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"George, J"
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Management of Graves Thyroidal and Extrathyroidal Disease: An Update
Abstract
Context
Invited update on the management of systemic autoimmune Graves disease (GD) and associated Graves orbitopathy (GO).
Evidence acquisition
Guidelines, pertinent original articles, systemic reviews, and meta-analyses.
Evidence synthesis
Thyrotropin receptor antibodies (TSH-R-Abs), foremost the stimulatory TSH-R-Abs, are a specific biomarker for GD. Their measurement assists in the differential diagnosis of hyperthyroidism and offers accurate and rapid diagnosis of GD. Thyroid ultrasound is a sensitive imaging tool for GD. Worldwide, thionamides are the favored treatment (12-18 months) of newly diagnosed GD, with methimazole (MMI) as the preferred drug. Patients with persistently high TSH-R-Abs and/or persistent hyperthyroidism at 18 months, or with a relapse after completing a course of MMI, can opt for a definitive therapy with radioactive iodine (RAI) or total thyroidectomy (TX). Continued long-term, low-dose MMI administration is a valuable and safe alternative. Patient choice, both at initial presentation of GD and at recurrence, should be emphasized. Propylthiouracil is preferred to MMI during the first trimester of pregnancy. TX is best performed by a high-volume thyroid surgeon. RAI should be avoided in GD patients with active GO, especially in smokers. Recently, a promising therapy with an anti-insulin-like growth factor-1 monoclonal antibody for patients with active/severe GO was approved by the Food and Drug Administration. COVID-19 infection is a risk factor for poorly controlled hyperthyroidism, which contributes to the infection–related mortality risk. If GO is not severe, systemic steroid treatment should be postponed during COVID-19 while local treatment and preventive measures are offered.
Conclusions
A clear trend towards serological diagnosis and medical treatment of GD has emerged.
Journal Article
Highly efficient and tunable spin-to-charge conversion through Rashba coupling at oxide interfaces
The spin–orbit interaction couples the electrons’ motion to their spin. As a result, a charge current running through a material with strong spin–orbit coupling generates a transverse spin current (spin Hall effect, SHE) and vice versa (inverse spin Hall effect, ISHE). The emergence of SHE and ISHE as charge-to-spin interconversion mechanisms offers a variety of novel spintronic functionalities and devices, some of which do not require any ferromagnetic material. However, the interconversion efficiency of SHE and ISHE (spin Hall angle) is a bulk property that rarely exceeds ten percent, and does not take advantage of interfacial and low-dimensional effects otherwise ubiquitous in spintronic hetero- and mesostructures. Here, we make use of an interface-driven spin–orbit coupling mechanism—the Rashba effect—in the oxide two-dimensional electron system (2DES) LaAlO
3
/SrTiO
3
to achieve spin-to-charge conversion with unprecedented efficiency. Through spin pumping, we inject a spin current from a NiFe film into the oxide 2DES and detect the resulting charge current, which can be strongly modulated by a gate voltage. We discuss the amplitude of the effect and its gate dependence on the basis of the electronic structure of the 2DES and highlight the importance of a long scattering time to achieve efficient spin-to-charge interconversion.
The Rashba effect at the LaAlO
3
/SrTiO
3
interface is shown to enable large and gate-tunable spin-to-charge conversion through the inverse Rashba–Edelstein effect.The spin current is injected, through spin pumping, from a NiFe film.
Journal Article
The negotiator : a memoir
The former Maine senator and Senate majority leader describes his career spent orchestrating peace and negotiations in Northern Ireland and the Middle East and investigating the use of performance-enhancing drugs in baseball.
Book
Building better monoclonal antibody-based therapeutics
Key Points
Monoclonal antibody (mAb)-based therapeutics are now standard in the treatment of cancer, and the numbers and varieties of clinically applicable mAb-based approaches continue to grow.
Effective mAb-based treatments of cancer include directly targeting the cancer, altering the host response to the cancer, delivering cytotoxic moieties to the cancer and retargeting T cells towards the cancer.
mAb-based treatments that directly target the cancer mediate their effects through direct signalling, antibody-dependent cellular cytotoxicity and complement-mediated lysis. Differentiating which of these mechanisms is most important for a given mAb can be difficult but is important when working to identify better mAb-based treatments.
mAb-based treatments that alter the host response can alter tumour angiogenesis or the T cell response through T cell checkpoint blockade. Checkpoint-blockade mAbs are showing particular promise.
mAb-based treatments that deliver cytotoxic agents to the cancer include radioimmunotherapy and antibody–drug conjugates (ADCs). ADCs are complex because of the need to match the target cancer to the right mAb, linker and drug, but early results are promising and many new ADCs are in development.
mAb-based treatments that retarget T cells towards cancer include bispecific antibodies and chimeric antigen receptor T cells. Both approaches are logistically challenging but have demonstrated exciting early results, particularly in B cell malignancies.
Each of these approaches has advantages and disadvantages that need to be considered in their development and evaluation.
Rapid progress is taking place in the development of new agents and the testing of new approaches, both alone and in combination, in each of these areas.
How can we improve the design of monoclonal antibodies (mAbs) to treat cancer? In this Review, George J. Weiner discusses the characteristics of mAbs that can affect their efficacy, the current approaches that use mAbs in cancer treatment and the numerous ways to enhance the potential of these mAb-based techniques.
For 20 years, monoclonal antibodies (mAbs) have been a standard component of cancer therapy, but there is still much room for improvement. Efforts continue to build better cancer therapeutics based on mAbs. Anticancer mAbs function through various mechanisms, including directly targeting the malignant cells, modifying the host response, delivering cytotoxic moieties and retargeting cellular immunity towards the malignant cells. Characteristics of mAbs that affect their efficacy include antigen specificity, overall structure, affinity for the target antigen and how a mAb component is incorporated into a construct that can trigger target cell death. This Review discusses the various approaches to using mAb-based therapeutics to treat cancer and the strategies used to take advantage of the unique potential of each approach, and provides examples of current mAb-based treatments.
Journal Article
Additive interfacial chiral interaction in multilayers for stabilization of small individual skyrmions at room temperature
Facing the ever-growing demand for data storage will most probably require a new paradigm. Nanoscale magnetic skyrmions are anticipated to solve this issue as they are arguably the smallest spin textures in magnetic thin films in nature. We designed cobalt-based multilayered thin films in which the cobalt layer is sandwiched between two heavy metals and so provides additive interfacial Dzyaloshinskii–Moriya interactions (DMIs), which reach a value close to 2 mJ m
–2
in the case of the Ir|Co|Pt asymmetric multilayers. Using a magnetization-sensitive scanning X-ray transmission microscopy technique, we imaged small magnetic domains at very low fields in these multilayers. The study of their behaviour in a perpendicular magnetic field allows us to conclude that they are actually magnetic skyrmions stabilized by the large DMI. This discovery of stable sub-100 nm individual skyrmions at room temperature in a technologically relevant material opens the way for device applications in the near future.
Magnetic skyrmions can be stabilized at room temperature in cobalt layers sandwiched between heavy metal layers due to engineering of the interfacial Dzyaloshinskii–Moriya interaction.
Journal Article
THE WAGE IMPACT OF THE MARIELITOS
This article brings a new perspective to the analysis of the wage effects of the Mariel boatlift crisis, in which an estimated 125,000 Cuban refugees migrated to Florida between April and October, 1980. The author revisits the question of wage impacts from such a supply shock, drawing on the cumulative insights of research on the economic impact of immigration. That literature shows that the wage impact must be measured by carefully matching the skills of the immigrants with those of the incumbent workforce. Given that at least 60% of the Marielitos were high school dropouts, this article specifically examines the wage impact for this low-skill group. This analysis overturns the prior finding that the Mariel boatlift did not affect Miami’s wage structure. The wage of high school dropouts in Miami dropped dramatically, by 10 to 30%, suggesting an elasticity of wages with respect to the number of workers between −0.5 and −1.5.
Journal Article