Magnitude and concurrence of anxiety and depression among attendees with multiple sclerosis at a tertiary care Hospital in Oman.
Anxiety, depression and functional impairments are commonly reported by persons with multiple sclerosis (PwMS) but no data, to our knowledge, has emerged from an Arab Islamic population. The study aims to investigate the prevalence of anxiety, depression and related disabilities among PwMS attending tertiary care in Sultan Qaboos University Hospital (SQUH), one of the urban hospitals in Oman. Consecutive and consenting PwMS (n = 57) and healthy subjects (n = 53) completed the following measures: Hospital Anxiety and Depression Scale (HADS) which was used to measure anxiety (cut-point >7) and depression (>7); and Expanded Disability Status Scale (EDSS) to measure the level of disability (≥5). Characteristics such as socio-demographic and clinical variables were also explored. Fifty seven subjects with multiple sclerosis (MS) met the inclusion criteria. The majority of them were females who were 40 years old or younger and the majority were employed and unmarried. Approximately 86 % of the participants were using beta interferon, 96 % scored ≥5 in EDSS. MS of the Relapsing-Remitting type constituted the majority of the cohort (94 %). Approximately 35 % and 51 % endorsed symptoms of anxiety and depression respectively. The MS group scored significantly higher than controls on HADS measurements of depression and anxiety. Disability and symptoms of anxiety and depression are common among the PwMS attendees of tertiary care hospital in Oman. Such psychosocial variables have been largely unreported emerging from non-western populations. As these variables are strong indicators of the burden of MS, resolute effort is needed to address such psychosocial dysfunctions in the algorithms of care for PwMS in the Arab Islamic part of the world.


Repair of truncus arteriosus and interrupted aortic arch.
A total of seven patients with truncus arteriosus and interrupted aortic arch (IAA) comprises our surgical experience in this condition. All underwent primary complete repair via median sternotomy between June 1985 and December 1989. Median age at repair was 8 days and median weight, 3.2 kg. Anatomy of these seven patients was truncus arteriosus type "1 1/2" in five patients and type II in two patients, IAA type B in six patients and type A in one patient. Aortic arch was reconstructed by direct anastomosis of ascending aorta and descending aorta. Right ventricle to pulmonary artery continuity was established with a porcine valved conduit in four patients, aortic homograft in two, and aortic homograft monocusp patch in one. Three patients have required five reoperations (three in one patient). One reoperation was due to compression of the left main bronchus from the reconstructed aorta, one was due to obstruction of the aorta at the site of IAA repair, and one was due to compression of the left main bronchus, right pulmonary artery, and residual stenosis across the hypoplastic ascending aorta. There were no early or late deaths and all seven survivors are currently well with a mean follow-up of 29 months from initial repair.


Local gene transfer of phVEGF-2 plasmid by gene-eluting stents: an alternative strategy for inhibition of restenosis.
Drug-eluting stents represent a useful strategy for the prevention of restenosis using various antiproliferative drugs. These strategies share the liability of impairing endothelial recovery, thereby altering the natural biology of the vessel wall and increasing the associated risk of stent thrombosis. Accordingly, we tested the hypothesis that local delivery via gene-eluting stent of naked plasmid DNA encoding for human vascular endothelial growth factor (VEGF)-2 could achieve similar reductions in neointima formation while accelerating, rather than inhibiting, reendothelialization. phVEGF 2-plasmid (100 or 200 microg per stent)-coated BiodivYsio phosphorylcholine polymer stents versus uncoated stents were deployed in a randomized, blinded fashion in iliac arteries of 40 normocholesterolemic and 16 hypercholesterolemic rabbits. Reendothelialization was nearly complete in the VEGF stent group after 10 days and was significantly greater than in control stents (98.7+/-1% versus 79.0+/-6%, P<0.01). At 3 months, intravascular ultrasound analysis revealed that lumen cross-sectional area (4.2+/-0.4 versus 2.27+/-0.3 mm(2), P<0.001) was significantly greater and percent cross-sectional narrowing was significantly lower (23.4+/-6 versus 51.2+/-10, P<0.001) in VEGF stents compared with control stents implanted in hypercholesterolemic rabbits. Transgene expression was detectable in the vessel wall along with improved functional recovery of stented segments, resulting in a 2.4-fold increase in NO production. Acceleration of reendothelialization via VEGF-2 gene-eluting stents provides an alternative treatment strategy for the prevention of restenosis. VEGF-2 gene-eluting stents may be considered as a stand-alone or combination therapy.


The role of data science and machine learning in Health Professions Education: practical applications, theoretical contributions, and epistemic beliefs.
Data science is an inter-disciplinary field that uses computer-based algorithms and methods to gain insights from large and often complex datasets. Data science, which includes Artificial Intelligence techniques such as Machine Learning (ML), has been credited with the promise to transform Health Professions Education (HPE) by offering approaches to handle big (and often messy) data. To examine this promise, we conducted a critical review to explore: (1) published applications of data science and ML in HPE literature and (2) the potential role of data science and ML in shifting theoretical and epistemological perspectives in HPE research and practice. Existing data science studies in HPE are often not informed by theory, but rather oriented towards developing applications for specific problems, uses, and contexts. The most common areas currently being studied are procedural (e.g., computer-based tutoring or adaptive systems and assessment of technical skills). We found that epistemic beliefs informing the use of data science and ML in HPE poses a challenge for existing views on what constitutes objective knowledge and the role of human subjectivity for instruction and assessment. As a result, criticisms have emerged that the integration of data science in the field of HPE is in danger of becoming technically driven and narrowly focused in its approach to teaching, learning and assessment. Our findings suggest that researchers tend to formalize around the epistemological stance driven largely by traditions of a research paradigm. Future data science studies in HPE need to involve both education scientists and data scientists to ensure mutual advancements in the development of educational theory and practical applications. This may be one of the most important tasks in the integration of data science and ML in HPE research in the years to come.


Phylogeography and Genetic Diversity of Francisella tularensis subsp. holarctica in France (1947-2018).
In France, tularemia is caused by Francisella tularensis subsp. holarctica and is a sporadic disease affecting mainly wildlife animals and humans. F. tularensis species presents low genetic diversity that remains poorly described in France, as only a few genomes of isolates from the country are available so far. The objective of this study was to characterize the genetic diversity of F. tularensis in France and describe the phylogenetic distribution of isolates through whole-genome sequencing and molecular typing. Whole genomes of 350 strains of human or animal origin, collected from 1947 to 2018 in France and neighboring countries, were sequenced. A preliminary classification using the established canonical single nucleotide polymorphism (canSNP) nomenclature was performed. All isolates from France (except four) belonged to clade B.44, previously described in Western Europe. To increase the resolution power, a whole-genome SNP analysis was carried out. We were able to accurately reconstruct the population structure according to the global phylogenetic framework, and highlight numerous novel subclades. Whole-genome SNP analysis identified 87 new canSNPs specific to these subclades, among which 82 belonged to clade B.44. Identifying genomic features that are specific to sublineages is highly relevant in epidemiology and public health. We highlighted a large number of clusters among a single clade (B.44), which shows for the first time some genetic diversity among F. tularensis isolates from France, and the star phylogeny observed in clade B.44-subclades revealed that F. tularensis biodiversity in the country is relatively recent and resulted from clonal expansion of a single population. No association between clades and hosts or clinical forms of the disease was detected, but spatiotemporal clusters were identified for the first time in France. This is consistent with the hypothesis of persistence of F. tularensis strains found in Western Europe in the environment, associated with slow replication rates. Moreover, the presence of identical genotypes across long periods of time, and across long distances, supports this hypothesis but also suggests long-distance dispersal of the bacterium.


Towards physiologically meaningful water-use efficiency estimates from eddy covariance data.
Intrinsic water-use efficiency (iWUE) characterizes the physiological control on the simultaneous exchange of water and carbon dioxide in terrestrial ecosystems. Knowledge of iWUE is commonly gained from leaf-level gas exchange measurements, which are inevitably restricted in their spatial and temporal coverage. Flux measurements based on the eddy covariance (EC) technique can overcome these limitations, as they provide continuous and long-term records of carbon and water fluxes at the ecosystem scale. However, vegetation gas exchange parameters derived from EC data are subject to scale-dependent and method-specific uncertainties that compromise their ecophysiological interpretation as well as their comparability among ecosystems and across spatial scales. Here, we use estimates of canopy conductance and gross primary productivity (GPP) derived from EC data to calculate a measure of iWUE (G1 , "stomatal slope") at the ecosystem level at six sites comprising tropical, Mediterranean, temperate, and boreal forests. We assess the following six mechanisms potentially causing discrepancies between leaf and ecosystem-level estimates of G1 : (i) non-transpirational water fluxes; (ii) aerodynamic conductance; (iii) meteorological deviations between measurement height and canopy surface; (iv) energy balance non-closure; (v) uncertainties in net ecosystem exchange partitioning; and (vi) physiological within-canopy gradients. Our results demonstrate that an unclosed energy balance caused the largest uncertainties, in particular if it was associated with erroneous latent heat flux estimates. The effect of aerodynamic conductance on G1 was sufficiently captured with a simple representation. G1 was found to be less sensitive to meteorological deviations between canopy surface and measurement height and, given that data are appropriately filtered, to non-transpirational water fluxes. Uncertainties in the derived GPP and physiological within-canopy gradients and their implications for parameter estimates at leaf and ecosystem level are discussed. Our results highlight the importance of adequately considering the sources of uncertainty outlined here when EC-derived water-use efficiency is interpreted in an ecophysiological context.


Bloch modes at the surface of a photonic crystal interacting with a waveguide.
We theoretically studied the influence of an infinite set of waveguides on the evanescent field of Bloch waves at the surface of a one-dimensional photonic crystal (PC) excited by a TE Gaussian beam undergoing total internal reflection. The set of waveguides is regarded as a periodic inhomogeneous medium with period a. Numerical results are presented for the case in which a is greater than λ, which is the wavelength used to excite the surface mode. When the waveguide tip is very close to the surface of the PC, a fraction of the surface wave is reflected by the tip, producing an interference pattern that can be observed in the near field. In this case, the system simulates scanning tunneling optical microscopy in 2D geometry, and an image of the field distribution of the surface mode is obtained by quantifying the flux energy throughout the waveguide.


Convective oxygen transport and tissue oxygen consumption in Weddell seals during aerobic dives.
Unlike their terrestrial counterparts, marine mammals stop breathing and reduce their convective oxygen transport while performing activities (e.g. foraging, courtship, aggressive interactions, predator avoidance and migration) that require sustained power output during submergence. Since most voluntary dives are believed to remain aerobic, the goal of this study was to examine the potential importance of the dive response in optimizing the use of blood and muscle oxygen stores during dives involving different levels of muscular exertion. To accomplish this, we designed a numerical model based on Fick's principle that integrated cardiac output (Vb), regional blood flow, convective oxygen transport (Q(O2)), muscle oxymyoglobin desaturation and regional rates of oxygen consumption (VO2). The model quantified how the optimal matching or mismatching of QO2 to VO2 affected the aerobic dive limit (ADL). We chose an adult Weddell seal Leptonycotes weddellii on which to base our model because of available data on the diving physiology and metabolism of this species. The results show that the use of blood and muscle oxygen stores must be completed at the same time to maximize the ADL for each level of VO2. This is achieved by adjusting Vb (range 19-94 % of resting levels) and muscle QO2 according to the rate of muscle oxygen consumption (VMO2). At higher values of VMO2, Vb and muscle perfusion must increase to maintain an appropriate QO2/VO2 ratio so that available blood and muscle oxygen stores are depleted at the same time. Although the dive response does not sequester blood oxygen exclusively for brain and heart metabolism during aerobic dives, as it does during forced submersion, a reduction in Vb and muscle perfusion below resting levels is necessary to maximize the ADL over the range of diving VO2 (approximately 2-9 ml O2 min-1 kg-1). Despite the reduction in Vb, convective oxygen transport is adequate to maintain aerobic metabolism and normal function in the splanchnic organs, kidneys and other peripheral tissues. As a result, physiological homeostasis is maintained throughout the dive. The model shows that the cardiovascular adjustments known as the dive response enable the diving seal to balance the conflicting metabolic demands of (1) optimizing the distribution and use of blood and muscle oxygen stores to maximize the ADL over the normal range of diving VO2 and (2) ensuring that active muscle receives adequate oxygen as VMO2 increases.


How does pain experience relate to the need for pain relief? A secondary exploratory analysis in a large sample of cancer patients.
To explore (1) the information obtained from related but conceptually different approaches to pain assessment and (2) the extent to which the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) can be used as a screening tool to predict patient-reported need for pain relief. Cancer patients randomly sampled from 56 hospital departments were included. Questionnaire items assessed patients' (a) pain experience using the EORTC QLQ-C30 pain scale and its two pain items separately (pain intensity and pain interference) and (b) pain burden and (c) need for pain relief using the Three-Levels-of-Needs Questionnaire (3LNQ). Of the 2364 patients contacted by mail, 1447 (61 %) completed the questionnaires. Among these, 51 % reported at least "a little" pain on the pain intensity item. The number of patients reporting pain to be a burden was similar, and pain experience and pain burden were highly correlated (correlation coefficients ranged from 0.85 to 0.91). Pain experience and pain burden were moderately correlated with the need for pain relief. A receiver-operating characteristic (ROC) curve analysis showed that the EORTC QLQ-C30 discriminated between patients with and without a need for pain relief to an acceptable degree (area under the curve (AUC) 0.73-0.77). The cut-point a little gave a sensitivity of 84 % and specificity of 59 % for the item "Have you had pain?" and a sensitivity of 72 % and a specificity of 72 % for the pain scale. The majority of patients who experienced pain felt it to be a problem. Pain experience and pain burden were substantially related to need for pain relief, and the latter could be predicted from the EORTC QLQ-C30.


The role of professional logics in quality register use: a realist evaluation.
Clinical practice improvements based on quality-register data are influenced by multiple factors. Although there is agreement that information from quality registers is valuable for quality improvement, practical ways of organising register use have been notoriously difficult to realise. The present study sought to investigate the mechanisms that lead various clinicians to use quality registers for improvement. This research involves studying individuals' decisions in response to a Swedish programme focusing on increasing the use of quality registers. Through a case study, we focused on heart failure care and its corresponding register: the Swedish Heart Failure Register. The empirical data consisted of a purposive sample collected longitudinally by qualitative methods between 2013 and 2015. In total, 18 semi-structured interviews were carried out. We used realist evaluation to identify contexts, mechanisms, and outcomes. We identified four contexts - registration, use of output data, governance, and improvement projects - that provide conditions for the initiation of specific mechanisms. Given a professional theoretical perspective, we further showed that mechanisms are based on the logics of either organisational improvement or clinical practice. The two logics offer insights into the ways in which clinicians choose to embrace or reject certain registers' initiatives. We identified a strong path dependence, as registers have historically been tightly linked to the medical profession's competence. Few new initiatives in the studied programme reach the clinical context. We explain this through the lack of an organisational improvement logic and its corresponding mechanisms in the context of the medical profession. Implementation programmes must understand the logic of clinical practice; that is, be integrated with the ways in which work is carried out in everyday practice. Programmes need to be better at helping core health professionals to reach the highest standards of patient care.


Mobile phones: the next step towards healthcare delivery in rural India?
Given the ubiquity of mobile phones, their use to support healthcare in the Indian context is inevitable. It is however necessary to assess end-user perceptions regarding mobile health interventions especially in the rural Indian context prior to its use in healthcare. This would contextualize the use of mobile phone communication for health to 70% of the country's population that resides in rural India. To explore the acceptability of delivering healthcare interventions through mobile phones among users in a village in rural Bangalore. This was an exploratory study of 488 mobile phone users, residing in a village, near Bangalore city, Karnataka, South India. A pretested, translated, interviewer-administered questionnaire was used to obtain data on mobile phone usage patterns and acceptability of the mobile phone, as a tool for health-related communication. The data is described using basic statistical measures. The primary use of mobile phones was to make or receive phone calls (100%). Text messaging (SMS) was used by only 70 (14%) of the respondents. Most of the respondents, 484 (99%), were willing to receive health-related information on their mobile phones and did not consider receiving such information, an intrusion into their personal life. While receiving reminders for drug adherence was acceptable to most 479 (98%) of our respondents, 424 (89%) preferred voice calls alone to other forms of communication. Nearly all were willing to use their mobile phones to communicate with health personnel in emergencies and 367 (75%) were willing to consult a doctor via the phone in an acute illness. Factors such as sex, English literacy, employment status, and presence of chronic disease affected preferences regarding mode and content of communication. The mobile phone, as a tool for receiving health information and supporting healthcare through mHealth interventions was acceptable in the rural Indian context.


Fast set-up asynchronous brain-switch based on detection of foot motor imagery in 1-channel EEG.
Bringing a Brain-Computer Interface (BCI) out of the lab one of the main problems has to be solved: to shorten the training time. Finding a solution for this problem, the use of a BCI will be open not only for people who have no choice, e.g., persons in a locked-in state, or suffering from a degenerating nerve disease. By reducing the training time to a minimum, also healthy persons will make use of the system, e.g., for using this kind of control for games. For realizing such a control, the post-movement beta rebound occurring after brisk feet movement was used to set up a classifier. This classifier was then used in a cue-based motor imagery system. After classifier adaptation, a self-paced brain-switch based on brisk foot motor imagery (MI) was evaluated. Four out of six subjects showed that a post-movement beta rebound after feet MI and succeeded with a true positive rate between 69 and 89%, while the positive predictive value was between 75 and 93%.


The oldest dinosaur? A Middle Triassic dinosauriform from Tanzania.
The rise of dinosaurs was a major event in vertebrate history, but the timing of the origin and early diversification of the group remain poorly constrained. Here, we describe Nyasasaurus parringtoni gen. et sp. nov., which is identified as either the earliest known member of, or the sister-taxon to, Dinosauria. Nyasasaurus possesses a unique combination of dinosaur character states and an elevated growth rate similar to that of definitive early dinosaurs. It demonstrates that the initial dinosaur radiation occurred over a longer timescale than previously thought (possibly 15 Myr earlier), and that dinosaurs and their immediate relatives are better understood as part of a larger Middle Triassic archosauriform radiation. The African provenance of Nyasasaurus supports a southern Pangaean origin for Dinosauria.


Use of Economic Compensation to Increase Demand for Voluntary Medical Male Circumcision in Kenya: Qualitative Interviews With Male Participants in a Randomized Controlled Trial and Their Partners.
Interventions to increase demand for medical male circumcision are urgently needed in eastern and southern Africa. Following promising evidence that providing economic compensation can increase male circumcision uptake in Kenya, there is a need to understand the role of this intervention in individuals' decision-making regarding circumcision and explore perceptions of the intervention and concerns such as coercion. As part of a randomized controlled trial in Kenya that found compensation in the form of food vouchers worth US $8.75-US $15.00 to be effective in increasing male circumcision uptake, we conducted qualitative in-depth interviews with 45 circumcised and uncircumcised male participants and 19 female partners to explore how compensation provision influenced the decision to get circumcised. Interview transcripts were coded and an inductive thematic analysis was conducted to identify patterns in decision-making. Interviews revealed that compensation promoted circumcision uptake by addressing a major barrier to male circumcision uptake: lost wages during and after the circumcision procedure. Participants who did not get circumcised perceived the compensation amounts to be insufficient for offsetting their costs associated with getting circumcised or reported having nonfinancial barriers that were not addressed by the intervention, such as fear of pain. Participants also reported that they did not feel compelled to get circumcised for financial gain. Female partners of circumcised participants felt that the intervention helped to motivate their partners to get circumcised. The results suggest that the provision of economic compensation is an acceptable intervention that can address an important barrier to male circumcision uptake. Providing compensation to circumcision clients in the form of food vouchers warrants further consideration in voluntary medical male circumcision demand creation efforts.


Runtime application of Hybrid-Asbru clinical guidelines.
Clinical guidelines are a major tool in improving the quality of medical care. However, to support the automation of guideline-based care, several requirements must be filled, such as specification of the guidelines in a machine-interpretable format and a connection to an Electronic Patient Record (EPR). For several different reasons, it is beneficial to convert free-text guidelines gradually, through several intermediate representations, to a machine-interpretable format. It is also realistic to consider the case when an EPR is unavailable. We propose an innovative approach to the runtime application of intermediate-represented Hybrid-Asbru guidelines, with or without an available EPR. The new approach capitalizes on our extensive work on developing the Digital electronic Guideline Library (DeGeL) framework. The new approach was implemented as the Spock system. For evaluation, three guidelines were specified in an intermediate format and were applied to a set of simulated patient records designed to cover prototypical cases. In all cases, the Spock system produced the expected output, and did not produce an unexpected one. Thus, we have demonstrated the capability of the Spock system to apply guidelines encoded in the Hybrid-Asbru intermediate representation, when an EPR is not available.


Making sense of scents: the colour and texture of odours.
The purpose of this study was to document colour and texture associations to odours using a variety of odours including both pleasant and unpleasant odours, some of which were likely to be unfamiliar. We asked non-synaesthetic adults (n = 78) to make colour and shape/texture associations to 22 odours. A subset of the participants (n = 41) smelled the odours a second time in order to identify them. Each odour stimulus was associated consistently to one or more specific colours and/or textures (all p's < 0.01 by binomial probability statistics). Associations to the four odours that were identified accurately (cinnamon, lemon, peppermint and licorice) seemed to be based on learning/memory (e.g. lemon = yellow). The associations to the 18 odours that were not identified accurately are less likely to be based on learning/memory (e.g. ginger = black, rough, sharp; lavender = green, white, liquid, sticky). We speculate that sensory associations to odours, like those to pitch and letters (e.g. Mondloch and Maurer, 2004; Spector and Maurer, 2008), may result from the joint influence of learning and natural biases linking dimensions across sensory systems. Such links may reflect inherent neural organization that is modifiable with learning and that can manifest as cross-modal associations or synaesthetic percepts.


Internalization of Titanium Dioxide Nanoparticles Is Mediated by Actin-Dependent Reorganization and Clathrin- and Dynamin-Mediated Endocytosis in H9c2 Rat Cardiomyoblasts.
Titanium dioxide nanoparticles (TiO2 NPs) are widely used for industrial and commercial applications. Once inside the body, they translocate into the bloodstream and reach different areas of the cardiovascular system including the heart, increasing the risk of developing cardiovascular diseases; consequently, the investigation of their interaction with cardiac cells is required. We previously showed that TiO2 NPs are internalized by H9c2 rat cardiomyoblasts, and here, we examined the molecular mechanisms underlying this process. TiO2 NPs internalization was evaluated by transmission electron microscopy, time-lapse microscopy, and flow cytometry. Changes in the actin cytoskeleton were studied by phalloidin staining. Endocytic uptake mechanisms for nanoparticles were probed with chemical inhibitors, whereas clathrin and dynamin expression was measured by Western blot. Cellular uptake of TiO2 NPs occurred early after 30 min exposure, and large aggregates were observed after 1 h. Actin cytoskeleton reorganization included cell elongation plus lower density and stability of actin fibers. Cytochalasin-D inhibited TiO2 NPs uptake, indicating actin-mediated internalization. Dynamin and clathrin levels increased early after TiO2 NPs exposure, and their inhibition reduced nanoparticle uptake. Therefore, TiO2 NPs internalization by H9c2 rat cardiomyoblasts involves actin cytoskeleton reorganization and clathrin/dynamin-mediated endocytosis.


Tuning the binding energy of excitons in the MoS2 monolayer by molecular functionalization and defective engineering.
First-principle calculations within many-body perturbation theory are carried out to investigate the influence of the adsorbed molecules and sulfur (S) defects on the electronic and optical properties of the MoS2 monolayer. The exciton binding energy in the range of 0.05 eV to 1.14 eV is observed as a function of molecular coverage, when NO and 1,3,5-triazin (C3H3N3) are adsorbed on the pristine surface. These results can be explained by the interaction between the exciton and the adsorbed molecule. Furthermore, the combined effect of molecular functionalization and defective doping is studied. Our results show that both the electronic and optical band gaps of the MoS2 monolayer strongly depend on the molecular species and the defective coverage, and can be tuned up to ∼2 eV. This work demonstrates the great potential of controlling the MoS2 monolayer's excitonic properties by molecular functionalization and defective engineering.


Toxicity of atrazine- and glyphosate-based formulations on Caenorhabditis elegans.
Atrazine and Glyphosate are herbicides massively used in agriculture for crop protection. Upon application, they are available to the biota in different ecosystems. The aim of this research was to evaluate the toxicity of Glyphosate and Atrazine based formulations (GBF and ABF, respectively). Caenorhabditis elegans was exposed to different concentrations of each single formulation, and to the mixture. Lethality, locomotion, growth, and fertility were measured as endpoints. Effects on gene expression were monitored utilizing green fluorescence protein transgenic strains. ABF caused lethality of 12%, 15%, and 18% for 6, 60, and 600 μM, respectively, displaying a dose dependence trend. GBF produced lethality of 20%, 50%, and 100% at 0.01, 10, and 100 μM, respectively. Locomotion inhibition ranged from 21% to 89% at the lowest and maximum tested concentrations for Atrazine; whereas for Glyphosate, exposure to 10 μM inhibited 87%. Brood size was decreased by 67% and 93% after treatment to 0.06 and 6 μM Atrazine, respectively; and by 23% and 93% after exposure to 0.01 and 10 μM Glyphosate, respectively. There were no significant differences in growth. Changes in gene expression occurred in all genes, highlighting the expression of sod-1, sod-4, and gpx-4 that increased more than two-fold after exposure to 600 μM ABF and 10 μM GBF. The effects observed for the mixture of these formulations were additive for lethality, locomotion and fertility. In short, GBF, ABF, and their mixture induced several toxic responses related to oxidative stress on C. elegans.


The future of the pharmaceutical sciences and graduate education: recommendations from the AACP Graduate Education Special Interest Group.
Despite pharma's recent sea change in approach to drug discovery and development, U.S. pharmaceutical sciences graduate programs are currently maintaining traditional methods for master's and doctoral student education. The literature on graduate education in the biomedical sciences has long been advocating educating students to hone soft skills like communication and teamwork, in addition to maintaining excellent basic skills in research. However, recommendations to date have not taken into account the future trends in the pharmaceutical industry. The AACP Graduate Education Special Interest Group has completed a literature survey of the trends in the pharmaceutical industry and graduate education in order to determine whether our graduate programs are strategically positioned to prepare our graduates for successful careers in the next few decades. We recommend that our pharmaceutical sciences graduate programs take a proactive leadership role in meeting the needs of our future graduates and employers. Our graduate programs should bring to education the innovation and collaboration that our industry also requires to be successful and relevant in this century.


Epidemiology of 10,000 high school football injuries: patterns of injury by position played.
With more than 1.1 million high school athletes playing annually during the 2005-06 to 2009-10 academic years, football is the most popular boys' sport in the United States. Using an internet-based data collection tool, RIO, certified athletic trainers (ATs) from 100 nationally representative US high schools reported athletic exposure and football injury data during the 2005-06 to 2009-10 academic years. Participating ATs reported 10,100 football injuries corresponding to an estimated 2,739,187 football-related injuries nationally. The injury rate was 4.08 per 1000 athlete-exposures (AEs) overall. Offensive lineman collectively (center, offensive guard, offensive tackle) sustained 18.3% of all injuries. Running backs (16.3%) sustained more injuries than any other position followed by linebackers (14.9%) and wide receivers (11.9%). The leading mechanism of injury was player-player contact (64.0%) followed by player-surface contact (13.4%). More specifically, injury occurred most commonly when players were being tackled (24.4%) and tackling (21.8%). Patterns of football injuries vary by position. Identifying such differences is important to drive development of evidence-based, targeted injury prevention efforts.


Excretion of thiosulphate, the main detoxification product of sulphide, by the lugworm arenicola marina L
Thiosulphate, the main sulphide detoxification product, is accumulated in the body fluids of the lugworm Arenicola marina. The aim of this study was to elucidate the fate of thiosulphate. Electrophysiological measurements revealed that the transepithelial resistance of body wall sections was 76+/-34 capomega cm2 (mean +/- s.d., N=14), indicating that the body wall of the lugworm is a leaky tissue in which mainly paracellular transport along cell junctions takes place. The body wall was equally permeable from both sides to thiosulphate, the permeability coefficient of which was 1. 31x10(-)3+/-0.37x10(-)3 cm h-1 (mean +/- s.d., N=30). No evidence was found for a significant contribution of the gills or the nephridia to thiosulphate permeation. Thiosulphate flux followed the concentration gradient, showing a linear correlation (r=0.997) between permeated and supplied (10-100 mmol l-1) thiosulphate. The permeability of thiosulphate was not sensitive to the presence of various metabolic inhibitors, implicating a permeation process independent of membrane proteins and showing that the lugworm does not need to use energy to dispose of the sulphide detoxification product. The present data suggest a passive permeation of thiosulphate across the body wall of A. marina. In live lugworms, thiosulphate levels in the coelomic fluid and body wall tissue decreased slowly and at similar rates during recovery from sulphide exposure. The decline in thiosulphate levels followed a decreasing double-exponential function. Thiosulphate was not further oxidized to sulphite or sulphate but was excreted into the sea water.


Clinical impact of endocapillary proliferation with modified cutoff points in IgA nephropathy patients.
Predictive values of mesangial proliferation (M), endocapillary proliferation (E), segmental glomerulosclerosis (S), and crescents (C) among 19 validation studies of the Oxford Classification of IgA nephropathy (IgAN) were discrepant, especially in Asian patients. These validation studies indicate that cutoffs of MESC score in the Oxford Classification may not be generalizable. Thus, we aimed to improve the clinical value of MESC scores by modifying the cutoff points. A total of 104 patients with IgAN were diagnosed from 2001 to 2012 vai renal biopsy and retrospectively evaluated at Nagoya University Hospital. The cutoff point for modified (M´E´S´C´) was determined using the receiver operating characteristic curve in association with renal outcome in the training cohort. Clinical values of the Oxford MESTC vs M´E´S´C´ cutoff points were analyzed using Kaplan-Meier and Cox regression in association with poor renal outcome in the validation and the entire cohort. Of 104 patients, 12.5% reached poor renal outcome over a median of 6.25 [4.16-9.61] years of follow-up. The modified cutoffs were defined as ≥40%, ≥10%, ≥20%, and ≥5% in the glomeruli for M´E´S´, and C´ respectively. In univariate analysis, E´, S ´, and T were significantly associated with poor renal outcome, whereas Oxford MESC, M´, and C´ in the training and validation cohort were not associated with poor renal outcome. Using multivariate analysis in the presence of estimated glomerular filtration rate (eGFR), only E´ was a significant predictive factor for poor renal outcome. The E´ with modified cutoff point of 10% significantly improved predictive value for poor renal outcome in IgAN. Therefore, the clinical value of modified cutoff points for M´E´S´C´ scores should be validated with various cohort studies in different regions.


Inappropriate oral formulations and information in paediatric trials.
Previously, quality of formulations information provided for oral medications used in paediatric clinical trials published in 10 highly cited journals between 2002 and 2004 raised concerns. This short report explores if there was any subsequent improvement on how the formulations used in trials involving children <12 years reported in the same journals. Studies published between 2004 and 2008 were hand-searched and classified as containing adequate, some or no formulation information. Those involving solid dosage forms were further analysed. Only 31% (44/140) of publications provided adequate information, 5% less compared to 2002-2004 (28/76). There was a significant 12% rise (p<0.05) of no formulation information at all (37/140) and in tablets/capsules use (53/140), of which 3/4 gave no administration details, even for those under 6 years old, but a 12% decline in suitable paediatric formulations use (52/140 compared to 37/76). Contrary to expectations, overall quality of formulation information reported markedly deteriorated, jeopardising validity of clinical outcomes. The situation may reflect continued lack of awareness among investigators and other stakeholders of the importance of using suitable age-appropriate formulations.


Characterization of Antioxidant Potential of Seaweed Extracts for Enrichment of Convenience Food.
In recent years, there has been a growing interest in natural antioxidants as replacements of synthetic compounds because of increased safety concerns and worldwide trend toward the usage of natural additives in foods. One of the richest sources of natural antioxidants, nowadays largely studied for their potential to decrease the risk of diseases and to improve oxidative stability of food products, are edible brown seaweeds. Nevertheless, their antioxidant mechanisms are slightly evaluated and discussed. The aims of this study were to suggest possible mechanism(s) of Fucus vesiculosus antioxidant action and to assess its bioactivity during the production of enriched rye snacks. Chemical and cell-based assays indicate that the efficient preventive antioxidant action of Fucus vesiculosus extracts is likely due to not only the high polyphenol content, but also their good Fe2+-chelating ability. Moreover, the data collected during the production of Fucus vesiculosus-enriched rye snacks show that this seaweed can increase, in appreciable measure, the antioxidant potential of enriched convenience cereals. This information can be used to design functional foods enriched in natural antioxidant ingredients in order to improve the health of targeted consumers.


TprA/PhrA Quorum Sensing System Has a Major Effect on Pneumococcal Survival in Respiratory Tract and Blood, and Its Activity Is Controlled by CcpA and GlnR.
Streptococcus pneumoniae is able to cause deadly diseases by infecting different tissues, each with distinct environmental and nutritional compositions. We hypothesize that the adaptive capabilities of the microbe is an important facet of pneumococcal survival in fluctuating host environments. Quorum-sensing (QS) mechanisms are pivotal for microbial host adaptation. We previously demonstrated that the TprA/PhrA QS system is required for pneumococcal utilization of galactose and mannose, neuraminidase activity, and virulence. We also showed that the system can be modulated by using linear molecularly imprinted polymers. Due to being a drugable target, we further studied the operation of this QS system in S. pneumoniae. We found that TprA controls the expression of nine different operons on galactose and mannose. Our data revealed that TprA expression is modulated by a complex regulatory network, where the master regulators CcpA and GlnR are involved in a sugar dependent manner. Mutants in the TprA/PhrA system are highly attenuated in their survival in nasopharynx and lungs after intranasal infection, and growth in blood after intravenous infection.


Identification of dynamic changes in proteins associated with the cellular cytoskeleton after exposure to okadaic acid.
Exposure of cells to the diarrhetic shellfish poison, okadaic acid, leads to a dramatic reorganization of cytoskeletal architecture and loss of cell-cell contact. When cells are exposed to high concentrations of okadaic acid (100-500 nM), the morphological rearrangement is followed by apoptotic cell death. Okadaic acid inhibits the broad acting Ser/Thr protein phosphatases 1 and 2A, which results in hyperphosphorylation of a large number of proteins. Some of these hyperphosphorylated proteins are most likely key players in the reorganization of the cell morphology induced by okadaic acid. We wanted to identify these phosphoproteins and searched for them in the cellular lipid rafts, which have been found to contain proteins that regulate cytoskeletal dynamics and cell adhesion. By using stable isotope labeling by amino acids in cell culture cells treated with okadaic acid (400 nM) could be combined with control cells before the isolation of lipid rafts. Protein phosphorylation events and translocations induced by okadaic acid were identified by mass spectrometry. Okadaic acid was shown to regulate the phosphorylation status and location of proteins associated with the actin cytoskeleton, microtubules and cell adhesion structures. A large number of these okadaic acid-regulated proteins have previously also been shown to be similarly regulated prior to cell proliferation and migration. Our results suggest that okadaic acid activates general cell signaling pathways that induce breakdown of the cortical actin cytoskeleton and cell detachment.


Effects of type 1 diabetes mellitus on cardiac function: a study of monozygotic twins.
To investigate left ventricular size and function in type 1 diabetes and their relation with diabetes duration, glycaemic control, autonomic dysfunction, and complications of diabetes. Cross sectional study using a pulsed wave Doppler echocardiogram to assess left ventricular dimensions, wall thickness, and transmitral blood flow velocity signals. 40 monozygotic twin pairs (23 male, mean age 26 years) discordant for type 1 diabetes and 40 non-diabetic singleton controls with no clinical evidence of cardiac ischaemia. For all Doppler echocardiographic measurements there were strong correlations between monozygotic twins but not between twins and control subjects. Left ventricular dimensions, wall thickness and systolic function, peak E velocity, and the velocity integrals of early left ventricular filling were similar in all three groups. Peak A velocity and the velocity integrals of late ventricular filling (mean (SD)) were greater in diabetic twins (45 (12) v 38 (8) cm/s, P = 0.002; and 32 (11) v 26 (6), P = 0.0002). Diabetic twins had lower E/A ratio (1.59 (0.39) v 1.83 (0.39), P < 0.001), greater atrial filling fraction to total diastolic filling (28 (6) v 25 (5)%, P = 0.002), and prolonged isovolumic relaxation time (72 (12) v 63 (9) ms, P < 0.001). The differences in Doppler findings between diabetic and non-diabetic twins were related to disease duration whereas the prolongation of the isovolumic relaxation time was related to cardiac autonomic dysfunction. These results show that twins with type 1 diabetes have left ventricular diastolic dysfunction related to diabetes duration and cardiac autonomic dysfunction but not to glycaemic control or microvascular complications. In addition, genetic factors contribute to left ventricular dimension and function.


Osteological associations with unique tooth development in manatees (Trichechidae, Sirenia): a detailed look at modern Trichechus and a review of the fossil record.
Modern manatees have a unique type of tooth development, continually forming identical new molars in the posterior end of each quadrant of their mouths, and then progressively moving teeth anteriorly, only to reabsorb roots and spit out worn crowns. This process is not only developmentally complex, but requires space in the oral cavity that imposes its own limitations on other uses of that space. To gain a clearer understanding of the anatomical constraints on the evolution of this unique developmental process, we identified the specialized craniodental features in modern Trichechus that permit this specialization using visual observation and CT. Furthermore, to better understand the evolution of these traits, we review the fossil record of trichechids for these traits, including CT analysis of the skull of Miosiren kocki, a possible early member of the family from the Early Miocene of Belgium.


The experimental tobacco marketplace: Effects of low-ventilated cigarette exposure.
Regulating filter ventilation will change the relative reinforcing value of products resulting in nicotine/tobacco users facing the explore/exploit dilemma (ie, choice between unfamiliar and familiar options). This study examined the effects of price increases in higher-ventilated cigarettes (HVCs) and exposure to lower-ventilated cigarettes (LVCs) on explore/exploit patterns of tobacco-product purchasing in the Experimental Tobacco Marketplace (ETM). HVC smokers (N = 20) completed one assessment session and 3 ETM sessions separated by weeks of at-home LVC exposure. In each ETM session, participants made 7-days of tobacco-product purchases as HVCs price increased across trials. Prohibitive prices of HVC decreased the likelihood of HVCs purchases and increased the likelihood of LVC purchases. Initial exposure (week 1) to LVC reduced the number of cigarettes purchased when HVC prices were high and increased exploration of alternative tobacco products. Successive exposure to LVC (repeated access in weeks 2,5,6,9,10) decreased likelihood of HVCs and alternative product purchases and increased the likelihood of LVCs purchases. Regulating filter ventilation may initially increase exploration of alternative tobacco products but lead to exploitation of LVCs over time. Tobacco control strategies should take advantage of this transition period when smokers seek information on unfamiliar products to implement harm reduction strategies.


The 2016 Royal Australian and New Zealand College of Psychiatrists guidelines for the management of schizophrenia and related disorders.
The Royal Australian and New Zealand College of Psychiatrists (RANZCP) clinical practice guidelines for the management of schizophrenia and related disorders provide evidence-based recommendations for optimising treatment and prognosis. This update to the 2005 RANZCP guidelines has a greater emphasis on psychosocial treatments, physical health comorbidities and vocational rehabilitation. Main recommendations: The guidelines advise a clinical staging approach and deliver specific recommendations for:•comprehensive treatment using second generation antipsychotic agents continuously for 2-5 years;•early treatment of comorbid substance use;•community treatment after initial contact, during crises and after discharge from hospital;•physical health monitoring and management of comorbidities, particularly metabolic health;•interventions to optimise recovery of social function and return to study or work; and•management of schizophrenia in specific populations and circumstances. Changes in management as a result of the guidelines: The guidelines provide benchmarks against which the performance of services and clinical teams can be assessed. Measuring treatment response and clinical outcome is essential. General practitioners have an important role, particularly in monitoring and reducing the high cardiovascular risk in this population. Clinical services focusing on early detection, treatment and recovery need continuous funding to be proactive in implementing the guidelines and closing the gap between what is possible and what actually occurs.


Musculoskeletal manifestations of physical abuse after intimate partner violence.
Domestic violence is the most common cause of nonfatal injury to women in the United States, with an estimated cost of $50 billion annually. Little is known about the spectrum of musculoskeletal injuries in victims of domestic violence. We examined the characteristics of abused women, the prevalence of musculoskeletal injuries, and the variables associated with increasing frequency of physical violence against women. We identified all female survivors of intimate partner violence who were referred to the Minnesota Domestic Abuse Program from January 1, 2002, through December 31, 2003. Characteristics of each woman's background, abuse history, and injuries were obtained by a trained program therapist in an in-depth, 2-hour intake interview. Specific data forms were completed for each interview. Five forms of experienced abuse were explored (physical, emotional, psychological, sexual, and financial). Injuries were subcategorized as (1) head and neck, (2) musculoskeletal, (3) chest, (4) abdomen, and (5) skin (integumentary system). We conducted regression analyses to determine factors associated with the frequency of physical abuse. Of 270 potentially eligible women, 263 (97%) with complete records were included. Women were commonly Caucasian (62%) in their third decade of life with one or more children (87%). A history of abuse was recalled by over half of the women (54%). The most prevalent forms of abuse were emotional (84%), psychological (68%), physical (43%), sexual (41%), and financial (38%). Child protective services were concomitantly involved in half of the women living in abusive relationships. Among those women who reported physical abuse, 36% sought medical attention. We identified 144 injuries in 218 physically abused women. Head and neck injuries were the most prevalent after intimate partner violence (40%). Musculoskeletal injuries were the second most common manifestation of intimate partner violence (28%). The spectrum of injuries included sprains (n = 21 injuries), fracture/dislocations (n = 17 injuries), and foot injuries (n = 2 injuries). Our analysis identified seven variables associated with increasing physical abuse frequency. These included (1) younger age (p = 0.04); (2) shorter length of relationship (p = 0.049); (3) emotional abuse (p = 0.02); (4) psychological abuse (p = 0.003); (5) sexual abuse (p = 0.004); (6) drug dependency (p = 0.05); and (7) alcohol dependency (p = 0.045). Among women presenting to a domestic violence therapy program seeking counseling, head and neck and musculoskeletal injuries were most common. Frequency of physical abuse was most likely to be associated with younger women who are in short-term relationships, have chemical and alcohol dependency, and concomitant emotional, psychological, and sexual abuse. Recognizing musculoskeletal injuries in women as a potential result of intimate partner violence is warranted. Identifying children exposed to abusive situations may further alert treating surgeons to the potential for intimate partner violence in the mother.


PCR amplification of alleles at the DIS80 locus: comparison of a Finnish and a North American Caucasian population sample, and forensic casework evaluation.
Allele and genotype frequencies for the highly polymorphic D1S80 locus were determined in a Finnish population sample by using PCR followed by high-resolution PAGE and silver staining, a procedure called the amplified-fragment-length polymorphism (Amp-FLP) technique. In 140 unrelated Finnish individuals 15 alleles and 43 phenotypes were observed. The D1S80 locus demonstrated a heterozygosity of .77, and the power of discrimination was .92 in this sample representing a genetically isolated Finnish population. The distribution of observed genotypes conformed to Hardy-Weinberg expectations. In 36 mother-child pairs Mendelian inheritance for the alleles at the D1S80 locus could be demonstrated in all cases, and no mutations were observed. The usefulness of the D1S80 locus for forensic casework was assessed by using Amp-FLP analysis of the D1S80 locus in 36 forensic cases including 18 rapes, 14 homicides, and 4 other violent crimes. In most cases valuable information was obtained using the Amp-FLP technique, and in no case was there indication of either false-positive or false-negative results.


Gβγ directly modulates vesicle fusion by competing with synaptotagmin for binding to neuronal SNARE proteins embedded in membranes.
Gi/o-coupled G protein-coupled receptors can inhibit neurotransmitter release at synapses via multiple mechanisms. In addition to Gβγ-mediated modulation of voltage-gated calcium channels (VGCC), inhibition can also be mediated through the direct interaction of Gβγ subunits with the soluble N-ethylmaleimide attachment protein receptor (SNARE) complex of the vesicle fusion apparatus. Binding studies with soluble SNARE complexes have shown that Gβγ binds to both ternary SNARE complexes, t-SNARE heterodimers, and monomeric SNAREs, competing with synaptotagmin 1(syt1) for binding sites on t-SNARE. However, in secretory cells, Gβγ, SNAREs, and synaptotagmin interact in the lipid environment of a vesicle at the plasma membrane. To approximate this environment, we show that fluorescently labeled Gβγ interacts specifically with lipid-embedded t-SNAREs consisting of full-length syntaxin 1 and SNAP-25B at the membrane, as measured by fluorescence polarization. Fluorescently labeled syt1 undergoes competition with Gβγ for SNARE-binding sites in lipid environments. Mutant Gβγ subunits that were previously shown to be more efficacious at inhibiting Ca2+-triggered exocytotic release than wild-type Gβγ were also shown to bind SNAREs at a higher affinity than wild type in a lipid environment. These mutant Gβγ subunits were unable to inhibit VGCC currents. Specific peptides corresponding to regions on Gβ and Gγ shown to be important for the interaction disrupt the interaction in a concentration-dependent manner. In in vitro fusion assays using full-length t- and v-SNAREs embedded in liposomes, Gβγ inhibited Ca2+/synaptotagmin-dependent fusion. Together, these studies demonstrate the importance of these regions for the Gβγ-SNARE interaction and show that the target of Gβγ, downstream of VGCC, is the membrane-embedded SNARE complex.


Modelling the impact of the tier system on SARS-CoV-2 transmission in the UK between the first and second national lockdowns.
To measure the effects of the tier system on the COVID-19 pandemic in the UK between the first and second national lockdowns, before the emergence of the B.1.1.7 variant of concern. This is a modelling study combining estimates of real-time reproduction number Rt (derived from UK case, death and serological survey data) with publicly available data on regional non-pharmaceutical interventions. We fit a Bayesian hierarchical model with latent factors using these quantities to account for broader national trends in addition to subnational effects from tiers. The UK at lower tier local authority (LTLA) level. 310 LTLAs were included in the analysis. Reduction in real-time reproduction number Rt . Nationally, transmission increased between July and late September, regional differences notwithstanding. Immediately prior to the introduction of the tier system, Rt averaged 1.3 (0.9-1.6) across LTLAs, but declined to an average of 1.1 (0.86-1.42) 2 weeks later. Decline in transmission was not solely attributable to tiers. Tier 1 had negligible effects. Tiers 2 and 3, respectively, reduced transmission by 6% (5%-7%) and 23% (21%-25%). 288 LTLAs (93%) would have begun to suppress their epidemics if every LTLA had gone into tier 3 by the second national lockdown, whereas only 90 (29%) did so in reality. The relatively small effect sizes found in this analysis demonstrate that interventions at least as stringent as tier 3 are required to suppress transmission, especially considering more transmissible variants, at least until effective vaccination is widespread or much greater population immunity has amassed.


The child survival hypothesis.
Summary Because of current interest in the child survival hypothesis, we have reviewed available evidence bearing upon the relationships of infant and child mortality to fertility and contraceptive behaviour. The evidence is drawn from time series data for local and national vital events, from special in-depth studies of the infant mortality-fertility relationships in family formation, and from service statistics from health and family planning programmes. As a result of this review, we suggest five clarifications which should be made in redefining the child survival hypothesis and assessing its potential programme implications. The child survival hypothesis states that improved child survival will contribute to increased family planning motivation and consequent fertility decline. The evidence presented here suggests that the effect is not automatic and probably not a necessary pre-condition for fertility decline. There is certainly not a reflexive one-to-one replacement, but a partial effect may still be important. In the clearly demonstrated reduction in inter-pregnancy intervals after a child death, the major component is undoubtedly the removal of the biological protection of lactational amenorrhoea. A separate but somewhat smaller effect has been demonstrated in situations where lactation did not seem to have been the explanation. It is expected that increased child survival will contribute to fertility decline mainly in countries experiencing rapid mortality decline and population growth. The replacement of children who die is probably not so much 'volitional' as a result of alterations in sub-conscious expectations. It is apparent that in traditional agrarian populations, few direct and manipulable means of influencing motivation for fertility limitation are available, and, therefore, it must be stressed that integrated health and family planning programmes do provide opportunities for immediate programme development. By making parents aware of improved changes of survival through health services in which they develop confidence, the spontaneous linkages between mortality and fertility can presumably be reinforced. Family planning services must be provided as an essential initial step in programme development, but they can be made more effective, as well as politically more acceptable if appropriately integrated with maternal and child health and nutrition services.


Automated layer segmentation of macular OCT images using dual-scale gradient information.
A novel automated boundary segmentation algorithm is proposed for fast and reliable quantification of nine intra-retinal boundaries in optical coherence tomography (OCT) images. The algorithm employs a two-step segmentation schema based on gradient information in dual scales, utilizing local and complementary global gradient information simultaneously. A shortest path search is applied to optimize the edge selection. The segmentation algorithm was validated with independent manual segmentation and a reproducibility study. It demonstrates high accuracy and reproducibility in segmenting normal 3D OCT volumes. The execution time is about 16 seconds per volume (480x512x128 voxels). The algorithm shows potential for quantifying images from diseased retinas as well.


Speed characteristics of speed pedelecs, pedelecs and conventional bicycles in naturalistic urban and rural traffic conditions.
To assess the potential impact of the higher speeds of pedal-assisted bicycles on safety, this study compared conventional bicycles, pedelecs and speed pedelecs (hereafter called s-pedelecs) on mean speeds, speed variability, harsh braking events (decelerations > 2 m/s2), and mean speeds above the speed limit (MSAL) in rural and urban areas in the Netherlands Data were collected in daily traffic, while the legal maximum speed for speed-pedelecs was 25 km/h, and pedelecs and s-pedelecs shared the infrastructure with conventional bicycles. Data were collected, using two-wheelers equipped with accelerometers and GPS. Personality factors - sensation seeking and risk taking - were measured with surveys. Regular commuters used one of the three bicycle types for two weeks. Participant bias was intentionally included by allowing participants to select a bicycle type of their preference, resulting in 12 conventional bicycle riders (71 % women), 14 pedelec riders (67 % women) and 20 s-pedelec riders (25 % women). S-pedelecs were much faster than conventional bicycles, amounting to a speed difference with conventional bicycles of 10.4 km/h in urban areas (M =28.2 km/h vs. 17.8 km/h) and of 13.2 km/h in rural areas (M = 31.4 km/h vs. 18.2 km/h). The speed differences between pedelecs and conventional bicycles were much smaller: 2.3 km/h in urban areas (20.1 km/h vs 17.8 km/h) and 4 km/h in rural areas (22.2 km/h vs. 18.2 km/h). Compared to conventional bicycles, s-pedelecs varied their speed to a greater extent and also braked harshly more frequently, showing a greater need for speed adjustment. These adjustments were larger at higher speeds. In contrast, pedelecs did not differ from conventional bicycles on speed variation. MSAL for s-pedelec riders differed by gender. For men the MSAL was 87 % on urban sections and 91 % on rural sections. For women, the MSAL was lower, respectively 23 and 69 %. None of the personality factors were associated with speed variability, harsh braking or MSAL. However, sensation seeking was associated with higher mean speeds on all three bicycle types. To conclude, pedelecs and conventional bicycles are similar in speed patterns, whereas the speed patterns of s-pedelecs differ significantly from the former two. The safety implications are discussed.


Shedding of glycan-modifying enzymes by signal peptide peptidase-like 3 (SPPL3) regulates cellular N-glycosylation.
Protein N-glycosylation is involved in a variety of physiological and pathophysiological processes such as autoimmunity, tumour progression and metastasis. Signal peptide peptidase-like 3 (SPPL3) is an intramembrane-cleaving aspartyl protease of the GxGD type. Its physiological function, however, has remained enigmatic, since presently no physiological substrates have been identified. We demonstrate that SPPL3 alters the pattern of cellular N-glycosylation by triggering the proteolytic release of active site-containing ectodomains of glycosidases and glycosyltransferases such as N-acetylglucosaminyltransferase V, β-1,3 N-acetylglucosaminyltransferase 1 and β-1,4 galactosyltransferase 1. Cleavage of these enzymes leads to a reduction in their cellular activity. In line with that, reduced expression of SPPL3 results in a hyperglycosylation phenotype, whereas elevated SPPL3 expression causes hypoglycosylation. Thus, SPPL3 plays a central role in an evolutionary highly conserved post-translational process in eukaryotes.


Are Cardiac Autonomic Nervous System Activity and Perceived Stress Related to Functional Somatic Symptoms in Adolescents? The TRAILS Study.
Stressors have been related to medically insufficiently explained or functional somatic symptoms (FSS). However, the underlying mechanism of this association is largely unclear. In the current study, we examined whether FSS are associated with different perceived stress and cardiac autonomic nervous system (ANS) levels during a standardized stressful situation, and whether these associations are symptom-specific. We examined 715 adolescents (16.1 years, 51.3% girls) from the Dutch cohort study Tracking Adolescents' Individual Lives Sample during the Groningen Social Stress Test (GSST). FSS were assessed by the Youth Self-Report, and clustered into a cluster of overtiredness, dizziness and musculoskeletal pain and a cluster of headache and gastrointestinal symptoms. Perceived stress levels (i.e. unpleasantness and arousal) were assessed by the Self-Assessment Manikin, and cardiac ANS activity by assessing heart rate variability (HRV-HF) and pre-ejection period (PEP). Perceived stress and cardiac ANS levels before, during, and after the GSST were studied as well as cardiac ANS reactivity. Linear regression analyses were used to examine the associations. Perceived arousal levels during (beta = 0.09, p = 0.04) and after (beta = 0.07, p = 0.047) the GSST, and perceived unpleasantness levels before (beta = 0.07, p = 0.048) and during (beta = 0.12, p = 0.001) the GSST were related to FSS during the past couple of months. The association between perceived stress and FSS was stronger for the FSS cluster of overtiredness, dizziness and musculoskeletal pain than for the cluster of headache and gastrointestinal symptoms. Neither ANS activity levels before, during, and after the GSST, nor maximal HF-HRV and PEP reactivity were related to FSS. This study suggests that perceived stress levels during social stress are related to FSS, whereas cardiac ANS activity and reactivity are not related to FSS.


Role of miR-24, Furin, and Transforming Growth Factor-β1 Signal Pathway in Fibrosis After Cardiac Infarction.
BACKGROUND Cardiac fibrosis after primary infarction is a type of pathological phenomena as shown by increased collagen in myocardial cells. Transforming growth factor (TGF)-β1 is a critical factor participating in myocardial fibrosis. A previous study has shown the inhibitory role on TGF-β1 by microRNA-24 (miR-24) via targeting Furin. This study thus investigated the role of miR-24 and Furin/TGF-β1 in rat myocardial fibrosis. MATERIAL AND METHODS A total of 40 adult SD rats (both males and females) were prepared for myocardial infarction model by ligating the descending branch of left coronary artery after anesthesia. HE staining was performed to observe myocardial fibrosis after 1, 2, and 4 weeks. Tissue RNA was extracted to detect mRNA levels of Furin, TGF-β1, and miR-24 by real-time PCR. Western blotting was used to quantify protein expression of Furin and TGF-β1 in myocardial tissues. RESULTS Increased connective tissues were observed in myocardial tissues at 4 weeks after infarction by HE staining, which also revealed widening of the intra-myocardial cleft, along with more inflammatory cells and fibroblast hypertrophy. miR-24 expression was significantly depressed at 2 and 4 weeks after cardiac infarction (p<0.05). mRNA levels of Furin and TGF-β1 were elevated after infarction (p<0.05). With prolonged time periods of myocardial infarction, protein levels of Furin and TGF-β1 were further increased. The level of miR-24 was positively correlated with left ventricular end-diastolic diameter, left ventricular systolic diameter, and left ventricular ejection fraction. However, the level of Furin or TGF-β1 was negatively correlated with the above parameters. CONCLUSIONS This study demonstrated the important role of abnormal expression of miR-24 in myocardial fibrosis after infarction, and may provide drug targets for treating myocardial fibrosis.


Common oral conditions in older persons.
Older persons are at risk of chronic diseases of the mouth, including dental infections (e.g., caries, periodontitis), tooth loss, benign mucosal lesions, and oral cancer. Other common oral conditions in this population are xerostomia (dry mouth) and oral candidiasis, which may lead to acute pseudomembranous candidiasis (thrush), erythematous lesions (denture stomatitis), or angular cheilitis. Xerostomia caused by underlying disease or medication use may be treated with over-the-counter saliva substitutes. Primary care physicians can help older patients maintain good oral health by assessing risk, recognizing normal versus abnormal changes of aging, performing a focused oral examination, and referring patients to a dentist, if needed. Patients with chronic, disabling medical conditions (e.g., arthritis, neurologic impairment) may benefit from oral health aids, such as electric toothbrushes, manual toothbrushes with wide-handle grips, and floss-holding devices.


Evaluation of a Shaker Dust Collector for Use in a Recirculating Ventilation System.
General ventilation with recirculated air may be cost-effective to control the concentration of low-toxicity, contaminants in workplaces with diffuse, dusty operations, such as in agriculture. Such systems are, however, rarely adopted with little evidence showing improved air quality and ability to operate under harsh conditions. The goal of this work was to examine the initial and long-term performance of a fabric-filter shaker dust collector (SDC) in laboratory tests and as deployed within a recirculating ventilation system in an agricultural building. In laboratory tests, collection efficiency and pressure drop were tracked over several filter loading cycles, and the recovery of filter capacity (pressure drop) from filter shaking was examined. Collection efficiencies of particles larger than 5 μm was high (>95%) even when the filter was pristine, showing effective collection of large particles that dominate inhalable concentrations typical of agricultural dusts. For respirable-sized particles, collection efficiencies were low when the filter was pristine (e.g., 27% for 1 μm) but much higher when a dust cake developed on the filter (>99% for all size particles), even after shaking (e.g., 90% for 1 μm). The first shake of a filter was observed to recovery a substantial fraction of filter capacity, with subsequent shakes providing little benefit. In field tests, the SDC performed effectively over a period of three months in winter when incorporated in a recirculating ventilation system of a swine farrowing room. Trends in collection efficiency and pressure drop with loading were similar to those observed in the laboratory with overall collection efficiencies high (>80%) when pressure drop exceeded 230 Pa, or 23% of the maximum loading recommended by the manufacturer. This work shows that the SDC can function effectively over the harsh winter in swine rearing operations. Together with findings of improved air quality in the farrowing room reported in a companion manuscript, this article provides evidence that an SDC represents a cost-effective solution to improve air quality in agricultural settings.


Cellular evaluation of diselenonicotinamide (DSNA) as a radioprotector against cell death and DNA damage.
Diselenonicotinamide (DSNA), a synthetic organoselenium compound, was evaluated for its radioprotective effect in cellular models. A clonogenic assay in Chinese Hamster Ovary (CHO) cells and an apoptosis assay in murine splenic lymphocytes indicated that pre-treatment with DSNA at a concentration of 25 μM significantly protected them from radiation-induced cell death. Upon irradiation (1-12 Gy), dose-response studies were carried out under similar treatment conditions, and its dose modification factor (DMF) was estimated to be 1.26. Furthermore, DSNA showed its radioprotective effect, even when administered after exposure to radiation. Mechanistic investigation revealed that DSNA increased the intracellular levels of GPx and GSH in irradiated cells. In line with this observation, the addition of a pharmacological inhibitor of GPx cycle, abrogated the activity of DSNA. The radioprotective effect of DSNA was also complemented by its ability to prevent radiation-induced DNA damage as monitored by micronucleus and γ-H2AX assays. Furthermore, treatment with DSNA did not show much change in the expressions of Nrf2 dependent genes (γ-GCL and HO-1), but the presence of a pharmacological inhibitor of Nrf2 abrogated the radioprotective activity of DSNA against cell death and DNA damage. Additionally, ATRA treatment also inhibited the DSNA-mediated up-regulation of a repair gene RAD51, suggesting possible involvement of basal Nrf2 in the anti-genotoxic effect of DSNA. In conclusion, the present study demonstrates radioprotection by a synthetic organoselenium compound containing nutritionally important moieties like selenium and nicotinamide.


Potential impact of single-risk-factor versus total risk management for the prevention of cardiovascular events in Seychelles.
To assess the prevalence of cardiovascular (CV) risk factors in Seychelles, a middle-income African country, and compare the cost-effectiveness of single-risk-factor management (treating individuals with arterial blood pressure ≥ 140/90 mmHg and/or total serum cholesterol ≥ 6.2 mmol/l) with that of management based on total CV risk (treating individuals with a total CV risk ≥ 10% or ≥ 20%). CV risk factor prevalence and a CV risk prediction chart for Africa were used to estimate the 10-year risk of suffering a fatal or non-fatal CV event among individuals aged 40-64 years. These figures were used to compare single-risk-factor management with total risk management in terms of the number of people requiring treatment to avert one CV event and the number of events potentially averted over 10 years. Treatment for patients with high total CV risk (≥ 20%) was assumed to consist of a fixed-dose combination of several drugs (polypill). Cost analyses were limited to medication. A total CV risk of ≥ 10% and ≥ 20% was found among 10.8% and 5.1% of individuals, respectively. With single-risk-factor management, 60% of adults would need to be treated and 157 cardiovascular events per 100000 population would be averted per year, as opposed to 5% of adults and 92 events with total CV risk management. Management based on high total CV risk optimizes the balance between the number requiring treatment and the number of CV events averted. Total CV risk management is much more cost-effective than single-risk-factor management. These findings are relevant for all countries, but especially for those economically and demographically similar to Seychelles.


The relationship between vascular oxygen distribution and tissue oxygenation.
Tumour oxygenation could be investigated through several methods that use various measuring principles and can therefore highlight its different aspects. The results have to be subsequently correlated, but this might not be straightforward due to intrinsic limitations of the measurement methods. This study describes an analysis of the relationship between vascular and tissue oxygenations that may help the interpretation of results. Simulations have been performed with a mathematical model that calculates the tissue oxygenation for complex vascular arrangements by taking into consideration the oxygen diffusion into the tissue and its consumption at the cells. The results showed that while vascular and tissue oxygenations are deterministically related, the relationship between them is not unequivocal and this could lead to uncertainties when attempting to correlate them. However, theoretical simulation could bridge the gap between the results obtained with various methods.


Novel insights in dopamine receptor physiology.
The dopaminergic system has a pivotal role in the central nervous system but also plays important roles in the periphery, mainly in the endocrine system. Dopamine exerts its functions via five different receptors, named D(1)-D(5), belonging to the category of G protein coupled membrane receptors. Dopamine receptors are heterogeneously expressed in different cells, tissues and organs, where they stimulate or inhibit different functions, including neurotransmission and hormone synthesis and secretion. In particular, the dopamineric system has a pivotal role in the physiological regulation of the hypothalamus-pituitary-adrenal axis. Recent data have demonstrated the expression and function of dopamine receptors not only in endocrine organs but also in endocrine tumors, mainly those belonging to the hypothalamus-pituitary-adrenal axis, and also in the so-called 'neuroendocrine' tumors. These data confirm the important role of the dopaminergic system in this endocrine axis, as well as in the neuroendocrine system. This review summarizes the main structural and functional characteristics of dopamine receptors, emphasizing the most recent novelties, and focused on the physiological and pathological regulation of the hypothalamus-pituitary-adrenal axis by the dopaminergic system. In addition, the recent findings on the relationship between dopamine receptors and neuroendocrine tumors are summarized.


Association of OPRD1 polymorphisms with heroin dependence in a large case-control series.
Genes encoding the opioid receptors (OPRM1, OPRD1 and OPRK1) are obvious candidates for involvement in risk for heroin dependence. Prior association studies commonly had samples of modest size, included limited single nucleotide polymorphism (SNP) coverage of these genes and yielded inconsistent results. Participants for the current investigation included 1459 heroin-dependent cases ascertained from maintenance clinics in New South Wales, Australia, 1495 unrelated individuals selected from an Australian sample of twins and siblings as not meeting DSM-IV criteria for lifetime alcohol or illicit drug dependence (non-dependent controls) and 531 controls ascertained from economically disadvantaged neighborhoods in proximity to the maintenance clinics. A total of 136 OPRM1, OPRD1 and OPRK1 SNPs were genotyped in this sample. After controlling for admixture with principal components analysis, our comparison of cases to non-dependent controls found four OPRD1 SNPs in fairly high linkage disequilibrium for which adjusted P values remained significant (e.g. rs2236857; OR 1.25; P=2.95×10(-4) ) replicating a previously reported association. A post hoc analysis revealed that the two SNP (rs2236857 and rs581111) GA haplotype in OPRD1 is associated with greater risk (OR 1.68; P=1.41×10(-5) ). No OPRM1 or OPRK1 SNPs reached more than nominal significance. Comparisons of cases to neighborhood controls reached only nominal significance. Our results replicate a prior report providing strong evidence implicating OPRD1 SNPs and, in particular, the two SNP (rs2236857 and rs581111) GA haplotype in liability for heroin dependence. Support was not found for similar association involving either OPRM1 or OPRK1 SNPs.


Adhesion molecules intercellular adhesion molecule-1 (ICAM-1), ICAM-3 and B7 are not expressed by epithelium in normal or inflamed colon.
Adhesion molecules are involved in facilitating cell-mediated immune events. Because lymphocyte-epithelial cell interaction has been implicated in the pathogenesis of colonic inflammation, we analysed expression of a range of adhesion molecules on colonic epithelium in vitro and in vivo using flow cytometry, immunohistochemistry and in situ hybridization. Expression of ICAM-1 by cell lines HT29 and int407 was increased by proinflammatory cytokines interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and IL-1 but not by IL-6. Vascular cell adhesion molecule (VCAM) and E-selectin were not expressed. Immunohistochemistry using sections of inflamed colon from 16 patients with ulcerative colitis (UC), five patients with Crohn's disease (CD) and seven patients with normal colonoscopic biopsies, showed no expression of ICAM-1 on colonic epithelium. VCAM was seen in isolated lymphoid aggregates and E-selectin was expressed on endothelium. In situ hybridization showed no ICAM-1 or ICAM-3 mRNA in colonic epithelium. B7, the ligand for CD28, was not found on normal or inflamed colonic epithelium. The adhesion molecules ICAM-1, ICAM-3 and B7 are not involved in lymphocyte-epithelial cell interaction in the normal or inflamed colon. This may have implications for the development of T cell tolerance to intestinal luminal antigens.


Possible association between HLA antigens and the response to interferon in Japanese patients with chronic hepatitis C.
Correlation between the major histocompatibility complex class I antigens (HLA-A, -B and -C) and the elimination from serum of hepatitis C virus in patients with chronic hepatitis C has not been understood. We analyzed HLA phenotypes and their relationship to the efficacy of interferon treatment. Of the 172 patients who were treated with 9 million units of interferon-alpha 2a three times a week for 6 months, 54 patients were responders and 118 patients were non-responders. No significant difference was observed between the 172 patients and 199 healthy subjects with regard to the frequencies of HLA-A, -B and -C antigen phenotypes. However, HLA-B55, B62, CW3 and CW4 frequencies were significantly higher in responders than in non-responders to the interferon treatment. CW4 was found to link with B62, but other phenotypes were independent each other. Patients with HLA B55, B62 and CW3 had a significantly lower viral load, and showed a better response to interferon. These results suggest that HLA system does not have an influence on the evolution towards chronicity of the disease due to hepatitis C virus, but HLA B55, B62 or CW4, and CW3 may be a virus quantity-regulating factors which then affect to response to the interferon treatment, indicating that these HLA antigens in conjunction with a viral peptide is a key target antigen for cytotoxic T lymphocytes in patients with chronic hepatitis C.


The cytoplasmic domain of the gamete membrane fusion protein HAP2 targets the protein to the fusion site in Chlamydomonas and regulates the fusion reaction.
Cell-cell fusion between gametes is a defining step during development of eukaryotes, yet we know little about the cellular and molecular mechanisms of the gamete membrane fusion reaction. HAP2 is the sole gamete-specific protein in any system that is broadly conserved and shown by gene disruption to be essential for gamete fusion. The wide evolutionary distribution of HAP2 (also known as GCS1) indicates it was present in the last eukaryotic common ancestor and, therefore, dissecting its molecular properties should provide new insights into fundamental features of fertilization. HAP2 acts at a step after membrane adhesion, presumably directly in the merger of the lipid bilayers. Here, we use the unicellular alga Chlamydomonas to characterize contributions of key regions of HAP2 to protein location and function. We report that mutation of three strongly conserved residues in the ectodomain has no effect on targeting or fusion, although short deletions that include those residues block surface expression and fusion. Furthermore, HAP2 lacking a 237-residue segment of the cytoplasmic region is expressed at the cell surface, but fails to localize at the apical membrane patch specialized for fusion and fails to rescue fusion. Finally, we provide evidence that the ancient HAP2 contained a juxta-membrane, multi-cysteine motif in its cytoplasmic region, and that mutation of a cysteine dyad in this motif preserves protein localization, but substantially impairs HAP2 fusion activity. Thus, the ectodomain of HAP2 is essential for its surface expression, and the cytoplasmic region targets HAP2 to the site of fusion and regulates the fusion reaction.


Modeling categorization of scenes containing consistent versus inconsistent objects.
How does object perception influence scene perception? A recent study of ultrarapid scene categorization (O. R. Joubert, G. A. Rousselet, D. Fize, & M. Fabre-Thorpe, 2007) reported facilitated scene categorization when scenes contained consistent objects compared to when scenes contained inconsistent objects. One proposal for this consistent-object advantage is that ultrarapid scene categorization is influenced directly by ultrarapid recognition of particular objects within the scene. We instead asked whether a simpler mechanism that relied only on scene categorization without any explicit object recognition could explain this consistent-object advantage. We combined a computational model of scene recognition based on global scene statistics (A. Oliva & A. Torralba, 2001) with a diffusion model of perceptual decision making (R. Ratcliff, 1978). This model is sufficient to account for the consistent-object advantage. The simulations suggest that this consistent-object advantage need not arise from ultrarapid object recognition influencing ultrarapid scene categorization, but from the inherent influence certain objects have on the global scene statistics diagnostic for scene categorization.


Integrating mass spectrometry with MD simulations reveals the role of lipids in Na+/H+ antiporters.
Na+/H+ antiporters are found in all kingdoms of life and exhibit catalysis rates that are among the fastest of all known secondary-active transporters. Here we combine ion mobility mass spectrometry and molecular dynamics simulations to study the conformational stability and lipid-binding properties of the Na+/H+ exchanger NapA from Thermus thermophilus and compare this to the prototypical antiporter NhaA from Escherichia coli and the human homologue NHA2. We find that NapA and NHA2, but not NhaA, form stable dimers and do not selectively retain membrane lipids. By comparing wild-type NapA with engineered variants, we show that the unfolding of the protein in the gas phase involves the disruption of inter-domain contacts. Lipids around the domain interface protect the native fold in the gas phase by mediating contacts between the mobile protein segments. We speculate that elevator-type antiporters such as NapA, and likely NHA2, use a subset of annular lipids as structural support to facilitate large-scale conformational changes within the membrane.


Venovenous Extracorporeal Membrane Oxygenation in Pediatric Respiratory Failure.
Conventional treatment of respiratory failure involves positive pressure ventilation that can worsen lung damage. Extracorporeal membrane oxygenation (ECMO) is typically used when conventional therapy fails. In this study, we evaluated the use of venovenous (VV)-ECMO for the treatment of severe pediatric respiratory failure at our institution. A retrospective analysis of pediatric patients (age 1-18) placed on ECMO in the last 15 years (1999-2014) by the pediatric surgery team for respiratory failure was performed. Five pediatric patients underwent ECMO (mean age 10 years; range, 2-16). All underwent VV-ECMO. Diagnoses were status asthmaticus (2), acute respiratory distress syndrome due to septic shock (1), aspergillus pneumonia (1), and respiratory failure due to parainfluenza (1). Two patients had severe barotrauma prior to ECMO initiation. Average oxygenation index (OI) prior to cannulation was 74 (range 23-122). No patients required conversion to VA-ECMO. The average ECMO run time was 4.4 days (range 2-6). The average number of days on the ventilator was 15 (range 4-27). There were no major complications due to the procedure. Survival to discharge was 100%. Average follow up is 4.4 years (range 1-15). A short run of VV-ECMO can be lifesaving for pediatric patients in respiratory failure. Survival is excellent despite severely elevated oxygen indices. VV-ECMO may be well tolerated and can be considered for severe pediatric respiratory failure.


Phylogeny, evolutionary trends and classification of the Spathelia-Ptaeroxylon clade: morphological and molecular insights.
The Spathelia-Ptaeroxylon clade is a group of morphologically diverse plants that have been classified together as a result of molecular phylogenetic studies. The clade is currently included in Rutaceae and recognized at a subfamilial level (Spathelioideae) despite the fact that most of its genera have traditionally been associated with other families and that there are no obvious morphological synapomorphies for the clade. The aim of the present study is to construct phylogenetic trees for the Spathelia-Ptaeroxylon clade and to investigate anatomical characters in order to decide whether it should be kept in Rutaceae or recognized at the familial level. Anatomical characters were plotted on a cladogram to help explain character evolution within the group. Moreover, phylogenetic relationships and generic limits within the clade are also addressed. A species-level phylogenetic analysis of the Spathelia-Ptaeroxylon clade based on five plastid DNA regions (rbcL, atpB, trnL-trnF, rps16 and psbA-trnH) was conducted using Bayesian, maximum parsimony and maximum likelihood methods. Leaf and seed anatomical characters of all genera were (re)investigated by light and scanning electron microscopy. With the exception of Spathelia, all genera of the Spathelila-Ptaeroxylon clade are monophyletic. The typical leaf and seed anatomical characters of Rutaceae were found. Further, the presence of oil cells in the leaves provides a possible synapomorphy for the clade. The Spathelia-Ptaeroxylon clade is well placed in Rutaceae and it is reasonable to unite the genera into one subfamily (Spathelioideae). We propose a new tribal classification of Spathelioideae. A narrow circumscription of Spathelia is established to make the genus monophyletic, and Sohnreyia is resurrected to accommodate the South American species of Spathelia. The most recent common ancestor of Spathelioideae probably had leaves with secretory cavities and oil cells, haplostemonous flowers with appendaged staminal filaments, and a tracheidal tegmen.


Short-term adolescent nicotine exposure in rats elicits immediate and delayed deficits in T-lymphocyte function: critical periods, patterns of exposure, dose thresholds.
Prenatal nicotine exposure elicits lasting deficiencies in T-lymphocyte mitogenesis, and the period of vulnerability extends into adolescence, the stage at which smoking typically commences. We explored the importance of nicotine exposure patterns (continuous infusion vs. repeated subcutaneous injections), dose-effect relationships, and specificity of the effects. Adolescent rats were given nicotine infusions for 1 week beginning on postnatal day (PN) 30, using a regimen (6 mg/kg/day) that produces plasma nicotine levels (25 ng/ml) similar to those in smokers; another group received 2 mg/kg/day. At the end of the infusion period (PN37), T-lymphocyte mitogenic responses to concanavalin A were deficient in the group receiving 6 mg/kg/day; values for the 2 mg/kg/day group were intermediate between controls and the 6 mg/kg/day group. One week after the termination of nicotine treatment, responses returned to normal, only to reemerge in young adulthood (PN65), at which stage adverse effects were significant even for the group that received 2 mg/kg/day. In contrast to the T-cell alterations, B-lymphocyte responses were unaffected. Administering the same total doses of nicotine by twice-daily subcutaneous injections over the 1-week treatment period (1 or 3 mg/kg per injection) did not evoke deficits in responses of either T-cells or B-cells, even though the high dose produced overt systemic toxicity and persistent weight loss. Our results indicate that adolescent nicotine exposure, even at levels below those associated with active smoking, elicits selective deficits in T-lymphocyte function. Although short-term adaptations may correct the effects, deficits reemerge in young adulthood despite cessation of nicotine exposure.


Colonial ascidians strongly preyed upon, yet dominate the substrate in a subtropical fouling community.
Higher diversity and dominance at lower latitudes has been suggested for colonial species. We verified this pattern in species richness of ascidians, finding that higher colonial-to-solitary species ratios occur in the tropics and subtropics. At the latitudinal region with the highest ratio, in southeastern Brazil, we confirmed that colonial species dominate space on artificial plates in two independent studies of five fouling communities. We manipulated settlement plates to measure effects of predation and competition on growth and survivorship of colonial versus solitary ascidians. Eight species were subjected to a predation treatment, i.e. caged versus exposed to predators, and a competition treatment, i.e. leaving versus removing competitors, to assess main and interactive effects. Predation had a greater effect on growth and survivorship of colonial compared to solitary species, whereas competition did not show consistent patterns. We hypothesize that colonial ascidians dominate at this subtropical site despite being highly preyed upon because they regrow when partially consumed and can adjust in shape and space to grow into refuges. We contend that these means of avoiding mortality from predation can have large influences on diversification patterns of colonial species at low latitudes, where predation intensity is greater.


High-yield, ultrafast, surface plasmon-enhanced, Au nanorod optical field electron emitter arrays.
Here we demonstrate the design, fabrication, and characterization of ultrafast, surface-plasmon enhanced Au nanorod optical field emitter arrays. We present a quantitative study of electron emission from Au nanorod arrays fabricated by high-resolution electron-beam lithography and excited by 35 fs pulses of 800 nm light. We present accurate models for both the optical field enhancement of Au nanorods within high-density arrays, and electron emission from those nanorods. We have also studied the effects of surface plasmon damping induced by metallic interface layers at the substrate/nanorod interface on near-field enhancement and electron emission. We have identified the peak optical field at which the electron emission mechanism transitions from a 3-photon absorption mechanism to strong-field tunneling emission. Moreover, we have investigated the effects of nanorod array density on nanorod charge yield, including measurement of space-charge effects. The Au nanorod photocathodes presented in this work display 100-1000 times higher conversion efficiency relative to previously reported UV triggered emission from planar Au photocathodes. Consequently, the Au nanorod arrays triggered by ultrafast pulses of 800 nm light in this work may outperform equivalent UV-triggered Au photocathodes, while also offering nanostructuring of the electron pulse produced from such a cathode, which is of interest for X-ray free-electron laser (XFEL) development where nanostructured electron pulses may facilitate more efficient and brighter XFEL radiation.


Asymmetric versus symmetric pulses for cortical microstimulation.
Intracortical microstimulation (ICMS), which has shown promise in the visual, auditory and somatosensory systems as a platform for sensory prostheses, typically relies on charged balanced, symmetric, biphasic stimulation. However, neural stimulation models as well as experiments conducted in cochlear implant users have suggested that charge balanced asymmetric pulses could generate lower detection thresholds for stimulation in terms of charge per phase. For this study, rats were chronically implanted with microelectrode arrays unilaterally in their right auditory cortex and then trained to detect ICMS delivered through a single electrode site in order to determine their behavioral threshold. This model was used in two experiments. The first experiment addressed the effect of lead phase direction, asymmetry, and phase duration on detection threshold. The second experiment fixed the cathode phase duration at 123 μs and varied only the phase asymmetry and lead phase direction. Taken together, the results of these experiments suggest that, for ICMS, the primary determinant of threshold level is cathode phase duration, and that asymmetry provides no significant advantage when compared to symmetric, cathode leading pulses. However, symmetric anode leading pulses of less than or equal to 205 μs per phase consistently showed higher thresholds when compared to all other pulses of equal cathode phase duration.


Direct phase detecting system.
A system for extracting the phase components of an optical traveling wave field has been constructed. This system consists of the Mach-Zehnder interferometer to capture the wave field as the hologram, a photoelectronic scanning system, and an analog computing circuit. The detected phase signal is immediately displayed on a cathode ray tube as continuous-tone patterns. The method has been confirmed through the experimental results.