Physical activity in U.S. youth aged 12-15 years, 2012.
Data from the combined National Health and Nutrition Examination Survey (NHANES) and the NHANES National Youth Fitness Survey, 2012. In 2012, about one-quarter of U.S. youth aged 12-15 years engaged in moderate-to-vigorous physical activity for at least 60 minutes daily. Basketball was the most common activity reported among active boys, followed by running, football, bike riding, and walking. Running was the most common activity among active girls, followed by walking, basketball, dancing, and bike riding. The percentage of male youth who were physically active for at least 60 minutes daily decreased as weight status increased. The 2008 Physical Activity Guidelines for Americans, which have been adopted by the First Lady's Let's Move! initiative and the American Academy of Pediatrics, recommend that youth participate in daily moderate-to-vigorous physical activity for at least 60 minutes (1-5). This report presents the most recent national data from 2012 on self-reported physical activity among youth aged 12-15 years, by sex and weight status. This report also describes the most common types of physical activities--outside of school-based physical education (PE) or gym classes--in which youth engage.


Foliar or root exposures to smelter particles: consequences for lead compartmentalization and speciation in plant leaves.
In urban areas with high fallout of airborne particles, metal uptake by plants mainly occurs by foliar pathways and can strongly impact crop quality. However, there is a lack of knowledge on metal localization and speciation in plants after pollution exposure, especially in the case of foliar uptake. In this study, two contrasting crops, lettuce (Lactuca sativa L.) and rye-grass (Lolium perenne L.), were exposed to Pb-rich particles emitted by a Pb-recycling factory via either atmospheric or soil application. Pb accumulation in plant leaves was observed for both ways of exposure. The mechanisms involved in Pb uptake were investigated using a combination of microscopic and spectroscopic techniques (electron microscopy, laser ablation, Raman microspectroscopy, and X-ray absorption spectroscopy). The results show that Pb localization and speciation are strongly influenced by the type of exposure (root or shoot pathway) and the plant species. Foliar exposure is the main pathway of uptake, involving the highest concentrations in plant tissues. Under atmospheric fallouts, Pb-rich particles were strongly adsorbed on the leaf surface of both plant species. In lettuce, stomata contained Pb-rich particles in their apertures, with some deformations of guard cells. In addition to PbO and PbSO4, chemical forms that were also observed in pristine particles, new species were identified: organic compounds (minimum 20%) and hexagonal platy crystals of PbCO3. In rye-grass, the changes in Pb speciation were even more egregious: Pb-cell wall and Pb-organic acid complexes were the major species observed. For root exposure, identified here as a minor pathway of Pb transfer compared to foliar uptake, another secondary species, pyromorphite, was identified in rye-grass leaves. Finally, combining bulk and spatially resolved spectroscopic techniques permitted both the overall speciation and the minor but possibly highly reactive lead species to be determined in order to better assess the health risks involved.


Quantum optical properties of a dipole emitter coupled to an ɛ-near-zero nanoscale waveguide.
We study quantum optical properties of a dipole emitter coupled to a rectangular nanoscale waveguide with dielectric core and silver cladding. We investigate enhanced spontaneous emission and the photonic Lamb shift for emitters whose resonant frequencies are near the waveguide frequency cutoff where the waveguide behaves as an ɛ-near-zero metamaterial. Via a dyadic Green's function-based field quantization scheme, we calculate the photonic Lamb shift as well as the spontaneous emission enhancement and spectrum. Using realistic parameters for typical quantum emitters, we suggest experimentally realizable schemes to observe relatively large photonic Lamb shifts in waveguides.


Self-assembly of CdTe nanocrystals into free-floating sheets.
In their physical dimensions, surface chemistry, and degree of anisotropic interactions in solution, CdTe nanoparticles are similar to proteins. We experimentally observed their spontaneous, template-free organization into free-floating particulate sheets, which resemble the assembly of surface layer (S-layer) proteins. Computer simulation and concurrent experiments demonstrated that the dipole moment, small positive charge, and directional hydrophobic attraction are the driving forces for the self-organization process. The data presented here highlight the analogy of the solution behavior of the two vastly different classes of chemical structures.


Report from AmSECT's International Consortium for Evidence-Based Perfusion: American Society of Extracorporeal Technology Standards and Guidelines for Perfusion Practice: 2013.
One of the roles of a professional society is to develop standards and guidelines of practice as an instrument to guide safe and effective patient care. The American Society of Extracorporeal Technology (AmSECT) first published its Essentials for Perfusion Practice, Clinical Function: Conduct of Extracorporeal Circulation in 1993. The International Consortium for Evidence-Based Perfusion (ICEBP), a committee within AmSECT, was tasked with updating this document in 2010. The aim of this report is to describe the method of development and content of AmSECT's new professional standards and guidelines. The ICEBP committee independently evaluated and provided input regarding the current "Essentials and Guidelines." Structural changes were made to the entire document, and a draft document was developed, presented, and circulated to the AmSECT Board of Directors and broader membership for comment. Informed by these reviews, a revised document was then presented to the Society for a membership vote. The final document consists of 15 areas of practice covered by 50 Standards and 38 Guidelines (see Appendix 1) with the first standard focusing on the development of institutional protocols to support their implementation and use. A majority of the membership voted to accept the document (81.2% of the voting membership accepting, 18.8% rejecting). After an audit of the balloting process by AmSECT's Ethics Committee, the results were reported to the membership and the document was officially adopted on July 24, 2013. The Standards and Guidelines will serve as a useful guide for cardiac surgical teams that wish to develop institution-specific standards and guidelines to improve the reliability, safety, and effectiveness of adult cardiopulmonary bypass. The ICEBP recognizes that the development of a Standards and Guidelines statement alone will not change care. Safe, reliable, and effective care will be best served through the development and implementation of institutional protocols based on these standards. AmSECT's Standards and Guidelines for Perfusion Practice reflect the changing landscape of our profession as we work toward a safer and optimal provision of cardiopulmonary bypass for all our patients as well as a work environment that is supportive of delivering this care. standards, guidelines, cardiopulmonary bypass, perfusion, cardiac surgery.


Bright single photon source based on self-aligned quantum dot-cavity systems.
We report on a quasi-planar quantum-dot-based single-photon source that shows an unprecedented high extraction efficiency of 42% without complex photonic resonator geometries or post-growth nanofabrication. This very high efficiency originates from the coupling of the photons emitted by a quantum dot to a Gaussian shaped nanohill defect that naturally arises during epitaxial growth in a self-aligned manner. We investigate the morphology of these defects and characterize the photonic operation mechanism. Our results show that these naturally arising coupled quantum dot-defects provide a new avenue for efficient (up to 42% demonstrated) and pure (g(2)(0) value of 0.023) single-photon emission.


Gold(i)- and rhodium(iii)-catalyzed formal regiodivergent C-H alkynylation of 1-arylpyrazolones.
Formal regiodivergent C-H alkynylation of 1-aryl-5-pyrazolones has been realized under the catalysis of Rh(iii) and Au(i) complexes by using a hypervalent iodine reagent as the alkyne source. Mechanistic studies indicate that the regioselectivity is ascribed to not only the choice of the catalyst but also the nature of the substrate. The substrate scope and functional group compatibility have been fully examined.


Analysis of 5 years of morbidity and mortality conferences in a metropolitan South African trauma service.
Since 2008 the Pietermaritzburg Metropolitan Trauma Service (PMTS) has run a structured, self-reporting, metropolitan morbidity and mortality conference (MMC). In 2012 a hybrid electronic medical registry (HEMR) was introduced to capture routine data and to generate reports on morbidity and mortality. This paper reviews our experience in setting up a metropolitan MMC and compares the quality of the reported morbidity data from the pre- and post-HEMR era. We compared data from the MMC before and after the introduction of the HEMR to audit the impact of these meetings on the reporting and analysis of surgical morbidity and mortality in our service. During the 4-year period from 2008 to 2011, a total of 208 MMCs were held. A total of 10 682 patients were admitted by the PMTS during that period, of whom 87% were males, and the mean age was 26 years. Penetrating trauma accounted for 40.9% (4 344/10 628) of the total workload. A total of 432 (4.1%) morbidities were identified. Of these, 36.6% (158) were related to human error, 32% (138/432) were related to surgical pathologies and the remaining 31.9% (136/432) were related to systemic diseases. There was an exponential increase in the reporting of morbidity each year. The total in-hospital mortality was 3% (358/10 682). Following the introduction of the HEMR, from 2012 to 2014, 6 217 patients were admitted. A total of 1 314 (21.1%) adverse events and 315 (5.1%) deaths were recorded by the HEMR. The adverse events were divided into 875 'pathology-related' morbidities and 439 'error-related' morbidities. The development of the MMC led to increased reporting of morbidity and mortality. The introduction of the HEMR resulted in a dramatic improvement in the capturing of morbidity and mortality data, suggesting that a paper-based self-reporting system tends to underestimate morbidity. Over one-third of all morbidities were related to human error. Common morbidities have been identified.


An efficient method for isolating individual long-chain alkenones for compound-specific hydrogen isotope analysis.
Hydrogen isotope ratios (2H/H or D/H) of long-chain unsaturated ketones (alkenones) preserved in lake and marine sediments hold great promise for paleoclimate studies. However, compound-specific hydrogen isotope analysis of individual alkenones has not been possible due to chromatographic coelution of alkenones with the same carbon chain length but different numbers of double bonds. Published studies have only reported the deltaD values of the mixture of coeluting alkenones. We developed an efficient procedure to isolate individual alkenones based on double-bond numbers using silica gel impregnated with silver nitrate. The chromatographic procedure is simple, inexpensive, and highly reproducible, offers 87-100% sample recovery, and allows for the first time hydrogen isotopic measurement on individual alkenones. deltaD values of specific di-, tri- and tetraunsaturated C37 alkenones produced by an Emiliania huxleyi culture, as well as those isolated from Greenland lake sediments, differ consecutively by 43-65 per thousand. These findings suggest that alkenones with different numbers of carbon-carbon double bonds express significantly different deltaD values and that coelution of different alkenones may lead to erroneous source water deltaD reconstructions. Our alkenone isolation approach opens a new avenue for paleoclimate reconstructions using hydrogen isotope ratios of individual alkenones.


Knowledge and networks - key sources of power in global health: Comment on "Knowledge, moral claims and the exercise of power in global health".
Shiffman rightly raises questions about who exercises power in global health, suggesting power is a complex concept, and the way it is exercised is often opaque. Power that is not based on financial strength but on knowledge or experience, is difficult to estimate, and yet it may provide the legitimacy to make moral claims on what is, or ought to be, on global health agendas. Twenty years ago power was exercised in a much less complex health environment. The World Health Organization (WHO) was able to exert its authority as world health leader. The landscape today is very different. Financial resources for global health are being competed for by diverse organisations, and power is diffused and somewhat hidden in such a climate, where each organization has to establish and make its own moral claims loudly and publicly. We observe two ways which allow actors to capture moral authority in global health. One, through power based on scientific knowledge and two, through procedures in the policy process, most commonly associated with the notion of broad consultation and participation. We discuss these drawing on one particular framework provided by Bourdieu, who analyses the source of actor power by focusing on different sorts of capital. Different approaches or theories to understanding power will go some way to answering the challenge Shiffman throws to health policy analysts. We need to explore much more fully where power lies in global health, and how it is exercised in order to understand underlying health agendas and claims to legitimacy made by global health actors today.


Murine cytomegalovirus m41 open reading frame encodes a Golgi-localized antiapoptotic protein.
Viruses have evolved various strategies to prevent premature apoptosis of infected host cells. Some of the viral genes mediating antiapoptotic functions have been identified by their homology to cellular genes, but others are structurally unrelated to genes of known function. In this study, we used a random, unbiased approach to identify such genes in the murine cytomegalovirus genome. From a library of random transposon insertion mutants, a mutant virus that caused premature cell death was isolated. The transposon was inserted within open reading frame m41. An independently constructed m41 deletion mutant showed the same phenotype, whereas deletion mutants lacking the adjacent genes m40 and M42 did not. Apoptosis occurred in different cell types, could be blocked by caspase inhibitors, and did not require p53. Within the murine cytomegalovirus genome, m41, m40, and m39 form a small cluster of genes of unknown function. They are homologous to r41, r40, and r39 of rat cytomegalovirus, but lack sequence homology to UL41, UL40, and UL37 exon 1 (UL37x1) which are located at the corresponding positions of the human cytomegalovirus genome. Unlike UL37x1 of human cytomegalovirus, which encodes a mitochondrion-localized inhibitor of apoptosis that is essential for virus replication, m41 encodes a protein that localizes to the Golgi apparatus. The murine cytomegalovirus m41 product is the first example of a Golgi-localized protein that prevents premature apoptosis and thus extends the life span of infected cells.


Timing of revascularization in patients with transient ST-segment elevation myocardial infarction: a randomized clinical trial.
Patients with acute coronary syndrome who present initially with ST-elevation on the electrocardiogram but, subsequently, show complete normalization of the ST-segment and relief of symptoms before reperfusion therapy are referred to as transient ST-segment elevation myocardial infarction (STEMI) and pose a therapeutic challenge. It is unclear what the optimal timing of revascularization is for these patients and whether they should be treated with a STEMI-like or a non-ST-segment elevation myocardial infarction (NSTEMI)-like invasive approach. The aim of the study is to determine the effect of an immediate vs. a delayed invasive strategy on infarct size measured by cardiac magnetic resonance imaging (CMR). In a randomized clinical trial, 142 patients with transient STEMI with symptoms of any duration were randomized to an immediate (STEMI-like) [0.3 h; interquartile range (IQR) 0.2-0.7 h] or a delayed (NSTEMI-like) invasive strategy (22.7 h; IQR 18.2-27.3 h). Infarct size as percentage of the left ventricular myocardial mass measured by CMR at day four was generally small and not different between the immediate and the delayed invasive group (1.3%; IQR 0.0-3.5% vs. 1.5% IQR 0.0-4.1%, P = 0.48). By intention to treat, there was no difference in major adverse cardiac events (MACE), defined as death, reinfarction, or target vessel revascularization at 30 days (2.9% vs. 2.8%, P = 1.00). However, four additional patients (5.6%) in the delayed invasive strategy required urgent intervention due to signs and symptoms of reinfarction while awaiting angiography. Overall, infarct size in transient STEMI is small and is not influenced by an immediate or delayed invasive strategy. In addition, short-term MACE was low and not different between the treatment groups.


Early hemodynamic assessment and treatment of elderly patients in the medical ICU.
The aim of this retrospective study was to analyze differences in the initial hemodynamic assessment and its impact on the treatment in patients aged 80 years or older compared to younger patients during the first 6 h after admission to the medical intensive care unit (ICU). We analyzed 615 consecutive patients admitted to the medical ICU of which 124 (20%) were aged 80 years or more. The older group had a significantly higher acute physiology and chronic health evaluation (APACHE II) score, an overall mortality in the ICU and a presence of pre-existing cardiac disease. Both groups did not differ in the presence of shock and shock types on admission. In 57% of older and in 56% of younger patients, transthoracic echocardiography was performed with a higher therapeutic impact in the older patients. Transesophageal echocardiography was performed in 3% of the patients in both groups for specific diagnostic problems. Early reassessment with transthoracic echocardiography was necessary in 5% of the older and in 6% of the younger patients and resulted in a change of the treatment in one third of the patients. Continuous invasive hemodynamic monitoring was used in 11% of the older and in 10% of the younger patients and resulted in a therapeutic change in 71% of the older and in 64% of the younger patients. Patients aged 80 years or older represent 20% of all admissions to the medical ICU. Once admitted the older patients were similarly hemodynamically assessed as the younger ones with a similar impact on the treatment.


Structural basis of mitochondrial tethering by mitofusin complexes.
Vesicle fusion involves vesicle tethering, docking, and membrane merger. We show that mitofusin, an integral mitochondrial membrane protein, is required on adjacent mitochondria to mediate fusion, which indicates that mitofusin complexes act in trans (that is, between adjacent mitochondria). A heptad repeat region (HR2) mediates mitofusin oligomerization by assembling a dimeric, antiparallel coiled coil. The transmembrane segments are located at opposite ends of the 95 angstrom coiled coil and provide a mechanism for organelle tethering. Consistent with this proposal, truncated mitofusin, in an HR2-dependent manner, causes mitochondria to become apposed with a uniform gap. Our results suggest that HR2 functions as a mitochondrial tether before fusion.


Parametric models to relate spike train and LFP dynamics with neural information processing.
Spike trains and local field potentials (LFPs) resulting from extracellular current flows provide a substrate for neural information processing. Understanding the neural code from simultaneous spike-field recordings and subsequent decoding of information processing events will have widespread applications. One way to demonstrate an understanding of the neural code, with particular advantages for the development of applications, is to formulate a parametric statistical model of neural activity and its covariates. Here, we propose a set of parametric spike-field models (unified models) that can be used with existing decoding algorithms to reveal the timing of task or stimulus specific processing. Our proposed unified modeling framework captures the effects of two important features of information processing: time-varying stimulus-driven inputs and ongoing background activity that occurs even in the absence of environmental inputs. We have applied this framework for decoding neural latencies in simulated and experimentally recorded spike-field sessions obtained from the lateral intraparietal area (LIP) of awake, behaving monkeys performing cued look-and-reach movements to spatial targets. Using both simulated and experimental data, we find that estimates of trial-by-trial parameters are not significantly affected by the presence of ongoing background activity. However, including background activity in the unified model improves goodness of fit for predicting individual spiking events. Uncovering the relationship between the model parameters and the timing of movements offers new ways to test hypotheses about the relationship between neural activity and behavior. We obtained significant spike-field onset time correlations from single trials using a previously published data set where significantly strong correlation was only obtained through trial averaging. We also found that unified models extracted a stronger relationship between neural response latency and trial-by-trial behavioral performance than existing models of neural information processing. Our results highlight the utility of the unified modeling framework for characterizing spike-LFP recordings obtained during behavioral performance.


Aspheric spectacles for correcting presbyopia with myopia and astigmatism.
The aim of this paper is to propose a method for designing aspheric spectacles capable of realizing good optical performance at both far and near vision for presbyopia. We have experimentally measured wavefront aberrations and axial lengths for eight myopic eyes. In consideration of the field of view (FOV), the rotation of the eyeball, and a small amount of accommodation retained for presbyopia, we constructed individual eye models and optimized all the spectacle-eye systems for visible wavelengths by Zemax's simulation. Finally, we evaluated the image quality by the modulation transfer function (MTF) and visual acuity (VA) with different pupil sizes (2, 2.8, 4 mm). Results show that when the pupil size is 2 mm or 2.8 mm, the spectacles designed for the full FOV (0° and ±4° FOV) provide a strong ability to transfer low contrast at both far and near vision, and the VA for all reaches 0.8, and up to 1.1 for eyes NO. 1, NO. 5, NO. 6, and NO. 8 for the 0° FOV. As the pupil size increases to 4 mm, the VA for all comes to 0.6 for the full FOV, indicating that presbyopia is able to acquire a good visual resolution at both far and near vision by the designed aspheric spectacles. Furthermore, we verified the visual continuity of the spectacle-eye systems by studying intermediate vision, which demonstrates that the method used in our design is accurate and practicable.


Role of suppressor of hairless in the delta-activated Notch signaling pathway.
The Notch protein (N) acts as a transmembrane receptor for intercellular signals controlling cell fate choices in vertebrates and invertebrates. Genetical and molecular evidence indicates that, during Drosophila neurogenesis, an evolutionarily conserved transcription factor, Suppressor of Hairless [Su(H)], transduces the signal of N activation by its ligand Delta (D1). Su(H) plays a direct role in the immediate response of the genome to N signaling by up-regulating the transcription of the Enhancer of split Complex [E(spl)-C] genes. These findings suggest that the N transduction pathway can be described as a simple, linear cascade of molecular activation. At the molecular level, the mechanism of Su(H) "activation" is yet unknown. Two non-exclusive models have been proposed. In the first one, Su(H) binds to inactive N at the membrane. The binding of D1 to N in the extracellular space somehow interferes with the N-mediated cytoplasmic retention of Su(H), resulting in the nuclear translocation and "activation" of Su(H). In the second model, DNA-bound Su(H) is proposed to be "activated" in the nucleus by the direct binding of a processed form of N, acting as a transcriptional coactivator. This nuclear N protein would be generated by the ligand-induced proteolytic cleavage of the N transmembrane receptor.


Probiotics Improve Chemerin Levels and Metabolic Syndrome Parameters in Obese Rats
Chemerin is a recently discovered adipokine that plays a role in adipocyte metabolism. It is a novel chemoattractant adipokine whose expression and secretion are increased by adipogenesis. To evaluate the effects of probiotic supplementation on chemerin level, inflammation, and metabolic syndrome components in obese Wistar rats. Animal experiment. We divided the experimental animals into three groups, each consisting of eight rats. Group 1 was the control group. Group 2 was the experimentally obese group, in which rats were fed with a high-fat diet. Group 3 was the obese intervention group, in which rats were supplemented with probiotics after obesity induction. At the end of the study, a statistically significant difference was found between the groups in final weights, weight changes, and body mass index values (p<0.05). Weight gain was 34.12±3.70 g in group 3 post-probiotic supplementation and 53.25±8.35 g in group 2 (p<0.05). Obese rats showed increased levels of fasting plasma glucose, insulin, insulin resistance (homeostatic model assessment-insulin resistance), total cholesterol, low-density lipoprotein cholesterol, inflammatory markers, and leptin compared to those in the control group. Chemerin levels were 14.31±13.34 ng/mL in group 2 and 2.67±2.42 ng/mL in group 3 (p<0.05). Probiotic supplementation (group 3) reduced weight gain, and there were positive effects on the levels of fasting plasma glucose, insulin, homeostatic model assessment-insulin resistance, triglycerides, inflammatory markers, leptin, and chemerin.


Cresyl saligenin phosphate, an organophosphorus toxicant, makes covalent adducts with histidine, lysine, and tyrosine residues of human serum albumin.
CBDP [2-(2-cresyl)-4H-1-3-2-benzodioxaphosphorin-2-oxide] is a toxic organophosphorus compound. It is generated in vivo from tri-ortho-cresyl phosphate (TOCP), a component of jet engine oil and hydraulic fluids. Exposure to TOCP was proven to occur on board aircraft by finding CBDP-derived phospho-butyrylcholinesterase in the blood of passengers. Adducts on BChE, however, do not explain the toxicity of CBDP. Critical target proteins of CBDP are yet to be identified. Our goal was to facilitate the search for the critical targets of CBDP by determining the range of amino acid residues capable of reacting with CBDP and characterizing the types of adducts formed. We used human albumin as a model protein. Mass spectral analysis of the tryptic digest of CBDP-treated human albumin revealed adducts on His-67, His-146, His-242, His-247, His-338, Tyr-138, Tyr-140, Lys-199, Lys-351, Lys-414, Lys-432, and Lys-525. Adducts formed on tyrosine residues were different from those formed on histidines and lysines. Tyrosines were organophosphorylated by CBDP, while histidine and lysine residues were alkylated. This is the first report of an organophosphorus compound with both phosphorylating and alkylating properties. The o-hydroxybenzyl adduct on histidine is novel. The ability of CBDP to form stable adducts on histidine, tyrosine, and lysine allows one to consider new mechanisms of toxicity from TOCP exposure.


Fusarium: more than a node or a foot-shaped basal cell.
Recent publications have argued that there are potentially serious consequences for researchers in recognising distinct genera in the terminal fusarioid clade of the family Nectriaceae. Thus, an alternate hypothesis, namely a very broad concept of the genus Fusarium was proposed. In doing so, however, a significant body of data that supports distinct genera in Nectriaceae based on morphology, biology, and phylogeny is disregarded. A DNA phylogeny based on 19 orthologous protein-coding genes was presented to support a very broad concept of Fusarium at the F1 node in Nectriaceae. Here, we demonstrate that re-analyses of this dataset show that all 19 genes support the F3 node that represents Fusarium sensu stricto as defined by F. sambucinum (sexual morph synonym Gibberella pulicaris). The backbone of the phylogeny is resolved by the concatenated alignment, but only six of the 19 genes fully support the F1 node, representing the broad circumscription of Fusarium. Furthermore, a re-analysis of the concatenated dataset revealed alternate topologies in different phylogenetic algorithms, highlighting the deep divergence and unresolved placement of various Nectriaceae lineages proposed as members of Fusarium. Species of Fusarium s. str. are characterised by Gibberella sexual morphs, asexual morphs with thin- or thick-walled macroconidia that have variously shaped apical and basal cells, and trichothecene mycotoxin production, which separates them from other fusarioid genera. Here we show that the Wollenweber concept of Fusarium presently accounts for 20 segregate genera with clear-cut synapomorphic traits, and that fusarioid macroconidia represent a character that has been gained or lost multiple times throughout Nectriaceae. Thus, the very broad circumscription of Fusarium is blurry and without apparent synapomorphies, and does not include all genera with fusarium-like macroconidia, which are spread throughout Nectriaceae (e.g., Cosmosporella, Macroconia, Microcera). In this study four new genera are introduced, along with 18 new species and 16 new combinations. These names convey information about relationships, morphology, and ecological preference that would otherwise be lost in a broader definition of Fusarium. To assist users to correctly identify fusarioid genera and species, we introduce a new online identification database, Fusarioid-ID, accessible at www.fusarium.org. The database comprises partial sequences from multiple genes commonly used to identify fusarioid taxa (act1, CaM, his3, rpb1, rpb2, tef1, tub2, ITS, and LSU). In this paper, we also present a nomenclator of names that have been introduced in Fusarium up to January 2021 as well as their current status, types, and diagnostic DNA barcode data. In this study, researchers from 46 countries, representing taxonomists, plant pathologists, medical mycologists, quarantine officials, regulatory agencies, and students, strongly support the application and use of a more precisely delimited Fusarium (= Gibberella) concept to accommodate taxa from the robust monophyletic node F3 on the basis of a well-defined and unique combination of morphological and biochemical features. This F3 node includes, among others, species of the F. fujikuroi, F. incarnatum-equiseti, F. oxysporum, and F. sambucinum species complexes, but not species of Bisifusarium [F. dimerum species complex (SC)], Cyanonectria (F. buxicola SC), Geejayessia (F. staphyleae SC), Neocosmospora (F. solani SC) or Rectifusarium (F. ventricosum SC). The present study represents the first step to generating a new online monograph of Fusarium and allied fusarioid genera (www.fusarium.org).


Equine myeloperoxidase: a novel biomarker in synovial fluid for the diagnosis of infection.
Equine joint infection is a life-threatening disorder, and confirmation of the diagnosis can be difficult. Synovial fluid biomarkers may assist the discrimination between infectious and noninfectious joint disease. This study investigates whether the immunological detection of total and enzymatically active myeloperoxidase (MPO) assists the diagnosis of joint infection in horses. The following 4 sample groups were included: healthy; osteochondritis dissecans (OCD); traumatic synovitis; and culture-confirmed infected joints. Synovial fluid was analysed for total MPO by a horse-specific sandwich enzyme-linked immunosorbent assay (ELISA) and for active MPO using the specific immunological extraction followed by enzymatic detection (SIEFED) technique. Western blot analysis was performed to confirm the antibody specificity. Synovial fluid from infected joints contained significantly more total and active MPO than samples from healthy joints, joints affected by OCD and joints with traumatic synovitis. Cut-off values were set at 5000 and 350 ng/ml for total and active MPO, respectively, with fair sensitivity, specificity, positive and negative predictive values and likelihood ratios for infection. Correlation coefficients were reported between the total as well as the active MPO levels and the routine synovial fluid parameters, i.e. the white blood cell count, the neutrophil count and the total protein level. No correlation was observed between MPO and either the age of the horse or the joint affected. Western blotting confirmed the antibody specificity for equine MPO. Synovial fluid MPO was identified as a very promising biomarker to augment the discrimination of infectious vs. noninfectious joint disease in horses. Both ELISA and SIEFED techniques can be used for its specific and rapid detection. The analysis of synovial fluid MPO can be used as a complementary test to aid in the discrimination between infectious and noninfectious joint disease, especially when the white blood cell counts and the total protein level are inconclusive.


Subunit diversity and tissue distribution of human glutathione S-transferases: interpretations based on electrospray ionization-MS and peptide sequence-specific antisera.
Uncertainties about the composition and identities of glutathione S-transferases (GSTs) in human tissue have impeded studies on their biological functions. A rigorous protocol has therefore been developed to characterize the human proteins. Cytosolic GST subunits were resolved by reverse-phase HPLC methods, individual components were assigned to Alpha, Mu and Pi classes on the basis of their immunoreactivities, and peptide-sequence-specific antisera were used to distinguish among five different Mu-class subunits (GSTM1-GSTM5). Each subunit type was characterized and identified unambiguously by electrospray ionization-MS. Acetylation of N-terminal residues in the GSTA1, GSTA2, GSTM3 and GSTM4 subunits were the only natural post-translational modifications detected. The unique structure of GSTM3, with N- and C-terminal peptide extensions predicted from cDNA sequences, was confirmed. Only testis and brain were rich sources of GSTM3 subunits. Subunit profiles were distinct and characteristic of the particular tissue type, and this tissue specificity in GST expression was evident even in organs from different individuals. For instance, livers had relatively simple GST compositions, consisting of a preponderance of Alpha-class subunits and GSTM1 (when present). By contrast, representation of most subunit types was a characteristic feature of testis, which had the highest levels of GSTs. GSTM4 and GSTM5 subunits, here identified for the first time in human tissue extracts, were minor components, with GSTM5 found only in brain, lung and testis. Specimens devoid of GSTM1 subunits, particularly those from null-genotype individuals, were readily discerned at the protein level. Liver was the only rich source of the GSTM1 subunit (although it also constituted a major fraction of adrenal GSTs), and so the functional consequences of the GSTM1 gene deletion are likely to vary in extrahepatic tissues.


A Systematic Review of the Effectiveness of Non-Invasive Brain Stimulation Techniques to Reduce Violence Proneness by Interfering in Anger and Irritability.
The field of neurocriminology has proposed several treatments (e.g., pharmacological, brain surgery, androgen-deprivation therapy, neurofeedback) to reduce violence proneness, but unfortunately, their effectiveness has been limited due to their side-effects. Therefore, it is necessary to explore alternative techniques to improve patients' behavioural regulation with minimal undesirable effects. In this regard, non-invasive brain stimulation techniques, which are based on applying changing magnetic fields or electric currents to interfere with cortical excitability, have revealed their usefulness in alleviating the symptomatology of several mental disorders. However, to our knowledge, there are no reviews that assess whether these techniques are useful for reducing violence proneness. Therefore, we conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria using the following databases: PsycINFO, PubMed, Dialnet, Psicodoc, Web of Knowledge, and the Cochrane Library. We initially identified 3746 entries, and eventually included 56 publications. Most of the studies were unanimous in concluding that the application of these techniques over the prefrontal cortex (PFC) was not sufficient to promote anger and irritability reductions in euthymic individuals of both genders. Nevertheless, the application of non-invasive brain stimulation techniques, especially transcranial direct current stimulation, over the right PFC seemed to reduce violent reactions in these individuals by interfering with the interpretation of the unfavourable situations (e.g., threating signals) or inner states that evoked anger. In antisocial and pathological populations, the conclusions were provided by a few pilot studies with important methodological weaknesses. The main conclusion of these studies was that bilateral stimulation of the PFC satisfactorily reduced anger and irritability only in inmates, patients with autism spectrum disorders (ASD), people who suffered a closed-head injury, and agitated patients with Alzheimer's disease. Moreover, combining these techniques with risperidone considerably reduced aggressiveness in these patients. Therefore, it is necessary to be cautious about the benefits of these techniques to control anger, due the methodological weaknesses of these studies. Nonetheless, they offer valuable opportunities to prevent violence by designing new treatments combining brain stimulation with current strategies, such as psychotherapy and psychopharmacology, in order to promote lasting changes.


Interfacial and distal-heme pocket mutations exhibit additive effects on the structure and function of hemoglobin.
Protein engineering strategies seek to develop a hemoglobin-based oxygen carrier with optimized functional properties, including (i) an appropriate O 2 affinity, (ii) high cooperativity, (iii) limited NO reactivity, and (iv) a diminished rate of auto-oxidation. The mutations alphaL29F, alphaL29W, alphaV96W and betaN108K individually impart some of these traits and in combinations produce hemoglobin molecules with interesting ligand-binding and allosteric properties. Studies of the ligand-binding properties and solution structures of single and multiple mutants have been performed. The aromatic side chains placed in the distal-heme pocket environment affect the intrinsic ligand-binding properties of the mutated subunit itself, beyond what can be explained by allostery, and these changes are accompanied by local structural perturbations. In contrast, hemoglobins with mutations in the alpha 1beta 1 and alpha 1beta 2 interfaces display functional properties of both "R"- and "T"-state tetramers because the equilibrium between quaternary states is altered. These mutations are accompanied by global structural perturbations, suggesting an indirect, allostery-driven cause for their effects. Combinations of the distal-heme pocket and interfacial mutations exhibit additive effects in both structural and functional properties, contribute to our understanding of allostery, and advance protein-engineering methods for manipulating the O 2 binding properties of the hemoglobin molecule.


Effects of age, speed of processing, and working memory on comprehension of sentences with relative clauses.
Two hundred participants, 50 in each of four age ranges (19-29, 30-49, 50-69, 70-90) were tested for working memory, speed of processing, and the processing of sentences with relative clauses. In Experiment 1, participants read four sentence types (cleft subject, cleft object, subject-subject, subject-object) in a word-by-word, non-cumulative, self-paced reading task and made speeded plausibility judgments about them. In Experiment 2, participants read two types of sentences, one of which contained a doubly center embedded relative clause. Older participants' comprehension was less accurate and there was age-related slowing of online processing times in all but the simplest sentences, which increased in syntactically complex sentences in Experiment 1. This pattern suggests an age-related decrease in the efficiency of parsing and interpretation. Slower speed of processing and lower working memory were associated with longer online processing times only in Experiment 2, suggesting that task-related operations are related to general speed of processing and working memory. Lower working memory was not associated with longer reading times in more complex sentences, consistent with the view that general working memory is not critically involved in online syntactic processing. Longer online processing at the most demanding point in the most demanding sentence was associated with better comprehension, indicating that it reflects effective processing under some certain circumstances. However, the poorer comprehension performance of older individuals indicates that their slower online processing reflects inefficient processing even at these points.


Demystifying visual awareness: Peripheral encoding plus limited decision complexity resolve the paradox of rich visual experience and curious perceptual failures.
Human beings subjectively experience a rich visual percept. However, when behavioral experiments probe the details of that percept, observers perform poorly, suggesting that vision is impoverished. What can explain this awareness puzzle? Is the rich percept a mere illusion? How does vision work as well as it does? This paper argues for two important pieces of the solution. First, peripheral vision encodes its inputs using a scheme that preserves a great deal of useful information, while losing the information necessary to perform certain tasks. The tasks rendered difficult by the peripheral encoding include many of those used to probe the details of visual experience. Second, many tasks used to probe attentional and working memory limits are, arguably, inherently difficult, and poor performance on these tasks may indicate limits on decision complexity. Two assumptions are critical to making sense of this hypothesis: (1) All visual perception, conscious or not, results from performing some visual task; and (2) all visual tasks face the same limit on decision complexity. Together, peripheral encoding plus decision complexity can explain a wide variety of phenomena, including vision's marvelous successes, its quirky failures, and our rich subjective impression of the visual world.


Feminist ethics and cultural ethos: revisiting a nursing debate.
In this article the author re-examines from a feminist perspective the now well-known debate between Yarling and McElmurry and Bishop and Scudder. The central point of this critique is that a feminist ethics requires we attend to the social and institutional form of life in which given practices exist. The endorsement of a single concept, even the extremely important one of care, is insufficient for a nursing ethics. Without attention to the institutional factors, which support or reform care, we have only a feminine ethics. In this author's view, nursing needs a feminist ethics.


Investigation of the radiation dose from cone-beam CT for image-guided radiotherapy: A comparison of methodologies.
Four methodologies were evaluated for quantifying kilovoltage cone-beam computed tomography (CBCT) dose: the Cone-Beam Dose Index (CBDI), IAEA Report 5 recommended methodology (IAEA), the AAPM Task Group 111 methodology (TG111), and the current dose metric; the Computed Tomography Dose Index (CTDI) on two commercial Varian cone-beam CT imaging systems; the Clinac iX On-Board Imager (OBI); and the TrueBeam X-ray Imaging system (XI). The TG111 methodology measured the highest overall dose (21.199 ± 0.035 mGy OBI and 22.420 ± 0.002 XI for pelvis imaging) due to the full scatter of the TG111 phantom and was within 5% of CTDI measurements taken using a full scatter TG111 phantom and 30-cm film strips. CBDI measured the second highest overall dose, within 10% of the TG111, with IAEA measuring the third highest dose. For head CBCT protocols, CBDI measured the highest dose, followed by IAEA. The CTDI method measured lowest across all scan modes highlighting its limitations for CBCT dosimetry. The XI imaging system delivered lower doses for head and thorax scan modes and similar doses to the OBI system for pelvis scan modes due to additional beam hardening filtration in the XI system. The TG111 method measured the highest dose in the center of a CBCT scan during image guidance procedures; however, CBDI provided a good approximation to TG111 with existing CTDI equipment and may be more applicable clinically.


The political and security dimensions of the humanitarian health response to violent conflict.
The nature of armed conflict throughout the world is intensely dynamic. Consequently, the protection of non-combatants and the provision of humanitarian services must continually adapt to this changing conflict environment. Complex political affiliations, the systematic use of explosive weapons and sexual violence, and the use of new communication technology, including social media, have created new challenges for humanitarian actors in negotiating access to affected populations and security for their own personnel. The nature of combatants has also evolved as armed, non-state actors might have varying motivations, use different forms of violence, and engage in a variety of criminal activities to generate requisite funds. New health threats, such as the COVID-19 pandemic, and new capabilities, such as modern trauma care, have also created new challenges and opportunities for humanitarian health provision. In response, humanitarian policies and practices must develop negotiation and safety capabilities, informed by political and security realities on the ground, and guidance from affected communities. More fundamentally, humanitarian policies will need to confront a changing geopolitical environment, in which traditional humanitarian norms and protections might encounter wavering support in the years to come.


The global spectrum of plant form and function.
Earth is home to a remarkable diversity of plant forms and life histories, yet comparatively few essential trait combinations have proved evolutionarily viable in today's terrestrial biosphere. By analysing worldwide variation in six major traits critical to growth, survival and reproduction within the largest sample of vascular plant species ever compiled, we found that occupancy of six-dimensional trait space is strongly concentrated, indicating coordination and trade-offs. Three-quarters of trait variation is captured in a two-dimensional global spectrum of plant form and function. One major dimension within this plane reflects the size of whole plants and their parts; the other represents the leaf economics spectrum, which balances leaf construction costs against growth potential. The global plant trait spectrum provides a backdrop for elucidating constraints on evolution, for functionally qualifying species and ecosystems, and for improving models that predict future vegetation based on continuous variation in plant form and function.


The effect of acute vs chronic magnesium supplementation on exercise and recovery on resistance exercise, blood pressure and total peripheral resistance on normotensive adults.
Magnesium supplementation has previously shown reductions in blood pressure of up to 12 mmHg. A positive relationship between magnesium supplementation and performance gains in resistance exercise has also been seen. However, no previous studies have investigated loading strategies to optimise response. The aim of this study was to assess the effect of oral magnesium supplementation on resistance exercise and vascular response after intense exercise for an acute and chronic loading strategy on a 2-day repeat protocol. The study was a randomised, double-blind, cross-over design, placebo controlled 2 day repeat measure protocol (n = 13). Intense exercise (40 km time trial) was followed by bench press at 80% 1RM to exhaustion, with blood pressure and total peripheral resistance (TPR) recorded. 300 mg/d elemental magnesium was supplemented for either a 1 (A) or 4 (Chr) week loading strategy. Food diaries were recorded. Dietary magnesium intake was above the Reference Nutrient Intake (RNI) for all groups. Bench press showed a significant increase of 7.7% (p = 0.031) [corrected] for A on day 1. On day 2 A showed no decrease in performance whilst Chr showed a 32.1% decrease. On day 2 post-exercise systolic blood pressure (SBP) was significantly lower in both A (p = 0.0.47) and Chr (p = 0.016) groups. Diastolic blood pressure (DBP) showed significant decreases on day 2 solely for A (p = 0.047) with no changes in the Chr. TPR reduced for A on days 1 and 2 (p = 0.031) with Chr showing an increase on day 1 (p = 0.008) and no change on day 2. There was no cumulative effect of Chr supplementation compared to A. A group showed improvement for bench press concurring with previous research which was not seen in Chr. On day 2 A showed a small non-significant increase but not a decrement as expected with Chr showing a decrease. DBP showed reductions in both Chr and A loading, agreeing with previous literature. This is suggestive of a different mechanism for BP reduction than for muscular strength. TPR showed greater reductions with A than Chr, which would not be expected as both interventions had reductions in BP, which is associated with TPR.


Loss of IL-4 secretion from human type 1a diabetic pancreatic draining lymph node NKT cells.
Altered frequency and function of peripheral invariant NKT (iNKT) cells have been implicated in the regulation of murine and human type 1a diabetes. To examine regulatory cells from the site of drainage of autoinflammatory tissue and autoantigenic T cell priming in diabetes, we directly cloned iNKT cells from human pancreatic draining lymph nodes (PLN). From 451 T cell clones from control and diabetic PLN, we derived 55 iNKT cells by two methods and analyzed function by cytokine secretion. iNKT cell clones isolated from control PLN secreted IL-4 and IFN-gamma upon TCR stimulation. For type 1a diabetic subjects, PLN iNKT cell clones from three samples secreted IFN-gamma and no IL-4. In a rare recent onset diabetic sample with islet-infiltrating CD4+ T cells, the phenotype of PLN iNKT cell clones was mixed. From normal and diabetic PLN, one-third of CD1d tetramer+-sorted T cell clones were reactive with CD1d transfectants or proliferated/secreted cytokine in response to alpha-galactosylceramide-pulsed PBMCs; tetramer-staining T cell clones from diabetic PLN did not secrete IL-4. This is the first report directly examining iNKT cells from lymph nodes draining the site of autoimmunological attack in humans; iNKT cells were altered in cytokine secretion as previously reported for circulating iNKT cells in human type 1a diabetes.


Analysis of test day yield data of Costa Rican dairy cattle.
Estimates of variance components for test day records in an animal model that considered multiple traits over multiple lactations were calculated using REML methodology. Test day records were classified into 11 periods within first and later lactations. Missing ancestors in the relationship matrix were classified in genetic groups. Data were collected from Costa Rican dairy farms. Estimates of components for total and additive genetic variance were clearly heterogeneous during the lactation. Heritabilities for traits in later parities were slightly higher than those for traits in first parity. Heritabilities were highest for records of midlactation. Phenotypic and genetic correlations for adjacent test days were close to 1. Phenotypic correlations were lower than genetic correlations. Heterogeneity of variances during the lactation suggests the adequacy of the multiple-trait test day model to describe milk yield during the lactation. When missing ancestors were allocated to a single base population instead of genetic groups, the estimates of residual variance were lower, and the estimates of genetic variance and genetic correlations were higher. When standardized records were used instead of actual test day records, the estimates of residual and total variance were lower, and the estimates of genetic variance were higher. Consequently, estimates of heritability and genetic correlations were also higher. Use of standardized data obtained by interpolation procedures is not advised for estimation of genetic variance components in a test day model.


Child development in developing countries: introduction and methods.
The Multiple Indicator Cluster Survey (MICS) is a nationally representative, internationally comparable household survey implemented to examine protective and risk factors of child development in developing countries around the world. This introduction describes the conceptual framework, nature of the MICS3, and general analytic plan of articles in this Special Section. The articles that follow describe the situations of children with successive foci on nutrition, parenting, discipline and violence, and the home environment. They address 2 common questions: How do developing and underresearched countries in the world vary with respect to these central indicators of children's development? How do key indicators of national development relate to child development in each of these substantive areas? The Special Section concludes with policy implications from the international findings.


The Impact of Collagen Fibril Polarity on Second Harmonic Generation Microscopy.
In this work, we report the implementation of interferometric second harmonic generation (SHG) microscopy with femtosecond pulses. As a proof of concept, we imaged the phase distribution of SHG signal from the complex collagen architecture of juvenile equine growth cartilage. The results are analyzed in respect to numerical simulations to extract the relative orientation of collagen fibrils within the tissue. Our results reveal large domains of constant phase together with regions of quasi-random phase, which are correlated to respectively high- and low-intensity regions in the standard SHG images. A comparison with polarization-resolved SHG highlights the crucial role of relative fibril polarity in determining the SHG signal intensity. Indeed, it appears that even a well-organized noncentrosymmetric structure emits low SHG signal intensity if it has no predominant local polarity. This work illustrates how the complex architecture of noncentrosymmetric scatterers at the nanoscale governs the coherent building of SHG signal within the focal volume and is a key advance toward a complete understanding of the structural origin of SHG signals from tissues.


Delivery efficiency of an Elekta linac under gated operation.
In this study, we have characterized the efficiency of an Elekta linac in the delivery of gated radiotherapy. We have explored techniques to reduce the beam-on delay and to improve the delivery efficiency, and have investigated the impact of frequent beam interruptions on the dosimetric accuracy of gated deliveries. A newly available gating interface was installed on an Elekta Synergy. Gating signals were generated using a surface mapping system in conjunction with a respiratory motion phantom. A series of gated deliveries were performed using volumetric modulated arc therapy (VMAT) treatment plans previously generated for lung cancer patients treated with stereotactic body radiotherapy. Baseline values were determined for the delivery times. The machine was then tuned in an effort to minimize beam-on delays and improve delivery efficiency. After that process was completed, the dosimetric accuracy of the gated deliveries was evaluated by comparing the measured and the planned coronal dose distributions using gamma index analyses. Comparison of the gated and the non-gated deliveries were also performed. The results demonstrated that, with the optimal machine settings, the average beam-on delay was reduced to less than 0.22 s. High dosimetric accuracy was demonstrated with gamma index passing rates no lower than 99.0% for all tests (3%/3 mm criteria). Consequently, Elekta linacs can provide a practical solution for gated VMAT treatments with high dosimetric accuracy and only a moderate increase in the overall delivery time.


Congenital toxoplasmosis in two health institutions in Trinidad.
Toxoplasmosis is the most widespread zoonosis and an important human disease particularly in children where it could cause visual and neurological impairment and mental retardation. This study was conducted to determine the prevalence of toxoplasmosis, especially congenital toxoplasmosis in patients at two health institutions in Trinidad A total of 504 cord blood samples of newborn babies were collected: 174 from a women's hospital and 330 from a general hospital. In order to elicit aternal and prenatal risk factors for toxoplasmosis, mothers of the newborns completed a questionnaire. Enzyme-immuno assay (EIA) was used to detect IgG and IgM to Toxoplasma gondii. Overall, of 504 serum samples tested, 220 (43.7%) were seropositive for IgG while the prevalence of congenital toxoplasmosis as reflected by IgM was 0.4%. The prevalence of IgG and IgM by health institutions was not significantly different (p > 0.05; chi-square). The prevalence of toxoplasmosis using IgG was highest in neonates of mothers who were of East Indian descent (54.1%), had four children (52.9%), kept cats in households (47.7%), practised outdoor gardening (50.8%), consumed raw meat (66.7%), had experienced miscarriage(s) (47.3%), stillbirths (66.7%), or who had eye problem(s) (52.9%) and mental retardation (50.0%). The study prevalence of congenital toxoplasmosis revealed a high seroprevalence oftoxoplasmosis in neonates but there was 0.4% serological evidence of congenital disease. It indicates a need for sensitization of the population and healthcare workers and for follow-up of infected children for clinical evidence of the disease. This would be necessary to fully appreciate the impact of toxoplasmosis in Trinidad and Tobago. The differences from comparison groups were however not statistically significant (p > 0.05; chi-square).


[Study on changes of mandibular movement by aging. 1. Analysis of sagittal movements].
It is known that the temporomandibular joint changes with age. However, it isn't clarified yet how these changes affect mandibular movements. Therefore, I investigated the changes which occur in mandibular movement with aging. This study details 62 cases whose age ranged from 20 to 79 years, and whose dentition was either complete or nearly so, and whose intercuspal position was firm. First, I investigated the path of protrusive movement at representative points on the mandible, such as incisor, canine, first molar, second molar, the condylar center and the kinematic axis point. Results were as follows: 1) Data obtained from the 20 to 29 year old age group differed little from the results of previous investigations, 2) The sagittal inclination of the condylar path became less acute in subjects 60 years and over than in the younger subjects. Second, I evaluated the vertical mobility of the condyle by the gap between opening path and closing path of the condyle in sagittal border movement and the location of the kinematic axis point. The results showed that the gap between the two paths of the condylar center was slightly larger and the kinematic axis point was tended to locate more anteriorly in subjects 50 years and up than in the others.


Regulation of Bone Marrow Angiogenesis by Osteoblasts during Bone Development and Homeostasis.
Bone marrow is a highly heterogeneous and vascularized tissue. The various cell types populating the bone marrow extensively communicate with each other, and cell-to-cell cross talk is likely to be essential for proper bone development and homeostasis. In particular, the existence of osteogenesis and angiogenesis coupling has been recently proposed. Despite its high degree of vascularization, a gradient of oxygenation is present in the bone marrow, and the endosteal surface of cortical bone appears to be among the most hypoxic areas in the body. Oxygen (O2) is both an essential metabolic substrate and a regulatory signal that is in charge of a specific genetic program. An important component of this program is the family of transcription factors known as hypoxia-inducible factors (HIFs). In this Perspective, we will summarize our current knowledge about the role of the HIF signaling pathway in controlling bone development and homeostasis, and especially in regulating the crosstalk between osteoblasts, progenitor cells, and bone marrow blood vessels.


Biochemical events initiated by exposure of human T lymphocyte clones to immunogenic and tolerogenic concentrations of antigen.
Interleukin 2-dependent helper T cells, cloned from human peripheral blood lymphocytes activated with strain A influenza virus hemagglutinin, proliferate in response to a 24-residue synthetic peptide (p20) of hemagglutinin, but become unresponsive to a subsequent immunogenic challenge when pretreated with a high concentration of p20. This phenomenon is associated with a loss of the T3 antigen complex, presumably in association with the T cell receptor. We have examined this phenomenon in more detail and show that in addition to changes in the expression of T3 molecules on the cell surface, high doses of p20 cause changes in the expression of certain biosynthetically and surface-labeled proteins, although total DNA and protein synthesis was unaltered. Thus, by examining these biochemical phenomena we can begin to define some of the processes which occur during antigen activation of human T lymphocytes at the clonal level.


Drowning deaths in people with epilepsy.
To determine the demographic characteristics and risk factors associated with death from drowning among people with epilepsy. Retrospective review of medical examiner's investigations into deaths from drowning from Jan. 1, 1981, to Dec. 31, 1990. Alberta. Personal data, medical history, circumstances surrounding the death, autopsy findings and results of postmortem toxicologic analyses. Of 482 deaths from drowning in Alberta during the study period, 25 (5%) were considered by the medical examiner's office to be directly related to seizures. Fifteen (60%) of the 25 deaths occurred while the person was taking a bath, unsupervised. Only one person (4%) died while taking a shower. The remaining deaths occurred on a river or lake (16%), in a private pool (8%), in a public pool (8%) and in a jacuzzi (4%). Two people fell out of moving boats while having a seizure; neither had been wearing a personal flotation device. Nineteen (83%) of 23 people who had been receiving anticonvulsant drug therapy had undetectable or subtherapeutic levels of one or more of the drugs at autopsy. Ethanol was not a factor in any of the deaths. Seizure-related drownings represent a small but potentially preventable proportion of all drownings. Enhanced seizure control and compliance with anticonvulsant drug therapy may prevent some of these deaths. In addition, all people with epilepsy, regardless of the level of control of their condition, should be encouraged to take showers while sitting instead of baths. The presence of people in the same house who are not directly supervising the person in the bathroom does not protect against drowning. Personal flotation devices should be worn at all times during boating activities.


Congenital Tuberculosis in a Neonate: A Case Report and Literature Review.
Congenital tuberculosis (TB) is difficult to detect because the disease presents few or no symptoms in the fetus during pregnancy and nonspecific symptoms in neonates. We reviewed 20 cases of congenital TB reported between 2011 and 2017 and report a case of a mother and her 8 days old neonate with congenital TB. In these 21 cases (including our case), the most common clinical presentations were respiratory distress, fever, and hepatosplenomegaly. The most common chest imaging findings were pneumonia, multiple pulmonary nodules, and miliary pattern. The mortality rate of infants with TB was increased ~2.2-fold if their mothers had no symptoms. The case reported herein concerns an 8 days old neonate with the rare presentation of a 2 days history of fever, followed by abdominal distension without respiratory symptoms. Computed tomography (CT) imaging exhibited a large amount of right pleural effusion. Multiple antimicrobial therapies were administered to the neonate; however, his symptoms persisted. Repeat CT was used to identify a progressed disease with multiple nodules over the lung, spleen, and hepatic hilar region. Standard anti-TB medications were prescribed, and the patient recovered gradually. Both gastric lavage and pleural effusion cultures confirmed the diagnosis of TB. The neonate's mother denied any TB contact history and the diagnosis of any medical disease during pregnancy, but she experienced a fulminant course of miliary TB and was admitted to the intensive care unit 24 days postpartum. She died despite receiving anti-TB treatment. In TB-endemic areas, congenital TB should be taken into consideration when neonates develop fever, respond poorly to antimicrobial treatment, and when their mothers deny any TB contact history.


Perioperative outcomes of major noncardiac surgery in adults with congenital heart disease.
An increasing number of patients with congenital heart disease are surviving to adulthood. Consensus guidelines and expert opinion suggest that noncardiac surgery is a high-risk event, but few data describe perioperative outcomes in this population. By using the Nationwide Inpatient Sample database (years 2002 through 2009), the authors compared patients with adult congenital heart disease (ACHD) who underwent noncardiac surgery with a non-ACHD comparison cohort matched on age, sex, race, year, elective or urgent or emergency procedure, van Walraven comborbidity score, and primary procedure code. Mortality and morbidity were compared between the two cohorts. A study cohort consisting of 10,004 ACHD patients was compared with a matched comparison cohort of 37,581 patients. Inpatient mortality was greater in the ACHD cohort (407 of 10,004 [4.1%] vs. 1,355 of 37,581 [3.6%]; unadjusted odds ratio, 1.13; P = 0.031; adjusted odds ratio, 1.29; P < 0.001). The composite endpoint of perioperative morbidity was also more commonly observed in the ACHD cohort (2,145 of 10.004 [21.4%] vs. 6,003 of 37,581 [16.0%]; odds ratio, 1.44; P < 0.001). ACHD patients comprised an increasing proportion of all noncardiac surgical admissions over the study period (P value for trend is <0.001), and noncardiac surgery represented an increasing proportion of all ACHD admissions (P value for trend is <0.001). Compared with a matched control cohort, ACHD patients undergoing noncardiac surgery experienced increased perioperative morbidity and mortality. Within the limitations of a retrospective analysis of a large administrative dataset, this finding demonstrates that this is a vulnerable population and suggests that better efforts are needed to understand and improve the perioperative care they receive.


Effects of habitat composition and landscape structure on worker foraging distances of five bumble bee species.
Bumble bees (Bombus spp.) are important pollinators of both crops and wildflowers. Their contribution to this essential ecosystem service has been threatened over recent decades by changes in land use, which have led to declines in their populations. In order to design effective conservation measures, it is important to understand the effects of variation in landscape composition and structure on the foraging activities of worker bumble bees. This is because the viability of individual colonies is likely to be affected by the trade-off between the energetic costs of foraging over greater distances and the potential gains from access to additional resources. We used field surveys, molecular genetics, and fine resolution remote sensing to estimate the locations of wild bumble bee nests and to infer foraging distances across a 20-km² agricultural landscape in southern England, UK. We investigated five species, including the rare B. ruderatus and ecologically similar but widespread B. hortorum. We compared worker foraging distances between species and examined how variation in landscape composition and structure affected foraging distances at the colony level. Mean worker foraging distances differed significantly between species. Bombus terrestris, B. lapidarius, and B. ruderatus exhibited significantly greater mean foraging distances (551, 536, and 501 m, respectively) than B. hortorum and B. pascuorum (336 and 272 m, respectively). There was wide variation in worker foraging distances between colonies of the same species, which was in turn strongly influenced by the amount and spatial configuration of available foraging habitats. Shorter foraging distances were found for colonies where the local landscape had high coverage and low fragmentation of semi-natural vegetation, including managed agri-environmental field margins. The strength of relationships between different landscape variables and foraging distance varied between species, for example the strongest relationship for B. ruderatus being with floral cover of preferred forage plants. Our findings suggest that management of landscape composition and configuration has the potential to reduce foraging distances across a range of bumble bee species. There is thus potential for improvements in the design and implementation of landscape management options, such as agri-environment schemes, aimed at providing foraging habitat for bumble bees and enhancing crop pollination services.


Association between a Functional HLA-G 14-bp Insertion/deletion Polymorphism and Susceptibility to Autoimmune Diseases: A Meta-analysis.
The aim of this study was to determine whether a functional human leukocyte antigen-G (HLA-G) 14-bp insertion (I)/deletion (D) polymorphism is associated with susceptibility to autoimmune diseases. A meta-analysis was conducted to assess the association between an HLA-G 14-bp I/D polymorphism and autoimmune diseases using 1) allele contrast, as well as 2) recessive, 3) dominant, and 4) codominant models. Sixteen articles that included 20 comparative studies with 3,555 patients and 5,225 controls were included in the meta-analysis. These studies were performed on nine Caucasian, six South American, three Asian, one Arab, and one African population samples. Our meta-analysis revealed no association between autoimmune diseases and the HLA-G 14-bp I/D polymorphism [odds ratio (OR) for allele I = 1.055; 95% confidence interval (CI) = 0.963-1.156; p = 0.251)]. However, meta-analysis according to autoimmune disease type revealed an association between systemic lupus erythematosus (SLE) and the II+ID genotype of the HLA-G 14-bp I/D polymorphism (OR = 1.205; 95% CI = 1.036-1.403; p = 0.016). Furthermore, analysis using a codominant model revealed an association between this polymorphism and SLE (OR for ID vs. DD = 1.203; 95% CI = 1.024-1.413; p = 0.024). In contrast, our meta-analysis revealed no association between rheumatoid arthritis (RA), multiple sclerosis (MS), or Crohn's disease (CD) and the HLA-G 14-bp I/D polymorphism. This meta-analysis showed that the HLA-G 14-bp I/D polymorphism is associated with susceptibility to a subgroup of autoimmune diseases such as SLE, but not RA, MS, or CD. These results support the existence of an association between the HLA-G gene and a subgroup of autoimmune diseases.


Influenza virus respiratory infection and transmission following ocular inoculation in ferrets.
While influenza viruses are a common respiratory pathogen, sporadic reports of conjunctivitis following human infection demonstrates the ability of this virus to cause disease outside of the respiratory tract. The ocular surface represents both a potential site of virus replication and a portal of entry for establishment of a respiratory infection. However, the properties which govern ocular tropism of influenza viruses, the mechanisms of virus spread from ocular to respiratory tissue, and the potential differences in respiratory disease initiated from different exposure routes are poorly understood. Here, we established a ferret model of ocular inoculation to explore the development of virus pathogenicity and transmissibility following influenza virus exposure by the ocular route. We found that multiple subtypes of human and avian influenza viruses mounted a productive virus infection in the upper respiratory tract of ferrets following ocular inoculation, and were additionally detected in ocular tissue during the acute phase of infection. H5N1 viruses maintained their ability for systemic spread and lethal infection following inoculation by the ocular route. Replication-independent deposition of virus inoculum from ocular to respiratory tissue was limited to the nares and upper trachea, unlike traditional intranasal inoculation which results in virus deposition in both upper and lower respiratory tract tissues. Despite high titers of replicating transmissible seasonal viruses in the upper respiratory tract of ferrets inoculated by the ocular route, virus transmissibility to naïve contacts by respiratory droplets was reduced following ocular inoculation. These data improve our understanding of the mechanisms of virus spread following ocular exposure and highlight differences in the establishment of respiratory disease and virus transmissibility following use of different inoculation volumes and routes.


A β-lactone-based antivirulence drug ameliorates Staphylococcus aureus skin infections in mice.
Skin infections caused by Staphylococcus aureus are a major clinical concern, especially if they are caused by multi-resistant strains. In these cases, a spread into deeper soft tissues or the bloodstream results in life-threatening conditions that are difficult to treat by conventional antibiotics. Previous in vitro experiments with a small β-lactone-based molecule demonstrated that antibiotic-sensitive and -resistant S. aureus strains are effectively disarmed in their virulence and corresponding pathogenicity. In this work, in vivo mouse studies show that this methodology is effective for the treatment of skin abscesses in mice. A single dose of the β-lactone significantly decreased abscess size even when applied 6 h post-infection. Although the molecule requires pharmacological optimization (improved stability, for example), this study emphasizes the potential value of antivirulence therapies.


Heterotrimeric G proteins and the single-transmembrane domain IGF-II/M6P receptor: functional interaction and relevance to cell signaling.
The G protein-coupled receptor (GPCR) family represents the largest and most versatile group of cell surface receptors. Classical GPCR signaling constitutes ligand binding to a seven-transmembrane domain receptor, receptor interaction with a heterotrimeric G protein, and the subsequent activation or inhibition of downstream intracellular effectors to mediate a cellular response. However, recent reports on direct, receptor-independent G protein activation, G protein-independent signaling by GPCRs, and signaling of nonheptahelical receptors via trimeric G proteins have highlighted the intrinsic complexities of G protein signaling mechanisms. The insulin-like growth factor-II/mannose-6 phosphate (IGF-II/M6P) receptor is a single-transmembrane glycoprotein whose principal function is the intracellular transport of lysosomal enzymes. In addition, the receptor also mediates some biological effects in response to IGF-II binding in both neuronal and nonneuronal systems. Multidisciplinary efforts to elucidate the intracellular signaling pathways that underlie these effects have generated data to suggest that the IGF-II/M6P receptor might mediate transmembrane signaling via a G protein-coupled mechanism. The purpose of this review is to outline the characteristics of traditional and nontraditional GPCRs, to relate the IGF-II/M6P receptor's structure with its role in G protein-coupled signaling and to summarize evidence gathered over the years regarding the putative signaling of the IGF-II/M6P receptor mediated by a G protein.


Sequence of Alzheimer disease biomarker changes in cognitively normal adults: A cross-sectional study.
To determine the ordering of changes in Alzheimer disease (AD) biomarkers among cognitively normal individuals. Cross-sectional data, including CSF analytes, molecular imaging of cerebral fibrillar β-amyloid (Aβ) with PET using the [11C] benzothiazole tracer Pittsburgh compound B (PiB), MRI-based brain structures, and clinical/cognitive outcomes harmonized from 8 studies, collectively involving 3,284 cognitively normal individuals 18 to 101 years of age, were analyzed. The age at which each marker exhibited an accelerated change (called the change point) was estimated and compared across the markers. Accelerated changes in CSF Aβ1-42 (Aβ42) occurred at 48.28 years of age and in Aβ42/Aβ40 ratio at 46.02 years, followed by PiB mean cortical standardized uptake value ratio (SUVR) with a change point at 54.47 years. CSF total tau (Tau) and tau phosphorylated at threonine 181 (Ptau) had a change point at ≈60 years, similar to those for MRI hippocampal volume and cortical thickness. The change point for a cognitive composite occurred at 62.41 years. The change points for CSF Aβ42 and Aβ42/Aβ40 ratio, albeit not significantly different from that for PiB SUVR, occurred significantly earlier than that for CSF Tau, Ptau, MRI markers, and the cognitive composite. Adjusted analyses confirmed that accelerated changes in CSF Tau, Ptau, MRI markers, and the cognitive composite occurred at ages not significantly different from each other. Our findings support the hypothesized early changes of amyloid in preclinical AD and suggest that changes in neuronal injury and neurodegeneration markers occur close in time to cognitive decline.


Metalloproteinases in degenerative aortic disease.
1. Atherosclerosis and aneurysm of the abdominal aorta are associated with thinning of the medial connective tissue. We have investigated the presence of the connective-tissue-degrading metalloproteinases in homogenates prepared from atherosclerotic, aneurysmal and control aortic media. 2. Gelatinase activity was much increased in homogenates from atherosclerotic and aneurysmal aorta [10.9 +/- 1.8 and 13.3 +/- 3.3 micrograms of gelatin hydrolysed h-1 (mg of protein)-1 respectively]. This gelatinase activity was highest at the luminal aspect of the aortic media, where the activity increased three- to five-fold after the destruction of alpha 2-macroglobulin. Zymograms demonstrated the principal gelatinase in atherosclerotic aorta to have a molecular mass of about 92 kDa, whereas in aneurysmal aorta there was a spectrum of gelatinase activity from 92 to 55 kDa. 3. Collagenase and stromelysin (proteoglycanase) could be detected by immunoblotting in homogenates of aneurysmal aorta, but rarely in atherosclerotic aorta and never in control aorta. Collagenase and stromelysin activities were low, but increased two- to three-fold after the destruction of tissue inhibitor of metalloproteinases. Collagenase and stromelysin activities were highest at the adventitial aspect of aneurysmal media. 4. The secretion of gelatinase by inflammatory cells at the intima of diseased aorta could have a pathological role in establishing atherosclerotic plaques and medial thinning. Secretion of collagenase, gelatinase and stromelysin from the adventitia could accelerate connective tissue degradation in the media of aneurysmal aorta.


When does Parkinson disease start?
There is convincing evidence that the Parkinson disease neurodegenerative process begins many years before the onset of motor manifestations. Initial estimates based on nigral neuropathological findings or striatal dopamine imaging suggested a 5- to 6-year preclinical period. However, more recent evidence of Lewy body pathology in other neuronal populations preceding nigral involvement suggests that the preclinical phase may be much longer. Epidemiologic studies of nonmotor manifestations, such as constipation, anxiety disorders, rapid eye movement sleep behavior disorder (RBD), and anemia, suggest that the preclinical period extends at least 20 years before the motor manifestations. Olfactory impairment and depression may also precede the onset of motor manifestations; however, the lag time may be shorter. Recognition of a nonmotor preclinical phase spanning 20 or more years should guide the search for predictive biomarkers and the identification of risk or protective factors for Parkinson disease.


Classification of gunshot injuries in civilians.
Gunshot injuries have become extremely prevalent among the United States civilian population because of increasing urban violence and the availability of handguns. However, the increasing prevalence of gunshot injuries in civilians dramatically contrasts with the paucity of scientific literature pertaining to the diagnosis, classification, and treatment of these injuries. The objective of the current study was to delineate the principal factors associated with gunshot injury severity in civilians, designate their importance in various injury patterns, and propose a new comprehensive classification system that may establish more uniform treatment approaches. The authors critically review existing gunshot injury classification systems with emphasis on the ballistic and clinical parameters that compose each system. The authors propose a new classification system based on five gunshot injury parameters: energy, vital structures involved, wound characteristics, fracture, and degree of contamination. This new classification scheme is applicable to all firearm injuries in civilians and assists with proper treatment selection. The proposed classification system is based on the authors' clinical experience in a Level I urban trauma center, and will require validation in a prospective clinical setting.


Decoding the signaling of a GPCR heteromeric complex reveals a unifying mechanism of action of antipsychotic drugs.
Atypical antipsychotic drugs, such as clozapine and risperidone, have a high affinity for the serotonin 5-HT(2A) G protein-coupled receptor (GPCR), the 2AR, which signals via a G(q) heterotrimeric G protein. The closely related non-antipsychotic drugs, such as ritanserin and methysergide, also block 2AR function, but they lack comparable neuropsychological effects. Why some but not all 2AR inhibitors exhibit antipsychotic properties remains unresolved. We now show that a heteromeric complex between the 2AR and the G(i)-linked GPCR, metabotropic glutamate 2 receptor (mGluR2), integrates ligand input, modulating signaling output and behavioral changes. Serotonergic and glutamatergic drugs bind the mGluR2/2AR heterocomplex, which then balances Gi- and Gq-dependent signaling. We find that the mGluR2/2AR-mediated changes in Gi and Gq activity predict the psychoactive behavioral effects of a variety of pharmocological compounds. These observations provide mechanistic insight into antipsychotic action that may advance therapeutic strategies for disorders including schizophrenia and dementia.


The analgesic effects of opioids and immersive virtual reality distraction: evidence from subjective and functional brain imaging assessments.
Immersive virtual reality (VR) is a novel form of distraction analgesia, yet its effects on pain-related brain activity when used adjunctively with opioid analgesics are unknown. We used subjective pain ratings and functional magnetic resonance imaging to measure pain and pain-related brain activity in subjects receiving opioid and/or VR distraction. Healthy subjects (n = 9) received thermal pain stimulation and were exposed to four intervention conditions in a within-subjects design: (a) control (no analgesia), (b) opioid administration [hydromorphone (4 ng/mL target plasma level)], (c) immersive VR distraction, and (d) combined opioid + VR. Outcomes included subjective pain reports (0-10 labeled graphic rating scales) and blood oxygen level-dependent assessments of brain activity in five specific, pain-related regions of interest. Opioid alone significantly reduced subjective pain unpleasantness ratings (P < 0.05) and significantly reduced pain-related brain activity in the insula (P < 0.05) and thalamus (P < 0.05). VR alone significantly reduced both worst pain (P < 0.01) and pain unpleasantness (P < 0.01) and significantly reduced pain-related brain activity in the insula (P < 0.05), thalamus (P < 0.05), and SS2 (P < 0.05). Combined opioid + VR reduced pain reports more effectively than did opioid alone on all subjective pain measures (P < 0.01). Patterns of pain-related blood oxygen level-dependent activity were consistent with subjective analgesic reports. These subjective pain reports and objective functional magnetic resonance imaging results demonstrate converging evidence for the analgesic efficacy of opioid administration alone and VR distraction alone. Furthermore, patterns of pain-related brain activity support the significant subjective analgesic effects of VR distraction when used as an adjunct to opioid analgesia. These results provide preliminary data to support the clinical use of multimodal (e.g., combined pharmacologic and nonpharmacologic) analgesic techniques.


Abnormal Haemodynamic Flow Patterns in Bicuspid Pulmonary Valve Disease.
Abnormal flow patterns in the aortas of those with bicuspid aortic valves (BAVs) are increasingly recognized as important in the pathogenesis of aortic dilatation but pulmonary flow patterns in bicuspid pulmonary valves have not been studied. Bicuspid pulmonary valve disease is rare and a small numbers of case reports describe concomitant pulmonary artery dilation similar to the dilation of the ascending aorta, which is often seen in BAVs disease. We examined three cases of bicuspid pulmonary valve disease, 10 healthy volunteers and 10 patients with BAV disease but a tricuspid pulmonary valve. All participants underwent anatomical and functional imaging of the pulmonary valve, pulmonary artery, and right ventricle as well as advanced time-resolved 3-dimensional cardiac magnetic resonance imaging (4D flow) to assess the flow pattern in the pulmonary artery. All patients with a bicuspid pulmonary valve had pulmonary artery dilation and showed distinct helical flow abnormalities with increased rotational flow and increased flow displacement compared to a mild left-handed flow pattern in the healthy volunteers. Additionally, there was marked asymmetry seen in the systolic wall shear stress (WSS) pattern, with the highest values in the anterior wall of the pulmonary artery. In comparison, patients with a BAV but a tricuspid pulmonary valve had normal flow patterns in the pulmonary artery. These haemodynamic findings are similar to recent studies in bicuspid aortic disease, and suggest the importance of flow patterns in the pathophysiology of vessel dilation in both aortic and pulmonary bicuspid valve disease.


Belowground nitrogen partitioning in experimental grassland plant communities of varying species richness.
Partitioning of soil nitrogen (N) by niche separation among species may be an important mechanism explaining species coexistence and positive biodiversity-productivity relationships in terrestrial plant communities. However, there is little experimental evidence for such partitioning, in particular, as assessed across a gradient of species richness. In experimental communities of one, three, and six temperate grassland species in the field, we tested whether increasing species richness (1) decreases niche breadths of individual species, (2) decreases niche overlap among species, and (3) increases niche breadth of whole communities. Six N sources consisting of three different chemical forms of 15N-labeled N (15NO3(-), 15NH4+, 13C2-15N-glycine) injected at two soil depths (3 and 12 cm) were applied to each community. The chemical form and the soil depth of N characterize the niches for which niche breadth (Levins' B) and overlap (proportional similarity) were measured. After 48 hours, aboveground plant material was harvested to measure 15N enrichment. As expected, niche breadth of single species and niche overlap among species decreased with increased species richness, but community niche breadth did not increase. The decrease in niche breadth and niche overlap mostly occurred among subordinate species or pairs of subordinate and dominant species, rather than among dominant species. Species in the six-species mixtures mostly preferred NO3(-) from shallow soil. This may be partly explained by the presence of legumes in all six-species mixtures which allowed "N sparing" (i.e., increased availability of soil N since legumes rely more on atmospheric N2 than on soil N). Niche separation with respect to N uptake from different chemical forms and soil depths did not contribute much to facilitating the coexistence of dominant species, nor do our results suggest it as a major driver of positive diversity-ecosystem functioning relationships. However, partitioning of N may be important for the persistence of subordinate species.


Generation X: implications for faculty recruitment and development in academic health centers.
Differences and tensions between the Baby Boom generation (born 1945-1962) and Generation X (born 1963-1981) have profound implications for the future of academic medicine. By and large, department heads and senior faculty are Boomers; today's residents and junior faculty are Generation X'ers. Looking at these issues in terms of the generations involved offers insights into a number of faculty development challenges, including inadequate and inexpert mentoring, work-life conflicts, and low faculty morale. These insights suggest strategies for strengthening academic medicine's recruitment and retention of Generation X into faculty and leadership roles. These strategies include (1) improving career and academic advising by specific attention to mentoring "across differences"--for instance, broaching the subject of formative differences in background during the initial interaction; adopting a style that incorporates information-sharing with engagement in problem solving; offering frequent, frank feedback; and refraining from comparing today to the glories of yesterday; to support such improvements, medical schools should recognize and evaluate mentoring as a core academic responsibility; (2) retaining both valued women and men in academic careers by having departments add temporal flexibility and create and legitimize less-than-full-time appointments; and (3) providing trainees and junior faculty with ready access to educational sessions designed to turn their "intellectual capital" into "academic career capital."Given the trends discussed in this article, such supports and adaptations are indicated to assure that academic health centers maintain traditions of excellence.


Incidence of epileptiform EEG activity in children during mask induction of anaesthesia with brief administration of 8% sevoflurane.
A high incidence of epileptiform activity in the electroencephalogram (EEG) was reported in children undergoing mask induction of anaesthesia with administration of high doses of sevoflurane for 5 minutes and longer. This study was performed to investigate whether reducing the time of exposure to a high inhaled sevoflurane concentration would affect the incidence of epileptiform EEG activity. It was hypothesized that no epileptiform activity would occur, when the inhaled sevoflurane concentration would be reduced from 8% to 4% immediately after the loss of consciousness. 70 children (age 7-96 months, ASA I-II, premedication with midazolam) were anaesthetized with 8% sevoflurane in 100% oxygen via face mask. Immediately after loss of consciousness, the sevoflurane concentration was reduced to 4%. EEGs were recorded continuously and were later analyzed visually with regard to epileptiform EEG patterns. Sevoflurane at a concentration of 8% was given for 1.2 ± 0.4 min (mean ± SD). In 14 children (20%) epileptiform EEG patterns without motor manifestations were observed (delta with spikes (DSP), rhythmic polyspikes (PSR), epileptiform discharges (PED) in 10, 10, 4 children (14%, 14%, 6%)). 38 children (54%) had slow, rhythmic delta waves with high amplitudes (DS) appearing on average before DSP. The hypothesis that no epileptiform potentials would occur during induction of anaesthesia with a reduction of the inspired sevoflurane concentration from 8% to 4% directly after LOC was not proved. Even if 8% sevoflurane is administered only briefly for induction of anaesthesia, epileptiform EEG activity may be observed in children despite premedication with midazolam.


Pharmacological challenge reveals long-term effects of perinatal phencyclidine on delayed spatial alternation in rats.
Administration of the N-methyl-D-aspartate (NMDA) antagonist phencyclidine (PCP) may produce alterations in behavior that resemble those that have been observed in animal models of schizophrenia. This study was designed to examine the effects of early postnatal injection of PCP on later acquisition and performance of a delayed spatial alternation task, a procedure that is sensitive to manipulations of the prefrontal cortex. At the beginning of the study, we injected cross-fostered female rat pups subcutaneously with either saline or 10 mg/kg PCP on postnatal (PN) days 7, 9, and 11. On PN34, the rats began training in a delayed spatial alternation task consisting of 10 daily trials with a 10-s intertrial interval. Although accuracy improved significantly faster in the saline-treated group than in the PCP-treated group, by PN70, both groups had acquired the task with approximately equal accuracies. Pharmacological challenges with the NMDA antagonists, PCP and ketamine, and with the dopamine modulator, amphetamine, decreased accuracy to a similar extent in both groups of rats when intertrial delays were held constant at 10 s; however, nicotine did not decrease accuracy in either group. In contrast, dizocilpine (a high-affinity NMDA open-channel blocker) produced a more pronounced decrease in accuracy in the PCP-treated rats than in the saline-treated rats. When delays were lengthened to 30 s, PCP also decreased accuracy in the PCP-treated rats to a greater extent than in saline-treated rats. These results suggest that perinatal administration of PCP may produce long-term alterations in cognition that are revealed by pharmacological challenge and manipulation of task difficulty.


Breast cancer risk by breast density, menopause, and postmenopausal hormone therapy use.
We determined whether the association between breast density and breast cancer risk and cancer severity differs according to menopausal status and postmenopausal hormone therapy (HT) use. We collected data on 587,369 women who underwent 1,349,027 screening mammography examinations; 14,090 women were diagnosed with breast cancer. We calculated 5-year breast cancer risk from a survival model for subgroups of women classified by their Breast Imaging Reporting and Data System (BIRADS) breast density, age, menopausal status, and current HT use, assuming a body mass index of 25 kg/m(2). Odds of advanced (ie, IIb, III, IV) versus early (ie, I, IIa) stage invasive cancer was calculated according to BIRADS density. Breast cancer risk was low among women with low density (BIRADS-1): women age 55 to 59 years, 5-year risk was 0.8% (95% CI, 0.6 to 0.9%) for non-HT users and 0.9% (95% CI, 0.7% to 1.1%) for estrogen and estrogen plus progestin users. Breast cancer risk was high among women with very high density (BIRADS-4), particularly estrogen plus progestin users: women age 55 to 59 years, 5-year risk was 2.4% (95% CI, 2.0% to 2.8%) for non-HT users, 3.0% (95% CI, 2.6% to 3.5%) for estrogen users, and 4.2% (95% CI, 3.7% to 4.6%) for estrogen plus progestin users. Advanced-stage breast cancer risk was increased 1.7-fold for postmenopausal HT users who had very high density (BIRADS-4) compared to those with average density (BIRADS-2). Postmenopausal women with high breast density are at increased risk of breast cancer and should be aware of the added risk of taking HT, especially estrogen plus progestin.


Dissociative electron attachment and anion-induced dimerization in pyruvic acid.
We report partial cross sections for the dissociative electron attachment to pyruvic acid. A rich fragmentation dynamics is observed. Electronic structure calculations facilitate the identification of complex rearrangement reactions that occur during the dissociation. Furthermore, a number of fragment anions produced at electron energies close to 0 eV are observed, that cannot originate from single electron-molecule collisions. We ascribe their production to secondary reactions of the transient anions with neutral molecules. Such reactions turn out to be unusually efficient; the most probable reason for this is that they proceed via the formation of a double-hydrogen-bonded complex followed by an ultrafast proton transfer between the reaction partners.