Prostaglandin profiles in relation to local circulatory changes following focal cerebral ischemia in cats.
We explored the temporal and topographic relations between local cerebral blood flow and regional brain prostaglandin profile following prolonged or transient occlusion of the middle cerebral artery in cats. Each experimental group was subjected to a sham operation, prolonged ischemia, or recirculation. Local cerebral blood flow was measured by the hydrogen clearance method. Following in situ freezing, cortical samples were obtained from each gyrus for determination of prostaglandin (PG) F2 alpha, PGE2, 6-keto-PGF1 alpha, and thromboxane (TX) B2 concentrations by radioimmunoassay. During prolonged ischemia, the concentrations of PGF2 alpha and PGE2 within the middle cerebral artery territory were significantly increased. Immediately after recirculation, there was a prominent but transient increase in PGF2 alpha and PGE2 in gyri that had been exposed to moderate ischemia (perifocal area). By contrast, the increases in these prostaglandins were slow and less prominent in gyri that had been exposed to severe ischemia (the focal area). The concentration of 6-keto-PGF1 alpha did not change during prolonged ischemia but transiently increased following recirculation in both the focal and perifocal areas. The TXB2 concentration did not change in any experimental group. Our study revealed a homogeneous increase in the regional brain content of PGE2 or PGF2 alpha in spite of the heterogeneous reduction of local cerebral blood flow during prolonged ischemia. Following recirculation, the focal and perifocal areas exhibited different patterns of prostanoid content. No correlation was found between local cerebral blood flow and the regional concentration of any prostaglandin examined.


Reply to comments on "Radiative transfer over small distances from a heated metal".
Some previous works showed that radiative transfer between two closely spaced, lossy media diverges as 1/L(2), where L is the spacing between the two media. This divergent power transfer clearly violates energy conservation. The explanation for this unphysical result is that too many optical modes were counted in those previous works, and many of those modes are physically unattainable. Moreover, many physically significant optical modes were not counted in the previous works.


First Report of Stem Blight of Eleocharis dulcis Caused by Phoma bellidis in China.
Eleocharis dulcis is a perennial herbaceous plant in the family Cyperaceae, which is native to China and India where it grows well in moist-to-wet soils. It is commonly used as a fruit or a vegetable. From August 2009 to December 2010, symptoms were observed on E. dulcis stems in Tuanfeng County, Hubei, China, with the crop area affected estimated to be more than 1,300 ha per year. Corm yield was reduced by 20% on average with as much as 60% yield losses in some fields. Lesions were initially small, red-brown, and oval or circular that enlarged to produce apical necrosis and extending until the stems withered, usually within 2 months. To obtain isolates, diseased tissue was disinfested for 1 min in 0.1% mercuric chloride solution, rinsed with sterilized water, and plated on potato dextrose agar. Isolates with similar morphological characteristics were consistently recovered. Three isolates, CTF-3, CTF-10, and CTF-11, were used to further evaluate characteristics of the pathogen. After 7 days, white colonies were 76 to 80 mm across on oatmeal agar (OA) with sparse aerial hyphae and a slight salmon color in the conidial masses. Pycnidia produced on OA were globose to subglobose, usually with one slightly ostiolar papilla, olivaceous to olivaceous black, and 93 to 245 μm in diameter. Conidia were hyaline, unicellular, ellipsoidal, mostly with two polar guttules, and 3.6 to 6.2 × 2.0 to 3.3 μm. Chlamydospores were absent. Growth of the isolates on malt extract agar (MEA) was slower than on OA, and the colony diameters at 7 days were 60 to 65 mm. The reactions with 1M NaOH were both positive on OA and MEA where the cultures initially changed to yellow green and gradually turned to red. The pathogen was identified as Phoma bellidis Neerg. based on descriptions in Boerema et al. (2). Pathogenicity tests were performed with the three isolates in the laboratory by spraying conidial suspensions (1 × 106 conidia/ml) containing 0.1% Tween 20 until runoff (30 ml per plant) onto stem surfaces of 50-day-old, 60 cm tall plants. For each isolate, there were 50 stems from five replicate plants that had multiple stems per plant. Control plants were treated with sterilized water containing 0.1% Tween 20 only. Plants were incubated with a 16-h photoperiod at 28°C and 90% relative humidity in an artificial climate chamber. Five days after inoculation, typical red-brown spots were observed on all inoculated stems but no symptoms were seen on water-treated control plants. Koch's postulates were fulfilled by reisolation of P. bellidis from diseased stems. The pathogenicity tests were repeated twice more with the same results. P. bellidis has only been reported previously on Bellis spp. from England, Denmark, Italy, the Netherlands, and Switzerland (1,2). Furthermore, there are only a few fungal diseases known to be associated with E. dulcis, and none so far that involve species of Phoma (3,4). To our knowledge, this is the first report of P. bellidis infecting E. dulcis worldwide. References: (1) M. M. Aveskamp et al. Stud. Mycol. 65:27, 2010. (2) G. H. Boerema et al. Phoma Identification Manual: Differentiation of Specific and Infra-Specific Taxa in Culture. CABI Publishing, Wallingford, UK, 2004. (3) P. L. Lentz. Am. Midl. Nat. 67:184, 1962. (4) L. Pan et al. J. Changjiang Vegetables (in Chinese) 14:10, 2010.


Simulating the effects of water limitation on plant biomass using a 3D functional-structural plant model of shoot and root driven by soil hydraulics.
Improved modelling of carbon assimilation and plant growth to low soil moisture requires evaluation of underlying mechanisms in the soil, roots, and shoots. The feedback between plants and their local environment throughout the whole spectrum soil-root-shoot-environment is crucial to accurately describe and evaluate the impact of environmental changes on plant development. This study presents a 3D functional structural plant model, in which shoot and root growth are driven by radiative transfer, photosynthesis, and soil hydrodynamics through different parameterisation schemes relating soil water deficit and carbon assimilation. The new coupled model is used to evaluate the impact of soil moisture availability on plant productivity for two different groups of flowering plants under different spatial configurations. In order to address different aspects of plant development due to limited soil water availability, a 3D FSP model including root, shoot, and soil was constructed by linking three different well-stablished models of airborne plant, root architecture, and reactive transport in the soil. Different parameterisation schemes were used in order to integrate photosynthetic rate with root water uptake within the coupled model. The behaviour of the model was assessed on how the growth of two different types of plants, i.e. monocot and dicot, is impacted by soil water deficit under different competitive conditions: isolated (no competition), intra, and interspecific competition. The model proved to be capable of simulating carbon assimilation and plant development under different growing settings including isolated monocots and dicots, intra, and interspecific competition. The model predicted that (1) soil water availability has a larger impact on photosynthesis than on carbon allocation; (2) soil water deficit has an impact on root and shoot biomass production by up to 90 % for monocots and 50 % for dicots; and (3) the improved dicot biomass production in interspecific competition was highly related to root depth and plant transpiration. An integrated model of 3D shoot architecture and biomass development with a 3D root system representation, including light limitation and water uptake considering soil hydraulics, was presented. Plant-plant competition and regulation on stomatal conductance to drought were able to be predicted by the model. In the cases evaluated here, water limitation impacted plant growth almost 10 times more than the light environment.


Are cranial biomechanical simulation data linked to known diets in extant taxa? A method for applying diet-biomechanics linkage models to infer feeding capability of extinct species.
Performance of the masticatory system directly influences feeding and survival, so adaptive hypotheses often are proposed to explain craniodental evolution via functional morphology changes. However, the prevalence of "many-to-one" association of cranial forms and functions in vertebrates suggests a complex interplay of ecological and evolutionary histories, resulting in redundant morphology-diet linkages. Here we examine the link between cranial biomechanical properties for taxa with different dietary preferences in crown clade Carnivora, the most diverse clade of carnivorous mammals. We test whether hypercarnivores and generalists can be distinguished based on cranial mechanical simulation models, and how such diet-biomechanics linkages relate to morphology. Comparative finite element and geometric morphometrics analyses document that predicted bite force is positively allometric relative to skull strain energy; this is achieved in part by increased stiffness in larger skull models and shape changes that resist deformation and displacement. Size-standardized strain energy levels do not reflect feeding preferences; instead, caniform models have higher strain energy than feliform models. This caniform-feliform split is reinforced by a sensitivity analysis using published models for six additional taxa. Nevertheless, combined bite force-strain energy curves distinguish hypercarnivorous versus generalist feeders. These findings indicate that the link between cranial biomechanical properties and carnivoran feeding preference can be clearly defined and characterized, despite phylogenetic and allometric effects. Application of this diet-biomechanics linkage model to an analysis of an extinct stem carnivoramorphan and an outgroup creodont species provides biomechanical evidence for the evolution of taxa into distinct hypercarnivorous and generalist feeding styles prior to the appearance of crown carnivoran clades with similar feeding preferences.


An RGS-containing sorting nexin controls Drosophila lifespan.
The pursuit of eternal youth has existed for centuries and recent data indicate that fat-storing tissues control lifespan. In a D. melanogaster fat body insertional mutagenic enhancer trap screen designed to isolate genes that control longevity, we identified a regulator of G protein signaling (RGS) domain containing sorting nexin, termed snazarus (sorting nexin lazarus, snz). Flies with insertions into the 5' UTR of snz live up to twice as long as controls. Transgenic expression of UAS-Snz from the snz Gal4 enhancer trap insertion, active in fat metabolic tissues, rescued lifespan extension. Further, the lifespan extension of snz mutants was independent of endosymbiont, e.g., Wolbachia, effects. Notably, old snz mutant flies remain active and fertile indicating that snz mutants have prolonged youthfulness, a goal of aging research. Since mammals have snz-related genes, it is possible that the functions of the snz family may be conserved to humans.


Quality of the bottom sediment prior to dredging in the Golden Horn of Istanbul.
The Golden Horn has experienced severe pollution due to uncontrolled domestic and industrial wastewater discharges until recent years. A restoration project has been developed by our universities, upon a request from Istanbul Metropolitan Municipality. Two principal alternatives for the dredging and disposal of the bottom sediments were considered: disposing on the land and disposing in the sea. Both of these alternatives include several sub-alternatives. Characterization of the sediment quality is crucially important for selecting the best alternative considering the cost, environmental impact and public acceptance. However, only a few and rather old studies were present with which it was not possible to get a comprehensive information on the critical sediment characteristics. Therefore, the aim of this study was determination of spatial distribution of sediment characteristics. The project area, at which the sediment quality determined, covers the part of the Golden Horn remaining at the upstream of Valide Sultan Bridge. The number of sampling stations were thirteen and the sediment samples were collected from 0.0m, 5.0m and 10.0m from the bottom surface. The following parameters were measured on each sample: Total solids, organic matter, total phosphorus, TKN, oil and grease, total sulphur, and sediment oxygen demand (SOD). Sediment oxygen demand parameter was further divided into three fractions, namely, biological (SOD-B) and chemical (SOD-C). Average organic content of the bottom sediment was around 10% while ammonia and sulfur exhibit very high levels. It is found that the bottom sediment is well stabilized with very low organic content below 5.0m from the bottom surface. It can be said that, removing the upper 5m of the bottom sediment will be enough for creating a relatively stable bottom surface which will cause oxygen depletion in the overlaying water at acceptable levels. High SOD values of the bottom sediment makes the alternatives considering disposal in the Marmara Sea and Black Sea inapplicable. High SOD-C values, especially, indicate that the sediment will cause a tremendous reduction in the oxygen concentration in a very short time at any marine environment, and even it may create anaerobic conditions. Therefore, disposal of dredged sediment into abandoned mines 4km from the Golden Horn by a pressure pipeline has been chosen as the best applicable alternative.


Prediction of coronary heart disease or heart failure using high-sensitivity cardiac troponin T: A pilot study.
High-sensitivity cardiac troponin T (hs-cTnT) is a good prognostic marker for mortality. However, it is uncertain if hs-cTnT can be used to detect sub-clinical cardiac disease. Pilot study in patients without known heart disease and elevated hs-cTnT measured at presentation to the emergency department. Hs-cTnT was measure with Roche Diagnostics. Echocardiography was used to assess structural heart disease and the participants underwent computed tomography angiography for assessment of coronary artery disease and agatston score. Ten patients were included in the final cohort. Median age was 68 years IQR (57-78) and 80% were female (n = 8). Six patients had a history of chronic obstructive lung disease and five patients had history of hypertension. The median level of hs-cTnT was 26 ng/L and values ranged from 19 ng/L to 495 ng/L. The median calcium score was 12. Three patients had signs of coronary artery disease. All patients had normal left ventricular ejection fraction with a median LVEF at 54.5%. Two patients were noted to have increased left ventricular mass index (LVMI). The majority of patients with hs-cTnT above the 99th percentile did not have structural heart disease or ischaemic coronary disease. However, 30% of the patient did have signs of coronary disease and might benefit from preventive medical treatment. Measuring hs-cTnT in the absence of acute illness might be a better approach for evaluation for sub-clinical cardiac disease.


Automatic decomposition of electrophysiological data into distinct nonsinusoidal oscillatory modes.
Neurophysiological signals are often noisy, nonsinusoidal, and consist of transient bursts. Extraction and analysis of oscillatory features (such as waveform shape and cross-frequency coupling) in such data sets remains difficult. This limits our understanding of brain dynamics and its functional importance. Here, we develop iterated masking empirical mode decomposition (itEMD), a method designed to decompose noisy and transient single-channel data into relevant oscillatory modes in a flexible, fully data-driven way without the need for manual tuning. Based on empirical mode decomposition (EMD), this technique can extract single-cycle waveform dynamics through phase-aligned instantaneous frequency. We test our method by extensive simulations across different noise, sparsity, and nonsinusoidality conditions. We find itEMD significantly improves the separation of data into distinct nonsinusoidal oscillatory components and robustly reproduces waveform shape across a wide range of relevant parameters. We further validate the technique on multimodal, multispecies electrophysiological data. Our itEMD extracts known rat hippocampal θ waveform asymmetry and identifies subject-specific human occipital α without any prior assumptions about the frequencies contained in the signal. Notably, it does so with significantly less mode mixing compared with existing EMD-based methods. By reducing mode mixing and simplifying interpretation of EMD results, itEMD will enable new analyses into functional roles of neural signals in behavior and disease.NEW & NOTEWORTHY We introduce a novel, data-driven method to identify oscillations in neural recordings. This approach is based on empirical mode decomposition and reduces mixing of components, one of its main problems. The technique is validated and compared with existing methods using simulations and real data. We show our method better extracts oscillations and their properties in highly noisy and nonsinusoidal datasets.


The diffusive vesicle supply center model for tip growth in fungal hyphae.
We propose the diffusive vesicle supply center model for tip growth in fungal hyphae. The model is based on the three-dimensional vesicle supply center (VSC) model [Gierz, G., Bartnicki-García, S., 2001. A three-dimensional model of fungal morphogenesis based on the vesicle supply center concept: J. Theor. Biol. 208, 151-164], but incorporates two aspects of a more realistic vesicle delivery mechanism: vesicle diffusion from the VSC and a finite rate constant for vesicle fusion with the cell membrane. We develop a framework to describe tip growth for a general class of models based on the vesicle supply center concept. Combining this with a method for calculating the steady state distribution of diffusive vesicles we iteratively solve for stationary cell shapes. These show a blunter tip than predicted by the original VSC model, which we attribute to increased forward-directed vesicle delivery via diffusion. The predicted distance between the VSC and the utmost tip of the cell is set by the ratio between the diffusion constant and the rate constant for vesicle exocytosis. Combined with the cell radius, these define the only dimensionless parameter for our model.


Capillary permeability and extracellular fluid volumes in pregnancy-induced hypertension.
1. Capillary permeability was determined by the disappearance rate of Evans Blue dye from plasma in healthy non-pregnant women, normal third-trimester primigravidae and primigravidae with pregnancy-induced hypertension. 2. Extracellular fluid volume was determined from the disappearance curves of injected mannitol in the same subjects and the plasma volume was measured by the Evans Blue dye dilution technique. 3. In normal pregnancy capillary permeability was not altered from that of non-pregnant subjects. Although extracellular fluid volume and plasma volume were increased in normal pregnant compared with non-pregnant women, the distribution of fluid between plasma volume and interstitial fluid volume was unaltered. 4. Women with established pregnancy-induced hypertension had a more rapid Evans Blue disappearance rate and a lower plasma volume than normal pregnant women, independent of the presence of proteinuria. Maternal plasma volume correlated positively and significantly with fetal birth weight in women with pregnancy-induced hypertension, emphasizing the important relationship between maternal plasma volume and fetal outcome. 5. The increased capillary permeability in women with pregnancy-induced hypertension was associated with a reduction in the plasma volume/interstitial fluid volume ratio but a normal extracellular fluid volume, suggesting that the reduced plasma volume did not result from sodium loss but rather from a redistribution of the total extracellular fluid volume. These changes did not differ significantly in subgroups with and without oedema.


A framework to evaluate the cost-effectiveness of the NADiA ProsVue slope to guide adjuvant radiotherapy among men with high-risk characteristics following prostatectomy for prostate cancer.
The NADiA ProsVue is a prognostic system that measures prostate-specific antigen slope to identify men at lower risk of clinical recurrence of prostate cancer after radical prostatectomy. We developed a decision-modeling framework to evaluate its cost-effectiveness to guide the use of adjuvant radiotherapy (ART). We populated the model using patient-level data and external sources. Patients were classified as intermediate risk or high risk on the basis of Cancer of the Prostate Risk Assessment-Postsurgical (CAPRA-S) nomogram and then stratified by the ProsVue slope (≤2 pg/mL/mo; >2 pg/mL/mo) and receipt of ART. In sensitivity analyses, we varied the effect of the ProsVue slope on the use of ART and other model parameters. The cost-effectiveness of the ProsVue-guided strategy varied widely because of small differences in quality-adjusted life-years (QALYs) at 10 years. In the intermediate-risk group, when the use of ART decreased from 20% (standard care) to 7.5% among patients with a ProsVue slope value of 2 pg/mL/mo or less, the incremental cost-effectiveness ratio was $25,160/QALY. In the high-risk group, the use of ART would have to decrease from 40% (standard care) to 11.5% among those with a ProsVue slope value of 2 pg/mL/mo or less to obtain a ratio of $50,000/QALY. The cost-effectiveness ratios were sensitive to varying benefits of salvage therapy, quality of life, and costs of ART and ProsVue testing. The effect of the ProsVue system on costs will be dependent on the extent to which ART decreases among men identified as having a low risk of recurrence. Its effect on QALYs will remain conditional on uncertain clinical and quality-of-life benefits associated with ART.


N-terminal domain of alphaB-crystallin provides a conformational switch for multimerization and structural heterogeneity.
The small heat shock protein (sHSP) αB-crystallin (αB) plays a key role in the cellular protection system against stress. For decades, high-resolution structural studies on heterogeneous sHSPs have been confounded by the polydisperse nature of αB oligomers. We present an atomic-level model of full-length αB as a symmetric 24-subunit multimer based on solid-state NMR, small-angle X-ray scattering (SAXS), and EM data. The model builds on our recently reported structure of the homodimeric α-crystallin domain (ACD) and C-terminal IXI motif in the context of the multimer. A hierarchy of interactions contributes to build multimers of varying sizes: Interactions between two ACDs define a dimer, three dimers connected by their C-terminal regions define a hexameric unit, and variable interactions involving the N-terminal region define higher-order multimers. Within a multimer, N-terminal regions exist in multiple environments, contributing to the heterogeneity observed by NMR. Analysis of SAXS data allows determination of a heterogeneity parameter for this type of system. A mechanism of multimerization into higher-order asymmetric oligomers via the addition of up to six dimeric units to a 24-mer is proposed. The proposed asymmetric multimers explain the homogeneous appearance of αB in negative-stain EM images and the known dynamic exchange of αB subunits. The model of αB provides a structural basis for understanding known disease-associated missense mutations and makes predictions concerning substrate binding and the reported fibrilogenesis of αB.


Methane removal and the proportional reductions in surface temperature and ozone.
Mitigating climate change requires a diverse portfolio of technologies and approaches, including negative emissions or removal of greenhouse gases. Previous literature focuses primarily on carbon dioxide removal, but methane removal may be an important complement to future efforts. Methane removal has at least two key benefits: reducing temperature more rapidly than carbon dioxide removal and improving air quality by reducing surface ozone concentration. While some removal technologies are being developed, modelling of their impacts is limited. Here, we conduct the first simulations using a methane emissions-driven Earth System Model to quantify the climate and air quality co-benefits of methane removal, including different rates and timings of removal. We define a novel metric, the effective cumulative removal, and use it to show that each effective petagram of methane removed causes a mean global surface temperature reduction of 0.21 ± 0.04°C and a mean global surface ozone reduction of 1.0 ± 0.2 parts per billion. Our results demonstrate the effectiveness of methane removal in delaying warming thresholds and reducing peak temperatures, and also allow for direct comparisons between the impacts of methane and carbon dioxide removal that could guide future research and climate policy. This article is part of a discussion meeting issue 'Rising methane: is warming feeding warming? (part 1)'.


Solution structure of the ubiquitin-conjugating enzyme UbcH5B.
The ubiquitination pathway is the main pathway for protein degradation in eukaryotic cells. The attachment of ubiquitin to a substrate protein is catalyzed by three types of enzymes, namely a ubiquitin activating enzyme (E1), a ubiquitin-conjugating enzyme (E2), and a ubiquitin ligase (E3). Here, the structure of the human ubiquitin-conjugating enzyme (E2) UbcH5B has been solved by a combination of homology modeling, NMR relaxation data and automated NOE assignments. Comparison to E2 structures solved previously by X-ray crystallography or NMR shows in all cases the same compact fold, but differences are observed in the orientation of both N and C-terminal alpha-helices. The N-terminal helix that is involved in binding to ubiquitin ligases (E3) displays a different position, which could have consequences for precise E2-E3 recognition. In addition, multiple conformations of the side-chain of Asn77 are found in solution, which contrasts the single hydrogen-bonded conformation in the crystal structures of E2 enzymes. The possible implication of this conformational freedom of Asn77 for its catalytic function is discussed.


Effects of total sleep deprivation on the perception of action capabilities.
Changes in a subject's state have been shown to modulate the perceptual update of his or her action capabilities. In parallel, sleep deprivation impairs in cognitive functions. It involves common neural structures that support the perception of successfully achieving a motor task. Thus, the study investigated the effect of 24 h of sleep deprivation on the perception of action capabilities. Twenty-four healthy participants were randomly separated into two groups (control group vs. 24 h sleep deprivation group). Participants in the control group slept at home according to their habitual sleep-wake schedule. The 24-h sleep deprivation group stayed awake in the laboratory. Participants estimated the limit of their maximal height of stepping-over a bar before and after the sleep intervention. These estimations were compared to each participant's actual maximal stepping-over height. Physical performance (measured by maximal voluntary quadriceps contraction and repetitive vertical jumping tests) and perceptual inhibition tests (measured by choice reaction time tasks) were also performed for three sessions at three time points t 0, t +12h, and t +24h with t 0 = 8:00 a.m. for all participants. Participants in the 24-h sleep deprivation group showed impairments in perceived over-stepping performance and impaired cognitive functioning (higher reaction time), while no changes were observed in actual performance in the over-stepping, voluntary quadriceps contraction, or jumping tasks. The cognitive processing of inputs that specify the estimated consequences of motor action is discussed as the main explanation for the inability to successfully update the perception of action capabilities after sleep deprivation.


X-ray structure of human stromelysin catalytic domain complexed with nonpeptide inhibitors: implications for inhibitor selectivity.
Effective inhibitors of matrix metalloproteinases (MMPs), a family of connective tissue-degrading enzymes, could be useful for the treatment of diseases such as cancer, multiple sclerosis, and arthritis. Many of the known MMP inhibitors are derived from peptide substrates, with high potency in vitro but little selectivity among MMPs and poor bioavailability. We have discovered nonpeptidic MMP inhibitors with improved properties, and report here the crystal structures of human stromelysin-1 catalytic domain (SCD) complexed with four of these inhibitors. The structures were determined and refined at resolutions ranging from 1.64 to 2.0 A. Each inhibitor binds in the active site of SCD such that a bulky diphenyl piperidine moiety penetrates a deep, predominantly hydrophobic S'1 pocket. The active site structure of the SCD is similar in all four inhibitor complexes, but differs substantially from the peptide hydroxamate complex, which has a smaller side chain bound in the S'1 pocket. The largest differences occur in the loop forming the "top" of this pocket. The occupation of these nonpeptidic inhibitors in the S'1 pocket provides a structural basis to explain their selectivity among MMPs. An analysis of the unique binding mode predicts structural modifications to design improved MMP inhibitors.


Acute septal panniculitis. A cutaneous marker of a very early stage of pancreatic panniculitis indicating acute pancreatitis.
Pancreatitis may occasionally be complicated by panniculitis as a result of the release of pancreatic enzymes. Pancreatic panniculitis is rare, occurring in 2-3% of all patients with pancreatic disorders, with a higher incidence among alcoholic males. A 29-year-old male was admitted to our Department with acute abdominal pain one day following alcohol consumption. On physical examination, tender erythematous plaques and nodules were present on the left ankle and the pretibial regions of both lower legs, a clinical sign of panniculitis indicating acute pancreatitis common in alcoholic patients. Abdominal ultrasonography showed a diffusely edematous pancreas suggestive of acute pancreatitis. Abdominal contrast enhanced computerized tomography revealed features suggestive of severe acute pancreatitis with pancreatic necrosis. A skin biopsy confirmed the diagnosis of septal panniculitis without vasculitis or fat necrosis, which is indicative of a very early stage of pancreatic panniculitis suggesting acute alcoholic pancreatitis. Septal panniculitis without vasculitis or fat necrosis is a cutaneous clinical marker which denotes a very early stage of pancreatic panniculitis associated with acute alcoholic pancreatitis. The treatment of pancreatic panniculitis is primarily supportive and depends on the underlying pancreatic pathology which may include surgery or endoscopic management.


Taiwanese fathers' experiences of having their child diagnosed with a developmental disability.
Receiving a diagnosis of a developmental disability in a child can be a crisis event for parents. Gender differences in parental roles are worth considering when exploring the impact of having a child with a disability. However, most studies on this topic have focused on the mother's experience, and little is known about what the father goes through as the parent of a child diagnosed with a disability. Even less is known regarding this experience in the context of the Chinese culture. The goal of this study was to explore fathers' experiences of having a child diagnosed with a developmental disability in a Chinese cultural context. This study used a hermeneutic phenomenological approach informed by the philosophical world views of Heidegger. The 16 fathers who participated in the study were purposively sampled from a teaching hospital in central Taiwan. Data were collected using in-depth and semistructured interviews and were analyzed using hermeneutic analysis. Data analysis revealed four shared meanings: losing hope, feelings of failure, being frustrated with family conflicts, and searching for positive coping strategies. Fathers feel shock and despair as well as personally devalued when learning that their child has been diagnosed with a developmental disability. Chinese cultural beliefs and values can elicit different experiences for fathers while helping them make sense of their experiences and accept their child in meaningful ways. Nurses can actively engage fathers as well as mothers to understand their feelings and thoughts about their child's disability to provide appropriate emotional and informational support. Providing support or referral is necessary particularly when fathers encounter issues with the child's grandparents. Nurses can assist fathers to find a way to make sense of having a child with a disability within their cultural frame of reference by adapting cultural beliefs and values to their situation and to make meaning of their child's life.


Consistently inconsistent: a snapshot of across- and within-state disparities in the prevalence of childhood overweight and obesity.
The epidemic of childhood overweight and obesity is characterized by known disparities. Less is known about how these disparities vary across and within the state in which a child lives. To examine the magnitude and patterns of across- and within-state differences in the prevalence of childhood overweight and obesity according to children's insurance type (public versus private), household income level, race (non-Hispanic black versus non-Hispanic white), and ethnicity (Hispanic versus non-Hispanic). State-level overweight and obesity prevalence rates for children aged 10-17 were calculated by using data from the 2003 National Survey of Children's Health. Statistical significance of across-state variation was assessed. Disparity ratios assessed within-state equity according to children's insurance type, income, race, and ethnicity. State ranks on overall prevalence and ranks on disparity indices were correlated and regression models were fit to examine within-state consistency, state-level clustering effects and whether the effect of child characteristics varied across key population subgroups. Prevalence of childhood overweight and obesity varied significantly across states. A total of 31 states had a prevalence lower than the national rate of 30.6% (14 statistically significant), and 20 had higher rates (9 statistically significant). Within-state disparity indices ranged from a low of 1.0 (no disparity) to a high of 3.44 (nearly 3.5 times higher). Correlations between state ranks on overall prevalence and their ranks on disparity indices were not significant for the insurance type, income, or race disparity groups examined. A modest state-clustering effect was found. Compared with non-Hispanic white children, the effect of lower household income and lower household education level education were significantly less for non-Hispanic black and Hispanic children, who were more likely to be overweight or obese regardless of these other factors. Disparities in the prevalence of childhood overweight and obesity vary significantly both within and across states. Patterns of variation are inconsistent within states, highlighting the need for states to undertake state- and population-specific analyses and interventions to address the epidemic.


A role for the intermediate affinity IL-2R in the protection against glucocorticoid-induced apoptosis.
Recent work has shown that T lymphocytes undergo apoptosis upon treatment with the glucocorticoid analogue dexamethasone. These cells can be protected from the effect of dexamethasone by interleukin-2 (IL-2) or IL-4. We were interested in analysing whether a transfected cell dependent on three different lymphokines could be protected by them from the effect of dexamethasone. In addition, we took advantage of our cellular system, in which we expressed intermediate- or high-affinity IL-2R independently, to analyse the role of these receptors in the protection from glucocorticoid-induced apoptosis. In this report we show that IL-2 rescues murine T cells expressing exogenous intermediate- (TS1 beta) or high-affinity (TS1 alpha beta) IL-2 receptor (IL-2R) from dexamethasone-induced apoptosis. This result suggests that intermediate-affinity IL-2R alone can replace high-affinity IL-2R for the protection from the effect of dexamethasone. In addition, IL-4 and IL-9 are rescue-factors, as well as IL-2, of glucocorticoid-treated TS1 beta and TS1 alpha beta cells. Our data suggest that the presence of the alpha-chain of the IL-2R is not required for rescue by IL-2 from the effect of dexamethasone. In addition, we show that proliferation is not required for preventing glucocorticoid-induced apoptosis. This result implies a new role for the intermediate-affinity IL-2R.


Artesunate Plus Amodiaquine (AS+AQ) Versus Artemether -Lumefantrine (AL) for the Treatment of Uncomplicated Plasmodium Falciparum Malaria in Sub-Saharan Africa-A Meta-Analysis.
The purpose of this study is to summarize the available data on the efficacy of Artesunate plus Amodiaquine (AS+AQ) versus Artemether -Lumefantrine (AL) for the treatment of uncomplicated Plasmodium falciparum malaria in sub-Saharan Africa using uncorrected parasitaemia as a clinically relevant endpoint. Studies and conference abstracts identified through Pubmed, Medline, Embase, Ansinet, AJOL, Bioline, Cochrane Infectious Diseases Group trials register, The Cochrane Controlled Trials Register, Science Citation Index, Lilacs, African Index Medicus, Clusty, Google, Yahoo and Microsoft search engines. Randomized controlled clinical trials comparing Artesunate-Amodiaquine versus Artemether-Lumefantrine, in Sub-Saharan Africa from January 2004 to June 2009, and which had at least 30 patients per study arm. The authors independently applied the inclusion criteria, assessed methodological quality and extracted data into a predesigned form. The outcome of interest was uncorrected day 28 parasitological failure. Data were then checked for agreement and double entered into RevMan version 5 for further analyses. Fifteen trials (4265 participants) met the inclusion criteria. Day 28 parasitological failure was lower for AL (286 of 2201 participants or 13.0 % failures) when compared with AS+AQ (446 of 2424 participants or 18.4% failures). The relative risk of parasitological failure with AS+AQ was higher when compared with AL (RR 1.65, 95% CI, 1.18-2.32). There were significant heterogeneity and inconsistencies in the studies. AL appears more effective at avoiding parasitological failure at days 28 than AS+AQ.


The role played by natural selection on Mendelian traits in humans.
Detecting whether and how natural selection has targeted regions of the human genome represents a complementary strategy for identifying functionally important loci and variants involved in disease resistance and adaptation to the environment. In contrast with most complex diseases or traits, the genetic architecture of most Mendelian traits is relatively well established. Most mutations associated with Mendelian disease-related traits are highly penetrant and kept at low population frequencies because of the effects of purifying selection. However, this is not always the case. Here, we review several examples of Mendelian mutations-associated with various disease conditions or other traits of anthropological interest-that have increased in frequency in the human population as a result of past positive selection. These examples clearly illustrate the value of a population genetics approach to unravel the biological mechanisms that have been central to our past and present survival against the selective pressures imposed by diseases and other environmental factors.


Transportable extracorporeal lung support for rescue of severe respiratory failure in combat casualties.
Advances in oxygenator membrane, vascular cannula, and centrifugal pump technologies led to the miniaturization of extracorporeal lung support (ECLS) and simplified its insertion and use. Support of combat injuries complicated by severe respiratory failure requires critical care resources not sustainable in the deployed environment. In response to this need, a unique international military-civilian partnership was forged to create a transportable ECLS capability to rescue combat casualties experiencing severe respiratory failure. A multidisciplinary training and consultative relationship developed between the US military at Landstuhl Regional Medical Center (LRMC) and the University Hospital Regensburg (UHR), a German regional "lung failure" center with expertise in ECLS. ECLS circuits used were pumpless arteriovenous extracorporeal lung assist (NovaLung iLA) and pump-driven venovenous extracorporeal membrane oxygenation (PLS Quadrox D Membrane Oxygenator with Rotaflow Centrifugal Pump). US casualties supported by ECLS between June 2005 and August 2011 were identified from the LRMC Trauma Program Registry for review. UHR cared for 10 US casualties supported by ECLS. The initial five patients were cannulated with arteriovenous circuits (pumpless arteriovenous extracorporeal lung assist), and the remaining five were cannulated with pump-driven venovenous circuits (extracorporeal membrane oxygenation). Four patients were cannulated in the war zone, and six patients were cannulated at LRMC after evacuation to Germany. All patients were transferred to UHR for continued management (mean, 9.6 ECLS days). In all cases, both hypoxemia and hypercapnia improved, allowing for decreased airway pressures. Nine patients were weaned from ECLS and extubated. One soldier died from progressive multiple-organ failure. ECLS should be considered in the management of trauma complicated by severe respiratory failure. Modern ECLS technology allows these therapies to be transported for initiation outside of specialized centers even in austere settings. Close collaboration with established centers potentially allows both military and civilian hospitals with infrequent ECLS requirements to use it for initial patient stabilization before transfer for continued care. Therapeutic/care management study, level V.


Staphylococcus lugdunensis infective endocarditis: description of 10 cases and analysis of native valve, prosthetic valve, and pacemaker lead endocarditis clinical profiles.
To evaluate the incidence and the clinical and echocardiographic features of infective endocarditis (IE) caused by Staphylococcus lugdunensis and to identify the prognostic factors of surgery and mortality in this disease. Prospective cohort study. Study at two centres (a tertiary care centre and a community hospital). 10 patients with IE caused by S lugdunensis in 912 consecutive patients with IE between 1990 and 2003. Prospective study of consecutive patients carried out by the multidisciplinary team for diagnosis and treatment of IE from the study institutions. English, French, and Spanish literature was searched by computer under the terms "endocarditis" and "Staphylococcus lugdunensis" published between 1989 and December 2003. Patient characteristics, echocardiographic findings, required surgery, and prognostic factors of mortality in left sided cases of IE. 10 cases of IE caused by S lugdunensis were identified at our institutions, representing 0.8% (four of 467), 1.5% (two of 135), and 7.8% (four of 51) of cases of native valve, prosthetic valve, and pacemaker lead endocarditis in the non-drug misusers. Native valve IE was present in four patients (two aortic, one mitral, and one pulmonary), prosthetic valve aortic IE in two patients, and pacemaker lead IE in the other four patients. All patients with left sided IE had serious complications (heart failure, periannular abscess formation, or shock) requiring surgery in 60% (three of five patients) of cases with an overall mortality rate of 80% (four of five patients). All patients with pacemaker IE underwent combined medical treatment and surgery, and mortality was 25% (one patient). In total 59 cases of IE caused by S lugdunensis were identified in a review of the literature. The combined analysis of these 69 cases showed that native valve IE (53 patients, 77%) is characterised by mitral valve involvement and frequent complications such as heart failure, abscess formation, and embolism. Surgery was needed in 51% of cases and mortality was 42%. Prosthetic valve endocarditis (nine of 60, 13%) predominated in the aortic position and was associated with abscess formation, required surgery, and high mortality (78%). Pacemaker lead IE (seven of 69, 10%) is associated with a better prognosis when antibiotic treatment is combined with surgery. S lugdunensis IE is an uncommon cause of IE, involving mainly native left sided valves, and it is characterised by an aggressive clinical course. Mortality in left sided native valve IE is high but the prognosis has improved in recent years. Surgery has improved survival in left sided IE and, therefore, early surgery should always be considered. Prosthetic valve S lugdunensis IE carries an ominous prognosis.


El nino chaos: overlapping of resonances between the seasonal cycle and the pacific ocean-atmosphere oscillator.
The El Niño-Southern Oscillation (ENSO) cycle is modeled as a low-order chaotic process driven by the seasonal cycle. A simple model suggests that the equatorial Pacific ocean-atmosphere oscillator can go into nonlinear resonance with the seasonal cycle and that with strong enough coupling between the ocean and the atmosphere, the system may become chaotic as a result of irregular jumping of the ocean-atmosphere system among different nonlinear resonances. An analysis of a time series from an ENSO prediction model is consistent with the low-order chaos mechanism.


From the determination of complex reaction mechanisms to systems biology.
This review presents several methods of determining complex chemical reaction mechanisms and their functions. One method is based on correlation functions of measured time series of concentrations of chemical species, another is on measurements of temporal responses of concentrations to various perturbations of arbitrary magnitude, the third deals with the analysis of oscillatory systems, and the fourth describes the use of genetic algorithms. All methods are applicable to chemical, biochemical, and biological reaction systems and to genetic networks. The methods depend on the design of appropriate experiments for the whole system and corresponding theories for interpretation that lead to information on the causal chemical connectivity of species, reaction pathways, reaction mechanisms, control centers in the system, and functions of the system. The first three methods require no assumption of a model or hypothesis, nor extensive calculations, unlike the interpretation of measurements made on a gene network at only one time. The methods offer advantageous approaches to systems biology.


Methotrexate treatment of squamous-cell head and neck cancers: dose-response evaluation.
Seventy-two patients with advanced squamous-cell carcinomas of the head and neck were randomised to receive weekly intravenous methotrexate at doses of either 50 mg/m2 (low dose), 500 mg/m2 (medium dose), or 5 g/m2 (high dose). Patients who failed to respond after four treatments at their initial dose were given four further treatments at the next higher dose. There were two complete responses and 21 partial responses to the initial dose--in 10 out of 22 patients given the high dose, seven out of 27 given the medium dose, six out of 23 given the low dose. A further five out of 16 patients responded after crossing over to a higher dose. Toxicity was more severe with the high-dose regimen. Responders survived significantly longer than non-responders (p less than 0.05), but there was no significant difference in durations of survival among the three treatment groups. Analysis of patients who completed the first four treatments indicated an improved response rate and duration of survival for the high-dose group. Because of toxicity associated with high-dose methotrexate this treatment produces no overall greater benefit than low-dose regimens.


Cost-effectiveness of adalimumab for early-stage Dupuytren's disease : an economic evaluation based on a randomized controlled trial and individual-patient simulation model.
To estimate the potential cost-effectiveness of adalimumab compared with standard care alone for the treatment of early-stage Dupuytren's disease (DD) and the value of further research from an NHS perspective. We used data from the Repurposing anti-TNF for Dupuytren's disease (RIDD) randomized controlled trial of intranodular adalimumab injections in patients with early-stage progressive DD. RIDD found that intranodular adalimumab injections reduced nodule hardness and size in patients with early-stage DD, indicating the potential to control disease progression. A within-trial cost-utility analysis compared four adalimumab injections with no further treatment against standard care alone, taking a 12-month time horizon and using prospective data on EuroQol five-dimension five-level questionnaire (EQ-5D-5L) and resource use from the RIDD trial. We also developed a patient-level simulation model similar to a Markov model to extrapolate trial outcomes over a lifetime using data from the RIDD trial and a literature review. This also evaluated repeated courses of adalimumab each time the nodule reactivated (every three years) in patients who initially responded. The within-trial economic evaluation found that adalimumab plus standard care cost £503,410 per quality-adjusted life year (QALY) gained versus standard care alone over a 12-month time horizon. The model-based extrapolation suggested that, over a lifetime, repeated courses of adalimumab could cost £14,593 (95% confidence interval £7,534 to £42,698) per QALY gained versus standard care alone. If the NHS was willing to pay £20,000/QALY gained, there is a 77% probability that adalimumab with retreatment is the best value for money. Repeated courses of adalimumab are likely to be a cost-effective treatment for progressive early-stage DD. The value of perfect parameter information that would eliminate all uncertainty around the parameters estimated in RIDD and the duration of quiescence was estimated to be £105 per patient or £272 million for all 2,584,411 prevalent cases in the UK. Cite this article: Bone Jt Open 2022;3(11):898-906.


BM28, a human member of the MCM2-3-5 family, is displaced from chromatin during DNA replication.
We have recently cloned and characterized a human member (BM28) of the MCM2-3-5 family of putative relication factors (Todorov, I.T., R. Pepperkok, R.N. Philipova, S. Kearsey, W. Ansorge, and D. Werner. 1994. J. Cell Sci. 107:253-265). While this protein is located in the nucleus throughout interphase, we report here a dramatic alteration in its nuclear binding during the cell cycle. BM28 is retained in the nucleus after Triton X-100 extraction in G1 and early S phase cells, but is progressively lost as S phase proceeds, and little BM28 is retained in detergent-extracted G2 nuclei. BM28 that is resistant to extraction in G1 nuclei is removed by DNase I digestion, suggesting that the protein is chromatin associated. In addition, we present evidence for variations in the electrophoretic mobility of BM28 that may reflect posttranslational modifications of BM28 during the cell cycle. During mitosis, BM28 is present as a fast-migrating form, but on entry into G1, the protein is converted into a slow-migrating form. With the onset of S phase, the slow-migrating form is progressively converted into the fast form. BM28 is phosphorylated at all stages of the cell cycle, but during interphase the fast form is hyperphosphorylated compared with the slow form. These apparent changes in modification may reflect or effect changes in the nuclear binding of BM28. The behavior of BM28 is not dissimilar to related proteins in Saccharomyces cerevisiae, such as Mcm2p, which are excluded from the nucleus after DNA replication. We speculate that BM28 may be involved in the control that limits eukaryotic DNA replication to one round per cell cycle.


Perceptions of Integration of the Clinical Pharmacist into the Patient Care Medical Home Model.
The patient-centered medical home (PCMH) model is a multidisciplinary, team-based approach to healthcare that focuses on actively involving the patient in clinical decision making. The Veterans Health Administration (VA), while desiring to be a national leader in the delivery of primary care services, used the principles of the PCMH model to design the patient-aligned care team (PACT). The purpose of this study, was to explore the perception of the PACT members after integration of a clinical pharmacist to the PACT. This was a single-center cross-sectional study conducted at an integrated Veterans Health Administration system. We electronically surveyed PACT staff practicing within VA-Tennessee Valley Health Care System as of October 1, 2016 using a modified version of the Medicine Medication Use Processes Matrix (MUPM) containing 19 items on five theoretical grouping of processes (evaluation and management, monitoring, medication review, documentation, and education) and two groupings(clinician satisfaction and access). Ninety-one complete responses were received. Perceptions were positive, with 79% rated as either 4 ("moderate contribution") or 5 ("major contribution"). Individual responses based on discipline, with the exception of the medical support assistant were rated positive, specifically job satisfaction. This study evaluated the perceptions of clinical pharmacist integration into the PACT model. Respondents perceived clinical pharmacist beneficial.


The efficacy of dandelion root extract in inducing apoptosis in drug-resistant human melanoma cells.
Notoriously chemoresistant melanoma has become the most prevalent form of cancer for the 25-29 North American age demographic. Standard treatment after early detection involves surgical excision (recurrence is possible), and metastatic melanoma is refractory to immuno-, radio-, and most harmful chemotherapies. Various natural compounds have shown efficacy in killing different cancers, albeit not always specifically. In this study, we show that dandelion root extract (DRE) specifically and effectively induces apoptosis in human melanoma cells without inducing toxicity in noncancerous cells. Characteristic apoptotic morphology of nuclear condensation and phosphatidylserine flipping to the outer leaflet of the plasma membrane of A375 human melanoma cells was observed within 48 hours. DRE-induced apoptosis activates caspase-8 in A375 cells early on, demonstrating employment of an extrinsic apoptotic pathway to kill A375 cells. Reactive Oxygen Species (ROS) generated from DRE-treated isolated mitochondria indicates that natural compounds in DRE can also directly target mitochondria. Interestingly, the relatively resistant G361 human melanoma cell line responded to DRE when combined with the metabolism interfering antitype II diabetic drug metformin. Therefore, treatment with this common, yet potent extract of natural compounds has proven novel in specifically inducing apoptosis in chemoresistant melanoma, without toxicity to healthy cells.


Fate of Cd during microbial Fe(III) mineral reduction by a novel and Cd-tolerant Geobacter species.
Fe(III) (oxyhydr)oxides affect the mobility of contaminants in the environment by providing reactive surfaces for sorption. This includes the toxic metal cadmium (Cd), which prevails in agricultural soils and is taken up by crops. Fe(III)-reducing bacteria can mobilize such contaminants by Fe(III) mineral dissolution or immobilize them by sorption to or coprecipitation with secondary Fe minerals. To date, not much is known about the fate of Fe(III) mineral-associated Cd during microbial Fe(III) reduction. Here, we describe the isolation of a new Geobacter sp. strain Cd1 from a Cd-contaminated field site, where the strain accounts for 10(4) cells g(-1) dry soil. Strain Cd1 reduces the poorly crystalline Fe(III) oxyhydroxide ferrihydrite in the presence of at least up to 112 mg Cd L(-1). During initial microbial reduction of Cd-loaded ferrihydrite, sorbed Cd was mobilized. However, during continuous microbial Fe(III) reduction, Cd was immobilized by sorption to and/or coprecipitation within newly formed secondary minerals that contained Ca, Fe, and carbonate, implying the formation of an otavite-siderite-calcite (CdCO3-FeCO3-CaCO3) mixed mineral phase. Our data shows that microbially mediated turnover of Fe minerals affects the mobility of Cd in soils, potentially altering the dynamics of Cd uptake into food or phyto-remediating plants.


Phylogenetic detection of numerous gene duplications shared by animals, fungi and plants.
Gene duplication is considered a major driving force for evolution of genetic novelty, thereby facilitating functional divergence and organismal diversity, including the process of speciation. Animals, fungi and plants are major eukaryotic kingdoms and the divergences between them are some of the most significant evolutionary events. Although gene duplications in each lineage have been studied extensively in various contexts, the extent of gene duplication prior to the split of plants and animals/fungi is not clear. Here, we have studied gene duplications in early eukaryotes by phylogenetic relative dating. We have reconstructed gene families (with one or more orthogroups) with members from both animals/fungi and plants by using two different clustering strategies. Extensive phylogenetic analyses of the gene families show that, among nearly 2,600 orthogroups identified, at least 300 of them still retain duplication that occurred before the divergence of the three kingdoms. We further found evidence that such duplications were also detected in some highly divergent protists, suggesting that these duplication events occurred in the ancestors of most major extant eukaryotic groups. Our phylogenetic analyses show that numerous gene duplications happened at the early stage of eukaryotic evolution, probably before the separation of known major eukaryotic lineages. We discuss the implication of our results in the contexts of different models of eukaryotic phylogeny. One possible explanation for the large number of gene duplication events is one or more large-scale duplications, possibly whole genome or segmental duplication(s), which provides a genomic basis for the successful radiation of early eukaryotes.


Rituximab Treatment in Myasthaenia Gravis: Report of two paediatric cases.
Myasthaenia gravis (MG) is an auto-immune disease involving the postsynaptic receptors in the neuromuscular junction. The condition is characterised by fatigable weakness of the skeletal muscles and is uncommon in children. Acetylcholinesterase inhibitors and immune-modifying medications are usually considered the mainstay of treatment. However, these medications have to be given on a lifelong basis so that patients remain in remission; furthermore, drug-related side-effects can have a major impact on quality of life. We report two paediatric cases who were treated for MG at the Sultan Qaboos University Hospital, Muscat, Oman, in 2007 and 2008, respectively. Rituximab was eventually administered to each patient after their condition failed to improve despite several years of standard treatment with acetylcholinesterase inhibitors and immune-modifying medications. Overall, rituximab resulted in complete remission in one case and significant clinical improvement in the other case.


3D printing of shape memory hydrogels with tunable mechanical properties.
Utilization of soft material like hydrogels for task-specific applications such as in soft robotics requires freedom in the manufacturing process and designability. Here, we have developed highly robust thermoresponsive poly(dimethyl acrylamide-co-stearyl acrylate and/or lauryl acrylate) (PDMAAm-co-SA and/or LA)-based shape memory gels (SMGs) using a customized optical 3D gel printer. This process enabled rapid and moldless fabrication of SMGs with a variety of shapes and sizes. By varying the compositions of the constituent monomers, a wide variety of SMGs with tunable mechanical, thermal, optical and swelling properties have been obtained. Printed SMGs with excellent fixity and recovery ratios have exhibited a wide range of values of Young's modulus (0.04-17.35 MPa) and strain (612-2363%) at room temperature when the acrylate co-monomer (SA and LA) content was varied and the value of strain has been found to be enhanced at elevated temperatures. Thermogravimetric analysis (TGA) of the SMGs shows one step peak degradation (407-417 °C) regardless of composition after an initial mass loss due to water evaporation. Dynamic mechanical analysis (DMA) and differential scanning calorimetry (DSC) revealed variable transition temperatures (29-49.5 °C) depending on the SA and LA content. SMGs with all of the composition ratios possess high transparency with variable swelling degrees in water and different organic solvents and exhibit refractive index values in the range of intraocular lenses, making them suitable for applications in the optical field. These unique properties of 3D printed SMGs with free formability and tunable properties are expected to generate rapid demand in a variety of sectors in biomedicine, robotics and sensing applications.


Screening for thoracolumbar spinal injuries in blunt trauma: an Eastern Association for the Surgery of Trauma practice management guideline.
Thoracolumbar spine (TLS) injuries have an incidence rate of 5% in blunt trauma patients. The Eastern Association for the Surgery of Trauma published Practice Management Guidelines for the Screening of Thoracolumbar Spine Fracture in 2007. The Practice Management Guidelines Committee was assembled to reevaluate the literature. A search of the United States National Library of Medicine and the National Institutes of Health database was performed using MEDLINE through PubMed (www.pubmed.gov). The search retrieved English-language articles from March 2005 to December 2011 that referenced traumatic TLS injuries and fractures. The questions posed were the following: (1) What is the appropriate imaging modality to screen patients for TLS injuries? (2) Which trauma patients require radiographic screening for TLS injuries? (3)Does a patient who is awake and alert without distracting injuries require radiologic workup to rule out TLS injuries? Thirty-seven articles that referenced traumatic TLS injuries in association with screening published between March 2005 and December 2011 were collected and disseminated to the committee. Twelve were found to be relevant. Nine publications from the previous 2006 guidelines were reviewed and referenced to create and validate the updated guidelines. Practice patterns have changed regarding screening blunt trauma patients for TLS injuries. Software reformatted multidetector computed tomographic scans are more sensitive and accurate than plain films. Multidetector computed tomographic scans have become the screening modality of choice and the criterion standard in screening for TLS injuries. The literature supports a Level 1 recommendation to validate this based on a preponderance of Class II data. Patients without altered mentation or significant mechanism may be excluded by clinical examination without imaging. Patients with gross neurologic deficits or concerning clinical examination findings with negative imaging should receive a magnetic resonance imaging expediently, and the spine service should be consulted.


Cancer risk management among female BRCA1/2, PALB2, CHEK2, and ATM carriers.
Identification of inherited breast cancer may guide cancer risk management. We sought to compare risk management practices across women with inherited breast cancer genes. Females with a pathogenic/likely pathogenic (P/LP) variant in BRCA1/2, PALB2, CHEK2, and/or ATM were surveyed about cancer risk management. Comparisons were made across genes. The 235 participants with P/LP variants (186 BRCA1/2, 28 PALB2, 15 CHEK2, and 6 ATM) had a median age of 54 and 61% had a prior breast cancer diagnosis. For women with P/LP variants in BRCA1/2, PALB2, and ATM/CHEK2, bilateral mastectomy (BM) rates were 79%, 61%, and 52%, and bilateral oophorectomy (BO) rates were 89%, 30%, and 37%, respectively. Among women with P/LP variants in PALB2 and ATM/CHEK2, 27% of those who had a BO had a family history of ovarian cancer. Contralateral mastectomy rates for women with P/LP variants in PALB2 and ATM/CHEK2 with unilateral breast cancer were 60% and 58%, and BM rates for those without breast cancer were 57% and 29%, respectively. These findings suggest high rates of both contralateral mastectomies among those with unilateral breast cancer and BM among those without a breast cancer diagnosis across women with P/LP variants in high and moderate penetrance breast cancer genes. BO was also often utilized for risk reduction across these women. These findings suggest potential overtreatment through risk-reducing surgery, and highlight the importance of promoting guideline-adherent, risk-appropriate care.


How do women interpret abortion information they find online?
We sought to assess how women interpret the information they find online about the overall safety and risk of infertility associated with abortion and cesarean delivery (CD). We conducted an exploratory, prospective study tracking the internet searches of 100 reproductive-aged individuals who identify as women. We directed participants to search for information about either (1) whether surgical abortion or CD is safe or (2) the risk of infertility following surgical abortion or CD. Our data collection had 3 phases: baseline survey, directed internet search, and a postsearch survey. We analyzed participants' pre- and postsurvey responses using bivariate tests and analyzed within-subject changes. We evaluated the sites they visited based on expert ratings of site content based on trustworthiness and slant. Women perceived abortion as safer and less likely to cause infertility after their web searches than before (70% perceived abortion in the United States as very/completely safe presearch vs 92% postsearch; p < 0.02). Women's perceptions about CD did not change. Participants sought information from web pages that experts largely deemed trustworthy and lacking in slant. Women's perceptions about abortion safety and risk can be influenced by information they find online; perceptions about CD safety and risk may be less influenced by online information. Disseminating high quality, user-friendly abortion information on highly ranked and easily findable websites can help women find evidence-based information and influence knowledge about abortion.


Novel Kunitz-like Peptides Discovered in the Zoanthid Palythoa caribaeorum through Transcriptome Sequencing.
Palythoa caribaeorum (class Anthozoa) is a zoanthid that together jellyfishes, hydra, and sea anemones, which are venomous and predatory, belongs to the Phyllum Cnidaria. The distinguished feature in these marine animals is the cnidocytes in the body tissues, responsible for toxin production and injection that are used majorly for prey capture and defense. With exception for other anthozoans, the toxin cocktails of zoanthids have been scarcely studied and are poorly known. Here, on the basis of the analysis of P. caribaeorum transcriptome, numerous predicted venom-featured polypeptides were identified including allergens, neurotoxins, membrane-active, and Kunitz-like peptides (PcKuz). The three predicted PcKuz isotoxins (1-3) were selected for functional studies. Through computational processing comprising structural phylogenetic analysis, molecular docking, and dynamics simulation, PcKuz3 was shown to be a potential voltage gated potassium-channel inhibitor. PcKuz3 fitted well as new functional Kunitz-type toxins with strong antilocomotor activity as in vivo assessed in zebrafish larvae, with weak inhibitory effect toward proteases, as evaluated in vitro. Notably, PcKuz3 can suppress, at low concentration, the 6-OHDA-induced neurotoxicity on the locomotive behavior of zebrafish, which indicated PcKuz3 may have a neuroprotective effect. Taken together, PcKuz3 figures as a novel neurotoxin structure, which differs from known homologous peptides expressed in sea anemone. Moreover, the novel PcKuz3 provides an insightful hint for biodrug development for prospective neurodegenerative disease treatment.


Surgery for giant tumours of the breast: a 15 year review.
Giant tumours of the breast tend to occur in the adolescent age group. Racial predilection has been noted in the literature. The mass often occupies most of the breast, leading to its distortion. Many authors have advocated a mastectomy for benign tumours that severely distort the breast. Giant benign tumours when treated by simple excision risk persistence of asymmetry. To avoid this asymmetry, some authors have resorted to excision and immediate reduction mammaplasty. The aim of this retrospective study was a report on giant tumours of the breast presenting to a plastic surgery unit and to analyse demographic factors, clinical presentations, tumour pathology, management, complications, as well as patient and breast outcomes. Medical records of patients with giant tumours were retrospectively analysed for assessing demographic factors, clinical presentation, tumour pathology, the technique of surgery performed and patient and breast outcomes in a single hospital setting. Breast outcomes were rated by panel of 4 experienced plastic surgeons using the 4 Point Likert scale. Their ratings were statistically analysed for inter-rater agreement. Twenty-three subjects were identified to have giant tumours of the breast. Of these South African patients, 19 were black, 3 were Indian and 1 was of mixed ethnicity. The age range was 12-49 years (y) with an average of 19y. All masses were palpable. The final pathological diagnosis was fibrocystic disease in 3, giant fibroadenoma in 14, phyllodes tumour in 4, and hamartoma in 2. The size range was 10-45 cm with a median size of 18 cm. All but one patient had simple excision followed by immediate reduction mammaplasty. Twenty patients were assessed after operation. A minimum of 1 to a maximum of 4 patients per reviewer showed unsatisfactory outcomes and a minimum of 18 to a maximum of 21 patients per reviewer showed satisfactory to excellent outcomes. The overall agreement between assessors for this was 84%. Benign giant tumours (> 10 cm) of the breast are suitably managed by excision of the mass and a reduction mammoplasty technique of reconstruction.


Through-focus phase retrieval and its connection to the spatial correlation for propagating fields.
Through-focus phase retrieval methods aim to retrieve the phase of an optical field from its intensity distribution measured at different planes in the focal region. By using the concept of spatial correlation for propagating fields, for both the complex amplitude and the intensity of a field, we can infer which planes are suitable to retrieve the phase and which are not. Our analysis also reveals why all techniques based on measuring the intensity at two Fourier-conjugated planes usually lead to a good reconstruction of the phase. The findings presented in this work are important for aberration characterization of optical systems, adaptive optics and wavefront metrology.


Acquired ocular visual impairment in children. 1960-1989.
To describe the causes, sites, and types of eye anomaly and associated handicaps in children identified in the last 30 years with ocular visual impairment of 20/200 (6/60) or worse in the better eye with correction. Trend study. Children in British Columbia younger than 19 years with visual loss diagnosed between January 1960 and December 1989 who were referred for multidisciplinary assessment. The incidence of acquired ocular visual impairment has decreased from 0.6 to less than 0.2 per 10,000 people aged 19 years or younger during the last 30 years. The most common cause was a genetic cause, followed by tumor, injury, infection and autoimmune disorders. Optic nerve atrophy and retinal disorders together resulted in more than 90% of all ocular lesions. Gender distribution revealed more males than females to be affected. Sixty-six percent of children had enough sight to read. The percentage of affected children with neurologic disabilities has increased overall in the last 30 years because more children with profound brain damage have survived. Acquired ocular visual impairment is rare. The incidence of such impairment has been reduced by two thirds in the last 30 years. This decline has had little impact, however, because most cases of blindness are due to congenital conditions. The number of cases of acquired blindness is only one fourth that of congenital blindness, which has begun to increase again owing to the reemergence of retinopathy of prematurity.


Aminophylline and fatigue of adductor pollicis in man.
1. The effect of intravenous aminophylline on the contractility of adductor pollicis has been studied in three subjects both in the fresh state and following the induction of muscle fatigue. 2. Aminophylline had no influence on the frequency-force relationship and relaxation rate of adductor pollicis in the fresh state. 3. Fatigue resulted in a selective depression of the force response to low and moderate frequencies of stimulation and a slight effect on maximum force production 10 and 35 min afterwards. 4. Aminophylline given prior to, during and/or after fatigue did not influence this selective low-frequency fatigue at 10 or 35 min. 5. Aminophylline at the concentrations obtained has no significant effect on muscle contractility or fatiguability in man.


Complete polarization controller based on magneto-optic crystals and fixed quarter wave plates.
We propose and demonstrate a polarization controller, which is a concatenation of three Faraday rotators based on magneto-optic crystals separated by two fixed quarter wave plates. Comparing with former schemes, this polarization controller is fast, accurate and stable because it is completely driven by electric signals and has no mechanically moving parts.It is simple-structured and low-cost. Moreover, it is programmable to convert an arbitrary state of polarization (SOP) from the input to any designated SOP at the output. It can also be used as a polarization scrambler. It has potential applications in the research of the polarization dependence of optical communication systems or the compensation of polarization mode dispersion (PMD), etc.


The Role of Neoadjuvant Chemoradiation Therapy in Patients With Borderline Resectable Pancreatic Cancer With Isolated Venous Vascular Involvement.
The rationale for neoadjuvant chemoradiation therapy (Neo-CRT) and the definition of borderline resectable pancreatic cancer (BRPC) are still controversial. In particular, surgical treatment of BRPC with isolated venous vascular involvement (IVVI) is debatable.From January 2000 to December 2013, 84 patients diagnosed with BRPC according to NCCN guidelines were identified, and 70 patients were found to have BRPC with IVVI. We divided all 70 patients into 3 groups: surgery first without Neo-CRT (Group 1); pancreatectomy following Neo-CRT (Group 2); and no operation following Neo-CRT (Group 3). Patient characteristics including oncologic outcomes were analyzed for each of the 3 patients groups.Thirty-seven patients were female and 33 were male, with a mean age of 61.7 ± 9.74 years. Among the 70 BRPC patients with IVVI, 28 patients (40%) belonged to Group 1, 30 patients (42.9%) belonged to Group 2, and 12 patients (17.1%) belonged to Group 3. Pathological tumor size (P < 0.001), pT stage (P = 0.001), pTNM stage (P=0.002), combined vascular resection (P = 0.003), completeness of adjuvant therapy (P = 0.004) were found to be statistically significantly different between Groups 1 and 2. In addition, disease-free survival (P = 0.055) and disease-specific survival (DSS) (P=0.006) were improved in Group 2. Interestingly, when comparing DSS, there was no statistically significant difference between Groups 1 and 3 (P = 0.991).The clinical practice of pancreatectomy following Neo-CRT in BRPC with IVVI provided favorable oncologic outcomes. The effect of Neo-CRT in BRPC with IVVI may be multifactorial, providing proper patient selection, complete adjuvant chemotherapy, and potential therapeutic (downstaging) effect.


Phylogenomics offers resolution of major tunicate relationships.
Tunicata, a diverse clade of approximately 3000 described species of marine, filter-feeding chordates, is of great interest to researchers because tunicates are the closest living relatives of vertebrates and they facilitate comparative studies of our own biology. The group also includes numerous invasive species that cause considerable economic damage and some species of tunicates are edible. Despite their diversity and importance, relationships among major lineages of Tunicata are not completely resolved. Here, we supplemented public data with transcriptomes from seven species spanning the diversity of Tunicata and conducted phylogenomic analyses on data sets of up to 798 genes. Sensitivity analyses were employed to examine the influences of reducing compositional heterogeneity and branch-length heterogeneity. All analyses maximally supported a monophyletic Tunicata within Olfactores (Vertebrata + Tunicata). Within Tunicata, all analyses recovered Appendicularia sister to the rest of Tunicata and confirmed (with maximal support) that Thaliacea is nested within Ascidiacea. Stolidobranchia is the sister taxon to all other tunicates except Appendicularia. In most analyses, phlebobranch tunicates were recovered paraphyletic with respect to Aplousobranchia. Support for this topology varied but was strong in some cases. However, when only the 50 best genes based on compositional heterogeneity were analysed, we recovered Phlebobranchia and Aplousobranchia reciprocally monophyletic with strong support, consistent with most traditional morphology-based hypotheses. Examination of internode certainty also cast doubt on results of phlebobranch paraphyly, which may be due to limited taxon sampling. Taken together, these results provide a higher-level phylogenetic framework for our closest living invertebrate relatives.


Preparing to care for paediatric trauma patients.
Considerable evidence has discussed the significant workload and advances in clinical care by UK Defence Medical Services (DMS) during recent conflicts in Iraq and Afghanistan. Although the DMS is not doctrinally staffed to deal with children on operations, severely ill and injured paediatric casualties continue to present to military medical facilities; therefore, staff must be competent to deliver the appropriate level of care. This paper reports the paediatric presentations to the emergency department (ED), at the Role 3 Medical Treatment Facility (MTF) in Camp Bastion, Afghanistan, over a 21-month period. The aim was to provide quantitative, statistical data of paediatric presentations seen by deployed ED nurses, to identify whether the current training was appropriate and to make recommendations for further training requirements for DMS ED nurses. All paediatric presentations to the MTF ED between January 2011 and September 2012 were analysed. The following aspects of the admission were analysed: date of admission, mechanism of injury, injury sustained, discharge, length of stay in the ED and length of stay in the R3. There were 159 paediatric presentations to the ED in 2011 of which 56% warranted admission to the intensive treatment unit (ITU). In contrast, over the shorter period in 2012, 79% of 73 paediatric presentations were admitted to the ITU. The most common mechanism of injury was hostile action. 13% of the patients who presented to the ED in 2011 did not survive to discharge, compared with 11% the following year. Although the exposure to paediatric polytrauma during the conflicts in Afghanistan and Iraq is not replicated in peace time roles, it is likely that wherever emergency nurses are deployed the treatment of children will continue. Analysis of the service evaluation has led to the recommendations for specific skills that emergency nurses could develop during the pre-deployment phase to better prepare for caring for such patients. These include recognition of the sick child/triage, paediatric drug calculations, awareness of the massive transfusion requirements for children and skills to gain intravenous/intraosseous access in a child.


An auxin signaling gene BnaA3.IAA7 contributes to improved plant architecture and yield heterosis in rapeseed.
Plant architecture is the key factor affecting overall yield in many crops. The genetic basis underlying plant architecture in rapeseed (Brassica napus), a key global oil crop, is elusive. We characterized an ethyl methanesulfonate (EMS)-mutagenized rapeseed mutant, sca, which had multiple phenotypic alterations, including crinkled leaves, semi-dwarf stature, narrow branch angles and upward-standing siliques. We identified the underlying gene, which encodes an Aux/IAA protein (BnaA3.IAA7). A G-to-A mutation changed the glycine at the 84th position to glutamic acid (G84E), disrupting the conserved degron motif GWPPV and reducing the affinity between BnaA3.IAA7 and TIR1 (TRANSPORT INHIBITOR RESPONSE 1) in an auxin dosage-dependent manner. This change repressed the degradation of BnaA3.IAA7 and therefore repressed auxin signaling at low levels of auxin that reduced the length of internodes. The G84E mutation reduced branch angles by enhancing the gravitropic response. The heterozygote +/sca closely resembled a proposed ideal plant architecture, displaying strong yield heterosis through single-locus overdominance by improving multiple component traits. Our findings demonstrate that a weak gain-of-function mutation in BnaA3.IAA7 contributes to yield heterosis by improving plant architecture and would be valuable for breeding superior rapeseed hybrid cultivars and such a mutation may increase the yield in other Brassica crops.


The relative proportions of fat, muscle and bone in the normal human forearm as determined by computed tomography.
Computed tomography has been used to establish the proportions of fat, muscle and bone present in the normal human forearm. Subjects were healthy young volunteers, eight males and eight females. A series of six cross-sectional scans at right angles to the long axis of the forearm was obtained, the scans being made at equidistant intervals between the olecranon process and the ulnar styloid. The volumes occupied by fat, muscle and bone were calculated for the complete forearm. Total forearm volume calculated by this method agreed closely with that measured by water displacement. For the male subjects, forearm composition was 72.1 +/- 4.4% muscle (mean +/- SD), 15.0 +/- 5.3% fat and 12.9 +/- 1.2% bone. Female forearms had less muscle (P less than 0.001) and more fat (P less than 0.001) than those of the male subjects: 58.5 +/- 4.0% muscle, 29.3 +/- 5.0% fat and 12.3 +/- 1.4% bone. Forearm muscle volume was significantly correlated (r = 0.75; P less than 0.05) with lean body mass in the male subjects; the range of values for lean body mass in the female subjects was too small to permit calculation of the equivalent relationship. Forearm fat content, as a percentage of total volume, was proportional to whole body fat content as estimated from skinfold thickness (males, r = 0.84; P less than 0.01; females, r = 0.77; P less than 0.05). These relationships enable estimates of the volumes of forearm tissue components to be derived from anthropometric measurements.


Potential ecological impacts of climate intervention by reflecting sunlight to cool Earth.
As the effects of anthropogenic climate change become more severe, several approaches for deliberate climate intervention to reduce or stabilize Earth's surface temperature have been proposed. Solar radiation modification (SRM) is one potential approach to partially counteract anthropogenic warming by reflecting a small proportion of the incoming solar radiation to increase Earth's albedo. While climate science research has focused on the predicted climate effects of SRM, almost no studies have investigated the impacts that SRM would have on ecological systems. The impacts and risks posed by SRM would vary by implementation scenario, anthropogenic climate effects, geographic region, and by ecosystem, community, population, and organism. Complex interactions among Earth's climate system and living systems would further affect SRM impacts and risks. We focus here on stratospheric aerosol intervention (SAI), a well-studied and relatively feasible SRM scheme that is likely to have a large impact on Earth's surface temperature. We outline current gaps in knowledge about both helpful and harmful predicted effects of SAI on ecological systems. Desired ecological outcomes might also inform development of future SAI implementation scenarios. In addition to filling these knowledge gaps, increased collaboration between ecologists and climate scientists would identify a common set of SAI research goals and improve the communication about potential SAI impacts and risks with the public. Without this collaboration, forecasts of SAI impacts will overlook potential effects on biodiversity and ecosystem services for humanity.


When do anesthesiologists delegate?
Nurse anesthetists (CRNAs) are a lower cost substitute for anesthesiologists in the delivery of anesthesia services. This article addresses the question of when anesthesiologists delegate in a team approach as opposed to using a solo arrangement. Logistic regression analysis was done using data from the 1986 Anesthesia Practice Survey and revealed that the team approach is more likely in areas with a relatively large supply of CRNAs; in hospitals with large surgical volumes, teaching facilities, and public hospitals; during emergency procedures, more lengthy procedures, and less complex surgeries; and among patients with poorer preoperative physical status. However, as the supply of anesthesiologists increases, the probability of CRNA use declines and in areas outside New England the "solo anesthesiologist" arrangement is significantly more common. Medicare and other third-party payers should eliminate regional variations in provider mix that are due to locational preferences and provider attitudes. Delegation to CRNAs can be encouraged by reducing what anesthesiologists are paid for practicing alone.


High-frequency oscillatory ventilation as a rescue therapy for adult trauma patients.
High-frequency oscillatory ventilation is an alternative ventilation mode that improves oxygenation in trauma patients in whom conventional ventilation strategies have been unsuccessful. To evaluate the effect of high-frequency oscillatory ventilation on oxygenation, survival, and parameters predictive of survival in trauma patients. A retrospective case series of 24 adult patients admitted to the trauma intensive care unit at a level I trauma center between November 2001 and July 2005 and treated with high-frequency oscillatory ventilation. Survivors and nonsurvivors were compared for mechanism and severity of injury, oxygenation parameters related to high-frequency oscillatory ventilation, and hospital course. Of the 8577 patients admitted during the study period, acute respiratory distress syndrome developed in 103 (1%). Of those 103 patients, 24 (23%) were treated with high-frequency oscillatory ventilation. Most of the patients treated with high-frequency oscillatory ventilation had sustained blunt trauma (79%). Oxygenation parameters improved significantly with high-frequency oscillatory ventilation in all patients, regardless of survival. Of the 24 patients treated with this ventilation mode, 15 (62%) survived. Survival did not correlate with improved oxygenation parameters but with the number of failed organ systems and injury severity. Although high-frequency oscillatory ventilation improves oxygenation, severity of traumatic injury and organ failure, not respiratory parameters, are predictors of survival. High-frequency oscillatory ventilation should be considered for pulmonary rescue of severely injured patients with acute respiratory distress syndrome.


Swallowing dysfunction after mechanical ventilation in trauma patients.
Swallowing dysfunction can occur after mechanical ventilation, leading to complications such as aspiration and pneumonia. After mechanical ventilation, authors have recommended evaluating patients with contrast studies or endoscopy to identify patients at risk for swallowing dysfunction and aspiration. The purpose of the study was to determine if a bedside swallowing evaluation (BSE) can identify patients with swallowing dysfunction after mechanical ventilation. This is a 1-year (2008) prospective study of all adult trauma patients admitted to the intensive care unit requiring mechanical ventilation. Upon separation from mechanical, all patients received a BSE. The BSE used mental status, facial symmetry, swallow reflex, and oral ice chips and water to identify swallowing dysfunction. Patients who passed the BSE were advanced to oral intake per physician orders, whereas patients who failed the BSE were allowed nothing by mouth. A total of 345 patients were included; 54 died before separation from mechanical ventilation and were excluded. The remaining 291 patients underwent BSE after separation from mechanical ventilation, with 143 (49%) passing and 148 (51%) failing. Patients who failed the BSE required mechanical ventilation longer than those who passed (14 ± 13 vs 5 ± 20 days, P = .001). In addition, only 23% of patients extubated within 72 hours failed the BSE, whereas 78% of those intubated more than 72 hours failed the BSE (P < .001). All patients who passed the BSE were discharged from the hospital without a clinical aspiration event. Independent risk factors for failure of BSE included tracheostomy, older age, prolonged mechanical ventilation, delirium tremens, traumatic brain injury, and spine fracture. Three (2%) patients who failed the BSE had a clinical aspiration event despite taking nothing by mouth. A simple BSE can be used to identify patients at risk for swallowing dysfunction after mechanical ventilation. More importantly, BSE can safely clear patients without swallowing dysfunction, avoiding costly and time-consuming contrast studies or endoscopic evaluation.


Design of optically stable reflector systems and prisms.
Utilizing an image orientation change merit function, we prove the finding of Schweitzer et al. [Appl. Opt. 37, 5190 (1998)] that only two types of optically stable reflector system exist, namely, preserving or retroreflecting. We also present an analytical method for designing optically stable reflector systems comprising multiple reflectors. It is shown that an infinite number of solutions can be obtained for systems comprising more than three reflectors. Furthermore, it is shown that by adding two parallel refracting flat boundary surfaces at the entrance and exit positions of the light ray in an optical system with multiple reflectors, an optically stable prism can be obtained.


Susceptibility of human male keratinocytes to MHC-restricted H-Y-specific lysis.
We studied the expression of the male-specific mH antigen H-Y on cultured human skin cells by investigating susceptibility to H-Y-specific cytolysis using conventional class I-restricted CTL clones in a modified cell-mediated cytotoxicity assay. In contrast to what was found in the rodent system, we observed H-Y-specific lysis of human male keratinocytes. Susceptibility for H-Y-specific lysis was efficiently enhanced by exposure of the keratinocytes to IFN-gamma. Our results demonstrate that human skin cells are equally sensitive for the activity of H-Y-specific CTLs as target cells of lymphoid origin. Finally, the cellular recognition of the H-Y mH antigen in the skin further supports its possible target function in the local graft versus host attack.


Pregnancy ambivalence and contraceptive use among young adults in the United States.
Pregnancy ambivalence, or conflicted desire about having a baby, has been associated with decreased contraceptive use and unintended pregnancy. However, prior studies have neither included men nor focused on young adults, even though people in their 20s have the highest rates of unintended pregnancy. Nationally representative data from 2008-2009 were used to examine pregnancy ambivalence and its association with contraceptive practices among 774 respondents who were 18-29 years old and in current sexual relationships. Bivariate and multivariate analyses assessed relationships between pregnancy ambivalence, contraceptive use, gender and other social, demographic and psychosocial variables. Forty-five percent of respondents exhibited pregnancy ambivalence. The proportion was higher among men than among women (53% vs. 36%), and the difference remained significant in the multivariate analysis (odds ratio, 2.9). Ambivalence was associated with lowered likelihood of contraceptive use, but this relationship was statistically significant only for men: Compared with men with clear intentions to avoid pregnancy, ambivalent men were less likely to have used any method of contraception in the last month (0.4). The association between men's pregnancy ambivalence and contraceptive practices suggests that women should not remain the sole targets of pregnancy prevention programs. Further research should explore whether clinical interventions that assess and address pregnancy ambivalence for both women and men could lead to improved contraceptive counseling and use.


Crystallographic Identification of Lipid as an Integral Component of the Epitope of HIV Broadly Neutralizing Antibody 4E10.
Numerous studies of the anti-HIV-1 envelope glycoprotein 41 (gp41) broadly neutralizing antibody 4E10 suggest that 4E10 also interacts with membrane lipids, but the antibody regions contacting lipids and its orientation with respect to the viral membrane are unknown. Vaccine immunogens capable of re-eliciting these membrane proximal external region (MPER)-like antibodies may require a lipid component to be successful. We performed a systematic crystallographic study of lipid binding to 4E10 to identify lipids bound by the antibody and the lipid-interacting regions. We identified phosphatidic acid, phosphatidylglycerol, and glycerol phosphate as specific ligands for 4E10 in the crystal structures. 4E10 used its CDRH1 loop to bind the lipid head groups, while its CDRH3 interacted with the hydrophobic lipid tails. Identification of the lipid binding sites on 4E10 may aid design of immunogens for vaccines that include a lipid component in addition to the MPER on gp41 for generation of broadly neutralizing antibodies.


Modifying the maternal microbiota alters the gut-brain metabolome and prevents emotional dysfunction in the adult offspring of obese dams.
Maternal obesity disturbs brain-gut-microbiota interactions and induces negative affect in the offspring, but its impact on gut and brain metabolism in the offspring (F1) are unknown. Here, we tested whether perinatal intake of a multispecies probiotic could mitigate the abnormal emotional behavior in the juvenile and adult offspring of obese dams. Untargeted NMR-based metabolomic profiling and gene-expression analysis throughout the gut-brain axis were then used to investigate the biology underpinning behavioral changes in the dams and their offspring. Prolonged high-fat diet feeding reduced maternal gut short-chain fatty acid abundance, increased markers of peripheral inflammation, and decreased the abundance of neuroactive metabolites in maternal milk during nursing. Both juvenile (postnatal day [PND] 21) and adult (PND112) offspring of obese dams exhibited increased anxiety-like behavior, which were prevented by perinatal probiotic exposure. Maternal probiotic treatment increased gut butyrate and brain lactate in the juvenile and adult offspring and increased the expression of prefrontal cortex PFKFB3, a marker of glycolytic metabolism in astrocytes. PFKFB3 expression correlated with the increase in gut butyrate in the juvenile and adult offspring. Maternal obesity reduced synaptophysin expression in the adult offspring, while perinatal probiotic exposure increased expression of brain-derived neurotrophic factor. Finally, we showed that the resilience of juvenile and adult offspring to anxiety-like behavior was most prominently associated with increased brain lactate abundance, independent of maternal group. Taken together, we show that maternal probiotic supplementation exerts a long-lasting effect on offspring neuroplasticity and the offspring gut-liver-brain metabolome, increasing resilience to emotional dysfunction induced by maternal obesity.


Apc inhibition of Wnt signaling regulates supernumerary tooth formation during embryogenesis and throughout adulthood.
The ablation of Apc function or the constitutive activation of beta-catenin in embryonic mouse oral epithelium results in supernumerary tooth formation, but the underlying mechanisms and whether adult tissues retain this potential are unknown. Here we show that supernumerary teeth can form from multiple regions of the jaw and that they are properly mineralized, vascularized, innervated and can start to form roots. Even adult dental tissues can form new teeth in response to either epithelial Apc loss-of-function or beta-catenin activation, and the effect of Apc deficiency is mediated by beta-catenin. The formation of supernumerary teeth via Apc loss-of-function is non-cell-autonomous. A small number of Apc-deficient cells is sufficient to induce surrounding wild-type epithelial and mesenchymal cells to participate in the formation of new teeth. Strikingly, Msx1, which is necessary for endogenous tooth development, is dispensable for supernumerary tooth formation. In addition, we identify Fgf8, a known tooth initiation marker, as a direct target of Wnt/beta-catenin signaling. These studies identify key mechanistic features responsible for supernumerary tooth formation.