cssi/SciSciGPT-SciSciNet huggingface dataset:
Twelve tips for reducing production time and increasing long-term usability of instructional video

The use of instructional video is increasing across all disciplines and levels of education. Although video has a number of distinct advantages for course delivery and student learning, it can also be time-consuming and resource-intensive to produce, which imposes a burden on busy faculty. With video poised to play a larger role in medical education, we need strategies for streamlining video production and ensuring that the video we produce is of lasting value. This article draws on learning research and best practices in educational technology, along with the author’s experience in online education and video production. It offers 12 practical tips for reducing the initial time investment in video production and creating video that can be reused long into the future. These tips can help faculty and departments create high-quality instructional video while using their time and resources more wisely.
Fluorescence and Coster - Kronig Yields of L Subshells in Hg from the Decay of Au-198 and Tl-204

Coincidences between $L$ x rays and $K\ensuremath{\alpha}$ x rays, emitted during the filling of $K$ and $L$ vacancies in Hg in the decay of $^{198}\mathrm{Au}$ and $^{204}\mathrm{Tl}$, are measured with high-resolution Si(Li) and Ge(Li) x-ray spectrometers in a fast-coincidence arrangement. The following $L$-subshell fluorescence and Coster-Kronig yields are measured: ${\ensuremath{\omega}}_{2}=0.316\ifmmode\pm\else\textpm\fi{}0.010$, ${\ensuremath{\omega}}_{3}=0.300\ifmmode\pm\else\textpm\fi{}0.010$, and ${f}_{23}=0.190\ifmmode\pm\else\textpm\fi{}0.010$.
Let Binders be Bygones: Topic Binders at a Cancer Hospital Library

ABSTRACTFor many years, The Learning Center library at the University of Texas MD Anderson Cancer Center maintained extensive topic binders on cancer types and related health topics. These large ring binders held miscellaneous print informational materials and were a complement to the library’s larger traditional consumer health collection of books, periodicals and AV items. Recently the binders were evaluated for their currency and usage and most of them weeded and discarded. Standards for maintaining the remaining binders and any future binders were established. The process for how these decisions were made may provide insight to other libraries utilizing a topic binder collection.
Effect of friction stir processed microstructure on tensile properties of an Al-Zn-Mg-Sc alloy upon subsequent aging heat treatment

Abstract An as-cast Al-Zn-Mg-Sc alloy was friction stir processed varying tool related parameters, yielding microstructures with different grain sizes (0.68, 1.8 and 5.5 μm). Significant increases in room temperature ductility were obtained in these materials with reasonable enhancement in strength. It is demonstrated that the type of microstructure produced by friction stir processing (FSP) has a significant influence on the choice of post-FSP heat treatment design for achieving improved tensile properties. It is also found that the ultrafine grained FSP material could not achieve the desired high strength during the post-FSP heat treatment without grain coarsening, whereas the micro-grained FSP materials could reach such strength levels (>560 MPa) under conventional age hardening heat treatment conditions.
Consistent Symbol Location Affects Motor Learning in Preschoolers Without Disabilities: Implications for Designing Augmentative and Alternative Communication Displays.

Purpose Designing augmentative and alternative communication (AAC) displays that minimize operational demands is an important aspect of AAC intervention. The current study compared the effect of 2 ...
Patent Term Restoration and Non‐Patent Exclusivity in the United States

The United States provides companies engaged in drug discovery and marketing with a variety of statutory tools to maximize the exclusivity period for their products and delay generic competition in the marketplace. These tools include patent protection and patent term restoration, as well as marketing, data, pediatric testing, and orphan drug exclusivity. These tools are widely accepted and relied upon in the U.S. for most traditional drug product. However, the use of these tools to maintain pharmaceutical development incentives is in constant tension with their negative impact on drug cost and availability. This chapter surveys the various U.S. drug exclusivity maximizing tools, how they differ, and how they can be used, singly or in combination, to extend the marketing advantage of innovator pharmaceutical company products. It also outlines the exclusivity regime for large molecule drugs, known as biologics, and touches on some of the areas of controversy associated with innovator firm efforts to extend the lifecycles of successful pharmaceutical products.
On the Combinatorics of Free Algebras

In this survey paper I discuss recent results concerning free algebraic systems and I mention some old results which motivated them. There is no attempt to be comprehensive. The selection of topics is eclectic and personal but with a special emphasis on results of a combinatorial nature.
An accessory technique for the intraoral removal of a fractured implant abutment screw.

Abstract As the use of dental implants becomes more prevalent, mechanical complications become more common. When an implant abutment screw fractures, it can be difficult to retrieve the retained fragment. The purpose of this article is to describe a technique to remove the abutment screw fragments without damaging the implant body or its screw threads.
Knowledge gaps in male fertility

The objective of this issue of Knowledge Gaps in Male Infertility is to highlight the several advances that have happened in the care of infertile men. Our goal in writing this is to identify what research is needed to move the field forward and, ultimately, imagine what issues need to be solved in order to bring male infertility care to the same level of diagnosis and treatment as female infertility.
Cerebral lymphomatoid granulomatosis. A report of two cases, with disseminated necrotizing leukoencephalopathy in one.

Neuropathologic findings in 2 cases of cerebral lymphomatoid granulomatosis with sequelae are presented. A 30-year old male with macular rash and pulmonary lymphomatoid granulomatosis responded to Prednisone therapy but developed acute intracranial hypertension with coma. A necrotizing hemorrhagic lesion was evident in the left putamen surrounded by diffuse and perivascular atypical lymphoplasmacytic infiltration. An 18-year old girl developed pulmonary lymphomatoid granulomatosis, diplopia, slurred speech and right hemiparesis. Brain scan, angiography and EEG suggested a left fronto-parietal mass assumed to represent lymphomatoid granulomatosis. She responded well to cerebral irradiation, intrathecal methotrexate and cytoxan but relapsed with seizures and increasing respiratory insufficiency. At autopsy, stigmata of cerebral lymphomatoid granulomatosis were absent but a parenchymatous degeneration consistent with disseminated necrotizing leukoencephalopathy following antileukemic therapy in children, was found.
Imaging of the Temporomandibular Joint in Juvenile Idiopathic Arthritis: How Does Quantitative Compare to Semiquantitative MRI Scoring?

Purpose Contrast-enhanced magnetic resonance imaging (MRI) is commonly used to evaluate temporomandibular joint (TMJ) disease in patients with juvenile idiopathic arthritis (JIA). However, MRI assessments have been limited by qualitative reporting, the presence of enhancement in normal joints, and a lack of standardized protocols. The purpose of the present study was to compare a quantitative MRI analysis using an enhancement ratio (ER) to a new semiquantitative system developed by Outcome Measures in Rheumatology and Clinical Trials (OMERACT). Materials and Methods We performed a retrospective cross-sectional study of children with JIA who had undergone TMJ MRI with gadolinium enhancement at Boston Children's Hospital. The predictor variables were demographic data (sex, age at MRI) and disease-related findings (JIA subtype and arthritis medication at MRI). The outcome variables were OMERACT scores and ER (ratio of TMJ synovium and longus capitis muscle pixel intensities). The ER was compared with the OMERACT total, inflammatory, and damage scores using Pearson's correlation analysis and multivariable linear regression. Statistical significance was evaluated using the Student t test and analysis of variance with significance set at P Results The sample included 50 subjects (84% female) with a mean age of 12.7 ± 3.9 years and 124 MRI scans. The mean ER was 2.5 ± 0.9 (normal, Conclusions Quantitative evaluation of TMJ synovial enhancement using the ER is easier to score and has superior intra- and interrater agreement; however, it can only assess inflammation. Semiquantitative assessment of TMJ using the OMERACT adds data about chronic changes. Using both systems might provide the most accurate assessment of JIA status.
Highly Aggressive and Radiation-Resistant, "Atypical" and Silent Pituitary Corticotrophic Carcinoma: A Case Report and Review of the Literature.

Background Pituitary tumors typically remain silent unless interaction with nearby structures occurs. Rare subsets of pituitary tumors display aggressive phenotypes: highly mitotic, locally invasive, metastatic, chemotherapy and radiation resistant, etc. Disease progression and response to therapy is ill-defined in these subtypes, and their true prognostic potential is debated. Thus, identifying tumor characteristics with prognostic value and efficacious treatment options remains a challenge in aggressive pituitary tumors. Case presentation A 45-year-old female presented with a nonfunctioning corticotropic pituitary macroadenoma with biomarkers suggestive of an "atypical" subtype: Ki-67 of 8-12%, increased mitosis, and locally invasive. Despite resections and radiation, growth continued, eventually affecting her vision. Although histologically ACTH positive, the patient remained clinically asymptomatic. Twelve months later, an episode of Cushing's disease-induced psychosis prompted a PET-CT scan, identifying sites of metastasis. Temozolomide was added to her medical regimen, and her metastatic liver lesions and boney metastases were treated with radiofrequency ablation and stereotactic body radiation therapy, respectively. Systemic treatment resulted in a drop in her ACTH levels, with her most recent scans/labs at 12 months following RFA suggesting remission. Conclusions This is a unique presentation of a pituitary tumor, displaying characteristics of both clinically silent corticotropic and "atypical" macroadenoma subtypes. Although initially ACTH positive while clinically silent, the patient's disease ultimately recurred metastatically with manifestations of Cushing's disease and psychosis. With the addition of temozolomide to her treatment plan, her primary and metastatic sites have responded favorably to radiation therapy. Thus, the addition of temozolomide may be beneficial in the treatment of aggressive pituitary tumors.
Validation of a CD30 Enzyme-Linked Immunosorbant Assay for the Rapid Detection of Breast Implant-Associated Anaplastic Large Cell Lymphoma.

BACKGROUND Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon type of non-Hodgkin lymphoma occurring in the fluid or capsule adjacent to textured breast implants. Diagnosis of BIA-ALCL of symptomatic patients requires demonstration of large anaplastic cells with uniform expression of CD30 protein on immunohistochemistry. OBJECTIVES The authors investigated a novel, rapid, office-based, and economic in-situ enzyme-linked immunosorbent assay (ELISA) for screening BIA-ALCL patients. METHODS A commercially available in-situ ELISA was standardized and validated for patients with confirmed BIA-ALCL diagnosis with clinical isolates. A panel of 9 pathologically confirmed BIA-ALCL patients was screened by serum, plasma, and periprosthetic effusion specimens and compared against serum, plasma, and nonneoplastic delayed seromas in 7 control patients. Statistical analysis demonstrated assay consistency and reliability. RESULTS All BIA-ALCL effusions demonstrated CD30 ELISA detection at full and all serial concentrations. BIA-ALCL serum specimens and all control specimens were negative at full concentration and serial dilutions (1:100, 1:250, 1:500, and 1:1000). BIA-ALCL plasma specimens were weakly positive at full concentration and revealed no activity with serial dilution. CONCLUSIONS This is the first study to demonstrate a viable alternative to CD30 immunohistochemistry for the screening of BIA-ALCL. Our study demonstrates 100% sensitivity in seroma fluid with no detectable CD30 in benign seroma samples. A CD30 ELISA represents a novel, low-cost screening test, which may be used to screen suspicious aspirations of delayed periprosthetic fluid collections in an office-based setting. LEVEL OF EVIDENCE: 3
Citizen Science During the Flint, Michigan Federal Water Emergency: Ethical Dilemmas and Lessons Learned

Editor's Note An Editor’s Note relating to this publication can be found here: http://doi.org/10.5334/cstp.264 A citizen science collaboration between Flint residents, the Virginia Tech “Flint Water Study” team, and others helped to uncover the Flint Lead-in-Drinking Water Crisis and a community-wide outbreak of Legionella. The resulting Federal Emergency declaration in January 2016 resulted in more than $600 million in relief funding, an acknowledged case of environmental injustice, and resignations/indictments of some public officials. But after responsible government entities apologized and attempted to make amends and help with the recovery, some “citizen scientists” began making public statements that were in direct conflict with public health messaging of scientific authorities. A general state of science anarchy resulted, which created further distrust and confusion. Some practices employed were consistent with a concept of “citizen engineering,” which aims to “undermine engineering [and science] expertise” in the name of “democratizing” science. “Citizen Engineers” view concepts of scientific rigor and objectivity as justification for abuse of power by authorities and scientists, and they embrace biases and conflicts of interest that scientists aspire to guard against. While there are ethical guidelines for professional scientists on research misconduct, no such framework exists for policing instances of unethical behavior by citizen scientists. Possible abuses of citizen science documented in Flint explored in this case study include: 1) collection of non-representative data that created unjustified fear among residents about the safety of water used for bathing and showering, 2) perceived financial conflicts of interest, and 3) falsification of data to obtain relief resources, support lawsuits, gain media attention, or support erroneous scientific conclusions. We also report the journey of an aspiring citizen scientist who openly acknowledged mistakes, made the “right” decision in relation to handling an ethical dilemma, and who was then publicly attacked for doing so. This experience highlights challenges to the practice of citizen science, especially during high profile emergency interventions and disasters involving environmental injustice.
A practical ansatz for evaluating the electronic friction tensor accurately, efficiently, and in a nearly black-box format

It is well-known that under conditions of fast electronic equilibration and weak nonadiabaticity, nonadiabatic effects induced by electron-hole pair excitations can be partly incorporated through a frictional force. However, ab initio computation of the electronic friction tensor suffers from numerical instability and usually demands a convergence check. In this study, we present an efficient and accurate interpolation method for computing the electronic friction tensor in a nearly black-box manner as appropriate for molecular dynamics. In almost all cases, our method agrees quite well with the exact friction tensor which is available for several quadratic Hamiltonians. As such, we outperform more conventional approaches that are based on the introduction of a broadening parameter. Future work will implement this interpolation approach within ab initio software packages.
A 2.4-mm 2 130-mW MMSE-Nonbinary LDPC Iterative Detector Decoder for 4 $\times$ 4 256-QAM MIMO in 65-nm CMOS

Iterative detection and decoding (IDD) employs a soft-in soft-out (SISO) detector and an SISO forward error correction (FEC) decoder in an iterative loop to improve the receiver performance in multiple-input multiple-output (MIMO) wireless communications. This paper describes a 256-QAM 4 $\times $ 4 prototype IDD design made up of a minimum mean square error (MMSE) detector and a nonbinary low-density parity-check (NBLDPC) decoder with the symbol size of the NBLDPC code matched to the modulation to enhance performance. By directly translating between nonbinary symbols and constellation points, the detector–decoder interface is simplified. We present a Gb/s MMSE detector using a shortened tandem scheduling, a low-latency dual-lookup reciprocal unit, an optimized interleaved microarchitecture, and a Gb/s NBLDPC decoder with efficient internal skipping paths and memory allocation. The designs were demonstrated in a 0.7-mm2 1.38-Gb/s MMSE detector and a 1.7-mm2 1.02-Gb/s-NBLDPC decoder that are integrated in a 65-nm CMOS test chip. The chip is measured to achieve 19.2 pJ/b in detection and 20.1 pJ/b/iteration in decoding.
Generality of Post-Antimicrobial Treatment Persistence of Borrelia burgdorferi Strains N40 and B31 in Genetically Susceptible and Resistant Mouse Strains.

ABSTRACT A basic feature of infection caused by Borrelia burgdorferi, the etiological agent of Lyme borreliosis, is that persistent infection is the rule in its many hosts. The ability to persist and evade host immune clearance poses a challenge to effective antimicrobial treatment. A link between therapy failure and the presence of persister cells has started to emerge. There is growing experimental evidence that viable but noncultivable spirochetes persist following treatment with several different antimicrobial agents. The current study utilized the mouse model to evaluate if persistence occurs following antimicrobial treatment in disease-susceptible (C3H/HeJ [C3H]) and disease-resistant (C57BL/6 [B6]) mouse strains infected with B. burgdorferi strains N40 and B31 and to confirm the generality of this phenomenon, as well as to assess the persisters’ clinical relevance. The status of infection was evaluated at 12 and 18 months after treatment. The results demonstrated that persistent spirochetes remain viable for up to 18 months following treatment, as well as being noncultivable. The phenomenon of persistence in disease-susceptible C3H mice is equally evident in disease-resistant B6 mice and not unique to any particular B. burgdorferi strain. The results also demonstrate that, following antimicrobial treatment, both strains of B. burgdorferi, N40 and B31, lose one or more plasmids. The study demonstrated that noncultivable spirochetes can persist in a host following antimicrobial treatment for a long time but did not demonstrate their clinical relevance in a mouse model of chronic infection. The clinical relevance of persistent spirochetes beyond 18 months following antimicrobial treatment requires further studies in other animal models.
Open Computing Infrastructure for Sharing Data Analytics to Support Building Energy Simulations

AbstractBuilding energy simulation plays an increasingly important role in building design and operation. This paper presents an open computing infrastructure, Virtual Information Fabric Infrastruc...
Cosmic ray measurements from Voyager 2 as it crossed into interstellar space

The interaction of the interstellar and solar winds is complex, as revealed by differences in intensities and anisotropies of low-energy ions (>0.5 MeV per nucleon) originating inside the heliosphere and those of higher-energy Galactic cosmic rays (>70 MeV per nucleon) originating outside, in the Milky Way. On 5 November 2018, Voyager 2 observed a sharp decrease in the intensity of low-energy ions and a simultaneous increase in the intensity of cosmic rays, indicating that Voyager 2 had crossed the heliopause at 119 au and entered interstellar space about six years after Voyager 1. Unlike Voyager 1, which found that two interstellar flux tubes had invaded the heliosheath and served as precursors to the heliopause, Voyager 2 found no similar precursors. However, just beyond the heliopause Voyager 2 discovered a boundary layer, in which low-energy particles streamed outward along the magnetic field and cosmic ray intensities were only 90% of those further out. As it crossed the heliopause, Voyager 2 observed a sharp decrease in measurements of the low-energy ions that originate within the heliosphere, and an increase in the cosmic rays from the Milky Way, without any of the precursor flux tubes that Voyager 1 experienced. Outside the heliopause, a boundary layer exists.
Electroencephalography and Event-Related Potential Biomarkers in Individuals at Clinical High Risk for Psychosis

Clinical outcomes vary among youths at clinical high risk for psychosis (CHR-P), with approximately 20% progressing to full-blown psychosis over 2 to 3 years and 30% achieving remission. Recent research efforts have focused on identifying biomarkers that precede psychosis onset and enhance the accuracy of clinical outcome prediction in CHR-P individuals, with the ultimate goal of developing staged treatment approaches based on the individual's level of risk. Identifying such biomarkers may also facilitate progress toward understanding pathogenic mechanisms underlying psychosis onset, which may support the development of mechanistically informed early interventions for psychosis. In recent years, electroencephalography-based event-related potential measures with established sensitivity to schizophrenia have gained traction in the study of CHR-P and its clinical outcomes. In this review, we describe the evidence for event-related potential abnormalities in CHR-P and discuss how they inform our understanding of information processing deficits as vulnerability markers for emerging psychosis and as indicators of future outcomes. Among the measures studied, P300 and mismatch negativity are notable because deficits predict conversion to psychosis and/or CHR-P remission. However, the accuracy with which these and other measures predict outcomes in CHR-P has been obscured in the prior literature by the tendency to only report group-level differences, underscoring the need for inclusion of individual predictive accuracy metrics in future studies. Nevertheless, both P300 and mismatch negativity show promise as electrophysiological markers of risk for psychosis, as target engagement measures for clinical trials, and as potential translational bridges between human studies and animal models focused on novel drug development for early psychosis.
Improving Ecological Behavior in Outdoor Recreation Through Mindfulness Interventions: A Mixed Methods Inquiry

Outdoor recreation professionals have long sought to impact environmental behavior of participants. Mindfulness and nature connection have recently been explored as possible constructs to impact environmental behavior. The purpose of this study was to better understand the impact of mindful outdoor recreation trips on college students’ nature connectedness and ecological behavior. We used explanatory mixed methods approach to explore the relationship between mindfulness, nature connection, and ecological behavior. Quantitative findings suggest that being mindfully outdoors has a positive effect on the degree to which nature is included in the sense of self and on ecological behavior. Qualitative findings support the quantitative findings and suggest that students use mindfulness to connect with nature and to care more for the environment. These findings suggest that the use of mindfulness interventions in outdoor education programming may improve nature connection and ecological behavior.Subscribe to JOREL
Determinants of Self-reported Health Outcomes in Adrenal Insufficiency: A Multisite Survey Study

CONTEXT Current evidence on determinants of adverse health outcomes in patients with adrenal insufficiency (AI) is scarce, especially in regards to AI subtypes. OBJECTIVE To determine predictors of adverse outcomes in different subtypes of AI. DESIGN AND SETTING Cross-sectional survey study at 2 tertiary centers. PARTICIPANTS A total of 696 patients with AI: primary AI (PAI, 42%), secondary AI (SAI, 32%), and glucocorticoid-induced AI (GIAI, 26%). INTERVENTION Patient-centered questionnaire. MAIN OUTCOME MEASURES Patients' knowledge, self-management of AI, self-perceived health, and adverse outcomes. RESULTS The incidence rate of adrenal crisis was 24/100 patient-years with 44% experiencing at least 1 adrenal crisis since diagnosis (59% in PAI vs 31% in SAI vs 37% in GIAI, P < .0001). All patients described high degrees of discomfort with self-management and receiving prompt treatment. Patients with PAI were most likely to develop adrenal crises (adjusted OR 2.8, 95% CI 1.9-4.0) despite reporting better self-perceived health (adjusted OR 3.3, 95% CI 2.1-5.3), understanding of their diagnosis (89% vs 74-81% in other subtypes, P = .002), higher comfort with self-management (62% vs 52-61% in other sub types, P = .005), and higher likelihood to receive prompt treatment for adrenal crises in the emergency department (42% vs 19-30% in other subtypes, P < .0001). CONCLUSIONS Patients with AI reported high degrees of discomfort with self-management and treatment delays when presenting with adrenal crises. Despite better self-perceived health and understanding of diagnosis, patients with PAI experienced the highest frequency of adrenal crises. A multidimensional educational effort is needed for patients and providers to improve the outcomes of all subtypes of AI.
Bilateral Cochlear Implants or Bimodal Hearing for Children with Bilateral Sensorineural Hearing Loss.

This review describes speech perception and language outcomes for children using bimodal hearing (cochlear implant (CI) plus contralateral hearing aid (HA)) as compared to children with bilateral CIs and contrasts said findings with the adult literature. There is a lack of clinical evidence driving recommendations for bimodal versus bilateral CI candidacy and as such, clinicians are often unsure about when to recommend a second CI for children with residual acoustic hearing. Thus, the goal of this review is to identify scientific information that may influence clinical decision making for pediatric CI candidates with residual acoustic hearing. Bilateral CIs are considered standard of care for children with bilateral severe-to-profound sensorineural hearing loss. For children with aidable acoustic hearing—even in just the low frequencies—an early period of bimodal stimulation has been associated with significantly better speech perception, vocabulary, and language development. HA audibility, however, is generally poorer than that offered by a CI resulting in interaural asymmetry in auditory access, speech perception, head shadow, as well as brainstem and cortical activity and development. Thus, there is a need to optimize “two-eared” hearing while maximizing a child’s potential with respect to hearing, speech, and language while ensuring that we limit asymmetrically driven auditory neuroplasticity. A recent large study of bimodal and bilateral CI users suggested that a period of bimodal stimulation was only beneficial for children with a better-ear pure tone average (PTA) ≤ 73 dB HL. This 73-dB-HL cutoff applied even to children who ultimately received bilateral CIs. Though we do not yet have definitive guidelines for determining bimodal versus bilateral CI candidacy, there is increasing evidence that (1) bilateral CIs yield superior outcomes for children with bilateral severe-to-profound hearing loss and (2) an early period of bimodal stimulation is beneficial for speech perception and language development, but only for children with better-ear PTA ≤ 73 dB HL. For children with residual acoustic hearing, even in just the low-frequency range, rapid sequential bilateral cochlear implantation following a trial period with bimodal stimulation will yield best outcomes for auditory, language, and academic development. Of course, there is also an increasing prevalence of cochlear implantation with acoustic hearing preservation allowing for combined electric and acoustic stimulation even following bilateral implantation.
Green building and policy innovation in the US Low-Income Housing Tax Credit programme

This article analyses the integration of green building with the largest low-income housing production programme in the US and the innovativeness of state housing agencies. Drawing on policy innova...
A Mixed Effect Location-Scale Model with Mixture Distributed Scale Random Effects to Analyze (Near) Identical Entries in Ecological Momentary Assessments.

Ecological Momentary Assessment (EMA) studies provide sufficient information to model both the mean (location) and the within-subject variance (scale) using the mixed effect location-scale model (M...
Leukocyte Heterogeneity in Pancreatic Ductal Adenocarcinoma: Phenotypic and Spatial Features Associated with Clinical Outcome

Immunotherapies targeting aspects of T cell functionality are efficacious in many solid tumors, but pancreatic ductal adenocarcinoma (PDAC) remains refractory to these treatments. Deeper understanding of the PDAC immune ecosystem is needed to identify additional therapeutic targets and predictive biomarkers for therapeutic response and resistance monitoring. To address these needs, we quantitatively evaluated leukocyte contexture in 135 human PDACs at single-cell resolution by profiling density and spatial distribution of myeloid and lymphoid cells within histopathologically defined regions of surgical resections from treatment-naive and presurgically (neoadjuvant)-treated patients and biopsy specimens from metastatic PDAC. Resultant data establish an immune atlas of PDAC heterogeneity, identify leukocyte features correlating with clinical outcomes, and, through an in silico study, provide guidance for use of PDAC tissue microarrays to optimally measure intratumoral immune heterogeneity. Atlas data have direct applicability as a reference for evaluating immune responses to investigational neoadjuvant PDAC therapeutics where pretherapy baseline specimens are not available. SIGNIFICANCE: We provide a phenotypic and spatial immune atlas of human PDAC identifying leukocyte composition at steady state and following standard neoadjuvant therapies. These data have broad utility as a resource that can inform on leukocyte responses to emerging therapies where baseline tissues were not acquired.This article is highlighted in the In This Issue feature, p. 1861.
Localization of signaling receptors maximizes cellular information acquisition in spatially-structured natural environments

Cells in natural environments like tissue or soil sense and respond to extracellular ligands with intricately structured and non-monotonic spatial distributions, sculpted by processes such as fluid flow and substrate adhesion. In this work, we show that spatial sensing and navigation can be optimized by adapting the spatial organization of signaling pathways to the spatial structure of the environment. We develop an information-theoretic framework for computing the optimal spatial organization of a sensing system for a given signaling environment. We find that receptor localization maximizes information acquisition in simulated natural contexts, including tissue and soil. Receptor localization extends naturally to produce a dynamic protocol for continuously redistributing signaling receptors, which when implemented using simple feedback, boosts cell navigation efficiency by 30-fold. Broadly, our work shows how cells can maximize the fidelity of information transfer by adapting the spatial organization of signaling molecules to the spatial structure of the environment.
H-1B Visas and the STEM Shortage: A Research Brief

The Senate introduced a landmark comprehensive immigration reform bill last month that has the potential to both increase the number of available H-1B visas for skilled foreigners working in specialty occupations and shift the U.S. employment-based visa system to a more merit-based scheme that favors science, technology, engineering, and mathematics (STEM) workers. As the Congressional process moves forward, debate continues over the role of immigrants in the U.S. labor market. Focusing on demand-side arguments, businesses say they cannot find the skills they need from the domestic labor pool and need access to a global pool of skilled workers. On the other hand, some analysts have argued that there are plenty of U.S. native-born workers who can do these jobs. Such positions fit into a broader literature analyzing whether or not there is a sufficient supply of STEM workers to meet employer demands and foster innovation. This article examines new and rarely-used metrics on the supply and demand for STEM occupations in an effort to inform public policy and better understand the market for STEM workers and H-1B visas.
Inhibitors of protein biosynthesis. II. Mode of action of anisomycin.

Anisomycin (2-p-methoxyphenylmethyl-3-acetoxy-4-hydroxypyrrolidine) inhibits protein synthesis in HeLa cells, rabbit reticulocytes, Saccharomyces fragilis, and cell-free extracts prepared from these sources, but it is inactive against extracts of Escherichia coli. Partial inhibition of deoxyribonucleic acid synthesis in HeLa cells is observed at anisomycin concentrations which produce 95% inhibition of protein synthesis. These effects on protein and DNA synthesis are rapid in onset and reversible. Anisomycin acts on the transfer reaction subsequent to the formation of aminoacyl transfer ribonucleic acid. In the presence of anisomycin, nascent peptide remains attached to polyribosomes. No derivative of anisomycin that was tested showed more than 1% of the inhibitory activity of the parent compound.
Hyperhomocysteinemia, MTHFR 677C→T Polymorphism, and Stroke

To the Editor: We welcome the report from Madonna and co-workers examining the role of prothrombotic and homocysteine (Hcy) pathway polymorphisms in risk of ischemic stroke in young adults.1 We wish to comment on several issues raised by their article relating to the design of studies of genetic risk factors for complex phenotypes such as ischemic stroke, which we believe to be important when interpreting their findings. As the report points out, genetic predisposition to a complex human phenotype such as stroke is unlikely to be mediated by a large influence of 1 or 2 genes. Many observers agree that it is likely to result from a combination of relatively small individual effects of several genes, each predisposing to stroke via their influence on intermediate phenotypic traits, such as hypertension or hyperlipidemia.2–4⇓⇓ This assumption has several implications for the design of epidemiological studies examining candidate genetic risk factors for stroke. First, given the small anticipated effect size associated with any single candidate polymorphism, the group sample sizes required to robustly demonstrate an association will be very large. This is important to avoid a potentially erroneous conclusion that no association exists (type 2 error). This point is particularly relevant in the case of the MTHFR 677C→T polymorphism. Most prospective and retrospective studies to date have indicated that mildly elevated …
Does going greek impair undergraduate academic performance? : A case study

Abstract. Controlling for SAT scores, college major, gender, and state of residence, university students were more likely to have joined a fraternity or sorority if they had come from in state and had higher verbal SAT scores, but lower math SAT scores, the opposite of what simple uncontrolled averages indicate. Controlling for the same variables, fraternity and sorority members suffered from 1 to 10 percent lower cumulative GPAs than non-Greek students. This negative effect was most pronounced for small fraternities and weakest for sororities.
Temporal Progression of Herpetomonas muscarum Leidy (Kinetoplastida: Trypanosomatidae) in the Midgut of Musca domestica L. (Diptera: Muscidae)

Herpetomonas muscarum Leidy (Kinetoplastida: Trypanosomatidae) is a protistan symbiont that colonizes the hindgut of the housefly, Musca domestica L. (Diptera: Muscidae). The temporal location and transition of this symbiont within the fly has been understudied. In this study, the progression of Herpetomonas within the mid and hindgut with reference to the peritrophic matrix (PM) was examined microscopically and was compared with the fate of a bacterium (GFP-tagged E. coli). The housefly PM is a double-layered, open-ended physical barrier that separates ingested substances from the midgut epithelium and terminates near the hindgut. In the midgut, bacteria were confined within the inner PM, lysed by digestive enzymes, and compacted into fecal pellets within 12 h. In contrast, Herpetomonas initially resided within the inner PM, but many protists moved to the interPM space within a few hours. Additionally, protists rapidly progressed to the open end of the PM at the midgut/hindgut junction, in as little as 4...
Antiangiogenic drugs synergize with a membrane macrophage colony-stimulating factor-based tumor vaccine to therapeutically treat rats with an established malignant intracranial glioma.

Combining a T9/9L glioma vaccine, expressing the membrane form of M-CSF, with a systemic antiangiogenic drug-based therapy theoretically targeted toward growth factor receptors within the tumor’s vasculature successfully treated >90% of the rats bearing 7-day-old intracranial T9/9L gliomas. The antiangiogenic drugs included ( Z )-3-[4-(dimethylamino)benzylidenyl]indolin-2-one (a platelet-derived growth factor receptor β and a fibroblast growth factor receptor 1 kinase inhibitor) and oxindole (a vascular endothelial growth factor receptor 2 kinase inhibitor). A total of 20–40% of the animals treated with the antiangiogenic drugs alone survived, while all nontreated controls and tumor vaccine-treated rats died within 40 days. In vitro, these drugs inhibited endothelial cells from proliferating in response to the angiogenic factors produced by T9/9L glioma cells and prevented endothelial cell tubulogenesis. FITC-labeled tomato lectin staining demonstrated fewer and constricted blood vessels within the intracranial tumor after drug therapy. Magnetic resonance imaging demonstrated that the intracranial T9 glioma grew much slower in the presence of these antiangiogenic drugs. These drugs did not affect in vitro glioma cell growth nor T cell mitogenesis. Histological analysis revealed that the tumor destruction occurred at the margins of the tumor, where there was a heavy lymphocytic infiltrate. Real-time PCR showed more IL-2-specific mRNA was present within the gliomas in the vaccinated rats treated with the drugs. Animals that rejected the established T9/9L glioma by the combination therapy proved immune against an intracranial rechallenge by T9/9L glioma, but showed no resistance to an unrelated MADB106 breast cancer.
Vernakalant, a mixed sodium and potassium ion channel antagonist that blocks K(v)1.5 channels, for the potential treatment of atrial fibrillation.

Abstract Despite being the most common arrhythmia currently treated by cardiologists, safe and effective treatments for atrial fibrillation (AF) remain elusive. To address this issue, Astellas Pharma Inc, Merck & Co Inc and Cardiome Pharma Corp are developing vernakalant (RSD-1235), a drug which dose-dependently inhibits sodium channels and several potassium repolarizing currents. Of particular note, vernakalant inhibits I(Kur) (K(v)1.5), a current that is more predominant in atrial than in ventricular tissue. Consistent with this observation, vernakalant produced increases in atrial refractory period with minimal actions on QTc interval or ventricular refractory period in both humans and animals. Intravenous vernakalant terminated recent-onset AF in several animal models, and also in patients with short-duration AF or AF following cardiac surgery enrolled in phase II and III clinical trials. Vernakalant was well tolerated and adverse reactions were transient and mild. Thus, vernakalant holds considerable promise for the treatment of recent-onset AF; however, given its relatively short half-life, continuous dosing may be required in order to maintain sinus rhythm following conversion from AF. The efficacy and safety of vernakalant for the long-term management of AF remains to be determined. Phase III clinical trials with intravenous vernakalant are ongoing, and phase II clinical trials are also being conducted with an oral formulation intended for chronic use.
Optimal Constraint Parameter Estimation for Constrained Image Restoration

Because of the presence of noise in blurred images, an image restoration algorithm must constrain the solution to achieve stable restoration results. Such constraints are often introduced by biasing the restoration toward the minimizer of a given functional. However, a proper choice of the degree of bias is critical to the success of this approach. Generally, the appropriate bias cannot be chosen a priori and must be estimated from the blurred and noisy image. Cross-validation is introduced as a method for estimating the optimal degree of bias for a general form of the constraint functional. Results show that this constraint is capable of improving restoration results beyond the capabilities of the traditional Tikhonov constraint.
Trajectories of smoking from adolescence to early adulthood and their psychosocial risk factors.

This study used semi-parametric group-based modeling to explore patterns of persistence and change in smoking behavior as well as risk factors associated with the developmental course of smoking from age 13 to 25. Drawing on data from the National Longitudinal Study of Adolescent Health, six distinct trajectories were identified: nonsmokers, experimenters, stable light smokers, quitters, late escalators, and stable high smokers. Baseline risk factors that were associated with greater likelihood of membership in all of the smoking trajectory groups compared to nonsmokers included alcohol use, deviance, peer smoking, and (with the exception of the late escalators) drug use. Deviance, peer smoking, alcohol and drug use also distinguished the likelihood of membership among several of the five smoking trajectory groups. The results add to basic etiologic research on developmental pathways of smoking in adolescence and young adulthood by providing evidence of heterogeneity in smoking behavior and prospectively linking different patterns of risk factors with the probability of trajectory group membership.
Seismic Performance of Multisimple-Span Bridges Retrofitted with Link Slabs

During earthquakes multisimple-span bridges are vulnerable to span separation at their expansion joints. A common way of preventing unseating of spans is to have cable or rod restrainers that provide connections between adjacent spans. Alternatively, dislocation of the girders can be controlled with a link slab that is the continuous portion of the bridge deck between simple spans. Seismic retrofit with link slab should be more cost-effective than the existing methods when it is performed during redecking or removal of expansion joints. Maintenance cost associated with expansion joints could also be reduced. This paper discusses the use of link slabs for retrofit of seismically deficient multisimple-span bridges with precast, prestressed concrete girders. The concept is equally applicable to bridges with steel girders. Analytical studies for typical overpasses were performed to investigate the effectiveness of the proposed link slab application. A simple preliminary design procedure was also developed.
Bacteriorhodopsin-based photo-electrochemical cell.

Abstract A simple solution-based electrochemical cell has been constructed and successfully employed in the detection of the photoelectric response upon photoexcitation of bacteriorhodopsin (bR) without external bias. Commercially-available indium tin oxide (ITO) glasses served as the optical windows and electrodes. Small amounts of bR suspensions (∼100 μL) were utilized as the photovoltaic medium to generate the proton gradient between two half-cells separated by a molecular porous membrane. Continuous broadband visible light (λ > 380 nm) and a short-pulse 532-nm laser were employed for the photoexcitation of bR. Upon the modulated cw broadband irradiation, an instantaneous rise and decay of the current was observed. Our observations of the pH-dependent photocurrent are consistent with previous reports in a bR thin film configuration, which also showed a polarity inversion at pH 5–6. This is due to the change of the priority of the proton release and proton uptake in the photocycle of bR. Studies on the ionic strength effect were also carried out at different KCl concentrations, which resulted in the acceleration of the rise and decay of the photoelectric response. This was accompanied by a decrease in the stationary photocurrent at higher KCl concentrations in the broadband excitation experiments. The solution-based electrochemical cell uses aqueous medium, which is required for the completion of the bR proton pumping function. Due to the generation of the stationary current, it is advantageous to convert solar energy into electricity without the need of film-based photovoltaic devices with external bias.
Glucose-Dependent Insulinotropic Polypeptide Stimulates Insulin Secretion via Increased Cyclic AMP and [Ca2+]iand a Wortmannin-Sensitive Signalling Pathway

Abstract The effect of wortmannin, a fungal metabolite which is known to inhibit phosphatidylinositol 3-kinase (PI3-kinase) at low concentrations, has been examined for its effect on insulin secretion stimulated by glucose-dependent insulinotropic polypeptide (GIP). Using a hamster derived clonal β-cell line, the HIT-T15 cell, wortmannin inhibited GIP-stimulated insulin secretion under both static incubation and perifusion conditions. In contrast, wortmannin did not inhibit glucose-stimulated or forskolin-stimulated insulin secretion. The inhibitory effect was of large magnitude, although always partial, and occurred within a few minutes of the onset of stimulation by GIP. Thus GIP, like vasoactive intestinal polypeptide (VIP) and pituitary adenylyl cyclase activating polypeptide (PACAP), exerts some of its stimulatory effect on insulin release via a wortmannin-sensitive signal transduction pathway.