Diagnostic yield of bone marrow aspiration in paediatric primary immune thrombocytopenia: impact of evolution and adherence to medical guidelines over the last 25 years.

The aim of this study is to analyse the diagnostic value of bone marrow aspiration (BMA) in a retrospective cohort of patients with suspected immune thrombocytopaenia (ITP). We further measure changes in the percentage of patients who underwent this study and whether testing or not was in accordance with current guidelines at the time of diagnosis. We conducted a chart review of 243 patients with ITP who underwent follow-up in our institution between 1995 and 2022. The patients were divided into historical cohorts based on the practice guidelines of the Spanish Society of Pediatric Hematology and Oncology (SEHOP) and the American Society of Hematology (ASH) in place at the time of follow-up. For each case, time of disease presentation or initial diagnosis was defined as that which occurred in the first 72 h following disease onset. Based on data from the historical cohorts studied, we observed a lower total number of BMAs at diagnosis over time (p < 0.005). A gradual reduction was seen in the number of BMAs with the introduction of guidelines, including a progressively lower number of BMAs performed without indication (p < 0.05). Subsequent to the initial diagnosis, the procedure played a decisive role in only 2 patients (0.58%), allowing for a diagnosis of acquired aplastic anaemia in both cases. In both of them on diagnosis, BMA did not appear to be indicated, although subsequent analysis after 72 h raised suspicion of bone marrow failure. CONCLUSION: BMA at presentation did not significantly alter the diagnosis in our cohort of patients with an initial suspicion of ITP, although the procedure was decisive in diagnosing 2 cases of acquired aplastic anaemia during the subsequent course of the disease. Regarding the number of aspirations performed, our findings show that increased physician compliance with current guidelines reduced the rate of unnecessary BMAs. WHAT IS KNOWN: • BMA is a supplementary test for the diagnosis of ITP. • The usefulness of this invasive diagnostic procedure is not clearly stated in current guidelines. WHAT IS NEW: • Adjustments to scientific guidelines have led to a reduction in the number of BMAs performed on our patients with suspected ITP in the last 27 years. • While the risks and benefits of BMA at the time of diagnosis are unclear in patients with suspected ITP, the procedure does not contribute significant information to support the diagnosis.

Optical Genome Mapping as a New Tool to Overcome Conventional Cytogenetics Limitations in Patients with Bone Marrow Failure.

Cytogenetic studies are essential in the diagnosis and follow up of patients with bone marrow failure syndromes (BMFSs), but obtaining good quality results is often challenging due to hypocellularity. Optical Genome Mapping (OGM), a novel technology capable of detecting most types chromosomal structural variants (SVs) at high resolution, is being increasingly used in many settings, including hematologic malignancies. Herein, we compared conventional cytogenetic techniques to OGM in 20 patients with diverse BMFSs. Twenty metaphases for the karyotype were only obtained in three subjects (15%), and no SVs were found in any of the samples. One patient with culture failure showed a gain in chromosome 1q by fluorescence in situ hybridization, which was confirmed by OGM. In contrast, OGM provided good quality results in all subjects, and SVs were detected in 14 of them (70%), mostly corresponding to cryptic submicroscopic alterations not observed by standard techniques. Therefore, OGM emerges as a powerful tool that provides complete and evaluable results in hypocellular BMFSs, reducing multiple tests into a single assay and overcoming some of the main limitations of conventional techniques. Furthermore, in addition to confirming the abnormalities detected by conventional techniques, OGM found new alterations beyond their detection limits.

Accuracy of Two Continuous Glucose Monitoring Devices During Aerobic and High-Intensity Interval Training in Individuals with Type 1 Diabetes.

Background: This study aimed to evaluate the accuracy of Dexcom G6 (DG6) and FreeStyle Libre-2 (FSL2) during aerobic training and high-intensity interval training (HIIT) in individuals with type 1 diabetes. Methods: Twenty-six males (mean age 29.3 ± 6.3 years and mean duration of diabetes 14.9 ± 6.1 years) participated in this study. Interstitial glucose levels were measured using DG6 and FSL2, while plasma glucose levels were measured every 10 min using YSI 2500 as the reference for glucose measurements in this study. The measurements began 20 min before the start of exercise and continued for 20 min after exercise. Seven measurements were taken for each subject and exercise. Results: Both DG6 and FSL2 devices showed significant differences compared to YSI glucose data for both aerobic and HIIT exercises. Continuous glucose monitoring (CGM) devices exhibited superior performance during HIIT than aerobic training, with DG6 showing a mean absolute relative difference of 14.03% versus 31.98%, respectively. In the comparison between the two devices, FSL2 demonstrated significantly higher effectiveness in aerobic training, yet its performance was inferior to DG6 during HIIT. According to the 40/40 criteria, both sensors performed similarly, with marks over 93% for all ranges and both exercises, and above 99% for HIIT and in the >180 mg/dL range, which is in accordance with FDA guidelines. Conclusions: The findings suggest that the accuracy of DG6 and FSL2 deteriorates during and immediately after exercise but remains acceptable for both devices during HIIT. However, accuracy is compromised with DG6 during aerobic exercise. This study is the first to compare the accuracy of two CGMs, DG6, and FSL2, during two exercise modalities, using plasma glucose YSI measurements as the gold standard for comparisons. It was registered at clinicaltrials.gov (NCT06080542).

Evaluación del incidentaloma adrenal / Evaluation of the adrenal incidentaloma

An adrenal incidentaloma is a mass detected by chance on an imaging test. It is important that general practitioners know how to manage it, since it is an increasingly frequent finding. It is necessary to assess whether it presents malignant characteristics in imaging tests and the possibility of subclinical hormonal hyperfunction. The basic hormonal study evaluates the overproduction of catecholamines with a study of fractionated metanephrines in plasma or in 24-hour urine, hypercortisolism with a dexamethasone suppression test, and, in patients with hypertension or hypokalemia, the possibility of hyperaldosteronism with determination of the plasma aldosterone/renin ratio. Surgical treatment is indicated in hyperfunctioning nodules, those with suspicion of malignancy or in large ones. (AU)

El incidentaloma adrenal es una masa detectada de forma casual en una prueba de imagen. Es importante que los médicos generalistas conozcan su manejo, ya que es un hallazgo cada vez más frecuente. Hay que valorar si presenta características de malignidad en las pruebas de imagen y la posibilidad de hiperfuncionalidad hormonal subclínica.El estudio hormonal básico evalúa la sobreproducción de catecolaminas con un estudio de metanefrinas fraccionadas en plasma o en orina de 24 horas, el hipercortisolismo con una prueba de frenación con dexametasona y, en pacientes con hipertensión o hipopotasemia, la posibilidad de hiperaldosteronismo con la determinación del cociente aldosterona/renina plasmáticas. El tratamiento quirúrgico está indicado en nódulos hiperfuncionantes, con sospecha de malignidad o en aquellos de gran tamaño. (AU)

No Evidence that CD33 rs12459419 Polymorphism Predicts Gemtuzumab Ozogamicin Response in Consolidation Treatment of Acute Myeloid Leukemia Patients: Experience of the PETHEMA Group.

Gemtuzumab ozogamicin (GO) is a conjugate of a monoclonal antibody and calicheamicin, which has been reapproved for the treatment of acute myeloid leukemia (AML). AML patients with the CD33 rs12459419 CC genotype might benefit from the addition of GO to intensive treatment in contrast to patients with CT/TT genotypes. Nevertheless, contradictory results have been reported. We sought to shed light on the prediction of GO response in AML patients with rs12459419 polymorphism who were treated with GO in the consolidation (n = 70) or reinduction (n = 20) phase. The frequency distribution of the rs12459419 polymorphism in the complete cohort of patients was 44.4% (n = 40), 50% (n = 45), and 5.6% (n = 5) for CC, CT, and TT genotypes, respectively. Regarding the patients treated with GO for consolidation, we performed a Kaplan-Meier analysis of overall survival and relapse-free survival according to the rs12459419 polymorphism (CC vs. CT/TT patients) and genetic risk using the European Leukemia Net (ELN) 2010 risk score. We also carried out a Cox regression analysis for the prediction of overall survival, with age and ELN 2010 as covariates. We found no statistical significance in the univariate or multivariate analysis. Additionally, we performed a global Kaplan-Meier analysis for the patients treated with GO for reinduction and did not find significant differences; however, our cohort was too small to draw any conclusion from this analysis. The use of GO in consolidation treatment is included in the approval of the compound; however, evidence regarding its efficacy in this setting is lacking. Rs12459419 polymorphism could help in the selection of patients who might benefit from GO. Regrettably, in our cohort, the rs12459419 polymorphism does not seem to be an adequate tool for the selection of patients who might benefit from the addition of GO in consolidation cycles.

Relaxation Dynamics of Biomass-Derived Copolymers With Promising Gas-Barrier Properties.

This article presents an experimental study on the relaxation dynamics of a series of random copolymers based on bio-friendly comonomers with interesting gas barrier properties. We analyze the relaxation response in the glassy and ultraviscous regime of poly (trimethylene furanoate/sebacate) random copolymers via dielectric spectroscopy. We report lower values of dynamic fragility [a dimensionless index introduced in 1985 (Angell, Relaxations in Complex Systems, 1985)] in comparison to popular polyesters widely used in industry, such as poly (ethylene terephthalate), suggesting that the amorphous phase of these furanoate-based polyesters adopt an efficient chain packing. This is consistent with their low permeability to gases. We also discuss on different equations (phenomenological and theory-based approaches) for fitting the temperature-evolution of the alpha relaxation time.

Association between BRCA2 alterations and intraductal and cribriform histologies in prostate cancer.

BACKGROUND: Intraductal (IDC) and cribriform (CRIB) histologies in prostate cancer have been associated with germline BRCA2 (gBRCA2) mutations in small retrospective series, leading to the recommendation of genetic testing for patients with IDC in the primary tumour. PATIENTS AND METHODS: To examine the association of gBRCA2 mutations and other tumour molecular features with IDC and/or cribriform (CRIB) histologies, we conducted a case-control study in which primary prostate tumours from 58 gBRCA2 carriers were matched (1:2) by Gleason Grade Group and specimen type to 116 non-carriers. Presence/absence of IDC and CRIB morphologies was established by two expert uropathologists blinded to gBRCA2 status. Fluorescent in-situ hybridization (FISH) and next-generation sequencing (NGS) were used to detect BRCA2 alterations, PTEN deletions and TMPRSS2-ERG fusions. Chi-squared tests were used to compare the frequency of IDC and CRIB in gBRCA2 carriers and controls and to assess associations with other variables. Logistic regression models were constructed to identify independent factors associated with both histology patterns. RESULTS: No significant differences between gBRCA2 carriers and non-carriers were observed in the prevalence of IDC (36% gBRCA2 versus 50% non-carriers, p = 0.085) or CRIB (53% gBRCA2 versus 43% non-carriers p = 0.197) patterns. However, IDC histology was independently associated with bi-allelic BRCA2 alterations (OR 4.3, 95%CI 1.1-16.2) and PTEN homozygous loss (OR 5.2, 95%CI 2.1-13.1). CRIB morphology was also independently associated with bi-allelic BRCA2 alterations (OR 5.6, 95%CI 1.7-19.3). CONCLUSIONS: While we found no association between gBRCA2 mutations and IDC or CRIB histologies, bi-allelic BRCA2 loss in primary prostate tumours was significantly associated with both variant morphologies, independently of other clinical-pathologic factors.

A Comprehensive Review of Continuous Glucose Monitoring Accuracy during Exercise Periods.

Continuous Glucose Monitoring (CGM) has been a springboard of new diabetes management technologies such as integrated sensor-pump systems, the artificial pancreas, and more recently, smart pens. It also allows patients to make better informed decisions compared to a few measurements per day from a glucometer. However, CGM accuracy is reportedly affected during exercise periods, which can impact the effectiveness of CGM-based treatments. In this review, several studies that used CGM during exercise periods are scrutinized. An extensive literature review of clinical trials including exercise and CGM in type 1 diabetes was conducted. The gathered data were critically analysed, especially the Mean Absolute Relative Difference (MARD), as the main metric of glucose accuracy. Most papers did not provide accuracy metrics that differentiated between exercise and rest (non-exercise) periods, which hindered comparative data analysis. Nevertheless, the statistic results confirmed that CGM during exercise periods is less accurate.

Range of Motion and Injury Occurrence in Elite Spanish Soccer Academies. Not Only a Hamstring Shortening-Related Problem.

Sanz, A, Pablos, C, Ballester, R, Sanchez-Alarcos, JV, and Huertas, F. Range of motion and injury occurrence in elite Spanish soccer academies. Not only a hamstring shortening-related problem. J Strength Cond Res 34(7): 1924-1932, 2020-Age-related development of range of motion (ROM) during an active hip flexion (active straight leg raise) and its relationship with hamstring injury occurrence were examined in 1657 young male soccer players (9-18 years of age). Age-related differences in ROM showed a significant decrease from U9 to U11 (p = 0.001), from U11 to U13 (p < 0.005), and from U9 to U13 (p < 0.001), whereas ROM increased from U13 to U15 and from U13 to U18 (both p's < 0.001). Interestingly, younger and older players reached similar ROM values (U9-U18, p = 0.87). Higher ROM was found in dominant than nondominant leg in all age groups (all ps < 0.001). No differences related to playing position were found on ROM (all ps > 0.478). During the follow-up period (11 months) 97 hamstring injuries were reported showing higher rates in the older age groups (p < 0.001) and outfield players (p < 0.001). Remarkably, no differences in ROM average were found between injured players and noninjured players (p = 0.152). Our results suggest that ROM during hip flexion does not only depend on the hamstrings shortening but also on the variables related to joint stability, motor control, and hip flexor muscle weakness. Sport scientists in youth sport soccer academies should develop age-specific screening and action plans to develop strength, motor control, and flexibility to optimize ROM and reduce injuries from the grassroots stages.

A Randomized, Placebo-Controlled Double-Blind Trial of a Closed-Loop Glucagon System for Postbariatric Hypoglycemia.

BACKGROUND: Postbariatric hypoglycemia (PBH) can threaten safety and reduce quality of life. Current therapies are incompletely effective. METHODS: Patients with PBH were enrolled in a double-blind, placebo-controlled, crossover trial to evaluate a closed-loop glucose-responsive automated glucagon delivery system designed to reduce severe hypoglycemia. A hypoglycemia detection and mitigation algorithm was embedded in the artificial pancreas system connected to a continuous glucose monitor (CGM, Dexcom) driving a patch infusion pump (Insulet) filled with liquid investigational glucagon (Xeris) or placebo (vehicle). Sensor/plasma glucose responses to mixed meal were assessed during 2 study visits. The system delivered up to 2 doses of study drug (300/150 µg glucagon or equal-volume vehicle) if triggered by the algorithm. Rescue dextrose was given for plasma glucose <55 mg/dL or neuroglycopenia. RESULTS: Twelve participants (11 females/1 male, age 52 ± 2, 8 ± 1 years postsurgery, mean ± SEM) completed all visits. Predictive hypoglycemia alerts prompted automated drug delivery postmeal, when sensor glucose was 114 ± 7 vs 121 ± 5 mg/dL (P = .39). Seven participants required rescue glucose after vehicle but not glucagon (P = .008). Five participants had severe hypoglycemia (<55 mg/dL) after vehicle but not glucagon (P = .03). Nadir plasma glucose was higher with glucagon vs vehicle (67 ± 3 vs 59 ± 2 mg/dL, P = .004). Plasma glucagon rose after glucagon delivery (1231 ± 187 vs 16 ± 1 pg/mL at 30 minutes, P = .001). No rebound hyperglycemia occurred. Transient infusion site discomfort was reported with both glucagon (n = 11/12) and vehicle (n = 10/12). No other adverse events were observed. CONCLUSION: A CGM-guided closed-loop rescue system can detect imminent hypoglycemia and deliver glucagon, reducing severe hypoglycemia in PBH. CLINICAL TRIALS REGISTRATION: NCT03255629.

Enhanced Accuracy of Continuous Glucose Monitoring during Exercise through Physical Activity Tracking Integration.

Current Continuous Glucose Monitors (CGM) exhibit increased estimation error during periods of aerobic physical activity. The use of readily-available exercise monitoring devices opens new possibilities for accuracy enhancement during these periods. The viability of an array of physical activity signals provided by three different wearable devices was considered. Linear regression models were used in this work to evaluate the correction capabilities of each of the wearable signals and propose a model for CGM correction during exercise. A simple two-input model can reduce CGM error during physical activity (17.46% vs. 13.8%, p < 0.005) to the magnitude of the baseline error level (13.61%). The CGM error is not worsened in periods without physical activity. The signals identified as optimal inputs for the model are "Mets" (Metabolic Equivalent of Tasks) from the Fitbit Charge HR device, which is a normalized measurement of energy expenditure, and the skin temperature reading provided by the Microsoft Band 2 device. A simpler one-input model using only "Mets" is also viable for a more immediate implementation of this correction into market devices.

[Diagnostic and therapeutic management in a series of 1156 patients with the diagnosis of prostate cancer in Castilla y Leon during 2014.] / Manejo diagnóstico y actitud terapeútica de 1156 pacientes diagnosticados de cáncer de próstata en la comunidad de Castilla y León durante el año 2014.

OBJECTIVES: To evaluate the current clinical practice for patients with Prostate Cancer (CP) in the Health Areas of Castilla y León (CyL) in 2014. METHODS: A retrospective multicenter study was designed to provide data on the diagnosis and treatment of PC in CyL: 87.8% of patients were screened. Descriptive statistics on variables related to characteristics of the patient, the tumor and the treatment modality of the first line to which it was submitted are provided. RESULTS: A total of 1156 new cases of PC were analyzed with a mean age of 68.2 years and a mean PSA of 8.40 ng/ml. The Gleason score (GS) showed 538 (46.2%), 418 (35.9 %) and 200 (17.1%) patients for GS ≤ 6, 7 and  ≥ 8 respectively. 91% of patients (1053 patients) are diagnosed at a localized stage. 56 (4.8%) patients received treatment with active surveillance/ watchful waiting, 423 (36.6%) radical prostatectomy (PR), 348 (30.1%) radiotherapy (RT), 98 (8.4%) brachytherapy (BT) and 170 (14.7%) hormone therapy (HT) respectively. CONCLUSIONS: Differed strategies still accounted for a small percentage of treatments. PR and RT/BT were of choice in patients with localized stages of the disease and younger than 70 years. More advanced stages and older patients were treated with HT mainly. Age is postulated as the main factor involved in therapeutic decision making.

OBJETIVO: Conocer la práctica clínica real en pacientes con Cáncer de Próstata (CP) en las Áreas Sanitarias de Castilla y León (CyL) en el año 2014. MATERIAL Y MÉTODOS: Se diseña un estudio multicéntrico con carácter retrospectivo para disponer de datos sobre el diagnóstico y tratamiento del CP en CyL: se logra una cobertura del 87,8% de los pacientes comunitarios. Se aporta estadística descriptiva sobre las variables referentes a características del paciente, del tumor y de la modalidad de tratamiento de primera línea a la que fue sometido. RESULTADOS: Se analizan 1.156 nuevos casos de CP con una edad media de 68,2 años y una mediana de PSA de 8,4 ng/ml. La puntuación de Gleason (PG) muestra 538 (46,2%), 418 (35,9%) y 200 (17,1%) pacientes para PG ≤  6, 7 y  ≥ 8 respectivamente. El 91,0% de los pacientes (1.053 pacientes) son diagnosticados en estadio localizado. 56 pacientes (4,8%) son tratados con estrategias diferidas (EDs), vigilancia activa/ observación, 423 (36,6%) con prostatectomia radical (PR), 348 (30,1%) con radioterapia, 98 (8,4%) con braquiterapia (BT) y 170 (14,7%) con hormonoterapia (HT). CONCLUSIONES: Las EDs aún supusieron un porcentaje pequeño de los tratamientos. PR y RT/BT fueron de elección en pacientes con estadios localizados de la enfermedad y menores de 70 años. Estadios más avanzados y pacientes mayores fueron tratados con HT principalmente. La edad se postula como el principal factor implicado en la toma de decisiones terapéuticas.

Manejo diagnóstico y actitud terapeútica de 1156 pacientes diagnosticados de cáncer de próstata en la comunidad de Castilla y León durante el año 2014 / Diagnostic and therapeutic management in a series of 1156 patients with the diagnosis of prostate cancer in Castilla y Leon during 2014

Objetivo: Conocer la práctica clínica real en pacientes con Cáncer de Próstata (CP) en las Áreas Sanitarias de Castilla y León (CyL) en el año 2014. Material y métodos: Se diseña un estudio multicéntrico con carácter retrospectivo para disponer de datos sobre el diagnóstico y tratamiento del CP en CyL: se logra una cobertura del 87,8% de los pacientes comunitarios. Se aporta estadística descriptiva sobre las variables referentes a características del paciente, del tumor y de la modalidad de tratamiento de primera línea a la que fue sometido. Resultados: Se analizan 1.156 nuevos casos de CP con una edad media de 68,2 años y una mediana de PSA de 8,4 ng/ml. La puntuación de Gleason (PG) muestra 538 (46,2%), 418 (35,9%) y 200 (17,1%) pacientes para PG ≤ 6, 7 y ≥ 8 respectivamente. El 91,0% de los pacientes (1.053 pacientes) son diagnosticados en estadio localizado. 56 pacientes (4,8%) son tratados con estrategias diferidas (EDs), vigilancia activa/ observación, 423 (36,6%) con prostatectomia radical (PR), 348 (30,1%) con radioterapia, 98 (8,4%) con braquiterapia (BT) y 170 (14,7%) con hormonoterapia (HT). Conclusiones: Las EDs aún supusieron un porcentaje pequeño de los tratamientos. PR y RT/BT fueron de elección en pacientes con estadios localizados de la enfermedad y menores de 70 años. Estadios más avanzados y pacientes mayores fueron tratados con HT principalmente. La edad se postula como el principal factor implicado en la toma de decisiones terapéuticas

Objectives: To evaluate the current clinical practice for patients with Prostate Cancer (CP) in the Health Areas of Castilla y León (CyL) in 2014. Methods: A retrospective multicenter study was designed to provide data on the diagnosis and treatment of PC in CyL: 87.8% of patients were screened. Descriptive statistics on variables related to characteristics of the patient, the tumor and the treatment modality of the first line to which it was submitted are provided. Results: A total of 1156 new cases of PC were analyzed with a mean age of 68.2 years and a mean PSA of 8.40 ng/ml. The Gleason score (GS) showed 538 (46.2%), 418 (35.9 %) and 200 (17.1%) patients for GS ≤6, 7 and ≥8 respectively. 91% of patients (1053 patients) are diagnosed at a localized stage. 56 (4.8%) patients received treatment with active surveillance/ watchful waiting, 423 (36.6%) radical prostatectomy (PR), 348 (30.1%) radiotherapy (RT), 98 (8.4%) brachytherapy (BT) and 170 (14.7%) hormone therapy (HT) respectively. Conclusions: Differed strategies still accounted for a small percentage of treatments. PR and RT/BT were of choice in patients with localized stages of the disease and younger than 70 years. More advanced stages and older patients were treated with HT mainly. Age is postulated as the main factor involved in therapeutic decision making

Imaging and bone marrow assessments improve minimal residual disease prediction in multiple myeloma.

The value of minimal residual disease (MRD) status by bone marrow and imaging analysis as independent prognostic factors has been well established in multiple myeloma (MM). Nevertheless data about their potential complementarity for a more accurate assessment are limited. With this aim, we retrospectively analyzed the prediction of outcome with the combination of PET-CT and MRD, assessed by multiparameter flow cytometry (MFC) in 103 patients with newly diagnosed MM. We confirmed the benefit in terms of progression-free survival (PFS), linked to the achievement of negativity by MFC (hazard ratio [HR] 0.53; 95% confidence interval [CI]: 0.28-0.98), and PET-CT (HR 0.18; 95% CI: 0.09-0.36) individually. By combining both techniques, patients who became MRD-/PET-, with a median of PFS 92 months, had significant prolonged median PFS (P < .001). This is compared with MRD+/PET- and PET+ patients (median PFS of 45 and 28 months, respectively). We observed a significant difference (P = .003) in overall survival (OS) outcomes between MRD-/PET- and MRD+/PET- patients (4-year OS 94.2% and 100%, respectively), vs PET+ patients (4-year OS 73.8%). All survival results were confirmed in a conditional landmark analysis. These findings support the potential complementarity between PET-CT and MFC, and highlight their better predictive capability when improving sensitivity.

Experimental Evidence for a State-Point-Dependent Density-Scaling Exponent of Liquid Dynamics.

A large class of liquids obey density scaling characterized by an exponent, which quantifies the relative roles of temperature and density for the dynamics. We present experimental evidence that the density-scaling exponent γ is state-point dependent for the glass formers tetramethyl-tetraphenyl-trisiloxane (DC704) and 5-polyphenyl ether (5PPE). A method is proposed that from dynamic and thermodynamic properties at equilibrium estimates the value of γ. The method applies at any state point of the pressure-temperature plane, both in the supercooled and the normal liquid regimes. We find that γ is generally state-point dependent, which is confirmed by reanalyzing data for 20 metallic liquids and two model liquids.

Isochronal superposition and density scaling of the α-relaxation from pico- to millisecond.

The relaxation dynamics in two van der Waals bonded liquids and one hydrogen-bonding molecular liquid are studied as a function of pressure and temperature by incoherent neutron scattering using simultaneous dielectric spectroscopy. The dynamics are studied in a range of alpha relaxation times from pico- to milliseconds, primarily in the equilibrium liquid state. In this range, we find that isochronal superposition and density scaling work not only for the two van der Waals liquids but also for the hydrogen-bonding liquid, though the density scaling exponent is much smaller for the latter. Density scaling and isochronal superposition are seen to break down for intra-molecular dynamics when it is separated in time from the alpha relaxation, in close agreement with previous observations from molecular dynamics simulations.

Evaluation of an Artificial Pancreas with Enhanced Model Predictive Control and a Glucose Prediction Trust Index with Unannounced Exercise.

BACKGROUND: We investigated the safety and efficacy of the addition of a trust index to enhanced Model Predictive Control (eMPC) Artificial Pancreas (AP) that works by adjusting the responsiveness of the controller's insulin delivery based on the confidence intervals around predictions of glucose trends. This constitutes a dynamic adaptation of the controller's parameters in contrast with the widespread AP implementation of individualized fixed controller tuning. MATERIALS AND METHODS: After 1 week of sensor-augmented pump (SAP) use, subjects completed a 48-h AP admission that included three meals/day (carbohydrate range 29-57 g/meal), a 1-h unannounced brisk walk, and two overnight periods. Endpoints included sensor glucose percentage time 70-180, <70, >180 mg/dL, number of hypoglycemic events, and assessment of the trust index versus standard eMPC glucose predictions. RESULTS: Baseline characteristics for the 15 subjects who completed the study (mean ± SD) were age 46.1 ± 17.8 years, HbA1c 7.2% ± 1.0%, diabetes duration 26.8 ± 17.6 years, and total daily dose (TDD) 35.5 ± 16.4 U/day. Mean sensor glucose percent time 70-180 mg/dL (88.0% ± 8.0% vs. 74.6% ± 9.4%), <70 mg/dL (1.5% ± 1.9% vs. 7.8% ± 6.0%), and number of hypoglycemic events (0.6 ± 0.6 vs. 6.3 ± 3.4), all showed statistically significant improvement during AP use compared with the SAP run-in (P < 0.001). On average, the trust index enhanced controller responsiveness to predicted hyper- and hypoglycemia by 26% (P < 0.005). CONCLUSIONS: In this population of well-controlled patients, we conclude that eMPC with trust index AP achieved nearly 90% time in the target glucose range. Additional studies will further validate these results.

High-pressure cell for simultaneous dielectric and neutron spectroscopy.

In this article, we report on the design, manufacture, and testing of a high-pressure cell for simultaneous dielectric and neutron spectroscopy. This cell is a unique tool for studying dynamics on different time scales, from kilo- to picoseconds, covering universal features such as the α relaxation and fast vibrations at the same time. The cell, constructed in cylindrical geometry, is made of a high-strength aluminum alloy and operates up to 500 MPa in a temperature range between roughly 2 and 320 K. In order to measure the scattered neutron intensity and the sample capacitance simultaneously, a cylindrical capacitor is positioned within the bore of the high-pressure container. The capacitor consists of two concentric electrodes separated by insulating spacers. The performance of this setup has been successfully verified by collecting simultaneous dielectric and neutron spectroscopy data on dipropylene glycol, using both backscattering and time-of-flight instruments. We have carried out the experiments at different combinations of temperature and pressure in both the supercooled liquid and glassy state.