cssi/SciSciGPT-SciSciNet huggingface dataset:
Cancer-related information needs and cancer's impact on control over life influence health-related quality of life among adolescents and young adults with cancer.

Author(s): DeRouen, Mindy C; Smith, Ashley Wilder; Tao, Li; Bellizzi, Keith M; Lynch, Charles F; Parsons, Helen M; Kent, Erin E; Keegan, Theresa HM; AYA HOPE Study Collaborative Group | Abstract: ObjectiveAdolescents and young adults (AYAs) diagnosed with cancer between 15 and 39 years of age often report need for greater amounts of cancer-related information and perceive that cancer has had a negative impact on control over their life. We examined whether unmet information need and perceived control over life are associated with health-related quality of life (HRQOL).MethodsWe examined data from 484 AYA cancer survivors recruited from population-based cancer registries in 2007-2008. Participants completed surveys a median of 11 months after diagnosis. Multivariable linear regression analyses estimated associations of unmet cancer-related information needs and impact of cancer on control over life on HRQOL (SF-12).ResultsTwo-thirds of AYAs reported an intermediate or high level of unmet information need, and half (47%) reported a negative impact of cancer on control. Greater unmet information need was associated with lower overall mental and physical HRQOL and lower levels of all HRQOL subscales except vitality. A negative impact on control over life was associated with lower overall mental HRQOL as well as lower HRQOL across all subscales except general health perceptions (all p l0.05). In multivariable analyses, perceived control and unmet information need were independently associated with HRQOL (p-values for interaction g0.1).ConclusionsAdolescent and young adult patients with cancer have high levels of unmet cancer-related information needs and perceived negative impact of cancer on control over life; both were independently associated with lower HRQOL. Addressing unmet information needs among AYA cancer survivors and finding ways to increase their sense of control may help improve HRQOL in this understudied population.
THE GROWTH OF CUCUMIS MELO SEEDLINGS AT DIFFERENT TEMPERATURES.

The work of Julius Sachs (10) published in 1860, and in particular his discussion of the results, served to introduce two concepts into plant physiology, that of minimal, optimal, and maximal temperatures, and that of the grand period of seedling growth. Each of these phenomena has received the attention of numerous workers since that time but there have been relatively few attempts to combine the two fields of interest and to follow the course of growth of seedlings cultured in darkness at several constant temperatures throughout their entire growth period. The work of Sierp (11), Hamada (4), and Silberschmidt (12) on the growth of oat coleoptiles belongs in this class, as does that of Edwards, Pearl, and Gould (1) on Celosia crislata seedlings. Silberschmidt also tested pea and rice seedlings and contributed an interesting analysis of the problem. The present paper deals with the growth of Cucumis melo seedlings in darkness at seven constant temperatures between 15 ° and 40°C. inclusive. While we have accumulated in this laboratory during the past 10 years a considerable volume of unpublished observations on the effect of temperature on the growth of canteloup seedlings, so far as is known the only published work on the temperature relations of growth in this species are those of de Vries (14) who found greater growth at the end of a 48 hour period at 37.2 ° than at any of the other three temperatures he tested. Gregory (3) has made interesting temperature tests of another sort on Cucumis salivus seedlings grown in light which indicate a much lower optimal temperature range than was found in de Vries' experiments or in those presented here.
Proposal of a model of mammalian neural induction

How does the vertebrate embryo make a nervous system? This complex question has been at the center of developmental biology for many years. The earliest step in this process - the induction of neural tissue - is intimately linked to patterning of the entire early embryo, and the molecular and embryological of basis these processes are beginning to emerge. Here, we analyze classic and cutting-edge findings on neural induction in the mouse. We find that data from genetics, tissue explants, tissue grafting, and molecular marker expression support a coherent framework for mammalian neural induction. In this model, the gastrula organizer of the mouse embryo inhibits BMP signaling to allow neural tissue to form as a default fate-in the absence of instructive signals. The first neural tissue induced is anterior and subsequent neural tissue is posteriorized to form the midbrain, hindbrain, and spinal cord. The anterior visceral endoderm protects the pre-specified anterior neural fate from similar posteriorization, allowing formation of forebrain. This model is very similar to the default model of neural induction in the frog, thus bridging the evolutionary gap between amphibians and mammals.
Evaluating the impact of a pre-rotation workshop on student preparation for clinical advanced pharmacy practice experiences

*Objectives: This pilot study was designed to evaluate the impact of a pre-rotation workshop (PRW) on pharmacy students’ clinical skills and preparation for clinical Advanced Pharmacy Practice Experiences (APPE) involving direct patient care. Methods: Randomized controlled trial of an educational intervention with Institutional Review Board approval. PRW activities designed to simulate rotation activities around five competencies, patient charts, medication histories, SOAP notes, patient presentations, and professionalism. Endpoints were evaluated using clinical rotation preceptors’ evaluation of performance and students’ performance on objective structured clinical exams (OSCE). Results: Eight fourth-year students and eight GPA matched controls (20% of the total class) were selected to voluntarily participate. The PRW demonstrated a positive impact on students’ clinical skills and preparation for rotations by improving OSCE performance. However, no significant differences were found between groups when comparing preceptor evaluations of skills on rotations. These results are limited by the small sample size, potential OSCE “test-wiseness” effects, lack of OSCE evaluator blinding to study groups, potential case specificity effects due to the limited number of cases used on the OSCE and possible lack of sensitivity of the rotation evaluation tool to capture true differences among the experimental and control group participants. Conclusion: The PRW was successful at advancing students’ clinical skills and preparation for rotations and may be considered as a tool to help bridge didactic to clinical experiences in the Pharm.D. curriculum.
Eye Contact, Sex, and the Violation of Personal Space

Summary In a public elevator in a downtown office building three experiments examined relationships among varying degrees of eye contact, sex of participants, and violations of personal space. The first experiment forced Ss (86 males and 61 females) to violate the personal space of two male or two female confederates (Cs) who were either directing their gazes at the Ss or were diverting their gazes as the Ss entered the elevator. The results indicated that male Ss chose to violate the personal space of the C who diverted his gaze regardless of the sex of that C, while female Ss chose to violate the personal space of the male C who diverted his gaze and the female C who directed her gaze at the entering Ss. In the second experiment, the Ss (68 males and 44 females) were again forced to violate the personal space of two Cs of the same sex. In each of two conditions, one of the Cs avoided the possibility of gazing at entering Ss, while the second C only diverted his gaze. Ss chose to violate the personal spa...
Protocols for self-organization of a wireless sensor network

We present a suite of algorithms for self-organization of wireless sensor networks in which there is a scalably large number of mainly static nodes with highly constrained energy resources. The protocols further support slow mobility by a subset of the nodes, energy-efficient routing, and formation of ad hoc subnetworks for carrying out cooperative signal processing functions among a set of the nodes.
Electron Microscopic Study of Development in a Sea Cucumber, Stichopus tremulus (Holothuroidea), from Unfertilized Egg through Hatched Blastula

In this, the first fine structural study of sea cucumber embryology, eggs and embryos of Stichopus tremulus developing at 7.5°C are described from spawning through hatched blastulae. Spawned eggs are at about first meiotic metaphase and are surrounded by a jelly layer that remains around the embryos until hatching. No vitelline coat can be demonstrated, but whether it is truly absent or removed by electron microscopic processing is not known. Insemination initiates a rapid cortical reaction, completed within 2 min., which involves a wave of cortical granule exocytosis and fertilization envelope formation. The compactly fibrous fertilization envelope is about 50 nm thick and appears to consist entirely of ejected cortical granule material (if one assumes that there is no vitelline coat). As the fertilization envelope elevates, no hyaline layer appears in the perivitelline space. The first and second polar bodies are emitted, respectively, at about 9 and 15 min. after insemination. The first seven or so cleavages are equal, radial, and occur approximately every 4 hr. The blastocoel opens up at the four-cell stage and, during the earlier cleavages, remains connected with the perivitelline space via numerous gaps between the roughly spherical blastomeres. At the 64-cell stage, these gaps begin to close as the blastomeres start to become cuboidal; in addition, an embryonic cuticle is produced on the apical surface of each blastomere. In embryos of several hundred cells, the blastomeres become associated apicolaterally by junctional complexes, each consisting of a zonula adherens and a septate junction. Several hours before hatching, a single cilium is produced at the apical surface of most blastomeres. At hatching (about 50 hr after insemination), the ciliated blastula leaves behind the fertilization envelope and jelly layer. Swimming blastulae soon begin to elongate in the animal-vegetal axis, and a basal lamina develops on blastomere surfaces facing the blastocoel. The discussion includes a fine structural comparison of egg coats among the five classes of the phylum Echinodermata.
A generative Bayesian model to identify cancer driver genes

Cancer is a disease characterized largely by the accumulation of somatic mutations during the lifetime of a patient. Distinguishing driver mutations from passenger mutations had posed a challenge in modern cancer research. With the state of art of microarray technologies and clinical studies, a large numbers of candidate genes are extracted. Extracting informative genes out of them is essential. In our project we aim to find the cancer driver genes using somatic mutation data and protein protein interaction data. We developed a generative mixture model coupled with Bayesian parameter estimation to estimate background mutation rates and driver probabilities of each gene as well as the proportion of drivers among all sequenced genes. We choose suitable prior distributions for modelling both driver probabilities and background mutations of each gene. We apply our method to ovarian cancer data and numerically estimated the solution. Upon convergence, we are able to discover and identify some new candidate cancer driver genes.
Utilizing Twitter for Concept Learning

Despite the perception that face-to-face classrooms provide speaking opportunities, studies by,, and have conveyed that there is limited interaction in a traditional college lecture setting. Social media networks such as Twitter provide an opportunity for instructors to utilize popular mobile technology to create a discussion beyond the classroom. Twitter's 140-character maximum creates an efficient method of communication that can be spaced over time. Spacing practice has the potential for improving classroom learning. This mixed-methods study utilizing a convenience sample tested if Twitter could serve as a more effective method of review than a traditional paper study guide in an introductory college history course. No significant differences were found in in the posttest performance of both groups. Participants found Twitter easy to use, were unconcerned about their privacy on social media, and reported that Twitter did not increase student engagement when used only as an information distribution tool.
Survival of Liriomyza trifolii (Diptera: Agromyzidae) in Detached Chrysanthemum Leaves

The influence of leaf detachment and leaf storage conditions on survival of Liriomyza trifolii (Burgess) eggs, larvae, and reared pupae was studied. When kept at 26 ± 1°C and at approximately 100%relative humidity (RH) so that leaf fresh weight and turgidity were maintained, chrysanthemum ( Dendranthema grandifiora Tzvelev. cv. Iceberg) leaves that were detached immediately after oviposition yielded as many leafminers as did leaves left on plants. Detached foliage kept at 26°C but at a lower and fluctuating relative humidity (80 ± 20%) did not yield leafminers if harvested immediately after oviposition. If, however, leaves were detached two days after oviposition (first instars present) and stored at 26 ± 1°C and approximately 80% RH, the leafminer yield was comparable to that from undetached leaves. When stored on or under greenhouse benches (8-32°C, 10-80% RH), leaves that were detached three days after oviposition (second instars present) yielded as many leafminers as leaves on plants. The results emphasize the importance of maintaining greenhouses that are free of plant litter as part of a leafminer control program. For the researcher, the study indicates that L. trifolii can be reared experimentally by using detached leaves rather than whole plants.
Reused Platform for Application Software in Naval C2 System

To increase the efficiency of integrated joint operations,a software reuse platform is developed based on advanced software architecture which can manage complex organization and system,and not only stand for the tendency of the new C2 platform,but also integrate the legacy systems.Based on the service-oriented technology,the architecture for application software in naval C2 system has been designed,and three integrated methods are proposed,then the reused platform for application software is developed which can assemble the system agilely,and match the changeable requirement quickly,and will increase the flexibility and fitness of naval application software significantly.
Eulerian multiphase conjugate model development and validation for flow boiling in micro-pin field

Chip-embedded micrometer scale two-phase cooling technology can be essential to fully optimize the benefits of improved integration density of three-dimensional (3D) stacking in high performance integrated circuits (ICs) for future computing systems; but is faced with significant developmental challenges including high fidelity modeling. In the present work, an Eulerian multiphase model has been developed for simulating two-phase evaporative cooling through chip embedded microscale cavities populated with pin-fins. First the model is used to predict the flow and heat transfer characteristics for coolant R1234ze flowing through a two-port ∼10 mm long micro-cavity populated with 80 µm diameter pin-fins arranged in an in-line manner. The flow is sub-cooled in the initial section of the cavity and saturated in the remaining. The results were compared to experimental data available from fundamental experiments, focusing on the model capability to predict the correct flow pattern, temperature profile and pressure drop.
Reading Greek and Roman Historical Sources

Today we are so far removed from a world where servitude in manual labor was the norm that empathy alone is often our faulty guide to historical understanding. For instance, in Spartacus’s day, Enna was a center of the slave economy on the island of Sicily and of the slave wars against the Roman state; now it is the home of Marina Taglialavore, the inventor of a new computer chip that has revolutionized the reading of images. Any hope of crossing this chasm to better historical understanding must begin with the fundamentals of reading the original documents that have been translated into English in this book.
Finding Opportunities to Enhance Evidence-Based Treatment Through Provider Feedback: A Qualitative Study

ABSTRACTThe Child System and Treatment Enhancement Projects (Child STEPs) clinical trials have endeavored to help bridge the gap between science and practice in children’s mental health services. The current study used an inductive coding approach to analyze feedback from 2 qualitative focus groups comprising 15 community mental health providers in the Los Angeles area. It explored the factors influencing provider implementation experiences with an innovative modular treatment design during the Child STEPs in California randomized effectiveness trial. Themes from the focus group discussions—including consultation, flexibility, treatment fit, study influences, and context—are presented and their implications explored. Two potential avenues for addressing provider concerns were considered: design strategies and supportive strategies. Primarily in the service context of Los Angeles, provider feedback suggested that the treatment’s fit to diverse client populations was a central concern and that the ongoing c...
Gaba-Ergic Dysfunction in Tourette Syndrome

Researchers at the FDA, Silver Spring, MD; Department of Neurology, University of Pittsburgh Medical School, PA; National Institute of Mental Health, NIH, Bethesda, MD; and other centers used a PET study to assess the involvement of the GABA-ergic system in 11 adult Tourette syndrome patients compared to 11 healthy controls.
George Catlin and Sir Thomas Phillipps: A Nineteenth-Century Friendship

In George Catlin and Sir Thomas Phillipps we encounter two fascinating characters, both of whom were major cultural figures in their own time and both of whom made lasting contributions to history. Catlin and Phillipps were in the business of discovery and recovery. Catlin devoted his life to recording Native American tribes at the time of Indian Removal, when Indians were being subjected not only to the loss of their land but also to the rapid and irrevocable disruption of their societies. Phillipps haunted auction rooms and bookshops and mined monasteries, city halls, aristocratic libraries, and country churches for historical . . .
Joint Hypermobility Syndrome: Recognizing a Commonly Overlooked Cause of Chronic Pain

Joint hypermobility syndrome, also known as benign hypermobility syndrome, is a connective tissue disease characterized by joint instability, chronic pain, and minor skin changes. It shares many clinical features of Ehlers-Danlos syndrome, Hypermobility Type; enough so that many authorities consider them as one disease process. Approximately 3% of the general population is believed to have joint hypermobility syndrome, but despite this high prevalence, due to lack of awareness, heterogeneity of clinical presentation, and reliance on physical examination for diagnosis, it is largely overlooked by primary care physicians as well as by specialists. This leads to delayed or missed opportunities for diagnosis, and inappropriate interventions that frustrate both providers and patients. We review the literature regarding the pathophysiology, diagnosis, treatment options, and prognosis of joint hypermobility syndrome, and advocate for primary care physicians to consider it in the differential diagnosis of patients with chronic pain.
EMPC-based design of energy storage units for electric power networks

The economic benefit realized from energy storage units on the electric grid is linked to the control policy selected to govern grid operations. Thus, the optimal sizing and placement (OSP) of such units is also dependent on the operating policy of the power network. In this work, we first introduce economic model predictive control (EMPC) as a viable economic dispatch policy for transmission networks with energy storage. However, the numeric basis of EMPC makes it ill-suited for the OSP problem. In contrast, the method of economic linear optimal control (ELOC) can be easily adapted to the OSP problem. However, the relaxation of point-wise-in-time constraints, inherent to ELOC, will introduce a systematic underestimation of operating costs. Thus, we introduce a novel 2-step OSP algorithm that begins with the ELOC-based approach to determine the placement of energy storage units. Then, an EMPC-based gradient search is used to determine optimal sizes.
The Task of the Translator

This discussion reflects closely on Dominique Scarfone’s call to consider psychoanalysis as a practice founded on ethics, and to rely on this premise in charting a fundamental common ground such th...
A rewarding experience for a pediatric urologist.

When I reflect on some of the most rewarding experiences in my practice, one of the most personally rewarding cases was on a fertility preservation consultation with a 12-year-old boy who had just been diagnosed with Ewing’s sarcoma and told that the treatment would leave him infertile.
Reading recovery© won't fix poor core tier-one reading instruction

This essay challenges whether or not the use of district money for Reading Recovery© (RR) instruction is an effective expenditure of funds that results in sustained improvement in student reading o...
Neural architecture: from cells to circuits.

Circuit operations are determined jointly by the properties of the circuit elements and the properties of the connections among these elements. In the nervous system, neurons exhibit diverse morpho...
NEUROLARYNGOLOGY: Past, Present, and Future

The term neurolaryngology has come into use over the last 20 years or so. Although the word sounds somewhat like neurotology, there are few similarities in the ways that the two fields originated and developed. Neurotology developed at the intersection of otology and neurosurgery. It is generally considered to encompass otologic surgical procedures within the intracranial space and nonsurgical management of those disorders that sometimes require such surgery. Neurolaryngology arose from collaborations between laryngologists and neurologists who recognized that neurologic disorders could impair laryngeal function, and that neurogenic etiology could be discerned frequently for seemingly idiopathic hoarseness and dysphagia. The focus of neurolaryngology is the management of neurogenic dysfunction of the larynx and pharynx, including central and peripheral disorders. The focus is functional management, and thus surgical procedures are primarily rehabilitative and not extirpative.
Medical applications of stereolithography: An overview

Stereolithography or three-dimensional printing (3DP) is a fast-growing field, with increasing number of health-care applications. As an industry, stereolithography is expected to grow from an estimated $700 million to nearly $9 billion in revenue over the next few years, mainly due to continued advancements and practical implementations of the technology. More established applications of 3DP in medicine involve the creation of wearable assist devices, prosthetics, and orthotics. Research is ongoing in the area of incorporating biologic (including genetic) implementations of 3DP technology, with the long-term goal of three-dimensional printing of organs and tissues that can be subsequently implanted into human body. Given that applications of 3DP in health-care have only recently begun to proliferate, there continues to be paucity of literature in this important and rapidly evolving area of research. In the current review, we sought to present a comprehensive and most current high-level overview of 3DP, with the goal of catalyzing better general understanding and promoting research in 3DP for biomedical applications. The following core competencies are addressed in this article: Medical knowledge, Systems-Based Practice.
Photoacoustic Flow System for the Detection of Ovarian Circulating Tumor Cells Utilizing Copper Sulfide Nanoparticles

The development of cell-specific photoacoustic (PA) contrast agents within systems of fluidic flow provides opportunities for the accurate detection of early stage cancer metastasis. Despite the promise of exogenous contrast agents for use in clinical settings, applications are currently limited by both material biocompatibility and target specificity. In this study, folic acid functionalized copper sulfide nanoparticles (FA-CuS NPs) are synthesized to enable ovarian-cancer-specific binding and PA detection in a custom flow system. Folate receptors, known to be overexpressed on the surface of ovarian cancer cells, have remained an ideal candidate for specific targeting through functionalization on nanoparticles and other contrast agents. In combination with copper sulfide nanoparticles' strong absorbance in the near-infrared (NIR), these FA-CuS NPs are an ideal contrast agent capable of being detected by photoacoustic flow cytometry. For the first time, this study shows a potential PA contrast agent to accurately identify ovarian circulating tumor cells in flow.
Estimating Quality of Life Decrements Due to Diabetes Complications in the United States: The Health Utility Index (HUI) Diabetes Complication Equation

Health utility decrements associated with diabetes mellitus complications are essential for calculating quality-adjusted life-years (QALYs) in patients for use in economic evaluation of diabetes interventions. Previous studies mostly focused on assessing the impact of complications on health utility at event year based on cross-sectional data. This study aimed to separately estimate health utility decrements associated with current and previous diabetes complications. The Health Utilities Index Mark 3 (HUI-3) was used to measure heath utility in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial (N = 8713). Five macrovascular complications (myocardial infarction [MI], congestive heart failure [CHF], stroke, angina, and revascularization surgery [RS]) and three microvascular complications (nephropathy [renal failure], retinopathy [severe vision loss], and neuropathy [severe pressure sensation loss]) were included in a set of alternative modelling approaches including the ordinary least squares (OLS) model, fixed effects model, and random effects model to estimate the complication-related health utility decrements. All macrovascular complications were associated with decrements of HUI-3 scores: MI (event year: − 0.042, successive years: − 0.011), CHF (event year: − 0.089, successive years: − 0.041), stroke (event year: − 0.204, successive years: − 0.101), angina (event year: − 0.010, successive years: − 0.032), and revascularization (event year: − 0.038, successive years: − 0.016) (all p < 0.05). For microvascular complications, severe vision loss (− 0.057), and severe pressure sensation loss (− 0.066) were significantly associated with decrements of HUI-3 scores (both p < 0.05). Hypoglycemia (both severe and symptomatic) was found to be associated with a 0.036 decrement of health utility at event year, and a 0.033 decrement of health utility at successive years. Results from an OLS model are preferred for supporting a microsimulation model while a fixed effects model is preferred to describe direct health impacts from complications. Macrovascular and microvascular complications caused QALY decrements in patients with type 2 diabetes. While only part of the total impaired QALY is experienced during the event year, further QALY decrements for successive years were quite substantial.
A preoperative predictive model for prolonged post-anaesthesia care unit stay after outpatient surgeries.

Study objectiveTo create a preoperative predictive model for prolonged post-anaesthesia care unit (PACU) stay for outpatient surgery and compare with an existing (University of California-San Diego...
Lack of Value of Clinical Predictors of Heparin Induced Thrombocytopenia (HIT) in Complex Patients.

HIT is a devastating complication of heparin use that can result in thrombosis and death. However, it can be difficult to diagnose. Although the clinical hallmark of HIT is a drop in platelet counts in patients receiving heparin, in complex patients there may be many confounding reasons for thrombocytopenia and thrombosis. One proposed diagnostic tool for HIT is to quantitate the percent drop in platelet count from the highest level. Also Warkentin has proposed the “4T’s” scoring system where 4 clinical indicators (% drop in platelet count, timing of heparin dosing, presence of thrombosis, and lack of other causes of thrombocytopenia) are used to derive a score to indicate High, Intermediate, or Low probability of HIT.(Curr Hem Rep, 2 , 148–157) We sought to verify the predictive value of these clinical systems. Over a 30 month period, we reviewed the charts of 544 patients who were suspected of having HIT. 61% of these patients were in intensive care units, 47% were peri-operative, and 22% were cardiac patients. HIT was diagnosed by a combination of review of the clinical course plus results of platelet activation assay, and with at least 2 faculty hematologist agreeing on the diagnosis. Data was abstracted concerning platelet count, timing and use of heparin, presence of thrombosis, and other causes of thrombocytopenia including infection and major surgery. 18 out of 544 patients (3.3%) had heparin induced thrombocytopenia. 16 of 18 patients received therapeutic standard heparin and 2 patients received only prophylactic doses of LMWH. There was no difference in nadir platelet count nor percent drop in HIT (75±79,000/Ul, 65±26%) vs those without HIT (90±71,000/uL, 53±24%). Two major causes of thrombocytopenia in this population were infections and surgery. 175 patients (32%) had positive blood cultures with a mean platelet drop of 55±23% preceding the positive cultures. 47% had major surgery with a mean platelet drop afterwards of 60±22%. A drop in platelets of over 50% had a 82% sensitivity for HIT but only a 43% specificity. Using different cut-offs did not reveal a value with better predictability. Interestingly, only 2 (11%) of the HIT patients scored on the 4T’s as High probability with 39% being Intermediate and 50% as Low. This was due to presence of other causes of thrombocytopenia in patients and the fact that 30% of the HIT patients were on heparin longer that 10 days. 4% of the non-HIT group scored as High and 28% as Intermediate but close review of their subsequent clinic course did not reveal evidence for HIT. Simple clinical tools for diagnosing HIT are of limited utility in ill and complex patients due to other competing causes of thrombocytopenia and the potential for long duration of heparin exposure.
Multienergy operation analysis in a superconducting linac based on off-frequency detune method

The free-electron laser facilities driven by a superconducting radio-frequency (SRF) linac provide high-repetition-rate electron beam, which makes it feasible to feed multiple undulator lines at the same time. In this paper, we study a method of controlling the energy of multiple electron bunches by off-frequency detuning in the SRF linac. Based on the theoretical analysis, we present the available discrete frequency detunes and the optimal linac energy allocation solutions with given energy overhead and periodic energy pattern. The required off-frequency detune is not larger than half of the beam repetition rate, which can be realized with the frequency tuner in SRF cavities. We adopt the configuration of the high energy upgrade of the Linac Coherent Light Source II (LCLS-II-HE) as an example to discuss the possible schemes in practice to support two undulator lines simultaneously. We also discuss the energy jitter increase due to the off-crest acceleration, the tunable energy range with fixed total SRF linac energy capacity, the beam energy chirp and lattice design for multienergy beam transport.
A carbonate-rich lake solution to the phosphate problem of the origin of life

Phosphate is central to the origin of life because it is a key component of nucleotides in genetic molecules, phospholipid cell membranes, and energy transfer molecules such as adenosine triphosphate. To incorporate phosphate into biomolecules, prebiotic experiments commonly use molar phosphate concentrations to overcome phosphate’s poor reactivity with organics in water. However, phosphate is generally limited to micromolar levels in the environment because it precipitates with calcium as low-solubility apatite minerals. This disparity between laboratory conditions and environmental constraints is an enigma known as “the phosphate problem.” Here we show that carbonate-rich lakes are a marked exception to phosphate-poor natural waters. In principle, modern carbonate-rich lakes could accumulate up to ∼0.1 molal phosphate under steady-state conditions of evaporation and stream inflow because calcium is sequestered into carbonate minerals. This prevents the loss of dissolved phosphate to apatite precipitation. Even higher phosphate concentrations (>1 molal) can form during evaporation in the absence of inflows. On the prebiotic Earth, carbonate-rich lakes were likely abundant and phosphate-rich relative to the present day because of the lack of microbial phosphate sinks and enhanced chemical weathering of phosphate minerals under relatively CO2-rich atmospheres. Furthermore, the prevailing CO2 conditions would have buffered phosphate-rich brines to moderate pH (pH 6.5 to 9). The accumulation of phosphate and other prebiotic reagents at concentration and pH levels relevant to experimental prebiotic syntheses of key biomolecules is a compelling reason to consider carbonate-rich lakes as plausible settings for the origin of life.
Policies and procedures governing patient portal use at an Academic Medical Center.

Background and objective Patient portal use has increased over the last two decades in response to consumer demand and government regulation. Despite growing adoption, few guidelines exist to direct successful implementation and governance. We describe the policies and procedures that have governed over a decade of continuous My Health at Vanderbilt (MHAV) patient portal use. Methods We examined MHAV usage data between May 2007 and November 2017. We classified patient portal activity into eight functional categories: Appointment, Billing, Document Access, Genetics, Health Result, Immunization, Medication, and Messaging. We describe our operating policies and measure portal uptake, patient account activity, and function use over time. Results By the end of the study period, there were 375 517 registered accounts. Policies made MHAV available to competent adults and adolescents 13 and over. Patients signed up for a limited access account online, which could be upgraded to a full-access account after identity verification. Patients could assign proxy accounts to family and caregivers, which permitted nonpatient access to select MHAV functions. Laboratory and radiology results were accessible via MHAV. Results were classified into three groups based on sensitivity, which govern the length of delay before results appeared in MHAV. Discussion and conclusion Patient portals offer significant opportunity to engage patients in their healthcare. However, there remains a need to understand how policies can promote uptake and use. We anticipate that other institutions can apply concepts from our policies to support meaningful patient portal engagement.
RNA-Binding Specificity of the Human Fragile X Mental Retardation Protein.

Abstract Fragile X syndrome is the most common form of inherited intellectual disability and is caused by a deficiency of the fragile X mental retardation protein (FMRP) in neurons. FMRP regulates the translation of numerous mRNAs within dendritic synapses, but how FMRP recognizes these target mRNAs remains unknown. FMRP has KH0, KH1, KH2, and RGG domains, which are thought to bind to specific RNA recognition elements (RREs). Several studies used high-throughput methods to identify various RREs in mRNAs that FMRP may bind to in vivo. However, there is little overlap in the mRNA targets identified by each study, suggesting that the RNA-binding specificity of FMRP is still unknown. To determine the specificity of FMRP for the RREs, we performed quantitative in vitroRNA binding studies with various constructs of human FMRP. Unexpectedly, our studies show that the KH domains do not bind to the previously identified RREs. To further investigate the RNA-binding specificity of FMRP, we developed a new method called Motif Identification by Analysis of Simple sequences (MIDAS) to identify single-stranded RNA sequences bound by KH domains. We find that the FMRP KH0, KH1, and KH2 domains bind weakly to the single-stranded RNA sequences suggesting that they may have evolved to bind more complex RNA structures. Additionally, we find that the RGG motif of human FMRP binds with a high affinity to an RNAG-quadruplex structure that lacks single-stranded loops, double-stranded stems, or junctions.
Epistemology and Methodology in Ethics

This Element introduces several prominent themes in contemporary work on the epistemology and methodology of ethics. Topics addressed include skeptical challenges in ethics, epistemic arguments in metaethics, what (if anything) is epistemically distinctive of the ethical. Also considered are methodological questions in ethics, including questions about which ethical concepts we should investigate, and what our goals should be in ethical inquiry.
Immunogenicity analysis of sequential inoculation of different strains of poliomyelitis vaccines in Shanghai

Objective: To evaluate the immunogenicity of different strains of inactivated poliomyelitis vaccines (IPV) by sequential program. Methods: This parallel-group controlled trial was conducted in immunization clinics in Shanghai from March 2016 to September 2017. Sabin strains inactivated poliomyelitis vaccines (sIPV), WPV strains inactivated poliomyelitis vaccines (wIPV) and live poliomyelitis Type Ⅰ Type Ⅲ vaccine (bOPV) as the investigational vaccine were used at 2, 3, 4 months old in 325 infants in Shanghai. Infants vaccinated by four sequential program were divided into 4 groups: sIPV+sIPV+bOPV, sIPV+wIPV+bOPV, wIPV+sIPV+bOPV and wIPV+wIPV+bOPV. A total of 230 investigators' blood samples were collected before primary immunization and 163 investigators' blood samples were collected after primary immunization. A total of 151 investigators (36, 44, 30 and 41 in each group) finished primary immunization and blood sampling before and after the primary immunization. The geometric mean titer (GMT) of poliovirus typesⅠ and Ⅲ neutralizing antibody was tested and calculated, and the positive results of antibody before and after primary immunization were analyzed. Results: Among the 151 investigators, the age were (2.27±0.61) months and birth weight were (3.27±0.43) kg, and 70 were male. The positive rates of typeⅠwas 98.68% (149 cases), and type Ⅲ was 97.35% (147 cases); the number of investigators tested in each group was 36, 44, 30 and 41, respectively; the positive rates of typeⅠwas 97.22% (35 cases), 100.00% (44 cases), 96.67% (29 cases) and 100.00% (41 cases) (P=0.345); the positive rates of type Ⅲ were 97.22% (35 cases), 95.45% (42 cases), 96.67% (29 cases) and 100.00% (41 cases) (P=0.614). Conclusion: Using sIPV and wIPV simultaneously or alternately for sequential immunization of poliomyelitis vaccines showed good immunogenicity for infants at appropriate age.
Novel Variants of ELP2 and PIAS1 in the Interferon Gamma Signaling Pathway Are Associated with Non-Small Cell Lung Cancer Survival.

Background: Interferon gamma (IFNγ) is a pleiotropic cytokine that plays critical immunomodulatory roles in intercellular communication in innate and adaptive immune responses. Despite recognition of IFNγ signaling effects on host defense against viral infection and its utility in immunotherapy and tumor progression, the roles of genetic variants of the IFNγ signaling pathway genes in cancer patient survival remain unknown. Methods: We used a discovery genotyping dataset from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (n=1,185) and a replication genotyping dataset from the Harvard Lung Cancer Susceptibility Study (n=984) to evaluate associations between 14,553 genetic variants in 150 IFNγ pathway genes and survival of non-small cell lung cancer (NSCLC). Results: The combined analysis identified two independent potentially functional single-nucleotide polymorphisms (SNPs), ELP2 rs7242481G>A and PIAS1 rs1049493T>C, to be significantly associated with NSCLC survival, with a combined hazards ratio (HR) of 0.85 [95% CI= 0.78-0.92, P<0.0001] and 0.87 (0.81-0.93, P<0.0001), respectively. Expression quantitative trait loci analyses showed that the survival-associated ELP2 rs7242481A allele was significantly associated with increased mRNA expression levels of ELP2 in 373 lymphoblastoid cell lines and 369 whole blood samples. The PIAS1 rs1049493C allele was significantly associated with decreased mRNA expression levels of PIAS1 in 383 normal lung tissues and 369 whole blood samples. Conclusions: Genetic variants of IFNγ signaling genes are potential prognostic markers for NSCLC survival, likely through modulating the expression of key genes involved in host immune response. Impact: Once validated, these variants could be useful predictors of NSCLC survival.
Ubiquity and functional uniformity in CO2 concentrating mechanisms in multiple phyla of Bacteria is suggested by a diversity and prevalence of genes encoding candidate dissolved inorganic carbon transporters

Autotrophic microorganisms catalyze the entry of dissolved inorganic carbon (DIC; = CO2 + HCO3- + CO32-) into the biological component of the global carbon cycle, despite dramatic differences in DIC abundance and composition in their sometimes extreme environments. "Cyanobacteria" are known to have CO2 concentrating mechanisms (CCMs) to facilitate growth under low CO2 conditions. These CCMs consist of carboxysomes, containing enzymes ribulose 1,5-bisphosphate oxygenase and carbonic anhydrase, partnered to DIC transporters. CCMs and their DIC transporters have been studied in a handful of other prokaryotes, but it was not known how common CCMs were beyond "Cyanobacteria". Since it had previously been noted that genes encoding potential transporters were found neighboring carboxysome loci, α-carboxysome loci were gathered from bacterial genomes, and potential transporter genes neighboring these loci are described here. Members of transporter families whose members all transport DIC (CHC, MDT and Sbt) were common in these neighborhoods, as were members of the SulP transporter family, many of which transport DIC. 109 of 115 taxa with carboxysome loci have some form of DIC transporter encoded in their genomes, suggesting that CCMs consisting of carboxysomes and DIC transporters are widespread not only among "Cyanobacteria", but also among members of "Proteobacteria" and "Actinobacteria".
The cerebral microvasculature: Basic and clinical perspectives on stroke and glioma

Microvascular networks are vital components of the cardiovascular system, performing many key roles in maintaining the health and homeostasis of the tissues and organs in which they develop. As discussed in this review, the molecular and cellular components within the microcirculation orchestrate critical processes to establish functional capillary beds, including organization of endothelial cell (EC) polarity, guiding investment of vascular pericytes (PCs), and building the specialized extracellular matrix (ECM) that comprises the vascular basement membrane (vBM). Herein, we further discuss the unique features of the microvasculature in the central nervous system (CNS), focusing on the cells contributing to the neurovascular unit (NVU) that form and maintain the blood-brain barrier (BBB). With a focus on vascular PCs, we offer basic and clinical perspectives on neurovascular-related pathologies that involve defects within the cerebral microvasculature. Specifically, we present microvascular anomalies associated with glioblastoma multiforme (GBM) including defects in vascular-immune cell interactions and associated clinical therapies targeting microvessels (ie, vascular-disrupting/anti-angiogenic agents and focused ultrasound). We also discuss the involvement of the microcirculation in stroke responses and potential therapeutic approaches. Our goal was to compare the cellular and molecular changes that occur in the microvasculature and NVU, and to provide a commentary on factors driving disease progression in GBM and stroke. We conclude with a forward-looking perspective on the importance of microcirculation research in developing clinical treatments for these devastating conditions.
Pregnancy during the pandemic: the impact of COVID-19-related stress on risk for prenatal depression.

BACKGROUND: Pregnant women may be especially susceptible to negative events (i.e. adversity) related to the coronavirus disease 2019 (COVID-19) pandemic and negative affective responses to these events (i.e. stress). We examined the latent structure of stress and adversity related to the COVID-19 pandemic among pregnant women, potential antecedents of COVID-19-related stress and adversity in this population, and associations with prenatal depressive symptoms. METHOD: We surveyed 725 pregnant women residing in the San Francisco Bay Area in March-May 2020, 343 of whom provided addresses that were geocoded and matched by census tract to measures of community-level risk. We compared their self-reported depressive symptoms to women matched on demographic factors and history of mental health difficulties who were pregnant prior to the pandemic. RESULTS: Women who were pregnant during the pandemic were nearly twice as likely to have possible depression than were matched women who were pregnant prior to the pandemic. Individual- and community-level factors tied to socioeconomic inequality were associated with latent factors of COVID-19-related stress and adversity. Beyond objective adversity, subjective stress responses were strongly associated with depressive symptoms during the pandemic. CONCLUSIONS: Highlighting the role of subjective responses in vulnerability to prenatal depression and factors that influence susceptibility to COVID-19-related stress, these findings inform the allocation of resources to support recovery from this pandemic and future disease outbreaks. In addition to policies that mitigate disruptions to the environment due to the pandemic, treatments that focus on cognitions about the self and the environment may help to alleviate depressive symptoms in pregnant women.