool that has the ability to use multiple areas of stored clinical data to group individuals according to pre-defined characteristics such as diagnostic codes, laboratory values or medications. We examined the external validity of a phenotyping algorithm, developed previously by Turer et al and validated in a single health system in Texas, that assesses pediatric providers’ attention to obesity and overweight using structured data from the electronic health record (EHR), to three pediatric primary care practices affiliated with Yale New Haven Health. Well child visit encounters were labeled either “no attention”, “attention to BMI only”, “attention to comorbidity only,” or “attention to BMI and comorbidity”. The performance of the algorithm was evaluated on the ability to predict “no attention”, using chart review as the reference standard. The application of the minimally altered algorithm yielded a sensitivity of 94.0% and a specificity of 79.2% for predicting “no attention”, compared to a sensitivity of 97.9% and a specificity of 94.8% in the original study. Our findings suggest that while electronic phenotyping using structured EHR inputs provides a better evaluation of clinic encounters than use of diagnostic codes alone, methods that incorporate information in unstructured (“free text”) clinical notes may yield better results

Markery proliferacji i inwazyjności w guzach przysadki wydzielających hormon wzrostu

Introduction In the search for markers of invasiveness of pituitary adenomas, we studied the expression of Ki-67 antigen, TOPO 2A (topoisomerase 2 alpha), AIP (Aryl Hydrocarbon Receptor-Interacting Protein) and VEGF (Vascular Endothelial Growth Factor) in somatotropinomas. Material and Methods We retrospectively studied a group of 31 patients who underwent pituitary tumour surgery. Expression of Ki-67, TOPO 2A, AIP and VEGF in surgical specimens was determined by immunohistochemistry. Relations between quantitatively determined markers and clinical symptoms, tumour features, and MR imaging, were analysed. Acromegaly was confirmed by hormonal tests in all patients studied. Local invasiveness (cavernous sinus penetration, optic chiasm compression or suprasellar extension) was observed in 18/31 patients (58,1%). Results Ki-67 was expressed in 77.4%, TOPO 2A in 87.1%, AIP in 83.8%, and VEGF in 87.1% of 31 cases of somatropinoma. Median values of Ki-67, TOPO 2A, AIP and cytoplasmic VEGF indices were 1.2% [IQR=2.2], 1.5% [IQR=1.6], 21.26% [IQR=20.1] and 20.4% [IQR=15.4], respectively. Ki-67, TOPO 2A, AIP and VEGF expression was not correlated with age nor with patient gender (p > 0.05). Only Ki-67 and TOPO 2A correlated with tumour size (for Ki-67: r=0.42, p=0.025; for TOPO 2A: r=0.53, p=0.003). Ki-67 and TOPO 2A levels were significantly higher in invasive compared to noninvasive somatropinomas (Ki67 mean values: 1.85±1.33% vs. 0.95±1.07%, p=0.024; TOPO 2A mean values: 2.19±1.63% vs. 1.45±1.23%, , p=0.011). Conclusions Ki-67, TOPO 2A, AIP and VEGF were expressed in over 70% of all somatotropinomas. Only Ki-67 and TOPO 2A expression correlated with tumour size and tumour invasiveness.Wstęp: W poszukiwaniu markerów inwazyjności gruczolaków przysadki badano ekspresję antygenu Ki-67, TOPO 2A (topoisomerase 2 alpha), AIP (Aryl Hydrocarbon Receptor-Interacting Protein) oraz VEGF (Vascular Endothelial Growth Factor) w guzach wydzielających hormon wzrostu. Materiał i metody: Badano retrospektywnie grupę 31 pacjentów, operowanych z powodu guza przysadki. Ekspresję Ki-67, TOPO 2A, AIP oraz VEGF badano immunohistochemicznie w tkankach uzyskanych chirurgicznie. Analizowano relacje między ilościową ekspresją markerów a objawami klinicznymi, cechami guza i obrazem MR. Testami hormonalnymi potwierdzono akromegalię u wszystkich badanych pacjentów. Miejscową inwazyjność, zdefiniowaną jako naciekanie zatoki jamistej, kompresję skrzyżowania wzrokowego, wzrost nadsiodłowy guza obserwowano u 18/31 (58,15) pacjentów. Wyniki: Ekspresję Ki-67 stwierdzono w 77,4%, TOPO 2A w 87,1%, AIP w 83,8%, oraz VEGF w 87,1% przypadków samatotropinoma (n = 31). Wartości median indeksów Ki-67, TOPO 2A, AIP i cytoplazmatycznego VEGF wynosiły 1,2% [IQR = 2,2], 1,5% [IQR = 1,6], 21,26% [IQR = 20,1] i 20,4% [IQR = 15,4], odpowiednio. Indeksy Ki-67, TOPO 2A, AIP i VEGF nie korelowały z wiekiem i płcią pacjentów (p > 0,05). Tylko Ki-67 i TOPO 2A korelowało z wielkością guza (dla Ki-67: r = 0,42, p = 0,025; dla TOPO 2A: r = 0,53, p = 0,003). Indeksy Ki-6 oraz TOPO 2A były znamiennie wyższe w guzach inwazyjnych w porównaniu z guzami nieinwazyjnymi (średnie Ki-67: 1,85 ± 1,33% vs 0,95 ± 1,07%, p = 0,024 oraz średnie TOPO 2A: 2,19 ± 1,63% vs 1,45 ± 1,23%, p = 0,011). Wnioski: Ekspresję Ki-67, TOPO 2A, AIP i VEGF stwierdzono w ponad 70% wszystkich somatotropinoma. Tylko ekspresja Ki-67 oraz TOPO 2A korelowała z wielkością guza i jego inwazyjnością

Nanostructure Accelerators: Novel concept and path to its realization

TeV/m acceleration gradients using crystals as originally envisioned by R. Hofstadter, an early pioneer of HEP, have remained unrealizable. Fundamental obstacles that have hampered efforts on particle acceleration using bulk-crystals arise from collisional energy loss and emittance degradation in addition to severe beam disruption despite the favorable effect of particle channeling along interatomic planes in bulk. We aspire for the union of nanoscience with accelerator science to not only overcome these problems using nanostructured tubes to avoid direct impact of the beam on bulk ion-lattice but also to utilize the highly tunable characteristics of nanomaterials. We pioneer a novel surface wave mechanism in nanostructured materials with a strong electrostatic component which not only attains tens of TeV/m gradients but also has focusing fields. Under our initiative, the proof-of-principle demonstration of tens of TeV/m gradients and beam nanomodulation is underway. Realizable nanostructure accelerators naturally promise new horizons in HEP as well as in a wide range of areas of research that utilize beams of high-energy particles or photons.Comment: submission to Snowmass'21 Accelerator Frontie

Experimental study for microwave-induced thermoacoustic tomography

Microwave-Induced Thermoacoustic Tomography (MI-TAT) is a noninvasive hybrid modality which improves contrast by using thermoelastic wave generation induced by microwave absorption. Ultrasonography is widely used in medical practice as a low-cost alternative and supplement to magnetic resonance imaging (MRI). Although ultrasonography has relatively high image resolution (depending on the ultrasonic wavelength at diagnostic frequencies), it suffers from low image contrast of soft tissues. In this work samples are irradiated with sub- microsecond electromagnetic pulses inducing acoustic waves in the sample that are then detected with an unfocused transducer. The advantage of this hybrid modality is the ability to take advantage of the microwave absorption coefficients which provide high contrast in samples. This in combination with the superior spatial resolution of ultrasound waves is important to providing a low-cost effective imaging technique. Here we propose to use this hybrid imaging technique to image composite materials to further investigate the NDE applications for MI-TAT.</p

Approaching Petavolts per meter plasmonics using structured semiconductors

A new class of strongly excited plasmonic modes that open access to unprecedented Petavolts per meter electromagnetic fields promise wide-ranging, transformative impact. These modes are constituted by large amplitude oscillations of the ultradense, delocalized free electron Fermi gas which is inherent in conductive media. Here structured semiconductors with appropriate concentration of n-type dopant are introduced to tune the properties of the Fermi gas for matched excitation of an electrostatic, surface "crunch-in" plasmon using readily available electron beams of ten micron overall dimensions and hundreds of picoCoulomb charge launched inside a tube. Strong excitation made possible by matching results in relativistic oscillations of the Fermi electron gas and uncovers unique phenomena. Relativistically induced ballistic electron transport comes about due to relativistic multifold increase in the mean free path. Acquired ballistic transport also leads to unconventional heat deposition beyond the Ohm's law. This explains the absence of observed damage or solid-plasma formation in experiments on interaction of conductive samples with electron bunches shorter than $\rm 10^{-13} seconds$. Furthermore, relativistic momentum leads to copious tunneling of electron gas allowing it to traverse the surface and crunch inside the tube. Relativistic effects along with large, localized variation of Fermi gas density underlying these modes necessitate the kinetic approach coupled with particle-in-cell simulations. Experimental verification of acceleration and focusing of electron beams modeled here using tens of Gigavolts per meter fields excited in semiconductors with $\rm 10^{18}cm^{-3}$ free electron density will pave the way for Petavolts per meter plasmonics.Comment: 16 pages, 10 figure

Spatial signatures of anesthesia-induced burst-suppression differ between primates and rodents

During deep anesthesia, the electroencephalographic (EEG) signal of the brain alternates between bursts of activity and periods of relative silence (suppressions). The origin of burst-suppression and its distribution across the brain remain matters of debate. In this work, we used functional magnetic resonance imaging (fMRI) to map the brain areas involved in anesthesia-induced burst-suppression across four mammalian species: humans, long-tailed macaques, common marmosets, and rats. At first, we determined the fMRI signatures of burst-suppression in human EEG-fMRI data. Applying this method to animal fMRI datasets, we found distinct burst-suppression signatures in all species. The burst-suppression maps revealed a marked inter-species difference: in rats, the entire neocortex engaged in burst-suppression, while in primates most sensory areas were excluded-predominantly the primary visual cortex. We anticipate that the identified species-specific fMRI signatures and whole-brain maps will guide future targeted studies investigating the cellular and molecular mechanisms of burst-suppression in unconscious states

General anaesthesia decreases the uniqueness of brain functional connectivity across individuals and species

The human brain is characterized by idiosyncratic patterns of spontaneous thought, rendering each brain uniquely identifiable from its neural activity. However, deep general anaesthesia suppresses subjective experience. Does it also suppress what makes each brain unique? Here we used functional MRI scans acquired under the effects of the general anaesthetics sevoflurane and propofol to determine whether anaesthetic-induced unconsciousness diminishes the uniqueness of the human brain, both with respect to the brains of other individuals and the brains of another species. Using functional connectivity, we report that under anaesthesia individual brains become less self-similar and less distinguishable from each other. Loss of distinctiveness is highly organized: it co-localizes with the archetypal sensory–association axis, correlating with genetic and morphometric markers of phylogenetic differences between humans and other primates. This effect is more evident at greater anaesthetic depths, reproducible across sevoflurane and propofol and reversed upon recovery. Providing convergent evidence, we show that anaesthesia shifts the functional connectivity of the human brain closer to the functional connectivity of the macaque brain in a low-dimensional space. Finally, anaesthesia diminishes the match between spontaneous brain activity and cognitive brain patterns aggregated from the Neurosynth meta-analytic engine. Collectively, the present results reveal that anaesthetized human brains are not only less distinguishable from each other, but also less distinguishable from the brains of other primates, with specifically human-expanded regions being the most affected by anaesthesia.</p

Subtraction of correlated noise in global networks of gravitational-wave interferometers

The recent discovery of merging black holes suggests that a stochastic gravitational-wave background is within reach of the advanced detector network operating at design sensitivity. However, correlated magnetic noise from Schumann resonances threatens to contaminate observation of a stochastic background. In this paper, we report on the first effort to eliminate intercontinental correlated noise from Schumann resonances using Wiener filtering. Using magnetometers as proxies for gravitational-wave detectors, we demonstrate as much as a factor of two reduction in the coherence between magnetometers on different continents. While much work remains to be done, our results constitute a proof-of-principle and motivate follow-up studies with a dedicated array of magnetometers

Blinded and unblinded sample size reestimation procedures for stepped-wedge cluster randomized trials.

The ability to accurately estimate the sample size required by a stepped-wedge (SW) cluster randomized trial (CRT) routinely depends upon the specification of several nuisance parameters. If these parameters are misspecified, the trial could be overpowered, leading to increased cost, or underpowered, enhancing the likelihood of a false negative. We address this issue here for cross-sectional SW-CRTs, analyzed with a particular linear-mixed model, by proposing methods for blinded and unblinded sample size reestimation (SSRE). First, blinded estimators for the variance parameters of a SW-CRT analyzed using the Hussey and Hughes model are derived. Following this, procedures for blinded and unblinded SSRE after any time period in a SW-CRT are detailed. The performance of these procedures is then examined and contrasted using two example trial design scenarios. We find that if the two key variance parameters were underspecified by 50%, the SSRE procedures were able to increase power over the conventional SW-CRT design by up to 41%, resulting in an empirical power above the desired level. Thus, though there are practical issues to consider, the performance of the procedures means researchers should consider incorporating SSRE in to future SW-CRTs