cssi/SciSciGPT-SciSciNet huggingface dataset:
MicroRNAs Enhance Keratinocyte Proliferative Capacity in a Stem Cell-Enriched Epithelium.

MicroRNAs are critical regulators of stem cell behavior. The miR-103/107 family is preferentially expressed in the stem cell-enriched corneal limbal epithelium and plays an important role in coordinating several intrinsic characteristics of limbal epithelial stem cells. To elucidate further the mechanisms by which miRs-103/107 function in regulating limbal epithelial stem cells, we investigate the global effects of miRs-103/107 on gene expression in an unbiased manner. Using antagomirs-103/107, we knocked down endogenous miRs-103/107 in keratinocytes and conducted an mRNA profiling study. We show that miRs-103/107 target mitogen-activated protein kinase kinase kinase 7 (MAP3K7) and thereby negatively regulate the p38/AP-1 pathway, which directs epithelial cells towards a differentiated state. Pharmacological inhibition of p38 increases holoclone colony formation, a measure of proliferative capacity. This suggests that the negative regulation of p38 by miRs-103/107 contributes to enhanced proliferative capacity, which is a hallmark of stem cells. Since miRs-103/107 also promote increased holoclone colony formation by regulating JNK activation through non-canonical Wnt signaling, we believe that this microRNA family preserves “stemness” by mediating the crosstalk between the Wnt/JNK and MAP3K7/p38/AP-1 pathways.
Evaluation of Range-Corrected Density Functionals for the Simulation of Pyridinium-Containing Molecular Crystals

The problem of nonlocal interactions in density functional theory calculations has in part been mitigated by the introduction of range-corrected functional methods. While promising solutions, the continued evaluation of range corrections in the structural simulations of complex molecular crystals is required to judge their efficacy in challenging chemical environments. Here, three pyridinium-based crystals, exhibiting a wide range of intramolecular and intermolecular interactions, are used as benchmark systems for gauging the accuracy of several range-corrected density functional techniques. The computational results are compared to low-temperature experimental single-crystal X-ray diffraction and terahertz spectroscopic measurements, enabling the direct assessment of range correction in the accurate simulation of the potential energy surface minima and curvatures. Ultimately, the simultaneous treatment of both short- and long-range effects by the ωB97-X functional was found to be central to its rank as t...
Induction of Trypsin Inhibitors in Soybean Leaves by Mexican Bean Beetle (Coleoptera: Coccinellidae) Defoliation

Trypsin inhibitory activity (TIA) was found in soybean, GLycine max (L.) Merrill, leaf extracts. Foliage of eight field-grown soybean accessions, from maturity groups V and VII, was assayed for TIA during an infestation of Mexican bean beetle (MBB), Epilachna varivestis Mulsant. Small quantities of TIA were found in prebloom foliage (6.3–15.9 μg trypsin inhibited per gram of leaf). As the plants matured and MBB defoliation increased, TIA in all lines increased from 4- to 23-fold. Amount of TIA was correlated to degree of defoliation. Two types of trypsin inhibitors, differing in molecular weight, were found. The inhibitor(s) with the smaller molecular weight was detected only in plants with feeding damage and, by late pod stage, accounted for 50–80% of total TIA in most plants.
Experimental and Computational Analysis of High Angle of Attack Perching Maneuvers

Experimental and numerical investigations are performed in an effort to elucidate the necessity of inclusion of three-dimensional effects in the determination of lift and drag forces during rapid pitching and impulsively started maneuvers to/at high angle of attack. Following the guidelines of the NATO RTO AVT 202 test case, wind tunnel data was acquired for pure pitching cases from 0 to 45 degrees for an AR 4 flat plate using the University of Dayton Low Speed Wind Tunnel (UD-LWST) and compared to a 2D Discrete Vortex Method (DVM). Results show that the DVM compares well to the wind tunnel data in the pre-stall region before the deformation of the wake at the trailing edge by the trailing edge vortex and show similar trends in the post-stall region. It is believed that these differences in post-stall occur due to 3D effects and discussion is provided to support this assertion. The DVM is also used to compare results of a 45 degree linearly accelerated impulsive start case to data obtained in an experiment at the AFRL Horizontal Freesurface Water Tunnel under conditions identical to the simulation. Comparing these results again demonstrates the that DVM matches well to the water tunnel data except in a region where it is believed 3D instabilities are responsible for effects in the flowfield that are not adequately modeled by the 2D DVM.
The Kennedy Court: Reflections on the First Amendment Ruling in Christian Legal Society v. Martinez

(2011). The Kennedy Court: Reflections on the First Amendment Ruling in Christian Legal Society v. Martinez. Free Speech Yearbook: Vol. 45, No. 1, pp. 31-45.
The Reliability and Validity of the Pediatric Appropriateness Evaluation Protocol

Researchers at Yale-New Haven Hospital (New Haven, Connecticut) tested the reliability and validity of the Pediatric Appropriateness Evaluation Protocol (PAEP) through a comparison of inter-rater agreement between experienced pediatricians and less experienced clinicians. The PAEP is a diagnosis-independent instrument with 26 criteria in three categories used to assess appropriate hospital use in pediatrics. Pediatrician raters, using clinical judgment alone, and clinicians (fellows in pediatrics and nurse practitioners), using both clinical judgment and the PAEP, reviewed a sample of 47 days and judged which inpatient days were medically appropriate. A day was judged appropriate if any of the 26 criteria were fulfilled for that day and inappropriate if none of the criteria was fulfilled. The PAEP was found to be a reliable and valid instrument with a 93% sensitivity and a 78% specificity for detecting medically inappropriate days.
T1 Measurement to Study the Penetration of BNCT Agents Into Canine Tumors Caused by Blood Brain Barrier Damage

The blood brain barrier (BBB), maintained primarily by cerebral capillary endothelial cells, protects the brain by limiting the uptake and circulation of drugs1. It has been observed that the BBB is disrupted during brain tumor growth. The fenestrated capillaries allow large molecules, such as protein and blood products, to penetrate through the BBB and be taken up by tumors cells2. As a consequence, certain boron agents for Boron Neutron Capture Therapy (BNCT), such as borocaptate sodium (BSH)3, are able to penetrate the disrupted BBB and enter tumor tissues. The study of BBB disruption by tumor growth will assist in understanding the mechanism of this penetration and provide a background for BSH pharmacokinetics.
Survival analysis of AIDS patients of 15 years or above years old after initiation antiretroviral treatment in Henan province during 2005 to 2014

OBJECTIVE: To investigate the survival rate of AIDS patients after receiving antiretroviral therapy(ART) in Henan province and to determine factors associated with survival status. METHODS: Database of AIDS patients receiving ART were downloaded from China Information System for Disease Preventioin and Control-AIDS retrospective study method was conducted to analyze the information. INCLUSION CRITERIA: initially received national free ART during January 2005 to December 2014; aged 15 years or above; and with relatively complete baseline information and follow-up information. The accumulated survival rate of AIDS patients was calculated by life table method and the influencing factors were analyzed by Cox proportional hazard model. RESULTS: Total 30 376 AIDS patients were enrolled in this study. During the follow-up period a total of 3 927 cases died from HIV/AIDS related diseases. The mortality of all patients was 3.2/100 person year. After 1 5 10 years after the initiation of ART the rates of accumulate survival rate were 93.7% 85.3% and 78.4% respectively. Stepwise regression was used to conduct the time multiple factors analysis the results showed that man (HR=1.28 95%CI: 1.20-1.37) older age (HR=1.20 95% CI: 1.16-1.24) others marital status except marrage or cohabitation (HR=1.2095% CI: 1.12-1.29) more number of symptoms (HR=1.11 95%CI: 1.07-1.14) initial treatment were main stavudine (D4T) or zidovudine (AZT)+ didanosine(DDI)+ nevirapine (NVP) or efevirenz (EFV) (HR=1.12 95% CI: 1.04-1.20) missing drug in the past 7 days (HR=18.3695%CI: 17.08-19.74) among AIDS patients had high mortality risk homosexuality sexual transmission (HR=0.59 95% CI: 0.40-0.87) higher baseline count of CD4(+)T lymphocyte (relative to 0-200 cells/microl group HR (95%CI) were 0.57 (0.53-0.62) 0.43(0.37-0.49) 0.33 (0.27-0.40) in 201-350 cells/microl group 351-500 cells/microl group and >/=501 cells/microl group respectively) higher educations (HR=0.89 95% CI: 0.83-0.95) had low mortality risk. CONCLUSION: Survival rate was higher after initial antiretroviral treatment among AIDS patients in Henan province. AIDS patient will have shorter survival time after antiviral treatment under one or more following conditions: higher age male initial treatment with D4T or AZT + DDI + NVP or EFV lower baseline CD4 (+) T lymphocyte count ever missed antiviral drugs in past 7 days of latest follow-up.
Effect of regular emptying of the gallbladder on gallstone formation in the rabbit.

The importance of regular gallbladder evacuation in the prevention of gallstones was tested. Fourteen rabbits were fed dihydrocholesterol which causes gallstones. Seven were injected with cholecystokinin (CCK) twice daily and the other 7 with placebo. Stones formed in all rabbits that received CCK as well as in all of those that did not. The failure of CCK to prevent stone formation may be due to two phenomena that were observed: failure of the gallbladder to empty all of its contents after CCK administration, and the inclusion of concretions in the mucus on the wall of the gallbladder.
Devices to Treat Hypertension in Chronic Kidney Disease

Hypertension is common in chronic kidney disease (CKD), and can be a cause or consequence of CKD. The prevalence of resistant hypertension is reported to be as high as 23 % in CKD, and prevalence increases as the estimated glomerular filtration rate (eGFR) declines. Suboptimal control rates of hypertension and limited advances in pharmacologic options have increased interest in the use of device therapy as potential complementary or alternative treatment modalities for hypertension. However, before routine use of these devices can be recommended for hypertension management, better understanding is needed regarding the safety, efficacy, and durability of their effects. This is especially true in CKD patients, as all large clinical trials studying device therapy have excluded patients with moderate-to-severe CKD and end-stage renal disease on dialysis. Additionally, studies do not show a universal blood pressure-lowering response with device therapy—patient subgroups that are more likely to respond need to be identified, and practical clinical markers that can assess adequacy of the intervention are needed. It should also be noted that none of the device therapies are currently approved for clinical use in the USA. Appropriate evaluation of patients with resistant hypertension, with emphasis on lifestyle modifications and appropriate antihypertensive medication use remains the cornerstone of management of these patients. Close collaboration between internists, interventionalists, and hypertension specialists is essential in the clinical and research arena of resistant hypertension, particularly when designing future research studies with device therapies, and determining their place in the treatment of hypertension.
CFD simulations of polymer devolatilization in steam contactors

ABSTRACTRemoval of volatiles and other unwanted products in a polymer mix is a critical step in polymer manufacturing. This process serves many purposes, such as improvement in the physical and chemical properties of the polymer, elimination of odours, recovery of monomers and solvents, and fulfilment of environmental regulations. In this study, the mixture of polymer and solvent, or cement, is mixed with superheated steam which causes the unwanted solvent to evaporate. As the cement droplets lose solvent and dry out, they are ejected as cement ‘crumb’ from the mixing device. This process is modelled using computational fluid dynamics (CFD) to gain insight into the complex phenomena. The model simulates the heat transfer and phase changes associated with cement and steam, via 3D axisymmetric calculations. Using an Eulerian–Lagrangian approach, the superheated steam is modelled as the continuous phase and tracked in an Eulerian frame, while the cement droplets are treated using a Lagrangian tracking method...
PSA screening rates in older men in the United States based on nine-year estimated remaining life expectancy.

e16006 Background: PSA screening for prostate cancer (PCa) is controversial, but informed decision making is recommended for men with an estimated 10 years of remaining life expectancy (RLE). The a...
Differentiating HIV-Associated Neurocognitive Disorders From Alzheimer's Disease: an Emerging Issue in Geriatric NeuroHIV.

The purpose of this review was to examine characteristics that may distinguish HIV-associated neurocognitive disorder (HAND) from early Alzheimer’s disease (AD). Cerebrospinal fluid (CSF) AD biomarkers are perturbed in HIV, yet these alterations may be limited to settings of advanced dementia or unsuppressed plasma HIV RNA. Neuropsychological testing will require extensive batteries to maximize utility. Structural imaging is limited for early AD detection in the setting of HIV, but proper studies are absent. While positron-emission tomography (PET) amyloid imaging has altered the landscape of differential diagnosis for age-associated neurodegenerative disorders, costs are prohibitive. Risk for delayed AD diagnosis in the aging HIV-infected population is now among the most pressing issues in geriatric neuroHIV. While clinical, imaging, and biomarker characterizations of AD are extensively defined, fewer data define characteristics of HIV-associated neurocognitive disorder in the setting of suppressed plasma HIV RNA. Data needed to inform the phenotype of AD in the setting of HIV are equally few.
A 1V 0.25uW inverter-stacking amplifier with 1.07 noise efficiency factor

This paper presents a highly power efficient amplifier. By stacking inverters and splitting the capacitor feedback network, the proposed amplifier achieves 6-time current reuse, thereby significantly boosting gm and lowering noise but without increasing power. A novel biasing scheme is devised to ensure robust operation under 1V supply. A prototype in 180nm CMOS has 5.5uV rms noise within 10kHz BW while consuming only 0.25uW, leading to a noise efficiency factor (NEF) of 1.07, which is the best among reported amplifiers.
Evaluating the MoA/human relevance framework for F-344 rat liver epithelioid granulomas with mineral oil hydrocarbons

Toxicology feeding studies of mineral oil hydrocarbons (MOHs), within the carbon number range C22-C28, results in species-specific epithelioid granulomas in the liver of F-344 rats but not in other rat strains, or species. While MOH has been detected, and some pathological effects have been shown to occur in other organs/tissues of F-344 rats and other rat strains/species, it is generally accepted that the effect of toxicological concern is species-specific inflammatory liver granuloma. As oil retention and other MOH-related nontoxic pathological changes in the liver are observed in humans, some have hypothesized that the potential for oil accumulation over a lifetime, through dietary sources, may predispose humans to similar liver effects as observed in F-344 rats. To address this concern, a mode of action/human relevance framework (MoA/HRF) analysis for MOH-induced epithelioid granuloma in the F-344 rat model was developed. The key events for the development of liver epithelioid granulomas were identified as increased MOH intestinal absorption, preferential tissue retention and ultimately formation of necrotic granulomas encased by infiltrating inflammatory lymphocytes. The hypothesized MoA was evaluated using the modified Bradford Hill considerations for causality and was considered to be established in the F-344 rodent model. However, key strain/species differences in the rate of intestinal absorption, tissue retention of MOH and inflammatory response to MOH in the liver were identified. Overall, the F-344 rat MoA was not considered to be relevant to humans, consistent with data showing no evidence for the formation of epithelioid granulomas with humans even in cases of massive ingestion of MOHs.
Impact of Asynchronous Training on Radiology Learning Curve among Emergency Medicine Residents and Clerkship Students.

CONTEXT Web-based learning (WBL) modules are effectively used to improve medical education curriculum; however, they have not been evaluated to improve head computed tomography (CT) scan interpretation in an emergency medicine (EM) setting. OBJECTIVE To evaluate the effectiveness of a WBL module to aid identification of cranial structures on CT and to improve ability to distinguish between normal and abnormal findings. DESIGN Prospective, before-and-after trial in the Emergency Department of an academic center. Baseline head CT knowledge was assessed via a standardized test containing ten head CT scans, including normal scans and those showing hemorrhagic stroke, trauma, and infection (abscess). All trainees then participated in a WBL intervention. Three weeks later, they were given the same ten CT scans to evaluate in a standardized posttest. MAIN OUTCOME MEASURES Improvement in test scores. RESULTS A total of 131 EM clerkship students and 32 EM residents were enrolled. Pretest scores correlated with stage of training, with students and first-year residents demonstrating the lowest scores. Overall, there was a significant improvement in percentage of correctly classified CT images after the training intervention from a mean pretest score of 32% ± 12% to posttest score of 67% ± 13% (mean improvement = 35% ± 13%, p < 0.001). Among subsets by training level, all subgroups except first-year residents demonstrated a statistically significant increase in scores after the training. CONCLUSION Incorporating asynchronous WBL modules into EM clerkship and residency curriculum provides early radiographic exposure in their clinical training and can enhance diagnostic head CT scan interpretation.
Fusion calculations for 40 Ca + 40 , 44 , 48 Ca

Calculations are carried out for the {sup 40}Ca+{sup 40,44,48}Ca fusion reactions, taking into account both the low-lying inelastic excitations and the dominant single-nucleon transfer reactions which couple directly to the entrance channels. The results agree well with the {sup 40}Ca+{sup 40}Ca fusion data but they underpredict the low-energy {sup 40}Ca+{sup 44,48}Ca measurements.
Mechanisms of cortisol - Substance use development associations: Hypothesis generation through gene enrichment analysis.

Abstract There are many theories about the mechanisms of associations between hypothalamic-pituitary-adrenal (HPA) function (indexed by cortisol) and substance use. However, the potential for genes that contribute to both HPA function and substance use to confound the association (e.g., genetic confounding) has largely been ignored. We explore the potential role of genetics in cortisol-substance use associations, build a conceptual framework placing theories and mechanisms for how cortisol and substance use are related into a developmental progression, and develop new hypotheses based on our findings. We conclude that the relationship between cortisol function and substance use is complex, occurs at multiple levels of analysis, and is bidirectional at multiple phases of the substance use progression. Additionally, there is potential for genetic confounding in cortisol-substance use associations, and thus a need for genetically informed designs to investigate how and why cortisol function is associated with substance use phenotypes from initiation through disorder. Gene-environment interplay and developmental context are likely to impact the effectiveness of prevention and intervention efforts to reduce substance use problems.
Improving undergraduate competence in multicultural gerontology practice with fresh pedagogies: A digital storytelling case example

Building on a student-led digital storytelling project, the author suggests that expanding definitions of two core constructs of social work education and practice, experiential learning and cultural competence, can improve outcomes for diverse older clients by increasing competence in multicultural gerontology practice. Using a variety of media, digital storytelling focuses on stories that are not often heard, like those of diverse older adults. Student-led projects provide opportunities for students to engage with experiential learning, a high-impact pedagogy. Beyond describing a one-semester digital storytelling project that occurred in an undergraduate gerontology practice course, the article shares findings from the project's evaluation. The evaluation yielded recommendations, such as encouraging social work faculty to provide opportunities for experiential learning across the curriculum, and improving competence in multicultural gerontology practice through creative pedagogies. Ultimately, the author suggests that fresh pedagogical approaches that expand core social work constructs can improve outcomes for diverse older adults by promoting multicultural gerontology practice competence.
Lock removal for concurrent trace programs

We propose a trace-based concurrent program analysis to soundly remove redundant synchronizations such as locks while preserving the behaviors of the concurrent computation. Our new method is computationally efficient in that it involves only thread-local computation and therefore avoids interleaving explosion, which is known as the main hurdle for scalable concurrency analysis. Our method builds on the partial-order theory and a unified analysis framework; therefore, it is more generally applicable than existing methods based on simple syntactic rules and ad hoc heuristics. We have implemented and evaluated the proposed method in the context of runtime verification of multithreaded Java and C programs. Our experimental results show that lock removal can significantly speed up symbolic predictive analysis for detecting concurrency bugs. Besides runtime verification, our new method will also be useful in applications such as debugging, performance optimization, program understanding, and maintenance.
10 – PEST CONTROL: WEEDS, INSECTS, PATHOGENS, AND RODENTS

Forages are beset with a myriad of pests that include weeds and the associated competition, insects, diseases, rodents, and herbivorous animals. The mix of pest problems varies from locale to locale. Regardless of location or the crop grown, it behooves the grower to be aware of potential pest damage. To avert losses, a grower must know the potential pests, be able to identify them and their symptoms, know and practice the best control methods, and have a sense of when a pest becomes important from the economic point of view. Efforts to avert the consequences of pest infestations involve selecting and practicing techniques best suited for control, including cultivar selection, rotation, and cultivation. Only recently has the use of chemical pesticides become an important part of this integrated control effort. In the forage crops used for hay, breeding pest resistance into new cultivars has long been recognized as the first line of defense, and the efforts accumulated over time are impressive. Pest-management strategies include basic knowledge, development of sources of information, and ready access to information on the ecological basis for the pest problem, pest and predator populations and life cycles, and analysis of the costs and benefits of pest-control techniques.
Collaborative Goals for Communicative Life Participation in Aphasia: The FOURC Model

Purpose Collaborative goal setting is at the heart of person-centered rehabilitation but can be challenging, particularly in the area of aphasia. The purpose of this clinical focus article is to present a step-by-step model for forming a collaborative partnership with clients to develop an intervention plan that follows the client's lead, addresses communicative participation, and integrates multiple treatment strategies. Method We introduce the rationale and core features of a 4-step and 4-pronged process (the FOURC model) and illustrate its application through 3 cases of people with aphasia who were treated in outpatient rehabilitation. Conclusions The model invites client initiative in a clinically feasible manner while supporting the clinician's role in guiding the intervention based on professional expertise and growing familiarity with the case. Outcomes observed in case studies include strengthened motivation and improved real-life communication.
Harms and benefits of opioids for management of non-surgical acute and chronic low back pain: a systematic review

Background Consequences of prescription opioid use involve harms, addiction, tolerance and death. Despite routine prescription, opioids are not recommended for initial intervention by any major multidisciplinary low back pain (LBP) guideline. Objective Our primary purpose was to improve overall understanding of the harms and benefits associated with oral opioid interventions prescribed for treatment of acute or chronic back pain. Our second goal was to evaluate pain intensity and to compare and contrast these data with the harms. Our last objective was to evaluate conflicts of interest among the study authors and the findings. Design/data/eligibility criteria Studies incorporating oral prescription opioid management of non-surgical LBP were evaluated. After systematic assessment, no studies that met inclusion included participants with specifically acute LBP. Therefore, extracted data reflects only populations with subacute and chronic LBP. Data on reported harms, severe harms, pain outcomes and withdrawal rates were extracted and meta-analyses were completed for opioid versus placebo trials and opioids versus non-opioid trials. Results Fourteen studies met inclusion/exclusion requirements. All trials involved short-term management with limited follow-up. A high percentage of harms were identified across most studies. Opioids were not shown to be superior to other medications, and only showed superiority to placebo comparators (at cost of additional harms). Conclusion This review identified trends of higher harms rates and higher percentages of severe harms in opioid arms for the management of subacute and chronic LBP. The majority of trials that demonstrated benefits with opioids also had potential conflicts of interest. Lastly, non-opioid medications demonstrated statistically significant pain improvement compared with opioids. We feel that the results of the trial are supportive of current LBP guidelines and do not condone the initial use of opioids in management of subacute or chronic LBP. Trial registration number CRD42017070914
General Anesthesia Does Not Have Persistent Effects on Attention in Rodents

Background: Studies in animals have shown that general anesthesia can cause persistent spatial memory impairment, but the influence of anesthetics on other cognitive functions is unclear. This study tested whether exposure to general anesthesia without surgery caused a persistent deficit in attention in rodents. Methods: To evaluate whether anesthesia has persistent effects on attention, rats were randomized to three groups. Group A was exposed for 2 h to isoflurane anesthesia, and tested the following seven days for attentional deficits. Group B was used as a control and received room air before attentional testing. Since there is some evidence that a subanesthetic dose of ketamine can improve cognition and reduce disorders of attention after surgery, rats in group C were exposed to isoflurane anesthesia in combination with a ketamine injection before cognitive assessment. Attention was measured in rats using the 5-Choice Serial Reaction Time Task, for which animals were trained to respond with a nose poke on a touchscreen to a brief, unpredictable visual stimulus in one of five possible grid locations to receive a food reward. Attention was analyzed as % accuracy, % omission, and premature responses. Results: Evaluating acute attention by comparing baseline values with data from the day after intervention did not reveal any differences in attentional measurements. No significant differences were seen in % accuracy, % omission, and premature responses for the three groups tested for 7 consecutive days. Conclusion: These data in healthy rodents suggest that general anesthesia without surgery has no persistent effect on attention and the addition of ketamine does not alter the outcome.
Peacebuilding and the Performing Arts Through the Collaborative Lens

In “Peacebuilding and the Performing Arts through the Collaborative Lens,” Culbertson explores relationships between peacebuilding and performing arts organizations, showing how these relationships can be mutually reinforcing in some situations, while working at cross purposes in others. By considering instrumental, interactional and transformational collaborations, he demonstrates how relationships between performing arts and peacebuilding organizations take on a wide variety of distinct forms, each with its own strengths and weaknesses. For Culbertson, successful collaborative relationships require peacebuilders who understand the inherent capacity of the performing arts, as well as performing artists who engage the peacebuilding endeavor critically and creatively.
Development of a Lung Rescue Team to Improve Care of Subjects With Refractory Acute Respiratory Failure.

BACKGROUND: A lung-protective mechanical ventilation strategy has become the hallmark of ventilation management for patients with acute respiratory failure. However, some patients progress to more severe forms of acute respiratory failure with refractory hypoxemia. In such circumstances, individualized titration of mechanical ventilation according to the patient9s specific respiratory and cardiovascular pathophysiology is desirable. A lung rescue team (LRT) was recently established at our institution to improve the medical care of patients with acute respiratory failure when conventional treatment fails. The aim of this report is to describe the consultation processes, the cardiopulmonary assessment, and the procedures of the LRT. METHODS: This was a retrospective review of the LRT management of patients with acute respiratory failure and refractory hypoxemia at Massachusetts General Hospital in Boston, Massachusetts. The LRT is composed of a critical care physician, the ICU respiratory therapist on duty, the ICU nurse on duty, and 2 critical care fellows. In the LRT approach, respiratory mechanics are evaluated through lung recruitment maneuvers and decremental PEEP trials by means of 3 tools: esophageal manometry, echocardiography, and electrical impedance tomography lung imaging. RESULTS: The LRT was consulted 89 times from 2014 to 2019 for evaluation and management of severely critically ill patients with acute respiratory failure and refractory hypoxemia on mechanical ventilation. The LRT was requested a median of 2 (interquartile range 1–6) d after intubation to optimize mechanical ventilation and to titrate PEEP in 77 (86%) subjects, to manage ventilation in 8 (9%) subjects on extracorporeal membrane oxygenation (ECMO), and to manage weaning strategy from mechanical ventilation in 4 (5%) subjects. The LRT found consolidations with atelectasis responsive to recruitment maneuvers in 79% (n = 70) of consultations. The LRT findings translated into a change of care in 81% (n = 72) of subjects. CONCLUSIONS: The LRT individualized the management of severe acute respiratory failure. The LRT consultations were shown to be effective, safe, and efficient, with an impact on decision-making in the ICU.
Rubber toughening of polyamides with functionalized block copolymers: 2. Nylon-6,6

Abstract The toughening of nylon-6,6 using triblock copolymers of the type styrene-(ethylene-co-butylene)-styrene (SEBS) and a maleic anhydride (MA) functionalized version (SEBS-g-MA) is examined and compared with the behaviour reported for nylon-6 in the accompanying paper. Nylon-6,6 can be made super-tough by blending with SEBS-g-MA, and addition of SEBS merely reduced toughness. For nylon-6 super-toughness was achieved only with certain combinations of SEBS and SEBS-g-MA since with just the latter the rubber particles (∼ 0.05 μm) generated were too small for effective toughening. The SEBS served to raise particle size to within the optimal range. In contrast, blends of nylon-6,6 with SEBS-g-MA give rubber particles that are within the optimal size range (just less than 1 μm); however, these particles have a very complex structure. For blends containing both SEBS and SEBS-g-MA, there seem to be two distributions of shapes but not size. Evidence is shown that the extent of grafting to nylon-6,6 is less than that in nylon-6 for similar conditions. It is proposed that the large difference in morphology found for nylon-6,6 versus that for nylon-6 stems from basic chemical differences between the two polyamides rather than rheological or processing factors. Nylon-6 is monofunctional while nylon-6,6 is difunctional in their reactions with anhydride. The possible consequences of this are discussed.
Impaired Gut-Systemic Signaling Drives Total Parenteral Nutrition-Associated Injury.

Background: Total parenteral nutrition (TPN) provides all nutritional needs intravenously. Although lifesaving, enthusiasm is significantly tempered due to side effects of liver and gut injury, as well as lack of mechanistic understanding into drivers of TPN injury. We hypothesized that the state of luminal nutritional deprivation with TPN drives alterations in gut–systemic signaling, contributing to injury, and tested this hypothesis using our ambulatory TPN model. Methods: A total of 16 one-week-old piglets were allocated randomly to TPN (n = 8) or enteral nutrition (EN, n = 8) for 3 weeks. Liver, gut, and serum were analyzed. All tests were two-sided, with a significance level of 0.05. Results: TPN resulted in significant hyperbilirubinemia and cholestatic liver injury, p = 0.034. Hepatic inflammation (cluster of differentiation 3 (CD3) immunohistochemistry) was higher with TPN (p = 0.021). No significant differences in alanine aminotransferase (ALT) or bile ductular proliferation were noted. TPN resulted in reduction of muscularis mucosa thickness and marked gut atrophy. Median and interquartile range for gut mass was 0.46 (0.30–0.58) g/cm in EN, and 0.19 (0.11–0.29) g/cm in TPN (p = 0.024). Key gut–systemic signaling regulators, liver farnesoid X receptor (FXR; p = 0.021), liver constitutive androstane receptor (CAR; p = 0.014), gut FXR (p = 0.028), G-coupled bile acid receptor (TGR5) (p = 0.003), epidermal growth factor (EGF; p = 0.016), organic anion transporter (OAT; p = 0.028), Mitogen-activated protein kinases-1 (MAPK1) (p = 0.037), and sodium uptake transporter sodium glucose-linked transporter (SGLT-1; p = 0.010) were significantly downregulated in TPN animals, whereas liver cholesterol 7 alpha-hydroxylase (CyP7A1) was substantially higher with TPN (p = 0.011). Conclusion: We report significant alterations in key hepatobiliary receptors driving gut–systemic signaling in a TPN piglet model. This presents a major advancement to our understanding of TPN-associated injury and suggests opportunities for strategic targeting of the gut–systemic axis, specifically, FXR, TGR5, and EGF in developing ameliorative strategies.
Using motivational interviewing to enhance emerging adults' engagement in weight loss: The Live Well RVA pilot randomized clinical trial.

Background Emerging adults (ages 18-25) are at high risk for overweight/obesity, yet traditional adult behavioural weight loss (BWL) interventions do not meet the needs of individuals at this developmental stage. Motivational interviewing (MI) is an evidence-based approach to promote behaviour change but has not been tested for weight loss in this population. The study aimed to test the feasibility and preliminary efficacy of an MI-enhanced weight loss programme to promote engagement, retention and weight loss in emerging adults. Methods Emerging adults with overweight/obesity (N = 47, 81% female, 47% racial/ethnic minority, body mass index [BMI] = 33.2 ± 4.6 kg/m2) were randomized to either standard BWL or MI-enhanced BWL (MIBWL). Weight was assessed objectively at baseline and posttreatment (3 months). Engagement (in-person session attendance [weeks 1 and 2], online self-monitoring [weeks 3-12] and online content viewing [weeks 3-12]) was tracked throughout the program. Results Though results did not reach the level of statistical significance, participants in MIBWL demonstrated greater programme engagement (77% vs. 61.0%, p = .11; Cohen d = .48), retention (71% vs. 48.0%, p = .10; Cohen h = .47) and intent-to-treat weight loss (-3.3% vs. -2.2%, p = .37; Cohen d = .26) compared with those in BWL. Conclusions Effect sizes suggest that MI might be a viable approach to enhance engagement and retention in weight loss programmes targeting emerging adults. This finding is meaningful, given the documented challenges with engagement and retention in this vulnerable population and the relationship between engagement and better weight loss outcomes. The results of this small pilot study support efforts to replicate these findings within the context of a fully powered trial.
Haloxyfop determination by gas chromatography/tandem mass spectrometry in eggs.

Rationale Haloxyfop is a pre/post-emergence herbicide with known organ toxicities and teratogenic effects in mammals. The European Union Commission on Food Safety has an established maximum residue limit of 10 μg/kg in all agricultural products including eggs. A sensitive highly specific method would be of value in determination of haloxyfop residues in foodstuffs such as eggs. Methods The Michigan State University Veterinary Diagnostic Lab (MSU VDL) developed a method for the extraction of haloxyfop from eggs based on popular QuEChERS (quick, easy, cheap, effective, rugged, and safe) methodologies, essentially providing acetonitrile extracts following treatment with high ionic strength additives. Extracts derivatized with trimethylsilyl (TMS) groups were examined by gas chromatography/tandem mass spectrometry using developed multiple reaction monitoring (MRM) methodology. Results The MSU VDL received eggs from chickens exposed to 760 μg/kg haloxyfop in flaxseed. Haloxyfop-TMS m/z 374→73 MRM setting enabled quantitation across the 1-50 ppb range in comparison with an ibuprofen MRM transition as internal standard. Conclusions The determined limit of quantitation was 2.5 ng/g, and the method successfully identified haloxyfop residues in five of six batches of the chicken eggs, with nonzero values ranging from 2.7 to 14.5 ng/g. These values were consistent with flaxseed incorporation into the diet at 4-7% and known excretion into eggs at 2-3% of daily haloxyfop exposure, and establish the utility of the method in identifying regulatory noncompliance and adulteration of food sources.
Can NSAIDs be used safely for analgesia in patients with CKD?: PRO.

Nearly 60% of patients with CKD suffer pain. Of those patients with CKD who have pain, most rate their pain as moderate or severe in intensity. Undermanaged pain is associated with higher rates of mood disorders, maladaptive coping, and decreased quality of life for patients with CKD (1). In general, nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended as first-line for analgesia and also act as antipyretics and anti-inflammatory medications. Estimates indicate that 98 million patients annually are prescribed NSAIDs (2), which likely represents only a fraction of total use given widespread nonprescription access. Epidemiologic studies suggest that 70%–80% of all NSAID users consume over-the-counter products like ibuprofen or naproxen (3,4). In the National Health and Nutrition Examination Survey, routine NSAID use was common in patients with CKD and use increased with increasing CKD severity (3). NSAIDs have well-known adverse effects in CKD patients. These risks can broadly be categorized into affecting the kidneys, gastrointestinal (GI) tract, or cardiovascular system. Among these risks, it is the direct and indirect nephrotoxicity that has primarily led to hesitation with the use of NSAIDs in patients with CKD. In one study, patients with CKD were more likely to receive an opioid than an NSAID or gabapentinoid across the entire spectrum of CKD (5). The highest rates of opioid prescribing were in patients with the lowest GFR. Indirect nephrotoxicity from NSAIDs is linked to altered intraglomerular hemodynamics. NSAIDs inhibit PG synthesis, which decreases afferent arteriolar vasodilation and can reduce glomerular pressure. This is especially prominent in patients with already jeopardized renal perfusion as in shock or intravascular volume depletion. For this reason, use of NSAIDs in acutely ill patients with AKI, acute kidney disease, or in the midst of renal recovery remains ill-advised. Patterns of direct nephrotoxicity include interstitial nephritis, papillary necrosis, and …
Logic Encryption for Resource Constrained Designs

Logic Encryption is a hardware security technique that protects integrated circuit designs that are fabricated at untrusted pure play foundries from being pirated or maliciously modified. In the technique, logic gates are added to the design that are driven by an added key input bus, such that the correct behavior of the circuit is recovered with only the exact correct key input pattern. However, the power, performance, and area (PPA) cost of implementing logic encryption has often been ignored in the literature in favor of increasing the level of security provided. This has proved to be a significant hurdle in transitioning the method to use in commercial-grade designs and a systematic methodology of constraining the cost of logic encryption is needed. In this paper, we propose a generalized Constraint-Directed Logic Encryption (CDLE) methodology. In CDLE, the potential design space of encrypted versions of a circuit is searched to apply logic encryption under PPA constraints. Two example CDLE methods are proposed. The first is a concurrent tree search method which uses commercial tools to sample designs for their PPA cost and determine the optimal encryption strategy. In this method, PPA cost is accurately analyzed at the cost of heavy runtime. The second is a machine learning approach which estimates the PPA cost to predict the optimal encryption strategy. The machine learning model developed in this work is limited, but the results are promising as a direction for study in logic encryption. Detailed experimental results evaluating both methods are presented.
Ways and Means: Teaching Political Strategy and Heresthetic by Simulating the Budget Process

Simulations offer opportunities for students to receive instruction in political strategies and practice developing political skills without the real-world consequences faced by policymakers. Budge...
Systemic inhibition of PTPN22 augments anticancer immunity

Both epidemiologic and cellular studies in the context of autoimmune diseases have established that protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a key regulator of T cell receptor (TCR) signaling. However, its mechanism of action in tumors and its translatability as a target for cancer immunotherapy have not been established. Here we show that a germline variant of PTPN22, rs2476601, portended a lower likelihood of cancer in patients. PTPN22 expression was also associated with markers of immune regulation in multiple cancer types. In mice, lack of PTPN22 augmented antitumor activity with greater infiltration and activation of macrophages, natural killer (NK) cells, and T cells. Notably, we generated a novel small molecule inhibitor of PTPN22, named L-1, that phenocopied the antitumor effects seen in genotypic PTPN22 knockout. PTPN22 inhibition promoted activation of CD8+ T cells and macrophage subpopulations toward MHC-II expressing M1-like phenotypes, both of which were necessary for successful antitumor efficacy. Increased PD1-PDL1 axis in the setting of PTPN22 inhibition could be further leveraged with PD1 inhibition to augment antitumor effects. Similarly, cancer patients with the rs2476601 variant responded significantly better to checkpoint inhibitor immunotherapy. Our findings suggest that PTPN22 is a druggable systemic target for cancer immunotherapy.
Measuring Early Childhood Mathematical Cognition: Validating and Equating Two Forms of the Research-Based Early Mathematics Assessment:

Psychometric work with young children faces the particular challenge that children’s attention spans are relatively short, and therefore, shorter assessments are required while retaining comprehens...
Functional Liquid Metal Nanoparticles: Synthesis and Applications

Room temperature liquid metals are an emerging class of functional materials with applications in a variety of soft intelligent systems. In recent years, efforts have been made to integrate liquid metal alloys such as eutectic gallium-indium (EGaIn) and eutectic gallium-indium-tin (Galinstan) into wearable electronics, soft robotics, and biomedical devices. One main methodology is reducing the size of liquid metal (LM) droplets to micro and nanoscale level. In this review, we present an overview of recent progress in synthesizing liquid nanoparticles with a focus on the role of processing parameters on their structure and surface properties. Next, the liquid metal nanoparticles are discussed as the functional units in polymer nanocomposites with enhanced electrical and thermal properties. Ultimately, the applications of LM nanoparticles and nanocomposites are presented, followed by a brief outlook on the challenges and future developments of advanced liquid metal material systems.
A Framework for Assessing the Impact of Disease Treatment.

OBJECTIVES To address ongoing pandemics and epidemics, policy makers need good data on not only the need for treatments but also on new interventions' impacts. We present a mathematical model of medicines' health consequences using disease surveillance data to inform health policy and scientific research that can be extended to address the current public health crisis. METHODS The Global Health Impact (GHI) index calculates the amount of mortality and morbidity averted by key medicines for malaria, TB, HIV/AIDS, and several NTDs using data on outcomes in the absence of treatment, treatment effectiveness, and access to needed treatment. Country-level data were extracted from data repositories maintained by the Global Burden of Disease study, Global Health Observatory, WHO, UNICEF, and a review of the scientific literature. RESULTS The index aggregates drug impact by country, disease, company, and treatment regimen to identify the spatial and temporal patterns of treatment impact and can be extended across multiple diseases. Approximately 62 million life-years were saved by key drugs that target malaria, TB, HIV/AIDS, and NTDs in our latest model year. Malaria and TB medicines together were responsible for alleviating 95% of this burden, while HIV/AIDS and NTD medicines contribute 4% and 1% respectively. However, the burden of disease in the absence of treatment was nearly evenly distributed among malaria, TB, and HIV/AIDS. CONCLUSIONS A common framework that standardizes health impact across diseases and their interventions can aid in identifying current shortcomings on a global scale.