Generalisation for neural networks through data sampling and training procedures, with applications to streamflow predictions

International audienceSince the 1990s, neural networks have been applied to many studies in hydrology and water resources. Extensive reviews on neural network modelling have identified the major issues affecting modelling performance; one of the most important is generalisation, which refers to building models that can infer the behaviour of the system under study for conditions represented not only in the data employed for training and testing but also for those conditions not present in the data sets but inherent to the system. This work compares five generalisation approaches: stop training, Bayesian regularisation, stacking, bagging and boosting. All have been tested with neural networks in various scientific domains; stop training and stacking having been applied regularly in hydrology and water resources for some years, while Bayesian regularisation, bagging and boosting have been less common. The comparison is applied to streamflow modelling with multi-layer perceptron neural networks and the Levenberg-Marquardt algorithm as training procedure. Six catchments, with diverse hydrological behaviours, are employed as test cases to draw general conclusions and guidelines on the use of the generalisation techniques for practitioners in hydrology and water resources. All generalisation approaches provide improved performance compared with standard neural networks without generalisation. Stacking, bagging and boosting, which affect the construction of training sets, provide the best improvement from standard models, compared with stop-training and Bayesian regularisation, which regulate the training algorithm. Stacking performs better than the others although the benefit in performance is slight compared with bagging and boosting; furthermore, it is not consistent from one catchment to another. For a good combination of improvement and stability in modelling performance, the joint use of stop training or Bayesian regularisation with either bagging or boosting is recommended. Keywords: neural networks, generalisation, stacking, bagging, boosting, stop-training, Bayesian regularisation, streamflow modellin

Dopaminergic therapy increases Go timeouts in the Go/No-Go task in patients with parkinson’s disease

Parkinson’s disease (PD) is characterized by resting tremor, rigidity and bradykinesia. Dopaminergic medications such as L-dopa treat these motor symptoms, but can have complex effects on cognition. Impulse control is an essential cognitive function. Impulsivity is multifaceted in nature. Motor impulsivity involves the inability to withhold pre-potent, automatic, erroneous responses. In contrast, cognitive impulsivity refers to improper risk-reward assessment guiding behavior. Informed by our previous research, we anticipated that dopaminergic therapy would decrease motor impulsivity though it is well known to enhance cognitive impulsivity. We employed the Go/No-go paradigm to assess motor impulsivity in PD. Patients with PD were tested using a Go/No-go task on and off their normal dopaminergic medication. Participants completed cognitive, mood, and physiological measures. PD patients on medication had a significantly higher proportion of Go trial Timeouts (i.e., trials in which Go responses were not completed prior to a deadline of 750 ms) compared to off medication (p = 0.01). No significant ON-OFF differences were found for Go trial or No-go trial response times (RTs), or for number of No-go errors. We interpret that dopaminergic therapy induces a more conservative response set, reflected in Go trial Timeouts in PD patients. In this way, dopaminergic therapy decreased motor impulsivity in PD patients. This is in contrast to the widely recognized effects of dopaminergic therapy on cognitive impulsivity leading in some patients to impulse control disorders. Understanding the nuanced effects of dopaminergic treatment in PD on cognitive functions such as impulse control will clarify therapeutic decisions

Latent variables and structural equation models for longitudinal relationships: an illustration in nutritional epidemiology

<p>Abstract</p> <p>Background</p> <p>The use of structural equation modeling and latent variables remains uncommon in epidemiology despite its potential usefulness. The latter was illustrated by studying cross-sectional and longitudinal relationships between eating behavior and adiposity, using four different indicators of fat mass.</p> <p>Methods</p> <p>Using data from a longitudinal community-based study, we fitted structural equation models including two latent variables (respectively baseline adiposity and adiposity change after 2 years of follow-up), each being defined, by the four following anthropometric measurement (respectively by their changes): body mass index, waist circumference, skinfold thickness and percent body fat. Latent adiposity variables were hypothesized to depend on a cognitive restraint score, calculated from answers to an eating-behavior questionnaire (TFEQ-18), either cross-sectionally or longitudinally.</p> <p>Results</p> <p>We found that high baseline adiposity was associated with a 2-year increase of the cognitive restraint score and no convincing relationship between baseline cognitive restraint and 2-year adiposity change could be established.</p> <p>Conclusions</p> <p>The latent variable modeling approach enabled presentation of synthetic results rather than separate regression models and detailed analysis of the causal effects of interest. In the general population, restrained eating appears to be an adaptive response of subjects prone to gaining weight more than as a risk factor for fat-mass increase.</p

IRF7-Associated Immunophenotypes Have Dichotomous Responses to Virus/Allergen Coexposure and OM-85-Induced Reprogramming

High risk for virus-induced asthma exacerbations in children is associated with an IRF7lo immunophenotype, but the underlying mechanisms are unclear. Here, we applied a Systems Biology approach to an animal model comprising rat strains manifesting high (BN) versus low susceptibility (PVG) to experimental asthma, induced by virus/allergen coexposure, to elucidate the mechanism(s)-of-action of the high-risk asthma immunophenotype. We also investigated potential risk mitigation via pretreatment with the immune training agent OM-85. Virus/allergen coexposure in low-risk PVG rats resulted in rapid and transient airways inflammation alongside IRF7 gene network formation. In contrast, responses in high-risk BN rats were characterized by severe airways eosinophilia and exaggerated proinflammatory responses that failed to resolve, and complete absence of IRF7 gene networks. OM-85 had more profound effects in high-risk BN rats, inducing immune-related gene expression changes in lung at baseline and reducing exaggerated airway inflammatory responses to virus/allergen coexposure. In low-risk PVG rats, OM-85 boosted IRF7 gene networks in the lung but did not alter baseline gene expression or cellular influx. Distinct IRF7-associated asthma risk immunophenotypes have dichotomous responses to virus/allergen coexposure and respond differentially to OM-85 pretreatment. Extrapolating to humans, our findings suggest that the beneficial effects OM-85 pretreatment may preferentially target those in high-risk subgroups

Interakcije nekih plijesni i aflatoksinogenog soja Asspergillus flavus NRRL 3251

The objective of this study was to evaluate biotic interaction between some mould species and active producer of aflatoxin B1 Aspergillus flavus NRRL 3251, co-cultured in yeast-extract sucrose (YES) broth. Twenty-five mould strains of Alternaria spp., Cladosporium spp., Mucor spp., A. flavus and A. niger, used as biocompetitive agents, were isolated from outdoor and indoor airborne fungi, scrapings of mouldy household walls, and from stored and post-harvest maize. Aflatoxin B1 was extracted from mould biomasses with chloroform and detected using the multitoxin TLC method. The results confirm antagonistic interaction between all strains tested. With Alternaria spp. and Cladosporium spp., aflatoxin B1 production decreased 100 %, compared to detection in a single culture of A. flavus NRRL 3251 (Cmean=18.7 µg mL-1). In mixed cultures with Mucor spp., aflatoxin B1 levels dropped to (5.6-9.3) µg mL-1, and the inhibition was from 50 % to 70 %. Four of five aflatoxin non-producing strains of A. flavus interfered with aflatoxin production in mixed culture, and reduced AFB1 productivity by 100 %. One strain showed a lower efficacy in inhibiting AFB1 production (80 %) with a detectable amount of AFB1 3.7 µg mL-1 when compared to control. A decrease in toxin production was also observed in dual cultivation with A. niger strains. It resulted in 100 % reduction in three strains), 90 % reduction in one strain (Cmean=1.9 µg mL-1) and 80 % reduction in one strain (Cmean=3.7 µg mL-1) inhibition.Cilj rada bio je procijeniti biotske interakcije između sojeva različitih vrsta plijesni i kontrolnog soja Aspergillus flavus NRRL 3251, producenta aflatoksina B1 (AFB1). Inhibitorno djelovanje u miješanim kulturama na tvorbu AFB1 ispitano je na dvadeset pet sojeva Alternaria, Cladosporium, Mucor i Aspergillus vrsta izoliranih iz zraka, strugotina pljesnivih zidova te uskladištenog i prezimljenog kukuruza. Biosinteze su provedene u tekućoj hranjivoj podlozi s kvaščevim ekstraktom (YESbujon). Ekstrakcije AFB1 iz biomase izvršene su multitoksinskom metodom tankoslojne kromatografije. Rezultati biotskih interakcija pokazali su antagonistički odnos svih testiranih sojeva. Alternaria i Cladosporium vrste simultano inokulirane sporama A. flavus NRRL 3251 inhibirale su tvorbu AFB1 100 % u odnosu na dokazani toksin u kontrolnoj biosintezi (konc. 18,7 µg mL-1). U miješanim kulturama vrstama roda Mucor dokazane su padajuće koncentracije AFB1 (9,3 µg mL-1, 7,5 µg mL-1 i 5,6 µg mL-1), odnosno inhibicija tvorbe toksina 50 % do 70 %. Atoksinogeni sojevi A. flavus inhibirali su tvorbu AFB1 80 % (1 soj, konc. 3,7 µg mL-1) i 100 % (4 soja). Antagonističko djelovanje prema toksinogenom soju, smanjujući tvorbu AFB1 u rasponu 80 % do 100 % (konc. 1,9 µg mL-1 i 3,7 µg mL-1), dokazano je u uzgojnim biosintezama s A. niger

Living Alone, Patient Sex and Mortality After Acute Myocardial Infarction

BACKGROUND: Psychosocial factors, including social support, affect outcomes of cardiovascular disease, but can be difficult to measure. Whether these factors have different effects on mortality post-acute myocardial infarction (AMI) in men and women is not clear. OBJECTIVE: To examine the association between living alone, a proxy for social support, and mortality postdischarge AMI and to explore whether this association is modified by patient sex. DESIGN: Historical cohort study. PARTICIPANTS/SETTING: All patients discharged with a primary diagnosis of AMI in a major urban center during the 1998–1999 fiscal year. MEASUREMENTS: Patients’ sociodemographic and clinical characteristics were obtained by standardized chart review and linked to vital statistics data through December 2001. RESULTS: Of 880 patients, 164 (18.6%) were living alone at admission and they were significantly more likely to be older and female than those living with others. Living alone was independently associated with mortality [adjusted hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.0–2.5], but interacted with patient sex. Men living alone had the highest mortality risk (adjusted HR 2.0, 95% CI 1.1–3.7), followed by women living alone (adjusted HR 1.2, 95% CI 0.7–2.2), men living with others (reference, HR 1.0), and women living with others (adjusted HR 0.9, 95% CI 0.5–1.5). CONCLUSIONS: Living alone, an easily measured psychosocial factor, is associated with significantly increased longer-term mortality for men following AMI. Further prospective studies are needed to confirm the usefulness of living alone as a prognostic factor and to identify the potentially modifiable mechanisms underlying this increased risk

The analysis of latent fingermarks on polymer banknotes using MALDI-MS

In September 2016, the UK adopted a new Bank of England (BoE) £5 polymer banknote, followed by the £10 polymer banknote in September 2017. They are designed to be cleaner, stronger and have increased counterfeit resilience; however, fingermark development can be problematic from the polymer material as various security features and coloured/textured areas have been found to alter the effectiveness of conventional fingermark enhancement techniques (FETs). As fingermarks are one of the most widely used forms of identification in forensic cases, it is important that maximum ridge detail be obtained in order to allow for comparison. This research explores the use of matrix-assisted laser desorption/ionisation mass spectrometry (MALDI-MS) profiling and imaging for the analysis of fingermarks deposited on polymer banknotes. The proposed methodology was able to obtain both physical and chemical information from fingermarks deposited in a range of scenarios including; different note areas, depletion series, aged samples and following conventional FETs. The analysis of forensically important molecular targets within these fingermarks was also explored, focussing specifically on cocaine. The ability of MALDI-MS to provide ridge detail and chemical information highlights the forensic applicability of this technique and potential for the analysis of fingermarks deposited onto this problematic surface

The clinical application of genome-wide sequencing for monogenic diseases in Canada: Position statement of the Canadian College of medical geneticists

Purpose and scope: The aim of this Position Statement is to provide recommendations for Canadian medical geneticists, clinical laboratory geneticists, genetic counsellors and other physicians regarding the use of genome-wide sequencing of germline DNA in the context of clinical genetic diagnosis. This statement has been developed to facilitate the clinical translation and development of best practices for clinical genome-wide sequencing for genetic diagnosis of monogenic diseases in Canada; it does not address the clinical application of this technology in other fields such as molecular investigation of cancer or for population screening of healthy individuals. Methods of statement development: Two multidisciplinary groups consisting of medical geneticists, clinical laboratory geneticists, genetic counsellors, ethicists, lawyers and genetic researchers were assembled to review existing literature and guidelines on genome-wide sequencing for clinical genetic diagnosis in the context of monogenic diseases, and to make recommendations relevant to the Canadian context. The statement was circulated for comment to the Canadian College of Medical Geneticists (CCMG) membership-at-large and, following incorporation of feedback, approved by the CCMG Board of Directors. The CCMG is a Canadian organisation responsible for certifying medical geneticists and clinical laboratory geneticists, and for establishing professional and ethical standards for clinical genetics services in Canada. Results and conclusions: Recommendations include (1) clinical genome-wide sequencing is an appropriate approach in the diagnostic assessment of a patient for whom there is suspicion of a significant monogenic disease that is associated with a high degree of genetic heterogeneity, or where specific genetic tests have failed to provide a diagnosis; (2) until the benefits of reporting incidental findings are established, we do not endorse the intentional clinical analysis of disease-associated genes other than those linked to the primary indication; and (3) clinicians should provide genetic counselling and obtain informed consent prior to undertaking clinical genome-wide sequencing. Counselling should include discussion of the limitations of testing, likelihood and implications of diagnosis and incidental findings, and the potential need for further analysis to facilitate clinical interpretation, including studies performed in a research setting. These recommendations will be routinely reevaluated as knowledge of diagnostic and clinical utility of clinical genome-wide sequencing improves. While the document was developed to direct practice in Canada, the applicability of the statement is broader and will be of interest to clinicians and health jurisdictions internationally

Family-focused contextual factors associated with lifestyle patterns in young children from two mother-offspring cohorts : GUSTO and EDEN

Background Integrated patterns of energy balance-related behaviours of preschool children in Asia are sparse, with few comparative analyses. Purpose Using cohorts in Singapore (GUSTO) and France (EDEN), we characterized lifestyle patterns of children and investigated their associations with family-focused contextual factors. Methods Ten behavioural variables related to child's diet, walking, outdoor play and screen time were ascertained by parental questionnaires at age 5-6 years. Using principal component analysis, sex-specific lifestyle patterns were derived independently for 630 GUSTO and 989 EDEN children. Contextual variables were organised into distal (family socio-economics, demographics), intermediate (parental health, lifestyle habits) and proximal (parent-child interaction factors) levels of influence and analysed with hierarchical linear regression. Results Three broadly similar lifestyle patterns were identified in both cohorts: "discretionary consumption and high screen time", "fruit, vegetables, and low screen time" and "high outdoor playtime and walking". The latter two patterns showed small differences between cohorts and sexes. The "discretionary consumption and high screen time" pattern was consistently similar in both cohorts; distal associated factors were lower maternal education (EDEN boys), no younger siblings (GUSTO boys) and Malay/Indian ethnicity (GUSTO), while intermediate and proximal associated factors in both cohorts and sexes were poor maternal diets during pregnancy, parents allowing high child control over food intake, snacking between meals and having television on while eating. Conclusions Three similar lifestyle patterns were observed among preschool children in Singapore and France. There were more common associated proximal factors than distal ones. Cohort specific family-focused contextual factors likely reflect differences in social and cultural settings. Findings will aid development of strategies to improve child health.Peer reviewe

Uptake and factors that influence the use of ‘sit less, move more’ occupational intervention strategies in Spanish office employees

Background Little is known about the types of ‘sit less, move more’ strategies that appeal to office employees, or what factors influence their use. This study assessed the uptake of strategies in Spanish university office employees engaged in an intervention, and those factors that enabled or limited strategy uptake. Methods The study used a mixed method design. Semi-structured interviews were conducted with academics and administrators (n = 12; 44 ± 12 mean SD age; 6 women) at three points across the five-month intervention, and data used to identify factors that influenced the uptake of strategies. Employees who finished the intervention then completed a survey rating (n = 88; 42 ± 8 mean SD age; 51 women) the extent to which strategies were used [never (1) to usually (4)]; additional survey items (generated from interviewee data) rated the impact of factors that enabled or limited strategy uptake [no influence (1) to very strong influence (4)]. Survey score distributions and averages were calculated and findings triangulated with interview data. Results Relative to baseline, 67% of the sample increased step counts post intervention (n = 59); 60% decreased occupational sitting (n = 53). ‘Active work tasks’ and ‘increases in walking intensity’ were the strategies most frequently used by employees (89% and 94% sometimes or usually utilised these strategies); ‘walk-talk meetings’ and ‘lunchtime walking groups’ were the least used (80% and 96% hardly ever or never utilised these strategies). ‘Sitting time and step count logging’ was the most important enabler of behaviour change (mean survey score of 3.1 ± 0.8); interviewees highlighted the motivational value of being able to view logged data through visual graphics in a dedicated website, and gain feedback on progress against set goals. ‘Screen based work’ (mean survey score of 3.2 ± 0.8) was the most significant barrier limiting the uptake of strategies. Inherent time pressures and cultural norms that dictated sedentary work practices limited the adoption of ‘walk-talk meetings’ and ‘lunch time walking groups’. Conclusions The findings provide practical insights into which strategies and influences practitioners need to target to maximise the impact of ‘sit less, move more’ occupational intervention strategies