cssi/SciSciGPT-SciSciNet huggingface dataset:
Trends in utilization of FDA expedited drug development and approval programs, 1987-2014: cohort study

Objective To evaluate the use of special expedited development and review pathways at the US Food and Drug Administration over the past two decades. Design Cohort study. Setting FDA approved novel therapeutics between 1987 and 2014. Population Publicly available sources provided each drug’s year of approval, their innovativeness (first in class versus not first in class), World Health Organization Anatomic Therapeutic Classification, and which (if any) of the FDA’s four primary expedited development and review programs or designations were associated with each drug: orphan drug, fast track, accelerated approval, and priority review. Main outcome measures Logistic regression models evaluated trends in the proportion of drugs associated with each of the four expedited development and review programs. To evaluate the number of programs associated with each approved drug over time, Poisson models were employed, with the number of programs as the dependent variable and a linear term for year of approval. The difference in trends was compared between drugs that were first in class and those that were not. Results The FDA approved 774 drugs during the study period, with one third representing first in class agents. Priority review (43%) was the most prevalent of the four programs, with accelerated approval (9%) the least common. There was a significant increase of 2.6% per year in the number of expedited review and approval programs granted to each newly approved agent (incidence rate ratio 1.026, 95% confidence interval 1.017 to 1.035, P Conclusions In the past two decades, drugs newly approved by the FDA have been associated with an increasing number of expedited development or review programs. Though expedited programs should be strictly limited to drugs providing noticeable clinical advances, this trend is being driven by drugs that are not first in class and thus potentially less innovative.
Characterizing a Riboflavin-Dendrimer Platform for Targeted Drug Delivery Applications

Riboflavin ligands present an alternative pathway for targeted drug delivery as riboflavin receptors are over-expressed in breast and prostate cancer cells. We have examined dendrimers conjugated with riboflavin for targeting riboflavin binding protein, which acts as a model protein for the riboflavin receptor. Isothermal titration calorimetry (ITC) was used for determining the thermodynamic parameters for this binding interaction while varying location and average number of riboflavin attached to the dendrimer. Differential scanning calorimetry (DSC) was additionally used to confirm the trends observed by ITC. By characterizing the binding interactions between riboflavin dendrimer conjugates and the riboflavin binding protein, the efficacy of this platform for a targeted approach of drug delivery can be predicted more accurately. The riboflavin dendrimer conjugates will be used in future studies to target riboflavin receptors for cellular uptake as a potential route for the selective delivery of drug molecules to cancer cells that over-express riboflavin receptors.
Comparison of ultrasound radiation force and fluid pressure generated waves in arterial vessels

Pulse wave velocity (PWV) is widely used for estimating the stiffness of an artery. It is well known that a stiffened artery can be associated with various diseases and with aging. The pulse wave generated by the blood pressure in the artery is a fluid-borne pressure wave. In a series of recent studies, we propose directly generating a bending wave in the arterial wall using the ultrasound radiation force and measuring the wave velocity in the arterial wall. With the bending wave method, the wave velocity can be measured accurately over a few millimeters. The bending wave in the artery is a structure-borne wave. In this paper the mechanism of these two kinds of waves are studied. It is found by experiment that the pressure wave velocity decreases with frequency while the bending wave velocity increases with frequency.
Business: Making Cents of Coding Systems: Billing for Professional Services

Abstract Administrators and supervisors face daily challenges over issues such as program funding, service fees, correct coding procedures, and the ever-changing healthcare regulations. Receiving e...
Sum rule for deep-inelastic electroproduction from polarized protons

A sum rule is derived for the asymmetry in deep-inelastic scattering of polarized electrons from polarized protons: ∫01dξgep(ξ)≈0.15gA. The result follows from the quark light-cone algebra and the assumption that strange quarks do not contribute to the asymmetry. The latter is justified by conventional parton-model arguments.
Similarities and differences in the conformation of protein-DNA complexes at the U1 and U6 snRNA gene promoters

Most small nuclear RNAs (snRNAs) are synthesized by RNA polymerase II, but U6 snRNA is synthesized by RNA polymerase III. In the fruit fly Drosophila melanogaster the RNA polymerase specificity of the snRNA genes is determined by a few nucleotide differences within the proximal sequence element (PSE), a conserved sequence located ∼40–65 bp upstream of the transcription start site. The PSE is essential for transcription of both RNA polymerase II-transcribed and RNA polymerase III-transcribed snRNA genes and is recognized in Drosophila by a multi-subunit protein factor termed DmPBP. Previous studies that employed site-specific protein–DNA photocrosslinking indicated that the conformation of the DNA–protein complex is different depending upon whether DmPBP is bound to a U1 or U6 PSE sequence. These conformational differences of the complex probably represent an early step in determining the selection of the correct RNA polymerase. We have now obtained evidence that DmPBP modestly bends the DNA upon interacting with the PSE and that the direction of DNA bending is similar for both the U1 and U6 PSEs. Under the assumption that DmPBP does not significantly twist the DNA, the direction of the bend in both cases is toward the face of the DNA helix contacted by the 45 kDa subunit of DmPBP. Together with data from partial proteolysis assays, these results indicate that the conformational differences in the complexes of DmPBP with the U1 and U6 PSEs more likely occur at the protein level rather than at the DNA level.
Electrical, optical, and fluidic interconnect networks for 3D heterogeneous integrated systems

Three-dimensional (3D) system integration is widely accepted as a key enabler for future systems. Although there are a number of approaches to 3D integration, none have addressed the need for cooling in a 3D stack of high-performance chips (microprocessors). This is a significant omission and imposes a constraint on the ability to fully utilize the benefits of 3D technology. Thus, new 3D integration technologies are needed for high-performance applications as well as those that require the integration of photonics within the 3D stack.
Magnetism and Faraday Rotation in Ce-Substituted Orthoferrite

The authors presented the magnetic and magnetooptical effects of Ce3+ in a rare earth (RE) orthoferrite structure based on the perovskite formula (RE)FeO3. Magnetooptical behavior was quantified by measuring the Faraday rotation and the magnetic hysteresis loops were measured by using an ADE vibration sample magnetometer.
An unusual cause for an irregularly irregular pulse.

70-YEAR-OLD woman with metastatic cancer (later deemed pancreatic) came urgently to surgery because of large bowel obstruction. Approximately 1.5 L of ascitic fluid was initially present. The blood loss during exploration, debulking, and construction of an ileostomy was 700 mL. The preoperative electrocardiogram indicated a right bundle-branch block and a left anterior hemiblock. A recent preoperative echocardiogram showed a small pericardial effusion, normal valvular function, and diffuse left ventricular hypokinesis (ejection fraction of 38%). The initial decompression and drainage of the abdomen appeared well tolerated, but the problem shown in Figure 1 occurred during the progress of the surgery. At an FIO2 of 0.7, an arterial blood sample exhibited a pH of 7.43, a pO2 of 273 mmHg, a pCO2 of of 46 mmHg, and a hemoglobin level of 12.9 g/dL. Ionized calcium, sodium, and potassium were 1.08, 134, and 4.2 mmol/L, respectively. Capnograph contour and ventilation pressure patterns were unremarkable, but the pulse oximetry waveform mimicked the arterial trace. What arrhythmia is responsible for the observed arterial pressure waveform?
Re-evaluation of mid-Holocene deposits at Quebrada Puripica, northern Chile

Duringthe middle Holocene (8^3 ka), wetland deposits accumulated in areas with emerg ent water tables in the central Atacama Desert (22^24‡S), producinga stratig raphic unit (Unit C) that can be mapped and correlated across different basins and geomorphic settings. Wherever mapped, Unit C is located between 6 and 30 m above modern wetlands, and includes thick sequences of diatomite and organic mats. The origin, depositional environment, and paleoclimatic significance of Unit C is controversial and currently under debate. Grosjean [Science 292 (2001) 2391a] suggests the unit developed under a regime of falling lake and ground-water levels, whereas evidence presented here suggests that Unit C formed during a period of rising ground-water levels and increased vegetation cover. The debate is embedded in broader discussions about geomorphic processes in ground-water-fed streams, as well as the history and forcingof climate variability in the central Andes. The central Atacama and Andes are remote, with few opportunities for different researchers to examine the same site. One exception is a sequence of mid-Holocene deposits at the confluence of Quebrada Seca and R| ¤o Puripica in northern Chile (23‡S). Grosjean et al. [Quat. Res. 48 (1997) 239^246] initially suggested the deposits accumulated in temporary lake basins, which formed when recurringdebris flows from a side canyon (Quebrada Seca) dammed the main channel (R|¤o Puripica) duringa period of drought and reduced stream flow. Upon our visit to the site, we found evidence that clearly demonstrates the deposits were not formed in temporary lakes, but rather were deposited in a wetland environment. Disagreement remains about the climatic interpretation of wetland deposits. Grosjean [Science 292 (2001) 2391a] now suggests that local ground-water levels rise and wetland deposits aggrade in deep canyon systems, such as R| ¤o Puripica, when stream power and channel erosion is reduced duringprolong ed dry spells. However, sedimentological evidence and the presence of Unit C in many depositional environments, not just deep canyons, indicate that it formed during a period of higher regional ground-water levels that were sustained by enhanced precipitation and recharge in the High Andes. ? 2003 Elsevier Science B.V. All rights reserved.
Risk factors for 30-day readmission among patients with culture-positive severe sepsis and septic shock: A retrospective cohort study.

BACKGROUND With decreasing mortality in sepsis, attention has shifted to longer-term consequences associated with survivorship. Thirty-day readmission as a component of healthcare utilization is an important outcome. OBJECTIVE To examine the frequency of and risk factors for 30-day readmission among patients surviving sepsis. DESIGN Single-center retrospective cohort. METHODS/SETTING We examined 30-day readmission risk among survivors of hospitalization with culture-positive severe sepsis or septic shock. Extended spectrum β-lactamase (ESBL) organisms were identified via molecular laboratory testing. Healthcare-associated (HCA) was defined by 1 of the following: (1) recent hospitalization, (2) immune suppression, (3) nursing home residence, (4) hemodialysis, (5) prior antibiotics, and (6) index bacteremia hospital-acquired (onset >2 days following admission). Acute kidney injury (AKI) was defined according to the RIFLE (Risk, Injury, Failure, Loss, End-stage) criteria. Logistic regression modeled predictors of 30-day readmission. RESULTS Among 1697 sepsis survivors, 543 (32.0%) required 30-day readmission. Readmitted patients had a higher chronic (median Charlson score 5 vs 4, P < 0.001) but not acute (median APACHE [Acute Physiology and Chronic Health Evaluation] II score 15 and 15, P = 0.275) illness burden, and higher prevalence of HCA sepsis (94.2% vs 90.2%, P = 0.014) than nonreadmitted survivors. In logistic regression, 3 factors increased (Organism: ESBL [odds ratio {OR}: 4.50, 95% confidence interval {CI}: 1.43–14.19], RIFLE: Injury or RIFLE: Failure [OR: 1.95, 95% CI: 1.300–2.93], and Organism: Bacteroides spp [OR: 2.04, 95% CI: 1.06–3.95]) and 2 reduced (Source: Urine [OR: 0.58, 95% CI: 0.35–0.98], Organism: Escherichia coli [OR: 0.49, 95% CI: 0.27–0.90]) the odds of 30-day readmission. CONCLUSIONS One-third of survivors of severe sepsis/septic shock required 30-day readmission. Mild-to-moderate AKI nearly doubled its risk. Journal of Hospital Medicine 2015;10:678–685. © 2015 Society of Hospital Medicine
All You Ever Wanted To Know About MIRV and ICBM Calculations But Were Not Cleared To Ask

This paper (1) explains the variables and methods used to calculate the MIRV threat to the fixed-site land-based ICBM forces of the United States and the Soviet Union; (2) attempts to reconstruct the calculations presented in the 1969 ABM debate by Albert Wohlstetter, George Rathjens, and John S. Foster about the number of Minutemen which could be expected to survive an attack by forces of various sizes and characteristics; and (3) applies these methods, together with some plausible assumptions about classified variables, to two other security issues: the import of the SALT limitation on the size of the Soviet SS-9 force and the character of the threat to the Soviet fixed-site ICBM force posed by the American MIRV program.
Comparison of retracking algorithms using airborne radar and laser altimeter measurements of the Greenland ice sheet

Compares four continental ice sheet radar altimeter retracking algorithms using airborne radar and laser altimeter data taken over the Greenland ice sheet in 1991. The refurbished Advanced Application Flight Experiment (AAFE) airborne radar altimeter has a large range window and stores the entire return waveform during flight. Once the return waveforms are retracked, or post-processed to obtain the most accurate altitude measurement possible, they are compared with the high-precision Airborne Oceanographic Lidar (AOL) altimeter measurements. The AAFE waveforms show evidence of varying degrees of both surface and volume scattering from different regions of the Greenland ice sheet. The AOL laser altimeter, however, obtains a return only from the surface of the ice sheet. Retracking altimeter waveforms with a surface scattering model results in a good correlation with the laser measurements in the wet and dry-snow zones, but in the percolation region of the ice sheet, the deviation between the two data sets is large due to the effects of subsurface and volume scattering. The Martin et al. model results in a lower bias than the surface scattering model, but still shows an increase in the noise level in the percolation zone. Using an offset center of gravity algorithm to retrack altimeter waveforms results in measurements that are only slightly affected by subsurface and volume scattering and, despite a higher bias, this algorithm works well in all regions of the ice sheet. A cubic spline provides retracked altitudes that agree with AOL measurements over all regions of Greenland. This method is not sensitive to changes in the scattering mechanisms of the ice sheet and it has the lowest noise level and bias of all the retracking methods presented. >
Entry and Exit Mechanisms at the cis-Face of the Golgi Complex

Vesicular transport of protein and lipid cargo from the endoplasmic reticulum (ER) to cis-Golgi compartments depends on coat protein complexes, Rab GTPases, tethering factors, and membrane fusion catalysts. ER-derived vesicles deliver cargo to an ER-Golgi intermediate compartment (ERGIC) that then fuses with and/or matures into cis-Golgi compartments. The forward transport pathway to cis-Golgi compartments is balanced by a retrograde directed pathway that recycles transport machinery back to the ER. How trafficking through the ERGIC and cis-Golgi is coordinated to maintain organelle structure and function is poorly understood and highlights central questions regarding trafficking routes and organization of the early secretory pathway.
Sensitization of Hematopoietic Stem and Progenitor Cells to Trimetrexate Using Nucleoside Transport Inhibitors

Antifolates such as methotrexate (MTX) and trimetrexate (TMTX) are widely used in the treatment of cancer and nonmalignant disorders. Transient, yet sometimes severe myelosuppression is an important limitation to the use of these drugs. It has previously been shown that clonogenic myeloid progenitors and colony-forming units-spleen are resistant to antifolates, suggesting that myelotoxicity occurs late in hematopoietic development. The goal of this study was to define the mechanisms by which primitive hematopoietic cells resist the toxic effects of antifolate drugs. To test the hypothesis that myeloid progenitors may salvage extracellular nucleotide precursors to resist TMTX toxicity, a defined liquid culture system was developed to measure TMTX toxicity in expanding progenitor populations. These in vitro experiments showed that both human and murine progenitors can resist TMTX toxicity by importing thymidine and hypoxanthine from the serum. As predicted from these findings, several drugs that block thymidine transport sensitized progenitors to TMTX in vitro, although to differing degrees. These nucleoside transport inhibitors were used to test whether progenitors and hematopoietic stem cells (HSCs) could be sensitized to TMTX in vivo. Treatment of mice with TMTX and nitrobenzylmercaptopurineriboside phosphate (NBMPR-P), a potent transport inhibitor, caused significant depletions of clonogenic progenitors within the bone marrow (20-fold) and spleen (6-fold). Furthermore, NBMPR-P administration dramatically sensitized HSCs to TMTX, with dual-treated mice showing a greater than 90% reduction in bone marrow repopulating activity. These studies demonstrate that both myeloid progenitor cells and HSCs resist TMTX by using nucleotide salvage mechanisms and that these pathways can be pharmacologically blocked in vivo using nucleoside transport inhibitors. These results have important implications regarding the use of transport inhibitors for cancer therapy and for using variants of dihydrofolate reductase for in vivo selection of genetically modified HSCs.
Modulation of BCAM/Lu and ICAM-4 Expression on Red Blood Cell Membranes in Physiological Stress Conditions

Using single-molecule atomic force microscopy (AFM) experiments, we report that epinephrine, a hormone secreted during stress and strenuous exercise, increases both the frequency and strength of adhesion events of sickle cell trait erythrocytes to the endothelial extracellular matrix (ECM). The specific interactions quantified include Lutheran (BCAM/Lu) and intercellular adhesion molecule-4 (ICAM-4) on the RBC surface with ECM laminin and endothelial αv β3 , respectively. These data present significant evidence of the role of epinephrine in BCAM/Lu-laminin and ICAM-4-αv β3 bonding, and suggest mechanisms of vaso-occlusion during physical exertion in SCT.© 2011 ASME
Transnational Religious Connections

Globalization, defined as the increasing flow of people, information, goods, services, and other resources across national boundaries, is altering social contexts in ways that influence religious prac tices. Increasingly, religion is not only instantiated in local communities and national societes, but is also linked with networks that span societal borders. Immigration is the most studied example. However, other flows of people and resources need to be considered, as do the transnational political and economic influences that shape religion. We review recent work in these disparate literatures and show how they point to the growing variety and importance of religious connections that span borders. We discuss evidence of the ways in which religious communities in the United States connect with peo ple in other societies and consider these and other multilateral influences in parts of the Global South.
Locomotion and activity phasing of some medium-sized mammals.

Six carnivores and a monkey studied in the laboratory spent most of their active time treading a wheel. Some of the animals had essentially the same phasing of activity known or presumed in the wild, namely the pig-tail macaque (diurnal), ringtail (nocturnal), and bobcat (arrhythmic). The tayra and grison were diurnal, raising the possibility that the nocturnal activity reported in the field is a consequence of man's encroachments. The bimodal activity of the grison (and to a lesser extent the tayra), including a mid-day siesta, concurs with behavior under semicaptive field conditions. Both the bobcat and domestic cat were arrhythmic, with pronounced peaking of activity during artificial twilights. The red fox was primarily nocturnal with activity peaking during periods of twilight but, as in the field, daytime activity also occurred. The macaque, grison, and tayra were relatively insensitive to temporary abrupt changes in light intensity during their activity periods. The ringtail was more like nocturnal rodents, being fairly rigidly bound by conditions of illumination. The red fox and bobcat were inhibited by dim light and darkness. The bobcat was entrained to a 4-hour “day” by alternating dawns and dusks every 2 hours. Gaits ranged from the slow “deliberate” walk of the cats to occasional galloping by the red fox, ringtail, and cats. In addition to walking, the macaque and tayra engaged in acrobatics. All seven animals showed strong tendencies to tread in one direction, despite starting and stopping hundreds of times.
Efficacy analysis of social organizations-enrolled intervention among MSM in Quanzhou,Fujian Province

Objective To improve the AIDS-related knowledge and the efficacy of change of risk behaviors among men who have sex with men(MSM),by cooperation with social organizations,and carry out AIDS prevention and control activities among MSM.Methods Local MSM-related organizations launched intervention at accumulative places of MSM in Quanzhou.KAP changes before and after the intervention among MSM were compared.Results After intervention,in the target group,the rate of people knowing the 5risk behaviors which could get one infected with HIV increased from 33.4%to 46.5%.The rate of people knowing that 100% use of condoms correctly and consistently can reduce the spread of HIV increased from 59.9%to 81.6%.The rate of people knowing that it is more likely to be infected with HIV after had been infected with venereal diseases increased from 41.4%to 59.0%.The rate of people who use condoms in same sex activities increased from 41.4% to 54.5%.The rate of people who voluntarily go to the CDC for consulting and testing services increased from 37.3%to 54.5%.All above differences are statistically significant(P0.01).Conclusion In cooperation with the local MSM-related social organizations,interventions carried out by the partner educators in the organizations can effectively improve AIDS-related knowledge and change the risk sexual behaviors among MSM.
Fast Background Removal in 3D Fluorescence Microscopy Images Using One-Class Learning

With the recent advances of optical tissue clearing technology, current imaging modalities are able to image large tissue samples in 3D with single-cell resolution. However, the severe background noise remains a significant obstacle to the extraction of quantitative information from these high-resolution 3D images. Additionally, due to the potentially large sizes of 3D image data (over 1011 voxels), the processing speed is becoming a major bottleneck that limits the applicability of many known background correction methods. In this paper, we present a fast background removal algorithm for large volume 3D fluorescence microscopy images. By incorporating unsupervised one-class learning into the percentile filtering approach, our algorithm is able to precisely and efficiently remove background noise even when the sizes and appearances of foreground objects vary greatly. Extensive experiments on real 3D datasets show our method has superior performance and efficiency comparing with the current state-of-the-art background correction method and the rolling ball algorithm in ImageJ.
On the negative feedback regulation of gonadotropins in castrate and intact cattle with comparison of two FSH radioimmunoassays.

Two homologous radioimmunoassays for bovine follicle stimulating hormone (bFSH) were utilized in comparing the differential regulation of FSH and luteinizing hormone (LH) in response to ovariectomy or administration of gonadal steroids in cattle. There appeared to be significant LH cross-reactivity in one of the bFSH systems (bFSH-HS-2-17), but not in the other (bFSH-BP3). Concentrations of FSH in plasma measured by these two systems suggested both qualitative and quantitative differences. Following ovariectomy in heifers, LH concentrations in plasma were increased by 7.5 h, while FSH (measured in the bFSH-BP3 system) was not significantly elevated until 18 h. Administration of 200 micrograms of estradiol-17 beta to ovariectomized heifers inhibited levels of FSH in plasma but large doses of testosterone (100 mg), androstenedione (400 mg) and dihydrotestosterone (800 mg) had no effect. Similarly, LH was not affected by the androgens, while estradiol induced LH surges, leading to increased mean LH concentrations. In contrast to the results in heifers, LH concentrations in plasma from steers were inhibited by administration of androgens as well as by estradiol. In steers, FSH (bFSH-BP3) was marginally inhibited by estradiol and not at all by the androgens. Differences in the secretory patterns of FSH and LH also occurred in intact heifers during the estrous cycle. The 72-h period preceding estrus (follicular phase) was characterized by rapidly declining serum progesterone concentrations, followed by concurrent increases in both LH and estradiol. The circulating levels of bFSH (BP3) tended to decline during this interval. Overall, during the estrous cycle, progesterone levels were positively correlated with bFSH-BP3 (r = .37) and negatively correlated with LH (r = -.39). The gonadotropins were not significantly related (r = -.15). These relationships are consistent with the concept that LH controls the final stages of follicular development in cattle and that FSH may exert only a permissive effect.
Improving Patient Discharge Communication

Transitional care communication events—such as discharge from hospital—are complex and dynamic: impromptu questions are asked and answered, documents are discussed and signed, and health-care profe...
WASP and WAVE Family Protein Complexes

Publisher Summary Arp2/3 is inactive and is unable to trigger de novo actin polymerization. It must be activated by binding to members of the WASP/WAVE family of scaffold proteins to effectively stimulate actin polymerization. The WASP/WAVE family members (WASP, N-WASP, WAVE-1, WAVE-2, and WAVE-3) are activated by Cdc42 and Rac. Thus, a linear pathway (Cdc42/Rac→WASP/WAVE→Arp2/3) translates cellular cues into the assembly of actin filaments. Protein complexes organized by the WASP/WAVE proteins, however, modulate this basic pathway. This chapter summarizes how the WASP and WAVE family protein complexes are organized and are thought to function. WASP/N-WASP and WAVE proteins function as scaffolds to organize protein complexes that modulate dynamic actin turnover through Arp2/3. These protein complexes serve to optimize subcellular targeting of WASP/WAVE, and to act as positive and negative feedback information loops to regulate actin dynamics. Thus, these complexes are likely to serve as sophisticated non-linear signaling pathways that function between Rho-GTPases and Arp2/3. Components of the WASP and WAVE complexes may also function to tie actin regulation to other pathways by interacting with separate protein complexes. Finally, it is likely that new regulatory complexes await discovery. In this regard, WASH (Wiskott-Aldrich Syndrome Protein and SCAR Homolog) has recently been identified as a potential new member of the WASP/WAVE family of Arp2/3 activators.
Management of the Distal Radioulnar Joint in Rheumatoid Arthritis

The distal radioulnar joint (DRUJ) is frequently problematic in rheumatoid arthritis, but the signs and symptoms are variable in timing and severity. Because of the risk of tendon ruptures associated with chronic synovitis, examinations should be repeated regularly. The three traditional surgical options for advanced arthritis are the Darrach resection, Sauve–Kapandji procedure, and hemiresection of the distal ulna. Distal ulna stabilization using a local tenodesis or capsular flap and a soft tissue interposition are often used to reduce radioulnar impingement. If the rheumatoid disease is quiescent, the joint is not subluxated, and the bone quality is adequate, then implant arthroplasty can be considered.
Health Information Technologies—Academic and Commercial Evaluation (HIT-ACE) methodology: description and application to clinical feedback systems

Health information technologies (HIT) have become nearly ubiquitous in the contemporary healthcare landscape, but information about HIT development, functionality, and implementation readiness is frequently siloed. Theory-driven methods of compiling, evaluating, and integrating information from the academic and commercial sectors are necessary to guide stakeholder decision-making surrounding HIT adoption and to develop pragmatic HIT research agendas. This article presents the Health Information Technologies—Academic and Commercial Evaluation (HIT-ACE) methodology, a structured, theory-driven method for compiling and evaluating information from multiple sectors. As an example demonstration of the methodology, we apply HIT-ACE to mental and behavioral health measurement feedback systems (MFS). MFS are a specific class of HIT that support the implementation of routine outcome monitoring, an evidence-based practice. HIT-ACE is guided by theories and frameworks related to user-centered design and implementation science. The methodology involves four phases: (1) coding academic and commercial materials, (2) developer/purveyor interviews, (3) linking putative implementation mechanisms to hit capabilities, and (4) experimental testing of capabilities and mechanisms. In the current demonstration, phase 1 included a systematic process to identify MFS in mental and behavioral health using academic literature and commercial websites. Using user-centered design, implementation science, and feedback frameworks, the HIT-ACE coding system was developed, piloted, and used to review each identified system for the presence of 38 capabilities and 18 additional characteristics via a consensus coding process. Bibliometic data were also collected to examine the representation of the systems in the scientific literature. As an example, results are presented for the application of HIT-ACE phase 1 to MFS wherein 49 separate MFS were identified, reflecting a diverse array of characteristics and capabilities. Preliminary findings demonstrate the utility of HIT-ACE to represent the scope and diversity of a given class of HIT beyond what can be identified in the academic literature. Phase 2 data collection is expected to confirm and expand the information presented and phases 3 and 4 will provide more nuanced information about the impact of specific HIT capabilities. In all, HIT-ACE is expected to support adoption decisions and additional HIT development and implementation research.
MXP: Modular eXpandable framework for building bioinformatics Pipelines

Background: Pipelines are a natural tool in bioinformatics applications. Virtually any meaningful processing of biological data involves the execution of multiple software tools, and this execution must be arranged in a coherent manner. Many tools for the building of pipelines were developed over time and used to facilitate work with increasing volume of bioinformatics data. Here we present a flexible and expandable framework for building pipelines, MXP, which we hope will find its own niche in bioinformatics applications. Results: We developed MXP and tested it on various tasks in our organization, primarily for building pipelines for GWAS (Genome-Wide Association Studies) and post-GWAS analysis. It was proven to be sufficiently flexible and useful. Conclusions: MXP implements a number of novel features which, from our point of view, make it to be more suitable and more convenient for building bioinformatics pipelines.
Culture and Conflict: Science and Social Controversy

Misconceptions relating to dialog and science drive a great deal of the conflict relating to science in America; we’ll next explore the topic of teaching about socially, but not scientifically, controversial topics like climate change and evolution, and how traditional teaching methods that ignore the alienating potential of the culture of science are especially unsuccessful when applied to such topics. Ways in which the culture of science causes conflict, including exclusive language, failing to address identity issues, and insufficient attention to underlying concepts, are addressed. The ways language and misconceptions impact the teaching of controversial topics are addressed, and methods by which these topics can be more effectively addressed in the classroom are presented.
Ionic influences on the prolonged depolarization of turtle cones in situ

1. The effects of ion channel blockers and ion substitutions on the prolonged depolarization of cones in the retina of the turtle (Pseudemys scripta elegans) were studied by intracellular recording. 2. The results of current injection experiments indicate that the prolonged depolarization is regenerative and accompanied by a reduction in the cone's input resistance. 3. The addition of cobalt (5–10 mM) or the removal of extracellular calcium suppressed the prolonged depolarization. Raising extracellular calcium or adding strontium (10 mM) lowered the threshold and increased the duration of the response. 4. Unlike the feedback spikes of turtle cones studied by Piccolino and Gerschenfeld, the prolonged depolarization was not blocked by the organic calcium channel blocker, D600. 5. Adding a calcium chelator, ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), to the electrolyte caused a progressive shortening of the prolonged depolarization until it was ultimately abolished. 6. Lowering extracellular sodium or use of the potassium channel blockers tetraethylammonium (TEA) and 4-aminopyridine (4-AP) had little effect on the prolonged depolarization. 7. Removing chloride from the superfusate induced a significant enhancement of the prolonged depolarization. In normal superfusate, the response tended to be of larger amplitude when recorded with electrodes containing chloride [1.5 M KCl + 1.5 M potassium acetate (KA)] rather than KA or potassium methylsulfate (KM) alone. 8. The results suggest that the prolonged depolarization is initiated by the regenerative activation of voltage-sensitive calcium channels and sustained by a calcium-dependent chloride efflux. The present findings are also discussed in relation to the functional significance of the prolonged depolarization and mechanisms for the surround antagonism of cones in situ.
Framing Tibet: A comparative study of Chinese and American newspapers, 2008-2011

Contemporary Tibet is the subject of one of the world’s longest running ethno-territorial conflicts, dating from just after the People’s Republic of China was founded in 1949 (Sautman & Dreyer, 2006). And due to the huge difference between U.S. and China on political as well as culture dimension, the understanding of Tibet is also varies. Since observing media frames is one of the ways to better understanding the relationship between U.S. vs. Tibet and China vs. Tibet according to Gamson and Modigliani (1987): a media frame as “a central organizing idea or story line that provides meaning to an unfolding strip of events... The frame suggests what the controversy is about, the essence of the issue” (p. 143). Therefore, this study identifies the news frames present in American and Chinese newspapers’ coverage about the Tibet issue, and ascertain differences between the two nations in the performance of the framing function. The study also aims to determine framing patterns: How did these frames change over the years.
Deterrence Now: History: deterrence in the Cold War

Deterrence is an old practice in international politics and other areas of behavior. It has been given plenty of thought and study, yet is not easy to understand or explain. The onset of the Cold War provoked enormous interest in deterrence because its role in international politics, particularly at the global level, promised to be critical. However ancient it is in some ways, the greatest part of what we think we know about it was gleaned in the last six decades of systematic thinking and research on deterrence. I won't inflict a lengthy review of its modern history. However, certain comments about deterrence theory and deterrence during the Cold War will be useful for what comes later. I briefly outline what we thought we were doing in managing the Cold War via nuclear deterrence and assess, briefly, the actual role it played in preventing another great war. What the parties thought they were doing was not always what they were doing and the role of nuclear deterrence was not entirely what it seemed. For those familiar with all this, apologies and a request that you grimace and bear it. The origins of Cold War deterrence The essence of deterrence is that one party prevents another from doing something the first party does not want by threatening to harm the other party seriously if it does.
Risk of infectious, hematological, and gastrointestinal side effects in patients treatedwith ibrutinib: A systematic review and meta-analysis of randomized controlled trials.

e18265Background: Bruton’s tyrosine kinase (BTK) is essential for signaling of B-cell and chemokine receptors. Ibrutinib targets BTK and has become frontier in many hematologic malignancies. We und...
Prevalence of childhood asthma in US military and non-military families: Comparisons by rural–urban residence and geographic region:

ObjectiveWe sought to determine variables associated with asthma among children from military and non-military families.MethodsWe performed secondary data analysis on the 2016 Behavioral Risk Facto...
Uncertainties and limitations of using carbon-13 and oxygen-18 leaf isotope exchange to estimate the temperature response of mesophyll CO2 conductance in C3 plants

The internal CO2 gradient imposed by mesophyll conductance (gm ) reduces substrate availability for C3 photosynthesis. With several assumptions, estimates of gm can be made from coupled leaf gas exchange with isoflux analysis of carbon ∆13 C-gm and oxygen in CO2 , coupled with transpired water (H2 O) ∆18 O-gm to partition gm into its biochemical and anatomical components. However, these assumptions require validation under changing leaf temperatures. To test these assumptions, we measured and modeled the temperature response (15-40°C) of ∆13 C-gm and ∆18 O-gm along with leaf biochemistry in the C3 grass Panicum bisulcatum, which has naturally low carbonic anhydrase activity. Our study suggests that assumptions regarding the extent of isotopic equilibrium (θ) between CO2 and H2 O at the site of exchange, and that the isotopic composition of the H2 O at the sites of evaporation ( δ w - e 18 ) and at the site of exchange ( δ w - ce 18 ) are similar, may lead to errors in estimating the ∆18 O-gm temperature response. The input parameters for ∆13 C-gm appear to be less sensitive to temperature. However, this needs to be tested in species with diverse carbonic anhydrase activity. Additional information on the temperature dependency of cytosolic and chloroplastic pH may clarify uncertainties used for ∆18 O-gm under changing leaf temperatures.
The natural history of group B streptococcal colonization in the pregnant woman and her offspring: I. Colonization studies

A longitudinal study of colonization by group B streptococcus (GBS) was conducted in 93 pregnant women and 92 of their infants. Positive cultures were obtained from vaginal swab specimens on at least one occasion during pregnancy from 20.4% of the women. Three types of carriage were observed: chronic, transient, and intermittent. At the time of delivery, 12.9% of the mothers were colonized by GBS. GBS colonization occurred in 41.7% of the infants of the mothers colonized intrapartum. Only 1.2% of infants intrapartum culture-negative mothers were colonized. Infants colonized at birth were culture negative by 4 months of age. This study suggests that interruption of vertical transmission of GBS from mother to infant not only would influence the incidence of early-onset GBS disease but also might reduce the incidence of late-onset GBS disease.
Simulation and Characterization of Si-based Microchannel for Module Level Cooling

Microwave modules have been increasingly complex and highly integrated, while power dissipation and signal gain increased accordingly. To satisfying this requirement, the third generation semiconductor high performance ICs, such as GaN chips, have been widely used in arrayed T/R unit and power amplifier modules, leading to sharply rise in power consumption and heat flux. Traditional cooling technologies such as natural convection and contact-type heat conduction cannot remove heat effectively, therefore, the forced highly efficient liquid cooling technique has been adopted. In this paper, three dimensional computational fluid dynamic (CFD) models are developed in ANSYS CFX to understand the flow resistance characteristics, heat dissipation capacity of different kind microfluidic structures (Two kinds of microfluidic structures had been designed and simulated, respectively, straight- through channel and variable cross-section channel), all simulated microfluidic structures have been manufactured by using deep silicon etching and Si-Si bonding. The GaN switch chip and power amplifier chip in this simulation are simplified to block heat generation with uniform heat source surface. In order to determine the flow state, turbulence and laminar flow effect have been taken into consideration respectively, which were verified by thermal characteristic. To verify the simulation results, power amplifier modules with different microfluidic structure integrated have been designed and assembled, the liquid cooling experimental setup have been built to characterize different kinds of microfluidic structures. The test results make a good agreement with our simulations, proving that the CFD modeling and simulation are reasonable.
Climate Change and Great Salt Lake

Terminal lakes are highly susceptible to climate change impacts since water that enters through precipitation, runoff, and groundwater must be balanced with water that leaves through evaporation. A change in this equation can lead to a decline in elevation, which can be tragic for the ecosystem, particularly if the closed basin is shallow. Great Salt Lake faces many threats that will impact the volume of water in the depression of the Bonneville Basin where it resides. If the lake’s level declines, salinity increases, and wetlands are altered. Salinity is a driver of microbial diversity and, as this foundation of the ecosystem is altered, so will be the rest of the food web, affecting large numbers of avian migrators along the Pacific and Central fly-ways. Human population growth and water diversions for agriculture have put a strain on Great Salt Lake, resulting in a terminal lake whose trajectory is downward in surface area. How might anthropogenic climate change impact this scenario? Alterations in temperature can influence the timing of snowmelt and change evapotranspiration. As temperatures increase and droughts persist, climate change will amplify the decline in lake elevation, creating more dust from the exposed lakebed. Dust blowing into inhabited valleys will worsen air quality with particulates and may be laden with the pollutants collected by the lake. Early melting of the snowpack in the Wasatch Mountains due to higher temperatures would be further impacted as airborne dust from the dry shorelines is deposited during storms and can reduce the albedo of snow, altering groundwater recharge of the watershed. The current status of Great Salt Lake, with no water rights of its own and increasing pressures for water use upstream, does not bode well for the survival of this critical ecosystem given climate change predictions for the southwestern United States.
Determinantal Expressions in Multi-Species TASEP

Consider an inhomogeneous multi-species TASEP with drift to the left, and define a height function which equals the maximum species number to the left of a lattice site. For each fixed time, the multi-point distributions of these height functions have a determinantal structure. In the homogeneous case and for certain initial conditions, the fluctuations of the height function converge to Gaussian random variables in the large-time limit. The proof utilizes a coupling between the multi-species TASEP and a coalescing random walk, and previously known results for coalescing random walks.
Working together: Using student-driven UX projects to improve library websites

Web design standards have evolved considerably since the introduction of smartphones and tablets, but many academic library websites have fallen behind, perhaps due to a lack of internal user exper...
Synaptotagmin-like protein 2a regulates lumen formation via Weibel-Palade body apical secretion of angiopoietin-2 during angiogenesis

ObjectiveVascular lumen formation requires the redistribution of intracellular proteins to instruct apico-basal polarity, thereby enforcing maturation of both luminal and basal domains. In the absence of proper apical signaling, lumen formation can be distorted leading to lumen collapse and cessation of blood flow. Synaptotagmin-like protein-2a (Slp2a) has been implicated in apical membrane signaling; however, the role of Slp2a in vascular lumen formation has never been assessed. Approach and ResultsOur results demonstrate that Slp2a is required for vascular lumen formation. Using a 3- dimensional sprouting assay, sub-cellular imaging, and zebrafish blood vessel development we establish that Slp2a resides at the apical membrane acting as a tether for Rab27a that decorates Weibel-Palade bodies (WPBs). Unique to endothelial tissue, we show that Slp2a regulates exocytic activity of WPBs, thus regulating release of WPB contents into the luminal space during angiogenesis. Angiopoietin-2 is a Tie-2 receptor ligand that is selectively released from WPB secretory granules. We identify a critical role for angiopoietin-2 in regulating endothelial lumenization and show that in the absence of Slp2a, WPB contents cannot fuse with the apical membrane. This disrupts the release of angiopoietin-2 and blocks Tie-2 signaling necessary for proper lumen formation. ConclusionsOur results demonstrate a novel requirement of Slp2a for vascular lumen formation. Moreover, we show that Slp2a is required for the exocytic release of WPB secretory granule cargo during vascular lumen development, and thus is a core upstream component of the WPB secretory pathway. Furthermore, we provide evidence that WPB-housed angiopoietin-2 is required for vascular lumen formation. HIGHLIGHTSO_LISynaptotagmin-like protein-2a (Slp2a) is required for vascular lumen formation via its interaction with Rab27a and Weibel Palade Body secretory granules. C_LIO_LISlp2a is recruited to the apical membrane where it regulates secretion of Weibel Palade Body components into the luminal space. C_LIO_LIIn the absence of Slp2a, Weibel Palade Body-housed angiopoietin-2 ligand cannot be exocytosed, this impedes activation of Tie-2 signaling required for lumen biogenesis. C_LIO_LIKnockout of Slp2a or Tie-2 in zebrafish blunts the formation of vascular lumens during angiogenic development. C_LI