Sex differences in neuropsychological function and post-concussion symptoms of concussed collegiate athletes.
Our purpose was to determine whether sex differences exist with respect to post-concussion symptoms and neurocognitive function in concussed collegiate athletes. A prospective dependent-sample cohort design was used to compare baseline and post-concussion neuropsychological test scores and endorsed symptoms as functions of serial post-concussion assessment with respect to time and sex. The Immediate Post-concussion Assessment and Cognitive Testing (ImPACT) battery was administered to a multicenter analysis group of 79 concussed athletes. This computerized neuropsychological test was given to the athletes during the preseason and, on average, 2 and 8 days postinjury. Multivariate analyses revealed no significant between-group differences on baseline test performance with respect to sex on any of the ImPACT composite scores or on the total symptom score. Multivariate analyses of post-concussion data revealed a significant main effect of time on ImPACT scores, but no main effect of sex was identified, and no time-by-sex interaction existed. Post hoc analysis revealed that concussed female athletes performed significantly worse than concussed male athletes on visual memory tasks (P = 0.001), and analysis of endorsed post-concussion symptoms revealed that concussed men were significantly more likely than concussed women to report post-concussion symptoms of vomiting (P = 0.001) and sadness (P = 0.017). Athletes' scores were examined individually using the reliable-change methodology. At 2 days post-injury, 58% of concussed athletes had one or more reliable incidents of performance decline or increases in symptom reporting. At 8 days post-concussion, 30% of concussed athletes were still showing one or more reliable change from preseason values. College athletes exhibit differences on visual memory composite scores and symptoms post-concussion as a function of sex. These data support the importance of evaluating neuropsychological status and post-concussion symptoms in concussed athletes. In addition, these data illustrate the importance of analyzing an individual athlete's recovery pattern, because individual differences in recovery trajectories may be overshadowed by global norm-group comparisons.


Fluorescent sensors using DNA-functionalized graphene oxide.
In the past few years, graphene oxide (GO) has emerged as a unique platform for developing DNA-based biosensors, given the DNA adsorption and fluorescence-quenching properties of GO. Adsorbed DNA probes can be desorbed from the GO surface in the presence of target analytes, producing a fluorescence signal. In addition to this initial design, many other strategies have been reported, including the use of aptamers, molecular beacons, and DNAzymes as probes, label-free detection, utilization of the intrinsic fluorescence of GO, and the application of covalently linked DNA probes. The potential applications of DNA-functionalized GO range from environmental monitoring and cell imaging to biomedical diagnosis. In this review, we first summarize the fundamental surface interactions between DNA and GO and the related fluorescence-quenching mechanism. Following that, the various sensor design strategies are critically compared. Problems that must be overcome before this technology can reach its full potential are described, and a few future directions are also discussed.


SIMS(DAIRY): a modelling framework to identify sustainable dairy farms in the UK. Framework description and test for organic systems and N fertiliser optimisation.
Multiple demands are placed on farming systems today. Society, national legislation and market forces seek what could be seen as conflicting outcomes from our agricultural systems, e.g. food quality, affordable prices, a healthy environmental, consideration of animal welfare, biodiversity etc., Many of these demands, or desirable outcomes, are interrelated, so reaching one goal may often compromise another and, importantly, pose a risk to the economic viability of the farm. SIMS(DAIRY), a farm-scale model, was used to explore this complexity for dairy farm systems. SIMS(DAIRY) integrates existing approaches to simulate the effect of interactions between farm management, climate and soil characteristics on losses of nitrogen, phosphorus and carbon. The effects on farm profitability and attributes of biodiversity, milk quality, soil quality and animal welfare are also included. SIMS(DAIRY) can also be used to optimise fertiliser N. In this paper we discuss some limitations and strengths of using SIMS(DAIRY) compared to other modelling approaches and propose some potential improvements. Using the model we evaluated the sustainability of organic dairy systems compared with conventional dairy farms under non-optimised and optimised fertiliser N use. Model outputs showed for example, that organic dairy systems based on grass-clover swards and maize silage resulted in much smaller total GHG emissions per l of milk and slightly smaller losses of NO(3) leaching and NO(x) emissions per l of milk compared with the grassland/maize-based conventional systems. These differences were essentially because the conventional systems rely on indirect energy use for 'fixing' N compared with biological N fixation for the organic systems. SIMS(DAIRY) runs also showed some other potential benefits from the organic systems compared with conventional systems in terms of financial performance and soil quality and biodiversity scores. Optimisation of fertiliser N timings and rates showed a considerable scope to reduce the (GHG emissions per l milk too).


Cow characteristics associated with the variation in number of contacts between dairy cows.
In modern freestall barns where large groups of cows are housed together, the behavior displayed by herd mates can influence the welfare and production of other individuals. Therefore, understanding social interactions in groups of dairy cows is important to enhance herd management and optimize the outcomes of both animal health and welfare in the future. Many factors can affect the number of social contacts in a group. This study aimed to identify which characteristics of a cow are associated with the number of contacts it has with other group members in 2 different functional areas (feeding and resting area) to increase our understanding of the social behavior of dairy cows. Inside 2 herds housed in freestall barns with around 200 lactating cows each, cow positions were recorded with an ultra-wideband real-time location system collecting all cows' positions every second over 2 wk. Using the positioning data of the cows, we quantified the number of contacts between them, assuming that cows spending time in proximity to one another (within a distance of 2.5 m for at least 10 min per day) were interacting socially. We documented in which barn areas these interactions occurred and used linear mixed models to investigate if lactation stage, parity, breed, pregnancy status, estrus, udder health, and claw health affect the number of contacts. We found variation in the number of contacts a cow had between individuals in both functional areas. Cows in later lactation had more contacts in the feeding area than cows in early lactation. Furthermore, in one herd, higher parity cows had fewer contacts in the feeding area than first parity cows, and in the other herd, cows in third parity or higher had more contacts in the resting area. This study indicates that cow characteristics such as parity and days in milk are associated with the number of contacts a cow has daily to its herd mates and provides useful information for further research on social interactions of dairy cows.


An evaluation of the prescribing patterns for under-five patients at a Tertiary Paediatric Hospital in Sierra Leone.
There is limited information on pediatric prescribing in Sierra Leone. This study evaluated prescribing patterns for under-five patients at Ola During Children's Hospital (ODCH) and assessed the extent of rational prescribing. A descriptive, cross-sectional, retrospective study of 294 prescriptions, selected by systematic random sampling was conducted at the outpatient department of ODCH. The World Health Organisation prescribing indicators were analyzed using the SPSS package 16.0. The index of rational drug prescribing (IRDP) was calculated to assess rational prescribing. The average number of medicines per prescription was 3.77. The percentage of medicines prescribed by generic names was 71.0%, while 74.8% and 21.1% of prescriptions had an antibiotic and injection, respectively. The percentage of medicines prescribed from the national essential medicines list was 70.6%. The most commonly prescribed pharmacological groups of medicines were vitamins (85.37%) and antibiotics (82.99%). The IRDP was 2.71, instead of the ideal value of 5. Pediatric prescribing patterns at the outpatient department of ODCH cannot be said to be entirely rational, especially with regards to antibiotic and injection prescribing.


Diagnostic ultrasound induced inertial cavitation to non-invasively restore coronary and microvascular flow in acute myocardial infarction.
Ultrasound induced cavitation has been explored as a method of dissolving intravascular and microvascular thrombi in acute myocardial infarction. The purpose of this study was to determine the type of cavitation required for success, and whether longer pulse duration therapeutic impulses (sustaining the duration of cavitation) could restore both microvascular and epicardial flow with this technique. Accordingly, in 36 hyperlipidemic atherosclerotic pigs, thrombotic occlusions were induced in the mid-left anterior descending artery. Pigs were then randomized to either a) ½ dose tissue plasminogen activator (0.5 mg/kg) alone; or same dose plasminogen activator and an intravenous microbubble infusion with either b) guided high mechanical index short pulse (2.0 MI; 5 usec) therapeutic ultrasound impulses; or c) guided 1.0 mechanical index long pulse (20 usec) impulses. Passive cavitation detectors indicated the high mechanical index impulses (both long and short pulse duration) induced inertial cavitation within the microvasculature. Epicardial recanalization rates following randomized treatments were highest in pigs treated with the long pulse duration therapeutic impulses (83% versus 59% for short pulse, and 49% for tissue plasminogen activator alone; p<0.05). Even without epicardial recanalization, however, early microvascular recovery occurred with both short and long pulse therapeutic impulses (p<0.005 compared to tissue plasminogen activator alone), and wall thickening improved within the risk area only in pigs treated with ultrasound and microbubbles. We conclude that although short pulse duration guided therapeutic impulses from a diagnostic transducer transiently improve microvascular flow, long pulse duration therapeutic impulses produce sustained epicardial and microvascular re-flow in acute myocardial infarction.


Meeting report: the role of environmental lighting and circadian disruption in cancer and other diseases.
Light, including artificial light, has a range of effects on human physiology and behavior and can therefore alter human physiology when inappropriately timed. One example of potential light-induced disruption is the effect of light on circadian organization, including the production of several hormone rhythms. Changes in light-dark exposure (e.g., by nonday occupation or transmeridian travel) shift the timing of the circadian system such that internal rhythms can become desynchronized from both the external environment and internally with each other, impairing our ability to sleep and wake at the appropriate times and compromising physiologic and metabolic processes. Light can also have direct acute effects on neuroendocrine systems, for example, in suppressing melatonin synthesis or elevating cortisol production that may have untoward long-term consequences. For these reasons, the National Institute of Environmental Health Sciences convened a workshop of a diverse group of scientists to consider how best to conduct research on possible connections between lighting and health. According to the participants in the workshop, there are three broad areas of research effort that need to be addressed. First are the basic biophysical and molecular genetic mechanisms for phototransduction for circadian, neuroendocrine, and neurobehavioral regulation. Second are the possible physiologic consequences of disrupting these circadian regulatory processes such as on hormone production, particularly melatonin, and normal and neoplastic tissue growth dynamics. Third are effects of light-induced physiologic disruption on disease occurrence and prognosis, and how prevention and treatment could be improved by application of this knowledge.


Brain basis of cognitive resilience: Prefrontal cortex predicts better reading comprehension in relation to decoding.
The ultimate goal of reading is to understand written text. To accomplish this, children must first master decoding, the ability to translate printed words into sounds. Although decoding and reading comprehension are highly interdependent, some children struggle to decode but comprehend well, whereas others with good decoding skills fail to comprehend. The neural basis underlying individual differences in this discrepancy between decoding and comprehension abilities is virtually unknown. We investigated the neural basis underlying reading discrepancy, defined as the difference between reading comprehension and decoding skills, in a three-part study: 1) The neuroanatomical basis of reading discrepancy in a cross-sectional sample of school-age children with a wide range of reading abilities (Experiment-1; n = 55); 2) Whether a discrepancy-related neural signature is present in beginning readers and predictive of future discrepancy (Experiment-2; n = 43); and 3) Whether discrepancy-related regions are part of a domain-general or a language specialized network, utilizing the 1000 Functional Connectome data and large-scale reverse inference from Neurosynth.org (Experiment-3). Results converged onto the left dorsolateral prefrontal cortex (DLPFC), as related to having discrepantly higher reading comprehension relative to decoding ability. Increased gray matter volume (GMV) was associated with greater discrepancy (Experiment-1). Region-of-interest (ROI) analyses based on the left DLPFC cluster identified in Experiment-1 revealed that regional GMV within this ROI in beginning readers predicted discrepancy three years later (Experiment-2). This region was associated with the fronto-parietal network that is considered fundamental for working memory and cognitive control (Experiment-3). Processes related to the prefrontal cortex might be linked to reading discrepancy. The findings may be important for understanding cognitive resilience, which we operationalize as those individuals with greater higher-order reading skills such as reading comprehension compared to lower-order reading skills such as decoding skills. Our study provides insights into reading development, existing theories of reading, and cognitive processes that are potentially significant to a wide range of reading disorders.


Catalysis-Hub.org, an open electronic structure database for surface reactions.
We present a new open repository for chemical reactions on catalytic surfaces, available at https://www.catalysis-hub.org . The featured database for surface reactions contains more than 100,000 chemisorption and reaction energies obtained from electronic structure calculations, and is continuously being updated with new datasets. In addition to providing quantum-mechanical results for a broad range of reactions and surfaces from different publications, the database features a systematic, large-scale study of chemical adsorption and hydrogenation on bimetallic alloy surfaces. The database contains reaction specific information, such as the surface composition and reaction energy for each reaction, as well as the surface geometries and calculational parameters, essential for data reproducibility. By providing direct access via the web-interface as well as a Python API, we seek to accelerate the discovery of catalytic materials for sustainable energy applications by enabling researchers to efficiently use the data as a basis for new calculations and model generation.


Sham acupuncture may be as efficacious as true acupuncture: a systematic review of clinical trials.
This study sought to determine whether sham acupuncture is as efficacious as true acupuncture, as defined by traditional acupuncture theories. A systematic review was conducted of clinical trials that used sham acupuncture controls with needle insertion at wrong points (points not indicated for the condition) or non-points (locations that are not known acupuncture points). This study used a convenience sample of 229 articles resulting from a PubMed search using the keyword "acupuncture" and limited to "clinical trials" published in English in 2005 or 2006. Studies were categorized by use of wrong points versus non-points and the use of normal insertion and stimulation versus superficial insertion or minimal stimulation. Thirty-eight acupuncture trials were identified. Most studies (22/38 = 58%) found no statistically significant difference in outcomes, and most of these (13/22 = 59%) found that sham acupuncture may be as efficacious as true acupuncture, especially when superficial needling was applied to non-points. The findings cast doubt on the validity of traditional acupuncture theories about point locations and indications. Scientific rationales for acupuncture trials are needed to define valid controls, and the theoretical basis for traditional acupuncture practice needs to be re-evaluated.


Conversion from calcineurin inhibitor-based immunosuppression to mammalian target of rapamycin inhibitors or belatacept in renal transplant recipients.
The calcineurin inhibitors (CNIs) remain the standard of care for maintenance immunosuppression following renal transplantation. CNIs have demonstrated their effectiveness in reducing acute cellular rejection; however, some evidence suggests that these compounds negatively affect native renal function and are associated with allograft injury in renal transplant recipients. CNIs have also been linked with hypertension, new-onset diabetes after transplantation, tremor, and thrombotic microangiopathy, which have significant consequences for long-term allograft function and patient health overall. Thus, converting patients to a non-CNI-based regimen may improve renal function and also provide extrarenal benefits. A number of studies have been conducted that explore CNI conversion strategies in renal transplant recipients in an effort to improve long-term allograft function and survival. These include converting to alternative, non-nephrotoxic, maintenance immunosuppressants, such as the mammalian target of rapamycin inhibitors (sirolimus and everolimus) and the costimulation blocker belatacept. In this review of literature, evidence for the potential renal and extrarenal benefits of conversion to these non-CNI-based regimens is evaluated. Clinical challenges, including the adverse event profiles of non-CNI-based regimens and the selection of candidates for conversion, are also examined.


Systematics and plastid genome evolution of the cryptically photosynthetic parasitic plant genus Cuscuta (Convolvulaceae).
The genus Cuscuta L. (Convolvulaceae), commonly known as dodders, are epiphytic vines that invade the stems of their host with haustorial feeding structures at the points of contact. Although they lack expanded leaves, some species are noticeably chlorophyllous, especially as seedlings and in maturing fruits. Some species are reported as crop pests of worldwide distribution, whereas others are extremely rare and have local distributions and apparent niche specificity. A strong phylogenetic framework for this large genus is essential to understand the interesting ecological, morphological and molecular phenomena that occur within these parasites in an evolutionary context. Here we present a well-supported phylogeny of Cuscuta using sequences of the nuclear ribosomal internal transcribed spacer and plastid rps2, rbcL and matK from representatives across most of the taxonomic diversity of the genus. We use the phylogeny to interpret morphological and plastid genome evolution within the genus. At least three currently recognized taxonomic sections are not monophyletic and subgenus Cuscuta is unequivocally paraphyletic. Plastid genes are extremely variable with regards to evolutionary constraint, with rbcL exhibiting even higher levels of purifying selection in Cuscuta than photosynthetic relatives. Nuclear genome size is highly variable within Cuscuta, particularly within subgenus Grammica, and in some cases may indicate the existence of cryptic species in this large clade of morphologically similar species. Some morphological characters traditionally used to define major taxonomic splits within Cuscuta are homoplastic and are of limited use in defining true evolutionary groups. Chloroplast genome evolution seems to have evolved in a punctuated fashion, with episodes of loss involving suites of genes or tRNAs followed by stabilization of gene content in major clades. Nearly all species of Cuscuta retain some photosynthetic ability, most likely for nutrient apportionment to their seeds, while complete loss of photosynthesis and possible loss of the entire chloroplast genome is limited to a single small clade of outcrossing species found primarily in western South America.


The Employability Process of Spanish Retired Elite Athletes: Gender and Sport Success Comparison.
The aims of the study were: (i) to describe the work integration after retirement in elite athletes, (ii) to compare the working integration of women and men, and Olympic and non-Olympic athletes, and (iii) to specify the factors that affect their employment status and current monthly income. A total of 476 former elite athletes were surveyed. Non-parametric statistics were applied to compare the differences between groups and a classification tree analysis was performed for the dependent variables. The former elite athlete's unemployment rate was better than the general population. At the gender comparison, a wage gap appeared between women and men. At the comparison between Olympic and non-Olympic athletes, the link to first employment differed in both groups. In the prediction models, finishing higher education arose as a key factor of the working status and the monthly salary. Among those without higher education studies, planning arose as a factor determining their salary, while among those with high qualifications, gender was the key factor. This study supports the importance of a holistic view of athletic career development and it offers practical insights into the process of reaching first employment after retirement.


Hybrid lethal systems in the Drosophila melanogaster species complex. II. The Zygotic hybrid rescue (Zhr) gene of D. melanogaster.
Hybrid females from Drosophila simulans females x Drosophila melanogaster males die as embryos while hybrid males from the reciprocal cross die as larvae. We have recovered a mutation in melanogaster that rescues the former hybrid females. It was located on the X chromosome at a position close to the centromere, and it was a zygotically acting gene, in contrast with mhr (maternal hybrid rescue) in simulans that rescues the same hybrids maternally. We named it Zhr (Zygotic hybrid rescue). The gene also rescues hybrid females from embryonic lethals in crosses of Drosophila mauritiana females x D. melanogaster males and of Drosophila sechellia females x D. melanogaster males. Independence of the hybrid embryonic lethality and the hybrid larval lethality suggested in a companion study was confirmed by employing two rescue genes, Zhr and Hmr (Hybrid male rescue), in doubly lethal hybrids. A model is proposed to explain the genetic mechanisms of hybrid lethalities as well as the evolutionary pathways.


Evolution of chemokine receptors is driven by mutations in the sodium binding site.
Chemokines and their receptors (members of the GPCR super-family) are involved in a wide variety of physiological processes and diseases; thus, understanding the specificity of the chemokine receptor family could help develop new receptor specific drugs. Here, we explore the evolutionary mechanisms that led to the emergence of the chemokine receptors. Based on GPCR hierarchical classification, we analyzed nested GPCR sets with an eigen decomposition approach of the sequence covariation matrix and determined three key residues whose mutation was crucial for the emergence of the chemokine receptors and their subsequent divergence into homeostatic and inflammatory receptors. These residues are part of the allosteric sodium binding site. Their structural and functional roles were investigated by molecular dynamics simulations of CXCR4 and CCR5 as prototypes of homeostatic and inflammatory chemokine receptors, respectively. This study indicates that the three mutations crucial for the evolution of the chemokine receptors dramatically altered the sodium binding mode. In CXCR4, the sodium ion is tightly bound by four protein atoms and one water molecule. In CCR5, the sodium ion is mobile within the binding pocket and moves between different sites involving from one to three protein atoms and two to five water molecules. Analysis of chemokine receptor evolution reveals that a highly constrained sodium binding site characterized most ancient receptors, and that the constraints were subsequently loosened during the divergence of this receptor family. We discuss the implications of these findings for the evolution of the chemokine receptor functions and mechanisms of action.


Conceptualizing Landscapes Through Language: The Role of Native Language and Expertise in the Representation of Waterbody Related Terms.
Landscapes are essential to human life: they provide a multitude of material (food, water, pollination) and nonmaterial (beauty, tranquility, recreation) values. Their importance is enshrined in international conventions and treaties, committing signatories to protecting, monitoring, and managing all landscapes. Yet, relatively little is known about how people conceptualize "landscape" and its constituents. There is emerging evidence that conceptualizations of landscape entities may influence landscape management. This in turn raises the question as to how people speaking different languages, and with differing levels of expertise, may differ in conceptualizing landscape domains as a whole. In this paper, we investigated how people conceptualize landscape-related terms in a specific domain-waterbodies-by comparing German and English-speaking experts and nonexperts. We identified commonly used waterbody terms in sustainability discourses in both languages, and used those terms to collect sensory, motor, and affective ratings from participants. Speakers of all groups appear to conceptualize the domain of waterbody terms in comparable ways. Nevertheless, we uncovered subtle differences across languages for nonexperts. For example, there were differences in which waterbodies were associated with calm happiness in each language. In addition, olfaction seemingly plays a role in English speakers' conceptualization of waterbodies, but not German speakers. Taken together, this suggests the ways in which people relate to landscape although shared in many respects may also be shaped in part by their specific language and culture.


Minerva: an alignment- and reference-free approach to deconvolve Linked-Reads for metagenomics.
Emerging Linked-Read technologies (aka read cloud or barcoded short-reads) have revived interest in short-read technology as a viable approach to understand large-scale structures in genomes and metagenomes. Linked-Read technologies, such as the 10x Chromium system, use a microfluidic system and a specialized set of 3' barcodes (aka UIDs) to tag short DNA reads sourced from the same long fragment of DNA; subsequently, the tagged reads are sequenced on standard short-read platforms. This approach results in interesting compromises. Each long fragment of DNA is only sparsely covered by reads, no information about the ordering of reads from the same fragment is preserved, and 3' barcodes match reads from roughly 2-20 long fragments of DNA. However, compared to long-read technologies, the cost per base to sequence is far lower, far less input DNA is required, and the per base error rate is that of Illumina short-reads. In this paper, we formally describe a particular algorithmic issue common to Linked-Read technology: the deconvolution of reads with a single 3' barcode into clusters that represent single long fragments of DNA. We introduce Minerva, a graph-based algorithm that approximately solves the barcode deconvolution problem for metagenomic data (where reference genomes may be incomplete or unavailable). Additionally, we develop two demonstrations where the deconvolution of barcoded reads improves downstream results, improving the specificity of taxonomic assignments and of k-mer-based clustering. To the best of our knowledge, we are the first to address the problem of barcode deconvolution in metagenomics.


Heat-Related Training and Educational Material Needs among Oil Spill Cleanup Responders.
Heat-related illness (HRI), injury, and death among oil spill cleanup responders can be prevented through training and educational materials. This study assessed heat-related training and educational materials currently used and desired by oil spill cleanup responders. A needs assessment was completed by 65 oil spill cleanup responders regarding their occupational heat-related experiences and training needs. Oil spill cleanup responders reported participating on average in 37 oil spill cleanup activities per year. Most reported experiencing additional HRI risk factors, such as high temperatures and humidity and wearing personal protective equipment and clothing ensembles, respirators, and personal flotation devices. Many reported experiencing symptoms of HRI (profuse sweating, headache, weakness, decreased urine output, high body temperatures) and experiencing heat exhaustion. Although multiple prevention controls were reported, only 1 in 4 reported using an acclimatization plan. The most common training delivery method and education received included just-in-time training and printed materials. The most desirable future training delivery methods and education products were smartphone or tablet applications, printed materials, and online training. Findings from this study may be beneficial to safety and health professionals and health educators, particularly those interested in developing heat stress training and educational materials for oil spill cleanup responders.


Molecular determinants of membrane potential dependence in vertebrate gap junction channels.
The conductance, g(j), of many gap junctions depends on voltage between the coupled cells (transjunctional voltage, V(j)) with little effect of the absolute membrane potential (V(m)) in the two cells; others show combined V(j) and V(m) dependence. We examined the molecular determinants of V(m) dependence by using rat connexin 43 expressed in paired Xenopus oocytes. These junctions have, in addition to V(j) dependence, V(m) dependence such that equal depolarization of both cells decreases g(j). The dependence of g(j) on V(m) was abolished by truncation of the C-terminal domain (CT) at residue 242 but not at 257. There are two charged residues between 242 and 257. In full-length Cx43, mutations neutralizing either one of these charges, Arg243Gln and Asp245Gln, decreased and increased V(m) dependence, respectively, suggesting that these residues are part of the V(m) sensor. Mutating both residues together abolished V(m) dependence, although there is no net change in charge. The neutralizing mutations, together or separately, had no effect on V(j) dependence. Thus, the voltage sensors must differ. However, V(j) gating was somewhat modulated by V(m), and V(m) gating was reduced when the V(j) gate was closed. These data suggest that the two forms of voltage dependence are mediated by separate but interacting domains.


Anatomical study to investigate the feasibility of pedicled nerve, free vessel gastrocnemius muscle transfer for restoration of biceps function.
A challenging problem is the patient with a total brachial plexus injury with nerve root avulsions. In these patients nerve repair is not possible and no local functioning muscles are available for transfer. Current techniques involve either nerve repair using donor nerves from the contralateral limb or free muscle transfer neurotized by intercostal nerves. The problem with both these techniques is that they are dependent on neural regeneration, which is imperfect. To overcome the problem we propose a technique of transferring a distant muscle whilst retaining its neural supply. Gastrocnemius is a strong muscle and one suitable for free tissue transfer. This study assessed the possibility of transferring gastrocnemius on its neural supply by determining the length of nerve available and whether it was possible to dissect the nerve to gastrocnemius from the main body of the sciatic nerve. We found that the latter was possible, and that the length of dissected nerve would allow transfer of the innervated muscle from the calf to the axilla.


Anti-Apoptotic Gene Delivery with cyclo-(d-Trp-Tyr) Peptide Nanotube via Eye Drop Following Corneal Epithelial Debridement.
Corneal keratocyte apoptosis triggered by cornel debridement is one mechanism of corneal disorders. In this study, the feasibility of cyclo-(d-Trp-Tyr) peptide nanotubes (PNTs) as carriers of caspase 3 silence shRNA delivery was assessed. A model of epithelial injury by epithelial debridement was applied to investigate the feasibility of PNTs as gene delivery carriers on corneal injury. First, the PNTs were found within 2 μm in length and 300 nm in width by an atomic force microscope and confocal laser microscope system. Plasmid DNAs were observed to be associated with PNTs by atomic force microscope and confocal laser scanning microscope. The plasmids were associated with tyrosine of PNTs with a binding constant of 2.7 × 108 M-1. The stability of plasmid DNA with PNTs against the DNase was found at 60 min. Using thioflavin T pre-stained PNTs on the corneal eye drop delivery, the distribution of PNTs was in the epithelial and stroma regions. After corneal debridement, the rhodamine-labeled plasmid DNA and thioflavin T pre-stained PNTs were also delivered and could be observed in the stroma of cornea. PNTs complexed with anti-apoptotic plasmid caspase 3 silencing shRNA eye drop delivery decreased 41% of caspase 3 activity after the first dose by caspase 3 activity and Western blot analysis.


The Military Injuries: Understanding Post-Traumatic Epilepsy Study: Understanding Relationships among Lifetime Traumatic Brain Injury History, Epilepsy, and Quality of Life.
Understanding risk for epilepsy among persons who sustain a mild (mTBI) traumatic brain injury (TBI) is crucial for effective intervention and prevention. However, mTBI is frequently undocumented or poorly documented in health records. Further, health records are non-continuous, such as when persons move through health systems (e.g., from Department of Defense to Veterans Affairs [VA] or between jobs in the civilian sector), making population-based assessments of this relationship challenging. Here, we introduce the MINUTE (Military INjuries-Understanding post-Traumatic Epilepsy) study, which integrates data from the Veterans Health Administration with self-report survey data for post-9/11 veterans (n = 2603) with histories of TBI, epilepsy and controls without a history of TBI or epilepsy. This article describes the MINUTE study design, implementation, hypotheses, and initial results across four groups of interest for neurotrauma: 1) control; 2) epilepsy; 3) TBI; and 4) post-traumatic epilepsy (PTE). Using combined survey and health record data, we test hypotheses examining lifetime history of TBI and the differential impacts of TBI, epilepsy, and PTE on quality of life. The MINUTE study revealed high rates of undocumented lifetime TBIs among veterans with epilepsy who had no evidence of TBI in VA medical records. Further, worse physical functioning and health-related quality of life were found for persons with epilepsy + TBI compared to those with either epilepsy or TBI alone. This effect was not fully explained by TBI severity. These insights provide valuable opportunities to optimize the resilience, delivery of health services, and community reintegration of veterans with TBI and complex comorbidity.


Roundup causes embryonic development failure and alters metabolic pathways and gut microbiota functionality in non-target species.
Research around the weedkiller Roundup is among the most contentious of the twenty-first century. Scientists have provided inconclusive evidence that the weedkiller causes cancer and other life-threatening diseases, while industry-paid research reports that the weedkiller has no adverse effect on humans or animals. Much of the controversial evidence on Roundup is rooted in the approach used to determine safe use of chemicals, defined by outdated toxicity tests. We apply a system biology approach to the biomedical and ecological model species Daphnia to quantify the impact of glyphosate and of its commercial formula, Roundup, on fitness, genome-wide transcription and gut microbiota, taking full advantage of clonal reproduction in Daphnia. We then apply machine learning-based statistical analysis to identify and prioritize correlations between genome-wide transcriptional and microbiota changes. We demonstrate that chronic exposure to ecologically relevant concentrations of glyphosate and Roundup at the approved regulatory threshold for drinking water in the US induce embryonic developmental failure, induce significant DNA damage (genotoxicity), and interfere with signaling. Furthermore, chronic exposure to the weedkiller alters the gut microbiota functionality and composition interfering with carbon and fat metabolism, as well as homeostasis. Using the "Reactome," we identify conserved pathways across the Tree of Life, which are potential targets for Roundup in other species, including liver metabolism, inflammation pathways, and collagen degradation, responsible for the repair of wounds and tissue remodeling. Our results show that chronic exposure to concentrations of Roundup and glyphosate at the approved regulatory threshold for drinking water causes embryonic development failure and alteration of key metabolic functions via direct effect on the host molecular processes and indirect effect on the gut microbiota. The ecological model species Daphnia occupies a central position in the food web of aquatic ecosystems, being the preferred food of small vertebrates and invertebrates as well as a grazer of algae and bacteria. The impact of the weedkiller on this keystone species has cascading effects on aquatic food webs, affecting their ability to deliver critical ecosystem services. Video Abstract.


BoHV-1-Vectored BVDV-2 Subunit Vaccine Induces BVDV Cross-Reactive Cellular Immune Responses and Protects against BVDV-2 Challenge.
The bovine respiratory disease complex (BRDC) remains a major problem for both beef and dairy cattle industries worldwide. BRDC frequently involves an initial viral respiratory infection resulting in immunosuppression, which creates a favorable condition for fatal secondary bacterial infection. Current polyvalent modified live vaccines against bovine herpesvirus type 1(BoHV-1) and bovine viral diarrhea virus (BVDV) have limitations concerning their safety and efficacy. To address these shortcomings and safety issues, we have constructed a quadruple gene mutated BoHV-1 vaccine vector (BoHV-1 QMV), which expresses BVDV type 2, chimeric E2 and Flag-tagged Erns-fused with bovine granulocyte monocyte colony-stimulating factor (GM-CSF) designated here as QMV-BVD2*. Here we compared the safety, immunogenicity, and protective efficacy of QMV-BVD2* vaccination in calves against BVDV-2 with Zoetis Bovi-shield Gold 3 trivalent (BoHV-1, BVDV types 1 and 2) vaccine. The QMV-BVD2* prototype subunit vaccine induced the BoHV-1 and BVDV-2 neutralizing antibody responses along with BVDV-1 and -2 cross-reactive cellular immune responses. Moreover, after a virulent BVDV-2 challenge, the QMV-BVD2* prototype subunit vaccine conferred a more rapid recall BVDV-2-specific neutralizing antibody response and considerably better recall BVDV types 1 and 2-cross protective cellular immune responses than that of the Zoetis Bovi-shield Gold 3.


Multifunctional theranostic agents based on prussian blue nanoparticles for tumor targeted and MRI-guided photodynamic/photothermal combined treatment.
The independence of photodynamic or photothermal modality create difficulties in the success of tumor therapy. In this current study, a multifunctional nanotheranostic agent of PDE-Ce6-HA was developed for tumor targeted and MRI-guided photodynamic/photothermal combined therapy (PDT/PTT). For this purpose, the near-infrared-absorbing nanoparticles of prussian blue were coated with polydopamine and successively conjugated with chlorin e6 (Ce6) for reactive oxygen species (ROS) generation. The resultant nanoparticles, denoted as PDE-Ce6, were then modified with hyaluronic acid (HA) through electrostatic interaction to yield the final therapeutic agent of PDE-Ce6-HA NPs. PDE-Ce6-HA NPs not only exhibited high colloid stability, good biocompatibility and suitable transverse relaxation rate (0.54 mM-1 s-1), but also high photothermal conversion efficiency (40.4%) and excellent ROS generation efficiency under NIR light irradiation. The confocal microscopy images demonstrated a selective uptake of PDE-Ce6-HA by CD44 overexpressed HeLa cells via HA-mediated endocytosis. Meanwhile, in vitro anti-cancer evaluation verified the significant photodynamic and photothermal combined effects of PDE-Ce6-HA on cancer cells. Moreover, PDE-Ce6-HA led to an increase of T1-MRI contrast in tumor site. Furthermore, in vivo anti-tumor evaluation proved that the PDE-Ce6-HA under both 808 and 670 nm laser showed significantly high tumor growth inhibition effects compared with individual PTT or PDT. Hence, PDE-Ce6-HA is applicable in tumor targeted and MRI-guided photodynamic/photothermal combined treatment.


Modafinil reverses phencyclidine-induced deficits in cognitive flexibility, cerebral metabolism, and functional brain connectivity.
In the present study, we employ mathematical modeling (partial least squares regression, PLSR) to elucidate the functional connectivity signatures of discrete brain regions in order to identify the functional networks subserving PCP-induced disruption of distinct cognitive functions and their restoration by the procognitive drug modafinil. We examine the functional connectivity signatures of discrete brain regions that show overt alterations in metabolism, as measured by semiquantitative 2-deoxyglucose autoradiography, in an animal model (subchronic phencyclidine [PCP] treatment), which shows cognitive inflexibility with relevance to the cognitive deficits seen in schizophrenia. We identify the specific components of functional connectivity that contribute to the rescue of this cognitive inflexibility and to the restoration of overt cerebral metabolism by modafinil. We demonstrate that modafinil reversed both the PCP-induced deficit in the ability to switch attentional set and the PCP-induced hypometabolism in the prefrontal (anterior prelimbic) and retrosplenial cortices. Furthermore, modafinil selectively enhanced metabolism in the medial prelimbic cortex. The functional connectivity signatures of these regions identified a unifying functional subsystem underlying the influence of modafinil on cerebral metabolism and cognitive flexibility that included the nucleus accumbens core and locus coeruleus. In addition, these functional connectivity signatures identified coupling events specific to each brain region, which relate to known anatomical connectivity. These data support clinical evidence that modafinil may alleviate cognitive deficits in schizophrenia and also demonstrate the benefit of applying PLSR modeling to characterize functional brain networks in translational models relevant to central nervous system dysfunction.


The protective effect of Tribulus terrestris in diabetes.
Tribulus terrestris L (TT) is used in the Arabic folk medicine to treat various diseases. The aim of this article was to investigate the protective effects of TT in diabetes mellitus (DM). Diabetes is known to increase reactive oxygen species (ROS) level that subsequently contributes to the pathogenesis of diabetes. Rats were divided into six groups and treated with either saline, glibenclamide (Glib), or TT for 30 days. Rats in group 1 were given saline after the onset of streptozotocin (STZ)-induced diabetes; the second diabetic group was administered Glib (10 mg/kg body weight). The third diabetic group was treated with the TT extract (2 g/kg body weight), while the first, second, and third nondiabetic groups were treated with saline solution, Glib, and TT extract, respectively. At the end of the experiment, serum and liver samples were collected for biochemical and morphological analysis. Levels of serum alanine aminotransferase (ALT) and creatinine were estimated. In addition, levels of malondialdehyde (MDA) and reduced glutathione (GSH) were assayed in the liver. The tested TT extract significantly decreased the levels of ALT and creatinine in the serum (P < 0.05) in diabetic groups and lowered the MDA level in liver (P < 0.05) in diabetic and (P < 0.01) nondiabetic groups. On the other hand, levels of reduced GSH in liver were significantly increased (P < 0.01) in diabetic rats treated with TT. Histopathological examination revealed significant recovery of liver in herb-treated rats. This investigation suggests that the protective effect of TT for STZ-induced diabetic rats may be mediated by inhibiting oxidative stress.


Displacement of Implant Abutments Following Initial and Repeated Torqueing.
To measure and compare the three-dimensional (3D) position of nine different abutments manufactured by different manufacturers after repeated torqueing on an internal-hexagon implant. Nine tapered implants were placed into an acrylic resin block. Five specimens each of nine different abutments (n = 45) were placed into one of nine implants. The abutments were handtightened and then torqued to the manufacturer-recommended torque of 30 Ncm. After 10 minutes, 30 Ncm of torque was reapplied. Another 10 minutes elapsed before testing was completed. Images were recorded in 12-second intervals. The spatial relationship of the abutments to the resin block was determined using 3D digital image correlation. Commercial image correlation software was used to analyze the displacements. Mean displacements for the abutments were calculated in three dimensions and overall for both torque applications. Statistical comparisons were done with a t test and a step-down Bonferroni correction. The overall 3D displacement of the Atlantis Titanium abutment after the second applied torque was significantly greater than that of two of the eight other abutments. Displacement in all three dimensions for the Atlantis Titanium abutment changed direction between the first and second torque applications. All abutments moved further in the same direction except for the Atlantis Titanium abutment, which moved back toward its original hand-tightened position horizontally after the second torque application. Re-torqueing of abutments after a 10-minute interval leads to minor displacement of varying degrees between the abutment and a tapered implant. A potential effect of embedment relaxation and/or manufacturing errors should be taken into consideration when selecting an abutment for a cement-retained crown on a tapered implant. Accordingly, clinicians may benefit from adjusting cement-retained implant crowns after re-torqueing the abutments to prevent potential occlusal and interproximal contact problems.


First Report of the Root-Knot Nematode Meloidogyne javanica on Buchu (Agathosma betulina) in South Africa.
Agathosma betulina, commonly known as buchu, has been used for centuries by the indigenous people of South Africa for medicinal purposes. Currently, the essential oils from buchu are used in medicine, food flavorings, and aromatic oils. Increased exploitation of natural growing buchu in the Fynbos biome and a worldwide shortage of buchu oil encouraged commercial cultivation in South Africa. The root-knot nematode (Meloidogyne spp.) is one of the most common plant-parasitic nematodes found on commercial crops grown in the Western Cape. It has also been isolated from the soil and roots of plants in the natural Fynbos vegetation (2). In June 2003, a nursery propagating buchu plants experienced problems with poor growth. Examination of the buchu roots under a stereo microscope showed extensive galling with large numbers of female root-knot nematodes with eggsacs. Nematode extractions of the soil were also done. Only second-stage juveniles of Meloidogyne spp. (311 per 250 ml of soil) were recovered. A polymerase chain reaction (PCR)-based diagnostic method (1) was used for the identification of the root-knot nematode species. Ten intact females were dissected from the roots and individually placed directly in 5 μl drops of 1× PCR reaction buffer (16 mM [NH4]2SO4, 67 mM tris-HCL, pH 8.8, 0.1% vol/vol Tween 20) ontaining 60 μg/ml of proteinase K. The tube was kept at -80°C for a minimum of 10 min. The tube was incubated at 60°C for 15 min and 5 min at 95°C. The PCR amplifications were then prepared directly in the same tube. Amplified DNA fragments were digested with HinfI and DraI. The digested DNA was loaded on a 2% agarose gel, separated by electrophoresis, and detected by ethidium bromide staining. The digested amplified DNA fragments correspond to those of Meloidogyne javanica. Morphological characteristics were used to verify the PCR-based identification of the nematode. To our knowledge, this is the first report of M. javanica causing extensive galling on the roots of Agathosma betulina. Visual damage to the roots indicates the root-knot nematode to be an important threat to the commercial cultivation of buchu. References: (1) R. Knoetze. Potential of the polymerase chain reaction for the identification of plant-parasitic nematodes. M.Sc. thesis. University of Stellenbosch, Stellenbosch, South Africa, 1999. (2) A. J. Meyer, S. Afr. J. Enol. Vitic., 20:75, 1999.


Inferring HIV-1 transmission networks and sources of epidemic spread in Africa with deep-sequence phylogenetic analysis.
To prevent new infections with human immunodeficiency virus type 1 (HIV-1) in sub-Saharan Africa, UNAIDS recommends targeting interventions to populations that are at high risk of acquiring and passing on the virus. Yet it is often unclear who and where these 'source' populations are. Here we demonstrate how viral deep-sequencing can be used to reconstruct HIV-1 transmission networks and to infer the direction of transmission in these networks. We are able to deep-sequence virus from a large population-based sample of infected individuals in Rakai District, Uganda, reconstruct partial transmission networks, and infer the direction of transmission within them at an estimated error rate of 16.3% [8.8-28.3%]. With this error rate, deep-sequence phylogenetics cannot be used against individuals in legal contexts, but is sufficiently low for population-level inferences into the sources of epidemic spread. The technique presents new opportunities for characterizing source populations and for targeting of HIV-1 prevention interventions in Africa.


Regulation of neurotrophic factors and energy metabolism by antidepressants in astrocytes.
There is growing evidence that astrocytes are involved in the neuropathology of major depression. In particular, decreases in glial cell density observed in the cerebral cortex of individuals with major depressive disorder are accompanied by a reduction of several astrocytic markers suggesting that astrocyte dysfunction may contribute to the pathophysiology of major depression. In rodents, glial loss in the prefrontal cortex is sufficient to induce depressive-like behaviors and antidepressant treatment prevents the stress-induced reduction of astrocyte number in the hippocampus. Collectively, these data support the existence of a link between astrocyte loss or dysfunction, depressive-like behavior and antidepressant treatment. Astrocytes are increasingly recognized to play important roles in neuronal development, neurotransmission, synaptic plasticity and maintenance of brain homeostasis. It is also well established that astrocytes provide trophic, structural, and metabolic support to neurons. In this article, we review evidence that antidepressants regulate energy metabolism and neurotrophic factor expression with particular emphasis on studies in astrocytes. These observations support a role for astrocytes as new targets for antidepressants. The contribution of changes in astrocyte glucose metabolism and neurotrophic factor expression to the therapeutic effects of antidepressants remains to be established.


Enteral tube feeding in the intensive care unit: factors impeding adequate delivery.
To evaluate those factors that impact on the delivery of enteral tube feeding. Prospective study. Medical intensive care units (ICU) and coronary care units at two university-based hospitals. Forty-four medical ICU/coronary care unit patients (mean age, 57.8 yrs; 70% male) who were to receive nothing by mouth and were placed on enteral tube feeding. Rate of enteral tube feeding ordered, actual volume delivered, patient position, residual volume, flush volume, presence of blue food coloring in oropharynx, and stool frequency were recorded every 4 hrs. Duration and reason for cessation of enteral tube feeding were documented. Physicians ordered a daily mean volume of enteral tube feeding that was 65.6% of goal requirements, but an average of only 78.1% of the volume ordered was actually infused. Thus, patients received a mean volume of enteral tube feeding for all 339 days of infusion that was 51.6% of goal (range, 15.1% to 87.1%). Only 14% of patients reached > or = 90% of goal feeding (for a single day) within 72 hrs of the start of enteral tube feeding infusion. Of 24 patients weighed before and after, 54% were noted to lose weight on enteral tube feeding. Declining albumin levels through the enteral tube feeding period correlated significantly with decreasing percent of goal calories infused (p = .042; r2 = .13). Diarrhea occurred in 23 patients (52.3%) for a mean 38.2% of enteral tube feeding days. In >1490 bedside evaluations, patients were observed to be in the supine position only 0.45%, residual volume of >200 mL was found 2.8%, and blue food coloring was found in the oropharynx 5.1% of the time. Despite this, cessation of enteral tube feeding occurred in 83.7% of patients for a mean 19.6% of the potential infusion time. Sixty-six percent of the enteral tube feeding cessations was judged to be attributable to avoidable causes. The current manner in which enteral tube feeding is delivered in the ICU results in grossly inadequate nutritional support. Barely one half of patient caloric requirements are met because of underordering by physicians and reduced delivery through frequent and often inappropriate cessation of feedings.


The Arabidopsis lyrata genome sequence and the basis of rapid genome size change.
We report the 207-Mb genome sequence of the North American Arabidopsis lyrata strain MN47 based on 8.3× dideoxy sequence coverage. We predict 32,670 genes in this outcrossing species compared to the 27,025 genes in the selfing species Arabidopsis thaliana. The much smaller 125-Mb genome of A. thaliana, which diverged from A. lyrata 10 million years ago, likely constitutes the derived state for the family. We found evidence for DNA loss from large-scale rearrangements, but most of the difference in genome size can be attributed to hundreds of thousands of small deletions, mostly in noncoding DNA and transposons. Analysis of deletions and insertions still segregating in A. thaliana indicates that the process of DNA loss is ongoing, suggesting pervasive selection for a smaller genome. The high-quality reference genome sequence for A. lyrata will be an important resource for functional, evolutionary and ecological studies in the genus Arabidopsis.


Aberrations of diffracted wave fields. I. Optical imaging.
The concept of aberrations of diffracted waves is revisited by using the Rayleigh-Sommerfeld theory of diffraction, and it is pointed out that these aberrations are in a class by themselves; they are only deceptively similar to the aberrations of a rotationally symmetric imaging system. Although an exact Fourier-transform expression can be written for the diffracted wave field, its numerical calculation is cumbersome because of the dependence of the aberrations of the diffracted wave on the observation point. This is true regardless of whether the diffracted wave field is observed on a plane or a hemisphere. It is shown that the Fresnel and Fraunhofer approximations, which neglect these aberrations and thereby simplify the calculations, are valid in imaging applications.


A tagged helper-free Friend virus causes clonal erythroblast immortality by specific proviral integration in the cellular genome.
A colinear molecular clone of the Lilly-Steeves polycythemia strain of Friend spleen focus-forming virus (SFFV) was modified by inserting a 215-base-pair tag of simian virus 40 DNA into its nonfunctional pol gene region. The DNA was then transfected into psi-2 packaging cells, and helper-free tagged SFFV was recovered in the culture medium. Injection of this helper-free virus into NIH/Swiss mice caused transient mild splenomegaly and formation of spleen foci at 9 to 10 days. Although the vast majority of infected erythroblast clones then differentiated and died out, rare cell clones that were present in only 20 to 30% of the mice grew extensively by 26 to 33 days to form transplantable leukemias. The clonality of these leukemias was established by Southern blot analysis of their DNAs by using several restriction endonucleases and the simian virus 40 tag as a hybridization probe. All transplantable leukemias lacked helper virus contamination and contained a single tagged SFFV provirus that expressed the mitogenic env gene product gp55. The SFFV proviruses in these leukemias also appeared to be integrated into a few tightly clustered sites in the cellular genome. Although the tagged SFFV caused polycythemia during the polyclonal early stage of erythroblastosis, growth of the helper-free clonal erythroleukemias caused severe anemia. These results suggest that a single SFFV can cause mitosis of erythroblasts, and that cell immortalization also occurs when the provirus integrates into a critical site in the host genome. We propose that mice with clonal-stage leukemia become anemic because the immortalizing proviral integrations interfere with the cellular commitment to differentiate.


Transcription Factor T-Bet in Atlantic Salmon: Characterization and Gene Expression in Mucosal Tissues during Aeromonas Salmonicida Infection.
The T-box transcription factor T-bet is expressed in a number of hematopoietic cell types in mammals and plays an essential role in the lineage determination of Th1 T-helper cells and is considered as an essential feature for both innate and adaptive immune responses in higher vertebrates. In the present study, we have identified and characterized the full-length Atlantic salmon T-bet cDNA (3502 bp). The putative primary structure of the polypeptide deduced from the cDNA sequence contained 612 aa, which possessed a T-box DNA binding domain. Phylogenetic study and gene synteny revealed it is as a homolog to mammalian T-bet. Quantitative PCR analysis of different tissues in healthy fish showed that salmon T-bet gene was highly expressed in spleen, followed by head kidney, and was expressed in intestine, skin, and liver at lower levels. Moreover, the time-dependent expression profile of T-bet, interferon gamma (IFNγ), interleukin-22 (IL-22), and natural killer enhancement factor in mucosal tissues during water-borne infection with live Aeromonas salmonicida, indicated the involvement of T-bet in mucosal immune response in Atlantic salmon.


In situ bidirectional human-robot value alignment.
A prerequisite for social coordination is bidirectional communication between teammates, each playing two roles simultaneously: as receptive listeners and expressive speakers. For robots working with humans in complex situations with multiple goals that differ in importance, failure to fulfill the expectation of either role could undermine group performance due to misalignment of values between humans and robots. Specifically, a robot needs to serve as an effective listener to infer human users' intents from instructions and feedback and as an expressive speaker to explain its decision processes to users. Here, we investigate how to foster effective bidirectional human-robot communications in the context of value alignment-collaborative robots and users form an aligned understanding of the importance of possible task goals. We propose an explainable artificial intelligence (XAI) system in which a group of robots predicts users' values by taking in situ feedback into consideration while communicating their decision processes to users through explanations. To learn from human feedback, our XAI system integrates a cooperative communication model for inferring human values associated with multiple desirable goals. To be interpretable to humans, the system simulates human mental dynamics and predicts optimal explanations using graphical models. We conducted psychological experiments to examine the core components of the proposed computational framework. Our results show that real-time human-robot mutual understanding in complex cooperative tasks is achievable with a learning model based on bidirectional communication. We believe that this interaction framework can shed light on bidirectional value alignment in communicative XAI systems and, more broadly, in future human-machine teaming systems.


Corrected and Republished from: The COP9 Signalosome Interacts with and Regulates Interferon Regulatory Factor 5 Protein Stability.
The transcription factor interferon regulatory factor 5 (IRF5) exerts crucial functions in the regulation of host immunity against extracellular pathogens, DNA damage-induced apoptosis, death receptor signaling, and macrophage polarization. Tight regulation of IRF5 is thus warranted for an efficient response to extracellular stressors and for limiting autoimmune and inflammatory responses. Here we report that the COP9 signalosome (CSN), a general modulator of diverse cellular and developmental processes, associates constitutively with IRF5 and promotes its protein stability. The constitutive CSN/IRF5 interaction was identified using proteomics and confirmed by endogenous immunoprecipitations. The CSN/IRF5 interaction occurred on the carboxyl and amino termini of IRF5; a single internal deletion (Δ455-466) was found to significantly reduce IRF5 protein stability. CSN3 was identified as a direct interacting partner of IRF5, and knockdown of this subunit with small interfering RNAs (siRNAs) resulted in enhanced degradation. Degradation was further augmented by knockdown of CSN1 and CSN3 together. The ubiquitin E1 inhibitor UBEI-41 or the proteasome inhibitor MG132 prevented IRF5 degradation, supporting that its stability is regulated by the ubiquitin-proteasome system. Importantly, activation of IRF5 by the death receptor ligand tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) resulted in enhanced degradation via loss of the CSN/IRF5 interaction. This study defines the CSN as a new interacting partner of IRF5 that controls its stability.


Anatomical anterior exenteration with urethral and vaginal preservation: illustrated surgical method.
We describe in detail a method for urethral and vaginal preservation in women considering orthotopic urinary tract reconstruction after bladder removal. We retrospectively reviewed the pathological reports of patients treated with anterior exenteration at our hospital between 1984 and 1997 for specific evidence of urethral, vaginal, cervical or uterine involvement by the primary bladder tumor. Based on our findings we describe our approach to anterior exenteration in 6 patients. A total of 46 patients were treated at our center with en bloc anterior exenteration and pelvic lymphadenectomy for primary bladder cancer between 1984 and 1997. In 7 patients (15%) pathological review of the surgical specimen documented urethral involvement by the primary tumor. In 1 patient (2%) microscopic evidence of tumor was identified in the cervix and 1 (2%) had tumor extension to the vagina documented in the final pathology report. The observed rates of vaginal and urethral involvement agree with those reported by others, and suggest that in the majority of women treated with anterior exenteration sacrifice of the urethra and vagina is usually not necessary from an oncological perspective. This procedure is particularly appropriate in women concerned with postoperative sexual function and those considering orthotopic reconstruction of the lower urinary tract after exenterative bladder cancer surgery.


CrmA orthologs from diverse poxviruses potently inhibit caspases-1 and -8, yet cleavage site mutagenesis frequently produces caspase-1-specific variants.
Poxviruses encode many proteins that enable them to evade host anti-viral defense mechanisms. Spi-2 proteins, including Cowpox virus CrmA, suppress anti-viral immune responses and contribute to poxviral pathogenesis and lethality. These proteins are 'serpin' protease inhibitors, which function via a pseudosubstrate mechanism involving initial interactions between the protease and a cleavage site within the serpin. A conformational change within the serpin interrupts the cleavage reaction, deforming the protease active site and preventing dissociation. Spi-2 proteins like CrmA potently inhibit caspases-1, -4 and -5, which produce proinflammatory cytokines, and caspase-8, which facilitates cytotoxic lymphocyte-mediated target cell death. It is not clear whether both of these functions are equally perilous for the virus, or whether only one must be suppressed for poxviral infectivity and spread but the other is coincidently inhibited merely because these caspases are biochemically similar. We compared the caspase specificity of CrmA to three orthologs from orthopoxviruses and four from more distant chordopoxviruses. All potently blocked caspases-1, -4, -5 and -8 activity but exhibited negligible inhibition of caspases-2, -3 and -6. The orthologs differed markedly in their propensity to inhibit non-mammalian caspases. We determined the specificity of CrmA mutants bearing various residues in positions P4, P3 and P2 of the cleavage site. Almost all variants retained the ability to inhibit caspase-1, but many lacked caspase-8 inhibitory activity. The retention of Spi-2 proteins' caspase-8 specificity during chordopoxvirus evolution, despite this function being readily lost through cleavage site mutagenesis, suggests that caspase-8 inhibition is crucial for poxviral pathogenesis and spread.


Design of organic dyes and cobalt polypyridine redox mediators for high-efficiency dye-sensitized solar cells.
Dye-sensitized solar cells (DSCs) with cobalt-based mediators with efficiencies surpassing the record for DSCs with iodide-free electrolytes were developed by selecting a suitable combination of a cobalt polypyridine complex and an organic sensitizer. The effect of the steric properties of two triphenylamine-based organic sensitizers and a series of cobalt polypyridine redox mediators on the overall device performance in DSCs as well as on transport and recombination processes in these devices was compared. The recombination and mass-transport limitations that, previously, have been found to limit the performance of these mediators were avoided by matching the properties of the dye and the cobalt redox mediator. Organic dyes with higher extinction coefficients than the standard ruthenium sensitizers were employed in DSCs in combination with outer-sphere redox mediators, enabling thinner TiO(2) films to be used. Recombination was reduced further by introducing insulating butoxyl chains on the dye rather than on the cobalt redox mediator, enabling redox couples with higher diffusion coefficients and more suitable redox potential to be used, simultaneously improving the photocurrent and photovoltage of the device. Optimization of DSCs sensitized with a triphenylamine-based organic dye in combination with tris(2,2'-bipyridyl)cobalt(II/III) yielded solar cells with overall conversion efficiencies of 6.7% and open-circuit potentials of more than 0.9 V under 1000 W m(-2) AM1.5 G illumination. Excellent performance was also found under low light intensity indoor conditions.


Brain correlates of verbal fluency in subthreshold psychosis assessed by functional near-infrared spectroscopy.
The prevalence of subthreshold psychotic symptoms in the general population has gained increasing interest as a possible precursor of psychotic disorders. The goal of the present study was to evaluate whether neurobiological features of subthreshold psychotic symptoms can be detected using verbal fluency tasks and functional near-infrared spectroscopy (fNIRS). A large data set was obtained from the Zurich Program for Sustainable Development of Mental Health Services (ZInEP). Based on the SCL-90-R subscales 'Paranoid Ideation' and 'Psychoticism' a total sample of 188 subjects was assigned to four groups with different levels of subthreshold psychotic symptoms. All subjects completed a phonemic and semantic verbal fluency task while fNIRS was recorded over the prefrontal and temporal cortices. Results revealed larger hemodynamic (oxy-hemoglobin) responses to the phonemic and semantic conditions compared to the control condition over prefrontal and temporal cortices. Subjects with high subthreshold psychotic symptoms exhibited significantly reduced hemodynamic responses in both conditions compared to the control group. Further, connectivity between prefrontal and temporal cortices revealed significantly weaker patterns in subjects with high subthreshold psychotic symptoms compared to the control group, possibly indicating less incisive network connections associated with subthreshold psychotic symptoms. The present findings provide evidence that subthreshold forms of psychotic symptoms are associated with reduced hemodynamic responses and connectivity in prefrontal and temporal cortices during verbal fluency that can be identified using fNIRS.


Implementing a successful data-management framework: the UK10K managed access model.
This paper outlines the history behind open access principles and describes the development of a managed access data-sharing process for the UK10K Project, currently Britain's largest genomic sequencing consortium (2010 to 2013). Funded by the Wellcome Trust, the purpose of UK10K was two-fold: to investigate how low-frequency and rare genetic variants contribute to human disease, and to provide an enduring data resource for future research into human genetics. In this paper, we discuss the challenge of reconciling data-sharing principles with the practicalities of delivering a sequencing project of UK10K's scope and magnitude. We describe the development of a sustainable, easy-to-use managed access system that allowed rapid access to UK10K data, while protecting the interests of participants and data generators alike. Specifically, we focus in depth on the three key issues that emerge in the data pipeline: study recruitment, data release and data access.


Oxantel pamoate-albendazole for Trichuris trichiura infection.
Infections with soil-transmitted helminths (Ascaris lumbricoides, hookworm, and Trichuris trichiura) are widespread and often occur concomitantly. These parasitic-worm infections are typically treated with albendazole or mebendazole, but both drugs show low efficacy against T. trichiura. Albendazole is the drug of choice against hookworm. In this double-blind trial conducted on Pemba Island, Tanzania, we randomly assigned children, 6 to 14 years of age, to receive one of four treatments: oxantel pamoate at a dose of 20 mg per kilogram of body weight, plus 400 mg of albendazole, administered on consecutive days; oxantel pamoate at a single dose of 20 mg per kilogram; albendazole at a single dose of 400 mg; or mebendazole at a single dose of 500 mg. We assessed the efficacy and safety profile of oxantel pamoate-albendazole when used in the treatment of T. trichiura infection (primary outcome) and concomitant soil-transmitted helminth infection (secondary outcome). Efficacy was determined by means of assessment of the cure rate and egg-reduction rate. Adverse events were assessed four times after treatment. Complete data were available for 458 children, of whom 450 were infected with T. trichiura, 443 with hookworm, and 293 with A. lumbricoides. The cure rate of T. trichiura infection was significantly higher with oxantel pamoate-albendazole than with mebendazole (31.2% vs. 11.8%, P=0.001), as was the egg-reduction rate (96.0% [95% confidence interval {CI}, 93.5 to 97.6] vs. 75.0% [95% CI, 64.2 to 82.0]). The cure rate with albendazole (2.6%) and the egg-reduction rate with albendazole (45.0%; 95% CI, 32.0 to 56.4) were significantly lower than the rates with mebendazole (P=0.02 for the comparison of cure rates). Oxantel pamoate had low efficacy against hookworm and A. lumbricoides. Adverse events (mainly mild) were reported by 30.9% of all children. Treatment with oxantel pamoate-albendazole resulted in higher cure and egg-reduction rates for T. trichiura infection than the rates with standard therapy. (Funded by the Medicor Foundation and the Swiss National Science Foundation; Current Controlled Trials number, ISRCTN54577342.).


Phase-only shaping algorithm for Gaussian-apodized Bessel beams.
Gaussian-apodized Bessel beams can be used to create a Bessel-like axial line focus at a distance from the focusing lens. For many applications it is desirable to create an axial intensity profile that is uniform along the Bessel zone. In this article, we show that this can be accomplished through phase-only shaping of the wavefront in the far field where the beam has an annular ring structure with a Gaussian cross section. We use a one-dimensional transform to map the radial input field to the axial Bessel field and then optimized the axial intensity with a Gerchberg-Saxton algorithm. By separating out the quadratic portion of the shaping phase the algorithm converges more rapidly.


Diabetes-induced coronary vascular dysfunction involves increased arginase activity.
Increases in arginase activity have been reported in a variety of disease conditions characterized by vascular dysfunction. Arginase competes with NO synthase for their common substrate arginine, suggesting a cause and effect relationship. We tested this concept by experiments with streptozotocin diabetic rats and high glucose (HG)-treated bovine coronary endothelial cells (BCECs). Our studies showed that diabetes-induced impairment of vasorelaxation to acetylcholine was correlated with increases in reactive oxygen species and arginase activity and arginase I expression in aorta and liver. Treatment of diabetic rats with simvastatin (5 mg/kg per day, subcutaneously) or L-citrulline (50 mg/kg per day, orally) blunted these effects. Acute treatment of diabetic coronary arteries with arginase inhibitors also reversed the impaired vasodilation to acetylcholine. Treatment of BCECs with HG (25 mmol/L, 24 hours) also increased arginase activity. This effect was blocked by treatment with simvastatin (0.1 micromol/L), the Rho kinase inhibitor Y-27632 (10 micromol/L), or L-citrulline (1 mmol/L). Superoxide and active RhoA levels also were elevated in HG-treated BCECs. Furthermore, HG significantly diminished NO production in BCECs. Transfection of BCECs with arginase I small interfering RNA prevented the rise in arginase activity in HG-treated cells and normalized NO production, suggesting a role for arginase I in reduced NO production with HG. These results indicate that increased arginase activity in diabetes contributes to vascular endothelial dysfunction by decreasing L-arginine availability to NO synthase.


Gata4 expression in lateral mesoderm is downstream of BMP4 and is activated directly by Forkhead and GATA transcription factors through a distal enhancer element.
The GATA family of zinc-finger transcription factors plays key roles in the specification and differentiation of multiple cell types during development. GATA4 is an early regulator of gene expression during the development of endoderm and mesoderm, and genetic studies in mice have demonstrated that GATA4 is required for embryonic development. Despite the importance of GATA4 in tissue specification and differentiation, the mechanisms by which Gata4 expression is activated and the transcription factor pathways upstream of GATA4 remain largely undefined. To identify transcriptional regulators of Gata4 in the mouse, we screened conserved noncoding sequences from the mouse Gata4 gene for enhancer activity in transgenic embryos. Here, we define the regulation of a distal enhancer element from Gata4 that is sufficient to direct expression throughout the lateral mesoderm, beginning at 7.5 days of mouse embryonic development. The activity of this enhancer is initially broad but eventually becomes restricted to the mesenchyme surrounding the liver. We demonstrate that the function of this enhancer in transgenic embryos is dependent upon highly conserved Forkhead and GATA transcription factor binding sites, which are bound by FOXF1 and GATA4, respectively. Furthermore, the activity of the Gata4 lateral mesoderm enhancer is attenuated by the BMP antagonist Noggin, and the enhancer is not activated in Bmp4-null embryos. Thus, these studies establish that Gata4 is a direct transcriptional target of Forkhead and GATA transcription factors in the lateral mesoderm, and demonstrate that Gata4 lateral mesoderm enhancer activation requires BMP4, supporting a model in which GATA4 serves as a downstream effector of BMP signaling in the lateral mesoderm.


Coping with ill-health: health care facility, chemist or medicinal plants? Health-seeking behaviour in a Kenyan wetland.
Sub-Saharan African wetlands, settlement areas to growing populations, expose their users to diseases as necessary health infrastructure remains underdeveloped. Mixed methods were adopted to assess the health-seeking behaviour of different exposure groups (farmers, pastoralists, service sector workers) in a Kenyan wetland community. Based on a cross-sectional survey (n = 400), syndromic surveillance was linked to health-seeking event analysis. In-depth interviews with community members (n = 20) and experts (n = 8) enabled the integration of healthcare user and provider perspectives. Health-seeking behaviour in the wetland was determined by physical/infrastructural, natural/environmental, financial/socioeconomic and social/demographic factors, as well as human/cultural aspects such as traditional preferences rooted in health beliefs. Community members had different strategies of coping with ill-health and few symptoms remained untreated. Whether via a health care facility admission, the visit of a chemist, or the intake of pharmaceuticals or medicinal plants: treatment was usually applied either via a healthcare service provider or by the community members themselves. An undersupply of easy-to-reach healthcare options was detected, and healthcare services were not available and accessible to all. The widely-practiced self-treatment of symptoms, e.g. by use of local medicinal plants, mirrors both potential healthcare gaps and cultural preferences of wetland communities. Integrated into an overall health-promoting wetland management approach, widely accepted (cultural) realities of health-seeking behaviours could complement health sector service provision and help ensure healthy lives and promote well-being for all in wetlands.


Segmentation by depth does not always facilitate visual search.
In visual search, target detection times are relatively insensitive to set size when targets and distractors differ on a single feature dimension. Search can be confined to only those elements sharing a single feature, such as color (Egeth, Virzi, & Garbart, 1984). These findings have been taken as evidence that elementary feature dimensions support a parallel segmentation of a scene into discrete sets of items. Here we explored if relative depth (signaled by binocular disparity) could support a similar parallel segmentation by examining the effects of distributing distracting elements across two depth planes. Three important empirical findings emerged. First, when the target was a feature singleton on the target depth plane, but a conjunction search among distractors on the nontarget plane, search efficiency increased compared to a single depth plane. Second, benefits of segmentation in depth were only observed when the target depth plane was known in advance. Third, no benefit of segmentation in depth was observed when both planes required a conjunction search, even with prior knowledge of the target depth plane. Overall, the benefit of distributing the elements of a search set across two depth planes was observed only when the two planes differed both in binocular disparity and in the elementary feature composition of individual elements. We conclude that segmentation of the search array into two depth planes can facilitate visual search, but unlike color or other elementary properties, does not provide an automatic, preattentive segmentation.


Solving the distal reward problem with rare correlations.
In the course of trial-and-error learning, the results of actions, manifested as rewards or punishments, occur often seconds after the actions that caused them. How can a reward be associated with an earlier action when the neural activity that caused that action is no longer present in the network? This problem is referred to as the distal reward problem. A recent computational study proposes a solution using modulated plasticity with spiking neurons and argues that precise firing patterns in the millisecond range are essential for such a solution. In contrast, the study reported in this letter shows that it is the rarity of correlating neural activity, and not the spike timing, that allows the network to solve the distal reward problem. In this study, rare correlations are detected in a standard rate-based computational model by means of a threshold-augmented Hebbian rule. The novel modulated plasticity rule allows a randomly connected network to learn in classical and instrumental conditioning scenarios with delayed rewards. The rarity of correlations is shown to be a pivotal factor in the learning and in handling various delays of the reward. This study additionally suggests the hypothesis that short-term synaptic plasticity may implement eligibility traces and thereby serve as a selection mechanism in promoting candidate synapses for long-term storage.


Performance of fixed-pressure valve with antisiphon device SPHERA(®) in hydrocephalus treatment and overdrainage prevention.
Patients with hydrocephalus and risk factors for overdrainage may be submitted to ventricular shunt (VS) implant with antisiphon device. The objective of this study was to prospectively evaluate for two years the clinical and tomographic results of the implant of fixed-pressure valves with antisiphon device SPHERA(®) in 35 adult patients, with hydrocephalus and risk factors for overdrainage. Of these, 3 had congenital hydrocephalus in adult patients with very dilated ventricles (Evans index >50%), 3 had symptomatic overdrainage after previous VS implant (subdural hematoma, hygroma or slit ventricle syndrome), 1 had previous chronic subdural hematoma, 15 had normal pressure hydrocephalus with final lumbar pressure <5 cm H(2)O after tap test (40 mL), 6 had pseudotumor cerebri, and 7 had hydrocephalus due to other causes. Clinical improvement was observed and sustained in 94.3% of the patients during the two-year period with no computed tomography (CT) evidence of hypo or overdrainage, and no immediate early or late significant complications.


Spatially resolved cell atlas of the mouse primary motor cortex by MERFISH.
A mammalian brain is composed of numerous cell types organized in an intricate manner to form functional neural circuits. Single-cell RNA sequencing allows systematic identification of cell types based on their gene expression profiles and has revealed many distinct cell populations in the brain1,2. Single-cell epigenomic profiling3,4 further provides information on gene-regulatory signatures of different cell types. Understanding how different cell types contribute to brain function, however, requires knowledge of their spatial organization and connectivity, which is not preserved in sequencing-based methods that involve cell dissociation. Here we used a single-cell transcriptome-imaging method, multiplexed error-robust fluorescence in situ hybridization (MERFISH)5, to generate a molecularly defined and spatially resolved cell atlas of the mouse primary motor cortex. We profiled approximately 300,000 cells in the mouse primary motor cortex and its adjacent areas, identified 95 neuronal and non-neuronal cell clusters, and revealed a complex spatial map in which not only excitatory but also most inhibitory neuronal clusters adopted laminar organizations. Intratelencephalic neurons formed a largely continuous gradient along the cortical depth axis, in which the gene expression of individual cells correlated with their cortical depths. Furthermore, we integrated MERFISH with retrograde labelling to probe projection targets of neurons of the mouse primary motor cortex and found that their cortical projections formed a complex network in which individual neuronal clusters project to multiple target regions and individual target regions receive inputs from multiple neuronal clusters.


Prevalence of anxiety disorders and anxiety subtypes in patients with Parkinson's disease.
Anxiety disorders are common in Parkinson's disease (PD), but are not well characterized. This study determined the prevalence and clinical correlates of all DSM-IV-TR anxiety disorder diagnoses in a sample of 127 subjects with idiopathic PD who underwent comprehensive assessments administered by a psychiatrist and neurologist. A panel of six psychiatrists with expertise in geriatric psychiatry and/or movement disorders established by consensus all psychiatric diagnoses. Current and lifetime prevalence of at least one anxiety disorder diagnosis was 43% (n = 55) and 49% (n = 63), respectively. Anxiety disorder not otherwise specified, a DSM diagnosis used for anxiety disturbances not meeting criteria for defined subtypes, was the most common diagnosis (30% lifetime prevalence, n = 38). Compared with nonanxious subjects, panic disorder (n = 13) was associated with earlier age of PD onset [50.3 (12.2) vs. 61.0 (13.7) years, P < 0.01], higher rates of motor fluctuations [77% (10/13) vs. 39% (25/64), P = 0.01] and morning dystonia [38% (5/13) vs. 13% (8/62), P < 0.03]. This high prevalence of anxiety disorders, including disturbances often not meeting conventional diagnostic criteria, suggests that anxiety in PD is likely underdiagnosed and undertreated and refined characterization of anxiety disorders in PD is needed. In addition, certain anxiety subtypes may be clinically useful markers associated with disease impact in PD.


Identification and expression of Hop, an atypical homeobox gene expressed late in lens fiber cell terminal differentiation.
To identify transcripts expressed late in lens fiber cell maturation that might regulate fiber cell fusion, organelle degradation, or other events associated with the maturation of lens fiber cells. cDNA libraries were prepared from microdissected regions of chicken embryo lenses using a PCR-based method. Subtractive hybridization was used to identify transcripts expressed exclusively in fiber cells that had detached from the lens capsule. Database searches and PCR amplification with degenerate primers were used to identify human, mouse, rat, rabbit, and bovine orthologs of one such sequence and to confirm its expression in the lenses of these animals. The ability of in vitro-transcribed and translated protein to bind DNA was assessed by mobility shift assays. The locus encoding this transcript and an area about 6 kb upstream of the translation start site were sequenced. The microscopic morphology of lenses from mice in which the locus encoding this protein had been disrupted by the insertion of a nuclear-targeted bacterial lacZ sequence were analyzed. Gene expression was analyzed by PCR, in situ hybridization, and by staining for beta-galactosidase activity in lenses expressing lacZ in place of the coding sequence. Knockout lenses expressing green fluorescent protein in a mosaic pattern were sectioned in the equatorial plane and viewed with a confocal microscope to assess the presence of cell-cell fusions during fiber cell maturation. Subtractive hybridization identified transcripts encoding Hop, a short, atypical homeodomain-containing protein that had previously been shown to be an important regulator of gene expression in the heart and lung. Chicken Hop did not bind to known homeodomain-binding sequences in DNA. In chicken embryos, Hop transcripts were first detected at E6. At all stages analyzed, Hop mRNA was only detected in cells that had detached from the lens capsule. Mice in which the Hop coding sequence was replaced with nuclear-targeted beta-galactosidase showed that Hop was expressed in the mouse lens in a similar pattern to the chicken lens. Characterization of lenses from mice lacking Hop revealed no morphological phenotype and no apparent defects in the degradation of nuclei or fiber cell fusion during fiber cell maturation. The expression pattern of Hop provides the first evidence that new transcription is initiated in lens fiber cells after they detach from the capsule. Hop may be the first of a class of genes with this pattern of expression. Although lens abnormalities have yet to be identified in mice lacking Hop, the genomic sequences that regulate Hop expression in the lens may be useful for expressing exogenous transcripts selectively in fiber cells just before they fuse with their neighbors and degrade their organelles.


Exercise prescription using the heart of claudication pain onset in patients with intermittent claudication.
To assess the acute metabolic and cardiovascular responses to walking exercise at an intensity corresponding to the heart rate of claudication pain onset and to investigate the effects of a 12-week walking training program at this intensity on walking capacity. Twenty-nine patients with intermittent claudication were randomly allocated to the walking training (n=17) or control (CO, n=12) group. The walking training group performed an acute exercise session comprising 15×2-min bouts of walking at the heart rate of claudication pain onset, with 2-min interpolated rest intervals. The claudication symptoms and cardiovascular and metabolic responses were evaluated. Walking training was then performed at the same intensity twice each week for 12 weeks, while the control group engaged in twice weekly stretching classes. The claudication onset distance and total walking distance were evaluated before and after the interventions. Brazilian Registry Clinical Trials: RBR-7M3D8W. During the acute exercise session, the heart rate was maintained within tight limits. The exercise intensity was above the anaerobic threshold and >80% of the heart rate peak and VO2peak. After the exercise training period, the walking exercise group (n=13) showed increased claudication onset distance (309±153 vs. 413±201m) and total walking distance (784±182 vs. 1,100±236m) compared to the control group (n=12) (p<0.05). Walking exercise prescribed at the heart rate of claudication pain onset enables patients with intermittent claudication to exercise with tolerable levels of pain and improves walking performance.


An intelligent telecardiology system using a wearable and wireless ECG to detect atrial fibrillation.
This study presents a novel wireless, ambulatory, real-time, and autoalarm intelligent telecardiology system to improve healthcare for cardiovascular disease, which is one of the most prevalent and costly health problems in the world. This system consists of a lightweight and power-saving wireless ECG device equipped with a built-in automatic warning expert system. This device is connected to a mobile and ubiquitous real-time display platform. The acquired ECG signals are instantaneously transmitted to mobile devices, such as netbooks or mobile phones through Bluetooth, and then, processed by the expert system. An alert signal is sent to the remote database server, which can be accessed by an Internet browser, once an abnormal ECG is detected. The current version of the expert system can identify five types of abnormal cardiac rhythms in real-time, including sinus tachycardia, sinus bradycardia, wide QRS complex, atrial fibrillation (AF), and cardiac asystole, which is very important for both the subjects who are being monitored and the healthcare personnel tracking cardiac-rhythm disorders. The proposed system also activates an emergency medical alarm system when problems occur. Clinical testing reveals that the proposed system is approximately 94% accurate, with high sensitivity, specificity, and positive prediction rates for ten normal subjects and 20 AF patients. We believe that in the future a business-card-like ECG device, accompanied with a mobile phone, can make universal cardiac protection service possible.


A mobile device reducing airborne particulate can improve air quality.
Surgical site infections are the second major cause of hospital acquired infections, accounting for a large part of overall annual medical costs. Airborne particulate is known to be a potential carrier of pathogenic bacteria. We assessed a mobile air particle filter unit for improvement of air quality in an operating room (OR). A new mobile air decontamination and recirculation unit, equipped with a crystalline ultraviolet C (Illuvia® 500 UV) reactor and a HEPA filter, was tested in an OR. Airborne particulate was monitored in four consecutive phases: I) device OFF and OR at rest; II) device OFF and OR in operation; III) device ON and OR in operation; IV) device OFF and OR in operation. We used a particle counter to measure airborne particles of different sizes: ≥0.3, ≥0.5, ≥1, ≥3, ≥5, >10 µm. Activation of the device (phases III) produced a significant reduction (p < 0.05) in airborne particulate of all sizes. Switching the device OFF (phase IV) led to a statistically significant increase (p < 0.05) in the number of particles of most sizes: ≥0.3, ≥0.5, ≥1, ≥3 µm. The device significantly reduced airborne particulate in the OR, improving air quality and possibly lowering the probability of surgical site infections.


Cytotoxic Homoisoflavones from the Bulbs of Bellevalia eigii.
Eight new and 10 known compounds were isolated from an organic extract of the bulbs of Bellevalia eigii as part of a search for anticancer leads from native plants of Jordan. Of these, the series of 16 homoisoflavonoids (1-16) comprise the seven new analogues 7-O-methyl-3'-hydroxy-3,9-dihydropunctatin (3), 6-hydroxy-7-O-methyl-3,9-dihydropunctatin (6), 7,4'-di-O-methyl-3'-hydroxy-3,9-dihydropunctatin (9), 7-O-methylpunctatin (10), 7-O-methyl-3'-hydroxypunctatin (13), 5-hydroxy-7,8-dimethoxychroman-4-one (14), and 7-O-methyl-8-demethoxy-3-hydroxy-3,9-dihydropunctatin (15). The known ferulic acid-derived acrylamide (17) and the new methylthioacrylate bellegimycin (18) are also reported. The structures were elucidated using a set of spectroscopic and spectrometric techniques; the absolute configurations of compounds 1-9, 15, and 16 were determined using ECD spectroscopy, while a modified Mosher's ester method was used for compound 18. Optical rotation data for the known compounds 1, 2, and 8 are reported here for the first time. The cytotoxic activities of all compounds were evaluated using the MDA-MB-435 (melanoma) and HT-29 (colon) cancer cell lines. Compounds 4 and 9 were the most potent on the latter cell line, with IC50 values of 1.0 and 1.1 μM, respectively. Compounds 1-18 were assessed for antimicrobial activity using a collection of bacteria and fungi; compounds 4 and 12 showed promising activity against the bacterium Mycobacterium smegmatis with MIC values of 17 and 24 μg/mL, respectively.


A model for the control of testosterone secretion.
We produce here a model to explain the control of testosterone secretion. In this model the hypothalamic secretion of the hormone LHRH (luteinizing hormone releasing hormone) is controlled by a combination of local testosterone concentration and of the local concentration of the pituitary hormone LH (luteinizing hormone). Since LHRH stimulates the release of LH, and LH in turn stimulates the release of testosterone, the three hormones constitute a three-component "feedback" network. We show how this model is able to account for the pulsatility of the release of these three hormones. Furthermore, the model is consistent with results obtained from a wide range of experimental manipulations of the system. For example, it accounts for the changes observed in hormone release patterns after castration. In particular, it follows that no "neural clock", or "neural pulse-generator", is required to force the system into pulsatile behaviour.