Integrating pressure sensor control into semi-solid extrusion 3D printing to optimize medicine manufacturing

Semi-solid extrusion (SSE) is a three-dimensional printing (3DP) process that involves the extrusion of a gel or paste-like material via a syringe-based printhead to create the desired object. In pharmaceuticals, SSE 3DP has already been used to manufacture formulations for human clinical studies. To further support its clinical adoption, the use of a pressure sensor may provide information on the printability of the feedstock material in situ and under the exact printing conditions for quality control purposes. This study aimed to integrate a pressure sensor in an SSE pharmaceutical 3D printer for both material characterization and as a process analytical technology (PAT) to monitor the printing process. In this study, three materials of different consistency were tested (soft vaseline, gel-like mass and paste-like mass) under 12 different conditions, by changing flow rate, temperature, or nozzle diameter. The use of a pressure sensor allowed, for the first time, the characterization of rheological properties of the inks, which exhibited temperature-dependent, plastic and viscoelastic behaviours. Controlling critical material attributes and 3D printing process parameters may allow a quality by design (QbD) approach to facilitate a high-fidelity 3D printing process critical for the future of personalized medicine

The atypical iron-coordination geometry of cytochrome f remains unchanged upon binding to plastocyanin, as inferred by XAS

The transient complex between cytochrome f and plastocyanin from the cyanobacterium Nostoc sp. PCC 7119 has been analysed by X-ray Absorption Spectroscopy in solution, using both proteins in their oxidized and reduced states. Fe K-edge data mainly shows that the atypical metal coordination geometry of cytochrome f, in which the N-terminal amino acid acts as an axial ligand of the heme group, remains unaltered upon binding to its redox partner, plastocyanin. This fact suggests that cytochrome f provides a stable binding site for plastocyanin and minimizes the reorganization energy required in the transient complex formation, which could facilitate the electron transfer between the two redox partners

Noncentral bimatrix variate generalised beta distributions

In this paper, we determine the density functions of nonsymmetrised doubly noncentral matrix variate beta type I and II distributions. The nonsymetrised density functions of doubly noncentral and noncentral bimatrix variate generalised beta type I and II distributions are also obtained.Comment: 14 page

Pacing strategies in men’s and women’s world record marathon performances and Olympic Games and World Championship’s winning performances

The aims of this study were to compare marathon pacing profiles between major championships winning races and world record (WR) races in men’s and women’s long-distance runners. Percentages of mean race speeds (%RS) for each 5 km section and last 2,195 m were compared between the latest 12 men’s and 8 women’s marathon WRs and the most recent 14 men’s and 14 women’s performances leading to either World Championship or Olympic Games (championships) gold medals, and between sexes in championships, through analysis of variance. Additionally, the coefficient of variation in pace (%CV) was compared through independent samples t-tests. %RS during the first 5 km was greater in WRs than championships in men (p = 0.010, d = 1.07), with a subsequent even pacing profile. More negative pacing profiles were adopted in championships than WRs in men (p < 0.001, d = 2.07). Women’s WR and championship performances were characterized by even and negative pacing profiles, with different %CV (p < 0.001, d = 1.89). Whereas marathon WRs are characterized by fast, even and sustained paces, slower paces and more negative pacing approaches with fast endspurts are adopted during winning major championship performances. These fast endspurts are specially used by women in championships

Implantación de metodología BIM en el Grado de Edificación. Modelo de taller-integrador en la asignatura de Expresión Gráfica de Tecnologías

Resumen: El concepto de BIM implica un cambio radical en la manera de afrontar el diseño arquitectónico y el proceso de ciclo de vida del proyecto y del edificio. Se trata de un sistema eficiente y abierto de comunicación y cooperación entre los distintos operadores del proceso constructivo y, por tanto, idóneo para su implantación en las Escuelas Técnicas de Ingeniería y Arquitectura. Esta comunicación defiende el reconocimiento de la metodología BIM como instrumento de trabajo colaborativo y coordinado para su aplicación en la docencia, a fin de que el flujo de información interdisciplinar sea eficiente. Se describe la experiencia de la implantación de esta metodología en el Grado de Edificación, a través de un modelo de taller-integrador en la asignatura de Expresión Gráfica de Tecnologías. Posteriormente, se recogen experiencias docentes derivadas de la innovación desarrollada, que llevan a seguir apostando por esta integración tecnológica, para cuya mejora se aportan finalmente una serie de recomendaciones. Abstract: The concept of BIM implies a radical change in the way of facing the architectural design and the life cycle process of the project and the building. It is an efficient and open system of communication and cooperation between the different operators within the construction process and, therefore, suitable for its implementation in the Technical Schools of Engineering and Architecture. This paper defends the recognition of the BIM methodology as a collaborative and coordinated tool for its application in teaching, so that the flow of interdisciplinary information is efficient. The experience of the implementation of this methodology in the Degree in Building is described, through a workshop-integrator model in the subject called Graphic Expression of Technologies. Subsequently, educational enquiries derived from the innovation developed are collected, which lead to continue supporting this technological integration. Finally, a series of recommendations for its improvement are provided

Usefulness of the Hepatocyte Growth Factor as a Predictor of Mortality in Patients Hospitalized With Acute Heart Failure Regardless of Ejection Fraction

Hepatocyte growth factor (HGF) plays a role in the improvement of cardiac function and remodeling. Their serum levels are strongly related with mortality in chronic systolic heart failure (HF). The aim of this study was to study prognostic value of HGF in acute HF, interaction with ejection fraction, renal function, and natriuretic peptides. We included 373 patients (age 76 ± 10 years, left ventricular ejection fraction [LVEF] 46 ± 14%, 48% men) consecutively admitted for acute HF. Blood samples were obtained at admission. All patients were followed up until death or close of study (>1 year, median 371 days). HGF concentrations were determined using a commercial enzyme-linked immunosorbent assay (human HGF immunoassay). The predictive power of HGF was estimated by Cox regression with calculation of Harrell C-statistic. HGF had a median of 1,942 pg/ml (interquartile rank 1,354). According to HGF quartiles, mortality rates (per 1,000 patients/year) were 98, 183, 375, and 393, respectively (p <0.001). In Cox regression analysis, HGF (hazard ratio1SD = 1.5, 95% confidence interval 1.1 to 2.1, p = 0.002) and N-terminal pro b-type natriuretic peptide (NT-proBNP; hazard ratio1SD = 1.8, 95% confidence interval 1.2 to 2.6, p = 0.002) were independent predictors of mortality. Interaction between HGF and LVEF, origin, and renal function was nonsignificant. The addition of HGF improved the predictive ability of the models (C-statistic 0.768 vs 0.741, p = 0.016). HGF showed a complementary value over NT-proBNP (p = 0.001): mortality rate was 490 with both above the median versus 72 with both below. In conclusion, in patients with acute HF, serum HGF concentrations are elevated and identify patients at higher risk of mortality, regardless of LVEF, ischemic origin, or renal function. HGF had independent and additive information over NT-proBNP

No additional value of conventional and high-sensitivity cardiac troponin over clinical scoring systems in the differential diagnosis of type 1 versus type 2 myocardial infarction.

BACKGROUND: The distinction of type 1 and type 2 myocardial infarction (MI) is of major clinical importance. Our aim was to evaluate the diagnostic ability of absolute and relative conventional cardiac troponin I (cTnI) and high-sensitivity cardiac troponin T (hs-cTnT) in the distinction between type 1 and type 2 MI in patients presenting at the emergency department with non-ST-segment elevation acute chest pain within the first 12 h. METHODS: We measured cTnI (Dimension Vista) and hs-cTnT (Cobas e601) concentrations at presentation and after 4 h in 200 patients presenting with suspected acute MI. The final diagnosis, based on standard criteria, was adjudicated by two independent cardiologists. RESULTS: One hundred and twenty-five patients (62.5%)were classified as type 1 MI and 75 (37.5%) were type 2 MI. In a multivariable setting, age (relative risk [RR]=1.43, p=0.040), male gender (RR=2.22, p=0.040), T-wave inversion (RR=8.51, p<0.001), ST-segment depression (RR=8.71, p<0.001) and absolute delta hs-cTnT (RR=2.10, p=0.022) were independently associated with type 1 MI. In a receiver operating characteristic curve analysis, the discriminatory power of absolute delta cTnI and hs-cTnT was significantly higher compared to relative c-TnI and hs-cTnT changes. The additive information provided by cTnI and hs-cTnT over and above the information provided by the "clinical" model was only marginal. CONCLUSIONS: The diagnostic information provided by serial measurements of conventional or hs-cTnT is not better than that yielded by a simple clinical scoring model. Absolute changes are more informative than relative troponin changes

Hazard-consistent response spectra in the Region of Murcia (Southeast Spain): comparison to earthquake-resistant provisions

Hazard-consistent ground-motion characterisations of three representative sites located in the Region of Murcia (southeast Spain) are presented. This is the area where the last three damaging events in Spain occurred and there is a significant amount of data for comparing them with seismic hazard estimates and earthquake-resistant provisions. Results of a probabilistic seismic hazard analysis are used to derive uniform hazard spectra (UHS) for the 475-year return period, on rock and soil conditions. Hazard deaggregation shows that the largest hazard contributions are due to small, local events for short-period target motions and to moderate, more distant events for long-period target motions. For each target motion and site considered, the associated specific response spectra (SRS) are obtained. It is shown that the combination of two SRS, for short- and long-period ground motions respectively, provides a good approximation to the UHS at each site. The UHS are compared to design response spectra contained in current Spanish and European seismic codes for the 475-year return period. For the three sites analysed, only the Eurocode 8 (EC8) type 2 spectrum captures the basic shape of the UHS (and not the EC8 type 1, as could be expected a priori). An alternative response spectrum, anchored at short- and long-period accelerations, is tested, providing a close match to the UHS spectra at the three sites. Results underline the important contribution of the frequent, low-to-moderate earthquakes that characterize the seismicity of this area to seismic hazard (at the 475-year return period)