cssi/SciSciGPT-SciSciNet huggingface dataset:
The Handling of K-Edge Effects in the Multiple Isotope Material Basis Set (MIMBS) Method of Isotope Identification

The multiple isotope material basis set (MIMBS) method for isotope identification combines the material basis set (MBS) model of gamma spectrum attenuation with ordinary response function fitting to identify shielded gamma-emitting isotopes, using low and medium resolution gamma detectors such as NaI(Tl) and LaBr 3 . We recently improved the MIMBS algorithm to handle low energy gamma emitters such as 133Xe or 241Am. A concern with fitting the low energy region (below approximately 90 keV) is that the underlying MBS model assumptions fail because of the inherent K-edge discontinuities in the attenuation versus energy curve for the different atomic species. For example, with basis attenuators of Al (Z=13) and Pb (Z=82) , the MBS model for the attenuation curve of Sn (Z=50) would have Al and Pb K-edge discontinuities at 1.55 and 88 keV, rather than at the Sn K-edge energy of 29.2 keV. Complex mixtures such as cargo would have a complex and unpredictable K-edge distribution. In this presentation we show that the effect of K-edge discontinuities on the improved multiple-thickness MIMBS algorithm for low energy isotope identification and spectrum simulation is small for common attenuator distributions.
Antecedent moisture controls on stream nitrate flux in an agricultural watershed.

Evaluating nitrate-N fluxes from agricultural landscapes is inherently complex due to the wide range of intrinsic and dynamic controlling variables. In this study, we investigate the influence of contrasting antecedent moisture conditions on nitrate-N flux magnitude and dynamics in a single agricultural watershed on intra-annual and rainfall-event temporal scales. High temporal resolution discharge and nitrate concentration data were collected to evaluate nitrate-N flux magnitude associated with wet (2009) and dry (2012) conditions. Analysis of individual rainfall events revealed a marked and consistent difference in nitrate-N flux response attributed to wet/dry cycles. Large-magnitude dilutions (up to 10 mg N L -1 ) persisted during the wet antecedent conditions (2009), consistent with a dominant baseflow contribution and excess groundwater release in relation to precipitation volume (discharge > > precipitation). Smaller-magnitude concentrations (<7 mg N L -1 ) were observed during the drought conditions of 2012, consistent with a quickflow-dominated response to rain events and infiltration/ storage of precipitation resulting in discharge < precipitation. Nitrate-N loads and yields from the watershed were much higher (up to an order of magnitude) in the wet year vs. the dry year. Our results suggest that the response of nitrate-N loading to rain events is highly dependent on intra-annual antecedent moisture conditions and subsurface hydrologic connectivity, which together dictate the dominant hydrologic pathways for stream recharge. Additionally, the results of our study indicate that continued pronounced wet/dry cycles may become more dominant as the short-term driver of future nitrate-N exports.
Statins and "chameleon-like" cutaneous eruptions: simvastatin-induced acral cutaneous vesiculobullous and pustular eruption in a 70-year-old man.

Background The statin medications for lowering of blood cholesterol can be associated with cutaneous lichenoid reactions but also a variety of other adverse cutaneous eruptions, including Stevens-Johnson syndrome, toxic epidermolytic necrolysis, porphyria cutanea tarda, linear IgA bullous dermatosis, and reaction patterns (lupus and dermatomyositis-like and pustular). Cutaneous eruptions ("eczema" in the product literature) owing to simvastatin are reported in approximately 1.5% individuals compared with placebo. Objective To correlate the clinical and microscopic features of an unusual vesiculobullous reaction to simvastatin. Methods Retrospective analysis of clinical information and skin biopsies. Results We present the case of a 70-year-old man with chronic vesiculobullous and pustular annular lesions on distal arms, legs, hands, and feet for 2 years. The eruption was recalcitrant to potent topical corticosteroids. Multiple biopsies at different times showed a spongiotic and lichenoid hypersensitivity reaction resembling contact dermatitis, purpuric drug eruption, and pustular folliculitis. The common themes in the histopathology were spongiosis with microvesiculation, focal lichenoid infiltrates, dermal hemorrhage, and chronic superficial inflammatory cell infiltrates with eosinophils. The eruption began when simvastatin was started, improved when it was stopped, recurred with rechallenge, and cleared when simvastatin was discontinued. Conclusions Acral cutaneous vesiculobullous eruption is an uncommon adverse drug eruption due to simvastatin, one of many different patterns possible. A high level of suspicion for an unexplained cutaneous eruption in an older individual on statins is important to identification of the disorder and discontinuation of the offending medication.
Cutting Loose. Abscission and Dehiscence in Arabidopsis

Delayed cell separation historically was one of the first agricultural traits selected for by man. Successful collection of fruits and seeds of crops such as wheat ( Triticum monococcum ), rice ( Oryza sativa ), and a variety of legumes was only possible due to the selection for delayed fruit
Dynamic antagonism between RNA-binding protein CUGBP2 and cyclooxygenase-2-mediated prostaglandin E2 in radiation damage

Damage to intestinal epithelium limits the use of ionizing radiation (IR) in cancer therapy. Prostaglandins (PGs), generated through the action of cyclooxygenase-1 (COX-1) and COX-2 protect the intestinal stem cells from IR. In previous studies, we demonstrated that the RNA-binding protein CUGBP2 regulates the stability and translation of COX-2 mRNA by interacting with AU-rich sequences in 3′ UTR. Here, we demonstrate a dynamic antagonistic relationship between CUGBP2 and COX-2. Both CUGBP2 and COX-2 are rapidly induced after IR in intestinal crypt epithelial cells in mice, but CUGBP2 protein expression is observed immediately and COX-2 protein expression is delayed. In contrast, administration of bacterial lipopolysaccharide induced COX-2 expression and PGE2, resulting in the inhibition of CUGBP2 expression and radioprotection of the intestine. These effects were reversed by NS398, a COX-2-specific inhibitor, suggesting that lipopolysaccharide-mediated inhibition of CUGBP2 is a PG-dependent mechanism. Furthermore, CUGBP2 expression is higher in COX-1–/– and COX-2–/– mice than wild-type controls at basal conditions, which is further increased after IR.
A layered approach to very large system specification

Many information system endeavors fail (in terms of cost overruns, late delivery, or absolute inability to meet real needs). This is primarily still a matter of lack of effective communication by the various participants. Some possible improvements are discussed. They include: (1) adoption of engineering practice over all concepts, such as performance and safety, in the early stages of the definition; (2) use of a layered approach, where the design progresses in a top-down fashion, with few constraints at the start and assertion of more constraints until the definition is formal at completion; (3) better interaction and diagnostics among the various definition parts. >
Combining Mentoring With Structured Group Activities A Potential After-School Context for Fostering Relationships Between Girls and Mentors

The current study explores the potential of one-on-one mentoring facilitated within a structured group format for developing connection and sustaining mentor-mentee relationships with early adolesc...
Kinetics of Protein-DNA Interaction: Facilitated Target Location in Sequence-Dependent Potential

Recognition and binding of specific sites on DNA by proteins is central for many cellular functions such as transcription, replication, and recombination. In the process of recognition, a protein rapidly searches for its specific site on a long DNA molecule and then strongly binds this site. Here we aim to find a mechanism that can provide both a fast search (1- 10 s) and high stability of the specific protein-DNA complex (Kd ¼ 10 � 15 -10 � 8 M). Earlier studies have suggested that rapid search involves sliding of the protein along the DNA. Here we consider sliding as a one-dimensional diffusion in a sequence- dependent rough energy landscape. We demonstrate that, despite the landscape's roughness, rapid search can be achieved if one-dimensional sliding is accompanied by three-dimensional diffusion. We estimate the range of the specific and nonspecific DNA-binding energy required for rapid search and suggest experiments that can test our mechanism. We show that optimal search requires a protein to spend half of its time sliding along the DNA and the other half diffusing in three dimensions. We also establish that, paradoxically, realistic energy functions cannot provide both rapid search and strong binding of a rigid protein. To reconcile these two fundamental requirements we propose a search-and-fold mechanism that involves the coupling of protein binding and partial protein folding. The proposed mechanism has several important biological implications for search in the presence of other proteins and nucleosomes, simultaneous search by several proteins, etc. The proposed mechanism also provides a new framework for interpretation of experimental and structural data on protein-DNA interactions.
Duck species co-occurrence in hunter daily bags

As multi-species harvest management gains support among waterfowl managers, increased understanding of duck species relationships during harvest is needed. We used U.S. Fish and Wildlife Service's Parts Collection Survey data from 2002 to 2011 to develop a matrix defining relationships among duck species harvested in the Central Flyway. We calculated conditional probabilities of co-occurrence in a hunter's daily bag (i.e., P(B|A), the probability that species B was in a hunter bag, given that species A was in the same bag). We then performed 12 scenarios of hypothetical changes to species-specific regulations. We used Central Flyway harvest estimates from 2011 and probabilities of co-occurrence to predict the effects of regulatory changes on harvest. Hunters were more likely to harvest 2 species of diving ducks (P(Diving|Diving) = 0.37) than to harvest a diving duck given that a dabbling duck was also harvested the daily bag (P(Diving|Dabbling) = 0.12). Hunters also were more likely to harvest 2 ducks of the same species (and sex in the case of mallards [Anas platyrhynchos]) within a daily bag (mean P(A|A) = 0.31) than 2 ducks of different species (mean P(B|A) = 0.13). Traditionally, managers have focused on single-species assessments when considering regulatory changes, but harvest regulation changes may affect multiple duck species if harvest is redistributed to other species. Our data show a range of co-occurrence patterns of species commonly or rarely harvested together. Examination of the relationships among duck species during harvest provides critical insight for the development of appropriate regulations for multi-species management. © 2015 The Wildlife Society.
Impaired liver regeneration and increased oval cell numbers following T cell-mediated hepatitis.

The regeneration of liver tissue following transplantation is often complicated by inflammation and tissue damage induced by a number of factors, including ischemia and reperfusion injury and immune reactions to the donor tissue. The purpose of the current study is to characterize the effects of T cell–mediated hepatitis induced by concanavalin A (ConA) on the regenerative response in vivo. Liver regeneration following a partial (70%) hepatectomy (pHx) was associated with elevations in serum enzymes and the induction of key cell cycle proteins (cyclin D, cyclin E, and Stat3) and hepatocyte proliferation. The induction of T cell–mediated hepatitis 4 days before pHx increased serum enzymes 48 hours after pHx, reduced early cyclin D expression and Stat3 activation, and suppressed hepatocyte proliferation. This inhibition of proliferation was also associated with increased expression of p21, the activation of Smad2, the induction of transforming growth factor beta and interferon gamma expression, and reduced hepatic interleukin 6 production. Moreover, the ConA pretreatment increased the numbers of separate oval cell-like CD117+ cells and hematopoietic-like Sca-1+ cell populations 48 hours following pHx. The depletion of natural killer (NK) cells, an important component of the innate immune response, did not affect liver injury or ConA-induced impairment of hepatocyte proliferation but did increase the numbers of both CD117-positive and Sca-1–positive cell populations. Finally, splenocytes isolated from ConA-pretreated mice exerted cytotoxicity toward autologous bone marrow cells in an NK cell–dependent manner. Conclusion: T cell–mediated hepatitis alters early cytokine responses, reduces hepatocellular regeneration, and induces NK cell–sensitive oval cell and hematopoietic-like cell expansion following pHx. (HEPATOLOGY 2007;46:229–241.)
Error Amplification and Disturbance Propagation in Vehicle Strings with Decentralized Linear Control

We consider the problem of controlling a string of vehicles moving in one dimension so that they all follow a lead vehicle with a constant spacing between successive vehicles. We examine the symmetric bidirectional control architecture, where the control action on a vehicle depends equally on the spacing errors with respect to its adjacent vehicles. Performance of this decentralized scheme in terms of spacing error amplification and disturbance propagation is investigated. The results established in this paper show that a symmetric bidirectional architecture with a linear controller suffers from fundamental limitations on closed loop performance that cannot be mitigated by appropriate control design.
EXTRAGALACTIC X‐RAY ASTRONOMY WITH THE EINSTEIN OBSERVATORY

The flight of the Einstein X-ray Observatory has brought about a qualitative change in observational capabilities in the 0.2-3.0 keV energy range, with a several hundred-fold increase in sensitivity over previous instruments that allows the detection and study of X-rays from objects as distant as quasars, at redshifts greater than 3.0. Attention is given to the progress that has been made in relating X-ray luminosity to such other properties of clusters of galaxies as morphological classification, central galaxy density, and spiral fractions. The high resolution 2.6 arcsec over 20 arcmin, and medium resolution 1.5 arcmin over 75 arcmin imaging detectors on Einstein have permitted detailed study of large and small scale structures, accurate brightness profiles, and approximate temperature distributions of clusters, as well as the investigation of individual galaxy interaction with the intracluster medium.
Compassion: An Evolutionary Analysis and Empirical Review

What is compassion? And how did it evolve? In this review, we integrate 3 evolutionary arguments that converge on the hypothesis that compassion evolved as a distinct affective experience whose primary function is to facilitate cooperation and protection of the weak and those who suffer. Our empirical review reveals compassion to have distinct appraisal processes attuned to undeserved suffering; distinct signaling behavior related to caregiving patterns of touch, posture, and vocalization; and a phenomenological experience and physiological response that orients the individual to social approach. This response profile of compassion differs from those of distress, sadness, and love, suggesting that compassion is indeed a distinct emotion. We conclude by considering how compassion shapes moral judgment and action, how it varies across different cultures, and how it may engage specific patterns of neural activation, as well as emerging directions of research.
Assessment of Nanostructured Capillary Wicks for Passive Two-Phase Heat Transport

The major factors limiting the thermal performance of passive two-phase heat-spreading devices are the ability of the wick structures to transport liquid by means of capillary forces and the thermal resistance posed by the wicks. Nanoscale geometric enhancements to the wick structure, through the use of carbon nanotubes and metallic nanowires, promise to enhance the capillary transport while at the same time decreasing the thermal resistance due to their high intrinsic thermal conductivity. We analyze the performance of nanostructured wicks in heat-spreading applications. We report that the flow resistance of nanostructures constitutes a major barrier to their use as passive flow-conveying media and identify geometrical parameters that yield high rates of thin-film evaporation while minimizing the flow resistance. The analysis shows that the use of nanostructures as the sole wicking element in a two-phase thermal spreader restricts its footprint area to a size of 4 cm2 for heat flux inputs as low as 1 W/c...
Suitability of the Medicinal Plant, Acorus calamus L., for Wetland Restoration

ABSTRACT: Socio-economically important plant species that are used in wetland restoration projects can act as economic incentives for conservation and restoration. We examined the suitability of a medicinal plant, Acorus calamus L. (sweetflag, Acoraceae), for use in wetland restoration. We subjected rhizomes of A. calamus to different levels of light (full light and shade), moisture (400 ml and 200 ml water biweekly), and nitrogen (10 µg ml-1 and 4 µg ml-1 nitrogen biweekly) in a greenhouse study mimicking different stages of wetland restoration. At the end of the experiment, the biomass and length of each rhizome, and number of mature buds, leaves, and roots, were recorded. Multivariate analysis of variance indicated that light (λ = 0.762), nitrogen (λ = 0.449), and moisture (λ = 0.508) had significant effects on rhizome growth. Our results indicate that A. calamus displays a high degree of morphological plasticity in biomass allocation patterns in response to environmental parameters. Furthermore, most ...
Targeting Metabolic Scavenging in Pancreatic Cancer

Pancreatic tumor metabolism is rewired to facilitate survival and growth in a nutrient-depleted environment. This leads to a unique dependence on metabolic recycling and scavenging pathways, including NAD salvage. Targeting this pathway in pancreatic cancer disrupts metabolic homeostasis and impairs tumor growth.
ApoE-/-Fas-/- C57BL/6 mice: a novel murine model simultaneously exhibits lupus nephritis, atherosclerosis, and osteopenia.

To establish a mouse model of accelerated atherosclerosis in lupus, we generated apolipoprotein E-deficient (apoE -/- ) and Fas 1pr/1pr (Fas - /- ) C57BL/6 mice. On a normal chow diet, 5 month old apoE -/- Fas -/- mice had enlarged glomerular tuft areas, severe proteinuria, increased circulating autoantibody levels, and increased apoptotic cells in renal and vascular lesions compared with either single knockout mice. Also, double knockout mice developed increased atherosclerotic lesions but decreased serum levels of total and non-HDL cholesterol compared with apoE -/- Fas +/+ littermates. Moreover, female apoE -/- Fas -/- mice had lower vertebral bone mineral density (BMD) and bone volume density (BV/TV) than age-matched female apoE -/- Fas +/+ mice. Compared with apoE -/ Fas +/+ and apoE +/+ Fas -/- mice, apoE -/- Fas -/- mice had decreased circulating oxidized phospholipid (OxPL) content on apoB-100 containing lipoprotein particles and increased serum IgG antibodies to OxPL, which were significantly correlated with aortic lesion areas (r = 0.58), glomerular tuft areas (r = 0.87), BMD (r = - 0.57), and BV/ TV (r = -0.72).jr These results suggest that the apoE -/- Fas -/- mouse model might be used to study atherosclerosis and osteopenia in lupus. Correlations of IgG anti-OxPL with lupus-like disease, atherosclerosis, and bone loss suggested a shared pathway of these disease processes.
Organized Programs to Prevent Lower-Extremity Amputations

Background: Diabetes-related lower-extremity amputations are largely preventable. Eighty-five percent of amputations are preceded by a foot ulcer. Effective management of ulcers, which leads to healing, can prevent limb loss. Methods: In a county hospital, we implemented a six-step approach to the diabetic limb at risk. We calculated the frequency and level of lower-extremity amputations for 12 months before and 12 months after implementation of the amputation prevention program. We also calculated the high-low amputation ratio for the years reviewed. The high-low amputation ratio is a quality measure for the success of amputation prevention measures and is calculated as the ratio of the number of high amputations (limb losses) over the number of low (partial foot) amputations. Results: The frequency of total amputations increased from 24 in year 1 to 46 in year 2. However, the number of limb losses decreased from 7 to 2 (72%). The high-low amputation ratio decreased eightfold in 1 year, which serves as a...
Play Therapy for Children With Intellectual Disabilities

Children with intellectual disabilities (IDs) experience cognitive limitations and challenges in adaptive behaviors that affect their emotional and social development. Play therapy has been suggested for several decades as an intervention to help children with IDs strengthen adaptive behaviors and develop stronger social relationships. This article reviews four historical approaches to utilizing play therapy for IDs, including structured and unstructured play therapy, imaginative play therapy, Theraplay, and child-centered play therapy, and makes recommendations for renewed research on play therapy for children with IDs.
Rainfall-Type Categorization of Radar Echoes Using Polar Coordinate Reflectivity Data

AbstractAn algorithm used to classify precipitation echoes by rain type without interpolating radar data to a constant height is detailed. The method uses reflectivity data without clutter along the lowest available scan angle so that the classifications yield a more accurate representation of the rain type observed at the surface. The algorithm is based on that of Steiner et al. but is executed within a polar coordinate system. An additional procedure allows for more small, isolated, and/or weak echo objects to be appropriately identified as convective. Echoes in the immediate vicinity of convective cores are included in a new transition category, which consists mostly of echoes for which a convective or stratiform determination cannot be confidently made. The new algorithm more effectively identifies shallow convection embedded within large stratiform regions, correctly identifies isolated shallow and weak convection as such, and more often appropriately identifies periods during which no stratiform pre...
Decarboxylation of Oleic Acid to Heptadecane over Pt Supported on Zeolite 5A Beads

The synthesis of Pt supported on zeolite 5A beads for the decarboxylation of oleic acid to heptadecane is demonstrated. The use of a microporous ZIF-67 crystalline layer on zeolite 5A beads not only improved the heptadecane selectivity but also, most importantly, improved the stability of the resultant catalyst. Heptadecane yields as high as ∼81% were observed for the fresh catalysts. The catalysts displayed only low to moderate loss of catalytic activity after two rounds of recycle. To our best knowledge, the catalytic performance of these catalysts is superior to those of the state-of-the-art catalysts at mild reaction conditions. In addition, as compared to powders, beads are much easier to recycle, can be fully recovered, and are more amenable for potential scale-up. The resultant catalysts are promising for the catalytic conversion of fatty acid molecules into gasoline/diesel-range hydrocarbons.
An Assessment of the Precision and Accuracy of Altimetry Retrievals for a Monterey Bay GNSS-R Experiment

Global navigation satellite systems (GNSS) provide signals of opportunity for bistatic radar remote sensing, called GNSS reflectometry (GNSS-R), that have potential to be used for ocean altimetry. These signals have advantages over traditional mono-static radar that include reduced cost, high density of measurements in time and space, and an inherent reference to a highly accurate time-space frame. Here, we examine GNSS-R data collected from an aircraft flying over Monterey Bay, California. A downward-looking dual-frequency left-hand circularly polarized patch antenna recorded reflected signals. An upward-looking commercial antenna recorded the direct signals. Dual-frequency carrier phase data from this antenna were also used to produce precise coordinates for the aircraft. The L1 P-code GPS data were collected over four days with two flights per day and consist of nine transects covering a $1^{\circ} \times 1^{\circ}$ grid. The performance of three timing retrieval algorithms has been evaluated based on measurement precision. From the observed cross-correlation waveform, the specular reflection timing was derived from the delay of the 70% peak correlation power (HALF method), the waveform leading edge peak first derivative (DER method), or the delay associated with a best fit function approximating the nominal waveform shape (PARA3 method). It was found that the HALF method produced the most precise measurements for a 5 s integration time with a standard deviation of $\sigma = 0.6$ m. The measurement accuracy is characterized by comparison with well-established models including neutral atmospheric delay, mean sea surface height, and ocean and solid Earth tides. Biases on the order of 1–4 m are observed with respect to a modeled mean sea surface and between each flight. However, the measurements are shown to track changes in sea surface height along the ground track to within 0.6 m.
Enabling technologies for robot assisted ultrasound tomography.

Currently available ultrasound (US) tomography systems suggest utilizing cylindrical transducers that can be used for a specific organ. In this paper, our focus is on an alternative way of creating US tomographic images that could be used for other anatomies and more general applications. This system consists of two conventional US probes facing each other while one or several of the transducers in one probe can act as the transmitter and the rest as the receiver. Aligning the two US probes is a challenging task. To address this issue, we propose a robot assisted US tomography system in which one probe is operated freehanded and another by a robotic arm. In this paper, enabling technologies for this system are described. With the current prototype, a reconstruction precision of 4.12, 1.73, and 2.23 mm for the three calibrations, and an overall alignment repeatability in the range of 5-9 mm were achieved. Copyright © 2016 John Wiley & Sons, Ltd.
Encounters with Iron: An Archaeometallurgical Reassessment of Early Anglo-Saxon Spearheads and Knives

Studies of early medieval weapon burials make surprisingly little mention of the material properties of the deposited weapons. How did these artefacts’ metallurgical properties, and people’s experiences making and shaping the materials from which they were made, relate to the social and ‘magical’ potential these weapons were ascribed? This article reassesses metallurgical data from fifty-two early Anglo-Saxon spearheads discovered in cemetery contexts, and 118 knives from cemeteries and settlements, and reinterprets their technological properties as a glimpse into the social experiences of their makers and users. The choices smiths made when forging these blades are visible in their surviving metallurgy, and reveal their makers’ desired outcomes — and their mixed results. The difficulties smiths negotiated while forging iron shaped the social biographies that blades accumulated after leaving the workshop. By studying the materials from which these artefacts were made, and the practices of the makers who s...
Selective and Aggregate Disclosure

We study the disclosure strategy of a firm's manager who may privately observe two signals that are informative about the firm's prospects. The two signals correspond to the firm's two business segments and are observationally correlated, i.e. the observation of one affects the likelihood of observing the other. If the manager makes a separate disclosure of each signal, we show that, there exists a selective disclosure equilibrium where the manager is falsely modest; i.e. he suppresses favorable information even if it is his only information. We then demonstrate that this equilibrium may result in lower welfare than an aggregate disclosure regime, where the manager is restricted to disclosing the aggregate of the two signals, even though it garbles information.
The Future of Clinical Trials in Cardiovascular Medicine.

Few medical disciplines have been as influenced by the results of randomized controlled trials as cardiovascular medicine. Whether for the treatment of hypertension, acute myocardial infarction, use of specific interventional techniques, devices, or primary prevention, the randomized trial has emerged as the principal method by which new therapies are evaluated. Results of clinical trials have transformed cardiovascular practice from one that was anecdote based to one that is evidence based. Before the first outcomes trial in cardiovascular disease, the VA Cooperative trial1,2 in the late 1960s, clinicians based their practice on tradition, often steeped in unjustified beliefs about untested therapies, or hopelessly confounded observational studies. The switch from empirical therapy to therapies based on the results of well-performed and informative clinical trials ushered in the evidenced-based era in cardiovascular medicine. Today, the introduction of a new therapy would be unheard of without the justifying results from a randomized clinical outcome trial. Yet clinical trials in cardiovascular medicine have grown in size, scope, and complexity. As therapeutic approaches in cardiovascular medicine have become more effective, the level of evidence required to support incremental new advances has increased substantially. This fact, in conjunction with real and perceived increases in regulatory requirements, and the mandate for better estimation of cardiovascular safety for noncardiovascular therapies, have resulted in bloated and prohibitively expensive trials. Thus, despite the success of clinical trials in cardiovascular medicine over the past 25 years, the ability to bring new cardiovascular therapies to patients will require new approaches to curtail cost and maintain quality of future trials. A clinical trial, defined as “a prospective study evaluating the effect and value of intervention(s) against a control in human beings,”3 is generally designed for 1 of 2 purposes: hypothesis generation or hypothesis testing. The former requires careful, detailed testing …
Adolescent Femoroacetabular Impingement: Gender Differences in Hip Morphology.

Purpose To compare the hip morphology of adolescent male patients and female patients who underwent hip arthroscopy for femoroacetabular impingement (FAI) and determine if gender differences exist. Methods We retrospectively reviewed the records of 177 adolescents, aged 13 to 18 years, who were treated for FAI with hip arthroscopy. We examined and analyzed preoperative magnetic resonance imaging (MRI) scans and plain radiographs, measuring the lateral center-edge angle, Tonnis angle, and alpha angle. The intraclass correlation coefficient between readers was calculated. We created multiple linear regression models incorporating age, gender, and body mass index (BMI) with the radiographic measurements. Intraoperative findings using the Outerbridge grading system, as well as procedure performed, were documented. We compared these findings with our preoperative imaging measurements using the χ 2 test and the Wilcoxon rank sum test. Results The intraclass correlation coefficient showed moderate to strong agreement between the 3 image readers. The BMI- and age-adjusted mean alpha angle was higher in male patients than female patients on both plain radiographs (55.9° vs 45.2°, P P P P = .0041). Conclusions Distinct differences between genders were seen both on preoperative imaging and at the time of hip arthroscopy. We found that male patients with FAI displayed a larger mean alpha angle, and therefore a more severe cam-type deformity, than female patients. Our study also found that male patients were more likely to show evidence of chondral damage than female patients at the time of surgery. Level of Evidence Level IV.
A Pilot Study Examining a Computer-Based Intervention to Improve Recognition and Understanding of Emotions in Young Children with Communication and Social Deficits.

Abstract Background A common social impairment in individuals with ASD is difficulty interpreting and or predicting emotions of others. To date, several interventions targeting teaching emotion recognition and understanding have been utilized both by researchers and practitioners. The results suggest that teaching emotion recognition is possible, but that the results do not generalize to non-instructional contexts. This study sought to replicate earlier findings of a positive impact of teaching emotion recognition using a computer-based intervention and to extend it by testing for generalization on live models in the classroom setting. Method Two boys and one girl, four to eight years in age, educated in self-contained classrooms for students with communication and social skills deficits, participated in this study. A multiple probe across participants design was utilized. Measures of emotion recognition and understanding were assessed at baseline, intervention, and one month post-intervention to determine maintenance effects. Social validity was assessed through parent and teacher questionnaires. Results All participants showed improvements in measures assessing their recognition of emotions in faces, generalized knowledge to live models, and maintained gains one month post intervention. Conclusions These preliminary results are encouraging and should be utilized to inform a group design, in order to test efficacy with a larger population.
Abstract 529: Muscle Sympathetic Nerve Activity is Higher in Winter than Other Seasons

Epidemiological data suggest that blood pressure tends to be higher in winter and lower in summer, particularly in the elderly. Moreover, hospitalization and mortality rates due to cardiovascular disease have higher rates in winter than summer. Whether autonomic adjustment including muscle sympathetic nerve activity (MSNA) varies with season is unclear. To test the hypothesis that resting MSNA varies along the seasons, we retrospectively analyzed the supine baseline (6 min) MSNA and heart rate (from ECG) of 57 healthy subjects (33M, 24F, 29 ± 1 yrs, range 22-64 yrs) from studies in our laboratory (room temperature ~23 °C). Each of these subjects from central Pennsylvania was studied during 2 or more seasons (total 231 visits). A linear-mixed effects model, which is an extension of the analysis of variance model accounting for repeated measurements (i.e. season) per subject, was used to assess the association of season with the cardiovascular outcomes. The Tukey-Kramer procedure was used to account for multiple comparisons testing between the seasons. MSNA burst rate in winter (21.3 ± 1.0 burst/min) was significantly greater than in summer (13.7 ± 1.0 burst/min, P P = 0.04) and fall (17.0 ± 1.2 burst/min, P P = 0.12; spring vs. fall, P = 0.99; summer vs. fall, P = 0.054). Heart rate (63.6 ± 1.1 vs. 60.8 ± 1.2 beats/min, P = 0.048) was significantly greater in winter compared to summer. Blood pressure (automated sphygmomanometry of the brachial artery) was not significantly different between seasons. The results suggest that baseline sympathetic nerve activity varies along the seasons, with peak levels evident in winter. We speculate that the seasonal MSNA variation may contribute to seasonal variations in cardiovascular morbidity and mortality.
A de novo missense mutation in TUBA1A results in reduced neural progenitor survival and differentiation

Mutations in tubulins have been implicated in numerous human neurobiological disorders collectively known as tubulinopathies. We identified a patient with severe cortical dysgenesis and a novel de novo heterozygous missense mutation in Tubulin Alpha 1a (TUBA1A, c.1225 G>T). Induced pluripotent stem cells derived from this individual were differentiated into two dimensional neural rosette clusters to identify underlying mechanisms for the severe cortical dysgenesis phenotype. Patient-derived clones showed evidence of impaired neural progenitor survival and differentiation with abnormal neural rosette formation, increases in cell death, and fewer post-mitotic neurons. These features correlate with the drastically underdeveloped cortical tissues seen in the proband. This is the first experimental evidence in human tissue suggesting a mechanism underlying the role for TUBA1A in cortical development.
Organizational and environmental determinants of ballistics imaging productivity in United States crime laboratories

This study employs a structural contingency theory framework to assess the influence of the formal organizational structure of crime laboratories and their environments, on the productivity of labs’ ballistics imaging systems. We contribute to the nascent evolution of organizational focus in forensics while exploring different ways in which overall lab performance can be conceptualized. We analyze data provided by the Bureau of Alcohol, Tobacco, Firearms and Explosives’ (ATF) National Integrated Ballistics Information Network (NIBIN), and data from the Bureau of Justice Statistics, Census of Publicly Funded Forensic Crime Laboratories, 2009. Three Negative Binomial models regressed the organizational and environmental variables on the productivity of crime labs, operationalized as their ability to produce bullet, brass, and total hits. Results indicate that in addition to the number of bullet and brass inputs, local labs are more productive in identifying ballistics imaging hits. Additionally, lar...
Using angling and electric fishing to estimate smallmouth bass abundance in a river

Estimating abundance is fundamental to effective fishery management but can be challenging in a river where spatial and temporal heterogeneity may preclude the consistent use of a single sampling gear and different gears have differing size selectivity and capture probabilities of fish. In this study, the number of smallmouth bass, Micropterus dolomieu Lacepede, was estimated based on mark–recapture data from angling and boat electric fishing in a 4.2‐km regulated section (mean width = 115 m) of the Broad River, South Carolina, USA. Closed‐population capture–mark–recapture models were fit in the Bayesian hierarchical modelling framework with an estimated number of 2,380 fish (95% credible interval: 1,578–3,693) over 200 mm TL, although simulations indicated that abundance would be slightly overestimated (<20%) when two gears selected for different individuals. Integrating two gear types into a mark–recapture study can provide a method for assessing abundance in spatially or temporally heterogeneous habitats.
Computational analysis of external heat transfer for a tubular Stirling convertor

Abstract Stirling convertors are an ideal choice for use in numerous energy conversion applications owing to their simplistic design, fuel independence, and robustness. The use of additive manufacturing allows for significant improvements in the overall system efficiency by removing the design limitations of traditional manufacturing techniques. This allows for the design of a novel burner–heater head interface that can vastly improve the external heat transfer. A numerical analysis of the combustion flow over an additively manufactured tubular heater head was conducted. It was shown that the use of flow guides improves the velocity distribution of the combustion gases over the heat acceptor tubes. Additionally, the use of a diffuser plate can be employed to further improve the heat transfer. The developed model can be used further to optimize the overall design of the heat acceptor, regenerator, and heat rejecter.
A k-Sample Problem with Censored Data

In this paper, we address the question of asymptotically efficient estimation in randomly right censored regression models. We allow the censoring distributions to depend on the covariate. For simplicity, we consider only situations in which the covariates come from a finite set. We provide a characterization of efficient estimates, describe a general method for the construction of such estimates and carry out this construction when the censoring distributions are known.
Production of an Expression System for a Synaptobrevin Fragment to Monitor Cleavage by Botulinum Neurotoxin B

Recombinant DNA techniques were used to develop an expression system for a 51-amino acid peptide fragment that encompasses residues 44–94 of human synaptobrevin 2. This protein is associated with secretory vesicles of nerve terminals and is a substrate for four of the seven serotypes of botulinum neurotoxin (BoNT). The DNA for the recombinant peptide was amplified by the polymerase chain reaction and cloned into the pTrxFus vector. The resulting synaptobrevin peptide was expressed as a thioredoxin fusion protein in E. coli and released into the medium by osmotic lysis. The 18.7-kDa thioredoxin-synaptobrevin protein, designated as TSB-51, is intended for use in a cell-free assay to test potential inhibitors of BoNT/B-mediated proteolysis of synaptobrevin with the ultimate aim of developing clinically effective therapeutic agents to counteract botulism. Incubation of TSB-51 with the purified light chain of BoNT/B resulted in proteolysis which was evident within 30 min and increased with time until completion (∼4 hr). Cleavage of TSB-51 appeared to be at the appropriate BoNT/B cleavage site as indicated by a reduced intensity of the 18.7-kDa band and the appearance of a band at 16.4 kDa on Tris-tricene polyacrylamide gradient gels. The concentration of free Zn2+ had a significant effect on the cleavage rate; low Zn2+ concentrations stimulated substrate cleavage, whereas high concentrations were inhibitory. Cleavage was not significantly depressed by the naturally occurring metalloprotease inhibitor phosphoramidon when tested at concentrations up to 5 mM. TSB-51 appears to be a useful substrate for studying BoNT/B and is expected to aid in the discovery of effective BoNT inhibitors.
Development of macrolide resistance in Bordetella bronchiseptica is associated with the loss of virulence.

Background Why resistance to specific antibiotics emerges and spreads rapidly in some bacteria confronting these drugs but not others remains a mystery. Resistance to erythromycin in the respiratory pathogens Staphylococcus aureus and Streptococcus pneumoniae emerged rapidly and increased problematically. However, resistance is uncommon amongst the classic Bordetella species despite infections being treated with this macrolide for decades. Objectives We examined whether the apparent progenitor of the classic Bordetella spp., Bordetella bronchiseptica, is able to rapidly generate de novo resistance to antibiotics and, if so, why such resistance might not persist and propagate. Methods Independent strains of B. bronchiseptica resistant to erythromycin were generated in vitro by successively passaging them in increasing subinhibitory concentrations of this macrolide. Resistant mutants obtained were evaluated for their capacity to infect mice, and for other virulence properties including adherence, cytotoxicity and induction of cytokines. Results B. bronchiseptica rapidly developed stable and persistent antibiotic resistance de novo. Unlike the previously reported trade-off in fitness, multiple independent resistant mutants were not defective in their rates of growth in vitro but were consistently defective in colonizing mice and lost a variety of virulence phenotypes. These changes rendered them avirulent but phenotypically similar to the previously described growth phase associated with the ability to survive in soil, water and/or other extra-mammalian environments. Conclusions These observations raise the possibility that antibiotic resistance in some organisms results in trade-offs that are not quantifiable in routine measures of general fitness such as growth in vitro, but are pronounced in various aspects of infection in the natural host.
Rapid antimicrobial susceptibility testing and β-lactam-induced cell morphology changes of Gram-negative biological threat pathogens by optical screening.

For Yersinia pestis, Burkholderia pseudomallei, and Burkholderia mallei, conventional broth microdilution (BMD) is considered the gold standard for antimicrobial susceptibility testing (AST) and, depending on the species, requires an incubation period of 16–20 h, or 24–48 h according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. After a diagnosis of plague, melioidosis or glanders during an outbreak or after an exposure event, the timely distribution of appropriate antibiotics for treatment or post-exposure prophylaxis of affected populations could reduce mortality rates. Herein, we developed and evaluated a rapid, automated susceptibility test for these Gram-negative bacterial pathogens based on time-lapse imaging of cells incubating in BMD microtitre drug panels using an optical screening instrument (oCelloScope). In real-time, the instrument screened each inoculated well containing broth with various concentrations of antibiotics published by CLSI for primary testing: ciprofloxacin (CIP), doxycycline (DOX) and gentamicin (GEN) for Y. pestis; imipenem (IPM), ceftazidime (CAZ) and DOX for B. mallei; and IPM, DOX, CAZ, amoxicillin-clavulanic acid (AMC) and trimethoprim-sulfamethoxazole (SXT) for B. pseudomallei. Based on automated growth kinetic data, the time required to accurately determine susceptibility decreased by ≥70% for Y. pestis and ≥ 50% for B. mallei and B. pseudomallei compared to the times required for conventional BMD testing. Susceptibility to GEN, IPM and DOX could be determined in as early as three to six hours. In the presence of CAZ, susceptibility based on instrument-derived growth values could not be determined for the majority of B. pseudomallei and B. mallei strains tested. Time-lapse video imaging of these cultures revealed that the formation of filaments in the presence of this cephalosporin at inhibitory concentrations was detected as growth. Other β-lactam-induced cell morphology changes, such as the formation of spheroplasts and rapid cell lysis, were also observed and appear to be strain- and antibiotic concentration-dependent. A rapid, functional AST was developed and real-time video footage captured β-lactam-induced morphologies of wild-type B. mallei and B. pseudomallei strains in broth. Optical screening reduced the time to results required for AST of three Gram-negative biothreat pathogens using clinically relevant, first-line antibiotics compared to conventional BMD.
Dental clearance and postoperative heart infections: Observations from a preoperative evaluation clinic for day-admission surgery.

Every year, two-million hospitalised patients develop healthcare-associated infections with a consequent mortality eclipsing 90,000. The literature suggests that dental infections are one of many p...