cssi/SciSciGPT-SciSciNet huggingface dataset:
Dexamethasone Therapy for Acute Lymphoblastic Leukemia Increases Sleep During the Night and During the Day In Young Children

Abstract 258 Dexamethasone (Dex) or prednisone (Pred) are used in Acute Lymphoblastic Leukemia (ALL) therapy. It has long been recognized that dexamethasone effects both daytime behavior and nighttime sleep. The most commonly reported adverse effect of dexamethasone on sleep is sleep onset and sleep maintenance insomnia. An actigraph, recording 24 hours a day for 28 days, was used to evaluate sleep and wakefulness of patients with ALL in maintenance. Patients treated with Dex were evaluated at 3 windows: Dex-on days (1-5), Dex-washout days (6-15) and Dex-off days (16-28). Daytime and nighttime sleep parameters were analyzed from aggregated patient data for all three windows using the median and range. The non-parametric Friedman test was used to compare these parameters over the three windows, and the Wilcoxon Signed Rank Test was used for paired comparisons (used Bonferoni correction). Sleep patterns were also measured using the Childhood Sleep Habit9s Questionnaire (CSHQ). The group included 41 ALL patients (29 received Dex, 8 received Pred, and 4 did not receive steroids); 18 females (43.9%), 23 males (56.09%); median age 5 years (range 2 –16). In the Dex treated group, wake during the 5 days of Dex treatment showed less daytime activity mean, greater total daytime sleep minutes, and greater numbers of sleep episodes (>5 minutes) compared to Dex-washout and Dex-off. Sleep during the 5 days of Dex treatment showed: earlier sleep onset time, increased number of sleep minutes, higher sleep efficiency, fewer number of wake episodes (>5 minutes) compared to Dex-washout days (6-15) and Dex-off days (16-28). The effect of dexamethasone on wake and sleep was greatest during the 5 days of treatment, was intermediate during the 10 day washout window and was least during the 13 days at the end of the treatment cycle. This effect was more evident in a subgroup of 28 children treated with Dex who are younger than 10 years old. No significant differences were found for age groups (less than 5 years vs. 5 years or above), gender and steroids (Dex vs. Pred). Interestingly, using the CSHQ 14/23 patients (61%) were identified as poor sleepers with a CSHQ score > 41; mean score for the whole group was 45. CSHQ wake up time strongly correlated with the actigraph data wake up time (r= 0.83). These findings suggest young children with standard risk ALL dexamethasone experience increased sleep both during the day and night. The increase in daytime sleepiness in these children cannot be attributed to nighttime sleep disruption; in fact these children went to sleep earlier and slept with fewer awakenings during dexamethasone treatment. The mechanisms for this change in daytime and nighttime sleep are not understood. Cerebral spinal fluid and plasma cytokines are being measured for these patients to evaluate their role in regulating their sleep. Disclosures: No relevant conflicts of interest to declare.
Single low doses of MPTP decrease tyrosine hydroxylase expression in the absence of overt neuron loss

Parkinson's disease (PD) is the second most common age-related neurodegenerative disease. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a prototypical neurotoxicant used in mice to mimic primary features of PD pathology including striatal dopamine depletion and dopamine neuron loss in the substantia nigra pars compacta (SNc). In the literature, there are several experimental paradigms involving multiple doses of MPTP that are used to elicit dopamine neuron loss. However, a recent study reported that a single low dose caused significant loss of dopamine neurons. Here, we determined the effect of a single intraperitoneal injection of one of three doses of MPTP (0.1, 2 and 20mg/kg) on dopamine neurons, labeled by tyrosine hydroxylase (TH+), and total neuron number (Nissl+) in the SNc using unbiased stereological counting. Data reveal a significant loss of neurons in the SNc (TH+ and Nissl+) only in the group treated with 20mg/kg MPTP. Groups treated with lower dose of MPTP (0.1 and 2mg/kg) only showed significant loss of TH+ neurons rather than TH+ and Nissl+ neurons. Striatal dopamine levels were decreased in the groups treated with 2 and 20mg/kg MPTP and striatal terminal markers including, TH and the dopamine transporter (DAT), were only decreased in the groups treated with 20mg/kg MPTP. These data demonstrate that lower doses of MPTP likely result in loss of TH expression rather than actual dopamine neuron loss in the SN. This finding reinforces the need to measure both total neuron number along with TH+ cells in determining dopamine neuron loss.
Tetraparesis Following Dental Extraction: Case Report and Discussion of Preventive Measures for Cervical Spinal Hyperextension Injury

This concerns a patient with compression myelopathy following passive hyperextension of the cervical spine during a dental procedure. Although he had been asymptomatic prior to the procedure, subsequent cervical spinal imaging revealed advanced spondylosis and spinal stenosis. Spinal stenosis is often asymptomatic for a long time. However, when radiculomyelopathy occurs after minor trauma to the head or neck, the patient is often found to have spinal stenosis. Specifically, hyperextension of a cervical spine with spondylotic changes can lead to compression myelopathy. Acquired spinal stenosis correlates positively with aging. As the size of the elderly population continues to increase the prevalence of cervical spondylotic radiculo-myelopathy will likely increase as well. Since appropriate precautions against potential neurologic damage can be undertaken, we suggest radiographic screening for pre-existing spinal stenosis prior to a procedure requiring hyperextension of the neck. Preventive measures for individuals with asymptomatic spondylotic changes and education of all health-care professionals to avoid abrupt or prolonged hyperextension of the cervical spine is emphasized.
Parameters Of Motion and EMG Activities During Some Simple Motor Tasks in Normal Subjects and Cerebellar Patients

Although the analysis of the connections and properties of the elements of the cerebellar cortex and nuclei has added much to our knowledge (Eccles, Ito, & Szentagothai, 1964; Llinas, 1969), the problem of defining the roles exerted by the cerebellum on motor activities remains widely open. One way of approaching part of this problem is to ask questions concerning the utilization of sensory input data in the control of ongoing movements and how this utilization is affected by cerebellar lesions. Indeed, anatomical and physiological data indicate that several sensory inputs are used in the tasks performed by the cerebellum. When movements of the limbs are considered, a prominent role in their control should be assigned to those input signals generated by motion, that is, by the event which the cerebellum is contributing to control. Therefore, an analysis of the input-output relations between parameters of the motion and motor outputs to agonist and antagonist, both under normal conditions and following cerebellar lesions, becomes a logical necessity. By this approach one can hope to find clues as to the logic by which different types of movements are controlled by the system which comprises the cerebellum.
Fertility Preservation Services for Women With Newly Diagnosed Cancer: A National Assessment.

Objective To study the resources available for cancer patients once referred for fertility preservation. Materials and methods Cross-sectional study clinics that are members of the Society for Assisted Reproductive Technology assess support for fertility preservation. Results Surveys were distributed to a total of 1135 members at 394 Society for Assisted Reproductive Technology clinics. Responses were received from 99 individuals representing a total of 84 unique clinics (21.3%). Most clinics (76%) are able to see new cancer patients within 24 to 48 hours after a referral. Clinics most commonly offer oocyte freezing and embryo freezing (96% and 98%, respectively), with a significantly smaller portion of clinics offering ovarian tissue freezing (26%). Although most clinics offer fertility preservation for breast cancer, hematologic cancers and ovarian cancer, only 31% of clinics offer fertility preservation for pediatric premenarchal cancers. Clinics that receive >20 referrals from oncology centers annually are more likely to be in the Northeast and have an academic affiliation. These clinics are more likely to provide support for patients during their cancer treatment, more likely to have long-term follow-up with cancer patients and similarly more likely to have cancer patients return to take advantage of their treatment. Conclusions There are significant geographic and clinic variations in support for fertility preservation. Clinics overall are able to expeditiously see patients to avoid delays in oncologic treatment. Clinics that provide additional support and long-term care tend to have a larger oncologic volume and have more patients who utilize their fertility treatment upon completion of cancer therapy.
Low Rate of Cervical Cancer Screening among Women with Hematologic Malignancies after Stem Cell Transplant.

Abstract Annual cervical cancer screening with Papanicolaou (Pap) and human papillomavirus (HPV) testing after stem cell transplant (SCT) is recommended, but the uptake is unknown. We aimed to determine the prevalence and predictors of cervical cancer screening in patients with hematologic malignancies. We searched MarketScan Commercial Claims database for women who underwent allogeneic or autologous SCT. The primary outcome was cervical cancer screening, defined as procedures or abnormal results for HPV and/or Pap testing according administrative codes within 2 years after SCT. A multivariable logistic regression model was fitted with cancer type, SCT year, age, geographic area, insurance plan, comorbidity, and presence of graft-versus-host disease (GVHD).The study included 1484 patients; 1048 patients (70.6%) had autologous and 436 (29.4%) allogeneic SCT. Mean age was 52.5 years. Overall, 660 patients (44.5%) had screening within 2 years after SCT, 214 (49.1%) with allogeneic SCT and 446 (42.6%) with autologous SCT (P = .02). In the allogeneic SCT group, patients with GVHD had a lower rate of screening than patients without GVHD (42.5% versus 55.4%, P
ABO hemolytic disease of the fetus and newborn: thirteen years of data after implementing a universal bilirubin screening and management program.

ABO hemolytic disease occurs among neonates with blood groups A or B delivered to group O women. Extreme neonatal hyperbilirubinemia due to ABO disease has been reported, but its frequency is not well known. We sought to determine the odds of developing severe ABO hemolytic disease in the 13 years since adopting universal bilirubin screening/management in the Intermountain Healthcare system. We conducted a retrospective analysis of neonates born between 2004 and 2016, defining “severe hemolytic disease” as; (1) total serum bilirubin (TSB) >25 mg/dL, or (2) hospital readmission for jaundice, or (3) bilirubin encephalopathy. Neonates born to group O (+) mothers were included and considered either; (1) Controls (not at risk for ABO disease because they were group O), (2) Study subjects (at risk for ABO disease because they were group A or B). Of 400,531 live births, 47% were to group O women; 86% of whom were group O (+). Overall, 42,529 (27%) neonates born to group O (+) women had their blood group determined; 29,729 (68%) were O, 10,682 (25%) A, and 3109 (7%) B. Peak TSBs during the first 10 days were higher in group A (11.0 ± 4.2 mg/dL) and B (11.5 ± 4.3) than group O neonates (10.3 ± 4.1). However the relative risks of a TSB ≥25 mg/dL, readmission for jaundice, or kernicterus, were the same in the control vs. study groups. In our health system, severe hemolytic disease in neonates born to group O (+) woman is not more likely in group A or B neonates than in controls (group O). We recognize that in other practices, particularly those who do not have a universal bilirubin screening/management program, ABO hemolytic disease severity might be different than in our system.
Pathogenic CTC1 mutations cause global genome instabilities under replication stress

Coats plus syndrome is a complex genetic disorder that can be caused by mutations in genes encoding the CTC1-STN1-TEN1 (CST) complex, a conserved single-stranded DNA binding protein complex. Studies have demonstrated that mutations identified in Coats plus patients are defective in telomere maintenance, and concluded that Coats plus may be caused by telomere dysfunction. Recent studies have established that CST also plays an important role in countering replication stress and protecting the stability of genomic fragile sites. However, it is unclear whether instabilities at genomic regions may promote Coats plus development. Here, we characterize eleven reported disease-causing CTC1 missense and small deletion mutations in maintaining genome stability. Our results show that these mutations induce spontaneous chromosome breakage and severe chromosome fragmentation that are further elevated by replication stress, leading to global genome instabilities. These mutations abolish or reduce CST interaction with RAD51, disrupt RAD51 foci formation, and/or diminish binding to GC-rich genomic fragile sites under replication stress. Furthermore, CTC1 mutations limit cell proliferation under unstressed condition and significantly reduce clonal viability under replication stress. Results also suggest that the aa 600-989 region of CTC1 contains a RAD51-interacting domain. Our findings thus provide molecular evidence linking replication-associated genomic defects with CP disease pathology.
The Absorption Cross Section of Copper for Thermal Neutrons

The rate of neutron absorption in several gold and copper samples has been measured in the PCTR for two different configurations of the fuel and moderator. From these rates, and the corresponding c...
Active Two-Terminal Devices for Terahertz Power Generation by Multiplication

Devices from two major groups of active two-terminal devices, i.e., transit-time diodes and transferred-electron devices, have been employed successfully to generate RF power levels of more than 1 mW at frequencies above 200 GHz. The extraction of higher harmonics from the internal frequency multiplication in these inherently nonlinear devices has often been the means for reaching submillimeter-wave frequencies. The RF power levels at high millimeter-wave and even submillimeter-wave frequencies are also high enough to reach higher terahertz frequencies with external frequency multiplication. At frequencies up to 300 GHz, Si IMPATT diodes yielded the highest RF power levels from any fundamental solid-state source, e.g., 50 mW at 245 GHz and 7.5 mW at 285 GHz. However, the RF power of more than 1 mW from InP Gunn devices around 315 GHz is the highest from any such fundamental RF source above 300 GHz. GaAs TUNNETT diodes yielded 100 ± 5 mW in the fundamental mode at 100–107 GHz. Operating as efficient self-oscillating frequency multipliers, they generated RF power levels of more than 10 mW at 202 GHz and more than 4 mW at 235 GHz. GaAs IMPATT diodes, e.g., yielded 2 mW at 232 GHz and 1 mW at 242 GHz. This paper reviews the power generation capabilities and basic properties of these two-terminal devices as fundamental RF sources. It compares the abovementioned devices, but also other two-terminal devices such as RTDs and SLEDs directly at the RF power level, but also in terms of RF power per unit area as a figure of merit. The paper also compares up-conversion efficiencies and dc power consumption of these two-terminal devices.
The impact of tellurite glass on contact resistance of the fire through dielectric (FTD) c-Si solar cell with lightly doped emitter

In this paper, the influence of Te-glass frit on silver screen-printed contact formation in crystalline Si solar cell is reported. During fire through dielectric (FTD) contact process, the Te-glass frit enhances the formation of Ag 2 Te and PbTe in the reformed glass underlying the front Ag gridline. The presence of Ag 2 Te, which is a semi-metal, heightens the electron tunneling probability and in turn reduces the contact resistivity. The formation of the Ag 2 Te and PbTe is supported by Raman spectra peaks at 79 cm−1, 119 cm−1, 145 cm−1, 183 cm−1, 195 cm−1 and 660 cm1 for the Ag pastes after HNO 3 treatment. SEM also reveals that most metal crystallites are embedded in the glass layer rather than silicon. This means that, these glass layers play important role in the electron tunneling from Si into the Ag gridline.
High-pressure blood flow restriction with very low load resistance training results in peripheral vascular adaptations similar to heavy resistance training.

OBJECTIVE To investigate vascular adaptations to eight weeks of resistance exercise, with and without different pressures of blood flow restriction (BFR), in the upper and lower body. APPROACH Forty individuals (men = 20, women = 20) completed eight weeks of resistance exercise at very low loads (15% of one-repetition maximum (1RM)), with two levels of BFR (40% arterial occlusion pressure (AOP), 80% AOP), without BFR, and 70% of 1RM. Vascular conductance and venous compliance were measured via plethysmography before and following training in the forearms and in the calves. MAIN RESULTS Values reported as means (95% confidence intervals). Pre to post changes in vascular conductance occurred only in the high-pressure conditions (upper body: +8.29 (3.01-13.57) ml · mmHg-1; lower body: +7.86 (3.37-12.35) ml · mmHg-1) and high-load conditions (upper body: +8.60 (3.45-13.74) ml · mmHg-1); lower body: +7.20 (2.71-11.69) ml · mmHg-1) only. In the upper body, the change was significantly greater in the high-pressure and high-load conditions compared to the change observed in the low-pressure condition (-0.41 (-5.56, 4.73) ml · mmHg-1). These changes were not greater than the change observed in the low-load condition without pressure (+1.81 (-3.47, 7.09) ml · mmHg-1). In the lower body, the change in the high-pressure and high-load conditions were significantly greater than the changes observed with low-load training with (-0.86 (-5.60, 3.87) ml · mmHg-1) and without (-1.22 (-5.71, 3.27) ml · mmHg-1) a low pressure. Venous compliance increased in all groups in the upper body (+0.003 (.000 08, 0.006) ml · 100 ml-1 · mmHg-1) only, with no changes in the lower body. SIGNIFICANCE High-pressure BFR causes adaptations in vascular function following eight weeks of training at mechanical loads not typically associated with such adaptations.
Decentralized network level adaptive signal control by multi-agent deep reinforcement learning

Abstract Adaptive traffic signal control systems are deployed to accommodate real-time traffic conditions. Yet travel demand and behavior of the individual vehicles might be overseen by their model-based control algorithms and aggregated input data. Recent development of artificial intelligence, especially the success of deep learning, makes it possible to utilize information of individual vehicles to control the traffic signals. Several pioneering studies developed model-free control algorithms using deep reinforcement learning. However, those studies are limited to isolated intersections and their effectiveness was only evaluated in ideal simulated traffic conditions by hypothetical benchmarks. To fill the gap, this study proposes a network-level decentralized adaptive signal control algorithm using one of the famous deep reinforcement methods, double dueling deep Q network in the multi-agent reinforcement learning framework. The proposed algorithm was evaluated by the real-world coordinated actuated signals in a simulated suburban traffic corridor which emulates the real-field traffic condition. The evaluation results showed that the proposed deep-reinforcement-learning-based algorithm outperforms the benchmark. It is able to reduce 10.27% of the travel time and 46.46% of the total delay.
Probabilistic Prognostic Estimates of Survival in Metastatic Cancer Patients (PPES-Met) Utilizing Free-Text Clinical Narratives.

We propose a deep learning model - Probabilistic Prognostic Estimates of Survival in Metastatic Cancer Patients (PPES-Met) for estimating short-term life expectancy (>3 months) of the patients by analyzing free-text clinical notes in the electronic medical record, while maintaining the temporal visit sequence. In a single framework, we integrated semantic data mapping and neural embedding technique to produce a text processing method that extracts relevant information from heterogeneous types of clinical notes in an unsupervised manner, and we designed a recurrent neural network to model the temporal dependency of the patient visits. The model was trained on a large dataset (10,293 patients) and validated on a separated dataset (1818 patients). Our method achieved an area under the ROC curve (AUC) of 0.89. To provide explain-ability, we developed an interactive graphical tool that may improve physician understanding of the basis for the model’s predictions. The high accuracy and explain-ability of the PPES-Met model may enable our model to be used as a decision support tool to personalize metastatic cancer treatment and provide valuable assistance to the physicians.
Monotonicity of Entropy in Positively Correlated Ising Trees

This paper provides results concerning the monotonicity of entropy within a family of Ising models defined by a positively correlated statistic on a tree. It uses a message passing approach to show that the marginal entropy at any set of sites is monotone decreasing in each of the exponential parameters indexing the model.
Portosystemic shunt embolization in overt hepatic encephalopathy

Hepatic encephalopathy develops in up to 50% of cirrhotic patients and up to 80% have precipitating factors. Medical therapy options are mainly limited to nonabsorbable disaccharides and nonabsorbable antibiotics. The majority of patients who recover from an episode of overt hepatic encephalopathy require maintenance medications. However, a small fraction of patients develop recurrent or persistent HE despite optimal medication use. Moreover, this group of patients usually does not have identifiable precipitating factors. In these challenging cases, clinicians should search for a large portosystemic shunt with contrast-enhanced computed topography or magnetic resonance imaging. Patients with preserved liver function with low Model for End-Stage Liver Disease (MELD) score (arbitrarily defined as ≤15) should be considered for shunt embolization. Previous case series have shown improvement of hepatic encephalopathy in 59% to 90% of patients.
Utilization of deceased organ donors based on HIV, hepatitis B virus, and hepatitis C virus screening test results.

Background Potential deceased organ donors are screened for human immunodeficiency virus (HIV-1), hepatitis B virus (HBV), and hepatitis C virus (HCV) with serologic tests and nucleic acid tests (NATs). The results of these tests on the utilization of donors have not been directly measured. Methods Twenty-six organ procurement organizations (OPOs) provided primary HIV, HBV, and HCV screening results and utilization information for donor referrals evaluated from 2004 to 2017. Additional information regarding donor organ utilization was obtained from the Organ Procurement and Transplantation Network database. Data were analyzed using logistic regression. Results Test results were submitted for 38 166 potential deceased organ donors; 31 (0.1%) were HIV NAT-negative but seropositive, 5.2% were HBV core antibody-positive and NAT-negative, while 1.8% were HCV antibody-positive and NAT-negative. Organ utilization of HBV and/or HCV NAT-negative organs increased over time despite positive antibody status. Conclusions Nucleic acid test detected infections in seronegative donors, especially for HCV. The use of NAT for deceased donor screening correlated with increased utilization of donor organs.
Employed the Fingerprint Recognition Technology to Manage Smart Warehouse

We used the technology of fingerprint identification to monitor and manage the despondence information and data of warehouse. As for the warehouse environment’s temperature and humidity that can too be real-time monitored to ensure the quality of goods. We also proposed an innovative and practical monitoring method that can be used in warehouse whose space is up to 100 square meters. The administrators can instantly know the status of the warehouse through the mobile devices. The results of experiments, the accuracy of fingerprint analysis shows the fingerprint identification to be suitable to the access control mechanism of warehouse.
Robust Reinforcement Learning using Adversarial Populations

Reinforcement Learning (RL) is an effective tool for controller design but can struggle with issues of robustness, failing catastrophically when the underlying system dynamics are perturbed. The Robust RL formulation tackles this by adding worst-case adversarial noise to the dynamics and constructing the noise distribution as the solution to a zero-sum minimax game. However, existing work on learning solutions to the Robust RL formulation has primarily focused on training a single RL agent against a single adversary. In this work, we demonstrate that using a single adversary does not consistently yield robustness to dynamics variations under standard parametrizations of the adversary; the resulting policy is highly exploitable by new adversaries. We propose a population-based augmentation to the Robust RL formulation in which we randomly initialize a population of adversaries and sample from the population uniformly during training. We empirically validate across a variety of benchmarks that the use of an adversarial population results in a less exploitable, more robust policy. Finally, we demonstrate that this approach provides comparable robustness and generalization as domain randomization on these benchmarks while avoiding a ubiquitous domain randomization failure mode.
The poly (ADP-ribose) polymerase (PARP) inhibitor ABT-888 potentiates the topoisomerase I poison irinotecan

1590 Chemical synthetic lethality is a novel concept in cancer chemotherapy. The approach is based on exploiting drugs that impair DNA-damage repair in tumors with a genetic defect in a DNA repair pathway; thus, achieving tumor cell kill by combining two otherwise non-lethal effects. If standard DNA-damaging agents are added that require either of the blocked pathways to repair their lesions, potentiation of the lethal effects are expected. In this study, we explored the effectiveness of chemical synthetic lethality by combining the PARP inhibitor ABT-888 and irinotecan in breast, ovarian, colon and lung cancer cell lines with known aberrations in DNA repair. The methyltetrazolium (MTT) assay was used to assess the cytotoxic activity of single agents versus their combination in MCF-7, MDA-MD-231, T47D and MX-1 breast cancer cell lines, in A2780 and A2780cis ovarian cancer cells, the H460, A549, H226 and HOP92 lung lines, as well as the HT29 and HCT116 colon cancer lines. Combination studies were performed at a fixed dose (210 nM) of ABT-888 with 8 irinotecan concentrations between 10 pM to 100 µM. The ABT-888 concentration reflects drug plasma levels that can be achieved in mice and humans. ABT-888 showed minimum single agent activity with an inhibitory concentration 50 % (IC50) of >80 µM in all but the MX-1 cell line, which had an IC50 of 4 µM. Single agent irinotecan IC50s ranged from 1-10 µM. ABT-888 was able to potentiate irinotecan cytotoxicity in 4/12 cell lines, namely the 2 breast cancer cell lines T47D (10,000-fold) and MX-1 (200-fold), the ovarian line A2780 (20-fold) and the lung cancer cell line HOP62 (9-fold). Upon investigation of DNA repair abnormalities in the responsive cell lines, potential determinants of response emerged: a) mutations in the BRCA1 tumor suppressor protein as found in the MX-1 cell line confer ABT-888 single agent activity; b) elevated protein levels of the nucleotide excision repair enzyme ERCC1 sensitize to the ABT-888/irinotecan combination in T47D, A2780, and HOP62 cells; and c) p53 mutations enhance tumor cell kill by the ABT-888/irinotecan combination in cell lines with high ERCC1 levels such as T47D. To confirm the involvement of PARP inhibition and irinotecan-mediated DNA single strand breaks in the induction of lethal double strand breaks (DSB), we measured the occurrence of phosphorylated H2AX (γ-H2AX), which is an indicator of the recruitment of repair factors to DSB sites. γ-H2AX was readily induced in T47D cells after 4 hrs and was further increased at 24 hrs after addition of the combination, but not by single agent irinotecan. Concomitantly PARP levels were reduced. Our data suggest that the combination of ABT-888 and irinotecan might be effective in breast, ovarian, lung and colon cancer patients and should be tested in clinical trials. The latter should assess BRCA1 and p53 mutational status, as well as the measurement of ERCC1 and γ-H2AX levels as response correlates.
Relationship between industry royalty and licensing payments and patent authorship among orthopedic spine surgeons.

Abstract BACKGROUND CONTEXT The Physician Payments Sunshine Act requires manufacturers of drugs, medical devices, medical supplies, and biologics to record all financial relationships with physicians in the Open Payments database with the goal of increasing transparency for patients and the general public. The majority of total money going to orthopedic surgeons has been found to go to a small number of surgeons in the form of royalties and licensing payments. This category of payment is intended to compensate physicians for use of their intellectual property. However, little research has been done to investigate the degree to which these physicians own intellectual property. PURPOSE To the authors’ knowledge, the association between patents and industry payments to orthopedic surgeons has not been explored. We quantify the association between the patents and academic productivity of orthopedic spine surgeons and the amount of royalty and licensing fees they receive. We then compared this with the associations observed for other categories of payments. STUDY DESIGN Cross-sectional study METHODS Top royalty and licensing earners, defined as those who collectively earned 50% of all royalty and licensing payments over the period August 2013–December 2018, were identified. The h-index, publication count, and patent count of this group were compared with top earners of other payment categories using the Mann-Whitney U test. The association between (1) earnings and patent counts, (2) earnings and manuscript counts, and (3) earnings and h-index among the top royalty and licensing earners was assessed using Spearman correlation. RESULTS Top royalty and licensing earners had significantly more patents than every comparison group except the top earners of money derived from ownership in a biomedical company. For this one exception, there was a trend toward the top eight royalty and licensing earners having more patents (p=.054). The top royalty and licensing earners had significantly more manuscripts than three of the five comparison groups and significantly higher h-indices than four of the five comparison groups. Among the top royalty and licensing earners, receiving more royalty and licensing payments was associated with holding more patents, but not with publishing more papers or having higher h-indices. CONCLUSIONS There is a strong association between the number of patents authored by individual orthopedic spine surgeons and the amount of royalty and licensing fees they receive from industry. This supports the hypothesis that these payments serve as compensation to inventor-surgeons for their intellectual property. CLINICAL SIGNIFICANCE Our findings provide new, important context for the largest category of industry payments to orthopedic spine surgeons and suggests that physicians’ patents should be considered when evaluating financial transactions between industry and physicians.
Care Ethics in Online Teaching

As a teacher educator, I sought to understand how to cultivate care ethics in my online teaching over a three-year period. Through surveys, student work, interviews, my course materials and teachin...
Student Performance in Online Classes at a Hispanic-Serving Institution: A Study of the Impact of Student Characteristics in Online Learning

As online enrollment increases in the United States, it is important to understand the impact of course modality on student outcomes. In particular, there has been limited research on the effect of course enrollment at Hispanic-serving institutions (HSI). The current study evaluated the effect of online course enrollment on student grades and on student withdrawal rates by comparing outcomes in online and face-to-face classes. The main innovation of this study is to use propensity score analysis to control for 15 different student characteristics as a way to control for the selection bias introduced when students self-select into different course modalities. The study used data from a large, public, HSI in the mountain west during the 2017-2018 and 2018-2019 academic years. Baseline results on a two-sample t- test indicated that online students have significantly higher course grades, and non-significantly different withdrawal rates before controlling for student characteristics. The study used a propensity score analysis (PSA) to control for 15 confounding covariates after testing three different PSA models: near-neighbor matching, Mahalanobis’ metric, and optimal matching. After evaluating each model for validity and sensitivity, a near-neighbor 1:2 matching PSA shows a non-significant difference in student grades, and higher withdrawal rates in online classes than face-to-face classes. Given these results, institutions should ensure that they are providing adequate academic support for online students to improve retention and success rates for online students.
Effect of Water Volume Fraction on Electrical Conductivity and Ion Diffusivity in Agarose Gels

Electrical conductivity of agarose gels in 0.15 M KCl was measured. From the experimental data, a functional relation of solute diffusivity to tissue permeability and solute size was derived. This relationship agreed with the experimental results on macromolecule diffusivity in agarose gel published in the literature.
The Coase Theorem, Land Use Entitlements, and Rational Government

This essay constitutes chapter 6 of my forthcoming book, Zoning Rules! The Economics of Land Use Regulation, which the Lincoln Institute of Land Policy will publish in 2015. This chapter offers a formal structure with which to analyze land use controversies and an evaluation of its relevance. The first part introduces the Coase theorem and applies it to a famous dispute between feuding hotel owners in Miami Beach, Florida. A modification of elementary supply and demand curves, “the entitlements diagram,” is developed in this highly localized context and deployed to illustrate the Coasian approach. I then expand the analysis to include local public goods in a less famous but more practical example involving a rezoning by a successful developer in Lebanon, New Hampshire. The expansion of the entitlements analysis to include local government decisions requires a model of governance that relies on someone called the “median voter,” who is usually in the majority of local elections. The median voter model is the workhorse of local public economics, but it is nonetheless controversial in the legal academy. Many believe that the preferences of the majority do not actually prevail and, when the majority does rule, it is unlikely to respond rationally to economic incentives. I review the econometric evidence that confirms that the median voter's preferences determine government policies and that those policies rationally advance the interests of the majority. The evidence is more controversial in the case of compensation for regulatory takings. It is explored using the experience from a voter initiative in Oregon in 2003, which called for compensation for land use regulation but resulted almost invariably in deregulation. Despite this special example, I conclude from other examples that local governments and the zoning laws they enact are generally no less economically rational than their purely private cousins, modern American business corporations.
Cyclic Nucleotides and Blood Vessel Contraction

The sections in this article are: 1 Effects of Vasoactive Agents on Cyclic Nucleotide Levels 2 Effects of Externally Applied Cyclic Nucleotides 3 Adenylate and Guanylate Cyclases 4 Cyclic Nucleotide Phosphodiesterases and Phosphodiesterase Inhibitors 4.1 Distribution 4.2 Multiple Forms of Phosphodiesterase 4.3 Inhibitors 4.4 Comparative Studies in Hypertensive Rats 5 Cyclic Nucleotide-Dependent Protein Kinases 6 Interactions Between Cyclic Nucleotides and Ca2+ 7 Conclusion
Significance of urethral vascular pulsations in genuine stress urinary incontinence.

Abstract Urodynamic tracings of 100 women with genuine stress incontinence revealed urethral vascular pulsations in 15 patients, while 85 lacked vascular pulsations. The presence of vascular pulsations correlated with the maximal urethral closure pressure and identified a subgroup of genuine stress incontinence with normal sphincter strength and reflex activity. The only identifiable cause of stress incontinence for each patient in this group was a deficiency in the anatomic supports of the urethrovesical junction responsible for poor transmission of intra-abdominal pressure to the urethra during stress. Those patients lacking vascular pulsations demonstrated resting sphincter weakness as well as decompensation of the sphincteric mechanism with changes in bladder volume and posture. In most women with genuine stress incontinence, the etiology is a combination of urethral sphincter dysfunction and poor anatomic support of the urethrovesical junction.
Discovery and development of orexin receptor antagonists as therapeutics for insomnia

Insomnia persistently affects the quality and quantity of sleep. Currently approved treatments for insomnia primarily target γ-aminobutyric acid-A (GABA-A) receptor signalling and include benzodiazepines and GABA-A receptor modulators. These drugs are used to address this sleep disorder, but have the potential for side effects such as tolerance and dependence, making them less attractive as maintenance therapy. Forward and reverse genetic approaches in animals have implicated orexin signalling (also referred to as hypocretin signalling) in the control of vigilance and sleep/wake states. Screening for orexin receptor antagonists using in vitro and in vivo methods in animals has identified compounds that block one or other of the orexin receptors (single or dual orexin receptor antagonists [SORAs and DORAs], respectively) in animals and humans. SORAs have primarily been used as probes to further elucidate the roles of the individual orexin receptors, while a number of DORAs have progressed to clinical development as pharmaceutical candidates for insomnia. The DORA almorexant demonstrated significant improvements in a number of clinically relevant sleep parameters in animal models and in patients with insomnia but its development was halted. SB-649868 and suvorexant have demonstrated efficacy and tolerability in Phase II and III trials respectively. Furthermore, suvorexant is currently under review by the Food and Drug Administration for the treatment of insomnia. Based on the publication of recent non-clinical and clinical data, orexin receptor antagonists potentially represent a targeted, effective and well-tolerated new class of medications for insomnia. Linked ArticlesThis article is part of a themed section on Orexin Receptors. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-2
The fused multiply-add instruction leads to algorithms for extended-precision floating point: applications to java and high-performance computing

Portability in Java requires that all architectures produce the same result for a particular floating-point calculation. Conceptually, the best defnition for this result is the correctly rounded value of the infinitely precise result. Although this is likely an unattainable goal in general, it should be striven for when attainable with reasonable performance. Although many architectures implement IEEE double-precision arithmetic in hardware, providing the correctly rounded result for the basic operations (+,-,*,/) with good performance, most do not provide hardware support for extended precison arithmetic. The performance and accuracy of the resulting software implementations can be poor.Many machines provide a double-precision fused multiply-add (FMA) instruction that computes d = a * b + c with d correctly rounded. Using the FMA instruction, higher performance algorithms for extended-precision arithmetic can be divised. We present examples of such algorithms for the basic operations, +,-,*,/. The algorithms always compute the exact result for each of the operations. This contributes to the Java goal of portability by providing a large Spectrum of architectures on which it is possible to efficiently implement correctly rounded extended precision floating point. The FMA is also valuable in large-scale computation of linear algebra problems, where the accumulation of dot products is a basic operation. Performing this accumulation in extended precision greatly increases the size of problem that may be solved before roundoff error becomes a limiting factor. It also produces a much faster way, over just using IEEE arithmetic, of doing the more accurate computation.Given two integers a and b, there exist unique integers q and r such that a = bq + r with 0 ≤ r < b. In number theory, this lemma is the computational basis for proving the Fundamental Theorem of Arithmetic.Note that a = bq + r has the same form as the FMA. The exact nature of the FMA and this lemma allow us to define multiplication and division of IEEE numbers exactly. Furthermore, the FMA instruction provides a much faster way to perform these exact computations. Thus, we will demonstrate a clear need for Java to accept the FMA as a standard instruction.Finally, we demonstrate the accuracy of the algorithms on example problems (matrix multiplication, 2 × 2 determinant, complex multiplication, and triangle area calculation), for which existing computer arithmetic gives completely inaccurate results in certain instances.
The Black-Green-White Divide: The Impact of Diversity in Environmental Nonprofit Organizations

Nonprofits are the lifeblood of the environmental movement. Environmental organizations are the dominant force in framing and pursuing environmental protection goals, and environmental justice advocates have focused on the elimination of environmental discrimination and pursuit of policies to halt the inequitable imposition of environmental hazards on communities of color. Environmental justice advocates have bemoaned the dearth of mainstream environmental organization support for environmental equity goals. The author describes this gulf as the black-green-white divide that separates black and white environmentalism. This divide threatens to be the fault line of the modern environmental movement. While much has been written about the racial disconnect between the environmental justice movement and the traditional environmental movement, this piece adds to this discussion in two ways. First, the article exemplifies the tragic consequences of this divide through a case study of an ongoing controversy over the construction of a bridge between two predominately African American communities on the shores of a lake which shoulders a hazardous waste site. Second, using the principles of corporate governance, the author suggests that the fiduciary duty of obedience to organizational mission obligates environmental justice organization boards of directors to diversify composition and should encourage environmental nonprofits to institute staff and information gathering resources that enable them to aptly recognize the impact of environmental racism on communities of color.
Novel QTL associated with the Fusarium head blight resistance in Truman soft red winter wheat

Fusarium head blight (FHB) mainly caused by Fusarium graminearum Schwabe causes devastating losses in wheat globally. ‘Truman’ winter wheat, developed and released by the University of Missouri has excellent broad-based FHB resistance in a superior soft red winter wheat background. This research identified QTL associated with greenhouse type II resistance and field resistance for incidence, severity, Fusarium damaged kernels (FDK), and deoxynivalenol (DON) based on phenotypic data collected in Missouri, Kentucky and Indiana. Two years of replicated phenotypic data were collected on a set of 167 recombinant inbred lines. Genetic linkage maps were constructed using 160 SSR and 530 DArT polymorphic markers. Across years, QTL for type II resistance were identified on chromosomes 1BSc, 2BL, 2DS and 3BSc, for incidence on 2ASc, 2DS, and 3DS and for severity on 2DS and 3BSc. QTL were also detected for incidence on 1DLc and 2DS and for severity on 1BL, 3AL and 3BLC from data collected in Indiana and Kentucky, respectively. Common QTL for FDK on chromosomes 2ASc and 3BLc and for DON on chromosomes 2ASc and 2DS were identified from data from both Missouri and Kentucky, respectively with additional individual QTL for FDK and DON identified from tests at each independent location. All alleles were from Truman and associated with significant reductions in the respective traits. QTL on 2ASC, 2DS and 3DS may be novel and once further validated, should diversify the FHB gene pool globally and be useful for enhancing FHB resistance through marker assisted selection.
Identification and control of inter-area modes

Inter-area oscillations in power systems are becoming common occurrence due to loading increase of tie-lines. Their control is crucial to maintain stability of the system. This paper addresses the identification of the inter-area modes by classifying the modes as local or inter-area using controllability and observability indices. Then power system stabilizers are considered for the control of these modes. Feasibility of control structures is determined using high order residues. A large size system with 9 control areas and 19 generators is used to illustrate the proposed methodologies. >
Falls in Older Adults

Falls are prevalent among older adults and can lead to injury, hospitalization, and increased healthcare costs. Environmental hazards, medications, vision problems, and impairments in strength, gait, or balance can increase fall risk. A multifactorial fall-risk assessment including a fall history, physical exam, gait and balance evaluation, and environmental assessment is recommended for all older adults who present with a fall or problem with gait or balance. Multiple-component exercise programs, tai chi, vitamin D supplementation, withdrawal of psychotropic medications, and early cataract surgery have all been shown to reduce fall rates. Multifactorial interventions that include medication review, vision correction, management of orthostasis, environmental modification, and balance, strength, and gait training can also be beneficial in preventing falls.