Enhanced detection of artifacts in EEG data using higher-order statistics and independent component analysis.
Detecting artifacts produced in EEG data by muscle activity, eye blinks and electrical noise is a common and important problem in EEG research. It is now widely accepted that independent component analysis (ICA) may be a useful tool for isolating artifacts and/or cortical processes from electroencephalographic (EEG) data. We present results of simulations demonstrating that ICA decomposition, here tested using three popular ICA algorithms, Infomax, SOBI, and FastICA, can allow more sensitive automated detection of small non-brain artifacts than applying the same detection methods directly to the scalp channel data. We tested the upper bound performance of five methods for detecting various types of artifacts by separately optimizing and then applying them to artifact-free EEG data into which we had added simulated artifacts of several types, ranging in size from thirty times smaller (-50 dB) to the size of the EEG data themselves (0 dB). Of the methods tested, those involving spectral thresholding were most sensitive. Except for muscle artifact detection where we found no gain of using ICA, all methods proved more sensitive when applied to the ICA-decomposed data than applied to the raw scalp data: the mean performance for ICA was higher and situated at about two standard deviations away from the performance distribution obtained on raw data. We note that ICA decomposition also allows simple subtraction of artifacts accounted for by single independent components, and/or separate and direct examination of the decomposed non-artifact processes themselves.


A cross-validation scheme for machine learning algorithms in shotgun proteomics.
Peptides are routinely identified from mass spectrometry-based proteomics experiments by matching observed spectra to peptides derived from protein databases. The error rates of these identifications can be estimated by target-decoy analysis, which involves matching spectra to shuffled or reversed peptides. Besides estimating error rates, decoy searches can be used by semi-supervised machine learning algorithms to increase the number of confidently identified peptides. As for all machine learning algorithms, however, the results must be validated to avoid issues such as overfitting or biased learning, which would produce unreliable peptide identifications. Here, we discuss how the target-decoy method is employed in machine learning for shotgun proteomics, focusing on how the results can be validated by cross-validation, a frequently used validation scheme in machine learning. We also use simulated data to demonstrate the proposed cross-validation scheme's ability to detect overfitting.


Core clerkship directors: their current resources and the rewards of the role.
To conduct a national multidisciplinary investigation assessing core clinical clerkships and their directors, variances in resources from national guidelines, and the impact of the clerkship director role on faculty members' academic productivity, advancement, and satisfaction. A multidisciplinary working group of the Alliance for Clinical Education (ACE), representing all seven core clinical disciplines, created and distributed a survey to clerkship directors at 125 U.S. MD-granting medical schools, in academic year 2006-2007. A total of 544 clerkship directors from Internal Medicine (96), Family Medicine (91), Psychiatry, (91), Pediatrics (79), Surgery (71), Neurology (60), and Obstetrics-Gynecology (56) responded, representing over 60% of U.S. core clinical clerkships. The clerkship directors were similar across disciplines in demographics and academic productivity, though clinical and clerkship activities varied. Departmental staff support for clerkships averaged 0.69 people, distinctly less than the ACE's 2003 guideline of a full-time coordinator in all disciplines' clerkships. Clerkship directors reported heavy clinical responsibilities, which, as in previous studies, were negatively related to academic productivity. However, many clerkship directors felt the role enhanced their academic advancement; a large majority felt it significantly enhanced their career satisfaction. The resources and rewards of the clerkship director role were similar across disciplines. Expectations of clerkship directors were considerable, including responsibility for clinical material and the learning environment. Resources for many fall short of those stated in the ACE guidelines, particularly regarding support staff. However, the findings indicate that the clerkship director role can have benefits for academic advancement and strongly enhances career satisfaction.


Environmental determinants of children's physical activity in residential children's homes.
Children in residential children's homes (RCH) may be at increased risk for physical inactivity due to decreased access to opportunities for activity. Little is known about environmental determinants of physical activity for children in RCH. Thirty-minute blocks of MVPA and Total METs were measured using the 3-Day Physical Activity Recall (3DPAR). A staff interview, based on the Structural Ecologic Model of Health Behavior, assessed physical activity opportunities, structures, characteristics, policies, and social environment. Wilcoxon 2-sample tests were used to examine differences in environment by location and presence of a recreation director. Mixed model ANOVAs assessed the differences in child level activity by environmental variables. There were significant correlations between opportunities and characteristics of physical activity, facilities, and equipment with total METS for children. Children in homes with a recreation director and homes in rural locations reported more physical activity. Only rural location had a significant effect on physical activity. Presence of a recreation director was significant in several models. Rural location may be conducive for increased physical activity in children at RCH. Employing a recreation director or other trained personnel may be an important policy determinant of physical activity for children.


Apple polyphenols and fibers attenuate atherosclerosis in apolipoprotein E-deficient mice.
Atherosclerosis, which is closely linked to nutritional habits, is a major cause of mortality in Western countries. Most of the previous investigations carried out on health effects of apples have been focused on their capacity to lower lipid concentration as well as on their antioxidant effects. The aim of the present study was to investigate the antiatherosclerotic effects of apple polyphenols and fibers. A crude apple polyphenol extract and low-viscosity apple fibers isolated from cider apples were administered separately or in association with the diet of apo E-deficient mice. After 4 months of supplementation, lipemia and oxidative stress biomarkers were measured and atheroslerotic lesions assessed by histomorphometry. Total plasmatic cholesterol and triacylgycerol levels were not affected by supplementation, and hepatic cholesterol level was lower in the group supplemented with both fibers and polyphenols. Uric acid concentrations and antioxidant capacity (FRAP) in plasma were reduced in all groups supplemented with polyphenols or fibers. The mean lesion area was reduced by 17, 38, and 38%, respectively, for the polyphenol, fiber, and polyphenol + fiber groups. Apple constituents supplied at nutritional doses therefore limit the development of atherosclerotic lesions in the aorta of apo E-deficient mice. On the basis of the results, we hypothesize that apple fibers and polyphenols may play a role in preventing atherosclerosis disease by decreasing uric acid plasma level.


Localization of calcium pump activity in smooth muscle.
A microsomal fraction isolated from longitudinal smooth muscle of guinea pig ileum actively sequesters calcium ion in the presence of magnesium and adenosine triphosphate in a fashion previously described for microsomes of the rabbit aorta. This activity in guinea pig ileum appears to be associated primarily with the plasma membrane as is found in the red cell. By contrast the uptake of calcium in aortic smooth muscle appears to be associated to an appreciable extent with intracellular membranes, possibly analogous to the sarcoplasmic reticulum of skeletal muscle.


Corrective osteotomy for intra-articular malunion of the distal part of the radius.
Corrective osteotomy is an appealing treatment for malunited articular fractures of the distal part of the radius since articular incongruity may be the factor most strongly associated with arthrosis and diminished function after such fractures. Enthusiasm for osteotomy has been limited by concerns regarding the difficulty of the technique and the potential for additional injury, osteonecrosis, and nonunion. Twenty-three skeletally mature patients were evaluated at an average of thirty-eight months after corrective osteotomy for an intra-articular malunion of the distal part of the radius. The indication for the osteotomy included dorsal or volar subluxation of the radiocarpal joint in fourteen patients and articular incongruity of > or =2 mm as measured on a posteroanterior radiograph in seventeen patients. Six patients had combined intra-articular and extra-articular malunion. The average interval from the injury to the osteotomy was six months. The average maximum step-off or gap of the articular surface prior to the operation was 4 mm. One patient had a subsequent partial wrist arthrodesis because of radiocarpal arthrosis, and three patients had additional surgery because of dysfunction of the distal radioulnar joint. One patient had a rupture of the extensor pollicis longus, which was treated with a tendon transfer. The final articular incongruity averaged 0.4 mm, and the final grip strength averaged 85% of that on the contralateral side. The rate of excellent or good results was 83% according to the rating systems of Fernandez and of Gartland and Werley, and 43% according to a modification of the rating system of Green and O'Brien. The results of corrective osteotomy for the treatment of intra-articular malunion are comparable with those of osteotomy for the treatment of extra-articular malunion. Intra-articular osteotomy can be performed with acceptable safety and efficacy, it improves wrist function, and it may help to limit the need for salvage procedures such as partial or total wrist arthrodesis.


Unique equilibrium in contests with incomplete information.
Considered are imperfectly discriminating contests in which players may possess private information about the primitives of the game, such as the contest technology, valuations of the prize, cost functions, and budget constraints. We find general conditions under which a given contest of incomplete information admits a unique pure-strategy Nash equilibrium. In particular, provided that all players have positive budgets in all states of the world, existence requires only the usual concavity and convexity assumptions. Information structures that satisfy our conditions for uniqueness include independent private valuations, correlated private values, pure common values, and examples of interdependent valuations. The results allow dealing with inactive types, asymmetric equilibria, population uncertainty, and the possibility of resale. It is also shown that any player that is active with positive probability ends up with a positive net rent.


Favourable long term prognosis in stable angina pectoris: an extended follow up of the angina prognosis study in Stockholm (APSIS).
To evaluate the long term prognosis of patients with stable angina pectoris. Registry based follow up (median 9.1 years) of patients participating in the APSIS (angina prognosis study in Stockholm), which was a double blind, single centre trial of antianginal drug treatment. 809 patients (31% women) with stable angina pectoris < 70 (mean (SD) 59 (7) years at inclusion) and an age and sex matched reference population from the same catchment area. Double blind treatment with metoprolol or verapamil during 3.4 years (median), followed by referral for usual care with open treatment. Cardiovascular (CV) death and non-fatal myocardial infarction (MI) in the APSIS cohort and total mortality in comparison with reference subjects. 123 patients died (41 MI, 36 other CV causes) and 72 had non-fatal MI. Mortality (19% v 6%, p < 0.001) and fatal MI (6.6% v 1.6%, p < 0.001) were increased among male compared with female patients. Diabetes, previous MI, hypertension, and male sex independently predicted CV mortality (p < 0.001). Diabetes greatly increased the risk in a small subgroup of female patients. Male patients had higher mortality than men in the reference population during the first three years (cumulative absolute difference 3.8%) but apparently not thereafter. Female patients had similar mortality to women in the reference population throughout the 9.1 years of observation. Female patients with stable angina had similar mortality to matched female reference subjects but male patients had an increased risk. Diabetes, previous MI, hypertension, and male sex were strong risk factors for CV death or MI.


Use of historic metabolic biotransformation data as a means of anticipating metabolic sites using MetaPrint2D and Bioclipse.
Predicting metabolic sites is important in the drug discovery process to aid in rapid compound optimisation. No interactive tool exists and most of the useful tools are quite expensive. Here a fast and reliable method to analyse ligands and visualise potential metabolic sites is presented which is based on annotated metabolic data, described by circular fingerprints. The method is available via the graphical workbench Bioclipse, which is equipped with advanced features in cheminformatics. Due to the speed of predictions (less than 50 ms per molecule), scientists can get real time decision support when editing chemical structures. Bioclipse is a rich client, which means that all calculations are performed on the local computer and do not require network connection. Bioclipse and MetaPrint2D are free for all users, released under open source licenses, and available from http://www.bioclipse.net.


Algorithm for detecting seam cracks in steel plates using a Gabor filter combination method.
Presently, product inspection based on vision systems is an important part of the steel-manufacturing industry. In this work, we focus on the detection of seam cracks in the edge region of steel plates. Seam cracks are generated in the vertical direction, and their width range is 0.2-0.6 mm. Moreover, the gray values of seam cracks are only 20-30 gray levels lower than those of the neighboring surface. Owing to these characteristics, we propose a new algorithm for detecting seam cracks using a Gabor filter combination method. To enhance the performance, we extracted features of seam cracks and employed a support vector machine classifier. The experimental results show that the proposed algorithm is suitable for detecting seam cracks.


T2 tumors larger than five centimeters in diameter can be upgraded to T3 in non-small cell lung cancer.
Among the TNM criteria, tumor size is a well-assessed factor in the prognosis of small tumors. A 3-cm cutoff point separates T1 from T2 tumors, whereas a size larger than 3 cm is not ascribed any prognostic value. Instead, N2 is considered to be the worst prognostic factor for intrathoracic extended disease. The prognosis of 545 patients with non-small cell lung cancer larger than 3 cm in diameter (T2, T3, and T4) was studied. These tumors were completely resected by pneumonectomy (n = 126) or lobectomy (n = 411) or were partially resected (n = 8). Survivals were compared according to the following factors: tumor size (3.1-5 cm, 5.1-7 cm, >7 cm), nodal status, age, sex, histologic type, degree of pleural involvement, operative procedure, stage, and T factor. For the multivariate analysis, the Cox proportional hazard model was used with the same variables. The univariate analysis showed that age, sex, degree of pleural involvement, operative procedure, tumor size, nodal status, and stage were all significant prognostic factors. Further comparison of survival between different tumor sizes (< or =5 cm vs >5 cm) in the same nodal category demonstrated a significantly poor prognosis for larger tumors in N0 (P =.00374) and N2+N3 (P =.0157), but not in N1 (P =.3452). T2 tumors (n = 349) were divided, according to size, into T2a (n = 238) and T2b (n = 111), and survival was compared with those in T3 and T4. The 5-year survivals were 51.3%, 35.1%, 47.8%, and 25.3%, respectively. The difference between T2a and T2b was statistically significant (log-rank P =.0170, Breslow P =.0055). A tumor size of more than 5 cm in diameter was indicative of a poor prognosis in non-small cell lung cancer, because patients with T2b tumors had a significantly different survival from that of patients with T2a tumors, and the survival curve was located between those for patients with T3 and T4 tumors. Consequently, T2b might be upgraded to at least T3.


Making and Breaking of Lead Halide Perovskites.
A new front-runner has emerged in the field of next-generation photovoltaics. A unique class of materials, known as organic metal halide perovskites, bridges the gap between low-cost fabrication and exceptional device performance. These compounds can be processed at low temperature (typically in the range 80-150 °C) and readily self-assemble from the solution phase into high-quality semiconductor thin films. The low energetic barrier for crystal formation has mixed consequences. On one hand, it enables inexpensive processing and both optical and electronic tunability. The caveat, however, is that many as-formed lead halide perovskite thin films lack chemical and structural stability, undergoing rapid degradation in the presence of moisture or heat. To date, improvements in perovskite solar cell efficiency have resulted primarily from better control over thin film morphology, manipulation of the stoichiometry and chemistry of lead halide and alkylammonium halide precursors, and the choice of solvent treatment. Proper characterization and tuning of processing parameters can aid in rational optimization of perovskite devices. Likewise, gaining a comprehensive understanding of the degradation mechanism and identifying components of the perovskite structure that may be particularly susceptible to attack by moisture are vital to mitigate device degradation under operating conditions. This Account provides insight into the lifecycle of organic-inorganic lead halide perovskites, including (i) the nature of the precursor solution, (ii) formation of solid-state perovskite thin films and single crystals, and (iii) transformation of perovskites into hydrated phases upon exposure to moisture. In particular, spectroscopic and structural characterization techniques shed light on the thermally driven evolution of the perovskite structure. By tuning precursor stoichiometry and chemistry, and thus the lead halide charge-transfer complexes present in solution, crystallization kinetics can be tailored to yield improved thin film homogeneity. Because degradation of the as-formed perovskite film is in many ways analogous to its initial formation, the same suite of monitoring techniques reveals the moisture-induced transformation of low band gap methylammonium lead iodide (CH3NH3PbI3) to wide band gap hydrate compounds. The rate of degradation is increased upon exposure to light. Interestingly, the hydration process is reversible under certain conditions. This facile formation and subsequent chemical lability raises the question of whether CH3NH3PbI3 and its analogues are thermodynamically stable phases, thus posing a significant challenge to the development of transformative perovskite photovoltaics. Adequately addressing issues of structural and chemical stability under real-world operating conditions is paramount if perovskite solar cells are to make an impact beyond the benchtop. Expanding our fundamental knowledge of lead halide perovskite formation and degradation pathways can facilitate fabrication of stable, high-quality perovskite thin films for the next generation of photovoltaic and light emitting devices.


Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society-USA panel.
New trial data and drug regimens that have become available in the last 2 years warrant an update to guidelines for antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected adults in resource-rich settings. To provide current recommendations for the treatment of adult HIV infection with ART and use of laboratory-monitoring tools. Guidelines include when to start therapy and with what drugs, monitoring for response and toxic effects, special considerations in therapy, and managing antiretroviral failure. Data that had been published or presented in abstract form at scientific conferences in the past 2 years were systematically searched and reviewed by an International Antiviral Society-USA panel. The panel reviewed available evidence and formed recommendations by full panel consensus. Treatment is recommended for all adults with HIV infection; the strength of the recommendation and the quality of the evidence increase with decreasing CD4 cell count and the presence of certain concurrent conditions. Recommended initial regimens include 2 nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine) plus a nonnucleoside reverse transcriptase inhibitor (efavirenz), a ritonavir-boosted protease inhibitor (atazanavir or darunavir), or an integrase strand transfer inhibitor (raltegravir). Alternatives in each class are recommended for patients with or at risk of certain concurrent conditions. CD4 cell count and HIV-1 RNA level should be monitored, as should engagement in care, ART adherence, HIV drug resistance, and quality-of-care indicators. Reasons for regimen switching include virologic, immunologic, or clinical failure and drug toxicity or intolerance. Confirmed treatment failure should be addressed promptly and multiple factors considered. New recommendations for HIV patient care include offering ART to all patients regardless of CD4 cell count, changes in therapeutic options, and modifications in the timing and choice of ART in the setting of opportunistic illnesses such as cryptococcal disease and tuberculosis.


Molecular structure of DNA by scanning tunneling microscopy.
Uncoated DNA molecules marked with an activated tris(l-aziridinyl) phosphine oxide (TAPO) solution were deposited on gold substrates and imaged in air with the use of a high-resolution scanning tunneling microscope (STM). Constant-current and gap-modulated STM images show clear evidence of the helicity of the DNA structure: pitch periodicity ranges from 25 to 35 angstroms, whereas the average diameter is 20 angstroms. Molecular structure within a single helix turn was also observed.


Comparative in vitro activities of posaconazole, voriconazole, itraconazole, and amphotericin B against Aspergillus and Rhizopus, and synergy testing for Rhizopus.
We compared the in vitro activities of posaconazole, voriconazole, itraconazole, and amphotericin B against clinical isolates of Aspergillus spp. and Rhizopus spp., and explored the in vitro interaction between posaconazole and amphotericin B against Rhizopus spp. Clinical strains of 82 Aspergillus spp. (43 Aspergillus fumigatus, 29 A. flavus, 7 A. niger, 2 A. terreus, 1 A. nidulans) and 11 Rhizopus oryzae isolates were tested in accordance with CLSI M38-A microdilution guidelines. In vitro activity of posaconazole against Aspergillus spp. was also investigated with the Etest. The combination of posaconazole and amphotericin B against R. oryzae isolates was investigated by the checkerboard methodology. Voriconazole was the most active drug in vitro against Aspergillus spp., followed by posaconazole, itraconazole, and amphotericin B, in order of decreasing activity. In studies with R. oryzae isolates, posaconazole was found to be the most potent drug followed by itraconazole and amphotericin B. Voriconazole had no meaningful activity against Rhizopus. Posaconazole Etest MICs (microg/ml) with Aspergillus spp. were found to be considerably lower than those obtained with the CLSI microdilution method (4-9 and 3-7 two-fold lower than CLSI MICs at 24 and 48 h, respectively). The interaction between posaconazole and amphotericin B was indifferent for all R. oryzae isolates tested; importantly no antagonism was observed.


Comparison between the use of 99% ethanol and 3% polidocanol in percutaneous echoguided sclerotherapy treatment of simple renal cysts.
In this study, we compared and valued efficacy and safety of percutaneous echoguided sclerotherapy (PES) using 3% polidocanol with that using 99% ethanol in the treatment of patients with simple renal cysts. PES was performed for 65 simple renal cysts. Under ultrasonographic guidance the cyst was punctured using an 18 gauge needle. Sclerotherapy was performed with ethanol in 55% (36/65) of cases and with polidocanol in the remaining 45% (29/65). Patients were followed up with an ultrasound examination at 4 months, 8 months, and then at yearly intervals. A reduction of 50% or greater in cyst diameter was considered successful. The median followup period for the ethanol and polidocanol groups was 24.6 and 22.8 months, respectively. The successful outcome ratio of the polidocanol group was significantly higher (90% vs. 61%, respectively) than the one of the ethanol group (P = 0.003). The partial regression of the ethanol and polidocanol groups were 6% versus 7%, respectively. The failure ratio of the polidocanol group was significantly lower (3% vs. 33%, respectively) than that of the ethanol group (P = 0.004). Neither infectious complications nor hyperthermia occurred in all treated cases. However, these methods are not completely free from symptoms. All these symptoms disappeared few hours after the procedure. Polidocanol is a safe and effective sclerosing agent for renal cysts, with superior clinical results than ethanol. Therefore, polidocanol can be an alternative to ethanol in sclerotherapy of renal cysts.


Effect of Relative Arrangement of Cationic and Lipophilic Moieties on Hemolytic and Antibacterial Activities of PEGylated Polyacrylates.
Synthetic amphiphilic polymers have been established as potentially efficient agents to combat widespread deadly infections involving antibiotic resistant superbugs. Incorporation of poly(ethylene glycol) (PEG) side chains into amphiphilic copolymers can reduce their hemolytic activity while maintaining high antibacterial activity. Our study found that the incorporation of PEG has substantially different effects on the hemolytic and antibacterial activities of copolymers depending on structural variations in the positions of cationic centers relative to hydrophobic groups. The PEG side chains dramatically reduced the hemolytic activities in copolymers with hydrophobic hexyl and cationic groups on the same repeating unit. However, in case of terpolymers with cationic and lipophilic groups placed on separate repeating units, the presence of PEG has significantly lower effect on hemolytic activities of these copolymers. PEGylated terpolymers displayed substantially lower activity against Staphylococcus aureus (S. aureus) than Escherichia coli (E. coli) suggesting the deterring effect of S. aureus' peptidoglycan cell wall against the penetration of PEGylated polymers. Time-kill studies confirmed the bactericidal activity of these copolymers and a 5 log reduction in E. coli colony forming units was observed within 2 h of polymer treatment.


Quasiperiodic one-dimensional photonic crystals with adjustable multiple photonic bandgaps.
We propose an elegant approach to produce photonic bandgap (PBG) structures with multiple photonic bandgaps by constructing quasiperiodic photonic crystals (QPPCs) composed of a superposition of photonic lattices with different periods. Generally, QPPC structures exhibit both aperiodicity and multiple PBGs due to their long-range order. They are described by a simple analytical expression, instead of quasiperiodic tiling approaches based on substitution rules. Here we describe the optical properties of QPPCs exhibiting two PBGs that can be tuned independently. PBG interband spacing and its depth can be varied by choosing appropriate reciprocal lattice vectors and their amplitudes. These effects are confirmed by the proof-of-concept measurements made for the porous silicon-based QPPC of the appropriate design.


The health effects of a forest environment on subclinical cardiovascular disease and heath-related quality of life.
Assessment of health effects of a forest environment is an important emerging area of public health and environmental sciences. To demonstrate the long-term health effects of living in a forest environment on subclinical cardiovascular diseases (CVDs) and health-related quality of life (HRQOL) compared with that in an urban environment. This study included the detailed health examination and questionnaire assessment of 107 forest staff members (FSM) and 114 urban staff members (USM) to investigate the long-term health effects of a forest environment. Air quality monitoring between the forest and urban environments was compared. In addition, work-related factors and HRQOL were evaluated. Levels of total cholesterol, low-density lipoprotein cholesterol, and fasting glucose in the USM group were significantly higher than those in the FSM group. Furthermore, a significantly higher intima-media thickness of the internal carotid artery was found in the USM group compared with that in the FSM group. Concentrations of air pollutants, such as NO, NO2, NOx, SO2, CO, PM2.5, and PM10 in the forest environment were significantly lower compared with those in the outdoor urban environment. Working hours were longer in the FSM group; however, the work stress evaluation as assessed by the job content questionnaire revealed no significant differences between FSM and USM. HRQOL evaluated by the World Health Organization Quality of Life-BREF questionnaire showed FSM had better HRQOL scores in the physical health domain. This study provides evidence of the potential beneficial effects of forest environments on CVDs and HRQOL.


Thermodynamics of chemical Marangoni-driven engines.
The goal of this paper is to perform a general thermodynamic study of Marangoni-driven engines in which chemical energy is directly transformed into mechanical motion. Given that this topic has not been discussed before, we will explore here the most basic and fundamental aspects of the phenomena at work, which leads to a number of interesting observations typical of controversies in classical thermodynamics. Starting with a discussion of a few key motivating examples of chemical Marangoni-driven phenomena - tears of wine, an oscillating pendant droplet, "beating" oil lens, and traveling waves in a circular container - and contrasting homogeneous versus inhomogeneous thermodynamic systems we naturally arrive at alternative ways of storing and generating energy with the help of inhomogeneities in the bulk and surface properties of the working media. Of particular interest here are systems with interfaces - hence, in this context we discuss the nature and efficiency of the corresponding thermodynamic cycles leading to work done as a result of a non-uniform distribution of surface tension, which is in turn induced by a non-uniform surface active substance (surfactant) distribution, for both soluble and insoluble surfactants. Based on the relevant physical parameters of the working medium we can also evaluate the isothermality, i.e. temperature variations, dissipative losses, energy output and efficiency, entropy generation, and the period of such cycles in real processes. The role of singularity formation at the interface for the existence of such thermodynamic cycles is unraveled as well. Finally the discussion is concluded with a few ideas for potential applications of Marangoni-driven engines.


Climate change-induced vegetation change as a driver of increased subarctic biogenic volatile organic compound emissions.
Emissions of biogenic volatile organic compounds (BVOCs) have been earlier shown to be highly temperature sensitive in subarctic ecosystems. As these ecosystems experience rapidly advancing pronounced climate warming, we aimed to investigate how warming affects the BVOC emissions in the long term (up to 13 treatment years). We also aimed to assess whether the increased litterfall resulting from the vegetation changes in the warming subarctic would affect the emissions. The study was conducted in a field experiment with factorial open-top chamber warming and annual litter addition treatments on subarctic heath in Abisko, northern Sweden. After 11 and 13 treatment years, BVOCs were sampled from plant communities in the experimental plots using a push-pull enclosure technique and collection into adsorbent cartridges during the growing season and analyzed with gas chromatography-mass spectrometry. Plant species coverage in the plots was analyzed by the point intercept method. Warming by 2 °C caused a 2-fold increase in monoterpene and 5-fold increase in sesquiterpene emissions, averaged over all measurements. When the momentary effect of temperature was diminished by standardization of emissions to a fixed temperature, warming still had a significant effect suggesting that emissions were also indirectly increased. This indirect increase appeared to result from increased plant coverage and changes in vegetation composition. The litter addition treatment also caused significant increases in the emission rates of some BVOC groups, especially when combined with warming. The combined treatment had both the largest vegetation changes and the highest BVOC emissions. The increased emissions under litter addition were probably a result of a changed vegetation composition due to alleviated nutrient limitation and stimulated microbial production of BVOCs. We suggest that the changes in the subarctic vegetation composition induced by climate warming will be the major factor indirectly affecting the BVOC emission potentials and composition.


Serum IL-33 Is a Novel Diagnostic and Prognostic Biomarker in Acute Ischemic Stroke.
Interleukin-33 (IL-33), a newly recognized IL-1 family member, is expressed in various tissues and cells, and involved in pathogenesis of many human diseases. For example, IL-33 plays a protective role in cardiovascular diseases. However, the role of IL-33 in acute ischemic stroke (AIS) remains unclear. This study aims to investigate whether IL-33 level in AIS patient serum can be used as a potential diagnostic and prognostic marker. The study included two hundred and six patients with first-ever ischemic stroke, who were admitted within 72 hours after stroke onset. The serum level of IL-33 was measured with ELISA and the severity of AIS patients on admission was evaluated based on the National Institutes of Health Stroke Scale (NIHSS) score. The functional outcome at 3 months was determined using the Barthel index (BI). We found that serum IL-33 was significantly higher (P < 0.001) in patients with AIS [57.68 ng/L (IQR, 44.95-76.73)] compared with healthy controls [47.48 ng/L (IQR, 38.67-53.78)]. IL-33 was an independent diagnostic biomarker for AIS with an OR of 1.051 (95%Cl, 1.018-1.085; P=0.002). Serum IL-33 was higher (P < 0.05) in the stroke patients with small cerebral infarction volume compared to AIS patients with large cerebral infarction. In addition, serum IL-33 was also significantly higher (P = 0.001) in the patients with mild stroke, compared to the patients with severe stroke. Furthermore, serum IL-33 level in AIS patients with a worse outcome was higher (P < 0.001) compared to AIS patients with a better outcome. IL-33 was also an independent predictor for the functional outcome with an adjusted OR of 0.932 (95% CI, 0.882-0.986). Our results suggest that the lower level of serum IL-33 is associated with large infarction volume and greater stroke severity in AIS patients. Thus, IL-33 can be used as a novel and independent diagnostic and predicting prognostic marker in AIS.


Optogenetic sensors in the zebrafish heart: a novel in vivo electrophysiological tool to study cardiac arrhythmogenesis.
Cardiac arrhythmias are among the most challenging human disorders to diagnose and treat due to their complex underlying pathophysiology. Suitable experimental animal models are needed to study the mechanisms causative for cardiac arrhythmogenesis. To enable in vivo analysis of cardiac cellular electrophysiology with a high spatial and temporal resolution, we generated and carefully validated two zebrafish models, one expressing an optogenetic voltage indicator (chimeric VSFP-butterfly CY) and the other a genetically encoded calcium indicator (GCaMP6f) in the heart. Methods: High-speed epifluorescence microscopy was used to image chimeric VSFP-butterfly CY and GCaMP6f in the embryonic zebrafish heart, providing information about the spatiotemporal patterning of electrical activation, action potential configuration and intracellular Ca2+ dynamics. Plotting VSFP or GCaMP6f signals on a line along the myocardial wall over time facilitated the visualization and analysis of electrical impulse propagation throughout the heart. Administration of drugs targeting the sympathetic nervous system or cardiac ion channels was used to validate sensitivity and kinetics of both zebrafish sensor lines. Using the same microscope setup, we imaged transparent juvenile casper fish expressing GCaMP6f, demonstrating the feasibility of imaging cardiac optogenetic sensors at later stages of development. Results: Isoproterenol slightly increased heart rate, diastolic Ca2+ levels and Ca2+ transient amplitudes, whereas propranolol caused a profound decrease in heart rate and Ca2+ transient parameters in VSFP-Butterfly and GCaMP6f embryonic fish. Ikr blocker E-4031 decreased heart rate and increased action potential duration in VSFP-Butterfly fish. ICa,L blocker nifedipine caused total blockade of Ca2+ transients in GCaMP6f fish and a reduced heart rate, altered ventricular action potential duration and disrupted atrial-ventricular electrical conduction in VSFP-Butterfly fish. Imaging of juvenile animals demonstrated the possibility of employing an older zebrafish model for in vivo cardiac electrophysiology studies. We observed differences in atrial and ventricular Ca2+ recovery dynamics between 3 dpf and 14 dpf casper fish, but not in Ca2+ upstroke dynamics. Conclusion: By introducing the optogenetic sensors chimeric VSFP-butterfly CY and GCaMP6f into the zebrafish we successfully generated an in vivo cellular electrophysiological readout tool for the zebrafish heart. Complementary use of both sensor lines demonstrated the ability to study heart rate, cardiac action potential configuration, spatiotemporal patterning of electrical activation and intracellular Ca2+ homeostasis in embryonic zebrafish. In addition, we demonstrated the first successful use of an optogenetic sensor to study cardiac function in older zebrafish. These models present a promising new research tool to study the underlying mechanisms of cardiac arrhythmogenesis.


Planning for assisted colonization of plants in a warming world.
Assisted colonization is one way of facilitating range shifts for species that are restricted in their ability to move in response to climate change. Here we conceptualize and apply a new decision framework for modelling assisted colonization of plant species prior to in situ realization. Three questions were examined: a) Is species translocation useful in a certain area? b) where, and c) how long will it be successful in the future? Applying our framework to Carex foetida in Italy at the core of its distribution and its southern edge revealed that assisted colonization could be successful in short-term (2010-2039) climate conditions, partially in medium (2040-2069) but not in long-term (2070-2099) scenarios. We show that, for some species, it is likely that assisted colonization would be successful in some portions of the recipient site under current and short-term climate conditions, but over the mid- and long-term, climate changes will make species translocation unsuccessful. The proposed decision framework can help identify species that will need different conservation actions (seed banks and/or botanical gardens) when assisted colonization is unlikely to be successful. Furthermore it has broad applicability, as it can support planning of assisted migration in mountainous areas in the face of climate change.


A qualitative study of primary care professionals' views of case finding for depression in patients with diabetes or coronary heart disease in the UK.
Routinely conducting case finding (also commonly referred to as screening) in patients with chronic illness for depression in primary care appears to have little impact. We explored the views and experiences of primary care nurses, doctors and managers to understand how the implementation of case finding/screening might impact on its effectiveness. Two complementary qualitative focus group studies of primary care professionals including nurses, doctors and managers, in five primary care practices and five Community Health Partnerships, were conducted in Scotland. We identified several features of the way case finding/screening was implemented that may lead to systematic under-detection of depression. These included obstacles to incorporating case finding/screening into a clinical review consultation; a perception of replacing individualised care with mechanistic assessment, and a disconnection for nurses between management of physical and mental health. Far from being a standardised process that encouraged detection of depression, participants described case finding/screening as being conducted in a way which biased it towards negative responses, and for nurses, it was an uncomfortable task for which they lacked the necessary skills to provide immediate support to patients at the time of diagnosis. The introduction of case finding/screening for depression into routine chronic illness management is not straightforward. Routinized case finding/screening for depression can be implemented in ways that may be counterproductive to engagement (particularly by nurses), with the mental health needs of patients living with long term conditions. If case finding/screening or engagement with mental health problems is to be promoted, primary care nurses require more training to increase their confidence in raising and dealing with mental health issues and GPs and nurses need to work collectively to develop the relational work required to promote cognitive participation in case finding/screening.


Selective breeding for a behavioral trait changes digit ratio.
The ratio of the length of the second digit (index finger) divided by the fourth digit (ring finger) tends to be lower in men than in women. This 2D:4D digit ratio is often used as a proxy for prenatal androgen exposure in studies of human health and behavior. For example, 2D:4D ratio is lower (i.e. more "masculinized") in both men and women of greater physical fitness and/or sporting ability. Lab mice have also shown variation in 2D:4D as a function of uterine environment, and mouse digit ratios seem also to correlate with behavioral traits, including daily activity levels. Selective breeding for increased rates of voluntary exercise (wheel running) in four lines of mice has caused correlated increases in aerobic exercise capacity, circulating corticosterone level, and predatory aggression. Here, we show that this selection regime has also increased 2D:4D. This apparent "feminization" in mice is opposite to the relationship seen between 2D:4D and physical fitness in human beings. The present results are difficult to reconcile with the notion that 2D:4D is an effective proxy for prenatal androgen exposure; instead, it may more accurately reflect effects of glucocorticoids, or other factors that regulate any of many genes.


Antibodies to cyclic citrullinated peptides in psoriatic arthritis.
To determine the presence and clinical significance of antibodies to cyclic citrullinated peptides (anti-CCP) in psoriatic arthritis (PsA). We performed a cross-sectional study on 102 outpatients (56 men) with PsA consecutively recruited from a tertiary referral center. Median disease duration was 36 months (interquartile range 21-81). All patients were investigated for peripheral joint and axial involvement, enthesitis, and dactylitis. Laboratory investigations included anti-CCP, assessed by enzyme-linked immunosorbent assay and IgM rheumatoid factor (RF). Plain radiographs of pelvis, wrists, hands, and feet were performed in all cases. Anti-CCP were detected in 16/102 patients, 8/68 with symmetric polyarthritis, 1/8 with asymmetric polyarthritis, 2/20 with mono-oligoarthritis, 1/2 with mutilating arthritis, and 0/4 with exclusive axial or distal interphalangeal (DIP) involvement. The male:female ratio as well as frequency of dactylitis, enthesitis, and nonexclusive axial or DIP joint involvement were similar in the anti-CCP positive and negative groups. Anti-CCP positive patients were more frequently treated with disease modifying antirheumatic drugs and showed higher number of involved joints, and higher frequency of erosive arthritis and positive RF. Using multiple logistic regression, anti-CCP (but not RF) were significantly associated with erosive arthritis (odds ratio 9.8; 95% confidence interval 1.87-51.8) and > or = 10 involved joints (17.99; 3.6-89.2). Anti-CCP can be found in a small but significant proportion of patients with a clinical picture of PsA and are associated with erosive arthritis and multiple joint involvement.


What is a clinical trial protocol?
Trial protocols are documents that describe the objectives, design, methodology, statistical considerations and aspects related to the organization of clinical trials. Trial protocols provide the background and rationale for conducting a study, highlighting specific research questions that are addressed, and taking into consideration ethical issues. Trial protocols must meet a standard that adheres to the principles of Good Clinical Practice, and are used to obtain ethics approval by local Ethics Committees or Institutional Review Boards.


The Challenge of Urban Heat Exposure under Climate Change: An Analysis of Cities in the Sustainable Healthy Urban Environments (SHUE) Database.
The so far largely unabated emissions of greenhouse gases (GHGs) are expected to increase global temperatures substantially over this century. We quantify the patterns of increases for 246 globally-representative cities in the Sustainable Healthy Urban Environments (SHUE) database. We used an ensemble of 18 global climate models (GCMs) run under a low (RCP2.6) and high (RCP8.5) emissions scenario to estimate the increase in monthly mean temperatures by 2050 and 2100 based on 30-year averages. Model simulations were from the Coupled Model Inter-comparison Project Phase 5 (CMIP5). Annual mean temperature increases were 0.93 degrees Celsius by 2050 and 1.10 degrees Celsius by 2100 under RCP2.6, and 1.27 and 4.15 degrees Celsius under RCP8.5, but with substantial city-to-city variation. By 2100, under RCP2.6 no city exceeds an increase in Tmean > 2 degrees Celsius (relative to a 2017 baseline), while all do under RCP8.5, some with increases in Tmean close to, or even greater than, 7 degrees Celsius. The increases were greatest in cities of mid to high latitude, in humid temperate and dry climate regions, and with large seasonal variation in temperature. Cities are likely to experience large increases in hottest month mean temperatures under high GHG emissions trajectories, which will often present substantial challenges to adaptation and health protection.


Different attitudes during breastfeeding consultations when infant formula was given: a phenomenographic approach.
WHO and UNICEF believe that both antenatal and maternity care organizations are in an excellent position to protect and, if necessary, reinstate a culture that promotes breastfeeding, and that they are responsible for doing so. In Sweden, the number of breastfeeding women has been decreasing annually since 1996. Thus the aim of this study is to identify, describe and analyze the attitude midwives have towards the mother, child and breastfeeding when infant formula is given. From the theoretical standpoint of Buber's I-Thou and I-It concept, the different attitudes during breastfeeding consultations are interpreted. By using a phenomenographic approach based on 101 accounts of varying lengths from 39 midwives, different attitudes or approaches were identified. Four different approaches are distinguished in the breastfeeding consultation. The first is the family as a whole, the second is mother and child as separate and equal, the third views the mother as superior and the fourth views the child as superior. The approach of the midwife is related to how she defines the overall perspective of the mother-child relationship and how she looks upon her relationship to the mother-child dyad. Her approach varies depending on whether she meets the mother and child as a subject, similar to herself, or whether she sees one of them as an object. A midwife may also take an outside position, as an object, thus excluding a genuine relationship with the mother. The results also indicate that health care professionals focus on parts of the whole instead of maintaining a holistic perspective.


COVID-19 and missed routine immunizations: designing for effective catch-up in Canada.
COVID-19 has led to disruption in routine immunization programs around the globe and here in Canada. The National Advisory Committee on Immunization (NACI) in Canada has indicated that this sets the stage for serious outbreaks of vaccine-preventable diseases. The World Health Organization has evidence-based guidance on how to address missed opportunities for vaccination, albeit predominately applicable for low- and middle-income countries. In Canada, immunization applies beyond infant and childhood immunization, with immunization across the life course being recommended by NACI. Three components stand out and must be integrated and used concurrently for best effect on catch-up in Canada: (1) Identify who has been missed across the life course; (2) detect delivery gaps, adapt and adjust, and develop multipronged tailored strategies for catch-up; and (3) communicate, document, evaluate and readjust the immunization programs. All must be adapted to the reality of the evolving COVID-19 pandemic. We cannot go back to a pre-COVID-19 world. However, ensuring that routine immunization and catch-up programs are done well during this pandemic strengthens the immunization foundation in Canada for when COVID-19 vaccines become available.


Predictors of dementia misclassification when using brief cognitive assessments.
Brief cognitive assessments can result in false-positive and false-negative dementia misclassification. We aimed to identify predictors of misclassification by 3 brief cognitive assessments; the Mini-Mental State Examination (MMSE), Memory Impairment Screen (MIS) and animal naming (AN). Participants were 824 older adults in the population-based US Aging, Demographics and Memory Study with adjudicated dementia diagnosis (DSM-III-R and DSM-IV criteria) as the reference standard. Predictors of false-negative, false-positive and overall misclassification by the MMSE (cut-point <24), MIS (cut-point <5) and AN (cut-point <9) were analysed separately in multivariate bootstrapped fractional polynomial regression models. Twenty-two candidate predictors included sociodemographics, dementia risk factors and potential sources of test bias. Misclassification by at least one assessment occurred in 301 (35.7%) participants, whereas only 14 (1.7%) were misclassified by all 3 assessments. There were different patterns of predictors for misclassification by each assessment. Years of education predicts higher false-negatives (odds ratio [OR] 1.23, 95% confidence interval [95% CI] 1.07-1.40) and lower false-positives (OR 0.77, 95% CI 0.70-0.83) by the MMSE. Nursing home residency predicts lower false-negatives (OR 0.15, 95% CI 0.03-0.63) and higher false-positives (OR 4.85, 95% CI 1.27-18.45) by AN. Across the assessments, false-negatives were most consistently predicted by absence of informant-rated poor memory. False-positives were most consistently predicted by age, nursing home residency and non-Caucasian ethnicity (all p < 0.05 in at least 2 models). The only consistent predictor of overall misclassification across all assessments was absence of informant-rated poor memory. Dementia is often misclassified when using brief cognitive assessments, largely due to test specific biases.


Identification of a putative nuclear localization sequence within ANG II AT(1A) receptor associated with nuclear activation.
Angiotensin II (ANG II) type 1 (AT(1)) receptors, similar to other G protein-coupled receptors, undergo desensitization and internalization, and potentially nuclear localization, subsequent to agonist interaction. Evidence suggests that the carboxy-terminal tail may be involved in receptor nuclear localization. In the present study, we examined the carboxy-terminal tail of the receptor for specific regions responsible for the nuclear translocation phenomenon and resultant nuclear activation. Human embryonic kidney cells stably expressing either a wild-type AT(1A) receptor-green fluorescent protein (AT(1A)R/GFP) construct or a site-directed mutation of a putative nuclear localization sequence (NLS) [K307Q]AT(1A)R/GFP (KQ/AT(1A)R/GFP), were examined for differences in receptor nuclear trafficking and nuclear activation. Receptor expression, intracellular signaling, and ANG II-induced internalization of the wild-type/GFP construct and of the KQ/AT(1A)R/GFP mutant was similar. Laser scanning confocal microscopy showed that in cells expressing the AT(1A)R/GFP, trafficking of the receptor to the nuclear area and colocalization with lamin B occurred within 30 min of ANG II (100 nM) stimulation, whereas the KQ/AT(1A)R/GFP mutant failed to demonstrate nuclear localization. Immunoblotting of nuclear lysates with an anti-GFP antibody confirmed these observations. Nuclear localization of the wild-type receptor correlated with increase transcription for both EGR-1 and PTGS-2 genes while the nuclear-deficient KQ/AT(1A)R/GFP mutant demonstrated increases for only the EGR-1 gene. These results suggest that a NLS (KKFKKY; aa307-312) is located within the cytoplasmic tail of the AT(1A) receptor and that nuclear localization of the receptor corresponds with specific activation of transcription for the COX-2 gene PTGS-2.


Massachusetts health reform and disparities in coverage, access and health status.
Massachusetts health reform has achieved near-universal insurance coverage, yet little is known about the effects of this legislation on disparities. Since racial/ethnic minorities and low-income individuals are over-represented among the uninsured, we assessed the effects of health reform on disparities. Cross-sectional survey data from the Behavioral Risk Factor Surveillance Survey (BRFSS), 2006-2008. Adults from Massachusetts (n = 36,505) and other New England states (n = 63,263). Self-reported health coverage, inability to obtain care due to cost, access to a personal doctor, and health status. To control for trends unrelated to reform, we compared adults in Massachusetts to those in all other New England states using multivariate logistic regression models to calculate adjusted predicted probabilities. Overall, the adjusted predicted probability of health coverage in Massachusetts rose from 94.7% in 2006 to 97.7% in 2008, whereas coverage in New England remained around 92% (p < 0.001 for difference-in-difference). While cost-related barriers were reduced in Massachusetts, there were no improvements in access to a personal doctor or health status. Although there were improvements in coverage and cost-related barriers for some disadvantaged groups relative to trends in New England, there was no narrowing of disparities in large part because of comparable or larger improvements among whites and the non-poor. Achieving equity in health and health care may require additional focused intervention beyond health reform.


Sickle erythrocyte-endothelial interactions in microcirculation: the role of von Willebrand factor and implications for vasoocclusion.
To determine the role of von Willebrand factor (vWF) in adhesion of sickle (SS) erythrocytes in microvascular flow conditions, we have perfused the ex vivo mesocecum vasculature of the rat with desmopressin, an analogue of vasopressin that causes the release of endothelial vWF. Analysis of vWF in the venous effluent of the isolated vasculature showed mainly the presence of extra-large molecular weight forms characteristic of endothelial vWF, which in the presence of desmopressin showed an average increase of 54%. Also, desmopressin induced a significant increase in adhesion of washed oxygenated (oxy) unseparated SS erythrocytes, accompanied by a persistent microvascular obstruction and a pronounced increase in the peripheral resistance (PRU). In contrast, infusion of SS deformable discocytes (SS2) in desmopressin-perfused vasculature resulted in a significant adhesion but not in persistent vasoocclusion, showing that SS2 discocytes alone are not sufficient for microvascular obstruction. Furthermore, SS4 erythrocytes (dense discocytes and irreversibly sickled erythrocytes) caused a persistent microvascular blockage and a significantly higher PRU than SS2 discocytes. However, the increase in PRU for SS4 erythrocytes following desmopressin treatment was 50% less compared with a corresponding increase for SS2 discocytes over the control values, which showed a smaller effect of desmopressin on the hemodynamic behavior of SS4 dense erythrocytes. Incubation of desmopressin-treated vasculature with anti-vWF antibodies resulted in a pronounced decrease in adhesion and significantly improved hemodynamic behavior of SS cells. Also, in untreated vasculature, similarly incubated with anti-vWF antibodies, there was almost complete inhibition of adhesion. Under the described perfusion conditions, antibodies to fibronectin and thrombospondin, as well as incubation of SS erythrocytes with anti-vWF antibodies did not affect adhesion. These results are compatible with a model for SS vasoocclusion in which extra-large vWF-mediated adhesion of deformable SS erythrocytes is the first step followed by an accelerated entrapment of dense SS erythrocytes.


Demonstration of an E-mailed worksite nutrition intervention program.
Dietary fat and low fruit and vegetable intake are linked to many chronic diseases, and U.S. population intake does not meet recommendations. Interventions are needed that incorporate effective behavior-change principles and that can be delivered inexpensively to large segments of the population. Employees at a corporate worksite were invited to participate in a program, delivered entirely by e-mail, to reduce dietary fat and increase fruit and vegetable intake. Behavior-change principles underlying the intervention included tailoring to the participant's dietary lifestyle, baseline assessment and feedback about dietary intake, family participation, and goal setting. Assessment, tailoring, and delivery was fully automated. The program was delivered weekly to participants' e-mail inboxes for 12 weeks. Each e-mail included information on nutrition or on the relationship between diet and health, dietary tips tailored to the individual, and small goals to try for the next week. In this nonrandomized pilot study, we assessed technical feasibility, acceptability to employees, improvement in Stage of Change, increase in fruit and vegetable consumption, and decrease in fat intake. Approximately one third (n = 84) of employees who were offered the 12-week program signed up for it, and satisfaction was high. There was significant improvement in Stage of Change: 74% of those not already at the top had forward movement (P < .001). In addition, results suggest significant increase in fruit and vegetable consumption (0.73 times/day, P < .001) and significant decrease in intake of fat sources (-0.39 times/day, P < .001). This inexpensive program is feasible and appears to be effective. A randomized controlled trial is needed.


Characterizing Articulation in Apraxic Speech Using Real-Time Magnetic Resonance Imaging.
Real-time magnetic resonance imaging (MRI) and accompanying analytical methods are shown to capture and quantify salient aspects of apraxic speech, substantiating and expanding upon evidence provided by clinical observation and acoustic and kinematic data. Analysis of apraxic speech errors within a dynamic systems framework is provided and the nature of pathomechanisms of apraxic speech discussed. One adult male speaker with apraxia of speech was imaged using real-time MRI while producing spontaneous speech, repeated naming tasks, and self-paced repetition of word pairs designed to elicit speech errors. Articulatory data were analyzed, and speech errors were detected using time series reflecting articulatory activity in regions of interest. Real-time MRI captured two types of apraxic gestural intrusion errors in a word pair repetition task. Gestural intrusion errors in nonrepetitive speech, multiple silent initiation gestures at the onset of speech, and covert (unphonated) articulation of entire monosyllabic words were also captured. Real-time MRI and accompanying analytical methods capture and quantify many features of apraxic speech that have been previously observed using other modalities while offering high spatial resolution. This patient's apraxia of speech affected the ability to select only the appropriate vocal tract gestures for a target utterance, suppressing others, and to coordinate them in time.


Formation of Nanofoam carbon and re-emergence of Superconductivity in compressed CaC6.
Pressure can tune material's electronic properties and control its quantum state, making some systems present disconnected superconducting region as observed in iron chalcogenides and heavy fermion CeCu2Si2. For CaC6 superconductor (Tc of 11.5 K), applying pressure first Tc increases and then suppresses and the superconductivity of this compound is eventually disappeared at about 18 GPa. Here, we report a theoretical finding of the re-emergence of superconductivity in heavily compressed CaC6. The predicted phase III (space group Pmmn) with formation of carbon nanofoam is found to be stable at wide pressure range with a Tc up to 14.7 K at 78 GPa. Diamond-like carbon structure is adhered to the phase IV (Cmcm) for compressed CaC6 after 126 GPa, which has bad metallic behavior, indicating again departure from superconductivity. Re-emerged superconductivity in compressed CaC6 paves a new way to design new-type superconductor by inserting metal into nanoporous host lattice.


Yellow fever virus maintenance in Trinidad and its dispersal throughout the Americas.
Trinidad, like many other American regions, experiences repeated epizootics of yellow fever virus (YFV). However, it is unclear whether these result from in situ evolution (enzootic maintenance) or regular reintroduction of YFV from the South American mainland. To discriminate between these hypotheses, we carried out a Bayesian phylogeographic analysis of over 100 prM/E gene sequences sampled from 8 South American countries. These included newly sequenced isolates from the recent 2008-2009 Trinidad epizootic and isolates derived from mainland countries within the last decade. The results indicate that the most recent common ancestor of the 2008-2009 epizootic existed in Trinidad 4.2 years prior to 2009 (95% highest probability density [HPD], 0.5 to 9.0 years). Our data also suggest a Trinidad origin for the progenitor of the 1995 Trinidad epizootic and support in situ evolution of YFV between the 1979 and 1988-1989 Trinidad epizootics. Using the same phylogeographic approach, we also inferred the historical spread of YFV in the Americas. The results suggest a Brazilian origin for YFV in the Americas and an overall dispersal rate of 182 km/year (95% HPD, 52 to 462 km/year), with Brazil as the major source population for surrounding countries. There is also strong statistical support for epidemiological links between four Brazilian regions and other countries. In contrast, while there were well-supported epidemiological links within Peru, the only statistically supported external link was a relatively weak link with neighboring Bolivia. Lastly, we performed a complete analysis of the genome of a newly sequenced Trinidad 2009 isolate, the first complete genome for a genotype I YFV isolate.


Influence of core-finishing intervals on tensile strength of cast posts-and-cores luted with zinc phosphate cement.
The core finishing of cast posts-and-cores after luting is routine in dental practice. However, the effects of the vibrations produced by the rotary cutting instruments over the luting cements are not well-documented. This study evaluated the influence of the time intervals that elapsed between the cementation and the core-finishing procedures on the tensile strength of cast posts-and-cores luted with zinc phosphate cement. Forty-eight bovine incisor roots were selected, endodontically treated, and divided into four groups (n = 12): GA, control (without finishing); GB, GC, and GD, subjected to finishing at 20 minutes, 60 minutes, and 24 hours after cementation, respectively. Root canals were molded, and the resin patterns were cast in copper-aluminum alloy. Cast posts-and-cores were luted with zinc phosphate cement, and the core-finishing procedures were applied according to the groups. The tensile tests were performed at a crosshead speed of 0.5 mm/min for all groups, 24 hours after the core-finishing procedures. The data were subjected to one-way analysis of variance (ANOVA) and Tukey's test (α = 0.05). No significant differences were observed in the tensile strengths between the control and experimental groups, regardless of the time interval that elapsed between the luting and finishing steps. Within the limitations of the present study, it was demonstrated that the core-finishing procedures and time intervals that elapsed after luting did not appear to affect the retention of cast posts-and-cores when zinc phosphate cement was used.


Increased mortality associated with the early coagulopathy of trauma in combat casualties.
Recent civilian studies have documented a relationship between increased mortality and the presence of an early coagulopathy of trauma diagnosed in the emergency department (ED). We hypothesized that acute coagulopathy (international normalized ratio >/=1.5) in combat casualties was associated with increased injury severity and mortality as is seen in civilian trauma patients. A retrospective study of combat casualties who received a blood transfusion at a single combat support hospital between September 2003 and December 2004 was performed. Coagulation status, pH, base deficit, and temperature were recorded at arrival to the ED. These were analyzed by Injury Severity Score (ISS), associated injury patterns, and mortality. A total of 3,287 patients were treated at the combat support hospital during the study period. Of these, 391 patients were transfused and primarily admitted, thus meeting the study criteria, 347 had coagulation data, and 92% had a penetrating mechanism. The prevalence of acute coagulopathy in transfused casualties measured with point-of-care devices at arrival in the ED was 38%. Mortality in those who were coagulopathic at arrival to the ED was 24% (32/133) versus 4% (8/214) in those not presenting with coagulopathy (p < 0.001). The prevalence of mortality by coagulopathy increased as ISS increased. Coagulopathy and acidosis were associated with mortality, odds ratio (OR), 5.38 [95% confidence interval (CI), 1.55-11.37] and 6.9 (95% CI, 2.1-19.5), respectively. Temperature did not affect outcomes (OR, 1.1; 95% CI, 0.4-2.6). The early coagulopathy of trauma was rapidly diagnosed in the ED and present in more than one-third of combat casualties who received a transfusion, similar to the incidence found in civilian trauma patients. Coagulopathy, independent of hypothermia but strongly correlated with acidosis and ISS, was associated with mortality in combat casualties, similar to that found in civilian trauma patients. Early diagnosis and treatment of acute traumatic coagulopathy with new resuscitation paradigms may improve outcomes.


A novel Pseudomonas aeruginosa bacteriophage, Ab31, a chimera formed from temperate phage PAJU2 and P. putida lytic phage AF: characteristics and mechanism of bacterial resistance.
A novel temperate bacteriophage of Pseudomonas aeruginosa, phage vB_PaeP_Tr60_Ab31 (alias Ab31) is described. Its genome is composed of structural genes related to those of lytic P. putida phage AF, and regulatory genes similar to those of temperate phage PAJU2. The virion structure resembles that of phage AF and other lytic Podoviridae (S. enterica Epsilon 15 and E. coli phiv10) with similar tail spikes. Ab31 was able to infect P. aeruginosa strain PA14 and two genetically related strains called Tr60 and Tr162, out of 35 diverse strains from cystic fibrosis patients. Analysis of resistant host variants revealed different phenotypes, including induction of pigment and alginate overproduction. Whole genome sequencing of resistant variants highlighted the existence of a large deletion of 234 kbp in two strains, encompassing a cluster of genes required for the production of CupA fimbriae. Stable lysogens formed by Ab31 in strain Tr60, permitted the identification of the insertion site. During colonization of the lung in cystic fibrosis patients, P. aeruginosa adapts by modifying its genome. We suggest that bacteriophages such as Ab31 may play an important role in this adaptation by selecting for bacterial characteristics that favor persistence of bacteria in the lung.


itMatters: Optimization of an online intervention to prevent sexually transmitted infections in college students.
ObjectiveTo describe an iterative approach to developing an online intervention targeting the intersection of alcohol use and sexual behaviors among first year college students. Methods and Participants: Using the multiphase optimization strategy (MOST), we conducted two iterative optimization trials to: (1) identify candidate intervention components (i.e., descriptive norms, injunctive norms, outcome expectancies, perceived benefits of protective behavioral strategies, and self-efficacy to use strategies); (2) revise components; and (3) identify the optimized intervention. Participants were first year college students at six geographically diverse universities (optimization trial 1 N = 5,880; optimization trial 2 N = 3,551) Results: For both optimization trials, the results indicated that only descriptive and injunctive norms produced a significant effect (p<.05). Conclusions: The iterative process of MOST allowed us to develop an optimized intervention which is an essential tool to maximize intervention effectiveness and efficiency to improve uptake, sustainability, and public health impact.


No clear effect of admixture between two European invading outbreaks of Diabrotica virgifera virgifera in natura.
In this study, we challenged the hypothesis that admixture may have had a positive impact in the context of the European invasion of the western corn rootworm (WCR), Diabrotica virgifera virgifera, LeConte. This beetle was introduced in Europe from the USA several times since the 1980's. The multiple introductions of this major pest of cultivated corn led to the formation of two major outbreaks in North Western (NW) Italy and in Central and South Eastern (CSE) Europe that eventually merged into a secondary contact zone where insects from both outbreaks interbreed. We collected about 600 insects from this contact zone and genotyped them using 13 microsatellite markers. Three types of information were obtained from the collected individuals: (i) their survival under starvation; (ii) their admixed status, determined through a Bayesian method of genetic clustering and (iii) their mating probability, studied via the detection, isolation and genotyping of sperm in female spermathecae. Twenty six % and 12% of the individuals were assigned to the NW Italy or the CSE Europe parental types, respectively, and 23% and 39% to the F1 and backcross hybrid types, respectively. Globally, our results do not reveal any significant impact of the admixed status on the mating probability and on the choice of mating partners. However the admixed status had a sex- and sampling site-dependent effect on survival in adults under starvation. In addition sex had an effect on survival, with mortality hazard about 3 times larger in males than in females. The consequences of these findings for the evolution of the admixture zone of northern Italy are discussed.


Enhancing optical absorption of metal-organic frameworks for improved visible light photocatalysis.
NH2-MIL-125(Ti) has been post-synthetically functionalized with dye-like molecular fragments. The new material (methyl red-MIL-125(Ti)) exhibits improved light absorption over a wide range of the visible spectrum, and shows enhanced photocatalytic oxidation activity under visible light illumination. The consequences of functionalization and the bottlenecks in MOF photochemistry are studied in detail.


Excess dietary carbohydrate affects mitochondrial integrity as observed in brown adipose tissue.
Hyperglycemia affects over 400 million individuals worldwide. The detrimental health effects are well studied at the tissue level, but the in vivo effects at the organelle level are poorly understood. To establish such an in vivo model, we used mice lacking TXNIP, a negative regulator of glucose uptake. Examining mitochondrial function in brown adipose tissue, we find that TXNIP KO mice have a lower content of polyunsaturated fatty acids (PUFAs) in their membrane lipids, which affects mitochondrial integrity and electron transport chain efficiency and ultimately results in lower mitochondrial heat output. This phenotype can be rescued by a ketogenic diet, confirming the usefulness of this model and highlighting one facet of early cellular damage caused by excess glucose influx.


Kin selection and the evolution of sexual conflict.
Males and females do not always share the same evolutionary interests. This is particularly true in the case of multiple mating, where male-male competition can often lead to adaptations that are harmful to the female, and females can evolve counter adaptations to reduce the benefits males gain from such traits. Although social evolution has made substantial progress from kin selection theory, most studies of sexual conflict have ignored the effects of genetic relatedness. Here, I use a model of male harm and female resistance to investigate how kin selection affects the evolution of sexual conflict. Building on models of social evolution, I show that relatedness inhibits sexual conflict, in terms of male harm, whereas it has no effect on the evolution female resistance. This study examines a previously neglected mechanism that can potentially help to resolve sexual conflict over mating and highlights the potential importance of considering relatedness in empirical studies of sexual conflict.


Topical and peripherally acting analgesics.
Acute nociceptive, inflammatory, and neuropathic pain all depend to some degree on the peripheral activation of primary sensory afferent neurons. The localized peripheral administration of drugs, such as by topical application, can potentially optimize drug concentrations at the site of origin of the pain, while leading to lower systemic levels and fewer adverse systemic effects, fewer drug interactions, and no need to titrate doses into a therapeutic range compared with systemic administration. Primary sensory afferent neurons can be activated by a range of inflammatory mediators such as prostanoids, bradykinin, ATP, histamine, and serotonin, and inhibiting their actions represents a strategy for the development of analgesics. Peripheral nerve endings also express a variety of inhibitory neuroreceptors such as opioid, alpha-adrenergic, cholinergic, adenosine and cannabinoid receptors, and agonists for these receptors also represent viable targets for drug development. At present, topical and other forms of peripheral administration of nonsteroidal anti-inflammatory drugs, opioids, capsaicin, local anesthetics, and alpha-adrenoceptor agonists are being used in a variety of clinical states. There also are some clinical data on the use of topical antidepressants and glutamate receptor antagonists. There are preclinical data supporting the potential for development of local formulations of adenosine agonists, cannabinoid agonists, cholinergic ligands, cytokine antagonists, bradykinin antagonists, ATP antagonists, biogenic amine antagonists, neuropeptide antagonists, and agents that alter the availability of nerve growth factor. Given that activation of sensory neurons involves multiple mediators, combinations of agents targeting different mechanisms may be particularly useful. Topical analgesics represent a promising area for future drug development.


A Population Phylogenetic View of Mitochondrial Heteroplasmy.
The mitochondrion has recently emerged as an active player in myriad cellular processes. Additionally, it was recently shown that >200 diseases are known to be linked to variants in mitochondrial DNA or in nuclear genes interacting with mitochondria. This has reinvigorated interest in its biology and population genetics. Mitochondrial heteroplasmy, or genotypic variation of mitochondria within an individual, is now understood to be common in humans and important in human health. However, it is still not possible to make quantitative predictions about the inheritance of heteroplasmy and its proliferation within the body, partly due to the lack of an appropriate model. Here, we present a population-genetic framework for modeling mitochondrial heteroplasmy as a process that occurs on an ontogenetic phylogeny, with genetic drift and mutation changing heteroplasmy frequencies during the various developmental processes represented in the phylogeny. Using this framework, we develop a Bayesian inference method for inferring rates of mitochondrial genetic drift and mutation at different stages of human life. Applying the method to previously published heteroplasmy frequency data, we demonstrate a severe effective germline bottleneck comprised of the cumulative genetic drift occurring between the divergence of germline and somatic cells in the mother, and the separation of germ layers in the offspring. Additionally, we find that the two somatic tissues we analyze here undergo tissue-specific bottlenecks during embryogenesis, less severe than the effective germline bottleneck, and that these somatic tissues experience little additional genetic drift during adulthood. We conclude with a discussion of possible extensions of the ontogenetic phylogeny framework and its possible applications to other ontogenetic processes in addition to mitochondrial heteroplasmy.


Loss of myogenin in postnatal life leads to normal skeletal muscle but reduced body size.
Although the mechanisms regulating the formation of embryonic skeletal muscle in vertebrates are well characterized, less is known about postnatal muscle formation even though the largest increases in skeletal muscle mass occur after birth. Adult muscle stem cells (satellite cells) appear to recapitulate the events that occur in embryonic myoblasts. In particular, the myogenic basic helix-loop-helix factors, which have crucial functions in embryonic muscle development, are assumed to have similar roles in postnatal muscle formation. Here, we test this assumption by determining the role of the myogenic regulator myogenin in postnatal life. Because Myog-null mice die at birth, we generated mice with floxed alleles of Myog and mated them to transgenic mice expressing Cre recombinase to delete Myog before and after embryonic muscle development. Removing myogenin before embryonic muscle development resulted in myofiber deficiencies identical to those observed in Myog-null mice. However, mice in which Myog was deleted following embryonic muscle development had normal skeletal muscle, except for modest alterations in the levels of transcripts encoding Mrf4 (Myf6) and Myod1 (MyoD). Notably, Myog-deleted mice were 30% smaller than control mice, suggesting that the absence of myogenin disrupted general body growth. Our results suggest that postnatal skeletal muscle growth is controlled by mechanisms distinct from those occurring in embryonic muscle development and uncover an unsuspected non-cell autonomous role for myogenin in the regulation of tissue growth.


The rise of the hominids as an adaptive shift in fallback foods: plant underground storage organs (USOs) and australopith origins.
We propose that a key change in the evolution of hominids from the last common ancestor shared with chimpanzees was the substitution of plant underground storage organs (USOs) for herbaceous vegetation as fallback foods. Four kinds of evidence support this hypothesis: (1) dental and masticatory adaptations of hominids in comparison with the African apes; (2) changes in australopith dentition in the fossil record; (3) paleoecological evidence for the expansion of USO-rich habitats in the late Miocene; and (4) the co-occurrence of hominid fossils with root-eating rodents. We suggest that some of the patterning in the early hominid fossil record, such as the existence of gracile and robust australopiths, may be understood in reference to this adaptive shift in the use of fallback foods. Our hypothesis implicates fallback foods as a critical limiting factor with far-reaching evolutionary effects. This complements the more common focus on adaptations to preferred foods, such as fruit and meat, in hominid evolution.


Analgesic Effects of Locally Administered Ketorolac-based Analgesics After Breast Surgery: A Meta-Analysis of Randomized Controlled Trials.
Reducing postoperative pain following breast surgery is crucial for rapid recovery and shortening hospital stay. Ketorolac, a nonsteroidal anti-inflammatory drug, has been used as a postoperative analgesic in many surgical procedures. We conducted a systemic review and meta-analysis on the efficacy of locally administered ketorolac-based analgesics in managing pain after breast surgery. We searched the PubMed, Embase, Cochrane Library, Scopus, and ClinicalTrials.gov registry for randomized control trials (RCTs) published up to September 2016. The primary outcome was pain level assessed using a visual analog scale (VAS) at 1 and 6 hours following breast surgery. We reviewed 4 RCTs with 255 patients. For meta-analysis, VAS at 1 and 6 hours of 3 similar RCTs were compared. At 1 hour, VAS scores were significantly lower in patients administered a ketorolac solution [weighted mean difference (WMD)=-2.04; 95% confidence interval (CI): -3.08 to -1.00] or ketorolac-bupivacaine solution (WMD=-2.30; 95% CI, -4.07 to -0.54) than in controls. At 6 hours, the ketorolac-bupivacaine solution reduced VAS scores significantly (WMD=-1.40; 95% CI, -2.48 to -0.32) compared with controls. However, at 1 hour, the ketorolac solution was significantly more effective than the bupivacaine solution was (WMD=-1.70; 95% CI, -2.81 to -0.59). The effects of ketorolac-based analgesics vary as per the surgery and disease type. Locally administered ketorolac-based analgesics decreased postoperative pain in breast surgery patients, and the effect of local ketorolac was better than local bupivacaine. Therefore, ketorolac-based analgesics demonstrate considerable local infiltration during pain management after breast surgery.


Low-loss asymptotically single-mode propagation in large-core OmniGuide fibers.
We present the light-propagation characteristics of OmniGuide fibers, which guide light by concentric multi-layer dielectric mirrors having the property of omnidirectional reflection. We show how the lowest-loss TE_01 mode can propagate in a single-mode fashion through even large-core fibers, with other modes eliminated asymptotically by their higher losses and poor coupling, analogous to hollow metallic microwave waveguides. Dispersion, radiation leakage, material absorption, nonlinearities, bending, acircularity, and interface roughness are considered with the help of leaky modes and perturbation theory, and both numerical results and general scaling relations are presented. We show that cladding properties such as absorption and nonlinearity are suppressed by many orders of magnitude due to the strong confinement in a hollow core, and other imperfections are tolerable, promising that the properties of silica fibers may be surpassed even when nominally poor materials are employed.


APOE ε4 and the associations of seafood and long-chain omega-3 fatty acids with cognitive decline.
To examine the association between consumption of seafood and long-chain n-3 fatty acids with change in 5 cognitive domains over an average of 4.9 years. From an ongoing longitudinal, community-based epidemiologic study of aging and dementia (the Rush Memory and Aging Project), we included 915 participants (age 81.4 ± 7.2 years, 25% men) who had completed at least one follow-up cognitive assessment and dietary data. Diet was assessed by semiquantitative food frequency questionnaire. Scores for global cognitive function and 5 cognitive domains (episodic, semantic, and working memory, perceptual speed, and visuospatial ability) were assessed using 19 cognitive tests. Mixed models adjusted for multiple risk factors of cognitive change were used to assess the associations. Consumption of seafood was associated with slower decline in semantic memory (β = 0.024; p = 0.03) and perceptual speed (β = 0.020; p = 0.05) in separate models adjusted for age, sex, education, participation in cognitive activities, physical activity, alcohol consumption, smoking, and total energy intake. In secondary analyses, APOE ε4 carriers demonstrated slower rates of decline in global cognition and in multiple cognitive domains with weekly seafood consumption and with moderate to high long-chain n-3 fatty acid intake from food. These associations were not present in APOE ε4 noncarriers. Higher intake levels of α-linolenic acid were associated with slower global cognitive decline, but also only in APOE ε4 carriers. These results suggest protective relations of one meal per week of seafood and long-chain n-3 fatty acids against decline in multiple cognitive domains. The role of APOE ε4 in this association needs further study.


Long Term Hippocampal and Cortical Changes Induced by Maternal Deprivation and Neonatal Leptin Treatment in Male and Female Rats.
Maternal deprivation (MD) during neonatal life has diverse long-term behavioral effects and alters the development of the hippocampus and frontal cortex, with several of these effects being sexually dimorphic. MD animals show a marked reduction in their circulating leptin levels, not only during the MD period, but also several days later (PND 13). A neonatal leptin surge occurs in rodents (beginning around PND 5 and peaking between PND 9 and 10) that has an important neurotrophic role. We hypothesized that the deficient neonatal leptin signaling of MD rats could be involved in the altered development of their hippocampus and frontal cortex. Accordingly, a neonatal leptin treatment in MD rats would at least in part counteract their neurobehavioural alterations. MD was carried out in Wistar rats for 24 h on PND 9. Male and female MD and control rats were treated from PND 9 to 13 with rat leptin (3 mg/kg/day sc) or vehicle. In adulthood, the animals were submitted to the open field, novel object memory test and the elevated plus maze test of anxiety. Neuronal and glial population markers, components of the glutamatergic and cannabinoid systems and diverse synaptic plasticity markers were evaluated by PCR and/or western blotting. Main results include: 1) In some of the parameters analyzed, neonatal leptin treatment reversed the effects of MD (eg., mRNA expression of hippocampal IGF1 and protein expression of GFAP and vimentin) partially confirming our hypothesis; 2) The neonatal leptin treatment, per se, exerted a number of behavioral (increased anxiety) and neural effects (eg., expression of the following proteins: NG2, NeuN, PSD95, NCAM, synaptophysin). Most of these effects were sex dependent. An adequate neonatal leptin level (avoiding excess and deficiency) appears to be necessary for its correct neuro-programing effect.


Modulation of small GTPases by Legionella.
The pathogenic bacterium Legionella pneumophila interacts intimately with signaling molecules during the infection of eukaryotic host cells. Among a diverse set of regulatory molecules, host small GTPases appear to be prominent and significant targets. Small GTPases are molecular switches that regulate cellular signaling via their respective nucleotide-bound states: When bound to GDP, they are inactive, but become activated upon binding to GTP. Legionella secretes specific bacterial proteins into the cytosol of the host cell that most prominently modulate the activities of small GTPases involved in vesicular trafficking, but probably also other G-proteins. The master regulators of vesicular trafficking, i.e., Rab and Arf proteins, are majorly targeted G-proteins of Legionella proteins, and among these, Rab1 experiences the most diverse modifications. Generally, the activities of small GTPases are modulated by GDP/GTP exchange (activation), GTP hydrolysis (deactivation), membrane recruitment, post-translational modifications (phosphocholination, adenylylation), and tight and competitive binding. Here, we discuss the consequences and molecular details of the modulation of small GTPases for the infection by Legionella, with a special but not exclusive focus on Rab and Arf proteins.


Primary pericardial tumors.
Primary pericardial tumors are rare and may be classified as benign or malignant. The most common benign lesions are pericardial cysts and lipomas. Mesothelioma is the most common primary malignant pericardial neoplasm. Other malignant tumors include a wide variety of sarcomas, lymphoma, and primitive neuroectodermal tumor. When present, signs and symptoms are generally nonspecific. Patients often present with dyspnea, chest pain, palpitations, fever, or weight loss. Although the imaging approach usually begins with plain radiography of the chest or transthoracic echocardiography, the value of these imaging modalities is limited. Cross-sectional imaging, on the other hand, plays a key role in the evaluation of these lesions. Computed tomography and magnetic resonance imaging allow further characterization and may, in some cases, provide diagnostic findings. Furthermore, the importance of cross-sectional imaging lies in assessing the exact location of the tumor in relation to neighboring structures. Both benign and malignant tumors may result in compression of vital mediastinal structures. Malignant lesions may also directly invade structures, such as the myocardium and great vessels, and result in metastatic disease. Imaging plays an important role in the detection, characterization, and staging of pericardial tumors; in their treatment planning; and in the posttreatment follow-up of affected patients. The prognosis of patients with benign tumors is good, even in the few cases in which surgical intervention is required. On the other hand, the length of survival for patients with malignant pericardial tumors is, in the majority of cases, dismal.


Preoperative Warming Versus no Preoperative Warming for Maintenance of Normothermia in Women Receiving Intrathecal Morphine for Cesarean Delivery: A Single-Blinded, Randomized Controlled Trial.
Rates of hypothermia for women undergoing spinal anesthesia for cesarean delivery are high and prevention is desirable. This trial compared the effectiveness of preoperative warming versus usual care among women receiving intrathecal morphine, which is thought to exacerbate perioperative heat loss. A prospective, single-blinded, randomized controlled trial compared 20 minutes of forced air warming (plus intravenous fluid warming) versus no active preoperative warming (plus intravenous fluid warming) in 50 healthy American Society of Anesthesiologists graded II women receiving intrathecal morphine as part of spinal anesthesia for elective cesarean delivery. The primary outcome of maternal temperature change was assessed via aural canal and bladder temperature measurements at regular intervals. Secondary outcomes included maternal thermal comfort, shivering, mean arterial pressure, agreement between aural temperature, and neonatal outcomes (axillary temperature at birth, Apgar scores, breastfeeding, and skin-to-skin contact). The intention-to-treat population was analyzed with descriptive statistics, general linear model analysis, linear mixed-model analysis, χ test of independence, Mann-Whitney, and Bland-Altman analysis. Full ethical approval was obtained, and the study was registered on the Australia and New Zealand Clinical Trials Registry (Trial No: 367160, registered at http://www.ANZCTR.org.au/). Intention-to-treat analysis (n = 50) revealed no significant difference in aural temperature change from baseline to the end of the procedure between groups: F (1, 47) = 1.2, P = .28. There were no other statistically significant differences between groups in any of the secondary outcomes. A short period of preoperative warming is not effective in preventing intraoperative temperature decline for women receiving intrathecal morphine. A combination of preoperative and intraoperative warming modalities may be required for this population.


Renal cell-expressed TNF receptor 2, not receptor 1, is essential for the development of glomerulonephritis.
TNF is essential for the development of glomerulonephritis, an immune-mediated disorder that is a major cause of renal failure worldwide. However, TNF has proinflammatory and immunosuppressive properties that may segregate at the level of the 2 TNF receptors (TNFRs), TNFR1 and TNFR2. TNFR1-deficient mice subjected to immune complex-mediated glomerulonephritis developed less proteinuria and glomerular injury, and fewer renal leukocyte infiltrates at early time points after disease induction, and this was associated with a reduced systemic immune response to nephrotoxic rabbit IgG. However, proteinuria and renal pathology were similar to those in wild-type controls at later time points, when lack of TNFR1 resulted in excessive renal T cell accumulation and an associated reduction in apoptosis of these cells. In sharp contrast, TNFR2-deficient mice were completely protected from glomerulonephritis at all time points, despite an intact systemic immune response. TNFR2 was induced on glomerular endothelial cells of nephritic kidneys, and TNFR2 expression on intrinsic cells, but not leukocytes, was essential for glomerulonephritis and glomerular complement deposition. Thus, TNFR1 promotes systemic immune responses and renal T cell death, while intrinsic cell TNFR2 plays a critical role in complement-dependent tissue injury. Therefore, therapeutic blockade specifically of TNFR2 may be a promising strategy in the treatment of immune-mediated glomerulonephritis.


Sequencing of Culex quinquefasciatus establishes a platform for mosquito comparative genomics.
Culex quinquefasciatus (the southern house mosquito) is an important mosquito vector of viruses such as West Nile virus and St. Louis encephalitis virus, as well as of nematodes that cause lymphatic filariasis. C. quinquefasciatus is one species within the Culex pipiens species complex and can be found throughout tropical and temperate climates of the world. The ability of C. quinquefasciatus to take blood meals from birds, livestock, and humans contributes to its ability to vector pathogens between species. Here, we describe the genomic sequence of C. quinquefasciatus: Its repertoire of 18,883 protein-coding genes is 22% larger than that of Aedes aegypti and 52% larger than that of Anopheles gambiae with multiple gene-family expansions, including olfactory and gustatory receptors, salivary gland genes, and genes associated with xenobiotic detoxification.


Temperature dependence of ionic transport and norepinephrine stimulation of rat aorta during DOCA hypertension.
Temperature perturbation was used to determine whether increased turnover of Na, K, and Cl at 37 degrees C in aortas from rats made hypertensive with deoxycorticosterone acetate salt treatment (DOCH) reflects an increased number of transport sites that individually maintain relatively normal function. Decreasing temperature reduced the resting effluxes of 42K, 36Cl, and 24Na (active and passive) from control and DOCH in parallel fashion. The slope of the Arrhenius plots (activation energies) and the transition temperatures at which major changes in slope occurred were similar in controls and DOCH. In contrast to the results for resting effluxes, the temperature dependence for the effects of norepinephrine (NE) on contraction and on 42K and 36Cl effluxes in DOCH differed from controls. At 20 degrees C, the responses to NE were either abolished or greatly suppressed in DOCH, as compared to controls, while no significant differences between the two groups were observed at 30 degrees C. These results indicate that alterations in resting 42K, 36Cl, and 24Na effluxes in DOCH may result from an increased number of transport sites in the membranes of vascular smooth muscle. The concept that alterations occurred in the integral components of the membrane is also supported by the observation that increased resting 42K and 36Cl effluxes in DOCH at 37 degrees C persisted in aortas that had undergone cold storage for 2 days before incubation at 37 degrees C. The altered temperature dependence for the effects of NE on DOCH, compared to controls, indicates that the involvement of agonist-receptor-membrane events may be dissociated from the alterations in resting ionic fluxes.