cssi/SciSciGPT-SciSciNet huggingface dataset:
Dysregulation of miRNAs In AL Amyloidosis

Abstract 4648 Bone marrow plasma cells (BMPC) were purified from aspirates obtained from patients with AL amyloidosis using anti-CD138 immunomagnetic beads, and from controls. Expression levels of micro RNAs (miRNAs) were compared by microarray. The levels of ten miRNAs were found to be increased more than 1.5-fold in BMPC of AL amyloidosis patients. These results were confirmed using stem-loop RT-qPCR for miR-148a, miR-26a, and miR-16, the most highly upregulated miRNAs in the AL samples. miR-16, a micro RNA linked to other hematopoietic diseases, was significantly increased in the AL group at baseline and also in treated patients with persistent monoclonal plasma cells in the bone marrow, but not in patients who achieved a hematologic remission after therapy and normal polyclonal BMPCs. miR-16 can be derived from the miR-16-1/mirR-15a cluster on chromosome 13 or the miR-16-2/miR-15b cluster on chromosome 3. The expression of miR-15b was much higher than miR15a in AL and control BMPC samples; this suggests that miR-16 in plasma cells is mostly derived from chromosome 3. The anti-apoptosis gene BCL-2, a putative target mRNA that can be down-regulated by miR-16, was present in the BMPCs from the AL group despite the elevated levels of miR-16. Our data suggest that miRNAs are dysregulated in clonal plasma cells from AL amyloidosis patients and that abnormal levels of miRNAs may be potential biomarkers for disease. Disclosures: No relevant conflicts of interest to declare.
The Retroperitoneal Approach to Endometriosis.

Abstract Study Objective To demonstrate principles of laparoscopic management of deeply infiltrating endometriosis requiring retroperitoneal entry. Design Step-by-step demonstration and explanation of technique using videos from patients with deeply infiltrating stage IV endometriosis who failed medical management (Canadian Task Force classification IIIB). This study was exempt from Institutional Review Board review. Setting Large academic medical center. Interventions Laparoscopic surgical excision of endometriosis requiring retroperitoneal dissection. Conclusion Surgical excision of endometriosis is an essential tool for the management of symptomatic disease. Chronic inflammation may lead to distorted anatomy and limit the ability to identify pelvic landmarks, precluding the use of blunt dissection. High surgical morbidity may result from unintentional injury to the ureters or retroperitoneal pelvic vessels. Knowledge of pelvic anatomy defines a safe space for sharp entry into the retroperitoneum, ureterolysis using blunt and sharp dissection, identification of pelvic vasculature, and judicious application of electrosurgery. With appropriate technique, the rate of intraoperative complications, including bowel, bladder, and ureteral injury as well as hematoma and bleeding, is approximately 1%. Postoperative complications, including drop in hemoglobin, urinary retention, cystitis, and abdominal wall hematoma, are usually minor, and reoperation rates are well under 1%. Thorough dissection of the retroperitoneum facilitates complete excision of endometriosis with minimum morbidity.
A century later, resolving Joseph Grinnell's “striking case of adventitious coloration”

ABSTRACT In 1921, The Auk published an unresolved mystery submitted by Joseph Grinnell, founding director of the Museum of Vertebrate Zoology at the University of California, Berkeley. He had collected two Oak Titmice (Baeolophus inornatus) whose breast feathers appeared to be yellow; the feathers were covered in microscopic particles. He invited readers to further investigate the nature of these particles. Nearly a century later, we have determined that Grinnell's mysterious grains are willow (Salix) pollen, a diagnosis he rejected because the size of the particles had been mismeasured, and because he lacked a plausible explanation for how the birds would become coated in pollen. We investigated this case using Grinnell's own specimens, field notes, and correspondence, a testament to Grinnell's dedication to scientific rigor through carefully documented and curated natural history collections.
Energy-Aware Standby-Sparing on Heterogeneous Multicore Systems

Standby-sparing systems where one processor is used as primary while another one is deployed as spare have been used to provide high reliability to real-time embedded systems. To reduce the energy consumption, the primary uses DVFS while the spare employs DPM to postpone the backup tasks. In this paper, we re-visit the problem for heterogeneous multicore systems that include both high-performance and low-power cores. We identify and address the two main dimensions of the problem, namely, what type of core to use as the primary or backup, and how to make frequency assignments on the primary to maximize energy savings.
Direct growth of graphene on dielectric substrates: Epitaxy at incommensurate and reactive interfaces

Direct growth of graphene by industrially scalable methods on suitable dielectric substrates is critical to the development of practical electronic and spintronic devices. Graphene growth by molecular beam epitaxy on the commensurate substrate h-BN(0001) and on other weakly interacting substrates has previously been demonstrated. We have been able to use MBE to grow graphene on incommensurate Co3O4(111), which we find involves formation of a deformed interfacial C layer due to some C atoms forming covalent bonds to oxide O sites, followed by epitaxial graphene growth in subsequent layers. These results suggest that similar graphene growth may be achievable on other p-type spinel-structured oxides, opening the door to new electronic or spintronic applications.
Teaching English-Spanish cognate-recognition strategies through the Américas Book Award-winners and honor picture books

ABSTRACTCognates are words that are the same or nearly the same orthographically and semantically in English and Spanish. The majority of the more than 20,000 cognates are academic vocabulary words comprised of Latin and Greek roots and affixes. Several thousand cognates can be found in the picture books that have earned the Americas Book Award, which was established to honor quality multicultural books that portray Latino cultures in a positive light. The authors present lessons for teaching primary school Latino ELLs about cognates through the Americas Award picture books, as they educate their students about their rich Latino cultures.
Robotic Care of Children, the Elderly, and the Sick (with Oren Etzioni)

As Artificial Intelligence technology seems poised for a major take-off and changing societal dynamics are creating a high demand for caregivers for elders, children, and those infirmed, AI-based robotic caregivers may well be used much more often. This chapter examines the ethical concerns raised by the use of AI caregivers and concludes that many of these concerns are avoided when AI caregivers operate as partners to human caregivers rather than substitutes. Furthermore, most of the remaining concerns are minor and are faced by human caregivers as well. The chapter then argues that because AI caregivers’ systems are learning systems that could therefore stray from their initial guidelines, a layer of AI-based oversight is necessary to protect patients. Such layers of oversight are already employed across many areas of human service provision, and a similar method could help to ensure that AI caregivers act in ways that are ethical, legal, and in accordance with predetermined guidelines.
Novel Uses of Lumen-Apposing Metal Stents

The lumen apposing metal stent (LAMS) has historically been used for drainage of pancreatic fluid collections. The unique design of this stent has allowed endoscopists to develop novel uses, including drainage of abscesses adjacent to gastrointestinal lumens, maintaining patency in gastrointestinal strictures, and creating a fistulous tract to bypass altered or compromised anatomy. These alternative uses for the LAMS take advantage of its ability to form a sealed, well-approximated anastomosis. Future applications of the LAMS are continuously being developed as clinicians provide minimally invasive approaches for management of these disease processes.
Origin of Phobos and Deimos by the impact of a Vesta-to-Ceres sized body with Mars

It has been proposed that Mars' moons formed from a disk produced by a large impact with the planet. However, whether such an event could produce tiny Phobos and Deimos remains unclear. Using a hybrid N-body model of moon accumulation that includes a full treatment of moon-moon dynamical interactions, we first identify new constraints on the disk properties needed to produce Phobos and Deimos. We then simulate the impact formation of disks using smoothed particle hydrodynamics, including a novel approach that resolves the impact ejecta with order-of-magnitude finer mass resolution than existing methods. We find that forming Phobos-Deimos requires an oblique impact by a Vesta-to-Ceres sized object with ~10-3 times Mars' mass, a much less massive impactor than previously considered.
Perinatal anxiety: approach to diagnosis and management in the obstetric setting.

Anxiety is common in women during the perinatal period, manifests with various symptoms and severity, and is associated with significant maternal morbidity and adverse obstetric and neonatal outcomes. Given the intimate relationship and frequency of contact, the obstetric provider is positioned optimally to create a therapeutic alliance and to treat perinatal anxiety. Time constraints, absence of randomized controlled trials, mixed quality of data, and concern for potential adverse reproductive outcomes all limit the clinician's ability to initiate informed risk-benefit discussions. Clear understanding of the role of the obstetric provider in the identification, stabilization, and initiation of medication and/or referral to psychotherapy for women with perinatal anxiety disorders is critical to maternal and neonatal wellbeing. Informed by our clinical practice as perinatal psychiatric providers, we have provided a concise summary of current research on the approach to the treatment of perinatal anxiety disorders in the obstetric setting that includes psychotherapy and supportive interventions, primary and adjuvant psychiatric medication, and general prescribing pearls. Medications that we examined include antidepressants, benzodiazepines, sedative-hypnotics, antihistamines, quetiapine, buspirone, propranolol, and melatonin. Further research into management of perinatal anxiety, particularly psychopharmacologic management, is warranted.
Fundamentals of Thermal Sterilization Processes

A cell is considered dead when it can no longer reproduce under conditions known to promote growth of that microorganism. A strict definition of a sterilization process is one in which all viable cells in a given population are inactivated by some physical or chemical means, and inactivation is irreversible. However, as currently defined in the pharmaceutical industry, the effectiveness of a sterilization process is determined by the statistical probability of a non-sterile unit (PNSU) in a lot or batch of product.
The ethics of infinite impact

Transhumanism, the research program devoted to increasing our physical and mental abilities and lengthening our lifespan, casts light on the term ‘responsible innovation’. The goals of the transhum...
Estimation of attenuator mask from region of interest (ROI) dose-reduced images for brightness equalization using convolutional neural networks

Region-of-Interest (ROI) fluoroscopy uses a differential x-ray attenuator to reduce the dose to the patient in the periphery region while maintaining regular dose within the ROI treatment area, resulting in an image with differential brightness regions. The brightness difference can be corrected by subtracting a mask of the ROI attenuator from the dose-reduced image. The purpose of this work is to implement a Convolutional-Neural-Network (CNN) capable of deriving a mask of the ROI attenuator from the dose-reduced images, which can be used to equalize the brightness in the dose-reduced images without a pre-acquired mask. A data set of 10,000 ROI dose reduced images of various objects including anthropomorphic head and chest phantoms were generated with different ROI positions and sizes. A 22 layer CNN was developed to derive a mask of the ROI attenuator from the dose reduced image. The network was trained on 30% and tested on 15% of the images from the ROI image data set. The trained CNN was used on the remaining 55% of the data set to generate the ROI mask, and the average computation time for each image was calculated to be 70 ms. The Mean-Square-Error (MSE) for the testing data set was calculated to be 2.03e-05. For the remaining data set of 5500 images the average MSE between the network output and the corresponding expected ROI mask was calculated to be 2.21e-05. The masks generated by the CNN were successfully used to restore and equalize the brightness of the dose reduced images.
Tmem2 restricts atrioventricular canal differentiation by regulating degradation of hyaluronic acid.

Background Atrioventricular valve development relies upon the precisely defined dimensions of the atrioventricular canal (AVC). Current models suggest that Wnt signaling plays an important role atop a pathway that promotes AVC development. The factors that confine AVC differentiation to the appropriate location, however, are less well understood. Results Transmembrane protein 2 (Tmem2) is a key player in restricting AVC differentiation: in zebrafish, tmem2 mutants display an expansion of AVC characteristics, but the molecular mechanism of Tmem2 function in this context remains unclear. Through structure-function analysis, we demonstrate that the extracellular portion of Tmem2 is crucial for its role in restricting AVC boundaries. Importantly, the Tmem2 ectodomain contains regions implicated in the depolymerization of hyaluronic acid (HA). We find that tmem2 mutant hearts exhibit excess HA deposition alongside broadened distribution of Wnt signaling. Moreover, addition of ectopic hyaluronidase can restore the restriction of AVC differentiation in tmem2 mutants. Finally, we show that alteration of a residue important for HA depolymerization impairs the efficacy of Tmem2 function during AVC development. Conclusions Taken together, our data support a model in which HA degradation, regulated by Tmem2, limits the distribution of Wnt signaling and thereby confines the differentiation of the AVC.
Massively parallel, time-resolved single-cell RNA sequencing with scNT-Seq

Single-cell RNA sequencing offers snapshots of whole transcriptomes but obscures the temporal dynamics of RNA biogenesis and decay. Here we present single-cell new transcript tagging sequencing (scNT-Seq), a method for massively parallel analysis of newly-transcribed and pre-existing RNAs from the same cell. This droplet microfluidics-based method enables high-throughput chemical conversion on barcoded beads, efficiently marking metabolically labeled newly-transcribed RNAs with T-to-C substitutions. By simultaneously measuring new and old transcriptomes, scNT-Seq reveals neuronal subtype-specific gene regulatory networks and time-resolved RNA trajectories in response to brief (minutes) versus sustained (hours) neuronal activation. Integrating scNT-Seq with genetic perturbation reveals that DNA methylcytosine dioxygenases may inhibit stepwise transition from pluripotent embryonic stem cell state to intermediate and totipotent two-cell-embryo-like (2C-like) states by promoting global RNA biogenesis. Furthermore, pulse-chase scNT-Seq enables transcriptome-wide measurements of RNA stability in rare 2C-like cells. Time-resolved single-cell transcriptomic analysis thus opens new lines of inquiry regarding cell-type-specific RNA regulatory mechanisms.
Near-Wall heat transfer of solid particles in particle-laden turbulent flows

Abstract The focus of this study is on the near-wall thermal interaction of micro-particles in a vertical turbulent channel flow. Three mechanisms for the heat transfer of solid particles and the wall, when the distance between the particles and wall is less than half of the particle's radius, have been considered. The first two mechanisms are the solid-solid (Qss) and the solid-fluid-solid (Qsfsc) heat transfer of wall-colliding particles. The time of collision and the contact area are calculated based on the elastic Hertzian contact equations. The third mechanism is the solid-fluid-solid (Qsfsp) heat transfer for particles that do not hit the wall but move closely parallel to the wall. Mathematical models for these three mechanisms are implemented into an Eulerian-Lagrangian direct numerical simulation (DNS) solver for a particle Stokes number of St = 192, and a constant particle mass loading of φm= 0.54. Comparing these three mechanisms, it is shown that the heat transfer rate via the third mechanism (Qsfsp) is significantly larger than the ones of the two other mechanisms (Qss, Qsfsc). This can be contributed to the fact that some of the near wall particles stay in the laminar sublayer for a large time interval and by moving parallel to the wall they have enough time to have direct thermal interaction with the wall. The overall heat transfer rate of particle-laden flow, however, is almost unaffected by the inclusion of these thermal interactions at this mass loading and particle Stokes number. The only effect of including these near-wall particle interactions is to slightly decrease the slope of the temperature profile, the convective heat transfer, and the fluid-particle temperature difference at the near wall region.
Evaluation of benefits at a regional scale of new strategies to improve the seismic performance of low-rise residential construction

Light-frame low-rise wood dwellings have typically had adequate levels of safety in terms of collapse prevention. Nevertheless, damage to this type of construction due to earthquakes has resulted in large economic losses and thousands of displaced families. This paper evaluates the benefits, on a regional scale, of using a recently developed design and construction method referred to as unibody. This cost-effective method increases the lateral strength and, particularly, the lateral stiffness of walls of wood-frame houses, leading to significant reductions in lateral displacement demands. For houses at a given distance from the seismic source, reduced displacement demands translate into much smaller probabilities of damage. Consequently, for a region affected by a seismic event, this translates into a much smaller area of damaged houses. It is found that, for short-period structures, increasing the lateral stiffness is more efficient than increasing the lateral strength. Thus, when using unibody construction, which greatly increases the lateral stiffness of wood-frame houses, the number of damaged residential units is greatly reduced. It is shown that these relationships are strongly nonlinear and are positively combined resulting in a substantial reduction of seismic risk on a regional scale.
AN UNSTEADY ‘WALL OF SEPARATION’: A FEW CONSIDERATIONS

This is a polemical essay concerning the "wall of separation" between church and state in the United States of America. The author observes that there is a political struggle between defenders of religion, primarily Christians, on the one hand, and secularists on the other. Typical reasons given by secularists for a hard and fast division between church and state, and/or religion and politics, are historical, constitutional, and cultural. Underlying all of these reasons perhaps is the idea that faith is cognitively inferior to knowledge and therefore has no place in the public square. The author vigorously contests each aspect of the secularists' position and explores in further detail the epistemological distinctions between faith and knowledge.
Characterizing the function of EPB41L4A in the predisposition to papillary thyroid carcinoma

Papillary thyroid carcinoma (PTC) is the most common histotype of thyroid carcinoma. The heritability of PTC is high compared to other cancers, but its underlying causes are unknown. A recent genome-wide association study revealed the association of a variant at the 5q22 locus, rs73227498, with PTC predisposition. We report that rs17134155, a variant in high linkage disequilibrium with rs73227498, is located in an enhancer region downstream of coding transcripts of EPB41L4A. Rs17134155 showed significant enhancer activity in luciferase assays, and haplotypes containing the protective allele of this variant conferred a significantly lower risk of PTC. While the index SNP, rs73227498, acted as a significant cis-eQTL for expression of EPB41L4A, rs17134155 was a significant cis-sQTL for the alternative splicing of a non-coding transcript of EPB41L4A, called EPB41L4A-203. We also performed knockdown of EPB41L4A followed by microarray analysis. Some of the top differentially-expressed genes were represented among regulators of the WNT/β-catenin signaling pathway. Our results indicate that an enhancer region at 5q22 regulates the expression and splicing of EPB41L4A transcripts. We also provide evidence that EPB41L4A expression is involved in regulating growth and differentiation pathways, suggesting that decreased expression of EPB41L4A is a mechanism in the predisposition to PTC.
Impact of Diabetes Prevention Guideline Adoption on Health Outcomes: A Pragmatic Implementation Trial.

Limited research exists to evaluate nutrition guideline impact on clinical practice and patient health outcomes. In this study we investigate (1) the impact of guideline training on the implementation of the diabetes prevention Evidence-Based Nutrition Practice Guideline (EBNPG), and (2) the relationship between EBNPG congruence and resulting health outcomes in patients with prediabetes. We conducted an implementation study in which registered dietitian nutritionists (RDNs) provided nutrition care with 3-month follow-up to 102 pre-diabetes patients before and after a professional training on the implementation of the Diabetes Prevention EBNPG. Using the RDNs’ Nutrition Care Process (NCP) documentation, we measured percent guideline congruence and health outcomes (body weight, waist circumference, fasting glucose, glycosylated hemoglobin), and modeled health outcomes. Guideline congruence improved after training by 4.3% (P
Psychophysical chemosensory dysfunction in eating disorders: a qualitative systematic review.

Patients with chemosensory dysfunction experience significant quality of life disruptions, including reduced enjoyment of eating. While chemosensory dysfunction has been associated with eating disorders, the relationship is poorly understood. This systematic review aims to characterize psychophysical gustation and olfaction in patients with eating disorders. Systematic review of investigations assessing psychophysical chemosensory function in patients with organic eating disorders. 26 studies were included. Five studies assessed both chemosenses, while 12 and 9 assessed exclusively gustation or olfaction, respectively. In total, 779 patients were included [72.4% anorexia nervosa (AN), 26.7% bulimia nervosa (BN), 0.8% combined AN/BN]. Patients with eating disorders experienced rates of hypogeusia up to 87% in AN and 84.6% in BN. There was evidence for alterations in psychophysical olfaction, but orientation of trends were less clear. Chemosensory dysfunction was more evident in AN patients. Treatment correlated with improved chemosensory function. Despite heterogeneity in study methodology and results, this review demonstrates that patients with eating disorders experience some degree of chemosensory dysfunction, particularly in gustation. This symptomatology overlaps with those experienced by patients with other causes of chemosensory impairment. These findings suggest potential broad psychosocial, dietary, and mental health implications in patient populations experiencing chemosensory dysfunction. Level II.
The Duty to Transform: Properly Refining the Body and (Re)defining Oneself in Thailand

Current analyses of Asian cosmetic surgery and other beautification practices assess their use for economic gain (e.g., increasing chances of gaining employment when photos are required with applic...
High School Seniors Who Used E-Cigarettes May Have Otherwise Been Cigarette Smokers: Evidence From Monitoring the Future (United States, 2009-2018).

Introduction Studies have indicated that youth who use e-cigarettes are more likely to progress to cigarette smoking; however, the likelihood that these youth would have used tobacco products in the pre-vaping era is unclear. Aims and methods This study sought to determine whether youth who used e-cigarettes in 2014-2018 would have likely been smokers in the period preceding e-cigarette availability. Analyzing Monitoring the Future 12th grade data (United States, 2009-2018), we forecasted the prevalence of current smoking with logistic regression-derived propensity scores. Models predicted smoking for all subsequent years, incorporating sociodemographic, family, alcohol, and school-related variables, and a linear time trend. We compared forecasted to observed smoking prevalence annually, and prevalence of current e-cigarette use among nonsmokers across smoking propensity tertiles. Results Until 2014, observed smoking prevalence mirrored forecasted prevalence. Afterward, forecasted rates consistently overestimated prevalence. Among nonsmoking youth, e-cigarette use was lowest among those with lowest predicted probability of cigarette smoking (3.8%; 95% confidence interval [CI]: 3.3, 4.4) and highest among those with highest probability (23.5%; 95% CI: 22.2, 24.9). Conclusions Youth e-cigarette use has increased rapidly, with high prevalence among nonsmoking youth. However, the decline in current smoking among 12th graders has accelerated since e-cigarettes have become available. E-cigarette use is largely concentrated among youth who share characteristics with smokers of the pre-vaping era, suggesting e-cigarettes may have replaced cigarette smoking. Implications Among nonsmoking youth, vaping is largely concentrated among those who would have likely smoked prior to the introduction of e-cigarettes, and the introduction of e-cigarettes has coincided with an acceleration in the decline in youth smoking rates. E-cigarettes may be an important tool for population-level harm reduction, even considering their impact on youth.
Did It Work? Reflections and Five Humble Questions to Guide Assessment:

Assessments often fail to clearly answer whether a program “worked” or not. Here, I reflect on the broader purpose of assessment, and offer five questions to consider before undertaking an evaluati...
The Role of Imaging Informatics in Disaster Preparedness During the COVID-19 Pandemic.

Disaster preparedness is a major but necessary undertaking for every health care facility. The 2019 coronavirus (SARS-CoV-2) provided an unforeseen opportunity to compare the response of two radiology departments, University Health System A (UHSA) and University Health System B (UHSAB). Preparing for this disaster was unique since though unexpected, was thought to be detected early enough to allow for sufficient preparation. Unlike many other disasters which are short-term, single events, this has been an on-going event. Changes at both health systems included workflow alterations for exposure reduction to faculty, trainees, and staff. UHSA was able to quickly divert workflow to previously deployed home workstations, while University of Utah Health Sciences Center required 2 to 3 weeks to procure and initialize enough remote workstations to significantly affect departmental operations. Other measures such as universal masking, temperature screening at facility entrances, virtual appointments, and physical barriers were used by both systems to limit patient-to-patient, patient-to-staff, staff-to-patient, and staff-staff physical interaction to help decrease exposure risk. The goal of these preparations is to allow each department to fulfill imaging needs in support of the organizational clinical mission with the flexibility to adapt to the unique and dynamic nature of this disaster.
AP pelvis radiograph is insufficient for diagnosis of U-type sacral fractures.

We investigated the sensitivity of a screening test for pelvic ring disruption, the AP pelvis radiograph, for clinically serious U-type sacral fractures which merit consultation with an orthopedic trauma specialist and may require transfer to a higher level of care. Retrospective clinical cohort of 63 consecutive patients presenting with U-type sacral fractures at one level 1 trauma referral center from January 2006 through December 2019. The sensitivity of the first AP pelvis radiograph obtained on admission, interpreted without reference to antecedent or concomitant pelvis computed tomography (CT) by a radiologist and a panel of three blinded orthopedic traumatologists, was determined against a reference diagnosis made from review of all pelvis radiographs, CT images, operative reports, and clinical documentation. Sensitivity of AP pelvis radiograph for U-type sacral fractures was 2% as interpreted by a radiologist and mean 12% (range 5–27%) as interpreted by orthopedic traumatologists with poor inter-rater agreement (Fleiss’ κ = 0.11). 94% of sacra were at obscured by radiographic artifact. The sensitivity of an AP pelvis radiograph is poor for U-type sacral fractures, whether interpreted by radiologists or orthopedic traumatologists. Pelvis CT should be considered as a screening test to rule out sacral fracture when the patient reports posterior pelvic pain, even if plain radiography demonstrates no injury or a minimally displaced pelvic ring disruption. Diagnostic level III
US Primary Care Providers’ Experiences and Practices Related to Routine Pediatric Vaccination During the COVID-19 Pandemic

Abstract Objective To describe, among pediatricians (Peds) and family physicians (FPs), 1) changes made to routine childhood vaccination delivery as a result of the pandemic, and 2) perceived barriers to delivering vaccinations from March 2020 through the time of the survey. Methods A nationally representative survey among Peds and FPs was administered by mail or Internet in October-December 2020. Results Response rate was 64% (579/909). For children aged 0–2 years, among those who vaccinated that age group pre-pandemic (Peds n=265, FPs n=222), 5% of Peds and 15% of FPs reported they had stopped vaccinating these children at any time. For children aged 4–6 years (Peds n=264, FPs n=229), 19% of Peds and 17% of FPs reported they had stopped vaccinating at any time. For children aged 11–18 years (Peds n=265, FPs n=251), 24% of Peds and 19% of FPs reported they had stopped vaccinating at any time. Nearly all reported returning to pre-pandemic vaccination services at the time of the survey. Factors most frequently reported as major/moderate barriers to providing vaccinations included fewer in-person visits because patients/parents were concerned about risk of SARS-CoV-2 infection (Peds, 52%; FPs, 54%), fewer in-person visits for sports clearance (Peds, 39%; FPs, 44%), and fewer back-to-school in-person visits because some children were in virtual learning (Peds, 25%; FPs, 33%). Conclusions Although some physicians reported interrupting vaccination services at some point during the pandemic, the majority reported continuing to provide vaccinations throughout, with essentially all returning to pre-pandemic vaccination services by end of 2020.
Multiple Subpial Transection: A Physiological Approach to Epilepsy Surgery

A discussion of multiple subpial transection (MST) in a text devoted to corpus callosotomy and its consequences requires some explanation. Callosotomy is the prototype of disconnection procedures in which the main goal is the prevention of spread of epileptic discharge from one hemisphere to the other. Elimination of this main route of interhemispheric communication reduces the likelihood that the two sides of the brain will be concurrently engulfed in paroxysmal activity. The occurrence of those particularly threatening symptoms (loss of consciousness, sudden falling or massive spasms) that depend on bihemispheric discharge is thereby prevented. What callosotomy does not do is interfere in any way with the generation of the primary epileptogenic disturbance.
Spectral properties of fluorochromes used in flow cytometry.

Publisher Summary Proper selection of the excitation wavelength and the choice of emission filters and the dichroic mirrors of flow cytometers require the knowledge of spectral properties of the fluorochrome to be used. Methods described contain information regarding the excitation and emission properties of the dyes. However, as in designing new staining reactions or selecting combinations of multiple dyes for different cell constituents in a single staining mixture, there is a need for rapid review of the spectral properties of numerous probes. Most of the reagents that have application in flow cytometry (FCM) are derivatives of a smaller group of dyes, such as fluorescein, rhodamine, coumarin, acridine, xanthene, or thiazine. Many groups of reagents thus share similar spectral properties with these dyes. Chemical modifications changes spectral characteristics of the probe not only by shifting the excitation and/or emission band in either direction but also by altering the luminescence quantum yield. Caution should be exercised in projecting the spectral properties of the derivatives based on spectral data of the parent dye.
Application of capillary electrophoresis to pharmaceutical analysis: Determination of alendronate in dosage forms

A method using capillary electrophoresis (CE) for the determination of alendronate (a non-chromophoric compound) in pharmaceutical dosage forms is described. Direct UV detection is based on the on-line formation of a chromophoric complex between alendronate and Cu2+ ions present in the electrolyte solution. The CE method has been validated to address the quantitative aspects for practical applications. Tablet dosage forms can be suitably assayed by the proposed method. Analysis of intravenous solutions encounters interference from citrate anion, a strong metal-chelating agent, present in the formulation, resulting in low and irreproducible assay results. The developed CE method obviates any derivatization procedure and involves minimum sample preparation
Self torture and group beneficence

Moral puzzles about actions which bring about very small or what are said to be imperceptible harms or benefits for each of a large number of people are well known. Less well known is an argument by Warren Quinn that standard theories of rationality can lead an agent to end up torturing himself or herself in a completely foreseeable way, and that this shows that standard theories of rationality need to be revised. We show where Quinn's argument goes wrong, and apply this to the moral puzzles.
Therapeutic Equivalence of a Generic Slow-Release Theophylline Tablet

Study Objective. To evaluate the relative bioavailability and clinical efficacy of two slow-release theophylline products. Design. Randomized, double-blind, crossover trial. Setting. A university-affiliated clinical research center. Patients. Fourteen adults with asthma. Interventions. The patients received a generic slow-release theophylline tablet or Theo-Dur at bedtime for 5 nights. Measurements and Main Results. Serum drug concentrations were measured after the last dose. Attenuation of exercise-induced bronchospasm (EIB) was included as a surrogate for efficacy. There was no significant difference in extent of absorption. The mean differences between the generic product and Theo-Dur in area under the curve was -13.9 μg/ml.hr -1 (95% CI-41 to 12.9, p=0.3) and in peak concentration (C max ), -0.5 μg/ml (95% CI -1.7 to 2.7, p=0.6). In contrast, the generic product was absorbed more rapidly; the mean differences in the time to peak concentration (T max ) was -3.0 hours (95% CI -4.3 to -1.7, p=0.0003), in trough concentration (C min ), -0.9 μg/ml (95% CI -1.9 to -0.01, p=0.05), and in fluctuation between C max and C min , +128% (95% CI 40 to 217, p=0.008). Neither product effectively attenuated EIB, since mean serum concentrations during the exercise challenges were unexpectedly below 10 μg/ml after both products. Conclusion. These two products are not bioequivalent, but the difference in absorption rates is unlikely to be clinically important in most patients (i.e., they are therapeutic equivalents)
Synthetic Biology: A Unifying View and Review Using Analog Circuits

We review the field of synthetic biology from an analog circuits and analog computation perspective, focusing on circuits that have been built in living cells. This perspective is well suited to pictorially, symbolically, and quantitatively representing the nonlinear, dynamic, and stochastic (noisy) ordinary and partial differential equations that rigorously describe the molecular circuits of synthetic biology. This perspective enables us to construct a canonical analog circuit schematic that helps unify and review the operation of many fundamental circuits that have been built in synthetic biology at the DNA, RNA, protein, and small-molecule levels over nearly two decades. We review 17 circuits in the literature as particular examples of feedforward and feedback analog circuits that arise from special topological cases of the canonical analog circuit schematic. Digital circuit operation of these circuits represents a special case of saturated analog circuit behavior and is automatically incorporated as well. Many issues that have prevented synthetic biology from scaling are naturally represented in analog circuit schematics. Furthermore, the deep similarity between the Boltzmann thermodynamic equations that describe noisy electronic current flow in subthreshold transistors and noisy molecular flux in biochemical reactions has helped map analog circuit motifs in electronics to analog circuit motifs in cells and vice versa via a ‘cytomorphic’ approach. Thus, a body of knowledge in analog electronic circuit design, analysis, simulation, and implementation may also be useful in the robust and efficient design of molecular circuits in synthetic biology, helping it to scale to more complex circuits in the future.
Computer systems that learn: classification and prediction methods from statistics, neural nets, machine learning, and expert systems

Preface 1 Overview of Learning Systems 1.1 What is a Learning System? 1.2 Motivation for Building Learning Systems 1.3 Types of Practical Empirical Learning Systems 1.3.1 Common Theme: The Classification Model 1.3.2 Let the Data Speak 1.4 What's New in Learning Methods 1.4.1 The Impact of New Technology 1.5 Outline of the Book 1.6 Bibliographical and Historical Remarks 2 How to Estimate the True Performance of a Learning System 2.1 The Importance of Unbiased Error Rate Estimation 2.2. What is an Error? 2.2.1 Costs and Risks 2.3 Apparent Error Rate Estimates 2.4 Too Good to Be True: Overspecialization 2.5 True Error Rate Estimation 2.5.1 The Idealized Model for Unlimited Samples 2.5.2 Train-and Test Error Rate Estimation 2.5.3 Resampling Techniques 2.5.4 Finding the Right Complexity Fit 2.6 Getting the Most Out of the Data 2.7 Classifier Complexity and Feature Dimensionality 2.7.1 Expected Patterns of Classifier Behavior 2.8 What Can Go Wrong? 2.8.1 Poor Features, Data Errors, and Mislabeled Classes 2.8.2 Unrepresentative Samples 2.9 How Close to the Truth? 2.10 Common Mistakes in Performance Analysis 2.11 Bibliographical and Historical Remarks 3 Statistical Pattern Recognition 3.1 Introduction and Overview 3.2 A Few Sample Applications 3.3 Bayesian Classifiers 3.3.1 Direct Application of the Bayes Rule 3.4 Linear Discriminants 3.4.1 The Normality Assumption and Discriminant Functions 3.4.2 Logistic Regression 3.5 Nearest Neighbor Methods 3.6 Feature Selection 3.7 Error Rate Analysis 3.8 Bibliographical and Historical Remarks 4 Neural Nets 4.1 Introduction and Overview 4.2 Perceptrons 4.2.1 Least Mean Square Learning Systems 4.2.2 How Good Is a Linear Separation Network? 4.3 Multilayer Neural Networks 4.3.1 Back-Propagation 4.3.2 The Practical Application of Back-Propagation 4.4 Error Rate and Complexity Fit Estimation 4.5 Improving on Standard Back-Propagation 4.6 Bibliographical and Historical Remarks 5 Machine Learning: Easily Understood Decision Rules 5.1 Introduction and Overview 5.2 Decision Trees 5.2.1 Finding the Perfect Tree 5.2.2 The Incredible Shrinking Tree 5.2.3 Limitations of Tree Induction Methods 5.3 Rule Induction 5.3.1 Predictive Value Maximization 5.4 Bibliographical and Historical Remarks 6 Which Technique is Best? 6.1 What's Important in Choosing a Classifier? 6.1.1 Prediction Accuracy 6.1.2 Speed of Learning and Classification 6.1.3 Explanation and Insight 6.2 So, How Do I Choose a Learning System? 6.3 Variations on the Standard Problem 6.3.1 Missing Data 6.3.2 Incremental Learning 6.4 Future Prospects for Improved Learning Methods 6.5 Bibliographical and Historical Remarks 7 Expert Systems 7.1 Introduction and Overview 7.1.1 Why Build Expert Systems? New vs. Old Knowledge 7.2 Estimating Error Rates for Expert Systems 7.3 Complexity of Knowledge Bases 7.3.1 How Many Rules Are Too Many? 7.4 Knowledge Base Example 7.5 Empirical Analysis of Knowledge Bases 7.6 Future: Combined Learning and Expert Systems 7.7 Bibliographical and Historical Remarks References Author Index Subject Index
Effects of Distress and Eustress on Changes in Fatigue from Waking to Working.

Background As a potential indicator of strain, fatigue is an important outcome in occupational health research. The current study examined the influence of positive (eustress) and negative (distress) work experiences on changes in fatigue from morning to at-work. It was expected that within-person changes in fatigue from waking to working would be moderated by employees' experiences of stress, pain, happiness, and meaningfulness at work. Methods Data on 1,195 full-time working adults were collected through the Bureau of Labor Statistics' 2010 American Time Use Study (ATUS) using a day reconstruction method to assess fatigue at two time points (morning and during work) and employees' eustress and distress experiences during work. Results Multilevel modeling showed that the indicators of distress, stress and pain, predicted higher morning fatigue and stronger increases in fatigue during the workday. The indicators of eustress, happiness and meaningfulness, predicted lower fatigue at both time points but not temporal changes. Conclusions These results contribute to understanding changes in employees' fatigue and suggest that the differential effects of distress and eustress experiences at work may be important to consider in fatigue management interventions.
Mechanisms and models of REM sleep control

The first sections of this paper survey the history and recent developments relevant to the major neurotransmitters and neuromodulators involved in REM sleep control. The last portion of this paper proposes a structural model of cellular interaction that produces the REM sleep cycle, and constitutes a further revision of the reciprocal interaction model This paper proposes seven criteria to define a causal role in REM sleep control for putative neuro-transmitters/modulators. The principal criteria are measurements during behavioral state changes of the extracellular concentrations of the putative substances, and electrophysiological recording of their neuronal source. A cautionary note is that, while pharmacological manipulations are suggestive, they alone do not provide definitive causal evidence. The extensive body of in vivo and in vitro evidence supporting cholinergic promotion of REM sleep via LDT/PPT neuronal activity is surveyed. An interesting question raised by some studies is whether cholinergic influences in rat are less puissant than in cat. At least some of the apparent lesser REM-inducing effect of carbachol in the rat may be due to incomplete control of circadian influences; almost all experiments have been run only in the daytime, inactive period, when REM sleep is more prominent, rather than in the REM-sparse nighttime inactive period. Monoaminergic inhibition of cholinergic neurons, once thought to be the most shaky proposal of the reciprocal interaction model, now enjoys considerable support from both in vivo and in vitro data. However, the observed time course of monoaminergic neurons, their "turning off" discharge activity as REM sleep is approached and entered would seem to be difficult to produce from feedback inhibition, as originally postulated by the reciprocal interaction model. New data suggest the possibility that GABAergic inhibition of Locus Coeruleus and Dorsal Raphe monoaminergic neurons may account for the "REM-off" neurons turning off. However, the source(s) of GABAergic influences suggested by anatomical studies has yet to be definitively identified by electrophysiological recordings of GABAergic neurons that show the requisite inverse time course of activity relative to monoaminergic neurons. New and still preliminary microdialysis data suggest that reticular formation neurons, the effector neurons for REM sleep phenomena, might be disinhibited during REM sleep by decreased GABAergic influence, perhaps stemming from REM-on cholinergic neuronal inhibition of reticular formation GABAergic neurons. Whether the postulated cholinergic inhibition of GABAergic neurons is present is testable with in vitro recordings and double labeling. Taking into account the observed data on neuro-modulators/transmitters, a structural model incorporating interaction of REM-on and REM-off neurons and GABAergic influences is proposed. Finally, with respect to orexin and REM sleep, it is hypothesized that orexinergic activity may be a principal factor controlling REM sleep's absence from the active period in strongly circadian animals such as rat and man.
Calculation of Leakage and Particle Loss in Filter Cassettes

Experimental evidence of aerosol bypass leakage around the filter in plastic filter cassettes prompted an investigation using computational fluid dynamics to explain particle penetration through the leak. Axi-symmetric models of a cassette with several leak dimensions were constructed. The models predicted that submicrometer particles penetrated the leak, but that larger particles impacted on the filter surface. Experimental data from another study clearly indicated that larger solid particles were being lost from the surface of the filter during sampling. When particle bounce was invoked as an explanation for this loss of sampled solid particles, the theoretical loss from the filter in cassettes with large leaks exhibited characteristics similar to the experimental data. For small leaks, the mass loss behavior appeared to be more complex.
The effects of heat sinks and environmental pressure on the transient thermal response of a resistance temperature detector (RTD)

Compactness and portability of MEMS sensors and actuators with dedicated power sources are governed not only by the size of the system components but also by the size and durability of the power source itself. This work is part of a project on the characterization and modeling of heat transfer of an on-chip assembly of RTDs (resistance temperature detectors), microthermocouples and thin films of different materials. In this paper, we investigate the effects of conductive and convective heat transfer on the response of an RTD. Especially, the effects of a range of pressures from atmospheric to near-vacuum conditions at different applied voltages on the electrical energy consumption of an on-chip RTD are investigated. The transient temperature - time response as well as the power consumption of the RTD under the aforementioned conditions are also reported. Conductive effects are far more important than any other heat transfer mechanism; these effects are quantified.