cssi/SciSciGPT-SciSciNet huggingface dataset:
The Prostacyclin Analog Treprostinil Inhibits Ano1-Encoded Ca2+-Activated Cl− Channels and Mouse Pulmonary Arterial Tone Through Stimulation of cAMP-Dependent Signaling Pathway

Ca2+-activated Cl- channels (CaCCs) encoded by the gene Tmem16a or Anoctamin1 (ANO1) produce membrane depolarization and contraction of vascular smooth muscle cells (VSMCs) when stimulated by endogenous vasoconstrictors acting on Gq-protein coupled receptors. Treprostinil (TPL) is one of several prostacyclin analogs clinically used to treat patients diagnosed with pulmonary arterial hypertension (PAH). TPL reduces pulmonary arterial tone in PAH patients by binding to the IP prostanoid receptor. Activation of this Gs-coupled receptor leads to elevation in cAMP levels causing vasorelaxation by reducing intracellular [Ca2+]i. In this study, we examined whether TPL could exert vasorelaxation of mouse pulmonary arteries (mPA) by inhibiting, at least in part, ANO1-encoded CaCCs. TPL dose-dependently inhibited the contraction of mPA elicited by 10 μM 5-HT (IC50 ≈ 500 nM). The specific ANO1 inhibitor T16Ainh-A01 also dose-dependently inhibited the 5-HT-induced contraction of mPA but had no effect on the KCl-induced contraction (85.4 mM) at concentrations ≤ 10 μM. 200 nM TPL produced a rightward shift of the dose-response curve to T16AInh-A01, suggesting that TPL may inhibit CaCCs. Consistent with this hypothesis, Ca2+-activated Cl- currents (elicited by 1 μM free Ca2+ in the pipette solution) recorded in HEK-293 cells transfected with mouse ANO1 were significantly reduced by TPL (1 μM), or the adenylate cyclase activator Forskolin (10 μM). These preliminary results suggest that elevation of cAMP levels (perhaps through a phosphorylation step involving Protein Kinase A) may down-regulate ANO1-encoded CaCCs and attenuate the depolarization and vasoconstriction triggered by 5-HT. Our findings also suggest that part of the beneficial effects of TPL in PAH patients might be attributable to an interaction with ANO1 channels.
Quantifying atmospheric methane emissions from oil and natural gas production in the Bakken shale region of North Dakota

We present in situ airborne measurements of methane (CH4) and ethane (C2H6) taken aboard a NOAA DHC-6 Twin Otter research aircraft in May 2014 over the Williston Basin in northwestern North Dakota, a region of rapidly growing oil and natural gas production. The Williston Basin is best known for the Bakken shale formation, from which a significant increase in oil and gas extraction has occurred since 2009. We derive a CH4 emission rate from this region using airborne data by calculating the CH4 enhancement flux through the planetary boundary layer downwind of the region. We calculate CH4 emissions of (36 ± 13), (27 ± 13), (27 ± 12), (27 ± 12), and (25 ± 10) × 103 kg/h from five transects on 3 days in May 2014 downwind of the Bakken shale region of North Dakota. The average emission, (28 ± 5) × 103 kg/h, extrapolates to 0.25 ± 0.05 Tg/yr, which is significantly lower than a previous estimate of CH4 emissions from northwestern North Dakota and southeastern Saskatchewan using satellite remote sensing data. We attribute the majority of CH4 emissions in the region to oil and gas operations in the Bakken based on the similarity between atmospheric C2H6 to CH4 enhancement ratios and the composition of raw natural gas withdrawn from the region.
Surgical therapy for Crohn's disease.

SUMMARY Most patients with Crohn’s disease will require at least one operation for that condition, either an operation to correct a complication of Crohn’s disease (abscess, fistula, or bleeding) or for intractability (the failure of medical management to provide relief of disabling symptoms). Proper timing of surgery and careful preoperative preparation of the patient with special attention to control sepsis and to improving nutritional status will make the operation safer. Because of the tendency for Crohn’s disease to progress despite medical or surgical therapy recurrences after operation are common and the surgical procedure should be limited to correcting the complication at hand. For Crohn’s disease of the small bowel or of the terminal ileum and right colon, a conservative intestinal resection and anastomosis is usually the procedure of choice; nonresective procedures such as bypass and strictureplasty are useful in special situations. More than half of the patients so treated will eventually develop recurrence that may require one or more subsequent operations. The adverse effects of resection will be minimized by conservative surgery and by careful long-term management of the altered intestinal physiology. Some patients with Crohn’s colitis have limited colonic disease where continence can be preserved by resection and anastomosis, although the recurrence rate is high. Total proctocolectomy for Crohn’s colitis provides much better assurance of long-term freedom from recurrence but at the cost to the patient of a permanent ileostomy. Surgery for Crohn’s disease is not curative but offers effective palliation for the complications of this progressive and poorly understood condition.
Muscle blood flow in trained rats with peripheral arterial insufficiency.

The influence of exercise training on the recovery of muscle blood flow was assessed in rats with bilateral stenosis of the femoral artery, sufficient to limit exercise hyperemia in the distal hindlimb but not alter resting blood flow. Muscle blood flow was measured with 141Ce-labeled microspheres (15 microns) during treadmill running at 20 m/min in normal (n = 10), acute stenosed (n = 9), sedentary stenosed (n = 10) and trained stenosed (n = 13) animals. Treadmill training by a progressively intense program (up to 1 h/day, 7 days/wk for 6 wk) improved exercise tolerance evident both in duration and intensity of exercise. Total hindlimb blood flow (ml.min-1.100 g-1) was not different (P greater than 0.05) between all stenosed groups but was only 46-63% that of the normal group (P less than 0.05). Acute stenosis reduced distal blood flow to only 22% of that in the proximal hindlimb tissue. A significant (P less than 0.05) but limited recovery of distal limb blood flow (to 44% of proximal) occurred in sedentary stenosed rats after 6 wk of cage activity. Training further increased (P less than 0.05) distal limb blood flow to 69% of proximal. This partial recovery of distal limb blood flow could reflect a greater collateral vessel function or an enhanced vascularity of the distal limb tissue. Our results illustrate that peripheral adaptations occur within the ischemic hindlimb of trained animals to redistribute the limited O2 delivery to the active muscles most affected by stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Tests of Significance I

The last two topics have introduced you to statistical inference, where the goal is to make a statement about a population parameter based on a sample statistic. The confidence intervals that you have studied allow you to estimate a population parameter at a certain confidence level with an interval of values.
TLR2 Plays a Key Role in Platelet Hyperreactivity and Accelerated Thrombosis Associated With Hyperlipidemia.

Rationale: Platelet hyperreactivity, which is common in many pathological conditions, is associated with increased atherothrombotic risk. The mechanisms leading to platelet hyperreactivity are complex and not yet fully understood. Objective: Platelet hyperreactivity and accelerated thrombosis, specifically in dyslipidemia, have been mechanistically linked to the accumulation in the circulation of a specific group of oxidized phospholipids (oxPC CD36 ) that are ligands for the platelet pattern recognition receptor CD36. In the current article, we tested whether the platelet innate immune system contributes to responses to oxPC CD36 and accelerated thrombosis observed in hyperlipidemia. Methods and Results: Using in vitro approaches, as well as platelets from mice with genetic deletion of MyD88 (myeloid differentiation factor 88) or TLRs (Toll-like receptors), we demonstrate that TLR2 and TLR6 are required for the activation of human and murine platelets by oxPC CD36 . oxPC CD36 induce formation of CD36/TLR2/TLR6 complex in platelets and activate downstream signaling via TIRAP (Toll-interleukin 1 receptor domain containing adaptor protein)-MyD88-IRAK (interleukin-1 receptor–associated kinase)1/4-TRAF6 (TNF receptor–associated factor 6), leading to integrin activation via the SFK (Src family kinase)-Syk (spleen tyrosine kinase)-PLCγ2 (phospholipase Cγ2) pathway. Intravital thrombosis studies using ApoE −/− mice with genetic deficiency of TLR2 or TLR6 have demonstrated that oxPC CD36 contribute to accelerated thrombosis specifically in the setting of hyperlipidemia. Conclusions: Our studies reveal that TLR2 plays a key role in platelet hyperreactivity and the prothrombotic state in the setting of hyperlipidemia by sensing a wide range of endogenous lipid peroxidation ligands and activating innate immune signaling cascade in platelets.
"The impact of personal and company purpose on engagement, life satisfaction and commitment"

Companies are seeking to focus, energize, and retain good employees by achieving both engagement and commitment. Yet, according to Gallup, less than 33% of the US workforce felt engaged with their ...
Digital Phenotyping In Bipolar Disorder

Background Diagnostic categories of psychiatric illnesses based on subjective clinical assessments have been the standard for phenotyping in genetics studies. This is a significant problem for disorders such as bipolar, wherein the course of the illness is an important element of the phenotype. Digit phenotypes, assessed using mobile devices, offer an objective method of gathering data to describe phenotypes for translational research. It has been established that speech patterns are altered in mood disorders. The challenge is to monitor moods over extended periods of time using speech or other mobile-based methods and technology on personal devices. Technology is likely to be incorporated into the ongoing assessment and monitoring of individuals if it is passive and integrated into daily routines; mobile smartphones are ideal. Methods Individuals with rapid cycling bipolar disorder (51) and healthy controls (9) were ascertained from a prospective longitudinal study of bipolar disorder. They were provided with a smartphone pre-loaded with “PRIORI”, an app that securely recorded and encrypted all outgoing speech from all telephone calls sent and received. Two android-based phones were used, the Samsung Galaxy S3 and S5. Weekly assessment calls with a clinician included a depression and mania rating scale (HamD) and (YMRS). The encrypted calls were transferred to a central secure server for processing. Pre-processing included a de-clipping algorithm as it was found that the S3 was “clipping” the audio. The audio was segmented and features of rhythm were extracted and support vector machines were used to classify the speech. This presentation focuses on a subset of 217 acoustic features and solely on assessment calls with the clinician. Results Initial analyses included 37 individuals with two or more episodes wherein HamD > 10 and YMRS 10 and HamD Discussion Digital phenotypes derived from speech captured from mobile devices predict mood states. There are many challenges in addressing the comparability of data collected from across devices with different acoustic sensitivity. We demonstrate that through preprocessing, feature extraction, and data modeling techniques it is possible to mitigate the effects of differing amounts of clipping, loudness, and noise. The goal for a digital phenotyping system is to be passive, requiring no active input from the patient or the clinic. This will greatly improve phenotyping in genetic research over the current methods using structured clinical assessments using standard categorical criteria; digital phenotyping is likely to be able to classify and refine human disease by analyzing physiological patterns (such as speech) over time. However, several confounding factors need to be addressed and the refinement of techniques developed in this study increases device comparability in determining the digital phenotypes.
Sociocultural Dynamics of the Prairie Potawatomi Drum Cult

The Drum Cult, a revitalization movement founded by the Santee Dakota prophetess Wananikwe in 1872, was diffused to the Prairie Potawatomi in Kansas in the early 1880s. This paper discusses contemp...
An Infant Born to a Mother With Anti–N-Methyl-d-Aspartate Receptor Encephalitis

Abstract Background Anti–N-Methyl-D-Aspartate receptor (NMDAR) encephalitis is an autoimmune disorder that often affects women of childbearing age, and maternal-fetal transfer of anti-NMDAR antibodies during pregnancy has been documented in both symptomatic and asymptomatic women. The effects of these antibodies on the fetus, however, are incompletely understood. Patient Description This term infant exhibited depressed respiratory effort, poor feeding, and abnormal movements after birth. Magnetic resonance imaging revealed diffuse cerebral edema with ischemic and hemorrhagic injury. Her mother had experienced anti-NMDAR encephalitis secondary to an ovarian teratoma 18 months earlier. The baby's serum NMDAR antibody titer was elevated at 1:320. Intravenous immunoglobulin did not result in clinical improvement, and care was withdrawn on day of life 20. Her mother had an elevated serum NMDAR antibodies (1:80), positive CSF antibody titers, and a new ovarian teratoma. Conclusion Routine testing of NMDAR antibodies in pregnant women with a previous history of anti-NMDAR encephalitis may be warranted. Infants born to these mothers should be closely monitored throughout pregnancy and after birth.
Your Exclusion, My Inclusion: Reflections on a Career Working With the Most Challenging and Vulnerable in Diabetes.

EDITOR’S NOTE: This article is adapted from the address Dr. Harris delivered as the recipient of the American Diabetes Association’s Richard R. Rubin Award for 2017. This award recognizes a behavioral researcher who has made outstanding, innovative contributions to the study and understanding of the behavioral aspects of diabetes in diverse populations. Dr. Harris delivered the address in June 2017 at the Association’s 77th Scientific Sessions in San Diego, Calif.
A pilot study of direct delivery of hydroxypropyl-beta-cyclodextrin to the lung by the nasal route in a mouse model of Niemann-Pick C1 disease: motor performance is unaltered and lung disease is worsened

We have tested the efficacy of hydroxypropyl-beta-cyclodextrin (HPBCD) delivered by the nasal route in the mouse model of juvenile Niemann-Pick C1 disease (NPC1), as pulmonary disease has not responded to systemic therapy with this drug. Since mice have no gag reflex, coating of the nasal cavity, with possible access to the brain, would be followed by delivery of HPBCD to the lung. While foamy macrophages, containing stored cholesterol, were found in the Npc1 nmf164 homozygous mice, a marked inflammatory response was found with inhaled HPBCD, both in mutant and wild-type animals. Slight inflammation also occasionally occurred with saline inhalation. There was no difference between the saline-treated, HPBCD-treated, and untreated Npc1 nmf164 homozygous mice for weight, balance beam performance, or coat hanger performance. Interestingly, there was a trend to longer survival in the HPBCD-treated Npc1 nmf164 homozygous mice, which, when combined with the survival times of the saline-treated survivals (each of which was not different), became significant.
A signal-independent background-calibrating 20b 1MS/S SAR ADC with 0.3ppm INL

The SAR ADC is the architecture of choice for high-precision Nyquist ADCs (>16b) with MS/s speed. To achieve the required linearity performance, precision SAR ADCs require calibration to correct mismatch errors in the capacitive digital-to-analog converter (CDAC). One-time factory calibration suffers from aging, temperature sensitivity, and package and PCB stress while foreground calibration precludes continuous ADC operation. This paper presents a 20b 1MS/s SAR ADC with signal-independent background-calibration to address this challenge.
Exploiting superword-level locality in multimedia extension architectures

In this paper, we describe an algorithm and implementation of locality optimizations for architectures with instruction sets such as Intel’s SSE and Motorola’s AltiVec that support operations on superwords, i.e., aggregate objects consisting of several machine words. We treat the large superword register file as a compiler-controlled cache, thus avoiding unnecessary memory accesses by exploiting reuse in superword registers. This research is distinguished from previous work on exploiting reuse in scalar registers because it considers not only temporal but also spatial reuse. As compared to optimizations to exploit reuse in cache, the compiler must also manage replacement, and thus, explicitly name registers in the generated code. We describe an implementation of our approach integrated with a compiler that exploits superword-level parallelism (SLP). We present a set of results derived automatically on 4 multimedia kernels and 2 scientific benchmarks. Our results show speedups ranging from 1.3 to 3.1X on the 6 programs as compared to using SLP alone, and we eliminate the majority of memory accesses.
Abstract 5009: Defined factors overcome T-cell exhaustion via abscopal effect

Irreversible exhaustion of tumor-associated T cells is an important factor limiting the efficacy of PD-1 blockade in a number of cancers. Recent data suggest that PD-1 blockade functions largely by augmenting T cell costimulation. Given that activated APCs provide necessary T-cell costimulation, we hypothesized that enforced activation of intratumoral APCs would prime tumor-specific T cells and synergize with PD-1 blockade to overcome T-cell exhaustion. After screening various agents in syngeneic murine models, we found that dual CD40/TLR4 activation within a single tumor triggers a systemic tumor-specific CD8 T-cell response that is dependent on BATF3+ dendritic cells. Remarkably, this approach abolishes exhausted PD-1+ intratumoral T cells in treated as well as distant tumors while sparing more proximal T cells outside the tumors. In addition to treating large established tumors, this approach also confers persistent immunity allowing animals to reject reimplanted tumors 90 days after treatment. Dual CD40/TLR4 activation within a single tumor is thus a promising method for overcoming tumor-associated T-cell exhaustion in a manner that may provide durable systemic control of metastatic human cancers while sparing healthy tissues. Citation Format: Danny Khalil, Luis Felipe Campesato, Sadna Budhu, Yanyun Li, Caitlin Jones, Nathan Suek, Cailian Liu, Billel Gasmi, Rachel Giese, Stephane Pourpe, Taha Merghoub, Jedd D. Wolchok. Defined factors overcome T-cell exhaustion via abscopal effect [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5009.
The histological diagnosis of IgG4-related disease on small biopsies: challenges and pitfalls.

Aims The pathological diagnosis of IgG4-related disease (IgG4-RD) relies on histology, IgG4-positive cells, and an increased IgG4/IgG ratio. Small biopsies from patients with a presumptive diagnosis of IgG4-RD often fail to meet consensus histological criteria. The aims of this study were to evaluate consecutive small biopsies from patients with a presumptive diagnosis of IgG4-RD, and to assess the significance of the pathological findings. Methods and results We evaluated 55 small biopsies from patients with a presumptive diagnosis of IgG4-RD. The retrospective cohort comprised 71 patients with IgG4-RD and 57 mimics. We performed immunohistochemistry (IHC) and in-situ hybridisation (ISH) for IgG4 and IgG. Twenty-six patients from the prospective cohort met the histological criteria for IgG4-RD (definite); 29 patients lacked one or more pathological features (borderline). Twenty biopsies (36%) lacked both storiform fibrosis and obliterative phlebitis, and nine (16%) lacked an increase in the number of IgG4-positive plasma cells. Ninety-three per cent of patients showed an IgG4/total IgG ratio of >40% (>30% by ISH). There were no differences in the incidence of multiorgan disease (P = 0.9), serum IgG4 levels (P = 0.6) and response to therapy between the definite and borderline groups. A strong correlation (Pearson 0.77) between the IHC and ISH platforms was noted with regard to the IgG4/total IgG ratio. Conclusion Patients with a presumptive diagnosis of IgG4-RD but lacking the characteristic pathological features of this disease appear to be clinically similar to those who meet the current pathological criteria. An elevated IgG4/total IgG ratio is the most sensitive pathological feature, and ISH provides a robust quantification platform. We recommend evaluating tumefactive lymphoplasmacytic infiltrates with an increased IgG4/IgG ratio, regardless of histological features, for IgG4-RD.
Debating Gun Control in Canada and the United States: Divergent Policy Frames and Political Cultures:

The weakness of the antigun lobby in the United States is attributed to the “collective action problem” of trying to mobilize “free riders” behind a public purpose. But the Coalition for Gun Contro...
Absorption of strontium by foods prepared in drinking water

Abstract Strontium (Sr) is a natural element, ubiquitous in the environment and known to occur in water, food, air, and soils. Strontium is present in media as a salt or an ionized divalent cation. The Sr ion (dissociated) is toxicokinetically important because it is easily absorbed into systemic circulation when inhaled with particulates or ingested with water or foods. Dietary exposure can be influenced by using tap water containing dissolved Sr in food preparation. Research was conducted to determine the amount of Sr transferred from water to individual foods during preparation. Strontium transferred to broccoli, lentils, and spaghetti at all levels tested (1.5, 10, and 50 mg/L) as evidenced by the residual Sr in the pour-off water following food preparation (33–64%). The data from the cooking study support the hypothesis that cooking of foods with water containing Sr adds to total dietary exposure. This information can inform the determination of the relative source contribution (RSC) that is typically used in developing drinking water advisory guidelines. These cooking study results indicate that food prepared in water containing Sr should be considered as part of the food in a dietary exposure assessment.
Relationships between stress, demographics and dietary intake behaviours among low-income pregnant women with overweight or obesity.

Objective To identify demographic risk factors associated with high stress and examine the relationships between levels of stress, demographics and dietary fat, fruit and vegetable intakes in low-income pregnant women with overweight or obesity. Design A cross-sectional study. Setting Participants were recruited from the Special Supplemental Nutrition Program for Women, Infants, and Children in Michigan, USA.ParticipantsParticipants (n 353) were non-Hispanic Black (black) or White (white). Results Women aged 35 years or older (OR=4·09; 95% CI 1·45, 11·51) and who had high school or less education (OR=1·88; 95% CI 1·22, 2·89) or were unemployed (OR=1·89; 95% CI 1·15, 3·12) were significantly more likely to report high stress than women who were younger, had at least some college education or were employed/homemakers. However, race and smoking status were not associated with level of stress. Women with high stress reported significantly lower fruit and vegetable intakes but not fat intake than women with low stress. Women aged 35 years or older reported significantly higher vegetable but not fat or fruit intake than women who were 18-24 years old. Black women reported significantly higher fat but not fruit or vegetable intake than white women. Education, employment and smoking status were not significantly associated with dietary intake of fat, fruits and vegetables. Conclusions Nutrition counselling on reducing fat and increasing fruit and vegetable intakes may consider targeting women who are black or younger or who report high stress, respectively.
A Novel Culinary Medicine Course for Undergraduate Medical Education.

Traditional nutrition education in medical school has been inadequate to prepare future physicians to counsel patients on practical dietary changes that can prevent and treat food-related disease. ...
Altering critical depinning current via domain wall pile-up in magnetic nanowires

Abstract An important role of domain wall pile-up in current-driven domain wall depinning in magnetic nanowires is revealed using micromagnetic simulations. It is found that the critical current for domain wall depinning can be substantially reduced and conveniently tuned by controlling domain wall number in the pile-up at pinning site, in analogy to dislocation pile-up responsible for Hall–Petch effect in mechanical strength. Domain wall pinning and depinning at an s-shape bend is considered, and the effects of curvature and current crowding in magnetic circuit on domain wall behaviors are discussed.
Opening the time window

AbstractThe recently completed EXTEND trial tested the idea that tissue plasminogen activator thrombolysis can be safely extended up to 9 h after stroke onset if automated perfusion imaging indicat...
Power consumption estimation for mask image projection stereolithography additive manufacturing using machine learning based approach

Abstract Additive manufacturing (AM) or 3D printing has been implemented in a wide range of areas, owing to its superior capabilities of fabricating complex geometries with high design freedom compared to traditional manufacturing. In recent years, the potential environmental impacts that can be caused by AM processes and materials have attracted increasing attentions. Research efforts have been conducted to study and attempt to enhance the environmental performance of AM. In current literature on AM energy consumption, most studies focus on the production stage and investigate the relation between energy consumption and process parameters (i.e., layer thickness). In this work, multiple geometry characteristics (e.g., surface areas and shapes) at each printing layer are studied and linked with the power consumption of mask image projection stereolithography using machine learning based approach. The established models will be able to provide AM designers with a useful tool for estimating power consumption based on layer-wise geometry information in the design stage and promote the awareness of cleaner production in AM. In this work, effective features are selected and/or extracted from layer-wise geometry characteristics and used to train and test machine learning models. According to our results, the shallow neural network has the lowest averaged root-mean-square error (RMSE) of 0.75% considering both training and testing, and the stacked autoencoders (SAE) structure has the best testing performance with RMSE of 0.85%.
Spectral-density estimation with the Gaussian integral transform

The spectral-density operator $\stackrel{\ifmmode \hat{}\else \^{}\fi{}}{\ensuremath{\rho}}(\ensuremath{\omega})=\ensuremath{\delta}(\ensuremath{\omega}\ensuremath{-}\stackrel{\ifmmode \hat{}\else \^{}\fi{}}{H})$ plays a central role in linear response theory as its expectation value, the dynamical response function, can be used to compute scattering cross sections. In this work, we describe a near optimal quantum algorithm providing an approximation to the spectral density with energy resolution $\mathrm{\ensuremath{\Delta}}$ and error $\ensuremath{\epsilon}$ using $O\left(\sqrt{{log}_{2}\left(1/\ensuremath{\epsilon}\right)\left[{log}_{2}\left(1/\mathrm{\ensuremath{\Delta}}\right)+{log}_{2}\left(1/\ensuremath{\epsilon}\right)\right]}/\mathrm{\ensuremath{\Delta}}\right)$ operations. This is achieved without using expensive approximations to the time-evolution operator, but instead exploiting qubitization to implement an approximate Gaussian integral transform of the spectral density. We also describe appropriate error metrics to assess the quality of the spectral function approximations more generally.
Experimental evaluation of ultrasonic velocities and anisotropy in the Tuscaloosa Marine Shale Formation

AbstractThe Tuscaloosa Marine Shale (TMS) Formation is a clay- and organic-rich emerging shale play with a considerable amount of hydrocarbon resources. Despite its substantial potential, there hav...
The Impact of an Intraoperative Clinical Decision Support Tool to Optimize Perioperative Glycemic Management

With the transition from Vanderbilt’s Perioperative Information Management System (VPIMS) to Epic’s Best Practice Advisory (BPA) framework, a replacement intraoperative glucose clinical decision support (CDS) system was designed. We examined changes in the frequency of intraoperative glucose monitoring, hyper- and hypoglycemia rates in the post-anesthesia care unit (PACU), to determine the impact of the changes on glucose management. Data were collected into three phases: 1) VPIMS CDS, 2) No CDS, and 3) BPA CDS. One-way ANOVA was conducted to test the significance of changes in the frequency of glucose monitoring and abnormal glucose across phases. Interrupted time series segmented analysis was performed to assess the autocorrelation and trend over times. A total of 3706 cases were analyzed. The monitoring rate fell from 84.5% in VPIMS CDS to 67.6% in No CDS (p < .001) and increased to 83.1% in BPA CDS (p < .001). The PACU hyperglycemia rate increased from VPIMS CDS to No CDS (5.2% to 10.4%, p < .001) and decreased from No CDS to BPA CDS (10.4% to 7.2%, p = 0.031). The segmented analysis demonstrated immediate changes in the intraoperative monitoring frequency (p < .001) and postoperative hyperglycemia rate (p = 0.002) with the replacement of CDS. The temporary removal of CDS was associated with a significant reduction in intraoperative glucose monitoring and increased hyperglycemia in the PACU. Implementation of the BPA CDS led to a significant improvement in the intraoperative glucose monitoring and glucose management in the PACU.
Nearest Neighbor Search for Hyperbolic Embeddings

Embedding into hyperbolic space is emerging as an effective representation technique for datasets that exhibit hierarchical structure. This development motivates the need for algorithms that are able to effectively extract knowledge and insights from datapoints embedded in negatively curved spaces. We focus on the problem of nearest neighbor search, a fundamental problem in data analysis. We present efficient algorithmic solutions that build upon established methods for nearest neighbor search in Euclidean space, allowing for easy adoption and integration with existing systems. We prove theoretical guarantees for our techniques and our experiments demonstrate the effectiveness of our approach on real datasets over competing algorithms.
Leveraging the Electronic Medical Record to Increase Distribution of Low Literacy Asthma Education in the Emergency Department.

Abstract Objective Though low literacy asthma education is effective at reducing emergency department (ED) use, few interventions are administered in the ED. The aim was to increase the number of parents of children with asthma receiving education in the ED to 50% receiving written and 30% receiving video education over 12 months. Methods Using quality improvement methods, the team planned interventions including improvement of nursing workflow and availability of written and video education. Nurse champions performed peer-to-peer education regarding educational materials and health literacy-focused communication. An asthma education order opening the nursing flowsheet, which linked to written and video materials and documentation was created. The order was placed in highly used ED asthma order sets. The percent of parents receiving written or video education was followed on statistical process control charts. Balancing measures included: ED length of stay, discharge length, 30 day ED return visits, and 365 day return visits with hospitalization. Results The mean number of parents receiving written education at baseline was 28% and improved to 52%. Special cause variation was noted after order roll-out. Video education increased from a baseline of 0% of parents receiving to 32% with special cause variation after order roll-out. No special cause was noted in balancing measures. Revisits with hospitalization within 365 days showed a decreasing trend after order roll-out. Conclusions Implementation of workflow improvement, education, and the addition of a functional education order in an existing order set led to a meaningful improvement in distribution of a low literacy asthma education intervention.
Characteristics That Make Linear Time-Invariant Dynamic Systems Difficult for Humans to Control

We present results from an experiment in which 55 human subjects interact with a dynamic system 40 times over a one-week period. The subjects are divided into five groups. For each interaction, a subject performs a command-following task, where the reference command is the same for all subjects and all trials; however, each group interacts with a different linear time-invariant dynamic system. We use a subsystem identification algorithm to estimate the control strategy that each subject uses on each trial. The experimental and identification results are used to examine the impact of the system characteristics (e.g., poles, zeros, relative degree, system order, phase lag) on the subjects’ command-following performance and the control strategies that the subjects learn. Results demonstrate that phase lag (which arises from higher relative degree and nonminimum-phase zeros) tends to make dynamic systems more difficult for humans to control, whereas higher system order does not necessarily make a system more difficult to control. The identification results demonstrate that improvement in performance is attributed to: 1) using a comparatively accurate approximation of the inverse dynamics in feedforward; and 2) using a feedback controller with comparatively high gain. Results also demonstrate that system phase lag is an important impediment to a subject's ability to approximate the inverse dynamics in feedforward, and that a key aspect of approximating the inverse dynamics in feedforward is learning to use the correct amount of phase lead in feedforward.
Emerging Concepts in Vascular Dementia: A Review.

Abstract Objective Vascular dementia (VaD) is the second most common cause of dementia and a major health concern worldwide. A comprehensive review on VaD is warranted for better understanding and guidance for the practitioner. We provide an updated overview of the epidemiology, pathophysiological mechanisms, neuroimaging patterns as well as current diagnostic and therapeutic approaches. Materials and methods A narrative review of current literature in VaD was performed based on publications from the database of PubMed, Scopus and Google Scholar up to January, 2021. Results VaD can be the result of ischemic or hemorrhagic tissue injury in a particular region of the brain which translates into clinically significant cognitive impairment. For example, a cerebral infarct in the speech area of the dominant hemisphere would translate into clinically significant impairment as would involvement of projection pathways such as the arcuate fasciculus. Specific involvement of the angular gyrus of the dominant hemisphere, with resultant Gerstman's syndrome, could have a pronounced effect on functional ability despite being termed a “minor stroke”. Small vessel cerebrovascular disease can have a cumulate effect on cognitive function over time. It is unfortunately well recognized that “good” functional recovery in acute ischemic or haemorrhagic stroke, including subarachnoid haemorrhage, does not necessarily translate into good cognitive recovery. The victim may often be left unable to have gainful employment, drive a car safely or handle their affairs independently. Conclusions This review should serve as a compendium of updated information on VaD and provide guidance in terms of newer diagnostic and potential therapeutic approaches.
Conservation Easements: Perpetuity and Beyond

Perpetual conservation easements are intended to protect the particular land they encumber for the conservation purposes specified in the deed of conveyance “in perpetuity”—or at least until circumstances have changed so profoundly that continued protection of the land for those purposes is no longer feasible. To protect the public interest and investment in perpetual conservation easements, and, at the same time, permit adjustments to be made to respond to changing conditions, such easements should be treated like any other form of charitable asset acquired by a government or charitable entity for a particular charitable purpose—i.e., as subject to equitable charitable trust principles. This Article outlines the considerable support for applying charitable trust principles to perpetual conservation easements, including uniform laws, the Restatement of Property, federal tax law, and case activity on this
Promoter-dependent transcription by RNA polymerase II using immobilized enzyme complexes.

Abstract DNA fragments containing the adenovirus 2 major late or simian virus 40 early promoters were attached to a solid support via a biotin-streptavidin linkage at one end of the fragment, upstream of the RNA start site. Templates immobilized in this manner were incubated with HeLa cell nuclear extracts to form preinitiation complexes containing RNA polymerase II and accessory proteins required for faithful in vitro transcription. These complexes did not require ATP or dATP for assembly, were sensitive to 0.25% Sarkosyl, and were stable to extensive washing. Their incubation with specific combinations of nucleoside triphosphates resulted in the initiation of RNA chain polymerization in situ, while addition of the remaining nucleoside triphosphates was necessary to produce a full length runoff RNA. Transcriptional activity associated with preinitiation complexes was purified approximately 300-fold, relative to the unfractionated nuclear extract. The use of immobilized template permits considerable flexibility in experimental design, as substrates and inhibitors can be added and washed out of the reaction at each step. We exploited this property of the system to dissect the temporal substrate requirements for initiation of RNA synthesis. It is known from prior work that at least one step in the promoter-dependent RNA synthesis reaction requires an adenosine nucleotide that is hydrolyzable at the beta, gamma-position. This requirement is independent of the initiating nucleotide and can be satisfied by dATP, which is not ordinarily incorporated into the RNA product. We show here that the beta, gamma-hydrolyzable adenosine nucleotide must be present simultaneously with the initiating nucleoside triphosphates. No reaction occurred when complexes were incubated with dATP, washed to remove dATP, and incubated subsequently with the two initiating nucleotides.
Motion capture for a natural tree in the wind

Simulating the motion of a tree in the wind is a difficult problem because of the complexity of the tree's geometry and its associated wind dynamics. Physically-based animation of trees in the wind is computationally expensive, while noise-based approaches ignore important global effects, such as sheltering. Motion capture may help solve these problems. In this paper, we present new approaches to inferring a skeleton from tree motion data and repairing motion data using a rigid body model. While the rigid body model can be used to extract data, the data contains many gaps and errors for branches that bend. Motion data repair is critical because trees are not rigid bodies. These ideas allow the reconstruction of tree motion including global effects but without a complex physical model.
Political Parties and Election Fraud

Autocrats face a dilemma. Continue with fraudulent electoral practices and risk revolt, or reduce fraud and risk losing elections. One solution is to structure electoral governance such that it allows for independence and professionalism at the center, lending credibility to the electoral process, and partisan local-level administration, enabling fraud at the micro level. Partisan poll workers can help deliver the vote by the use of ‘smart fraud’ – fraud that minimizes the risk of being caught and is used only when needed. In Armenia, the ruling party’s vote share, as a proportion of all registered voters, increases with 8.2 percent in polling stations where the chairperson was randomly assigned to the ruling party. Fraud forensics suggests that one of the mechanisms behind this was falsification of the results protocol during the count. I conjecture that fraud is only used in high-stakes elections and that election observers are unable to detect it.
Graft-Versus-Host Disease Prophylaxis

Acute graft-versus-host disease (aGVHD) is the leading cause of nonrelapse mortality in allogeneic transplant patients. Efforts have been made to identify patient, donor, graft, and genetic risk factors for the development of aGVHD. Conditioning regimens and posttransplant medication management also have a significant impact on rates of both aGVHD and chronic GVHD (cGVHD). The combination of medications and doses used in conditioning regimens is associated with varying degrees of recipient toxicity and creates complex host/graft environments. As a result, maximizing posttransplant medication management has been an essential component of aGVHD prevention. The aim of recent efforts to prevent aGVHD has been to decrease host damage, reduce host inflammation, and regulate donor T cell quantity and type. This chapter focuses on standard management, new approaches, and future directions of GVHD prophylaxis, as they relate to conditioning regimens, donor T cell manipulation, and posttransplant medication management.
Development and Measurement of Preschoolers’ Quantitative Knowledge

The collection of studies in this special issue make an important contribution to our understanding and measurement of the core cognitive and noncognitive factors that influence children’s emerging quantitative competencies. The studies also illustrate how the field has matured, from a time when the quantitative competencies of infants and young children were studied in isolation of other cognitive abilities or social contexts. The studies illustrate how the basic knowledge gleaned from this early research can now be situated within the home environment, integrated with language development, and as related to children’s preparation for learning formal mathematics in school.
Efficiency of pyrimidine dimer formation in Escherichia coli across UV wavelengths

Aims: Inactivation of Escherichia coli as a function of ultraviolet (UV) wavelength was investigated by using the endonuclease-sensitive site (ESS) assay to quantify pyrimidine dimer formation. Methods and Results: Ultraviolet dose–response curves were determined based on both log reduction in colony-forming units (CFU) and endonuclease-sensitive sites per kb DNA (ESS/kb) for monochromatic 254-nm low-pressure (LP) UV, polychromatic medium-pressure (MP) UV, 228 and 289-nm UV irradiation. UV irradiation from LP and MP UV sources were approx. equal in both CFU reduction and pyrimidine dimer formation at all UV doses studied; 228-nm irradiation was less effective than LP or MP, and 289-nm irradiation was the least effective in both CFU reduction and pyrimidine dimer formation. These results are in qualitative agreement with the absorption spectrum of pyrimidine bases in DNA. Results indicated an approx. linear relationship between ESS/kb and log CFU reduction. Conclusions: Formation of pyrimidine dimers in genomic DNA is primarily responsible for UV inactivation of E. coli. Significance and Impact of the Study: This work contributed to fundamental understanding of UV disinfection and aids in UV reactor design.
Lymphocyte immunophenotyping in an elderly population: Age, sex and medication effects — a flow cytometry study

Flow cytometry studies of 179 individuals aged 55-95 years reveal correlations of various hematological and immune cell measures (quantification of leukocytes, leukocyte subtypes, platelets, and erythrocytes) with age, sex, common medications (aspirin, ulcer therapy, estrogen replacement therapy), and health history variables (minor arthritis, allergy, smoking, stress and exercise). Possible reasons for some of these findings are discussed.
In vitro studies in VCP-associated multisystem proteinopathy suggest altered mitochondrial bioenergetics

Mitochondrial dysfunction has recently been implicated as an underlying factor to several common neurodegenerative diseases, including Parkinson's disease, Alzheimer's and amyotrophic lateral sclerosis (ALS). Valosin containing protein (VCP)-associated multisystem proteinopathy is a new hereditary disorder associated with inclusion body myopathy, Paget disease of bone (PDB), frontotemporal dementia (FTD) and ALS. VCP has been implicated in several transduction pathways including autophagy, apoptosis and the PINK1/Parkin cascade of mitophagy. In this report, we characterized VCP patient and mouse fibroblasts/myoblasts to examine their mitochondrial dynamics and bioenergetics. Using the Seahorse XF-24 technology, we discovered decreased spare respiratory capacity (measurement of extra ATP that can be produced by oxidative phosphorylation in stressful conditions) and increased ECAR levels (measurement of glycolysis), and proton leak in VCP human fibroblasts compared with age- and sex-matched unaffected first degree relatives. We found decreased levels of ATP and membrane potential, but higher mitochondrial enzyme complexes II+III and complex IV activities in the patient VCP myoblasts when compared to the values of the control cell lines. These results suggest that mutations in VCP affect the mitochondria's ability to produce ATP, thereby resulting in a compensatory increase in the cells' mitochondrial complex activity levels. Thus, this novel in vitro model may be useful in understanding the pathophysiology and discovering new drug targets of mitochondrial dynamics and physiology to modify the clinical phenotype in VCP and related multisystem proteinopathies (MSP).
The effect of instruction on children's solutions of addition and subtraction word problems

This study investigated the effect of initial instruction on the processes children use to solve addition and subtraction word problems. Prior to instruction and following a two-month introductory unit on addition and subtraction, 43 first-grade children were individually tested on verbal problems representing different addition and subtraction situations. Prior to instruction, the children's solution processes directly modeled the action or relationships described in the problem. Following instruction, they generally used a separating strategy for all subtraction problems. Although they could solve the problems, few children could coordinate their solutions with the arithmetic sentence they wrote to represent the problem.
NASA in Crisis: The Space Agency's Public Relations Efforts Regarding the Hubble Space Telescope.

Abstract This study examines NASA's public relations efforts regarding the Hubble Space Telescope in 1990. It proposes that NASA's poor public relations exacerbated the problems caused by the telescope's spherical aberration. To a great extent, NASA brought the crisis on itself. It oversold the telescope before it was deployed; it failed to developed a clear plan for dealing with first-light images and early release of photographs; it provided misleading flight reports; and it reported prematurely and incorrectly that the Hubble could not produce photographs. NASA's poor handling of the Hubble, coupled with its poor handling of the Challenger explosion, suggests the agency must improve its crisis communications if it hopes to maintain the trust and support of Congress and the American people into the twenty-first century.