cssi/SciSciGPT-SciSciNet huggingface dataset:
Piggybac Mediated Gene Transfer To Correct Hemophilia A

Hemophilia A, caused by a deficiency in factor VIII (FVIII), is the most severe inherited bleeding disorder, affecting about 1 out of 5,000 males; those affected suffer disabling joint and muscle hemorrhages. Hemophilia A is an attractive gene therapy candidate, because even small increases in FVIII levels (5-10%) will alter the phenotype. Non-viral vector systems are used increasingly in gene targeting technologies and as tools for gene transfer applications. Nonviral DNA transposons are genetic elements consisting of inverted terminal DNA repeats which in their naturally occurring configuration flank a transposase coding sequence. The transposase follows a “cut and paste” mechanism to excise the transposon from its original genomic location and insert it into a new locus. The insect derived piggyBac (PB) can be engineered to carry a therapeutic transgene between the inverted terminal repeats. Advantages of this novel nonviral vector system include a large transgene cassette capacity, ease of production and purification, and potential for site-specific integration. We hypothesize that a PB transposon vector carrying a codon-optimized human FVIII cDNA along with a hyperactive transposase (iPB7) will confer persistent gene expression and correction of the hemophilia A bleeding phenotype. We engineered PB transposon to carry a codon-optimized human FVIII B-domain deleted cDNA (coFVIII-BDD). We evaluated the in vivo gene transfer efficiency in hemophilia A mice by hydrodynamic tail-vein injection using PB coFVIII-BDD driven by the murine albumin enhancer/human alpha anti-trypsin promoter. Factor VIII null mice received 25 micrograms each of the PB coFVIII-BDD transposon and iPB7 to determine long term expression and phenotypic correction. FVIII activity and antigen levels were measured prior to injection and then every 4 weeks for 24 weeks. Results revealed therapeutic levels (50-225%) of factor VIII activity and antigen post gene transfer with stable expression for 24 weeks in most mice. A goal of gene transfer based therapies is to develop the most efficacious expression vectors with the least toxicity. To assess endoplasmic reticulum stress in the livers of treated and untreated mice, we evaluated BiP, CHOP, and EDEM levels via q-PCR. All experimental mice, null mice, and transposon treated mice without the coFVIII-BDD cassette revealed no evidence of cell stress. These data indicate codon-optimized FVIII and the piggyBac transposon vector system may provide a safe long term gene transfer strategy. To evaluate phenotypic correction, a tail clip assay was performed at the end of the study. More than 75% of mice receiving PB coFVIII-BDD transposon and iPB7 demonstrated functional correction via tail clip. These data show that the PB vector can be used to deliver transgene expression to the liver and achieve long term expression and phenotypic correction. Disclosures: No relevant conflicts of interest to declare.
Leverage Cultural Resources and Creativity

One rarely goes to a museum to find a model of how to stimulate local economic development. That’s particularly true in Florence, Italy where you instead go to see treasures by Botticelli, da Vinci, Raphael, Caravaggio, and Titian. But Florence has a noted exception if you’re an economist: the Palazzo Strozzi. Since the end of World War II, the Palazzo Strozzi has been known as Florence’s largest space for temporary exhibitions. In the last decade, it has also become known for being an example of how to use art to stimulate economic development.
Flexible Method for Conjugation of Phenolic Lignin Model Compounds to Carrier Proteins

Linking lignin model compounds to carrier proteins is required either to raise antibodies to them or to structurally screen antibodies raised against lignins or models. This paper describes a flexible method to link phenolic compounds of interest to cationic bovine serum albumin (cBSA) without interfering with their important structural features. With the guaiacylglycerol-β-guaiacyl ether dimer, for example, the linking was accomplished in 89% yield with the number of dimers per carrier protein being as high as 50; NMR experiments on a 15N- and 13C-labeled conjugation product indicated that 13 dimers were added to the native lysine residues and the remainder (∼37) to the amine moieties on the ethylenediamine linkers added to BSA; ∼32% of the available primary amine groups on cBSA were therefore conjugated to the hapten. This loading is suitable for attempting to raise new antibodies to plant lignins and for screening.
Microstructural evolution of neutron irradiated 3C-SiC

Abstract The microstructural response of neutron irradiated 3C-SiC have been investigated over a wide irradiation temperature and fluence range via qualitative and quantitative synchrotron-based X-ray diffraction characterization. We identify several neutron fluence- and irradiation temperature-dependent changes in the microstructure, and directly highlight the specific defects introduced through the course of irradiation. By quantifying the microstructure, we aim to develop a more detailed understanding of the radiation response of SiC. Such studies are important to build mechanistic models of material performance and to understand the susceptibility of various microstructures to radiation damage for advanced energy applications.
Time-Frequency Analysis and Representations of the Discrete Heisenberg Group

The operators [ϱ ω (j, k, l)f](t) = e2πiωl e2πiωkt f(t + j) on \(L^{2}(\mathbb{R})\) constitute a representation of the discrete Heisenberg group. We investigate how this representation decomposes as a direct integral of irreducible representations. The answer is quite different depending on whether ω is rational or irrational, and in the latter case it provides illustrations of some interesting pathological phenomena.
Two forms of solidarity: Their relation to the capacity to think and to alienation

Self-reflective thinking guards against the flight to authoritarian fantasies and leaders—a flight seen recently, for example, in the election of Donald Trump as US president. The capacity to think reflectively requires a sense of security which, if not internalized, can come from a feeling of belonging. But, if we need to belong to feel secure, how free are we to think differently from the group? I propose two types of solidarity—true solidarity, where a sense of universal kinship fosters compassion and a sense of responsibility for care that makes it important to reflect on what we do; and false solidarity, a shared paranoid/manic fantasy of superiority to a despised group, in which personal thinking threatens a brittle sense of belonging. Right-wing populism is a way to cope with anxieties about economic/cultural dispossession through such fantasies of superiority. But the Left has its own false solidarity—a manic bond that refuses empathy with the pain of the dispossessed on the Right, and even attacks those on the Left who are deemed insufficiently attentive to particular social justice issues. False solidarity is likely to evoke a complementary reaction—similar aggressive, resistant attitudes—in those it targets, resulting in a political impasse. But humility and active compassion may open the way to real dialogue.
Restricted access to beneficial mutations slows adaptation and biases fixed mutations in diploids

Ploidy varies considerably in nature. Yet, our understanding of the impact of ploidy on adaptation is incomplete. Many microbial evolution experiments characterize adaptation in haploid organisms, but few focus on diploid organisms. Here, we perform a 4,000-generation evolution experiment using diploid strains of the yeast Saccharomyces cerevisiae. We show that the rate of adaptation and spectrum of beneficial mutations are influenced by ploidy. Haldane9s sieve effectively restricts access to beneficial mutations in diploid populations, leading to a slower rate of adaptation and a spectrum of beneficial mutations shifted towards dominant mutations. Genomic position also plays an important role, as the prevalence of homozygous mutations is largely dependent on their proximity to a recombination hotspot. Our results demonstrate key aspects of diploid adaptation that have previously been understudied and provide support for several proposed theories.
Further evaluation of animal systemic insecticides, 1965.

In screening tests, 27 insecticides were systemically active when administered orally or subcutaneously to guinea artificially infested with larvae of the screw-worm fly, Cochliomyia hominivorax (Goquerel); or the secondary screw-worm fly, C. macellaria (F.); and the black blow fly, Phormia regina (Meigen); and nymphal lone star ticks, Amblyomma americanum (L.); and fed upon by stable flies, Stomoxys calcitrans (L.). Of 39 insecticides administered to cattle for the systemic control of cattle grubs ( Hypoderma spp.), the following treatments were effective (> 90% control) in pre-venting grubs from encysting in the backs of the animals: Bayer 34727 ( O, O -dimethyl phosphorothioate O -ester with p -hydroxybenzonitrile) at 25 mg per kg by capsule and as a 0.5% spray; Bayer 37342 ( O, O -dimethyl O -[4-(methylthio)-3,5-xyly] phosphorothioate) in feed at 1 mg per kg per day for 10 days; CELA S-1942 [ 0 -(4-brorno-2.5-dichloropigs phenyl) O, O -dimethyl phosphorothioate] at 100 mg per kg by capsule; famphur in feed at 2.5 mg per kg per day for 10 days; menazon in feed at 5 mg per kg per day for 10 days and as 1.0 and 1.5% sprays; Shell SD-8949 [1-(2-bromo-4,5-dichlorophenyl)-2-chlorovinyl dimethyl phosadult phatel at 50 mg per kg by capsule; Stauffer N-3055 ( 0 -2,5-dichlorophenyl a-ethyl cthylphosphonothioate) at 10 mg per kg by capsule; Stauffer R-3828 [ S -( p -chloro-alphaphenylbenzyl) O, O -diethyl phosphorodithioatel in feed at 5 mg per kg per day for 10 days; and Vamidoate® ( O, O -dimethyl S-[2-[(1-methycarbamoyethyl) thio]ethyl] phos, phorodithioate) in feed at 2.5 and 5 mg per kg per day for 10 days.
Characterizing the Impacts of Deposition Techniques on the Performance of MnO2 Cathodes for Sodium Electrosorption in Hybrid Capacitive Deionization.

Capacitive deionization (CDI) is currently limited by poor ion-selectivity and low salt adsorption capacity of porous carbon electrodes. To enhance selectivity and capacity via sodium insertion reactions, carbon aerogel electrodes were modified by depositing amorphous manganese dioxide layers via cyclic voltammetry (CV) and electroless deposition (ED). MnO2-coated electrodes were evaluated in a hybrid capacitive deionization system to understand the relationship between oxide coating morphology, electrode capacitance, and sodium removal efficacy. Both deposition techniques increased electrode capacitance, but only ED electrodes improved desalination performance over bare aerogels. SEM imaging revealed ED deposition distributed MnO2 throughout the aerogel, while CV deposition created a discrete crust, indicating that CV electrodes were limited by diffusion. Sodium adsorption capacity of ED electrodes increased with MnO2 mass deposition, reaching a maximum of 0.77 mmol-Na+ per gram of cathode (2.29 mmol-Na+...
Calcium uptake and cytochrome c release from normal and ischemic brain mitochondria.

At abnormally elevated levels of intracellular Ca2+, mitochondrial Ca2+ uptake may compromise mitochondrial electron transport activities and trigger membrane permeability changes that allow for release of cytochrome c and other mitochondrial apoptotic proteins into the cytosol. In this study, a clinically relevant canine cardiac arrest model was used to assess the effects of global cerebral ischemia and reperfusion on mitochondrial Ca2+ uptake capacity, Ca2+ uptake-mediated inhibition of respiration, and Ca2+-induced cytochrome c release, as measured in vitro in a K+-based medium in the presence of Mg2+, ATP, and NADH-linked oxidizable substrates. Maximum Ca2+ uptake by frontal cortex mitochondria was significantly lower following 10 min cardiac arrest compared to non-ischemic controls. Mitochondria from ischemic brains were also more sensitive to the respiratory inhibition associated with accumulation of large levels of Ca2+. Cytochrome c was released from brain mitochondria in vitro in a Ca2+-dose-dependent manner and was more pronounced following both 10 min of ischemia alone and following 24 h reperfusion, in comparison to mitochondria from non-ischemic Shams. These effects of ischemia and reperfusion on brain mitochondria could compromise intracellular Ca2+ homeostasis, decrease aerobic and increase anaerobic cerebral energy metabolism, and potentiate the cytochrome c-dependent induction of apoptosis, when re-oxygenated mitochondria are exposed to abnormally high levels of intracellular Ca2+.
Teens' distracted driving behavior: Prevalence and predictors.

Abstract Introduction Teen drivers' over-involvement in crashes has been attributed to a variety of factors, including distracted driving. With the rapid development of in-vehicle systems and portable electronic devices, the burden associated with distracted driving is expected to increase. The current study identifies predictors of secondary task engagement among teenage drivers and provides basis for interventions to reduce distracted driving behavior. We described the prevalence of secondary tasks by type and driving conditions and evaluated the associations between the prevalence of secondary task engagement, driving conditions, and selected psychosocial factors. Methods The private vehicles of 83 newly-licensed teenage drivers were equipped with Data Acquisition Systems (DAS), which documented driving performance measures, including secondary task engagement and driving environment characteristics. Surveys administered at licensure provided psychosocial measures. Results Overall, teens engaged in a potentially distracting secondary task in 58% of sampled road clips. The most prevalent types of secondary tasks were interaction with a passenger, talking/singing (no passenger), external distraction, and texting/dialing the cell phone. Secondary task engagement was more prevalent among those with primary vehicle access and when driving alone. Social norms, friends' risky driving behaviors, and parental limitations were significantly associated with secondary task prevalence. In contrast, environmental attributes, including lighting and road surface conditions, were not associated with teens' engagement in secondary tasks. Conclusions Our findings indicated that teens engaged in secondary tasks frequently and poorly regulate their driving behavior relative to environmental conditions. Practical applications: Peer and parent influences on secondary task engagement provide valuable objectives for countermeasures to reduce distracted driving among teenage drivers.
Nanofluidics for cell and drug delivery

Management of chronic pathologies requires the development of novel strategies for the delivery of drugs and cell therapies, ad hoc. We have developed implantable micronanofluidic-based platforms that leverage molecular nanoconfinement for the controlled administration of drugs and transplantation of cells. These rely on silicon nanofabricated membranes and 3D-printed polymeric architectures that afford long term function in vivo without complex pumping mechanisms or actuation. In this work, we present our recent advances in zero-order drug delivery implants, remotely tunable delivery devices, and subcutaneous encapsulations for endocrine cells transplantation.
Jury Pool Underrepresentation in the Modern Era: Evidence from Federal Courts

Despite a constitutional mandate that jury pools in the United States be representative of their communities, almost no datasets exist that can describe typical levels and patterns of jury representation. We present data from federal courts on the composition of jury pools in 52 areas, representing 764 counties. We also compare current composition estimates to those available 20 years ago from published sources. Results show that, by far, some amount of underrepresentation in jury pools is the norm, and levels of attrition fail all but one proposed method for calculating and defining “not fair and reasonable” amounts of underrepresentation. On average, expected losses range between one and three members of each minority group from jury venires of 40 to 60 people. We find no evidence that the impact of attrition on Latino communities is greater than on African‐American communities and, unlike Latinos, no indicators of African‐American representation levels show improvement over time. We discuss the challenges of addressing racial/ethnic attrition in jury pools, which is evident but, given the repeated small‐group sampling of venires, may be small in effect in any single case.
Graphene-modified carbon/epoxy nanocomposites: Electrical, thermal and mechanical properties:

A primary limitation of fiber-reinforced polymer composites in aircraft applications is susceptibility to lightning because of poor electrical, thermal and electromagnetic properties. The current m...
The genetic and environmental effects of parental age on the expression of psychopathology in adoptees

OF THE THESIS THE GENETIC AND ENVIRONMENTAL EFFECTS OF PARENTAL AGE ON THE EXPRESSION OF PSYCHOPATHOLOGY IN ADOPTEES by Lyndon Joseph Aguiar Florida International University, 1999 Miami, Florida Professor Gordon E. Finley, Major Professor Secondary analysis of 581 adoptees was utilized to determine if parental age is related, either genetically or environmentally, to the development of psychopathology. The significant results showed that proband adoptees (with psychopathology in biologic relatives) with younger birthparents had increased alcohol abuse and those with younger birthfathers had increased antisocial personality while adoptees with older birthparents had increased depression. Analyses on control adoptees (with background free of known genetic disturbances) showed that those with younger adoptive mothers had increased antisocial personality and drug abuse and those with younger adoptive fathers had increased antisocial personality while adoptees with older adoptive fathers had increased depression.
An Interdisciplinary Approach to Surgical Skills Training Decreases Programmatic Costs.

Abstract Background Surgical resident duty hour limitations have necessitated operative skill training outside of the operating room. Although wet-lab skills training is ideal, materials and human resource requirements make wet labs-utilizing biologic samples cost prohibitive for many residency programs. To resolve this problem, our general surgery residency program collaborated with the Institution's School of Veterinary Medicine Surgery Residency program to pilot a cost-effective interdisciplinary surgical skills curriculum. Materials and methods The general surgery residency program manager and program director initiated a collaboration with the Veterinary Surgery Residency. Postgraduate year (PGY) 2 general surgery residents and PGY 1-3 veterinary surgery residents participated in monthly joint surgical skills practice sessions. A novel interdisciplinary surgical skills curriculum was implemented that incorporated skills beneficial to both sets of trainees utilizing donated canine cadavers. Results A total of nine joint skills sessions were conducted for nine general surgery residents and five veterinary surgery residents. A cost analysis was conducted for a surgical skills curriculum servicing both programs independently and compared to the actual costs of the collaborative curriculum. The cost analysis estimated total savings generated by the collaborative to be $27,323.79. Review of initial feedback from trainees suggest that skill sessions reinforce knowledge, and that the collaborative skills sessions were an enjoyable and valuable learning activity. Conclusions The skills curriculum collaborative has proven to be a cost-effective and high quality interdisciplinary pedagogic tool. The partnership allowed for mutually beneficial resource sharing and allowed for the initiation of a surgical skills wet lab that had previously been unavailable to both groups.
Synthesis of Cu-Trimesic Acid/Cu-1,4-Benzenedioic Acid via Microdroplets: Role of Component Compositions

Mixed-linker metal–organic frameworks (MOFs) offer great tunability in both pore structures and surface chemistry. This study reports the synthesis and characterization of model mixed-linker MOFs (i.e., Cu-TMA/Cu-BDC; BDC = 1,4-benzenedioic acid, TMA = trimesic acid) via a microdroplet-based spray process, to unravel the relationship between the properties of mixed-linker MOFs and the component compositions. The as-prepared mixed-linker MOFs exhibited distinct properties in terms of morphology, crystalline phase, surface chemistry, and pore structure. In particular, two-dimensional correlation spectroscopy (2D-COS) analysis was conducted to analyze the correlational features among surface functional groups, which are unattainable from traditional infrared and Raman spectra. The results from the 2D-COS analysis also suggest that the surface chemistry of the mixed-linker MOFs is adjustable by controlling the precursor conditions. Measurements of CO2 adsorption on the mixed-linker MOFs demonstrated the tunab...
Immunotherapy is associated with improved survival and decreased neurologic death after SRS for brain metastases from lung and melanoma primaries

Background The effect of immunotherapy on brain metastasis patients remains incompletely understood. Our goal was to evaluate its effect on survival, neurologic death, and patterns of failure after stereotactic radiosurgery (SRS) without prior whole-brain radiation therapy (WBRT) in patients with lung and melanoma primaries metastatic to the brain. Methods We performed a retrospective analysis of 271 consecutive lung or melanoma patients treated with upfront SRS for brain metastases between 2013 and 2018. Of these patients, 101 (37%) received immunotherapy and 170 (63%) did not. Forty-three percent were treated with nivolumab. Thirty-seven percent were treated with pembrolizumab. Fifteen percent were treated with ipilimumab. One percent were treated with a combination of nivolumab and ipilimumab. One percent were treated with atezolizumab. Three percent were treated with another immunotherapy regimen. Survival was estimated by the Kaplan-Meier method and cumulative incidences of neurologic death, and local and distant brain failure were estimated using death as a competing risk. Results The median overall survival (OS) of patients treated with immunotherapy vs without was 15.9 (95% CI: 13.3 to 24.8) vs 6.1 (95% CI: 5.1 to 8.8) months (P < .01). The 1-year cumulative incidence of neurologic death was 9% in patients treated with immunotherapy vs 23% in those treated without (P = .01), while nonneurologic death was not significantly different (29% vs 41%, P = .51). Median brain metastasis velocity (BMV) did not differ between groups, and rates of salvage SRS and WBRT were similar. Conclusions The use of immunotherapy in patients with lung cancer or melanoma metastatic to the brain treated with SRS is associated with improved OS and decreased incidence of neurologic death.
The Chatt reaction: conventional routes to homoleptic arenemetalates of d-block elements

Joseph Chatt was the first to discover in the early 1960s that previously unknown transition metal compounds were accessible and isolable via the reactions of alkali metal arene radical anions with transition metal precursors containing good leaving groups, such as weakly basic neutral or anionic ligands, especially halides. Later Peter Timms confirmed the importance of these early studies with the synthesis of several new bis(arene)metal(0) sandwich compounds by a variant of Chatt's route. Following a brief historical survey of alkali metal arene compounds, first examined in some detail by Wilhelm Schlenk, use of these reagents in the conventional syntheses of anionic homoleptic arene metal complexes of the d-block elements will be described. In several cases these species are quite useful because they function as storable “naked” atomic metal anion reagents, especially in their reactions with carbon monoxide and isocyanides. In view of Chatt's seminal contributions to an often unique route to organometallic and inorganic compounds, it is proposed that this valuable synthetic method be named the “Chatt reaction” in honor of a giant of chemistry.
A Comparison of Public and Privatized Approaches to Managed Behavioral Health Care for Persons with Serious Mental Illness

This article compares public and privatized approaches to managed behavioral health care for persons with serious mental illness in Massachusetts. Data from the Department of Mental Health (DMH) for 247 patients receiving care managed by DMH and 312 in a Medicaid carve-out were compared. Repeated measures multivariate analysis of variance models were used to examine adjusted changes in number of admissions, bed days, and facilities used from a baseline year before program implementation in 1992 through two follow-up years. Results were comparable for the two programs with similar reductions in the number of people receiving inpatient care but increases in admissions and bed days. Possible problems with continuity of care, indicated by individuals using multiple facilities, were identified for both. Given the evidence of comparable results, the choice between the two approaches is likely to be dictated by various pragmatic and subjective factors other than their demonstrated effectiveness.
Improving Accuracy of Inkjet Printed Core Body WRAP Temperature Sensor Using Random Forest Regression Implemented with an Android App

Inkjet printing (IJP) technology holds tremendous promise for the development of low cost, environment friendly and body-worn biomedical sensors. In this study, we have investigated the integration of a flexible body-worn disposable IJP Wireless Resistive Analog Passive (WRAP) temperature sensor with an android app for real-time monitoring of core body temperature with high accuracy using features extracted from the sensor response. Random Forest has been used for feature selection and regression. With 5-fold cross validation we have achieved an RMSE = 0.98, R-squared value = 0.99, and mean absolute error, MAE = 0.59 for temperature estimation. The model is applicable for the development of IJP body-worn sensors for various other physiological sensing e.g. breathing, heart rate.
Extracellular matrix and the immune system: friends or foes.

A new study describes antitumour cell activity inherent in the extracellular matrix of porcine urinary bladder, which is not the result of direct tumour cell killing but is indirectly mediated through immune cells. The findings highlight opportunities to explore shared interests of the tissue engineering and regenerative medicine and the immunology and cancer communities.
Historical range of variability for restoration and management in Wisconsin

In Wisconsin, as in other states, management goals sometimes include restoration of historical forest conditions, which may prepare forests to be more compatible with future climates, disturbances such as drought and fire, and forest health threats. We quantified historical (1830–1866) composition and structure to develop historical reference conditions for restoration and documented changes based on current (2005–2009) forest surveys in Wisconsin. We provided structural metrics, functional group composition, and forest types for 186 ecological land types, and we also summarized trends in composition and structure. Wisconsin forests historically were comprised of 46% oak or pine savanna or woodland, 6% pine forest, and 48% forests primarily consisting of late-successional eastern broadleaf forest species and early-successional northern mixed forest species; densities of these forest types ranged from 60 to 460 trees/ha. In the Eastern Broadleaf Forest ecological division, increased composition of the early-successional and mid-successional eastern broadleaf forest groups (from 10 to 40%) and (planted) pine group (8–23%) occurred along with decreased fire-tolerant oak composition (from 65 to 23%). Density increased in current forests compared to historical forests by a factor of 2.2; despite increased density, basal area increased only slightly due to the presence of larger diameter trees in historical tree surveys. In the Northern Mixed Forest ecological division, increased composition of the mid-successional eastern broadleaf forest group (from 12 to 24%) and late-successional northern mixed forest group (from 10 to 17%) occurred due to decreased composition of the fire-tolerant pine group (from 17 to 9%) and late-successional eastern broadleaf forest group (from 30 to 20%). Density remained similar in current forests compared to historical forests but current basal area was 50% of historical basal area. The transition from open fire-tolerant oak and pine forests, with rarity of early-successional tree species, to closed forests composed of a variety of early- and mid-successional tree species parallels results from other research. Replacement of open oak or pine forest ecosystems by dense forests has moved Wisconsin outside of the historical range of variability, likely reducing plant and wildlife species associated with open oak and pine ecosystems.
AI for Small Businesses and Consumers: Applications and Innovations

Small businesses are the lifeblood of the U.S. economy, representing an astounding 99.9 percent of all businesses, creating two-thirds of net new jobs, and accounting for 44 percent of economic activity. Yet, 50 percent of small businesses go out of business in the first 5 years. What's behind this dismal statistic? Among the top contributing factors is cash flow management. Owners who cannot efficiently manage the inflow and outflow of cash are almost certain to fail. And, those who can are more likely to break through the statistical 5-year barrier to build thriving businesses. In this talk, we'll describe novel applications of artificial intelligence and large-scale machine learning aimed at addressing the problem of forecasting cash flow for small businesses. These are sparse, high-dimensional correlated time series. We'll present new results on forecasting this type of time series, using scalable Gaussian Processes with kernels formed through the use of deep learning. These methods yield highly accurate predictions but also include a principled approach for generating confidence intervals.
Nitrogen Treatment in Soil Beneath High-Flow and Low-Flow Onsite Wastewater Systems

AbstractReducing nitrogen loading to water resources is a goal for resource managers in many regions experiencing water quality degradation. Onsite wastewater systems (OWS) are used for treating wa...
Neighborhood Racial/Ethnic Composition Trajectories and Black-White Differences in Preterm Birth among Women in Texas

The black-white disparity in preterm birth has been well documented in the USA. The racial/ethnic composition of a neighborhood, as a marker of segregation, has been considered as an underlying cause of the racial difference in preterm birth. However, past literature using cross-sectional measures of neighborhood racial/ethnic composition has shown mixed results. Neighborhoods with static racial/ethnic compositions over time may have different social, political, economic, and service environments compared to neighborhoods undergoing changing racial/ethnic compositions, which may affect maternal health. We extend the past work by examining the contribution of neighborhood racial/ethnic composition trajectories over 20 years to the black-white difference in preterm birth. We used natality files (N = 477,652) from birth certificates for all live singleton births to non-Hispanic black and non-Hispanic white women in Texas from 2009 to 2011 linked to the Neighborhood Change Database. We measured neighborhood racial/ethnic trajectories over 20 years. Hierarchical generalized linear models examined relationships between neighborhood racial/ethnic trajectories and preterm birth, overall and by mother's race. Findings showed that overall, living in neighborhoods with a steady high proportion non-Hispanic black was associated with higher odds of preterm birth, compared with neighborhoods with a steady low proportion non-Hispanic black. Furthermore, while black women's odds of preterm birth was relatively unaffected by neighborhood proportions of the Latinx or non-Hispanic white population, white women had the highest odds of preterm birth in neighborhoods characterized by a steady high proportion Latinx or a steady low proportion non-Hispanic white. Black-white differences were the highest in neighborhoods characterized by a steady high proportion white. Findings suggest that white women are most protected from preterm birth when living in neighborhoods with a steady high concentration of whites or in neighborhoods with a steady low concentration of Latinxs, whereas black women experience high rates of preterm birth regardless of proportion white or Latinx.
11 – Reading Text

Publisher Summary This chapter shows how to read text data (formatted or ASCII data) from the terminal or a file. It chapter covers the basics of reading text (ASCII) output from the terminal or a file. Text (ASCII) files have advantages and disadvantages as a means of storing data. The primary advantage of text files is that they are human readable (with a text editor). Additionally, a text editor can be used to create a text file to be read by the computer program. Finally, text files are relatively portable, and can be moved from one computer to another with little difficulty. The major disadvantages of text files are that input and output are slow relative to binary files (this is important for large files) and the transformation from internal binary numbers to formatted text characters and back to binary numbers is not exact. Interactive Data Language (IDL) usually handles simple cases with sensible default behavior. Some points to remember in this chapter are: READ reads input from the terminal, READF reads from a file. A file must be opened before reading anything from it. When reading is finished the files must be closed. Reading from and writing to the same file should be avoided. The /GET_LUN keyword should be used with the OPENR command and the FREE_LUN command to avoid having to provide logical unit numbers. Free-form and formatted (ASCII) output are for humans to read. They are a bad way to transfer data between programs. When writing data for computers to read, binary formats should be used.
Cost-Effectiveness of Initial Versus Delayed Lanreotide for Treatment of Metastatic Enteropancreatic Neuroendocrine Tumors.

BACKGROUND The Controlled Study of Lanreotide Antiproliferative Response in Neuroendocrine Tumors (CLARINET) trial showed prolonged progression-free survival in patients initially treated with lanreotide versus placebo. We evaluated the cost-effectiveness of upfront lanreotide versus active surveillance with lanreotide administered after progression in patients with metastatic enteropancreatic neuroendocrine tumors (NETs), both of which are treatment options recommended in NCCN Clinical Practice Guidelines in Oncology for Neuroendocrine and Adrenal Tumors. METHODS We developed a Markov model calibrated to the CLARINET trial and its extension. We based the active surveillance strategy on the CLARINET placebo arm. We calculated incremental cost-effectiveness ratios (ICERs) in dollars per quality-adjusted life-year (QALY). We modeled lanreotide's cost at $7,638 per 120 mg (average sales price plus 6%), used published utilities (stable disease, 0.77; progressed disease, 0.61), adopted a healthcare sector perspective and lifetime time horizon, and discounted costs and benefits at 3% annually. We examined sensitivity to survival extrapolation and modeled octreotide long-acting release (LAR) ($6,183 per 30 mg). We conducted one-way, multiway, and probabilistic sensitivity analyses. RESULTS Upfront lanreotide led to 5.21 QALYs and a cost of $804,600. Active surveillance followed by lanreotide after progression led to 4.84 QALYs and a cost of $590,200, giving an ICER of $578,500/QALY gained. Reducing lanreotide's price by 95% (to $370) or 85% (to $1,128) per 120 mg would allow upfront lanreotide to reach ICERs of $100,000/QALY or $150,000/QALY. Across a range of survival curve extrapolation scenarios, pricing lanreotide at $370 to $4,000 or $1,130 to $5,600 per 120 mg would reach ICERs of $100,000/QALY or $150,000/QALY, respectively. Our findings were robust to extensive sensitivity analyses. The ICER modeling octreotide LAR is $482,700/QALY gained. CONCLUSIONS At its current price, lanreotide is not cost-effective as initial therapy for patients with metastatic enteropancreatic NETs and should be reserved for postprogression treatment. To be cost-effective as initial therapy, the price of lanreotide would need to be lowered by 48% to 95% or 27% to 86% to reach ICERs of $100,000/QALY or $150,00/QALY, respectively.
Transmission Planning and Operation in the Wholesale Market Regime

The different incentives generation unit owners face for locating and operating their units in the wholesale market regime versus the vertically-integrated monopoly regime has wide-ranging implications for the design and operation of the transmission network in the two regimes. This logic implies different measures of grid reliability in the two regimes—engineering reliability in the vertically-integrated monopoly regime and economic reliability in the wholesale market regime. Because of the different planning criteria in the two regimes, the economically efficient choice of transmission capacity in the wholesale market regime is generally greater than that in the vertically-integrated monopoly regime. A number of arguments are presented for why the transmission planning and regulatory process for the wholesale market regime require substantially more engineering and economic modeling sophistication than is required in the vertically-integrated monopoly regime. A forward-looking framework is proposed for evaluating transmission network expansions in the wholesale market regime. This includes a general methodology for computing the distribution of realized economic benefits from an upgrade in the wholesale market regime. How the measurement of the economic benefits of transmission expansions to support the deployment of renewable resources differs between the wholesale market regime and vertically-integrated monopoly regime is also discussed.
Misinformation Inoculation and Literacy Support Tweetorials on COVID-19

Many expected federal public health agencies to provide timely and accurate information about the COVID-19 pandemic. That did not happen. In response, physicians and epidemiologists have explored n...
Current status: meeting the regulatory goals of your liver transplant program.

PURPOSE OF REVIEW The regulatory framework set by the Organ Procurement and Transplantation Network (OPTN) and Center for Medicare and Medicaid Services (CMS) for practice of liver transplantation in US is periodically updated and risk adjusted. Therefore, it is prudent for transplant centers to know the rules of engagement as it pertains to their practice. RECENT FINDINGS OPTN besides providing the regulatory oversight for safe and continued practice of transplant centers, provides necessary tools like: advanced statistical models and technological platforms to aid, and guide transplant centers including the necessary safeguards for high-quality transplant care.CMS regulations although had different thresholds to flag underperformance, often covered common grounds similar to the OPTN, therefore considered duplicative and unnecessary. But with much deliberation and consideration CMS undertook a major overhaul to the final rule for re-approval applications, a giant leap in the positive direction for transplant innovation and growth. SUMMARY The duplicative regulatory framework of OPTN and CMS has although achieved the goal of improving 1-year patient outcomes, it has proven costly in terms of slowing innovation, increasing organ discard and stunting growth of transplant volume. But the new updates in effect and also in the pipeline are a long-awaited opportunity for waiting transplant patients.
Biology and therapy of human small cell lung cancer (SCLC) in novel orthotopic nude mouse models

5136 SCLC is one of the most aggressive phenotypes of human lung cancer and conveys a poor prognosis due to the limited efficacy of existing treatment strategies. To provide clinically relevant strategies for studying new therapeutics and tumor biology, we developed three orthotopic models of human SCLC in nude mice. Three different human SCLC cell lines (H69A, a variant of the NCI-H69 cell line selected for invasiveness in vitro on semisolid agarose; NCI-H187; and NCI-N417) were studied. Tumor cells (1.5 x 106 cells in growth factor reduced Matrigel) were injected into the left lung of anesthetized nude mice. Tumors developed within 8 to 12 weeks and new cell lines were established from the lung tumors (H69ALu, H187Lu, and N417Lu) to select for a reproducible growth pattern for the orthotopic tumors and to minimize variation of tumor size. For each model, tumors started as a solitary mass in the left lung tumor that then spread to mediastinal and axillary lymph nodes, and to the right lung in a pattern similar to that observed in the clinic. N417Lu and H187Lu formed a 100 mm3 left lung mass within 30-40 days of injection, and mice were moribund within 50 to 60 days of injection. H69ALu tumors reached a volume of 100 mm3 within 60 days of injection and mice became moribund within 4 to 6 months. All tumors larger than 100mm3 expressed the proangiogenic factors bFGF and IL-8 (at the tumor periphery), and VEGF/VPF (tumor center and periphery).To compare the efficacy of different chemotherapeutic agents in each of our models, groups of mice (n = 5) were randomized to weekly i.p. treatment with saline (control), 6 mg/kg/mouse of cisplatin (CDDP), 50 mg/kg/mouse of paclitaxel, 125 mg/kg/mouse of irinotecan (CPT-11), or 40 mg/kg/mouse of etoposide. Therapy was initiated on day 10 (H187Lu and N417Lu) or day 20 (H69ALu) after tumor injection coincident with the formation of microscopic lesions. Therapy was well tolerated and mice were killed after five (H187Lu and N417Lu) or seven (H69ALu) weeks of therapy. Tumor burden was assessed by lung and tumor weight (g) and primary tumor volume (mm3). CPT-11 significantly inhibited the growth and progression of N417Lu tumors as compared to control (lung and tumor weight 0.23 ± 0.01 vs. 0.62 ± 0.15, p = 0.02; tumor volume 0.3 ± 0.1 vs. 364 ± 156, p = 0.03) and CDDP significantly inhibited the growth and progression of H69ALu tumors as compared to control (tumor volume 0.3 ± 0.1 vs. 100 ± 0.01, p = 0.04). The development of our orthotopic models of SCLC provides a better understanding the biology of this disease and will enable evaluation of novel therapeutic strategies (supported by a grant from the Department of Defense (DAMD 17-02-1-0706 to W.K.H.).
Abstract B22: Identifying protein interactors of oncogenic Kras in pancreatic cancer cells via proximity labelling

Kras is mutated in over 90% of pancreatic adenocarcinoma (PDAC), the most common type of pancreatic cancer. Under normal conditions, Kras is a tightly regulated signaling protein that can toggle between active and inactive states to control cell proliferation. Mutated Kras (G12D) predominantly remains active, thus constitutively promoting proliferation and tumorigenesis. Studies that target downstream pathways of Kras, Raf/ERK and PI3K/AKT, have had some preclinical success but minimal clinical impact on pancreatic cancer. Therefore, it remains possible that in the pancreatic cancer context other undiscovered or underappreciated protein-protein interactions exist, including transient ones. In order to identify such mutant specific interactions in mouse tumor cells, we compare the biotinylated proteins from BirA biotin ligase fusions to wild-type and mutant Kras, as well as localization controls. Conditions have been optimized such that enrichment of biotinylated endogenous Raf1 and B-raf in BirA-KrasG12D compared to BirA-KrasWT can be detected by both Western blot and mass spectrometry analysis. Mass spectrometry has also identified other candidate interactors of KrasG12D, which are being validated biochemically with functional genetic experiments to follow. Citation Format: Derek K. Cheng, David A. Tuveson. Identifying protein interactors of oncogenic Kras in pancreatic cancer cells via proximity labelling [abstract]. In: Proceedings of the AACR Special Conference on Targeting RAS-Driven Cancers; 2018 Dec 9-12; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(5_Suppl):Abstract nr B22.
Impact of Prediabetes and Type-2 Diabetes on Outcomes in Patients with COVID-19

Introduction. The true impact of prediabetes and type-2 diabetes in patients with COVID-19 remains unknown, with studies thus far providing conflicting evidence. Methods. This is a single-center retrospective observational study involving 843 hospitalized patients with SARS-CoV-2 infection. Primary outcomes, mortality, and mechanical ventilation use were compared among the three groups: control, prediabetes, and type-2 diabetes. Binomial regression analysis was used to determine predictors of mortality and mechanical ventilation requirement. Results. Age was a significant predictor of mortality. On stratifying our patients based on their age, older patients aged 55 years and above had no difference in mortality or mechanical ventilation requirement among the three groups of control, prediabetes, and type-2 diabetes. However, among the younger population aged less than 55 years, patients with type-2 diabetes had significantly higher mortality as compared with patients in control and prediabetes groups (27% vs 12.5% vs 9%, ). Additionally, newly diagnosed type-2 diabetes patients demonstrated lower mortality rate in comparison to previously known type-2 diabetes patients (18% vs 40%, ). Outcomes in the prediabetes group were similar to that in the control group. Admission hyperglycemia was associated with higher mortality regardless of diabetes status. Conclusion. In older patients aged 55 years and above, status of type-2 diabetes does not influence their mortality. However, in younger patients aged less than 55 years, the presence of type-2 diabetes is an important driver of mortality. Newly diagnosed type-2 diabetes, in comparison with previously diagnosed type-2 diabetes, may have better survival. Presence of prediabetes did not affect outcomes in patients with COVID-19 infection.
Decoding Neural Activity to Anticipate Eye Movements

Neural interfaces for motor control read out motor planning activity in the brain and use it to control a computer or physical device in order to restore or replace motor functions of the brain. Applications involving the readout of intended eye movements however remain comparatively undeveloped. In this study, we aim to develop decoding algorithms that can predict eye movement signals from neural responses during the planning period, before the animal makes an eye movement. The single-trial local field potentials of neurons in Frontal Eye Field (FEF), a cortical area that contributes to the control of eye movements, as well as, in area V4 of nonhuman primates are used to train the eye movement decoders. The algorithms identified and optimized in this study can facilitate the development of brain machine interface systems for eye movements, with an ultimate goal of providing assistive technologies to correct for the impaired gaze control in patients with eye movement disorders.