The Current Index to Statistics (CIS) is now hosted by the AMS.  It is available on the MathSciNet servers from the URL mathscinet.ams.org/cis.  The database is openly available using a brand new search interface.  Some history The Current Index to … Continue reading →

Mathematics is a useful tool in studying the growth of infections in a population, such as what occurs in epidemics.  A simple model is given by a first-order differential equation, the logistic equation, $frac{dx}{dy}=eta x(1-x)$ which is discussed in almost any … Continue reading →

Invitation Only Research Event

Event participants

Anita Isaacs, Professor of Political Science, Haverford College; Co-Director, Migration Encounters Project
Juan Ricardo Ortega, Principal Advisor for Central America, Inter-American Development Bank
Chair: Amy Pope, Associate Fellow, Chatham House; US Deputy Homeland Security Adviser for the Obama Administration (2015-17)

Invitation Only Research Event

Event participants

Dr Kurt Campbell, Chairman, CEO and Co-Founder, The Asia Group; Assistant Secretary of State for East Asian and Pacific Affairs, 2009-13
Chair: Dr Leslie Vinjamuri, Director, US and the Americas Programme, Chatham House

Invitation Only Research Event

Event participants

Laurence Broers, Associate Fellow, Russia and Eurasia Programme, Chatham House
Chair: Lubica Pollakova, Senior Programme Manager, Russia and Eurasia Programme

I cannot quite remember the exact day he called me, but I know that it was sometime in the early 1990s. Six weeks before that, he was selected as constituency caretaker for a rough garrison seat that was going through some changes, slowly but...

Welcome to this, trial run, of a new kind of BMJ podcast - here we’re going to be focusing on all things EBM. Duncan Jarvies, Helen Macdonald and Carl Heneghan - and occasional guests- will be back every month to discuss what's been happening in the world of evidence. We'll bring you our Verdict on what you should start or stop doing, geek out...

In every generation there are a few that know the secret; the counterintuitive effects of loop diuretics. In this podcast Steven Anisman, cardiologist at the Dartmouth Hitchcock Department of Cardiovascular Medicine, joins us to explain about the threshold effects of these drugs, and why that might change the way in which you think about...

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...

Mariano J Garcia
Feb 1, 1974; 23:105-111
Original Contribution

Long-term hyperglycemia in patients with diabetes leads to human serum albumin (HSA) glycation, which may impair HSA function as a transport protein and affect the therapeutic efficacy of anticoagulants in patients with diabetes. In this study, a novel mass spectrometry approach was developed to reveal the differences in the profiles of HSA glycation sites between patients with diabetes and healthy subjects. K199 was the glycation site most significantly changed in patients with diabetes, contributing to different interactions of glycated HSA and normal HSA with two types of anticoagulant drugs, heparin and warfarin. An in vitro experiment showed that the binding affinity to warfarin became stronger when HSA was glycated, while HSA binding to heparin was not significantly influenced by glycation. A pharmacokinetic study showed a decreased level of free warfarin in the plasma of diabetic rats. A preliminary retrospective clinical study also revealed that there was a statistically significant difference in the anticoagulant efficacy between patients with diabetes and patients without diabetes who had been treated with warfarin. Our work suggests that larger studies are needed to provide additional specific guidance for patients with diabetes when they are administered anticoagulant drugs or drugs for treating other chronic diseases.

Research Event

Event participants

Dr David Zweig, Chair Professor, Division of Social Science, Hong Kong University of Science and Technology
Chair: Dr Michal Meidan, Associate Fellow, Asia Programme, Chatham House

Members Event

Event participants

Professor Dieter Helm CBE, Professor of Energy Policy, University of Oxford

Chair: David Shukman, Science Editor, BBC News

Invitation Only Research Event

Fibroblast activation protein (FAP), which promotes tumor growth and progression, is overexpressed in cancer-associated fibroblasts of many human epithelial cancers. Because of its low expression in normal organs, FAP is an excellent target for theranostics. In this study, we used radionuclides with relatively long half-lives, ⁶⁴Cu (half-life, 12.7 h) and ²²⁵Ac (half-life, 10 d), to label FAP inhibitors (FAPIs) in mice with human pancreatic cancer xenografts. Methods: Male nude mice (body weight, 22.5 ± 1.2 g) were subcutaneously injected with human pancreatic cancer cells (PANC-1, n = 12; MIA PaCa-2, n = 8). Tumor xenograft mice were investigated after the intravenous injection of ⁶⁴Cu-FAPI-04 (7.21 ± 0.46 MBq) by dynamic and delayed PET scans (2.5 h after injection). Static scans 1 h after the injection of ⁶⁸Ga-FAPI-04 (3.6 ± 1.4 MBq) were also acquired for comparisons using the same cohort of mice (n = 8). Immunohistochemical staining was performed to confirm FAP expression in tumor xenografts using an FAP-α-antibody. For radioligand therapy, ²²⁵Ac-FAPI-04 (34 kBq) was injected into PANC-1 xenograft mice (n = 6). Tumor size was monitored and compared with that of control mice (n = 6). Results: Dynamic imaging of ⁶⁴Cu-FAPI-04 showed rapid clearance through the kidneys and slow washout from tumors. Delayed PET imaging of ⁶⁴Cu-FAPI-04 showed mild uptake in tumors and relatively high uptake in the liver and intestine. Accumulation levels in the tumor or normal organs were significantly higher for ⁶⁴Cu-FAPI-04 than for ⁶⁸Ga-FAPI-04, except in the heart, and excretion in the urine was higher for ⁶⁸Ga-FAPI-04 than for ⁶⁴Cu-FAPI-04. Immunohistochemical staining revealed abundant FAP expression in the stroma of xenografts. ²²⁵Ac-FAPI-04 injection showed significant tumor growth suppression in the PANC-1 xenograft mice, compared with the control mice, without a significant change in body weight. Conclusion: This proof-of-concept study showed that ⁶⁴Cu-FAPI-04 and ²²⁵Ac-FAPI-04 could be used in theranostics for the treatment of FAP-expressing pancreatic cancer. α-therapy targeting FAP in the cancer stroma is effective and will contribute to the development of a new treatment strategy.

Immunotherapy is becoming the mainstay for treatment of a variety of malignancies, but only a subset of patients responds to treatment. Tumor-infiltrating CD8-positive (CD8+) T lymphocytes play a central role in antitumor immune responses. Noninvasive imaging of CD8+ T cells may provide new insights into the mechanisms of immunotherapy and potentially predict treatment response. We are studying the safety and utility of ⁸⁹Zr-IAB22M2C, a radiolabeled minibody against CD8+ T cells, for targeted imaging of CD8+ T cells in patients with cancer. Methods: The initial dose escalation phase of this first-in-humans prospective study included 6 patients (melanoma, 1; lung, 4; hepatocellular carcinoma, 1). Patients received approximately 111 MBq (3 mCi) of ⁸⁹Zr-IAB22M2C (at minibody mass doses of 0.2, 0.5, 1.0, 1.5, 5, or 10 mg) as a single dose, followed by PET/CT scans at approximately 1–2, 6–8, 24, 48, and 96–144 h after injection. Biodistribution in normal organs, lymph nodes, and lesions was evaluated. In addition, serum samples were obtained at approximately 5, 30, and 60 min and later at the times of imaging. Patients were monitored for safety during infusion and up to the last imaging time point. Results: ⁸⁹Zr-IAB22M2C infusion was well tolerated, with no immediate or delayed side effects observed after injection. Serum clearance was typically biexponential and dependent on the mass of minibody administered. Areas under the serum time–activity curve, normalized to administered activity, ranged from 1.3 h/L for 0.2 mg to 8.9 h/L for 10 mg. Biodistribution was dependent on the minibody mass administered. The highest uptake was always in spleen, followed by bone marrow. Liver uptake was more pronounced with higher minibody masses. Kidney uptake was typically low. Prominent uptake was seen in multiple normal lymph nodes as early as 2 h after injection, peaking by 24–48 h after injection. Uptake in tumor lesions was seen on imaging as early as 2 h after injection, with most ⁸⁹Zr-IAB22M2C–positive lesions detectable by 24 h. Lesions were visualized early in patients receiving treatment, with SUV ranging from 5.85 to 22.8 in 6 target lesions. Conclusion: ⁸⁹Zr-IAB22M2C imaging is safe and has favorable kinetics for early imaging. Biodistribution suggests successful targeting of CD8+ T-cell–rich tissues. The observed targeting of tumor lesions suggests this may be informative for CD8+ T-cell accumulation within tumors. Further evaluation is under way.

Radiomics is a rapidly evolving field of research concerned with the extraction of quantitative metrics—the so-called radiomic features—within medical images. Radiomic features capture tissue and lesion characteristics such as heterogeneity and shape and may, alone or in combination with demographic, histologic, genomic, or proteomic data, be used for clinical problem solving. The goal of this continuing education article is to provide an introduction to the field, covering the basic radiomics workflow: feature calculation and selection, dimensionality reduction, and data processing. Potential clinical applications in nuclear medicine that include PET radiomics-based prediction of treatment response and survival will be discussed. Current limitations of radiomics, such as sensitivity to acquisition parameter variations, and common pitfalls will also be covered.

7 May 2020 , Volume 96, Number 3

15 April 2020

Knowledge of the molecular events in mitochondrial DNA (mtDNA) replication is crucial to understanding the origins of human disorders arising from mitochondrial dysfunction. Twinkle helicase is an essential component of mtDNA replication. Here, we employed atomic force microscopy imaging in air and liquids to visualize ring assembly, DNA binding, and unwinding activity of individual Twinkle hexamers at the single-molecule level. We observed that the Twinkle subunits self-assemble into hexamers and higher-order complexes that can switch between open and closed-ring configurations in the absence of DNA. Our analyses helped visualize Twinkle loading onto and unloading from DNA in an open-ringed configuration. They also revealed that closed-ring conformers bind and unwind several hundred base pairs of duplex DNA at an average rate of ∼240 bp/min. We found that the addition of mitochondrial single-stranded (ss) DNA–binding protein both influences the ways Twinkle loads onto defined DNA substrates and stabilizes the unwound ssDNA product, resulting in a ∼5-fold stimulation of the apparent DNA-unwinding rate. Mitochondrial ssDNA-binding protein also increased the estimated translocation processivity from 1750 to >9000 bp before helicase disassociation, suggesting that more than half of the mitochondrial genome could be unwound by Twinkle during a single DNA-binding event. The strategies used in this work provide a new platform to examine Twinkle disease variants and the core mtDNA replication machinery. They also offer an enhanced framework to investigate molecular mechanisms underlying deletion and depletion of the mitochondrial genome as observed in mitochondrial diseases.

In 2015, 43.3 million immigrants lived in the United States, comprising 13.5 percent of the population. The foreign-born population grew more slowly than in prior years, up 2 percent from 2014. Get sought-after data on U.S. immigration trends, including top countries of origin, Mexican migration, refugee admissions, illegal immigration, health-care coverage, and much more in this Spotlight article.

The United States is by far the world's top migration destination, home to roughly one-fifth of all global migrants. In 2016, nearly 44 million immigrants lived in the United States, comprising 13.5 percent of the country's population. Get the most sought-after data available on immigrants and immigration trends, including top countries of origin, legal immigration pathways, enforcement actions, health-care coverage, and much more.

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.

States are in the midst of designing new policies to hold schools accountable for the education of English Learner (EL) students, as mandated by the federal Every Student Succeeds Act (ESSA). This series of fact sheets sketches the characteristics of immigrant and EL students in 25 states, the gaps between their educational outcomes and those of their peers, and the accountability policies each state is developing.

From being a source of labor emigration to the Gulf region to a destination for refugees from Syria, sub-Saharan Africa, and elsewhere, Egypt has long experienced different forms of mobility. This article, which profiles the trends and policies that have shaped Egypt's migration history, focuses on its long-standing use of migration as a soft-power tool to achieve its foreign policy aims and as a safety valve for political discontent.

The impact of climate change as a driver of human migration is expected by many to dwarf all others. Still, certain frequently repeated forecasts of the number of people who stand to be displaced by climate change are not informed by a complete understanding of migration dynamics, as this report explains.

Philadelphia Phillies star Bryce Harper thinks Major League Baseball is "dumb" for its policy that makes the Olympics off-limits for baseball's best players.

Evan M. Benjamin
Jan 1, 2002; 20:
Practical Pointers

Korey K. Hood
Jun 1, 2006; 29:1389-1389
BR Epidemiology/Health Services/Psychosocial Research

Sunder Mudaliar
Jul 1, 2016; 39:1115-1122
Diabetes Care Symposium

As the world gets ready for the Special Olympics Sweden Invitational Games in February, one of the ADA’s member dentists will be watching as the Special Smiles program he founded will be used to screen and attend to the dental needs of the competing athletes.

The ADA Council on Ethics, Bylaws and Judicial Affairs’ ethics subcommittee authored an online essay as part of its Ethical Moment series in the May issue of The Journal of the American Dental Association, affirming that the ADA Principles of Ethics and Code of Professional Conduct is just as important as ever when making the difficult decisions they encounter on a daily basis.

Two of the authors of the American Dental Association's antibiotics guideline will discuss C. diff infections and antibiotic stewardship in dentistry April 21 as part of a free, online conference organized by the Peggy Lillis Foundation.

The American College of Emergency Physicians has endorsed the American Dental Association's clinical practice guideline on the use of antibiotics for the management of pulpal- and periapical-related pain and swelling.

OBJECTIVE

In 2017, the American Academy of Pediatrics introduced a new guideline (2017 Clinical Practice Guideline of the American Academy of Pediatrics [AAP 2017]) to diagnose arterial hypertension (HTN) in children that included revised, lower normative blood pressure (BP) values and cut points for diagnosing high BP in adolescents. We studied the impact of the new AAP 2017 guideline on prevalence of HTN in children with type 1 diabetes mellitus (T1DM).

OBJECTIVE

Type 2 diabetes develops for many years before diagnosis. We aimed to reveal early metabolic features characterizing liability to adult disease by examining genetic liability to adult type 2 diabetes in relation to metabolomic traits across early life.

Immigrant arrivals to the United States and the makeup of the foreign-born population have been changing in significant ways: Recent immigrants are more likely to be from Asia than from Mexico and the overall immigrant population is growing at a slower rate than before the 2008-09 recession. This useful article collects in one place some of the most sought-after statistics on immigrants in the United States.

Intensive farming, characterized by the overuse of antibiotics, large numbers of animals and limited genetic diversity, increases the odds of animal pathogens making the jump to humans and triggering an epidemic.

As the tropics get wetter, soils are likely experience greater rates of respiration and decomposition, limiting the carbon storage abilities of tropical soils and intensifying global warming.

Faced with high emigration rates and shrinking, aging populations, the Baltic states—Estonia, Latvia, and Lithuania—are exploring different ways to lure back nationals who have emigrated and establish or solidify ties with members of the diaspora. Of the three countries, Estonia is proving the most successful, while Latvia appears to be ignoring the looming demographic crisis and lacks an immigration plan.

I certainly do, it doesn't make sense how someone crazy recording someone getting killed isn't illegal but CP is! That shouldn't be because, they should be either running away or trying to stop that super duper crazy person. Why can't both of them be illegal?

Good or bad? Better or worse than Huckabee?