Structure of Health Information With Different Information Models: Evaluation Study With Competency Questions.

BACKGROUND: There is a flora of health care information models but no consensus on which to use. This leads to poor information sharing and duplicate modelling work. The amount and type of differences between models has, to our knowledge, not been evaluated. OBJECTIVE: This work aims to explore how information structured with various information models differ in practice. Our hypothesis is that differences between information models are overestimated. This work will also assess the usability of competency questions as a method for evaluation of information models within health care. METHODS: In this study, 4 information standards, 2 standards for secondary use, and 2 electronic health record systems were included as material. Competency questions were developed for a random selection of recommendations from a clinical guideline. The information needed to answer the competency questions was modelled according to each included information model, and the results were analyzed. Differences in structure and terminology were quantified for each combination of standards. RESULTS: In this study, 36 competency questions were developed and answered. In general, similarities between the included information models were larger than the differences. The demarcation between information model and terminology was overall similar; on average, 45% of the included structures were identical between models. Choices of terminology differed within and between models; on average, 11% was usable in interaction with each other. The information models included in this study were able to represent most information required for answering the competency questions. CONCLUSIONS: Different but same same; in practice, different information models structure much information in a similar fashion. To increase interoperability within and between systems, it is more important to move toward structuring information with any information model rather than finding or developing a perfect information model. Competency questions are a feasible way of evaluating how information models perform in practice.

Emission and time-resolved migration rates of aromatic diamines from two flexible polyurethane foams.

Performing risk assessments (RA) on household use of flexible polyurethane (PU) foams requires access to reliable data about emission and migration of potential diamine impurities. A toluene diisocyanate (TDI) and a methylene diphenyl diisocyanate (MDI) based foam were thermally treated to enable measurements on samples with defined concentrations of the corresponding diamines, toluene diamine (TDA), and methylene dianiline (MDA). The thermally treated foams used for emission testing contained up to 15 mg.kg-1 of TDA and 27 mg.kg-1 of MDA. Those used for migration testing contained 5.1 mg.kg-1 of TDA and 14.1 mg.kg-1 of MDA. Stability of the thermally generated diamines was sufficient for testing over a 37-day period. Analytical techniques that did not decompose the polymer matrix were applied. Emission rates for TDA and MDA isomers were less than the limit of quantitation (LOQ) of 0.008-0.07 µg.m-2.h-1. Migration was studied using samples of the same thermally treated foams over a 35-day period. Quantifiable migration of MDA from the MDI-based foam was only observed on Days 1 and 2. From Day 3 onward, migration rates were less than the LOQ. Quantifiable migration of TDA from the TDI-based foam rapidly decreased with time and was only observed on Days 1 thru 3. From Day 4 onward, migration rates were less than the LOQ. Theoretically, the migration rate should be inversely proportional to the square root of time (t) as t-0.5. This relationship was confirmed by the experimental data and enables extrapolating migration values to more extended time periods to conduct RAs.

Sampling chamber with minimal wall surface for simultaneous emission testing of diisocyanates and diamines from polyurethane products.

A sampling chamber was developed for emission testing of diisocyanates, methylene diphenyl diisocyanate (MDI), toluene diisocyanate (TDI), and corresponding diamines, methylene diphenyl diamine (MDA), and toluene diamine (TDA) from polyurethane (PU) product surfaces. In addition, a methodology for validation of the sampling chamber was presented, based on the introduction of generated standard atmospheres of the different diisocyanates and diamines to the sampling chamber system. Sampling of diisocyanates and diamines was performed on a circular glass fiber filter (150 mm diameter) impregnated with dihexyl amine (DHA) and acetic acid (AA) positioned inside a cylindrical stainless steel sampling chamber. The diisocyanates were immediately derivatized to DHA derivatives, and the amines were derivatized in a subsequent work-up procedure with ethyl chloroformate (ECF). The design of the sampling chamber and the presented methodology allowed for simultaneous sampling and analysis of diisocyanates and diamines of emission from a large surface area with minimal interior wall interaction in the sampling chamber. Performance characteristics of the sampling chamber for different sampling times and air humidity were obtained by determining collected amounts of the diisocyanates and diamines in the different parts of the sampling chamber. The repeatability of the collected amount on the impregnated filters in the sampling chamber was 15% with an overall recovery for 8 h of sampling in the range of 61% to 96%. The performance of the sampling chamber was not affected by air humidity (5%-75% RH), and no breakthrough during sampling was observed. LC-MS/MS determinations allowed for emission testing of diisocyanates and diamines on product surfaces as low as 10-30 ng m-2 h-1.

Elevated Adipocyte Membrane Phospholipid Saturation Does Not Compromise Insulin Signaling.

Increased saturated fatty acid (SFA) levels in membrane phospholipids have been implicated in the development of metabolic disease. Here, we tested the hypothesis that increased SFA content in cell membranes negatively impacts adipocyte insulin signaling. Preadipocyte cell models with elevated SFA levels in phospholipids were generated by disrupting the ADIPOR2 locus, which resulted in a striking twofold increase in SFA-containing phosphatidylcholines and phosphatidylethanolamines, which persisted in differentiated adipocytes. Similar changes in phospholipid composition were observed in white adipose tissues isolated from the ADIPOR2-knockout mice. The SFA levels in phospholipids could be further increased by treating ADIPOR2-deficient cells with palmitic acid and resulted in reduced membrane fluidity and endoplasmic reticulum stress in mouse and human preadipocytes. Strikingly, increased SFA levels in differentiated adipocyte phospholipids had no effect on adipocyte gene expression or insulin signaling in vitro. Similarly, increased adipocyte phospholipid saturation did not impair white adipose tissue function in vivo, even in mice fed a high-saturated fat diet at thermoneutrality. We conclude that increasing SFA levels in adipocyte phospholipids is well tolerated and does not affect adipocyte insulin signaling in vitro and in vivo.

TLCD1 and TLCD2 regulate cellular phosphatidylethanolamine composition and promote the progression of non-alcoholic steatohepatitis.

The fatty acid composition of phosphatidylethanolamine (PE) determines cellular metabolism, oxidative stress, and inflammation. However, our understanding of how cells regulate PE composition is limited. Here, we identify a genetic locus on mouse chromosome 11, containing two poorly characterized genes Tlcd1 and Tlcd2, that strongly influences PE composition. We generated Tlcd1/2 double-knockout (DKO) mice and found that they have reduced levels of hepatic monounsaturated fatty acid (MUFA)-containing PE species. Mechanistically, TLCD1/2 proteins act cell intrinsically to promote the incorporation of MUFAs into PEs. Furthermore, TLCD1/2 interact with the mitochondria in an evolutionarily conserved manner and regulate mitochondrial PE composition. Lastly, we demonstrate the biological relevance of our findings in dietary models of metabolic disease, where Tlcd1/2 DKO mice display attenuated development of non-alcoholic steatohepatitis compared to controls. Overall, we identify TLCD1/2 proteins as key regulators of cellular PE composition, with our findings having broad implications in understanding and treating disease.

Discovery by Virtual Screening of an Inhibitor of CDK5-Mediated PPARγ Phosphorylation.

Thiazolidinedione PPARγ agonists such as rosiglitazone and pioglitazone are effective antidiabetic drugs, but side effects have limited their use. It has been posited that their positive antidiabetic effects are mainly mediated by the inhibition of the CDK5-mediated Ser273 phosphorylation of PPARγ, whereas the side effects are linked to classical PPARγ agonism. Thus compounds that inhibit PPARγ Ser273 phosphorylation but lack classical PPARγ agonism have been sought as safer antidiabetic therapies. Herein we report the discovery by virtual screening of 10, which is a potent PPARγ binder and in vitro inhibitor of the CDK5-mediated phosphorylation of PPARγ Ser273 and displays negligible PPARγ agonism in a reporter gene assay. The pharmacokinetic properties of 10 are compatible with oral dosing, enabling preclinical in vivo testing, and a 7 day treatment demonstrated an improvement in insulin sensitivity in the ob/ob diabetic mouse model.

Emission of methylene diphenyl diisocyanate and methylene dianiline during use of cure-in-place methylene diphenyl diisocyanate-based consumer products.

The aim of this study was to provide realistic isocyanate and amine emission data when using different methylene diphenyl diisocyanate (MDI)-based polyurethane consumer products. Emission testing (air sampling) of diisocyanates and corresponding diamines was performed in a full-scale controlled-environment chamber during different work operations, such as gluing, mixing and foaming. The polyurethane products used were construction glue, one-component foam and two different two-component adhesives used in parquet flooring. Air sampling for isocyanates and amines was performed in the breathing zone of the worker and at different positions inside the controlled-environment chamber while the work operations were performed. Air sampling was also performed after the application, at different positions inside the chamber, to cover the post curing phase. Low air concentrations (0.1-0.7 µg MDI/m3, 0.03-0.2 µg isocyanate group (NCO)/m3) were found in the breathing zone and close to the work operation for some of the gluing applications. No methylene diphenyl diamine (MDA) concentrations above the limit of quantification were found for any of the applications in the breathing zone air. These results indicated that inhalation exposure to MDA or MDI would be expected to be minimal during application of do-it-yourself consumer products containing MDI.

Inhibition of SGLT2 Preserves Function and Promotes Proliferation of Human Islets Cells In Vivo in Diabetic Mice.

Dapagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor used for the treatment of diabetes. This study examines the effects of dapagliflozin on human islets, focusing on alpha and beta cell composition in relation to function in vivo, following treatment of xeno-transplanted diabetic mice. Mouse beta cells were ablated by alloxan, and dapagliflozin was provided in the drinking water while controls received tap water. Body weight, food and water intake, plasma glucose, and human C-peptide levels were monitored, and intravenous arginine/glucose tolerance tests (IVarg GTT) were performed to evaluate islet function. The grafted human islets were isolated at termination and stained for insulin, glucagon, Ki67, caspase 3, and PDX-1 immunoreactivity in dual and triple combinations. In addition, human islets were treated in vitro with dapagliflozin at different glucose concentrations, followed by insulin and glucagon secretion measurements. SGLT2 inhibition increased the animal survival rate and reduced plasma glucose, accompanied by sustained human C-peptide levels and improved islet response to glucose/arginine. SGLT2 inhibition increased both alpha and beta cell proliferation (Ki67+glucagon+ and Ki67+insulin+) while apoptosis was reduced (caspase3+glucagon+ and caspase3+insulin+). Alpha cells were fewer following inhibition of SGLT2 with increased glucagon/PDX-1 double-positive cells, a marker of alpha to beta cell transdifferentiation. In vitro treatment of human islets with dapagliflozin had no apparent impact on islet function. In summary, SGLT2 inhibition supported human islet function in vivo in the hyperglycemic milieu and potentially promoted alpha to beta cell transdifferentiation, most likely through an indirect mechanism.

Post Hoc Analysis of Predictors of Clinical Response to Repository Corticotropin Injection in Persistently Active Rheumatoid Arthritis.

INTRODUCTION: A phase IV clinical trial confirmed the safety and efficacy of repository corticotropin injection (RCI, Acthar® Gel) in patients with refractory rheumatoid arthritis (RA) that was nonresponsive to standard-of-care therapies. The objective of this post hoc analysis was to identify baseline demographics and clinical characteristics that may be predictors of response to RCI. METHODS: The phase IV trial was a two-part, randomized, placebo-controlled withdrawal study. Post hoc analysis was conducted with the open-label portion of the trial data, in which all 258 subjects received RCI (80 U) twice weekly for 12 weeks. Responders were subjects who achieved low disease activity (LDA) by a Disease Activity Score with 28-joint count and erythrocyte sedimentation rate (DAS28-ESR) of < 3.2 at week 12. Responders were compared with nonresponders by assessing the proportion of subjects in each group for demographics and clinical characteristics, including weight, disease duration, medical history including osteoarthritis and unrelated joint conditions, hemoglobin A1c, C-reactive protein, ESR, DAS28-ESR, Clinical Disease Activity Index (CDAI), depression, anxiety, tender joint count (TJC), and swollen joint count (SJC). Bivariate analysis followed by multiple logistic regression analysis were conducted to identify significant baseline predictors for the outcome of achieving LDA by week 12. RESULTS: Bivariate analysis showed that RCI responders had significantly lower baseline TJC (p = 0.0310), SJC (p = 0.0018), ESR (p = 0.0487), and CDAI (p = 0.0112) and shorter RA disease duration (p = 0.0446). Subjects were less likely to achieve LDA if they had osteoarthritis (p < 0.0001), other joint-related conditions unrelated to RA (p < 0.0001), anemia (p = 0.0132), depression (p = 0.0006), or prior or concomitant use of targeted-synthetic or biologic disease-modifying antirheumatic drugs (p < 0.0001). Multiple logistic regression analysis revealed that, of the above, only ongoing osteoarthritis (p = 0.0272) or other joint-related conditions (p = 0.0193) were significant negative predictors of RCI response. CONCLUSIONS: These results identify specific patient characteristics that may be considered predictors of positive or negative clinical response to RCI.

Post Hoc Analysis of the Correlation Between Patient-Reported Outcomes and Clinical Response to Repository Corticotropin Injection for Persistently Active Rheumatoid Arthritis.

PURPOSE: Approximately 6% of patients with rheumatoid arthritis (RA) in the USA have refractory disease that is resistant to standard-of-care therapies. A recent phase IV clinical trial affirmed the safety and efficacy of repository corticotropin injection (RCI; Acthar® Gel) for refractory RA. This post hoc analysis of the clinical trial data assessed whether changes in clinical measures correlated with patient-reported outcome (PRO) improvements. METHODS: Data were assessed from the trial's open-label period when patients received RCI (80 U) twice weekly for 12 weeks. Clinical assessments included hemoglobin A1c, C-reactive protein, erythrocyte sedimentation rate (ESR), total joint count (TJC), swollen joint count (SJC), Disease Activity Score with 28 joint count and ESR (DAS28-ESR), and Clinical Disease Activity Index (CDAI). PROs included pain (Visual Analog Scale), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F]), disability (Health Assessment Questionnaire-Disability Index [HAQ-DI]), and activity impairment (Work Productivity and Activity Impairment [WPAI] questionnaire). Patients grouped by minimal clinically important difference (MCID) improvement vs no improvement in PROs were compared with clinical measures at week 12. Correlations were determined by multivariable linear regression analysis and standardized coefficient estimates. RESULTS: RCI responders, defined as patients with DAS28-ESR < 3.2 at week 12, reported significantly greater PRO improvements for pain, disability, fatigue, activity impairment, current work impairment, and overall work impairment than nonresponders. Patients with MCID improvements in all PROs showed significantly greater decreases in mean values for TJC, DAS28-ESR, and CDAI, whereas those with pain, fatigue, and disability improvements had significantly greater SJC and ESR reductions. Multivariable linear regression analysis determined that improvement from baseline in all PROs correlated with significant decreases in TJC, DAS28-ESR, and CDAI. ESR reduction significantly correlated with improvements in pain and disability, but not fatigue or WPAI. CONCLUSIONS: These results confirm that clinical responses to RCI were directly correlated with patient perception of improvement.

A State-of-the Art Review of SNOMED CT Terminology Binding and Recommendations for Practice and Research.

BACKGROUND: Unambiguous sharing of data requires information models and terminology in combination, but there is a lack of knowledge as to how they should be combined, leading to impaired interoperability. OBJECTIVES: To facilitate creation of guidelines for SNOMED CT terminology binding we have performed a literature review to find existing recommendations and expose knowledge gaps. The primary audience is practitioners and researchers working with terminology binding. METHODS: PubMed, Scopus, and Web of Science were searched for papers containing "terminology binding," "subset," "map," "information model" or "implement" and the term "SNOMED." RESULTS: The search yielded 616 unique papers published from 2004 to 2020, from which 55 papers were selected and analyzed inductively. Topics described in the papers include problems related to input material, SNOMED CT, information models, and lack of appropriate tools as well as recommendations regarding competence. CONCLUSION: Recommendations are given for practitioners and researchers. Many of the stated problems can be solved by better co-operation between domain experts and informaticians and better knowledge of SNOMED CT. Settings where these competences either work together or where staff with knowledge of both act as brokers are well equipped for terminology binding. Tooling is not thoroughly researched and might be a possible way to facilitate terminology binding.

Fast Green's Function Method for Ultrafast Electron-Boson Dynamics.

The interaction of electrons with quantized phonons and photons underlies the ultrafast dynamics of systems ranging from molecules to solids, and it gives rise to a plethora of physical phenomena experimentally accessible using time-resolved techniques. Green's function methods offer an invaluable interpretation tool since scattering mechanisms of growing complexity can be selectively incorporated in the theory. Currently, however, real-time Green's function simulations are either prohibitively expensive due to the cubic scaling with the propagation time or do neglect the feedback of electrons on the bosons, thus violating energy conservation. We put forward a computationally efficient Green's function scheme which overcomes both limitations. The numerical effort scales linearly with the propagation time while the simultaneous dressing of electrons and bosons guarantees the fulfillment of all fundamental conservation laws. We present a real-time study of the phonon-driven relaxation dynamics in an optically excited narrow band-gap insulator, highlighting the nonthermal behavior of the phononic degrees of freedom. Our formulation paves the way to first-principles simulations of electron-boson systems with unprecedented long propagation times.

Intestinal sodium/glucose cotransporter 3 expression is epithelial and downregulated in obesity.

AIM: We aimed to determine whether the sodium/glucose cotransporter family member SGLT3, a proposed glucose sensor, is expressed in the intestine and/or kidney, and if its expression is altered in mouse models of obesity and in humans before and after weight-loss surgery. MAIN METHODS: We used in-situ hybridization and quantitative PCR to determine whether the Sglt3 isoforms 3a and 3b were expressed in the intestine and kidney of C57, leptin-deficient ob/ob, and diabetic BTBR ob/ob mice. Western blotting and immunohistochemistry were also used to assess SGLT3 protein levels in jejunal biopsies from obese patients before and after weight-loss Roux-en-Y gastric bypass surgery (RYGB), and in lean healthy controls. KEY FINDINGS: Sglt3a/3b mRNA was detected in the small intestine (duodenum, jejunum and ileum), but not in the large intestine or kidneys of mice. Both isoforms were detected in epithelial cells (confirmed using intestinal organoids). Expression of Sglt3a/3b mRNA in duodenum and jejunum was significantly lower in ob/ob and BTBR ob/ob mice than in normal-weight littermates. Jejunal SGLT3 protein levels in aged obese patients before RYGB were lower than in lean individuals, but substantially upregulated 6 months post-RYGB. SIGNIFICANCE: Our study shows that Sglt3a/3b is expressed primarily in epithelial cells of the small intestine in mice. Furthermore, we observed an association between intestinal mRNA Sglt3a/3b expression and obesity in mice, and between jejunal SGLT3 protein levels and obesity in humans. Further studies are required to determine the possible role of SGLT3 in obesity.

Sound analysis of the magnetically levitated left ventricular assist device HeartMate 3™.

INTRODUCTION: The HeartMate 3™ has shown lower rates of adverse events compared to previous devices due to the design and absence of mechanical bearings. For previous devices, sound analysis emerged as a way to assess pump function. The aims of this study were to determine if sound analysis can be applied to the HeartMate 3 in vivo and in vitro and to evaluate an electronic stethoscope. METHOD: Sound recordings were performed with microphones and clinical accessible electronic stethoscope. The recordings were studied in both the time and the frequency domains. Recordings from four patients were performed to determine if in vivo and in vitro recordings are comparable. RESULTS: The results show that it is possible to detect sound from HeartMate 3 and the sound spectrum is clear. Pump frequency and frequency of the pulsatile mode are easily determined. Frequency spectra from in vitro and in vivo recordings have the same pattern, and the major proportion (96.7%) of signal power is located at the pump speed frequency ±40 Hz. The recordings from the patients show low inter-individual differences except from location of peaks originating from pump speed and harmonics. Electronic stethoscopes could be used for sound recordings, but the dedicated equipment showed a clearer sound spectrum. DISCUSSION: The results show that acoustic analysis can also be performed with the HeartMate 3 and that in vivo and in vitro sound spectrum is similar. The frequency spectra are different from previous devices, and methods for assessing pump function or thrombosis need further evaluation.

Quantitative analysis of manual annotation of clinical text samples.

BACKGROUND: Semantic interoperability of eHealth services within and across countries has been the main topic in several research projects. It is a key consideration for the European Commission to overcome the complexity of making different health information systems work together. This paper describes a study within the EU-funded project ASSESS CT, which focuses on assessing the potential of SNOMED CT as core reference terminology for semantic interoperability at European level. OBJECTIVE: This paper presents a quantitative analysis of the results obtained in ASSESS CT to determine the fitness of SNOMED CT for semantic interoperability. METHODS: The quantitative analysis consists of concept coverage, term coverage and inter-annotator agreement analysis of the annotation experiments related to six European languages (English, Swedish, French, Dutch, German and Finnish) and three scenarios: (i) ADOPT, where only SNOMED CT was used by the annotators; (ii) ALTERNATIVE, where a fixed set of terminologies from UMLS, excluding SNOMED CT, was used; and (iii) ABSTAIN, where any terminologies available in the current national infrastructure of the annotators' country were used. For each language and each scenario, we configured the different terminology settings of the annotation experiments. RESULTS: There was a positive correlation between the number of concepts in each terminology setting and their concept and term coverage values. Inter-annotator agreement is low, irrespective of the terminology setting. CONCLUSIONS: No significant differences were found between the analyses for the three scenarios, but availability of SNOMED CT for the assessed language is associated with increased concept coverage. Terminology setting size and concept and term coverage correlate positively up to a limit where more concepts do not significantly impact the coverage values. The results did not confirm the hypothesis of an inverse correlation between concept coverage and IAA due to a lower amount of choices available. The overall low IAA results pose a challenge for interoperability and indicate the need for further research to assess whether consistent terminology implementation is possible across Europe, e.g., improving term coverage by adding localized versions of the selected terminologies, analysing causes of low inter-annotator agreement, and improving tooling and guidance for annotators. The much lower term coverage for the Swedish version of SNOMED CT compared to English together with the similarly high concept coverage obtained with English and Swedish SNOMED CT reflects its relevance as a hub to connect user interface terminologies and serving a variety of user needs.

Qualitative analysis of manual annotations of clinical text with SNOMED CT.

SNOMED CT provides about 300,000 codes with fine-grained concept definitions to support interoperability of health data. Coding clinical texts with medical terminologies it is not a trivial task and is prone to disagreements between coders. We conducted a qualitative analysis to identify sources of disagreements on an annotation experiment which used a subset of SNOMED CT with some restrictions. A corpus of 20 English clinical text fragments from diverse origins and languages was annotated independently by two domain medically trained annotators following a specific annotation guideline. By following this guideline, the annotators had to assign sets of SNOMED CT codes to noun phrases, together with concept and term coverage ratings. Then, the annotations were manually examined against a reference standard to determine sources of disagreements. Five categories were identified. In our results, the most frequent cause of inter-annotator disagreement was related to human issues. In several cases disagreements revealed gaps in the annotation guidelines and lack of training of annotators. The reminder issues can be influenced by some SNOMED CT features.

Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability.

Hyperphosphatemia is common in patients with chronic kidney disease and is increasingly associated with poor clinical outcomes. Current management of hyperphosphatemia with dietary restriction and oral phosphate binders often proves inadequate. Tenapanor, a minimally absorbed, small-molecule inhibitor of the sodium/hydrogen exchanger isoform 3 (NHE3), acts locally in the gastrointestinal tract to inhibit sodium absorption. Because tenapanor also reduces intestinal phosphate absorption, it may have potential as a therapy for hyperphosphatemia. We investigated the mechanism by which tenapanor reduces gastrointestinal phosphate uptake, using in vivo studies in rodents and translational experiments on human small intestinal stem cell-derived enteroid monolayers to model ion transport physiology. We found that tenapanor produces its effect by modulating tight junctions, which increases transepithelial electrical resistance (TEER) and reduces permeability to phosphate, reducing paracellular phosphate absorption. NHE3-deficient monolayers mimicked the phosphate phenotype of tenapanor treatment, and tenapanor did not affect TEER or phosphate flux in the absence of NHE3. Tenapanor also prevents active transcellular phosphate absorption compensation by decreasing the expression of NaPi2b, the major active intestinal phosphate transporter. In healthy human volunteers, tenapanor (15 mg, given twice daily for 4 days) increased stool phosphorus and decreased urinary phosphorus excretion. We determined that tenapanor reduces intestinal phosphate absorption predominantly through reduction of passive paracellular phosphate flux, an effect mediated exclusively via on-target NHE3 inhibition.

Secretagogin is increased in plasma from type 2 diabetes patients and potentially reflects stress and islet dysfunction.

Beta cell dysfunction accompanies and drives the progression of type 2 diabetes mellitus (T2D), but there are few clinical biomarkers available to assess islet cell stress in humans. Secretagogin, a protein enriched in pancreatic islets, demonstrates protective effects on beta cell function in animals. However, its potential as a circulating biomarker released from human beta cells and islets has not been studied. In this study primary human islets, beta cells and plasma samples were used to explore secretion and expression of secretagogin in relation to the T2D pathology. Secretagogin was abundantly and specifically expressed and secreted from human islets. Furthermore, T2D patients had an elevated plasma level of secretagogin compared with matched healthy controls, which was confirmed in plasma of diabetic mice transplanted with human islets. Additionally, the plasma secretagogin level of the human cohort had an inverse correlation to clinical assessments of beta cell function. To explore the mechanism of secretagogin release in vitro, human beta cells (EndoC-ßH1) were exposed to elevated glucose or cellular stress-inducing agents. Secretagogin was not released in parallel with glucose stimulated insulin release, but was markedly elevated in response to endoplasmic reticulum stressors and cytokines. These findings indicate that secretagogin is a potential novel biomarker, reflecting stress and islet cell dysfunction in T2D patients.

Sound analysis of a left ventricular assist device: A technical evaluation of iOS devices.

INTRODUCTION: The use of left ventricular assist device (LVAD) has grown rapidly. Adverse events do continue to occur. In recent years, analysis of LVAD sound recordings emerged as a means to monitor pump function and detect pump thrombosis. The aim of this study was to characterize the sounds from HeartMate II and to evaluate the use of handheld iOS devices for sound recordings. METHOD: Signal analysis of LVAD sound recordings, with dedicated recording equipment and iOS devices, was performed. Two LVADs running in mock loop circuits were compared to an implanted LVAD. Spectral analysis and parametric signal models were explored to quantify the sound and potentially detect changes in it. RESULTS: The sound recordings of two LVADs in individual mock loop circuits and a third one implanted in a patient appeared to be similar. Qualitatively, sound characteristics were preserved following changes in pump speed. Recordings using dedicated equipment showed that HeartMate II sound comprises low-frequency components corresponding to pump impeller rotation, as well as high-frequency components due to a pulse width modulation of the electric power to the pump. These different signal components interact and result in a complicated frequency spectrum. The iPhone and iPod recordings could not reproduce the sounds as well as the dedicated equipment. In particular, lower frequencies were affected by outside disturbances. DISCUSSION: This article outlines a systematic approach to LVAD sound analysis using signal processing methods to quantify and potentially detect changes, and describes some of the challenges, for example, with the use of inexpensive recording devices.

A computable pathology report for precision medicine: extending an observables ontology unifying SNOMED CT and LOINC.

BACKGROUND: The College of American Pathologists (CAP) introduced the first cancer synoptic reporting protocols in 1998. However, the objective of a fully computable and machine-readable cancer synoptic report remains elusive due to insufficient definitional content in Systematized Nomenclature of Medicine - Clinical Terms (SNOMED CT) and Logical Observation Identifiers Names and Codes (LOINC). To address this terminology gap, investigators at the University of Nebraska Medical Center (UNMC) are developing, authoring, and testing a SNOMED CT observable ontology to represent the data elements identified by the synoptic worksheets of CAP. METHODS: Investigators along with collaborators from the US National Library of Medicine, CAP, the International Health Terminology Standards Development Organization, and the UK Health and Social Care Information Centre analyzed and assessed required data elements for colorectal cancer and invasive breast cancer synoptic reporting. SNOMED CT concept expressions were developed at UNMC in the Nebraska Lexicon© SNOMED CT namespace. LOINC codes for each SNOMED CT expression were issued by the Regenstrief Institute. SNOMED CT concepts represented observation answer value sets. RESULTS: UNMC investigators created a total of 194 SNOMED CT observable entity concept definitions to represent required data elements for CAP colorectal and breast cancer synoptic worksheets, including biomarkers. Concepts were bound to colorectal and invasive breast cancer reports in the UNMC pathology system and successfully used to populate a UNMC biobank. DISCUSSION: The absence of a robust observables ontology represents a barrier to data capture and reuse in clinical areas founded upon observational information. Terminology developed in this project establishes the model to characterize pathology data for information exchange, public health, and research analytics.