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Simple Summary: With recent progress in radiation therapy, patients with bone metastases can be treated curatively, provided precise delineation of metastatic lesions is adequately identified. Tumor segmentation is a highly active area of research, but only limited studies have been on bone metastasis. This review aims to investigate methods for differentiating benign from malignant bone lesions and characterizing malignant bone lesions specifically in the context of bone metastases. While computer vision techniques have opened new opportunities for quantifying cancer growth with minimal expert supervision, fully automatic segmentation algorithms still require improvement. This is partly due to limited contrast between tumors and surrounding tissue and the lack of a widely agreed upon "gold standard" for defining these boundaries. Additionally, many studies do not provide evidence that their proposed methods are suitable for use in clinical practice. Purpose: To investigate the segmentation approaches for bone metastases in differentiating benign from malignant bone lesions and characterizing malignant bone lesions. Method: The literature search was conducted in Scopus, PubMed, IEEE and MedLine, and Web of Science electronic databases following the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A total of 77 original articles, 24 review articles, and 1 comparison paper published between January 2010 and March 2022 were included in the review. Results: The results showed that most studies used neural network-based approaches (58.44%) and CT-based imaging (50.65%) out of 77 original articles. However, the review highlights the lack of a gold standard for tumor boundaries and the need for manual correction of the segmentation output, which largely explains the absence of clinical translation studies. Moreover, only 19 studies (24.67%) specifically mentioned the feasibility of their proposed methods for use in clinical practice. Conclusion: Development of tumor segmentation techniques that combine anatomical information and metabolic activities is encouraging despite not having an optimal tumor segmentation method for all applications or can compensate for all the difficulties built into data limitations. [ABSTRACT FROM AUTHOR]

Background: Imaging data contains a substantial amount of information which can be difficult to evaluate by eye. With the expansion of high throughput microscopy methodologies producing increasingly large datasets, automated and objective analysis of the resulting images is essential to effectively extract biological information from this data. CellProfiler is a free, open source image analysis program which enables researchers to generate modular pipelines with which to process microscopy images into interpretable measurements. Results: Herein we describe CellProfiler 4, a new version of this software with expanded functionality. Based on user feedback, we have made several user interface refinements to improve the usability of the software. We introduced new modules to expand the capabilities of the software. We also evaluated performance and made targeted optimizations to reduce the time and cost associated with running common large-scale analysis pipelines. Conclusions: CellProfiler 4 provides significantly improved performance in complex workflows compared to previous versions. This release will ensure that researchers will have continued access to CellProfiler's powerful computational tools in the coming years. [ABSTRACT FROM AUTHOR]

Summary Image-based experiments can yield many thousands of individual measurements describing each object of interest, such as cells in microscopy screens. CellProfiler Analyst is a free, open-source software package designed for the exploration of quantitative image-derived data and the training of machine learning classifiers with an intuitive user interface. We have now released CellProfiler Analyst 3.0, which in addition to enhanced performance adds support for neural network classifiers, identifying rare object subsets, and direct transfer of objects of interest from visualization tools into the Classifier tool for use as training data. This release also increases interoperability with the recently released CellProfiler 4, making it easier for users to detect and measure particular classes of objects in their analyses. Availability CellProfiler Analyst binaries for Windows and MacOS are freely available for download at https://cellprofileranalyst.org/. Source code is implemented in Python 3 and is available at https://github.com/CellProfiler/CellProfiler-Analyst/. A sample dataset is available at https://cellprofileranalyst.org/examples , based on images freely available from the Broad Bioimage Benchmark Collection. [ABSTRACT FROM AUTHOR]

Background: It has been proved that increased motion variability can be indicative of lack of stability. Despite the extensive literature on single sit to stand/stand to sit postural transitions analysis in older people, no studies to this date have assessed the sit to stand to sit (STSTS) transition variability in older adults.Research Question: To investigate the variability in STSTS transition during the five times sit to stand (FTSS) test in older people with different fall histories.Methods: Seventy-five older (80.5 ± 7.5) and twenty-five younger (27.7 ± 6.5) subjects participated in the study. The older participants were categorized into three groups of non-fallers, once-fallers, and multiple-fallers based on their fall histories. Subjects were fitted with an IMU at their lower backs and asked to fully stand up and then sit down again five times in a row. The angular rotation of the trunk in the sagittal plane was recorded. Using the DTW method, the first STSTS transition of each subject was compared to the last transition and the variability was measured. The correlation between STSTS variability and older participants' Berg balance scale (BBS) was investigated.Results: The STSTS variability results were significantly different in older fallers (multiple-fallers and once-fallers) compared to both younger participants and older non-fallers. The results yielded a sensitivity of 85.4 % and a specificity of 83.3 % in recognizing older fallers from older non-fallers and a sensitivity and specificity of 86.7 % and 85.7 % respectively in recognizing older multiple-fallers from other older participants. The STSTS variability was found to be significantly correlated with BBS.Significance: The findings demonstrated a strong indication of variability in the STSTS transition in older fallers and a significant correlation between STSTS variability and BBS. The results suggest that variability analysis of the STSTS transition has the potential to be used for fall risk analysis in older adults. [ABSTRACT FROM AUTHOR]

We describe new open source software called QuantiFish for rapid quantitation of fluorescent foci in zebrafish larvae, to support infection research in this animal model. QuantiFish extends the conventional measurements of bacterial load and number of bacterial foci to include measures for dissemination of infection. These are represented by the proportions of bacteria between foci and their spatial distribution. We showcase these measures by comparison of intravenous and hindbrain routes of Mycobacterium marinum infection, which are indistinguishable by measurement of bacterial load and not consistently differentiated by the number of bacterial foci. The intravenous route showed dose dependent dissemination of infection, reflected by increased spatial dispersion of bacteria and lower proportions of bacteria distributed across many foci. In contrast, hindbrain infection resulted in localised disease, limited to a smaller area and higher proportions of bacteria distributed across fewer foci. The application of QuantiFish may extend beyond models of infection, to study other pathologies such as metastatic cancer. [ABSTRACT FROM AUTHOR]

A cross-sectional study of postural sway analysis in older non-fallers, once-fallers and multiple-fallers using five common standing tests was conducted. Eighty-six older subjects with an average age of 80.4 years (SD ± 7.9) participated in the study. The angular rotation and velocity of the trunk of the participants in the roll (lateral) and pitch (sagittal) planes were recorded using an inertial sensor mounted on their lower backs. The Gaussian Mixture Models (GMM), Expectation-Maximisation (EM) and the Minimum Message Length (MML) algorithms were applied to the acquired data to obtain an index indicative of the body sway. The standing with feet together and standing with one foot in front, sway index distinguished older fallers from non-fallers with specificity of 75.7% and 77.7%, respectively, and sensitivity of 78.6% and 82.1%, respectively. This compares favourably with the Berg Balance Scales (BBS) with specificity of 70.5% and sensitivity of 75.3%. The results suggest that the proposed method has potential as a protocol to diagnose balance disorder in older people. Graphical abstract. [ABSTRACT FROM AUTHOR]

Measuring dispersal in rare sessile benthic species is important in the development of conservation measures such as MPA networks. However, efforts to understand dispersal dynamics for many species of conservation concern are hampered by a lack of fundamental life-history information. Here we present the first description of larvae of the fan mussel, Atrina fragilis , and examine key life-history traits that affect dispersal. Larval identification was accomplished using complementary molecular and morphologic techniques. Atrina- specific primers were designed by aligning Atrina COI sequences available in GenBank. As none of these were from UK specimens, primers were designed in the most conserved regions found across A. fragilis and its closest relative A. chautardi. A monthly time-series of zooplankton samples (2014–2015) suggests that A. fragilis follows the same pattern in spawning observed for other pinnids at temperate latitudes, with peak spawning in summer and winter. Average shell growth was estimated to be 6 μm d–1 based on presumed daily growth lines on larval shells. Measurements of the larval shell visible through the juvenile shell indicate a length of up to 770 μm at settlement. Using presumed daily growth lines, this translates into a pelagic larval duration of around 4 months. [ABSTRACT FROM AUTHOR]

Obtaining oral communication competency is an important skill for engineering students to prepare them for interacting and working in any professional setting. For engineers, it is also important to be able to present technical information to non-technical audiences. To ensure oral competency, a non-graded formative assessment approach using video with self- and peer assessment was introduced into a final-year engineering thesis course. A low workload approach was used due to growing student numbers and higher pressures on academic staff. A quasi-experimental design was used to investigate the differences between traditional delivery, self-assessment and combined self-assessment with peer feedback. The study found that the formative models were seen by students to help develop their presentation skills. However, the results showed no significant improvement compared to the traditional method. This could be due to previous presentation practice within the degree or more probable, the lack of incentive for weaker students to engage and improve due to the ungraded nature of the activity. [ABSTRACT FROM AUTHOR]

Drug resistance is a challenge in anticancer therapy. In many cases, cancers can be resistant to the drug prior to exposure, that is, possess intrinsic drug resistance. However, we lack target-independent methods to anticipate resistance in cancer cell lines or characterize intrinsic drug resistance without a priori knowledge of its cause. We hypothesized that cell morphology could provide an unbiased readout of drug resistance. To test this hypothesis, we used HCT116 cells, a mismatch repair-deficient cancer cell line, to isolate clones that were resistant or sensitive to bortezomib, a well-characterized proteasome inhibitor and anticancer drug to which many cancer cells possess intrinsic resistance. We then expanded these clones and measured high-dimensional single-cell morphology profiles using Cell Painting, a high-content microscopy assay. Our imagingand computation-based profiling pipeline identified morphological features that differed between resistant and sensitive cells. We used these features to generate a morphological signature of bortezomib resistance. We then employed this morphological signature to analyze a set of HCT116 clones (five resistant and five sensitive) that had not been included in the signature training dataset, and correctly predicted sensitivity to bortezomib in seven cases, in the absence of drug treatment. This signature predicted bortezomib resistance better than resistance to other drugs targeting the ubiquitin-proteasome system, indicating specificity for mechanisms of resistance to bortezomib. Our results establish a proof-of-concept framework for the unbiased analysis of drug resistance using high-content microscopy of cancer cells, in the absence of drug treatment. [ABSTRACT FROM AUTHOR]

Aim Given the paucity of data on the distribution of habitats and species for most marine species, particularly those that are rare and in need of protection, there is a need to model species distributions. Using the fan mussel, Atrina fragilis (Pennant 1777), as our case species, the aim of the study was to predict new areas of occurrence for A. fragilis, estimate the extent of potentially suitable areas, determine the proportion of these areas that are included in the recently designated nature conservation MPAs off the west of Scotland and identify possible environmental drivers in the distribution of A. fragilis. Location West coast of Scotland, UK. Methods Using a point process framework, we modelled presence-only data, including historic records. A quadrat survey employing digital still photography was conducted in areas of high and low suitability to verify the model, and subsequently, a targeted survey was undertaken in areas predicted as highly suitable by the models using towed video cameras. Results Five environmental variables were of prime importance in explaining the distribution of A. fragilis. The results from the verification survey support model performance. Atrina fragilis was found in 80% of the targeted transects undertaken. Approximately 14% of the total area predicted as suitable for A. fragilis occurred within recently designated marine protected areas ( MPAs) indicating considerable potential for recolonization given suitable protection. Main conclusions The verified model suggests that limited presence-only and historical records of rare species can perform well within a SDM framework allowing the identification of further suitable areas. The prominence of bathymetric ruggedness in the models is unexpected, given the understood ecological niche for A. fragilis and pinnids in general, but is consistent with the fact that seabed topography can offer protection from fishing pressure. These results will inform restoration objectives of the MPA network. [ABSTRACT FROM AUTHOR]

The modeling and measurement of the biodynamic response of the seated human body has recently been an active research topic, with major applications to ergonomics and automotive suspension control system technologies. This paper presents a holistic literature survey of topics including the latest research in the area of vibration signal processing and modeling of the biodynamic response of the seated human to vibrations. This paper reviews recent sensing systems that are reported to measure the motion of the seated body. The data processing techniques that are currently accepted are surveyed and these include impedance, transmissibility measures, frequency response function estimation, and model development. A review of applications of biodynamic response analysis and modeling to seating vibration isolation technologies and vibration monitoring systems is presented within this paper. This survey paper provides a discussion on the direction that the future research in this field will aim toward based on the trends in the recent research and the introduction and application of new technologies. [ABSTRACT FROM PUBLISHER]

Systems that recognize patterns in human motion are central to improvements in automation and human computer interaction. This work addresses challenges which arise in the context of recognizing arbitrary human actions from body-worn sensors. Chiefly the invariance to temporal scaling of events, coping with unlabeled data and estimating an appropriate model complexity. In order to deal with the severe case of unlabeled data, a method is proposed based on dynamic time alignment of Gaussian mixture model clusters for matching actions in an unsupervised temporal segmentation. In facilitation of this, an extensive corpus of continuous motion sequences composed of everyday tasks was recorded as analysis scenarios. The technique achieved an average accuracy of 72% for correctly merging actions performed by different participants. With labeled data and recognition models designed for particular classes, an accuracy of 89% was achieved in classifying the motion of participants left out of the modeling process. These results are contrasted with benchmark methods for recognition in a systematic validation revealing, in particular, an improved performance for mixture model prediction utilizing segments. [ABSTRACT FROM AUTHOR]

Stirling et al. use two-photon excitation, confocal spectral microscopy and a novel ex vivo whole spinal cord model to assess the microglial response to spinal cord injury in real-time. Stimulation of microglia with a synthetic toll-like receptor 2 agonist, Pam2CSK4, modulated the microglial response and reduced white matter injury.Improving neurological outcome after spinal cord injury is a major clinical challenge because axons, once severed, do not regenerate but ‘dieback’ from the lesion site. Although microglia, the immunocompetent cells of the brain and spinal cord respond rapidly to spinal cord injury, their role in subsequent injury or repair remains unclear. To assess the role of microglia in spinal cord white matter injury we used time-lapse two-photon and spectral confocal imaging of green fluorescent protein-labelled microglia, yellow fluorescent protein-labelled axons, and Nile Red-labelled myelin of living murine spinal cord and revealed dynamic changes in white matter elements after laser-induced spinal cord injury in real time. Importantly, our model of acute axonal injury closely mimics the axonopathy described in well-characterized clinically relevant models of spinal cord injury including contusive-, compressive- and transection-based models. Time-lapse recordings revealed that microglia were associated with some acute pathophysiological changes in axons and myelin acutely after laser-induced spinal cord injury. These pathophysiological changes included myelin and axonal spheroid formation, spectral shifts in Nile Red emission spectra in axonal endbulbs detected with spectral microscopy, and ‘bystander’ degeneration of axons that survived the initial injury, but then succumbed to secondary degeneration. Surprisingly, modulation of microglial-mediated release of neurotoxic molecules failed to protect axons and myelin. In contrast, sterile stimulation of microglia with the specific toll-like receptor 2 agonist Pam2CSK4 robustly increased the microglial response to ablation, reduced secondary degeneration of central myelinated fibres, and induced an alternative (mixed M1:M2) microglial activation profile. Conversely, Tlr2 knock out: Thy1 yellow fluorescent protein double transgenic mice experienced greater axonal dieback than littermate controls. Thus, promoting an alternative microglial response through Pam2CSK4 treatment is neuroprotective acutely following laser-induced spinal cord injury. Therefore, anti-inflammatory treatments that target microglial activation may be counterintuitive after spinal cord injury. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Transected axons of the central nervous system fail to regenerate and instead die back away from the lesion site, resulting in permanent disability. Although both intrinsic (eg, microtubule instability, calpain activation) and extrinsic (ie, macrophages) processes are implicated in axonal dieback, the underlying mechanisms remain uncertain. Furthermore, the precise mechanisms that cause delayed 'bystander' loss of spinal axons, that is, ones that were not directly damaged by the initial insult, but succumbed to secondary degeneration, remain unclear. Our goal was to evaluate the role of intra-axonal Ca(2+) stores in secondary axonal degeneration following spinal cord injury. METHODS: We developed a 2-photon laser-induced spinal cord injury model to follow morphological and Ca(2+) changes in live myelinated spinal axons acutely following injury. RESULTS: Transected axons 'died back' within swollen myelin or underwent synchronous pan-fragmentation associated with robust Ca(2+) increases. Spared fibers underwent delayed secondary bystander degeneration. Reducing Ca(2+) release from axonal stores mediated by ryanodine and inositol triphosphate receptors significantly decreased axonal dieback and bystander injury. Conversely, a gain-of-function ryanodine receptor 2 mutant or pharmacological treatments that promote axonal store Ca(2+) release worsened these events. INTERPRETATION: Ca(2+) release from intra-axonal Ca(2+) stores, distributed along the length of the axon, contributes significantly to secondary degeneration of axons. This refocuses our approach to protecting spinal white matter tracts, where emphasis has been placed on limiting Ca(2+) entry from the extracellular space across cell membranes, and emphasizes that modulation of axonal Ca(2+) stores may be a key pharmacotherapeutic goal in spinal cord injury. Ann Neurol 2014;75:220-229. [ABSTRACT FROM AUTHOR]

Objective Transected axons of the central nervous system fail to regenerate and instead die back away from the lesion site, resulting in permanent disability. Although both intrinsic (eg, microtubule instability, calpain activation) and extrinsic (ie, macrophages) processes are implicated in axonal dieback, the underlying mechanisms remain uncertain. Furthermore, the precise mechanisms that cause delayed 'bystander' loss of spinal axons, that is, ones that were not directly damaged by the initial insult, but succumbed to secondary degeneration, remain unclear. Our goal was to evaluate the role of intra-axonal Ca2+ stores in secondary axonal degeneration following spinal cord injury. Methods We developed a 2-photon laser-induced spinal cord injury model to follow morphological and Ca2+ changes in live myelinated spinal axons acutely following injury. Results Transected axons 'died back' within swollen myelin or underwent synchronous pan-fragmentation associated with robust Ca2+ increases. Spared fibers underwent delayed secondary bystander degeneration. Reducing Ca2+ release from axonal stores mediated by ryanodine and inositol triphosphate receptors significantly decreased axonal dieback and bystander injury. Conversely, a gain-of-function ryanodine receptor 2 mutant or pharmacological treatments that promote axonal store Ca2+ release worsened these events. Interpretation Ca2+ release from intra-axonal Ca2+ stores, distributed along the length of the axon, contributes significantly to secondary degeneration of axons. This refocuses our approach to protecting spinal white matter tracts, where emphasis has been placed on limiting Ca2+ entry from the extracellular space across cell membranes, and emphasizes that modulation of axonal Ca2+ stores may be a key pharmacotherapeutic goal in spinal cord injury. Ann Neurol 2014;75:220-229 [ABSTRACT FROM AUTHOR]

HEAT level control (HLC) is one of the important elements for operating an iron-making blast furnace (BF). The goal of HLC is to maintain the hot metal temperature (HMT) as close to a preset aim as possible. HMT is an important indicator of both the product quality and fuel efficiency, and is measured from tapped out liquid iron. For instance, high values of HMT mean unnecessary fuel consumption together with sub-optimal hot metal chemistry, whilst low values of HMT may indicate insufficient fuel consumption, which may consequently lead to dangerous situation of freezing the slag inside the BF. Once an aim HMT is decided, based on production and plant constraints, several inputs of the BF can be adjusted by operators to control this HMT. However, any change of the inputs requires time to take effect, due to inherent time lags, and the best practice control relies heavily on an operator's experience and judgment. This is due to the complexity of the numerous BF processes, which essentially can be described as highly non-linear, stochastic and nonstationary in nature. The goal of this work is to employ a data mining approach to analyse the BF system and build a dynamical modelling system, which will generate a set of understandable symbolic rules for prediction of HMT changes. The model is regularly generated by decision tree applications, See5 and Cubist, in order to adapt any significant contextual variations of the BF. This rule based system can help the operators increase the BF's efficiency by making timely control adjustments with the goal of minimising variation of HMT with time. These models also provide a corpus of driving factors that can also be analysed by domain experts as an objective knowledge source. [ABSTRACT FROM AUTHOR]

Axonal degeneration causes morbidity in many neurological conditions including stroke, neurotrauma and multiple sclerosis. The limited ability of central nervous system (CNS) neurons to regenerate, combined with the observation that axonal damage causes clinical disability, has spurred efforts to investigate the mechanisms of axonal degeneration. Ca influx from outside the axon is a key mediator of injury. More recently, substantial pools of intra-axonal Ca sequestered in the ‘axoplasmic reticulum’ have been reported. These Ca stores are under the control of multimolecular ‘nanocomplexes’ located along the internodes under the myelin. The overactivation of these complexes during disease can lead to a lethal release of Ca from intra-axonal stores. Rich receptor pharmacology offers tantalizing therapeutic options targeting these nanocomplexes in the many diseases where axonal degeneration is prominent. [Copyright &y& Elsevier]

Background: One of the major obstacles to the exploitation of genetic variation in human medicine, veterinary medicine, and animal breeding is the difficulty in defining haplotypes in unrelated individuals. Results: We have developed a Multiplex Double Amplification Refractory Mutation System combined with Solid Phase PCR on Fluorescently labelled beads. The process is inherently amenable to automation. It provides a high degree of internal Quality Control, as each PCR product is represented in duplicate on the bead array, and each SNP is tested against multiple partners. This technique can resolve very complex genotypes into their constituent haplotypes; it defined all the alleles at 60 SNP in exon 2 of the ovine DRB1 MHC locus in a sample of 109 rams. These 60 SNP formed 33 DRB1 exon 2 alleles; two of which had not been previously identified; although both of them have been independently confirmed. Conclusion: This technique has the same resolution as allele specific sequencing. Sequencing has the advantage of identifying novel polymorphic sites but where all SNP sites have been identified this novel procedure can resolve all alleles and haplotypes and identify novel combinations of polymorphisms. This method is similar in price to direct sequencing and provides a low cost system for direct haplotyping of extended DNA sequences. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) induces a robust inflammatory response and the extravasation of leukocytes into the injured tissue. To further knowledge of the functions of neuroinflammation in SCI in mice, we depleted the early arriving neutrophils using an anti-Ly6G/Gr-1 antibody. Complete blood counts revealed that neutrophils increased~3-fold over uninjured controls and peaked at 6 -12 h after injury, and that anti-Ly6G/Gr-1 treatment reduced circulating neutrophils by>90% at these time points. Intravital and spinning disk confocal microscopy of the exposed posterior vein and postcapillary venules showed a significant reduction in rolling and adhering neutrophils in vivo after anti-Ly6G/Gr-1 treatment; this was accompanied by a parallel reduction in neutrophil numbers within the injured spinal cord at 24 and 48 h as determined by flow cytometry. The evolution of astrocyte reactivity, a wound healing response, was reduced in anti-Ly6G/Gr-1-treated mice, which also had less spared white matter and axonal preservation compared with isotype controls. These histological outcomes may be caused by alterations of growth factors and chemokines important in promoting wound healing. Importantly, anti-Ly6G/Gr-1 treatment worsened behavioral outcome as determined using the Basso Mouse Scale and subscores. Although the spectrum of cells affected by anti-Ly6G/Gr-1 antibody treatment cannot be fully ascertained at this point, the correspondence of neutrophil depletion and worsened recovery suggests that neutrophils promote recovery after SCI through wound healing and protective events that limit lesion propagation. [ABSTRACT FROM AUTHOR]

Abstract-Harmonic monitoring has become an important tool for harmonic management in distribution system. A comprehensive harmonic monitoring program has been designed and implemented on a typical electrical medium-voltage distribution system in Australia. The monitoring program involved measurements of the three-phase harmonic currents and voltages from the residential, commercial, and industrial load sectors. Data over a three year period have been downloaded and available for analysis. The large amount of acquired data makes it difficult to identify operational events that significantly impact the harmonics generated on the system. More sophisticated analysis methods are required to automatically determine which part of the measurement data are of importance. Based on this information, a closer inspection of smaller data sets can then be carried out to determine the reasons for its detection. In this paper, we classify the measurement data using unsupervised learning based on clustering techniques using the minimum message length technique, which can provide the engineers with a rapid, visually oriented method of evaluating the underlying operational information contained within the clusters. Supervised learning is then used to describe the generated clusters and to predict the occurrences of unusual clusters in future measurement data. [ABSTRACT FROM AUTHOR]

Several studies have shown that minocycline, a semisynthetic, second-generation tetracycline derivative, is neuroprotective in animal models of central nervous system trauma and several neurodegenerative diseases. Common to all these reports are the beneficial effects of minocycline in reducing neural inflammation and preventing cell death. Here, the authors review the proposed mechanisms of action of minocycline and suggest that minocycline may inhibit several aspects of the inflammatory response and prevent cell death through the inhibition of the p38 mitogen-activated protein kinase pathway, an important regulator of immune cell function and cell death. [ABSTRACT FROM AUTHOR]

We report for the first time, the presence of saxitoxin (STX) in a common cephalopod, Octopus (Abdopus) sp. 5, collected from Cooke Point on the northern coastline of Western Australia. Sodium channel and saxiphilin based radio-receptor assays detected saxitoxin-like binding in octopi extracts. Further analysis by liquid chromatography-fluorescence detection (LC-FLD) identified STX as the major contributing toxin in these samples. The presence of STX was confirmed by LC-mass spectrometry and comparison of fragmentation patterns with an authentic STX standard. LC-FLD quantitation and conversion of the Octopus sp. 5 extracts revealed toxin concentrations as high as 246μg STX/100g tissue, more than three times the US, European and Australian regulatory limit for human consumption of shellfish of 80μg STX/100g tissue. There was no evidence of tetrodotoxin or other paralytic shellfish toxin derivatives. This level and distribution of STX in octopi poses a potential public health risk, particularly when routine toxin screening of wild catch is not regulated. [Copyright &y& Elsevier]

Myelin-derived molecules inhibit axonal regeneration in the CNS. The Long–Evans Shaker rat is a naturally occurring dysmyelinated mutant, which although able to express the components of myelin lacks functional myelin in adulthood. Given that myelin breakdown exposes axons to molecules that are inhibitory to regeneration, we sought to determine whether injured dorsal column axons in a Shaker rat would exhibit a regenerative response absent in normally myelinated Long–Evans (control) rats. Although Shaker rat axons did not regenerate beyond the lesion, they remained at the caudal end of the crush site. Control rat axons, in contrast, retracted and died back from the edge of the crush. The absence of retraction/dieback in Shaker rats was associated with a reduced phagocytic reaction to dorsal column crush around the caudal edge of the lesion. Systemic injection of minocycline, a tetracycline derivative, in control rats reduced both the macrophage response and axonal retraction/dieback following dorsal column injury. In contrast, increasing macrophage activation by spinal injection of the yeast particulate zymosan had no effect on axonal retraction/dieback in Shaker rats. Schwann cell invasion was reduced in minocycline-treated control rats compared with untreated control rats, and was almost undetectable in Shaker rats, suggesting that like axonal retraction/dieback, spinal Schwann cell infiltration is dependent upon macrophage-mediated myelin degeneration. These results indicate that following spinal cord injury the phagocyte-mediated degeneration of myelin and subsequent exposure of inhibitory molecules to the injured axons contributes to their retraction/dieback. [ABSTRACT FROM AUTHOR]

Minocycline has been demonstrated to be neuroprotective after spinal cord injury (SCI). However, the cellular consequences of minocydine treatment on the secondary injury response are poorly understood. We examined the ability of minocycline to reduce oligodendrocyte apoptosis, microglial/macrophage activation, corticospinal tract (CST) dieback, and lesion size and to improve functional outcome after SCI. Adult rats were subjected to a C7-C8 dorsal column transection, and the presence of apoptotic oligodendrocytes was assessed within the ascending sensory tract (AST) and descending CST in segments (3-7 mm) both proximal and distal to the injury site. Surprisingly, the numbers of dying oligodendrocytes in the proximal and distal segments were comparable, suggesting more than the lack of axon- cell body contiguity played a role in their demise. Minocycline or vehicle control was injected into the intraperitoneal cavity 30 min and 8 hr after SCI and thereafter twice daffy for 2 d. We report a reduction of apoptotic oligodendrocytes and microglia within both proximal and distal segments of the AST after minocycline treatment, using immunostaining for active caspase-3 and Hoechst 33258 staining in combination with cell-specific markers. Activated microglial/macrophage density was reduced remote to the lesion as well as at the lesion site. Both CST dieback and lesion size were diminished after minocycline treatment. Footprint analysis revealed improved functional outcome after minocycline treatment. Thus, minocycline ameliorates multiple secondary events after SCI, rendering this clinically used drug an attractive candidate for SCI treatment trials. [ABSTRACT FROM AUTHOR]

d-Methylphenidate (d-MPH) was approved as a treatment for attention deficit hyperactivity disorder (ADHD) in children. The repeated-dose toxicity of the d enantiomer of d,l-methylphenidate (d,l-MPH) was assessed in male and female Beagle dogs. Dogs were orally dosed twice a day in equally divided doses 6 hours apart for total daily doses of 1, 3, and 10 mg/kg/day d-MPH or 20 mg/kg/day d,l-MPH for 90 days, followed by a 30-day recovery period. The top d-MPH dose of 10 mg/kg was equimolar to 20 mg/kg d,l-MPH in d-MPH content. The 10-mg/kg d-MPH and d,l-MPH doses were at least 13 times the maximum therapeutic dose giving rise to systemic exposures that were equivalent to or at least 2 times greater than those at the maximum therapeutic doses in children. The 10-mg/kg d-MPH and 20-mg/kg d,l-MPH doses had systemic exposures that were equivalent to or two to five times greater than the maximum therapeutic plasma levels in children respectively. There was no treatment-related mortality in all doses tested. Reversible salivation, hyperactivity, and diarrhea were seen in the high-dose d-MPH and d,l-MPH groups. Significant body weight loss and reduction in food consumption were observed in males for both high-dose groups with weights comparable to control values by the end of the recovery period. There were no abnormal clinical pathology or macroscopic or microscopic findings. Based on body weight changes, the no-observed-adverse-effect level (NOAEL) of d-MPH in beagle dogs was 3 mg/kg/day. [ABSTRACT FROM AUTHOR]

d,l-Methylphenidate (Ritalin®) is used to treat attention deficit hyperactivity disorder (ADHD) in children. The therapeutic effect is predominantly due to the d enantiomer. Dexmethylphenidate (d-MPH; Focalin®) was therefore developed for its better therapeutic index. The present study determined and compared the acute behavioral toxicity of d,l-MPH, d-MPH and l-MPH in rats after oral dosing. Comprehensive functional observational battery (FOB) evaluations and rota-rod tests were performed 30, 60 and 120 min after dosing. Ten rats/sex/dose were administered a single dose of vehicle, 2, 20, 100 mg/kg d,l-MPH and 1, 10, 50 mg/kg d-MPH or 1, 100, 500 mg/kg l-MPH. There was no mortality. Certain FOB evaluations were statistically significant from vehicle control at any of the time points with most occurring at 60 and 120 min in the high d,l-MPH dose. These included increases in rearing, difficulty in removal from box, arousal, click, tail-pinch and decreases in hind-limb splay distance, hind-limb grip strength and handling reactivity. Behavioral responses were also present at the mid-dose d,l-MPH and high dose d- and l-MPH. Responses in female were significantly different from males in d,l- and l-MPH groups suggesting a sex difference in sensitivity. In the rota-rod test, mean latency to remain on the rod was significantly less for males compared to control given high dose d-MPH and d,l-MPH. In females, latency times were significantly less for high doses of all three compounds. In summary, fewer significant FOBs were seen with d- and l-MPH compared to equimolar doses of d,l-MPH. l-MPH was the least potent in producing FOBs. These results were supported by rota-rod studies. [Copyright &y& Elsevier]

d-methylphenidate is an enantiomer of d,l-methylphenidate and was developed as an improved treatment for attention deficit hyperactivity disorder in children. The current study was performed to determine and compare the toxicity of 2–50 mg/kg per day d-MPH and 100 mg/kg per day d,l-MPH for 90 days in rats with the top d-MPH dose being equimolar to 100 mg/kg d,l-MPH. The top d-MPH and d,l-MPH doses were at least 67 times that of the human dose and produced systemic exposures that were over 10 times higher than those typically achieved in children. During the course of the study, one male each from the 50 mg/kg per day and d,l-MPH groups and one female from the 50 mg/kg group died. Incidences of material around nose/eyes, scabbing, foot swelling, alopecia and abrasions were evident at 50 mg/kg per day d-MPH and 100 mg/kg per day d,l-MPH doses. Body weight and its changes decreased in a dose-dependent manner for d-MPH males. There were significant changes in some clinical chemistry measurements at the terminal bleed in the high dose groups of both sexes although most of these changes were resolved by the recovery bleed. Differences in absolute and relative body and certain organ weights for high dose d-MPH and d,l-MPH groups were seen at terminal necropsy with the differences no longer present after the recovery period. No abnormal or gross histopathological changes were associated with any of these organ weight changes reported for the terminal and recovery periods. Based on body weight changes, the no observed adverse effect level for d-MPH in rats was 20 mg/kg. Overall, the toxicity profile observed in rats with 50 mg/kg per day d-MPH was comparable to that of an equimolar dose of d,l-MPH (100 mg/kg per day) when given repeatedly for 90 days using a twice a day dosing regimen. [Copyright &y& Elsevier]

d-Methylphenidate is an enantiomer of d,l-methylphenidate and was developed as an improved treatment for attention deficit hyperactivity disorder (ADHD) in children. The current study was performed to assess the potential perinatal and postnatal toxicity of both compounds in rats. About 125 presumed pregnant rats were assigned to five dose groups of 25 each. They were dosed with 2, 6, and 20 mg/kg/day d-methylphenidate and 40 mg/kg/day d,l-methylphenidate from gestation Day 7 to lactation Day 20. F1 generation rats were rebred to produce F2 fetuses. Various perinatal and postnatal measurements were made for the F0 and F1 rats. Among the significant findings were a reduction in maternal body weight gain for 20 mg/kg/day d-methylphenidate and d,l-methylphenidate and increased incidences of dilated pupil and vocalization for d,l-methylphenidate during the gestation period. Neither compound produced any other significant adverse findings in F0 and F1 generation rats at doses that were at least 25 times the maximum daily human therapeutic dose. [Copyright &y& Elsevier]

We have developed a novel assay for quantitation of human von Willebrand factor (vWF) messenger RNA (mRNA) using the ABI 7700™ quantitative PCR system (Applied Biosystems, Warrington, Cheshire, UK). To allow accurate measurement of the vWF mRNA concentration in samples, we have used 18S ribosomal RNA as an internal control. The specificity of the assay was demonstrated by polyacrylamide gel electrophoresis and ABI Prism® BigDye™ terminator cycle sequencing of the PCR product. We have also assessed the assay by using RNA from both a hepatocyte cell line which does not express vWF mRNA, and an endothelial cell line which does express vWF mRNA. By mixing varying amounts of these RNAs together, we were able to adjust the vWF quantity in known increments while keeping the 18S ribosomal RNA internal control constant. The quantitation of vWF mRNA correlated with the proportion of endothelial cell RNA (r2=0.912, p<0.001). [Copyright &y& Elsevier]

Presents a literature review on interleukin 6 (IL-6) and haemostasis. Significance of IL-6 in the treatment of haemostasis; Information on IL-6 and its receptors; Coverage of the IL-6 cytokine family.

Coagulation factor concentrates are known to inhibit a variety of immune reactions when assessed in vitro. This study assessed the immunomodulatory activity of a wide range of coagulation factor concentrates by measuring their inhibition of PHA-stimulated lymphocyte proliferation and reduction in IL-2 secretion. The hypothesis that TGF-β is responsible for most of these effects was tested by measuring biologically active TGF-β and immunoreactive TGF-β1 in the concentrates and comparing the levels recorded with immunosuppressive activity. In addition, the coagulation factors were compared directly with a standard preparation of TGF-β in a TGF-β-specific bioassay and in lymphocyte proliferation assays. Although there was a broad correlation between levels of total or active TGF-β and immunosuppressive activity across all of the coagulation factors tested, individual data sets showed clear discrepancies. Implying that TGF-β probably serves as a surrogate marker for other immunomodulatory contaminants and that neither TGF-β nor any other single substance could account for all of the immunosuppressive activity observed. Furthermore, there was a difference of more than 100-fold in the relative potencies of coagulation factors and pure TGF-β, when compared in immunosuppression assays, indicating that the different assays did not measure the same substance. Whereas anti-TGF-β antibody almost completely blocked the activity of coagulation factor concentrates (TGF-β-specific bioassay) and abrogated the effect of authentic TGF-β (immunosuppression assays) at high concentrations it achieved <50% reversal of the immunosuppressive effects of coagulation factors in immunosuppression assays. These findings indicated that TGF-β accounted for only a minor proportion of the immunosuppressive activity in most coagulation factor concentrates. [ABSTRACT FROM AUTHOR]

1. The methane mono-oxygenase from Methylosinus trichosporium OB3b was soluble. The only suitable electron donor was NAD(P)H, neither sodium L-ascorbate nor electrons derived from the oxidation of methanol could substitute for NAD(P)H. Evidence is presented for the existence of an NAD+-linked formaldehyde dehydrogenase. 2. Monooxygenase activity was not inhibited by a range of potential inhibitors including potassium cyanide, amytal, carbon monoxide or various metal-chelating agents, although 8-hydroxy-quinoline and ethyne were effective in this respect. 3. Although the enzyme preparations were unstable on storage, the crude extract could be resolved into two components by ion-exchange chromatography. Activity could be restored to one of the components on addition of purified components from Methylococcus capsulatus (Bath). 4. Cross-reactivity of mono-oxygenase components and other similarities between the enzymes from M. trichosporium and M. capsulatus are discussed. The properties of the M. trichosporium methane mono-oxygenase reported here are contrasted with the properties of the same enzyme reported by others. [ABSTRACT FROM AUTHOR]

MPAs are expected to improve the conservation status of rare and important habitats and species. However, the reduction in anthropogenic pressure due to such management measures is rarely estimated. Although MPA networks may cover a large proportion of the seabed, designated areas that prohibit damaging fishing activity are often much smaller. This case study compares fishing pressure inside and outside areas covered by Scottish MPAs and MPA management measures, further relating its distribution to bottom ruggedness, which influences benthic communities and their exposure to mobile bottom fishing. While 7% of the study region was found to be within MPA boundaries, only 2.5% of the region was subject to management measures that restrict mobile bottom fishing. Taking historical levels of fishing as a benchmark, management measures have been applied to <0.6% of the swept area of existing mobile bottom fishing activity. This may be explained by the higher average seabed ruggedness within MPA management measures, which was also where some key species of conservation interest were found. These findings suggest that protection has been focussed in areas that already act as natural refugia for sensitive benthic species and lie away from the majority of fishing activity. While the measures do not reduce fishing pressure markedly, they do protect relatively pristine habitats from future fishing impacts. MPA management measures had higher average seabed ruggedness, suggesting a bias in protection for species and habitats within such areas. [ABSTRACT FROM AUTHOR]

Ryanodine receptors (RyRs) mediate calcium release from calcium stores and have been implicated in axonal degeneration. Here, we use an intravital imaging approach to determine axonal fate after spinal cord injury (SCI) in real-time and assess the efficacy of ryanodine receptor inhibition as a potential therapeutic approach to prevent intra-axonal calcium-mediated axonal degeneration. Adult 6-8 week old Thy1YFP transgenic mice that express YFP in axons, as well as triple transgenic Avil-Cre:Ai9:Ai95 mice that express the genetically-encoded calcium indicator GCaMP6f in tdTomato positive axons, were used to visualize axons and calcium changes in axons, respectively. Mice received a mild SCI at the T12 level of the spinal cord. Ryanodine, a RyR antagonist, was given at a concentration of 50 μM intrathecally within 15 min of SCI or delayed 3 h after injury and compared with vehicle-treated mice. RyR inhibition within 15 min of SCI significantly reduced axonal spheroid formation from 1 h to 24 h after SCI and increased axonal survival compared with vehicle controls. Delayed ryanodine treatment increased axonal survival and reduced intra-axonal calcium levels at 24 h after SCI but had no effect on axonal spheroid formation. Together, our results support a role for RyR in secondary axonal degeneration. [ABSTRACT FROM AUTHOR]

Cryptococcus neoformans is an opportunistic human pathogen, which causes serious disease in immunocompromised hosts. Infection with this pathogen is particularly relevant in HIV+ patients, where it leads to around 200,000 deaths per annum. A key feature of cryptococcal pathogenesis is the ability of the fungus to survive and replicate within the phagosome of macrophages, as well as its ability to be expelled from host cells via a novel non-lytic mechanism known as vomocytosis. Here we show that cryptococcal vomocytosis from macrophages is strongly enhanced by viral coinfection, without altering phagocytosis or intracellular proliferation of the fungus. This effect occurs with distinct, unrelated human viral pathogens and is recapitulated when macrophages are stimulated with the anti-viral cytokines interferon alpha or beta (IFNα or IFNβ). Importantly, the effect is abrogated when type-I interferon signalling is blocked, thus underscoring the importance of type-I interferons in this phenomenon. Lastly, our data help resolve previous, contradictory animal studies on the impact of type I interferons on cryptococcal pathogenesis and suggest that secondary viral stimuli may alter patterns of cryptococcal dissemination in the host. Author summary: Infectious diseases are typically studied in isolation, but in real life people often encounter multiple infections simultaneously. Here we investigate how the innate immune response to the fatal fungus Cryptococcus neoformans is influenced by viral coinfection. Whilst virally-infected macrophages retain a normal capacity to engulf and kill Cryptococci, they demonstrate a dramatically enhanced propensity to expel them through vomocytosis. Activation of vomocytosis is driven by type-I interferons, generic 'antiviral' molecules, which signal back to the infected macrophage, triggering expulsion of the fungus. We propose that this hitherto unobserved phenomenon represents a 'reprioritisation' pathway for innate immune cells, by which they can alter the frequency with which they expel one pathogen depending on the level of threat from a secondary infection. [ABSTRACT FROM AUTHOR]

CellProfiler is a widely used software for creating reproducible, reusable image analysis workflows without needing to code. In addition to the >90 modules that make up the main CellProfiler program, CellProfiler has a plugins system that allows for the creation of new modules which integrate with other Python tools or tools that are packaged in software containers. The CellProfiler‐plugins repository contains a number of these CellProfiler modules, especially modules that are experimental and/or dependency‐heavy. Here, we present an upgraded CellProfiler‐plugins repository, an example of accessing containerised tools, improved documentation and added citation/reference tools to facilitate the use and contribution of the community. [ABSTRACT FROM AUTHOR]

Focuses on Hemophilia B or Christmas disease, which is an X-linked recessive disorder caused by mutations of the gene encoding coagulation factor IX. Description by Crossley, et al of a Leyden-like mutation; Report which emphasizes the importance of HNF-4 in hemophilia B-Leyden; More.

The most common side-effect of chemotherapy is fatigue. Because of its impact on Physical Performance Status (PPS), the degree of fatigue is a factor considered in chemotherapy administration. Conventionally, a questionnaire-based method known as the ECOG table, devised by the Eastern Cooperation Oncology Group (ECOG), is employed to assess the chemotherapy-induced fatigue. The approach is qualitative, subjective, inaccurate and prone to error. To achieve a more reliable method, an objective, quantitative and precise method is proposed to assess the PPS of different groups of cancer patients. The approach was developed based on a six-minute walk test (6MWT) during which the kinematic data of 23 body segments were measured using body-mounted inertial sensors. The data streams were subsequently segmented by a clustering algorithm known as ‘minimum-message-length-encoding’ (MML) producing a Gaussian mixture model (GMM). Several postural states were captured from the model to derive a holistic index representing the PPS of a patient undergoing chemotherapy. The proposed method was validated by applying it to simulated and real data. For the simulation study, a typical gait behaviour simulating post-chemotherapy conditions was devised in consultation with an oncologist while the real data comprised the gait information obtained from 4 cancer patients. The results indicate that the proposed algorithm clearly identifies the characteristics of ambulatory motion affected by chemotherapy and provides a more accurate measure of fatigue that can assist oncologists to make a more objective decision regarding continuation or termination of treatment. [ABSTRACT FROM AUTHOR]

Falls in older adults represent the most common cause of injuries and a major cause of mortality in this vulnerable population. The morbidity and mortality rate of falls among older people makes balance analysis in older adults very important. Therefore, this study aims to explore different metrics that can potentially be used to identify early indications of balance loss and fall risk. To that end, the motion strategies and chest and pelvis coordination of a group of younger, a group of older non-faller and a group of older faller participants while conducting the functional reach test were investigated. To analyse the motion strategies of the different participant groups, four metrics of maximum angular rotation of chest, maximum angular rotation of pelvis, time warped chest and pelvis angular rotation difference, and the mean continuous relative phase of the chest and pelvis were assessed. In this study younger participants are found to have larger maximum chest rotation, maximum pelvis rotation, and time warped chest and pelvis angular rotation difference compared to older participants. However, these metrics were not significantly different in older non-fallers compared to older fallers. Meanwhile, the mean continuous relative phase of the chest and pelvis was the only metric found to be significantly different among all three participant groups. This metric is indicative of the chest and pelvis coordination which is associated with the ability to construct proper coordination and maintain balance. The mean continuous relative phase yielded the sensitivity of 92.3% and specificity of 73.7% in recognizing older fallers from older non-fallers. The results suggest that this metric might be useful in identifying the risk of falling in older population, thus, it should be further studied in a prospective study. [ABSTRACT FROM AUTHOR]

ABSTRACT This paper reports an investigation into the effect of carbon dioxide (CO2) gas on various ultra wideband channel coefficients. Measurements were conducted using apparatus consisting of a rubberized tube (6 mm diameter) connected to a source of CO2 or nitrogen (N2). For support, the rubberized tube was wrapped twice around a PVC pipe (160 mm diameter). The rubberized tube was flushed with 100% CO2 several times before being sealed in the tube at atmospheric pressure. In between measurement trials, removal of CO2 was achieved by flushing with pure nitrogen. A Vector Network Analyzer (VNA) using two identical directional antennas, with the wrapped section of tubing placed in-between, measured the channel coefficients over ultra wideband frequency spans of (0.3-8) GHz and (1-2) GHz. Significant magnitude differences between the baseline condition and that of CO2 were observed. We found the same signature of difference curves over the same frequency spans for different measurements. Difference in shape in the frequency band of (1-2) GHz is the same as that of the measured difference over 1-2 GHz in entire frequency band of 300 MHz to 8 GHz for the measured channel coefficients. © 2016 Wiley Periodicals, Inc. Microwave Opt Technol Lett 58:1543-1546, 2016 [ABSTRACT FROM AUTHOR]

This paper proposes the application of an improved extended active observer (IEAOB) based teleoperation controller for both master and slave manipulators. The proposed approach successfully deals with all the major problems in teleoperation systems associated with force/position tracking, external force estimation, communication delay compensation, and suppression of disturbances such as robot inertial parameter variation, unmodeled dynamics, measurement noise, and frictions in joints. As an enhancement of the extended active observer (EAOB) reported earlier, the proposed IEAOB relies on an accurate model of system rigid-body dynamics and measured motion to estimate external torque and friction torque, which are both subsequently used in the design of master and slave controllers. Stability of the entire teleoperation system is verified through stability analysis. In order to demonstrate effectiveness of the approach, the IEAOB-based teleoperation controller is applied to a pair of 3-DOF Phantom haptic devices connected via a communication channel with time-varying delays. The performance of the proposed algorithm is compared with the Nicosia observer-based teleoperation controller. The experimental results show that the proposed approach is superior to the Nicosia observer-based approach for a time variant non-linear teleoperation system in tracking force and position and suppressing disturbance in the presence of time varying delays. Meanwhile, another contact motion experiment with a force sensor is conducted on Phantom Omni haptic device; the result demonstrates the force estimation feasibility of IEAOB in practical applications. [ABSTRACT FROM AUTHOR]

This paper discusses the progress of the landslide susceptibility mapping in the wider Sydney Basin area to facilitate engineering and geological studies and land-use zoning; using induced decision trees. This study investigates the effect of the basic unit of this spatial modelling work (pixel resolution) on the accuracy of the modelling outcome, and reports on the effectiveness of using See5 pruned decision trees to model the landslide susceptibility of the Sydney Basin. Landslide susceptibility was determined from the landslide confidence value derived from the Laplace ratio of the rule based predicted classes. The modelling work has been carried out at 2 m, 5 m, 10 m, 15 m, 20 m, 25 m, 30 m, and 40 m pixel resolutions for a trial area within the Sydney Basin. Ten different GIS based datasets derived from the same original datasets have been used each time as landslide causative factors. The optimum tree pruning parameters for each pixel resolution were identified by analysing the behaviour of misclassification errors. Performance of the models at different pixel resolutions was compared using ROC curves and five-fold cross validation accuracy. High density ALS elevation point clouds and large scale datasets allowed model development at a higher resolution (2 m) but the decision tree model at 10 m resolution performed better than the rest. The ratio between the square root of the mean landslide area of the inventory and the area covered by a single pixel has been developed as a worthwhile quantitative measurement of the adequacy of the model resolution. The validation results of the final modelling outcome show that landslide susceptibility descriptors fulfil the requirements of the LRM guidelines. The model has a conservative success of 90% according to the field validation and a cross validation accuracy of 92%. [ABSTRACT FROM AUTHOR]

The vagus nerve is comprised primarily of non-myelinated sensory neurons whose cell bodies are located in the nodose ganglion (NG). The vagus has widespread projections that supply most visceral organs, including the bladder. Due to its non-spinal route, the vagus nerve itself is not directly damaged from spinal cord injury (SCI). Because most viscera, including bladder, are dually innervated by spinal and vagal sensory neurons, an impact of SCI on the sensory component of vagal circuitry may contribute to post-SCI visceral pathologies. To determine if SCI, in male Wistar rats, might impact neurochemical characteristics of NG neurons, immunohistochemical assessments were performed for P2X3 receptor expression, IB4 binding, and Substance-P expression, three known injury-responsive markers in sensory neuronal subpopulations. In addition to examining the overall population of NG neurons, those innervating the urinary bladder also were assessed separately. All three of the molecular markers were represented in the NG from non-injured animals, with the majority of the neurons binding IB4. In the chronically injured rats, there was a significant increase in the number of NG neurons expressing P2X3 and a significant decrease in the number binding IB4 compared to non-injured animals, a finding that held true also for the bladder-innervating population. Overall, these results indicate that vagal afferents, including those innervating the bladder, display neurochemical plasticity post-SCI that may have implications for visceral homeostatic mechanisms and nociceptive signaling. [ABSTRACT FROM AUTHOR]

A novel nonlinear teleoperation algorithm for simultaneous inertial parameters and force estimation at the master and slave sides of the teleoperation system is proposed. The scheme, called Extended Active Observer (EAOB), is an extension of the existing active observer. It provides effective force tracking at the master side with accurate position tracking at the slave side in the presence of inertial parameter variation and measurement noise. The proposed method only requires the measurement of robot position, and as a result significantly reduces the difficulty and cost of implementing bilateral teleoperation systems. The approach is described and its stability is analytically verified. The performance of the method is validated through computer simulation and compared with the Nicosia observer-based controller. According to the results, EAOB outperforms the Nicosia observer method and effectively rejects noise. [ABSTRACT FROM AUTHOR]

Historically, the immune response after spinal cord injury was considered largely detrimental owing to the release of neurotoxic factors. While there is validity to this view, there is much greater heterogeneity of immune cells than was previously realized. Associated with this heterogeneity of immune cell subtypes, there is diversity of functions of immune cells that is still poorly understood after spinal cord injury. Modulating the immune system requires improved understanding of the major players: those immune cell subtypes that are more detrimental than beneficial and those that are important in repair. In this review we will discuss the early findings that supported the use of various anti-inflammatory medications as well as the evolving concept that not all immune subtypes are detrimental and some might even be beneficial. In the last section we will highlight the need to characterize better the role of immune cell subsets in the hopes of developing potential therapeutic targets for the future. [ABSTRACT FROM AUTHOR]

Abstract: The current control methods applied to robotic manipulators either require full state and force measurements, or use the state and force estimation in the absence of any kind of disturbance. As an alternative approach, a new adaptive motion control approach for robotic manipulators extending the existing active observer for simultaneous inertial parameters and force estimation is proposed. The scheme provides accurate force and full state estimation in the presence of robot inertial parameter variations and measurement noise, both subsequently used in the design of a controller. Since the proposed method relies mainly on the position of the plant, it significantly reduces the difficulty and cost of implementation. The velocity, parameter and force signals are estimated from the position. The approach is applied to a typical two-degree-of-freedom (2DOF) robotic manipulator through computer simulation. The results are encouraging and demonstrate the noise rejection ability of the scheme. [Copyright &y& Elsevier]

The blue skate (Dipturus batis) has a patchy distribution across the North‐East Atlantic Ocean, largely restricted to occidental seas around the British Isles following fisheries‐induced population declines and extirpations. The viability of remnant populations remains uncertain and could be impacted by continued fishing and by‐catch pressure, and the projected impacts of climate change. We genotyped 503 samples of D. batis, obtained opportunistically from the widest available geographic range, across 6 350 single nucleotide polymorphisms (SNPs) using a reduced‐representation sequencing approach. Genotypes were used to assess the species' contemporary population structure, estimate effective population sizes and identify putative signals of selection in relation to environmental variables using a seascape genomics approach. We identified genetic discontinuities between inshore (British Isles) and offshore (Rockall and Faroe Island) populations, with differentiation most pronounced across the deep waters of the Rockall Trough. Effective population sizes were largest in the Celtic Sea and Rockall, but low enough to be of potential conservation concern among Scottish and Faroese sites. Among the 21 candidate SNPs under positive selection was one significantly correlated with environmental variables predicted to be affected by climate change, including bottom temperature, salinity and pH. The paucity of well‐annotated elasmobranch genomes precluded us from identifying a putative function for this SNP. Nevertheless, our findings suggest that climate change could inflict a strong selective force upon remnant populations of D. batis, further constraining its already‐restricted habitat. Furthermore, the results provide fundamental insights on the distribution, behaviour and evolutionary biology of D. batis in the North‐East Atlantic that will be useful for the establishment of conservation actions for this and other critically endangered elasmobranchs. [ABSTRACT FROM AUTHOR]

Vulnerable marine ecosystems (VMEs) are particularly susceptible to bottom-fishing activity as they are easily disturbed and slow to recover. A data-driven approach was developed to provide management options for the protection of VMEs under the European Union "deep-sea access regulations." A total of two options within two scenarios were developed. The first scenario defined VME closure areas without consideration of fishing activity. Option 1 proposed closures for the protection of VME habitats and likely habitat, while Option 2 also included areas where four types of VME geophysical elements were present. The second scenario additionally considered fishing. This scenario used VME biomass—fishing intensity relationships to identify a threshold where effort of mobile bottom-contact gears was low and unlikely to have caused significant adverse impacts. Achieving a high level of VME protection requires the creation of many closures (> 100), made up of many small (∼50 km2) and fewer larger closures (> 1000 km2). The greatest protection of VMEs will affect approximately 9% of the mobile fleet fishing effort, while closure scenarios that avoid highly fished areas reduce this to around 4–6%. The framework allows managers to choose the level of risk-aversion they wish to apply in protecting VMEs by comparing alternative strategies. [ABSTRACT FROM AUTHOR]

Microparticles (MPs) are considered to be important biological effectors of several different physiological and pathological processes. There is increasing evidence of their role in haemostasis and thrombosis, and also of their importance in cancer cell survival, invasiveness and metastasis. The level of circulating MPs has been assessed in many different disease states, and there are reports that patients with malignancy and patients with thrombosis have increased levels of circulating MPs and MP-dependent thrombogenic potential. Research into the function and effect of MPs is currently hampered by a lack of standardization in the methods used to identify and quantify them. As these methods improve it is likely that MP assays will be of use both diagnostically and therapeutically in the future. [ABSTRACT FROM AUTHOR]