Cross-sectional and prospective associations between moderate to vigorous physical activity and sedentary time with adiposity in children.
Physical activity (PA) and sedentary time (SED) have both been suggested as potential risk factors for adiposity in children. However, there is paucity of data examining the temporal associations between these variables. This study aimed to analyze the cross-sectional and prospective associations between PA, SED and body composition in children. A total of 510 children (age at baseline 10.1±0.8, age at follow-up 11.8±0.9) from six Portuguese schools from the Oeiras Municipality participated in this study. PA and SED were measured by accelerometry and trunk fat mass (TFM) and body fat mass (BFM) were measured by dual energy X-ray absorptiometry. Fat mass index (FMI) was calculated as BFM divided by height squared. Several regression models adjusted for age, sex, maturity status, follow-up duration, baseline levels of the outcome variable and SED or moderate to vigorous PA (MVPA) were performed. MVPA (min per day) was cross-sectionally inversely associated with adiposity indexes (FMI, TFM and BFM). Adiposity indexes were inversely associated with time in MVPA. In prospective analyses, MVPA was associated with a lower levels of FMI (β=-0.37, 95% confidence interval (CI): -0.49 to -0.26, P<0.001), TFM (β=-0.20, 95% CI: -0.29 to -0.10, P<0.001) and BFM (β=-0.37, 95% CI: -0.49 to -0.26, P<0.001). When the model was adjusted for age, sex, maturity status and for baseline levels of the outcome variables MVPA remained a significant predictor of lower adiposity indexes (FMI: β=-0.09, 95% CI: -0.16 to -0.01, P<0.05; TFM: β=-0.08, 95% CI: -0.15 to -0.01, P<0.05; BFM: β=-0.07, 95% CI: -0.15 to 0.00, P<0.05). Adiposity was not associated with MVPA when modeled as the exposure in prospective analyses. SED was not related with adiposity indexes, except for the relationship with FMI. In cross-sectional and prospective analyses, MVPA is associated with lower adiposity independent of covariates and SED. Results suggest that promoting MVPA is important for preventing gain in adiposity in healthy children.


Periampullary and pancreatic incidentaloma: a single institution's experience with an increasingly common diagnosis.
While incidental masses in certain organs have received particular attention, periampullary and pancreatic incidentalomas (PIs) remain poorly characterized. We reviewed 1944 consecutive pancreaticoduodenectomies (PD) over an 8-year period (April 1997 to October 2005). A total of 118 patients (6% of all PDs) presented with an incidental finding of a periampullary or pancreatic mass. The PI patients were analyzed and compared with the rest of the cohort (NI, nonincidentaloma group, n = 1826). Thirty-one percent of the PI patients (n = 37) had malignant disease (versus 76% of the NI patients, P < 0.001), 47% (n = 55) had premalignant disease, and the remaining 22% (n = 26) had little or no risk for malignant progression. The 3 most common diagnoses in the PI group were IPMN without invasive cancer (30%), cystadenoma (17%), and pancreatic ductal adenocarcinoma (10%). The PI group had a higher overall complication rate (55% versus 43%, P = 0.02), due in part to a significantly increased rate of pancreatic fistulas (18.4% PI versus 8.5% NI, P < 0.001). Patients in the PI group with malignant disease had a superior long-term survival (median, 30 months, P = 0.01) compared with patients in the NI group with malignant disease (median, 21 months). Incidentally discovered periampullary and pancreatic masses comprise a substantial proportion of patients undergoing PD. Roughly three fourths of these lesions are malignant or premalignant, and amenable to curative resection. Resected malignant PIs have favorable pathologic features as compared with resected malignant NIs, and resection of these early lesions in asymptomatic individuals is associated with improved survival, compared with patients with symptomatic disease.


Nab-Paclitaxel and Gemcitabine in Advanced Pancreatic Cancer: The One-year Experience of the National Cancer Institute of Naples.
Pancreas adenocarcinoma is the sixth cause of cancer-related death worldwide with an increasing mortality in the Western countries. Recently, the association between nab-paclitaxel (nab-P) and gemcitabine (GEM) has significantly improved progression-free and overall survival. Patients affected by metastatic pancreas adenocarcinoma were treated at the Department of Abdominal Oncology of the National Cancer Institute of Naples from July 2015 to July 2016 with nab-P at 125 mg per square meter of body-surface area followed by GEM at 1,000 mg per square meter on days 1, 8 and 15 every 4 weeks. Computed tomography (CT) was performed every three months of therapy. Toxicity was graded with National Cancer Institute-Common Toxicity Criteria (NCI-CTC) v4.0. Objective responses were evaluated with Response Evaluation Criteria in Solid Tumors (RECIST). Analysis of time-to-progression is only descriptive. Pain was evaluated with a visual analogue scale (VAS). Twenty-three patients were treated. Median age was 67 years (range=45-81); 8 patients were ≥70 years old. Performance status (PS) Eastern Cooperative Oncology Group (ECOG) was 2 in 8 patients, 1 in 10 and 0 in 5. Twelve patients presented with diffuse hepatic metastases, 4 with carcinosis, 7 with more than one organ involvement. Nab-P was reduced at 100 mg per square meter in all patients. The most common G3/G4 adverse events were neutropenia (13.0% G4, 8.6% G3; none was febrile), neuropathy (30.4% G3) and asthenia (G3 17.3%). The disease control rate was 43.4% (partial response+stable disease (PR+SD) 10/23). The median time-to-progression was 7.9 months (95% confidence interval (CI)=5.8-11.2). After three months of therapy the PS improved in 14 patients, as well as pain in 18 patients. We present an experience with nab-P and GEM association in a series with poor PS and highly metastatic disease relatively to a previous randomized study. The schedule is feasible, with nab-P at 100 mg per square meter achieving a good disease control rate, as well as a clinical benefit.


Asthma: resource use and costs for inhaled corticosteroid vs leukotriene modifier treatment--a meta-analysis.
To compare the effects of inhaled corticosteroid treatment with leukotriene modifier treatment on medical resource use and costs for asthma patients. Meta-analysis combining results from published and unpublished studies. Studies were identified from the MEDLINE and EMBASE databases and the GlaxoSmithKline internal database study registers. Two independent reviewers evaluated the identified studies; studies meeting specified inclusion criteria were abstracted and summarized by meta-analysis with a random effects model. Hospitalization rate, emergency department visit rate, emergency department costs, drug costs, total asthma-related costs, and total medical care costs. Patients taking inhaled corticosteroids had: a significantly lower annual rate of hospitalization than those taking leukotriene modifiers (2.2% vs 4.3%, respectively; P<.05); a greater decline in hospitalization rate (before vs after therapy initiation) than those taking leukotriene modifiers (decline of 2.4% vs 0.55%; P<.01); a lower annual rate of emergency department visits than those taking leukotriene modifiers (6.2% vs 7.7%; P<.005); lower total asthma-related medical costs than those taking leukotriene modifiers (P<.05) and a 17% reduction in overall total medical care costs (P not significant). Patients with asthma treated with inhaled corticosteroids have significantly fewer asthma-related hospitalizations and emergency department visits and lower total asthma-related health care costs than patients treated with leukotriene modifiers. These meta-analysis findings are consistent with results from randomized controlled trials showing improvements in lung function for patients taking inhaled corticosteroids as opposed to leukotriene modifiers.


Role of Indian hedgehog signaling in palatal osteogenesis.
Cleft lip-cleft palate is a common congenital disability and represents a large biomedical burden. Through the use of animal models, the molecular underpinnings of cleft palate are becoming increasingly clear. Indian hedgehog (Ihh) has been shown to be associated with craniofacial development and to be active in the palatine bone. The authors hypothesize that Indian hedgehog activity plays a role in osteogenesis within the secondary palate and that defects in this pathway may inhibit osteogenesis of the secondary palate. Palates were isolated from wild-type mice during the period of palate development (embryonic days 9.5 to 17.5). Quantitative real-time polymerase chain reaction was used for detecting gene expression during osteogenic differentiation and cellular differentiation (Shh, Ihh, Ptc1, Gli1, Gli2, Gli3, Runx2, Alp, and Col1a1). Next, palates were analyzed by hematoxylin and eosin, aniline blue, pentachrome, and in situ hybridization to assess osteogenesis of the palatal shelf and expression of hedgehog pathway genes. Finally, the palates of Indian hedgehog-null mice were analyzed to determine the effect of genetic deficiency on palatal development osteogenesis. Increased Indian hedgehog and osteogenic signaling coincided with ossification and fusion of the palate in wild-type mice. This included a fivefold to 150-fold peak in expression of hedgehog elements, including Ihh, at embryonic day 15.5 as compared with embryonic day 9.5. Contrarily, loss of Indian hedgehog by genetic knockout (Ihh-/-) resulted in decreased secondary palate ossification. The authors' results suggest a role for hedgehog signaling during palatal ossification. The hedgehog pathway is activated during palatal fusion, and deletion of Indian hedgehog leads to diminished ossification of the secondary hard palate.


Li-ion diffusion in Li intercalated graphite C6Li and C12Li probed by μ+SR.
In order to study a diffusive behavior of Li+ in Li intercalated graphites, we have measured muon spin relaxation (μ+SR) spectra for C6Li and C12Li synthesized with an electrochemical reaction between Li and graphite in a Li-ion battery. For both compounds, it was found that Li+ ions start to diffuse above 230 K and the diffusive behavior obeys a thermal activation process. The activation energy (Ea) for C6Li is obtained as 270(5) meV, while Ea = 170(20) meV for C12Li. Assuming a jump diffusion of Li+ in the Li layer of C6Li and C12Li, a self-diffusion coefficient DLi at 310 K was estimated as 7.6(3) × 10-11 (cm2 s-1) in C6Li and 14.6(4) × 10-11 (cm2 s-1) in C12Li.


The transcription factor RFX3 directs nodal cilium development and left-right asymmetry specification.
There are five members of the RFX family of transcription factors in mammals. While RFX5 plays a well-defined role in the immune system, the functions of RFX1 to RFX4 remain largely unknown. We have generated mice with a deletion of the Rfx3 gene. RFX3-deficient mice exhibit frequent left-right (LR) asymmetry defects leading to a high rate of embryonic lethality and situs inversus in surviving adults. In vertebrates, specification of the LR body axis is controlled by monocilia in the embryonic node, and defects in nodal cilia consequently result in abnormal LR patterning. Consistent with this, Rfx3 is expressed in ciliated cells of the node and RFX3-deficient mice exhibit a pronounced defect in nodal cilia. In contrast to the case for wild-type embryos, for which we document for the first time a twofold increase in the length of nodal cilia during development, the cilia are present but remain markedly stunted in mutant embryos. Finally, we show that RFX3 regulates the expression of D2lic, the mouse orthologue of a Caenorhabditis elegans gene that is implicated in intraflagellar transport, a process required for the assembly and maintenance of cilia. In conclusion, RFX3 is essential for the differentiation of nodal monocilia and hence for LR body axis determination.


Veterinarians' role for pet owners facing pet loss.
Owners' satisfaction with, and expectations from, their veterinarians around euthanasia, including questions on disposal of pet remains subject to animal species, clients' gender, age, family conditions, area of living and type of veterinary clinic visited were evaluated by questionnaire. Questionnaires were to be filled out by clients consecutively visiting the individual practices and hospitals for any kind of consultations. Of 2350 questionnaires distributed, 2008 were returned and available for analysis. Owner satisfaction concerning the procedure of euthanasia was high (92 per cent, 1173/1272). After the event of euthanasia, 14 per cent (170/1250) had changed their veterinarian, even though 75 per cent of these 170 had been satisfied with the procedure. Most owners (88 per cent) expected veterinarians to talk about their pet's final destination, and 38 per cent expected this to happen early in the pet's life. For 81 per cent clients, the veterinarian was the primary informant about the possibilities concerning the disposal of pet remains, and 33 per cent indicated their veterinarian as the contact person to talk about pet loss. Area of living, or veterinary specialisation, only marginally influenced the answers. Veterinarians play an important role to inform their clients concerning questions around euthanasia and the care of pet remains, and to support them during the process of mourning.


Dissection of a synthesized quantitative trait to characterize transgene interactions.
Six transgenic tobacco lines, each homozygous for the beta-glucuronidase (GUS) gene at a different locus, and wild type were selfed and intercrossed to evaluate GUS activity in all possible hemizygous, homozygous and dihybrid combinations of GUS alleles. The transgenic lines are characterized by their GUS activity (two low, three intermediate, one high), T-DNA complexity (four single-copy, two more complex single-locus) and the presence of the chicken lysozyme matrix-associated region (MAR) around the full T-DNA (two lines). Gene action and interaction was analyzed by weighted linear regression with parameters for additivity, dominance and epistasis. The analysis showed that each of the four single-copy lines acted fully additively. In contrast, the two complex single-locus lines showed classical single-locus overdominance and were epistatic dominant over all other GUS alleles. The latter is manifested in severe suppression of GUS activity in dihybrid lines, irrespective of the presence of MAR elements around the GUS gene. Such elements apparently do not protect against epistatic dominance. The quantitative data suggested that the epistatic dominance and overdominance are based on the same molecular mechanism. Our approach of a genetic analysis of quantitative variation in well-characterized transgenic lines provides a powerful tool to gain insight into complex plant traits.


Categorical and dimensional stability of comorbid personality disorder symptoms in DSM-IV major depressive disorder: a prospective study.
To investigate the categorical and dimensional temporal stability of Axis II personality disorders among depressive patients, and to determine whether variations in Axis I comorbid disorders or self-reported personality traits predict changes in researcher-assigned personality disorder symptoms. Patients with DSM-IV major depressive disorder (MDD) in the Vantaa Depression Study (N = 269) were interviewed with the World Health Organization Schedules for Clinical Assessment in Neuropsychiatry, version 2.0, and the Structured Clinical Interview for DSM-III-R Axis II Disorders and were assessed with the 57-item Eysenck Personality Inventory at baseline, 6 months, and 18 months. Baseline interviews occurred between February 1, 1997, and May 31, 1998; follow-up interviews were 6 months and 18 months after baseline for each patient. Of the patients included in the study, 193 remained unipolar and could be interviewed at both follow-ups. The covariation of the severity of depression, anxiety, alcohol use, and reported neuroticism and extraversion with assigned personality disorder symptoms was investigated by using general estimation equations. The diagnosis of personality disorder persisted at all time points in about half (43%) of the 81 MDD patients diagnosed with personality disorder at baseline. The number of positive personality disorder criteria declined, particularly during the first 6 months, by a mean of 3 criteria. The decline in reported personality disorder symptoms covaried significantly with declines in the severity of depressive and anxiety symptoms (depressive: P = .02 for paranoid, P = .02 for borderline, and P = .01 for avoidant; anxiety: P = .08 for paranoid, P = .01 for borderline, and P < .001 for avoidant). Changes in patients' perceptions of self as measured by neuroticism covaried with changes in paranoid (P = .01) and borderline (P < .001) personality disorder symptoms. Among MDD patients, the categorical stability of concurrent personality disorder diagnoses assigned while depressed is relatively poor, but the dimensional stability is moderate. The remission of depression as well as variations in Axis I comorbidity, particularly anxiety disorders, influences personality disorder diagnoses. These diagnostic difficulties most likely reflect broader variations in patients' perceptions of self over time, not merely psychometric problems related to the pertinent diagnostic criteria.


Transcriptional study of appetite regulating genes in the brain of zebrafish (Danio rerio) with impaired leptin signalling.
The hormone leptin is a key regulator of body weight, food intake and metabolism. In mammals, leptin acts as an anorexigen and inhibits food intake centrally by affecting the appetite centres in the hypothalamus. In teleost fish, the regulatory connections between leptin and other appetite-regulating genes are largely unknown. In the present study, we used a zebrafish mutant with a loss of function leptin receptor to investigate brain expression patterns of 12 orexigenic and 24 anorexigenic genes under different feeding conditions (normal feeding, 7-day fasting, 2 and 6-hours refeeding). Expression patterns were compared to wild-type zebrafish, in order to identify leptin-dependent differentially expressed genes under different feeding conditions. We provide evidence that the transcription of certain orexigenic and anorexigenic genes is influenced by leptin signalling in the zebrafish brain. We found that the expression of orexigenic genes was not affected by impaired leptin signalling under normal feeding conditions; however, several orexigenic genes showed increased transcription during fasting and refeeding, including agrp, apln, galr1a and cnr1. This suggests an inhibitory effect of leptin signal on the transcription of these orexigenic genes during short-term fasting and refeeding in functional zebrafish. Most pronounced effects were observed in the group of anorexigenic genes, where the impairment of leptin signalling resulted in reduced gene expression in several genes, including cart family, crhb, gnrh2, mc4r, pomc and spx, in the control group. This suggests a stimulatory effect of leptin signal on the transcription of these anorexigenic genes under normal feeding condition. In addition, we found multiple gain and loss in expression correlations between the appetite-regulating genes, in zebrafish with impaired leptin signal, suggesting the presence of gene regulatory networks downstream of leptin signal in zebrafish brain. The results provide the first evidence for the effects of leptin signal on the transcription of various appetite-regulating genes in zebrafish brain, under different feeding conditions. Altogether, these transcriptional changes suggest an anorexigenic role for leptin signal, which is likely to be mediated through distinct set of appetite-regulating genes under different feeding conditions.


Knowledge Discovery for Higher Education Student Retention Based on Data Mining: Machine Learning Algorithms and Case Study in Chile.
Data mining is employed to extract useful information and to detect patterns from often large data sets, closely related to knowledge discovery in databases and data science. In this investigation, we formulate models based on machine learning algorithms to extract relevant information predicting student retention at various levels, using higher education data and specifying the relevant variables involved in the modeling. Then, we utilize this information to help the process of knowledge discovery. We predict student retention at each of three levels during their first, second, and third years of study, obtaining models with an accuracy that exceeds 80% in all scenarios. These models allow us to adequately predict the level when dropout occurs. Among the machine learning algorithms used in this work are: decision trees, k-nearest neighbors, logistic regression, naive Bayes, random forest, and support vector machines, of which the random forest technique performs the best. We detect that secondary educational score and the community poverty index are important predictive variables, which have not been previously reported in educational studies of this type. The dropout assessment at various levels reported here is valid for higher education institutions around the world with similar conditions to the Chilean case, where dropout rates affect the efficiency of such institutions. Having the ability to predict dropout based on student's data enables these institutions to take preventative measures, avoiding the dropouts. In the case study, balancing the majority and minority classes improves the performance of the algorithms.


Particle depletion of diesel exhaust restores allergen-induced lung-protective surfactant protein D in human lungs.
Exposure to air pollution is linked with increased asthma morbidity and mortality. To understand pathological processes linking air pollution and allergen exposures to asthma pathophysiology, we investigated the effect of coexposure to diesel exhaust (DE) and aeroallergen on immune regulatory proteins in human airways. Fourteen allergen-sensitised participants completed this randomised, double-blinded, cross-over, controlled exposure study. Each participant underwent four exposures (allergen-alone exposure, DE and allergen coexposure, particle-depleted DE (PDDE) and allergen coexposure, and sham exposure) on different order-randomised dates, each separated by a 4-week washout. Serum and bronchoalveolar lavage (BAL) were assayed for pattern recognition molecules, cytokines, chemokines and inflammatory mediators. In human airways, allergen-alone exposure led to accumulation of surfactant protein D (SPD; p=0.02). Coexposure to allergen and DE did not elicit the same increase of SPD as did allergen alone; diesel particulate reduction restored allergen-induced SPD accumulation. Soluble receptor for advanced glycation end products was higher with particle reduction than without it. In the systemic circulation, there was a transient increase in SPD and club cell protein 16 (CC16) 4 hours after allergen alone. CC16 was augmented by PDDE, but not DE. % eosinophils in BAL (p<0.005), eotaxin-3 (p<0.0001), interleukin 5 (IL-5; p<0.0001) and thymus and activation regulated chemokine (p=0.0001) were each increased in BAL by allergen. IL-5, SPD and % eosinophils in BAL were correlated with decreased FEV1. Short-term coexposure to aeroallergen and DE alters immune regulatory proteins in lungs; surfactant levels are dependent on particle depletion. NCT02017431.


Vocal Fold Immobility due to Birth Trauma: A Systematic Review and Pooled Analysis.
Objectives To describe the present understanding of birth trauma-related vocal fold immobility and quantitatively compare it with idiopathic congenital vocal fold immobility to explore whether it is a discrete entity. Data Sources PubMed, Ovid, and Cochrane databases. Review Methods English-language, observational, or experimental studies involving infants with idiopathic congenital or birth trauma-related vocal fold immobility were included. Data from these studies were pooled with our institution's vocal fold immobility database, with the resultant idiopathic congenital and birth trauma cohorts compared regarding patterns and outcomes of immobility. Results The search returned 288 articles, with 24 meeting inclusion criteria. Of studies reviewing all-cause immobility, 8 of 9 (88.9%) identified birth trauma as an etiology, although birth trauma definitions and proposed mechanisms of immobility varied. The study subjects, combined with our institution's database, yielded 188 idiopathic congenital and 113 birth trauma cases. Compared with idiopathic congenital cases, birth trauma cases had a higher proportion of unilateral immobility (72 of 113 [63.7%] vs 52 of 188 [27.7%], P < .001) and rate of resolution (41 of 51 [80.4%] vs 91 of 159 [57.2%], P = .003). Resolution occurred in 24 of 26 (91.3%) unilateral and 17 of 25 (68.0%) bilateral birth trauma cases and in 30 of 40 (75.0%) unilateral and 59 of 109 (54.1%) bilateral idiopathic congenital cases ( P = .11 and .20, respectively). Conclusion While the definition and mechanism of birth trauma-related vocal fold immobility warrant further investigation, these findings suggest that it is distinct from idiopathic congenital vocal fold immobility, with a unique presentation and potentially more favorable outcomes. This can inform counseling and management for infants with otherwise unexplained immobility but known birth trauma.


Herbal remedies use by breast cancer patients in the West Bank of Palestine.
Recent ethnopharmacological surveys showed that herbal remedies are the most preferred modality of complementary and alternative medicine (CAM). In Palestine as in many other countries, herbal remedies are widely used in the treatment of many diseases. The aim of this study was to investigate the use of herbal remedies by women living with breast cancer in the West Bank of Palestine. This study was a questionnaire based cross-sectional descriptive study on the use of herbal remedies by breast cancer patients in the West Bank. A questionnaire was distributed to 115 patients at outpatient cancer clinics in face to face interviews. The study had a response rate of 89.6%. Of all respondents, 68% were herbal remedies users. Women with breast cancer used 46 plant species belonging to 32 families. Of these, Brassicaceae and Lamiaceae were the most prevalent. Ephedra alata was the most commonly used plant species in the treatment of breast cancer. Leaves and seeds were the most commonly used parts and decoction was the most commonly used method of preparation. Herbal remedies users were more likely to use herbal remedies instead of chemotherapy. The most commonly stated reason for using herbal remedies was the belief in boosting the patient's immune system to fight cancer. The use of herbal remedies is prevalent in breast cancer patients in Palestine. The use of herbal remedies was associated with educational level, time since diagnosis, type of surgery use, and use of endocrine therapy. It was apparent that the majority of users were satisfied with herbal remedies use. Clinical trials and pharmacological tests are required to be established for the presence of side effects, toxicity and efficacy for these herbal remedies.


HieranoiDB: a database of orthologs inferred by Hieranoid.
HieranoiDB (http://hieranoiDB.sbc.su.se) is a freely available on-line database for hierarchical groups of orthologs inferred by the Hieranoid algorithm. It infers orthologs at each node in a species guide tree with the InParanoid algorithm as it progresses from the leaves to the root. Here we present a database HieranoiDB with a web interface that makes it easy to search and visualize the output of Hieranoid, and to download it in various formats. Searching can be performed using protein description, identifier or sequence. In this first version, orthologs are available for the 66 Quest for Orthologs reference proteomes. The ortholog trees are shown graphically and interactively with marked speciation and duplication nodes that show the inferred evolutionary scenario, and allow for correct extraction of predicted orthologs from the Hieranoid trees.


Multimodal physiological sensing for the assessment of acute pain.
Pain assessment is a challenging task encountered by clinicians. In clinical settings, patients' self-report is considered the gold standard in pain assessment. However, patients who are unable to self-report pain are at a higher risk of undiagnosed pain. In the present study, we explore the use of multiple sensing technologies to monitor physiological changes that can be used as a proxy for objective measurement of acute pain. Electrodermal activity (EDA), photoplethysmography (PPG), and respiration (RESP) signals were collected from 22 participants under two pain intensities (low and high) and on two different anatomical locations (forearm and hand). Three machine learning models were implemented, including support vector machines (SVM), decision trees (DT), and linear discriminant analysis (LDA) for the identification of pain. Various pain scenarios were investigated, identification of pain (no pain, pain), multiclass (no pain, low pain, high pain), and identification of pain location (forearm, hand). Reference classification results from individual sensors and from all sensors together were obtained. After feature selection, results showed that EDA was the most informative sensor in the three pain conditions, 93.2±8% in identification of pain, 68.9±10% in the multiclass problem, and 56.0±8% for the identification of pain location. These results identify EDA as the superior sensor in our experimental conditions. Future work is required to validate the obtained features to improve its feasibility in more realistic scenarios. Finally, this study proposes EDA as a candidate to design a tool that can assist clinicians in the assessment of acute pain of nonverbal patients.


BRG1 chromatin remodeling activity is required for efficient chromatin binding by repressor element 1-silencing transcription factor (REST) and facilitates REST-mediated repression.
Chromatin remodeling enzymes such as SWI/SNF use the hydrolysis of ATP to power the movement of nucleosomes with respect to DNA. BRG1, one of the ATPases of the SWI/SNF complex, can be recruited by both activators and repressors, although the precise role of BRG1 in mechanisms of repression has thus far remained unclear. One transcription factor that recruits BRG1 as a corepressor is the repressor element 1-silencing transcription factor (REST). Here we address for the first time the mechanism of BRG1 activity in gene repression. We found that BRG1 enhanced REST-mediated repression at some REST target genes by increasing the interaction of REST with the local chromatin at its binding sites. Furthermore, REST-chromatin interactions, mediated by BRG1, were enhanced following an increase in histone acetylation in a manner dependent on the BRG1 bromodomain. Our data suggest that BRG1 facilitates REST repression by increasing the interaction between REST and chromatin. Such a mechanism may be applicable to other transcriptional repressors that utilize BRG1.


Comparing Error Correction to Errorless Learning: A Randomized Clinical Trial.
Errorless learning and error correction procedures are commonly used when teaching tact relations to individuals diagnosed with autism spectrum disorder (ASD). Research has demonstrated the effectiveness of both procedures, as well as compared them. The majority of these studies have been completed through the use of single-subject experimental designs. Evaluating both procedures using a group design may contribute to the literature and help disseminate research related to the behavioral science of language to a larger audience. The purpose of the present study was to compare an errorless learning procedure to an error correction procedure to teach tact relations to 28 individuals diagnosed with ASD through a randomized clinical trial. Several variables were assessed, including the number of stimulus sets with which participants reached the mastery criterion, responding during pre- and postprobes, responding during teaching, efficiency, and the presence of aberrant behavior. The results indicated that both procedures were effective, efficient, and unlikely to evoke aberrant behavior, despite participants in the error correction condition engaging in significantly more independent correct responses and independent incorrect responses.


An evaluation of four automatic methods of segmenting the subcortical structures in the brain.
The automation of segmentation of subcortical structures in the brain is an active research area. We have comprehensively evaluated four novel methods of fully automated segmentation of subcortical structures using volumetric, spatial overlap and distance-based measures. Two methods are atlas-based - classifier fusion and labelling (CFL) and expectation-maximisation segmentation using a brain atlas (EMS), and two incorporate statistical models of shape and appearance - profile active appearance models (PAM) and Bayesian appearance models (BAM). Each method was applied to the segmentation of 18 subcortical structures in 270 subjects from a diverse pool varying in age, disease, sex and image acquisition parameters. Our results showed that all four methods perform on par with recently published methods. CFL performed better than the others according to all three classes of metrics. In summary over all structures, the ranking by the Dice coefficient was CFL, BAM, joint EMS and PAM. The Hausdorff distance ranked the methods as CFL, joint PAM and BAM, EMS, whilst percentage absolute volumetric difference ranked them as joint CFL and PAM, joint BAM and EMS. Furthermore, as we had four methods of performing segmentation, we investigated whether the results obtained by each method were more similar to each other than to the manual segmentations using Williams' Index. Reassuringly, the Williams' Index was close to 1 for most subjects (mean=1.02, sd=0.05), indicating better agreement of each method with the gold standard than with the other methods. However, 2% of cases (mainly amygdala and nucleus accumbens) had values outside 3 standard deviations of the mean.


Repulsive van der Waals forces enable Pickering emulsions with non-touching colloids.
Emulsions stabilized by solid particles, called Pickering emulsions, offer promising applications in drug delivery, cosmetics, food science and the manufacturing of porous materials. This potential stems from their high stability against coalescence and 'surfactant-free' nature. Generally, Pickering emulsions require that the solid particles are wetted by both phases and as a result, the adsorption free energy is often large with respect to the thermal energy (kBT). Here we provide the first experimental proof for an alternative scenario: non-touching (effectively non-wetting), charged, particles that are completely immersed in the oil phase through a balance of charge induced attractions and repulsions caused by van der Waals forces. These particles nonetheless stabilize the emulsion. The main advantage of this novel adsorption mechanism is that these particles can easily be detached from the interface simply by adding salt. This not only makes the finding fundamentally of interest, but also enables a triggered de-emulsification and particle recovery, which is useful in fields like enhanced oil recovery, heterogeneous catalysis, and emulsion polymerization.


3D printed hollow core terahertz Bragg waveguides with defect layers for surface sensing applications.
We study a 3D-printed hollow core terahertz (THz) Bragg waveguide for resonant surface sensing applications. We demonstrate theoretically and confirm experimentally that by introducing a defect in the first layer of the Bragg reflector, thereby causing anticrossing between the dispersion relations of the core-guided mode and the defect mode, we can create a sharp transmission dip in the waveguide transmission spectrum. By tracking changes in the spectral position of the narrow transmission dip, one can build a sensor, which is highly sensitive to the optical properties of the defect layer. To calibrate our sensor, we use PMMA layers of various thicknesses deposited onto the waveguide core surface. The measured sensitivity to changes in the defect layer thickness is found to be 0.1 GHz/μm. Then, we explore THz resonant surface sensing using α-lactose monohydrate powder as an analyte. We employ a rotating THz Bragg fiber and a semi-automatic powder feeder to explore the limit of the analyte thickness detection using a surface modality. We demonstrate experimentally that powder layer thickness variations as small as 3μm can be reliably detected with our sensor. Finally, we present a comparative study of the time-domain spectroscopy versus continuous wave THz systems supplemented with THz imaging for resonant surface sensing applications.


Recognition of emotions in music by children and adults.
32 children 5 to 6 yr. old, 32 9 to 11 yr. old, and 32 adults linked musical fragments to emotions in a similar manner, older subjects being more accurate. Some emotions were more difficult than others; anger and fear were often confused. Older subjects gave better justifications for their choices.


Activation of an excluded immunoglobulin allele in a human B lymphoma cell line.
Mature B cells that express surface immunoglobulin (Ig) are usually committed to their original Ig product. It was shown that such a cell can replace its light chain by rearranging and expressing a new light chain from the other allele. Anti-idiotype antibodies were used to isolate idiotypic variants from a surface IgM+lambda+ human B cell tumor line. The variants expressed a new lambda light chain. Both the original and the new lambda transcripts were present in the variant cells, but only the new one was expressed as a protein on the cell surface. Therefore, although the cell exhibited allelic exclusion and had only one Ig receptor at a time, the commitment to a particular light chain gene was reversible.


Simulating species loss following perturbation: assessing the effects on process rates.
We removed stream-living macroinvertebrate shredder species in the sequences in which they are predicted to disappear, in response to two common types of anthropogenic disturbances: acidification and organic pollution, and analysed the effects on leaf breakdown rates. The experiment was performed in field microcosms using three shredder species. Species identity significantly affected leaf breakdown rates, while species richness per se was non-significant. The simulated sequential species loss showed large effects on leaf breakdown rates, with observed rates being significantly higher than expected from single-species treatments in two, out of four, two-species, and in all four three-species treatments. The invertebrates used in this study were taxonomically distinct (Insecta: Plecoptera and Trichoptera; Crustacea: Amphipoda), and of different sizes, hence a high degree of complementarity was probably present. A method to study the effects of species loss, characteristic of perturbation type, could be more useful than a random approach when investigating the impact of perturbation. Our results may have general applicability for investigations on the effects of diversity loss on ecosystem functioning in any ecosystem exposed to human perturbations, given that the order of extinction is known or can easily be assessed.


MiR-379/411 cluster regulates IL-18 and contributes to drug resistance in malignant pleural mesothelioma.
Malignant pleural mesothelioma (MPM) is a rapidly fatal malignancy that is increasing in incidence in Japan. In this study, we performed gene and microRNA (miRNA) expression profiling to identify novel therapeutic targets in MPM cells. Based on relative sensitivities to pemetrexed (PEM) and the histone deacetylase (HDAC) inhibitor, vorinostat (SAHA), 211H cells were determined to be the only sensitive MPM cell line out of the 6 tested. On the same series of cell lines, we performed whole genome transcriptomic profiling via DNA microarrays and pathway analysis of the derived data. Of particular note, IL-18 gene expression levels were significantly higher in the cell lines that were either drug resistant or displayed intermediate sensitivity, compared to the sensitive 211H cell line. Pathway analysis revealed IL-18 as an important gene associated with drug sensitivity of MPM cells. A relationship between IL-18 overexpression and drug resistance was also observed following targeted assessment of 10 cytokine genes using quantitative RT-PCR. miRNA expression profiles were evaluated in the MPM cell line panel in order to discern the mechanism of IL-18 induction in the drug-resistant lines. We found that miR-379 and miR-411 belonged to the same cluster of miRNAs located on chromosome 14q32 that commonly target the IL-18 gene. Luciferase reporter assays revealed that miR-379 and miR-411 directly target the IL-18 gene. Introduction of miR-379 plus miR-411, as well as IL-18 silencing, significantly suppressed the invasive capacity of MESO1 cells in vitro. Furthermore, the use of either PEM or SAHA together with miR-379 plus miR-411 mimics mediated increased sensitivity to these drugs in MESO1 cells. These results suggest that the miR-379/411 cluster may provide new therapeutic opportunities for advanced MPM patients, depending on the nature of IL-18 gene expression.


Effect of extracellular potassium on the transport of sodium and potassium in rat thymocytes.
1. The effect of extracellular potassium on the transport of sodium and potassium in rat thymocytes has been studied in vitro. 2. A significant increase in the rate constant for total and ouabain-sensitive sodium efflux was demonstrated at an extracellular potassium concentration of 1 mmol/l as compared with that at either 0 or 2 mmol/l. 3. At potassium concentrations below 3 mmol/l ouabain-sensitive sodium influx was observed suggesting sodium-sodium exchange catalysed by the sodium pump. 4. Both total and ouabain-insensitive potassium efflux rose with external potassium. A small ouabain-sensitive potassium efflux was observed at all levels of external potassium studied. 5. Total and ouabain-insensitive potassium influx increased with external potassium, but did not appear to saturate. Ouabain-sensitive potassium influx reached a maximum at an external potassium concentration of 2 mmol/l then decreased with increasing external potassium.


Correlation of laparoscopic experience with differential functional brain activation: a positron emission tomography study with oxygen 15-labeled water.
Regions of functional brain activation differ between novice and expert laparoscopists. We compared novice and expert laparoscopists using positron emission tomography (PET) during the peg transfer task of the McGill Inanimate System for Training and Evaluation of Laparoscopic Skills (MISTELS) protocol. The first scan (rest) was performed with the subject's eyes closed. The second scan (video 1) was performed while watching a peg transfer video. The third scan (peg 1) was acquired during the peg transfer task. The forth scan (peg 2) was performed after practicing 15 minutes. The fifth scan (video 2) was performed after peg 2 as the subject watched a video clip of a laparoscopic partial nephrectomy. The sixth scan (peg 3) was conducted during the final peg transfer task after 15 more minutes of practice. Feinstein Institute for Medical Research. Five novice and 5 expert laparoscopists. Differences in brain activation as determined by changes in regional cerebral blood flow on PET scans with oxygen 15-labeled water. The first analysis examined group differences between the 3 peg scans and the rest scan. The novice group had a significantly (P < .001) higher activation (with deactivation in the expert group) in the left precentral gyrus and insula and the right precuneus and inferior occipital gyrus. The second analysis compared the 2 video scans and the rest scan. In contrast to the expert group, the novices had significantly (P < .001) higher activation in the right precuneus and cuneus but deactivation in the bilateral posterior cerebellum. This study demonstrates differential regional brain activation patterns between novice and expert laparoscopists during surgery-related motor and visual association tasks.


Cloning, sequencing, and functional characterization of the two subunits of the pseudorabies virus DNA polymerase holoenzyme: evidence for specificity of interaction.
The pseudorabies virus (PRV) genes encoding the two subunits of the DNA polymerase were located on the genome by hybridization to their herpes simplex virus type 1 (HSV-1) homologs, pol and UL42, and subsequently were sequenced. Like the HSV-1 homologs, in vitro translation products of the PRV gene encoding the catalytic subunit (pol) possessed activity in the absence of the Pol accessory protein (PAP). However, the PRV PAP stimulated the activity of Pol fourfold in the presence of 150 mM KCl, using an activated calf thymus DNA template. The stimulation of Pol activity by PAP under high-salt conditions and the inhibition of Pol activity by PAP when assayed in low salt (0 mM KCl) together were used to determine the specificity with which PAP interacted with Pol. Despite functional similarity, HSV-1 UL42 and PRV PAP could neither stimulate the noncognate Pols at high salt nor inhibit them at low salt. Furthermore, a PRV Pol mutant lacking the 30 C-terminal amino acids retained basal Pol activity but could be neither stimulated nor inhibited by the PRV PAP. Sequence comparisons of the Pol proteins of the alphaherpesviruses reveal a conserved domain in the C terminus which terminates immediately before the last 41 residues of both PRV and HSV-1 proteins. These results indicate that the ability and specificity for interaction of the PRV Pol with PAP most likely resides predominantly in the extreme Pol C terminus.


One hundred questions of importance to the conservation of global biological diversity.
We identified 100 scientific questions that, if answered, would have the greatest impact on conservation practice and policy. Representatives from 21 international organizations, regional sections and working groups of the Society for Conservation Biology, and 12 academics, from all continents except Antarctica, compiled 2291 questions of relevance to conservation of biological diversity worldwide. The questions were gathered from 761 individuals through workshops, email requests, and discussions. Voting by email to short-list questions, followed by a 2-day workshop, was used to derive the final list of 100 questions. Most of the final questions were derived through a process of modification and combination as the workshop progressed. The questions are divided into 12 sections: ecosystem functions and services, climate change, technological change, protected areas, ecosystem management and restoration, terrestrial ecosystems, marine ecosystems, freshwater ecosystems, species management, organizational systems and processes, societal context and change, and impacts of conservation interventions. We anticipate that these questions will help identify new directions for researchers and assist funders in directing funds.


Optimal entry point and trajectory for endoscopic third ventriculostomy: evaluation of 53 patients with volumetric imaging guidance.
An optimal entry point for endoscopic third ventriculostomy (ETV) helps protect critical structures from undue manipulation. A commonly accepted ideal entry point is 3 cm from the midline and 1 cm anterior to the coronal suture. The authors of this study reexamine this ideal entry point. Trajectory views from MR images or CT scans used for cranial image guidance in 53 patients (age range 3-85 years) who had undergone ETV were retrospectively evaluated. The trajectory from the tuber cinereum back through the center of the foramen of Monro was projected to the surface of the head. The relation of the entry point to the midline and the coronal suture was established. The mean perpendicular distance from the ideal entry point to the midline was 30.1 ± 7 mm (median 31.9 mm, range 12.5-42.2 mm). The mean perpendicular distance to the coronal suture was 8.9 ± 14.1 mm posterior (median 10.4 mm), ranging from 30.6 mm anterior to 35.8 mm posterior. The entry point tended to be located more posteriorly in women and adults: 5.8 ± 15.4 mm posterior in males versus 13.1 ± 13.2 mm posterior in females (p = 0.08) and 9.1 ± 14.8 mm posterior in adults versus 8.2 ± 11.7 mm posterior in children (p = 0.84). While the entry point may need to be modified from the ideal trajectory for other anatomical reasons, such as a trajectory through the motor cortex, in general, the authors found that the optimal entry point for ETV was more posterior than previously published and highly variable. Using image guidance or a customized trajectory based on analysis of a patient's own imaging is highly preferable to using an empirical ideal trajectory.


Kinetics of nutrient removal and expression of extracellular polymeric substances of the microalgae, Chlorella sp. and Micractinium sp., in wastewater treatment.
Two species of green algae, Chlorella sp. and Micractinium sp., were cultivated in primary effluent wastewater and high-strength wastewater (a mixture of anaerobic digestion centrate and primary effluent) to study nutrient removal and EPS (extracellular polymeric substances) expression during their growth. The high N concentration and P-limited condition in the mixed wastewater (total N=197 mg/L; N/P mass ratio=56) led to about 3 times greater specific N removal rate than the primary effluent set, indicating that algal cells growing in N-rich wastewater had N over-uptake. Both Chlorella and Micractinium grown in the high-strength wastewater also produced larger amounts of protein EPS, possibly accounting for higher N uptake in those cultivation sets. These results suggest that different types of wastewater could cause different nutrient removal kinetics and EPS expression by algae, which may subsequently influence harvesting and anaerobic digestion of their biomass.


Rapid disappearance of statin, a nonproliferating and senescent cell-specific protein, upon reentering the process of cell cycling.
Statin, a 57,000-D protein characteristically found in nonreplicating cells, was identified by a monoclonal antibody produced by hybridomas established from mice injected with extracts of in vitro aged human fibroblasts (Wang, E., 1985, J. Cell Biol., 100:545-551). Fluorescence staining with the antibody shows that the expression of statin disappears upon reinitiation of the process for cell replication. The rapid de-expression is observed in fibroblasts involved in the in vitro wound-healing process, as well as in cells that have been subcultured after trypsinization and replated from a confluent culture. Kinetic analysis shows that 50% of the cell population lose their statin expression at 12 h after replating, before the actual events of mitosis. Immunogold labeling with highly purified antibodies localizes the protein at the nuclear envelope in nonreplicating cells, but not in their replicating counterparts. Immunoblotting analysis confirms the disappearance of statin in cells that have reentered the cycling process. Using the technique of flow cytometry to examine the large number of nonreplicating fibroblasts in confluent cultures, we have found that statin is mostly expressed in those cells showing the least amount of DNA content, whose growth is blocked at the G0/G1 stage of the cell cycle. This close correlation is rapidly altered once the cells are released from the confluent state. These results suggest that the expression of statin may be regulated by a fine mechanism controlling the transition from the nonreplicating to the replicating state, and that the protein is structurally associated with the nuclear envelope.


Biological responses of preosteoblasts to particulate and ion forms of Co-Cr alloy.
This study compared the particulate and ion forms of a cobalt-chrome (Co-Cr) alloy on the differentiation/activation of preosteoblasts. Mouse preosteoblasts (MC3T3-E1) were cultured in an osteoblast-induction medium in the presence of particulate and ion forms of a Co-Cr alloy, followed by cell proliferation and cytotoxicity evaluations. The maturation and function of osteoblasts were assessed by alkaline phosphatase (ALP) assay and related gene expressions. Both particulate and ion forms of the metals significantly reduced the proliferation of MC3T3-E1 cells in a dose-dependent manner. Similarly, cells challenged with high concentrations of particles and ions exhibited a marked cytotoxic effect and diminished expression of ALP. Real-time (RT) polymerase chain reaction (PCR) data have suggested that cells with Co-Cr particles dramatically promoted over-expression of monocyte chemo-attractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), whereas Co(2+) ions treatment predominately up-regulated expressions of receptor activator of nuclear factor kappa-B ligand (RANKL), nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), and down-regulated expression of osteoprotegerin (OPG) and Osterix (Osx). Overall, this study provides evidence that both Co-Cr alloy particles and metal ions interfered with the MC3T3-E1 cells for their growth, maturation, and functions. Further, Co-Cr particles exhibited stronger effects on inflammatory mediators, while metal ions showed more influence on inhibition of osteoblast differentiation and promotion of osteoclastogenesis.


The trajectories and correlation between physical limitation and depression in elderly residents of Beijing, 1992-2009.
Physical limitation and psychological distress have been reported to be related, but studies describing the change of instrumental activities of daily living (IADLs) and depression syndrome over time or exploring the link pattern for their development are limited. The study was to assess distinctive patterns for the development of physical limitation and depression and to explore their correlation to form a proper prevention strategy. Dual trajectory analysis was conducted using data from the Beijing Longitudinal Study of Aging (BLSA) 1992-2009 hosted by Xuanwu hospital for subjects with full information on depression and physical limitation for all available visits. Physical limitation was measured by the Instrumental Activities of Daily Living (IADL) scale and depression by the Center for Epidemiological Studies Depression scale (CES-D). The covariates were gender, age at baseline and number of chronic conditions. Three heterogeneous trajectories for physical limitation and two distinct groups for an increase in depression were detected. Among them, 10.13% of subjects experienced an increase in physical limitation, while 13.22% demonstrated a high, stable level of depressive mood. In all, 80.4% of the subjects enjoyed a relatively low, stable level of IADL and CES-D scores. People in the late increase group for IADL score were more likely to have depressive mood when adjusted for gender, age and number of chronic conditions (OR=3.900, 95%CI=1.347-11.290). The development of physical limitation among the elderly may significantly increase the risk for depressive symptoms.


Controversies in Inflammatory Bowel Disease: Exploring Clinical Dilemmas Using Cochrane Reviews.
A symposium organized by the Cochrane IBD Group and presented at the 2017 Digestive Disease Week annual meeting reviewed the recent literature on several controversial topics in inflammatory bowel disease (IBD) management including the efficacy of oral aminosalicylates for induction and maintenance of Crohn's disease (CD), the feasibility of drug withdrawal in patients with quiescent CD, and strategies for detecting colon cancer in patients with IBD. This article summarizes the data presented at that session.


Association Between Vitamin D Levels and Treatment Response to Direct-Acting Antivirals in Chronic Hepatitis C: A Real-World Study.
Low serum vitamin D levels in chronic hepatitis C (CHC) is associated with advanced liver fibrosis; and there remains an imprecise relationship with the treatment response based on the vitamin D levels. Previous studies have shown conflicting results on the vitamin D levels, and association with treatment response in CHC treated with interferon-based regimens. Patients with CHC treated with direct-acting antivirals (DAAs) between January 2016 and December 2017 in the community clinic setting were retrospectively analyzed. Pretreatment baseline patient characteristics, treatment efficacy with the sustained virologic response at 12 weeks post-treatment (SVR 12) were assessed in CHC patients with deficient, insufficient, and normal levels of vitamin D measured before the initiation of DAA therapy. Two hundred and ninety-one patients were included in the study. Direct-acting antivirals included in the study were ledipasvir/sofosbuvir ± ribavirin, ombitasvir + paritaprevir + ritonavir + dasabuvir ± ribavirin, and sofosbuvir/velpatasvir. An overall sustained virologic response was achieved in 95% (n = 276) of patients. SVR 12 rates among patients with vitamin D deficiency, vitamin D insufficiency and normal vitamin D levels were 92%, 96.2%, and 97.2% respectively and was not statically significant (P = 0.214). A total of 71 patients were cirrhotic. The prevalence of vitamin D insufficiency (20 - 29.9 ng/mL) and deficiency (< 20 ng/mL) was significantly higher in cirrhotic patients (P = 0.01). Despite this, pretreatment vitamin D levels did not show any impact on the virologic response. The most common adverse effect observed was fatigue. None of the patients had to discontinue the treatment due to adverse events. DAAs are safe and effective with a high overall SVR 12 in CHC and treatment response does not depend on the pretreatment vitamin D levels. The prevalence of both vitamin D insufficiency and deficiency was observed to be higher in cirrhotic cohorts compared to non-cirrhotic counterparts.


Positive selection shaped the convergent evolution of independently expanded kallikrein subfamilies expressed in mouse and rat saliva proteomes.
We performed proteomics studies of salivas from the genome mouse (C57BL/6 strain) and the genome rat (BN/SsNHsd/Mcwi strain). Our goal was to identify salivary proteins with one or more of three characteristics that may indicate that they have been involved in adaptation: 1) rapid expansion of their gene families; 2) footprints of positive selection; and/or 3) sex-limited expression. The results of our proteomics studies allow direct comparison of the proteins expressed and their levels between the sexes of the two rodent species. Twelve members of the Mus musculus species-specific kallikrein subfamily Klk1b showed sex-limited expression in the mouse saliva proteomes. By contrast, we did not find any of the Rattus norvegicus species-specific kallikrein subfamily Klk1c proteins in male or female genome rat, nor transcripts in their submandibular glands. On the other hand, we detected expression of this family as transcripts in the submandibular glands of both sexes of Sprague-Dawley rats. Using the CODEML program in the PAML package, we demonstrate that the two rodent kallikrein subfamilies have apparently evolved rapidly under the influence of positive selection that continually remodeled the amino acid sites on the same face in the members of the subfamilies. Thus, although their kallikrein subfamily expansions were independent, this evolutionary pattern has occurred in parallel in the two rodent species, suggesting a form of convergent evolution at the molecular level. On the basis of this new data, we suggest that the previous speculative function of the species-specific rodent kallikreins as important solely in wound healing in males be investigated further. In addition to or instead of that function, we propose that their sex-limited expression, coupled with their rapid evolution may be clues to an as-yet-undetermined interaction between the sexes.


Prevalence and risk factors of HSV-2 infection and HSV-2/HIV coinfection in men who have sex with men in China: a multisite cross-sectional study.
To determine the prevalence and risk factors of herpes simplex virus type 2 (HSV-2) infection and its coinfection with human immunodeficiency virus (HIV) in men who have sex with men (MSM) in China. A convenience sample of 1462 MSM were recruited from different settings (an STD clinic, a health center, and MSM venues) in 3 cities in China. Blood specimens were collected for testing for antibodies to HSV-2 and HIV to determinate the seroprevalence of HSV-2 infection and HSV-2/HIV coinfection. Information on sociodemographic and behavioral characteristics was collected to determine the risk factors associated with the infections. The prevalence of HSV-2 infection in 1462 MSM was 16.0% (95% confidence interval [CI], 14.2%-18.0%), the prevalence of HIV infection in this population was 9.5% (95% CI, 8.1%-11.1%), and the rate of coinfection of HSV-2 and HIV was 3.2% (95% CI, 2.4%-4.3%). Multivariate logistic regression analysis showed that risk factors for HSV-2 infection included age older than 30 years, education level lower than senior high school, involvement in commercial sex work, and HIV-positive status. Education level lower than junior high school and history of sexual abuse were associated with HSV-2/HIV coinfection. The high prevalence of HSV-2 infection and HSV-2/HIV coinfection among MSM in China suggests that an increased focus on HSV control is warranted within China's prevention and intervention programs targeted toward MSM.


Identification of a sphingolipid α-glucuronosyltransferase that is essential for pollen function in Arabidopsis.
Glycosyl inositol phosphorylceramide (GIPC) sphingolipids are a major class of lipids in fungi, protozoans, and plants. GIPCs are abundant in the plasma membrane in plants, comprising around a quarter of the total lipids in these membranes. Plant GIPCs contain unique glycan decorations that include a conserved glucuronic acid (GlcA) residue and various additional sugars; however, no proteins responsible for glycosylating GIPCs have been identified to date. Here, we show that the Arabidopsis thaliana protein INOSITOL PHOSPHORYLCERAMIDE GLUCURONOSYLTRANSFERASE1 (IPUT1) transfers GlcA from UDP-GlcA to GIPCs. To demonstrate IPUT1 activity, we introduced the IPUT1 gene together with genes for a UDP-glucose dehydrogenase from Arabidopsis and a human UDP-GlcA transporter into a yeast mutant deficient in the endogenous inositol phosphorylceramide (IPC) mannosyltransferase. In this engineered yeast strain, IPUT1 transferred GlcA to IPC. Overexpression or silencing of IPUT1 in Nicotiana benthamiana resulted in an increase or a decrease, respectively, in IPC glucuronosyltransferase activity in vitro. Plants in which IPUT1 was silenced accumulated IPC, the immediate precursor, as well as ceramides and glucosylceramides. Plants overexpressing IPUT1 showed an increased content of GIPCs. Mutations in IPUT1 are not transmitted through pollen, indicating that these sphingolipids are essential in plants.


Elimination of glycerol and replacement with alternative products in ethanol fermentation by Saccharomyces cerevisiae.
Glycerol is a major by-product of ethanol fermentation by Saccharomyces cerevisiae and typically 2-3% of the sugar fermented is converted to glycerol. Replacing the NAD(+)-regenerating glycerol pathway in S. cerevisiae with alternative NADH reoxidation pathways may be useful to produce metabolites of biotechnological relevance. Under fermentative conditions yeast reoxidizes excess NADH through glycerol production which involves NADH-dependent glycerol-3-phosphate dehydrogenases (Gpd1p and Gpd2p). Deletion of these two genes limits fermentative activity under anaerobic conditions due to accumulation of NADH. We investigated the possibility of converting this excess NADH to NAD(+) by transforming a double mutant (gpd1∆gpd2∆) with alternative oxidoreductase genes that might restore the redox balance and produce either sorbitol or propane-1,2-diol. All of the modifications improved fermentative ability and/or growth of the double mutant strain in a self-generated anaerobic high sugar medium. However, these strain properties were not restored to the level of the parental wild-type strain. The results indicate an apparent partial NAD(+) regeneration ability and formation of significant amounts of the commodity chemicals like sorbitol or propane-1,2-diol. The ethanol yields were maintained between 46 and 48% of the sugar mixture. Other factors apart from the maintenance of the redox balance appeared to influence the growth and production of the alternative products by the genetically manipulated strains.


Mortality and morbidity among farmers, nonfarming rural men, and urban referents: a prospective population-based study.
A cohort of 1,220 farmers, 1,130 nonfarming rural men, and 1,087 urban referents from Sweden were monitored for 12 years. Farmers had lower mortality than urban referents for all causes of death (hazard ratio [HR] = 0.51; 95% confidence interval [CI], 0.37-0.71), cancer (HR = 0.44; 95% CI, 0.24-0.78) and cardiovascular diseases (HR = 0.60; 95% CI, 0.36-0.99). Nonfarming rural men had lower mortality than urban referents for all causes of deaths (HR = 0.81; 95% CI, 0.70-0.94). Farmers and nonfarming rural men had significantly lower morbidity risks of cancer and of psychiatric disorders than urban referents. Farmers had significantly lower risk of endocrine disorders, cardiovascular disorders, and respiratory disorders. In general, morbidity was lower among nonfarming rural men compared with urban referents and was even lower among farmers. Urban referents had, however, significantly less musculoskeletal disorder morbidity. An urban-rural factor and a farming occupational or lifestyle factor results in lower mortality and morbidity rates except concerning musculoskeletal disorders.


The lysosome: from waste bag to potential therapeutic target.
Lysosomes are ubiquitous membrane-bound intracellular organelles with an acidic interior. They are central for degradation and recycling of macromolecules delivered by endocytosis, phagocytosis, and autophagy. In contrast to the rather simplified view of lysosomes as waste bags, nowadays lysosomes are recognized as advanced organelles involved in many cellular processes and are considered crucial regulators of cell homeostasis. The function of lysosomes is critically dependent on soluble lysosomal hydrolases (e.g. cathepsins) as well as lysosomal membrane proteins (e.g. lysosome-associated membrane proteins). This review focuses on lysosomal involvement in digestion of intra- and extracellular material, plasma membrane repair, cholesterol homeostasis, and cell death. Regulation of lysosomal biogenesis and function via the transcription factor EB (TFEB) will also be discussed. In addition, lysosomal contribution to diseases, including lysosomal storage disorders, neurodegenerative disorders, cancer, and cardiovascular diseases, is presented.


Fra-1 regulates its target genes via binding to remote enhancers without exerting major control on chromatin architecture in triple negative breast cancers.
The ubiquitous family of dimeric transcription factors AP-1 is made up of Fos and Jun family proteins. It has long been thought to operate principally at gene promoters and how it controls transcription is still ill-understood. The Fos family protein Fra-1 is overexpressed in triple negative breast cancers (TNBCs) where it contributes to tumor aggressiveness. To address its transcriptional actions in TNBCs, we combined transcriptomics, ChIP-seqs, machine learning and NG Capture-C. Additionally, we studied its Fos family kin Fra-2 also expressed in TNBCs, albeit much less. Consistently with their pleiotropic effects, Fra-1 and Fra-2 up- and downregulate individually, together or redundantly many genes associated with a wide range of biological processes. Target gene regulation is principally due to binding of Fra-1 and Fra-2 at regulatory elements located distantly from cognate promoters where Fra-1 modulates the recruitment of the transcriptional co-regulator p300/CBP and where differences in AP-1 variant motif recognition can underlie preferential Fra-1- or Fra-2 bindings. Our work also shows no major role for Fra-1 in chromatin architecture control at target gene loci, but suggests collaboration between Fra-1-bound and -unbound enhancers within chromatin hubs sometimes including promoters for other Fra-1-regulated genes. Our work impacts our view of AP-1.


Total apolipoprotein E levels and specific isoform composition in cerebrospinal fluid and plasma from Alzheimer's disease patients and controls.
The apolipoprotein E (ApoE) ε4 allele is the strongest risk factor of sporadic Alzheimer's disease (AD), however, the fluid concentrations of ApoE and its different isoforms (ApoE2, ApoE3 and ApoE4) in AD patients and among APOE genotypes (APOE ε2, ε3, ε4) remain controversial. Using a novel mass spectrometry-based method, we quantified total ApoE and specific ApoE isoform concentrations and potential associations with age, cognitive status, cholesterol levels and established AD biomarkers in cerebrospinal fluid (CSF) from AD patients versus non-AD individuals with different APOE genotypes. We also investigated plasma total ApoE and ApoE isoform composition in a subset of these individuals. In total n = 43 AD and n = 43 non-AD subjects were included. We found that CSF and plasma total ApoE levels did not correlate with age or cognitive status and did not differ between AD and non-AD subjects deeming ApoE as an unfit diagnostic marker for AD. Also, whereas CSF ApoE levels did not vary between APOE genotypes APOE ε4 carriers exhibited significantly decreased plasma ApoE levels attributed to a specific decrease in the ApoE4 isoform concentrations. CSF total ApoE concentrations were positively associated with CSF, total tau, tau phosphorylated at Thr181 and Aβ1-42 of which the latter association was weaker and only present in APOE ε4 carriers indicating a differential involvement of ApoE in tau versus Aβ-linked neuropathological processes. Future studies need to elucidate whether the observed plasma ApoE4 deficiency is a life-long condition in APOE ɛ4 carriers and whether this decrease in plasma ApoE predisposes APOE ɛ4 carriers to AD.


A consortia of clinical E. coli strains with distinct in-vitro adherent/invasive properties establish their own co-colonization niche and shape the intestinal microbiota in inflammation-susceptible mice.
Inflammatory bowel disease (IBD) patients experience recurrent episodes of intestinal inflammation and often follow an unpredictable disease course. Mucosal colonization with adherent-invasive Escherichia coli (AIEC) are believed to perpetuate intestinal inflammation. However, it remains unclear if the 24-year-old AIEC in-vitro definition fully predicts mucosal colonization in-vivo. To fill this gap, we have developed a novel molecular barcoding approach to distinguish strain variants in the gut and have integrated this approach to explore mucosal colonization of distinct patient-derived E. coli isolates in gnotobiotic mouse models of colitis. Germ-free inflammation-susceptible interleukin-10-deficient (Il10-/-) and inflammation-resistant WT mice were colonized with a consortia of AIEC and non-AIEC strains, then given a murine fecal transplant to provide niche competition. E. coli strains isolated from human intestinal tissue were each marked with a unique molecular barcode that permits identification and quantification by barcode-targeted sequencing. 16S rRNA sequencing was used to evaluate the microbiome response to E. coli colonization. Our data reveal that specific AIEC and non-AIEC strains reproducibly colonize the intestinal mucosa of WT and Il10-/- mice. These E. coli expand in Il10-/- mice during inflammation and induce compositional dysbiosis to the microbiome in an inflammation-dependent manner. In turn, specific microbes co-evolve in inflamed mice, potentially diversifying E. coli colonization patterns. We observed no selectivity in E. coli colonization patterns in the fecal contents, indicating minimal selective pressure in this niche from host-microbe and interbacterial interactions. Because select AIEC and non-AIEC strains colonize the mucosa, this suggests the in vitro AIEC definition may not fully predict in vivo colonization potential. Further comparison of seven E. coli genomes pinpointed unique genomic features contained only in highly colonizing strains (two AIEC and two non-AIEC). Those colonization-associated features may convey metabolic advantages (e.g., iron acquisition and carbohydrate consumption) to promote efficient mucosal colonization. Our findings establish the in-vivo mucosal colonizer, not necessarily AIEC, as a principal dysbiosis driver through crosstalk with host and associated microbes. Furthermore, we highlight the utility of high-throughput screens to decode the in-vivo colonization dynamics of patient-derived bacteria in murine models.


Are non-fungible payments attractive when they reduce risk exposure? Evidence from Colombia.
We conducted a lab-in-the-field experiment in which 214 Colombian rural workers must choose between cash or voucher payment for completing a real effort task. Although the voucher may be perceived as non-fungible, it halves the probability of suffering a negative shock that will reduce the participant's payment by two-thirds. Participants made four decisions in which we vary the voucher values such that this payment method offers, in expectation, between 88% to 123% of the cash payment (fixed across decisions). We find that uptake rates go from 32% to 56%, from the least to the most generous voucher. These rates are consistently larger compared to a reference sample of undergrad students from the same region (p-values from the χ2 tests for all four decisions fall below 0.035). Our between-subjects variations reveal that presenting the vouchers in descending order yields a higher uptake than the ascending order (p < 0.001 for the corresponding coefficient in a tobit and ordered logit regressions including municipality characteristics, an effect driven by the two decisions with the lowest voucher values, with p-values of 0.008 and 0.072 in the χ2 tests, respectively). We interpret this result as an endowment effect of the voucher's risk reduction.


Using Functional Near Infrared Spectroscopy (fNIRS) to Study Dynamic Stereoscopic Depth Perception.
The parietal cortex has been widely implicated in the processing of depth perception by many neuroimaging studies, yet functional near infrared spectroscopy (fNIRS) has been an under-utilised tool to examine the relationship of oxy- ([HbO]) and de-oxyhaemoglobin ([HbR]) in perception. Here we examine the haemodynamic response (HDR) to the processing of induced depth stimulation using dynamic random-dot-stereograms (RDS). We used fNIRS to measure the HDR associated with depth perception in healthy young adults (n = 13, mean age 24). Using a blocked design, absolute values of [HbO] and [HbR] were recorded across parieto-occipital and occipital cortices, in response to dynamic RDS. Control and test images were identical except for the horizontal shift in pixels in the RDS that resulted in binocular disparity and induced the percept of a 3D sine wave that 'popped out' of the test stimulus. The control stimulus had zero disparity and induced a 'flat' percept. All participants had stereoacuity within normal clinical limits and successfully perceived the depth in the dynamic RDS. Results showed a significant effect of this complex visual stimulation in the right parieto-occipital cortex (p < 0.01, η(2) = 0.54). The test stimulus elicited a significant increase in [HbO] during depth perception compared to the control image (p < 0.001, 99.99 % CI [0.008-0.294]). The similarity between the two stimuli may have resulted in the HDR of the occipital cortex showing no significant increase or decrease of cerebral oxygenation levels during depth stimulation. Cerebral oxygenation measures of [HbO] confirmed the strong association of the right parieto-occipital cortex with processing depth perception. Our study demonstrates the validity of fNIRS to investigate [HbO] and [HbR] during high-level visual processing of complex stimuli.


Comparative quantitative structure-activity-activity relationships for toxicity to Tetrahymena pyriformis and Pimephales promelas.
An approach for predicting acute aquatic toxicity, in the form of a quantitative structure-activity-activity relationship (QSAAR), is described. This study assessed relative toxic effects to a fish, Pimephales promelas, and a ciliate, Tetrahymena pyriformis, and attempted to form relationships between them. A good agreement between toxic potencies (R2 = 0.754) was found for a chemically diverse dataset of 364 compounds, when using toxicity to the ciliate as a surrogate to that for fish. This relationship was extended by adding three theoretical structural descriptors of the molecules. The inclusion of these descriptors improved the relationship further (R2 = 0.824). The structural features that were found to improve the extrapolation between the toxicity to the two different species were related to the electron distribution of the carbon skeleton of the toxicant, its hydrogen-bonding ability, and its relative nitrogen content. Such a QSAAR approach provides a potential tool for predicting the toxicities of chemicals for environmental risk assessment and thus for reducing animal tests.


Rathke's cleft cyst with non-hemorrhagic rupture resulting in alteration of signal intensity for a short period: a case report.
In a case of 23-year-old female with Rathke's cleft cyst (RCC), unusual changes with size and morphology on computed tomography (CT) and magnetic resonance images (MRI) were noted in a short period of 3 weeks after spontaneous rupture. The CT noted that the intracystic isodensity was changed to hyperdensity. And MRI showed not only a decrease in size of the lesion but also changing from hypo- and hyperintensity in T1- and T2-weighted images to hyperintensity in both T1- and T2-weighted images. The intraoperative findings disclosed that the cyst content was milky-like, but not hemorrhagic. We considered that the leakage of cyst content to the cerebrospinal fluid pathway caused not only inflammatory reaction but also waxing and waning of both the cyst size and intralesional protein concentration, which resulted in unusual changing CT and MR appearance. We should take into consideration that the nature of RCC can be altered by not only intracystic hemorrhage but also non-hemorrhagic rupture even for a short period.


Stochastic tissue window normalization of deep learning on computed tomography.
Tissue window filtering has been widely used in deep learning for computed tomography (CT) image analyses to improve training performance (e.g., soft tissue windows for abdominal CT). However, the effectiveness of tissue window normalization is questionable since the generalizability of the trained model might be further harmed, especially when such models are applied to new cohorts with different CT reconstruction kernels, contrast mechanisms, dynamic variations in the acquisition, and physiological changes. We evaluate the effectiveness of both with and without using soft tissue window normalization on multisite CT cohorts. Moreover, we propose a stochastic tissue window normalization (SWN) method to improve the generalizability of tissue window normalization. Different from the random sampling, the SWN method centers the randomization around the soft tissue window to maintain the specificity for abdominal organs. To evaluate the performance of different strategies, 80 training and 453 validation and testing scans from six datasets are employed to perform multiorgan segmentation using standard 2D U-Net. The six datasets cover the scenarios, where the training and testing scans are from (1) same scanner and same population, (2) same CT contrast but different pathology, and (3) different CT contrast and pathology. The traditional soft tissue window and nonwindowed approaches achieved better performance on (1). The proposed SWN achieved general superior performance on (2) and (3) with statistical analyses, which offers better generalizability for a trained model.


"That was a good shift".
Purpose The purpose of this paper is to investigate a boundary spanning, interprofessional collaboration between advanced practice nurses (APNs) and junior doctors to support junior doctors' learning and improve patient management during the overtime shift. Design/methodology/approach A mixed methods evaluation of an intervention in an adult tertiary referral hospital, to enhance interprofessional collaboration on overtime shifts. Phase 1 compared tasks and ward rounds on 86 intervention shifts with 106 "regular" shifts, and examined the effect on junior doctor patient management testing a model using regression techniques. Phase 2 explored the experience of the intervention for stakeholders. 91 junior doctors participated (89 percent response rate) on 192 overtime shifts. Junior doctors, APNs and senior medical professionals/administrators participated in interviews. Findings The intervention was associated with an increase in self-initiated ward rounds by junior doctors, partially explained by junior doctors completing fewer tasks skilled nurses could also complete. The intervention significantly reduced doctors' engagement in tasks carried over from day shifts as well as first year (but not more experienced) junior doctors' total tasks. Interviews suggested the initiative reduced junior doctors' work pressure and promoted a safe team climate, situation awareness, skills, confidence, and well-being. Originality/value Junior doctors overtime shifts (5 p.m. to 11 p.m.) are important, both for hospitals to maintain patient care after hours and for junior doctors to learn and develop independent clinical decision making skills. However, junior doctors frequently report finding overtime shifts challenging and stressful. Redesigning overtime shifts to facilitate interprofessional collaboration can improve patient management and junior doctors' learning and well-being.


High cardiorespiratory fitness in early to late middle age preserves the cortical circuitry associated with brain-heart integration during volitional exercise.
This study tested the hypothesis that high cardiorespiratory fitness (peak oxygen uptake) preserves the cortical circuitry associated with cardiac arousal during exercise in middle- to older-aged individuals. Observations of changes in heart rate (HR) and in cortical blood oxygenation level-dependent (BOLD) images were made in 52 healthy, active individuals (45-73 yr; 16 women, 36 men) across a range of fitness (26-66 ml·kg-1·min-1). Seven repeated bouts of isometric handgrip (IHG) at 40% maximal voluntary contraction force were performed with functional magnetic resonance imaging at 3 T, with each contraction lasting 20 s and separated by 40 s of rest. HR responses to IHG showed high variability across individuals. Linear regression revealed that cardiorespiratory fitness was not a strong predictor of the HR response (r2 = 0.09). In a region-of-interest analysis both the IHG task and the HR time course correlated with increased cortical activation in the bilateral insula and decreased activation relative to baseline in the anterior and posterior cingulate and medial prefrontal cortex (MPFC). t-Test results revealed greater deactivation at the MPFC with higher fitness levels beyond that of guideline-based activity. Therefore, whereas high cardiorespiratory fitness failed to affect absolute HR responses to IHG in this age range, a select effect was observed in cortical regions known to be associated with cardiovascular arousal.NEW & NOTEWORTHY Our first observation suggests that fitness does not strongly predict the heart rate (HR) response to a volitional handgrip task in middle- to older-aged adults. Second, the BOLD response associated with the handgrip task, and with the HR time course, was associated with response patterns in the cortical autonomic network. Finally, whereas high cardiorespiratory fitness failed to affect absolute HR responses to isometric handgrip in this age range, a select effect was observed in cortical regions known to be associated with cardiovascular arousal, beyond that achieved through healthy active living.


SynChro: a fast and easy tool to reconstruct and visualize synteny blocks along eukaryotic chromosomes.
Reconstructing synteny blocks is an essential step in comparative genomics studies. Different methods were already developed to answer various needs such as genome (re-)annotation, identification of duplicated regions and whole genome duplication events or estimation of rearrangement rates. We present SynChro, a tool that reconstructs synteny blocks between pairwise comparisons of multiple genomes. SynChro is based on a simple algorithm that computes Reciprocal Best-Hits (RBH) to reconstruct the backbones of the synteny blocks and then automatically completes these blocks with non-RBH syntenic homologs. This approach has two main advantages: (i) synteny block reconstruction is fast (feasible on a desk computer for large eukaryotic genomes such as human) and (ii) synteny block reconstruction is straightforward as all steps are integrated (no need to run Blast or TribeMCL prior to reconstruction) and there is only one parameter to set up, the synteny block stringency [Formula: see text]. Benchmarks on three pairwise comparisons of genomes, representing three different levels of synteny conservation (Human/Mouse, Human/Zebra Finch and Human/Zebrafish) show that Synchro runs faster and performs at least as well as two other commonly used and more sophisticated tools (MCScanX and i-ADHoRe). In addition, SynChro provides the user with a rich set of graphical outputs including dotplots, chromosome paintings and detailed synteny maps to visualize synteny blocks with all homology relationships and synteny breakpoints with all included genetic features. SynChro is freely available under the BSD license at http://www.lcqb.upmc.fr/CHROnicle/SynChro.html.


The impact of antecedent fire area on burned area in southern California coastal ecosystems.
Frequent wildfire disasters in southern California highlight the need for risk reduction strategies for the region, of which fuel reduction via prescribed burning is one option. However, there is no consensus about the effectiveness of prescribed fire in reducing the area of wildfire. Here, we use 29 years of historical fire mapping to quantify the relationship between annual wildfire area and antecedent fire area in predominantly shrub and grassland fuels in seven southern California counties, controlling for annual variation in weather patterns. This method has been used elsewhere to measure leverage: the reduction in wildfire area resulting from one unit of prescribed fire treatment. We found little evidence for a leverage effect (leverage = zero). Specifically our results showed no evidence that wildfire area was negatively influenced by previous fires, and only weak relationships with weather variables rainfall and Santa Ana wind occurrences, which were variables included to control for inter-annual variation. We conclude that this is because only 2% of the vegetation burns each year and so wildfires rarely encounter burned patches and chaparral shrublands can carry a fire within 1 or 2 years after previous fire. Prescribed burning is unlikely to have much influence on fire regimes in this area, though targeted treatment at the urban interface may be effective at providing defensible space for protecting assets. These results fit an emerging global model of fire leverage which position California at the bottom end of a continuum, with tropical savannas at the top (leverage = 1: direct replacement of wildfire by prescribed fire) and Australian eucalypt forests in the middle (leverage ~ 0.25).


DNA microarrays in clinical oncology.
Aberrant gene expression is critical for tumor initiation and progression. However, we lack a comprehensive understanding of all genes that are aberrantly expressed in human cancer. Recently, DNA microarrays have been used to obtain global views of human cancer gene expression and to identify genetic markers that might be important for diagnosis and therapy. We review clinical applications of these novel tools, discuss some important recent studies, identify promising avenues of research in this emerging field of study, and discuss the likely impact that expression profiling will have on clinical oncology.


A Bottom-up Approach to Data Annotation in Neurophysiology.
Metadata providing information about the stimulus, data acquisition, and experimental conditions are indispensable for the analysis and management of experimental data within a lab. However, only rarely are metadata available in a structured, comprehensive, and machine-readable form. This poses a severe problem for finding and retrieving data, both in the laboratory and on the various emerging public data bases. Here, we propose a simple format, the "open metaData Markup Language" (odML), for collecting and exchanging metadata in an automated, computer-based fashion. In odML arbitrary metadata information is stored as extended key-value pairs in a hierarchical structure. Central to odML is a clear separation of format and content, i.e., neither keys nor values are defined by the format. This makes odML flexible enough for storing all available metadata instantly without the necessity to submit new keys to an ontology or controlled terminology. Common standard keys can be defined in odML-terminologies for guaranteeing interoperability. We started to define such terminologies for neurophysiological data, but aim at a community driven extension and refinement of the proposed definitions. By customized terminologies that map to these standard terminologies, metadata can be named and organized as required or preferred without softening the standard. Together with the respective libraries provided for common programming languages, the odML format can be integrated into the laboratory workflow, facilitating automated collection of metadata information where it becomes available. The flexibility of odML also encourages a community driven collection and definition of terms used for annotating data in the neurosciences.


Dopamine, Neurochemical Processes, and Oxygen Toxicity at Pressure.
All mammals, including man, exposed to breathing gas mixtures at high pressures exhibit central nervous system disturbances, which differ according to the gas used. With the use of compressed air, the increased oxygen partial pressure induces hyperoxic disturbances that consist of epileptic seizures that occur, on average, after 30 min exposure to 2.8 ATA in man or to 5 ATA in rats. Increased oxygen partial pressure induces reactive oxygen species and reactive nitrogen species production that could be related to neurotransmitter changes reported for the preepileptic phase or at pressures that produce epileptic seizures. In rats, oxygen pressures lower than 5 ATA induce a decrease of dopamine release in the stratum that could be due to disturbances of neurotransmitter regulatory processes that are different from those implicated for hyperbaric oxygen-induced epileptic seizures. © 2016 American Physiological Society. Compr Physiol 6:1339-1344, 2016.


The main trends in the palaeodemography of the 7th-18th century population of Latvia.
The study represents palaeodemographic research of osteological material of 3304 individuals from the funds of the Anthropological Laboratory of the Institute of History of the University of Latvia in Riga, dating from the 7th to the 18th century AD. Compensated life expectancy at birth is varying between 20.3 and 22.2 years during the research period. Crude mortality has changed between 49.3 and 45% per hundred. In the early period (7th-13th century) there is a significant male prevalence (2.2-1.4); female life expectancy at the age of 20 is on average 6.6 years less than for males. This difference decreases to 5.4 years in the 13th-18th century. According to historical demography, female life span exceeded male only in the 2nd half of 19th century. The palaeodemographic data indicate that in the 7th-18th century, women in Latvia gave birth to a mean of 4-5 children (the figure includes childless women), of whom half, at most 2-2.5, reached reproductive age, on account of high child mortality. The net reproductive rate R0 (the number of descendants per individual of the parents' generation) varies between 1 and 1.25 in the study period. Concerning the completely excavated cemeteries of Lejasbiteni (7th-10h century) and Daudziesi (16th-17th century), it was possible to calculate the size and structure of the populations that had used these cemeteries. They were similar, having 45.3-49.9% of children up to an age of 14 and 24-28% individuals over the age of 30. According to historical demography, radical improvement of the demographic situation in Latvia began in the second half of the 19th century, when the process of demographic transition in Latvia started.


Specification of anterior-posterior differences within the AB lineage in the C. elegans embryo: a polarising induction.
In a C. elegans embryo the third cleavages of descendants of the anterior blastomere AB of the 2-cell stage create pairs of blastomeres that develop differently. By laser ablation experiments we show that the fates of all the posterior daughters of this division depend on an induction occurring three cleavages before these blastomeres are born. The time of induction precludes a direct effect on cell fate. Alternatively, we suggest that the induction creates a heritable cell polarity which is propagated through several divisions. We suggest a model to demonstrate how a signal could be propagated through several rounds of cell division. An important implication of our observations is that this early induction acts to specify blastomere identity, not tissue type. A detailed lineage analysis revealed that altering the inductive signal alters complex lineage patterns as a whole. The induction described here, together with two inductions described previously can be used to illustrate how the anterior portion of the C. elegans embryo can be successively subdivided into blastomeres with unique developmental potential.


Annotation and sequence diversity of transposable elements in common bean (Phaseolus vulgaris).
Common bean (Phaseolus vulgaris) is an important legume crop grown and consumed worldwide. With the availability of the common bean genome sequence, the next challenge is to annotate the genome and characterize functional DNA elements. Transposable elements (TEs) are the most abundant component of plant genomes and can dramatically affect genome evolution and genetic variation. Thus, it is pivotal to identify TEs in the common bean genome. In this study, we performed a genome-wide transposon annotation in common bean using a combination of homology and sequence structure-based methods. We developed a 2.12-Mb transposon database which includes 791 representative transposon sequences and is available upon request or from www.phytozome.org. Of note, nearly all transposons in the database are previously unrecognized TEs. More than 5,000 transposon-related expressed sequence tags (ESTs) were detected which indicates that some transposons may be transcriptionally active. Two Ty1-copia retrotransposon families were found to encode the envelope-like protein which has rarely been identified in plant genomes. Also, we identified an extra open reading frame (ORF) termed ORF2 from 15 Ty3-gypsy families that was located between the ORF encoding the retrotransposase and the 3'LTR. The ORF2 was in opposite transcriptional orientation to retrotransposase. Sequence homology searches and phylogenetic analysis suggested that the ORF2 may have an ancient origin, but its function is not clear. These transposon data provide a useful resource for understanding the genome organization and evolution and may be used to identify active TEs for developing transposon-tagging system in common bean and other related genomes.


GAMBLINGLESS: FOR LIFE study protocol: a pragmatic randomised trial of an online cognitive-behavioural programme for disordered gambling.
The prevalence of disordered gambling worldwide has been estimated at 2.3%. Only a small minority of disordered gamblers seek specialist face-to-face treatment, and so a need for alternative treatment delivery models that capitalise on advances in communication technology, and use self-directed activity that can complement existing services has been identified. As such, the primary aim of this study is to evaluate an online self-directed cognitive-behavioural programme for disordered gambling (GamblingLess: For Life). The study will be a 2-arm, parallel group, pragmatic randomised trial. Participants will be randomly allocated to a pure self-directed (PSD) or guided self-directed (GSD) intervention. Participants in both groups will be asked to work through the 4 modules of the GamblingLess programme over 8 weeks. Participants in the GSD intervention will also receive weekly emails of guidance and support from a gambling counsellor. A total of 200 participants will be recruited. Participants will be eligible if they reside in Australia, are aged 18 years and over, have access to the internet, have adequate knowledge of the English language, are seeking help for their own gambling problems and are willing to take part in the intervention and associated assessments. Assessments will be conducted at preintervention, and at 2, 3 and 12 months from preintervention. The primary outcome is gambling severity, assessed using the Gambling Symptom Assessment Scale. Secondary outcomes include gambling frequency, gambling expenditure, psychological distress, quality of life and additional help-seeking. Qualitative interviews will also be conducted with a subsample of participants and the Guides (counsellors). The study has been approved by the Deakin University Human Research and Eastern Health Human Research Ethics Committees. Findings will be disseminated via report, peer-reviewed publications and conference presentations. ACTRN12615000864527; results.