cssi/SciSciGPT-SciSciNet huggingface dataset:
Validation of a Teaching Effectiveness Assessment in Psychiatry Continuing Medical Education.

Little is known about factors associated with effective continuing medical education (CME) in psychiatry. The authors aimed to validate a method to assess psychiatry CME teaching effectiveness and to determine associations between teaching effectiveness scores and characteristics of presentations, presenters, and participants. This cross-sectional study was conducted at the Mayo Clinic Psychiatry Clinical Reviews and Psychiatry in Medical Settings. Presentations were evaluated using an eight-item CME teaching effectiveness instrument, its content based on previously published instruments. Factor analysis, internal consistency and interrater reliabilities, and temporal stability reliability were calculated. Associations were determined between teaching effectiveness scores and characteristics of presentations, presenters, and participants. In total, 364 participants returned 246 completed surveys (response rate, 67.6%). Factor analysis revealed a unidimensional model of psychiatry CME teaching effectiveness. Cronbach α for the instrument was excellent at 0.94. Item mean score (SD) ranged from 4.33 (0.92) to 4.71 (0.59) on a 5-point scale. Overall interrater reliability was 0.84 (95% CI, 0.75–0.91), and temporal stability was 0.89 (95% CI, 0.77–0.97). No associations were found between teaching effectiveness scores and characteristics of presentations, presenters, and participants. This study provides a new, validated measure of CME teaching effectiveness that could be used to improve psychiatry CME. In contrast to prior research in other medical specialties, CME teaching effectiveness scores were not associated with use of case-based or interactive presentations. This outcome suggests the need for distinctive considerations regarding psychiatry CME; a singular approach to CME teaching may not apply to all medical specialties.
Validating Sidescan Sonar as a Fish Survey Tool over Artificial Reefs

ABSTRACT Bollinger, M.A. and Kline, R.J., 2017. Validating sidescan sonar as a fish survey tool over artificial reefs. Visual observation methods via SCUBA are commonly used to survey artificial reef fish, although conditions in the Gulf of Mexico often make surveys difficult or even dangerous for divers. In this study, sidescan sonar was used to quantify water-column fish abundance and was compared to the established visual observation methods on SCUBA over four reef sites. Calibrated intensity values measured from sidescan sonar echo returns were used to estimate fish body length and to calculate scaled biomass (g/m2 reef) from a pooled fish length–weight relationship of commonly observed reef fish in the area. Sidescan sonar methods were equivalent to SCUBA surveys for measuring fish abundance over the same reef areas; however, overall reef-associated abundances measured with sidescan were significantly higher because the sidescan could measure a larger water-column area and furthermore allowed for a r...
Haecceity: Laying Out a Plane for Post Qualitative Inquiry:

This article traces 25 years of scholarship that used the concept haecceity to slowly deconstruct or deterritorialize conventional qualitative methodology and think post qualitative inquiry, which ...
Preoperative Prostate MRI: A Road Map for Surgery.

OBJECTIVE. MRI of the prostate is widely used in prostate cancer for local staging. The purpose of this article is to show how preoperative prostate MRI findings may be used as a road map for surge...
Drinking Attitudes and Beliefs

How do parents’ drinking affect the likelihood of their children drinking? What are the expectations of the effect of drinking for one’s self and for others? What are the perceived benefits of drinking by men and women? What is the relationship between alcohol expectancies and abstinence, level of drinking, and problematic outcomes? What rationales are used for drinking and which ones are used to curb ones’ drinking? Do positive attitudes encourage drinking and do negative attitudes discourage drinking? What are the Puerto Rican norms concerning how much to drink and where? How much permission is given for persons to drink at different ages? How do Puerto Ricans view alcoholism and drunkenness? Who goes for help and where?
Client predictors of the therapeutic alliance in individual resiliency training for first episode psychosis.

Abstract Individuals experiencing their first episode of psychosis (FEP) are often reluctant to seek treatment, and are difficult to engage and retain in mental health services. The therapeutic alliance (TA), or the affective and collaborative bond between therapist and client, is predictive of better treatment outcomes for clients with FEP; thus, it is important to understand the predictors of the TA in order to determine how best to foster a positive alliance with these individuals. The primary aim of the present study was to examine whether baseline client characteristics, including severity of symptoms, social functioning, and insight, were associated with the TA. The exploratory aim was to examine associations between demographic variables (age, race, and gender) and the TA. The present study included a subsample of participants (n = 134) who received Individual Resiliency Training (IRT) as part of the NAVIGATE treatment in the Recovery After An Initial Schizophrenia Episode Early Treatment Program study. Four trained research assistants rated the TA from early audiotaped sessions of IRT. Multilevel modeling was utilized given the nested data structure. Results indicated that more severe positive and less severe negative symptoms were significantly and uniquely associated with a better therapeutic alliance, as was female gender. The findings suggest that client symptom profiles should be considered when developing a TA with FEP clients.
Chapter 12 – Overview of Bone Structure and Strength

Many individuals who fracture do not have bone mineral density values in the osteoporotic range, suggesting that a better understanding of the factors that influence bone strength and fracture risk may improve identification of those at the highest risk for fracture. This chapter outlines the key determinants of bone strength, focusing on age-related changes and the contribution of bone morphology and microarchitecture to bone strength and fracture risk.
Comparative response to selection of two reciprocal recurrent procedures in BS21 and BS22 maize populations

Reciprocal recurrent selection (RRS) has proven to be a successful method for improving the performance of a cross population and to increase the heterosis between populations. However, RRS has not been widely adopted by the commercial breeders because RRS is not as efficient to recover inbred lines as other methods of inbred development. Use of two inbred lines as testers instead of the opposite population as reciprocal tester in a modified RRS (MRRS) scheme could overcome this limitation. A breeding research program was initiated in 1974 at Iowa State University to evaluate the modified RRS procedure and RRS in BS21 and BS22 maize populations. The modification used inbred line A632 as tester for BS21 and inbred line H99 as tester for BS22. After six cycles of selection were completed in BS21 and BS22 using MRRS and RRS, an experiment was conducted to evaluate the response to selection. The populations per se, testcrosses to inbred testers, and crosses between cycle populations of RRS and MRRS were evaluated in replicated yield trials. There were significant increases in grain yield in all six cross populations as a consequence of selection. The rate of direct response was greater for the RRS procedure than for the MRRS [4.4, 1.6, and 2.8 %cycle*' for BS21(R)xBS22(R), H99xBS22(HI), and A632xBS21(HI), respectively]. RRS was as effective as MRRS for improving the grain yield of the populations in crosses with the inbred lines, but MRRS was not as effective as RRS in the improvement of the cross population BS21xBS22, with a significantly lower rate of increase in yield of 1.6%cycle'V Realized heritability and response to selection for yield were 25 to 50% of their predicted values.
Assessing morphologic controls on atoll island alongshore sediment transport gradients due to future sea-level rise

Atoll islands’ alongshore sediment transport gradients depend on how island and reef morphology affect incident wave energy. It is unclear, though, how potential atoll morphologic configurations influence shoreline erosion and/or accretion patterns, and how these relationships will respond to future sea-level rise (SLR). Schematic atoll models with varying morphologies were used to evaluate the relative control of individual morphological parameters on alongshore transport gradients. Incident wave transformations were simulated using a physics-based numerical model and alongshore erosion and accretion was calculated using empirical formulae. The magnitude of the transport gradients increased with SLR: initial erosion or accretion patterns intensified. Modeled morphologic parameters that significantly influenced alongshore transport were the atoll diameter, reef flat width, reef flat depth, and island width. Modeled atolls with comparably small diameters, narrow and deep reef flats with narrow islands displayed greater magnitudes of erosion and/or accretion, especially with SLR. Windward island shorelines are projected to accrete toward the island’s longitudinal ends and lagoon due to SLR, whereas leeward islands erode along lagoon shorelines and extend toward the island ends. Oblique island, oriented parallel to the incident deepwater wave direction, shorelines are forecast to build out leeward along the reef rim and toward the lagoon while eroding along regions exposed to direct wave attack. These findings make it possible to evaluate the relative risk of alongshore erosion/accretion on atolls due to SLR in a rapid, first-order analysis.
Gossypol but not cottonseed extracts or lipopolysaccharides stimulates HuR gene expression in mouse cells

Abstract Human antigen R (HuR) stabilizes cytokine mRNAs and plays an important role in tumorigenesis and inflammation. Plant extracts and compounds that can regulate HuR gene expression may have nutritional and therapeutic value, but little research has been done in this area. This study evaluated the effect of cottonseed extracts, anti-nutritional gossypol and endotoxin lipopolysaccharides (LPS) on HuR gene expression in mouse macrophages. Mouse RAW264.7 macrophages were treated with multiple concentrations of glanded and glandless cottonseed extracts, gossypol and LPS for 2–24 h. qPCR assay showed that cottonseed extracts and LPS had minor effect on HuR gene expression. However, gossypol increased HuR mRNA levels 16 fold in cells treated for 24 h. Immunoblotting confirmed that gossypol increased HuR protein in macrophages. These results showed that gossypol is a strong stimulator of HuR gene expression.
Niemann-Pick Type C Disease Reveals a Link between Lysosomal Cholesterol and PtdIns(4,5)P2 That Regulates Neuronal Excitability

There is increasing evidence that the lysosome is involved in the pathogenesis of a variety of neurodegenerative disorders. Thus, mechanisms that link lysosome dysfunction to the disruption of neuronal homeostasis offer opportunities to understand the molecular underpinnings of neurodegeneration and potentially identify specific therapeutic targets. Here, using a monogenic neurodegenerative disorder, NPC1 disease, we demonstrate that reduced cholesterol efflux from lysosomes aberrantly modifies neuronal firing patterns. The molecular mechanism linking alterations in lysosomal cholesterol egress to intrinsic tuning of neuronal excitability is a transcriptionally mediated upregulation of the ABCA1 transporter, whose PtdIns(4,5)P2-floppase activity decreases plasma membrane PtdIns(4,5)P2. The consequence of reduced PtdIns(4,5)P2 is a parallel decrease in a key regulator of neuronal excitability, the voltage-gated KCNQ2/3 potassium channel, which leads to hyperexcitability in NPC1 disease neurons. Thus, cholesterol efflux from lysosomes regulates PtdIns(4,5)P2 to shape the electrical and functional identity of the plasma membrane of neurons in health and disease.
Genetics and breeding of soybeans lacking the Kunitz trypsin inhibitor.

The major trypsin inhibitor present in soybean [Glycine max (L.) Merrill] seed is the Kunitz trypsin inhibitor or soybean trypsin inhibitor A2 (SBTI-A2). Four forms of SBTI-A2 have been identified in the U.S. soybean germplasm collection. Three of the forms designated Ti a, Ti b, and Ti c are electrophoretically distinguishable from one another by their different Rf values of 0.79, 0.75, and 0.83, respectively. The three forms are inherited as codominant alleles in a multiple allelic series at a single locus. The fourth form which is the absence of SBTI-A2 is found in P.I. 157440 and P.I. 196168. The allele lacking SBTI-A2 is designated ti and is inherited as a simple recessive to the other three SBTI-A2 forms. Ti a is the most common SBTI-A2 allele in the germplasm collection. Ti b primarily is found in Japan and Korea. Ti c is associated with the Tohoku District, Japan. P.I. 157440 and P.I. 196168 are from Korea. Linkage studies revealed that the Ti and Ap loci are linked by 16.2 ± 1.5 map units. Three isolines of soybeans lacking the Kunitz trypsin inhibitor, derived by backcrossing P.I. 157440 to three commercial cultivars (Ti a Ti a), were released to the research community. Results of preliminary feeding trials, with chicks and young pigs, revealed that gain/feed was significantly higher in lines lacking the Kunitz trypsin inhibitor than cultivars containing the inhibitor. However, the gain/feed was lower in both feeds than commercially processed soybean meal.
Enforcement trends in the city of St. Louis from 2007 to 2017: Exploring variability in arrests and criminal summonses over time and across communities

The goal of this study is twofold: (a) to describe trends in enforcement activity in the city of St. Louis from 2007 through 2017 and (b) to document community variation in these trends. Five types of enforcement actions are examined: felony, misdemeanor, municipal, and bench warrant arrests and criminal summonses-in-lieu of arrest. Results indicate that enforcement activity decreased over the study period, particularly for nonfelony arrests among Blacks. City-wide trends obscure some variability in neighborhood enforcement. Neighborhood trends in enforcement varied by type of action, but in all cases, trends were conditioned by racial composition. For example, misdemeanor and bench warrant arrests exhibited steeper declines in neighborhoods with a higher percentage of Black residents, resulting in a narrowing of the race gap. In contrast, differences in criminal summonses across neighborhoods of varying racial compositions increased. The effects persisted net of measures of economic disadvantage, community location, residential mobility, household composition, calls for service, and population size. The findings highlight the importance of disaggregating enforcement trends by race and place and documenting changes in less serious, but more prevalent, types of law enforcement activity.
Identification of Nonhost Cover Crops of the Three-Cornered Alfalfa Hopper (Spissistilus festinus)

The three-cornered alfalfa hopper, Spissistilus festinus (Say) (Hemiptera: Membracidae) was identified as a vector of grapevine red blotch virus (GRBV) in a greenhouse study. GRBV impacts berry maturation, resulting in reduced accumulation of total soluble solids, increased titratable acidity, and altered levels of secondary metabolites that affect color, flavor, and aroma of finished wine made from infected grapes. S. festinus feeds and reproduces on a variety of plant species found in and around vineyards, including certain cover crops and weeds. The suitability of 15 commonly planted cover crops for S. festinus adult feeding and oviposition was determined. In no-choice tests, purple vetch, berseem clover, annual ryegrass, buckwheat, Trios triticale, and Zorro fescue supported survival of adult S. festinus, oviposition, and emergence of nymphs. In contrast, orchard grass, creeping red fescue, fawn tall fescue, hard fescue, and California poppy did not support survival of adult S. festinus, nor were nymphs observed. Relative preference for hosts that supported nymph emergence was determined in choice tests. The legume species (purple vetch and berseem clover) exhibited higher nymph emergence than the nonlegume cover crops (Zorro fescue, Trios triticale, buckwheat, and annual ryegrass). Cultivating cover crops that do not support S. festinus survival or oviposition may aid in reducing the risk of S. festinus moving into and establishing in vineyards.
PolyPy: A Web-Platform for Generating Quasi-Random Python Code and Gaining Insights on Student Learning

This Innovative Practice Full paper introduces PolyPy, a freely available web-platform that allows instructors to automate the creation of many different coding question instances from a single template. Interactive web platforms offer a way of engaging students with practice material while also providing them with real-time feedback. However, many of these platforms depend on manually pre-setting a static pool of questions and answers, which limits 1) the number of unique coding challenges presented to students, 2) the ability of instructors to dynamically customize challenges, and 3) the ability to recognize and adapt to individual student needs. PolyPy bypasses these limitations by providing a flexible and easy-to-use framework that lets instructors define question templates. These templates contain segments that can exhibit one of many pre-set values; we refer to these segments as “randomizable elements.” The question instances are generated (from the templates) on-the-fly every time a student requests a new question via the student interface. To verify the correctness of students’ answers, PolyPy interprets these question instances and compares their output to the students’ submissions in real-time. All students’ attempts, both correct and incorrect, are stored and can be accessed by instructors; this information can be used to gain insight on the strengths and weaknesses of student comprehension. This paper presents the PolyPy system architecture and describes the student and instructor interfaces. It reports promising preliminary results of students’ use of PolyPy along with feedback obtained regarding their learning experience.
Studying immunotherapy resistance in a melanoma autologous humanized mouse xenograft

Resistance to immunotherapy is a significant challenge, and the scarcity of human models hinders the identification of the underlying mechanisms. To address this limitation, we constructed an autologous humanized mouse (aHM) model with hematopoietic stem and progenitor cells (HSPC) and tumors from 2 melanoma patients progressing to immunotherapy. Unlike mismatched humanized mouse (mHM) models, generated from cord blood-derived HSPCs and tumors from different donors, the aHM recapitulates a patient-specific tumor microenvironment (TME). When patient tumors were implanted on aHM, mHM, and NOD/SCID/IL2rg-/- (NSG) cohorts, tumors appeared earlier and grew faster on NSG and mHM cohorts. We observed that immune cells differentiating in the aHM were relatively more capable of circulating peripherally, invading into tumors and interacting with the TME. A heterologous, human leukocyte antigen (HLA-A) matched cohort also yielded slower growing tumors than non-HLA-matched mHM, indicating that a less permissive immune environment inhibits tumor progression. When the aHM, mHM, and NSG cohorts were treated with immunotherapies mirroring what the originating patients received, tumor growth in the aHM accelerated, similar to the progression observed in the patients. This rapid growth was associated with decreased immune cell infiltration, reduced interferon gamma (IFNγ)-related gene expression, and a reduction in STAT3 phosphorylation, events that were replicated in vitro using tumor-derived cell lines. IMPLICATIONS: Engrafted adult HSPCs give rise to more tumor infiltrative immune cells, increased HLA matching leads to slower tumor initiation and growth, and continuing immunotherapy past progression can paradoxically lead to increased growth.
Factors associated with neonatal resuscitation knowledge and comfort across academic anesthesia institutions.

Neonatal resuscitation training is a requirement for all obstetric anesthesia fellows. However, while the majority of anesthesiologists who work on labor and delivery report having been involved in...
The influence of cognitive behavioral therapy on lumbar spine surgery outcomes: a systematic review and meta-analysis

As more patients undergo lumbar spine surgery, novel interventions may improve physical and mental health outcomes. Few studies summarize the benefit of cognitive behavioral therapy (CBT) among lumbar spine surgery patients. This study collects randomized control trial data to investigate the influence of CBT on patient reported outcomes among lumbar spine surgery patients. Our study used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and a medical library expert assisted in searching PubMed/MEDLINE, Scopus, CINAHL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, PsycINFO, and Google Scholar. We calculated standardized mean differences (SMD) to evaluate the effect size of CBT versus control groups with a sensitivity analysis. Our meta-analysis included seven studies with a total of 531 patients. The majority of included studies evaluated lumbar fusion, with preoperative CBT performed by physiotherapists. The largest effects were observed for overall quality of life (SMD = 0.55 [95% CI 0.05, 1.05], p < 0.001, I2 = 86.7%) and psychological outcomes (SMD = 0.61 [95% CI 0.28, 0.94], p < 0.001, I2 = 89.7%) though disability and pain outcomes also favored CBT intervention. Included studies demonstrated low overall bias but large heterogeneity. Sensitivity analysis demonstrated negligible study design differences and revealed moderators including CBT session frequency and final follow-up duration (p < 0.001). Compared to usual care or alternative therapy control arms, CBT delivered the most improvement with overall quality of life and psychological outcomes. Among appropriately selected patients, CBT could improve perioperative disability, pain, quality of life, and psychological health following lumbar spine surgery.
Implications of incorporating geosynthetics in airfield pavements

Abstract A majority of literature indicates that geosynthetic inclusion in flexible pavement bases, subjected to highway loading, improves performance by reducing rutting or vertical pressure on weak subgrade layers. Instances where geosynthetics were less successful in highway pavements included strong subgrade soils and/or thick pavement layers. Thus, understanding the improvement that can be expected from geosynthetic inclusion in airfield pavements, that are often more substantial than highway pavements, requires an evaluation of existing airfield pavement assets and design methodology. To achieve this objective, a number of tasks were performed: (1) review of in-service pavement thickness and subgrade strength to quantify military airfield pavement characteristics, (2) review of current Department of Defense (DOD) design methodologies to determine if geosynthetic inclusion can be adequately characterized in existing design procedures for new airfields, (3) evaluation to determine if (and in what conditions) an expected performance improvement is financially viable, and (4) implementation in military airfields in manners other than new construction. Results indicated that airfield pavements were generally thicker and stronger than highway pavements, and that in-service airfield pavements exceeded the pavement characteristics where geosynthetics have been identified to provide a meaningful performance improvement. A review of the existing DOD design methodology indicated that any improvement from geosynthetic inclusion in thicker pavements was hidden within the variability of the data used to formulate the existing design methodology. An initial cost evaluation suggested that design life extension (if any) could be the preferred means of quantifying geosynthetic improvement and that the reduction in aggregate thickness attributed to geosynthetic inclusion did not seem to provide an initial cost savings for military airfields. Geosynthetic inclusion in airfield damage repair or as a crack mitigation technique may be more beneficial than aggregate base reinforcement in new construction.
Carcinoma of the cervix associated with pregnancy

Abstract We have studied 182 cases of carcinoma of the cervix associated with pregnancy. In this series, the stage of pregnancy did not affect the cure rate. Irradiation alone appeared to be adequate treatment, and vaginal delivery was not found to be hazardous.
Transient and persistent acute kidney injury phenotypes following the Norwood operation: a retrospective study.

BACKGROUND Acute kidney injury is a common complication following the Norwood operation. Most neonatal studies report acute kidney injury peaking within the first 48 hours after cardiac surgery. The aim of this study was to evaluate if persistent acute kidney injury (>48 postoperative hours) after the Norwood operation was associated with clinically relevant outcomes. METHODS Two-centre retrospective study among neonates undergoing the Norwood operation. Acute kidney injury was initially identified as developing within the first 48 hours after cardiac surgery and stratified into transient (≤48 hours) and persistent (>48 hours) using the neonatal modification of the Kidney Disease: Improving Global Outcomes serum creatinine criteria. Severe was defined as stage ≥2. Primary and secondary outcomes were mortality and duration of ventilation and hospital length of stay. RESULTS One hundred sixty-eight patients were included. Transient and persistent acute kidney injuries occurred in 24 and 17%, respectively. Cardiopulmonary bypass and aortic cross clamp duration, and incidence of cardiac arrest were greater among those with persistent kidney injury. Mortality was four times higher (41 versus 12%, p < 0.001) and mechanical ventilation duration 50 hours longer in persistent acute kidney injury patients (158 versus 107 hours; p < 0.001). In multivariable analysis, persistent acute kidney injury was not associated with mortality, duration of ventilation or length of stay. Severe persistent acute kidney injury was associated with a 59% increase in expected ventilation duration (aIRR:1.59, 95% CI:1.16, 2.18; p = 0.004). CONCLUSIONS Future large studies are needed to determine if risk factors and outcomes change by delineating acute kidney injury into discrete timing phenotypes.
HIGGS BOSON AND WLWL SCATTERING AT e−e− COLLIDERS

We discuss the Standard-Model Higgs boson production in the channels e−e−→e−e−H, e−νW−H, and e−e−ZH. We also illustrate the enhancements in the W–W– cross section that would result from a strongly-interacting Higgs sector or from a H−− resonance in a doublet + triplet scalar field model.
PD-1 in hippocampal neurons regulates excitability, synaptic plasticity, and cognition

SUMMARY Immunotherapy using monoclonal antibodies against programmed cell death protein 1 (PD-1) demonstrated improved survival in cancer patients through immune activation. Here we show that functional PD-1 is expressed in mouse and primate hippocampal neurons and PD-1 inhibition improves cognition in physiological and pathological conditions. Mice lacking the Pdcd1 gene encoding PD-1 exhibit enhanced long-term potentiation (LTP) and learning and memory. These behavioral and cellular changes can be recapitulated by selective deletion of Pdcd1 in hippocampal excitatory neurons but not in microglia. Perfusion of mouse or nonhuman primate brain slices with anti-PD-1 antibody is sufficient to increase excitability in CA1 hippocampal neurons. Conversely, re-expression of Pdcd1 in PD-1 deficient hippocampal neurons suppresses memory and LTP. Traumatic brain injury impairs learning and memory, which is improved by intraventricular administration of anti-PD-1. These findings suggest that anti-PD-1 treatment has therapeutic potential to counteract cognitive decline. Highlights Adult mice lacking Pdcd1 in hippocampal neurons exhibit enhanced memory and LTP Anti-PD-1 antibody treatment increases CA1 neuron excitability in brain slices of mice and primates Re-expression of Pdcd1 in PD-1 deficient hippocampal neurons impairs memory and LTP Cognitive deficits after traumatic brain injury are improved by anti-PD-1 treatment
Ownership Structure, Potential Competition, and the Free-Rider Problem on Tender Offers

Bagnoli and Lipman (1988) have shown that ownership structure is a significant determinant of the division of the gains in tender offers. This article extends their model to allow for potential competition and for the bidder to acquire a toehold. We show that for some optimal bids the number of shares expected to be tendered is less than the number required for control. Moreover, announcement day returns are predicted to vary cross-sectionally as they reflect both the degree to which the bid is anticipated and the bargaining power of the target's shareholders. We show that "free-rider" type results in which the target's shareholders capture all of the gains are due to extreme modeling assumptions.
Countries for Old Men: An Analysis of the Age Wage Gap

In the last three decades, the wages of older workers in many high-income countries grew at a much faster rate than the wages of younger workers. This paper uses extensive administrative data from Italy and Germany to provide an analysis of this age wage gap. First, the widening of the age wage gap stemmed from the increasing difficulty of younger workers to reach high-paying jobs. Second, a large part of the deterioration in the careers of younger workers occurred within firms. Third, different appropriation of firm-specific rents can explain more than half of the widening in the age wage gap. The last portion of the analysis shows that the effects are larger for firms with constraints in adding higher-ranked jobs to their organization, highlighting the role of career spillovers in widening the age wage gap.
Meaningfully Explaining Model Mistakes Using Conceptual Counterfactuals.

Understanding and explaining the mistakes made by trained models is critical to many machine learning objectives, such as improving robustness, addressing concept drift, and mitigating biases. However, this is often an ad hoc process that involves manually looking at the model's mistakes on many test samples and guessing at the underlying reasons for those incorrect predictions. In this paper, we propose a systematic approach, conceptual counterfactual explanations(CCE), that explains why a classifier makes a mistake on a particular test sample(s) in terms of human-understandable concepts (e.g. this zebra is misclassified as a dog because of faint stripes). We base CCE on two prior ideas: counterfactual explanations and concept activation vectors, and validate our approach on well-known pretrained models, showing that it explains the models' mistakes meaningfully. In addition, for new models trained on data with spurious correlations, CCE accurately identifies the spurious correlation as the cause of model mistakes from a single misclassified test sample. On two challenging medical applications, CCE generated useful insights, confirmed by clinicians, into biases and mistakes the model makes in real-world settings. The code for CCE is publicly available and can easily be applied to explain mistakes in new models.
Comprehensive molecular characterization of lung tumors implicates AKT and MYC signaling in adenocarcinoma to squamous cell transdifferentiation.

BACKGROUND Lineage plasticity, the ability to transdifferentiate among distinct phenotypic identities, facilitates therapeutic resistance in cancer. In lung adenocarcinomas (LUADs), this phenomenon includes small cell and squamous cell (LUSC) histologic transformation in the context of acquired resistance to targeted inhibition of driver mutations. LUAD-to-LUSC transdifferentiation, occurring in up to 9% of EGFR-mutant patients relapsed on osimertinib, is associated with notably poor prognosis. We hypothesized that multi-parameter profiling of the components of mixed histology (LUAD/LUSC) tumors could provide insight into factors licensing lineage plasticity between these histologies. METHODS We performed genomic, epigenomics, transcriptomics and protein analyses of microdissected LUAD and LUSC components from mixed histology tumors, pre-/post-transformation tumors and reference non-transformed LUAD and LUSC samples. We validated our findings through genetic manipulation of preclinical models in vitro and in vivo and performed patient-derived xenograft (PDX) treatments to validate potential therapeutic targets in a LUAD PDX model acquiring LUSC features after osimertinib treatment. RESULTS Our data suggest that LUSC transdifferentiation is primarily driven by transcriptional reprogramming rather than mutational events. We observed consistent relative upregulation of PI3K/AKT, MYC and PRC2 pathway genes. Concurrent activation of PI3K/AKT and MYC induced squamous features in EGFR-mutant LUAD preclinical models. Pharmacologic inhibition of EZH1/2 in combination with osimertinib prevented relapse with squamous-features in an EGFR-mutant patient-derived xenograft model, and inhibition of EZH1/2 or PI3K/AKT signaling re-sensitized resistant squamous-like tumors to osimertinib. CONCLUSIONS Our findings provide the first comprehensive molecular characterization of LUSC transdifferentiation, suggesting putative drivers and potential therapeutic targets to constrain or prevent lineage plasticity.
Laboratory tests for paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disorder that is often suspected in a patient presenting with non-immune hemolytic anemia associated with pancytopenia or venous thrombosis. This disorder is a consequence of acquired somatic mutations in the phosphatidylinositol glycan class A (PIG-A) gene in the hematopoietic stem cells (HSC) of patients. The presence of these mutations leads to production of blood cells with decreased glycosyl phosphatidylinositol-anchored cell surface proteins, making red blood cells derived from the clone more sensitive to complement mediated hemolysis. The diagnosis of PNH may be difficult in some cases due a low proportion of PNH cells in the blood and occasionally due to difficulties in selecting the most appropriate diagnostic studies. The latest generation of tests allow for detection of very small populations of PNH cells, for following the natural course and response to therapy of the disease, and for helping to decide when to initiate therapy with monoclonal antibody targeting the terminal complement protein C5 (Eculizumab), anticoagulation, and in some cases allogeneic HSC transplant. In this article, we review the different diagnostic tests available to clinicians for PNH diagnosis.
The political economy of intellectual property law

Landes and Posner apply public-choice theory to the growth and character of intellectual property protection over the last half-century. The authors argue that public-choice theory alone cannot explain the coincidence of the deregulation movement and the rapid growth of intellectual property protection. Political forces and ideological currents associated with the deregulation movement, combined with interest-group pressures, best explain the increases in intellectual property protection since 1976.
The Ghost of an Earthquake

Seismic activity can cause Earth9s crust and upper mantle to deform and then relax slowly, and this relaxation can be detected decades after the original event. In his Perspective, Hammond discusses results reported in the same issue by Gourmelen and Amelung in which satellite-based radar (InSAR) was used to detect the surface deformation in the Basin and Range province of the western United States caused by earthquakes in the early to mid-20th century. The data indicate that disagreements between geodetic mapping (such as obtained by Global Positioning System measurements) and paleoseismic observations may be explained by postseismic relaxation. Moreover, the results suggest that magnitude information about past earthquakes might be retrieved by such postseismic analysis.
Characterization and immunotherapeutic potential of gammadelta T-cells in patients with glioblastoma.

Classical immunotherapeutic approaches to glioblastoma multiforme (GBM) have shown mixed results, and therapies focused on innate lymphocyte activity against GBM have not been rigorously evaluated. We examined peripheral blood lymphocyte phenotype,  T-cell number, mitogenic response, and cytotoxicity against GBM cell lines and primary tumor explants from GBM patients at selected time points prior to and during GBM therapy. Healthy volunteers served as controls and were grouped by age. T-cell infiltration of tumors from these patients was assessed by staining for CD3 and T-cell receptor . Our findings revealed no differ ences in counts of mean absolute T-cells, T-cell subsets CD3 1 CD4 1 and CD3 1 CD8 1 , and natural killer cells from healthy volunteers and patients prior to and immediately after GBM resection. In contrast,  T-cell counts and mitogen-stimulated proliferative response of  T-cells were markedly decreased prior to GBM resection and throughout therapy. Expanded/activated  T-cells from both patients and healthy volunteers kill GBM cell lines D54, U373, and U251, as well as primary GBM, without cytotoxicity to primary astrocyte cultures. Perivascular T-cell accumulation was noted in paraffin sections, but no organized T-cell invasion of the tumor parenchyma was seen. Taken together, these data suggest that  T-cell depletion and impaired function occur prior to or concurrent with the growth of the tumor. The signifi
Outcomes of Patients With Severe Chronic Lung Disease Who Are Undergoing Transcatheter Aortic Valve Replacement

Background In this study, we sought to determine the clinical outcomes after transcatheter aortic valve replacement (TAVR) among patients with chronic lung disease (CLD) and to evaluate the safety of transaortic versus transapical alternate access approaches in patients with varying severities of CLD. Methods Clinical records for patients undergoing TAVR from 2011 to 2014 in The Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry were linked to Medicare hospital claims (n = 11,656). Clinical outcomes were evaluated across strata of CLD severity, and the risk-adjusted association between access route and post-TAVR mortality was determined among patients with severe CLD. Results In this cohort (median age, 84 years; 51.7% female), moderate to severe CLD was present in 27.7% (14.3%, moderate; 13.4%, severe). Compared with patients with no or mild CLD, patients with severe CLD had a higher rate of post-TAVR mortality to 1-year (32.3% versus 21.0%; adjusted hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.31 to 1.66), as did those with moderate CLD (25.5%; adjusted HR, 1.16; 95% CI, 1.03 to 1.30). The adjusted rate of mortality was similar for transapical versus transaortic approaches to 1 year (adjusted HR, 1.17; 95% CI, 0.83 to 1.65). Conclusions Moderate or severe CLD is associated with an increased risk of death to 1-year after TAVR, and among patients with severe CLD, the risk of death appears to be similar with either transapical or transaortic alternate-access approaches. Further study is necessary to understand strategies to mitigate risk associated with CLD and the long-term implications of these findings.
Structure-function relationships in novel peptide dodecamers with broad-spectrum bactericidal and endotoxin-neutralizing activities

A series of designed peptide 33-mers (βpep peptides) are known to be bactericidal [Mayo, Haseman, Ilyina and Gray (1998) Biochim. Biophys. Acta 1425, 81–92]. Here dodecapeptides (SC-1–SC-8), which ‘walk through’the sequence of βpep-25, were investigated for their ability to kill Gram-negative and -positive bacteria and to neutralize endotoxin. SC-4 (KLFKRHLKWKI I-NH 2 ; the -NH 2 at the right of each sequence indicates amidation of the C-terminal carboxylate group) is the most effective, more so than βpep-25, at killing Gram-negative bacteria with nanomolar LD 50 values. Against Gram-positive bacteria, SC-4 also shows good activity with submicromolar LD 50 values. Leakage studies indicate rapid bacterial membrane permeability, with t ½ values of 10–15min. SC-4 in the micromolar range also effectively neutralizes endotoxin and is not haemolytic below 10 -4 M. For all SC peptides, CD and NMR data indicate the presence of both 3 10 - and α-helix. For SC-4, nuclear-Overhauser-effect-based computational modelling yields an amphipathic helix with K1, K4, R5, and K8 arrayed on the same face (K is lysine, R is arginine). Activity differences among SC peptides and single-site variants of SC-4 allow some structure–function relationships to be deduced. Relative to other known bactericidal peptides in the linear peptide, helix-forming category, SC-4 is the most potent broad-spectrum antibacterial identified to date. The present study contributes to the development of agents involved in combating the ever-recurring problem of drug-resistant micro-organisms.
Efficient learning from explanation of prediction errors in streaming data

Streaming data from different kinds of sensors contributes to Big Data in a significant way. Recognizing the norms and abnormalities in such spatiotemporal data is a challenging problem. We present a general-purpose biologically-plausible computational model, called SELP, for learning the norms or invariances as features in an unsupervised and online manner from explanations of saliencies or surprises in the data. Given streaming data, this model runs a relentless cycle of Surprise → Explain → Learn → Predict involving the real external world and its internal model, and hence the name. The key characteristic of the model is its efficiency, crucial for streaming Big Data applications, which stems from two functionalities exploited at each sampling instant - it operates on the change in the state of data between consecutive sampling instants as opposed to the entire state of data, and it learns only from surprise or prediction error to update its internal state as opposed to learning from the entire input. The former allows the model to concentrate its computational resources on spatial regions of the data changing most frequently and ignore others, while the latter allows it to concentrate on those instants of time when its prediction is erroneous and ignore others. The model is implemented in a neural network architecture. We show the performance of the network in learning and retaining sequences of handwritten numerals. When exposed to natural videos acquired by a camera mounted on a cat's head, the neurons learn receptive fields resembling simple cells in the primary visual cortex. The model leads to an agent-dependent framework for mining streaming data where the agent interprets and learns from the data in order to update its internal model.
Nitric oxide and the cerebral-blood-flow response to somatosensory activation following deafferentation.

The single-vibrissa stimulation model in the rat was utilized to study the microvascular coupling between functional activation and local cerebral blood flow (LCBF) in both normal cortex and in cortex that had been peripherally deafferented. In addition, the role of chronic nitric oxide synthase (NOS) inhibition on the LCBF response to vibrissa stimulation was examined. One-day-old rats underwent deafferentation of all vibrissae on one side of the face, sparing C3, and received daily administration of either saline or Nω-nitro-l-arginine (l-NA). After seven weeks of treatment, LCBF was measured autoradiographically in conscious rats with [14C]N-isopropyl-p-iodoamphetamine while C3 was stimulated bilaterally. Stimulation produced a greater increase in LCBF in the deafferented cortex of both the saline (30.4%) and l-NA treated (25.7%) animals than in the intact cortex (19.9% and 16%, respectively). The area of activation of LCBF (0.176 mm2) was comparable to the area metabolically activated (0.149 mm2), and the increase in area of LCBF activation following deafferentation (169%) was smaller than the increase in area that was metabolically activated (287%). Chronic inhibition of NOS did not alter the spatial extent of the blood-flow response.
Abstract B81: A spatial analysis of racial variation in post-treatment outcomes in prostate cancer

Prostate cancer exhibits marked geographic variation with regard to incidence, tumor characteristics, disease progression, and mortality at the local, national, and international level. Within the United States, African American men are approximately twice as likely as white men to die from the disease. It is hypothesized that racial variations in post-diagnosis treatment contribute in part to this disparity. The purpose of this study is to investigate the independent effect of race on the probability of recurrent prostate cancer among patients receiving definitive therapy (surgery or radiation) while adjusting for patient- and area- level characteristics. Incident prostate cancer cases among African American and white men that received definitive therapy within 6 months of diagnosis and were reported to the SEER-Medicare linked database between 1995 and 2002 were identified. Spatial patterning in receipt of definitive therapy treatment by race was mapped using GIS and statistically evaluated using Moran9s I global index of spatial autocorrelation. A series of hierarchical logistic regression models with county level random effects were used to characterize the relationship between race and the probability of receipt of post-treatment PSA screening and recurrent prostate cancer. African American men were slightly less likely than white men to receive post-treatment surveillance (OR= 0.99,95% CI= 0.88,1.78) and to be diagnosed with recurrent prostate cancer (OR= 0.98,95% CI= 0.86,1.12), although the difference was not statistically significant. Our findings might underestimate receipt of post-treatment PSA surveillance due to limitations inherent in the use of SEER-Medicare data. Researchers should continue to investigate the implications of access to care and healthcare utilization by various populations and their effect on prostate health. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B81.
Alternative estimators in logistic regression when the data are collinear

Logistic regression using conditional maximum likelihood estimation has recently gained widespread use. Many of the applications of logistic regression have been in situations in which the independent variables are collinear. It is shown that collinearity among the independent variables seriously effects the conditional maximum likelihood estimator in that the variance of this estimator is inflated in much the same way that collinearity inflates the variance of the least squares estimator in multiple regression. Drawing on the similarities between multiple and logistic regression several alternative estimators, which reduce the effect of the collinearity and are easy to obtain in practice, are suggested and compared in a simulation study.