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Background: Adiponectin is an adipocyte-derived hormone that acts as a marker of insulin sensitivity. Bloodspot sampling by fingerstick onto filter paper may increase the feasibility of large-scale studies of the determinants of insulin sensitivity. We first describe the validation of an enzyme-linked immunoassay (ELISA) for quantifying adiponectin from dried blood spots and then demonstrate its application in a large trial (PROBIT). Methods: We quantified adiponectin from 3-mm diameter discs (≈3 µL of blood) punched from dried blood spots obtained from: i) whole blood standards (validation); and ii) PROBIT trial samples (application) in which paediatricians collected blood spots from 13,879 children aged 11.5 years from 31 sites across Belarus. We examined the distribution of bloodspot adiponectin by demographic and anthropometric factors, fasting insulin and glucose. Results: In the validation study, mean intra-assay coefficients of variation (n = 162) were 15%, 13% and 10% for ‘low’ (6.78 µg/ml), ‘medium’ (18.18 µg/ml) and 'high’ (33.13 µg/ml) internal quality control (IQC) samples, respectively; the respective inter-assay values (n = 40) were 23%, 21% and 14%. The correlation coefficient between 50 paired whole bloodspot versus plasma samples, collected simultaneously, was 0.87 (95% CI: 0.78 to 0.93). Recovery of known quantities of adiponectin (between 4.5 to 36 µg/ml) was 100.3–133%. Bloodspot adiponectin was stable for at least 30 months at −80°C. In PROBIT, we successfully quantified fasting adiponectin from dried blood spots in 13,329 of 13,879 (96%) children. Mean adiponectin (standard deviation) concentrations were 17.34 µg/ml (7.54) in boys and 18.41 µg/ml (7.92) in girls and were inversely associated with body mass index, fat mass, triceps and subscapular skin-fold thickness, waist circumference, height and fasting glucose. Conclusions: Bloodspot ELISA is suitable for measuring adiponectin in very small volumes of blood collected on filter paper and can be applied to large-scale studies. [ABSTRACT FROM AUTHOR]

The mass digitization of books is changing the way information is created, disseminated and displayed. Electronic book readers (e-readers) generally refer to two main display technologies: the electronic ink (E-ink) and the liquid crystal display (LCD). Both technologies have advantages and disadvantages, but the question whether one or the other triggers less visual fatigue is still open. The aim of the present research was to study the effects of the display technology on visual fatigue. To this end, participants performed a longitudinal study in which two last generation e-readers (LCD, E-ink) and paper book were tested in three different prolonged reading sessions separated by - on average - ten days. Results from both objective (Blinks per second) and subjective (Visual Fatigue Scale) measures suggested that reading on the LCD (Kindle Fire HD) triggers higher visual fatigue with respect to both the E-ink (Kindle Paperwhite) and the paper book. The absence of differences between E-ink and paper suggests that, concerning visual fatigue, the E-ink is indeed very similar to the paper. [ABSTRACT FROM AUTHOR]

Background: The practice of giving certain authors equal credit in original research publications was increasingly common in some specialty. This study aimed to investigate the prevalence and characteristics of designating some authors with equally credited authors (ECAs) in major anaesthesia journals. Methodology/Principal Findings: The practice of giving authors equal credit was searched and identified in the three major anaesthesia journals between January 1, 2002 and December 31, 2011. Papers with ECAs had a higher proportion of the total number of articles in 2011 versus published in 2002 (Anesthesiology, 8.8% vs. 0.9%; British Journal of Anaesthesia, 8.8% vs. 0%; Anesthesia & Analgesia, 3.4% vs. 0.3%; totally, 6.4% vs. 0.4%). A significant increasing trend in annual proportion of articles with ECA was found in the three journals. The first two authors listed in the byline had equal credit in most cases. Conclusions/Significance: The practice of giving authors equal credit in original research papers is increasingly common in major anaesthesia journals. It may be warranted for the journals to guide the authors how to regard this practice. [ABSTRACT FROM AUTHOR]

The study of individual differences encompasses broad constructs including intelligence, creativity, and personality. However, substantially less research is devoted to the study of specific aptitudes in spite of their importance to educational, occupational, and avocational success. We sought to determine subcortical brain structural correlates of several broad aptitudes including Math, Vocabulary, Foresight, Paper Folding, and Inductive Reasoning in a large (N = 107), healthy, young (age range  = 16–29) cohort. Subcortical volumes were measured using an automated technique (FreeSurfer) across structures including bilateral caudate, putamen, globus pallidus, thalamus, nucleus accumbens, hippocampus, amygdala, and five equal regions of the corpus callosum. We found that performance on measures of each aptitude was predicted by different subcortical structures: Math – higher right nucleus accumbens volume; Vocabulary – higher left hippocampus volume; Paper Folding – higher right thalamus volume; Foresight – lower right thalamus and higher mid anterior corpus callosum volume; Inductive Reasoning – higher mid anterior corpus callosum volume. Our results support general findings, within the cognitive neurosciences, showing lateralization of structure-function relationships, as well as more specific relationships between individual structures (e.g., left hippocampus) and functions relevant to particular aptitudes (e.g., Vocabulary). [ABSTRACT FROM AUTHOR]

Background: We sought to analyze the growing worldwide trends of intracranial aneurysm research, investigate China's recent contribution, and compare the contributions of mainland China, Taiwan, and Hong Kong. Methods: Global and China intracranial aneurysm-related publications were retrieved from the Web of Science database from 1991 to 2012. Excel 2007, Matlab, and Thomson Data Analyzer (TDA) software were used to analyze the search results for number of publications, cited frequency, h-index, and organization contributions. Results: 16468 global papers were identified that were cited 273500 times until 2013-08-15. The United States accounted for 31.497% of the articles, 58.64% of the citations, and the highest h-index (127). Japan and Germany followed in frequency. China's articles ranked eighth (third in 2012) in total number, with most of the contributions occurring since 2002 (91.33%). China was at the early stage of the logic growth curve (exponential growth), with the citation frequency and h-index per year increasing. The quality of the publications was low. The main research centers were located in Beijing, Shanghai, Taiwan, and Hong Kong. The main Asian funding body was the National Natural Science Foundation of China. The number of publications and frequency of citations of papers from mainland China was greater than that of Taiwan or Hong Kong. Conclusion: Global intracranial aneurysm research has been developing swiftly since 1991, with the United States making the largest contribution. Research in China started later, in 2002. Since then, China has increased its rate of publication, and became the third largest contributor by 2012. [ABSTRACT FROM AUTHOR]

Knowledge of how a population of cancerous cells progress through the cell cycle is vital if the population is to be treated effectively, as treatment outcome is dependent on the phase distributions of the population. Estimates on the phase distribution may be obtained experimentally however the errors present in these estimates may effect treatment efficacy and planning. If mathematical models are to be used to make accurate, quantitative predictions concerning treatments, whose efficacy is phase dependent, knowledge of the phase distribution is crucial. In this paper it is shown that two different transition rates at the - checkpoint provide a good fit to a growth curve obtained experimentally. However, the different transition functions predict a different phase distribution for the population, but both lying within the bounds of experimental error. Since treatment outcome is effected by the phase distribution of the population this difference may be critical in treatment planning. Using an age-structured population balance approach the cell cycle is modelled with particular emphasis on the - checkpoint. By considering the probability of cells transitioning at the - checkpoint, different transition functions are obtained. A suitable finite difference scheme for the numerical simulation of the model is derived and shown to be stable. The model is then fitted using the different probability transition functions to experimental data and the effects of the different probability transition functions on the model's results are discussed. [ABSTRACT FROM AUTHOR]

Background: More than two-thirds of the world's HIV-positive individuals live in sub-Saharan Africa, where genetic susceptibility to kidney disease is high and resources for kidney disease screening and antiretroviral therapy (ART) toxicity monitoring are limited. Equations to estimate glomerular filtration rate (GFR) from serum creatinine were derived in Western populations and may be less accurate in this population. Methods: We compared results from published GFR estimating equations with a direct measure of GFR by iohexol clearance in 99 HIV-infected, ART-naïve Kenyan adults. Iohexol concentration was measured from dried blood spots on filter paper. The bias ratio (mean of the ratio of estimated to measured GFR) and accuracy (percentage of estimates within 30% of the measured GFR) were calculated. Results: The median age was 35 years, and 60% were women. The majority had asymptomatic HIV, with median CD4+ cell count of 355 cells/mm3. Median measured GFR was 115 mL/min/1.73 m2. Overall accuracy was highest for the Chronic Kidney Disease Epidemiology Consortium (CKD-EPI) equation. Consistent with a prior report, bias and accuracy were improved by eliminating the coefficient for black race (85% of estimates within 30% of measured GFR). Accuracy of all equations was poor in participants with GFR 60–90 mL/min/1.73 m2 (<65% of estimates within 30% of measured GFR), although this subgroup was too small to reach definitive conclusions. Conclusions: Overall accuracy was highest for the CKD-EPI equation. Eliminating the coefficient for race further improved performance. Future studies are needed to determine the most accurate GFR estimate for use in individuals with GFR <90 mL/min/1.73 m2, in whom accurate estimation of kidney function is important to guide drug dosing. Direct measurement of GFR by iohexol clearance using a filter paper based assay is feasible for research purposes in resource-limited settings, and could be used to develop more accurate GFR estimates in African populations. [ABSTRACT FROM AUTHOR]

Flux balance analysis and constraint based modeling have been successfully used in the past to elucidate the metabolism of single cellular organisms. However, limited work has been done with multicellular organisms and even less with humans. The focus of this paper is to present a novel use of this technique by investigating human nutrition, a challenging field of study. Specifically, we present a steady state constraint based model of skeletal muscle tissue to investigate amino acid supplementation's effect on protein synthesis. We implement several in silico supplementation strategies to study whether amino acid supplementation might be beneficial for increasing muscle contractile protein synthesis. Concurrent with published data on amino acid supplementation's effect on protein synthesis in a post resistance exercise state, our results suggest that increasing bioavailability of methionine, arginine, and the branched-chain amino acids can increase the flux of contractile protein synthesis. The study also suggests that a common commercial supplement, glutamine, is not an effective supplement in the context of increasing protein synthesis and thus, muscle mass. Similar to any study in a model organism, the computational modeling of this research has some limitations. Thus, this paper introduces the prospect of using systems biology as a framework to formally investigate how supplementation and nutrition can affect human metabolism and physiology. [ABSTRACT FROM AUTHOR]

Information theory is a powerful tool to express principles to drive autonomous systems because it is domain invariant and allows for an intuitive interpretation. This paper studies the use of the predictive information (PI), also called excess entropy or effective measure complexity, of the sensorimotor process as a driving force to generate behavior. We study nonlinear and nonstationary systems and introduce the time-local predicting information (TiPI) which allows us to derive exact results together with explicit update rules for the parameters of the controller in the dynamical systems framework. In this way the information principle, formulated at the level of behavior, is translated to the dynamics of the synapses. We underpin our results with a number of case studies with high-dimensional robotic systems. We show the spontaneous cooperativity in a complex physical system with decentralized control. Moreover, a jointly controlled humanoid robot develops a high behavioral variety depending on its physics and the environment it is dynamically embedded into. The behavior can be decomposed into a succession of low-dimensional modes that increasingly explore the behavior space. This is a promising way to avoid the curse of dimensionality which hinders learning systems to scale well. [ABSTRACT FROM AUTHOR]

Heterotrimeric G-proteins modulate many processes essential for embryonic development including cellular proliferation, migration, differentiation, and survival. Although most research has focused on identifying the roles of the various αsubtypes, there is growing recognition that similarly divergent βγ dimers also regulate these processes. In this paper, we show that targeted disruption of the mouse Gng5 gene encoding the γ5 subtype produces embryonic lethality associated with severe head and heart defects. Collectively, these results add to a growing body of data that identify critical roles for the γ subunits in directing the assembly of functionally distinct G-αβγ trimers that are responsible for regulating diverse biological processes. Specifically, the finding that loss of the G-γ5 subtype is associated with a reduced number of cardiac precursor cells not only provides a causal basis for the mouse phenotype but also raises the possibility that G-βγ5 dependent signaling contributes to the pathogenesis of human congenital heart problems. [ABSTRACT FROM AUTHOR]

During the last decade markerless motion capture techniques have gained an increasing interest in the biomechanics community. In the clinical field, however, the application of markerless techniques is still debated. This is mainly due to a limited number of papers dedicated to the comparison with the state of the art of marker based motion capture, in term of repeatability of the three dimensional joints' kinematics. In the present work the application of markerless technique to data acquired with a marker-based system was investigated. All videos and external data were recorded with the same motion capture system and included the possibility to use markerless and marker-based methods simultaneously. Three dimensional markerless joint kinematics was estimated and compared with the one determined with traditional marker based systems, through the evaluation of root mean square distance between joint rotations. In order to compare the performance of markerless and marker-based systems in terms of clinically relevant joint angles estimation, the same anatomical frames of reference were defined for both systems. Differences in calibration and synchronization of the cameras were excluded by applying the same wand calibration and lens distortion correction to both techniques. Best results were achieved for knee flexion-extension angle, with an average root mean square distance of 11.75 deg, corresponding to 18.35% of the range of motion. Sagittal plane kinematics was estimated better than on the other planes also for hip and ankle (root mean square distance of 17.62 deg e.g. 44.66%, and 7.17 deg e.g. 33.12%), meanwhile estimates for hip joint were the most incorrect. This technique enables users of markerless technology to compare differences with marker-based in order to define the degree of applicability of markerless technique. [ABSTRACT FROM AUTHOR]

This paper describes the design and implementation of a wireless neural telemetry system that enables new experimental paradigms, such as neural recordings during rodent navigation in large outdoor environments. RoSco, short for Rodent Scope, is a small lightweight user-configurable module suitable for digital wireless recording from freely behaving small animals. Due to the digital transmission technology, RoSco has advantages over most other wireless modules of noise immunity and online user-configurable settings. RoSco digitally transmits entire neural waveforms for 14 of 16 channels at 20 kHz with 8-bit encoding which are streamed to the PC as standard USB audio packets. Up to 31 RoSco wireless modules can coexist in the same environment on non-overlapping independent channels. The design has spatial diversity reception via two antennas, which makes wireless communication resilient to fading and obstacles. In comparison with most existing wireless systems, this system has online user-selectable independent gain control of each channel in 8 factors from 500 to 32,000 times, two selectable ground references from a subset of channels, selectable channel grounding to disable noisy electrodes, and selectable bandwidth suitable for action potentials (300 Hz–3 kHz) and low frequency field potentials (4 Hz–3 kHz). Indoor and outdoor recordings taken from freely behaving rodents are shown to be comparable to a commercial wired system in sorting for neural populations. The module has low input referred noise, battery life of 1.5 hours and transmission losses of 0.1% up to a range of 10 m. [ABSTRACT FROM AUTHOR]

Leishmaniasis remains one of the world's most devastating neglected tropical diseases. It mainly affects developing countries, where it often co-exists with chronic malnutrition, one of the main risk factors for developing the disease. Few studies have been published, however, on the relationship between leishmaniasis progression and malnutrition. The present paper reports the influence of protein malnutrition on the immune response and visceral disease development in adult hamsters infected with Leishmania infantum fed either standard or low protein diets. The low protein diet induced severe malnutrition in these animals, and upon infection with L. infantum 33% had severe visceral leishmaniasis compared to only 8% of animals fed the standard diet. The infected, malnourished animals showed notable leukocyte depletion, mild specific antibody responses, impairment of lymphoproliferation, presence of parasites in blood (16.67% of the hamsters) and significant increase of the splenic parasite burden. Animals fed standard diet suffered agranulocytosis and monocytopenia, but showed stronger specific immune responses and had lower parasite loads than their malnourished counterparts. The present results show that protein malnutrition promotes visceral leishmaniasis and provide clues regarding the mechanisms underlying the impairment of the immune system. [ABSTRACT FROM AUTHOR]

Open vascular reconstructions frequently fail due to the development of recurrent disease or intimal hyperplasia (IH). This paper reports a novel drug delivery method using a rapamycin-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs)/pluronic gel system that can be applied periadventitially around the carotid artery immediately following the open surgery. In vitro studies revealed that rapamycin dispersed in pluronic gel was rapidly released over 3 days whereas release of rapamycin from rapamycin-loaded PLGA NPs embedded in pluronic gel was more gradual over 4 weeks. In cultured rat vascular smooth muscle cells (SMCs), rapamycin-loaded NPs produced durable (14 days versus 3 days for free rapamycin) inhibition of phosphorylation of S6 kinase (S6K1), a downstream target in the mTOR pathway. In a rat balloon injury model, periadventitial delivery of rapamycin-loaded NPs produced inhibition of phospho-S6K1 14 days after balloon injury. Immunostaining revealed that rapamycin-loaded NPs reduced SMC proliferation at both 14 and 28 days whereas rapamycin alone suppressed proliferation at day 14 only. Moreover, rapamycin-loaded NPs sustainably suppressed IH for at least 28 days following treatment, whereas rapamycin alone produced suppression on day 14 with rebound of IH by day 28. Since rapamycin, PLGA, and pluronic gel have all been approved by the FDA for other human therapies, this drug delivery method could potentially be translated into human use quickly to prevent failure of open vascular reconstructions. [ABSTRACT FROM AUTHOR]

Previous studies have suggested that murine peritoneal cavity-derived B-1a cells possess similarities with described regulatory B cell subsets. The aim of the current study was to examine the potential immunoregulatory function of peritoneal cavity-derived B(-1a) cells. In vitro activation of peritoneal cavity-derived B- and B-1a cells shows that activation of these B cells with anti-CD40 and LPS induces these cells to secrete more IL-10, IL-6 and IgM as compared to splenic B cells. In a suppression assay, CD40/TLR4-activated peritoneal cavity B cells possess regulatory B cell functions as they inhibit the capacity of CD4+ T cells to produce both tumor necrosis factor-α and interferon-γ. Splenic B cells did not show this, whereas non-activated peritoneal cavity B cells augmented the capacity of CD4+ T cells to produce tumor necrosis factor-α, while the ability to produce interferon-γ was not altered. The current paper compares splenic B cells to peritoneal cavity B(-1a) cells in an in vitro activation- and an suppression-assay and concludes that peritoneal cavity B(-1a) cells possess properties that appear similar to splenic autoimmune-suppressive regulatory B cell subsets described in the literature. [ABSTRACT FROM AUTHOR]

This paper examines the role of inhibition in generating the receptive-field properties of local edge detector (LED) ganglion cells in the rabbit retina. We confirm that the feed-forward inhibition is largely glycinergic but, contrary to a recent report, our data demonstrate that the glycinergic inhibition contributes to temporal tuning for the OFF and ON inputs to the LEDs by delaying the onset of spiking; this delay was more pronounced for the ON inputs (∼340 ms) than the OFF inputs (∼12 ms). Blocking glycinergic transmission reduced the delay to spike onset and increased the responses to flickering stimuli at high frequencies. Analysis of the synaptic conductances indicates that glycinergic amacrine cells affect temporal tuning through both postsynaptic inhibition of the LEDs and presynaptic modulation of the bipolar cells that drive the LEDs. The results also confirm that presynaptic GABAergic transmission contributes significantly to the concentric surround antagonism in LEDs; however, unlike presumed LEDs in the mouse retina, the surround is only partly generated by spiking amacrine cells. [ABSTRACT FROM AUTHOR]

The delivery of drugs to specific neural targets faces two fundamental problems: (1) most drugs do not cross the blood-brain barrier, and (2) those that do, spread to the entire brain. To date, there exists only one non-invasive methodology with the potential to solve these problems: selective blood-brain barrier (BBB) opening using micro-bubble enhanced focused ultrasound. We have recently developed a single-element 500-kHz spherical transducer ultrasound setup for targeted BBB opening in the non-human primate that does not require simultaneous MRI monitoring. So far, however, the targeting accuracy that can be achieved with this system has not been quantified systematically. In this paper, the accuracy of this system was tested by targeting caudate nucleus and putamen of the basal ganglia in two macaque monkeys. The average lateral targeting error of the system was ∼2.5 mm while the axial targeting error, i.e., along the ultrasound path, was ∼1.5 mm. We have also developed a real-time treatment monitoring technique based on cavitation spectral analysis. This technique also allowed for delineation of a safe and reliable acoustic parameter window for BBB opening. In summary, the targeting accuracy of the system was deemed to be suitable to reliably open the BBB in specific sub-structures of the basal ganglia even in the absence of MRI-based verification of opening volume and position. This establishes the method and the system as a potentially highly useful tool for brain drug delivery. [ABSTRACT FROM AUTHOR]

Osteosarcoma is the most common primary malignant tumor of bone usually occurring in young adolescent and children. This disease has a poor prognosis, because of the metastases in the period of tumor progression, which are usually developed previous to the clinical diagnosis. In this paper, a 2000-year-old ancient bone remain with osteogenic sarcoma was analyzed searching for tumor biomarkers which are closely related to this disease. After a specific extraction SDS-PAGE gel electrophoresis followed by tryptic digestion was performed. After the digestion the samples were measured using MALDI TOF/TOF MS. Healthy bone samples from same archaeological site were used as control samples. Our results show that in the pathological skeletal remain several well known tumor biomarkers are detected such as annexin A10, BCL-2-like protein, calgizzarin, rho GTPase-activating protein 7, HSP beta-6 protein, transferrin and vimentin compared to the control samples. The identified protein biomarkers can be useful in the discovery of malignant bone lesions such as osteosarcoma in the very early stage of the disease from paleoanthropological remains. [ABSTRACT FROM AUTHOR]

It is known that gamma activity is generated by local networks. In this paper we introduced a new approach for estimation of functional connectivity between neuronal networks by measuring temporal relations between peaks of gamma event amplitudes. We have shown in freely moving rats that gamma events recorded between electrodes 1.5 mm apart in the majority of cases, are generated by different neuronal modules interfering with each other. The map of functional connectivity between brain areas during the resting state, created based on gamma event temporal relationships is in agreement with anatomical connections and with maps described by fMRI methods during the resting state. The transition from the resting state to exploratory activity is accompanied by decreased functional connectivity between most brain areas. Our data suggest that functional connectivity between interhemispheric areas depends on GABAergic transmission, while intrahemispheric functional connectivity is kainate receptor dependent. This approach presents opportunities for merging electrographic and fMRI data on brain functional connectivity in normal and pathological conditions. [ABSTRACT FROM AUTHOR]

Background: In developing countries hip osteoarthritis constitutes a major public health issue as it is highly prevalent in all age ranges of population, including the young. It often remains untreated because of the low accessibility of total hip prostheses. Hip arthrodesis still represents a major treatment option, but, for several reasons which are discussed in this paper, is nowadays infrequently performed. By means of reporting the results of a new simple technique, using a self-devised plate, the relevancy of hip arthrodesis in this particular environment is emphasized. Methods and Findings: Our series included 35 patients with painful hip osteoarthritis who underwent a hip fusion with the anterolateral arthrodesis plate. Two of them had a concurrent femoral osteotomy for correction of a vicious position of the limb and another patient had a femoral diaphysis osteotomy and placement of a Wagner elongating device in order to proceed with a limb lengthening by callotasis. The follow-up period averaged 16,9 months (9 to 34). All hips, except two, achieved solid fusion between 6 and 15 months after surgery. One failure of fusion was in the oldest patient, who presented a loosening of plate and screws due to an advanced degree of osteoporosis; the other was in a young patient who admitted having walked on his leg too soon. Patient satisfaction was high. We concluded that this technique is reliable and effective. Conclusions: The results of this study should convince the hesitant surgeon and patient to consider hip arthrodesis an acceptable treatment option for disabling hip arthritis, compared to no treatment at all. [ABSTRACT FROM AUTHOR]

Purpose: This paper describes a novel method to automatically segment the human brainstem into midbrain and pons, called LABS: Landmark-based Automated Brainstem Segmentation. LABS processes high-resolution structural magnetic resonance images (MRIs) according to a revised landmark-based approach integrated with a thresholding method, without manual interaction. Methods: This method was first tested on morphological T1-weighted MRIs of 30 healthy subjects. Its reliability was further confirmed by including neurological patients (with Alzheimer's Disease) from the ADNI repository, in whom the presence of volumetric loss within the brainstem had been previously described. Segmentation accuracies were evaluated against expert-drawn manual delineation. To evaluate the quality of LABS segmentation we used volumetric, spatial overlap and distance-based metrics. Results: The comparison between the quantitative measurements provided by LABS against manual segmentations revealed excellent results in healthy controls when considering either the midbrain (DICE measures higher that 0.9; Volume ratio around 1 and Hausdorff distance around 3) or the pons (DICE measures around 0.93; Volume ratio ranging 1.024–1.05 and Hausdorff distance around 2). Similar performances were detected for AD patients considering segmentation of the pons (DICE measures higher that 0.93; Volume ratio ranging from 0.97–0.98 and Hausdorff distance ranging 1.07–1.33), while LABS performed lower for the midbrain (DICE measures ranging 0.86–0.88; Volume ratio around 0.95 and Hausdorff distance ranging 1.71–2.15). Conclusions: Our study represents the first attempt to validate a new fully automated method for in vivo segmentation of two anatomically complex brainstem subregions. We retain that our method might represent a useful tool for future applications in clinical practice. [ABSTRACT FROM AUTHOR]

Women experiencing greater childhood adversity exhibit faster reproductive trajectories. One possible psychological mechanism underlying this phenomenon is an increased interest in infants. Interest in infants is thought to be an adaptation important for successful rearing as it motivates the acquisition of caretaking skills. We investigated the relationships between childhood adversity, intended reproductive timing and interest in infants in a sample of English adolescent girls. Specifically we sought to investigate the relationship between 1) childhood adversity and intended reproductive timing; 2) childhood adversity and interest in infants; and 3) intended reproductive timing and interest in infants. Additionally we explored different methods of measuring interest in infants using self-reported fondness for babies, a forced choice adult versus infant paper-based preference task and a novel computer based attention task using adult and infant stimuli. In total 357 girls aged nine to 14 years participated in the study, which took place in schools. Participants completed the two interest in infants tasks before moving on to a childhood adversity questionnaire. Girls with more childhood adversity reported earlier ideal ages at parenthood. We found some evidence that, contrary to our predictions, girls with less childhood adversity were more interested in infants. There was no relationship between intended reproductive timing and interest in infants. The different measurements for interest in infants were only weakly related, if at all, highlighting the complexity of measuring this construct. Our findings suggest that rather than interest in infants being a mechanism for the effect of childhood adversity on early reproductive timing it might instead be an indicator of future reproductive strategies. [ABSTRACT FROM AUTHOR]

Cortical spreading depression (CSD) is a pathophysiological phenomenon, which underlies some neurological disorders, such as migraine and stroke, but its mechanisms are still not completely understood. One of the striking facts is that the spatiotemporal evolution of CSD wave is varying. Observations in experiments reveal that a CSD wave may propagate through the entire cortex, or just bypass some areas of the cortex. In this paper, we have applied a 2D reaction-diffusion equation with recovery term to study the spatiotemporal evolution of CSD. By modulating the recovery rate from CSD in the modeled cortex, CSD waves with different spatiotemporal evolutions, either bypassing some areas or propagating slowly in these areas, were present. Moreover, spiral CSD waves could also be induced in case of the transiently altered recovery rate, i.e. block release from the absolute refractory period. These results suggest that the refractory period contributes to the different propagation patterns of CSD, which may help to interpret the mechanisms of CSD propagation. [ABSTRACT FROM AUTHOR]

Sudden cardiac death is often caused by cardiac arrhythmias. Recently, special attention has been given to a certain arrhythmogenic condition, the long-QT syndrome, which occurs as a result of genetic mutations or drug toxicity. The underlying mechanisms of arrhythmias, caused by the long-QT syndrome, are not fully understood. However, arrhythmias are often connected to special excitations of cardiac cells, called early afterdepolarizations (EADs), which are depolarizations during the repolarizing phase of the action potential. So far, EADs have been studied mainly in isolated cardiac cells. However, the question on how EADs at the single-cell level can result in fibrillation at the tissue level, especially in human cell models, has not been widely studied yet. In this paper, we study wave patterns that result from single-cell EAD dynamics in a mathematical model for human ventricular cardiac tissue. We induce EADs by modeling experimental conditions which have been shown to evoke EADs at a single-cell level: by an increase of L-type Ca currents and a decrease of the delayed rectifier potassium currents. We show that, at the tissue level and depending on these parameters, three types of abnormal wave patterns emerge. We classify them into two types of spiral fibrillation and one type of oscillatory dynamics. Moreover, we find that the emergent wave patterns can be driven by calcium or sodium currents and we find phase waves in the oscillatory excitation regime. From our simulations we predict that arrhythmias caused by EADs can occur during normal wave propagation and do not require tissue heterogeneities. Experimental verification of our results is possible for experiments at the cell-culture level, where EADs can be induced by an increase of the L-type calcium conductance and by the application of I blockers, and the properties of the emergent patterns can be studied by optical mapping of the voltage and calcium. [ABSTRACT FROM AUTHOR]

Accurate and robust brain extraction is a critical step in most neuroimaging analysis pipelines. In particular, for the large-scale multi-site neuroimaging studies involving a significant number of subjects with diverse age and diagnostic groups, accurate and robust extraction of the brain automatically and consistently is highly desirable. In this paper, we introduce population-specific probability maps to guide the brain extraction of diverse subject groups, including both healthy and diseased adult human populations, both developing and aging human populations, as well as non-human primates. Specifically, the proposed method combines an atlas-based approach, for coarse skull-stripping, with a deformable-surface-based approach that is guided by local intensity information and population-specific prior information learned from a set of real brain images for more localized refinement. Comprehensive quantitative evaluations were performed on the diverse large-scale populations of ADNI dataset with over 800 subjects (55∼90 years of age, multi-site, various diagnosis groups), OASIS dataset with over 400 subjects (18∼96 years of age, wide age range, various diagnosis groups), and NIH pediatrics dataset with 150 subjects (5∼18 years of age, multi-site, wide age range as a complementary age group to the adult dataset). The results demonstrate that our method consistently yields the best overall results across almost the entire human life span, with only a single set of parameters. To demonstrate its capability to work on non-human primates, the proposed method is further evaluated using a rhesus macaque dataset with 20 subjects. Quantitative comparisons with popularly used state-of-the-art methods, including BET, Two-pass BET, BET-B, BSE, HWA, ROBEX and AFNI, demonstrate that the proposed method performs favorably with superior performance on all testing datasets, indicating its robustness and effectiveness. [ABSTRACT FROM AUTHOR]

In sensory neural system, external asynchronous stimuli play an important role in perceptual learning, associative memory and map development. However, the organization of structure and dynamics of neural networks induced by external asynchronous stimuli are not well understood. Spike-timing-dependent plasticity (STDP) is a typical synaptic plasticity that has been extensively found in the sensory systems and that has received much theoretical attention. This synaptic plasticity is highly sensitive to correlations between pre- and postsynaptic firings. Thus, STDP is expected to play an important role in response to external asynchronous stimuli, which can induce segregative pre- and postsynaptic firings. In this paper, we study the impact of external asynchronous stimuli on the organization of structure and dynamics of neural networks through STDP. We construct a two-dimensional spatial neural network model with local connectivity and sparseness, and use external currents to stimulate alternately on different spatial layers. The adopted external currents imposed alternately on spatial layers can be here regarded as external asynchronous stimuli. Through extensive numerical simulations, we focus on the effects of stimulus number and inter-stimulus timing on synaptic connecting weights and the property of propagation dynamics in the resulting network structure. Interestingly, the resulting feedforward structure induced by stimulus-dependent asynchronous firings and its propagation dynamics reflect both the underlying property of STDP. The results imply a possible important role of STDP in generating feedforward structure and collective propagation activity required for experience-dependent map plasticity in developing in vivo sensory pathways and cortices. The relevance of the results to cue-triggered recall of learned temporal sequences, an important cognitive function, is briefly discussed as well. Furthermore, this finding suggests a potential application for examining STDP by measuring neural population activity in a cultured neural network. [ABSTRACT FROM AUTHOR]

Objectives: To extend existing research on the US health disadvantage relative to Europe by studying the relationships of disability with age from midlife to old age in the US and four European regions (England/Northern and Western Europe/Southern Europe/Eastern Europe) including their wealth-related differences, using a flexible statistical approach to model the age-functions. Methods: We used data from three studies on aging, with nationally representative samples of adults aged 50 to 85 from 15 countries (N = 48225): the US-American Health and Retirement Study (HRS), the English Longitudinal Study of Ageing (ELSA) and the Survey of Health, Ageing and Retirement in Europe (SHARE). Outcomes were mobility limitations and limitations in instrumental activities of daily living. We applied fractional polynomials of age to determine best fitting functional forms for age on disability in each region, while controlling for socio-demographic characteristics and important risk factors (hypertension, diabetes, obesity, smoking, physical inactivity). Results: Findings showed high levels of disability in the US with small age-related changes between 50 and 85. Levels of disability were generally lower in Eastern Europe, followed by England and Southern Europe and lowest in Northern and Western Europe. In these latter countries age-related increases of disability, though, were steeper than in the US, especially in Eastern and Southern Europe. For all countries and at all ages, disability levels were higher among adults with low wealth compared to those with high wealth, with largest wealth-related differences among those in early old age in the USA. Conclusions: This paper illustrates considerable variations of disability and its relationship with age. It supports the hypothesis that less developed social policies and more pronounced socioeconomic inequalities are related to higher levels of disability and an earlier onset of disability. [ABSTRACT FROM AUTHOR]

In this paper we introduce a new method to expressly use live/corporeal data in quantifying differences of time series data with an underlying limit cycle attractor; and apply it using an example of gait data. Our intention is to identify gait pattern differences between diverse situations and classify them on group and individual subject levels. First we approximated the limit cycle attractors, from which three measures were calculated: δM amounts to the difference between two attractors (a measure for the differences of two movements), δD computes the difference between the two associated deviations of the state vector away from the attractor (a measure for the change in movement variation), and δF, a combination of the previous two, is an index of the change. As an application we quantified these measures for walking on a treadmill under three different conditions: normal walking, dual task walking, and walking with additional weights at the ankle. The new method was able to successfully differentiate between the three walking conditions. Day to day repeatability, studied with repeated trials approximately one week apart, indicated excellent reliability for δM (ICCave > 0.73 with no differences across days; p > 0.05) and good reliability for δD (ICCave  =  0.414 to 0.610 with no differences across days; p > 0.05). Based on the ability to detect differences in varying gait conditions and the good repeatability of the measures across days, the new method is recommended as an alternative to expensive and time consuming techniques of gait classification assessment. In particular, the new method is an easy to use diagnostic tool to quantify clinical changes in neurological patients. [ABSTRACT FROM AUTHOR]

In this paper, we describe the effects of the combination of topographical, mechanical, chemical and intracellular electrical stimuli on a co-culture of fibroblasts and skeletal muscle cells. The co-culture was anisotropically grown onto an engineered micro-grooved (10 µm-wide grooves) polyacrylamide substrate, showing a precisely tuned Young’s modulus (∼ 14 kPa) and a small thickness (∼ 12 µm). We enhanced the co-culture properties through intracellular stimulation produced by piezoelectric nanostructures (i.e., boron nitride nanotubes) activated by ultrasounds, thus exploiting the ability of boron nitride nanotubes to convert outer mechanical waves (such as ultrasounds) in intracellular electrical stimuli, by exploiting the direct piezoelectric effect. We demonstrated that nanotubes were internalized by muscle cells and localized in both early and late endosomes, while they were not internalized by the underneath fibroblast layer. Muscle cell differentiation benefited from the synergic combination of topographical, mechanical, chemical and nanoparticle-based stimuli, showing good myotube development and alignment towards a preferential direction, as well as high expression of genes encoding key proteins for muscle contraction (i.e., actin and myosin). We also clarified the possible role of fibroblasts in this process, highlighting their response to the above mentioned physical stimuli in terms of gene expression and cytokine production. Finally, calcium imaging-based experiments demonstrated a higher functionality of the stimulated co-cultures. [ABSTRACT FROM AUTHOR]

The 5-lipoxygenase (5LO) enzyme is widely distributed within the central nervous system. Previous works showed that this protein is up-regulated in Alzheimer’s disease (AD), and plays an active role in the development of brain amyloidosis in the APP transgenic mice. In the present paper, we studied the effect of its pharmacological inhibition on the entire AD-like phenotype of a mouse model with plaques and tangles, the 3×Tg mice. Compared with mice receiving placebo, the group treated with zileuton, a specific 5LO inhibitor, manifested a significant improvement of their memory impairments. The same animals had a significant reduction in Aβ levels and deposition, which was secondary to a down-regulation of the γ-secretase pathway. Additionally, while total tau levels were unchanged for both groups, zileuton-treated mice had a significant reduction in its phosphorylation state and insoluble forms, secondary to a decreased activation of the cdk5 kinase. These data establish a functional role for 5LO in the pathogenesis of the full spectrum of the AD-like phenotype and represent the successful completion of the initial step for the preclinical development of 5LO inhibitors as viable therapeutic agents for AD. [ABSTRACT FROM AUTHOR]

Background: Swallowing dysfunction (also known as dysphagia), which results in a deterioration of nutritional intake, slows rehabilitation and causes aspiration pneumonia, is very common following neurological impairments. Although videofluorographic (VF) examination is widely used for detecting aspiration, an objective and non-invasive method for assessing swallowing function has yet to be established because of a lack of adequate devices and protocols. In this paper, a bend sensor whose resistance is altered by bending was introduced to monitor swallowing-related laryngeal movement. Methods: Six healthy male volunteers were recruited in the present study. Specific time points on the signal waveform produced by the bend sensor were defined to describe laryngeal movement by differential analysis. Additionally, the physiological significance of the obtained waveform was confirmed by analyzing the sequential correlations between the signal waveform from the bend sensor and hyoid bone kinetics simultaneously recorded by VF. Results: Seven time points were successfully defined on the signal waveform to reference laryngeal movement. Each time point was well correlated with certain VF events, with evidence of no significant time lags, and there were positive correlations between waveform time points and matched VF events. Furthermore, obvious similarities were noticed between the duration of each phase on the signal waveform and the duration of the matched hyoid bone activity. Conclusions: The present monitoring system using a bend sensor might be useful for observing the temporal aspects of laryngeal movement during swallowing, and it was well coordinated with hyoid bone movement. [ABSTRACT FROM AUTHOR]

The oxytocin (Oxt) and vasopressin (Avp) magnocellular neurons (MCNs) in the hypothalamus are the only neuronal phenotypes that are present in the supraoptic nucleus (SON), and are characterized by their robust and selective expression of either the Oxt or Avp genes. In this paper, we take advantage of the differential expression of these neuropeptide genes to identify and isolate these two individual phenotypes from the rat SON by laser capture microdissection (LCM), and to analyze the differential expression of several of their transcription factor mRNAs by qRT-PCR. We identify these neuronal phenotypes by stereotaxically injecting recombinant Adeno-Associated Viral (rAAV) vectors which contain cell-type specific Oxt or Avp promoters that drive expression of EGFP selectively in either the Oxt or Avp MCNs into the SON. The fluorescent MCNs are then dissected by LCM using a novel Cap Road Map protocol described in this paper, and the purified MCNs are extracted for their RNAs. qRT-PCR of these RNAs show that some transcription factors (RORA and c-jun) are differentially expressed in the Oxt and Avp MCNs. [ABSTRACT FROM AUTHOR]

We analyzed the spike discharge patterns of two types of neurons in the rodent peripheral gustatory system, Na specialists (NS) and acid generalists (AG) to lingual stimulation with NaCl, acetic acid, and mixtures of the two stimuli. Previous computational investigations found that both spike rate and spike timing contribute to taste quality coding. These studies used commonly accepted computational methods, but they do not provide a consistent statistical evaluation of spike trains. In this paper, we adopted a new computational framework that treated each spike train as an individual data point for computing summary statistics such as mean and variance in the spike train space. We found that these statistical summaries properly characterized the firing patterns (e. g. template and variability) and quantified the differences between NS and AG neurons. The same framework was also used to assess the discrimination performance of NS and AG neurons and to remove spontaneous background activity or “noise” from the spike train responses. The results indicated that the new metric system provided the desired decoding performance and noise-removal improved stimulus classification accuracy, especially of neurons with high spontaneous rates. In summary, this new method naturally conducts statistical analysis and neural decoding under one consistent framework, and the results demonstrated that individual peripheral-gustatory neurons generate a unique and reliable firing pattern during sensory stimulation and that this pattern can be reliably decoded. [ABSTRACT FROM AUTHOR]

Biological fluids fulfill key functionalities such as hydrating, protecting, and nourishing cells and tissues in various organ systems. They are capable of these versatile tasks owing to their distinct structural and viscoelastic properties. Characterizing the viscoelastic properties of bio-fluids is of pivotal importance for monitoring the development of certain pathologies as well as engineering synthetic replacements. Laser Speckle Rheology (LSR) is a novel optical technology that enables mechanical evaluation of tissue. In LSR, a coherent laser beam illuminates the tissue and temporal speckle intensity fluctuations are analyzed to evaluate mechanical properties. The rate of temporal speckle fluctuations is, however, influenced by both optical and mechanical properties of tissue. Therefore, in this paper, we develop and validate an approach to estimate and compensate for the contributions of light scattering to speckle dynamics and demonstrate the capability of LSR for the accurate extraction of viscoelastic moduli in phantom samples and biological fluids of varying optical and mechanical properties. [ABSTRACT FROM AUTHOR]

The expression of HDAC2 is reported as reduced in chronic obstructive pulmonary disease (COPD). We assessed HDAC2 expression within the airways of smokers and subjects with COPD and effects of inhaled corticosteroids (ICS), using immuno-histology to contrast with previous molecular methodology. Endobronchial biopsies (ebb) from current smokers with COPD (COPD-CS; n = 15), ex-smokers with COPD (COPD-ES; n = 17), smokers with normal lung function (NS; n = 16) and normal controls (NC; n = 9) were immunostained for HDAC2. A double-blinded, randomized, placebo-controlled 6 months intervention study assessed effects of ICS on HDAC2 in 34 COPD subjects. There was no difference in epithelial HDAC2 staining in all groups. There was a significant reduction in total cell numbers in the lamina propria (LP) in COPD-CS and NS (p<0.05). LP cellularity correlated inversely with smoking history in COPD-CS (R = −0.8, p<0.003). HDAC2 expression increased markedly in NS (p<0.001); in contrast COPD-CS was associated with suppressed signal (p<0.03), while normal in COPD-ES. ICS did not affect HDAC2 cell staining. Our findings suggest that airway HDAC2 expression is increased in the LP by smoking itself, but is reduced in COPD. Ex-smokers have normalised HDAC2 cell expression, but ICS had no effect. The paper emphasise the pit-falls of relying on molecular data alone to define airway changes. Clinical Trial Registration Information: Name of registry: The Australian New Zealand Clinical Trials Registry (ANZCTR) Registry number: ACTRN12612001111864 [ABSTRACT FROM AUTHOR]

A loss of sperm viability and functionality during sperm transfer and storage within the female reproductive tract can have important fitness implications by disrupting fertilization and impairing offspring development and survival. Consequently, mechanisms that mitigate the temporal decline in sperm function are likely to be important targets of selection. In many species, ovarian fluid is known to regulate and maintain sperm quality. In this paper, we use the guppy Poecilia reticulata, a highly polyandrous freshwater fish exhibiting internal fertilization and sperm storage, to determine whether ovarian fluid (OF) influences the decline in sperm viability (the proportion of live sperm in the ejaculate) over time and whether any observed effects depend on male sexual ornamentation. To address these questions we used a paired experimental design in which ejaculates from individual males were tested in vitro both in presence and absence of OF. Our results revealed that the temporal decline in sperm viability was significantly reduced in the presence of OF compared to a saline control. This finding raises the intriguing possibility that OF may play a role in mediating the decline in sperm quality due to the deleterious effects of sperm ageing, although other possible explanations for this observation are discussed. Interestingly, we also show that the age-related decline in sperm viability was contingent on male sexual ornamentation; males with relatively high levels of iridescence (indicating higher sexual attractiveness) exhibited a more pronounced decline in sperm viability over time than their less ornamented counterparts. This latter finding offers possible insights into the functional basis for the previously observed trade-off between these key components of pre- and postcopulatory sexual selection. [ABSTRACT FROM AUTHOR]

Background: It has been confirmed that tumor necrosis factor-alpha (TNFα), a macrophage-derived pro-inflammatory cytokine, plays an important role in the pathogenesis of psoriasis vulgaris and psoriatic arthritis (PsV&PsA). In contrast, the reported association of TNFα gene promoter region single nucleotide polymorphisms (SNPs) and PsV&PsA has remained controversial. Accordingly, we performed a meta-analysis to provide new evidence that SNPs in the TNFα gene promoter region alter not only the risk of psoriasis vulgaris (PsV) or psoriatic arthritis (PsA) but also of PsV&PsA. Methods: Interrelated literature dated to October 2012 was acquired from the PubMed, ScienceDirect, and SpringerLink databases. The number of the genotypes and/or alleles for the TNFα promoter in the PsV and PsA and control subjects was obtained. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to calculate the risk of PsV and/or PsA with TNFα promoter SNPs. Results: A total of 26 papers of 2159 for PsV (2129 normal controls) and 2360 for PsA (2997 normal controls) were included in our meta-analysis. The results showed that the variant genotype and allele of TNFα -308A/G was protective in pooled groups of patients with PsV&PsA (OR = 0.682, 0.750; 95% CI, 0.596-0.779, 0.653-0.861). However, the variant genotypes and alleles of TNFα -238A/G and -857T/C had an increased risk of PsV&PsA (OR = 2.493, 2.228, 1.536, 1.486, 95% CI, 1.777-3.498, 1.628-3.049, 1.336-1.767, 1.309-1.685). Moreover, the meta-analysis revealed a significant association between TNFα -238A/G and -857T/C polymorphism and PsA susceptibility (OR = 2.242, 2.052, 1.419, 1.465; 95% CI, 1.710-2.941, 1.614-2.610, 1.214-1.658, 1.277-1.681). In contrast, the variant genotypes and alleles of TNFα -308A/G proved to be protective against PsV (OR = 0.574, 0.650, 95% CI, 0.478-0.690, 0.556-0.759), whereas TNFα -238A/G was found to have a risk association (OR = 2.636, 2.223, 95% CI, 1.523-4.561, 1.317-3.751). Conclusions: SNPs in the TNFα gene promoter region alter the risk of PsV and/or PsA. [ABSTRACT FROM AUTHOR]

Brodmann’s 100–year–old summary map has been widely used for cortical localization in neuroscience. There is a pressing need to update this map using non–invasive, high–resolution and reproducible data, in a way that captures individual variability. We demonstrate here that standard HARDI data has sufficiently diverse directional variation among grey matter regions to inform parcellation into distinct functional regions, and that this variation is reproducible across scans. This characterization of the signal variation as non–random and reproducible is the critical condition for successful cortical parcellation using HARDI data. This paper is a first step towards an individual cortex–wide map of grey matter microstructure, The gray/white matter and pial boundaries were identified on the high–resolution structural MRI images. Two HARDI data sets were collected from each individual and aligned with the corresponding structural image. At each vertex point on the surface tessellation, the diffusion–weighted signal was extracted from each image in the HARDI data set at a point, half way between gray/white matter and pial boundaries. We then derived several features of the HARDI profile with respect to the local cortical normal direction, as well as several fully orientationally invariant features. These features were taken as a fingerprint of the underlying grey matter tissue, and used to distinguish separate cortical areas. A support–vector machine classifier, trained on three distinct areas in repeat 1 achieved 80–82% correct classification of the same three areas in the unseen data from repeat 2 in three volunteers. Though gray matter anisotropy has been mostly overlooked hitherto, this approach may eventually form the foundation of a new cortical parcellation method in living humans. Our approach allows for further studies on the consistency of HARDI based parcellation across subjects and comparison with independent microstructural measures such as ex–vivo histology. [ABSTRACT FROM AUTHOR]

A variety of cardiac arrhythmias are initiated by a focal excitation that disrupts the regular beating of the heart. In some cases it is known that these excitations are due to calcium (Ca) release from the sarcoplasmic reticulum (SR) via propagating subcellular Ca waves. However, it is not understood what are the physiological factors that determine the timing of these excitations at both the subcellular and tissue level. In this paper we apply analytic and numerical approaches to determine the timing statistics of spontaneous Ca release (SCR) in a simplified model of a cardiac myocyte. In particular, we compute the mean first passage time (MFPT) to SCR, in the case where SCR is initiated by spontaneous Ca sparks, and demonstrate that this quantity exhibits either an algebraic or exponential dependence on system parameters. Based on this analysis we identify the necessary requirements so that SCR occurs on a time scale comparable to the cardiac cycle. Finally, we study how SCR is synchronized across many cells in cardiac tissue, and identify a quantitative measure that determines the relative timing of SCR in an ensemble of cells. Using this approach we identify the physiological conditions so that cell-to-cell variations in the timing of SCR is small compared to the typical duration of an SCR event. We argue further that under these conditions inward currents due to SCR can summate and generate arrhythmogenic triggered excitations in cardiac tissue. [ABSTRACT FROM AUTHOR]

Recently, a combination of non-invasive neuroimaging techniques and graph theoretical approaches has provided a unique opportunity for understanding the patterns of the structural and functional connectivity of the human brain (referred to as the human brain connectome). Currently, there is a very large amount of brain imaging data that have been collected, and there are very high requirements for the computational capabilities that are used in high-resolution connectome research. In this paper, we propose a hybrid CPU-GPU framework to accelerate the computation of the human brain connectome. We applied this framework to a publicly available resting-state functional MRI dataset from 197 participants. For each subject, we first computed Pearson’s Correlation coefficient between any pairs of the time series of gray-matter voxels, and then we constructed unweighted undirected brain networks with 58 k nodes and a sparsity range from 0.02% to 0.17%. Next, graphic properties of the functional brain networks were quantified, analyzed and compared with those of 15 corresponding random networks. With our proposed accelerating framework, the above process for each network cost 80∼150 minutes, depending on the network sparsity. Further analyses revealed that high-resolution functional brain networks have efficient small-world properties, significant modular structure, a power law degree distribution and highly connected nodes in the medial frontal and parietal cortical regions. These results are largely compatible with previous human brain network studies. Taken together, our proposed framework can substantially enhance the applicability and efficacy of high-resolution (voxel-based) brain network analysis, and have the potential to accelerate the mapping of the human brain connectome in normal and disease states. [ABSTRACT FROM AUTHOR]

Context: Though the cardiovascular diseases are the leading cause of mortality in India, little is known about the human and economic loss attributed to the disease. The aim of this paper is to account the age and sex pattern of mortality, hospitalisation and the cost of hospitalisation for cardiovascular diseases in India. Data and Methods: Data for the present study has been drawn from multiple sources; 52nd and 60th rounds of the National Sample Survey, Special Survey of Death, 2001–03 and the Sample Registration System 2004–2010. Under the changing demographics and constant assumptions of mortality, hospitalisation and cost of hospitalisation, we have estimated the deaths, hospitalisation and cost of hospitalisation for cardiovascular diseases in India during 2004 to 2021. Descriptive analyses and multivariate techniques were used to understand the socio-economic differentials in cost of hospitalisation for cardiovascular diseases in India. Findings: In India, the cardiovascular diseases accounted for an estimated 1.4 million deaths in 2004 and it is likely to be 2.1 million in 2021. An estimated 6.7 million people were hospitalised for cardiovascular diseases in 2004, and projected to be 10.9 million by 2021. Unlike mortality, majority of the hospitalisation due to cardiovascular diseases will be in the prime working age group (25–59). The estimated cost of hospitalisation for cardiovascular diseases was 94/− billion rupees in 2004 and expected to be 152/− billion rupees by 2021, at 2004 prices. The cost of hospitalisation for cardiovascular diseases was significantly high in private health centres, high fertility states and among high socio-economic groups. Conclusion: The cardiovascular mortality and hospitalisation will be largely concentrated in the prime working age group and the cost of hospitalisation is expected to increase substantially in coming years. This calls for mobilising resources, increasing access to health insurance and devising strategies for the prevention, control and treatment of cardiovascular diseases in India. [ABSTRACT FROM AUTHOR]

: In three to five percent of active cases of tuberculosis, skeletal lesions develop. Typically, these occur on the vertebrae and are destructive in nature. In this paper, we examined cases of skeletal tuberculosis from a skeletal collection (Galler Collection) with focus on the manifestation of bony changes due to tuberculosis in various body regions in association with antibiotic introduction. This skeletal collection was created in 1925–1977 by a pathologist at the University Hospital in Zürich, Ernst Galler. It includes the remains of 2426 individuals with documented clinical histories as well as autopsies. It contained 29 cases of skeletal tuberculosis lesions. We observed natural healing of vertebral lesions through several processes including fusion of vertebrae, bone deposition and fusion of posterior elements. In these cases, we observed a higher frequency and proportion of bone deposition and fusion of posterior vertebral elements where pharmacological agents were used. There were also four cases of artificial healing through surgically induced posterior spinal fusion. With the introduction of pharmaceutical treatments, the number of individuals with multiple tuberculous foci decreased from 80% to 25% when compared to individuals who did not receive any drug therapy. Investigation of comorbidities showed that pneumonia, pleuritis and being underweight were consistently present, even with pharmaceutical treatment. Our results have applications in palaeopathological diagnoses where healing and consequent bone deposition may complicate differential diagnoses. [ABSTRACT FROM AUTHOR]

Background: Calcium phosphate cement (CPC) can be molded or injected to form a scaffold in situ, which intimately conforms to complex bone defects. Bioactive glass (BG) is known for its unique ability to bond to living bone and promote bone growth. However, it was not until recently that literature was available regarding CPC-BG applied as an injectable graft. In this paper, we reported a novel injectable CPC-BG composite with improved properties caused by the incorporation of BG into CPC. Materials and Methods: The novel injectable bioactive cement was evaluated to determine its composition, microstructure, setting time, injectability, compressive strength and behavior in a simulated body fluid (SBF). The in vitro cellular responses of osteoblasts and in vivo tissue responses after the implantation of CPC-BG in femoral condyle defects of rabbits were also investigated. Results: CPC-BG possessed a retarded setting time and markedly better injectability and mechanical properties than CPC. Moreover, a new Ca-deficient apatite layer was deposited on the composite surface after immersing immersion in SBF for 7 days. CPC-BG samples showed significantly improved degradability and bioactivity compared to CPC in simulated body fluid (SBF). In addition, the degrees of cell attachment, proliferation and differentiation on CPC-BG were higher than those on CPC. Macroscopic evaluation, histological evaluation, and micro-computed tomography (micro-CT) analysis showed that CPC-BG enhanced the efficiency of new bone formation in comparison with CPC. Conclusions: A novel CPC-BG composite has been synthesized with improved properties exhibiting promising prospects for bone regeneration. [ABSTRACT FROM AUTHOR]

Several works have reported on the reconstruction of 2D/3D limb kinematics from low-frequency EEG signals using linear regression models based on positive correlation values between the recorded and the reconstructed trajectories. This paper describes the mathematical properties of the linear model and the correlation evaluation metric that may lead to a misinterpretation of the results of this type of decoders. Firstly, the use of a linear regression model to adjust the two temporal signals (EEG and velocity profiles) implies that the relevant component of the signal used for decoding (EEG) has to be in the same frequency range as the signal to be decoded (velocity profiles). Secondly, the use of a correlation to evaluate the fitting of two trajectories could lead to overly-optimistic results as this metric is invariant to scale. Also, the correlation has a non-linear nature that leads to higher values for sinus/cosinus-like signals at low frequencies. Analysis of these properties on the reconstruction results was carried out through an experiment performed in line with previous studies, where healthy participants executed predefined reaching movements of the hand in 3D space. While the correlations of limb velocity profiles reconstructed from low-frequency EEG were comparable to studies in this domain, a systematic statistical analysis revealed that these results were not above the chance level. The empirical chance level was estimated using random assignments of recorded velocity profiles and EEG signals, as well as combinations of randomly generated synthetic EEG with recorded velocity profiles and recorded EEG with randomly generated synthetic velocity profiles. The analysis shows that the positive correlation results in this experiment cannot be used as an indicator of successful trajectory reconstruction based on a neural correlate. Several directions are herein discussed to address the misinterpretation of results as well as the implications on previous invasive and non-invasive works. [ABSTRACT FROM AUTHOR]

Ocean acidification, a decrease in the pH in marine waters associated with rising atmospheric CO2 levels, is a serious threat to marine ecosystems. In this paper, we determine the effects of long-term exposure to near-future levels of ocean acidification on the growth, condition, calcification, and survival of juvenile red king crabs, Paralithodes camtschaticus, and Tanner crabs, Chionoecetes bairdi. Juveniles were reared in individual containers for nearly 200 days in flowing control (pH 8.0), pH 7.8, and pH 7.5 seawater at ambient temperatures (range 4.4–11.9 °C). In both species, survival decreased with pH, with 100% mortality of red king crabs occurring after 95 days in pH 7.5 water. Though the morphology of neither species was affected by acidification, both species grew slower in acidified water. At the end of the experiment, calcium concentration was measured in each crab and the dry mass and condition index of each crab were determined. Ocean acidification did not affect the calcium content of red king crab but did decrease the condition index, while it had the opposite effect on Tanner crabs, decreasing calcium content but leaving the condition index unchanged. This suggests that red king crab may be able to maintain calcification rates, but at a high energetic cost. The decrease in survival and growth of each species is likely to have a serious negative effect on their populations in the absence of evolutionary adaptation or acclimatization over the coming decades. [ABSTRACT FROM AUTHOR]

Photographs of mistletoe (Viscum album L.) berries taken by a permanently fixed camera during their development in autumn were subjected to an outline shape analysis by fitting path curves using a mathematical algorithm from projective geometry. During growth and maturation processes the shape of mistletoe berries can be described by a set of such path curves, making it possible to extract changes of shape using one parameter called Lambda. Lambda describes the outline shape of a path curve. Here we present methods and software to capture and measure these changes of form over time. The present paper describes the software used to automatize a number of tasks including contour recognition, optimization of fitting the contour via hill-climbing, derivation of the path curves, computation of Lambda and blinding the pictures for the operator. The validity of the program is demonstrated by results from three independent measurements showing circadian rhythm in mistletoe berries. The program is available as open source and will be applied in a project to analyze the chronobiology of shape in mistletoe berries and the buds of their host trees. [ABSTRACT FROM AUTHOR]

Calpain is an intracellular Ca2+ -activated protease that is involved in numerous Ca2+ dependent regulation of protein function in many cell types. This paper tests a hypothesis that calpains are involved in Ca2+ -dependent increase of the late sodium current (INaL) in failing heart. Chronic heart failure (HF) was induced in 2 dogs by multiple coronary artery embolization. Using a conventional patch-clamp technique, the whole-cell INaL was recorded in enzymatically isolated ventricular cardiomyocytes (VCMs) in which INaL was activated by the presence of a higher (1μM) intracellular [Ca2+] in the patch pipette. Cell suspensions were exposed to a cell- permeant calpain inhibitor MDL-28170 for 1–2 h before INaL recordings. The numerical excitation-contraction coupling (ECC) model was used to evaluate electrophysiological effects of calpain inhibition in silico. MDL caused acceleration of INaL decay evaluated by the two-exponential fit (τ1 = 42±3.0 ms τ2 = 435±27 ms, n = 6, in MDL vs. τ1 = 52±2.1 ms τ2 = 605±26 control no vehicle, n = 11, and vs. τ1 = 52±2.8 ms τ2 = 583±37 ms n = 7, control with vehicle, P<0.05 ANOVA). MDL significantly reduced INaL density recorded at –30 mV (0.488±0.03, n = 12, in control no vehicle, 0.4502±0.0210, n = 9 in vehicle vs. 0.166±0.05pA/pF, n = 5, in MDL). Our measurements of current-voltage relationships demonstrated that the INaL density was decreased by MDL in a wide range of potentials, including that for the action potential plateau. At the same time the membrane potential dependency of the steady-state activation and inactivation remained unchanged in the MDL-treated VCMs. Our ECC model predicted that calpain inhibition greatly improves myocyte function by reducing the action potential duration and intracellular diastolic Ca2+ accumulation in the pulse train. Conclusions: Calpain inhibition reverses INaL changes in failing dog ventricular cardiomyocytes in the presence of high intracellular Ca2+. Specifically it decreases INaL density and accelerates INaL kinetics resulting in improvement of myocyte electrical response and Ca2+ handling as predicted by our in silico simulations. [ABSTRACT FROM AUTHOR]

Rhodococcus equi is a facultative intracellular pathogen of macrophages and the causative agent of foal pneumonia. R. equi virulence is usually assessed by analyzing intracellular growth in macrophages by enumeration of bacteria following cell lysis, which is time consuming and does not allow for a high throughput analysis. This paper describes the use of an impedance based real-time method to characterize proliferation of R. equi in macrophages, using virulent and attenuated strains lacking the vapA gene or virulence plasmid. Image analysis suggested that the time-dependent cell response profile (TCRP) is governed by cell size and roundness as well as cytoxicity of infecting R. equi strains. The amplitude and inflection point of the resulting TCRP were dependent on the multiplicity of infection as well as virulence of the infecting strain, thus distinguishing between virulent and attenuated strains. [ABSTRACT FROM AUTHOR]

In this paper, we investigate a new paradigm for studying the development of the colour ‘signal’ by having observers discriminate and categorize the same set of controlled and calibrated cardinal coloured stimuli. Notably, in both tasks, each observer was free to decide whether two pairs of colors were the same or belonged to the same category. The use of the same stimulus set for both tasks provides, we argue, an incremental behavioural measure of colour processing from detection through discrimination to categorisation. The measured data spaces are different for the two tasks, and furthermore the categorisation data is unique to each observer. In addition, we develop a model which assumes that the principal difference between the tasks is the degree of similarity between the stimuli which has different constraints for the categorisation task compared to the discrimination task. This approach not only makes sense of the current (and associated) data but links the processes of discrimination and categorisation in a novel way and, by implication, expands upon the previous research linking categorisation to other tasks not limited to colour perception. [ABSTRACT FROM AUTHOR]

The movement of organisms is subject to a multitude of influences of widely varying character: from the bio-mechanics of the individual, over the interaction with the complex environment many animals live in, to evolutionary pressure and energy constraints. As the number of factors is large, it is very hard to build comprehensive movement models. Even when movement patterns in simple environments are analysed, the organisms can display very complex behaviours. While for largely undirected motion or long observation times the dynamics can sometimes be described by isotropic random walks, usually the directional persistence due to a preference to move forward has to be accounted for, e.g., by a correlated random walk. In this paper we generalise these descriptions to a model in terms of stochastic differential equations of Langevin type, which we use to analyse experimental search flight data of foraging bumblebees. Using parameter estimates we discuss the differences and similarities to correlated random walks. From simulations we generate artificial bumblebee trajectories which we use as a validation by comparing the generated ones to the experimental data. [ABSTRACT FROM AUTHOR]