cssi/SciSciGPT-SciSciNet huggingface dataset:
Treatment trends for patients with brain metastases: Does practice reflect the data?

BACKGROUND Published guidelines regarding the optimal treatment strategies for brain metastases focus on patients with ≤3 lesions. As delivery techniques for stereotactic radiosurgery (SRS) improve, radiation oncologists are increasingly using it for patients with >3 metastases. In the current study, the authors sought to characterize practice patterns among practitioners to identify areas of controversy. METHODS A survey of practicing radiation oncologists was distributed via e-mail. Responses were collected from April 1 to May 5, 2016. Survey data were analyzed. RESULTS A total of 711 currently practicing radiation oncologists responded, for a response rate of 12.5%. Specialists in central nervous system tumors (CNS specialists) were more likely to treat higher numbers of patients with brain metastases with SRS. There was a significant difference in the optimal “cutoff number” used when deciding how many lesions to treat with SRS versus whole-brain radiotherapy. Cutoff numbers were significantly higher for high-volume CNS specialists (≥10 patients/month) than for either low-volume CNS specialists (5-9 patients/month) or high-volume, non-CNS specialists (8.1 vs 5.6 and 5.1, respectively; P<.001). A majority of respondents (56%) identified patients with 4 to 6 brain metastases as being the most challenging patients to treat. CONCLUSIONS To the authors’ knowledge, there appears to be no consensus regarding the optimal treatment strategy among patients with >3 brain metastases, and practice patterns are heterogeneous. Radiation oncologists, especially high-volume CNS specialists, are treating significantly more brain metastases with SRS than what currently is recommended by published consensus guidelines. Providers struggle with patients with a moderate intracranial disease burden. Further prospective studies are needed to support these practice patterns and guide decision making. Cancer 2017;123:2274–2282. © 2017 American Cancer Society.
Exposing wiktionary translations with performance in mind

In this paper, we explore some of the challenges to extracting Wiktionary data so it can be used for machine translation. We provide a use case of considerations made in the development of a web service that transforms raw data in a wiktionary xml dump file into a web-service that provides language translation. Our case study focuses on the performance of this service in comparison to a service using remote calls to the Wiktionary API.
Autophagic clearance of proteasomes in yeast requires the conserved sorting nexin Snx4

Turnover of the 26S proteasome by autophagy is an evolutionarily conserved process that governs cellular proteolytic capacity and eliminates inactive particles. In most organisms, proteasomes are located in both the nucleus and cytoplasm. However, the specific autophagy routes for nuclear and cytoplasmic proteasomes are unclear. Here, we investigate the spatial control of autophagic proteasome turnover in budding yeast (Saccharomyces cerevisiae). We found that nitrogen starvation–induced proteasome autophagy is independent of known nucleophagy pathways but is compromised when nuclear protein export is blocked. Furthermore, via pharmacological tethering of proteasomes to chromatin or the plasma membrane, we provide evidence that nuclear proteasomes at least partially disassemble before autophagic turnover, whereas cytoplasmic proteasomes remain largely intact. A targeted screen of autophagy genes identified a requirement for the conserved sorting nexin Snx4 in the autophagic turnover of proteasomes and several other large multisubunit complexes. We demonstrate that Snx4 cooperates with sorting nexins Snx41 and Snx42 to mediate proteasome turnover and is required for the formation of cytoplasmic proteasome puncta that accumulate when autophagosome formation is blocked. Together, our results support distinct mechanistic paths in the turnover of nuclear versus cytoplasmic proteasomes and point to a critical role for Snx4 in cytoplasmic agglomeration of proteasomes en route to autophagic destruction.
Comparison of Late Urinary Symptoms Following SBRT and SBRT with IMRT Supplementation for Prostate Cancer.

Background Prostate cancer survivors commonly experience late-onset lower urinary tract symptoms following radiotherapy. We aimed to compare lower urinary tract symptoms in patients treated with stereotactic body radiotherapy (SBRT) to those treated with a combination of lower dose SBRT and supplemental intensity-modulated radiotherapy (SBRT + IMRT). Methods Subjects with localized prostate carcinoma scheduled to receive SBRT or a combination of SBRT and IMRT were enrolled and followed for up to 2 years after treatment completion. Participants treated with SBRT received 35-36.25 Gy in 5 fractions, while those treated with SBRT + IMRT received 19.5 Gy of SBRT in 3 fractions followed by 45-50.4 Gy of IMRT in 25-28 fractions. Urinary symptoms were measured using the American Urological Association (AUA) Symptom Score. Results Two hundred patients received SBRT (52% intermediate risk, 37.5% low risk according to D'Amico classification) and 145 patients received SBRT + IMRT (61.4% high risk, 35.2% intermediate risk). Both groups experienced a transient spike in urinary symptoms 1 month after treatment. More severe late urinary flare (increase in AUA scores ≥ 5 points from baseline to 1 year after treatment completion and an AUA score ≥ 15 at 1 year after treatment) was experienced by patients who received SBRT compared to those treated with SBRT + IMRT. Conclusion Participants who received SBRT and supplemental IMRT experienced less severe late urinary flare 1 year after treatment compared to those who received higher dose SBRT alone. This information can be used by clinicians to provide patients with anticipatory counseling to mitigate any psychological burden that comes with unanticipated late urinary toxicities.
Enterprise Microblogging to Augment the Subinternship Clinical Learning Experience: A Proof-of-Concept Quality Improvement Study.

Background: Although the Clerkship Directors in Internal Medicine (CDIM) has created a core subinternship curriculum, the traditional experiential subinternship may not expose students to all topics. Furthermore, academic institutions often use multiple clinical training sites for the student clerkship experience. Objective: The objective of this study was to sustain a Web-based learning community across geographically disparate sites via enterprise microblogging to increase subintern exposure to the CDIM curriculum. Methods: Internal medicine subinterns used Yammer, a Health Insurance Portability and Accountability Act (HIPAA)–secure enterprise microblogging platform, to post questions, images, and index conversations for searching. The subinterns were asked to submit 4 posts and participate in 4 discussions during their rotation. Faculty reinforced key points, answered questions, and monitored HIPAA compliance. Results: In total, 56 medical students rotated on an internal medicine subinternship from July 2014 to June 2016. Of them, 84% returned the postrotation survey. Over the first 3 months, 100% of CDIM curriculum topics were covered. Compared with the pilot year, the scale-up year demonstrated a significant increase in the number of students with >10 posts (scale-up year 49% vs pilot year 19%; P=.03) and perceived educational experience (58% scale-up year vs 14% pilot year; P=.006). Few students (6%) noted privacy concerns, but fewer students in the scale-up year found Yammer to be a safe learning environment. Conclusions: Supplementing the subinternship clinical experience with an enterprise microblogging platform increased subinternship exposure to required curricular topics and was well received. Future work should address concerns about safe learning environment.
Study on Effect of Speaker Variability and Driving Conditions on the Performance of an ASR Engine Inside a Vehicle

Spoken dialogue based information retrieval systems are being used inside vehicles. The user satisfaction of using such a system depends on how an ASR engine performs. However, the performance of an ASR is affected by speaker variability, driving conditions, etc. In this chapter, we report the study that we performed to analyze these effects of speaker variability, different driving conditions and the effect of driving task on the ASR performance. This study consists of experimental design, data collection and systematically testing an ASR engine using this data. From the obtained results, it can be observed that (I) the ASR performance exhibits (a) significant speaker variability since the stress of driving task varies from speaker to speaker, (b) significant performance degradation across driving conditions since the noise type and level varies and (c) significant effect of driving task on recognition performance, and (II) the effect of live noise on recognition performance is not same as adding car noise to the pre-recorded speech data. The former observations are important since by just training an ASR engine on lots of speech data will not help and it is essential to include stress factors and cognition load in ASR engines to improve its performance.
The Role of Followership During Periods of Absent Leadership

The Role of Followership During Periods of Absent Leadership by Robert Alan Leonard MBA, University of Baltimore, 1993 BA, Loyola College in Maryland, 1987 Dissertation Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Management
Sex differences in antidepressant efficacy

Sex differences have been observed across many psychiatric diseases, especially mood disorders. For major depression, the most prevalent psychiatric disorder, females show a roughly two-fold greater risk as compared to males. Depression is sexually dimorphic with males and females exhibiting differences in clinical presentation, course, and response to antidepressant treatment. In this review, we first discuss sex differences observed in depressed patients, as well as animal models that reveal potential underlying mechanisms. We then discuss antidepressant treatments including their proposed mechanism of action and sex differences observed in treatment response. We include possible mechanisms underlying these sex differences with particular focus on synaptic transmission.
On Ash Deposition Rates from Air and Oxy-Combustion of Pulverized Coal, Petroleum Coke, and Biomass

This paper presents a synthesis of a large body of experimental data on growth rates of ash deposits from the air and oxy-combustion of multiple pulverized solid fuels, including coal, biomass, and their blends. The experimental data were obtained from 35 tests in a 100 kW (rated) entrained-flow combustor that allowed for self-sustained combustion of solid fuels. Ash deposition rates were measured using a wall-temperature-controlled ash deposition probe. The collected deposits were divided into tightly bound “inside deposits” adjacent to the heat transfer surface and loosely bound “outside deposits” that grow further out. Ash aerosol particle size distributions (psd’s) and size-segregated compositions were obtained through electric mobility, light scattering, and impactor methods. Rates of ash deposition for both inside and outside deposits are presented. Rates of growth of the inside deposit were proportional to the sub-micrometer particle (PM1) concentration in the flue gas but correlated poorly with th...
Ultrafast dynamics of the photo-induced phase transition in vanadium dioxide (Conference Presentation)

Interest in the phase-changing material vanadium dioxide as a potential reconfigurable or modulating element in optical and electronic applications has been a major driver for research since the material was first characterized half a century ago. The thermally induced phase transition occurs near 70˚C, and comprises an insulator-to-metal transition with a four-orders-of-magnitude increase in free-carrier density, and a nearly, but not quite, simultaneous structural phase transition from the monoclinic ground state to the rutile (tetragonal) excited state. Although early switching experiments focused on the thermally driven phase transition, a laser-driven phase transition in vanadium dioxide was observed already in 1965. However, a detailed understanding of the mechanisms underlying the photo-induced phase transition (PIPT) remained elusive, especially for the ultrafast PIPT, first demonstrated two decades ago. This review discusses the current understanding of the PIPT as revealed both in recent experiments and theory for both VO2 thin films and single crystals during the past decade. Specific issues to be considered include the partitioning of laser-imparted energy into electronic and phononic degrees of freedom during the PIPT; band-gap collapse and the dynamical evolution of the rutile structural phase; effects of coupling between thin film and substrate; variations in PIPT dynamics with laser wavelength and material optical properties; and ultimate limitations on the switching speed and energy cost for the transition. This detailed mechanistic understanding has specific implications for applications of the PIPT in silicon photonics, which will be discussed in conclusion.
Characterization of wellbore casing corrosion product as a permeable porous medium

Abstract Leakage along wellbores is of concern for a variety of applications, including sub-surface fluid storage facilities, geothermal wells, and CO2 storage wells. We have investigated whether corroded casing is permeable to gas and can serve as a leakage pathway along wellbores. Three specimens were prepared from laboratory steel plates corroded using different mechanisms to reflect different possible field conditions and produce a variety of corrosion rates. Single-phase gas flow measurements were made under a range of gas pressures to investigate flow in both the viscous and visco-inertial flow regimes. Tests were conducted at different confining stresses (range from 3.45 to 13.79 MPa) following both loading and unloading paths. The gas flow test results suggest corroded casing can serve as a significant leakage path along the axis of a wellbore. Transmissivity was found to be sensitive to the variation in confining stress suggesting that the corrosion product is deformable. Gas slip factors and the coefficients of inertial resistance of the corrosion product were comparable to those available in the literature for other porous media. Post-test examination of the corrosion product revealed it to be a heterogeneous, mesoporous material with mostly non-uniform slit type porosity. There was no discernable difference in the composition of corrosion product from specimens corroded by different mechanisms.
Introduction and the genome of travel behavior

Abstract Every three years, the International Association for Travel Behavior Research organizes a conference that spans the entire spectrum of the most important developments in travel behavior research (see IATBR.ORG ). This is a unique opportunity for researchers from around the world to meet and exchange ideas about new issues and methods used to understand and predict behavior. In 2018, the conference took place on the University of California, Santa Barbara campus from July 15th to 20th ( www.iatbr2018.org and IATBR2018). The conference theme, Mapping the Travel Behavior Genome, highlights the great progress in developing tools to understand and map the fundamental elements of travel behavior. The conference included methods to unravel human activity-travel behavior, showcasing state-of-the-art advancements in research and practical applications. This includes the biological, motivational, cognitive, situational, and dispositional factors that drive activity-travel behavior. The conference also addressed critical issues in developing urgently needed theories and analytical methods to address imminent upheavals that transform our lives.
Tele-ECHO for Point-of-Care Ultrasound in Rural Kenya: A Feasibility Study

Background Geographical isolation limits continuous point-of-care ultrasound (PoCUS) education for healthcare providers in rural Kenya. This study evaluates the use of the Project ECHO (Extension for Community Healthcare Outcomes) videoconference platform to connect health care providers in rural Kenya with PoCUS trainers at Brown University. Methods Twelve PoCUS trainees from 11 clinics were included in the study. Every week, trainees participated in a 2-hour Tele-ECHO session via Zoom. Attendance was logged onto iECHO. A Qualtrics survey was used to collect participant feedback. Results Trainees faced difficulty with computer-based Wi-Fi connection and mostly used smartphone-based Internet. Whatsapp messaging was preferable to email for Tele-ECHO notifications. Work obligations kept some trainees from participating. The majority of participating trainees felt that the didactic material was relevant to their practice. Conclusion Telementoring through Project ECHO was found to be an acceptable adjunct to PoCUS training for rural trainees. Internet access was primarily smartphone-based.
Granular Jamming Feet Enable Improved Foot-Ground Interactions for Robot Mobility on Deformable Ground

Recent studies on dynamic legged locomotion have focused on incorporating passive compliant elements into robot legs which can help with energy efficiency and stability, enabling them to work in wide range of environments. In this work, we present the design and testing of a soft robotic foot capable of active stiffness control using granular jamming. This foot is designed and tested to be used on soft, flowable ground such as sand. Granular jamming feet enable passive foot shape change when in contact with the ground for adaptability to uneven surfaces, and can also actively change stiffness for the ability to apply sufficient propulsion forces. We seek to study the role of shape change and stiffness change in foot-ground interactions during foot-fall impact and shear. We have measured the acceleration during impact, surface traction force, and the force to pull the foot out of the medium for different states of the foot. We have demonstrated that the control of foot stiffness and shape using the proposed foot design leads to improved locomotion, specifically a 52% reduced foot deceleration at the joints after impact, 63% reduced depth of penetration in the sand on impact, higher shear force capabilities for a constant depth above the ground, and 98% reduced pullout force compared to a rigid foot.
Strongly correlated electron behavior in a new member of the A n +1 B n X 3 n +1 homologous series: Ce 7 Co 6 Ge 19

While $f$-electron intermetallics are well-known as hosts for complex valence behavior, magnetism, and unconventional superconductivity, it remains a persistent challenge to design specific phenomena. Some guidance is provided by studies of large families of materials, such as those based on the ${\mathrm{AlB}}_{2}, {\mathrm{AuCu}}_{3}$, and ${\mathrm{BaAl}}_{4}$ structural subunits, where systematic trends in their electronic behavior have been observed. This suggests that an effective approach in developing designer materials is to incorporate multimodal stacking arrangements of well-understood building blocks. Here, we report results for ${\mathrm{Ce}}_{7}{\mathrm{Co}}_{6}{\mathrm{Ge}}_{19}$, the $n=6$ member of a new homologous series, ${{A}_{n}}_{+1}{B}_{n}{X}_{3n+1}$, that consists of subunits previously identified as having potential for unconventional magnetic behavior. We show that ${\mathrm{Ce}}_{7}{\mathrm{Co}}_{6}{\mathrm{Ge}}_{19}$ exhibits complex magnetism with evidence for frustration and Kondo lattice behavior that is directly related to what is seen in other $n$ value analogs. Here, the added structural units introduce additional magnetic degrees of freedom, demonstrating that it is possible to rationally design magnetic complexity, and possibly other phenomena in this family of intermetallics.
Value-Based Optimization of Healthcare Resource Allocation for COVID-19 Hot Spots

With the emerging COVID-19 crisis, a critical task for public health officials and policy makers is to decide how to prioritize, locate, and allocate scarce resources. To answer these questions, decision makers need to be able to determine the location of the required resources over time based on emerging “hot spot” locations. Hot spots are defined as concentrated areas with sharp increases in COVID-19 cases. Hot spots place stress on existing healthcare resources, resulting in demand for resources potentially exceeding current capacity. This research will describe a value-based resource allocation approach that seeks to coordinate demand, as defined by uncertain epidemiological forecasts, with the value of adding additional resources such as hospital beds. Value is framed as a function of the expected usage of a marginal resource (bed, ventilator, etc.). Subject to certain constraints, allocation decisions are operationalized using a nonlinear programming model, allocating new hospital beds over time and across a number of geographical locations. The results of the research show a need for a value-based approach to assist decision makers at all levels in making the best possible decisions in the current highly uncertain and dynamic COVID environment.
“Effective Schooling” in the Age of Capital: Critical Insights from Advocacy Anthropology, Anthropology of Education, and Critical Disability Studies

This paper argues that the ideological and material reproduction of “effective schooling” in the Age of Capital functions to normalize and perpetuate the unequal social relations and oppressive dynamics that characterize free market economies and their accompanying political and cultural practices in the historical and educational context of the United States of America. I argue that the intersection of three perspectives furthers the work of scholars grounded in the various disciplines—advocacy anthropology, the anthropology of education, and the mutual engagement of anthropology and critical disability studies—and demonstrates that a multi-inter- transdisciplinary lens is essential for deepening an understanding of the discourses as well as the concrete practices that push ‘disorderly’ student subjects into precarious circumstances that threaten their physical, emotional, and psychological integrity.
Estimated Projection of US Cancer Incidence and Death to 2040.

Importance Coping with the current and future burden of cancer requires an in-depth understanding of trends in cancer incidences and deaths. Estimated projections of cancer incidences and deaths will be important to guide future research funding allocations, health care planning, and health policy efforts. Objective To estimate cancer incidences and deaths in the United States to the year 2040. Design and Setting This cross-sectional study’s estimated projection analysis used population growth projections and current population-based cancer incidence and death rates to calculate the changes in incidences and deaths to the year 2040. Cancer-specific incidences and deaths in the US were estimated for the most common cancer types. Demographic cancer-specific delay-adjusted incidence rates from the Surveillance, Epidemiology, and End Results Program were combined with US Census Bureau population growth projections (2016) and average annual percentage changes in incidence and death rates. Statistical analyses were performed from July 2020 to February 2021. Main Outcomes and Measures Total cancer incidences and deaths to the year 2040. Results This study estimated that the most common cancers in 2040 will be breast (364 000 cases) with melanoma (219 000 cases) becoming the second most common cancer; lung, third (208 000 cases); colorectal remaining fourth (147 000 cases); and prostate cancer dropping to the fourteenth most common cancer (66 000 cases). Lung cancer (63 000 deaths) was estimated to continue as the leading cause of cancer-related death in 2040, with pancreatic cancer (46 000 deaths) and liver and intrahepatic bile duct cancer (41 000 deaths) surpassing colorectal cancer (34 000 deaths) to become the second and third most common causes of cancer-related death, respectively. Breast cancer (30 000 deaths) was estimated to decrease to the fifth most common cause of cancer death. Conclusions and Relevance These findings suggest that there will be marked changes in the landscape of cancer incidence and deaths by 2040.
Gone Bananas? Current and Future Impact of Fusarium Wilt on Production

Banana (Musa spp.) is one of the world’s most valuable primary agricultural commodities. Production, worth an estimated $50 billion per annum, occurs in over 130 countries. Exported fruit are key commodities in several producing countries yet they comprise less than 15% of the total annual output of 150 million metric tons. Diseases are the most significant biotic constraints for both export and smallholder production. Notably, tropical race 4 (TR4) of Fusarium wilt (aka Panama disease) affects the Cavendish subgroup, which is now responsible for 47% of all production (virtually all exported fruit and over 30% of all remaining production). The recent outbreak of TR4 in Colombia threatens future export production in tropical America, where most export production occurs. This chapter presents an overview of the disease and its causal agent, Fusarium oxysporum f. sp. cubense . Although there is a substantial positive literature on biological, chemical or cultural measures, management is largely restricted to using resistant cultivars where the pathogen has established.
The young and the vestless.

A new lower Cambrian fossil locality in South China offers spectacular glimpses into the post-larval development of a wide variety of soft-bodied early marine animals, knowledge of which has been confined to their mature stages until now.
Management Policy and Estimated Returns on School Trust Lands

Every state entering the Union since 1803 received land grants from the federal government for the support of their respective public school systems. Inherent in this federal grant is the fiduciary duty to prudently and effectively manage these assets for the beneficiary, their school systems. We develop a framework that measures the present value of the beneficiary's economic benefits to assist managers of school trust lands in determining future management policy. Using this framework, we assess whether managers of state school trust lands are currently meeting their fiduciary responsibilities of maximum economic benefit for their beneficiaries or whether changes in management policy are needed. The present value of realized economic returns from grazing lease revenues and capital appreciation are compared with the present value of income streams that may be generated from alternative investments available to the land trustees if the land were sold and the proceeds reinvested in U.S. Treasury securities. Market values and capital appreciation for school trust lands in Wyoming are estimated using hedonic models formulated from ranch sales data. Because we are comparing a risky return on land investments with a riskless return on Treasury bonds, we observe, in most cases, that the sale of land and reinvestment of proceeds will increase economic benefits on school trust lands.
Gender Equality Discussion within the G20

This note discusses W20’s contributions to the gender equality agenda and policies promoted by the G20 and the G20 member states. The first part analyses the progress made by G20 countries on gender equality as framed by W20 recommendations. The assessment focuses on improvements on the main pillars and relies on existing standardized indicators and research reports.3 The second part draws some lessons from the previous analysis, identifying several areas where the W20 Saudi Arabia could help strengthen the overall W20 mission as well as its effectiveness in advancing gender equity at the global level. Finally, the last part of the note identifies three areas of priority for the W20, hence offering some guidance on potential topics of discussion for the W20 Saudi Arabia.
Reflections from the Forgotten Front Line": A qualitative study of factors affecting wellbeing among long-term care workers in New York City during the COVID-19 pandemic."

While long-term care (LTC)1 facilities serving older adults have long struggled with low employee morale and high rates of staff turnover, the COVID-19 pandemic brought unprecedented challenges to these facilities and the frontline staff working in them. This study aimed to explore factors that influenced the personal and professional wellbeing of care providers working in LTC facilities across New York City (NYC) during the pandemic. Fourteen semi-structured qualitative interviews were conducted with frontline care providers working in LTC facilities across NYC. Interviews were audio-recorded, transcribed, and systematically coded according to both pre-existing and emergent topics. Four main themes emerged from the data: the toll of the virus; home and work-life balance stressors; workplace stressors; and participants' recommendations for facility leadership. Findings from this study may inform strategies for supporting the wellbeing of frontline care providers in LTC environments, especially during future public health emergencies.
Sleep patterns of US healthcare workers during the first wave of the COVID-19 pandemic

During the first few months of the COVID-19 outbreak, healthcare workers (HCW) faced levels of personal risk, emotional distress, and professional strain not seen in their lifetimes. This study described how these stressors influenced various aspects of their sleep patterns. From May 19 to June 20, 2020, an electronic, cross-sectional survey was administered to a convenience sample of in- and outpatient HCW in a large, nonprofit healthcare system. Respondents described the pandemic’s initial impact on personal and professional life and various sleep dimensions: regularity, efficiency, duration, timing, quality, and daytime sleepiness. Two hundred seven providers responded, representing 17 different healthcare roles. Most (82%) were women with a median age of 39 years (IQR1–3, 31–53). A majority of respondents (81%) worked in an inpatient setting, with half (46%) primarily on the “frontline.” Approximately one-third of respondents (37%) were physicians and one-quarter (28%) were nurses. Overall, 68% of HCW reported at least one aspect of sleep worsened during the beginning of the pandemic; the most impacted were daytime sleepiness (increased in 43%) and sleep efficiency (worse in 37%). After adjusting for COVID exposure and burnout, frontline providers had twofold higher odds of poor pandemic sleep, aOR 2.53, 95%CI 1.07–5.99. Among frontline providers, physicians were fivefold more likely to develop poor pandemic sleep compared to nurses (OR 5.73, 95%CI 1.15–28.57). During the initial wave of COVID-19, a majority of HCW reported a decline in sleep with an increase in daytime sleepiness and insomnia. Frontline workers, specifically physicians, were at higher risk.
Natural circularly permuted group II introns in bacteria produce RNA circles

SUMMARY Group II self-splicing introns are large structured RNAs that remove themselves from transcripts while simultaneously sealing the resulting gaps. Some representatives can subsequently reverse splice into DNA, accounting for their pervasive distribution in bacteria. The catalytically active tertiary structure of each group II intron is assembled from six domains that are arranged in a conserved order. Here we report structural isomers of group II introns, called CP group II ribozymes, wherein the characteristic order of domains has been altered. Domains five and six, which normally reside at the 3´ end of group II introns, instead occupy the 5´ end to form circularly permuted variants. These unusual group II intron derivatives are catalytically active and generate large linear branched and small circular RNAs, reaction products that are markedly different from those generated by canonical group II introns. The biological role of CP group II ribozymes is currently unknown.
Ellen R. Grass Lecture: First Seizure in a Child

ABSTRACT.Paroxysmal disorders are characterized by the sudden onset of neurological dysfunction. The diagnosing physician almost never witnesses the paroxysmal event. Most “spells” are not seizures, and epilepsy is not a diagnosis of exclusion. Once the diagnosis of a seizure is established, further evaluation and management must be individualized. Critical factors in formulating a plan include a complete description of the event, which sometimes requires videotape, the age of the child, the association of fever, the family history, the neurological examination, and almost always an electroencephalogram. Some first seizures in children do not require initiating prophylactic treatment: others always do.
Targeted Bayesian Learning

TMLE is a loss-based semiparametric estimation method that yields a substitution estimator of a target parameter of the probability distribution of the data that solves the efficient influence curve estimating equation and thereby yields a double robust locally efficient estimator of the parameter of interest under regularity conditions. The Bayesian paradigm is concerned with including the researcher’s prior uncertainty about the probability distribution through a prior distribution on a statistical model for the probability distribution, which combined with the likelihood yields a posterior distribution of the probability distribution that reflects the researcher’s posterior uncertainty. Just like model-based maximum likelihood learning, Bayesian learning is intrinsically nontargeted by working with the prior and posterior distributions of the whole probability distribution of the observed data structure and is thereby very susceptible to bias due to model misspecification or nontargeted model selection.
ORIGINAL RESEARCH—PEYRONIE'S DISEASE: Testosterone Deficiency and Peyronie's Disease: Pilot Data Suggesting a Significant Relationship

ABSTRACT Introduction As testosterone (T) has been shown to influence wound healing, and serum T declines in the age group at risk for Peyronie's disease (PD), we explored the possibility that low serum T may be associated with PD. Aim The purpose of this study was to evaluate the relationship between serum T concentrations and features of PD. Methods Medical records were reviewed for 121 consecutive patients with PD seen over a 2-year period. All patients were assessed for sociodemographic data, medical history, comorbid medical conditions, findings on physical examination, and severity of curvature. Laboratory testing included serum concentrations of total testosterone (TT) and free testosterone (FT). Testosterone deficiency (TD) was defined as TT values less than 300 ng/dL and/or FT less than 1.5 ng/dL. Main Outcome Measures Prevalence of TD in men with PD and correlation of TT and FT with severity of curvature and plaque size. Results Mean patient age was 53.9 ± 10.6 years (range 28–77). Penile curvature was 50.2 ± 23.6 degrees (range 10–120). Mean TT was 411.6 ± 203.6 ng/dL (range 69–877), and mean FT was 1.12 ± 0.58 ng/dL (range 0.13–5.06). Low T was identified in 29.5% by TT alone and in 74.4% overall. Severity of curvature was greater for men with TD compared with men with normal T (54.3 vs. 37.1 degrees, P = 0.006). Men with low FT had greater penile curvature than men with normal FT (37.5 vs. 55.9 degrees, respectively, P = 0.003). Severity of penile curvature correlated significantly with FT ( r = −0.314, P = 0.016) and estradiol/T ( r = 0.476, P = 0.0001) but not TT ( r = −0.199, P = 0.138). Conclusions This pilot study suggests a possibly important relationship between low T and PD. Further prospective studies are needed to confirm this relationship. Moreno SA, and Morgentaler A. Testosterone deficiency and Peyronie's disease: Pilot data suggesting a significant relationship. J Sex Med 2009;6:1729–1735.
Molecular contrast in interferometric imaging

Interferometric imaging offers many advantages for biomedical applications such as optical sectioning/depth resolution. Inclusion of molecular contrast information improves utility but requires additional efforts to either isolate spectroscopic information or detect contrast agents.
Activation of protein kinase C by naturally occurring ether-linked diglycerides.

Abstract Recent studies have demonstrated that ether-linked diglycerides are endogenous constituents of biologic tissues and accumulate during agonist stimulation (Daniel, L. W., Waite, M., and Wykle, R. L. (1986) J. Biol. Chem. 261, 9128-9132) and myocardial ischemia (Ford, D. A., and Gross, R. W. (1989) Circ. Res. 64, 173-177). Although protein kinase C previously had been thought to specifically require 1,2-diacyl-sn-glycerol (DAG) molecular species for activation, the present study demonstrates that purified rat brain protein kinase C is activated by naturally occurring ether-linked diglycerides (e.g. 1-O-hexadec-1'-enyl-2-octa-dec-9'-enoyl-sn-glycerol and 1-O-hexadecyl-2-octa-dec-9'-enoyl-sn-glycerol) with a similar dose response curve to that for DAG molecular species. Although in vitro assays demonstrated that DAG could partially activate protein kinase C in the absence of free calcium, activation by ether-linked diglycerides required free calcium concentrations found only in stimulated cells (greater than 1 microM [Ca2+]free). To substantiate these findings the alpha and beta isoforms of protein kinase C from rat brain cortical grey matter were resolved by hydroxylapatite chromatography. Although the beta isoform of protein kinase C was substantially activated by DAG in the absence of free calcium, activation by ether-linked diglycerides had an absolute requirement for physiologic increments in free calcium ion found in stimulated cells. Since ether lipids are localized in specific subcellular membrane compartments, accumulate during several pathophysiologic perturbations and are effective activators of protein kinase C with separate and distinct calcium requirements in comparison to DAG, these results suggest that ether-linked diglycerides are important and potentially specific biologic activators of one or more isoforms of protein kinase C.
Control, timing, and data acquisition for the Argonne Wakefield Accelerator (AWA)

The AWA is a new facility primarily designed for wakefield acceleration experiments at the 100 MV/m scale, which incorporates a high current linac and rf photocathode electron source, a low emittance rf electron gun for witness beam generation, and associated beamlines and diagnostics. The control system is based on VME and CAMAC electronics interfaced to a high performance workstation and provides some distributed processing capability. In addition to the control of linac rf, laser optics, and beamlines, the system is also used for aquisition of video data both from luminescent beam position monitors and from streak camera pulse length diagnostics. Online image feature extraction will permit wakefields to be computed during the course of data taking. The linac timing electronics and its interface to the control system is described. >
Evidence that activation of the respiratory burst oxidase in a cell-free system from human neutrophils is accomplished in part through an alteration of the oxidase-related 67-kDa cytosolic protein.

Sodium dodecyl sulfate (SDS) is able to activate the respiratory burst oxidase in a system containing cytosol and solubilized membranes from human neutrophils. When SDS was used to treat cytosol in an otherwise identical system in which the solubilized membrane solution was omitted, the ability of the SDS-treated cytosol to support O2- production was lost in a first-order reaction whose rate constant was virtually identical to the rate constant for the first-order activation of the oxidase in the complete system. Studies with chronic granulomatous disease cytosols showed that the component whose activity was lost was the oxidase-related 67-kDa cytosolic protein. The similarity in the rates of oxidase activation and p67 inactivation suggested that the activation of the respiratory burst oxidase in the cell-free system could involve an SDS-mediated alteration in p67. Further support for this idea was provided by kinetic experiments demonstrating that, although the yield of oxidase showed a 2.5-order dependence on cytosol concentration, oxidase activation was nevertheless kinetically irreversible. These two findings, incompatible in general, can be reconciled by a mechanism in which SDS acts specifically on a single oxidase component (i.e. p67), but with an effect that depends on circumstances: oxidase activation, if the SDS-sensitive component is part of a completely assembled oxidase precursor; loss of p67 activity, if not.
The management of pregnancy complicated by heart disease.

Abstract In a review of the histories of 41,361 women delivered at the Pennsylvania Hospital during the years 1937 to 1952, inclusive, the total number with heart disease was found to be 565, an incidence of 1.12 per cent. The maternal mortality rate in the pregnant cardiac patient was 2.6 per cent (15 maternal deaths). The fetal mortality rate was 12.3 per cent (70 fetal deaths). Heart disease has occupied the most prominent position as a cause of maternity mortality, accounting for 27.2 per cent of the maternal deaths from all causes during the sixteen years reviewed in our hospital. Acute congestive failure was the cause of death in 11 of the 15 deaths. Infection was the precipitating factor in 7 cases. Prematurity was the leading cause of death in the babies. The pregnant cardiac patients were divided into two groups: those delivered from 1937 to 1947, and those delivered from 1948 to 1952. The purpose was to analyze the groups in relation to the establishment of the Cardiac-Obstetric Clinic in 1948. Only one maternal death from heart disease has occurred since its inception, that of an unregistered patient. From the analysis of our patients, we believe the problems of management of pregnancy with heart disease should include the following: 1. 1. An understanding of the physiological changes in the circulation in the normal pregnant woman and the changes in the pregnant woman with heart disease 2. 2. The diagnosis and assessment of the pregnant woman with heart disease 3. 3. Proper and adequate treatment during pregnancy, delivery, and pucrperium The different phases of treatment are diseussed in detail. Certain techniques in treatment, such as the increased use of forceps for delivery, conduction block anesthesia, and use of digitalis therapy are emphasized. Close cooperation between the cardiologist and the obstetrician at all times is strongly advocated.
RNase T affects Escherichia coli growth and recovery from metabolic stress.

Abstract To determine the essentiality and role of RNase T in RNA metabolism, we constructed an Escherichia coli chromosomal rnt::kan mutation by using gene replacement with a disrupted, plasmid-borne copy of the rnt gene. Cell extracts of a strain with mutations in RNases BN, D, II, and I and an interuppted rnt gene were devoid of RNase T activity, although they retained a low level (less than 10%) of exonucleolytic activity on tRNA-C-C-[14C]A due to two other unidentified RNases. A mutant lacking tRNA nucleotidyltransferase in addition to the aforementioned RNases accumulated only about 5% as much defective tRNA as did RNase T-positive cells, indicating that this RNase is responsible for essentially all tRNA end turnover in E. coli. tRNA from rnt::kan strains displayed a slightly reduced capacity to be aminoacylated, raising the possibility that RNase T may also participate in tRNA processing. Strains devoid of RNase T displayed slower growth rates than did the wild type, and this phenotype was accentuated by the absence of the other exoribonucleases. A strain lacking RNase T and other RNases displayed a normal response to UV irradiation and to the growth of bacteriophages but was severely affected in its ability to recover from a starvation regimen. The data demonstrate that the absence of RNase T affects the normal functioning of E. coli, but it can be compensated for to some degree by the presence of other RNases. Possible roles of RNase T in RNA metabolism are discussed.
Nicotine-induced tolerance and dependence in rats and mice: studies involving schedule-controlled behavior.

Publisher Summary This chapter evaluates nicotine-induced tolerance and dependence using schedule-controlled behavior as a major dependent variable. The reasons for using this approach are two-fold. First, operant behavior has been observed to be extremely sensitive to drug-induced disruption. Second, with an operant model, one has the capacity to evaluate both pharmacological and behavioral mechanisms of tolerance development. The tolerance may be related to the up-regulation of nicotinic receptors suggesting a desensitization of the nicotinic receptor. This chapter characterizes the development of tolerance to nicotine's disruptive effects on schedule-controlled behavior and determined whether tolerance to nicotine-induced behavioral disruption is a function of either/or both behavioral (pre-administration) or pharmacological mechanisms (post-administration). The tolerance development to nicotine involves an acetylcholine-sensitive cholinergic neuron is determined. Operant procedures useful to detecting nicotine-induced dependence as measured by behavioral disruption after the cessation of chronic nicotine administration are evaluated.
Real-time correction of rigid body motion-induced phase errors for diffusion-weighted steady-state free precession imaging.

Purpose Diffusion contrast in diffusion-weighted steady-state free precession magnetic resonance imaging (MRI) is generated through the constructive addition of signal from many coherence pathways. Motion-induced phase causes destructive interference which results in loss of signal magnitude and diffusion contrast. In this work, a three-dimensional (3D) navigator-based real-time correction of the rigid body motion-induced phase errors is developed for diffusion-weighted steady-state free precession MRI. Methods The efficacy of the real-time prospective correction method in preserving phase coherence of the steady state is tested in 3D phantom experiments and 3D scans of healthy human subjects. Results In nearly all experiments, the signal magnitude in images obtained with proposed prospective correction was higher than the signal magnitude in images obtained with no correction. In the human subjects, the mean magnitude signal in the data was up to 30% higher with prospective motion correction than without. Prospective correction never resulted in a decrease in mean signal magnitude in either the data or in the images. Conclusions The proposed prospective motion correction method is shown to preserve the phase coherence of the steady state in diffusion-weighted steady-state free precession MRI, thus mitigating signal magnitude losses that would confound the desired diffusion contrast. Magn Reson Med 73:565–576, 2015. © 2014 Wiley Periodicals, Inc.
Differential Roles for Wiskott-Aldrich Syndrome Protein in Immune Synapse Formation and IL-2 Production

Wiskott-Aldrich syndrome protein (WASP)-deficient T cells exhibit defects in IL-2 production that are widely believed to stem from primary defects in actin remodeling and immune synapse formation. Surprisingly, however, we find that WASP-deficient T cells responding to Ag-specific APCs polymerize actin and organize talin and PKCθ normally, forming an immune synapse that is stable for at least 3 h. At low doses of peptide, WASP-deficient T cells show less efficient talin and PKCθ polarization. Thus, although WASP may facilitate immune synapse formation at low peptide concentrations, WASP is not required for this process. Defects in IL-2 production are observed even under conditions in which immune synapse formation proceeds normally, suggesting that the role of WASP in regulating IL-2 production is independent of its role in immune synapse formation.