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

Most replicated genetic determinants for type 1 diabetes are common (minor allele frequency [MAF] >5%). We aimed to identify novel rare or low-frequency (MAF <5%) single nucleotide polymorphisms with large effects on risk of type 1 diabetes. We undertook deep imputation of genotyped data followed by genome-wide association testing and meta-analysis of 9,358 type 1 diabetes case and 15,705 control subjects from 12 European cohorts. Candidate variants were replicated in a separate cohort of 4,329 case and 9,543 control subjects. Our meta-analysis identified 27 independent variants outside the MHC, among which 3 were novel and had MAF <5%. Three of these variants replicated with P_replication < 0.05 and P_combined < P_discovery. In silico analysis prioritized a rare variant at 2q24.3 (rs60587303 [C], MAF 0.5%) within the first intron of STK39, with an effect size comparable with those of common variants in the INS and PTPN22 loci (combined [from the discovery and replication cohorts] estimate of odds ratio [OR_combined] 1.97, 95% CI 1.58–2.47, P_combined = 2.9 x 10^–9). Pharmacological inhibition of Stk39 activity in primary murine T cells augmented effector responses through enhancement of interleukin 2 signaling. These findings provide insight into the genetic architecture of type 1 diabetes and have identified rare variants having a large effect on disease risk.

WASHINGTON, CMC – The World Bank has predicted the sharpest decline of remittances to Latin America and the Caribbean, saying that global remittances on a whole are projected to fall by about 20 percent in 2020 due to the economic crisis...

Led by vice president of home clubhouse operations Rick Stowe, who began working for the club in 1981 and became head of the clubhouse in 1997, the Reds have a well-oiled machine with regard to packing up and moving out.

The Reds want to use Raisel Iglesias in the most intense moments, even if that means using someone else in the ninth.

Reduced storage of dietary fatty acids (DFAs) in abdominal adipose tissues with enhanced cardiac partitioning has been shown in subjects with type 2 diabetes (T2D) and prediabetes. We measured DFA metabolism and organ partitioning using positron emission tomography with oral and intravenous long-chain fatty acid and glucose tracers during a standard liquid meal in 12 obese subjects with T2D before and 8–12 days after bariatric surgery (sleeve gastrectomy or sleeve gastrectomy and biliopancreatic diversion with duodenal switch). Bariatric surgery reduced cardiac DFA uptake from a median (standard uptake value [SUV]) 1.75 (interquartile range 1.39–2.57) before to 1.09 (1.04–1.53) after surgery (P = 0.01) and systemic DFA spillover from 56.7 mmol before to 24.7 mmol over 6 h after meal intake after surgery (P = 0.01), with a significant increase in intra-abdominal adipose tissue DFA uptake from 0.15 (0.04–0.31] before to 0.49 (0.20–0.59) SUV after surgery (P = 0.008). Hepatic insulin resistance was significantly reduced in close association with increased DFA storage in intra-abdominal adipose tissues (r = –0.79, P = 0.05) and reduced DFA spillover (r = 0.76, P = 0.01). We conclude that bariatric surgery in subjects with T2D rapidly reduces cardiac DFA partitioning and hepatic insulin resistance at least in part through increased intra-abdominal DFA storage and reduced spillover.

Research Event

Event participants

Toby Fisher, Barrister, Landmark Chambers; Representative of the South African Human Rights Commission, Marikana Commission of Inquiry
Gary White, Director of Operations, Ineqe Group; Expert Witness on Policing, Marikana Commission of Inquiry
Chair: Muzong Kodi, Associate Fellow, Africa Programme

bmj;369/may07_9/m1832/FAF1faYara/ReutersThe meeting in Rome of Domenico di Massa with his granddaughter Cecilia for the first time in two months was echoed across Italy as families emerged onto the...

PET using radiolabeled prostate-specific membrane antigen (PSMA) is now being more widely adopted as a valuable tool to evaluate patients with prostate cancer (PC). Recently, 3 different criteria for interpretation of PSMA PET were published: the European Association of Nuclear Medicine (EANM) criteria, the Prostate Cancer Molecular Imaging Standardized Evaluation criteria, and the PSMA Reporting and Data System. We compared these 3 criteria in terms of interreader, intrareader, and intercriteria agreement. Methods: Data from 104 patients prospectively enrolled in research protocols at our institution were retrospectively reviewed. The cohort consisted of 2 groups: 47 patients (mean age, 64.2 y old) who underwent Glu-NH-CO-NH-Lys-(Ahx)-[⁶⁸Ga(HBED-CC)] (⁶⁸Ga-PSMA11) PET/MRI for initial staging of biopsy-proven intermediate- or high-risk PC, and 57 patients (mean age, 70.5 y old) who underwent ⁶⁸Ga-PSMA11 PET/CT because of biochemically recurrent PC. Three nuclear medicine physicians independently evaluated all ⁶⁸Ga-PSMA11 PET/MRI and PET/CT studies according to the 3 interpretation criteria. Two of them reevaluated all studies 6 mo later in the same manner and masked to the initial reading. The Gwet agreement coefficient was calculated to evaluate interreader, intrareader, and intercriteria agreement based on the following sites: local lesion (primary tumor or prostate bed after radical prostatectomy), lymph node metastases, and other metastases. Results: In the PET/MRI group, interreader, intrareader, and intercriteria agreement ranged from substantial to almost perfect for any site according to all 3 criteria. In the PET/CT group, interreader agreement ranged from substantial to almost perfect except for judgment of distant metastases based on the PSMA Reporting and Data System (Gwet agreement coefficient, 0.57; moderate agreement), in which the most frequent cause of disagreement was lung nodules. Intrareader agreement ranged from substantial to almost perfect for any site according to all 3 criteria. Intercriteria agreement for each site was also substantial to almost perfect. Conclusion: Although the 3 published criteria have good interreader and intrareader reproducibility in evaluating ⁶⁸Ga-PSMA11 PET, there are some factors causing interreader disagreement. Further work is needed to address this issue.

¹⁸F-PSMA-1007 is a novel prostate-specific membrane antigen (PSMA)–based radiopharmaceutical for imaging prostate cancer (PCa). The aim of this study was to compare the diagnostic accuracy of ¹⁸F-PSMA-1007 with ⁶⁸Ga-PSMA-11 PET/CT in the same patients presenting with newly diagnosed intermediate- or high-risk PCa. Methods: Sixteen patients with intermediate- or high-risk PCa underwent ¹⁸F-PSMA-1007 and ⁶⁸Ga-PSMA-11 PET/CT within 15 d. PET findings were compared between the 2 radiotracers and with reference-standard pathologic specimens obtained from radical prostatectomy. The Cohen -coefficient was used to assess the concordance between ¹⁸F-PSMA-1007 and ⁶⁸Ga-PSMA-11 for detection of intraprostatic lesions. The McNemar test was used to assess agreement between intraprostatic PET/CT findings and histopathologic findings. Sensitivity, specificity, positive predictive value, and negative predictive value were reported for each radiotracer. SUV_max was measured for all lesions, and tumor-to-background activity was calculated. Areas under receiver-operating-characteristic curves were calculated for discriminating diseased from nondiseased prostate segments, and optimal SUV cutoffs were calculated using the Youden index for each radiotracer. Results: PSMA-avid lesions in the prostate were identified in all 16 patients with an almost perfect concordance between the 2 tracers ( ranged from 0.871 to 1). Aside from the dominant intraprostatic lesion, similarly detected by both radiotracers, a second less intense positive focus was detected in 4 patients only with ¹⁸F-PSMA-1007. Three of these secondary foci were confirmed as Gleason grade 3 lesions, whereas the fourth was shown on pathologic examination to represent chronic prostatitis. Conclusion: This pilot study showed that both ¹⁸F-PSMA-1007 and ⁶⁸Ga-PSMA-11 identify all dominant prostatic lesions in patients with intermediate- or high-risk PCa at staging. ¹⁸F-PSMA-1007, however, may detect additional low-grade lesions of limited clinical relevance.

Caribbean Coffee Traders Limited, CCTL, is moving ahead with plans for a US$30-million bond placement, the proceeds from which it will likely use to expand the Starbucks chain it operates in three regional markets. The initial franchise agreement...

Invitation Only Research Event

Event participants

Andrew Grant, Carbon Tracker Initiative
Chair: Siân Bradley, Research Fellow, Energy, Environment and Resources, Chatham House

Research Event

As policymakers in a number of countries, the United States among them, debate limiting family-based immigration, this issue brief explores family-migration trends and policies in the United States, Australia, Canada, the United Kingdom, and several other European countries. Family admissions play a key role, even in countries that prioritize economic or other immigration streams.

As federal and state governments ramp up efforts to implement the Workforce Innovation and Opportunity Act, these fact sheets compare key characteristics of the foreign born and the U.S. born that are relevant to understanding needs for adult education and workforce training services. The fact sheets cover the United States, the 20 states and 25 counties with the largest immigrant populations, and New York City.

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.

OBJECTIVE

To characterize the status of cardiometabolic risk factors after late relapse of type 2 diabetes mellitus (T2DM) and to identify factors predicting relapse after initial diabetes remission following bariatric surgery to construct prediction models for clinical practice.

Conservation officials in Ontario are asking members of the public to be on the lookout for a former pet snake that was mistakenly released into the wild near a conservation area.

Firefighters in Arizona came to the rescue of a puppy that plunged into a 15-foot-deep hole at a construction site.

The Air Force and Marines have both reported engaging in training maneuvers in the East and South China Sea in recent weeks amid escalating tensions in the region.

Top Pentagon officials told lawmakers Wednesday that a proposed nationwide network to provide 5G and internet-of-things services was "too risky to be worth it."

Khalid A. Jadoon
Oct 1, 2016; 39:1777-1786
Emerging Technologies and Therapeutics

Vanita R. Aroda
Sep 1, 2019; 42:1724-1732
Emerging Therapies: Drugs and Regimens

OBJECTIVE

To evaluate the respective contributions of short-term glycemic variability and mean daily glucose (MDG) concentration to the risk of hypoglycemia in type 1 diabetes.

Caribbean immigrants represent 10 percent of the 44.5 million immigrants in the United States, with the vast majority coming from just five countries: Cuba, the Dominican Republic, Jamaica, Haiti, and Trinidad and Tobago. Depending on their origin country and period of arrival, immigrants from the Caribbean have varying skill levels, racial composition, language background, and motivations for migration, as this article explores.

The high-stakes gambit taken by Turkish President Recep Tayyip Erdoğan to allow tens of thousands of asylum seekers and migrants free movement to the Greek border demonstrated the fragility of the EU-Turkey deal and the European Union's broader approach to outsource migration management to third countries. This article examines the causes for the tensions, the EU approach to external partnerships, and a hardening European attitude towards unwanted arrivals.

Presentación del reporte que refleja el contenido de encuentros del grupo de estudio sobre la migración México-Estados Unidos convocado por El Colegio de México y el Migration Policy Institute (MPI).

MPI and MPI Europe experts discuss the effects of the coronavirus pandemic on asylum systems in Europe and North America, as well as in developing regions, where 85 percent of refugees live. During this freeform conversation, our analysts also assess the implications for the principle of asylum and the future for a post-World War II humanitarian protection system that is under threat.

Durante su primera visita oficial a Washington, DC, la Secretaria de Gobierno Olga Sánchez Cordero presento un discurso público sobre la nueva política migratoria de México en el Instituto de Políticas Migratorias.

This event organized by the Migration Policy Institute and American Enterprise Institute features a conversation on U.S.-Mexico border conditions, as well as policy responses and regional cooperation on illegal immigration. 

This event features a smart conversation by a range of experts on U.S.-Mexico border conditions, looking at policy responses by both countries and regional cooperation.

Dr. Loree Bolin’s humanitarian work has drawn accolades from the dental community in her home state of Washington, and now Dr. Bolin is being recognized nationally by being named the recipient of the ADA’s 2020 Humanitarian Award, bestowed by the ADA Board of Trustees.

The Central Arizona Dental Society hosted a Mission of Mercy event Dec. 13-14 at the Arizona State Fairgrounds in Phoenix, providing treatment to 1,785 patients totaling just over $2 million in free dental service.

Greater compliance with dietary guidelines may reduce the chance of untreated caries in adults, according to a study published in the February issue of The Journal of the American Dental Association.

It’s a conviction that was published in the November issue of The Journal of the American Dental Association and the basis for the October 2019 forum that Dr. Francisco Ramos-Gomez fostered, where dentists, physicians, nurses and public health and public policy experts proposed, discussed and recommended solutions for preventing early childhood caries through the lens of social justice, health equity and human rights.

Circulating levels of perfluorodecanoic acid, a type of perfluoroalkyl acid, may be associated with dental caries in children, according to a study published in the fall 2019 issue of the Journal of Public Health Dentistry.

Titled “Compendium of Innovations in Oral Health Service Delivery,” the 64-page digital booklet features organizations from across the country that have found success through varied measures in expanding oral care to underserved populations.

The American Dental Association is applauding the U.S. Department of Health and Human Services’ decision to appoint a chief dental officer at the Centers for Medicare & Medicaid but would like to confirm the position is exclusive to CMS.

The Association continues to wait for clear guidance from the U.S. Department of Treasury and Small Business Administration on the best way to help dentists considering applying for Paycheck Protection Program 7(a) loans and Economic Injury Disaster Loans.

Traveling with purpose is what has led Nevada City, California-based general dentist Dr. Jean Creasey to a rural district in the southwestern region of Uganda over the past 15 years as a member of the Kellermann Foundation, treating and helping educate the villagers on the importance of good oral health as a way to a better future.

Scottsdale, Ariz. — In February, the Arizona Dental Association was fully prepared to host the Western Regional Dental Experience April 2-4 at the Renaissance Phoenix Glendale Hotel and Spa.

A microbe found in mosquitoes that appears to block malaria could be used to control spread of the disease in humans, according to researchers in Kenya and Britain.

OBJECTIVE

The association between high glycemic variability and all-cause mortality has been widely investigated in epidemiological studies but rarely validated in glucose-lowering clinical trials. We aimed to identify the prognostic significance of visit-to-visit HbA_1c variability in treated patients in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial population.

OBJECTIVE

Although blood pressure variability is increasingly appreciated as a risk factor for cardiovascular disease, its relationship with heart failure (HF) is less clear. We examined the relationship between blood pressure variability and risk of HF in two cohorts of type 2 diabetes participating in trials of glucose and/or other risk factor management.

OBJECTIVE

The role of U300 glargine insulin for the inpatient management of type 2 diabetes (T2D) has not been determined. We compared the safety and efficacy of glargine U300 versus glargine U100 in noncritically ill patients with T2D.