Network-Wide Adaptive Burst Detection Depicts Neuronal Activity with Improved Accuracy.
Neuronal networks are often characterized by their spiking and bursting statistics. Previously, we introduced an adaptive burst analysis method which enhances the analysis power for neuronal networks with highly varying firing dynamics. The adaptation is based on single channels analyzing each element of a network separately. Such kind of analysis was adequate for the assessment of local behavior, where the analysis focuses on the neuronal activity in the vicinity of a single electrode. However, the assessment of the whole network may be hampered, if parts of the network are analyzed using different rules. Here, we test how using multiple channels and measurement time points affect adaptive burst detection. The main emphasis is, if network-wide adaptive burst detection can provide new insights into the assessment of network activity. Therefore, we propose a modification to the previously introduced inter-spike interval (ISI) histogram based cumulative moving average (CMA) algorithm to analyze multiple spike trains simultaneously. The network size can be freely defined, e.g., to include all the electrodes in a microelectrode array (MEA) recording. Additionally, the method can be applied on a series of measurements on the same network to pool the data for statistical analysis. Firstly, we apply both the original CMA-algorithm and our proposed network-wide CMA-algorithm on artificial spike trains to investigate how the modification changes the burst detection. Thereafter, we use the algorithms on MEA data of spontaneously active chemically manipulated in vitro rat cortical networks. Moreover, we compare the synchrony of the detected bursts introducing a new burst synchrony measure. Finally, we demonstrate how the bursting statistics can be used to classify networks by applying k-means clustering to the bursting statistics. The results show that the proposed network wide adaptive burst detection provides a method to unify the burst definition in the whole network and thus improves the assessment and classification of the neuronal activity, e.g., the effects of different pharmaceuticals. The results indicate that the novel method is adaptive enough to be usable on networks with different dynamics, and it is especially feasible when comparing the behavior of differently spiking networks, for example in developing networks.


Qualitative analysis of naturalistic decision making in adults with chronic heart failure.
Self-care of heart failure has been described as a naturalistic decision-making process, but the data available to defend this description are anecdotal. The aim of this study was to explore the process used by adults with chronic heart failure to make decisions about their symptoms. This was a secondary analysis of data obtained from four mixed methods studies. The full data set held qualitative data on 120 adults over the age of 18 years. For this analysis, maximum variation sampling was used to purposively select a subset of 36 of the qualitative interviews to reanalyze. In this sample, equally distributed by gender, 56% Caucasian, between 40 and 98 years, the overarching theme was that decisions about self-care reflect a naturalistic decision-making process with components of situation awareness with mental simulation of a plausible course of action and an evaluation of the outcome of the action. In addition to situation awareness and mental simulation, three key factors were identified as influencing self-care decision making: (a) experience; (b) decision characteristics such as uncertainty, ambiguity, high stakes, urgency, illness, and involvement of others in the decision-making process; and (c) personal goals. These results support naturalistic decision making as the process used by this sample of adults with heart failure to make decisions about self-care.


Distinct anatomical subtypes of the behavioural variant of frontotemporal dementia: a cluster analysis study.
The behavioural variant of frontotemporal dementia is a progressive neurodegenerative syndrome characterized by changes in personality and behaviour. It is typically associated with frontal lobe atrophy, although patterns of atrophy are heterogeneous. The objective of this study was to examine case-by-case variability in patterns of grey matter atrophy in subjects with the behavioural variant of frontotemporal dementia and to investigate whether behavioural variant of frontotemporal dementia can be divided into distinct anatomical subtypes. Sixty-six subjects that fulfilled clinical criteria for a diagnosis of the behavioural variant of frontotemporal dementia with a volumetric magnetic resonance imaging scan were identified. Grey matter volumes were obtained for 26 regions of interest, covering frontal, temporal and parietal lobes, striatum, insula and supplemental motor area, using the automated anatomical labelling atlas. Regional volumes were divided by total grey matter volume. A hierarchical agglomerative cluster analysis using Ward's clustering linkage method was performed to cluster the behavioural variant of frontotemporal dementia subjects into different anatomical clusters. Voxel-based morphometry was used to assess patterns of grey matter loss in each identified cluster of subjects compared to an age and gender-matched control group at P < 0.05 (family-wise error corrected). We identified four potentially useful clusters with distinct patterns of grey matter loss, which we posit represent anatomical subtypes of the behavioural variant of frontotemporal dementia. Two of these subtypes were associated with temporal lobe volume loss, with one subtype showing loss restricted to temporal lobe regions (temporal-dominant subtype) and the other showing grey matter loss in the temporal lobes as well as frontal and parietal lobes (temporofrontoparietal subtype). Another two subtypes were characterized by a large amount of frontal lobe volume loss, with one subtype showing grey matter loss in the frontal lobes as well as loss of the temporal lobes (frontotemporal subtype) and the other subtype showing loss relatively restricted to the frontal lobes (frontal-dominant subtype). These four subtypes differed on clinical measures of executive function, episodic memory and confrontation naming. There were also associations between the four subtypes and genetic or pathological diagnoses which were obtained in 48% of the cohort. The clusters did not differ in behavioural severity as measured by the Neuropsychiatric Inventory; supporting the original classification of the behavioural variant of frontotemporal dementia in these subjects. Our findings suggest behavioural variant of frontotemporal dementia can therefore be subdivided into four different anatomical subtypes.


A role for AGL ubiquitination in the glycogen storage disorders of Lafora and Cori's disease.
Cori's disease is a glycogen storage disorder characterized by a deficiency in the glycogen debranching enzyme, amylo-1,6-glucosidase,4-alpha-glucanotransferase (AGL). Here, we demonstrate that the G1448R genetic variant of AGL is unable to bind to glycogen and displays decreased stability that is rescued by proteasomal inhibition. AGL G1448R is more highly ubiquitinated than its wild-type counterpart and forms aggresomes upon proteasome impairment. Furthermore, the E3 ubiquitin ligase Malin interacts with and promotes the ubiquitination of AGL. Malin is known to be mutated in Lafora disease, an autosomal recessive disorder clinically characterized by the accumulation of polyglucosan bodies resembling poorly branched glycogen. Transfection studies in HepG2 cells demonstrate that AGL is cytoplasmic whereas Malin is predominately nuclear. However, after depletion of glycogen stores for 4 h, approximately 90% of transfected cells exhibit partial nuclear staining for AGL. Furthermore, stimulation of cells with agents that elevate cAMP increases Malin levels and Malin/AGL complex formation. Refeeding mice for 2 h after an overnight fast causes a reduction in hepatic AGL levels by 48%. Taken together, these results indicate that binding to glycogen crucially regulates the stability of AGL and, further, that its ubiquitination may play an important role in the pathophysiology of both Lafora and Cori's disease.


Itinerant ferromagnetism in a Fermi gas of ultracold atoms.
Can a gas of spin-up and spin-down fermions become ferromagnetic because of repulsive interactions? We addressed this question, for which there is not yet a definitive theoretical answer, in an experiment with an ultracold two-component Fermi gas. The observation of nonmonotonic behavior of lifetime, kinetic energy, and size for increasing repulsive interactions provides strong evidence for a phase transition to a ferromagnetic state. Our observations imply that itinerant ferromagnetism of delocalized fermions is possible without lattice and band structure, and our data validate the most basic model for ferromagnetism introduced by Stoner.


Folate, vitamin B6, and B12 intakes in relation to risk of stroke among men.
Folate, vitamin B6, and B12 deficiency are related to elevated blood homocysteine level. However, the effects of intakes of these vitamins on risk of stroke are still uncertain. This study examines intakes of folate, vitamin B6, and B12 in relation to risk of ischemic and hemorrhagic stroke. We enrolled 43 732 men, aged 40 to 75 years, who were free of cardiovascular diseases and diabetes at baseline. Participants were followed from 1986 to 2000. Dietary information was assessed every 4 years using a detailed and validated semiquantitative food frequency questionnaire. The main outcome measures were incident ischemic and hemorrhagic strokes. A total of 725 incident strokes, including 455 ischemic, 125 hemorrhagic, and 145 unknown types of stroke, were documented during the 14-year follow-up. After adjustment for major lifestyle and dietary factors, intake of folate was associated with a significantly lower risk of ischemic but not hemorrhagic stroke. The multivariate relative risk of ischemic stroke was 0.71 (95% CI, 0.52 to 0.96; P for trend=0.05) for men in the highest quintile of intake compared with those who in the lowest quintile. Intake of vitamin B12, but not B6, was also inversely associated with risk of ischemic stroke. Our findings suggest that increased folate intake is associated with decreased risk of ischemic stroke in men.


The non-transcranial TMS-evoked potential is an inherent source of ambiguity in TMS-EEG studies.
Transcranial Magnetic Stimulation (TMS) excites populations of neurons in the stimulated cortex, and the resulting activation may spread to connected brain regions. The distributed cortical response can be recorded with electroencephalography (EEG). Since TMS also stimulates peripheral sensory and motor axons and generates a loud "click" sound, the TMS-evoked EEG potentials (TEPs) reflect not only neural activity induced by transcranial neuronal excitation but also neural activity due to somatosensory and auditory processing. In 17 healthy young individuals, we systematically assessed the contribution of multisensory peripheral stimulation to TEPs using a TMS-compatible EEG system. Real TMS was delivered with a figure-of-eight coil over the left para-median posterior parietal cortex or superior frontal gyrus with the coil being oriented perpendicularly or in parallel to the target gyrus. We also recorded the EEG responses evoked by realistic sham stimulation over the posterior parietal and superior frontal cortex, mimicking the auditory and somatosensory sensations evoked by real TMS. We applied state-of-the-art procedures to attenuate somatosensory and auditory confounds during real TMS, including the placement of a foam layer underneath the coil and auditory noise masking. Despite these precautions, the temporal and spatial features of the cortical potentials evoked by real TMS at the prefrontal and parietal site closely resembled the cortical potentials evoked by realistic sham TMS, both for early and late TEP components. Our findings stress the need to include a peripheral multisensory control stimulation in the design of TMS-EEG studies to enable a dissociation between truly transcranial and non-transcranial components of TEPs.


Effect of galactose on systemic hemodynamics and blood flow rate in normal and tumor tissues in rats.
The effect of galactose on systemic hemodynamics and blood flow rate of Walker 256 carcinomas and several normal tissues of unanesthetized, unrestrained female Sprague-Dawley rats was measured, using the radioactive microsphere technique, prior to and at 30 and 60 min after galactose administration (6 g/kg body weight, i.v.). Whereas heart rate remained unchanged following injection, cardiac output (CO) and cardiac index decreased by 35% (P less than 0.05). Mean arterial pressure immediately decreased during the injection but then increased reaching a value 10% (P less than 0.05) above the baseline 30 min following injection. Stroke volume (SV) decreased by 30% (P less than 0.05) and total peripheral resistance increased by 65% (P less than 0.05). Redistribution of blood flow, expressed as %CO, among normal tissues was seen to the brain, kidneys, liver, jejunum, and hindlimb muscle and away from the pancreas, stomach, and skin. Changes in %CO to the spleen, colon, forelimb muscle, and peritumor tissue were not significant. Blood flow rate in most normal tissues either decreased or remained constant following injection. An exception was in the liver where blood flow significantly increased. Blood flow significantly decreased in the tumor (approximately 60%) and this reduction in blood flow was larger than the reduction in CO. These results suggest that (a) the effect of galactose on systemic hemodynamics and blood flow rate are similar to those produced by glucose; (b) reduction in blood flow rate in tumors is due to both systemic and local effects; and (c) changes in blood flow to normal tissues should not be disregarded when using galactose in combination with hyperthermia and/or chemotherapy for cancer treatment.


GPU-assisted computation of centroidal Voronoi tessellation.
Centroidal Voronoi tessellations (CVT) are widely used in computational science and engineering. The most commonly used method is Lloyd's method, and recently the L-BFGS method is shown to be faster than Lloyd's method for computing the CVT. However, these methods run on the CPU and are still too slow for many practical applications. We present techniques to implement these methods on the GPU for computing the CVT on 2D planes and on surfaces, and demonstrate significant speedup of these GPU-based methods over their CPU counterparts. For CVT computation on a surface, we use a geometry image stored in the GPU to represent the surface for computing the Voronoi diagram on it. In our implementation a new technique is proposed for parallel regional reduction on the GPU for evaluating integrals over Voronoi cells.


Mediterranean Diet and Workplace Health Promotion.
Analytical and experimental studies confirm relationships between the consumption of certain foods and cardiovascular disease, diabetes, and cancer. Mediterranean diet patterns have long been associated with a reduced risk of major diseases and many favorable health outcomes. Data from observational, longitudinal, and randomized controlled trials have demonstrated that Mediterranean-style diets can improve body mass index and body weight, reduce the incidence of diabetes mellitus and metabolic syndrome risk factors, decrease cardiovascular morbidity and coronary heart disease mortality, as well as decrease all-cause mortality. Recently, efforts have attempted to improve dietary habits in the workplace, by modifying food selection, eating patterns, meal frequency, and the sourcing of meals taken during work. Evidence supporting the Mediterranean diet and the potential cardioprotective role of healthier diets in the workplace are reviewed here, and promising strategies to improve metabolic and cardiovascular health outcomes are also provided.


From Policy Statement to Practice: Integrating Social Needs Screening and Referral Assistance With Community Health Workers in an Urban Academic Health Center.
Purpose: Social and economic factors have been shown to affect health outcomes. In particular, social determinants of health (SDH) are linked to poor health outcomes in children. Research and some professional academies support routine social needs screening during primary care visits. Translating this recommendation into practice remains challenging due to the resources required and dearth of evidence-based research to guide health center level implementation. We describe our experience implementing a novel social needs screening program at an academic pediatric clinic. Methods: The Community Linkage to Care (CLC) pilot program integrates social needs screening and referral support using community health workers (CHWs) as part of routine primary care visits. Our multidisciplinary team performed process mapping, developed workflows, and led ongoing performance improvement activities. We established key elements of the CLC program through an iterative process We conducted social needs screens at 65% of eligible well-child visits from May 2017 to April 2018; 19.7% of screens had one or more positive responses. Childcare (48.8%), housing quality and/or availability (39.9%), and food insecurity (22.8%) were the most frequently reported needs. On average, 76% of providers had their patients screened on more than half of eligible well-child visits. Discussion: Our experience suggests that screening for social needs at well-child visits is feasible as part of routine primary care. We attribute progress to leveraging resources, obtaining provider buy-in, and defining program components to sustain activities.


Post-traumatic growth during the COVID-19 pandemic in carers of children in Portugal and the UK: cross-sectional online survey.
Although the negative effects of the COVID-19 pandemic on mental health have attracted interest, little attention has focused on its positive effects and possible post-traumatic growth. To assess anxiety, well-being and post-traumatic growth in carers of children aged 6-16 years in Portugal and the UK. A cross-sectional online survey of volunteers conducted at the peak of the first wave of COVID-19 during lockdown (1 May to 27 June 2020). A total of 385 caregivers (Portuguese, n = 185; UK, n = 200), predominantly mothers (n = 341, 88.6%), completed the survey. The majority were working exclusively from home (n = 271, 70.4%), almost half reported a reduction in income (n = 174, 45.2%), most children were home taught (n = 358, 93%), and 75 (19.5%) identified a family member with suspected or confirmed COVID-19 infection. In total, 341 caregivers (88.6%) identified positives arising from COVID-19, most commonly related to the post-traumatic growth domains of improved relationships, a greater appreciation of life, discovering and embracing new possibilities, and positive spiritual change. A comparison of those who did (n = 341) and did not (n = 34) report any positives found a significant difference in well-being scores (t373 = 2.24, P = 0.025) but not in anxiety scores (t373 = 0.75, P = 0.45). Despite experiencing considerable adversity, examples of post-traumatic growth during the lockdown were common. Although the voluntary online nature of our survey is a limitation, our findings suggest that further research exploring post-traumatic growth following pandemics is warranted.


Asthmatic response to milk ingestion challenge in adults: a comparison of the open and double-blind challenges.
Cow's milk allergy can participate in pathophysiological mechanisms underlying bronchial asthma in some adult patients. This role should ultimately be confirmed by means of a milk ingestion challenge. In this study, the diagnostic value of the open food ingestion challenge (OFICH) and the double-blind placebo-controlled food challenge (DBPCFC) techniques with milk were compared in adult patients suffering from bronchial asthma with suspected milk allergy. In 87 asthmatics with a suspected history and positive skin tests for milk, the 87 OFICHs and DBPCFCs were performed in combination with spirometry and followed up to 72 h after the challenge. Of 87 patients, 74 (85%) developed a positive asthmatic response (AR) (20 immediate, 33 late, 6 dual late and 15 delayed; p < 0.01) and 13 (15%) developed a negative AR (p > 0.1) to OFICH. Seventy-five (86%) developed a positive AR (17 immediate, 35 late, 8 dual late and 15 delayed; p < 0.01) and 12 (14%) developed a negative AR (p > 0.05) to DBPCFC. The correlation between the OFICH and DBPCFC was statistically significant (p < 0.01). All placebo control challenges were negative (p > 0.2). In some adults with bronchial asthma, involvement of an allergy to cow's milk results in the appearance of various AR types (immediate, late, dual late or delayed). The milk allergy can be confirmed by open or double-blind techniques, combined with spirometry. No significant differences were found between the OFICH and DBPCFC results. OFICH with natural milk combined with spirometry seems, therefore, to be an adequate technique for the detection of milk allergy in asthmatics. The DBPCFC can be performed as an additional check, if necessary.


A cargo-sorting DNA robot.
Two critical challenges in the design and synthesis of molecular robots are modularity and algorithm simplicity. We demonstrate three modular building blocks for a DNA robot that performs cargo sorting at the molecular level. A simple algorithm encoding recognition between cargos and their destinations allows for a simple robot design: a single-stranded DNA with one leg and two foot domains for walking, and one arm and one hand domain for picking up and dropping off cargos. The robot explores a two-dimensional testing ground on the surface of DNA origami, picks up multiple cargos of two types that are initially at unordered locations, and delivers them to specified destinations until all molecules are sorted into two distinct piles. The robot is designed to perform a random walk without any energy supply. Exploiting this feature, a single robot can repeatedly sort multiple cargos. Localization on DNA origami allows for distinct cargo-sorting tasks to take place simultaneously in one test tube or for multiple robots to collectively perform the same task.


Review of STI and HIV epidemiological data from 1990 to 2001 in urban Burkina Faso: implications for STI and HIV control.
To better understand the sexually transmitted infection (STI)/HIV dynamics in an urban west African setting in order to adapt STI/HIV control efforts accordingly. Review of STI and HIV epidemiological studies performed over the past decade in Bobo-Dioulasso, the second city of Burkina Faso. Trends in STI prevalence among commercial sex workers and the general population were assessed over time through studies that used the same recruitment and laboratory diagnostic procedures. Variations in aetiologies of vaginal discharge, urethral discharge, and genital ulcers were also evaluated among patients consulting for genital infection complaints. Antenatal clinic based surveys provided data to assess HIV trend among the general population. We observed an important decline of classic bacterial STI such as syphilis, Neisseria gonorrhoea, Chlamydia trachomatis, and Haemophilus ducrey infections in all study groups. Trichomoniasis also declined but to a lesser extent. HIV infection followed the same trend at the same time, with a significant decline in the 15-19 year age group of pregnant women, suggesting a possible decrease of HIV incidence. Although no evidence of a causal relation can be drawn from this review, adoption of safer sex behaviour, introduction of the syndromic management (SM) approach, or higher antibiotic use may have contributed to these changes. Classic bacterial STI declined over the past decade in parallel with a stabilisation of HIV infection. Variations in syndromes aetiology and sexual behaviours should be monitored as part of STI surveillance in order to improve STI syndromic management algorithms and to adapt HIV/STI prevention efforts.


EPS8 upregulates FOXM1 expression, enhancing cell growth and motility.
Previous studies from our laboratory have indicated that overexpression of the epidermal growth factor receptor pathway substrate 8 (EPS8) enhances cell proliferation, migration and tumorigenicity in vivo, although the mechanisms involved remain unexplored. A microarray screen to search for potential mediators of EPS8 identified upregulation of multiple cell cycle-related targets such as the transcription factor FOXM1 and several of its reported downstream mediators, including cdc20, cyclin B1, cyclin A, aurora-B kinase and cdc25C in cells with elevated EPS8, as well as matrix metalloproteinase-9, which we reported previously to be upregulated by EPS8-dependent mechanisms. Cells engineered to overexpress FOXM1 showed increased proliferation, similar to EPS8-overexpressing cells. Conversely, targeted knockdown of FOXM1 in EPS8-overexpressing cells reduced proliferation. Cotransfection of EPS8 with a FOXM1-luciferase reporter plasmid into 293-T- or SVpgC2a-immortalized buccal keratinocytes demonstrated that EPS8 enhances FOXM1 promoter activity, whereas chromatin immunoprecipitation assays revealed elevated levels of acetylated histone H3 associated with the FOXM1 promoter in cells expressing high levels of EPS8. Treatment of EPS8-overexpressing cells with inhibitors of phosphoinositide 3-OH kinase or AKT reduced expression of FOXM1 and aurora-B kinase, a transcriptional target of FOXM1. Overexpression of EPS8 induced expression of the chemokine ligands CXCL5 and CXCL12 in a FOXM1-dependent manner, which was blocked by LY294002 or a dominant-negative form of AKT. Additionally, overexpression of FOXM1 enhanced cell migration, whereas targeted knockdown of CXCL5 or inhibition of AKT reduced migration of EPS8-expressing cells. These data suggest that EPS8 enhances cell proliferation and migration in part by deregulating FOXM1 activity and inducing CXC-chemokine expression, mediated by PI3K- and AKT-dependent mechanisms.


Patterns and predictors of changes in active commuting over 12 months.
To assess the predictors of uptake and maintenance of walking and cycling, and of switching to the car as the usual mode of travel, for commuting. 655 commuters in Cambridge, UK reported all commuting trips using a seven-day recall instrument in 2009 and 2010. Individual and household characteristics, psychological measures relating to car use and environmental conditions on the route to work were self-reported in 2009. Objective environmental characteristics were assessed using Geographical Information Systems. Associations between uptake and maintenance of commuting behaviours and potential predictors were modelled using multivariable logistic regression. Mean within-participant changes in commuting were relatively small (walking: +3.0 min/week, s.d.=66.7; cycling: -5.3 min/week, s.d.=74.7). Self-reported and objectively-assessed convenience of public transport predicted uptake of walking and cycling respectively, while convenient cycle routes predicted uptake of cycling and a pleasant route predicted maintenance of walking. A lack of free workplace parking predicted uptake of walking and alternatives to the car. Less favourable attitudes towards car use predicted continued use of alternatives to the car. Improving the convenience of walking, cycling and public transport and limiting the availability of workplace car parking may promote uptake and maintenance of active commuting.


CASA in invertebrates.
Sperm movement has been described in several phyla of invertebrates. Yet, sperm motility has only been quantified using computer-aided sperm analysis (CASA-Mot) in externally fertilising species (broadcast spawners) of two phyla, molluscs and echinoderms. In the present study we quantified in detail the nature of the sperm tracks, percentage motility groupings and detailed kinematics of rapid-, medium- and slow-swimming spermatozoa in the oyster Crassostrea gigas and four species never previously studied by CASA-Mot, namely the molluscs Choromytilus meridionalis, Donax serra and Haliotis midae and the echinoderm Parechinus angulosus. A feature common to all these species are the helical tracks, the diameter of which seems to be species specific. Using CASA-Mot, the behaviour of spermatozoa was also studied over time and in the presence of egg water and Ca2+ modulators such as caffeine and procaine hydrochloride. For the first time, we show that hyperactivation can be induced in all species in the presence of egg water (sea water that was mixed with mature eggs and then centrifuged) and/or caffeine, and these hyperactivated sperm tracks were characterised using CASA-Mot. We relate the different patterns of sperm motility and behaviour to reproductive strategies such as broadcast spawning and spermcasting, and briefly review studies using CASA-Mot on other invertebrates.


Genetic variation of the VP1 gene of the virulent duck hepatitis A virus type 1 (DHAV-1) isolates in Shandong province of China.
To investigate the relationship of the variation of virulence and the external capsid proteins of the pandemic duck hepatitis A virus type 1 (DHAV-1) isolates, the virulence, cross neutralization assays and the complete sequence of the virion protein 1 (VP1) gene of nine virulent DHAV-1 strains, which were isolated from infected ducklings with clinical symptoms in Shandong province of China in 2007-2008, were tested. The fifth generation duck embryo allantoic liquids of the 9 isolates were tested on 12-day-old duck embryos and on 7-day-old ducklings for the median embryonal lethal doses (ELD(50)s) and the median lethal doses (LD(50)s), respectively. The results showed that the ELD(50)s of embryonic duck eggs of the 9 DHAV-1 isolates were between 1.9 × 10(6)/mL to 1.44 × 10(7)/mL, while the LD(50)s were 2.39 × 10(5)/mL to 6.15 × 10(6)/mL. Cross-neutralization tests revealed that the 9 DHAV-1 isolates were completely neutralized by the standard serum and the hyperimmune sera against the 9 DHAV-1 isolates, respectively. Compared with other virulent, moderate virulent, attenuated vaccine and mild strains, the VP1 genes of the 9 strains shared 89.8%-99.7% similarity at the nucleotide level and 92.4%-99.6% at amino acid level with other DHAV-1 strains. There were three hypervariable regions at the C-terminus (aa 158-160, 180-193 and 205-219) and other variable points in VP1 protein, but which didn't cause virulence of DHAV-1 change.


Exhaled breath to screen for malignant pleural mesothelioma: a validation study.
Malignant pleural mesothelioma (MPM) is predominantly caused by asbestos exposure and has a poor prognosis. Breath contains volatile organic compounds (VOCs) and can be explored as an early detection tool. Previously, we used multicapillary column/ion mobility spectrometry (MCC/IMS) to discriminate between patients with MPM and asymptomatic high-risk persons with a high rate of accuracy. Here, we aim to validate these findings in different control groups.Breath and background samples were obtained from 52 patients with MPM, 52 healthy controls without asbestos exposure (HC), 59 asymptomatic former asbestos workers (AEx), 41 patients with benign asbestos-related diseases (ARD), 70 patients with benign non-asbestos-related lung diseases (BLD) and 56 patients with lung cancer (LC).After background correction, logistic lasso regression and receiver operating characteristic (ROC) analysis, the MPM group was discriminated from the HC, AEx, ARD, BLD and LC groups with 65%, 88%, 82%, 80% and 72% accuracy, respectively. Combining AEx and ARD patients resulted in 94% sensitivity and 96% negative predictive value (NPV). The most important VOCs selected were P1, P3, P7, P9, P21 and P26.We discriminated MPM patients from at-risk subjects with great accuracy. The high sensitivity and NPV allow breath analysis to be used as a screening tool for ruling out MPM.


Roles of 5-lipoxygenase and cyclooxygenase-2 in the biosynthesis of hemiketals E2 and D2 by activated human leukocytes.
The 2 hemiketal (HK) eicosanoids HKD2 and HKE2 are the major products of the biosynthetic crossover of the 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) pathways. HKs result from the rearrangement of a di-endoperoxide intermediate formed in the COX-2-dependent oxygenation of 5S-hydroxyeicosatetraenoic acid (5S-HETE). We analyzed HK biosynthesis in human leukocytes stimulated ex vivo and defined the biosynthetic roles of 5-LOX and COX-2, using inhibitors and incubations with exogenous substrates. Activation of leukocytes with LPS followed by treatment with the calcium ionophore A23187 resulted in the formation of PGE2, 5-HETE, and LTB4 as the principal metabolites of COX-2 and 5-LOX, respectively. The formation of HKD2 and HKE2 was highest after 15 min LPS treatment, and at that time, levels were similar to PGE2, but less than 5-HETE and LTB4 The time course of HK formation paralleled that of 5-HETE and LTB4, implying the availability of the 5S-HETE substrate as a limiting factor in biosynthesis rather than expression levels of COX-2. Specific inhibitors of COX-2 and 5-LOX decreased formation of HKD2 and HKE2 Platelets did not form HKs from exogenous 5S-HETE, implying that COX-1 is not involved. HKs are early products during an inflammatory event and require cells that express 5-LOX and COX-2 for their biosynthesis.-Giménez-Bastida, J. A., Shibata, T., Uchida, K., Schneider, C. Roles of 5-lipoxygenase and cyclooxygenase-2 in the biosynthesis of hemiketals E2 and D2 by activated human leukocytes.


The role of rehearsal on the output order of immediate free recall of short and long lists.
Participants tend to initiate immediate free recall (IFR) of short lists of words with the very first word on the list. Three experiments examined whether rehearsal is necessary for this recent finding. In Experiment 1, participants were presented with lists of between 2 and 12 words for IFR at a fast, medium, or slow rate, with and without articulatory suppression (AS). The tendency to initiate output with the first item for short lists (a) did not change greatly when presentation rate was increased from a medium to a fast rate under normal conditions, (b) was reduced but not eliminated by AS, and (c) was maintained at slower rates when rehearsal was allowed but decreased at slower rates when rehearsal was prevented. In Experiment 2, the overt rehearsal methodology was used, and the tendency to initiate output with the first item for short lists was present even in the absence of overt rehearsal. Experiment 3 re-examined IFR under normal encoding conditions and replicated the main findings from the normal encoding conditions of Experiment 1 while using the presentation rates and list lengths of Experiment 2. We argue that rehearsal is not strictly necessary for the tendency to initiate recall with the first item under normal conditions, but rehearsal nevertheless contributes to this effect at slower rates.


Association of genetic mutations in Plasmodium vivax dhfr with resistance to sulfadoxine-pyrimethamine: geographical and clinical correlates.
Mutations in the Plasmodium falciparum gene (dhfr) encoding dihydrofolate reductase are associated with resistance to antifols. Plasmodium vivax, the more prevalent malaria parasite in Asia and the Americas, is considered antifol resistant. Functional polymorphisms in the dhfr gene of P. vivax (pvdhfr) were assessed by PCR-restriction fragment length polymorphism using blood samples taken from 125 patients with acute vivax malaria from three widely separated locations, Thailand (n = 100), India (n = 16), and Madagascar and the Comoros Islands (n = 9). Upon evaluation of the three important codons (encoding residues 57, 58, and 117) of P. vivax dhfr (pvdhfr), double- or triple-mutation genotypes were found in all but one case from Thailand (99%), in only three cases from India (19%) and in no cases from Madagascar or the Comoros Islands (P < 0.0001). The dhfr PCR products of P. vivax from 32 Thai patients treated with the antifolate sulfadoxine-pyrimethamine (S-P) were investigated. All samples showed either double (53%) or triple (47%) mutations. Following treatment, 34% of the patients had early treatment failures and only 10 (31%) of the patients cleared their parasitemias for 28 days. There were no significant differences in cure rates, but parasite reduction ratios at 48 h were significantly lower for patients whose samples showed triple mutations than for those whose samples showed double mutations (P = 0.01). The three mutations at the pvdhfr codons for residues 57, 58, and 117 are associated with high levels of S-P resistance in P. vivax. These mutations presumably arose from selection pressure.


Aetiology of community-acquired pneumonia: a prospective study among adults requiring admission to hospital.
The prevalence of microorganisms causing community-acquired pneumonia in patients who required admission to hospital was investigated and the percentage of cases whose aetiology remained unknown due to the study design and logistical problems estimated. Between January 1991 and April 1993 all patients with community-acquired pneumonia admitted to six hospitals were included in the study. Aetiological diagnosis, categorised as definite, probable and possible, was based on the results of routine microbiological and serological tests. Three hundred and thirty four patients with a median age of 65 (range 17-92) years were enrolled in the study. The diagnosis of community-acquired pneumonia was definite in 108 cases, and probable or possible in 73 and 27 cases, respectively, including dual infections. Streptococcus pneumoniae was the predominant pathogen (27%) followed by viruses and Haemophilus influenzae (both about 8%) and Mycoplasma pneumoniae (6%). Chlamydia spp (3%) and Legionella pneumophila (2%) were less frequently detected. No diagnosis was made in 45% of the cases. With adjustment for anti-microbial therapy before admission and for other logistical considerations, it is estimated that the aetiology could have been ascertained in 65% of the cases. Streptococcus pneumoniae is the most frequently detected cause of community-acquired pneumonia. The inability to detect a micro-organism results mainly from the use of routine diagnostic tests and, to a lesser extent, from logistical problems or the use of antibiotics before admission.


Coevolution of activating and inhibitory receptors within mammalian carcinoembryonic antigen families.
Most rapidly evolving gene families are involved in immune responses and reproduction, two biological functions which have been assigned to the carcinoembryonic antigen (CEA) gene family. To gain insights into evolutionary forces shaping the CEA gene family we have analysed this gene family in 27 mammalian species including monotreme and marsupial lineages. Phylogenetic analysis provided convincing evidence that the primordial CEA gene family in mammals consisted of five genes, including the immune inhibitory receptor-encoding CEACAM1 (CEA-related cell adhesion molecule) ancestor. Our analysis of the substitution rates within the nucleotide sequence which codes for the ligand binding domain of CEACAM1 indicates that the selection for diversification is, perhaps, a consequence of the exploitation of CEACAM1 by a variety of viral and bacterial pathogens as their cellular receptor. Depending on the extent of the amplification of an ancestral CEACAM1, the number of CEACAM1-related genes varies considerably between mammalian species from less than five in lagomorphs to more than 100 in bats. In most analysed species, ITAM (immunoreceptor tyrosine-based activation motifs) or ITAM-like motif-containing proteins exist which contain Ig-V-like, ligand binding domains closely related to that of CEACAM1. Human CEACAM3 is one such protein which can function as a CEACAM1 decoy receptor in granulocytes by mediating the uptake and destruction of specific bacterial pathogens via its ITAM-like motif. The close relationship between CEACAM1 and its ITAM-encoding relatives appears to be maintained by gene conversion and reciprocal recombination. Surprisingly, secreted CEACAMs resembling immunomodulatory CEACAM1-related trophoblast-specific pregnancy-specific glycoproteins (PSGs) found in humans and rodents evolved only in a limited set of mammals. The appearance of PSG-like genes correlates with invasive trophoblast growth in these species. These phylogenetic studies provide evidence that pathogen/host coevolution and a possible participation in fetal-maternal conflict processes led to a highly species-specific diversity of mammalian CEA gene families.


How do I sound to me? Perceived changes in communication in Parkinson's disease.
To examine self and carer perceived changes in communication associated with Parkinson's disease and relate these to speech intelligibility, gender, age and other disease measures. Cross-sectional survey of a hospital- and community-based sample of 176 people with Parkinson's disease and their carers using a questionnaire based on semantic differential techniques. One hundred and four people with Parkinson's disease with no history of communication difficulties prior to onset of their Parkinson's disease and 45 primary carers who returned completed questionnaires. Differences in ratings for ;before' the onset of Parkinson's disease versus present status. There was a strong perception of negative impact on communication between 'before' and 'now', irrespective of age and gender and largely independent of disease severity and duration, intelligibility and cognitive status. Activities of daily living (assessed by Unified Parkinson's Disease Rating Scale (UPDRS) II) and depression rating scale scores had the strongest association with change (adjusted R(2) 0.27). There was a significant correlation between the rank order of perceived change in features examined in people with Parkinson's disease versus their carers, though in general carers rated change as having less impact. Parkinson's disease exercises a strong influence on communication even before apparent alterations to intelligibility or motor status (UPDRS).


Conservation of bacterial protein synthesis machinery: initiation and elongation in Mycobacterium smegmatis.
Most of our understanding of ribosome function is based on experiments utilizing translational components from Escherichia coli. It is not clear to which extent the details of translation mechanisms derived from this single organism are true for all bacteria. Here we investigate translation factor-dependent reactions of initiation and elongation in a reconstituted translation system from a Gram-positive bacterium Mycobacterium smegmatis. This organism was chosen because mutations in rRNA have very different phenotypes in E. coli and M. smegmatis, and the docking site for translational GTPases, the L12 stalk, is extended in the ribosomes from M. smegmatis compared to E. coli. M. smegmatis genes coding for IF1, IF2, IF3, EF-G, and EF-Tu were identified by sequence alignments; the respective recombinant proteins were prepared and studied in a variety of biochemical and biophysical assays with M. smegmatis ribosomes. We found that the activities of initiation and elongation factors and the rates of elemental reactions of initiation and elongation of protein synthesis are remarkably similar with M. smegmatis and E. coli components. The data suggest a very high degree of conservation of basic translation mechanisms, probably due to coevolution of the ribosome components and translation factors. This work establishes the reconstituted translation system from individual purified M. smegmatis components as an alternative to that from E. coli to study the mechanisms of translation and to test the action of antibiotics against Gram-positive bacteria.


Screening for tuberculosis infection in urban children.
To determine the proportion of children who are at high risk for tuberculosis (TB) as defined by the American Academy of Pediatrics (AAP) criteria, the rate of compliance with visits for tuberculin skin test (TST) interpretation, and the prevalence of TB infection. A cross-sectional study of 401 children, 12 months to 18 years of age, who attended a hospital-based, urban pediatric clinic for well-child visits was undertaken from April 13, 1994, through August 30, 1994. Respondents completed a self-administered questionnaire, an intradermal TST was applied, and an appointment was scheduled for skin test interpretation in 48 to 72 hours. Hospital-based, pediatric primary care center in Rochester, NY, serving children of low to moderate income (67% were receiving Medicaid). Of the 401 children, 342 (85%) had at least 1 risk factor for TB identified: 96 (24%) reported contact with persons who were considered to be at high risk for TB; 170 (42%) had at least 1 parent who was born in a high prevalence country; and 269 (67%) reported a household income of less than $15,500. Of the 401 children, 300 returned for TST interpretation, 257 (64%) by 48 to 72 hours and an additional 43 (11%) by 96 hours. Four (1.3%) of the 300 children had a positive TST (ie, induration > or = 10 mm). All 4 of the children who were TST positive had at least 1 parent from a high-risk country and were identified using AAP-defined risk criteria. The mean age of children who were TST positive was 15.3 years (range 13-17 years) compared with 8.1 years for those who were TST negative (P < .01). The positive predictive value of the questionnaire, which included income as a risk factor for TB, was only 1.5 (95% confidence interval = 0.5-4.0); when household income was not considered a risk factor, the positive predictive value was 2.0 (95% confidence interval = 0.7, 5.5). The estimated cost per child who was TST positive ranged from $430 for those who had contact with an incarcerated adult to $855 per child who was TST positive identified by using AAP-defined criteria. The overall sensitivity of the AAP-defined criteria and having at least 1 parent from a TB-endemic country were high. However, because of the low prevalence of TB infection, the positive predictive value of these criteria was very low. These data support AAP recommendations only to skin test children who are at high risk for TB, but they also suggest that annual testing may not be cost-effective for many communities in the United States.


A noninvasive approach for assessing tumor hypoxia in xenografts: developing a urinary marker for hypoxia.
Tumor hypoxia modifies the efficacy of conventional anticancer therapy and promotes malignant tumor progression. Human chorionic gonadotropin (hCG) is a glycoprotein secreted during pregnancy that has been used to monitor tumor burden in xenografts engineered to express this marker. We adapted this approach to use urinary beta-hCG as a secreted reporter protein for tumor hypoxia. We used a hypoxia-inducible promoter containing five tandem repeats of the hypoxia-response element (HRE) ligated upstream of the beta-hCG gene. This construct was stably integrated into two different cancer cell lines, FaDu, a human head and neck squamous cell carcinoma, and RKO, a human colorectal cancer cell line. In vitro studies showed that tumor cells stably transfected with this plasmid construct secrete beta-hCG in response to hypoxia or hypoxia-inducible factor 1alpha (HIF-1alpha) stabilizing agents. The hypoxia responsiveness of this construct can be blocked by treatment with agents that affect the HIF-1alpha pathways, including topotecan, 1-benzyl-3-(5'-hydroxymethyl-2'-furyl)indazole (YC-1), and flavopiridol. Immunofluorescent analysis of tumor sections and quantitative assessment with flow cytometry indicate colocalization between beta-hCG and 2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide (EF5) and beta-hCG and pimonidazole, two extrinsic markers for tumor hypoxia. Secretion of beta-hCG from xenografts that contain these stable constructs is directly responsive to changes in tumor oxygenation, including exposure of the animals to 10% O2 and tumor bed irradiation. Similarly, urinary beta-hCG levels decline after treatment with flavopiridol, an inhibitor of HIF-1 transactivation. This effect was observed only in tumor cells expressing a HRE-regulated reporter gene and not in tumor cells expressing a cytomegalovirus-regulated reporter gene. The 5HRE beta-hCG reporter system described here enables serial, noninvasive monitoring of tumor hypoxia in a mouse model by measuring a urinary reporter protein.


The MAP kinase kinase MKK2 affects disease resistance in Arabidopsis.
The Arabidopsis mitogen-activated protein kinase (MAPK) kinase 2 (MKK2) was shown to mediate cold and salt stress responses through activation of the two MAP kinases MPK4 and MPK6. Transcriptome analysis of plants expressing constitutively active MKK2 (MKK2-EE plants) showed altered expression of genes induced by abiotic stresses but also a significant number of genes involved in defense responses. Both MPK4 and MPK6 became rapidly activated upon Pseudomonas syringae pv. tomato DC3000 infection and MKK2-EE plants showed enhanced levels of MPK4 activation. Although MKK2-EE plants shared enhanced expression of genes encoding enzymes of ethylene (ET) and jasmonic acid (JA) synthesis, ET, JA, and salicylic acid (SA) levels did not differ dramatically from those of wild-type or mkk2-null plants under ambient growth conditions. Upon P. syringae pv. tomato DC3000 infection, however, MKK2-EE plants showed reduced increases of JA and SA levels. These results indicate that MKK2 is involved in regulating hormone levels in response to pathogens. MKK2-EE plants were more resistant to infection by P. syringae pv. tomato DC3000 and Erwinia carotovora subsp. carotovora, but showed enhanced sensitivity to the fungal necrotroph Alternaria brassicicola. Our data indicate that MKK2 plays a role in abiotic stress tolerance and plant disease resistance.


Hyper-spectral confocal nano-imaging with a 2D super-lens.
Achieving sub-100 nm resolution over a broad visible bandwidth has long been an elusive goal in the nano-imaging of cell-surface interfaces. While metamaterial super-lenses and near-field optics have been previously demonstrated, these techniques can operate only at one wavelength, and do not provide accesses to the cell-surface interfaces. Here, we investigate a broadband 2D lens comprised of an oblate spheroidal dielectric cavity embedded just beneath a planar metal surface. The lens operates by adiabatically focusing asymmetric plasmon energies at sub-100 nm scale on the low-index side of the thin metal film formed between the cavity top and the planar metal surface. We then proposed the use of our lens in a high-resolution far-field confocal microscopy setup. Due to the surface-field nature of our lens, the presented system holds potential as an indispensable tool for cell-surface interfacial studies that require sub-100 nm hyper-spectral imaging analysis.


Bcl-2 family interactome analysis using bacterial surface display.
Members of the Bcl-2 family of proteins have opposing roles in programmed cell death; family members can play either pro-apoptotic or anti-apoptotic roles. Heterodimeric interactions between pro-apoptotic and anti-apoptotic members of the Bcl-2 family are critical for the regulation of apoptosis and are important targets for cancer therapeutics. Bcl-2 family interactions are mediated by the highly-conserved BH3 domain, corresponding to a single amphipathic α-helix, which binds in a hydrophobic cleft of its Bcl-2 family interaction partner. Here, using a high-throughput peptide-protein interaction assay based on bacterial cell surface display and flow cytometry, we present quantitative data for a near-complete set of 17 BH3 domains from the human genome binding to each of the 5 anti-apoptotic Bcl-2 family members. Biophysical insights into the affinity and specificity of these interactions are provided by analysis of the interactome data. In addition we carried out a truncation study of the Bim BH3 domain to define the core residues responsible for anti-apoptotic protein binding. The interactome data from this study has implications both in basic research on apoptosis and in the design of peptidic cancer therapeutics.


An implementation study of oral and blood-based HIV self-testing and linkage to care among men in rural and peri-urban KwaZulu-Natal, South Africa.
In South Africa, HIV-infected men are less likely than women to test and know their status (the first UNAIDS "90-90-90" target), and men have worse outcomes across the HIV care cascade. HIV self-testing (HIVST) may address this testing disparity but questions remain over the most effective distribution strategy and linkage following a positive test result. We implemented a men-focused HIVST distribution programme to evaluate components contributing to participation and retention. We conducted an implementation study of multi-venue HIVST kit distribution in rural and peri-urban KwaZulu-Natal (KZN), South Africa. We distributed HIVST kits at community points, workplaces and social venues for on site or take-home use. Clients could choose blood-based or oral-fluid-based HIVST kits and elect to watch an in-person or video demonstration. We provided a USD2 incentive to facilitate reporting test results by phone or SMS. Persons with reactive HIVST results were provided immediate confirmatory tests (if used HIVST on site) or were referred for confirmatory testing (if took HIVST off site) and linkage to care for ART initiation. We describe the testing and linkage cascade in this sample and describe predictors of reactive HIVST results and linkage. Between July and November 2018, we distributed 4496 HIVST kits in two regions of KZN (96% to men, median age 28 (IQR 23 to 35). Most participants (58%) chose blood-based HIVST and 42% chose oral-swab kits. 11% of men were testing for the first time. A total of 3902 (83%) of testers reported their test result to the study team, with 314 (8%) screening positive for HIV. Among 274 men with reactive HIVST results, 68% linked to ART; no significant predictors of linkage were identified. 10% of kit users reported they would prefer a different type (oral vs. blood) of kit for repeat testing than the type they used. HIVST is acceptable to men and rapid distribution with optional testing support is feasible in rural and peri-urban settings. HIVST kits successfully reached younger men and identified undetected infections. Both oral and blood-based HIVST were selected. Scaling up HIVST distribution and guidance may increase the number of first-time testers among men and help achieve the first UNAIDS "90" for men in South Africa.


Signatures of human-commensalism in the house sparrow genome.
House sparrows (Passer domesticus) are a hugely successful anthrodependent species; occurring on nearly every continent. Yet, despite their ubiquity and familiarity to humans, surprisingly little is known about their origins. We sought to investigate the evolutionary history of the house sparrow and identify the processes involved in its transition to a human-commensal niche. We used a whole genome resequencing dataset of 120 individuals from three Eurasian species, including three populations of Bactrianus sparrows, a non-commensal, divergent house sparrow lineage occurring in the Near East. Coalescent modelling supports a split between house and Bactrianus sparrow 11 Kya and an expansion in the house sparrow at 6 Kya, consistent with the spread of agriculture following the Neolithic revolution. Commensal house sparrows therefore likely moved into Europe with the spread of agriculture following this period. Using the Bactrianus sparrow as a proxy for a pre-commensal, ancestral house population, we performed a comparative genome scan to identify genes potentially involved with adaptation to an anthropogenic niche. We identified potential signatures of recent, positive selection in the genome of the commensal house sparrow that are absent in Bactrianus populations. The strongest selected region encompasses two major candidate genes; COL11A-which regulates craniofacial and skull development and AMY2A, part of the amylase gene family which has previously been linked to adaptation to high-starch diets in humans and dogs. Our work examines human-commensalism in an evolutionary framework, identifies genomic regions likely involved in rapid adaptation to this new niche and ties the evolution of this species to the development of modern human civilization.


The sociobiology of sex: inclusive fitness consequences of inter-sexual interactions.
The diversity of social interactions between sexual partners has long captivated biologists, and its evolution has been interpreted largely in terms of 'direct fitness' pay-offs to partners and their descendants. Inter-sexual interactions also have 'indirect effects' by affecting the fitness of relatives, with important consequences for inclusive fitness. However, inclusive fitness arguments have received limited consideration in this context, and definitions of 'direct' and 'indirect' fitness effects in this field are often inconsistent with those of inclusive fitness theory. Here, we use a sociobiology approach based on inclusive fitness theory to distinguish between direct and indirect fitness effects. We first consider direct effects: we review how competition leads to sexual conflict, and discuss the conditions under which repression of competition fosters sexual mutualism. We then clarify indirect effects, and show that greenbeard effects, kin recognition and population viscosity can all lead to episodes of indirect selection on sexual interactions creating potential for sexual altruism and spite. We argue that the integration of direct and indirect fitness effects within a sociobiology approach enables us to consider a more diverse spectrum of evolutionary outcomes of sexual interactions, and may help resolving current debates over sexual selection and sexual conflict.


Prevalence of asthma-related symptoms and bronchial responsiveness to exercise in children aged 13-14 yrs in Barcelona, Spain.
It is not clear whether asymptomatic bronchial responsiveness is a risk factor for development of asthma. A cross-sectional study was conducted to determine the prevalence of asthma among schoolchildren from Barcelona (Spain). The association between respiratory symptoms and bronchial responsiveness to exercise was examined. For this study 3,033 schoolchildren aged 13-14 yrs were studied from the general population. Participants answered a respiratory questionnaire and a self-reporting video-questionnaire. A total of 2,842 children underwent bronchial responsiveness testing by exercise challenge. The study was part of the International Study of Asthma and Allergies in Childhood (ISAAC) project. The prevalence of "current asthma" (recent wheezing and bronchial responsiveness to exercise) was 4% and the prevalence of "wheezing only" 10%. A fall in peak expiratory flow rate (PEFR) > or = 15% after exercise testing was found in 324 (11%) children, 29 (9%) of whom presented clinical symptoms of asthma. Bronchial responsiveness to exercise was significantly associated with all items of the asthma questionnaire. The prevalence of asthma-related symptoms in this inner-city area was lower than frequently reported rates in other countries, although the prevalence of exercise-induced bronchoconstriction was relatively high, and threefold greater than in a geographical area in the vicinity of Barcelona. These findings are consistent with the current view that asthma-related symptoms and bronchial responsiveness to exercise have different meanings in a community survey, and that local environmental factors could influence the prevalence of bronchial responsiveness.


Fresh frozen plasma should be given earlier to patients requiring massive transfusion.
Acidosis, hypothermia, and coagulopathy were identified more than 20 years ago as a deadly triad for patients presenting with exsanguinating hemorrhage. This led to fundamental changes in initial management of severely injured patients. Despite major advances, hemorrhage remains a leading cause of early death in trauma patients. Recent studies report most severely injured patients to be coagulopathic at admission, before resuscitation interventions, and that traditional massive transfusion practice grossly underestimates needs. The hypothesis for this study is that our pre-intensive care unit (ICU) massive transfusion (MT) protocol does not adequately correct coagulopathy, and that early uncorrected coagulopathy is predictive of mortality. Data maintained in our Trauma Research Database were reviewed. Univariate logistic regression analysis was used to analyze the association of early ICU international normalized ratio (INR) and outcomes, including survival. Ninety-seven of 200 patients admitted during 51 months (ending January 2003) and resuscitated using our standardized ICU shock resuscitation protocol received MT (> or =10 units packed red blood cells [PRBC]) during hospital day 1 (age, 39 +/- 2; ISS, 29 +/- 1; survival, 70%.) All patients required emergency operating room and/or interventional radiology procedures and arrived in the ICU 6.8 +/- 0.3 hours after admission. Coagulopathy, present at hospital admission (pre-ICU INR, 1.8 +/- 0.2), persisted at ICU admission (initial ICU INR, 1.6 +/- 0.1). Pre-ICU resuscitation, 9 +/- 1 L crystalloid fluid, 12 +/- 1 units PRBC, 5 +/- 0.4 units fresh frozen plasma (FFP), was consistent with our MT protocol by which FFP was not given until after 6 units PRBC. ICU resuscitation involved 11 +/- 1 L lactated Ringer's solution (LR) and 10 +/- 1 units PRBC. Mean pH was normal within 8 hours. Mean temperature increased from approximately 35 degrees C to >37 degrees C within 4 hours. In the ICU during resuscitation, patients received 10 +/- 1 units FFP for coagulopathy; the ratio of FFP:PRBC was 1:1. Mean INR decreased to 1.4 +/- 0.03 within 8 hours and remained nearly constant for the remaining 16 hours of ICU resuscitation, indicating moderate coagulopathy. Statistical analysis found severity of coagulopathy (INR) at ICU admission associated with survival outcome (p = 0.02; area under receiver operator curve [ROC] = 0.71.) These data indicate acidosis and hypothermia to be well managed. Coagulopathy was not corrected in the ICU despite adherence to pre-ICU MT and ICU protocols, likely because of inadequate pre-ICU intervention. More aggressive pre-ICU intervention to correct coagulopathy may be effective in decreasing PRBC requirement during ICU resuscitation, and, because of the association with increased mortality, could improve outcome. We have revised our pre-ICU MT protocol to emphasize early FFP in a FFP:PRBC ratio of 1:1. We think that treatment of coagulopathy can be improved with the development of standardized protocols, both empiric and data driven.


Long-term high frequency deep brain stimulation of the nucleus accumbens drives time-dependent changes in functional connectivity in the rodent limbic system.
Deep brain stimulation of the ventral striatum is an effective treatment for a variety of treatment refractory psychiatric disorders yet the mechanism of action remains elusive. We examined how five days of stimulation affected rhythmic brain activity in freely moving rats in terms of oscillatory power within, and coherence between, selected limbic regions bilaterally. Custom made bipolar stimulating/recording electrodes were implanted, bilaterally, in the nucleus accumbens core. Local field potential (LFP) recording electrodes were implanted, bilaterally in the prelimbic and orbitofrontal cortices and mediodorsal thalamic nucleus. Stimulation was delivered bilaterally with 100 μs duration constant current pulses at a frequency of 130 Hz delivered at an amplitude of 100 μA using a custom-made stimulation device. Synchronized video and LFP data were collected from animals in their home cages before, during and after stimulation. Signals were processed to remove movement and stimulation artifacts, and analyzed to determine changes in spectral power within, and coherence between regions. Five days stimulation of the nucleus accumbens core yielded temporally dynamic modulation of LFP power in multiple bandwidths across multiple brain regions. Coherence was seen to decrease in the alpha band between the mediodorsal thalamic nucleus and core of the nucleus accumbens. Coherence between each core of the nucleus accumbens bilaterally showed rich temporal dynamics throughout the five day stimulation period. Stimulation cessation revealed significant "rebound" effects in both power and coherence in multiple brain regions. Overall, the initial changes in power observed with short-term stimulation are replaced by altered coherence, which may reflect the functional action of DBS.


Contextual Factors and Spatial Patterns of Childhood Malnutrition in Provinces of Burkina Faso.
Approximately 45% of all children's deaths are associated with malnutrition, and sub-Saharan Africa is hardest hit by this phenomenon. However, information on geographical variations of malnutrition in developing countries is limited. This study examined the geographical distribution and community characteristics associated with child malnutrition in Burkina Faso. Data from the 2011 Burkina Faso Demographic Health Survey were analyzed. A general Kriging interpolation method was used to generate spatial malnutrition patterns. The global Moran's I test was used to identify significant malnutrition spatial patterns. Generalized estimating equations (GEEs) were fitted to examine the association between community level factors and malnutrition. Average rates of stunting and wasting in the communities were 32.48% and 15.05%, respectively. Stunting hotspots were observed in the eastern and northeastern parts of Burkina Faso (i.e. Oudolan, Séno and Yagha, among others), while high rates of wasting were observed in the north-central part. The GEE results revealed lower stunting rates in communities with a higher percentage of households with improved sanitation. Communities with higher rates of professionally assisted births were associated with low wasting rates, while communities with higher rates of households with a low wealth index reported higher rates of wasting. Spatial statistical models of malnutrition prevalence are useful for indicating hotspots over wide areas and hence, for guiding intervention strategies. This study revealed significant geographical patterns and community factors associated with childhood malnutrition. These factors should be considered in future programs aimed at reducing malnutrition in Burkina Faso.


The impact of air pollution on the incidence of diabetes and survival among prevalent diabetes cases.
Growing evidence implicates ambient air pollutants in the development of major chronic diseases and premature mortality. However, epidemiologic evidence linking air pollution to diabetes remains inconclusive. This study sought to determine the relationships between selected air pollutants (nitrogen dioxide [NO2], fine particulate matter [PM2.5], ozone [O3], and oxidant capacity [Ox; the redox-weighted average of O3 and NO2]) and the incidence of diabetes, as well as the risk of cardiovascular or diabetes mortality among individuals with prevalent diabetes. We followed two cohorts, which included 4.8 million Ontario adults free of diabetes and 452,590 Ontario adults with prevalent diabetes, from 2001 to 2015. Area-level air pollution exposures were assigned to subjects' residential areas, and outcomes were ascertained using health administrative data with validated algorithms. We estimated hazard ratios for the association between each air pollutant and outcome using Cox proportional hazards models, and modelled the shape of the concentration-response relationships. Over the study period, 790,461 individuals were diagnosed with diabetes. Among those with prevalent diabetes, 26,653 died from diabetes and 64,773 died from cardiovascular diseases. For incident diabetes, each IQR increase in NO2 had a hazard ratio of 1.04 (95% CI: 1.03-1.05). This relationship was relatively robust to all sensitivity analyses considered, and exhibited a near-linear shape. There were also positive associations between incident diabetes and PM2.5, O3, and Ox, but these estimates were somewhat sensitive to different models considered. Among those with prevalent diabetes, almost all pollutants were associated with increased diabetes and cardiovascular mortality risk. The strongest association was observed between diabetes mortality and exposure to NO2 (HR = 1.08, 95% CI: 1.02-1.13). Selected air pollutants, especially NO2, were linked to an increased risk of incident diabetes, as well as risk of cardiovascular or diabetes mortality among persons with prevalent diabetes. As NO2 is frequently used as a proxy for road traffic exposures, this result may indicate that traffic-related air pollution has the strongest effect on diabetes etiology and survival after diabetes development.


Migraine associated with gastrointestinal disorders: A pathophysiological explanation.
Migraine is a highly prevalent, disabling, and costly disorder worldwide. From a long time ago, headaches have been known to be associated with gastrointestinal (GI) disorders. Headaches originating from gastric complaints were appreciated by Persian Medicine (PM) scholars. Today, functional GI disorders are shown to have high comorbidity with migraines; however, a causal relationship is not accepted today and pathophysiological explanations for this comorbidity are scarce. Therefore, based on the PM philosophy and the existing evidence, we aimed to propose an explanation for the co-morbidity of migraine and GI disorders. Noxious stimuli from the GI tract are relayed to the nucleus tractus solitarius (NTS) in the brain stem, which is located close to the trigeminal nucleus caudalis (TNC). TNC has shown projections to (NTS) through which frequent GI stimuli may antidromically reach the TNC and finally result in neurogenic inflammation. In addition, immune products, particularly histamine, are released in the submucosa of the GI tract and absorbed into the systemic circulation, which renders migraineurs more prone to attacks.


Counseling psychology trainees' perceptions of training and commitments to social justice.
This mixed methods study examined social justice commitments of counseling psychology graduate trainees. In the quantitative portion of the study, a national sample of trainees (n = 260) completed a web-based survey assessing their commitments to social justice and related personal and training variables. Results suggested that students desired greater social justice training than what they experienced in their programs. In the qualitative portion, we used a phenomenological approach to expand and elaborate upon quantitative results. A subsample (n = 7) of trainees who identified as strong social justice activists were interviewed regarding their personal, professional, and training experiences. Eleven themes related to participants' meanings of and experiences with social justice emerged within 4 broad categories: nature of social justice, motivation for activism, role of training, and personal and professional integration. Thematic findings as well as descriptive statistics informed the selection and ordering of variables in a hierarchical regression analysis that examined predictors of social justice commitment. Results indicated that trainees' perceptions of training environment significantly predicted their social justice commitment over and above their general activist orientation and spirituality. Findings are discussed collectively, and implications for training and future research are provided.


Gene rearrangements in hormone receptor negative breast cancers revealed by mate pair sequencing.
Chromosomal rearrangements in the form of deletions, insertions, inversions and translocations are frequently observed in breast cancer genomes, and a subset of these rearrangements may play a crucial role in tumorigenesis. To identify novel somatic chromosomal rearrangements, we determined the genome structures of 15 hormone-receptor negative breast tumors by long-insert mate pair massively parallel sequencing. We identified and validated 40 somatic structural alterations, including the recurring fusion between genes DDX10 and SKA3 and translocations involving the EPHA5 gene. Other rearrangements were found to affect genes in pathways involved in epigenetic regulation, mitosis and signal transduction, underscoring their potential role in breast tumorigenesis. RNA interference-mediated suppression of five candidate genes (DDX10, SKA3, EPHA5, CLTC and TNIK) led to inhibition of breast cancer cell growth. Moreover, downregulation of DDX10 in breast cancer cells lead to an increased frequency of apoptotic nuclear morphology. Using whole genome mate pair sequencing and RNA interference assays, we have discovered a number of novel gene rearrangements in breast cancer genomes and identified DDX10, SKA3, EPHA5, CLTC and TNIK as potential cancer genes with impact on the growth and proliferation of breast cancer cells.


Synthesis, crystal structure and photophysical properties of lanthanide coordination polymers of 4-[4-(9H-carbazol-9-yl)butoxy]benzoate: the effect of bidentate nitrogen donors on luminescence.
A new aromatic carboxylate ligand, 4-[4-(9H-carbazol-9-yl)butoxy]benzoic acid (HL), has been synthesized by the replacement of the hydroxyl hydrogen of 4-hydroxy benzoic acid with a 9-butyl-9H-carbazole moiety. The anion derived from HL has been used for the support of a series of lanthanide coordination compounds [Ln = Eu (1), Gd (2) and Tb (3)]. The new lanthanide complexes have been characterized by a variety of spectroscopic techniques. Complex 3 was structurally authenticated by single-crystal X-ray diffraction and found to exist as a solvent-free 1D coordination polymer with the formula [Tb(L)(3)](n). The structural data reveal that the terbium atoms in compound 3 reside in an octahedral ligand environment that is somewhat unusual for a lanthanide. It is interesting to note that each carboxylate group exhibits only a bridging-bidentate mode, with a complete lack of more complex connectivities that are commonly observed for extended lanthanide-containing solid-state structures. Examination of the packing diagram for revealed the existence of two-dimensional molecular arrays held together by means of CH-π interactions. Aromatic carboxylates of the lanthanides are known to exhibit highly efficient luminescence, thus offering the promise of applicability as optical devices. However, due to difficulties that arise on account of their polymeric nature, their practical application is somewhat limited. Accordingly, synthetic routes to discrete molecular species are highly desirable. For this purpose, a series of ternary lanthanide complexes was designed, synthesized and characterized, namely [Eu(L)(3)(phen)] (4), [Eu(L)(3)(tmphen)] (5), [Tb(L)(3)(phen)] (6) and [Tb(L)(3)(tmphen)] (7) (phen = 1,10-phenanthroline and tmphen = 3,4,7,8-tetramethyl-1,10-phenanthroline). The photophysical properties of the foregoing complexes in the solid state at room temperature have been investigated. The quantum yields of the ternary complexes 4 (9.65%), 5 (21.00%), 6 (14.07%) and 7 (32.42%), were found to be significantly enhanced in the presence of bidentate nitrogen donors when compared with those of the corresponding binary compounds 1 (0.11%) and 3 (1.45%). Presumably this is due to effective energy transfer from the ancillary ligands.


A cross-domain growth analysis: externalizing and internalizing behaviors during 8 years of childhood.
In a sample of 405 children assessed in kindergarten through the seventh grade, we determined the basic developmental trajectories of mother-reported and teacher-reported externalizing and internalizing behaviors using cross-domain latent growth modeling techniques. We also investigated the effects of race, socioeconomic level, gender, and sociometric peer-rejection status in kindergarten on these trajectories. The results indicated that, on average, the development of these behaviors was different depending upon the source of the data. We found evidence of the codevelopment of externalizing and internalizing behaviors within and across reporters. In addition, we found that African-American children had lower levels of externalizing behavior in kindergarten as reported by mothers than did European-American children but they had greater increases in these behaviors when reported by teachers. Children from homes with lower SES levels had higher initial levels of externalizing behaviors and teacher-reported internalizing behaviors. Males showed greater increases in teacher-reported externalizing behavior over time than did the females. Rejected children had trajectories of mother-reported externalizing and internalizing behavior that began at higher levels and either remained stable or increased more rapidly than did the trajectories for non-rejected children which decreased over time.


Overweight and obesity in non-pregnant women of childbearing age in South Africa: subgroup regression analyses of survey data from 1998 to 2017.
Overweight and obesity in adults are increasing globally and in South Africa (SA), contributing substantially to deaths and disability from non-communicable diseases. Compared to men, women suffer a disproportionate burden of obesity, which adversely affects their health and that of their offspring. This study assessed the changing patterns in prevalence and determinants of overweight and obesity among non-pregnant women in SA aged 15 to 49 years (women of childbearing age (WCBA)) between 1998 and 2017. This paper conducts secondary data analysis of seven consecutive nationally representative household surveys-the 1998 and 2016 SA Demographic and Health Surveys, 2008, 2010-2011, 2012, 2014-2015 and 2017 waves of the National Income Dynamics Survey, containing anthropometric and sociodemographic data. The changing patterns of the overweight and obesity prevalence were assessed across key variables. The inferential assessment was based on a standard t-test for the prevalence. Adjusted odds ratios from logistic regression analysis were used to examine the factors associated with overweight and obesity at each time point. Overweight and obesity prevalence among WCBA in SA increased from 51.3 to 60.0% and 24.7 to 35.2%, respectively, between 1998 and 2017. The urban-rural disparities in overweight and obesity decreased steadily between 1998 and 2017. The prevalence of overweight and obesity among WCBA varied by age, population group, location, current smoking status and socioeconomic status of women. For most women, the prevalence of overweight and/or obesity in 2017 was significantly higher than in 1998. Significant factors associated with being overweight and obese included increased age, self-identifying with the Black African population group, higher educational attainment, urban area residence, and wealthier socioeconomic quintiles. Smoking was inversely related to being overweight and obese. The increasing trend in overweight and obesity in WCBA in SA demands urgent public health attention. Increased public awareness is needed about obesity and its health consequences for this vulnerable population. Efforts are needed across different sectors to prevent excessive weight gain in WCBA, focusing on older women, self-identified Black African population group, women with higher educational attainment, women residing in urban areas, and wealthy women.


Synthesis of Janus Au nanorods/polydivinylbenzene hybrid nanoparticles for chemo-photothermal therapy.
Chemo-photothermal therapy has attracted tremendous attention due to its synergistic effect in killing cancer cells, making it one of the most efficient therapies. Although most of the applied core-shell hybrid nanoparticles (NPs) can perform such a function, the lowering of their thermal efficiency through polymer coating and limited drug loading capacity severely limit their performance. Janus NPs with exposed metal and a polymer/silica matrix show improved chemo- and photothermal-efficiency, but have a complicated synthesis, and their loading capacity for hydrophobic drugs still needs to be optimized. Herein, we report the facile synthesis of Janus NPs comprising Au nanorods (NRs) and a hydrophobic polydivinylbenzene (PDVB) matrix. The UV-vis extinction of the Janus NPs is in the near infrared region (the region used in medicine), which makes it an ideal candidate for photothermal therapy, and the hydrophobic PDVB component is a good anticancer drug (curcumin) carrier for chemotherapy. With this combination of chemo- and photothermal-effects, a significant decrease in cell viability, migration, and invasion was realised, making the material a promising biomedical candidate for the treatment of cancer.


Neurodevelopmental and neurobehavioral characteristics in males and females with CDKL5 duplications.
Point mutations and genomic deletions of the CDKL5 (STK9) gene on chromosome Xp22 have been reported in patients with severe neurodevelopmental abnormalities, including Rett-like disorders. To date, only larger-sized (8-21 Mb) duplications harboring CDKL5 have been described. We report seven females and four males from seven unrelated families with CDKL5 duplications 540-935 kb in size. Three families of different ethnicities had identical 667kb duplications containing only the shorter CDKL5 isoform. Four affected boys, 8-14 years of age, and three affected girls, 6-8 years of age, manifested autistic behavior, developmental delay, language impairment, and hyperactivity. Of note, two boys and one girl had macrocephaly. Two carrier mothers of the affected boys reported a history of problems with learning and mathematics while at school. None of the patients had epilepsy. Similarly to CDKL5 mutations and deletions, the X-inactivation pattern in all six studied females was random. We hypothesize that the increased dosage of CDKL5 might have affected interactions of this kinase with its substrates, leading to perturbation of synaptic plasticity and learning, and resulting in autistic behavior, developmental and speech delay, hyperactivity, and macrocephaly.


High-dose dietary zinc oxide mitigates infection with transmissible gastroenteritis virus in piglets.
Zinc (Zn) supplementation has been shown to reduce the incidence of diarrhea and to protect animals from intestinal diseases, but the mechanisms of this protective effect against virus infection in vivo have not yet been elucidated. Transmissible gastroenteritis virus (TGEV) causes diarrhea in piglets with an age-dependent decrease of severity. We used 60 weaned piglets that were divided into three groups to evaluate the effect of different Zn levels added to a conventional diet (50 mg Zn/kg diet, Znlow, control group). The other groups received the diet supplemented with ZnO at final concentrations of 150 mg Zn/kg diet (Znmed), or 2,500 mg/kg diet (Znhigh). Oral challenge infection with TGEV was performed when the pigs had been fed for 1 week with the respective diet. Half of the piglets of each group were sacrificed at day 1 and 18 after challenge infection. Fecal consistency was improved and body weights increased in the Znhigh group when compared to the other groups, but no direct effect of Zn concentrations in the diet on fecal TGEV shedding and mucosal immune responses was detectable. However, in the Znhigh group, we found a prevention of villus atrophy and decreased caspase-3-mediated apoptosis of jejunal epithelium. Furthermore, pigs receiving high Zn diet showed a down-regulation of interferon (IFN)-α, oligoadenylate synthetase (OAS), Zn transporter SLC39A4 (ZIP4), but up-regulation of metallothionein-1 (MT1), as well as the Zn transporters SLC30A1 (ZnT1) and SLC30A5 (ZnT5). In addition, forskolin-induced chloride secretion and epithelial resistance were controlled at a physiological level in the Znhigh but not the other groups. Finally, in the Znhigh group, we documented an earlier and higher systemic TGEV-specific serum antibody response. These results suggest that high dietary Zn could provide enhanced protection in the intestinal tract and stimulate the systemic humoral immune response against TGEV infection.


Dynamin controls neuropeptide secretion by organizing dense-core vesicle fusion sites.
Synaptic vesicles (SVs) release neurotransmitters at specialized active zones, but release sites and organizing principles for the other major secretory pathway, neuropeptide/neuromodulator release from dense-core vesicles (DCVs), remain elusive. We identify dynamins, yeast Vps1 orthologs, as DCV fusion site organizers in mammalian neurons. Genetic or pharmacological inactivation of all three dynamins strongly impaired DCV exocytosis, while SV exocytosis remained unaffected. Wild-type dynamin restored normal exocytosis but not guanosine triphosphatase-deficient or membrane-binding mutants that cause neurodevelopmental syndromes. During prolonged stimulation, repeated use of the same DCV fusion location was impaired in dynamin 1-3 triple knockout neurons. The syntaxin-1 staining efficiency, but not its expression level, was reduced. αSNAP (α-soluble N-ethylmaleimide-sensitive factor attachment protein) expression restored this. We conclude that mammalian dynamins organize DCV fusion sites, downstream of αSNAP, by regulating the equilibrium between fusogenic and non-fusogenic syntaxin-1 promoting its availability for SNARE (SNAP receptor) complex formation and DCV exocytosis.


Stereotactic Radiosurgery for Spetzler-Martin Grade I and II Arteriovenous Malformations: International Society of Stereotactic Radiosurgery (ISRS) Practice Guideline.
No guidelines have been published regarding stereotactic radiosurgery (SRS) in the management of Spetzler-Martin grade I and II arteriovenous malformations (AVMs). To establish SRS practice guidelines for grade I-II AVMs on the basis of a systematic literature review. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant search of Medline, Embase, and Scopus, 1986-2018, for publications reporting post-SRS outcomes in ≥10 grade I-II AVMs with a follow-up of ≥24 mo. Primary endpoints were obliteration and hemorrhage; secondary outcomes included Spetzler-Martin parameters, dosimetric variables, and "excellent" outcomes (defined as total obliteration without new post-SRS deficit). Of 447 abstracts screened, 8 were included (n = 1, level 2 evidence; n = 7, level 4 evidence), representing 1102 AVMs, of which 836 (76%) were grade II. Obliteration was achieved in 884 (80%) at a median of 37 mo; 66 hemorrhages (6%) occurred during a median follow-up of 68 mo. Total obliteration without hemorrhage was achieved in 78%. Of 836 grade II AVMs, Spetzler-Martin parameters were reported in 680: 377 were eloquent brain and 178 had deep venous drainage, totaling 555/680 (82%) high-risk SRS-treated grade II AVMs. The literature regarding SRS for grade I-II AVM is low quality, limiting interpretation. Cautiously, we observed that SRS appears to be a safe, effective treatment for grade I-II AVM and may be considered a front-line treatment, particularly for lesions in deep or eloquent locations. Preceding publications may be influenced by selection bias, with favorable AVMs undergoing resection, whereas those at increased risk of complications and nonobliteration are disproportionately referred for SRS.


A 13 C NMR study of photosynthate transport and metabolism in the lichen Xanthoria calcicola Oxner.
13 C nuclear magnetic resonance (NMR) spectroscopy was applied to the lichen Xanthoria calcicola Oxner. The in vivo spectra were poorly resolved and although the line-broadening effect of variations in the bulk magnetic susceptibility could be eliminated by spinning the sample at the magic angle, the spectra were still relatively Uninformative in comparison with the spectra of methanol extracts of the tissue. The synthesis of ribitol by the algal symbiont and its subsequent metabolism to mannitol by the fungus was followed using pulse-chase experiments. The fine structure in the spectra provided support for the role of the pentose phosphate pathway in the conversion of ribitol to mannitol. Preliminary experiments, in which the conditions of the pulse-chase experiment were altered, showed that the incorporation of 13 C into mannitol was reduced at a lower temperature, and in thalli of low moisture content, and was abolished by darkness.


Out of the blue: the evolution of horizontally polarized signals in Haptosquilla (Crustacea, Stomatopoda, Protosquillidae).
The polarization of light provides information that is used by many animals for a number of different visually guided behaviours. Several marine species, such as stomatopod crustaceans and cephalopod molluscs, communicate using visual signals that contain polarized information, content that is often part of a more complex multi-dimensional visual signal. In this work, we investigate the evolution of polarized signals in species of Haptosquilla, a widespread genus of stomatopod, as well as related protosquillids. We present evidence for a pre-existing bias towards horizontally polarized signal content and demonstrate that the properties of the polarization vision system in these animals increase the signal-to-noise ratio of the signal. Combining these results with the increase in efficacy that polarization provides over intensity and hue in a shallow marine environment, we propose a joint framework for the evolution of the polarized form of these complex signals based on both efficacy-driven (proximate) and content-driven (ultimate) selection pressures.


Participation in cardiac rehabilitation and survival after coronary artery bypass graft surgery: a community-based study.
Cardiac rehabilitation (CR) is recommended for all patients after coronary artery bypass surgery, yet little is known about the long-term mortality effects of CR in this population. We performed a community-based analysis on residents of Olmsted County, Minnesota, who underwent coronary artery bypass surgery between 1996 and 2007. We assessed the association between subsequent outpatient CR attendance and long-term survival. Propensity analysis was performed. Cox proportional hazards regression was then used to assess the association between CR attendance and all-cause mortality adjusted for the propensity to attend CR. We identified 846 eligible patients (age 66±11 years, 76% men, and 96% non-Hispanic whites) who survived at least 6 months after surgery, of whom 582 (69%) attended CR. During a mean (±SD) follow-up of 9.0±3.7 years, the 10-year all-cause Kaplan-Meier mortality rate was 28% (193 deaths). Adjusted for the propensity to attend CR, participation in CR was associated with a 10-year relative risk reduction in all-cause mortality of 46% (hazard ratio, 0.54; 95% confidence interval, 0.40-0.74; P<0.001) and a 10-year absolute risk reduction of 12.7% (number needed to treat=8). There was no evidence of a differential effect of CR on mortality with respect to age (≥65 versus <65 years), sex, diabetes, or prior myocardial infarction. CR attendance is associated with a significant reduction in 10-year all-cause mortality after coronary artery bypass surgery. Our results strongly support national standards that recommend CR for this patient group.


Exercise capacity and extent of resection as predictors of surgical risk in lung cancer.
Lung resection remains the most effective treatment for non-small cell lung cancer (NSCLC). However, there is no consensus about reliable operative risk assessment in these patients. The aim of this study was to identify predictors of postoperative complications and death after lung resection for NSCLC. In this prospective trial, 125 of 142 (88%) consecutive NSCLC patients from 1990 to August 1997 had complete data sets. All underwent functional assessment including spirometry and cardiopulmonary exercise tests and lung resection via thoracotomy. Complications occurred in 31 of 125 (25%) patients including 2 (1.6%) deaths. On logistic regression analysis, only maximal oxygen uptake (V'O2,max) x kg body weight(-1) expressed as a percentage of the predicted value (p<0.0001) and the estimated extent of lung tissue resection (p=0.02) were independent predictors of postoperative complications. Six of seven patients with a V'O2,max x kg body weight(-1) of <60% pred, but only eight of 65 with values >90% pred, exhibited postoperative complications. Maximal oxygen uptake and the estimated extent of lung tissue resection are independent predictors of postoperative complications. These simple parameters should be integrated into the preoperative decision analysis for operability in patients undergoing lung resection for lung cancer.


Formative Evaluation of Open Goals: A UK Community-Based Multi-Sport Family Programme.
Community parks provide opportunities for physical activity (PA) and facilitate social interactions. This formative evaluation assesses the implementation of 'Open Goals' (OG), a novel multi-sport programme aiming to increase family PA and community cohesion, delivered weekly by Liverpool Football Club's charitable foundation to local parks in Liverpool, North West England. Three Open Goals parks were chosen for the evaluation settings. Formative evaluation measures included: System for Observing Play and Recreation in Communities (SOPARC) observations (n = 10), direct session observations (n = 8), semi-structured interviews with Open Goals coaching staff (n = 3), and informal feedback from families (n = 5) about their experiences of Open Goals. Descriptive statistics and thematic analysis were applied to quantitative and qualitative data, respectively. Within the three evaluation parks, Open Goals reached 107 participants from May-July 2019, through 423 session attendances. Fidelity of the programme was high (M = 69% of session content delivered as intended). Overall park use when OG was offered compared to when it was not offered was not statistically significant (p = 0.051), however, target area use was significantly increased (p = 0.001). Overall physical activity levels in parks were significantly (p = 0.002) higher when Open Goals was being offered, compared to when it was not. Coaches reported that engagement in OG positively affected family co-participation and children's behavioural development. Contextual issues included environmental and social barriers to programme engagement, including the co-participation element of the programme and criticism of the marketing of OG. It is evident that community-based multi-sport PA programmes endorsed by professional football clubs are well positioned to connect with local communities in deprived areas and to encourage PA and community engagement. This study suggests that such programmes may have the ability to improve park usage in specific areas, along with improving physical activity levels among families, although further research is required. Effective marketing strategies are needed for promotional purposes. Upskilling of coaches in the encouragement of family co-participation may support regular family engagement in PA in local parks.


INECO Frontal Screening (IFS): a brief, sensitive, and specific tool to assess executive functions in dementia.
Although several brief sensitive screening tools are available to detect cognitive dysfunction, few have been developed to quickly assess executive functioning (EF) per se. We designed a new brief tool to evaluate EF in neurodegenerative diseases. Patients with an established diagnosis of behavioral variant frontotemporal dementia (bvFTD; n = 22), Alzheimer disease (AD; n = 25), and controls (n = 26) were assessed with a cognitive screening test, the INECO Frontal Screening (IFS), and EF tests. Clinical Dementia Rating Scale (CDR) scores were obtained for all patients. Internal consistency of the IFS was very good (Cronbach's alpha = .80). IFS total (out of 30 points) was 27.4 (SD = 1.6) for controls, 15.6 (SD = 4.2) for bvFTD, and 20.1 (SD = 4.7) for AD. Using a cutoff of 25 points, sensitivity of the IFS was 96.2%, and specificity 91.5% in differentiating controls from patients with dementia. The IFS correlated significantly with the CDR and executive tasks. The IFS total discriminated controls from demented patients, and bvFTD from AD. IFS is a brief, sensitive, and specific tool for the detection of executive dysfunction associated with neurodegenerative diseases. The IFS may be helpful in the differential diagnosis of FTD and AD.


Lymphocytic hypophysitis in a dog with diabetes insipidus.
An 8-year-old male German longhaired pointer was referred for diabetes insipidus responsive to treatment with desmopressin. The dog had polyuria and polydipsia, exercise intolerance and a dull hair coat. Plasma concentrations of thyroid-stimulating hormone, thyroxine, growth hormone (GH) and insulin-like growth factor-1 were decreased; plasma adrenocorticotropic hormone (ACTH) was slightly elevated and plasma α-melanocyte-stimulating hormone (MSH) was within the reference range. Computed tomography revealed a heterogeneously contrast-enhancing pituitary mass compressing the hypothalamus. Transsphenoidal hypophysectomy was performed and microscopical examination of the surgical biopsy samples revealed hypophysitis without evidence of pituitary adenoma. The hypophysitis was characterized by marked lymphocytic infiltration of the adenohypophysis that contained a mixed population of neuroendocrine cells expressing GH, ACTH or α-MSH. The lymphocytes were identified as T cells, resulting in a final diagnosis of lymphocytic hypophysitis strongly resembling human primary lymphocytic hypophysitis.