Methods for Handling Missing Variables in Risk Prediction Models.
Prediction models should be externally validated before being used in clinical practice. Many published prediction models have never been validated. Uncollected predictor variables in otherwise suitable validation cohorts are the main factor precluding external validation. We used individual patient data from 9 different cohort studies conducted in the United States, Europe, and Latin America that included 7,892 patients with chronic obstructive pulmonary disease who enrolled between 1981 and 2006. Data on 3-year mortality and the predictors of age, dyspnea, and airflow obstruction were available. We simulated missing data by omitting the predictor dyspnea cohort-wide, and we present 6 methods for handling the missing variable. We assessed model performance with regard to discriminative ability and calibration and by using 2 vignette scenarios. We showed that the use of any imputation method outperforms the omission of the cohort from the validation, which is a commonly used approach. Compared with using the full data set without the missing variable (benchmark), multiple imputation with fixed or random intercepts for cohorts was the best approach to impute the systematically missing predictor. Findings of this study may facilitate the use of cohort studies that do not include all predictors and pave the way for more widespread external validation of prediction models even if 1 or more predictors of the model are systematically missing.


Prospective memory training in older adults and its relevance for successful aging.
In research on cognitive plasticity, two training approaches have been established: (1) training of strategies to improve performance in a given task (e.g., encoding strategies to improve episodic memory performance) and (2) training of basic cognitive processes (e.g., working memory, inhibition) that underlie a range of more complex cognitive tasks (e.g., planning) to improve both the training target and the complex transfer tasks. Strategy training aims to compensate or circumvent limitations in underlying processes, while process training attempts to augment or to restore these processes. Although research on both approaches has produced some promising findings, results are still heterogeneous and the impact of most training regimes for everyday life is unknown. We, therefore, discuss recent proposals of training regimes aiming to improve prospective memory (i.e., forming and realizing delayed intentions) as this type of complex cognition is highly relevant for independent living. Furthermore, prospective memory is associated with working memory and executive functions and age-related decline is widely reported. We review initial evidence suggesting that both training regimes (i.e., strategy and/or process training) can successfully be applied to improve prospective memory. Conceptual and methodological implications of the findings for research on age-related prospective memory and for training research in general are discussed.


"It feels like I'm the dirtiest person in the world.": Exploring the experiences of healthcare providers who survived MERS-CoV in Saudi Arabia.
In summer 2015, a Saudi 1000-bed tertiary care hospital experienced a serious outbreak among patients of Middle Eastern Respiratory Syndrome (MERS); during which, some healthcare providers contracted the virus, but none died. The outbreak provoked not only fear and stress; but also professional, emotional, ethical, and social conflicts and tension among healthcare providers and patients alike. Therefore, this study aims to explore what healthcare providers, who survived coronavirus infection, have experienced as a MERS patient and how the infection affected their relationship with their colleagues. Semi-structured, face-to-face interviews were conducted individually with seven survivors (healthcare providers). Each interview lasted up to 90min, and the data were analyzed using the thematic analysis technique. Within the participants' rich and illuminating experiences, four themes were identified: caring for others in the defining moments, perceived prejudice behaviours and stigmatization, lived moments of traumatic fear and despair, and denial and underestimation of the seriousness of the disease at the individual and organizational levels. Survivors still suffered as a result of their traumatic experiences, which might negatively influence their performance. As these survivors are vulnerable, it is their organization's responsibility to provide a system that embraces HCPs during and after disastrous events.


Whirlpool-associated folliculitis caused by Pseudomonas aeruginosa: report of an outbreak and review.
An outbreak of folliculitis caused by Pseudomonas aeruginosa serotype O:7 occurred among the guests of a hotel in St. John's, Newfoundland, Canada, and the source of the infection was traced to the hotel whirlpool. Of 36 persons who used the whirlpool, 26 (72%) developed folliculitis within 1 to 5 days after exposure; the attack rate was significantly higher for children (90%) than for adults (50%). The rash characteristics were consistent with those of Pseudomonas folliculitis previously described (T. L. Gustafson, J. D. Band, R. H. Hutcheson, Jr., and W. Schaffner, Rev. Infect. Dis. 5:1-8, 1983). This is considered to be the first outbreak in which P. aeruginosa serotype O:7 has been incriminated. Published reports to date of outbreaks of Pseudomonas folliculitis associated with the use of whirlpools, hot tubs, swimming pools, etc., were reviewed.


[Results of combined and complex treatment for indolent and aggressive non-Hodgkin lymphoma of the stomach].
There were retrospectively assessed long-term outcomes of 125 patients with primary non-Hodgkin's lymphoma of the stomach (indolent--50, aggressive--75) using different programs of combined and complex treatment. The immediate results of the treatment in the group of indolent lymphomas were: complete remission 39 (78%), partial remission 7 (14%), the stabilization 3 (6%), progression 1 (2%) while in the group of aggressive lymphomas: complete remission 56 (74.7%), partial remission 8 (10.7%), without effect 3 (4%) and progression 8 (10.7%). It was revealed that primary indolent lymphomas of the stomach the efficiency of complex treatment is comparable to the efficiency of local methods of treatment (surgery, radiotherapy or its combination). The combination of chemotherapy and local methods of treatment gave better results compared with chemotherapy (a 5-year overall survival is 100% and 72% respectively). In the group of aggressive lymphomas the best rates in all types of survival were demonstrated by the subgroup of complex treatment as compared with the subgroup of local methods of treatment especially in terms of overall survival (100% and 65% respectively), and as compared with the subgroup where only chemotherapy was conducted, particularly in terms of disease-free survival (100% and 40% respectively). As an adjuvant therapy after surgical treatment it was preferable to use chemotherapy because such treatment program demonstrated the best rates of overall survival, which reached 92% on a 5-year and a 10-year milestone.


Delays in the diagnosis of six cancers: analysis of data from the National Survey of NHS Patients: Cancer.
The aim of this paper is to describe and compare components of diagnostic delay (patient, primary care, referral, secondary care) for six cancers (breast, colorectal, lung, ovarian, prostate and non-Hodgkin's lymphoma), and to compare delays in patients who saw their GP prior to diagnosis with those who did not. Secondary data analysis of The National Survey of NHS Patients: Cancer was undertaken (65 192 patients). Breast cancer patients experienced the shortest total delays (mean 55.2 days), followed by lung (88.5), ovarian (90.3), non-Hodgkin's lymphoma (102.8), colorectal (125.7) and prostate (148.5). Trends were similar for all components of delay. Compared with patient and primary care delays, referral delays and secondary care delays were much shorter. Patients who saw their GP prior to diagnosis experienced considerably longer total diagnostic delays than those who did not. There were significant differences in all components of delay between the six cancers. Reducing diagnostic delays with the intention of increasing the proportion of early stage cancers may improve cancer survival in the UK, which is poorer than most other European countries. Interventions aimed at reducing patient and primary care delays need to be developed and their effect on diagnostic stage and psychological distress evaluated.


A Retrospective Study of Ipilimumab Plus Nivolumab in Anti-PD-L1/PD-1 Refractory Merkel Cell Carcinoma.
Merkel cell carcinoma (MCC) is a very rare but highly aggressive cutaneous neuroendocrine carcinoma and is associated with chronic exposure to ultraviolet light and the Merkel cell polyoma virus. The incidence rate of MCC is increasing and MCC is associated with high rates of recurrence and mortality. Immune checkpoint inhibitors (ICIs) offer durable responses and significant clinical benefit with 2 agents-avelumab (anti-PD-L1) and pembrolizumab (anti-PD-1)-currently approved by the U.S. Food and Drug Administration for the treatment of advanced MCC. Despite the advances in systemic therapy options for MCC, ~50% of patients with advanced MCC treated with ICI progress on therapy. There is a paucity of studies assessing second-line systemic therapy following primary/acquired resistance to ICIs. Current management in this setting remains a clinical challenge especially in trial ineligible patients. We evaluated objective response to ipilimumab plus nivolumab in metastatic MCC refractory to anti-PD-(L)1 therapy. Thirty-one percent of patients experienced a grade III or grade IV immune-related adverse event (irAE) due to ipilimumab plus nivolumab. No patients (0/13) achieved a complete or partial response via RECISTv1.1/irRECIST. Twenty-three percent (3/13) of patients achieved stable disease as the best overall response but progressed shortly thereafter. The median progression-free survival was 1.3 months (90% CI 1.1-1.5) from the initiation of ipi-nivo. The median overall survival was 4.7 months (95% CI 3-17). This study suggests limited, if any, clinical benefit of ipi-nivo in patients with advanced anti-PD-L1/anti-PD-1 refractory MCC.


Antifungal susceptibility of epigallocatechin 3-O-gallate (EGCg) on clinical isolates of pathogenic yeasts.
This is the first report to investigate the antifungal susceptibility of 21 clinical isolates of seven Candida species to epigallocatechin 3-O-gallate (EGCg) and to compare with six antifungal agents, amphotericin B (AMPH), fluconazole (FLCZ), flucytosin (5FC), itraconazole (ITCZ), micafungin (MCFG), and miconazole (MCZ), using a method following the National Committee for Clinical Laboratory Standards (NCCLS) M27-A guidelines. Among the tested species, Candida glabrata exhibited the highest susceptibility to EGCg (MIC50, 0.5-1 microg/ml and MIC90, 1-2 microg/ml) compared favorably with FLCZ, although they were slightly less susceptible than to AMPH, 5FC, MCFG, ITCZ, and MCZ. Candida guilliemondii and Candida parapsilosis (MIC50, 1-4 microg/ml and MIC90, 2-16 microg/ml) were also susceptible to EGCg, although they appear to be slightly less susceptible to EGCg than C. glabrata and the other antifungal agents tested. Moreover, the susceptibility of Candida krusei strains (MIC50, 2 microg/ml and MIC90, 4-8 microg/ml) to EGCg was approximately 2- to 8-fold higher than those of 5FC and FLCZ. Our data indicate that EGCg can inhibit clinically pathogenic Candida species, although the concentrations of EGCg for antifungal susceptibility were slightly higher than those of tested antifungal agents on the whole. Based on these results, we suggest that EGCg may be effectively used as a possible agent or adjuvant for antifungal therapy in Candidiasis.


Strain differences in the impact of dietary restriction on fetal growth and pregnancy in mice.
The association between suboptimal intrauterine environment and developmental origins of adult health and disease is variable, suggesting that genotype may contribute to eventual outcome. The objective of this study was to characterize maternal and fetal responses to maternal dietary restriction during pregnancy in 2 phylogenetically distant strains of mice. Pregnant A/J (n=35) and C57BL/6J (B6) (n=36) mice underwent either a 30% dietary restriction (DR) from day 6.5 until day 17.5 of gestation or were fed ad libitum. Seven mothers from each strain and diet were randomly selected for dissection on day 18.5 to assess fetal body and organ weights and maternal endocrine status through the collection of serum to measure progesterone, corticosterone, cortisol, and estradiol levels. The remaining mice were allowed to deliver spontaneously to assess gestational effects. Both strains showed similar responses to maternal DR during pregnancy in terms of reductions in maternal weight gain during pregnancy, reductions in fetal body weight, increased pup death within 24 hours of birth, and decreased placental 11beta-HSD2 protein expression. The impact of maternal DR was greater in B6 mice than A/J when assessing reductions in fetal kidney weight, embryo-placenta ratio, increases in placental weight, fetal brain-liver ratio, and maternal corticosterone and cortisol levels. Moreover, preterm delivery was significantly increased in DR B6 mice compared to DR A/J mice. The observed strain variations in response to dietary restriction may offer a unique opportunity to investigate gene-environment interactions associated with developmental origins of adult health and disease.


Neural Networks to Predict Radiographic Brain Injury in Pediatric Patients Treated with Extracorporeal Membrane Oxygenation.
Brain injury is a significant source of morbidity and mortality for pediatric patients treated with Extracorporeal Membrane Oxygenation (ECMO). Our objective was to utilize neural networks to predict radiographic evidence of brain injury in pediatric ECMO-supported patients and identify specific variables that can be explored for future research. Data from 174 ECMO-supported patients were collected up to 24 h prior to, and for the duration of, the ECMO course. Thirty-five variables were collected, including physiological data, markers of end-organ perfusion, acid-base homeostasis, vasoactive infusions, markers of coagulation, and ECMO-machine factors. The primary outcome was the presence of radiologic evidence of moderate to severe brain injury as established by brain CT or MRI. This information was analyzed by a neural network, and results were compared to a logistic regression model as well as clinician judgement. The neural network model was able to predict brain injury with an Area Under the Curve (AUC) of 0.76, 73% sensitivity, and 80% specificity. Logistic regression had 62% sensitivity and 61% specificity. Clinician judgment had 39% sensitivity and 69% specificity. Sequential feature group masking demonstrated a relatively greater contribution of physiological data and minor contribution of coagulation factors to the model's performance. These findings lay the foundation for further areas of research directions.


Dietary patterns in infancy: the importance of maternal and family influences on feeding practice.
It is not known what constitutes an optimal diet in infancy. There are relatively few studies of weaning practice in the UK, and there is a need for prospective data on the effects of infant diet and nutrition on health in later life. We describe the dietary patterns, defined using principal components analysis of FFQ data, of 1434 infants aged 6 and 12 months, born between 1999 and 2003. The two most important dietary patterns identified at 6 and 12 months were very similar. The first pattern was characterised by high consumption of fruit, vegetables and home-prepared foods ('infant guidelines' pattern). The second pattern was characterised by high consumption of bread, savoury snacks, biscuits and chips ('adult foods' pattern). Dietary pattern scores were correlated at 6 and 12 months (r 0.46 'infant guidelines'; r 0.45 'adult foods'). These patterns, which reflect wide variations in weaning practice, are associated with maternal and family characteristics. A key influence on the infant diet is the quality of the maternal diet. Women who comply with dietary recommendations, and who have high intakes of fruit and vegetables, wholemeal bread and rice and pasta, are more likely to have infants who have comparable diets--with high 'infant guidelines' pattern scores. Conversely, women whose own diets are characterised by high intakes of chips, white bread, crisps and sweets are more likely to have infants who have high 'adult foods' pattern scores. The effects of these patterns on growth and development, and on long-term outcomes need to be investigated.


Validation of the analytical performance of the NOVEOS™ System, a system which improves upon the third-generation in vitro allergy testing technology.
Objectives Detection of allergen-specific immunoglobulin E (sIgE) is important for the diagnosis of allergy. IgE sensitization is commonly demonstrated in vivo by skin prick testing (SPT), or in vitro utilizing automated systems. Recently, HYCOR® Biomedical launched its new system for allergen sIgE testing called the NOVEOS™ Immunoanalyzer. This study aims to evaluate the analytical performance of the NOVEOS system in a bi-center study at Philipps-University Marburg (Site-1) and Charité Medical University Berlin (Site-2), respectively. Methods The analytical performance was evaluated based on the guidelines I/LA20-A3, EP5-A3, EP17-A2, EP6-A, EP7-A3, and EP9-A3 of the Clinical and Laboratory Standards Institute (CLSI). Results The conducted repeatability and within-laboratory precision tests provided acceptable performance with 3.0%-11.9% coefficient of variation across both sites. The limit of blank (LoB) and limit of detection (LoD) were <0.1 kU/L at both centers. A within-parameter linearity for all tested allergens was reported at both sites. Of note, no significant interference was observed for high levels of biotin, methylprednisolone, diphenhydramine, omalizumab, or ranitidine. Method comparison between the NOVEOS calibration and the latest World Health Organization (WHO) reference standard showed good agreement at both sites. Conclusions The results from the analytical performance of the NOVEOS allergen sIgE assay and instrument testing at both sites were comparable. Overall, a good precision and linearity as well as a detection limit <0.1 kU/L were observed, with minimal impact of common interfering substances on patient recoveries. The NOVEOS is calibrated to the latest WHO reference standard and adds benefits like a small sample size and para-magnetic microparticles that improve upon third-generation allergen sIgE assays' design and performance.


Mechanical properties of all-suture anchors for rotator cuff repair.
All-suture anchors are increasingly used in rotator cuff repair procedures. Potential benefits include decreased bone damage. However, there is limited published evidence for the relative strength of fixation for all-suture anchors compared with traditional anchors. A total of four commercially available all-suture anchors, the 'Y-Knot' (ConMed), Q-FIX (Smith & Nephew), ICONIX (Stryker) and JuggerKnot (Zimmer Biomet) and a traditional anchor control TWINFIX Ultra PK Suture Anchor (Smith & Nephew) were tested in cadaveric human humeral head rotator cuff repair models (n = 24). This construct underwent cyclic loading applied by a mechanical testing rig (Zwick/Roell). Ultimate load to failure, gap formation at 50, 100, 150 and 200 cycles, and failure mechanism were recorded. Significance was set at p < 0.05. Overall, mean maximum tensile strength values were significantly higher for the traditional anchor (181.0 N, standard error (se) 17.6) compared with the all-suture anchors (mean 133.1 N se 16.7) (p = 0.04). The JuggerKnot anchor had greatest displacement at 50, 100 and 150 cycles, and at failure, reaching statistical significance over the control at 100 and 150 cycles (22.6 mm se 2.5 versus 12.5 mm se 0.3; and 29.6 mm se 4.8 versus 17.0 mm se 0.7). Every all-suture anchor tested showed substantial (> 5 mm) displacement between 50 and 100 cycles (6.2 to 14.3).All-suture anchors predominantly failed due to anchor pull-out (95% versus 25% of traditional anchors), whereas a higher proportion of traditional anchors failed secondary to suture breakage. We demonstrate decreased failure load, increased total displacement, and variable failure mechanisms in all-suture anchors, compared with traditional anchors designed for rotator cuff repair. These findings will aid the surgeon's choice of implant, in the context of the clinical scenario.Cite this article: N. S. Nagra, N. Zargar, R. D. J. Smith, A. J. Carr. Mechanical properties of all-suture anchors for rotator cuff repair. Bone Joint Res 2017;6:82-89. DOI: 10.1302/2046-3758.62.BJR-2016-0225.R1.


[Health 2.0 for psychiatrists].
The internet used to be mainly 'one-way traffic' (1.0). Nowadays it is becoming easy for internet users to communicate with each other via the web (2.0). To describe the concept of Health 2.0 and to explore the possibilities of 2.0-technology for psychiatry. Information was sourced from the literature and the internet. results Health 2.0 makes it possible for patients and health professionals to exchange information on such a large scale that new knowledge is generated. This will alter the relationship between doctor and patient. Increasingly, the patient is able to take the initiative. The interactive and open character of the internet leads to new discussions and can eventually improve psychiatric care. Health 2.0 is an important development for psychiatrists.


Coherence analysis in the myoclonus of corticobasal degeneration.
We investigated whether myoclonus in corticobasal degeneration (CBD) is cortical or subcortical in origin. Many authors have suggested that the myoclonus in CBD is a subtype of cortical myoclonus, despite the fact that back-averaging fails to detect a cortical correlate to spontaneous or action induced jerks and giant sensory evoked potentials are seldom found. Electroencephalographic-electromyographic (EEG-EMG) and EMG-EMG frequency analysis may be more sensitive to cortical drives when EMG bursts occur at a high frequency and at low amplitudes as in CBD. We evaluated EEG-EMG and EMG-EMG coherence and phase in 5 patients with clinically probable CBD and unilateral, action-induced and stimulus-sensitive myoclonus. We found negligible corticomuscular coherence despite a dramatically exaggerated EMG-EMG coherence. We conclude that an inflated EMG-EMG coherence is found in some patients with CBD and that this is unlikely to be due to an exaggerated cortical drive.


Comprehensive expressional analyses of antisense transcripts in colon cancer tissues using artificial antisense probes.
Recent studies have identified thousands of sense-antisense gene pairs across different genomes by computational mapping of cDNA sequences. These studies have shown that approximately 25% of all transcriptional units in the human and mouse genomes are involved in cis-sense-antisense pairs. However, the number of known sense-antisense pairs remains limited because currently available cDNA sequences represent only a fraction of the total number of transcripts comprising the transcriptome of each cell type. To discover novel antisense transcripts encoded in the antisense strand of important genes, such as cancer-related genes, we conducted expression analyses of antisense transcripts using our custom microarray platform along with 2376 probes designed specifically to detect the potential antisense transcripts of 501 well-known genes suitable for cancer research. Using colon cancer tissue and normal tissue surrounding the cancer tissue obtained from 6 patients, we found that antisense transcripts without poly(A) tails are expressed from approximately 80% of these well-known genes. This observation is consistent with our previous finding that many antisense transcripts expressed in a cell are poly(A)-. We also identified 101 and 71 antisense probes displaying a high level of expression specifically in normal and cancer tissues respectively. Our microarray analysis identified novel antisense transcripts with expression profiles specific to cancer tissue, some of which might play a role in the regulatory networks underlying oncogenesis and thus are potential targets for further experimental validation. Our microarray data are available at http://www.brc.riken.go.jp/ncrna2007/viewer-Saito-01/index.html.


Controlling aggregation of cholesterol-modified DNA nanostructures.
DNA nanotechnology allows for the design of programmable DNA-built nanodevices which controllably interact with biological membranes and even mimic the function of natural membrane proteins. Hydrophobic modifications, covalently linked to the DNA, are essential for targeted interfacing of DNA nanostructures with lipid membranes. However, these hydrophobic tags typically induce undesired aggregation eliminating structural control, the primary advantage of DNA nanotechnology. Here, we study the aggregation of cholesterol-modified DNA nanostructures using a combined approach of non-denaturing polyacrylamide gel electrophoresis, dynamic light scattering, confocal microscopy and atomistic molecular dynamics simulations. We show that the aggregation of cholesterol-tagged ssDNA is sequence-dependent, while for assembled DNA constructs, the number and position of the cholesterol tags are the dominating factors. Molecular dynamics simulations of cholesterol-modified ssDNA reveal that the nucleotides wrap around the hydrophobic moiety, shielding it from the environment. Utilizing this behavior, we demonstrate experimentally that the aggregation of cholesterol-modified DNA nanostructures can be controlled by the length of ssDNA overhangs positioned adjacent to the cholesterol. Our easy-to-implement method for tuning cholesterol-mediated aggregation allows for increased control and a closer structure-function relationship of membrane-interfacing DNA constructs - a fundamental prerequisite for employing DNA nanodevices in research and biomedicine.


Twins Assessing Their Own and Parental Intelligence: Examining the Raters' Agreement and the Effect of Raters' and Targets' Gender.
The goal of this study was to explore the raters' agreement and the effect of raters' and targets' gender on self- and parental intelligence assessments in the sample of Croatian twins. Twins were asked to assess their own and their parents' overall intelligence, as well as specific abilities from the Gardner's theory of multiple intelligences. Data was analysed to explore: i) twins' agreement in parental assessments and behavioural genetic analysis of the overall intelligence estimates; ii) gender differences in self- assessments; and iii) raters' and targets' gender effects on parental assessments. The twins' mean correlation in their assessments of overall parental intelligence was .60. The differences between monozygotic and dizygotic twin correlations were nonsignificant for all of the estimated abilities, and model fitting analysis indicates that hypothesis about genetic effect on parental assessment of intelligence should be rejected. The hypotheses about males' higher self-assessments for overall intelligence and for the masculine types of abilities - logical-mathematical, body-kinesthetic and spatial abilities - were confirmed. For the feminine types of abilities - verbal/linguistic, inter- and intra- personal intelligences - there were no significant gender effects. Both target and rater effect were found for the parental estimates of intelligence. Fathers were estimated higher on overall intelligence, logical-mathematical, body-kinesthetic and spatial abilities, while mothers were estimated higher on interpersonal and intrapersonal intelligence. The effect of the raters' gender was found for overall intelligence as well as for inter- and intra- personal intelligences, where males gave higher estimates of parental intelligences than females.


Diagnostic utility of Wada Memory Asymmetries: sensitivity, specificity, and likelihood ratio characterization.
The authors used logistic regression, dichotomous and multiple level likelihood ratios, and receiver operating characteristic (ROC) analyses to examine Wada Memory Asymmetries (WMAs) in 324 patients who subsequently underwent temporal lobe (TL) surgery (left TL surgery = 172; right TL surgery = 152) using the Medical College of Georgia Wada protocol. Logistic regression correctly classified 84% of left TL patients and 77% of right TL patients using WMA. Corresponding dichotomous likelihood ratios (LRs) were: LR+ = 3.64; LR- = 0.21. The area under the curve using ROC was similarly highly significant (.886, standard error = .018, p < .001). When classifying patients using multiple level LRs, 40 left TL patients (23.3%) obtained asymmetry scores greater than +4, whereas no right TL patients obtained asymmetry scores in this range. No left TL patients obtained a WMA of -8 or less, although 12 right TL patients (7.9%) obtained a difference score of -8. Multiple level LRs indicate impressive diagnostic sensitivity for certain WMA ranges, greatly increasing the probability of undergoing either left or right TL surgery depending on WMA magnitude.


Towards Open-World Person Re-Identification by One-Shot Group-Based Verification.
Solving the problem of matching people across non-overlapping multi-camera views, known as person re-identification (re-id), has received increasing interests in computer vision. In a real-world application scenario, a watch-list (gallery set) of a handful of known target people are provided with very few (in many cases only a single) image(s) (shots) per target. Existing re-id methods are largely unsuitable to address this open-world re-id challenge because they are designed for (1) a closed-world scenario where the gallery and probe sets are assumed to contain exactly the same people, (2) person-wise identification whereby the model attempts to verify exhaustively against each individual in the gallery set, and (3) learning a matching model using multi-shots. In this paper, a novel transfer local relative distance comparison (t-LRDC) model is formulated to address the open-world person re-identification problem by one-shot group-based verification. The model is designed to mine and transfer useful information from a labelled open-world non-target dataset. Extensive experiments demonstrate that the proposed approach outperforms both non-transfer learning and existing transfer learning based re-id methods.


Cardiovascular risk factors in the Bedouin population: management and compliance.
Until three decades ago coronary heart disease and stroke were considered rare in the Israeli Bedouin population. Today, this population shows increasing high prevalence compared to the Jewish population. To evaluate the prevalence of diagnosed cardiovascular risk factors among Bedouins (hypertension, diabetes mellitus, dyslipidemia), and to assess compliance with follow-up tests and drug treatment. The study included all listed patients aged 20 years and older in eight clinics in major Bedouin towns, and in two large teaching clinics in Beer Sheva (Jewish population). Risk factor data were extracted from the clinics' computerized databases. For those diagnosed with hypertension, diabetes or dyslipidemia, drug purchasing data were collected from the pharmacy database to determine compliance with treatment, and from the central laboratory mainframe (HbAlc and low density lipoprotein-cholesterol) to evaluate follow-up and control. A significantly higher prevalence of diabetes in all age groups was found in the Bedouin population compared to the Jewish population; age-adjusted results show a prevalence of 12% vs. 8% respectively (P < 0.001). The prevalence of dyslipidemia and age-adjusted hypertension was lower among Bedouins (5.8% vs. 18.2%, P < 0.01 and 17% vs. 21%, P < 0.001 respectively). Two-thirds of hypertensive Bedouin patients and 72.9% of diabetic Bedouin patients were not compliant with treatment. For dyslipidemia only 10.4% of the Bedouins were compliant compared with 28.2% in the Jewish population (P < 0.001). Compliance with drug therapy and follow-up tests was found to be a major problem in the Bedouin population.


Sorting sortases: a nomenclature proposal for the various sortases of Gram-positive bacteria.
Bacterial surface proteins constitute a diverse group of molecules with important functions, such as adherence, invasion, signaling and interaction with the host immune system or the environment. In Gram-positive bacteria, many surface proteins are anchored to the cell wall envelope by an enzyme named sortase, which recognizes a conserved carboxylic sorting motif. The sequence of the prototype staphylococcal SrtA has been widely used to identify homologs in bacterial genomes, revealing a profusion of sortases in almost all Gram-positive bacteria, often with more than one sortase-like protein per genome [M.J. Pallen, A.C. Lam, M. Antonio, K. Dunbar, Trends Microbiol. 9 (2001) 97-102]. In light of increasing reports on the identification and/or characterization of paralogous sortase genes, a classification of sortases now appears necessary. This report provides an analysis of sixty-one sortases from complete Gram-positive genomes, and suggests the existence of four structural groups of sortases. We propose the classification of sortases into 4 classes designated A, B, C and D. This classification should help to discriminate between sortases in the future.


Comparative analysis of weighted gene co-expression networks in human and mouse.
The application of complex network modeling to analyze large co-expression data sets has gained traction during the last decade. In particular, the use of the weighted gene co-expression network analysis framework has allowed an unbiased and systems-level investigation of genotype-phenotype relationships in a wide range of systems. Since mouse is an important model organism for biomedical research on human disease, it is of great interest to identify similarities and differences in the functional roles of human and mouse orthologous genes. Here, we develop a novel network comparison approach which we demonstrate by comparing two gene-expression data sets from a large number of human and mouse tissues. The method uses weighted topological overlap alongside the recently developed network-decomposition method of s-core analysis, which is suitable for making gene-centrality rankings for weighted networks. The aim is to identify globally central genes separately in the human and mouse networks. By comparing the ranked gene lists, we identify genes that display conserved or diverged centrality-characteristics across the networks. This framework only assumes a single threshold value that is chosen from a statistical analysis, and it may be applied to arbitrary network structures and edge-weight distributions, also outside the context of biology. When conducting the comparative network analysis, both within and across the two species, we find a clear pattern of enrichment of transcription factors, for the homeobox domain in particular, among the globally central genes. We also perform gene-ontology term enrichment analysis and look at disease-related genes for the separate networks as well as the network comparisons. We find that gene ontology terms related to regulation and development are generally enriched across the networks. In particular, the genes FOXE3, RHO, RUNX2, ALX3 and RARA, which are disease genes in either human or mouse, are on the top-10 list of globally central genes in the human and mouse networks.


St. John's wort - an overview.
This article aims to summarize the current state of knowledge on St. John's wort (Hypericum perforatum L.) which is one of the oldest and best investigated medicinal herbs. Dried alcoholic extracts are the most important preparations on the market although a variety of other preparations are available. Depressive disorders according to modern diagnostic standards are the best known and most widely investigated indication although the more traditional, broader indication of 'psycho-vegetative disorders, depressive disorders, anxiety and/or nervous agitation', including diagnoses such as somatoform disorders, might more adequately describe what Hypericum extracts are actually used for by many practitioners. The exact mechanisms of action are still unclear, but the available research clearly shows that various bioactive constituents contribute to the clinical effects reported, often in a synergistic manner. Hypericum extracts have consistently shown activity in pharmacological models related to antidepressant effects. Randomized clinical trials show that Hypericum extracts are more effective than placebo and similarly effective as standard antidepressants while having better tolerability in the acute treatment of major depressive episodes. The most important risk associated with Hypericum extracts are interactions with other drugs. Therefore, physicians need to be informed whether their patients take St. John's wort products. If the risk of interactions is adequately taken into account, high quality Hypericum extracts are an effective and safe tool in the hand of qualified health profession-als in primary care.


Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer.
Activation in transformed cells of normal stem cells' self-renewal pathways might contribute to the survival life cycle of cancer stem cells and promote tumor progression. The BMI-1 oncogene-driven gene expression pathway is essential for the self-renewal of hematopoietic and neural stem cells. We applied a mouse/human comparative translational genomics approach to identify an 11-gene signature that consistently displays a stem cell-resembling expression profile in distant metastatic lesions as revealed by the analysis of metastases and primary tumors from a transgenic mouse model of prostate cancer and cancer patients. To further validate these results, we examined the prognostic power of the 11-gene signature in several independent therapy-outcome sets of clinical samples obtained from 1,153 cancer patients diagnosed with 11 different types of cancer, including 5 epithelial malignancies (prostate, breast, lung, ovarian, and bladder cancers) and 5 nonepithelial malignancies (lymphoma, mesothelioma, medulloblastoma, glioma, and acute myeloid leukemia). Kaplan-Meier analysis demonstrated that a stem cell-like expression profile of the 11-gene signature in primary tumors is a consistent powerful predictor of a short interval to disease recurrence, distant metastasis, and death after therapy in cancer patients diagnosed with 11 distinct types of cancer. These data suggest the presence of a conserved BMI-1-driven pathway, which is similarly engaged in both normal stem cells and a highly malignant subset of human cancers diagnosed in a wide range of organs and uniformly exhibiting a marked propensity toward metastatic dissemination as well as a high probability of unfavorable therapy outcome.


The network of sheep movements within Great Britain: Network properties and their implications for infectious disease spread.
During the 2001 foot and mouth disease epidemic in the UK, initial dissemination of the disease to widespread geographical regions was attributed to livestock movement, especially of sheep. In response, recording schemes to provide accurate data describing the movement of large livestock in Great Britain (GB) were introduced. Using these data, we reconstruct directed contact networks within the sheep industry and identify key epidemiological properties of these networks. There is clear seasonality in sheep movements, with a peak of intense activity in August and September and an associated high risk of a large epidemic. The high correlation between the in and out degree of nodes favours disease transmission. However, the contact networks were largely dissasortative: highly connected nodes mostly connect to nodes with few contacts, effectively slowing the spread of disease. This is a result of bipartite-like network properties, with most links occurring between highly active markets and less active farms. When comparing sheep movement networks (SMNs) to randomly generated networks with the same number of nodes and node degrees, despite structural differences (such as disassortativity and higher frequency of even path lengths in the SMNs), the characteristic path lengths within the SMNs are close to values computed from the corresponding random networks, showing that SMNs have 'small-world'-like properties. Using the network properties, we show that targeted biosecurity or surveillance at highly connected nodes would be highly effective in preventing a large and widespread epidemic.


Variation among extracted lines of Drosophila melanogaster in triacylglycerol and carbohydrate storage.
Whole larvae and whole adult extracts from 26 second chromosome replacement lines of Drosophila melanogaster were analyzed to determine the amounts of stored triacylglycerols and carbohydrates as well as the activities of 13 enzymes in relevant biochemical pathways. Analysis of covariance revealed significant differences among lines in stored lipids and carbohydrates, as well as in activities of most of the enzymes. Significant broad-sense genetic correlations (among adjusted line means) were detected for a number of enzyme pairs. Multiple regression techniques were applied to assess the extent to which the amounts of stored triacylglycerols and carbohydrates could be predicted from the enzyme activities. Significant regressions were found in both adults and larvae, suggesting that modulation of enzyme activities is reflected in different sizes of storage pools. The population genetic consequences of natural selection acting on a phenotype such as energy storage is considered in light of models of metabolic flux in biochemical pathways.


Waste Reduction Behaviors at Home, at Work, and on Holiday: What Influences Behavioral Consistency Across Contexts?
Demand for materials is increasing, along with the environmental damage associated with material extraction, processing transport and waste management. While many people state they recycle at home, adoption of sustainable waste practices in the workplace and other contexts (particularly, on holiday) is often lower. Understanding how to promote more sustainable behaviors (including, but also going beyond, recycling) across a range of contexts remains a key challenge for policy-makers and researchers. The Theory of Planned Behavior (TPB) has been applied to a range of environmentally-friendly behaviors but the relative importance of the model's predictors has not yet been explored across a range of contexts. Here, we test the TPB across workplace (laboratory and office), home and holiday contexts, and examine whether consistency across contexts is a function of pro-environmental identity. Following ten semi-structured interviews, we undertook an online survey with laboratory workers (primarily in the UK; N = 213) to examine the predictors of recycling and waste reduction habits across these contexts. Interview findings indicate a range of motivations and barriers to recycling in the workplace, and inconsistency across home and work behaviors. Expanding the focus to include holiday as well as workplace and home contexts, our survey analysis shows that the proportion of waste recycled in the home is higher (67%) than in the workplace (39%) and on holiday (38%). Further, the TPB explained around twice as much variance in home recycling compared to work or holiday recycling; but overall did not provide a good explanation for recycling. The study highlights the importance of both contextual (e.g., facilities) and individual (e.g., identity) factors in shaping waste behaviors. We find significant correlations amongst different waste reduction behaviors within and between contexts, though within-context (e.g., home) behaviors are generally more strongly related. Future research should move beyond the TPB to expand the range of contextual (e.g., organizational) factors explored in contexts beyond the home, including workplace and holiday contexts. Given the different drivers-of and barriers-to waste reduction within and between contexts, a range of interventions will be required to promote recycling, reduction and reuse behaviors across these contexts.


Design and development of an affordable haptic robot with force-feedback and compliant actuation to improve therapy for patients with severe hemiparesis.
The study describes the design and development of a single degree-of-freedom haptic robot, Haptic Theradrive, for post-stroke arm rehabilitation for in-home and clinical use. The robot overcomes many of the weaknesses of its predecessor, the TheraDrive system, that used a Logitech steering wheel as the haptic interface for rehabilitation. Although the original TheraDrive system showed success in a pilot study, its wheel was not able to withstand the rigors of use. A new haptic robot was developed that functions as a drop-in replacement for the Logitech wheel. The new robot can apply larger forces in interacting with the patient, thereby extending the functionality of the system to accommodate low-functioning patients. A new software suite offers appreciably more options for tailored and tuned rehabilitation therapies. In addition to describing the design of the hardware and software, the paper presents the results of simulation and experimental case studies examining the system's performance and usability.


The evaluation of land consolidation policy in improving agricultural productivity in China.
China is presently undergoing rapid economic development and unprecedented urbanization. Concerns over food security have prompted the Chinese government to implement large-scale land consolidation projects. However, no formal evaluation has been conducted on such projects. Thus, effectiveness of land consolidation policy remains uncertain. We obtained detailed geo-spatial information for 5328 land consolidation projects implemented between 2006 and 2010, and used time-series MODIS NDVI (2006-2016) data to assess effectiveness of China's land consolidation policy in improving agricultural productivity. Our results show that the overall effectiveness of land consolidation in improving agricultural productivity is low, which lies in contrast to optimistic estimates based on regional statistical analysis and theoretical approaches. For projects (n = 560) implemented in 2006, about 29.5% showed significant (p < 0.05) increasing trends of MODIS NDVI after implementation of land consolidation. For 2007-2010, lower percentages (e.g., 25.9% in 2007 and 13.5% in 2010) of projects showed significant increasing trends. Furthermore, we found effectiveness of land consolidation projects displayed clear regional differences and driving factors are inconsistent with policy design. We anticipate our research to be a starting point for a more comprehensive evaluation involving longer time-series and higher spatial resolution data.


The mitochondrial 2-oxoadipate and 2-oxoglutarate dehydrogenase complexes share their E2 and E3 components for their function and both generate reactive oxygen species.
Herein are reported unique properties of the novel human thiamin diphosphate (ThDP)-dependent enzyme 2-oxoadipate dehydrogenase (hE1a), known as dehydrogenase E1 and transketolase domain-containing protein 1 that is encoded by the DHTKD1 gene. It is involved in the oxidative decarboxylation of 2-oxoadipate (OA) to glutaryl-CoA on the final degradative pathway of L-lysine and is critical for mitochondrial metabolism. Functionally active recombinant hE1a has been produced according to both kinetic and spectroscopic criteria in our toolbox leading to the following conclusions: (i) The hE1a has recruited the dihydrolipoyl succinyltransferase (hE2o) and the dihydrolipoyl dehydrogenase (hE3) components of the tricarboxylic acid cycle 2-oxoglutarate dehydrogenase complex (OGDHc) for its activity. (ii) 2-Oxoglutarate (OG) and 2-oxoadipate (OA) could be oxidized by hE1a, however, hE1a displays an approximately 49-fold preference in catalytic efficiency for OA over OG, indicating that hE1a is specific to the 2-oxoadipate dehydrogenase complex. (iii) The hE1a forms the ThDP-enamine radical from OA according to electron paramagnetic resonance detection in the oxidative half reaction, and could produce superoxide and H2O2 from decarboxylation of OA in the forward physiological direction, as also seen with the 2-oxoglutarate dehydrogenase hE1o component. (iv) Once assembled to complex with the same hE2o and hE3 components, the hE1o and hE1a display strikingly different regulation: both succinyl-CoA and glutaryl-CoA significantly reduced the hE1o activity, but not the activity of hE1a.


Interaction of Rac with p67phox and regulation of phagocytic NADPH oxidase activity.
Rho and Rac, two members of the Ras superfamily of guanosine triphosphate (GTP)-binding proteins, regulate a variety of signal transduction pathways in eukaryotic cells. Upon stimulation of phagocytic cells, Rac enhances the activity of the enzyme nicotinamide adenine dinucleotide phosphate (reduced) (NADPH) oxidase, resulting in the production of superoxide radicals. Activation of the NADPH oxidase requires the assembly of a multimolecular complex at the plasma membrane consisting of two integral membrane proteins, gp91phox and p21phox, and two cytosolic proteins, p67phox and p47phox. Rac1 interacted directly with p67phox in a GTP-dependent manner. Modified forms of Rac with mutations in the effector site did not stimulate oxidase activity or bind to p67phox. Thus, p67phox appears to be the Rac effector protein in the NADPH oxidase complex.


Delimiting species using single-locus data and the Generalized Mixed Yule Coalescent approach: a revised method and evaluation on simulated data sets.
DNA barcoding-type studies assemble single-locus data from large samples of individuals and species, and have provided new kinds of data for evolutionary surveys of diversity. An important goal of many such studies is to delimit evolutionarily significant species units, especially in biodiversity surveys from environmental DNA samples. The Generalized Mixed Yule Coalescent (GMYC) method is a likelihood method for delimiting species by fitting within- and between-species branching models to reconstructed gene trees. Although the method has been widely used, it has not previously been described in detail or evaluated fully against simulations of alternative scenarios of true patterns of population variation and divergence between species. Here, we present important reformulations to the GMYC method as originally specified, and demonstrate its robustness to a range of departures from its simplifying assumptions. The main factor affecting the accuracy of delimitation is the mean population size of species relative to divergence times between them. Other departures from the model assumptions, such as varying population sizes among species, alternative scenarios for speciation and extinction, and population growth or subdivision within species, have relatively smaller effects. Our simulations demonstrate that support measures derived from the likelihood function provide a robust indication of when the model performs well and when it leads to inaccurate delimitations. Finally, the so-called single-threshold version of the method outperforms the multiple-threshold version of the method on simulated data: we argue that this might represent a fundamental limit due to the nature of evidence used to delimit species in this approach. Together with other studies comparing its performance relative to other methods, our findings support the robustness of GMYC as a tool for delimiting species when only single-locus information is available.


Anaerobic respiration pathways and response to increased substrate availability of Arctic wetland soils.
The availability of labile carbon (C) compounds in Arctic wetland soils is expected to increase due to thawing permafrost and increased fermentation as a result of decomposition of organic matter with warming. How microbial communities respond to this change will affect the balance of CO2 and CH4 emitted during anaerobic organic matter decomposition, and ultimately the net radiative forcing of greenhouse gas emissions from these soils. While soil water content limits aerobic respiration, the factors controlling methanogenesis and anaerobic respiration are poorly defined in suboxic Arctic soils. We conducted incubation experiments on two tundra soils from field sites on the Seward Peninsula, Alaska, with contrasting pH and geochemistry to determine the pathways of anaerobic microbial respiration and changes with increasing substrate availability upon warming. In incubation of soils from the circumneutral Teller site, the ratio of CO2 to CH4 dropped from 10 to <2 after 60 days, indicating rapid depletion of alternative terminal electron acceptors (TEAs). Addition of acetate stimulated production of CO2 and CH4 in a nearly 1 : 1 ratio, consistent with methanogenesis, and the composition of the microbial community shifted to favor clades capable of utilizing the added acetate such as the Fe(iii)-reducing Geobacter and the methanogenic archaea Methanosarcina. In contrast, both CO2 and CH4 production declined with acetate addition during incubation of soils from the more acidic Council site, and fermentative microorganisms increased in abundance despite the high availability of fermentation products. These results demonstrate that the degree to which increasing substrate availability stimulates greenhouse gas production in tundra wetlands will vary widely depending on soil pH and geochemistry.


Medium-range order in sodium phosphate glasses: a quantitative rotational echo double resonance solid state NMR study.
Sodium ultraphosphate glasses (Na(2)O)(x)(P(2)O(5))(1-x) show a strongly non-linear dependence of the glass transition temperatures T(g)(x) on composition. To explore the structural origins of this behaviour, local and medium range ordering processes have been investigated by state-of-the-art (23)Na high-resolution and dipolar NMR spectroscopies. In particular, (31)P(23)Na) and (23)Na((31)P) rotational echo double resonance (REDOR) experiments have been analyzed to yield quantitative constraints for the structural description of these glasses. The sodium ions are found to be randomly distributed and, for x < 0.25, spatially correlated with a single metaphosphate-type Q((2)) unit at a distance of 330 pm. In this region, unusual compositional trends observed for the (23)Na chemical shifts and nuclear electric quadrupolar coupling constants, measured by triple-quantum magic-angle spinning (TQMAS) NMR, suggest a systematic decrease of Na coordination number with x. At higher sodium contents (x > 0.25), the magnitude of the (31)P((23)Na) dipolar interaction increases markedly, indicating a significantly increased extent of Q((2))-Na-Q((2)) crosslinking. Based on these results, a comprehensive description of medium-range order in sodium ultraphosphate glasses is developed, suggesting that the T(g)(x) dependence is closely linked to changes in the relative phosphorus/sodium distance distributions.


Phase Locking the Spin Precession in a Storage Ring.
This Letter reports the successful use of feedback from a spin polarization measurement to the revolution frequency of a 0.97 GeV/c bunched and polarized deuteron beam in the Cooler Synchrotron (COSY) storage ring in order to control both the precession rate (≈121 kHz) and the phase of the horizontal polarization component. Real time synchronization with a radio frequency (rf) solenoid made possible the rotation of the polarization out of the horizontal plane, yielding a demonstration of the feedback method to manipulate the polarization. In particular, the rotation rate shows a sinusoidal function of the horizontal polarization phase (relative to the rf solenoid), which was controlled to within a 1 standard deviation range of σ=0.21 rad. The minimum possible adjustment was 3.7 mHz out of a revolution frequency of 753 kHz, which changes the precession rate by 26 mrad/s. Such a capability meets a requirement for the use of storage rings to look for an intrinsic electric dipole moment of charged particles.


Knowledge Graphs in Practice: Characterizing their Users, Challenges, and Visualization Opportunities.
This study presents insights from interviews with nineteen Knowledge Graph (KG) practitioners who work in both enterprise and academic settings on a wide variety of use cases. Through this study, we identify critical challenges experienced by KG practitioners when creating, exploring, and analyzing KGs that could be alleviated through visualization design. Our findings reveal three major personas among KG practitioners - KG Builders, Analysts, and Consumers - each of whom have their own distinct expertise and needs. We discover that KG Builders would benefit from schema enforcers, while KG Analysts need customizable query builders that provide interim query results. For KG Consumers, we identify a lack of efficacy for node-link diagrams, and the need for tailored domain-specific visualizations to promote KG adoption and comprehension. Lastly, we find that implementing KGs effectively in practice requires both technical and social solutions that are not addressed with current tools, technologies, and collaborative workflows. From the analysis of our interviews, we distill several visualization research directions to improve KG usability, including knowledge cards that balance digestibility and discoverability, timeline views to track temporal changes, interfaces that support organic discovery, and semantic explanations for AI and machine learning predictions.


Varicella-zoster virus (VZV) transcription during latency in human ganglia: construction of a cDNA library from latently infected human trigeminal ganglia and detection of a VZV transcript.
The entire varicella-zoster virus (VZV) genome appears to be present in latently infected human ganglia, but the extent of virus DNA transcription is unknown. Conventional methods to study virus gene transcripts by Northern (RNA) blotting are not feasible, since ganglia are small and VZV DNA is not abundant. To circumvent this problem, we prepared radiolabeled cDNA from ganglionic RNA, hybridized it to Southern blots containing VZV DNA, and demonstrated the presence of a transcript within the SalI C fragment of the virus genome (R. Cohrs, R. Mahalingam, A. N. Dueland, W. Wolf, M. Wellish, and D. H. Gilden, J. Infect. Dis. 166:S24-S29, 1992). To further map VZV transcripts, in the work described here we constructed a cDNA library from poly(A)+ RNA obtained from latently infected human ganglia. Phage DNA isolated from the library was used in PCR amplifications to detect VZV-specific inserts. The specificity of the PCRs was provided by selection of a primer specific for VZV gene 17, 18, 19, 20, or 21 and a second vector-specific primer. VZV gene 21-specific sequences were identified by PCR amplification. The PCR product contained the XhoI cloning site and poly(A)+ sequences between vector and VZV gene 21 sequences. The sequence motif at the 3' end of VZV gene 21, determined by cloning and sequencing of the PCR product, consisted of 49 to 51 nucleotide bases of 3'-untranslated DNA, the termination codon for the VZV gene 21 open reading frame, and DNA sequences reading into the VZV gene 21 open reading frame.


Contribution of whole-body 18FDG PET imaging in the management of cervical cancer.
The objective of this study was to assess the contribution of [(18)F]fluoro-2-deoxy-D-glucose positron emission tomography ((18)FDG PET) imaging in the management of cervical cancer. Fully corrected whole-body PET was performed in 60 patients (pts) with proven cervical cancer. In pretreatment staging, 22 pts underwent PET in addition to routine protocol including International Federation of Obstetrics and Gynecology (FIGO) staging and pelvic magnetic resonance imaging (MRI). Eighteen of them had pelvic lymphadenectomy. After treatment, PET was performed in 38 pts routinely followed up by clinical and radiological examinations. Results of PET and routine protocols were compared to final diagnoses, including histological findings in 31 pts and clinical outcomes in the other cases. Median follow-up time was 12 +/- 7.3 months. In all but 2 patients (FIGO stage IA), both PET and MRI detected the primary tumor. In 6 pts, MRI alone noted loco-regional tumor spread but PET localized 9 unsuspected extrapelvic nodal sites (6 para-aortic, 2 mediastinal, and 1 supra-clavicular). However, PET missed 8 microscopic pelvic nodal metastases. In 18% of the patients, PET staging significantly influenced the treatment choices. In follow-up, PET accurately diagnosed a recurrent disease in 13 pts with falsely negative or equivocal conventional imaging (CI). Ten patients with a negative PET were still in complete remission after a minimal follow-up time of 12 months. Overall, the agreement of PET with final diagnosis was significantly better than that of routine protocol (P < 0.05). Whole-body (18)FDG PET appears useful in the management of cervical cancer, in particular for staging extrapelvic metastases or optimally detecting a recurrence. MRI is better indicated for evaluating the loco-regional status of the disease.


Home nebulizers in childhood asthma. Parental perceptions and practices.
Seventy five percent of 91 parents of asthmatic children (aged 6 months to 15.4 years) with home nebulizers, responded to a questionnaire that sought to document parental experience with this form of therapy. The most common indications for acquiring a nebulizer were inability to use metered dose inhalers and poor response or intolerance to oral medications. When the children were classified into those who used the nebulizer daily (27/69) and those who used it less than daily (42/69), we found that the daily users were more likely to be in the severest category of asthma, by parental assessment, prior to the home nebulization program (p = 0.0035). Retrospective, uncontrolled comparison before and after the acquisition of a home nebulizer showed significant decreases both in hospital admissions (1.7 vs 0.7; p less than 0.001) and total in-patient days (4.1 vs 1.7; p less than 0.0001). Home nebulizers are well tolerated by parents and children alike and may be associated with decreased morbidity.


Adult age differences in the functional neuroanatomy of verbal recognition memory.
Adult age differences are frequently observed in the performance of memory tasks, but the changes in neural function mediating these differences are largely unknown. We used (H2)15O positron emission tomography (PET) to measure changes in regional cerebral blood flow (rCBF) during Encoding, Baseline, and Retrieval conditions of a recognition memory task. Twelve young adults (20-29 years) and 12 older adults (62-79 years) participated. During each task condition, participants made a two-choice manual response to each of 64 words. Analyses of the performance data yielded evidence of age-related slowing of encoding and retrieval processes, and an age-related decline in the accuracy of yes/no recognition (d'). The rCBF activation associated with both encoding and retrieval was greater for older adults than for young adults, but this pattern was more clearly evident for memory retrieval. For young adults, rCBF activation during retrieval occurred primarily in right prefrontal cortex, whereas older adults exhibited a more bilateral pattern of prefrontal activation. Regression analyses predicting reaction time in the memory task from regional PET counts confirmed that the neural system mediating memory retrieval is more widely distributed for older adults than for young adults. Both age groups exhibited some decrease in rCBF activation in the second half of the test session, relative to the first half. The practice-related decrease in rCBF activation was more prominent for young adults, suggesting that the older adults' recruitment of additional neural systems reflects a more continual allocation of attention to support task performance.


Advances in Zika Virus⁻Host Cell Interaction: Current Knowledge and Future Perspectives.
Emerging mosquito-transmitted RNA viruses, such as Zika virus (ZIKV) and Chikungunya represent human pathogens of an immense global health problem. In particular, ZIKV has emerged explosively since 2007 to cause a series of epidemics in the South Pacific and most recently in the Americas. Although typical ZIKV infections are asymptomatic, ZIKV infection during pregnancy is increasingly associated with microcephaly and other fetal developmental abnormalities. In the last few years, genomic and molecular investigations have established a remarkable progress on the pathogenic mechanisms of ZIKV infection using in vitro and in vivo models. Here, we highlight recent advances in ZIKV-host cell interaction studies, including cellular targets of ZIKV, ZIKV-mediated cell death mechanisms, host cell restriction factors that limit ZIKV replication, and immune evasion mechanisms utilized by ZIKV. Understanding of the mechanisms of ZIKV⁻host interaction at the cellular level will contribute crucial insights into the development of ZIKV therapeutics and vaccines.


Important changes in the timing of influenza epidemics in the WHO European Region over the past 20 years: virological surveillance 1996 to 2016.
IntroductionThe global epidemiology of many infectious diseases is changing, but little attention has been paid to whether the timing of seasonal influenza epidemics changed in recent years. This study investigated whether the timing of the peak of influenza epidemics has changed in countries of the World Health Organization (WHO) European Region between 1996 and 2016. Methods: Surveillance data were obtained from the WHO FluNet database. For each country and season (July to June of the next year), the peak was defined as the week with the highest 3-week moving average for reported cases. Linear regression models were used to test for temporal trends in the timing of the epidemic peak in each country and to determine whether this differed geographically. Results: More than 600,000 influenza cases were included from 38 countries of the WHO European Region. The timing of the epidemic peak changed according to a longitudinal gradient, occurring progressively later in Western Europe (e.g. by 2.8 days/season in Spain) and progressively earlier in Eastern Europe (e.g. by 3.5 days/season in the Russian Federation). Discussion: These results were confirmed in several sensitivity analyses. Our findings have implications for influenza control and prevention measures in the WHO European Region, for instance for the implementation of influenza vaccination campaigns.


American Indians with substance use disorders: treatment needs and comorbid conditions.
American Indians and Alaska Natives (AI/ANs) experience significant disparities in health status and access to care. Furthermore, only limited data are available on substance use, mental health disorders, and treatment needs for this population. Addressing such disparities and developing culturally relevant, effective interventions for AI/AN communities require participatory research. The Western States Node of the National Institute on Drug Abuse Clinical Trials Network partnered with two American Indian substance abuse treatment programs: an urban health center and a reservation-based program to assess client characteristics, drug use patterns, and treatment needs. Data collected by staff members at the respective programs from urban (n = 74) and reservation (n = 121) clients were compared. Additional sub-analysis examined patients reporting regular opioid use and mood disorders. Findings indicate that urban clients were more likely to report employment problems, polysubstance use, and a history of abuse. Reservation-based clients reported having more severe medical problems and a greater prevalence of psychiatric problems. Clients who were regular opioid users were more likely to report having a chronic medical condition, suicidal thoughts, suicide attempts, polysubstance abuse, and IV drug use. Clients who reported a history of depression had twice as many lifetime hospitalizations and more than five times as many days with medical problems. Findings from this project provide information about the patterns of substance abuse and the importance of comprehensive assessments of trauma and comorbid conditions. Results point to the need for integrative coordinated care and auxiliary services for AI/AN clients seeking treatment for substance use disorders.


Biochemical and hematological changes among anemic and non-anemic pregnant women attending antenatal clinic at the Bolgatanga regional hospital, Ghana.
Anemia in pregnancy may not only be associated with maternal morbidity and mortality but can also be detrimental to the fetus. A definitive diagnosis of anemia is a pre-requisite to unravelling possible cause(s), to allow appropriate treatment intervention. It is hypothesised that measured hemoglobin (HGB), complemented by biochemical and other hematological parameters would enhance anemia diagnosis. This was a cross-sectional study among 400 pregnant women comprising 253 anemic and 147 non-anemic pregnant women, attending an antenatal clinic at Bolgatanga Regional Hospital, Ghana. Venous blood was collected and hemoglobin genotype, complete blood count and biochemical parameters [ferritin, iron, total iron binding capacity (TIBC), transferrin saturation (TfS), C-reactive protein (CRP) and bilirubin] were determined. Thick blood films were prepared for malaria parasitemia, while early morning stool and midstream urine samples were examined for enteric and urogenital parasites, respectively. There were significantly reduced levels of HGB (p < 0.0001), HCT (p < 0.0001), MCV (p < 0.0001), iron (0.0273), ferritin (p = 0.018) and transferrin saturation (0.0391) and increased WBC (p = 0.006), RDW (p = 0.0480), TIBC (p = 0.0438) and positivity of CRP in anemic, compared to non-anemic pregnant women. Anemic women were associated with increased proportion of hemoglobinopathies (AS, SS and SC), Plasmodium falciparum, Schistosoma hematobium and intestinal parasite infections. Anemic pregnant women are associated with a significant derangement in hematological and iron indices that implicate iron deficiency. This was influenced by hemoglobinopathies and parasitic infections.


A novel experimental apparatus to study the impact of white noise and 1/f noise on animal populations.
This paper reports on the design and construction of a novel apparatus that allows a set of aquatic microcosms to experience complex temporal environmental fluctuations. Replicate microcosms were maintained in 18 water baths with independent environmental controls. We give results from a preliminary experiment designed to look at the effects of varying temperatures with different variance spectra (i.e. white noise or 1/f noise) on single species population dynamics. Matching time series (with identical elements, differently ordered) of environmental temperatures with different Fourier spectra were created for use as input to the apparatus using a novel spectral mimicry method. The apparatus functioned well during the course of the experiment making this an extremely useful research tool. This apparatus now provides ecologists with a means of studying how environmental variability and directional trends in this variability, are filtered and translated by real populations and micro-ecosystems.


Yoga for schizophrenia: a systematic review and meta-analysis.
The aim of this review was to systematically review and meta-analyze the effects of yoga on symptoms of schizophrenia, quality of life, function, and hospitalization in patients with schizophrenia. MEDLINE/Pubmed, Scopus, the Cochrane Library, PsycInfo, and IndMED were screened through August 2012. Randomized controlled trials (RCTs) comparing yoga to usual care or non-pharmacological interventions were analyzed when they assessed symptoms or quality of life in patients with schizophrenia. Cognitive function, social function, hospitalization, and safety were defined as secondary outcomes. Risk of bias was assessed using the risk of bias tool recommended by the Cochrane Back Review Group. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated. Five RCTs with a total of 337 patients were included; 2 RCTs had low risk of bias. Two RCTs compared yoga to usual care; 1 RCT compared yoga to exercise; and 2 3-arm RCTs compared yoga to usual care and exercise. No evidence was found for short-term effects of yoga compared to usual care on positive symptoms (SMD = -0.58; 95% CI -1.52 to 0.37; P = 0.23), or negative symptoms (SMD = -0.59; 95% CI -1.87 to 0.69; P = 0.36). Moderate evidence was found for short-term effects on quality of life compared to usual care (SMD = 2.28; 95% CI 0.42 to 4.14; P = 0.02). These effects were only present in studies with high risk of bias. No evidence was found for short-term effects on social function (SMD = 1.20; 95% CI -0.78 to 3.18; P = 0.23). Comparing yoga to exercise, no evidence was found for short-term effects on positive symptoms (SMD = -0.35; 95% CI -0.75 to 0.05; P = 0.09), negative symptoms (SMD = -0.28; 95% CI -1.42 to 0.86; P = 0.63), quality of life (SMD = 0.17; 95% CI -0.27 to 0.61; P = 0.45), or social function (SMD = 0.20; 95% CI -0.27 to 0.67; P = 0.41). Only 1 RCT reported adverse events. This systematic review found only moderate evidence for short-term effects of yoga on quality of life. As these effects were not clearly distinguishable from bias and safety of the intervention was unclear, no recommendation can be made regarding yoga as a routine intervention for schizophrenia patients.


Cardiopulmonary resuscitation in real life: the most frequent fears of lay rescuers.
Surviving cardiac arrest depends on early cardiopulmonary resuscitation (CPR). Only one third of cardiac arrest victims receive prompt CPR in spite of well-attended Basic Life Support (BLS) courses. Our study aimed to investigate that how many lay rescuers, capable of performing CPR, would do so, and to analyse their impeding fears. After each BLS course for lay rescuers (American Heart Association (AHA) CPR for family and friends), an anonymous questionnaire was distributed asking participants whether they would perform CPR on an adult or on a child in a real case of cardiac arrest. In the case of a negative response, we questioned them why. A total of 1000 questionnaires were analysed. The sample group was predominantly made up of males (77.7%), Italians (82.2%), individuals aged between 26 and 35 years (41.2%) and individuals possessing a high-school diploma (61.8%). The percentages that would perform CPR on an unknown adult or child were different (86.2% vs. 73.9% p = 0.005). The prevalent fears were regarding infection, being incapable, legal implications and causing damage and fear in general. The first three differ significantly in adult and paediatric cases. Subdividing the population according to sex, age and education did not demonstrate significant differences regarding willingness to perform adult or paediatric CPR. This descriptive study demonstrates that the percentage that would really perform CPR is too low, particularly in the case of a child. Part of the course should be dedicated to discussing these arguments to ensure that all those capable of performing good CPR would immediately do so.


Altered formation of topotecan-stabilized topoisomerase I-DNA adducts in human leukemia cells.
Topotecan (TPT) is a topoisomerase I (topo I) poison that has shown promising antineoplastic activity in solid tumors and acute leukemia. In the present study, a band depletion assay was used to evaluate the ability of TPT to stabilize topo I-DNA adducts in human leukemia cell lines and in clinical leukemia samples ex vivo. This assay showed that 50% of the cellular topo I in HL-60 human myelomonocytic leukemia cells became covalently bound to DNA at an extracellular TPT concentration of 4 micromol/L. In contrast, in 13 clinical specimens of human leukemia harvested before treatment of patients with TPT, the TPT concentration required to stabilize 50% of the cellular topo I in topo I-DNA complexes ranged from 3 to greater than 100 micromol/L (median, 30 micromol/ L). Flow microfluorimetry showed that cellular TPT accumulation varied over only a twofold range and failed to provide evidence for transport-mediated resistance in the clinical samples. These observations raise the possibility that formation of topo I-DNA adducts is diminished in many specimens of refractory/relapsed acute leukemia by a mechanism that might alter topo I sensitivity to TPT.


Hospital readmissions for catheter-related bloodstream infection and use of ethanol lock therapy: comparison of patients receiving parenteral nutrition or intravenous fluids in the home vs a skilled nursing facility.
Catheter-related bloodstream infection (CRBSI) is the most serious long-term infectious complication of long-term home parenteral nutrition (PN). Ethanol is being used more commonly as a catheter locking solution in the home PN setting for prevention of CRBSI; however, no current literature reports the use of ethanol lock (ETL) in skilled nursing facility (SNF) patients. The authors evaluated the number of hospital readmissions for CRBSI and length of stay between SNF (not receiving ETL) and home patients (receiving or not receiving ETL) receiving PN or intravenous fluid therapy. SNF patients had a significantly longer length of stay (LOS) for CRBSI hospital admissions compared with patients receiving PN at home with or without ETL (P < .001; 16 vs 8 vs 8 days). There was no LOS difference for CRBSI between home patients with or without ETL. Home PN patients not receiving ETL were more likely to have a CRBSI from Staphylococcus sp (48% vs 27%; P = .015), whereas SNF PN patients not receiving ETL were more likely to have a CRBSI from Enterococcus sp (16% vs 3%; P = .004). Despite different causative organisms and medical acuity likely affecting the differences observed in LOS, the SNF population is another setting ETL can be used to prevent CRBSI.


Climate and lawn management interact to control C4 plant distribution in residential lawns across seven U.S. cities.
In natural grasslands, C4 plant dominance increases with growing season temperatures and reflects distinct differences in plant growth rates and water use efficiencies of C3 vs. C4 photosynthetic pathways. However, in lawns, management decisions influence interactions between planted turfgrass and weed species, leading to some uncertainty about the degree of human vs. climatic controls on lawn species distributions. We measured herbaceous plant carbon isotope ratios (δ13 C, index of C3 /C4 relative abundance) and C4 cover in residential lawns across seven U.S. cities to determine how climate, lawn plant management, or interactions between climate and plant management influenced C4 lawn cover. We also calculated theoretical C4 carbon gain predicted by a plant physiological model as an index of expected C4 cover due to growing season climatic conditions in each city. Contrary to theoretical predictions, plant δ13 C and C4 cover in urban lawns were more strongly related to mean annual temperature than to growing season temperature. Wintertime temperatures influenced the distribution of C4 lawn turf plants, contrary to natural ecosystems where growing season temperatures primarily drive C4 distributions. C4 cover in lawns was greatest in the three warmest cities, due to an interaction between climate and homeowner plant management (e.g., planting C4 turf species) in these cities. The proportion of C4 lawn species was similar to the proportion of C4 species in the regional grass flora. However, the majority of C4 species were nonnative turf grasses, and not of regional origin. While temperature was a strong control on lawn species composition across the United States, cities differed as to whether these patterns were driven by cultivated lawn grasses vs. weedy species. In some cities, biotic interactions with weedy plants appeared to dominate, while in other cities, C4 plants were predominantly imported and cultivated. Elevated CO2 and temperature in cities can influence C3 /C4 competitive outcomes; however, this study provides evidence that climate and plant management dynamics influence biogeography and ecology of C3 /C4 plants in lawns. Their differing water and nutrient use efficiency may have substantial impacts on carbon, water, energy, and nutrient budgets across cities.


Gene expression in TGFbeta-induced epithelial cell differentiation in a three-dimensional intestinal epithelial cell differentiation model.
The TGFbeta1-induced signal transduction processes involved in growth and differentiation are only partly known. The three-dimensional epithelial differentiation model, in which T84 epithelial cells are induced to differentiate either with TGFbeta1 or IMR-90 mesenchymal cell-secreted soluble factors, is previously shown to model epithelial cell differentiation seen in intestine. That model has not been used for large scale gene expression studies, such as microarray method. Therefore the gene expression changes were studied in undifferentiated and differentiated three-dimensional T84 cultures with cDNA microarray method in order to study the molecular changes and find new players in epithelial cell differentiation. The expression of 372 genes out of 5188 arrayed sequences was significantly altered, and 47 of them were altered by both mediators. The data were validated and the altered genes are presented in ontology classes. For the genes tested the expressions in protein level were in accordance with the mRNA results. We also found 194 genes with no known function to be potentially important in epithelial cell differentiation. The mRNA expression changes induced by TGFbeta1 were bigger than changes induced by soluble factors secreted by IMR-90 mesenchymal cells. The gene expression data was depicted in already known signaling pathway routes. Our results reveal potential new signaling pathways and several new genes affected by TGFbeta in epithelial cell differentiation. The differentiation induced by TGFbeta1 appears to be more potent than the differentiation induced by mesenchymal cells. This study indicates that our cell culture model is a suitable tool in studying regulatory mechanisms during epithelial cell differentiation in intestine. Furthermore the present results indicate that our model is a good tool for finding new players acting in the differentiation of epithelial cells.


A life-span theory of control.
A life-span theory of development is presented that is based on the concepts of primary and secondary control. Primary control refers to behaviors directed at the external environment and involves attempts to change the world to fit the needs and desires of the individual. Secondary control is targeted at internal processes and serves to minimize losses in, maintain, and expand existing levels of primary control. Secondary control helps the individual to cope with failure and fosters primary control by channeling motivational resources toward selected action goals throughout the life course. Primary control has functional primacy over secondary control. An analysis of extensive and diverse literatures spanning infancy through old age shows that trade-offs between primary and secondary control undergo systematic shifts across the life course in response to the opportunities and constraints encountered.


Urinary iodide concentration in hyperthyroid cats.
To compare concentrations of urinary iodide (UI) in euthyroid and untreated hyperthyroid cats. 118 euthyroid and 88 hyperthyroid client-owned cats from 2 nonreferral veterinary practices. Iodide concentration was measured in 5 urine samples collected every 3 to 12 months from selected cats, and variability of results between euthyroid cats and hyperthyroid cats prior to the diagnosis of hyperthyroidism was evaluated via 1-way ANOVA, after logarithmic transformation of UI concentrations (logUIs). The UI concentration in hyperthyroid cats was measured at diagnosis and 2 to 6 weeks and 3 to 6 months after treatment for hyperthyroidism. The pretreatment logUI in hyperthyroid cats was compared with that in euthyroid cats, taking into account the effects of renal function on UI concentration. Iodine intake was estimated in euthyroid cats following calculation of the volume of daily urine output, with a fixed value for iodine concentration in feces. The variability of UI concentrations did not differ significantly between hyperthyroid (n = 10) and euthyroid (8) cats. The logUI increased 2 to 6 weeks after initiation of treatment in hyperthyroid cats (n = 80) and was lower in azotemic versus nonazotemic cats. Hyperthyroid cats had a lower logUI than euthyroid cats, and there was no evidence of deficient iodine intake in euthyroid cats. The logUI was lower in cats with azotemia and with untreated hyperthyroidism, compared with that in euthyroid cats from the same population. Additional studies are needed to determine whether iodine intake plays a role in the development of hyperthyroidism in cats.


Worry is reasonable: the role of explanations in pessimism about future personal events.
This experiment examines one component of worry, elevated subjective probabilities of negative events, and attempts to elucidate the cognitive processes on which this is based. The results suggest that the pessimistic subjective probabilities shown by chronic worriers can be understood using general theories of judgment, specifically, by the use of the availability heuristic (Tversky & Kahneman, 1973). However, it is the availability of a particular pattern of cognitions--an increased accessibility of explanations for why a negative event would occur, combined with a reduced accessibility of explanations for why it would not--that is important. The results are integrated within a description of the worry process, and possible clinical applications through the use of reason-generation techniques are discussed.


Vitamin D and pelvic floor disorders in women: results from the National Health and Nutrition Examination Survey.
To estimate the prevalence of vitamin D deficiency in women with pelvic floor disorders and to evaluate possible associations between vitamin D levels and pelvic floor disorders. Using 2005-2006 National Health and Nutrition Examination Survey data, we performed a cross-sectional analysis of nonpregnant women older than 20 years of age with data on both pelvic floor disorders and vitamin D measurements (n=1,881). Vitamin D levels lower than 30 ng/mL were considered insufficient. The prevalence of demographic factors, pelvic floor disorders, and vitamin D levels were determined, accounting for the multi-stage sampling design; odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate associations between vitamin D levels and pelvic floor disorders with control for known risk factors. One or more pelvic floor disorders were reported by 23% of women. Mean vitamin D levels were significantly lower for women reporting at least one pelvic floor disorder and for those with urinary incontinence, irrespective of age. In adjusted logistic regression models, we observed significantly decreased risks of one or more pelvic floor disorders with increasing vitamin D levels in all women aged 20 or older (OR, 0.94; 95% CI, 0.88-0.99) and in the subset of women 50 years and older (OR, 0.92; 95% CI, 0.85-0.99). Additionally, the likelihood of urinary incontinence was significantly reduced in women 50 and older with vitamin D levels 30 ng/mL or higher (OR, 0.55; 95% CI, 0.34-0.91). Higher vitamin D levels are associated with a decreased risk of pelvic floor disorders in women. III.


Haematopoietic and endothelial progenitor cells are deficient in quiescent systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is associated with a high prevalence of cardiovascular disease. Circulating endothelial progenitor cells (EPCs) contribute to vascular regeneration and repair, thereby protecting against atherosclerotic disease. EPCs are derived from CD34+ haematopoietic stem cells (HSCs), which have an increased propensity for apoptosis in the bone marrow of patients with SLE. To determine whether circulating HSCs and EPCs are reduced in SLE, contributing to an increased cardiovascular risk. Progenitor cells were sampled from 15 female patients with SLE in prolonged clinical remission from their disease and 15 matched healthy controls. HSC and CD34+KDR+ EPCs were quantified by flow cytometry. Annexin V staining was used to identify apoptotic cells. Patients with SLE had reduced levels of circulating CD34+ HSCs and CD34+KDR+ EPCs, associated with increased HSC apoptosis. Compared with controls, the fraction of HSCs that could be identified as EPCs was higher in patients with SLE, consistent with a primary defect of HSCs. EPC outgrowth from mononuclear cells, which depends mainly on CD34- cells, was unaffected. Patients with SLE have lower levels of circulating HSCs and EPCs, even during clinical remission. The data suggest that increased HSC apoptosis is the underlying cause for this depletion. These observations indicate that progenitor cell-mediated endogenous vascular repair is impaired in SLE, which may contribute to the accelerated development of atherosclerosis.


The safety and clinical usefulness of dobutamine stress echocardiography among octogenarians.
Increasing numbers of octogenarians are being referred for investigation of chest pain. While dobutamine stress echocardiography (DSE) has been shown to be useful in younger patients, its role among octogenarians remains unclear. This investigation aimed to investigate the safety and prognostic benefits of DSE on cardiac events and total mortality in octogenarians. 550 consecutive patients aged ≥80 years underwent DSE for suspected cardiac chest pain. All subjects were followed-up prospectively until March 2011, and the study end-points were a major cardiac event and total mortality. One hundred and eighty-three (33%) patients had a positive DSE result, 271 (49%) had a normal study, and 164 (30%) had fixed-wall motion abnormalities. During a mean follow-up of 2.14±1.13 years, there were 217 (39%) cardiac events and 63 (11%) deaths, of which 46 (73%) were cardiac. The absolute risk of cardiac events increased with burden of ischaemia on DSE, from 13%/year (none), to 26%/year (1-3 ischaemic (LV) segments), and 38%/year (>3 ischaemic LV segments), p<0.001. Any ischaemia was associated with an additional 13 cardiac events per 100 person-years. In multivariate analysis, compared with non-ischaemic patients, the relative hazard of cardiac events for 1-3 and >3 ischaemic LV segments were 1.34 (95% CI 1.13 to 1.29) and 1.86 (95% CI 1.16 to 2.98), respectively. Addition of echocardiographic parameters to basic models improved the C statistic from 0.77 to 0.89 (p<0.001). Among octogenarians referred with suspected cardiac chest pain, DSE is safe and, importantly, identifies a subset at high risk of cardiac events.


The phylogeny of Heliconia (Heliconiaceae) and the evolution of floral presentation.
Heliconia (Heliconiaceae, order Zingiberales) is among the showiest plants of the Neotropical rainforest and represent a spectacular co-evolutionary radiation with hummingbirds. Despite the attractiveness and ecological importance of many Heliconia, the genus has been the subject of limited molecular phylogenetic studies. We sample seven markers from the plastid and nuclear genomes for 202 samples of Heliconia. This represents ca. 75% of accepted species and includes coverage of all taxonomic subgenera and sections. We date this phylogeny using fossils associated with other families in the Zingiberales; in particular we review and evaluate the Eocene fossil Ensete oregonense. We use this dated phylogenetic framework to evaluate the evolution of two components of flower orientation that are hypothesized to be important for modulating pollinator discrimination and pollen placement: resupination and erect versus pendant inflorescence habit. Our phylogenetic results suggest that the monophyletic Melanesian subgenus Heliconiopsis and a small clade of Ecuadorian species are together the sister group to the rest of Heliconia. Extant diversity of Heliconia originated in the Late Eocene (39Ma) with rapid diversification through the Early Miocene, making it the oldest known clade of hummingbird-pollinated plants. Most described subgenera and sections are not monophyletic, though closely related groups of species, often defined by shared geography, mirror earlier morphological cladistic analyses. Evaluation of changes in resupination and inflorescence habit suggests that these characters are more homoplasious than expected, and this largely explains the non-monophyly of previously circumscribed subgenera, which were based on these characters. We also find strong evidence for the correlated evolution of resupination and inflorescence habit. The correlated model suggests that the most recent common ancestor of all extant Heliconia had resupinate flowers and erect inflorescences. Finally, we note our nearly complete species sampling and dated phylogeny allow for an assessment of taxonomic history in terms of phylogenetic diversity. We find approximately half of the currently recognized species, corresponding to half of the phylogenetic diversity, have been described since 1975, highlighting the continued importance of basic taxonomic research and conservation initiatives to preserve both described and undiscovered species of Heliconia.


Aripiprazole/Methylphenidate Combination in Children and Adolescents with Disruptive Mood Dysregulation Disorder and Attention-Deficit/Hyperactivity Disorder: An Open-Label Study.
Disruptive mood dysregulation disorder (DMDD) is characterized by nonepisodic irritability and has a high rate of comorbidity with attention-deficit/hyperactivity disorder (ADHD). This is the first study to explore the effects of aripiprazole combined with methylphenidate on clinical symptoms and cognitive functions in patients with DMDD and ADHD. Patients with DMDD and ADHD (the DMDD-ADHD Group, n = 24; aged 7-17 years) completed a 6-week, open-label trial of aripiprazole and methylphenidate. The pre- and posttreatment outcome measures included the parent-rated Swanson, Nolan, and Pelham Scale-version IV, Child Behavior Checklist, and self-reported Beck Youth Inventories-II, as well as a neuropsychological battery composed of the Children's Color Trail Test and Conner's Continuous Performance Test. The comparison group consisting of patients with ADHD (the ADHD Group, n = 27) was recruited to investigate the differences in clinical and neuropsychological profiles between the two groups at baseline. The DMDD-ADHD Group showed worse irritability, disruptive behaviors, anxious/depressed symptoms, and social problems relative to the ADHD Group at baseline assessments. The combination treatment significantly improved irritability, externalizing symptoms, depression, anxiety, attention, social problems, and reaction time variability. The effect sizes of reductions in parent-rated irritability, oppositional defiant symptoms, and inattention were comparable (Cohen's d = 1.26, 1.11, and 1.40, respectively). This pilot study showed the tolerability of the aripiprazole/methylphenidate combination by patients with DMDD and ADHD and its efficaciousness for treating clinical symptoms and for improving cognitive function. Further randomized, controlled, cross-over studies are needed.


Impact of age, sex, socioeconomic status, and physical activity on associated movements and motor speed in preschool children.
Young children generally show contralateral associated movements (CAMs) when they are making an effort to perform a unimanual task. CAM and motor speed are two relevant aspects of motor proficiency in young children. These CAMs decrease over age, while motor speed increases. As both CAM and motor speed are associated with age, we were interested in whether these two parameters are also linked with each other. In this study, three manual dexterity tasks with the dominant and nondominant hands (pegboard, repetitive hand, and repetitive finger tasks) were used to investigate the effect of covariates (age, sex, socioeconomic status, total physical activity) on both motor speed and CAMs in preschool children. There was a significant age effect for both motor speed and CAMs in all tasks when the dominant hand was used. When the nondominant hand was used, the decrease in the intensity of CAMs over age was not consistently significant. The influence of physical activity and socioeconomic status on motor proficiency was small. Furthermore, the correlation between motor speed and CAMs, although significant, was low. Motor speed improved with age over three fine motor tasks in preschool children. Decrease in CAMs was observed but it was not always significant when the nondominant hand was working. Motor speed and CAMs were only weakly associated. We conclude that the excitatory pathways responsible for motor speed and inhibitory pathways responsible for reducing CAMs occupy two different domains in the brain and therefore mostly behave independently of each other.