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Malignant mesothelioma with EWSR1-ATF1 fusion is a rare malignancy described in young adults without asbestos exposure. To the best of our knowledge, outcomes to local and systemic therapies for this subtype of malignant mesothelioma have not been described. This case report describes the clinical course of a 19-year-old man diagnosed with malignant peritoneal mesothelioma with EWSR1-ATF1 fusion localized to the abdomen. His disease followed an aggressive course and resulted in limited survival (18 mo). There was treatment resistance to several lines of conventional local and systemic treatments for peritoneal mesothelioma and biologically targeted MET inhibition with crizotinib. More research is required in this rare subtype of peritoneal mesothelioma.

Coal particles, a typical of organic matter with high carbon content, widely diffused in soil environment due to massive consumption of coal energy for centuries. Even in small amounts presented in soils, coal particles can produce obvious overestimation of soil organic carbon (SOC) and thus increase an uncertainty of soil C sequestration assessment. However, there is a lack of determination methods for distinguishing coal-derived C from SOC. This study takes the Jiaozuo mining area as the study area, which has a history of anthracite mining for more than 100 years and where coal-contaminated soils are widespread. The hyperspectral characteristics of the mine soils were analyzed by collecting coal particles and coal-free soils and then mixing known quantities of the two samples manually. Based on eight spectral mathematical transformation and two spectral feature screening methods (i.e., traditional correlation coefficiencies, and comprehensive competitive adaptive reweighted sampling (CARS)), six inversion models including spectral feature index models (i.e., deviation of arch (IDOA), difference index (ID), ratio index (IR)), and three machine learning models (i.e., partial least squares regression (PLSR), support vector machine (SVM) and random forest (RF)), were established to inversing coal-derived C content. The applicability of the established optimal inversion model was also examined. It was found that in the wavelength range from 350 nm to 2500 nm, the spectral curves of coal particles are obviously different from those of plant-derived organic matter and coal-free soils. Moreover, the spectral reflectance (R) of coal-contaminated soils decreases with increasing coal-derived C content. These findings provide a theoretical basis for the application of hyperspectral remote sensing technology to quantitatively inverse coal-derived C of mine soils. The CARS-extracted feature wavebands of coal-derived C distributed evenly in the wavelength range between 350 nm and 2500 nm, and the number of feature waveband extracted by the CARS was far higher than that by traditional correlation coefficiency methods. After mathematical transformation of R data, the estimated accuracies of coal-derived C content produced by the IDOA, ID and IR inversion models were significantly enhanced, among which, the DI model of 1/R spectral transformation exhibited the highest estimation accuracy. Compared with the traditional index models, the three machine learning models combined with CARS further enhanced estimation accuracy of coal-derived C content. Among the three machine learning models, the 1/R-CARS-RF inversion model produced the highest estimation accuracy, showing \begin{document}$R_{\rm{m}}^2 $\end{document}=0.998, RMSE=0.348, RPD=29.943 for its validation set. The applicability test showed that the 1/R-CARS-RF model exhibited a good applicability for different coal-contaminated soils in the Jiaozuo mining area as observed 1.88% for RMSE and 4.97 for RPD. Therefore, it can be expected that hyperspectral remote sensing technology has a promising application prospect for determining coal-derived C content in mine soils. In addition, this study can provide a methodology support for distinguishing coal-derived C from SOC in mine soils and accurately assessing soil carbon sequestration.

Electric vehicles are having significant priority in transportation including goods, public transport etc. among many technologies in electric vehicle, brushless DC (BLDC) motors operated eclectic drives are mostly used. Speed sensorless control is required to implement for obtaining a best performance. At the same time, a sliding mode controller (SMC) can be able to produce the ultimate response under various conditions. Hence sensorless speed control with SMC of BLDC motor is implemented in this paper to drive the electric vehicle. In order to develop speed sensorless of motor, a model reference adaptive control (MRAC) system is developed. However, obtaining a fastest response is very important in electric vehicle speed control. Hence a TS-Fuzzy model is developed to use in the place of conventional PI controllers. Extensive results are collected for presentation by establishing Hardware – in the – Loop (HIL) with the help of two OPAL-RT devices.

Grid connected renewable energy sources based electric power generation systems are increasing day by day to meet the electrical demand without burning any fossil fuels. Doubly fed induction generators (DFIGs) are widely used in wind turbines due to advantages that they can allow the amplitude and frequency of their output voltages to be maintained at a constant value, no matter the speed of the wind blowing on the wind turbine rotor. Moreover, the DFIG provides a huge possibility to improve network dynamic behavior by using the power electronic converters with sufficient control arrangements. Many different structure and control algorithms can be used for control of power converters. However, conventional controllers cannot perform with full efficiency during rapid changes in wind speed. Hence, Takagi–Sugeno–Kang (TSK) Fuzzy controllers based novel control technique is proposed in this paper for performing many tasks on grid connected DFIG systems. The proposed control scheme is tested under variations of voltage, frequency, wind speed, and reactive power load. To achieve the realistic responses, the Hardware-in the-Loop (HIL) is implemented with the help of OPAL-RT modules for presenting extensive results.

This review article delves into the strategic integration of renewable energy sources within smart cities, emphasizing the role of electric vehicles (EVs) in ensuring stability. Smart cities, at the forefront of sustainable urban development, prioritize energy systems that are both clean and renewable. The integration of various renewable energy resources, including solar, wind, geothermal, hydropower, ocean, and biofuels, into the energy systems of smart cities is explored, considering both technical and economic aspects. The rapid adoption of these technologies provides a foundation for a low-carbon economy, ensuring a cleaner and more sustainable urban environment. However, challenges persist, particularly in optimizing energy systems for renewable integration, stability, operational range, and cost-effectiveness. Additionally, the evolution of smart cities has brought forth advanced energy conservation systems, addressing energy management at both building and city levels. Innovative solutions, such as advanced infrastructure and energy trading strategies in distributed systems, are proposed. The role of EVs in the smart grid is also highlighted, addressing challenges posed by renewable energy’s intermittent output. The potential of EVs to counteract these fluctuations, especially under the vehicle-to-grid (V2G) framework, is discussed, offering insights into future research avenues for a harmonious and sustainable energy ecosystem in smart cities.

STUDY OBJECTIVE: Clerkship directors design and implement educational programs for students. Scholarly productivity is necessary for academic advancement. We define characteristics of emergency medicine clerkship directors and evaluate determinants of scholarly productivity and job satisfaction. METHODS: This is a cross-sectional survey. Clerkship directors for emergency medicine senior rotations completed a confidential online questionnaire. Demographic data were analyzed with descriptive statistics. Scholarly productivity and job satisfaction indices were created for multivariate analysis. RESULTS: One hundred eleven (82%) of 136 directors responded (age 38.9+/-7.0 years; men 72.1%; junior academic rank 72.1%; served as clerkship directors for < or =5 years 77.4%; formal training in education: medical education fellowship 36%, teaching credential 12.7%, emergency medicine subspecialty fellowship 6.3%; support for clerkship director's activities: clinical hours reduction 2.7+/-2.3 weekly; minimal training for clerkship director's role 85.6%; ongoing professional development 40.5%; scholarly productivity: < or =5 peer-reviewed publications 78.4%, grant 28%, textbook chapter 65%; plan to be clerkship director in 5 years 63%; perceived support from supervisor 88%; perceived value from colleagues 81%; perception that clerkship directors is as important as residency director 47.8%). Multivariate regression shows a significant effect of medical education fellowship (P =.013) and subspecialty training (P =.044). Departmental support enhances the effect of medical education (P =.008) or subspecialty (P =.026) fellowships and improves productivity for senior faculty (P =.047). Multivariate regression explaining job satisfaction shows a positive effect of reduced clinical hours (P =.038) and increased faculty development (P =.033). CONCLUSION: Most emergency medicine clerkship directors are junior faculty with minimal release time or training for their positions. [ABSTRACT FROM AUTHOR]

Background: Experimentation confirmed the conclusion that bone allografts, like other tissue and organ allografts, are immunogenic. These immune responses cause resorption of allograft, thus lowering the bone formation capacity of the graft. An attempt has been made in this study to prevent immune reactions and achieve enhanced regeneration of allograft-demineralized freeze-dried bone matrix by incorporating it with an immunosuppressive drug Cyclosporine-A (CsA) in the treatment of human periodontal infrabony defects. Materials and Methods: Fifteen patients showing clinical evidence of almost bilateral infrabony defects requiring bone grafting procedures were selected. In each patient, the infrabony defect of one side of the arch was designated as Group A (control site) and the infrabony defect of the contralateral side of the same arch was designated as Group B (test site). Results: On comparative evaluation of the two groups (by Student t-test), the mean values of reduction in probing depth (P=0.81 NS ) and gain in clinical attachment level (P=1.00 NS ) of Group B were found to be greater than that of Group-A, but the differences were statistically non-significant. The mean linear bone fill (P=0.010 FNx08 ) of Group B was also detected to be higher than that of Group A, and the difference was found to be statistically significant. Conclusion: Increase in linear bone fill in Group B signifies the role of CsA in augmenting the regenerative potential of allograft by eliminating immune reactions.

Objectives: Many a times in clinical periodontology, the decision whether to prescribe prophylactic antibiotics or not , is perplexing.The present study was conducted to compare the bacteremias induced after periodontal flap surgeries with and without prophylactic antibiotics. Materials and Methods: The occurrence of postoperative bacteremia following periodontal flap surgery was studied in 30 patients. On these patients, 30 quadrant wise flap surgeries were carried out without any preoperative prophylactic antibiotics and 30 surgeries carried out after prophylactic administration of amoxycillin preoperatively. A blood sample was taken from each patient at the time of maximum surgical trauma and was cultured for micro-organisms and antibiotic sensitivity. Results: 18 out of 60 blood samples were positive for micro-organisms. There was a significant reduction in post operative bacteremia after amoxycillin prophylaxis (x - 7.96 with P< 0.01) as post operative bacteremia was found in 14 of the non medicated patients as compared to only 4 of the pre medicated patients. The micro-organisms encountered in the study are as follows:- 1) Staphylococcus albus coagulase negative, 2) Klebsiella, 3) Psedomonas aerugenosa, 4) Streptococcus viridans, 5) Alpha hemolytic streptococcus, 6) Neisseria catarrhalis Conclusion: On the basis of the study, it is concluded that the incidence of postoperative bacteremia following periodontal flap surgery is not as high as previously reported. The clinical results show that Amoxicillin is highly effective in reducing postoperative bacteremia in periodontal flap surgery and thus in preventing the possible sequelae (Infective Endocarditis and other systemic maladies) in susceptible patients. However, cefotaxime and cephalexin may prove to be more effective in preventing the same.

Background: Microbial colonization of the barrier membranes used for guided tissue regeneration is inevitable and can lead to delayed healing. Aims: Antimicrobial coating of the membrane with 25% doxycycline paste has been attempted to prevent infection and achieve enhanced regeneration in periodontal infrabony defects. Materials and Methods: Twenty-four patients with 2-walled or 3-walled infrabony defects were selected and randomly divided into two equal groups. Infrabony defects of group A were treated with a biodegradable membrane coated with 25% doxycycline while those of group B were treated with membrane alone. Clinical assessment of probing depth and attachment level and radiographic evaluation of the defect depth was done preoperatively and at 12 and 24 weeks postoperatively. Statistical Analysis: The relative efficacy of the two treatment modalities were evaluated using the paired Student′s t- test and the comparative evaluation between the two groups was done using the independent Student′s t -test. Results: Both the groups exhibited a highly significant reduction in probing depth and gain in clinical attachment level and linear bone fill at the end of 24 weeks. Comparative evaluation between the two study groups revealed a significant reduction in probing depth ( P = 0.016 FNx01 ) and linear bone fill ( P = 0.02 FNx01 ) in group A as compared to group B. Mean gain in attachment level was greater for group A than for group B but the difference was statistically nonsignificant ( P = 0.065 NS ). Conclusions: The results suggest that doxycycline is beneficial in reducing membrane-associated infection and can potentiate regeneration through host modulation.

Abstract Purpose Metallic skin closure staples and vessel ligation clips should be tested at 3-Tesla to characterize MRI issues in order to ensure patient safety. Therefore, metallic surgical implants were assessed at 3-Tesla for magnetic field interactions, MRI-related heating, and artifacts. Methods A skin closure staple (Visistat Skin Stapler, staple, Polytetrafluoroethylene, PTFE, coated 316L/316LVM stainless steel; Teleflex Medical, Durham, NC) and a vessel ligation clip (Hemoclip Traditional, stainless steel; Teleflex Medical, Durham, NC) that represented the largest metallic sizes made from materials with the highest magnetic susceptibilities (i.e., based on material information) among 61 other surgical implants (52 metallic implants, 9 nonmetallic implants) underwent evaluation for magnetic field interactions, MRI-related heating, and artifacts using standardized techniques. MRI-related heating was assessed by placing each implant in a gelled-saline-filled phantom with MRI performed using a transmit/receive RF body coil at an MR system reported, whole body averaged SAR of 2.9-W/kg for 15-min. Artifacts were characterized using T1-weighted, SE and GRE pulse sequences. Results Each surgical implant showed minor magnetic field interactions (20- and 27-degrees, which is acceptable from a safety consideration). Heating was not substantial (highest temperature change, ≤ 1.6°C). Artifacts may create issues if the area of interest is in the same area or close to the respective surgical implant. Conclusions The results demonstrated that it would be acceptable for patients with these metallic surgical implants to undergo MRI at 3-Tesla or less. Because of the materials and dimensions of the surgical implants that underwent testing, these findings pertain to 61 additional similar implants.

Abstract Background Lyme neuroborreliosis (LNB) may present as meningitis, cranial neuropathy, acute radiculoneuropathy or, rarely, as encephalomyelitis. We hypothesized that glia, upon exposure to Borrelia burgdorferi, the Lyme disease agent, produce inflammatory mediators that promote the acute cellular infiltration of early LNB. This inflammatory context could potentiate glial and neuronal apoptosis. Methods We inoculated live B. burgdorferi into the cisterna magna of rhesus macaques and examined the inflammatory changes induced in the central nervous system (CNS), and dorsal root nerves and ganglia (DRG). Results ELISA of the cerebrospinal fluid (CSF) showed elevated IL-6, IL-8, CCL2, and CXCL13 as early as one week post-inoculation, accompanied by primarily lymphocytic and monocytic pleocytosis. In contrast, onset of the acquired immune response, evidenced by anti-B. burgdorferi C6 serum antibodies, was first detectable after 3 weeks post-inoculation. CSF cell pellets and CNS tissues were culture-positive for B. burgdorferi. Histopathology revealed signs of acute LNB: severe multifocal leptomeningitis, radiculitis, and DRG inflammatory lesions. Immunofluorescence staining and confocal microscopy detected B. burgdorferi antigen in the CNS and DRG. IL-6 was observed in astrocytes and neurons in the spinal cord, and in neurons in the DRG of infected animals. CCL2 and CXCL13 were found in microglia as well as in endothelial cells, macrophages and T cells. Importantly, the DRG of infected animals showed significant satellite cell and neuronal apoptosis. Conclusion Our results support the notion that innate responses of glia to B. burgdorferi initiate/mediate the inflammation seen in acute LNB, and show that neuronal apoptosis occurs in this context.

Monogenic syndromes are associated with neurodevelopmental changes that result in cognitive impairments, neurobehavioral phenotypes including autism and attention deficit hyperactivity disorder (ADHD), and seizures. Limited studies and resources are available to make meaningful headway into the underlying molecular mechanisms that result in these symptoms. One such example is DeSanto-Shinawi Syndrome (DESSH), a rare disorder caused by pathogenic variants in the WAC gene. Individuals with DESSH syndrome exhibit a recognizable craniofacial gestalt, developmental delay/intellectual disability, neurobehavioral symptoms that include autism, ADHD, behavioral difficulties and seizures. However, no thorough studies from a vertebrate model exist to understand how these changes occur. To overcome this, we developed both murine and zebrafish Wac/wac deletion mutants and studied whether their phenotypes recapitulate those described in individuals with DESSH syndrome. We show that the two Wac models exhibit craniofacial and behavioral changes, reminiscent of abnormalities found in DESSH syndrome. In addition, each model revealed impacts to GABAergic neurons and further studies showed that the mouse mutants are susceptible to seizures, changes in brain volumes that are different between sexes and relevant behaviors. Finally, we uncovered transcriptional impacts of Wac loss of function that will pave the way for future molecular studies into DESSH. These studies begin to uncover some biological underpinnings of DESSH syndrome and elucidate the biology of Wac, with advantages in each model.

Background: The role of fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in indolent lymphoma has been minimally studied., Objective: This study aims to assess the value of FDG-PET/CT in predicting the prognosis of indolent lymphoma., Methods: We prospectively recruited 42 patients with indolent lymphoma. A total of 2 patients were excluded, and 40 underwent baseline PET/CT and follow-up at various time points. A total of 9 patients were observed only, 7 received 4 doses of rituximab alone, and 24 received chemoimmunotherapy. Metabolic response on follow-up PET/CT was assessed using the maximum standardized uptake value (SUVmax) and Deauville criteria (DC). We aimed to obtain the best SUVmax and DC to predict optimal survival rates, risk stratification, and optimize therapeutic strategies. The mean follow-up from the initial diagnosis was 33.83 months., Results: SUVmax <4.35 at interim PET/CT provided the best discrimination, with a progression-free survival (PFS) of 100% and a median survival time of 106.67 months compared with SUVmax ≥4.35 (P=.04), which had a PFS of 43.8% and a median survival time of 50.17 months. This cutoff was also valuable in predicting overall survival at baseline, that is, 100% overall survival with baseline SUVmax <4.35, versus 58.4% for SUVmax ≥4.35 (P=.13). The overall survival of patients with a baseline DC score <3.0 was 100%, with a median overall survival of 106.67 months., Conclusions: We demonstrated the utility of PET/CT in indolent lymphomas. SUVmax (<4.35 vs ≥4.35) on interim PET/CT performed best in predicting PFS., (©Nawal Faiez AlShehry, Raja Shanker, Syed Ziauddin Ahmed Zaidi, Fahad AlGhmlas, Ibraheem Hussein Motabi, Shahid Iqbal, Ahmad Ali Butt, Hassan AlShehri, Imran Khan Tailor, Syed Yasir Altaf, Mubarak AlGhamdi, Mohammed Marie, Mansour AlFayez, Kamal Al Zahrani, Mohammed Dwaimah, Tahani Al-Halouli, Wafaa Al-Shakweer, Maied Zaher AlShehery, Abdul Rehman Zia Zaidi, Atta Munawar Gill, Belal Mohammed Albtoosh, Musab Ahmed. Originally published in JMIR Formative Research (https://formative.jmir.org), 12.11.2021.)

This study is a qualitative analysis of facilitators and barriers in the dissemination of Family Check-Up (FCU), a U.S.-developed preventive intervention in Sweden. The FCU is inherently culturally flexible because it was designed to be tailored to each family's needs and context, including cultural norms and values. We present the FCU implementation framework (IF) as a conceptual framework for cross-country transport of the FCU and evidence-based programs (EBP) more generally. The FCU IF draws from implementation science literature and involves specifying barriers and facilitators related to implementation drivers (e.g., competency) at each implementation phase and applying these data to inform phase-specific, readiness-building activities for each driver. In addition to driver-related influences, barriers and facilitators specific to the FCU and the collaborative partnership between the U.S. and Swedish purveyors emerged in the data. The partnership's reliance on a hybrid bottom-up, top-down approach that balanced the Swedish purveyor's autonomy and cultural expertise with guidance from the U.S. purveyor facilitated adaptation of the FCU for Sweden. Relying on previously collected data, we also explored similarities and differences in barriers and facilitators to FCU scale-up in the United States versus Sweden. In general, across drivers, the same barriers and facilitators were salient. This study suggests that dissemination of culturally flexible EBPs guided by a dynamic implementation framework can facilitate cross-country transport of EBPs. This study promotes a culture of prevention by highlighting barriers, facilitators, and readiness-building strategies that influence the cross-cultural transportability of EBPs that prevent the onset and escalation of child problem behavior.

Treatment of aromatic N-substituted N-heterocyclic carbenes (NHCs) with trimethyl-gallium and -indium yielded the new Lewis acid-base adducts, IMes·GaMe 3 (1), SIMes·GaMe 3 (2), IPr·GaMe 3 (3), SIPr·GaMe 3 (4), IMes·InMe 3 (5), SIMes·InMe 3 (6), IPr·InMe 3 (7), and SIPr·InMe 3 (8), with all complexes being identified by X-ray diffraction, IR, and multinuclear NMR analyses. Complex stability was found to be largely dependent on the nature of the constituent NHC ligands. Percent buried volume (%V Bur ) and topographic steric map analyses were employed to quantify and elucidate the observed trends. Additionally, a detailed bond snapping energy (BSE) decomposition analysis focusing on both steric and orbital interactions of the M-NHC bond (M = Al, Ga and In) has been performed.

The influence of plant traits on forest fire behaviour has evolutionary, ecological and management implications, but is poorly understood and frequently discounted. We use a process model to quantify that influence and provide validation in a diverse range of eucalypt forests burnt under varying conditions. Measured height of consumption was compared to heights predicted using a surface fuel fire behaviour model, then key aspects of our model were sequentially added to this with and without species-specific information. Our fully specified model had a mean absolute error 3.8 times smaller than the otherwise identical surface fuel model (p < 0.01), and correctly predicted the height of larger (≥1 m) flames 12 times more often (p < 0.001). We conclude that the primary endogenous drivers of fire severity are the species of plants present rather than the surface fuel load, and demonstrate the accuracy and versatility of the model for quantifying this.

Highly active and selective aerobic oxidation of KA-oil to cyclohexanone (precursor for adipic acid and ɛ-caprolactam) has been achieved in high yields using continuous-flow chemistry by utilizing uncapped noble-metal (Au, Pt & Pd) nanoparticle catalysts. These are prepared using a one-step in situ methodology, within three-dimensional porous molecular architectures, to afford robust heterogeneous catalysts. Detailed spectroscopic characterization of the nature of the active sites at the molecular level, coupled with aberration-corrected scanning transmission electron microscopy, reveals that the synthetic methodology and associated activation procedures play a vital role in regulating the morphology, shape and size of the metal nanoparticles. These active centers have a profound influence on the activation of molecular oxygen for selective catalytic oxidations., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Treatment of a series of aromatic NHCs (IMes, SIMes, IPr and SIPr) with trimethylaluminium produced their corresponding Lewis acid-base adducts: IMes·AlMe3 (1), SIMes·AlMe3 (2), IPr·AlMe3 (3), and SIPr·AlMe3 (4). These complexes expand the few known examples of saturated NHC stabilised Group 13 complexes. Furthermore, compounds 1-4 show differential stability depending on the nature of the NHC ligand. Analyses of topographic steric maps and NHC %V(Bur) were used to explain these differences. All the compounds have been fully characterised by multinuclear NMR spectroscopy, IR and single crystal X-ray analysis together with computational studies.

By using platinum nanoparticle catalysts that are generated in situ by extrusion from a porous copper chlorophosphate framework, the role of oxidants in the selective oxidation of benzyl alcohol to benzaldehyde was evaluated, with a view to establishing structure-property relationships. With a detailed study of the kinetic properties of the oxidation reaction, it has been determined that the aerobic oxidation pathways progress with lower levels of product selectivity and higher activation energies (72.4 kJ mol -1 ) than the peroxide-based ones (23.6 kJ mol -1 ); affording valuable insights in the design of solid catalysts for selective oxidation reactions. Furthermore, through the use of X-ray absorption spectroscopy, the effect of calcination temperature on the degree of extrusion and its influence on nanoparticle formation have been evaluated, leading to the establishment of structure-activity correlations between the observed activation energies and the proportion of nanoparticle species generated., (Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The frontispiece shows a novel in situ method of generating metal nanoparticles within porous molecular frameworks, thereby affording highly active and selective single-site heterogeneous catalysts for industrially significant aerobic oxidations. The Communication on page 1226 by Robert Raja and Andy Hor et al. highlights the importance of spectroscopic and kinetic studies in establishing structureproperty correlations that are fundamental in the design of sustainable heterogeneous catalysts., (Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We measured total and free plasma concentrations of ropivacaine following high-volume, high-dose local infiltration analgesia in 28 patients aged 65 years or over undergoing unilateral total knee arthroplasty. Patients received infiltration of ropivacaine 400 mg followed by infusion at 20 mg.h(-1) through an intra-articular catheter. Total and free plasma levels of ropivacaine were measured at specified time intervals during a 24-h period after tourniquet release. Patients were monitored for symptoms and signs of local anaesthetic toxicity. Total levels of plasma ropivacaine varied from 0.147 to 3.093 μg.ml(-1) (mean (SD) 1.105 (0.518) μg.ml(-1) ). Free levels of plasma ropivaca-ine varied from 0.001 to 0.104 μg.ml(-1) (mean (SD) 0.037 (0.020) μg.ml(-1) ). Six samples had total plasma ropivacaine levels greater the toxic threshold of 2.2 μg.ml(-1) . No samples reached the toxic threshold for free venous ropivacaine concentration. We conclude that the use of high-dose ropivacaine infiltration and catheter infusion for total knee arthroplasty in an elderly population does not result in free plasma ropivacaine levels previously associated with toxicity but that raised total plasma levels may be observed., (© 2015 The Association of Anaesthetists of Great Britain and Ireland.)

The impacts of escalating wildfire in many regions - the lives and homes lost, the expense of suppression and the damage to ecosystem services - necessitate a more sustainable coexistence with wildfire. Climate change and continued development on fire-prone landscapes will only compound current problems. Emerging strategies for managing ecosystems and mitigating risks to human communities provide some hope, although greater recognition of their inherent variation and links is crucial. Without a more integrated framework, fire will never operate as a natural ecosystem process, and the impact on society will continue to grow. A more coordinated approach to risk management and land-use planning in these coupled systems is needed.

We measured total and free plasma concentrations of ropivacaine following high-volume, high-dose local infiltration analgesia in 19 patients aged 65 years or over undergoing unilateral total hip arthroplasty. The patients received 180 ml ropivacaine 0.2% (360 mg), which was injected into the deep and peri-capsular tissues, the gluteal muscles and fascia lata, and the subcutaneous tissues and skin. Patients were monitored for clinical symptoms and signs of systemic local anaesthetic toxicity. Total levels of plasma ropivacaine varied from 0.081 to 1.707 μg.ml(-1) (mean (SD) 0.953 (0.323) μg.ml(-1) ). Free levels of plasma ropivacaine varied from 0.000 to 0.053 μg.ml(-1) (mean (SD) 0.024 (0.011) μg.ml(-1) ). No samples reached the toxic threshold for venous ropivacaine concentration, although four patients exhibited mild symptoms consistent with local anaesthetic toxicity. One patient had episodes of complete heart block on ECG monitoring, but plasma ropivacaine levels were below toxic levels. We conclude that plasma levels for ropivacaine associated with toxicity in a volunteer population (total 2.2 μg.ml(-1) , free 0.15 μg.ml(-1) ) are not reached during local infiltration analgesia for hip arthroplasty in elderly patients., (© 2014 The Association of Anaesthetists of Great Britain and Ireland.)

Environmental disturbance underpins the dynamics and diversity of many of the ecosystems of the world, yet its influence on the patterns and distribution of genetic diversity is poorly appreciated. We argue here that disturbance history may be the major driver that shapes patterns of genetic diversity in many natural populations. We outline how disturbance influences genetic diversity through changes in both selective processes and demographically driven, selectively neutral processes. Our review highlights the opportunities and challenges presented by genetic approaches, such as landscape genomics, for better understanding and predicting the demographic and evolutionary responses of natural populations to disturbance. Developing this understanding is now critical because disturbance regimes are changing rapidly in a human-modified world., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The worldwide "wildfire" problem is headlined by the loss of human lives and homes, but it applies generally to any adverse effects of unplanned fires, as events or regimes, on a wide range of environmental, social, and economic assets. The problem is complex and contingent, requiring continual attention to the changing circumstances of stakeholders, landscapes, and ecosystems; it occurs at a variety of temporal and spatial scales. Minimizing adverse outcomes involves controlling fires and fire regimes, increasing the resistance of assets to fires, locating or relocating assets away from the path of fires, and, as a probability of adverse impacts often remains, assisting recovery in the short-term while promoting the adaptation of societies in the long-term. There are short- and long-term aspects to each aspect of minimization. Controlling fires and fire regimes may involve fire suppression and fuel treatments such as prescribed burning or non-fire treatments but also addresses issues associated with unwanted fire starts like arson. Increasing the resistance of assets can mean addressing the design and construction materials of a house or the use of personal protective equipment. Locating or relocating assets can mean leaving an area about to be impacted by fire or choosing a suitable place to live; it can also mean the planning of land use. Assisting recovery and promoting adaptation can involve insuring assets and sharing responsibility for preparedness for an event. There is no single, simple, solution. Perverse outcomes can occur. The number of minimizing techniques used, and the breadth and depth of their application, depends on the geographic mix of asset types. Premises for policy consideration are presented.

Losses to life and property from unplanned fires (wildfires) are forecast to increase because of population growth in peri-urban areas and climate change. In response, there have been moves to increase fuel reduction--clearing, prescribed burning, biomass removal and grazing--to afford greater protection to peri-urban communities in fire-prone regions. But how effective are these measures? Severe wildfires in southern Australia in 2009 presented a rare opportunity to address this question empirically. We predicted that modifying several fuels could theoretically reduce house loss by 76%-97%, which would translate to considerably fewer wildfire-related deaths. However, maximum levels of fuel reduction are unlikely to be feasible at every house for logistical and environmental reasons. Significant fuel variables in a logistic regression model we selected to predict house loss were (in order of decreasing effect): (1) the cover of trees and shrubs within 40 m of houses, (2) whether trees and shrubs within 40 m of houses was predominantly remnant or planted, (3) the upwind distance from houses to groups of trees or shrubs, (4) the upwind distance from houses to public forested land (irrespective of whether it was managed for nature conservation or logging), (5) the upwind distance from houses to prescribed burning within 5 years, and (6) the number of buildings or structures within 40 m of houses. All fuel treatments were more effective if undertaken closer to houses. For example, 15% fewer houses were destroyed if prescribed burning occurred at the observed minimum distance from houses (0.5 km) rather than the observed mean distance from houses (8.5 km). Our results imply that a shift in emphasis away from broad-scale fuel-reduction to intensive fuel treatments close to property will more effectively mitigate impacts from wildfires on peri-urban communities.

Laura Cereta is unique among Quattrocento female humanists in directly addressing the position of women as wives and as friends in her substantial corpus of erudite Latin epistolary prose. Questioning the ideals that governed intellectual, social, and personal expectations of matrimony, Cereta's letters reflect her self-consciously double status as humanist and spouse. Her fierce critique of marriage as a site of female oppression and complicity implies an alternative that requires of humanists, husbands, and wives a radical rethinking of marriage in terms of friendship, as well as of the very project of humanist epistolarity.

Introduction: The aim of this prospective audit was to assess the effectiveness and safety of rectal paraldehyde in the management of acute, including prolonged, tonic-clonic convulsions. There are very limited published data on its effectiveness and safety, and previous data have focused on its intramuscular route of administration., Methods: Four hospitals participated in the study. Information was collected on each dose of paraldehyde used for the treatment of a tonic-clonic convulsion over 1 year. Data were not included on patients treated with rectal paraldehyde for other seizure types or non-convulsive status epilepticus., Results: Data analysis was undertaken regarding 53 episodes in 30 patients. Patient's ages ranged from 5 months to 16 years (mean 6.12 years, median 5.91 years). A pre-existing diagnosis of epilepsy was recorded in 35 episodes (66%). The mean dose of paraldehyde was 0.65 ml/kg (SD 0.22, 95% CI 0.59 to 0.71) and median dose 0.79 ml/kg. Rectal paraldehyde terminated the convulsion in 33 (62.3%) of the 53 episodes. In the 35 episodes where a pre-existing diagnosis of epilepsy was recorded, paraldehyde stopped the convulsion on 26 (74.3%) occasions. There was no difference in the dose of paraldehyde between the episodes where the convulsion was or was not terminated. There was no recorded respiratory depression in any episode., Conclusions: This study provides unique evidence that rectal paraldehyde is effective and safe in treating acute prolonged tonic-clonic convulsions. This would appear to confirm that paraldehyde should remain a treatment for the management of prolonged tonic-clonic convulsions, including convulsive status epilepticus.

Disturbance is a key ecological process influencing the distribution and abundance of many elements of the earth's biota. Predicting the response of biota to disturbance is therefore important, but it nevertheless remains difficult to make accurate forecasts of response. We tested predictions from disturbance-related theories and concepts in 10 vegetation types at Booderee National Park (southeastern Australia) using a retrospective study of bird responses to fire history (over 35 years) on 110 sites and a prospective study following a single wildfire event in 2003 at 59 of these sites. Our data did not support predictions from the intermediate-disturbance hypothesis; observed bird species richness at a site was significantly (F(1,99) = 6.30, P = 0.014) negatively related to the number of fires since 1972 and was 8.7% lower (95% CI, 1.8-15.1%) for each additional fire. In contrast to fire history effects, we found that after the 2003 fire, the vast majority of individual species and the bird assemblage per se in most vegetation types recovered within two years. Thus, recovery after a single fire did not reflect long-term effects of multiple fires on overall bird species richness at a site. We postulated that the recovery of bird species richness and bird assemblage composition after the 2003 fire would be fastest in structurally simple vegetation types and slowest in structurally complex vegetation, but observed the opposite. Although observed bird species richness in vertically heterogeneous forest and woodland had returned to prefire levels by 2006, bird species richness in structurally simple vegetation types (e.g., sedgeland) had not. Postfire vegetation regeneration, together with a paucity of early-successional specialists, would explain the speed of recovery of the bird assemblage and why it changed relatively little during our investigation.

This article describes a case study in the use of the Family Check-Up (FCU), a family-based and ecological preventive intervention for children at risk for problem behavior. The FCU is an assessment-driven intervention that utilizes a health maintenance model; emphasizes motivation for change; and offers an adaptive, tailored approach to intervention. This case study follows one Caucasian family through their initial assessment and subsequent treatment for their toddler daughter's conduct problems over a 2-year period. Clinically meaningful improvements in child and family functioning were found despite the presence of child, parent, and neighborhood risk factors. The case is discussed with respect to the findings from a current multisite randomized control trial of the FCU and its application to other populations.

Background: The emergency medicine (EM) subinternship provides a varied experience for senior medical students depending on gender, specialty choice, and interest. A didactic curriculum can be standardized, but the clinical component is difficult to control. Students can be directed to see patients with specific chief complaints., Objectives: To assess whether a clinical requirement of 10 predetermined cases improves general knowledge as measured on an objective exam., Methods: This was a prospective, nonrandomized, case-controlled study at a public teaching hospital. Students were assigned to the control group (CG) or test group (TG) by alternating block rotations over 6 months. The CG saw emergency department (ED) patients according to interest and faculty direction. The TG was also required to identify ten specific chief complaints. Patient encounters were recorded in computerized logs. A 10-question pretest assessed preexisting knowledge of each chief complaint, and a 40-question final exam tested general EM knowledge. Descriptive statistics measured demographic data. Groups were compared by Fisher's exact test. Difference in means testing was performed to see if pre- to posttest differences varied by group. Multivariate analysis controlled for gender and specialty choice., Results: Eighteen CG students saw a mean of 57 patients, and 24 TG students saw a mean of 54 patients; 1 CG student (6%) and 7 TG students (31.8%) saw all 10 required cases (Fisher's exact test p = 0.044). Difference in means testing demonstrated a greater relative change in performance (13.4% points) by the TG relative to the CG on a general knowledge exam, compared with their performance on a brief pretest (p = 0.014). The authors performed multivariate regression controlling for pretest score, gender, and EM specialty choice, and neither gender nor intended EM specialty choice was a contributing factor to the improved performance. A greater relative change in performance (7% points) in the TG exam score was found when compared to the CG (p = 0.020)., Conclusions: Students who participated in the usual didactic curriculum and were required to see ED patients with representative chief complaints performed better on a general EM exam than those who employed common methods of choosing patients.

Context: Recombinant human GH was approved by the United States Food and Drug Administration in 2003 for the treatment of idiopathic short stature (ISS). However, to date, the safety of GH in this patient population has not been rigorously studied., Objective: The objective of this study was to address the safety of GH treatment in children with ISS compared with GH safety in patient populations for which GH has been approved previously: Turner syndrome (TS) and GH deficiency (GHD)., Design/setting: The rates of serious adverse events (SAEs) and adverse events (AEs) of particular relevance to GH-treated populations were compared across the three patient populations among five multicenter GH registration studies., Patients: Children with ISS, TS, or GHD were studied., Intervention: Treatment consisted of GH doses ranging from 0.18-0.37 mg/kg.wk., Main Outcome Measures: The main outcome measures were rates of SAEs and AEs of special relevance to patients receiving GH. Laboratory measures of carbohydrate metabolism were used as outcome measures for the ISS studies., Results: Within the ISS studies, comprising one double-blind, placebo-controlled study and one open-label, dose-response study, SAEs (mainly hospitalizations for accidental injury or acute illness unrelated to GH exposure) were reported for 13-14% of GH-treated patients. Overall AE rates (serious and nonserious) as well as rates of potentially GH-related AEs were similar in the GHD, TS, and ISS studies (for ISS studies combined: otitis media, 8%; scoliosis, 3%; hypothyroidism, 0.7%; changes in carbohydrate metabolism, 0.7%; hypertension, 0.4%). Measures of carbohydrate metabolism were not affected by GH treatment in patients with ISS. There was no significant GH effect on fasting blood glucose in either study (GH dose range, 0.22-0.37 mg/kg.wk) or on insulin sensitivity (placebo-controlled study only)., Conclusion: GH appears safe in ISS; however, the studies were not powered to assess the frequency of rare GH-related events, and longer-term follow-up studies of GH-treated patients with ISS are warranted.

Objective: To determine whether emergency medicine (EM)-bound and non-EM-bound senior medical students on the EM subinternship have a uniform experience with respect to number and acuity of patients seen and procedures performed., Methods: Prospective observational analysis of patient diagnosis and procedures recorded in logs by students at a public teaching hospital over 12 consecutive months. Logs were reviewed blindly and assigned an acuity level based on predetermined criteria. Preselected procedures were categorized as general or surgical and tallied. Identity, specialty choice, gender, and month of rotation for each student were identified., Results: Seventy of 74 students completed logs. On average, 34 EM-bound students saw 59.82 patients (95% CI = 55.19 to 64.45) and performed 10.58 procedures (95% CI = 8.62 to 12.56); 36 non-EM-bound students saw 51.17 patients (95% CI = 47.41 to 54.90) and performed 8.33 procedures (95% CI = 6.81 to 9.84). Univariate analysis showed EM-bound students saw more patients than non-EM-bound students, performed more surgical procedures, and saw higher-acuity patients (p = 0.004; 0.009; 0.016). Multivariate analyses controlled for EM specialty, gender, and month. Significant effects for EM specialty were found (ordinary least squares) for number of patients, procedures, and surgical procedures (p = 0.013; 0.048; 0.011). Logistic regression explaining acuity level showed EM specialty and gender were significant (p = 0.010; 0.038)., Conclusions: In an EM subinternship, experience was variable between EM-bound and non-EM-bound students. Male students saw lower-acuity patients. The EM-bound students saw more patients, higher-acuity patients, and performed more procedures than non-EM-bound cohorts. Emergency medicine educators responsible for medical education should be aware of these differences.

Objective: To describe 15 pediatric patients with opiate-induced respiratory depression., Design: In-house adverse drug reaction (ADR) report forms were reviewed to identify any patients with suspected opiate-induced respiratory depression. Case review was then performed., Setting: Large pediatric teaching hospital with regional specialties., Patients: Fifteen patients aged 2 days to 17 years (median 14 mo)., Main Outcome Measures: Respiratory depression resulting in apnea, hypoxia, cyanosis, reduced respiratory rate, or the need for naloxone following or during opiate administration was recorded., Results: Fifteen patients experienced some degree of respiratory depression over the 3 years of surveillance. Treatment included naloxone (12 patients), admission to the pediatric intensive care unit (8), ventilation (5), and reduction in dosage (1). Predisposing factors for respiratory depression included an age of less than 1 year, excessive dosage, concurrent medical problems, concurrent drugs, and medication errors., Conclusions: Opiate-induced respiratory depression in pediatric patients occurs infrequently, but may have serious consequences. Opiates are potent analgesics that children require and should receive. Safe use of opiates in pediatric patients, however, depends on the dosage, route and method of administration, consideration of any predisposing factors, and adequate monitoring. This article highlights some of the problems with opiate use in children and gives some recommendations on how these problems may be prevented.

Objective: To determine the steady-state plasma concentrations of midazolam in critically ill infants and children., Design: Prospective uncontrolled study conducted over 18 months., Setting: Regional pediatric intensive care unit in a children's hospital., Patients: Thirty-eight infants and children, aged 1 month to 13 years, requiring midazolam as sedation during mechanical ventilation. The patients were divided into three age groups: (1) infants less than 12 months (n = 16); (2) children 1-2 years (n = 12); and (3) children aged 3 years and older (n = 10)., Main Outcome Measures: A single blood sample was collected once steady-state plasma concentrations of midazolam were achieved during a continuous intravenous infusion. Plasma clearance was calculated from the plasma concentrations and infusion rate., Results: The plasma clearance was higher in children aged 3 years and older (median plasma clearance 13.0 mL/min/kg) than in infants and children 1-2 years old (median plasma clearance 3.1 and 2.3 mL/min/kg, respectively) (Kruskal-Wallis analysis of variance, p < 0.01). The midazolam infusion rates were similar for the three groups studied (Kruskal-Wallis analysis of variance, p > 0.05). The plasma concentrations of midazolam were significantly lower in children 3 years and older (median plasma concentration 128 ng/mL) than in infants and children 1-2 years old (median plasma concentrations 395 and 790 ng/mL, respectively) (Kruskal-Wallis analysis of variance, p < 0.05)., Conclusions: The plasma clearance in children 3 years and older was higher than in infants and children up to 2 years old. There was considerable interindividual variation in the steady-state plasma concentrations of midazolam in critically ill infants and children.

Sex steroid sulfotransferases (ST) sulfurylate and thus inactivate estrogens or androgens, producing an androgenized or estrogenized state in the liver. The expression of diabetes in a number of animal models is sexually dimorphic and has been associated with steroidal states. Although the viable yellow (Avy) mutation produces an insulin-resistant obesity syndrome in mice of both sexes, only males develop chronic hyperglycemia. Hyperglycemia was rapidly induced in Avy/a females by dexamethasone (dex). This treatment completely suppressed both endogenous plasma corticosterone and hepatic corticosterone-binding globulin (CBG) mRNA within 24 h. Hyperglycemia in dex-implanted Avy/a females was accompanied by aberrant shifts in hepatic androgen/estrogen balance. This was effected by induction of estrogen sulfotransferase (EST) mRNA together with a > 10-fold increase in enzymatic activity. Similar dex-induced increases in androgen ST or phenol ST were not observed. Prior implantation of estrogen prevented development of hyperglycemia. The time-dependent spontaneous reversal of dex-induced hyperglycemia correlated with re-expression of CBG mRNA transcripts and reduced levels of EST transcripts and enzyme activity. Although dex-induced hyperglycemia was limited to Avy/a females, dex elicited hyperinsulinemia in lean a/a control mice of both sexes and exacerbated constitutive hyperinsulinemia in Avy/a males and females. In summary, dex-induced hyperglycemia in Avy/a females was associated with increased catabolism of hepatic estrogens mediated by induction of EST.

Plasma insulin levels in yellow Avy/- mice begin to increase before the animals are overtly obese. Are the elevated insulin levels in yellow mice primary or secondary to the subsequent obesity? Elevated blood insulin levels in young preobese mice, due to synthesis and release of insulin by increased number of beta cells, would stimulate lipogenesis, resulting in excess lipid deposition and subsequent peripheral insulin resistance. Examination of this possibility was the objective of this study. The beta, alpha, and delta cells in the pancreata of 7-, 14-, and 21-day-old male yellow Avy/A and agouti A/a (BALB/c x VY)F1 hybrid mice were counted with immunohistochemical/morphometric techniques. The insulin and glucagon concentrations in pancreata from male and female mice of the same ages and genotypes were also assayed. In the 21-day-old male mice, the mean number of beta cells/pancreas was significantly greater in the yellow mice than in the agouti mice; however, insulin content and body weight were the same. This suggests that increased beta cell proliferation in yellow mice precedes any detectable genotype-specific increase in pancreatic insulin content or body weight.

The viable yellow A(vy) mutation results in a mottled yellow mouse that is obese, slightly larger than its nonyellow sibs, and more susceptible to tumor formation in those tissues sensitized by the strain genome. The mutation exhibits variable expressivity resulting in a continuum of coat color phenotypes, from clear yellow to pseudoagouti. The mouse agouti protein is a paracrine signaling molecule that induces hair follicle melanocytes to switch from the synthesis of black pigment to yellow pigment. Molecular cloning studies indicate that the obesity and growth effects of the A(vy) mutation result from ectopic expression of the normal agouti gene product. This review seeks to summarize the current state of knowledge regarding the obesity, stimulation of somatic growth, and enhancement of tumor formation caused by the A(vy) mutation, and to interpret these pleiotropic effects in terms of the normal function of the agouti protein.

Hypercorticism has been observed in numerous obese and diabetic animal models. Adrenalectomy reduces adiposity, hyperglycemia, hyperinsulinemia, and insulin resistance in these animals. The effects of adrenalectomy can be reversed by glucocorticoid replacement. Male and female viable yellow mice share all phenotypic expressions caused by the viable yellow mutation except that males are hyperglycemic and most females are either normoglycemic or only mildly hyperglycemic. The mechanisms that protect female viable yellow mice from hyperglycemia are not known. Implantation of dexamethasone pellets induced hyperglycemia in female viable yellow mice but had no effect on blood glucose of male viable yellow mice and male and female normal mice. The duration of dexamethasone-induced hyperglycemia correlated to the time endogenous plasma corticosterone levels were suppressed. Plasma insulin levels rose in normal mice but only transiently in viable yellow mice. Ciglitazone prevented and reversed dexamethasone-induced hyperglycemia in female viable yellow mice. Since female viable yellow mice, similar to male viable yellow mice, are obese, hyperinsulinemic and insulin resistant, and since dexamethasone is known to cause insulin resistance, these data suggest that dexamethasone increased insulin resistance to a degree that the protective mechanism was overwhelmed and hyperglycemia was induced. Ciglitazone, a compound known to improve insulin sensitivity, may prevent and reverse dexamethasone-induced hyperglycemia by ameliorating the additional insulin resistance caused by dexamethasone. On a molecular level, since dexamethasone suppresses glucose transport, an insulin-sensitive process in many tissues, whereas ciglitazone and other thiazolidinediones facilitate glucose transport, it is possible that ciglitazone prevents and reverses dexamethasone-induced hyperglycemia by regulating the glucose transport systems in insulin-sensitive tissues.

Compound M & B 39890A [N-(3-imidazol-1-ylpropyl)-2- (3-trifluoromethylbenzenesulphonamido)benzamide hydrochloride] had no effect on cellular cAMP and cGMP levels but significantly inhibited insulin and glucagon secretion from freshly isolated normal rat islets stimulated with 10 mM glucose and 20 mM arginine. Daily gavage of the compound for three days lowered the elevated blood glucose and plasma insulin levels in fed, male viable yellow obese-diabetic mice; the minimum effective dose was 25 mg/kg. However, M & B 39890A did not affect the blood glucose level of fasted diabetic mice. In addition, it had no effect on blood glucose levels of normal mice and streptozotocin-diabetic rats. M & B 39890A, fed in the diet at the concentration of 1 mg/g for 42 days, reversed the hyperglycemia of the fed diabetic mice without causing tachyphylaxis and improved the sensitivity to exogenous insulin as demonstrated by the lowering of blood glucose. When M & B 39890A was fed to young male mice destined to become diabetic, the development of hyperglycemia was prevented. Thus, M & B 39890A represents a new class of pharmacological agents that may prove to be effective for the chronic treatment of type II diabetics without the risk of hypoglycemia.

The role of islet amyloid polypeptide, also known as amylin, in insulin resistance and in the etiology of diabetes has been a subject of debate. Increased plasma amylin levels have been observed in both obese and type II diabetic patients. However, data on endogenous amylin levels with relation to pharmacological interventions have not been reported. In this study, chronic treatment of obese-diabetic viable yellow mice with ciglitazone was shown to significantly alter various parameters. Blood glucose and plasma insulin, triglyceride, and amylin levels were reduced and glucose tolerance in the presence of exogenous insulin was improved. Insulin/amylin ratios which were found to be significantly elevated in diabetic mice as compared to normal controls, were decreased after ciglitazone treatment. However, observed decreases in both amylin and insulin concentrations due to ciglitazone treatment and their subsequent increases upon withdrawal of treatment were correlated, suggesting cosecretion.

MTP-3115 is a newly-synthesized thiopyranopyrimidine compound with a structure similar to that of MTP-1403 and MTP-1307. However, the biological profile of MTP-3115 is different from that of MTP-1403 and MTP-1307 (previously reported). Similar to MTP-1403 and MTP-1307, MTP-3115 improves glucose tolerance in both normal and obese-diabetic viable yellow mice with equal potency. However, unlike MTP-1403 and MTP-1307, MTP-3115 also lowers blood glucose of fed and fasted normal and obese-diabetic viable yellow mice. Although the mechanisms of action of MTP-3115 are not elucidated, it is unlikely that its mode of action is similar to that of sulfonylureas because tolbutamide neither improves glucose tolerance nor lowers blood glucose in obese-diabetic viable yellow mice.

Carcinoembryonic antigen (CEA) has been measured by radioimmunoassay in samples obtained from all patients suffering from ulcerative proctocolitis and seen within a four-month period. The characteristics of this group of patients have been compared with reported epidemiological studies in this disease, and have been found to have a similar sex ratio and age of onset, but a more limited disease. Among 59 patients, 11 were found to have elevated circulating CEA values. One of the 11 had a colonic carcinoma and another was pregnant. Excluding these two patients, an overall prevalence of elevated CEA levels of 17.5% was found. The prevelance in ulcerative proctitis was 7.1%, and in colitis was 19.9%. The patients in whom elelvated plasma CEA values were found were compared with the remaining patients in relation to factors known to be associated with an increased propensity for the development of colorectal carcinoma complicating ulcerative colitis. There was no difference in mean age of the patients at disease onset, nor was there any difference in disease duration, extent, and control. A significant correlation was found between elevated plasma CEA levels and the severity of the initial attack. One patient with premalignant changes in the rectal mucosa had consistently normal concentrations of plasma CEA. There was no significant correlation between elevated plasma CEA values and disease activity. The mean age of the two groups of patients was similar. No carcinoma has manifested in any patient during follow-up periods of at least 18 months.