Using electronic health record data to develop inpatient mortality predictive model: Acute Laboratory Risk of Mortality Score (ALaRMS)

Objective: Using numeric laboratory data and administrative data from hospital electronic health record (EHR) systems, to develop an inpatient mortality predictive model. Methods: Using EHR data of 1 428 824 adult discharges from 70 hospitals in 2006–2007, we developed the Acute Laboratory Risk of Mortality Score (ALaRMS) using age, gender, and initial laboratory values on admission as candidate variables. We then added administrative variables using the Agency for Healthcare Research and Quality (AHRQ)'s clinical classification software (CCS) and comorbidity software (CS) as disease classification tools. We validated the model using 770 523 discharges in 2008. Results: Mortality predictors with ORs >2.00 included age, deranged albumin, arterial pH, bands, blood urea nitrogen, oxygen partial pressure, platelets, pro-brain natriuretic peptide, troponin I, and white blood cell counts. The ALaRMS model c-statistic was 0.87. Adding the CCS and CS variables increased the c-statistic to 0.91. The relative contributions were 69% (ALaRMS), 25% (CCS), and 6% (CS). Furthermore, the integrated discrimination improvement statistic demonstrated a 127% (95% CI 122% to 133%) overall improvement when ALaRMS was added to CCS and CS variables. In contrast, only a 22% (CI 19% to 25%) improvement was seen when CCS and CS variables were added to ALaRMS. Conclusions: EHR data can generate clinically plausible mortality predictive models with excellent discrimination. ALaRMS uses automated laboratory data widely available on admission, providing opportunities to aid real-time decision support. Models that incorporate laboratory and AHRQ's CCS and CS variables have utility for risk adjustment in retrospective outcome studies

On the uniqueness of the surface sources of evoked potentials

The uniqueness of a surface density of sources localized inside a spatial region $R$ and producing a given electric potential distribution in its boundary $B_0$ is revisited. The situation in which $R$ is filled with various metallic subregions, each one having a definite constant value for the electric conductivity is considered. It is argued that the knowledge of the potential in all $B_0$ fully determines the surface density of sources over a wide class of surfaces supporting them. The class can be defined as a union of an arbitrary but finite number of open or closed surfaces. The only restriction upon them is that no one of the closed surfaces contains inside it another (nesting) of the closed or open surfaces.Comment: 16 pages, 5 figure

Evaluación agronómica y productiva de diferentes soluciones nutritivas, en cultivo sin suelo, berenjena en ciclo de primavera y otoño

Las experiencias se desarrollaron en un túnel grande con cubierta de polietileno térmico, bajo sistema de cultivo sin suelo, utilizando fibra de coco como sustrato. Se comparó la respuesta de la berenjena (Solanum melongena) a 3 soluciones nutritivas con niveles crecientes de nitratos, fosfatos, amonio, potasio, calcio y magnesio. La dosis media se utilizó para formular una 4ª solución nutritiva, a la que se le añadió una enmienda orgánica húmica líquida. Para el estudio se utilizó berenjena del tipo intermedio cv. Cristal, en dos ciclos de cultivo distintos: primavera y otoño. Aunque en otoño se produjo una helada, acaecida en el mes de noviembre, los resultados productivos siguieron la pauta de los obtenidos en el ciclo de primavera. La menor producción precoz y final se obtuvo con la concentración de iones más baja. En el ciclo de primavera y otoño la dosis baja dio lugar a frutos de un menor calibre, aunque en este último ciclo no se detectaron diferencias significativas a nivel estadístico. El crecimiento de la planta también fue menor en ambos ciclos, para la concentración menor. No hubo diferencias en rendimiento, peso medio, ni desarrollo de la planta, entre la dosis más enriquecida y la intermedia, para ninguno de los ciclos estudiados. No se apreciaron diferencias entre la dosis intermedia y la adición de enmienda orgánica líquida, en producción, desarrollo de la planta ni en peso medio de los frutos en ninguno de los ciclos estudiados, y únicamente se apreció una mayor susceptibilidad a la helada, en la parcela a la que se le adicionó la enmienda orgánica líquida. Se midió el consumo de solución nutritiva, siendo el menor en ambos ciclos el correspondiente a la dosis D3, aunque la mayor eficiencia de riego se obtuvo en el ciclo de primavera con la dosis D1

Rhomboid domain containing 2 (RHBDD2): A novel cancer-related gene over-expressed in breast cancer

In the course of breast cancer global gene expression studies, we identified an uncharacterized gene known as RHBDD2 (Rhomboid domain containing 2) to be markedly over-expressed in primary tumors from patients with recurrent disease. In this study, we identified RHBDD2 mRNA and protein expression significantly elevated in breast carcinomas compared with normal breast samples as analyzed by SAGE (n=46) and immunohistochemistry (n=213). Interestingly, specimens displaying RHBDD2 over-expression were predominantly advanced stage III breast carcinomas (p=0.001). Western-blot, RT-PCR and cDNA sequencing analyses allowed us to identify two RHBDD2 alternatively spliced mRNA isoforms expressed in breast cancer cell lines. We further investigated the occurrence and frequency of gene amplification and over-expression affecting RHBDD2 in 131 breast samples. RHBDD2 gene amplification was detected in 21% of 98 invasive breast carcinomas analyzed. However, no RHBDD2 amplification was detected in normal breast tissues (n=17) or breast benign lesions (n=16) (p=0.014). Interestingly, siRNA mediated silencing of RHBDD2 expression results in a decrease of MCF7 breast cancer cells proliferation compared with the corresponding controls (p=0.001). In addition, analysis of publicly available gene expression data showed a strong association between high RHBDD2 expression and decreased overall survival (p=0.0023), relapsefree survival (p= 0.0013), and metastasis-free interval (p=0.006) in patients with primary ERnegative breast carcinomas. In conclusion, our findings suggest that RHBDD2 over-expression behaves as an indicator of poor prognosis and may play a role facilitating breast cancer progression

Focal, remote-controlled, chronic chemical modulation of brain microstructures

Direct delivery of fluid to brain parenchyma is critical in both research and clinical settings. This is usually accomplished through acutely inserted cannulas. This technique, however, results in backflow and significant dispersion away from the infusion site, offering little spatial or temporal control in delivering fluid. We present an implantable, MRI-compatible, remotely controlled drug delivery system for minimally invasive interfacing with brain microstructures in freely moving animals. We show that infusions through acutely inserted needles target a region more than twofold larger than that of identical infusions through chronically implanted probes due to reflux and backflow. We characterize the dynamics of in vivo infusions using positron emission tomography techniques. Volumes as small as 167 nL of copper-64 and fludeoxyglucose labeled agents are quantified. We further demonstrate the importance of precise drug volume dosing to neural structures to elicit behavioral effects reliably. Selective modulation of the substantia nigra, a critical node in basal ganglia circuitry, via muscimol infusion induces behavioral changes in a volume-dependent manner, even when the total dose remains constant. Chronic device viability is confirmed up to 1-y implantation in rats. This technology could potentially enable precise investigation of neurological disease pathology in preclinical models, and more efficacious treatment in human patients. Keywords: brain; drug delivery; substantia nigra; neural implant; PETNational Institutes of Health (U.S.) (Grant R01 EB016101)National Institute of Biomedical Imaging and Bioengineering (U.S.) (Grant R01 EB016101)National Cancer Institute (U.S.) (Grant P30-CA14051

Impact of Age on Consent in a Geriatric Orthopaedic Trauma Patient Population.

Introduction: Persistent misconceptions of frailty and dementia in geriatric patients impact physician-patient communication and leave patients vulnerable to disempowerment. Physicians may inappropriately focus the discussion of treatment options to health care proxies instead of patients. Our study explores the consenting process in a decision-making capable orthogeriatric trauma patient population to determine if there is a relationship between increased patient age and surgical consent by health care proxy. Methods: Patients aged 65 and older who underwent operative orthopaedic fracture fixation between 1 of 2 Level 1 Trauma Centers were retrospectively reviewed. Decision-making capable status was defined as an absence of patient history of cognitive impairment and a negative patient pre-surgical Confusion Assessment Method (CAM) and Mini-Cog Assessment screen. Provider of surgical consent was the main outcome and was determined by signature on the consent form. Results: 510 patients were included, and 276 (54.1%) patients were deemed capable of consent. In 27 (9.8%) of 276 decision-capable patients, physicians obtained consent from health care proxies. 20 of these 27 patients (74.1%) were 80 years of age or older. However, in patients aged 70 to 79, only 7 health care proxies provided consent. (p = 0.07). For every unit increase in age, the log odds of proxy consent increased by .0008 (p \u3c 0.001). Age (p \u3c 0.001), income level (p = 0.03), and physical presence of proxy at consult (p \u3c 0.001) were factors associated with significantly increased utilization of health care proxy provided consent. Language other than English was a significant predictor of proxy-provided consent (p = 0.035). 48 (22%) decision-making incapable patients provided their own surgical consent. Discussion: The positive linear association between age and health care proxy provided consent in cognitively intact geriatric orthopaedic patients indicates that increased patient age impacts the consenting process. Increased physician vigilance and adoption of institutional consenting guidelines can reinforce appropriate respect of geriatric patients\u27 consenting capacity

Time Variation of the Fine Structure Constant Driven by Quintessence

There are indications from the study of quasar absorption spectra that the fine structure constant $\alpha$ may have been measurably smaller for redshifts $z>2.$ Analyses of other data ($^{149}$Sm fission rate for the Oklo natural reactor, variation of $^{187}$Re $\beta$-decay rate in meteorite studies, atomic clock measurements) which probe variations of $\alpha$ in the more recent past imply much smaller deviations from its present value. In this work we tie the variation of $\alpha$ to the evolution of the quintessence field proposed by Albrecht and Skordis, and show that agreement with all these data, as well as consistency with WMAP observations, can be achieved for a range of parameters. Some definite predictions follow for upcoming space missions searching for violations of the equivalence principle.Comment: Final version, to be published in Phys Rev

Comportamiento agronómico de diferentes cvs. de alcachofa multiplicadas por semilla

Se estudia el comportamiento agronómico y las características morfológicas de una colección de 12 cultivares (cvs) de alcachofa (Cynara scolymus) multiplicadas por semilla, comparadas con los cvs. Blanca de Tudela y Violeta de Provence, de multiplicación vegetativa. Los cvs. multiplicados por semilla se sembraron el 14 de junio de 2005, transplantando toda la experiencia el 1 de agosto. Todas las plantas fueron sometidas a tres tratamientos sucesivos con ácido giberélico con una concentración de 30 ppm. con abono foliar al 0,1%, aplicaciones que se realizaron los días 20 de septiembre, 5 y 20 de octubre. El mayor rendimiento comercial se obtuvo con el cv. Madrigal que fue también el más tardío. La mayor precocidad correspondió al cv. Blanca de Tudela, sin diferencias estadísticamente significativas (e.s.) en la producción acumulada en enero respecto a los cvs. A-106, Victoria y Lorca. El peso medio de los capítulos osciló entre los 184 y 183 g de los cvs. AR-1 y Madrigal durante el mes de marzo, frente a 97 y 99 g de los cvs. Victoria y Lorca, en ese mismo mes

Three-dimensional cardiac fibre disorganization as a novel parameter for ventricular arrhythmia stratification after myocardial infarction

Aims: Myocardial infarction (MI) alters cardiac fibre organization with unknown consequences on ventricular arrhythmia. We used diffusion tensor imaging (DTI) of three-dimensional (3D) cardiac fibres and scar reconstructions to identify the main parameters associated with ventricular arrhythmia inducibility and ventricular tachycardia (VT) features after MI. Methods and results: Twelve pigs with established MI and three controls underwent invasive electrophysiological characterization of ventricular arrhythmia inducibility and VT features. Animal-specific 3D scar and myocardial fibre distribution were obtained from ex vivo high-resolution contrast-enhanced T1 mapping and DTI sequences. Diffusion tensor imaging-derived parameters significantly different between healthy and scarring myocardium, scar volumes, and left ventricular ejection fraction (LVEF) were included for arrhythmia risk stratification and correlation analyses with VT features. Ventricular fibrillation (VF) was the only inducible arrhythmia in 4 out of 12 infarcted pigs and all controls. Ventricular tachycardia was also inducible in the remaining eight pigs during programmed ventricular stimulation. A DTI-based 3D fibre disorganization index (FDI) showed higher disorganization within dense scar regions of VF-only inducible pigs compared with VT inducible animals (FDI: 0.36; 0.36-0.37 vs. 0.32; 0.26-0.33, respectively, P = 0.0485). Ventricular fibrillation induction required lower programmed stimulation aggressiveness in VF-only inducible pigs than VT inducible and control animals. Neither LVEF nor scar volumes differentiated between VF and VT inducible animals. Re-entrant VT circuits were localized within areas of highly disorganized fibres. Moreover, the FDI within heterogeneous scar regions was associated with the median VT cycle length per animal (R2 = 0.5320). Conclusion: The amount of scar-related cardiac fibre disorganization in DTI sequences is a promising approach for ventricular arrhythmia stratification after MI.The CNIC (Madrid, Spain) is supported by the Ministry of Science, Innovation and Universities and the Pro CNIC Foundation. The CNIC and the BSC (Barcelona, Spain) are Severo Ochoa Centers of Excellence (SEV-2015-0505 and SEV-2011-0067, respectively). This study was supported by grants from Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional (RD12/0042/0036, CB16/11/00458), Spanish Ministry of Science, Innovation and Universities (SAF2016-80324-R, PI16/02110, and DTS17/00136), and by the European Commission [ERA-CVD Joint Call (JTC2016/APCIN-ISCIII-2016), grant#AC16/00021]. The study was also partially supported by the Fundacion Interhospitalaria para la Investigacion Cardiovascular (FIC, Madrid, Spain), the Spanish Society of Cardiology (Dr. Pedro Zarco award) and the Heart Rhythm section of the Spanish Society of Cardiology (DFR). J.J. is supported by R01 Grant HL122352 from the National Heart Lung and Blood Institute, USA National Institutes of Health. J.A.S. is funded by the CompBioMed project, H2020-EU.1.4.1.3 European Union's Horizon 2020 research and innovation programme, grant#675451. D.G.L. has received financial support through the 'la Caixa' Fellowship Grant for Doctoral Studies, 'la Caixa' Banking Foundation, Barcelona, Spain.S