Using spectral and temporal filters with EEG signal to predict the temporal lobe epilepsy outcome after antiseizure medication via machine learning.
Epilepsy is a neurological disorder in which the brain is transiently altered. Predicting outcomes in epilepsy is essential for providing feedback that can foster improved outcomes in the future. This study aimed to investigate whether applying spectral and temporal filters to resting-state electroencephalography (EEG) signals could improve the prediction of outcomes for patients taking antiseizure medication to treat temporal lobe epilepsy (TLE). We collected EEG data from a total of 46 patients (divided into a seizure-free group (SF, n = 22) and a non-seizure-free group (NSF, n = 24)) with TLE and retrospectively reviewed their clinical data. We segmented spectral and temporal ranges with various time-domain features (Hjorth parameters, statistical parameters, energy, zero-crossing rate, inter-channel correlation, inter-channel phase locking value and spectral information derived from Fourier transform, Stockwell transform, and wavelet transform) and compared their performance by applying an optimal frequency strategy, an optimal duration strategy, and a combination strategy. For all time-domain features, the optimal frequency and time combination strategy showed the highest performance in distinguishing SF patients from NSF patients (area under the curve (AUC) = 0.790 ± 0.159). Furthermore, optimal performance was achieved by utilizing a feature vector derived from statistical parameters within the 39- to 41-Hz frequency band with a window length of 210 s, as evidenced by an AUC of 0.748. By identifying the optimal parameters, we improved the performance of the prediction model. These parameters can serve as standard parameters for predicting outcomes based on resting-state EEG signals.


The genera of Hyphomycetes - 2011 update.
This supplement to the taxonomic monograph The Genera of Hyphomycetes summarises information on 23 accepted new genera and c. 160 species described in 2011. These include three dematiaceous genera (Funbolia, Noosia, Pyrigemmula, all related to Dothideomycetes), a bulbil-producing genus, Spiroplana (Pleosporales), and two endophytic genera, the sterile Periglandula (Clavicipitaceae), and the hyaline, sympodial Micronematobotrys (Pyronemataceae). Slow-growing, morphologically-reduced, darkly pigmented fungi continue to be the source of new taxa, including the new genus Atramixtia (Dothioraceae). Eight new genera of darkly pigmented chlamydospore-like anamorphs were described from marine or subtidal environments (Glomerulispora, Halozoön, Hiogispora, Matsusporium, Moheitospora, Moleospora, Moromyces), mostly associated with subclades of the Lulworthiales. Several genera that are morphologically similar to but phylogenetically distinct from genera of the Capnodiales (Pseudopassalora, Scleroramularia) were introduced, as well as segregates from the classical concepts of Alternaria (Sinomyces), Chalara and Phialophora (Brachyalara, Infundichalara, Lasiadelphia), and Paecilomyces (Purpureocillium for the former Paecilomyces lilacinus complex). In addition, in anticipation of the new nomenclatural rules, newly configured formerly-teleomorph genera were proposed as segregates from classical hyphomycete genera in the Hypocreales, namely Acremonium (Cosmospora), Fusarium (Cyanonectria, Dialonectria, Geejayessia, Macroconia, Stylonectria), and Volutella (Pseudonectria) and the Trichocomaceae, Eurotiales, Penicillium (Talaromyces for the former Penicillium subg. Biverticillium). Standardized generic mini-diagnoses are provided for the accepted new genera, along with details of distribution, substrates, numbers of new species and phylogenetic affinities within the Dikarya. GenBank accession numbers for ITS DNA-barcodes are provided where available. New information on generic concepts of previously recognised genera, phylogenetic relationships, and corrections of factual errors are also included. Only two newly described genera, Fecundostilbum and Utrechtiana, seem to be synonyms of previously described genera.


Emotional well-being and time pressure.
We propose a conceptual model of how time pressure affects emotional well-being associated with mundane routine activities. A selective review of research in several areas affirms the plausibility of the conceptual model, which posits negative effects on emotional well-being of insufficient time allocated to restorative and other activities instrumental for attaining desirable work, family life, and leisure goals. Previous research also affirms that practicing time management can have indirect positive effects by decreasing time pressure, whereas material wealth can have both negative indirect effects and positive indirect effects by increasing and decreasing time pressure, respectively. Several issues remain to be studied empirically. The conceptual model is a ground for additional, preferably cross-cultural, research.


Genetic screening of 202 individuals with congenital limb malformations and requiring reconstructive surgery.
Congenital limb malformations (CLMs) are common and present to a variety of specialties, notably plastic and orthopaedic surgeons, and clinical geneticists. The authors aimed to characterise causative mutations in an unselected cohort of patients with CLMs requiring reconstructive surgery. 202 patients presenting with CLM were recruited. The authors obtained G-banded karyotypes and screened EN1, GLI3, HAND2, HOXD13, ROR2, SALL1, SALL4, ZRS of SHH, SPRY4, TBX5, TWIST1 and WNT7A for point mutations using denaturing high performance liquid chromatography (DHPLC) and direct sequencing. Multiplex ligation dependent probe amplification (MLPA) kits were developed and used to measure copy number in GLI3, HOXD13, ROR2, SALL1, SALL4, TBX5 and the ZRS of SHH. Within the cohort, causative genetic alterations were identified in 23 patients (11%): mutations in GLI3 (n = 5), HOXD13 (n = 5), the ZRS of SHH (n = 4), and chromosome abnormalities (n = 4) were the most common lesions found. Clinical features that predicted the discovery of a genetic cause included a bilateral malformation, positive family history, and having increasing numbers of limbs affected (all p<0.01). Additionally, specific patterns of malformation predicted mutations in specific genes. Based on higher mutation prevalence the authors propose that GLI3, HOXD13 and the ZRS of SHH should be prioritised for introduction into molecular genetic testing programmes for CLM. The authors have developed simple criteria that can refine the selection of patients by surgeons for referral to clinical geneticists. The cohort also represents an excellent resource to test for mutations in novel candidate genes.


Discovery of new enzymes and metabolic pathways by using structure and genome context.
Assigning valid functions to proteins identified in genome projects is challenging: overprediction and database annotation errors are the principal concerns. We and others are developing computation-guided strategies for functional discovery with 'metabolite docking' to experimentally derived or homology-based three-dimensional structures. Bacterial metabolic pathways often are encoded by 'genome neighbourhoods' (gene clusters and/or operons), which can provide important clues for functional assignment. We recently demonstrated the synergy of docking and pathway context by 'predicting' the intermediates in the glycolytic pathway in Escherichia coli. Metabolite docking to multiple binding proteins and enzymes in the same pathway increases the reliability of in silico predictions of substrate specificities because the pathway intermediates are structurally similar. Here we report that structure-guided approaches for predicting the substrate specificities of several enzymes encoded by a bacterial gene cluster allowed the correct prediction of the in vitro activity of a structurally characterized enzyme of unknown function (PDB 2PMQ), 2-epimerization of trans-4-hydroxy-L-proline betaine (tHyp-B) and cis-4-hydroxy-D-proline betaine (cHyp-B), and also the correct identification of the catabolic pathway in which Hyp-B 2-epimerase participates. The substrate-liganded pose predicted by virtual library screening (docking) was confirmed experimentally. The enzymatic activities in the predicted pathway were confirmed by in vitro assays and genetic analyses; the intermediates were identified by metabolomics; and repression of the genes encoding the pathway by high salt concentrations was established by transcriptomics, confirming the osmolyte role of tHyp-B. This study establishes the utility of structure-guided functional predictions to enable the discovery of new metabolic pathways.


The relationship between ERCC1 expression and clinical outcome in patients with FIGO stage I to stage II uterine cervical adenocarcinoma.
Several studies have suggested that excision repair cross-complementation group 1 (ERCC1), a protein involved in nucleotide excision repair, is associated with resistance to platinum agent-based chemotherapy or chemoradiotherapy with platinum agents in various types of cancer. Herein we evaluated ERCC1 protein expression in uterine cervical adenocarcinoma and the relationship between this expression, clinicopathological factors, and clinical outcome, particularly in patients receiving adjuvant cisplatin-based chemotherapy or chemoradiotherapy with cisplatin. Thirty-six patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB to stage IIB cervical adenocarcinoma who underwent radical hysterectomy were evaluated. Excision repair cross-complementation group 1 protein expression was examined by immunohistochemistry in tumor tissues. The relationship between ERCC1 expression levels and clinicopathological factors (age, FIGO stage, histological grade, tumor size, vascular invasion, cervical stromal invasion, and lymph node metastases) and prognosis was evaluated. No significant differences between ERCC1 expression levels and clinicopathological factors were observed. The patients in the ERCC1 high-expression group (n = 7) experienced significantly worse disease-free survival than the patients in the ERCC1 low-expression group (n = 29; P = 0.005). Among the 25 patients who received cisplatin-based chemotherapy or chemoradiotherapy with cisplatin, those with high ERCC1 expression (n = 5) also experienced significantly worse disease-free survival than those with low ERCC1 expression (n = 20; P = 0.002). Moreover, univariate and multivariate analyses revealed that high ERCC1 expression was an independent prognostic factor in patients receiving cisplatin-based chemotherapy or chemoradiotherapy with cisplatin. This is the first analysis of the association between ERCC1 expression and clinical outcomes in patients with uterine cervical adenocarcinoma. High ERCC1 protein expression was revealed to be associated with worse disease-free survival in the patients who received adjuvant cisplatin-based chemotherapy or chemoradiotherapy with cisplatin and was shown to be an independent prognostic factor. Further evaluation with a larger number of patients is required to confirm these preliminary observations.


Tree diversity and soil chemical properties drive the linkages between soil microbial community and ecosystem functioning.
Microbial respiration is critical for soil carbon balance and ecosystem functioning. Previous studies suggest that plant diversity influences soil microbial communities and their respiration. Yet, the linkages between tree diversity, microbial biomass, microbial diversity, and microbial functioning have rarely been explored. In this study, we measured two microbial functions (microbial physiological potential, and microbial respiration), together with microbial biomass, microbial taxonomic and functional profiles, and soil chemical properties in a tree diversity experiment in South China, to disentangle how tree diversity affects microbial respiration through the modifications of the microbial community. Our analyses show a significant positive effect of tree diversity on microbial biomass (+25% from monocultures to 24-species plots), bacterial diversity (+12%), and physiological potential (+12%). In addition, microbial biomass and physiological potential, but not microbial diversity, were identified as the key drivers of microbial respiration. Although soil chemical properties strongly modulated soil microbial community, tree diversity increased soil microbial respiration by increasing microbial biomass rather than changing microbial taxonomic or functional diversity. Overall, our findings suggest a prevalence of microbial biomass over diversity in controlling soil carbon dynamics.


An exploratory data analysis method to reveal modular latent structures in high-throughput data.
Modular structures are ubiquitous across various types of biological networks. The study of network modularity can help reveal regulatory mechanisms in systems biology, evolutionary biology and developmental biology. Identifying putative modular latent structures from high-throughput data using exploratory analysis can help better interpret the data and generate new hypotheses. Unsupervised learning methods designed for global dimension reduction or clustering fall short of identifying modules with factors acting in linear combinations. We present an exploratory data analysis method named MLSA (Modular Latent Structure Analysis) to estimate modular latent structures, which can find co-regulative modules that involve non-coexpressive genes. Through simulations and real-data analyses, we show that the method can recover modular latent structures effectively. In addition, the method also performed very well on data generated from sparse global latent factor models. The R code is available at http://userwww.service.emory.edu/~tyu8/MLSA/.


Self-help/mutual aid groups for health and psychosocial problems: Key features and their perspectives in the 21st century.
In this virtual special issue, a set of 26 papers previously published in the American Journal of Community Psychology (AJCP), focused on self-help/mutual aid groups (SH/MAGs), are being curated given their significant impact in this domain. SH/MAGs constitute an important component of the community psychology's proposal to address various psychosocial and health problems. The American Journal of Community Psychology has played an important role in exploring the characteristics of self-help/mutual aid groups in various fields. These articles cover important areas of the study of self-help/mutual-aid groups. More specifically, the selected articles address issues such as the definition and key characteristics of self-help/mutual aid groups, the main fields that are applied, such as mental health, addictions, and disabilities. The article also addresses important issues such as the place of self-help/mutual aid groups in health systems, the experiential knowledge generated within these groups and the relationship of health professionals with these groups. The aim is this VSI to contribute to contemporary discussion on self-help/mutual aid groups, their challenges, and their perspectives and to highlight the crucial role that community psychology has in this field.


The effect of physicians' awareness on influenza and pneumococcal vaccination rates and correlates of vaccination in patients with diabetes in Turkey: an epidemiological Study "diaVAX".
We aimed to examine the effect of increased physician awareness on the rate and determinants of influenza and pneumococcal vaccinations in diabetic patients. Diabetic patients (n = 5682, mean [SD] age: 57.3 [11.6] years, 57% female) were enrolled by 44 physicians between Sept 2010 and Jan 2011. The physicians were initially questioned regarding vaccination practices, and then, they attended a training program. During the last five years, the physicians recommended influenza and pneumococcal vaccinations to 87.9% and 83.4% of the patients, respectively; however; only 27% of the patients received the influenza and 9.8% received the pneumococcal vaccines. One year after the training, the vaccination rates increased to 63.3% and 40.7%, respectively. The logistic regression models revealed that variables which increased the likelihood of having been vaccinated against influenza were: longer duration of diabetes, presence of hyperlipidemia and more use of concomitant medications whereas more use of anti-hyperglycemic medications was associated with increased odds of vaccination. On the other hand, older age, longer duration of diabetes and presence of a cardiovascular disease were variables which decreased the likelihood of having been vaccinated against pneumococcal disease during the past five years. However, during the study period, variables which decreased the odds of having been vaccinated included: older age and anti-hyperglycemic medications for influenza, and presence of hyperlipidemia and a family history of hypertension for pneumococcal disease. While variables which increased the likelihood of vaccination in the same period were: increased number of co-morbidities for influenza, and family history of diabetes for pneumococcal disease. We conclude that increased awareness of physicians may help improve vaccination rates against influenza and pneumococcal disease. However, diabetic patients with more severe health conditions are less likely to having been vaccinated. More structural/systematic vaccination programs are needed to increase the vaccination rates in patients with diabetes.


Definition and Consensus Diagnostic Criteria for Neurosarcoidosis: From the Neurosarcoidosis Consortium Consensus Group.
The Neurosarcoidosis Consortium Consensus Group, an expert panel of physicians experienced in the management of patients with sarcoidosis and neurosarcoidosis, engaged in an iterative process to define neurosarcoidosis and develop a practical diagnostic approach to patients with suspected neurosarcoidosis. This panel aimed to develop a consensus clinical definition of neurosarcoidosis to enhance the clinical care of patients with suspected neurosarcoidosis and to encourage standardization of research initiatives that address this disease. The work of this collaboration included a review of the manifestations of neurosarcoidosis and the establishment of an approach to the diagnosis of this disorder. The proposed consensus diagnostic criteria, which reflect current knowledge, provide definitions for possible, probable, and definite central and peripheral nervous system sarcoidosis. The definitions emphasize the need to evaluate patients with findings suggestive of neurosarcoidosis for alternate causal factors, including infection and malignant neoplasm. Also emphasized is the need for biopsy, whenever feasible and advisable according to clinical context and affected anatomy, of nonneural tissue to document the presence of systemic sarcoidosis and support a diagnosis of probable neurosarcoidosis or of neural tissue to support a diagnosis of definite neurosarcoidosis. Diverse disease presentations and lack of specificity of relevant diagnostic tests contribute to diagnostic uncertainty. This uncertainty is compounded by the absence of a pathognomonic histologic tissue examination. The diagnostic criteria we propose are designed to focus investigations on NS as accurately as possible, recognizing that multiple pathophysiologic pathways may lead to the clinical manifestations we currently term NS. Research recognizing the clinical heterogeneity of this diagnosis may open the door to identifying meaningful biologic factors that may ultimately contribute to better treatments.


Regenerative properties of interferometricall-optical DPSK wavelength converters.
We discuss an all-optical DPSK wavelength conversion scheme comprising a delay-interferometer demodulation stage followed by a Mach-Zehnder interferometer, the arms of which are formed by nonlinear waveguides. If operated properly, the configuration shows regenerative behaviour. This is true for nonlinear waveguides with a dominant cross-gain nonlinearity (e. g., for an electro-absorption amplitude modulator) as well as for the case of a dominant cross-phase nonlinearity (e. g., for Kerr effect based phase modulator). In addition, we show that nonlinear materials exhibiting cross-gain modulation properties can provide a binary phase response so far only known from the transfer functions of digital electronics.


Simultaneous determination of irbesartan and hydrochlorothiazide in human plasma using HPLC coupled with tandem mass spectrometry: Application to bioequivalence studies.
A sensitive, specific and selective liquid chromatography/tandem mass spectrometric method has been developed and validated for the simultaneous determination of irbesartan and hydrochlorothiazide in human plasma. Plasma samples were prepared using protein precipitation with acetonitrile, the two analytes and the internal standard losartan were separated on a reverse phase C(18) column (50mmx4mm, 3microm) using water with 2.5% formic acid, methanol and acetonitrile (40:45:15, v/v/v (%)) as a mobile phase (flow rate of 0.70mL/min). Irbesartan and hydrochlorothiazide were ionized using ESI source in negative ion mode, prior to detection by multiple reaction monitoring (MRM) mode while monitoring at the following transitions: m/z 296-->269 and m/z 296-->205 for hydrochlorothiazide, 427-->175 for irbesartan. Linearity was demonstrated over the concentration range 0.06-6.00microg/mL for irbesartan and 1.00-112.00ng/mL for hydrochlorothiazide. The developed and validated method was successfully applied to a bioequivalence study of irbesartan (300mg) with hydrochlorothiazide (12.5mg) tablet in healthy volunteers (N=36).


"They can rest at home": an observational study of patients' quality of sleep in an Australian hospital.
Poor sleep is known to adversely affect hospital patients' recovery and rehabilitation. The aim of the study was to investigate the perceived duration and quality of patient sleep and identify any environmental factors associated with patient-reported poor sleep in hospital. A cross-sectional study was conducted involving 15 clinical units within a 672-bed tertiary-referral hospital in Australia. Semi-structured interviews to determine perceptions of sleep quantity and quality and factors that disturb nocturnal sleep were conducted with patients and nursing staff. Environmental noise, light and temperature were monitored overnight, with concurrent logging of noise sources by observers. Patients reported a mean reduction in hospital sleep duration, compared to home, of 1.8 h (5.3 vs. 7.1 h; p < 0.001). The proportions of patients reporting their sleep quality to be poor/very poor, fair and of good quality were 41.6, 34.2 and 24.2% respectively. Patients reported poorer sleep quality than nurses (p < 0.05). Patients, nurses and observers all reported the main factors associated with poor sleep as clinical care interventions (34.3%) and environmental noise (32.1%). Noise levels in all 15 clinical areas exceeded WHO recommended levels of < 30 dB [A] by 36.7 to 82.6%, with peak noise levels of 51.3 to 103.3 dB (A). Hospital in-patients are exposed to factors which reduce the duration and quality of their sleep. These extrinsic factors are potentially modifiable through behaviour change and reconfiguration of the clinical environment. The findings from this study provided the foundation for a quality improvement project currently underway to improve patients' sleep.


Dark chemical matter in public screening assays and derivation of target hypotheses.
Compounds that are consistently inactive in many screening assays, so-called dark chemical matter (DCM), have recently experienced increasing attention. One of the reasons is that many DCM compounds may not be fully inert biologically, but may provide interesting leads for obtaining compounds that are highly selective or active against unusual targets. In this study, we have systematically identified DCM among extensively assayed screening compounds and searched for analogs of these compounds that have known bioactivities. Analog series containing DCM and known bioactive compounds were generated on a large scale, making it possible to derive target hypotheses for more than 8000 extensively assayed DCM molecules.


Facioscapulohumeral muscular dystrophy and DUX4: breaking the silence.
Autosomal dominant facioscapulohumeral muscular dystrophy (FSHD) has an unusual pathogenic mechanism. FSHD is caused by deletion of a subset of D4Z4 macrosatellite repeat units in the subtelomere of chromosome 4q. Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues. In FSHD, the combination of inefficient chromatin silencing of the D4Z4 repeat and polymorphisms on the FSHD-permissive alleles that stabilize the DUX4 mRNAs emanating from the repeat result in inappropriate DUX4 protein expression in muscle cells. FSHD is thereby the first example of a human disease caused by the inefficient repression of a retrogene in a macrosatellite repeat array.


NADPH oxidase and aging drive microglial activation, oxidative stress, and dopaminergic neurodegeneration following systemic LPS administration.
Parkinson's disease is characterized by a progressive degeneration of substantia nigra (SN) dopaminergic neurons with age. We previously found that a single systemic lipopolysaccharide (LPS, 5 mg/kg, i.p.) injection caused a slow progressive loss of tyrosine hydroxylase immunoreactive (TH+IR) neurons in SN associated with increasing motor dysfunction. In this study, we investigated the role of NADPH oxidase (NOX) in inflammation-mediated SN neurotoxicity. A comparison of control (NOX2(+/+) ) mice with NOX subunit gp91(phox) -deficient (NOX2(-/-) ) mice 10 months after LPS administration (5 mg/kg, i.p.) resulted in a 39% (P < 0.01) loss of TH+IR neurons in NOX2(+/+) mice, whereas NOX2(-/-) mice did not show a significant decrease. Microglia (Iba1+IR) showed morphological activation in NOX2(+/+) mice, but not in NOX2(-/-) mice at 1 hr. Treatment of NOX2(+/+) mice with LPS resulted in a 12-fold increase in NOX2 mRNA in midbrain and 5.5-6.5-fold increases in NOX2 protein (+IR) in SN compared with the saline controls. Brain reactive oxygen species (ROS), determined using diphenyliodonium histochemistry, was increased by LPS in SN between 1 hr and 20 months. Diphenyliodonium (DPI), an NOX inhibitor, blocked LPS-induced activation of microglia and production of ROS, TNFα, IL-1β, and MCP-1. Although LPS increased microglial activation and ROS at all ages studied, saline control NOX2(+/+) mice showed age-related increases in microglial activation, NOX, and ROS levels at 12 and 22 months of age. Together, these results suggest that NOX contributes to persistent microglial activation, ROS production, and dopaminergic neurodegeneration that persist and continue to increase with age.


Magnetic resonance imaging of oscillating electrical currents.
Functional MRI has become an important tool of researchers and clinicians who seek to understand patterns of neuronal activation that accompany sensory and cognitive processes. However, the interpretation of fMRI images rests on assumptions about the relationship between neuronal firing and hemodynamic response that are not firmly grounded in rigorous theory or experimental evidence. Further, the blood-oxygen-level-dependent effect, which correlates an MRI observable to neuronal firing, evolves over a period that is 2 orders of magnitude longer than the underlying processes that are thought to cause it. Here, we instead demonstrate experiments to directly image oscillating currents by MRI. The approach rests on a resonant interaction between an applied rf field and an oscillating magnetic field in the sample and, as such, permits quantitative, frequency-selective measurements of current density without spatial or temporal cancellation. We apply this method in a current loop phantom, mapping its magnetic field and achieving a detection sensitivity near the threshold required for the detection of neuronal currents. Because the contrast mechanism is under spectroscopic control, we are able to demonstrate how ramped and phase-modulated spin-lock radiation can enhance the sensitivity and robustness of the experiment. We further demonstrate the combination of these methods with remote detection, a technique in which the encoding and detection of an MRI experiment are separated by sample flow or translation. We illustrate that remotely detected MRI permits the measurement of currents in small volumes of flowing water with high sensitivity and spatial resolution.


Sympathetic Markers are Different Between Clinical Responders and Nonresponders After Left Ventricular Assist Device Implantation.
Clinical response to left ventricular assist devices (LVADs), as measured by health-related quality of life, varies among patients after implantation; however, it is unknown which pathophysiological mechanisms underlie differences in clinical response by health-related quality of life. The purpose of this study was to compare changes in sympathetic markers (β-adrenergic receptor kinase-1 [βARK1], norepinephrine [NE], and 3,4-dihydroxyphenylglycol [DHPG]) between health-related quality of life clinical responders and nonresponders from pre- to post-LVAD implantation. We performed a secondary analysis on a subset of data from a cohort study of patients from pre- to 1, 3, and 6 months after LVAD implantation. Clinical response was defined as an increase of 5 points or higher on the Kansas City Cardiomyopathy Questionnaire Clinical Summary score from pre- to 6 months post-LVAD implantation. We measured plasma βARK1 level with an enzyme-linked immunosorbent assay and plasma NE and DHPG levels with high-performance liquid chromatography with electrochemical detection. Latent growth curve modeling was used to compare the trajectories of markers between groups. The mean (SD) age of the sample (n = 39) was 52.9 (13.2) years, and most were male (74.4%) and received LVADs as bridge to transplantation (69.2%). Preimplantation plasma βARK1 levels were significantly higher in clinical responders (n = 19) than in nonresponders (n = 20) (P = .001), but change was similar after LVAD (P = .235). Preimplantation plasma DHPG levels were significantly lower in clinical responders than in nonresponders (P = .002), but the change was similar after LVAD (P = .881). There were no significant differences in plasma NE levels. Preimplantation βARK1 and DHPG levels are differentiating factors between health-related quality of life clinical responders and nonresponders to LVAD, potentially signaling differing levels of sympathetic stimulation underlying clinical response.


Chimpanzee and human midfoot motion during bipedal walking and the evolution of the longitudinal arch of the foot.
The longitudinal arch of the human foot is commonly thought to reduce midfoot joint motion to convert the foot into a rigid lever during push off in bipedal walking. In contrast, African apes have been observed to exhibit midfoot dorsiflexion following heel lift during terrestrial locomotion, presumably due to their possession of highly mobile midfoot joints. This assumed dichotomy between human and African ape midfoot mobility has recently been questioned based on indirect assessments of in vivo midfoot motion, such as plantar pressure and cadaver studies; however, direct quantitative analyses of African ape midfoot kinematics during locomotion remain scarce. Here, we used high-speed motion capture to measure three-dimensional foot kinematics in two male chimpanzees and five male humans walking bipedally at similar dimensionless speeds. We analyzed 10 steps per chimpanzee subject and five steps per human subject, and compared ranges of midfoot motion between species over stance phase, as well as within double- and single-limb support periods. Contrary to expectations, humans used a greater average range of midfoot motion than chimpanzees over the full duration of stance. This difference was driven by humans' dramatic plantarflexion and adduction of the midfoot joints during the second double-limb support period, which likely helps the foot generate power during push off. However, chimpanzees did use slightly but significantly more midfoot dorsiflexion than humans in the single limb-support period, during which heel lift begins. These results indicate that both stiffness and mobility are important to longitudinal arch function, and that the human foot evolved to utilize both during push off in bipedal walking. Thus, the presence of human-like midfoot joint morphology in fossil hominins should not be taken as indicating foot rigidity, but may signify the evolution of pedal anatomy conferring enhanced push off mechanics.


Toward a human-centered hyperlipidemia management system: the interaction between internal and external information on relational data search.
In a distributed information search task, data representation and cognitive distribution jointly affect user search performance in terms of response time and accuracy. Guided by UFuRT (User, Function, Representation, Task), a human-centered framework, we proposed a search model and task taxonomy. The model defines its application in the context of healthcare setting. The taxonomy clarifies the legitimate operations for each type of search task of relational data. We then developed experimental prototypes of hyperlipidemia data displays. Based on the displays, we tested the search tasks performance through two experiments. The experiments are of a within-subject design with a random sample of 24 participants. The results support our hypotheses and validate the prediction of the model and task taxonomy. In this study, representation dimensions, data scales, and search task types are the main factors in determining search efficiency and effectiveness. Specifically, the more external representations provided on the interface the better search task performance of users. The results also suggest the ideal search performance occurs when the question type and its corresponding data scale representation match. The implications of the study lie in contributing to the effective design of search interface for relational data, especially laboratory results, which could be more effectively designed in electronic medical records.


Structural muscle damage and muscle strength after incremental number of isometric and forced lengthening contractions.
Exercise-induced muscle damage is characterized by histological changes, like Z-line streaming, inflammatory response and decreased muscle function reflected in a prolonged decline in maximal isometric muscle strength after eccentric work. It is assumed that force decrement is mainly related to the amount of structural damage. However, the relationship between number of eccentric contractions, magnitude of structural damage and force decrement is not very well documented. Therefore we studied the effect of an increasing number of both isometric and eccentric (forced lengthening) contractions on histological parameters of muscle damage and maximal isometric force in an experimental in situ rat model. Tibialis anterior muscles of male Wistar rats were subjected to an increasing number of either isometric or eccentric contractions and were examined for histological markers of muscle damage. The present study shows that muscle damage increases progressively with the number of forced lengthening contractions. Maximal isometric torque was found to decline after both types of exercise. However, the decline after forced lengthening exercise was more pronounced. Only a weak relationship between percentage of histological muscle damage and isometric torque after forced lengthening contractions was found. The findings of the present study suggest that the decline in muscle force after eccentric exercise may partly be attributed to other factors than structural damage.


Mre11-Sae2 and RPA Collaborate to Prevent Palindromic Gene Amplification.
Foldback priming at DNA double-stranded breaks is one mechanism proposed to initiate palindromic gene amplification, a common feature of cancer cells. Here, we show that small (5-9 bp) inverted repeats drive the formation of large palindromic duplications, the major class of chromosomal rearrangements recovered from yeast cells lacking Sae2 or the Mre11 nuclease. RPA dysfunction increased the frequency of palindromic duplications in Sae2 or Mre11 nuclease-deficient cells by ∼ 1,000-fold, consistent with intra-strand annealing to create a hairpin-capped chromosome that is subsequently replicated to form a dicentric isochromosome. The palindromic duplications were frequently associated with duplication of a second chromosome region bounded by a repeated sequence and a telomere, suggesting the dicentric chromosome breaks and repairs by recombination between dispersed repeats to acquire a telomere. We propose secondary structures within single-stranded DNA are potent instigators of genome instability, and RPA and Mre11-Sae2 play important roles in preventing their formation and propagation, respectively.


Increasing hepatitis C virus RNA levels in hemophiliacs: relationship to human immunodeficiency virus infection and liver disease. Multicenter Hemophilia Cohort Study.
We have previously observed an increased frequency of liver failure in human immunodeficiency virus (HIV)-infected hemophiliacs. The purpose of this study was to quantitate hepatitis C virus (HCV) RNA levels in serial samples from HIV-seropositive (HIV+) and HIV-seronegative (HIV-) hemophiliacs before and after HIV seroconversion, and to examine the relationship of HCV RNA levels to CD4 cell counts and to hepatic dysfunction over time. HCV RNA levels were measured on serial samples of serum stored frozen from 17 HCV+/HIV+ and 17 HCV+/HIV- subjects matched within 5 years of their birth dates. All were HCV+ before study entry. HCV RNA levels were quantitated by a branched DNA-enhanced label amplification (bDNA) assay. For samples less than the cut off, HCV RNA was measured by the nested polymerase chain reaction. Individual changes over time, clinical groups, and mean values within predetermined time windows were compared with Wilcoxon rank sum tests. Mean HCV RNA levels increased from 2.76 (standard error [SE] 1.33) x 10(5) to 2.84 (SE 1.39) x 10(6) eq/mL during the first 2 years after HIV seroconversion (P = .006). Baseline HCV RNA levels in the pre-HIV seroconversion group were not significantly different from the baseline levels in those who remained HIV (P = .79). Over the entire period of study, HCV RNA levels increased nearly threefold in those who remained HIV- (mean 9.47 [SE 4.78] x 10(5) to 2.81 [SE 1.13] x 10(6)/mL; P = .02). Among those who became HIV+, HCV RNA levels increased 58-fold (mean 2.85 [SE 1.26] x 10(5) to 1.66 [SE 0.57] x 10(7) eq/mL; P = .0001). The rate of increase in HCV RNA levels was eightfold faster for HIV+ subjects than for subjects who remained HIV- (P = .009). HCV RNA levels increased twofold higher in 5 subjects who developed liver failure compared with the 12 who did not (P = .43). HCV RNA levels correlated significantly with CD4 counts (R = -.33, P = .01) and serum aspartate aminotransferase levels (AST) (R = .36, P = .007). We conclude that HCV RNA levels are significantly higher in HIV+ than in HIV- multitransfused hemophiliacs. HCV load increases over time, is enhanced by HIV, and further increases as immune deficiency progresses. HCV RNA levels are directly associated with high AST levels. These findings suggest that HIV-induced immune deficiency may promote increased HCV replication.


Shipping routes through core habitat of endangered sperm whales along the Hellenic Trench, Greece: Can we reduce collision risks?
The Mediterranean sperm whale population is listed as 'Endangered". The Hellenic Trench is the core habitat of the eastern Mediterranean sperm whale sub-population that numbers two to three hundred individuals. Major shipping routes running on or very close to the 1000 m depth contour along the Hellenic Trench are causing an unsustainable number of ship-strikes with sperm whales reviewed in this paper. Sperm whale sighting and density data were combined with specific information on the vessel traffic in the area (e.g., types of vessels, traffic patterns, speed and traffic density), in order to estimate the risk of a whale/ship interaction. Routing options to significantly reduce ship strike risk by a small offshore shift in shipping routes were identified. The overall collision risk for sperm whales in the study area would be reduced by around 70%, while a maximum of 11 nautical miles would be added to major routes and only around 5 nautical miles for the majority of ships. No negative impacts were associated with re-routing by shipping away from sperm whale habitat and there would be additional shipping safety and environmental benefits. A significant contribution to the overall conservation status of the marine Natura2000 sites in the area and very important population units of threatened species such as Cuvier's beaked whales, monk seals and loggerhead turtles would be achieved, by the reduction of shipping noise and reduced risk of any oil spills reaching the coasts, which are also important touristic destinations in Greece.


Identification of connectivity in neural networks.
Analytical and experimental methods are provided for estimating synaptic connectivities from simultaneous recordings of multiple neurons. The results are based on detailed, yet flexible neuron models in which spike trains are modeled as general doubly stochastic point processes. The expressions derived can be used with nonstationary or stationary records, and can be readily extended from pairwise to multineuron estimates. Furthermore, we show analytically how the estimates are improved as more neurons are sampled, and derive the appropriate normalizations to eliminate stimulus-related correlations. Finally, we illustrate the use and interpretation of the analytical expressions on simulated spike trains and neural networks, and give explicit confidence measures on the estimates.


Disparities in care by insurance status for individuals with rheumatoid arthritis: analysis of the medical expenditure panel survey, 2006-2009.
Treatment guidelines for rheumatoid arthritis (RA) recommend early, aggressive treatment with nonbiologic and biologic disease-modifying antirheumatic drugs (DMARDs) to minimize long-term disability. We aimed to assess differences in medical resource utilization, drug therapy, and health outcomes among RA patients by insurance type in the United States. Individuals with a self-reported diagnosis of RA were identified in the Medical Expenditure Panel Survey (MEPS) database, 2006-2009. Data regarding sociodemographic characteristics, insurance type and status, and outcomes (including health care resource utilization, prescription medication use, health status, and patient-reported barriers to health care) were extracted. Multivariable regression analyses were used to examine the impact of insurance type (private, Medicare, Medicaid, or uninsured) on outcome measures while controlling for age group, sex, and race/ethnicity. A total of 693 individuals with a self-reported diagnosis of RA during the study period were identified; 423 were aged 18-64 years and 270 were aged ≥65 years. Among patients aged 18-64, those with Medicaid or who were uninsured were less likely than those with private insurance to visit a rheumatologist (adjusted odds ratio [aOR] 0.13 and 0.17, respectively; p < .001) and to receive biologic DMARDS (aOR 0.09 [p < .001] and 0.16 [p < .01], respectively); those with Medicaid were also less likely to receive nonbiologic DMARDS (aOR 0.26 [p < .01]). Those with Medicaid were more likely than those with private insurance to be unable/delayed in getting prescription drugs (aOR 2.9 [p < .05]), to experience cognitive, social, and physical limitations (aOR 8.7 [p < .001], 4.7 [p < .001], and 2.5 [p < .05], respectively); they also reported significantly lower general health and health-related quality of life. Patients aged ≥65 experienced greater equity in care and outcomes. Younger RA patients with Medicaid (including those who receive coverage under the Medicaid expansion component of the Affordable Care Act) may be at risk for inadequate treatment.


Beyond bilingualism: multilingual experience correlates with caudate volume.
The multilingual brain implements mechanisms that serve to select the appropriate language as a function of the communicative environment. Engaging these mechanisms on a regular basis appears to have consequences for brain structure and function. Studies have implicated the caudate nuclei as important nodes in polyglot language control processes, and have also shown structural differences in the caudate nuclei in bilingual compared to monolingual populations. However, the majority of published work has focused on the categorical differences between monolingual and bilingual individuals, and little is known about whether these findings extend to multilingual individuals, who have even greater language control demands. In the present paper, we present an analysis of the volume and morphology of the caudate nuclei, putamen, pallidum and thalami in 75 multilingual individuals who speak three or more languages. Volumetric analyses revealed a significant relationship between multilingual experience and right caudate volume, as well as a marginally significant relationship with left caudate volume. Vertex-wise analyses revealed a significant enlargement of dorsal and anterior portions of the left caudate nucleus, known to have connectivity with executive brain regions, as a function of multilingual expertise. These results suggest that multilingual expertise might exercise a continuous impact on brain structure, and that as additional languages beyond a second are acquired, the additional demands for linguistic and cognitive control result in modifications to brain structures associated with language management processes.


Loss of Tbx1 induces bone phenotypes similar to cleidocranial dysplasia.
T-box transcription factor, TBX1, is the major candidate gene for 22q11.2 deletion syndrome (DiGeorge/ Velo-cardio-facial syndrome) characterized by facial defects, thymus hypoplasia, cardiovascular anomalies and cleft palates. Here, we report that the loss of Tbx1 in mouse (Tbx1(-/-)) results in skeletal abnormalities similar to those of cleidocranial dysplasia (CCD) in humans, which is an autosomal-dominant skeletal disease caused by mutations in RUNX2. Tbx1(-/-) mice display short stature, absence of hyoid bone, failed closure of fontanelle, bifid xiphoid process and hypoplasia of clavicle and zygomatic arch. A cell-type-specific deletion of Tbx1 in osteochondro-progenitor (Tbx1(OPKO)) or mesodermal (Tbx1(MKO)) lineage partially recapitulates the Tbx1(-/-) bone phenotypes. Although Tbx1 expression has not been previously reported in neural crest, inactivation of Tbx1 in the neural crest lineage (Tbx1(NCKO)) leads to an absence of the body of hyoid bone and postnatal lethality, indicating an unanticipated role of Tbx1 in neural crest development. Indeed, Tbx1 is expressed in the neural crest-derived hyoid bone primordium, in addition to mesoderm-derived osteochondral progenitors. Ablation of Tbx1 affected Runx2 expression in calvarial bones and overexpression of Tbx1 induced Runx2 expression in vitro. Taken together, our current studies reveal that Tbx1 is required for mesoderm- and neural crest-derived osteoblast differentiation and normal skeletal development. TBX1 mutation could lead to CCD-like bone phenotypes in human.


Penetrance of Hemochromatosis in HFE Genotypes Resulting in p.Cys282Tyr and p.[Cys282Tyr];[His63Asp] in the eMERGE Network.
Hereditary hemochromatosis (HH) is a common autosomal-recessive disorder associated with pathogenic HFE variants, most commonly those resulting in p.Cys282Tyr and p.His63Asp. Recommendations on returning incidental findings of HFE variants in individuals undergoing genome-scale sequencing should be informed by penetrance estimates of HH in unselected samples. We used the eMERGE Network, a multicenter cohort with genotype data linked to electronic medical records, to estimate the diagnostic rate and clinical penetrance of HH in 98 individuals homozygous for the variant coding for HFE p.Cys282Tyr and 397 compound heterozygotes with variants resulting in p.[His63Asp];[Cys282Tyr]. The diagnostic rate of HH in males was 24.4% for p.Cys282Tyr homozygotes and 3.5% for compound heterozygotes (p < 0.001); in females, it was 14.0% for p.Cys282Tyr homozygotes and 2.3% for compound heterozygotes (p < 0.001). Only males showed differences across genotypes in transferrin saturation levels (100% of homozygotes versus 37.5% of compound heterozygotes with transferrin saturation > 50%; p = 0.003), serum ferritin levels (77.8% versus 33.3% with serum ferritin > 300 ng/ml; p = 0.006), and diabetes (44.7% versus 28.0%; p = 0.03). No differences were found in the prevalence of heart disease, arthritis, or liver disease, except for the rate of liver biopsy (10.9% versus 1.8% [p = 0.013] in males; 9.1% versus 2% [p = 0.035] in females). Given the higher rate of HH diagnosis than in prior studies, the high penetrance of iron overload, and the frequency of at-risk genotypes, in addition to other suggested actionable adult-onset genetic conditions, opportunistic screening should be considered for p.[Cys282Tyr];[Cys282Tyr] individuals with existing genomic data.


Effects of positive acceleration on the metabolism of endogenous carbon monoxide and serum lipid in atherosclerotic rabbits.
Atherosclerosis (AS) is caused mainly due to the increase in the serum lipid, thrombosis, and injuries of the endothelial cells. During aviation, the incremental load of positive acceleration that leads to dramatic stress reactions and hemodynamic changes may predispose pilots to functional disorders and even pathological changes of organs. However, much less is known on the correlation between aviation and AS pathogenesis. A total of 32 rabbits were randomly divided into 4 groups with 8 rabbits in each group. The control group was given a high cholesterol diet but no acceleration exposure, whereas the other 3 experimental groups were treated with a high cholesterol diet and acceleration exposure for 4, 8, and 12 weeks, respectively. In each group, samples of celiac vein blood and the aorta were collected after the last exposure for the measurement of endogenous CO and HO-1 activities, as well as the levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). As compared with the control group, the endocardial CO content and the HO-1 activity in aortic endothelial cells were significantly elevated at the 4th, 8th, and 12th weekend, respectively (P < 0.05 or <0.01). And these measures tended upward as the exposure time was prolonged. Levels of TC and LDL-C in the experimental groups were significantly higher than those in the control group, presenting an upward tendency. Levels of TG were found significantly increased in the 8-week-exposure group, but significantly declined in the 12-week-exposure group (still higher than those in the control group). Levels of the HDL-C were increased in the 4-week-exposure group, declined in the 8-week-exposure group, and once more increased in the 12-week-exposure group, without significant differences with the control group. Positive acceleration exposure may lead to a significant increase of endogenous CO content and HO-1 activity and a metabolic disorder of serum lipid in high-cholesterol diet-fed rabbits, which implicates that the acceleration exposure might accelerate the progression of AS.


Calreticulin mutants as oncogenic rogue chaperones for TpoR and traffic-defective pathogenic TpoR mutants.
Calreticulin (CALR) +1 frameshift mutations in exon 9 are prevalent in myeloproliferative neoplasms. Mutant CALRs possess a new C-terminal sequence rich in positively charged amino acids, leading to activation of the thrombopoietin receptor (TpoR/MPL). We show that the new sequence endows the mutant CALR with rogue chaperone activity, stabilizing a dimeric state and transporting TpoR and mutants thereof to the cell surface in states that would not pass quality control; this function is absolutely required for oncogenic transformation. Mutant CALRs determine traffic via the secretory pathway of partially immature TpoR, as they protect N117-linked glycans from further processing in the Golgi apparatus. A number of engineered or disease-associated TpoRs such as TpoR/MPL R102P, which causes congenital thrombocytopenia, are rescued for traffic and function by mutant CALRs, which can also overcome endoplasmic reticulum retention signals on TpoR. In addition to requiring N-glycosylation of TpoR, mutant CALRs require a hydrophobic patch located in the extracellular domain of TpoR to induce TpoR thermal stability and initial intracellular activation, whereas full activation requires cell surface localization of TpoR. Thus, mutant CALRs are rogue chaperones for TpoR and traffic-defective TpoR mutants, a function required for the oncogenic effects.


Bone microarchitectural analysis using ultra-high-resolution CT in tiger vertebra and human tibia.
To reveal trends in bone microarchitectural parameters with increasing spatial resolution on ultra-high-resolution computed tomography (UHRCT) in vivo and to compare its performance with that of conventional-resolution CT (CRCT) and micro-CT ex vivo. We retrospectively assessed 5 tiger vertebrae ex vivo and 16 human tibiae in vivo. Seven-pattern and four-pattern resolution imaging were performed on tiger vertebra using CRCT, UHRCT, and micro-CT, and on human tibiae using UHRCT. We measured six microarchitectural parameters: volumetric bone mineral density (vBMD), trabecular bone volume fraction (bone volume/total volume, BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), and connectivity density (ConnD). Comparisons between different imaging resolutions were performed using Tukey or Dunnett T3 test. The vBMD, BV/TV, Tb.N, and ConnD parameters showed an increasing trend, while Tb.Sp showed a decreasing trend both ex vivo and in vivo. Ex vivo, UHRCT at the two highest resolutions (1024- and 2048-matrix imaging with 0.25-mm slice thickness) and CRCT showed significant differences (p ≤ 0.047) in vBMD (51.4 mg/cm3 and 63.5 mg/cm3 versus 20.8 mg/cm3), BV/TV (26.5% and 29.5% versus 13.8 %), Tb.N (1.3 l/mm and 1.48 l/mm versus 0.47 l/mm), and ConnD (0.52 l/mm3 and 0.74 l/mm3 versus 0.02 l/mm3, respectively). In vivo, the 512- and 1024-matrix imaging with 0.25-mm slice thickness showed significant differences in Tb.N (0.38 l/mm versus 0.67 l/mm, respectively) and ConnD (0.06 l/mm3 versus 0.22 l/mm3, respectively). We observed characteristic trends in microarchitectural parameters and demonstrated the potential utility of applying UHRCT for microarchitectural analysis.


The attitude of Belgian social insurance physicians towards evidence-based practice and clinical practice guidelines.
Evidence-based medicine has broadened its scope and is starting to reach insurance medicine. Although still in its initial stages, physicians in the area of insurance medicine should keep up-to-date with the evidence on various diseases in order to correctly assess disability and to give appropriate advice about health care reimbursement. In order to explore future opportunities of evidence-based medicine to improve daily insurance medicine, there is a need for qualitative studies to better understand insurance physicians' perceptions of EBM. The present study was designed to identify the attitude of insurance physicians towards evidence-based medicine and clinical practice guidelines, and to determine their ability to access, retrieve and appraise the health evidence and the barriers for applying evidence to practice. A cross-sectional survey study was carried out among all Dutch-speaking insurance physicians employed at one of the six Belgian social insurance sickness funds and at the National Institute of Disability and Health care Insurance (n = 224). Chi-square tests were used to compare nominal and ordinal variables. Student's t-tests, ANOVA, Mann-Whitney and Kruskal-Wallis were used to compare means of continuous variables for different groups. The response rate was 48.7%. The majority of respondents were positive towards evidence-based medicine and clinical practice guidelines. Their knowledge of EBM was rather poor. Perceived barriers for applying evidence to practice were mainly time and lack of EBM skills. Although the majority of physicians were positive towards EBM and welcomed more guidelines, the use of evidence and clinical practice guidelines in insurance medicine is low at present. It is in the first place important to eradicate the perceived inertia which limits the use of EBM and to further investigate the EBM principles in the context of insurance medicine. Available high-quality evidence-based resources (at the moment mainly originating from other medical fields) need to be structured in a way that is useful for insurance physicians and global access to this information needs to be ensured.


Top-down population regulation of a top predator: lions in the Ngorongoro Crater.
Efforts to determine whether bottom-up or top-down processes regulate populations have been hampered by difficulties in accurately estimating the population's carrying capacity and in directly measuring food intake rate, the impacts of interspecific competition and exposure to natural enemies. We report on 40 years of data on the lion population in Ngorongoro Crater, Tanzania, which showed strong evidence of density-dependent regulation at 100-120 individuals but has remained below 60 individuals for the past decade despite consistently high prey abundance. The lions enjoy a higher per capita food-intake rate and higher cub recruitment at low population density, and interspecific competition has not increased in recent years. These animals have suffered from a number of severe disease outbreaks over the past 40 years, but, whereas the population recovered exponentially from a severe epizootic in 1963, three outbreaks between 1994 and 2001 have occurred in such rapid succession that the population has been unable to return to the carrying capacity. The Crater population may have become unusually vulnerable to infectious disease in recent years owing to its close proximity to a growing human population and a history of close inbreeding. The Crater lions may therefore provide important insights into the future of many endangered populations.


Acoustic telemetry reveals cryptic residency of whale sharks.
Although whale sharks (Rhincodon typus) have been documented to move thousands of kilometres, they are most frequently observed at a few predictable seasonal aggregation sites. The absence of sharks at the surface during visual surveys has led to the assumption that sharks disperse to places unknown during the long 'off-seasons' at most of these locations. Here we compare 2 years of R. typus visual sighting records from Mafia Island in Tanzania to concurrent acoustic telemetry of tagged individuals. Sightings revealed a clear seasonal pattern with a peak between October and February and no sharks observed at other times. By contrast, acoustic telemetry demonstrated year-round residency of R. typus. The sharks use a different habitat in the off-season, swimming deeper and further away from shore, presumably in response to prey distributions. This behavioural change reduces the sharks' visibility, giving the false impression that they have left the area. We demonstrate, for the first time to our knowledge, year-round residency of unprovisioned, individual R. typus at an aggregation site, and highlight the importance of using multiple techniques to study the movement ecology of marine megafauna.


The prestimulus default mode network state predicts cognitive task performance levels on a mental rotation task.
Linking individual task performance to preceding, regional brain activation is an ongoing goal of neuroscientific research. Recently, it could be shown that the activation and connectivity within large-scale brain networks prior to task onset influence performance levels. More specifically, prestimulus default mode network (DMN) effects have been linked to performance levels in sensory near-threshold tasks, as well as cognitive tasks. However, it still remains uncertain how the DMN state preceding cognitive tasks affects performance levels when the period between task trials is long and flexible, allowing participants to engage in different cognitive states. We here investigated whether the prestimulus activation and within-network connectivity of the DMN are predictive of the correctness and speed of task performance levels on a cognitive (match-to-sample) mental rotation task, employing a sparse event-related functional magnetic resonance imaging (fMRI) design. We found that prestimulus activation in the DMN predicted the speed of correct trials, with a lower amplitude preceding correct fast response trials compared to correct slow response trials. Moreover, we found higher connectivity within the DMN before incorrect trials compared to correct trials. These results indicate that pre-existing activation and connectivity states within the DMN influence task performance on cognitive tasks, both effecting the correctness and speed of task execution. The findings support existing theories and empirical work on relating mind-wandering and cognitive task performance to the DMN and expand these by establishing a relationship between the prestimulus DMN state and the speed of cognitive task performance.


Early and Late Outcomes Following Valve Sparing Aortic Root Reconstruction: The ANZSCTS Database.
Valve sparing aortic root reconstruction (VSARR) has become an alternative to traditional aortic root replacement with a valved conduit. There have been various modifications but the two broad types are aortic root reimplantation and the aortic root remodelling procedure. We present the early and late outcomes following valve sparing aortic root reconstruction surgery in Australia. We reviewed the ANZSCTS database for patients undergoing these procedures. Preoperative, intraoperative and postoperative variables were analysed. Multivariable regression was performed to determine independent predictors of 30-day mortality. We also obtained five- and 10-year survival estimates by cross-linking the ANZSCTS database with the Australian Institute of Health and Welfare's National Death Index. Between January 2001 and January 2012, 169 consecutive patients underwent VSARR procedures. The mean age of the study population was 54.4 years with 31.4% being females. Overall, nine patients (5.9%) died within 30 days post procedure and five patients (3%) had permanent strokes. However, out of 132 elective cases, only five patients died (3.8%). Independent predictors of 30-day mortality were female gender [OR 5.65(1.24-25.80), p=0.025], preoperative atrial arrhythmia [OR 6.07(1.14-32.35), p=0.035] and acute type A aortic dissection [OR 7.71(1.63-36.54), p=0.01]. Long-term survival was estimated as 85.3% and 72.7% at five- and 10-years, respectively. Along with an acceptable rate of early mortality and stroke, VSARR procedures provide good long-term survival according to the ANZSCTS database. As promising procedure for pathologies that impair the aortic root integrity, they can be adopted more widely, especially in Australian and New Zealand centres with experienced aortic units. Future studies are planned to assess freedom from valve deterioration and repeat surgery.


Control of schistosomiasis: report of a workshop.
Nineteen scientists, field workers, and representatives of funding agencies active in schistosomiasis research and control met in Bellagio, Italy in October 1977 to attempt to evaluate the effectiveness of current control methods and what might be accomplished with available technology. The deliberations included summaries of knowledge on the biology, transmission, and control of schistosomiasis and assessment of major control programs and methodologies. The groups concluded that in the major endemic areas considerable gains in control of schistosomiasis could be made with current technology. However, maintenance of control in most countries, and establishment of serious control programs in countries in which schistosomiasis is a less severe public health problem, would require development of less expensive modalities which would need little monitoring and possibly have benefits extending beyond schistosomiasis control.


Impaired osteogenic differentiation of mesenchymal stem cells derived from bone marrow of patients with lower-risk myelodysplastic syndromes.
The pathogenesis of myelodysplastic syndromes (MDS) has not been completely understood, and insufficiency of the hematopoietic microenvironment can be an important factor. Mesenchymal stem cells (MSCs) and osteoblasts are key components of the hematopoietic microenvironment. Here, we measured the expression of multiple osteogenic genes in 58 MSCs from MDS patients with different disease stages and subtypes by real-time PCR and compared the osteogenic differentiation of MSCs from 20 MDS patients with those of MSCs from eight normal controls quantitatively and dynamically. The mRNA level of Osterix and RUNX2, two key factors involved in the early differentiation process toward osteoblasts, was significantly reduced in undifferentiated MSCs from lower-risk MDS. After osteogenic induction, lower-risk MDS showed lower alkaline phosphatase activity, less intense alizarin red S staining, and lower gene expression of osteogenic differentiation markers; however, higher-risk MDS was normal. Finally, in bone marrow biopsy, the number of osteoblasts was significantly decreased in lower-risk MDS. These results indicate that MSCs from lower-risk MDS have impaired osteogenic differentiation functions, suggesting their insufficient stromal support in MDS.


Lipids as integral components in mussel adhesion.
Lipids are fundamental components of cells in organisms. Recent studies reveal that lipids are also present in cell-free bioadhesives. Examples include barnacle cement, sea star footprints, hairy and smooth pads of insects and gecko setae. Whether reliance on lipids is universal in bioadhesion is not known. In the present study, we demonstrated, for the first time, the involvement of lipids in mussel adhesion. We extracted, identified and localized lipids in the byssal threads. The lipids were confirmed as fatty acids by gas chromatograpy mass spectrometry. δ13C measurements of the fatty acids in the byssus were also conducted. Results show that byssal fatty acids, with concentrations ranging from 1.10-2.51 mg g-1 by thread dry weight depending on the mussel species, are localized both on the surface of and inside the byssal thread and plaque. Over half of the fatty acids were loosely attached to the surface while a small portion were tightly bound to the byssus. Most of the surface fatty acids disappear within a week of thread deposition. δ13C values of byssal fatty acids show isotope fractionation suggesting that thread fatty acids are derived from the foot. It is possible that fatty acids are key players in expelling water and preparing the substrate surface for adhesion. Using lipids in the adhesion process might be a common strategy for organisms in need of temporary or permanent attachment. The process of lipid participation may be as important as adhesive components for developing more efficient man-made glues.


Spectral analysis of phase shifting algorithms.
Systematic spectral analysis of Phase Shifting Interferometry (PSI) algorithms was first proposed in 1990 by Freischlad and Koliopoulos (F&K). This analysis was proposed with the intention that "in a glance" the main properties of the PSI algorithms would be highlighted. However a major drawback of the F&K spectral analysis is that it changes when the PSI algorithm is rotated or its reference signal is time-shifted. In other words, the F&K spectral plot is different when the PSI algorithm is rotated or its reference is time-shifted. However, it is well known that these simple operations do not alter the basic phase demodulation properties of PSI algorithms, except for an unimportant piston. Here we propose a new way to analyze the spectra of PSI algorithms which is invariant to rotation and/or reference time-shift among other advantages over the nowadays standard PSI spectral analysis by F&K.


mirPub: a database for searching microRNA publications.
Identifying, amongst millions of publications available in MEDLINE, those that are relevant to specific microRNAs (miRNAs) of interest based on keyword search faces major obstacles. References to miRNA names in the literature often deviate from standard nomenclature for various reasons, since even the official nomenclature evolves. For instance, a single miRNA name may identify two completely different molecules or two different names may refer to the same molecule. mirPub is a database with a powerful and intuitive interface, which facilitates searching for miRNA literature, addressing the aforementioned issues. To provide effective search services, mirPub applies text mining techniques on MEDLINE, integrates data from several curated databases and exploits data from its user community following a crowdsourcing approach. Other key features include an interactive visualization service that illustrates intuitively the evolution of miRNA data, tag clouds summarizing the relevance of publications to particular diseases, cell types or tissues and access to TarBase 6.0 data to oversee genes related to miRNA publications. mirPub is freely available at http://www.microrna.gr/mirpub/. firstname.lastname@example.com or email@example.com Supplementary data are available at Bioinformatics online.


Vidi, vini, vinci: External ophthalmomyiasis infection that occurred, and was diagnosed and treated in a single day: A rare case report.
Ophthalmomyiasis is an infestation of eye with larvae or maggots of certain flies. Oestrus ovis (sheep nasal botfly) belonging to family Oestridae is the most common cause of human myiasis. We describe here an acute presentation of a case of external ophthalmomyiasis, i.e., infestation of conjunctiva due to first instar larvae of Oestrus ovis. In this case report the occurrence, diagnosis and treatment all took place in the setting of a single day. Prompt treatment by removal of larvae mechanically followed by instillation of antibiotic and steroid eye drops helped to prevent serious complications. The taxonomic identification of fly is also important as some fly species are capable of penetrating deeper tissues of eyes, which is sight threatening.


Blockade of current through single calcium channels by Cd2+, Mg2+, and Ca2+. Voltage and concentration dependence of calcium entry into the pore.
We studied the blocking actions of external Ca2+, Mg2+, Ca2+, and other multivalent ions on single Ca channel currents in cell-attached patch recordings from guinea pig ventricular cells. External Cd or Mg ions chopped long-lasting unitary Ba currents promoted by the Ca agonist Bay K 8644 into bursts of brief openings. The bursts appear to arise from discrete blocking and unblocking transitions. A simple reaction between a blocking ion and an open channel was suggested by the kinetics of the bursts: open and closed times within a burst were exponentially distributed, the blocking rate varied linearly with the concentration of blocking ion, and the unblocking rate was more or less independent of the blocker concentration. Other kinetic features suggested that both Cd2+ and Mg2+ lodge within the pore. The unblocking rate was speeded by membrane hyperpolarization or by raising the Ba concentration, as if blocking ions were swept into the myoplasm by the applied electric field or by repulsive interaction with Ba2+. Ca ions reduced the amplitude of unitary Ba currents (50% inhibition at approximately 10 mM [Ca]o with 50 mM [Ba]o) without detectable flicker, presumably because Ca ions exit the pore very rapidly following Ba entry. However, Ca2+ entry and exit rates could be resolved when micromolar Ca blocked unitary Li+ fluxes through the Ca channel. The blocking rate was essentially voltage independent, but varied linearly with Ca concentration (rate coefficient, 4.5 X 10(8) M-1s-1); evidently, the initial Ca2+-pore interaction is outside the membrane field and much faster than the overall process of Ca ion transfer. The unblocking rate did not vary with [Ca]o, but increased steeply with membrane hyperpolarization, as if blocking Ca ions were driven into the cell. We suggest that Ca is both an effective permeator and a potent blocker because it dehydrates rapidly (unlike Mg2+) and binds to the pore with appropriate affinity (unlike Cd2+). There appears to be no sharp dichotomy between "permeators" and "blockers," only quantitative differences in how quickly ions enter and leave the pore.


Characterization of mixed-ligand shells on gold nanoparticles by transition metal and supramolecular surface probes.
We report herein two methods to characterize the surface of mixed-ligand shell gold nanoparticles, which was explored with gold nanoparticles containing varying molar ratios of 3-mercaptopropionic acid (MPA) and 3-mercapto-1-propanesulfonate (MPS) or 11-mercaptoundecanoic acid (MUA) and triethylene glycol mono-11-mercaptoundecyl ether (TEG) in their ligand shell. Incubation of gold nanoparticles with a solution containing the transition metal cation Ni2+ allows the extraction of Ni2+ depending on the number of negatively charged surface groups and the reaction of surface carboxylic acid groups with an aminomethyladamantane derivative allows the extraction of the supramolecular host molecule cucurbit[7]uril (CB7) depending on the number of reactive surface groups. In both the methods, the remaining surface probes in the supernatant could be conveniently quantified in a homogeneous solution after a simple centrifugation step. An excellent linear correlation between the amount of Ni2+ extracted and the ligand density of MPA and MPS in MPA/MPS gold nanoparticles or MUA in MUA/TEG gold nanoparticles afforded a simple and reliable assay method to determine the number of negatively charged surface groups. The supramolecular CB7 assay enabled the determination of the accessible ligand density of reactive surface carboxylic acid groups and revealed a striking difference in the number of surface groups that can be reacted with MPA/MPS gold nanoparticles or MUA/TEG gold nanoparticles, which suggests a simple method to probe the surface structure of mixed monolayer gold nanoparticles.


Innovative slow-release organic carbon-source material for groundwater in situ denitrification.
Slow-release organic carbon-source (SOC) material, a new kind of electron donor for in situ groundwater denitrification, was prepared and evaluated in this study. With starch as a biologically utilized carbon source and polyvinyl alcohol (PVA) as a frame, this material performed controllable carbon release rates and demonstrated stable behaviour during the simulated denitrification process. Raman spectrum analysis showed that the PVA skeleton formed cross-linking network structures for hydrogen-bonded water molecules reset in low temperatures, and the starchy molecules filled in the interspace of the skeleton to form a two-phase interlocking/disperse phase structure. In a static system, carbon release processes followed the Fickian law with (1.294-6.560)×10(-3) mg g(-1) s(-1/2) as the release coefficient. Under domestication and in situ groundwater simulation conditions, SOC material played a favourable role during denitrification, with 1.049±0.165 as an average carbon-nitrogen ratio. The denitrification process followed the law of zero-order kinetics, while the dynamics parameter kN was 0.563-8.753 gN m(-3) d(-1). Generally, SOC material was suggested to be a potential carbon source (electron donor) suitable for in situ groundwater denitrification.


The role of social attention in older adults' ability to interpret naturalistic social scenes.
Age-related differences on theory of mind (ToM) tasks are well established. However, the literature has been criticised for predominantly relying on tasks with poor ecological validity, and consequently it remains unclear whether these age differences extend to tasks with greater realism. In addition, we currently have a limited understanding of the factors that may contribute to age-related declines in ToM. To address these issues, we conducted two studies that assessed age differences in ToM using multimodal social scene stimuli. Study 1 also examined eye movements to assess whether biases in visual attention may be related to age-related difficulties in ToM, and Study 2 included an assessment of social attention (as indexed by biological motion perception) and working memory to assess whether these capacities may explain age difficulties in ToM. In both studies, the results showed that older adults performed worse than their younger counterparts on the ToM tasks, indicating that age-related difficulties in ToM extend to measures that more closely represent everyday social interactions. The eye-tracking data in Study 1 showed that older adults gazed less at the faces of protagonists in the social scenes compared with younger adults; however, these visual biases were not associated with ToM ability. Study 2 showed that older age was associated with a reduced ability to detect biological motion cues, and this mediated age-related variance in ToM ability. These findings are discussed in relation to competing theoretical frameworks of ageing that predict either improvements or declines in ToM with age.


Modified citrus pectin-monograph.
Modified citrus pectin (MCP), also known as fractionated pectin, is a complex polysaccharide obtained from the peel and pulp of citrus fruits. Modified citrus pectin is rich in galactoside residues, giving it an affinity for certain types of cancer cells. Metastasis is one of the most life-threatening aspects of cancer and the lack of effective anti-metastatic therapies has prompted research on MCP's effectiveness in blocking metastasis of certain types of cancers, including melanomas, prostate, and breast cancers.


Deconstructing chronic low back pain in the older adult--step by step evidence and expert-based recommendations for evaluation and treatment: part I: Hip osteoarthritis.
To present the first in a series of articles designed to deconstruct chronic low back pain (CLBP) in older adults. The series presents CLBP as a syndrome, a final common pathway for the expression of multiple contributors rather than a disease localized exclusively to the lumbosacral spine. Each article addresses one of twelve important contributors to pain and disability in older adults with CLBP. This article focuses on hip osteoarthritis (OA). The evaluation and treatment algorithm, a table articulating the rationale for the individual algorithm components, and stepped-care drug recommendations were developed using a modified Delphi approach. The Principal Investigator, a five-member content expert panel and a nine-member primary care panel were involved in the iterative development of these materials. The algorithm was developed keeping in mind medications and other resources available within Veterans Health Administration (VHA) facilities. As panelists were not exclusive to the VHA, the materials can be applied in both VHA and civilian settings. The illustrative clinical case was taken from one of the contributor's clinical practice. We present an algorithm and supportive materials to help guide the care of older adults with hip OA, an important contributor to CLBP. The case illustrates an example of complex hip-spine syndrome, in which hip OA was an important contributor to disability in an older adult with CLBP. Hip OA is common and should be evaluated routinely in the older adult with CLBP so that appropriately targeted treatment can be designed.


The flora phenotype ontology (FLOPO): tool for integrating morphological traits and phenotypes of vascular plants.
The systematic analysis of a large number of comparable plant trait data can support investigations into phylogenetics and ecological adaptation, with broad applications in evolutionary biology, agriculture, conservation, and the functioning of ecosystems. Floras, i.e., books collecting the information on all known plant species found within a region, are a potentially rich source of such plant trait data. Floras describe plant traits with a focus on morphology and other traits relevant for species identification in addition to other characteristics of plant species, such as ecological affinities, distribution, economic value, health applications, traditional uses, and so on. However, a key limitation in systematically analyzing information in Floras is the lack of a standardized vocabulary for the described traits as well as the difficulties in extracting structured information from free text. We have developed the Flora Phenotype Ontology (FLOPO), an ontology for describing traits of plant species found in Floras. We used the Plant Ontology (PO) and the Phenotype And Trait Ontology (PATO) to extract entity-quality relationships from digitized taxon descriptions in Floras, and used a formal ontological approach based on phenotype description patterns and automated reasoning to generate the FLOPO. The resulting ontology consists of 25,407 classes and is based on the PO and PATO. The classified ontology closely follows the structure of Plant Ontology in that the primary axis of classification is the observed plant anatomical structure, and more specific traits are then classified based on parthood and subclass relations between anatomical structures as well as subclass relations between phenotypic qualities. The FLOPO is primarily intended as a framework based on which plant traits can be integrated computationally across all species and higher taxa of flowering plants. Importantly, it is not intended to replace established vocabularies or ontologies, but rather serve as an overarching framework based on which different application- and domain-specific ontologies, thesauri and vocabularies of phenotypes observed in flowering plants can be integrated.


Positron emission tomography/computed tomography for optimized colon cancer staging and follow up.
Optimal management of colon cancer (CC) requires detailed assessment of extent of disease. This study prospectively investigates the diagnostic accuracy of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (PET/CT) for staging and detection of recurrence in primary CC. PET/CT for preoperative staging was performed in 66 prospectively included patients with primary CC. Diagnostic accuracy for PET/CT and CT was analyzed. In addition to routine follow up, 42 stages I-III CC patients had postoperative PET/CT examinations every 6 months for 2 years. Serological levels of tissue inhibitor of metalloproteinase-1 (TIMP-1), carcinoembryonic antigen, and liberated domain I of urokinase plasminogen activator receptor were analyzed. Accuracy for tumor, nodal, and metastases staging by PET/CT were 82% (95% confidence interval [CI]: 70; 91), 66% (CI: 51; 78), and 89% (CI: 79; 96); for CT the accuracy was 77% (CI: 64; 87), 60% (CI: 46; 73), and 69% (CI: 57; 80). Cumulative relapse incidences for stages I-III CC at 6, 12, 18, and 24 months were 7.1% (CI: 0; 15); 14.3% (CI: 4; 25); 19% (CI: 7; 31), and 21.4% (CI: 9; 34). PET/CT diagnosed all relapses detected during the first 2 years. High preoperative TIMP-1 levels were associated with significant hazards toward risk of recurrence and shorter overall survival. This study indicates PET/CT as a valuable tool for staging and follow up in CC. TIMP-1 provided prognostic information potentially useful in selection of patients for intensive follow up.


Dopamine-serotonin interactions in attention-deficit hyperactivity disorder (ADHD).
Poor control of attention-related and motor processes, often associated with behavioural or cognitive impulsivity, are typical features of children and adults with attention-deficit hyperactivity disorder (ADHD). Until recently clinicians have observed little need to improve on or add to the catecholaminergic model for explaining the features of ADHD. Recent genetic and neuroimaging studies however provide evidence for separate contributions of altered dopamine (DA) and serotonin (5-HT) function in this disorder. Genetic studies imply that for both DA and 5-HT systems variants may frequently occur in ADHD for neurotransmitter uptake, synthesis and breakdown functions. The separate distributions in the brain of mesolimbic DA transporter and mesocortical DA D4 binding sites, both strongly implicated in ADHD, draws attention to potentially differential contributions from the 5-HT system. However, the evidence here points less towards an anatomical differentiation, as towards one in terms of inhibitory/facilitatory pre/post-synaptic location of receptors in the 5-HT(1) and 5-HT(2) families. While the monoamine metabolite levels excreted in ADHD are often correlated, this may well flow from a starting point where 5-HT activity is anomalously higher or lower than the generally lower than normal levels for DA. It appears that perhaps both situations may arise reflecting different diagnostic subgroups of ADHD, and where impulsive characteristics of the subjects reflect externalizing behaviour or cognitive impulsivity. For these features there is clear evidence that DA and 5-HT neuronal systems can and do interact anomalously in ADHD at the level of the soma, the terminals and at a distance. Interactions mediated by macroglia are also likely. However, it remains difficult to ascribe specific mechanisms to their effects (in potentially different subgroups of patients) from this relatively new field of study that has as yet produced rather heterogeneous results.


Horizontal transfers and gene losses in the phospholipid pathway of bartonella reveal clues about early ecological niches.
Bartonellae are mammalian pathogens vectored by blood-feeding arthropods. Although of increasing medical importance, little is known about their ecological past, and host associations are underexplored. Previous studies suggest an influence of horizontal gene transfers in ecological niche colonization by acquisition of host pathogenicity genes. We here expand these analyses to metabolic pathways of 28 Bartonella genomes, and experimentally explore the distribution of bartonellae in 21 species of blood-feeding arthropods. Across genomes, repeated gene losses and horizontal gains in the phospholipid pathway were found. The evolutionary timing of these patterns suggests functional consequences likely leading to an early intracellular lifestyle for stem bartonellae. Comparative phylogenomic analyses discover three independent lineage-specific reacquisitions of a core metabolic gene-NAD(P)H-dependent glycerol-3-phosphate dehydrogenase (gpsA)-from Gammaproteobacteria and Epsilonproteobacteria. Transferred genes are significantly closely related to invertebrate Arsenophonus-, and Serratia-like endosymbionts, and mammalian Helicobacter-like pathogens, supporting a cellular association with arthropods and mammals at the base of extant Bartonella spp. Our studies suggest that the horizontal reacquisitions had a key impact on bartonellae lineage specific ecological and functional evolution.


Clinician predictions of intensive care unit mortality.
Predicting outcomes for critically ill patients is an important aspect of discussions with families in the intensive care unit. Our objective was to evaluate clinical intensive care unit survival predictions and their consequences for mechanically ventilated patients. Prospective cohort study. Fifteen tertiary care centers. Consecutive mechanically ventilated patients > or = 18 yrs of age with expected intensive care unit stay > or = 72 hrs. We recorded baseline characteristics at intensive care unit admission. Daily we measured multiple organ dysfunction score (MODS), use of advanced life support, patient preferences for life support, and intensivist and bedside intensive care unit nurse estimated probability of intensive care unit survival. The 851 patients were aged 61.2 (+/- 17.6, mean + SD) yrs with an Acute Physiology and Chronic Health Evaluation (APACHE) II score of 21.7 (+/- 8.6). Three hundred and four patients (35.7%) died in the intensive care unit, and 341 (40.1%) were assessed by a physician at least once to have a < 10% intensive care unit survival probability. Independent predictors of intensive care unit mortality were baseline APACHE II score (hazard ratio, 1.16; 95% confidence interval, 1.08-1.24, for a 5-point increase) and daily factors such as MODS (hazard ratio, 2.50; 95% confidence interval, 2.06-3.04, for a 5-point increase), use of inotropes or vasopressors (hazard ratio, 2.14; 95% confidence interval, 1.66-2.77), dialysis (hazard ratio, 0.51; 95% confidence interval, 0.35-0.75), patient preference to limit life support (hazard ratio, 10.22; 95% confidence interval, 7.38-14.16), and physician but not nurse prediction of < 10% survival. The impact of physician estimates of < 10% intensive care unit survival was greater for patients without vs. those with preferences to limit life support (p < .001) and for patients with less vs. more severe organ dysfunction (p < .001). Mechanical ventilation, inotropes or vasopressors, and dialysis were withdrawn more often when physicians predicted < 10% probability of intensive care unit survival (all ps < .001). Physician estimates of intensive care unit survival < 10% are associated with subsequent life support limitation and more powerfully predict intensive care unit mortality than illness severity, evolving or resolving organ dysfunction, and use of inotropes or vasopressors.


Junctional adhesion molecule-C is a soluble mediator of angiogenesis.
Junctional adhesion molecule-C (JAM-C) is an adhesion molecule expressed by endothelial cells (ECs) that plays a role in tight junction formation, leukocyte adhesion, and transendothelial migration. In the current study, we investigated whether JAM-C is found in soluble form and whether soluble JAM-C (sJAM-C) mediates angiogenesis. We found that JAM-C is present in soluble form in normal serum and elevated in rheumatoid arthritis (RA) serum. The concentration of sJAM-C is also elevated locally in RA synovial fluid compared with RA serum or osteoarthritis synovial fluid. sJAM-C was also present in the culture supernatant of human microvascular ECs (HMVECs) and immortalized human dermal microvascular ECs, and its concentration was increased following cytokine stimulation. In addition, sJAM-C cleavage from the cell surface was mediated in part by a disintegrin and metalloproteinases 10 and 17. In functional assays, sJAM-C was both chemotactic and chemokinetic for HMVECs and induced HMVEC tube formation on Matrigel in vitro. Neutralizing anti-JAM-C Abs inhibited RA synovial fluid-induced HMVEC chemotaxis and sJAM-C-induced HMVEC tube formation on Matrigel. sJAM-C also induced angiogenesis in vivo in the Matrigel plug and sponge granuloma models. Moreover, sJAM-C-mediated HMVEC chemotaxis was dependent on Src, p38, and PI3K. Our results show that JAM-C exists in soluble form and suggest that modulation of sJAM-C may provide a novel route for controlling pathological angiogenesis.


Clinical findings in cats with dilated cardiomyopathy and relationship of findings to taurine deficiency.
Between October 1986 and September 1988, 37 cats with moderate to severe idiopathic myocardial failure (dilated cardiomyopathy) were evaluated prospectively. Low plasma taurine concentration and diet history including foods that can cause taurine deficiency were documented in most of the cats. Comparison with a retrospectively studied population of 33 cats with dilated cardiomyopathy diagnosed between 1980 and 1986 demonstrated that the clinical and historical findings in the 33 retrospectively studied cats were similar to those in the 37 cats studied prospectively. Clinical findings in the 2 groups were also similar to findings previously reported in the literature. Because clinical findings and diet history were similar in the prospective and retrospective groups, we believe that many cats in the latter group had diet-induced taurine deficiency. These findings support the conclusion that most cases of dilated cardiomyopathy in cats have a common etiopathogenesis related to diet and as such are preventable.


Comparative population genomics in animals uncovers the determinants of genetic diversity.
Genetic diversity is the amount of variation observed between DNA sequences from distinct individuals of a given species. This pivotal concept of population genetics has implications for species health, domestication, management and conservation. Levels of genetic diversity seem to vary greatly in natural populations and species, but the determinants of this variation, and particularly the relative influences of species biology and ecology versus population history, are still largely mysterious. Here we show that the diversity of a species is predictable, and is determined in the first place by its ecological strategy. We investigated the genome-wide diversity of 76 non-model animal species by sequencing the transcriptome of two to ten individuals in each species. The distribution of genetic diversity between species revealed no detectable influence of geographic range or invasive status but was accurately predicted by key species traits related to parental investment: long-lived or low-fecundity species with brooding ability were genetically less diverse than short-lived or highly fecund ones. Our analysis demonstrates the influence of long-term life-history strategies on species response to short-term environmental perturbations, a result with immediate implications for conservation policies.


Active, passive and proprioceptive neuromuscular facilitation stretching are comparable in improving the knee flexion range in people with total knee replacement: a randomized controlled trial.
To compare the immediate and medium-term effects of three stretching methods on the knee flexion range in people with a total knee replacement. Randomized clinical trial. Rehabilitation hospital. 117 patients were recruited and 100 (mean age: 68.43 ± 7.95 years) of them completed the study. Patients receiving total knee replacement due to knee osteoarthritis were randomly assigned into 3 groups of: active stretching (group 1, n =32), passive stretching (group 2, n =35) and proprioceptive neuromuscular facilitation stretching (group 3, n =33). The immediate change in both active and passive knee flexion range after the first treatment session and the pattern of change in these ranges throughout the 2-week study period were compared among the three groups. All groups demonstrated significant improvement in knee ranges with time. The active range of group 1 improved by 19.9°, group 2 by 25.3° and group 3 by 22.5° throughout the 2-week period, whereas the improvements in the passive range were 18.8°, 24.5° and 22.7°, respectively. For between-group comparisons, no significant difference was found in both active (P = 0.647) and passive (P = 0.501) knee range immediately after stretching. For the changes at 2 weeks, there was also no significant difference among the groups in both active (P = 0.716) and passive (P = 0.959) knee ranges. This study revealed that all three modes of stretching were associated with an increase in the knee flexion range of patients after total knee replacement, with no statistically significant differences between the changes seen.


Race and the Geography of Opportunity in the Post-Prison Labor Market.
Research on racial disparities in post-prison employment has primarily focused on the differential effects of stigma on blacks and whites, but we otherwise know little about racial differences. This paper examines racial differences in post-prison employment by industry and geography. We find that the formerly incarcerated are most likely to find work in a small number of "felon-friendly" industries with formerly incarcerated whites having higher employment rates than blacks. Whites are more likely to be employed in felon-friendly industries associated with the primary labor market, particularly construction and manufacturing, which have higher wages and more job stability. To explain these racial differences, we investigate the degree to which employment among the formerly incarcerated is related to where felon-friendly employers are located and where individuals who work in felon-friendly industries live. We find that post-prison employment is associated more with proximity to workers in felon-friendly industries than with proximity to employers. Because formerly incarcerated whites are more likely to live near current workers in felon-friendly industries, the geography of opportunity in the post-prison labor market contributes to the racial disparity in post-prison employment.


High-energy X-ray focusing and applications to pair distribution function investigation of Pt and Au nanoparticles at high pressures.
We report development of micro-focusing optics for high-energy x-rays by combining a sagittally bent Laue crystal monchromator with Kirkpatrick-Baez (K-B) X-ray focusing mirrors. The optical system is able to provide a clean, high-flux X-ray beam suitable for pair distribution function (PDF) measurements at high pressure using a diamond anvil cell (DAC). A focused beam of moderate size (10-15 μm) has been achieved at energies of 66 and 81 keV. PDF data for nanocrystalline platinum (n-Pt) were collected at 12.5 GPa with a single 5 s X-ray exposure, showing that the in-situ compression, decompression, and relaxation behavior of samples in the DAC can be investigated with this technique. PDFs of n-Pt and nano Au (n-Au) under quasi-hydrostatic loading to as high as 71 GPa indicate the existence of substantial reduction of grain or domain size for Pt and Au nanoparticles at pressures below 10 GPa. The coupling of sagittally bent Laue crystals with K-B mirrors provides a useful means to focus high-energy synchrotron X-rays from a bending magnet or wiggler source.