Amyloid Deposition in Transplanted Human Pancreatic Islets: A Conceivable Cause of Their Long-Term Failure

Following the encouraging report of the Edmonton group, there was a rejuvenation of the islet transplantation field. After that, more pessimistic views spread when long-term results of the clinical outcome were published. A progressive loss of the β-cell function meant that almost all patients were back on insulin therapy after 5 years. More than 10 years ago, we demonstrated that amyloid deposits rapidly formed in human islets and in mouse islets transgenic for human IAPP when grafted into nude mice. It is, therefore, conceivable to consider amyloid formation as one potential candidate for the long-term failure. The present paper reviews attempts in our laboratories to elucidate the dynamics of and mechanisms behind the formation of amyloid in transplanted islets with special emphasis on the impact of long-term hyperglycemia

Differential Mitochondrial Gene Expression in Adipose Tissue Following Weight Loss Induced by Diet or Bariatric Surgery

Context: Mitochondria are essential for cellular energy homeostasis, yet their role in subcutaneous adipose tissue (SAT) during different types of weight-loss interventions remains unknown. Objective: To investigate how SAT mitochondria change following diet-induced and bariatric surgery-induced weight-loss interventions in 4 independent weight-loss studies. Methods: The DiOGenes study is a European multicenter dietary intervention with an 8-week low caloric diet (LCD; 800 kcal/d; n = 261) and 6-month weight-maintenance (n = 121) period. The Kuopio Obesity Surgery study (KOBS) is a Roux-en-Y gastric bypass (RYGB) surgery study (n = 172) with a 1-year follow-up. We associated weight-loss percentage with global and 2210 mitochondria-related RNA transcripts in linear regression analysis adjusted for age and sex. We repeated these analyses in 2 studies. The Finnish CRYO study has a 6-week LCD (800-1000 kcal/d; n = 19) and a 10.5-month follow-up. The Swedish DEOSH study is a RYGB surgery study with a 2-year (n = 49) and 5-year (n = 37) follow-up. Results: Diet-induced weight loss led to a significant transcriptional downregulation of oxidative phosphorylation (DiOGenes; ingenuity pathway analysis [IPA] z-scores: -8.7 following LCD, -4.4 following weight maintenance; CRYO: IPA z-score: -5.6, all P < 0.001), while upregulation followed surgery-induced weight loss (KOBS: IPA z-score: 1.8, P < 0.001; in DEOSH: IPA z-scores: 4.0 following 2 years, 0.0 following 5 years). We confirmed an upregulated oxidative phosphorylation at the proteomics level following surgery (IPA z-score: 3.2, P < 0.001). Conclusions: Differentially regulated SAT mitochondria-related gene expressions suggest qualitative alterations between weight-loss interventions, providing insights into the potential molecular mechanistic targets for weight-loss success.Peer reviewe

Development and validation of an interpretable machine learning-based calculator for predicting 5-year weight trajectories after bariatric surgery: a multinational retrospective cohort SOPHIA study

Background Weight loss trajectories after bariatric surgery vary widely between individuals, and predicting weight loss before the operation remains challenging. We aimed to develop a model using machine learning to provide individual preoperative prediction of 5-year weight loss trajectories after surgery. Methods In this multinational retrospective observational study we enrolled adult participants (aged $\ge$18 years) from ten prospective cohorts (including ABOS [NCT01129297], BAREVAL [NCT02310178], the Swedish Obese Subjects study, and a large cohort from the Dutch Obesity Clinic [Nederlandse Obesitas Kliniek]) and two randomised trials (SleevePass [NCT00793143] and SM-BOSS [NCT00356213]) in Europe, the Americas, and Asia, with a 5 year followup after Roux-en-Y gastric bypass, sleeve gastrectomy, or gastric band. Patients with a previous history of bariatric surgery or large delays between scheduled and actual visits were excluded. The training cohort comprised patients from two centres in France (ABOS and BAREVAL). The primary outcome was BMI at 5 years. A model was developed using least absolute shrinkage and selection operator to select variables and the classification and regression trees algorithm to build interpretable regression trees. The performances of the model were assessed through the median absolute deviation (MAD) and root mean squared error (RMSE) of BMI. Findings10 231 patients from 12 centres in ten countries were included in the analysis, corresponding to 30 602 patient-years. Among participants in all 12 cohorts, 7701 (75$\bullet$3%) were female, 2530 (24$\bullet$7%) were male. Among 434 baseline attributes available in the training cohort, seven variables were selected: height, weight, intervention type, age, diabetes status, diabetes duration, and smoking status. At 5 years, across external testing cohorts the overall mean MAD BMI was 2$\bullet$8 kg/m${}^2$ (95% CI 2$\bullet$6-3$\bullet$0) and mean RMSE BMI was 4$\bullet$7 kg/m${}^2$ (4$\bullet$4-5$\bullet$0), and the mean difference between predicted and observed BMI was-0$\bullet$3 kg/m${}^2$ (SD 4$\bullet$7). This model is incorporated in an easy to use and interpretable web-based prediction tool to help inform clinical decision before surgery. InterpretationWe developed a machine learning-based model, which is internationally validated, for predicting individual 5-year weight loss trajectories after three common bariatric interventions.Comment: The Lancet Digital Health, 202

Differential Mitochondrial Gene Expression in Adipose Tissue Following Weight Loss Induced by Diet or Bariatric Surgery

ContextMitochondria are essential for cellular energy homeostasis, yet their role in subcutaneous adipose tissue (SAT) during different types of weight-loss interventions remains unknown.ObjectiveTo investigate how SAT mitochondria change following diet-induced and bariatric surgery–induced weight-loss interventions in 4 independent weight-loss studies.MethodsThe DiOGenes study is a European multicenter dietary intervention with an 8-week low caloric diet (LCD; 800 kcal/d; n = 261) and 6-month weight-maintenance (n = 121) period. The Kuopio Obesity Surgery study (KOBS) is a Roux-en-Y gastric bypass (RYGB) surgery study (n = 172) with a 1-year follow-up. We associated weight-loss percentage with global and 2210 mitochondria-related RNA transcripts in linear regression analysis adjusted for age and sex. We repeated these analyses in 2 studies. The Finnish CRYO study has a 6-week LCD (800-1000 kcal/d; n = 19) and a 10.5-month follow-up. The Swedish DEOSH study is a RYGB surgery study with a 2-year (n = 49) and 5-year (n = 37) follow-up.ResultsDiet-induced weight loss led to a significant transcriptional downregulation of oxidative phosphorylation (DiOGenes; ingenuity pathway analysis [IPA] z-scores: −8.7 following LCD, −4.4 following weight maintenance; CRYO: IPA z-score: −5.6, all P ConclusionsDifferentially regulated SAT mitochondria-related gene expressions suggest qualitative alterations between weight-loss interventions, providing insights into the potential molecular mechanistic targets for weight-loss success.</p

Beslutstöd och automation i operativ tågtrafikstyrning (BAOT): slutrapport

Syftet med BAOT-projektet (Beslutstöd och Automation i Operativ Tågtrafikstyrning) har inte varit att utveckla nya beslutsstöd, utan att ta fram kunskap om behov, förutsättningar och krav på framtida beslutsstöd. Resultatet av projektet ska stödja den pågående och kommande utvecklingen av sådana. Sedan tidigare har forskning om nya styrprinciper, användargränssnitt och beslutsstöd för tågtrafikledning bedrivits i samverkan mellan institutionen för informationsteknologi, Uppsala universitet och Trafikverket. År 2015 presenterades en slutrapport från denna forskning: Sandblad B, Andersson AW, Tschirner S.: Framtida tågtrafikstyrning. Sammanfattande forskningsrapport samt slutrapport från FOT-projektet. (https://fudinfo.trafikverket.se/fudinfoexternwebb/pages/PublikationVisa.aspx?PublikationId=2848) Det tidigare forskningsarbetet har resulterat i en kunskapsbas om samspelet mellan människor i olika roller och de tekniska stödsystemen samt i en grundläggande analys av arbetet med att styra tågtrafik. Tillsammans med arbetsgrupper inom Trafikverket har förslag till nya principer och gränssnitt för operativ styrning, ”trafikstyrning genom omplanering i realtid”, tagits fram. Prototyper av de nya styrprinciperna och en ny generation av användargränssnitt har utvecklats. Grundläggande studier av praktiskt fungerande beslutsstöd för trafikledare har varit en del av denna tidigare forskning. Frågeställningar om krav på och nyttan av algoritmbaserade optimerande beslutsstöd har även studerats inom EU-projektet ONTIME. Slutsatser har dragits från detta arbete för att finna lämpliga svenska ansatser. Inom projektet BAOT har behov av, och krav på, framtida avancerade beslutsstöd för operativ trafikstyrning studeras, särskilt hur de kan integreras i aktuella svenska koncept för operativ tågtrafikstyrning. Det vid trafik¬ledningen i Boden införda systemet STEG utgör en grund för dessa studier. Det material som presenteras i denna rapport är avsett att utgöra en bas för fortsatt forskning. Det material som presenteras i denna rapport grundar sig på samverkan med andra forsknings-projekt, de kunskaper som genererats inom vår tidigare forskning samt på analyser och intervjuer genomföra med hjälp av erfarna trafikledare vid trafikledningen i Boden. Projektet ingår i branschprogrammet KAJT, Kapacitet i Järnvägstrafiken, http://www.kajt.org/BAOT - Beslutsstöd och automation i operativ tågtrafikstyrnin

Designing train driver advisory systems for situation awareness

During the past decade, train Driver Advisory Systems (DAS) have been an emerging topic. Many projects have been started with the goal to increase punctuality and decrease energy consumption. We found that many systems provide too little information, e.g. only a speed advice, and thus do neither improve drivers’ skills nor their Situation Awareness (SA) of the traffic situation. In collaboration with train drivers, we developed key concepts for future DAS. This paper discusses today’s problems and principles to solve them. We explain how SA can be supported and how this can improve overall quality of train traffic.Future Train Traffic Contro

Designing train driver advisory systems for situation awareness

During the past decade, train Driver Advisory Systems (DAS) have been an emerging topic. Many projects have been started with the goal to increase punctuality and decrease energy consumption. We found that many systems provide too little information, e.g. only a speed advice, and thus do neither improve drivers’ skills nor their Situation Awareness (SA) of the traffic situation. In collaboration with train drivers, we developed key concepts for future DAS. This paper discusses today’s problems and principles to solve them. We explain how SA can be supported and how this can improve overall quality of train traffic.Future Train Traffic Contro