cssi/SciSciGPT-SciSciNet huggingface dataset:
Differences in amniotic fluid patterns and fetal biometric parameters in third trimester pregnancies with and without diabetes.

Objective. The amniotic fluid index (AFI) has been increasingly used in the assessment of fetal well-being. We conducted the study to evaluate and compare the amniotic fluid index in third trimester normal and diabetic human pregnancy and to assess the correlation between the AFI and the fetal biometric parameters. Methods. Real-time ultrasound was performed to evaluate the AFI (four-quadrant technique), and to measure the biparietal diameter, head circumference, abdominal circumference, and femur length in 225 normal and 120 diabetic pregnant women from 27 to 42 weeks of gestation. Each patient was studied only once. Results. AFI in normal pregnancies was less than that in diabetic pregnancies throughout the gestational ages studied (27‐42 weeks). In normal pregnancy, the mean AFI was 14.0 cm at 27 weeks and decreased to 11.4 cm at 42 weeks (r ¼0.25, p ¼0.0005), whereas in diabetic pregnancies, the values remained stable throughout the gestational ages studied. There exist significant differences in AFI, estimated fetal weight, estimated fetal weight %, abdominal circumference, abdominal circumference %, and head circumference to abdominal circumference ratio between the two groups. In both normal and diabetic pregnancies, there is a positive correlation between the AFI and the percentile of abdominal circumference (p50.0001), and between the AFI and the percentile of estimated fetal weight (p50.0001). Conclusion. This study provides gestational age-specific values of the AFI in normal and diabetic pregnancies. Diabetic pregnancy has greater AFI values than normal pregnancy between 27 and 42 weeks. The AFI correlates to the percentile of the estimated fetal weight and the abdominal circumference in both groups, suggesting that there may be a relationship between increased AFI and large for gestational age fetus independent of diabetes.
Diagnostic Value of Plaster Models in Contemporary Orthodontics

Advances in digital technology have allowed for photographic images that can be immediately evaluated in the clinical setting. Clinical photography can currently be relied on to be of predictable diagnostic value, and unsatisfactory images can be immediately replaced. The purpose of the present study was to evaluate how information obtained from traditional plaster models contributed to the diagnosis and treatment planning of orthodontic patients who were originally evaluated by using digital photographs and radiographs alone. A sample of 20 orthodontic patients from the Department of Orthodontics at the University of Alabama at Birmingham was selected for this study. The sample was selected on the basis of Angle molar classification, comprised of 11 Class I, 7 Class II, and 2 Class III patients, to attempt to provide an average range of malocclusions as reported in the literature.1 Four orthodontists, provided with digital photographs, a panoramic radiograph, and a traced lateral cephalometric radiograph for each patient, were asked to complete a diagnostic questionnaire and to formulate a preliminary treatment plan for each record set. The orthodontists were then shown plaster models for each patient and the questionnaire and treatment plan were allowed to be revised for a final treatment plan if the orthodontists considered this to be appropriate. Any changes that the orthodontists deemed necessary for the diagnosis and formulation of the final treatment plan were recorded. A binomial probability and a Chi square analysis were used with a P = 0.05 level of significance. The results indicated a total of 83 changes of the 1600 diagnostic values among 20 diagnostic categories recorded. The five categories that were statistically significant included the anteroposterior relationship of the molars, the anteroposterior relationship of the cuspids, the amount of overbite, the amount of overjet, and the depth of the curve of Spee in the mandible. There were no clinically significant changes in treatment recommended by the orthodontists from their preliminary to their final treatment plans following examination of the study casts. The results of this study indicate that plaster models may not be needed for the planning of treatment of every orthodontic patient.
Obtaining absorption spectra from single textile fibers using a liquid crystal tunable filter microspectrophotometer

Visible absorption spectra were recorded for single textile fibers using a microspectrophotometer based on a liquid crystal tunable filter. Spectra compared well with results from a conventional instrument. Some advantages include very fast and simple sample preparation and easy comparison of multiple fibers at the same time. Advantages over extraction-dependent methods include the fact that it is applicable to extremely small sample size, not susceptible to artifacts induced by variable extraction efficiencies, non-destructive, and much easier. Because an immense amount of information is collected in one experiment, good signal averaging is possible, along with multiple comparisons for each data set. The addition of a camera, computer, and liquid crystal tunable filter can transform a standard microscope into a microspectrophotometer capable of performing similar work.
Increased glucose uptake in visceral versus subcutaneous adipose tissue revealed by PET imaging.

Objectives The current study tested the hypothesis that glucose utilization differs between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and investigated potential mechanisms for such a finding. Background VAT burden correlates better with cardiovascular risk than does SAT burden. Beyond volumetric measurement, glucose uptake in adipose tissue (AT) might reflect metabolic activity and provide pathophysiologic insight and aid risk stratification. Methods We retrospectively studied tissue-specific glucose uptake in vivo in clinically obtained whole-body fluorodeoxyglucose positron emission tomography (FDG-PET) scans in humans. We also assessed glucose uptake in vitro, using stromal vascular cells isolated from SAT and VAT of diet-induced obese C57BL/6 mice. Quantitative polymerase chain reaction (PCR) evaluated the expression of multiple genes involved in cellular glucose metabolism, including glucose transporters (GLUT-1, -3, and -4) and hexokinases (HK-1 and -2) in SAT and VAT of obese C57BL/6 mice. Results We analyzed whole-body FDG-PET scans from 31 obese and 26 lean patients. VAT exhibited higher FDG uptake compared with SAT (p Conclusions In humans in vivo, VAT has increased glucose uptake compared with SAT, as determined noninvasively with FDG PET imaging. Differential stromal metabolic activity may be 1 mechanism underlying differences in metabolic activity of visceral and subcutaneous AT.
Adjustable Decisions for Reducing the Price of Robustness of Capacity Expansion Planning

This paper proposes and implements robust optimization methodologies for making investment decisions in the capacity expansion planning (CEP) of power systems in an uncertain environment. Uncertainties of fuel prices, demand, and transmission capacity are captured in an uncertainty set. With adjustable robust optimization (ARO), we represent all the decision variables as affine functions of multiple uncertain data. This adjustability of decisions provides that the ARO solution has significant less price of robustness than in traditional robust optimization (RO). ARO models uncertainty in terms of parameter ranges, called “uncertainty sets.” An attractive attribute of utilizing uncertainty sets is that they facilitate computational tractability when simulating scenarios with multiple uncertainties. We study the 40-year planning of a 5-region, 13-technology US energy portfolio. Results show that 1) by appropriately selecting the decision rules in ARO, the price of robustness can be significantly reduced while maintaining the same levels of robustness; and 2) the RO-based models maintain high levels of robustness even under operational conditions provided by data coming from larger sizes of the uncertainty sets.
Radius of curvature metrology for segmented mirrors

Future space and ground telescopes will have apertures that are increasingly larger in size. The primary mirrors for these telescopes will be so large that they cannot be fabricated, transported, and/or launched as a single entity. One solution is to build a large mirror out of smaller segments. The biggest challenge in fabricating segmented mirrors is matching the individual pieces so they form a single, continuous surface. This requirement means that the radii of curvature must all match. We present a technique for matching the relative radii of curvature for segmented mirrors, and we include an error analysis of this method.
A novel interactivity environment for integrated intelligent transportation and telematic systems

Advances in intelligent transportation are rapidly sensing and connecting both highways and vehicles. This recent availability of high-speed communication and large quantities of information are rapidly changing the way we perceive transportation. In order to develop technologies and applications that are practical in this intelligent environment, it is important to consider specific ways to best use this infrastructure effectively. This paper focuses on the development of and experiments with a visualization environment that presents an interactive, immersive, and context-preserving display of outdoor information. The developed visualization integrates a variety of types of information about a section of interstate such as aerial photographs, maps, and live outdoor videos into a single interactive environment. Additionally, a wireless mobile testbed is presented that allows the undertaking of novel interactivity experiments among mobile participants without requiring a fully instrumented vehicle. These systems allow effective experimentation with and integration between highway and vehicle based real-world intelligent transportation systems.
Signaling the differences between cilia

Calcium ion channels that determine many of the properties of cilia are different in motile cilia as compared to primary cilia and flagella.
Calcium-dependent membrane association of a flagellar calcium sensor does not require calcium binding.

Flagellar calcium-binding protein (FCaBP) is a dually acylated Ca2+ sensor in the Trypanosoma cruzi flagellar membrane that undergoes a massive conformational change upon Ca2+ binding. It is similar to neuronal Ca2+ sensors, like recoverin, which regulate their binding partners through a calcium acyl switch mechanism. FCaBP is washed out of permeabilized cells with buffers containing EDTA, indicating Ca2+-dependent flagellar membrane association. We hypothesized that, like recoverin, FCaBP projects its acyl groups in the presence of Ca2+, permitting flagellar membrane and binding partner association and that it sequesters the acyl groups in low Ca2+, disassociating from the membrane and releasing its binding partner to perform a presumed enzymatic function. The X-ray crystal structure of FCaBP suggests that the acyl groups are always exposed, so we set out to test our hypothesis directly. We generated T. cruzi transfectants expressing FCaBP or Ca2+-binding mutant FCaBPE151Q/E188Q and recombinant wildtype and mutant proteins as well. Both FCaBP and FCaBPE151Q/E188Q were found to associate with lipid rafts, indicating the Ca2+-independence of this association. To our initial surprise, FCaBPE151Q/E188Q, like wildtype FCaBP, exhibited Ca2+-dependent flagellar membrane association, even though this protein does not bind Ca2+ itself [16]. One possible explanation for this is that FCaBPE151Q/E188Q, like some other Ca2+ sensors, may form dimers and that dimerization of FCaBPE151Q/E188Q with endogenous wildtype FCaBP might explain its Ca2+-dependent localization. Indeed both proteins are able to form dimers in the presence and absence of Ca2+. These results suggest that FCaBP possesses two distinct Ca2+-dependent interactions—one involving a Ca2+-induced change in conformation and another perhaps involving binding partner association.
Polynomial estimators

Minimal mean square error polynomial estimators are developed for time discrete systems. The estimation problem is formulated in Hilbert space with the optimal as the projection on the linear manifold generated by finite polynomials of the observer. The estimate is partitioned into a predictor and corrector where the corrector is expressed as the product of a weighting vector and residual. Methods of determing the residuals and the weighting vectors are developed. An example applying the techniques is included.
Persistence of virus in urine as factor in spread of infectious hepatitis in dogs.

ConclusionsThe virus of infectious hepatitis of dogs has been recovered from the urine at intervals of time extending from 3 days after inoculation to at least 161 days afterwards. Inasmuch as bloo...
Autoregulation of Glucose Metabolism in the Isolated Perfused Rat Liver.

SummaryRat livers perfused with 20 mM sodium lactate and increasing glucose concentrations from 0 to 1000 mg/100 ml come to a point of equilibrium at which glucose production equals glucose utilization. This occurs with an initial glucose concentration of about 200 mg/100 ml in the normal fasted rat, 60 mg/100 ml for the adrenalectomized rat and 340 mg/100 ml for the alloxan diabetic rat. An increase in glucose utilization was observed in diabetic livers between 300-600 mg 100 ml. This is thought to be due to the action of pyrophosphate phosphotransferase. There was a plateau in glucose utilization in diabetic livers between 600-1000 mg/100 ml initial glucose concentration in the medium, and it is thought this represents an equilibrium between glucose and glucose-6-phosphate.
Clival chordoma molecular subtypes and clinical behavior

10538 Background: Chordoma is a primary bone cancer of the axial skeleton with predilection for local invasion. Primary treatment modalities consist of surgery and radiation therapy with limited role for chemotherapy. Because patients with chordoma exhibit heterogeneous clinical history and response to therapy, we investigated potential markers predictive of clinical behavior. Methods: This study analyzed 35 clival chordoma specimens with documented immunohistochemistry (IHC) staining for Ki-67 proliferation index from 29 patients. Detailed additional pathologic studies were performed prospectively on 12 consecutive patients. This consisted of the following: IHC for brachyury, cytokeratin, p53, and epidermal growth factor receptor (EGFR); fluorescent in situ hybridization (FISH) analysis for EGFR amplification and presence of 1p36, 9p21, and 19q13 loci; polymerase chain reaction based loss of heterozygosity analysis (LOH) of 1p, 9p, 10q, 17p, and 19p loci. Results: All confirmed chordoma specimens were po...
Impact of age on pulmonary artery systolic pressures at rest and with exercise

Aim It is not well known if advancing age influences normal rest or exercise pulmonary artery pressures. The purpose of the study was to evaluate the association of increasing age with measurements of pulmonary artery systolic pressure at rest and with exercise.
Patient Navigation and Supportive Cancer Care

In a sense, the essence of patient navigation is support. Concepts of psychological, emotional, social, and spiritual human needs and strategies used to satisfy needs and adapt to demands and changes have been described by Maslow [1]. The concept of need is equated to necessity, an essential condition, not simply a deficiency [2]. In the event of extreme life events, such as the diagnosis of cancer, tasks associated with meeting personal needs may require skills that exceed an individual’s capabilities, in which case help and support from another person is necessary to satisfy unmet needs [2]. Hebert and Fillion [2, 3] reason the concept of need is the basis of patient-centered care and suggest that navigators not only detect needs but also devise and implement strategies to satisfy those needs.
Osteoarticular Allograft Reconstruction of the Proximal Humerus Following Limb-Sparing Surgery

After limb-sparing resection of the proximal humerus there are several options for reconstruction. These include leaving a flail shoulder, an arthrodesis using intercalary graft(s) between the scapula and the remaining humerus, or, if the glenoid is preserved, an arthroplasty. An arthroplasty can be achieved using a custom-made proximal humeral prosthesis, an osteoarticular allograft, a combination of allograft and prosthesis, or an interpositional arthroplasty (most commonly utilizing an autogenous fibula).
Meniscal Considerations in Cartilage Surgery

Preservation of the meniscus has become the standard in sports medicine after evidence emerged that there was progressive chondrosis following total meniscectomy as performed over 40 years ago. In this chapter, we will address pertinent aspects of meniscal preservation; specifically addressing how meniscus repairs and partial resection are relevant to the cartilage surgeon. This will include the concept of the meniscus being a load distributor more than a shock absorber; the subset of meniscus pathology in the anterior cruciate ligament (ACL)-deficient knee joint will also be discussed. To allow a practical framework from which to direct patient care, general guidelines will be presented that will include the outcomes of meniscus repair in cartilage patients regarding tear configuration, age, and degeneration of the knee joint.
Energy-Optimal Circuit Design

Energy efficiency is an emerging metric for the quality of integrated circuit designs. Applications ranging from wireless sensor networks to RFID tags to embedded microprocessors require extremely low power consumption to maintain good battery life. We advocate the use of aggressively scaled supply voltages in such applications to maximize energy efficiency. This paper reviews our recent progress in mapping out the low energy design space including the presence of an energy-optimal supply voltage, and also touches on complications arising from variability at low supply voltages. We conclude with a survey of open research directions in the ultra-low voltage design space.
Exploring New Spaces for Dialogue and Regional Cooperation in the Americas to Protect Migrants’ Human Rights

Although the U.S. is still the largest migration receiving country in the Americas with the strongest pull factors, migration processes are more complex and diverse than the perceived unidirectional South-North flows. As the authors in Chapters 8–13 argue, it is imperative that all states in the Americas come together in a coordinated effort with organized civil society, and the existing regional institutions, to work toward the development of new spaces for dialogue and regional cooperation to protect migrants’ dignity as well as their fundamental human rights.
Constructing Mobius Transformations with Spheres

Every Mobius transformation can be constructed by stereographic projection of the complex plane onto a sphere, followed by a rigid motion of the sphere and projection back onto the plane, illustrated in the video Mobius Transformations Revealed. In this article we show that, for a given Mobius transformation and sphere, this representation is unique. Acknowledgements: I would like to sincerely thank Dr. Jonathan Rogness for his generous assistance and support in this project. Page 116 RHIT Undergrad. Math. J., Vol. 13, No. 2
EpxMedTracking: Feasibility Evaluation of an SMS-Based Medication Adherence Tracking System in Community Practice

Background: Medication adherence remains a difficult problem to both assess and improve in patients. It is a multifactorial problem that goes beyond the commonly cited reason of forgetfulness. To date, eHealth (also known as mHealth and telehealth) interventions to improve medication adherence have largely been successful in improving adherence. However, interventions to date have used time- and cost-intensive strategies or focused solely on medication reminding, leaving much room for improvement in using a modality as flexible as eHealth. Objective: Our objective was to develop and implement a fully automated short message service (SMS)-based medication adherence system, EpxMedTracking, that reminds patients to take their medications, explores reasons for missed doses, and alerts providers to help address problems of medication adherence in real time. Methods: EpxMedTracking is a fully automated bidirectional SMS-based messaging system with provider involvement that was developed and implemented through Epharmix, Inc. Researchers analyzed 11 weeks of de-identified data from patients cared for by multiple provider groups in routine community practice for feasibility and functionality. Patients included were those in the care of a provider purchasing the EpxMedTracking tool from Epharmix and were enrolled from a clinic by their providers. The primary outcomes assessed were the rate of engagement with the system, reasons for missing doses, and self-reported medication adherence. Results: Of the 25 patients studied over the 11 weeks, 3 never responded and subsequently opted out or were deleted by their provider. No other patients opted out or were deleted during the study period. Across the 11 weeks of the study period, the overall weekly engagement rate was 85.9%. There were 109 total reported missed doses including “I forgot” at 33 events (30.3%), “I felt better” at 29 events (26.6%), “out of meds” at 20 events (18.4%), “I felt sick” at 19 events (17.4%), and “other” at 3 events (2.8%). We also noted an increase in self-reported medication adherence in patients using the EpxMedTracking system. Conclusions: EpxMedTracking is an effective tool for tracking self-reported medication adherence over time. It uniquely identifies actionable reasons for missing doses for subsequent provider intervention in real time based on patient feedback. Patients enrolled on EpxMedTracking also self-report higher rates of medication adherence over time while on the system. [JMIR Res Protoc 2017;6(5):e87]
Vitamin D Levels are Associated with Liver Disease Severity in Patients with Cirrhosis

Vitamin D deficiency is common in advanced liver disease but its clinical significance remains controversial. The aim of this study was to examine the correlation of 25-hydryoxyvitamin D levels with liver disease severity and calcium levels in adults with cirrhosis. This cross-sectional study included 180 adults with cirrhosis enrolled in a clinical cohort study at a single university hospital. The mean age was 58.8 (±9.2) years, and cirrhosis was attributed to alcohol use in 27.2%, hepatitis C in 35.0%, non-alcoholic steatohepatitis in 27.2%, and both alcohol and hepatitis C in 10.6%. The median model for end-stage liver disease-sodium (MELD-Na) score was 12.0 (interquartile range 9.0–16.0), and mean serum albumin levels were 3.4 (±0.7) gm/dl. Median serum 25-hydroxyvitamin D levels were 28.0 (interquartile range 20–38) ng/mL, with 16 patients (8.9%) having levels <12 ng/ml and 43 (23.9%) with 25(OH)D levels <20 ng/ml. No correlation was noted between levels of 25-hydroxyvitamin D and albumin-corrected calcium in the total group and in groups stratified by vitamin D supplementation. In contrast, both serum albumin (r = 0.32; P < 0.001) and MELD-Na scores were significantly correlated with 25-hydroxyvitamin D levels (r = –0.29; P < 0.001). Correlations between 25-hydroxyvitamin D levels and serum albumin (r = −0.39; P < 0.001) and MELD-Na scores did not change substantially after excluding 67 patients receiving vitamin D supplementation (r = −0.33; P = 0.009). In conclusion, total 25-hydroxyvitamin D levels correlate inversely with liver disease severity in adults with cirrhosis.
Abstract 126: Gene Deletion of Dipeptidyl Peptidase I Reduces Myocyte Loss and Preserves Cardiac Function After Myocardial Ischemia-Reperfusion Injury

Introduction and Hypothesis: Chronic inflammation predisposes tissue to adverse cardiac remodeling and contributes to heart failure (HF) progression. The mechanisms whereby inflammation contributes to cardiac remodeling after cardiac injury has largely focused on action of reactive oxygen species and cytokines/chemokines and their role on myocyte growth and extracellular matrix (ECM) remodeling. However, the role of inflammatory proteases on myocyte loss and adverse cardiac remodeling has not been studied and are the focus of this study. Methods and Results: We subjected wild type and mice lacking Dipeptidyl peptidase I (DPPI), a lysosomal enzyme involved in the cleavage and activation of major inflammatory serine proteases, to myocardial ischemia for 30 min followed by reperfusion for 24hrs (IRI) and assessed the role of DPPI gene deletion on inflammatory proteases activation, myocyte apoptosis and cardiac remodeling and function. DPPI KO mice show markedly reduced inflammatory serine protease activity in response to myocardial IRI compared to wild type mice. DPPI deletion also markedly reduced myocyte apoptosis, limited infarct size and improved cardiac function in response to IRI. The role of inflammatory serine proteases in cardiac remodeling was further demonstrated after in-vivo cardiac transfer of cathepsin G, a neutrophil derived serine protease that has been shown to induce myocyte death in-vitro. Mice with cathepsin G injection for 5 days show increased interstitial collagen degradation and myocyte apoptosis and presented cardiac dilatation and contractile dysfunction. Conclusions: These findings reveal the role of DPPI as a key mediator of postischemic/reperfusion injury and show that inflammatory derived proteases contribute to the pathological cardiac remodeling and dysfunction.
High Endothelial Cell N-Acetylglucosamine 6-O-Sulfotransferase

High endothelial cell (HEC)-specific N-acetylglucosamine 6-sulfotransferase (HEC- GlcNAc6ST) (Bistrup et al. 1999), or L-selectin ligand sulfotransferase (LSST) (Hiraoka et al. 1999), is a transmembrane protein of 386 amino acids with a short, N-terminal cytoplasmic tail and a large luminal C-terminal catalytic domain. This enzyme belongs to a recently identified family of carbohydrate sulfotransferases that modify the 6-hydroxyl of Gal, GalNAc, or GlcNAc residues (GST family) (Rosen et al. 1999; Hemmerich and Rosen 2000). In addition to HEC-GlcNAc6ST, there are two other GlcNAc-6 sulfotransferases in this family: N-acetylglucosamine 6- sulfotransferase [GlcNAc6ST (Uchimura et al. 1998a, b) or CHST2 (Li and Tedder 1999)] and intestinal N-acetylglucosamine 6-sulfotransferase (I-GlcNAc6ST) (Lee et al. 1999). Within their sulfotransferase domains, these three enzymes are more than 27% identical at the amino acid level and more than 56% similar. HEC-GlcNAc6ST is expressed in a limited number of tissues and is highly enriched in HECs (Bistrup et al. 1999; Hiraoka et al. 1999). In contrast, GlcNAc6ST is expressed ubiquitously (Uchimura et al. 1998b), and I-GlcNAc6ST is expressed almost exclusively in intestinal tissues (Lee et al. 1999). A recently identified chondroitin 6-O-sulfotransferase, designated C6ST-2 (Kitagawa et al. 2000), exhibits GalNAc 6-sulfotransferase activity toward chondroitin (Kitagawa et al. 2000). The other members of this novel family, keratan sulfate 6-sulfotransferase [KSGal6ST (Fukuta et al. 1997); CHST1 (Li and Tedder 1999)] and chondroitin 6-sulfotransferase (C6ST) (Fukuta et al. 1998), have galactose 6-sulfotransferase activity; in addition, C6ST catalyzes sulfation at C-6 of GalNAc in chondroitin sulfate (Fukuta et al. 1997).
Chapter 10 - Psychiatric epidemiology†

Neuropsychiatric disorders represent a significant cause of morbidity, accounting for over 10% of disability worldwide, more than is attributable to cardiovascular disease or cancer. In developed-market economies, this figure rises to one-fourth of all disability. Besides their direct effects on morbidity, mental disorders are also independently associated with elevations in all-cause mortality and are negative predictors of recovery when associated with medical illnesses like cardiovascular disease and diabetes mellitus. Several large-based epidemiological studies conducted over the last few decades have described the incidence and prevalence of major psychiatric conditions. These include the Epidemiologic Catchment Area study, the National Comorbidity Survey, National Comorbidity Survey Replication, and the World Mental Health Survey. Overall, these studies found lifetime prevalences of mental disorders ranging from one-quarter to nearly one-half of the population studied. US-based surveys report 1-year prevalence rates of nearly 30%. Anxiety disorders are the most common type of psychiatric illness diagnosed, followed by mood disorders. While the majority of psychiatric disorders are mild or moderate, there is evidence that, when untreated, these conditions can develop into more serious illness, arguing the importance of early detection. Despite the high burden of psychiatric illness, most patients with a mental illness do not receive treatment. This article provides an overview of the incidence and prevalence of common psychiatric disorders and characteristics of the manifestation of these disorders within a population.
Deeper sequencing at unexpected CRISPR/Cas9 off-target sites in vivo : A response to Editas, Intellia, Beacon, ToolGen and others

Here we provide additional confirmatory data and clarifying discussion, including information about the relatedness of the control and CRISPR-treated mice, as well as sequencing data showing extensive regions with heterozygosity and in some cases more than 2 alleles in CRISPR-treated mice throughout the genome. The control FVB mouse and parents of the CRISPR-treated mice were purchased directly through the JAX genetic stability program and were within one generation of one another. Furthermore, the heterozygous mutations were mostly within 7-10bp adjacent to NGG or NGA nucleotide sequences, the preferred Protospacer Adjacent Motif (PAM) for the SpCas9. The multiple alleles in these cases cannot simply be explained by parental inheritance. The summary statements in our Correspondence reflect observations of a secondary outcome following successful achievement of the primary outcome using CRISPR to treat blindness in Pde6b/rd1 mice. As the scientific community considers the role of WGS in off-target analysis, future in vivo studies are needed where the design and primary outcome focuses on CRISPR off-targeting. We agree that a range of WGS controls are needed that include parents, different gRNAs, different versions of Cas9, and different in vivo protocols. We look forward to the publication of such studies. Combined, these results will be essential to fully understand off-targeting and can be used to create better algorithms for off-target prediction. Overall, we are optimistic that some form of CRISPR therapy will be successfully engineered to treat blindness.
Abrogating Mitochondrial Dynamics in Mouse Hearts Accelerates Mitochondrial Senescence

Mitochondrial fusion and fission are critical to heart health; genetically interrupting either is rapidly lethal. To understand whether it is loss of, or the imbalance between, fusion and fission that underlies observed cardiac phenotypes, we engineered mice in which Mfn-mediated fusion and Drp1-mediated fission could be concomitantly abolished. Compared to fusion-defective Mfn1/Mfn2 cardiac knockout or fission-defective Drp1 cardiac knockout mice, Mfn1/Mfn2/Drp1 cardiac triple-knockout mice survived longer and manifested a unique pathological form of cardiac hypertrophy. Over time, however, combined abrogation of fission and fusion provoked massive progressive mitochondrial accumulation that severely distorted cardiomyocyte sarcomeric architecture. Mitochondrial biogenesis was not responsible for mitochondrial superabundance, whereas mitophagy was suppressed despite impaired mitochondrial proteostasis. Similar but milder defects were observed in aged hearts. Thus, cardiomyopathies linked to dynamic imbalance between fission and fusion are temporarily mitigated by forced mitochondrial adynamism at the cost of compromising mitochondrial quantity control and accelerating mitochondrial senescence.
Mind mapping: Using everyday language to explore social & psychological processes

Abstract The ways we express ourselves in writing and speaking reveal who we are. Historically, most psychologists, social media experts, and even computer scientists have focused more on what people were saying rather than how they were saying what they were saying. Language content is, of course, critical to basic communication. Equally interesting is an analysis of common words associated with speaking style — words such as pronouns, prepositions, articles, and other function words. An increasing number of studies have found that function words (also thought of as stop words) provide clues to deception, status, intelligence, emotional state, the quality of social relationships, and personality. In addition to summarizing recent research on the social dynamics of language, the talk will point to the natural alliance of computer science and the field of social and personality psychology..
Failure of p53 to repress c-FLIP under hypoxic conditions contributes to TRAIL resistance of cancer cells

3634 Cellular FLICE-like inhibitory protein (c-FLIP) is a well established antiapoptotic regulator of the Fas and TRAIL death-receptor signaling pathways. Overexpression of c-FLIP promotes resistance of cancer cells to TRAIL therapy. Here we show that c-FLIP is repressed in TRAIL-sensitive cancer cells cultured under hypoxic conditions similar to what is found in the tumor microenvironment. Further we show that repression of c-FLIP under hypoxic conditions is p53-dependent. Cells in the absence of p53 show higher basal levels of c-FLIP and fail to repress c-FLIP when exposed to hypoxia. Previously we have reported that HCT116 colon carcinoma cells null for p53 become more resistant to the effects of TRAIL under hypoxic conditions (0.2% O 2 ) while HCT116 cells wild-type for p53 do not (Mayes et. al. Cancer. Biol. Ther. 4:1068-1074, 2005). Here we show that p53-dependent repression of FLIP does not occur in HCT116 p53-null cells under hypoxic conditions, and that this may contribute to the hypoxia-induced resistance of these cells. Further we show that H460 lung carcinoma cells which are wild-type for p53 are dramatically sensitized to the effects of TRAIL under hypoxic conditions and that p53-dependent repression of FLIP correlates with TRAIL sensitization. This study is the first to show p53-dependent transcriptional repression of c-FLIP. Further, these findings show the importance of p53-status as well as p53-dependent repression of c-FLIP in determining cancer cell TRAIL-sensitivity under hypoxic conditions. This study has implications in guiding the use of TRAIL in the in vivo setting. In tumors with wild-type p53, hypoxic tumor cell fractions resistant to many therapies may in fact be sensitive to TRAIL therapy. Further, loss of wild-type p53 and p53-dependent repression of FLIP may be a mechanism by which cancer cells escape immune surveillance during tumorigenesis. This study demonstrates the importance of accounting for physiologic factors within the tumor microenvironment, such as hypoxia, when developing new agents such as TRAIL for cancer therapy.
Disruptive Technology: Economic Consequences of Artificial Intelligence and the Robotics Revolution

We examine the possible economic impact of lost wages and tax revenues that artificial intelligence and machine learning could have in the U.S. within the next couple of decades. Using a probability-weighted methodology, provide decile-grouped estimates for the possible monetary implications of significant job losses due to this disruptive technological revolution. Furthermore, we examine the implied tax revenue losses associated with the displacement of the employees in these occupations. Our results suggest that within a few decades the economic impact may very well be in the hundreds of billions in lost wages and hundreds of millions in lost tax revenue.
Pediatric Helicobacter pylori gastropathy demonstrates a unique pattern of gastric foveolar hyperplasia.

OBJECTIVES Helicobacter pylori (Hp) are the most common agents causing gastric mucosal injury worldwide. Foveolar hyperplasia is a key component of the stomach's reaction to injury. This study examines histopathologic characteristics associated with Helicobacter pylori and with non- Helicobacter pylori-associated gastropathy in children and adolescents, and compares the prevalence of foveolar hyperplasia among these disease subgroups and normal control subjects. METHODS Eighty-one gastric antral and corpus biopsies from subjects 2-19 years of age were studied. Twenty-two subjects with Helicobacter pylori gastritis were compared to 23 with non-Helicobacter pylori gastropathy and to 36 controls (normal biopsies). Foveolar length, full mucosal thickness, and the foveolar length: full mucosal thickness ratio were derived by a morphometric technique previously developed to analyze adult gastric tissue. RESULTS Compared to controls, Helicobacter pylori gastritis demonstrated significant increases in antral foveolar length (P < .0001), full mucosal thickness (P < .0001), as well as corpus foveolar length (P < .05) and corpus full mucosal thickness (P < .05). Non-Helicobacter pylori-associated gastropathy also was characterized by increased antral foveolar length (P < .0001) and full mucosal thickness (P < .001) but corresponding corpus measurements did not differ from controls. Antral foveolar length in non-Helicobacter pylori gastropathy was increased, when compared to Helicobacter pylori gastritis (P < .05), while corpus values were not. The non-Helicobacter pylori gastropathy group demonstrated increased antral foveolar length: full mucosal thickness ratios, compared with Helicobacter pylori gastritis (P < .001) and with normal controls (P < .0001). DISCUSSION An objective, quantitative approach to measuring foveolar hyperplasia in adults was successfully applied to pediatric biopsies and yielded a richer characterization of gastric pathology in children. Foveolar hyperplasia appears to be a generalized phenomenon in the presence of pediatric Helicobacter pylori gastritis but is limited to the antrum in non-Helicobacter pylori gastropathy.
In reinforcement learning, all objective functions are not equal

We study the learnability of value functions. We get the reward back propagation out of the way by fitting directly a deep neural network on the analytically computed optimal value function, given a chosen objective function. We show that some objective functions are easier to train than others by several magnitude orders. We observe in particular the influence of the parameter and the decomposition of the task into subtasks.
Gate Level Combinational Design

This chapter presented design and implementation of an iterative combinational circuit. The procedure we used for designing this circuit and entering it in Quartus II is typical of any large iterative circuit, such as ALUs. Using Quartus II, we showed steps for design entry and device programming on the UP2 board. Features of Quartus II that were not discussed in the previous chapter were discussed here. In the chapters that follow, only those features of Quartus II that we are seeing for the first time will be discussed.
Hand Function in Parkinson’s Disease

Parkinson’s disease (PD) patients have a number of functional hand impairments. The latency and rate of isometric force generation is impaired in PD. Motor dysfunction is also related to impaired integration of sensory feedback and motor output. Moreover, PD patients exhibit sensory deficits such as decreased spatial and temporal tactile discrimination thresholds of the fingertips. Impairments of reaching and grasping are seen as patients tend to exhibit difficulty in movement initiation to a target. There are deficits in hand preshaping to object geometry. There is a lack of coordination between the timing of the reach and grasp components. Patients have an overall dependence on visual cues to control movement. They exhibit impairments in the planning of where to place their digits, resulting in suboptimal performance of object manipulation. It is hypothesized that predictive force control deficits are a result of central impairments associated with the generation and/or retrieval of sensorimotor memories for movement planning.
The treatment of nerve, muscle, and joint injuries in soldiers by physical means.

(1918). The Treatment of Nerve, Muscle and Joint Injuries in Soldiers by Physical Means. American Physical Education Review: Vol. 23, No. 6, pp. 355-366.
Perennial Polypores of North America. Fomes with Colored Spores

(1952). Perennial Polypores of North America. Fomes with Colored Spores. Mycologia: Vol. 44, No. 2, pp. 228-238.
Learning for clinical named entity recognition without manual annotations

Abstract Background Named entity recognition (NER) systems are commonly built using supervised methods that use machine learning to learn from corpora manually annotated with named entities. However, manually annotating corpora is very expensive and laborious. Materials and methods In this paper, a novel method is presented for training clinical NER systems that does not require any manual annotations. It only requires a raw text corpus and a resource like UMLS that can give a list of named entities along with their semantic types. Using these two resources, annotations are automatically obtained to train machine learning methods. The method was evaluated on the NER shared-task datasets of i2b2 2010 and SemEval 2014. Results On the SemEval 2014 dataset for recognizing diseases and disorders, the method obtained F-measure of 0.693 for exact matching and of 0.773 allowing overlaps. This is comparable to many supervised systems in the past that had used manual annotations for training. On the i2b2 2010 dataset for recognizing problems, tests and treatments, the method obtained F-measures of 0.451, 0.338 and 0.204 respectively for exact matching and of 0.721, 0.587 and 0.475 respectively allowing overlaps. These results are better than an existing unsupervised method. Conclusions Experiments on standard datasets showed that the new method performed well. The method is general and could be applied to recognize entities of other types on other genres of text without needing manual annotations.
Another Look at the Abrasion Resistance of Concrete

The abrasion resistance of concrete is considered one of its most important properties in applications such as pavements. Despite the existence of significant amount of research data, the correlation between the abrasion resistance and the compressive strength of concrete remains debatable. This is, in part, due to the limitations of the existing abrasion resistance test methods. We introduce a new abrasion resistance test method that addresses the limitations of the existing test methods; using this new test, we investigate the influence of water-to-cement ratio, coarse aggregate type, and coarse aggregate volume fraction on the abrasion resistance of concrete. We also investigate whether a correlation exists between compressive strength and abrasion resistance of concrete.
Trimethoprim/Sulfamethoxazole Synergy and Prostatis

TMP/SMX is often effective in the treatment of bacterial prostatitis, but, because of the concentration of TMP in the prostatic fluid of dogs is four times that in plasma and the concentration of SMX in this fluid is only one-tenty of that in plasma, the question arises as to whether SMX contributes to the efficacy.
Serum free testosterone and asthma, asthma hospitalisations and lung function in British adults.

Objective We examined the relation between serum-free testosterone and asthma, wheeze, asthma hospitalisations and lung function in older adults. Design Cross-sectional study. Setting UK. Participants 256 419 adults aged 40 to 69 years, recruited from 2006 to 2010. Main outcome measures Multivariable logistic or linear regression was used for the analysis of free testosterone and physician-diagnosed asthma, current wheeze, asthma hospitalisations and lung function measures, which was adjusted for serum estradiol, smoking status and other covariates. Results Free testosterone levels above the lowest quartile (Q1) were significantly associated with lower odds of asthma in both women (adjusted OR (aOR) for Q4 (the highest quartile) versus Q1=0.67, 95% CI=0.64 to 0.71) and men (aOR for Q4 versus Q1=0.87, 95% CI=0.82 to 0.91). Among subjects with asthma, free testosterone levels above Q1 were significantly associated with lower odds of current wheeze in women (aOR range=0.78 to 0.87), and free testosterone levels in Q4 were associated with lower odds of current wheeze in men (aOR for Q4 versus Q1=0.86, 95% CI=0.77 to 0.95). Among women with asthma, free testosterone levels in Q4 were also associated with lower odds of ≥1 asthma hospitalisation. Among men, free testosterone was positively associated with FEV1 and FVC. Among women, free testosterone was negatively and weakly associated with FVC. Conclusion In a large study of British adults, elevated free testosterone levels are associated with lower odds of asthma and current wheeze in women and men, lower odds of asthma hospitalisations in women, and higher FEV1 and FVC in men. Dissemination to participants, and related patient and public communities The results of the study will be linked to the UK Biobank website.
Waiving Good-Bye to a Fundamental Right: Allocation of Authority between Attorneys and Clients and the Right to a Public Trial

Only a few courts have addressed the question of whether an attorney can decide to waive a client’s constitutional right to a public trial without the client’s consent and most of them are based on the notion that attorneys have the authority to make tactical decisions. None of them, however, has offered a convincing explanation as to why a tactical decision that affects a constitutional right should be considered to be a mere tactical decision (which the attorney would have the authority to make without the client’s consent) as opposed to a decision that affects a fundamental right (which the attorney could not make without the client’s consent). This essay explains the issue and addresses the need to develop a consistent approach to the subject. It concludes that courts should find that decisions that affect constitutional rights belong to the client and that it would be improper for an attorney to make such decisions without consultation.
Resilience, pain, and the brain: Relationships differ by sociodemographics.

Chronic musculoskeletal (MSK) pain is disabling to individuals and burdensome to society. A relationship between telomere length and resilience was reported in individuals with consideration for chronic pain intensity. While chronic pain associates with brain changes, little is known regarding the neurobiological interface of resilience. In a group of individuals with chronic MSK pain, we examined the relationships between a previously investigated resilience index, clinical pain and functioning measures, and pain-related brain structures, with consideration for sex and ethnicity/race. A cross-sectional analysis of 166 non-Hispanic Black and non-Hispanic White adults, 45-85 years of age with pain ≥ 1 body site (s) over the past 3 months was completed. Measures of clinical pain and functioning, biobehavioral and psychosocial resilience, and structural MRI were completed. Our findings indicate higher levels of resilience associate with lower levels of clinical pain and functional limitations. Significant associations between resilience, ethnicity/race, and/or sex, and pain-related brain gray matter structure were demonstrated in the right amygdaloid complex, bilateral thalamus, and postcentral gyrus. Our findings provide compelling evidence that in order to decipher the neurobiological code of chronic pain and related protective factors, it will be important to improve how chronic pain is phenotyped; to include an equal representation of females in studies including analyses stratifying by sex, and to consider other sociodemographic factors.