cssi/SciSciGPT-SciSciNet huggingface dataset:
Studies of mechanisms of niridazole‐elicited embryotoxicity: Evidence against a major role for covalent binding

Studies reported here were designed to examine the hypothesis that covalent binding of reactive intermediates to macromolecules of the conceptus represents a major mechanism for the embryotoxicity of niridazole (NDZ). The roles of embryonic thiol content and oxygenation on: 1) malformation incidence; 2) reductive metabolism; and 3) covalent binding to embryonic macromolecules of metabolites resulting from reductive biotransformation of NDZ were studied. Results were compared with those from studies with the nondysmorphogenic analog of NDZ, 4'-methylniridazole (MNDZ). Day 10 rat embryos were pretreated for 5 hours in vitro with either L-buthionine-S, R-sulfoximine (BSO) or N-acetylcysteine (NAC) to modulate their glutathione (GSH) content. BSO reduced GSH levels, but NAC was ineffective. Following pretreatment, embryos were cultured for an additional 15 hours in the presence of [14C]NDZ or [14C]MNDZ with an initial oxygen concentration of 5%. At the end of the culture period (day 11, AM), those embryos with active heartbeat and vitelline circulation were examined for asymmetric malformations. Drug metabolites were subjected to multiple extractions from the culture medium and subjected to quantitative high-performance liquid chromatography (HPLC) analysis. Homogenates of the embryos were extracted with trichloroacetic acid (TCA) to estimate the covalent binding of radiolabeled parent compound/metabolites. Autoradiographic analyses were performed on other embryos. BSO pretreatment, which reduces embryonic GSH tissue levels, dramatically increased both the conversion of NDZ to 1-thiocarbamoyl-2-imidazolidinone (TCI) (generated via reductive metabolism of NDZ) and covalently bound label but failed to increase embryotoxicity. NAC, by contrast, did not significantly affect embryonic GSH levels, TCI generation, or covalent binding. Because both rates of metabolism of NDZ to TCI and covalent binding could vary independently of malformation incidence, we concluded that they do not represent critical mechanistic factors for the embryotoxicity of NDZ and related nitroheterocycles.
Somatotopic organization of perioral musculature innervation within the pig facial motor nucleus.

The orbicularis oris and buccinator muscles of mammals form an important subset of the facial musculature, the perioral muscles. In many taxa, these muscles form a robust muscular hydrostat capable of
Melphalan plus total body irradiation (MEL-TBI) or cyclophosphamide (MEL-CY) as a conditioning regimen with second autotransplant in responding patients with myeloma is inferior compared to historical controls receiving tandem transplants with melphalan alone

The role of more intense conditioning for second transplant was evaluated in myeloma patients achieving at least partial remission (PR) after first transplant with melphalan at 200 mg/m2. Forty-three patients received more intensive conditioning for the second transplant. Nineteen patients received cyclophosphamide 120 mg/kg along with melphalan 200 g/m2 (MEL-CY; group 1) while 24 patients received total body irradiation (1125 cGy) in conjunction with melphalan 140 mg/m2 (MEL-TBI; group 2). Forty-three matched control patients were identified from 450 patients receiving melphalan alone for second transplant (MEL200; group 3). Engraftment and toxicities were comparable among the groups with the exception of increased treatment-related mortality of 8% in group 2 compared to none in groups 1 and 3 (P = 0.07). Despite identical CR rates of 74, 71 and 70%, respectively, in groups 1, 2 and 3 (P = 1.0), event-free survival (median: 27, 15 and 61; P < 0.0001) and overall survival (median: 39, 25 and 76 months; P = 0.003) were significantly decreased in patients receiving more intensive conditioning (groups 1 and 2). Lymphocyte recovery, evaluated as a surrogate for immune recovery, was inferior in more intensively treated patients (groups 1 and 2 compared to group 3). Our findings suggest that more intense conditioning appears to have no benefit in patients responding to their first cycle of high-dose therapy and may even be detrimental in this setting. Bone Marrow Transplantation (2000) 25, 483-487.
Remote vs. head-mounted eye-tracking: a comparison using radiologists reading mammograms

Eye position monitoring has been used for decades in Radiology in order to determine how radiologists interpret medical images. Using these devices several discoveries about the perception/decision making process have been made, such as the importance of comparisons of perceived abnormalities with selected areas of the background, the likelihood that a true lesion will attract visual attention early in the reading process, and the finding that most misses attract prolonged visual dwell, often comparable to dwell in the location of reported lesions. However, eye position tracking is a cumbersome process, which often requires the observer to wear a helmet gear which contains the eye tracker per se and a magnetic head tracker, which allows for the computation of head position. Observers tend to complain of fatigue after wearing the gear for a prolonged time. Recently, with the advances made to remote eye-tracking, the use of head-mounted systems seemed destined to become a thing of the past. In this study we evaluated a remote eye tracking system, and compared it to a head-mounted system, as radiologists read a case set of one-view mammograms on a high-resolution display. We compared visual search parameters between the two systems, such as time to hit the location of the lesion for the first time, amount of dwell time in the location of the lesion, total time analyzing the image, etc. We also evaluated the observers' impressions of both systems, and what their perceptions were of the restrictions of each system.
Condition assessment of the eastbound 6th Avenue Viaduct using strain gauges

This paper presents the procedure and results of a strain gauge study completed on the eastbound 6th Avenue Viaduct in Denver. The 6th Avenue Viaduct was modified in a 1997–1998 rehabilitation, making the entire superstructure continuous. New sliding bearing pads failed to properly accommodate expansion and contraction of the bridge superstructure due to temperature changes. Visible damage due to contraction of the superstructure in the winter of 1999–2000 prompted a study of substructure elements to determine the short-term safety and long-term viability of the bridge. Substructure elements were instrumented with a total of 62 strain gauges and two concrete crack gauges. Data were taken for a period of 3 months. Analysis of the data suggests that the bridge is safe for short-term use, but that the long-term viability of the structure has been compromised. Repair or replacement of substructure elements is recommended, along with frequent monitoring during the interim period.
Microbial biomass and population diversity in the upper water column of the Black Sea

Abstract Estimates of bacterial abundance, bacterial biomass and microplankton biomass in the Black Sea were made in the upper portion of the water column (0–500 m) during the second leg (14–28 May 1988) of the U.S.-Turkey Expedition aboard R.V. Knorr. The microbial biomass maximum at the interface between oxygenated and sulfide-rich waters, seen in previous years in the Black Sea and generally characteristic of redoxclines in other anoxic marine habitats, was absent on this occasion. In spite of the absence of a general enrichment in total microbial or bacterial biomass across the oxic-to-anoxic boundary, there were sharply delineated populations of microorganisms living at specific depths within the redoxcline. Among the microbial groups present were phototrophic bacteria, ciliates bearing attached bacteria and putative Achromatium cells.
Bioengineering materials: insights into smart materials designs

We have focused our research on biologically derived materials to gain insight into new types of materials with novel functions and new assembly and processing methods associated with these materials. Biological systems offer prototypical capabilities in sensing and responding to the environmental changes. The material designs, synthesis, regulation and assembly involved in these sensing and response processes should offer materials engineers incredible opportunities in the molecular-level design of new 'smart' materials with functions not achievable today. Specific examples are cited from our own studies that explore the biosynthesis, processing and properties of novel biological materials. It is our expectation that through the elucidation of the nature of these materials and the processes by which these materials are formed that new directions to the design of 'smart' functions may be garnered.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
A Fast Method for Designing Time-Optimal Gradient Waveforms for Arbitrary $k$ -Space Trajectories

A fast and simple algorithm for designing time-optimal waveforms is presented. The algorithm accepts a given arbitrary multidimensional k-space trajectory as the input and outputs the time-optimal gradient waveform that traverses k-space along that path in minimum time. The algorithm is noniterative, and its run time is independent of the complexity of the curve, i.e., the number of switches between slew-rate limited acceleration, slew-rate limited deceleration, and gradient amplitude limited regions. The key in the method is that the gradient amplitude is designed as a function of arc length along the k-space trajectory, rather than as a function of time. Several trajectory design examples are presented.
British Railroads and Engineers and the Beginnings of American Railroad Development

Practical demonstrations in Great Britain led some observers to conclude that the railroad would soon introduce “a new era in the business and arrangements of Society.” Thus inspired, promoters of the first American rail ventures began to draw heavily, both for practical information and equipment, upon the resources of the British pioneers, whose response was magnificently cooperative.
Segregation Analysis of HDL3-C Levels in Families of Patients Undergoing Coronary Arteriography at an Early Age

Abstract HDL cholesterol (HDL-C) level is a risk factor for coronary heart disease. Studies have shown a strong genetic influence on HDL-C levels in addition to environmental influences, but no definite major gene control has been demonstrated. Since HDL subfractions may better reflect the actions of distinct metabolic alterations than total HDL, we tested the hypothesis that the amount of cholesterol in the denser HDL3 subfraction (HDL3-C) is under the control of a major gene. The study population included 676 family members of 116 probands who underwent coronary arteriography at an early age (men ≤50 and women ≤60 years). HDL3-C level was measured by using enzymatic methods after preparative ultracentrifugation at a density of 1.125 g/mL. HDL3-C was adjusted for age, gender, alcohol consumption, and smoking, which combined accounted for 3% of its variance. Segregation analysis was conducted on adjusted HDL3-C by using regressive models. The familial correlations for HDL3-C levels were spouse .03±.08, pa...
Pupil Attendance in Resource Rooms as one Measure of the Time on Task Variable

According to the literature, pupil attendance appears to be related positively to pupil achievement, and in special education the amount of instructional time pupils need is specified in the individual educational plan. The authors of this study investigated the attendance of pupils scheduled to receive special education resource room instruction. They found that 22% of resource room contacts were missed. Of this 22%, 10% of the contacts were missed because students were absent from school; 6% were missing because of other school activities; and 6% because the resource rooms were closed.
Structural Basis for Polypyrimidine Tract Recognition by the Essential Pre-mRNA Splicing Factor U2AF65

The essential pre-mRNA splicing factor, U2AF(65), guides the early stages of splice site choice by recognizing a polypyrimidine (Py) tract consensus sequence near the 3' splice site. Since Py tracts are relatively poorly conserved in higher eukaryotes, U2AF(65) is faced with the problem of specifying uridine-rich sequences, yet tolerating a variety of nucleotide substitutions found in natural Py tracts. To better understand these apparently contradictory RNA binding characteristics, the X-ray structure of the U2AF(65) RNA binding domain bound to a Py tract composed of seven uridines has been determined at 2.5 A resolution. Specific hydrogen bonds between U2AF(65) and the uracil bases provide an explanation for polyuridine recognition. Flexible side chains and bound water molecules form the majority of the base contacts and potentially could rearrange when the U2AF(65) structure adapts to different Py tract sequences. The energetic importance of conserved residues for Py tract binding is established by analysis of site-directed mutant U2AF(65) proteins using surface plasmon resonance.
An embedded modeling language approach to interactive 3D and multimedia animation

While interactive multimedia animation is a very compelling medium, few people are able to express themselves in it. There are too many low-level details that have to do not with the desired content-e.g., shapes, appearance and behavior-but rather how to get a computer to present the content. For instance, behavior such as motion and growth are generally gradual, continuous phenomena. Moreover, many such behaviors go on simultaneously. Computers, on the other hand, cannot directly accommodate either of these basic properties, because they do their work in discrete steps rather than continuously, and they only do one thing at a time. Graphics programmers have to spend much of their effort bridging the gap between what an animation is and how to present it on a computer. We propose that this situation can be improved by a change of language, and present Fran, synthesized by complementing an existing declarative host language, Haskell, with an embedded domain-specific vocabulary for modeled animation. As demonstrated in a collection of examples, the resulting animation descriptions are not only relatively easy to write, but also highly composable.
Analysis of activity preferences as a function of differential consequences.

Individuals who do not possess the verbal skills to express meaningful choice in the absence of its consequences may have difficulty indicating their preference for protracted activities that are unavailable until some time in the future (e.g., taking a walk, riding a bike). When we examined the preferences of 4 individuals with developmental disabilities by showing them pictorial representations of various activities, their initial choices showed no clear preferences. In a subsequent condition, selecting a photograph resulted in brief access to the depicted activity. When selections produced differential consequences (i.e., access to the activity), clear preferences emerged. In addition, 3 individuals' preferences were later shifted to an initially less preferred but more socially desirable option by superimposing additional reinforcement contingencies for engaging in the less preferred activity. Results are discussed in terms of the conditions under which choice functions as an indicator of preference and how those conditions may be altered to improve the quality of choice making without limiting access to preferred options.
Discrete time-optimal command shapers and controls for multi-input multi-output systems

Flexible modes in many systems make fast maneuvers difficult. In order not to excite such modes, a finite impulse-response (FIR) "input shaper" can be used to prefilter inputs, reducing vibration at the expense of adding a delay equal to the length of the shaper. Given a system model in discrete time, the discrete time-optimal input shaper is the shortest prefilter that leads to zero vibration. The two cases where inputs are either unknown or known a priori are qualitatively different because the designer can take advantage of this knowledge to derive shorter shapers. The paper first reviews the case where inputs are unknown ("single-input shaping"). It then presents a method by which the search for optimal input shapers in both the known and unknown cases can be phrased as a quasiconvex optimization problem. The method is general, direct, and allows for the addition of derivative constraints to improve robustness. Finally, traditional optimal control and input shaping are compared for the case where inputs are known a priori, and it is shown that under certain conditions optimal discrete time input shaping and discrete time-optimal control are equivalent.
Ion Current in Hall Thrusters

To match the observed thrust and discharge current in Hall thrusters, computer simulations have typically assumed anomalous electron transport mechanisms, such as Bohm diffusion, to enhance electron mobility across magnetic field lines. Without enhanced electron transport, the simulations predict a much lower discharge current than observed, and too much of the potential drop is downstream of the channel exit. Rather than search for mechanisms to increase the electron scattering frequency, we seek to identify mechanisms that would increase the fraction of the current carried by ions, thus reducing the required electron current. We describe two mechanisms that enhance the current carried by ions. The first mechanism increases the ion current carried in the channel by simply including the effects of multiply charged ions on the plasma response. The importance of using accurate ionization cross sections and the need to include multiply charged ions even for discharge voltages of 300 V are discussed. The second mechanism is a process we term ldquoion reflux.rdquo In this process, current is carried by ions generated downstream of the channel exit. Portions of these ions impact the center of the thruster and are neutralized by cathode electrons. A large fraction of the resultant neutral atoms are reionized as they pass through the main exhaust beam. These newly born ions then carry additional current through the plume. Since neutrals freely move across magnetic field lines, ion reflux effectively enhances the cross-field electron transport. This second mechanism operates downstream of the exit plane and does not enhance electron transport in the acceleration region. Both of these mechanisms, i.e., multiply charged ions and ion reflux, reduce the need to invoke anomalous electron transport mechanisms in Hall thruster computer simulations. However, to date, no Hall thruster simulation has produced results in agreement with data without assuming some anomalous electron transport.
Comparison of cytogenetic and molecular genetic detection of t(8;21) and inv(16) in a prospective series of adults with de novo acute myeloid leukemia: a Cancer and Leukemia Group B Study.

PURPOSE: To prospectively compare cytogenetics and reverse transcriptase–polymerase chain reaction (RT-PCR) for detection of t(8;21)(q22;q22) and inv(16)(p13q22)/t(16;16)(p13;q22), aberrations characteristic of core-binding factor (CBF) acute myeloid leukemia (AML), in 284 adults newly diagnosed with primary AML. PATIENTS AND METHODS: Cytogenetic analyses were performed at local laboratories, with results reviewed centrally. RT-PCR for AML1/ETO and CBFβ/MYH11 was performed centrally. RESULTS: CBF AML was ultimately identified in 48 patients: 21 had t(8;21) or its variant and AML1/ETO, and 27 had inv(16)/t(16;16), CBFβ/MYH11, or both. Initial cytogenetic and RT-PCR analyses correctly classified 95.7% and 96.1% of patients, respectively (P = .83). Initial cytogenetic results were considered to be false-negative in three AML1/ETO-positive patients with unique variants of t(8;21), and in three CBFβ/MYH11-positive patients with, respectively, an isolated +22; del(16)(q22),+22; and a normal karyotype. The latte...
Reduced-complexity decoding of LDPC codes

Various log-likelihood-ratio-based belief-propagation (LLR-BP) decoding algorithms and their reduced-complexity derivatives for low-density parity-check (LDPC) codes are presented. Numerically accurate representations of the check-node update computation used in LLR-BP decoding are described. Furthermore, approximate representations of the decoding computations are shown to achieve a reduction in complexity by simplifying the check-node update, or symbol-node update, or both. In particular, two main approaches for simplified check-node updates are presented that are based on the so-called min-sum approximation coupled with either a normalization term or an additive offset term. Density evolution is used to analyze the performance of these decoding algorithms, to determine the optimum values of the key parameters, and to evaluate finite quantization effects. Simulation results show that these reduced-complexity decoding algorithms for LDPC codes achieve a performance very close to that of the BP algorithm. The unified treatment of decoding techniques for LDPC codes presented here provides flexibility in selecting the appropriate scheme from performance, latency, computational-complexity, and memory-requirement perspectives.
COMPARISON OF CHAINED AND TANDEM SCHEDULES OF REINFORCEMENT

The performance of 6 pigeons was compared on chained and tandem VI-FR and VI-DRL schedules of reinforcement. In the case of the chained schedules, varying the value of the FR or DRL schedule in the...
Tight Functional Coupling of Kinesin-1A and Dynein Motors in the Bidirectional Transport of Neurofilaments

We have tested the hypothesis that kinesin-1A (formerly KIF5A) is an anterograde motor for axonal neurofilaments. In cultured sympathetic neurons from kinesin-1A knockout mice, we observed a 75% reduction in the frequency of both anterograde and retrograde neurofilament movement. This transport defect could be rescued by kinesin-1A, and with successively decreasing efficacy by kinesin-1B and kinesin-1C. In wild-type neurons, headless mutants of kinesin-1A and kinesin-1C inhibited both anterograde and retrograde movement in a dominant-negative manner. Because dynein is thought to be the retrograde motor for axonal neurofilaments, we investigated the effect of dynein inhibition on anterograde and retrograde neurofilament transport. Disruption of dynein function by using RNA interference, dominant-negative approaches, or a function-blocking antibody also inhibited both anterograde and retrograde neurofilament movement. These data suggest that kinesin-1A is the principal but not exclusive anterograde motor for neurofilaments in these neurons, that there may be some functional redundancy among the kinesin-1 isoforms with respect to neurofilament transport, and that the activities of the anterograde and retrograde neurofilament motors are tightly coordinated.
Eculizumab in atypical haemolytic-uraemic syndrome allows cessation of plasma exchange and dialysis.

Disorders in complement regulation are a major cause of atypical haemolytic–uraemic syndrome (aHUS). Eculizumab, a monoclonal antibody targeting complement C5 and blocking the terminal complement cascade, should theoretically be useful in this disease, particularly when associated with specific complement pathway anomalies such as Factor H deficiency. Eculizumab is emerging as an effective treatment for post-transplant aHUS recurrence and may have a role in treating de novo aHUS, halting the haemolytic process. In this case report, we describe the fourth case of aHUS treated with eculizumab. In our patient, with a known complement Factor H mutation, not only has the disease process become quiescent but also this therapy has led to significantly improved renal function so that dialysis is no longer necessary.
Identification of ulcers in Wireless Capsule Endoscopy videos

Wireless Capsule Endoscopy (WCE) is a non invasive procedure which is used to view the lower gastrointestinal tract. Physicians can detect diseases such as bleeding, Crohn's disease, peptic ulcers, and colon cancer. In this paper a methodology is presented to identify peptic ulcers in the small intestine automatically. It first performs color transformation into the HSV color space; it utilizes log Gabor filters to find meaningful regions. A segmentation scheme is used to extract color information of these meaningful regions in the original RGB color space. Additionally, texture information is extracted and together with color values are fed into an artificial neural network for classification. Illustrative results from the methodology are also given in this paper.
Pseudohyphal growth of Cryptococcus neoformans is a reversible dimorphic transition in response to ammonium that requires Amt1 and Amt2 ammonium permeases.

ABSTRACT Cryptococcus neoformans is a human-pathogenic basidiomycete that commonly infects HIV/AIDS patients to cause meningoencephalitis (7, 19). C. neoformans grows as a budding yeast during vegetative growth or as hyphae during sexual reproduction. Pseudohyphal growth of C. neoformans has been observed rarely during murine and human infections but frequently during coculture with amoeba; however, the genetics underlying pseudohyphal growth are largely unknown. Our studies found that C. neoformans displays pseudohyphal growth under nitrogen-limiting conditions, especially when a small amount of ammonium is available as a sole nitrogen source. Pseudohyphal growth was observed with Cryptococcus neoformans serotypes A and D and Cryptococcus gattii. C. neoformans pseudohyphae bud to produce yeast cells and normal smooth hemispherical colonies when transferred to complete media, indicating that pseudohyphal growth is a conditional developmental stage. Subsequent analysis revealed that two ammonium permeases encoded by the AMT1 and AMT2 genes are required for pseudohyphal growth. Both amt1 and amt2 mutants are capable of forming pseudohyphae; however, amt1 amt2 double mutants do not form pseudohyphae. Interestingly, C. gattii pseudohypha formation is irreversible and involves a RAM pathway mutation that drives pseudohyphal development. We also found that pseudohyphal growth is related to the invasive growth into the medium. These results demonstrate that pseudohyphal growth is a common reversible growth pattern in C. neoformans but a mutational genetic event in C. gattii and provide new insights into understanding pseudohyphal growth of Cryptococcus.
AMINO ACID COMPOSITION AND NUTRITIONAL IMPLICATIONS OF MILK FERMENTED BY VARIOUS LACTIC CULTURES

A total of nine milk products were analyzed for total and free amino acids and total and nonprotein nitrogen. The products were: (1) whole milk (WM), (2) skim milk (SM), (3) WM fermented by Streptococcus thermophilus, (4) SM fermented by S. thermophilus, (5) WM fermented by Lactobacillus bulgaricus, (6) SM fermented by L. bulgaricus, (7) WM fermented by L. acidophilus, (8) SM fermented by L. acidophilus and (9) commercially prepared buttermilk. Essential amino acid content of the fermented milk was lower than that of the whole or skim milk. Fermentation of milk by lactic cultures decreased the total lysine (except butter milk) and methionine contents of all the samples. Since these two amino acids are limiting amino acids in protein malnourished areas, lactic fermentation of milk may be undesirable based on the chemical scores of the protein. However, the free amino acid content, including that of lysine and methionine, increases significantly upon lactic fermentation of milk. This predigestion of protein might result in an increased availability of the amino acids to offset the reduction in amino acids during fermentation and may even result in a better quality protein. Biological evaluation of the fermented milk proteins is necessary to evaluate their nutritional quality. L. bulgaricus was the most proteolytic of all the organisms used.
Experiences in converting to a minicomputer

This paper describes the transition from use of a shared, medium-scale computer for research, patient care, and financial computing for a small hospital to an in-house ‘mini' computer. The advantages and disadvantages of a variety of alternative solutions for computer processing are discussed. Although the support software supplied with the system was found adequate, some important limitations needed attention and several general-purpose programs proved useful to speed the conversion of programs in PL/1 to BASIC. Considering both the amount of time required for total conversion as well as the facilities lost in switching from a large-scale machine, the capacity, flexibility and economy of a smaller in-house computer were found sufficient to justify such a conversion.Cet article decrit les problemes qui se soot poses, clans un petit hopital, lors du passage d'un ordinateur de taille moyenne a un mini-ordinateur. Dans cet hopital l'ordinateur est utilise aussi bien pour la recherche que pour les soins et la...
Conduct and Discipline in Un Peacekeeping Operations: Culture, Political Economy and Gender

Systematic patterns of sexual exploitation and abuse have emerged around UN peacekeeping missions over the course of many years. These include, most egregiously, peacekeepers’ exchange of UN food supplies or money for sex with young girls and sometimes boys as well as sexual assault. This paper examines the cultural and political economic roots of the problem, focusing on the relationship between ideas and attitudes about culture, gender, sexuality, and peacekeeping as those influence the nature and extent of SEA. It offers a political economic and cultural framework for understanding the problem, which is proposed to replace frameworks currently in broad if often tacit use in the UN.
The Use of Cy Pres in Class Action Settlements: The Best of Bad Options

This paper first briefly traces the history of the cy pres doctrine and how it became a common and integral part of resolving class action lawsuits. It next examines the various approaches, perspectives, and recommendations of courts and scholars confronted with the increasing use of cy pres in class-action fund distribution. Finally, it concludes that, though still functionally and perhaps constitutionally problematic, cy pres may be the best of many bad alternatives when it comes to distributing funds resulting from a class action settlement.
Intersecting gender, evaluations, and examinations: Averting gender bias in an obstetrics and gynecology clerkship in the United States

Background: The purpose of this study was to determine whether gender bias was present in the final third-year medical student obstetrics/gynecology clerkship performance evaluation completed by faculty and resident physicians. Methods: This was a retrospective cohort study of third-year medical students over the course of ten years (2004 – 2014) at a private medical school in the northern US state of Wisconsin. Each student's performance during their required 6-week obstetrics/gynecology clerkship was assessed by a combination of the student's scores on a clinical performance evaluation and on a standardized national subject examination. The clinical performance evaluations are comprised of 10 domains, each using a 9-point Likert scale and completed by faculty and resident physicians. All clerkships at our institution use the same evaluation form, which was designed and validated by the medical education statistics department. Final obstetrics/gynecology clerkship average clinical evaluation scores (Scale 1-9) and obstetrics/gynecology standardized national subject examination scores (Percentile 1-99) were compared to see if a gender based difference between subject examination and performance evaluation scores existed. Results: 1,976 student records were analyzed. Mean standardized national subject exam scores were significantly higher for females [74.4 (8.1)] than males [72.9 (8.2)] (Possible range 1-99) with Cohen's d = 0.2 (P = 0.001). The average female score on the clinical evaluation was mean (SD) = 7.4 (0.9), compared to an average clinical evaluation score of 7.2 (1.0) for males (P = 0.001) (range 1-9). Performance on the standardized national subject exam was significantly correlated (r = 0.3, P = 0.001) with clinical evaluation scores, and when split by gender the strength of the correlation remained. Discussion: Medical student performance on the standardized national subject exam correlated with clinical evaluations independent of gender. Women had higher scores on both the subject examination and the clinical performance evaluations. There was no evidence of gender bias in the students' clinical evaluation scores.
Book Review: Julian Randall and Allan J. Sim, Managing People at Work

Julian Randall and Allan J. Sim, Managing People at Work. London: Routledge, 2014, 416 pp. £ 100, (ISBN: 978-0-415-53438-3 [HB])
A multistage decision support framework to guide tree species management under climate change via habitat suitability and colonization models, and a knowledge-based scoring system

No single model can capture the complex species range dynamics under changing climates—hence the need for a combination approach that addresses management concerns. A multistage approach is illustrated to manage forested landscapes under climate change. We combine a tree species habitat model—DISTRIB II, a species colonization model—SHIFT, and knowledge-based scoring system—MODFACs, to illustrate a decision support framework. Using shortleaf pine (Pinus echinata) and sugar maple (Acer saccharum) as examples, we project suitable habitats under two future climate change scenarios (harsh, Hadley RCP8.5 and mild CCSM RCP4.5 at ~2100) at a resolution of 10 km and assess the colonization likelihood of the projected suitable habitats at a 1 km resolution; and score biological and disturbance factors for interpreting modeled outcomes. Shortleaf pine shows increased habitat northward by 2100, especially under the harsh scenario of climate change, and with higher possibility of natural migration confined to a narrow region close to the current species range boundary. Sugar maple shows decreased habitat and has negligible possibility of migration within the US due to a large portion of its range being north of the US border. Combination of suitable habitats with colonization likelihoods also allows for identification of potential locations appropriate for assisted migration, should that be deemed feasible. The combination of these multiple components using diverse approaches leads to tools and products that may help managers make management decisions in the face of a changing climate.
How Ordering of Assignments Can Influence Beliefs about the Self and How These Beliefs Can Impact on Student Class Performance.

This research examines whether the ordering of the difficulty of exams can influence student beliefs about their academic abilities and the impact of these beliefs on their performance. The ordering of the difficulty of test items has shown to affect performance. Study One (n=91) examined college student differences in reaction to a difficult and an easy exam. Results suggest that the ordering of difficulty of exams may influence self-efficacy of students. Study Two (n = 178) examines whether this self-efficacy (and other beliefs about the self) can impact college student performance on actual exam scores over time. The results of this research suggest that the ordering of difficulty of assignments can affect student’s self-efficacy about the class. It finds that the impact on self-efficacy may affect overall performance early in the class but that this impact may not be long lasting. This is due to the positive evidence received later in the course that may contradict initial low performance and give confidence in the student’s ability to achieve high performance. The results have implications for segments of the student population that may be disproportionately impacted by self-perceptions such as the first generation student. Cette recherche examine dans quelle mesure le classement des examens selon leur difficulte influence les croyances des etudiants par rapport a leurs habiletes academiques d’une part, et l’impact de ces croyances sur leur performance d’autre part. Il a ete demontre que le classement des items d’un examen en fonction de leur difficulte a une incidence sur la performance. Etude #1 (n=91) porte sur les differences dans les reactions d’etudiants d’universite a un examen difficile et a un examen facile. Les resultats portent a croire que l’ordre de presentation des examens selon leur difficulte peut influencer l’auto-efficacite des etudiants. Etude #2 (n=178) evalue dans quelle mesure cette auto-efficacite (et d’autres croyances relatives a soi) influence, a la longue, la performance aux examens des etudiants universitaires. Les resultats semblent indiquer que la presentation des examens en fonction de leur difficulte peut affecter la perception d’auto-efficacite chez les etudiants et que cet impact peut avoir des incidences sur la performance globale au debut du cours mais que celles-ci peuvent etre de courte duree. Ce phenomene s’explique par les indications positives qui peuvent venir contredire le faible rendement initial et rehausser la confiance des etudiants en leur capacite de bien reussir. Ces resultats comportent des implications touchant les secteurs de la population estudiantine qui pourraient etre affectes de maniere disproportionnee par leur image de soi, tels les etudiants de premiere generation.
Coefficient of variation: the second-order alternative

ABSTRACTThe coefficient of variation V introduced by Karl Pearson over 100 years ago is one of the most important and widely used moment-based summary statistics. The V does, however, have some significant limitations: (1) it becomes problematic when the data are both positive and negative, (2) it generally lacks an upper bound so that interpretations of V-values become difficult, (3) it lacks an intuitive and meaningful interpretation, (4) it is highly sensitive to outliers, and (5) it is very much affected by the mean and errors or changes in the mean. In order to overcome such limitations, this paper introduces the second-order coefficient of variation V2 as a simple alternative to Pearson’s V. While V is based on a ratio of second-order to first-order moments, V2 is a ratio of second-order moments. The V2 is well defined for all real-valued variables and data. The sample form of the new coefficient is also a ratio of (Euclidean) distances and takes on values between 0 and 1, making interpretations int...
Pharmacogenomics and Pharmacoepigenomics in Pediatric Medicine

Abstract In the past several years, human genetics studies have progressed from monogenic to complex and common diseases because of the advancement in technologies. There is increased knowledge of the pharmacokinetics and pharmacogenomics of the drugs in adults as well as in children. These technological developments provided new diagnostic, prognostic, and therapeutic opportunities. We are now in a position to address many additional ambitious questions. For instance, in clinical medicine, interindividual variation in drug response is a major problem. Some of the heterogeneity of drug safety and efficacy among individuals can be explained by pharmacogenomics. It has also the potential to improve the treatment in both adults and children. In pediatrics however, there is ontogeny and metabolic capacity in children is different compared to adults. Several specific developmental changes may underlie some of the variability in drug response seen in children. They may also be responsible for adverse drug reactions (ADRs). Therefore, much of the diversity in drug effects cannot be explained by studying the genomic diversity alone. It is necessary to include the effect of growth (involves variations in gene expression) along with genetic differences when explaining the variability in treatment response. In this respect epigenomics may expand the scope of pharmacogenomics towards optimization of drug therapy. Future studies must focus on periods of maturation of the drug-metabolizing enzymes and polymorphisms in their genes by using candidate gene approach, gene expression analysis, genome-wide haplotype mapping, and proteomics. The integration of genetic data and clinical phenotypes along with the role of other factors is necessary to evaluate both efficacy and ADRs of any drug. It may require extensive genetic epidemiological studies spanning over many years.
Effectiveness of a Rapid Lumbar Spine MRI Protocol Using 3D T2-Weighted SPACE Imaging Versus a Standard Protocol for Evaluation of Degenerative Changes of the Lumbar Spine

OBJECTIVE. Reducing lumbar spine MRI scanning time while retaining diagnostic accuracy can benefit patients and reduce health care costs. This study compares the effectiveness of a rapid lumbar MRI protocol using 3D T2-weighted sampling perfection with application-optimized contrast with different flip-angle evolutions (SPACE) sequences with a standard MRI protocol for evaluation of lumbar spondylosis. MATERIALS AND METHODS. Two hundred fifty consecutive unenhanced lumbar MRI examinations performed at 1.5 T were retrospectively reviewed. Full, rapid, and complete versions of each examination were interpreted for spondylotic changes at each lumbar level, including herniations and neural compromise. The full examination consisted of sagittal T1-weighted, T2-weighted turbo spin-echo (TSE), and STIR sequences; and axial T1- and T2-weighted TSE sequences (time, 18 minutes 40 seconds). The rapid examination consisted of sagittal T1- and T2-weighted SPACE sequences, with axial SPACE reformations (time, 8 minutes...
The Chu-Vandermonde Identity via Leibniz′s Identity for Derivatives

We give a proof of the Chu–Vandermonde identity using only Leibniz′s identity for derivatives.
Analysis of cystic fibrosis–associated P67L CFTR illustrates barriers to personalized therapeutics for orphan diseases

Emerging knowledge indicates the difficulty in categorizing unusual cystic fibrosis (CF) mutations, with regard to both pathogenic mechanism and theratype. As case in point, we present data concerning P67L mutation of the cystic fibrosis transmembrane conductance regulator (CFTR), a defect carried by a small number of individuals with CF and sometimes attributed to a channel conductance abnormality. Findings from our laboratory and others establish that P67L causes protein misfolding, disrupts maturation, confers gating defects, is thermally stable, and exhibits near normal conductance. These results provide one framework by which rare CF alleles such as P67L can be more comprehensively profiled vis-a-vis molecular pathogenesis. We also demonstrate that emerging CF treatments - ivacaftor and lumacaftor - can mediate pronounced pharmacologic activation of P67L CFTR. Infrequent CF alleles are often improperly characterized, in part, due to the small numbers of patients involved. Moreover, access to new personalized treatments among patients with ultra-orphan genotypes has been limited by difficulty arranging phase III clinical trials, and off-label prescribing has been impaired by high drug cost and difficulty arranging third party reimbursement. Rare CFTR mutations such as P67L are emblematic of the challenges to "precision" medicine, including use of the best available mechanistic knowledge to treat patients with unusual forms of disease.
High-Sodium Diet Has Opposing Effects on Mean Arterial Blood Pressure and Cerebral Perfusion in a Transgenic Mouse Model of Alzheimer's Disease.

BACKGROUND Cerebral ionic homeostasis impairment, especially Ca2+, has been observed in Alzheimer's disease (AD) and also with hypertension. Hypertension and AD both have been implicated in impaired cerebral autoregulation. However, the relationship between the ionic homeostasis impairment in AD and hypertension and cerebral blood flow (CBF) autoregulation is not clear. OBJECTIVE To test the hypothesis that a high-salt diet regimen influences the accumulation of amyloid-β (Aβand CBF) and CBF, exacerbates cognitive decline, and increases the propensity to AD. METHODS Double transgenic mice harboring the amyloid-β protein precursor (APPswe), and presenilin-1 (PSEN1) along with control littermates, 2 months of age at initiation of special diet, were divided into 4 groups: Group A, APP/PS1 and Group B, controls fed a high-sodium (4.00%) chow diet for 3 months; Group C, APP/PS1 and Group D, controls fed a low-sodium (0.08%) regular chow diet for 3 months. Mean arterial blood pressure (MAP) and CBF were measured noninvasively using the tail MAP measurement device and magnetic resonance imaging, respectively. Aβ plaques numbers in the cortex and hippocampus of APP/PS1 were quantified. RESULTS In contrary to controls, APP/PS1 mice fed a high-salt diet did not show markedly elevated mean systolic and diastolic blood pressure (134±4.8 compared with 162±2.8 mmHg, and 114±5.0 compared with 137±20 mmHg, p< 0.0001). However, a high-salt diet increased CBF in both APP/PS1 and controls and did not alter the cerebral tissue integrity. Aβ plaques were significantly reduced in the cortex and hippocampus of mice fed a high-salt diet. CONCLUSION These data suggest that a high-salt diet differently affects MAP and CBF in APP/PS1 mice and controls.
ROLE OF CALCIUM AND ALBUMIN IN THE AUTOREGULATION OF RENAL BLOOD FLOW

Publisher Summary The kidney has the ability to keep its blood flow relatively constant over a wide range of renal perfusion pressure. This chapter explains that calcium infusion reduces the renal blood flow at which autoregulation occurs. It has been observed that raising perfusate albumin concentration, a maneuver that abolishes autoregulation, raises perfusate flow in isolated perfused kidneys. While conducting experiments on the role of calcium in the mechanisms controlling rennin secretion from isolated perfused kidneys, it also observes that autoregulation of perfusate flow is dependent on a specific level of ionized calcium concentration in the perfusion medium. The chapter discusses the mechanisms by which raising albumin concentration in the perfusion medium abolishes autoregulation and increases perfusate flow. The chapter reviews that autoregulation of renal perfusate flow is dependent on the ionized calcium concentration in the perfusion fluid. Raising albumin concentration abolishes autoregulation and increases flow by lowering extracellular ionized calcium and by raising intrarenal tissue pressure.
Describing habitat suitability of bobcats (Lynx rufus) using several sources of information obtained at multiple spatial scales

We investigated habitat use of bobcats (Lynx rufus) across spatial scales in New Hampshire, USA, by integrating independent sources of information into one statewide model of habitat suitability. First, statewide distribution of bobcats (second-order selection) was estimated using observations of bobcats solicited from the public. Probability functions indicated that areas where bobcats were not detected (no sightings) were characterized by high elevations and deep snow during winter. That pattern was corrob-orated by camera traps that were distributed among high and low-elevation landscapes. Second, bobcats equipped with GPS collars in two study areas were used to determine habitat use within established home ranges (third-order selection). Resource-selection probability functions developed from locations of marked bobcats indicated they selected forests, shrub/scrub, and wetlands, and avoided developed areas, agricultural areas, and open water relative to availability. Bobcats also avoided areas with high road densities and selected areas close to forest edges, and preferred rugged south-facing slopes. Finally, these measures of bobcat distribution were combined to obtain fine-scale estimates of bobcat habitat suitability across New Hampshire. A comparison of models of habitat suitability to an index of bobcat abundance (effort-corrected detections of bobcats by hunter) indicated that the hierarchical model (second-order multiplied by third-order of selection) provided a better description of statewide bobcat habitat than either single-scale analyses. As a result, we recommend caution when extrapolating information on the distribution of a species obtained at a limited spatial scale.