In this special edition of talk evidence, Helen Macdonald and Carl Henneghan talk about creating an evidence base from harms. We hear from a member of the pubic who experienced harm from a drug, and now advises the FDA. A former regulator who explains why reporting harms is so important. And finally, an investigative journalist who explains what...

We’re back for the December Talk Evidence, and this month we’re being very digital Firstly,(1.20) Helen tells us about arthritic fingers - should we be using prednisolone for treatment when people have painful osteoarthritis of the hand Then (13.30) Carl gets us all to check our fingers for clubbing, and we find out how useful it is as a test...

Welcome to the festive talk evidence, giving you a little EBM to take you into the new year. As always Duncan Jarvies is joined by Helen Macdonald (resting GP and editor at The BMJ) and Carl Heneghan (active GP, director of Oxford University’s CEBM and editor of BMJ Evidence) This month: (2.00) Helen look back at a Christmas article, which...

If you read the Christmas BMJ in the last few weeks, you might have noticed a lot around art and health - the way in which engagement in arts can help in prevention and treatment, but can also affect those more nebulous things which really matter to patients - loneliness, self expression, being connected to the wider community. That obviously...

Welcome to the festive talk evidence, giving you a little EBM to take you into the new year. As always Duncan Jarvies is joined by Helen Macdonald (resting GP and editor at The BMJ) and Carl Heneghan (active GP, director of Oxford University’s CEBM and editor of BMJ Evidence)* This month: (1.20) Carl tells us about new research on treating...

There comes a tipping point in all campaigns when the evidence is overwhelming and the only way to proceed is with action. According to David Williams, it’s time to tackle the disproportionate effects of race on patients in the UK. David Williams, from Harvard University, developed the Everyday Discrimination Scale that, in 1997, launched a new...

We're taking a break from the usual Talk Evidence to focus on the new corona virus that has emerged in China. With a brand new disease, we have to build our evidence base from scratch - basic virology, epidemiology, pathogenicity, transmissibility, and ultimately treatment are all unknowns. In this episode of Talk Evidence, we're trying to get...

We all know we should be doing more exercise, and one way to do that is by active commuting - journeying to work on foot or by bike. One thing preventing people from taking up cycling is the fear of being involved in road traffic accidents, and that the risk isn't worth the benefit of the extra exercise. It’s even more confusing when air...

The NHS is a world leader in sustainable healthcare - and it's the staff who have have been leading the charge. The For A Greener NHS campaign is asking everyone who has made a change to the way they work, to submit evidence and help shape the whole organisation's response to the climate emergency. In this podcast, Isobel Braithwaite, public...

This edition of talk evidence was recorded before the big increase in covid-19 infections in the UK, and then delayed by some self isolation. We'll be back with more evidence on the pandemic very soon. As always Duncan Jarvies is joined by Helen Macdonald (resting GP and editor at The BMJ) and Carl Heneghan (active GP, director of Oxford...

For the next few months Talk Evidence is going to focus on the new corona virus pandemic. There is an enormous amount of uncertainty about the disease, what the symptoms are, fatality rate, treatment options, things we shouldn't be doing. We're going to try to get away from the headlines and talk about what we need to know - to hopefully give...

For the next few months Talk Evidence is going to focus on the new corona virus pandemic. There is an enormous amount of uncertainty about the disease, what the symptoms are, fatality rate, treatment options, things we shouldn't be doing. We're going to try to get away from the headlines and talk about what we need to know - to hopefully give...

For the next few months Talk Evidence is going to focus on the new corona virus pandemic. There is an enormous amount of uncertainty about the disease, what the symptoms are, fatality rate, treatment options, things we shouldn't be doing. We're going to try to get away from the headlines and talk about what we need to know - to hopefully give...

For the next few months Talk Evidence is going to focus on the new corona virus pandemic. There is an enormous amount of uncertainty about the disease, what the symptoms are, fatality rate, treatment options, things we shouldn't be doing. We're going to try to get away from the headlines and talk about what we need to know - to hopefully give...

For the next few months Talk Evidence is going to focus on the new corona virus pandemic. There is an enormous amount of uncertainty about the disease, what the symptoms are, fatality rate, treatment options, things we shouldn't be doing. We're going to try to get away from the headlines and talk about what we need to know - to hopefully give...

For the next few months Talk Evidence is going to focus on the new corona virus pandemic. There is an enormous amount of uncertainty about the disease, what the symptoms are, fatality rate, treatment options, things we shouldn't be doing. We're going to try to get away from the headlines and talk about what we need to know - to hopefully give you...

For the next few months Talk Evidence is going to focus on the new corona virus pandemic. There is an enormous amount of uncertainty about the disease, what the symptoms are, fatality rate, treatment options, things we shouldn't be doing. We're going to try to get away from the headlines and talk about what we need to know - to hopefully give you...

Katalin Susztak
Jan 1, 2006; 55:225-233
Complications

Dilys J. Freeman
May 1, 2002; 51:1596-1600
Complications

Masayuki Saito
Jul 1, 2009; 58:1526-1531
Metabolism

Markus Tiedge
Nov 1, 1997; 46:1733-1742
Original Article

Marc Prentki
Mar 1, 1996; 45:273-283
Original Article

Christophe Bonny
Jan 1, 2001; 50:77-82
Islet Studies

Joachim Spranger
Mar 1, 2003; 52:812-817
Pathophysiology

G Perseghin
Aug 1, 1999; 48:1600-1606
Articles

Charles M. Alexander
May 1, 2003; 52:1210-1214
Complications

Miriam Cnop
Dec 1, 2005; 54:S97-S107
Section III: Inflammation and beta-Cell Death

Tatsuya Hayashi
Aug 1, 1998; 47:1369-1373
Rapid Publications

T Inoguchi
Nov 1, 2000; 49:1939-1945
Articles

Eve Van Cauter
Mar 1, 1992; 41:368-377
Original Article

D A Pan
Jun 1, 1997; 46:983-988
Original Article

D Koya
Jun 1, 1998; 47:859-866
Articles

Roger H Unger
Aug 1, 1995; 44:863-870
Perspectives in Diabetes

Andreas Festa
Apr 1, 2002; 51:1131-1137
Complications

The Diabetes Control and Complications Trial Research Group
Aug 1, 1995; 44:968-983
Original Article

Norikazu Maeda
Sep 1, 2001; 50:2094-2099
Pathophysiology

ME Griffin
Jun 1, 1999; 48:1270-1274
Articles

John W Baynes
Apr 1, 1991; 40:405-412
Perspectives in Diabetes

Steven E Kahn
Nov 1, 1993; 42:1663-1672
Original Article

HE Hohmeier
Mar 1, 2000; 49:424-430
Articles

Alexandra E. Butler
Jan 1, 2003; 52:102-110
Islet Studies

This study aims to model genetic, immunologic, metabolomics, and proteomic biomarkers for development of islet autoimmunity (IA) and progression to type 1 diabetes in a prospective high-risk cohort. We studied 67 children: 42 who developed IA (20 of 42 progressed to diabetes) and 25 control subjects matched for sex and age. Biomarkers were assessed at four time points: earliest available sample, just prior to IA, just after IA, and just prior to diabetes onset. Predictors of IA and progression to diabetes were identified across disparate sources using an integrative machine learning algorithm and optimization-based feature selection. Our integrative approach was predictive of IA (area under the receiver operating characteristic curve [AUC] 0.91) and progression to diabetes (AUC 0.92) based on standard cross-validation (CV). Among the strongest predictors of IA were change in serum ascorbate, 3-methyl-oxobutyrate, and the PTPN22 (rs2476601) polymorphism. Serum glucose, ADP fibrinogen, and mannose were among the strongest predictors of progression to diabetes. This proof-of-principle analysis is the first study to integrate large, diverse biomarker data sets into a limited number of features, highlighting differences in pathways leading to IA from those predicting progression to diabetes. Integrated models, if validated in independent populations, could provide novel clues concerning the pathways leading to IA and type 1 diabetes.

Permanent neonatal diabetes mellitus (PNDM) is caused by reduced β-cell number or impaired β-cell function. Understanding of the genetic basis of this disorder highlights fundamental β-cell mechanisms. We performed trio genome sequencing for 44 patients with PNDM and their unaffected parents to identify causative de novo variants. Replication studies were performed in 188 patients diagnosed with diabetes before 2 years of age without a genetic diagnosis. EIF2B1 (encoding the eIF2B complex α subunit) was the only gene with novel de novo variants (all missense) in at least three patients. Replication studies identified two further patients with de novo EIF2B1 variants. In addition to having diabetes, four of five patients had hepatitis-like episodes in childhood. The EIF2B1 de novo mutations were found to map to the same protein surface. We propose that these variants render the eIF2B complex insensitive to eIF2 phosphorylation, which occurs under stress conditions and triggers expression of stress response genes. Failure of eIF2B to sense eIF2 phosphorylation likely leads to unregulated unfolded protein response and cell death. Our results establish de novo EIF2B1 mutations as a novel cause of permanent diabetes and liver dysfunction. These findings confirm the importance of cell stress regulation for β-cells and highlight EIF2B1’s fundamental role within this pathway.

Children at increased genetic risk for type 1 diabetes (T1D) after environmental exposures may develop pancreatic islet autoantibodies (IA) at a very young age. Metabolic profile changes over time may imply responses to exposures and signal development of the first IA. Our present research in The Environmental Determinants of Diabetes in the Young (TEDDY) study aimed to identify metabolome-wide signals preceding the first IA against GAD (GADA-first) or against insulin (IAA-first). We profiled metabolomes by mass spectrometry from children’s plasma at 3-month intervals after birth until appearance of the first IA. A trajectory analysis discovered each first IA preceded by reduced amino acid proline and branched-chain amino acids (BCAAs), respectively. With independent time point analysis following birth, we discovered dehydroascorbic acid (DHAA) contributing to the risk of each first IA, and -aminobutyric acid (GABAs) associated with the first autoantibody against insulin (IAA-first). Methionine and alanine, compounds produced in BCAA metabolism and fatty acids, also preceded IA at different time points. Unsaturated triglycerides and phosphatidylethanolamines decreased in abundance before appearance of either autoantibody. Our findings suggest that IAA-first and GADA-first are heralded by different patterns of DHAA, GABA, multiple amino acids, and fatty acids, which may be important to primary prevention of T1D.

Western Bureau: Some displaced Iberostar employees in Rose Hall, St James, are angry with their employer, charging that they have been unable to benefit from the Government’s COVID-19 relief programme because of the hotel’s failure to pay over...

Tears flowed yesterday down the face of Donaree Anderson, cousin of 15-year-old Nyron Taylor, one of two children shot dead in west Kingston hours apart on Wednesday. Eight-year-old Toya Brown was the other child killed just days into the month...

Edmond Campbell/Senior Parliamentary Reporter Conceding that healthcare workers in the public sector are burnt out as they combat COVID-19, Health and Wellness Minister Dr Christopher Tufton says the Government is taking steps to boost its...

The People’s National Party (PNP) has asserted that the absence of a quarantine order for three St Mary communities is adding to the state of confusion. The 14-day measure began on Thursday in Dover, Enfield and Annotto Bay at 6 a.m. “The lack of...

DOVER, St Mary: Residents of Epsom and Dover in St Mary are on edge, but have accepted quarantine measures imposed by the Government to curtail the spread of the dreaded coronavirus in that parish. Security checkpoints at both ends of the parish...

The wet weather last Saturday (May 2) could not dampen the spirits of award-winning gospel artiste and ordained evangelist Kevin Downswell as he ventured into the St Catherine community of Central Village, where he spent some of his formative years...