As pitchers and catchers reported Tuesday to Ed Smith Stadium, it marked the end to an offseason of overhaul in Baltimore, and the dawn of a new era. The focus will shift even further, from the front office to the field, when the club's first full squad workouts commence on Monday.

Portmore United captain Rosario Harriott says the Premier League Clubs Association shouldn’t rush to call off this season of the Red Stripe Premier League (RSPL) because of the COVID-19 pandemic. The league was stopped indefinitely in mid-March...

The UK’s austerity programme has disproportionately affected children and people with disabilities, says David Taylor-Robinson, a senior clinical lecturer in public health at the University of Liverpool. He joins us to discuss why the evidence shows the vulnerable are hit hardest by the cuts to public services, despite the UN conventions on...

PTSD may develop after exposure to exceptionally threatening or horrifying events. About 3% of the adult population has PTSD at any one time, and more than 50% in survivors of rape. In this podcast Jonathan Bisson, professor of psychiatry at the School of Medicine in Cardiff joins us to talk about the evidence for diagnosis and treatment, and...

However well intentioned, working in detention centres amounts to complicity in torture, says David Berger, a district medical officer in emergency medicine at Broome Hospital in Australia. However, Steven Miles, chair in bioethics at the University of Minnesota thinks that they play an important role in telling the world about conditions in...

In February World Health Organization (WHO) declared the microcephaly epidemic in South America an international public health emergency. Today, the US Centers for Disease Control and Prevention, the CDC, has confirmed that it’s is Zika virus which is causing that microcephaly.  The outbreak was originally spotted in Recife, in Brazil, and it’s...

Medical error is not included on death certificates or in rankings of cause of death. Martin Makary, professor of surgery at Johns Hopkins University School of Medicine, joins us to explain why we don't measure medical error, and why it is so important that we start. Read the full analysis: http://www.bmj.com/content/353/bmj.i2139

Findings from a range of prospective cohort studies based around the world indicate that higher intelligence in children is related to a lower risk of all cause mortality in adulthood - and now a new study, published on bmj.com, is trying to dig into that association further, with a whole population cohort and data on cause specific...

Nausea and vomiting in pregnancy affects around 70% of pregnancies. It is mild for around 40% of women, moderate for 46%, and severe for 14%. By contrast, hyperemesis gravidarum is a complication of pregnancy rather than a normal part of it and occurs in around 1.5% of pregnancies. The psychosocial burden of HG can be heavy for women and their...

Stroke mortality rates have been declining in almost every country, and that reduction could result from a decline in disease occurrence or a decline in case fatality, or both. Broadly - is that decline down to better treatment or better prevention. Olena Seminog, a researcher, and and Mike Rayner, professor of population health, both from the...

Helen Macdonald and Carl Heneghan are back again talking about what's happened in the world of evidence this month. (1.05) Carl rants about bacon causing cancer (7.10) Helen talks about prostate cancer, and we hear from the author of the research paper which won Research Paper Of The Year at the BMJ awards. We also cover disease definition and...

Cochrane Austria have been asking the public what they'd like to know about health. Not whether the latest drug is more efficacious, but whether glacier stone power cures hangovers. Gerald Gartlehner, director of the Cochrane Austria Centre joins us to explain what they do, and how their evidence has been received. Read more about the project...

Last week the BMJ published it’s first special edition into Racism in Medicine. The issues tacked ranged from differential attainment in medical school, to the physiological effects that experiencing everyday discrimination has. The issue was guest edited by Victor Adebowale, the Chief Executive of the social care enterprise Turning Point, and...

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

EJ Kurth-Kraczek
Aug 1, 1999; 48:1667-1671
Articles

D Dabelea
Dec 1, 2000; 49:2208-2211
Articles

C. Ronald Kahn
Aug 1, 1994; 43:1066-1085
Banting Lecture

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.

PORT OF SPAIN, Trinidad, CMC – The Trinidad and Tobago government Saturday said it had uncovered a plot by persons to defraud the state and that a new mechanism would be put in place Monday in providing rental assistance to people impacted by...

She’s what you’d term the consummate creative – through the sensory ‘dry land tourist’ tales of her ‘Right Roun Di Corna’ blog to the pieces in her JadeLauren eyewear brand, Lauren Campbell is colouring the world with beauty, life, and bomb...

A single bout of exercise enhances insulin action in the exercised muscle. However, not all human studies find that this translates into increased whole-body insulin action, suggesting that insulin action in rested muscle or other organs may be decreased by exercise. To investigate this, eight healthy men underwent a euglycemic-hyperinsulinemic clamp on 2 separate days: one day with prior one-legged knee-extensor exercise to local exhaustion (~2.5 h) and another day without exercise. Whole-body glucose disposal was ~18% lower on the exercise day as compared with the resting day due to decreased (~37%) insulin-stimulated glucose uptake in the nonexercised muscle. Insulin signaling at the level of Akt2 was impaired in the nonexercised muscle on the exercise day, suggesting that decreased insulin action in nonexercised muscle may reduce GLUT4 translocation in response to insulin. Thus, the effect of a single bout of exercise on whole-body insulin action depends on the balance between local effects increasing and systemic effects decreasing insulin action. Physiologically, this mechanism may serve to direct glucose into the muscles in need of glycogen replenishment. For insulin-treated patients, this complex relationship may explain the difficulties in predicting the adequate insulin dose for maintaining glucose homeostasis following physical activity.

Optimal immune-based therapies for type 1 diabetes (T1D) should restore self-tolerance without inducing chronic immunosuppression. CD4⁺Foxp3⁺ regulatory T cells (T_regs) are a key cell population capable of facilitating durable immune tolerance. However, clinical trials with expanded T_regs in T1D and solid-organ transplant recipients are limited by poor T_reg engraftment without host manipulation. We showed that T_reg engraftment and therapeutic benefit in nonautoimmune models required ablative host conditioning. Here, we evaluated T_reg engraftment and therapeutic efficacy in the nonobese diabetic (NOD) mouse model of autoimmune diabetes using nonablative, combinatorial regimens involving the anti-CD3 (αCD3), cyclophosphamide (CyP), and IAC (IL-2/JES6–1) antibody complex. We demonstrate that αCD3 alone induced substantial T-cell depletion, impacting both conventional T cells (T_conv) and T_regs, subsequently followed by more rapid rebound of T_regs. Despite robust depletion of host T_conv and host T_regs, donor T_regs failed to engraft even with interleukin-2 (IL-2) support. A single dose of CyP after αCD3 depleted rebounding host T_regs and resulted in a 43-fold increase in donor T_reg engraftment, yet polyclonal donor T_regs failed to reverse diabetes. However, infusion of autoantigen-specific T_regs after αCD3 alone resulted in robust T_reg engraftment within the islets and induced remission in all mice. This novel combinatorial therapy promotes engraftment of autoantigen-specific donor T_regs and controls islet autoimmunity without long-term immunosuppression.

Autoimmunity against pancreatic β-cell autoantigens is a characteristic of childhood type 1 diabetes (T1D). Autoimmunity usually appears in genetically susceptible children with the development of autoantibodies against (pro)insulin in early childhood. The offspring of mothers with T1D are protected from this process. The aim of this study was to determine whether the protection conferred by maternal T1D is associated with improved neonatal tolerance against (pro)insulin. Consistent with improved neonatal tolerance, the offspring of mothers with T1D had reduced cord blood CD4⁺ T-cell responses to proinsulin and insulin, a reduction in the inflammatory profile of their proinsulin-responsive CD4⁺ T cells, and improved regulation of CD4⁺ T cell responses to proinsulin at 9 months of age, as compared with offspring with a father or sibling with T1D. Maternal T1D was also associated with a modest reduction in CpG methylation of the INS gene in cord blood mononuclear cells from offspring with a susceptible INS genotype. Our findings support the concept that a maternal T1D environment improves neonatal immune tolerance against the autoantigen (pro)insulin.

Invitation Only Research Event

Event participants

Professor Philippe Sands QC, Professor of Law, UCL 
Richard Burt, Managing Partner, McLarty Associates
Chair: Dr Leslie Vinjamuri, Director, US and Americas Programme; Dean, Queen Elizabeth II Academy, Chatham House

Members Event

Event participants

Penny Mordaunt MP, Member of Parliament for Portsmouth North; Secretary of State for Defence (2019); Secretary of State for International Development (2017-2019)

Chair: Thomas Raines, Director, Europe Programme, Chatham House

23 January 2020

Growing up with unauthorized immigrant parents puts children—nearly 80 percent of whom were born in the United States—at a disadvantage, with lower preschool enrollment, reduced socioeconomic progress, and higher rates of linguistic isolation and poverty. This fact sheet examines the number, characteristics, and socioeconomic status of children, both U.S.-citizen and noncitizen, who have unauthorized immigrant parents.

A high school diploma has been a core requirement of proposed DREAM Act legislation and the Deferred Action for Childhood Arrivals (DACA) program. Yet a fresh estimate of the number of unauthorized immigrants graduating annually from U.S. high schools has long been missing from the debate. This fact sheet provides up-to-date estimates for the United States and top 15 states, estimating 98,000 such students graduate yearly.

Development assistance may be a blunt tool for reshaping migration patterns—and indeed one that could increase flows over the short term. Shifting the focus away from increasing individuals’ skills and assets toward investments in the broader economic or governance structures that are a prerequisite for growth and stability may offer more alternatives to emigration in the long run.

Authoritarian states have long attempted to restrict citizens’ movement. But what happens when their reach extends beyond their borders? The October 2018 assassination of Saudi journalist Jamal Khashoggi brought into sharp relief the long arm of these regimes in reaching citizens abroad. This phenomenon, “transnational authoritarianism,” further shows that the relationship between migration and authoritarianism is becoming more complex.

Immigration has driven economic and social development in Australia for more than two centuries. Even as more than one-fourth of the country’s population is foreign born and Australia ranks third among top refugee resettlement countries worldwide, controversy surrounding its hardline treatment of asylum seekers arriving by boat has cast a shadow on its reputation as a welcoming country, as this article explores.

Migrants displaced by crisis do not benefit from international protection the way that refugees do. This article examines the experiences of labor migrants amid manmade and natural disasters in the Central African Republic, Côte d’Ivoire, Lebanon, Libya, South Africa, and Thailand, as well as stakeholder responses. Research demonstrates the agency and resilience of migrants, who develop flexible solutions in the face of crisis.

An MPI Leadership Visions discussion with the Foreign Minister of Mexico, Claudia Ruiz-Massieu, for her first public appearance in Washington, DC. 

Michigan coach Jim Harbaugh is urging the NFL and NCAA to amend their rules and provide flexibility to college football players who consider making the jump to the next level.

OBJECTIVE

Sustained excess BMI increases the risk of type 1 diabetes (T1D) in autoantibody-positive relatives without diabetes of patients. We tested whether elevated BMI also accelerates the progression of islet autoimmunity before T1D diagnosis.

A "Shoeless" Joe Jackson baseball card from 1910 sold at auction for $492,000 this week.

Joseph Henson
Jan 1, 2016; 39:130-138
IDF-ADA Translational Symposium

Jing Hughes
Apr 1, 2015; 38:e55-e57
e-Letters: Observations

Johanna M Mooy
Sep 1, 1995; 18:1270-1273
Short Report

Pell, a former Vatican treasurer, was aware of child abuse being committed by clergy by 1973, contrary to his long-held assertions that he knew nothing about the accusations.

Officials said 15 migrant workers were killed Friday when a cargo train ran them over as they slept on the tracks near Aurangabad, India.

Boeing announced Tuesday has presented its first unmanned aircraft to the Royal Australian Air Force.

The Air Force said Wednesday it will launch the sixth mission of the uncrewed X-37B spy plane May 16 from Florida with a record number of experiments on board.

Huntington Ingalls was awarded a $187.1 million contract modification Wednesday for the refueling complex overhaul of USS John C. Stennis, according to the Pentagon.