Adaptive matrix metrics for molecular descriptor assessment in QSPR classification

QSPR methods represent a useful approach in the drug discovery process, since they allow to predict in advance biological or physicochemical properties of a candidate drug. For this goal, it is necessary that the QSPR method be as accurate as possible to provide reliable predictions. Moreover, the selection of the molecular descriptors is an important task to create QSPR prediction models of low complexity which, at the same time, provide accurate predictions. In this work, a matrix-based method is used to transform the original data space of chemical compounds into an alternative space where compounds with different target properties can be better separated. For using this approach, QSPR is considered as a classification problem. The advantage of using adaptive matrix metrics is twofold: it can be used to identify important molecular descriptors and at the same time it allows improving the classification accuracy. A recently proposed method making use of this concept is extended to multi-class data. The new method is related to linear discriminant analysis and shows better results at yet higher computational costs. An application for relating chemical descriptors to hydrophobicity property shows promising results.Fil: Soto, Axel Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; ArgentinaFil: Strickert, Marc. Leibniz Institute of Plant Genetics and Crop Plant Research; AlemaniaFil: Vazquez, Gustavo Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentin

An Instrumented Glove to Assess Manual Dexterity in Simulation-Based Neurosurgical Education

ABSTRACT: The traditional neurosurgical apprenticeship scheme includes the assessment of trainee’s manual skills carried out by experienced surgeons. However, the introduction of surgical simulation technology presents a new paradigm where residents can refine surgical techniques on a simulator before putting them into practice in real patients. Unfortunately, in this new scheme, an experienced surgeon will not always be available to evaluate trainee’s performance. For this reason, it is necessary to develop automatic mechanisms to estimate metrics for assessing manual dexterity in a quantitative way. Authors have proposed some hardware-software approaches to evaluate manual dexterity on surgical simulators. This paper presents IGlove, a wearable device that uses inertial sensors embedded on an elastic glove to capture hand movements. Metrics to assess manual dexterity are estimated from sensors signals using data processing and information analysis algorithms. It has been designed to be used with a neurosurgical simulator called Daubara NS Trainer, but can be easily adapted to another benchtop- and manikin-based medical simulators. The system was tested with a sample of 14 volunteers who performed a test that was designed to simultaneously evaluate their fine motor skills and the IGlove’s functionalities. Metrics obtained by each of the participants are presented as results in this work; it is also shown how these metrics are used to automatically evaluate the level of manual dexterity of each volunteer

Modelling of a real CO2 booster installation and evaluation of control strategies for heat recovery applications in supermarkets

[EN] This paper compares and quantifies the energy, environmental and economic benefits of various control strategies recovering heat from a CO2 booster system in a supermarket for space heating with the purpose of understanding its potential for displacing natural gas fuelled boilers. A theoretical steady-state model that simulates the behaviour of the CO2 system is developed and validated against field measurements obtained from an existing refrigeration system in a food-retail building located in the United Kingdom. Five heat recovery strategies are analysed by modifying the mass flow and pressure level in the condenser. The model shows that a reduction of 48% in natural-gas consumption is feasible by the installation of a de-superheater and without applying any advanced operating strategy. However, the CO2 system can fully supply the entire space-heating requirements by adopting alternative control strategies, albeit by penalising the coefficient of performance (COP) of the compressor. Results show that the best energy strategy can reduce total consumption by 32%, while the best economic strategy can reduce costs by 6%. Findings from this work suggest that heat recovery systems can bring substantial benefits to improve the overall efficiency of energy-intensive buildings; nevertheless trade-offs need to be carefully considered and analysed on a site by site basis before embarking on such initiatives.This research was supported by funds provided via the Imperial-Sainsbury's Supermarkets Ltd. partnership. This work also was supported by the UK Engineering and Physical Sciences Research Council (EPSRC) [grant number EP/P004709/1]. Emilio J. Sarabia gratefully acknowledges financial support from Universitat Politecnica de Valencia Fellowship. Data supporting this publication can be obtained on request from [email protected] Escrivà, EJ.; Acha, S.; Le Brun, N.; Soto Francés, VM.; Pinazo Ojer, JM.; Markides, C.; Shah, N. (2019). Modelling of a real CO2 booster installation and evaluation of control strategies for heat recovery applications in supermarkets. International Journal of Refrigeration. 107:288-300. https://doi.org/10.1016/j.ijrefrig.2019.08.005S28830010

Implementing an innovative consent form: the PREDICT experience

<p>Abstract</p> <p>Background</p> <p>In the setting of coronary angiography, generic consent forms permit highly variable communication between patients and physicians. Even with the existence of multiple risk models, clinicians have been unable to readily access them and thus provide patients with vague estimations regarding risks of the procedure.</p> <p>Methods</p> <p>We created a web-based vehicle, PREDICT, for embedding patient-specific estimates of risk from validated multivariable models into individualized consent documents at the point-of-care. Beginning August 2006, outpatients undergoing coronary angiography at the Mid America Heart Institute received individualized consent documents generated by PREDICT. In February 2007 this approach was expanded to all patients undergoing coronary angiography within the four Kansas City hospitals of the Saint Luke's Health System. Qualitative research methods were used to identify the implementation challenges and successes with incorporating PREDICT-enhanced consent documents into routine clinical care from multiple perspectives: administration, information systems, nurses, physicians, and patients.</p> <p>Results</p> <p>Most clinicians found usefulness in the tool (providing clarity and educational value for patients) and satisfaction with the altered processes of care, although a few cardiologists cited delayed patient flow and excessive patient questions. The responses from administration and patients were uniformly positive. The key barrier was related to informatics.</p> <p>Conclusion</p> <p>This preliminary experience suggests that successful change in clinical processes and organizational culture can be accomplished through multidisciplinary collaboration. A randomized trial of PREDICT consent, leveraging the accumulated knowledge from this first experience, is needed to further evaluate its impact on medical decision-making, patient compliance, and clinical outcomes.</p

Mapping interactions with the chaperone network reveals factors that protect against tau aggregation.

A network of molecular chaperones is known to bind proteins ('clients') and balance their folding, function and turnover. However, it is often unclear which chaperones are critical for selective recognition of individual clients. It is also not clear why these key chaperones might fail in protein-aggregation diseases. Here, we utilized human microtubule-associated protein tau (MAPT or tau) as a model client to survey interactions between ~30 purified chaperones and ~20 disease-associated tau variants (~600 combinations). From this large-scale analysis, we identified human DnaJA2 as an unexpected, but potent, inhibitor of tau aggregation. DnaJA2 levels were correlated with tau pathology in human brains, supporting the idea that it is an important regulator of tau homeostasis. Of note, we found that some disease-associated tau variants were relatively immune to interactions with chaperones, suggesting a model in which avoiding physical recognition by chaperone networks may contribute to disease

Physical distress is associated with cardiovascular events in a high risk population of elderly men

Background Self-reported health perceptions such as physical distress and quality of life are suggested independent predictors of mortality and morbidity in patients with established cardiovascular disease. This study examined the associations between these factors and three years incidence of cardiovascular events in a population of elderly men with long term hyperlipidemia. Methods We studied observational data in a cohort of 433 men aged 64–76 years from a prospective, 2 × 2 factorial designed, three-year interventional trial. Information of classical risk factors was obtained and the following questionnaires were administered at baseline: Hospital Anxiety and Depression Scale, Physical Symptom Distress Index and Life Satisfaction Index. The occurrence of cardiovascular death, myocardial infarction, cerebrovascular incidences and peripheral arterial disease were registered throughout the study period. Continuous data with skewed distribution was split into tertiles. Hazard ratios (HR) were calculated from Cox regression analyses to assess the associations between physical distress, quality of life and cardiovascular events. Results After three years, 49 cardiovascular events were registered, with similar incidence among subjects with and without established cardiovascular disease. In multivariate analyses adjusted for age, smoking, systolic blood pressure, serum glucose, HADS-anxiety and treatment-intervention, physical distress was positively associated (HR 3.1, 95% CI 1.2 – 7.9 for 3rd versus 1st tertile) and quality of life negatively associated (HR 2.6, 95% CI 1.1–5.8 for 3rd versus 1st tertile) with cardiovascular events. The association remained statistically significant only for physical distress (hazard ratio 2.8 95% CI 1.2 – 6.8, p < 0.05) when both variables were evaluated in the same model. Conclusion Physical distress, but not quality of life, was independently associated with increased risk of cardiovascular events in an observational study of elderly men predominantly without established cardiovascular disease. Trial Registration Trial registration: NCT0076401

Patient-rated health status predicts prognosis following percutaneous coronary intervention with drug-eluting stenting

Purpose: In patients treated with percutaneous coronary intervention (PCI) with the paclitaxel-eluting stent, we examined whether patient-rated health status predicts adverse clinical events. Methods: Consecutive PCI patients treated with drug-eluting stenting (N = 870; 72.2% men; mean age = 62.6 ± 11.5) completed the EQ-5D post-PCI. The EQ-5D levels were dichotomized into 'no problems' (level 1) versus 'problems' (levels 2, 3); the visual analogue scale (VAS) was dichotomized using the 25th percentile (cut-off ≤60) indicating poor health status. Patients were followed up for 1-year clinical events (death or non-fatal myocardial infarction (MI)). Results: There were 53 deaths/MIs at follow-up. The EQ-5D health status dimensions mobility (HR:2.23; 95% CI:1.25-3.97), self-care (HR:3.09; 95% CI:1.54-6.20), and self-reported health status as measured with the EQ-VAS (HR:2.94; 95% CI:1.65-5.25) were independent predictors of death/MI and added to the predictive value of a model comprised of demographic and clinical characteristics. The EQ-5D dimensions usual activities, pain/discomfort, and anxiety/depression were not associated with adverse clinical events in adjusted analysis. Conclusions: Patient-rated health status predicted adverse clinical events at 1-year follow-up in PCI patients treated with drug-eluting stenting, with the risk being more than 2-fold indepe

Novel image–novel location object recognition task sensitive to age-related cognitive decline in nondemented elderly

Traditional tests used in the clinic to identify dementia, such as the mini-mental state examination (MMSE), are useful to identify severe cognitive impairments but might be less sensitive to detect more subtle age-related cognitive changes. Previously, the novel image–novel location (NINL) object recognition test was shown to be sensitive to detect effects of apolipoprotein E4, a risk factor for developing age-related cognitive decline and Alzheimer’s disease, in nondemented elderly. In the present longitudinal study, performance on the MMSE and the NINL tests were compared over a 4-year period. Individual NINL scores over this period were highly correlated. In addition, while MMSE scores did not change over the 4-year period, NINL scores did. In a final testing session of a subset of the participants, NINL scores correlated with logical memory and word recall lists, cognitive tasks used to detect dementia in the clinic, as well as clinical dementia rating scales. These results support that the NINL might be a valuable tool to assess age-related cognitive decline

10 Myr evolution of sedimentation rates in a deep marine to non-marine foreland basin system: Tectonic and sedimentary controls (Eocene, Tremp–Jaca Basin, Southern Pyrenees, NE Spain)

The propagation of the deformation front in foreland systems is typically accompanied by the incorporation of parts of the basin into wedge-top piggy-back basins, this process is likely producing considerable changes to sedimentation rates (SR). Here we investigate the spatial-temporal evolution of SR for the Tremp–Jaca Basin in the Southern Pyrenees during its evolution from a wedge-top, foreredeep, forebulge configuration to a wedge-top stage. SR were controlled by a series of tectonic structures that influenced subsidence distribution and modified the sediment dispersal patterns. We compare the decompacted SR calculated from 12 magnetostratigraphic sections located throughout the Tremp–Jaca Basin represent the full range of depositional environment and times. While the derived long-term SR range between 9.0 and 84.5 cm/kyr, compiled data at the scale of magnetozones (0.1–2.5 Myr) yield SR that range from 3.0 to 170 cm/kyr. From this analysis, three main types of depocenter are recognized: a regional depocenter in the foredeep depozone; depocenters related to both regional subsidence and salt tectonics in the wedge-top depozone; and a depocenter related to clastic shelf building showing transgressive and regressive trends with graded and non-graded episodes. From the evolution of SR we distinguish two stages. The Lutetian Stage (from 49.1–41.2 Ma) portrays a compartmentalized basin characterized by variable SR in dominantly underfilled accommodation areas. The markedly different advance of the deformation front between the Central and Western Pyrenees resulted in a complex distribution of the foreland depozones during this stage. The Bartonian–Priabonian Stage (41.2–36.9 Ma) represents the integration of the whole basin into the wedge-top, showing a generalized reduction of SR in a mostly overfilled relatively uniform basin. The stacking of basement units in the hinterland during the whole period produced unusually high SR in the wedge-top depozoneAgència de Gestió d'Ajuts Universitaris i de Recerca, Grant/Award Number: 2017SGR596; Secretaría de Estado de Investigación, Desarrollo e Innovación, Grant/Award Number: BES-2015-073302 and CGL2014-55900-P; Swiss National Science Foundation, Grant/Award Number: 200020_18201