cssi/SciSciGPT-SciSciNet huggingface dataset:
A New Chalcone Derivative (E)-3-(4-Methoxyphenyl)-2-methyl-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one Suppresses Prostate Cancer Involving p53-mediated Cell Cycle Arrests and Apoptosis

Previous studies suggested chalcones as antineoplastic drug candidates. We synthesized a new chalcone derivative (E)-3-(4-methoxyphenyl)-2-methyl-1- (3,4,5-trimethoxyphenyl)prop-2-en-1-one, (CHO27) with an up to 1000-fold increased cytotoxic potency relative to its parent compound in cell culture assays. CHO27 at low nanomolar levels, inhibited prostate cancer (PCa) cell growth through cell cycle arrest and caspase-dependent apoptosis. Activation of p53 accounted for, at least in part, the growth inhibition by CHO27 in vitro. Furthermore, i.p. administration of CHO27 suppressed the growth of established PCa 22Rv1 xenograft tumors accompanied with p53 and p21 Cip1 induction. CHO27 may be a lead for
Shades of Gray: The Paleoindian–Early Archaic “Transition” in the Northeast

While many earlier (and not a few contemporary) treatments of the Paleoindian-Early Archaic Transition in the Northeast (of North America) often stress clear-cut macro or quantum changes in climate with resultant dramatic shifts in techno-adaptive strategies, the actual situation is far more opaque. Using data from several key sites in the Northeast, a different view of this moment in time is offered. In this perspective, the “transition” is seen as a series of micro-adjustments in which sociotechnic and subsistence packages are gradationally and almost imperceptibly altered with some elements—like the fluting of projectile points—deleted and others added. Overall, however, there is no profound “signature” to the Paleoindian-Early Archaic Transition in this region.
327 Does a Single Dose of Dexamethasone for Croup Cause Adrenal Suppression?: A Prospective Study

65 (92.9%) 49 (94.2%) 1.3 0.3-5.5 Severe 69 (98.6%) 53 (100.0%) N/A* N/A* Return to School Mild 55 (77.5%) 47 (90.4%) 2.7 0.9-8.0 Severe 64 (90.1%) 50 (96.2%) 2.7 0.5-13.7 Reading/Studying Mild 53 (74.7%) 51 (96.2%) 8.7 1.9-39.2 Severe 58 (81.7%) 49 (96.1%) 5.5 1.2-25.5 *0’s in the 2x2 table Fisher’s exact test (FET), p¼1.00.
Factoring the Seriousness of the Offense into Fourth Amendment Equations - Warrantless Entries into Premises: The Legacy of Welsh v. Wisconsin

The development of workable rules for warrantless entry has no doubt been slowed by the Supreme Court's failure to consistently factor the seriousness of the offense into search and seizure equations. That failure and the Court's adoption of different approaches to factoring the seriousness of the offense into fourth amendment equations in different settings may well reflect the difficulties inherent in finding a viable methodology for distinguishing among and ranking offenses. Whatever approach is taken in other fourth amendment settings, the line between constitutionally permissible and impermissible warrantless entries into homes or other fixed, private, premises should be drawn to coincide with the line most jurisdictions use to distinguish misdemeanors from felonies.
Progress on the Three-Dimensional Structural Determination of Trypsin-Modified EF-TU-GDP

Elongation factor (EF-)Tu is a cytoplasmic protein whose primary function is to recognize and transport aminoacyl tRNAs to the ribosome during protein synthesis (for review, see 1,2). In order to carry out its function, EF-Tu binds to different ligands, including GDP, GTP, EF-Ts, aminoacyl-tRNA and ribosomal proteins, during each elongation cycle. Biochemical studies have indicated that EF-Tu undergoes a series of discrete conformational changes as the protein changes ligands. The long-term objective of the crystallographic studies is to determine the atomic details of the conformational changes during the elongation cycle by X-ray diffraction techniques.
Matrix Metalloprotease 3 Exacerbates Hemorrhagic Transformation and Worsens Functional Outcomes in Hyperglycemic Stroke

Background and Purpose— Acute hyperglycemia worsens the clinical outcomes and exacerbates cerebral hemorrhage after stroke. The mediators of hemorrhagic transformation (HT) in hyperglycemic stroke are not fully understood. Matrix metalloproteinase 3 (MMP3) plays a critical role in the tissue-type plasminogen activator–induced HT. However, the role of MMP3 in exacerbating the HT and worsening the functional outcomes in hyperglycemic stroke remains unknown. Methods— Control/normoglycemic and hyperglycemic (blood glucose, 140–200 mg/dL) male Wistar rats were subjected to middle cerebral artery occlusion for 90 minutes and either 24 hours or 7 days reperfusion. MMP3 was inhibited pharmacologically (UK 356618, 15 mg/kg IV at reperfusion) or knocked down in the brain by shRNA lentiviral particles (injected intracerebroventricular). Neurovascular injury was assessed at 24 hours, and functional outcomes were assessed at 24 hours, day 3, and day 7. MMP3 activity was measured in brain homogenate and cerebral macrovessels. Localization of MMP3 within the neurovascular unit after hyperglycemic stroke was demonstrated by immunohistochemistry. Results— Hyperglycemia significantly increased MMP3 activity in the brain after stroke, and this was associated with exacerbated HT and worsened functional outcomes. MMP3 inhibition significantly reduced HT and improved functional outcomes. Conclusions— MMP3 plays a critical role in mediating cerebrovascular injury in hyperglycemic stroke. Our findings point out MMP3 as a potential therapeutic target in hyperglycemic stroke.
Multi-Priority Cartesian Impedance Control

Manipulator compliance is well known to be important to robot manipulation and assembly. Recently, this has been highlighted by the development of new higly-compliant robot manipulators such as the Barrett arm or the DLR lightweight manipulator [1], [2]. It is also clear that dexterous manipulation involves touching the environment at different locations simultaneously (perhaps at different points on the robot hand or fingers). In these situations, it is particularly attractive to control the system using a multi-priority strategy where several contact points are commanded in parallel. Multi-priority Cartesian impedance control is the natural combination of these two ideas. The system realizes several impedances with different reference positions at different points on the robot with a specified order of priority. We find a controller that minimizes an arbitrary quadratic norm on the second-priority impedance error subject to constraints deriving from the first priority impedance task. We also show that the locally optimal controller does not require force feedback in its implementation for passive desired inertias. The results are illustrated in simulation.
Ion-Molecule Reactions between O - and O 2 at Thermal Energies and Above

The rate coefficients for the reactions of ${\mathrm{O}}^{\ensuremath{-}}$ ions with ${\mathrm{O}}_{2}$ molecules have been measured in a drift-tube mass spectrometer at 300 \ifmmode^\circ\else\textdegree\fi{}K as a function of $\frac{E}{N}$, the ratio of the electric drift field to the gas number density. Two different measurement techniques were employed. One technique was based on the observation of the attenuation of the parent ${\mathrm{O}}^{\ensuremath{-}}$ ion species with increasing drift distance; the other involved examination of the shape of the product ion arrival-time spectra. The rate coefficient for the reaction ${\mathrm{O}}^{\ensuremath{-}}$ + ${2\mathrm{O}}_{2}$ \ensuremath{\rightarrow} ${\mathrm{O}}_{3}^{\ensuremath{-}}$ + ${\mathrm{O}}_{2}$ was measured on the $\frac{E}{N}$ range 6-29 \ifmmode\times\else\texttimes\fi{} ${10}^{\ensuremath{-}17}$ V ${\mathrm{cm}}^{2}$. The rate coefficient was found to be (1.0 \ifmmode\pm\else\textpm\fi{} 0.2) \ifmmode\times\else\texttimes\fi{} ${10}^{\ensuremath{-}30}$ ${\mathrm{cm}}^{6}$/sec over the entire $\frac{E}{N}$ range. The reaction ${\mathrm{O}}^{\ensuremath{-}}$ + ${\mathrm{O}}_{2}$ \ensuremath{\rightarrow} ${\mathrm{O}}_{2}^{\ensuremath{-}}$ + O was observed with a rate that increased sharply with $\frac{E}{N}$. The rate coefficient was found to increase from (2.5 \ifmmode\pm\else\textpm\fi{} 1.5) \ifmmode\times\else\texttimes\fi{} ${10}^{\ensuremath{-}14}$ ${\mathrm{cm}}^{3}$/sec at an $\frac{E}{N}$ of 63 \ifmmode\times\else\texttimes\fi{} ${10}^{\ensuremath{-}17}$ V ${\mathrm{cm}}^{2}$ to a value of (3.4 \ifmmode\pm\else\textpm\fi{} 1.0) \ifmmode\times\else\texttimes\fi{} ${10}^{\ensuremath{-}12}$ ${\mathrm{cm}}^{3}$/sec at an $\frac{E}{N}$ of 140 \ifmmode\times\else\texttimes\fi{} ${10}^{\ensuremath{-}17}$ V/${\mathrm{cm}}^{2}$.
Some Albian (Cretaceous) asteroids (Echinodermata) from Texas and their paleobiological implications

An asteroid fauna is described from the Albian (Cretaceous) interval of the Washita Group of central Texas. New genera and species are Alkaidia sumralli, (Benthopectinidae), Capellia mauricei (Goniasteridae), and Betelgeusia reidi (Radiasteridae). Additional new genera are Fomalhautia (Goniasteridae), and Denebia and Altairia (Ophidiasteridae). Crateraster texensis (Goniasteridae), new combination, is similar to the European type species, C. quinqueloba. An unnamed species of Crateraster and an unassigned goniasterid are also present. All Washita genera are extinct, but all belong to extant families. The fauna is largely distinct from that of the somewhat younger European Cretaceous chalk. The Radiasteridae (e.g., Betelgeusia) is inferred to hold a basal position in the Paxillosida: Betelgeusia extends the range of the family back to the Cretaceous, closer to the diversification of the living asteroid orders. Asteroids capable of burying themselves in sediment (and only self-buriers) share some form of channelization for the passage of water currents between the primary ossicles of the body surface. Channels in Betelgeusia indicate semi-infaunal habits similar to those of living Astropecten and Luidia. Betelgeusia represents the third semi-infaunal paxillosidan family now known from the Cretaceous, although none are known from older rocks, suggesting a broadening of the asteroid adaptive zone during the Cretaceous. The Goniasteridae, Radiasteridae, and Benthopectinidae are less important in shelf settings today than they appear to have been during Washita deposition, whereas the Astropectinidae, Luidiidae, and the Echinasteridae are absent from the Washita although they are common today in similar settings.
STUDY ON IN-HOUSE EXPERIMENTS OF EOR BY NATURE GAS HUFF AND PUFF IN SMALL FAULT BLOCK CELL OIL RESERVOIR

According to he high remaining recoverable reserves,low formation energy,strong isolatisim of well A17-b region in a small fault block oil reservoir offshore,cannot complete development state of injection-production pattern development.using the reinjection of the natural gas and carring out the huff and puff technology measure of natural gas injection per well,it is one of the most feasible methods to enhance oil recovery.Aiming at the geological and development characteristics of the reservoir in WellA17-b area,based on the phase state analysis of the formation fluids,by the swelling experiment of nature gas and reservoir fluids to determine the drive mechanism of nature gas huff and puff,by the drive experiment with long cores of natuer gas huff and puff to illustrate natural gas huff and puff injection can enhance oil recovery well after depletion,of which the result of core test with 30 degrees is better than the others.
Superhydrophobic Surfaces Using Selected Zinc Oxide Microrod Growth on Ink-Jetted Patterns

The synthesis and properties of superhydrophobic surfaces based on binary surface topography made of zinc oxide (ZnO)microrod-decorated micropatterns are reported.ZnO is intrinsically hydrophilic but can be utilized to create hydrophobic surfaces by creating artificial roughness via microstructuring.Micron scale patterns consisting of nanocrystalhne ZnO seed particles were applied to glass substrates with a modified ink-jet printer.Microrods were then grown on the patterns by a hydrothermal process without any further chemical modification.Water contact angle(WCA)~1 up to 153°was achieved. Different micro array patterned surfaces with varying response of static contact angle or sessile droplet analysis are reported.
Milk-borne transmission of HIV. Characterization of productively infected cells in breast milk and interactions between milk and saliva

Objectives Definition of the cellular constituents of breast milk and infant saliva that are involved in milk-borne transmission of HIV infectivity. Study design/methods Productively infected cells in colostrum and milk of HIV-1-seropositive mothers were identified by in situ hybridization and immunocytochemistry. Additionally, normal cells from mature milk were infected in vitro to determine which cell types were capable of supporting productive HIV-1 infection. Cellular interactions and transfer of HIV-1 in saliva-milk mixtures were studied to monitor the viability of milk cells and the potential for transfer of infectious virus during ingestion of milk. Results Colostrum and early milk from HIV-1-seropositive mothers contained 0.1% to 1% productivity infected macrophages and T cells. Macrophages and epithelial cells from mature milk were susceptible to productive HIV infection in vitro. When milk was mixed with saliva, milk cells became disrupted or were bound and endocytized by salivary epithelial cells. Conclusions Productively infected milk cells may contribute directly to transmission of HIV infectivity in breastfed infants during both early and late lactation. Macrophages are the principal cellular carriers of productive HIV-1 infection in milk. Cellular complexes produced during milk-saliva interactions may play a key role in oral transmission of HIV.
Transvaginal pudendal nerve block; a simple procedure for effective anesthesia in operative vaginal delivery.

Abstract In over 97 per cent of 156 patients who had transvaginal pudendal block, the anesthesia was considered good or excellent. Results were best when hyaluronidase was combined with 1 per cent procaine and epinephrine. At this point it is well to remember, however, the caution of Eckenhoff and Kirby 13 that "addition of hyaluronidase to a local anesthetic is not a substitute for the proficiency of the anesthetist or surgeon in performing regional nerve blocks". The transvaginal procedure for obtaining a pudendal nerve block has the following advantages: 1.1. Simplicity of performance. It can be carried out without aid. 2.2. The site of injection is nearest to the nerve to be blocked, affording greater accuracy in direct nerve infiltration. 3.3. The method is safe for mother and infant. No hematoma, infection, or other complication has been encountered in the past five years while this procedure has been used.
Dietary flexibility of Australopithecus afarensis in the face of paleoecological change during the middle Pliocene: Faunal evidence from Hadar, Ethiopia.

One approach to understanding the context of changes in hominin paleodiets is to examine the paleodiets and paleohabitats of contemporaneous mammalian taxa. Recent carbon isotopic studies suggest that the middle Pliocene was marked by a major shift in hominin diets, characterized by a significant increase in C4 foods in Australopithecus-grade species, including Australopithecus afarensis. To contextualize previous isotopic studies of A. afarensis, we employed stable isotopes to examine paleodiets of the mammalian fauna contemporaneous with A. afarensis at Hadar, Ethiopia. We used these data to inform our understanding of paleoenvironmental change through the deposition of the Hadar Formation. While the majority of the taxa in the Hadar fauna were C4 grazers, most show little change in the intensity of C4 food consumption over the 0.5 million-year interval sampled. Two taxa (equids and bovins) do show increases in C4 consumption through the Hadar Formation and into the younger, overlying Busidima Formation. Changes in the distributions of C4-feeders, C3-feeders and mixed-C3/C4-feeders in the sampled intervals are consistent with evidence of dietary reconstructions based on ecomorphology, and with habitats reconstructed using community structure analyses. Meanwhile, A. afarensis is one of many mammalian taxa whose C4 consumption does not show directional change over the intervals sampled. In combination with a wide range of carbon and oxygen isotopic composition for A. afarensis as compared to the other large mammal taxa, these results suggest that the C3/C4 dietary flexibility of A. afarensis was relatively unusual among most of its mammalian cohort.
Clarithromycin increases neuronal excitability in CA3 pyramidal neurons through a reduction in GABAergic signaling

Clinical administration of the macrolide antibiotic clarithromycin has been associated with side effects such as mania, agitation, and delirium. Here, we investigated the adverse effects of this an...
A health care navigation tool assesses asthma self-management and health literacy.

Background Self-management of moderate-to-severe asthma depends on the patient's ability to (1) navigate (access health care to obtain diagnoses and treatment), (2) use inhaled corticosteroids (ICSs) properly, and (3) understand ICS function. Objective We sought to test whether navigation skills (medication recall, knowledge of copay requirements, and ability to provide information needed for a medical visit about a persistent cough unresponsive to medication) are related to other self-management skills and health literacy. Methods A 21-item Navigating Ability (NAV2) questionnaire was developed, validated, and then read to adults with moderate-to-severe asthma. ICS technique was evaluated by using scales derived from instructions in national guidelines; knowledge of ICS function was evaluated by using a validated 10-item questionnaire. Spearman correlation was computed between NAV2 score and these questionnaires and with numeracy (Asthma Numeracy Questionnaire) and print literacy (Short Test of Functional Health Literacy in Adults). Results Two hundred fifty adults participated: age, 51 ± 13 years; 72% female; 65% African American; 10% Latino; 50% with household income of less than $30,000/y; 47% with no more than a 12th-grade education; and 29% experienced hospitalizations for asthma in the prior year. A higher NAV2 score was associated with correct ICS technique (ρ = 0.24, P = .0002), knowledge of ICSs (ρ = 0.35, P P P Conclusions Patients with poor navigational ability are likely to have poor inhaler technique and limited understanding of ICS function, as well as limited numeracy and print literacy. Clinicians should consider these elements of self-management for their effect on asthma care and as a marker of more general health literacy deficits.
Multiscale Thermal Property Measurements for Biomedical Applications

Bioheat transfer-based innovations in health care include applications such as focal treatments for cancer and cardiovascular disease and the preservation of tissues and organs for transplantation. In these applications, the ability to preserve or destroy a biomaterial is directly dependent on its temperature history. Thus, thermal measurement and modeling are necessary to either avoid or induce the injury required. In this review paper, we will first define and discuss thermal conductivity and calorimetric measurements of biomaterials in the cryogenic ( 37 °C) regimes. For thermal conductivity measurements, we review the use of 3ω and laser flash techniques for measurement of thermal conductivity in thin (1 μm–2 mm thick), anisotropic, and/or multilayered tissues. At the nanoscale, we review the use of pump–probe and scanning probe methods to measure thermal conductivity at short temporal scales (10 ps–100 ns) and spatial scales (1 nm–1 μ...
Prestructural cartilage assessment using MRI.

Cartilage loss is irreversible, and to date, no effective pharmacotherapies are available to protect or regenerate cartilage. Quantitative prestructural/compositional MR imaging techniques have been developed to characterize the cartilage matrix quality at a stage where abnormal findings are early and potentially reversible, allowing intervention to halt disease progression. The goal of this article is to critically review currently available technologies, present the basic concept behind these techniques, but also to investigate their suitability as imaging biomarkers including their validity, reproducibility, risk prediction and monitoring of therapy. Moreover, we highlighted important clinical applications. This review article focuses on the currently most relevant and clinically applicable technologies, such as T2 mapping, T2*, T1ρ, delayed gadolinium enhanced MRI of cartilage (dGEMRIC), sodium imaging and glycosaminoglycan chemical exchange saturation transfer (gagCEST). To date, most information is available for T2 and T1ρ mapping. dGEMRIC has also been used in multiple clinical studies, although it requires Gd contrast administration. Sodium imaging and gagCEST are promising technologies but are dependent on high field strength and sophisticated software and hardware. Level of Evidence:5 J. Magn. Reson. Imaging 2016
The Development of Human Resources

(1968). The Development of Human Resources. Journal of Economic Issues: Vol. 2, No. 2, pp. 249-250.
A novel approach for monitoring vertical profiles of boundary-layer pollutants: Utilizing routine news helicopter flights

Abstract Air quality varies greatly in space and time across urban locales. However, criteria pollutants are typically monitored routinely at a relatively small number of surface sites within each metropolitan area, and routine vertical profiles of pollution are typically unavailable. We illustrate that a news helicopter provides an effective sensor platform to provide spatiotemporal analyses and vertical profiles of pollutant concentrations. We are unaware of any other air quality study that has utilized routine helicopter flights, despite the ubiquity of helicopters in urban environments across the world. Particulate and ozone concentration profiles have been collected since 2015 from sensors installed on a news helicopter that travels primarily over the metropolitan areas of northern Utah. The air quality data are retrieved in real time, archived, combined with surface-based observations, and disseminated in terms of time series and maps on a website for research, forecasting, and public awareness. Large vertical variations in particulate pollution concentrations were observed during the 2015–2016 winter associated with meteorological cold-air pool episodes. During the 2015 and 2016 summer seasons, ozone concentrations frequently exhibited complex spatial and temporal variations arising from many interrelated factors, including local terrain-forced circulations, lake breezes, and distant wildfires.
Noise and pitch interact during the cortical segregation of concurrent speech.

Behavioral studies reveal listeners exploit intrinsic differences in voice fundamental frequency (F0) to segregate concurrent speech sounds-the so-called "F0-benefit." More favorable signal-to-noise ratio (SNR) in the environment, an extrinsic acoustic factor, similarly benefits the parsing of simultaneous speech. Here, we examined the neurobiological substrates of these two cues in the perceptual segregation of concurrent speech mixtures. We recorded event-related brain potentials (ERPs) while listeners performed a speeded double-vowel identification task. Listeners heard two concurrent vowels whose F0 differed by zero or four semitones presented in either clean (no noise) or noise-degraded (+5 dB SNR) conditions. Behaviorally, listeners were more accurate in correctly identifying both vowels for larger F0 separations but F0-benefit was more pronounced at more favorable SNRs (i.e., pitch × SNR interaction). Analysis of the ERPs revealed that only the P2 wave (∼200 ms) showed a similar F0 x SNR interaction as behavior and was correlated with listeners' perceptual F0-benefit. Neural classifiers applied to the ERPs further suggested that speech sounds are segregated neurally within 200 ms based on SNR whereas segregation based on pitch occurs later in time (400-700 ms). The earlier timing of extrinsic SNR compared to intrinsic F0-based segregation implies that the cortical extraction of speech from noise is more efficient than differentiating speech based on pitch cues alone, which may recruit additional cortical processes. Findings indicate that noise and pitch differences interact relatively early in cerebral cortex and that the brain arrives at the identities of concurrent speech mixtures as early as ∼200 ms.
Using input-output correlations and a modified slide attack to compromise IEC 62055-41

Developed initially for pre-paid electricity meters in South Africa, the IEC 662055-41 standard is now the world's most ubiquitous open pre-paid metering standard. The standard is used in 35 million meters operated in 400 utilities in 30 countries. It now serves more users in Asia than in Africa. The standard uses 16 cycles of a block-cipher-like substitution and permutation process to both generate 20 digit tokens (through an encryption process) and to decode 20 digit tokens and determine the number of kWhs procured (through a decryption process), in conjunction with a 64 bit decoder key generated using the Data Encryption standard (DES). Despite its popularity, there is little work on the cryptology aspects of this standard. This paper discusses two types of cryptanalysis techniques used to attack this pre-paid metering standard. The first is a statistical analysis of the encrypted and decrypted inputs and outputs to determine if any correlation between them exists. The second is the use of slide attacks, a technique traditionally used for attacking block ciphers that use the same or ‘weak’ round keys for each encryption/decryption cycle. Using this second cryptanalysis attack, it is shown that 16 of the 64 bits of the decoder key can be exposed, an aspect not intended by its designers. Further combination with other techniques may be used to compromise the entire key.
Evaluation of the contribution of values clarification to a brief mindfulness meditation intervention for anxiety.

Objective Evaluate the incremental effects of a computerized values clarification (VC) activity on anxiety symptomology and quality of life over and above establishment of a mindfulness meditation (MM) practice. Method Anxious participants (N = 120, Female = 86; Mage = 22.26) were randomly assigned to a 2-week, 10-min daily MM practice + control task or a 2-week, 10-min daily MM practice + VC task. Pre-assessments and post-assessments included well-established and ideographic self-report measures. Results Overall decreases in past week and past 24-h anxiety symptom frequency, as well as increased quality of life during the previous 24-h cycle only. VC did not have a demonstrable impact on outcomes. Conclusions Though findings are preliminary, brief VC exercises may not enhance outcomes that follow from mindfulness practice. Additional research is needed to isolate specific and shared impacts of mindfulness-based and values-based treatment strategies on anxiety symptoms and quality of life.
Median Growth Percentiles (MGPs): Assessment of Intertemporal Stability and Correlations with Observational Scores.

While states are no longer required to set up teacher evaluation systems based in significant part on student test scores, quite a few continue to use value-added (VAMs) or student growth percentil...
Minimizing Restraint and Seclusion in Schools: A Response to Beaudoin and Moore

Abstract Increasing efforts have been made in the field of special education to identify positive, evidence-based practices (EBPs) to meet the needs of students who engage in problem behavior, with a major goal being to eliminate or limit the use of reactive measures such as restraint and seclusion (Snell & Walker, 2014). Various stakeholders, including families and self-advocates, have voiced concerns about the dangers of restraint and seclusion and the lack of protection afforded to students who engage in severe problem behavior. In the previous article in this issue of Intellectual and Developmental Disabilities, Beaudoin and Moore (2018) echo these concerns in their account of a family's experience with restraint as told from the perspective of a father whose son was subjected to restraint, resulting in a number of adverse short- and long-term consequences that affected the entire family. In response to Beaudoin and Moore, we provide readers with a brief review of the current status of restraint and s...
Unionizing a nonprofit human service organization: lessons from a children’s’ residential and community service agency

This case describes the unionization of residential counselors at a large nonprofit provider of foster care and mental health services in San Francisco, CA. Based on interviews with managers includ...
CFTR misfolds during native-centric simulations due to entropic penalties of native state formation

Cystic fibrosis (CF) is a common genetic disorder that affects approximately 70,000 people worldwide. It is caused by mutation-induced defects in synthesis, folding, processing, or function of the Cystic Fibrosis Transmembrane conductance Regulator protein (CFTR), a chloride-selective ion channel required for the proper functioning of secretory epithelia in tissues such as the lung, pancreas, and skin. The most common cause of CF is the single-residue deletion of F508 (F508del), a mutation present in one or both alleles in 90% of patients that induces severe folding defects and results in greatly reduced expression of the protein. Despite its medical importance, high-resolution mechanistic information about CFTR folding is lacking. In this study, we used molecular dynamics modeling with a native-centric force field to examine the folding and assembly of both full-length CFTR and the isolated first nucleotide-binding domain (NBD1). We observed that the protein was capable of substantial misfolding on both the intradomain and interdomain scale due to entropically favorable kinetic traps that exist on CFTR9s folding free energy surface. These results suggest that even wild type CFTR, in the absence of any disease-related mutations, has suboptimal folding efficiency. We speculate that such entropically-driven misfolding occurs in disease-prone mutants such as F508del and contributes to the protein9s poor in vivo activity.
Combined heart-lung transplantation for end-stage Eisenmenger's syndrome.

Between May, 1981, and December, 1984, thirteen combined heart-lung transplants were performed in 12 patients for the treatment of Eisenmenger’s syndrome. The age range of the recipients was 22 to 42 years. Two patients had undergone previous open cardiac operations; in addition, one had had closure of a persistent ductus arteriosus, one an open lung biopsy, one a pulmonary artery banding, and one patient received a second heart-lung transplant after 3 years. Four recipients died before hospital discharge, one at operation and three at 4, 10, and 33 days after operation. Early symptomatic results and cardiopulmonary function were excellent in all of the survivors. Two patients died 14 and 15 months after transplantation of accelerated graft arteriosclerosis and respiratory failure, respectively, and six remain alive 7 to 44 months after transplantation. Four of these surviving patients and the two patients who died late subsequently had major pulmonary complications. Symptoms included progressive breathlessness, cough (often productive), and fever with physical signs of diffuse crepitations and expiratory rhonchi. Serial pulmonary function tests showed progressive obstructive physiology in all six patients with superimposed restrictive defects in four. Histologic examination of tissue from open lung biopsy or autopsy displayed bronchiolitis obliterans in five of these patients, one of whom required retransplantation. It is possible that these late changes are the result of rejection, since similar changes in one other patient have now been reversed with augmented immunosuppression. Further understanding of the causes and manifestations of late pulmonary deterioration should improve the late functional results of this operation for Eisenmenger’s syndrome.
The Neurobiology of Differential Experience

The biology of the organism is demonstrably altered by experience. Environmentally impoverished rats consistently outweigh their littermates from the enriched environment (Bennett, Diamond, Krech, and Rosenzweig, 1964); this co-occurs with increases in several measures of skeletal size, including external dimensions of the skull but not including intracranial capacity (Diamond, Rosenzweig, and Krech, 1965). These results are at least partially explained by the fact that rats with impoverished experience are less active and eat more (Fiala, Snow, and Greenough, 1977). Cummins and Walsh (unpublished data, discussed in Walsh, 1980) report increases in several organs, including liver, spleen, testicles, and heart, corresponding to those obtained with body weight. These weight differences are not, however, indications of differences in the general health of the animals.
Relay Conjugation of Living Metathesis Polymers

The covalent coupling of complex macromolecules is a modern challenge in both chemistry and biology. The development of efficient and chemoselective methods for polymer coupling and functionalization are increasingly important for designing new advanced materials and interfacing with biochemical systems. Herein, we present a new strategy to directly conjugate living polymers prepared using ring-opening metathesis polymerization (ROMP) to both small molecules and synthetic macromolecules. Central to this methodology is a terminal alkyne that serves as a directing group to promote a rapid, intramolecular reaction with an otherwise unreactive olefin. This highly chemoselective relay conjugation is compatible with a range of monomer families and uses a bench-stable enyne motif that can be easily introduced to functional targets. The rapid rate of the conjugation reaction paves the way for greatly streamlined construction of complex macromolecular systems derived from metathesis polymerization techniques witho...
Characterization of bilirubin interference in three commonly used digoxin assays.

Abstract Background Due to the narrow therapeutic range of digoxin , determining serum/plasma digoxin concentrations is critical for assessing patients with congestive heart failure , atrial fibrillation , and certain types of arrhythmias. However, digoxin quantification by competitive immunoassays is susceptible to interferences that may alter the accuracy of its measurement in patient plasma. This study aimed to characterize the extent of bilirubin interference in three commonly used digoxin immunoassays. Methods Digoxin concentrations were compared using the Beckman Coulter® Unicel DxI 800, the Vitros® 4600, and the Roche Cobas® 8000 in neat or digoxin-spiked icteric and non-icetric plasma samples. A mixing study was performed to demonstrate how digoxin quantification is affected by bilirubin. An equation was derived that predicts the response of the DxI 800, given known bilirubin and digoxin concentrations. Results The DxI reported detectable concentrations of digoxin in high bilirubin samples with no added digoxin, while the Vitros® 4600 and Cobas® 8000 gave virtually undetectable results. Spiking digoxin into samples with elevated bilirubin concentrations resulted in a higher percent recovery for the DxI 800 when compared to the other two platforms. The mixing study also revealed an increase in the percent recovery in the DxI 800, while the Vitros® 4600 and Cobas® 8000 were comparable to the expected concentration of digoxin. Conclusions The DxI 800 is most prone to interference by bilirubin, while the Vitros® 4600 and Cobas® 8000 are relatively unaffected. Icteric samples should be interpreted with caution if digoxin quantification is needed, especially on the DxI 800 assay.
The Noticeability of Warnings on Alcoholic Beverage Containers

A public health warning is currently required for all alcoholic beverage containers in the United States. One factor in the effectiveness of this warning is its noticeability—the characteristics th...
Irish Fatherhood in the Twentieth Century

This chapter explores the various legal understandings attached to the notion of Irish fatherhood in the twentieth and twenty-first centuries, and the ramifications these frameworks have created for men wanting to be active parents to their children. Parenthood for much of the twentieth century was synonymous with motherhood according to the Irish courts, based on the perception that a biological mother’s right to be her child’s guardian was a natural product of her genetic link with her child, excluding any rights for fathers wanting to participate in the parenting process. Purvis argues that the Irish legal system has been one of the last bastions for outmoded beliefs about men, fatherhood and the role some parents wish to have in their children’s lives.
Diagnostic yield of magnetic resonance imaging for cholangiocarcinoma in primary sclerosing cholangitis: a meta-analysis

Aim of the study Combined magnetic resonance imaging and magnetic resonance cholangiopancreatography (MRI/MRCP) can identify biliary strictures and diagnose primary sclerosing cholangitis (PSC). Diagnosis of cholangiocarcinoma in patients with PSC remains challenging, and the accuracy of MRI/MRCP has not been completely established. We aimed to determine the sensitivity and specificity of MRI/MRCP in the diagnosis of cholangiocarcinoma among patients with PSC from the published literature. Material and methods We searched Embase, PubMed, Cochrane, Scopus, ClinicalTrials.gov, and abstracts from relevant scientific meetings and performed a systematic review and meta-analysis to estimate the diagnostic yield of MRI/MRCP in patients with PSC. Sensitivity and specificity were calculated from pooled estimates of cholangiocarcinoma cases identified and lesions missed. Modifying variables were included in a meta-regression model. Results Our literature search yielded 302 articles and 9 conference abstracts; 8 studies involving 846 liver patients from 5 countries were included in the final analysis. Of those, 531 had PSC and received MRI/MRCP. Thirty-six (6.8%) patients were diagnosed with cholangiocarcinoma (33 true positive, 3 false negative and 1 false positive). Pooled sensitivity was 98.9% (95% CI: 98.6-99.3%). Cholangiocarcinoma cases missed by MRI/MRCP were diagnosed as beading irregularities of the central hepatic ducts, or PSC-related diffuse stricture. Metaregression revealed that neither publication year, study design, nor sample size had a significant effect on observed cancer rates (p = 0.9, 0.3, and 0.3, respectively). Conclusions MRI/MRCP followed by endoscopic retrograde cholangiopancreatography (ERCP) is a sensitive and specific tool to diagnose cholangiocarcinoma among patients with PSC. Further research should estimate MRI/MRCP diagnostic accuracy for cholangiocarcinoma using prospective methodology and longer term outcomes.
Space Objects Classification via Light-Curve Measurements Using Deep Convolutional Neural Networks

This work presents a data-driven method for the classification of light curve measurements of Space Objects (SOs) based on a deep learning approach. Here, we design, train, and validate a Convolutional Neural Network (CNN) capable of learning to classify SOs from collected light-curve measurements. The proposed methodology relies on a physics-based model capable of accurately representing SO reflected light as a function of time, size, shape, and state of motion. The model generates thousands of light-curves per selected class of SO, which are employed to train a deep CNN to learn the functional relationship. between light-curves and SO classes. Additionally, a deep CNN is trained using real SO light-curves to evaluate the performance on real data, but limited training set. The CNNs are compared with more conventional machine learning techniques (bagged trees, support vector machines) and are shown to outperform such methods, especially when trained on real data.
Sleep Disturbance in Early Pregnancy, but Not Inflammatory Cytokines, May Increase Risk for Adverse Pregnancy Outcomes

It is unclear whether subjective or objective measures of sleep during pregnancy are more pertinent to pregnancy outcomes. Moreover, it is unclear as to whether subjective indices (i.e., those likely influenced by psychological thoughts and emotions) are more likely than objective measures to modify inflammatory cytokines. Subjective and objective measures of sleep were collected from 166 pregnant women. Sleep data, both aggregate and variability measures, from diary and actigraphy, were ascertained for three 2-week periods during early gestation (10–20 weeks). A fasting morning blood sample was assayed for the cytokines (IL-6, IFN-γ, and TNF-α). Sleep, stress, and depression questionnaires were also collected. Repeated measures ANOVAs, regression models, and independent t tests were used to analyze the data. Diary-assessed total sleep time (p < .05) and actigraphy-assessed sleep latency (p = .05) were negatively associated with gestational age. Variability in actigraphy-assessed sleep latency (p < .01) was negatively associated with infant weight. None of the cytokines was associated with any of the outcomes. t tests revealed that those with a complication were older (p < .05) and had higher pre-pregnancy BMI (p < .05), higher self-reported stress (p < .05), and lower IFN-γ (p < .05). Findings suggest that longer and more variable sleep latency, as well as shorter sleep duration, is associated with shorter gestational age or a lower birth weight infant. Overall, the findings suggest that among a low-risk, healthy sample of pregnant women, sleep disturbance does not pose a substantial risk for adverse delivery outcomes.
A Catalytic Route for Production of Alkanes from Hydropyrolysis of Biomass

In this work, we report a catalytic route to produce liquid alkanes from hydropyrolysis of biomass. This route uses a NiMo-HZSM-5 catalyst in-situ, and takes place primarily in three steps: 1) nick...
Assessment of Prevalence and Cost of Care Cascades After Routine Testing During the Medicare Annual Wellness Visit.

Importance For healthy adults, routine testing during annual check-ups is considered low value and may trigger cascades of medical services of unclear benefit. It is unknown how often routine tests are performed during Medicare annual wellness visits (AWVs) or whether they are associated with cascades of care. Objective To estimate the prevalence of routine electrocardiograms (ECGs), urinalyses, and thyrotropin tests and of cascades (further tests, procedures, visits, hospitalizations, and new diagnoses) that might follow among healthy adults receiving AWVs. Design, Setting, and Participants Observational cohort study using fee-for-service Medicare claims data from beneficiaries aged 66 years and older who were continuously enrolled in fee-for-service Medicare between January 1, 2013, and March 31, 2015; received an AWV in 2014; had no test-relevant prior conditions; did not receive 1 of the 3 tests in the 6 months before the AWV; and had no test-relevant symptoms or conditions in the AWV testing period. Data were analyzed from February 13, 2019, to June 8, 2020. Exposure Receipt of a given test within 1 week before or after the AWV. Main Outcomes and Measures Prevalence of routine tests during AWVs and cascade-attributable event rates and associated spending in the 90 days following the AWV test period. Patient, clinician, and area-level characteristics associated with receiving routine tests were also assessed. Results Among 75 275 AWV recipients (mean [SD] age, 72.6 [6.1] years; 48 107 [63.9%] women), 18.6% (14 017) received at least 1 low-value test including an ECG (7.2% [5421]), urinalysis (10.0% [7515]), or thyrotropin test (8.7% [6534]). Patients were more likely to receive a low-value test if they were younger (adjusted odds ratio [aOR], 1.69 for ages 66-74 years vs ages ≥85 years [95% CI, 1.53-1.86]), White (aOR, 1.32 compared with Black [95% CI, 1.16-1.49]), lived in urban areas (aOR, 1.29 vs rural [95% CI, 1.15-1.46]), and lived in high-income areas (aOR, 1.26 for >400% of the federal poverty level vs <200% of the federal poverty level [95% CI, 1.16-1.37]). A total of 6.1 (95% CI, 4.8-7.5) cascade-attributable events per 100 beneficiaries occurred in the 90 days following routine ECGs and 5.4 (95% CI, 4.2-6.5) following urinalyses, with cascade-attributable cost per beneficiary of $9.62 (95% CI, $6.43-$12.80) and $7.46 (95% CI, $5.11-$9.81), respectively. No cascade-attributable events or costs were found to be associated with thyrotropin tests. Conclusions and Relevance In this study, 19% of healthy Medicare beneficiaries received routine low-value ECGs, urinalyses, or thyrotropin tests during their AWVs, more often those who were younger, White, and lived in urban, high-income areas. ECGs and urinalyses were associated with cascades of modest but notable cost.
Physician Distress and Burnout: The Neurobiological Perspective

Physician burnout and other forms of occupational distress are a significant problem in modern medicine, especially during the coronavirus disease pandemic, yet few doctors are familiar with the neurobiology that contributes to these problems. Burnout has been linked to changes that reduce a physician's sense of control over their own practice, undermine connections with patients and colleagues, interfere with work-life integration, and result in uncontrolled stress. Brain research has revealed that uncontrollable stress, but not controllable stress, impairs the functioning of the prefrontal cortex, a recently evolved brain region that provides top-down regulation over thought, action, and emotion. The prefrontal cortex governs many cognitive operations essential to physicians, including abstract reasoning, higher-order decision making, insight, and the ability to persevere through challenges. However, the prefrontal cortex is remarkably reliant on arousal state and is impaired under conditions of fatigue and/or uncontrollable stress when there are inadequate or excessive levels of the arousal modulators (eg, norepinephrine, dopamine, acetylcholine). With chronic stress exposure, prefrontal gray matter connections are lost, but they can be restored by stress relief. Reduced prefrontal cortex self-regulation may explain several challenges associated with burnout in physicians, including reduced motivation, unprofessional behavior, and suboptimal communication with patients. Understanding this neurobiology may help physicians have a more informed perspective to help relieve or prevent symptoms of burnout and may help administrative leaders to optimize the work environment to create more effective organizations. Efforts to restore a sense of control to physicians may be particularly helpful.
Effects of anionic and nonionic surfactants on the dispersion and stability of nanoSiO2 in aqueous and cement pore solutions

Abstract It has been well recognized that the benefits and effectiveness of nanoparticles in cement-based materials could not be maximized if these are not well dispersed. To address this issue, in this study, different anionic (SDS and PCE) and nonionic surfactants (Tweens and Tritons) were used to disperse nanosilica (NS) in aqueous solution and cement pore solution. The results show that the dispersibility of NS in cement pore solution was improved, and the compressive strength of the cement-NS pastes increased linearly with critical micelle concentration (CMC) of nonionic surfactants. Among all surfactants studied, Triton X-405 led the paste to the highest increase in strength (33% at 1-day and 41% at 3-days) since it had the highest CMC. TEM and EDS analysis evidenced that this strength increase might be attributed to the nucleation of outer product CSH gel and its densification with calcite nanocrystals, attributed to Triton X-405 addition.