State of Harmonization of 24 Serum Albumin Measurement Procedures and Implications for Medical Decisions

BACKGROUND: Measurements of serum and plasma albumin are widely used in medicine, including as indicators of quality of patient care in renal dialysis centers. METHODS: Pools were prepared from residual patient serum (n = 50) and heparin plasma (n = 48) from patients without renal disease, and serum from patients with kidney failure before hemodialysis (n = 53). Albumin was measured in all samples and in ERM-DA470k/IFCC reference material (RM) by 3 immunochemical, 9 bromcresol green (BCG), and 12 bromcresol purple (BCP) methods. RESULTS: Two of 3 immunochemical procedures, 5 of 9 BCG, and 10 of 12 BCP methods recovered the RM value within its uncertainty. One immunochemical and 3 BCG methods were biased vs the RM value. Random error components were small for all measurement procedures. The Tina-quant immunochemical method was chosen as the reference measurement procedure based on recovery and results of error analyses. Mean biases for BCG vs Tina-quant were 1.5% to 13.9% and were larger at lower albumin concentrations. BCP methods\u27 mean biases were -5.4% to 1.2% irrespective of albumin concentration. Biases for plasma samples were generally higher than for serum samples for all method types. For most measurement procedures, biases were lower for serum from patients on hemodialysis vs patients without kidney disease. CONCLUSIONS: Significant differences among immunochemical, BCG, and BCP methods compromise interpretation of serum. albumin results. Guidelines and calculations for clinical management of kidney and other diseases must consider the method used for albumin measurement until harmonization can be achieved

Statistical analysis of the induced Basel 2006 earthquake sequence: introducing a probability-based monitoring approach for Enhanced Geothermal Systems

Geothermal energy is becoming an important clean energy source, however, the stimulation of a reservoir for an Enhanced Geothermal System (EGS) is associated with seismic risk due to induced seismicity. Seismicity occurring due to the water injection at depth have to be well recorded and monitored. To mitigate the seismic risk of a damaging event, an appropriate alarm system needs to be in place for each individual experiment. In recent experiments, the so-called traffic-light alarm system, based on public response, local magnitude and peak ground velocity, was used. We aim to improve the pre-defined alarm system by introducing a probability-based approach; we retrospectively model the ongoing seismicity in real time with multiple statistical forecast models and then translate the forecast to seismic hazard in terms of probabilities of exceeding a ground motion intensity level. One class of models accounts for the water injection rate, the main parameter that can be controlled by the operators during an experiment. By translating the models into time-varying probabilities of exceeding various intensity levels, we provide tools which are well understood by the decision makers and can be used to determine thresholds non-exceedance during a reservoir stimulation; this, however, remains an entrepreneurial or political decision of the responsible project coordinators. We introduce forecast models based on the data set of an EGS experiment in the city of Basel. Between 2006 December 2 and 8, approximately 11 500 m3 of water was injected into a 5-km-deep well at high pressures. A six-sensor borehole array, was installed by the company Geothermal Explorers Limited (GEL) at depths between 300 and 2700 m around the well to monitor the induced seismicity. The network recorded approximately 11 200 events during the injection phase, more than 3500 of which were located. With the traffic-light system, actions where implemented after an ML 2.7 event, the water injection was reduced and then stopped after another ML 2.5 event. A few hours later, an earthquake with ML 3.4, felt within the city, occurred, which led to bleed-off of the well. A risk study was later issued with the outcome that the experiment could not be resumed. We analyse the statistical features of the sequence and show that the sequence is well modelled with the Omori-Utsu law following the termination of water injection. Based on this model, the sequence will last 31+29/−14 years to reach the background level. We introduce statistical models based on Reasenberg and Jones and Epidemic Type Aftershock Sequence (ETAS) models, commonly used to model aftershock sequences. We compare and test different model setups to simulate the sequences, varying the number of fixed and free parameters. For one class of the ETAS models, we account for the flow rate at the injection borehole. We test the models against the observed data with standard likelihood tests and find the ETAS model accounting for the on flow rate to perform best. Such a model may in future serve as a valuable tool for designing probabilistic alarm systems for EGS experiment

Influência da umidade inicial na produção de holocelulases por espécies de Lentinula em biomassa de Eucalyptus benthamii.

Editores técnicos: Marcílio José Thomazini, Elenice Fritzsons, Patrícia Raquel Silva, Guilherme Schnell e Schuhli, Denise Jeton Cardoso, Luziane Franciscon. EVINCI. Resumos

Dose-controlled tDCS reduces electric field intensity variability at a cortical target site

Background: Variable effects limit the efficacy of transcranial direct current stimulation (tDCS) as a research and therapeutic tool. Conventional application of a fixed-dose of tDCS does not account for inter-individual differences in anatomy (e.g. skull thickness), which varies the amount of current reaching the brain. Individualised dose-control may reduce the variable effects of tDCS by reducing variability in electric field (E-field) intensities at a cortical target site. / Objective: To characterise the variability in E-field intensity at a cortical site (left primary motor cortex; M1) and throughout the brain for conventional fixed-dose tDCS, and individualised dose-controlled tDCS. / Methods: The intensity and distribution of the E-field during tDCS was estimated using Realistic Volumetric Approach to Simulate Transcranial Electric Stimulation (ROAST) in 50 individual brain scans taken from the Human Connectome Project, for fixed-dose tDCS (1 mA & 2 mA) and individualised dose-controlled tDCS targeting left M1. / Results: With a fixed-dose (1 mA & 2 mA), E-field intensity in left M1 varied by more than 100% across individuals, with substantial variation observed throughout the brain as well. Individualised dose-control ensured the same E-field intensity was delivered to left M1 in all individuals. Its variance in other regions of interest (right M1 and area underneath the electrodes) was comparable with fixed- and individualised-dose. / Conclusions: Individualised dose-control can eliminate the variance in E-field intensities at a cortical target site. Assuming that the current delivered to the brain directly determines its physiological and behavioural consequences, this approach may allow for reducing the known variability of tDCS effect

Self-reported quality of care for older adults from 2004 to 2011: a cohort study

Background: little is known about changes in the quality of medical care for older adults over time. Objective: to assess changes in technical quality of care over 6 years, and associations with participants' characteristics. Design: a national cohort survey covering RAND Corporation-derived quality indicators (QIs) in face-to-face structured interviews in participants' households. Participants: a total of 5,114 people aged 50 or more in four waves of the English Longitudinal Study of Ageing. Methods: the percentage achievement of 24 QIs in 10 general medical and geriatric clinical conditions was calculated for each time point, and associations with participants' characteristics were estimated using logistic regression. Results: participants were eligible for 21,220 QIs. QI achievement for geriatric conditions (cataract, falls, osteoarthritis and osteoporosis) was 41% [95% confidence interval (CI): 38–44] in 2004–05 and 38% (36–39) in 2010–11. Achievement for general medical conditions (depression, diabetes mellitus, hypertension, ischaemic heart disease, pain and cerebrovascular disease) improved from 75% (73–77) in 2004–05 to 80% (79–82) in 2010–11. Achievement ranged from 89% for cerebrovascular disease to 34% for osteoarthritis. Overall achievement was lower for participants who were men, wealthier, infrequent alcohol drinkers, not obese and living alone. Conclusion: substantial system-level shortfalls in quality of care for geriatric conditions persisted over 6 years, with relatively small and inconsistent variations in quality by participants' characteristics. The relative lack of variation by participants' characteristics suggests that quality improvement interventions may be more effective when directed at healthcare delivery systems rather than individuals

The A-kinase anchoring protein GSKIP regulates GSK3β activity and controls palatal shelf fusion in mice

A-kinase anchoring proteins (AKAPs) represent a family of structurally diverse proteins, all of which bind protein kinase A (PKA). A member of this family is Glycogen synthase kinase 3{beta} (GSK3{beta}) interaction protein (GSKIP). GSKIP interacts with PKA and also directly with GSK3{beta}. The physiological function of the GSKIP protein in vivo is unknown. We developed and characterized a conditional knockout mouse model and found that GSKIP deficiency caused lethality at birth. Embryos obtained through Caesarean section at embryonic day E18.5 were cyanotic, suffered from respiratory distress, and failed to initiate breathing properly. Additionally, all GSKIP-deficient embryos showed an incomplete closure of the palatal shelves accompanied by a delay in ossification along the fusion area of secondary palatal bones. On the molecular level, GSKIP deficiency resulted in decreased phosphorylation of GSK3{beta} at Ser9 starting early in development (E 10.5), leading to enhanced GSK3{beta} activity. At embryonic day 18.5 GSK3{beta} activity decreased to levels close to that of wild type. Our findings reveal a novel, crucial role for GSKIP in the coordination of GSK3{beta} signaling in palatal shelf fusion

Statistical Mechanics of Aggregation and Crystallization for Semiflexible Polymers

By means of multicanonical computer simulations, we investigate thermodynamic properties of the aggregation of interacting semiflexible polymers. We analyze a mesoscopic bead-stick model, where nonbonded monomers interact via Lennard-Jones forces. Aggregation turns out to be a process, in which the constituents experience strong structural fluctuations, similar to peptides in coupled folding-binding cluster formation processes. In contrast to a recently studied related proteinlike hydrophobic-polar heteropolymer model, aggregation and crystallization are separate processes for a homopolymer with the same small bending rigidity. Rather stiff semiflexible polymers form a liquid-crystal-like phase, as expected. In analogy to the heteropolymer study, we find that the first-order-like aggregation transition of the complexes is accompanied by strong system-size dependent hierarchical surface effects. In consequence, the polymer aggregation is a phase-separation process with entropy reduction.Comment: 5 pages, 3 figures, 1 tabl

Cross-cultural adaptation and validation of the voice handicap index into Italian

Objectives. To evaluate the internal consistency, reliability, and clinical validity of the Italian version of the Voice Handicap Index (VHI). Study Design. Cross-sectional survey study was carried out. Methods. One hundred and seventy-five patients with voice disorders, divided in four groups according to the etiology of the disease (neurogenic, structural, functional, and inflammatory), and 84 asymptomatic subjects were included in the study. Internal consistency was analyzed through Cronbach alpha coefficient. For the VHI test-retest reliability analysis, the Italian VHI was filled twice by 56 patients and 56 control subjects. The test-retest reliability was assessed through the Pearson correlation test. For the clinical validity assessment, the scores obtained in the pathological group were compared with those found in asymptomatic individuals through the Kruskal-Wallis test. Also, the correlation between VHI and the grade of voice disorder was assessed. Finally, the effect of age and gender on overall VHI and its three subscales was analyzed. Results. Optimal internal consistency was found (alpha = 0.93); the test-retest reliability in both groups was high (r > 0.86). Nonparametric Kruskal-Wallis analysis of variance for the overall VHI score and its three domains revealed a significant main effect for group (P = 0.000). The control group scored significantly lower than the four groups of voice-disordered patients. The overall VHI score positively correlated with the grade of voice disorder (r = 0.43). In the voice-disorder group, age and gender were not correlated to the overall VHI score and to their three domains. Conclusion. The Italian VHI is highly reproducible, and exhibits excellent clinical validity