Rotating traversable wormholes

The general form of a stationary, axially symmetric traversable wormhole is discussed. This provides an explicit class of rotating wormholes that generalize the static, spherically symmetric ones first considered by Morris and Thorne. In agreement with general analyses, it is verified that such a wormhole generically violates the null energy condition at the throat. However, for suitable model wormholes, there can be classes of geodesics falling through it which do not encounter any energy-condition-violating matter. The possible presence of an ergoregion surrounding the throat is also noted.Comment: 15 pages, harvmac; 1 figure in PicTeX; minor changes; to appear in Phys. Rev.

Insight Into Molecular Determinants of T3 vs T4 Recognition From Mutations in Thyroid Hormone Receptor α and β.

CONTEXT: The two major forms of circulating thyroid hormones (THs) are T3 and T4. T3 is regarded as the biologically active hormone because it binds to TH receptors (TRs) with greater affinity than T4. However, it is currently unclear what structural mechanisms underlie this difference in affinity. OBJECTIVE: Prompted by the identification of a novel M256T mutation in a resistance to TH (RTH)α patient, we investigated Met256 in TRα1 and the corresponding residue (Met310) in TRβ1, residues previously predicted by crystallographic studies in discrimination of T3 vs T4. METHODS: Clinical characterization of the RTHα patient and molecular studies (in silico protein modeling, radioligand binding, transactivation, and receptor-cofactor studies) were performed. RESULTS: Structural modeling of the TRα1-M256T mutant showed that distortion of the hydrophobic niche to accommodate the outer ring of ligand was more pronounced for T3 than T4, suggesting that this substitution has little impact on the affinity for T4. In agreement with the model, TRα1-M256T selectively reduced the affinity for T3. Also, unlike other naturally occurring TRα mutations, TRα1-M256T had a differential impact on T3- vs T4-dependent transcriptional activation. TRα1-M256A and TRβ1-M310T mutants exhibited similar discordance for T3 vs T4. CONCLUSIONS: Met256-TRα1/Met310-TRβ1 strongly potentiates the affinity of TRs for T3, thereby largely determining that T3 is the bioactive hormone rather than T4. These observations provide insight into the molecular basis for underlying the different affinity of TRs for T3 vs T4, delineating a fundamental principle of TH signaling

Development of a pediatric differentiated thyroid carcinoma registry within the EuRRECa project: rationale and protocol

Registry; Thyroid carcinoma; ChildhoodRegistro; Carcinoma de tiroides; InfanciaRegistre; Carcinoma de tiroides; InfànciaBackground Although differentiated thyroid carcinoma (DTC) is the most frequent endocrine pediatric cancer, it is rare in childhood and adolescence. While tumor persistence and recurrence are not uncommon, mortality remains extremely low. Complications of treatment are however reported in up to 48% of the survivors. Due to the rarity of the disease, current treatment guidelines are predominantly based on the results of small observational retrospective studies and extrapolations from results in adult patients. In order to develop more personalized treatment and follow-up strategies (aiming to reduce complication rates), there is an unmet need for uniform international prospective data collection and clinical trials. Methods and analysis The European pediatric thyroid carcinoma registry aims to collect clinical data for all patients ≤18 years of age with a confirmed diagnosis of DTC who have been diagnosed, assessed, or treated at a participating site. This registry will be a component of the wider European Registries for Rare Endocrine Conditions project which has close links to Endo-ERN, the European Reference Network for Rare Endocrine Conditions. A multidisciplinary expert working group was formed to develop a minimal dataset comprising information regarding demographic data, diagnosis, treatment, and outcome. We constructed an umbrella-type registry, with a detailed basic dataset. In the future, this may provide the opportunity for research teams to integrate clinical research questions. Ethics and dissemination Written informed consent will be obtained from all participants and/or their parents/guardians. Summaries and descriptive analyses of the registry will be disseminated via conference presentations and peer-reviewed publications.SFA and ALP are supported by the European Union’s Health Programme (2014–2020) on the EuRRECa project ‘777215/EuRRECa’ and the EuRR-Bone project ‘946831/EuRR-Bone’. The EuRRECa project is also grateful to the European Society of Endocrinology and the European Society for Paediatric Endocrinology for funding support

Preferences of patients, clinicians, and healthy controls for the management of a Bethesda III thyroid nodule

Background: Active surveillance is propagated as an alternative for hemithyroidectomy in the management of Bethesda III thyroid nodules. Methods: A cross-sectional survey questioned respondents on their willingness to accept risks related to active surveillance and hemithyroidectomy. Results: In case of active surveillance, respondents (129 patients, 46 clinicians, and 66 healthy controls) were willing to accept a risk of 10%–15% for thyroid cancer and 15% for needing more extensive surgery in the future. Respondents were willing to accept a risk of 22.5%–30% for hypothyroidism after hemithyroidectomy. Patients and controls were willing to accept a higher risk on permanent voice changes compared with clinicians (10% vs. 3%, p < 0.001). Conclusion: Real-life risks associated which active surveillance and hemithyroidectomy for Bethesda III nodules are equivalent or less than the risks people are willing to accept. Clinicians accepted less risk for permanent voice changes

FAMILIAL DYSALBUMINAEMIC HYPERTHYROXINEMIA INTERFERES WITH CURRENT FREE THYROID HORMONE IMMUNOASSAY METHODS

Familial dysalbuminaemic hyperthyroxinemia (FDH), most commonly due to an Arginine to Histidine mutation at residue 218 (R218H) in the albumin gene, causes artefactual elevation of free thyroid hormones in euthyroid individuals. We have evaluated the susceptibility of most current free thyroid hormone immunoassay methods used in the UK, Europe and Far East to interference by R218H FDH. Methods: Different, one- and two-step immunoassay methods were tested, measuring Free T4 (FT4) and Free T3 (FT3) in 37 individuals with genetically-proven R218H FDH. Results: With the exception of Ortho VITROS, FT4 measurements were raised in all assays, with greatest to lowest susceptibility to interference being Beckman ACCESS &gt; Roche ELECSYS &gt; FUJIREBIO Lumipulse &gt; Siemens CENTAUR &gt; Abbott ARCHITECT &gt; Perkin-Elmer DELFIA. Five different assays recorded high FT3 levels, with the Siemens CENTAUR method measuring high FT3 values in up to 30% of cases. However, depending on the assay method, FT4 measurements were unexpectedly normal in some, genetically-confirmed, affected relatives of index FDH cases. Conclusions: All FT4 immunoassays evaluated are prone to interference by R218H FDH, with their varying susceptibility not being related to assay architecture but likely due to differing assay conditions or buffer composition. Added susceptibility of many FT3 assays to measurement interference, resulting in high FT4 and FT3 with non-suppressed TSH levels, raises the possibility of R218H FDH being misdiagnosed as Resistance to Thyroid Hormone beta or TSH-secreting pituitary tumour, potentially leading to unnecessary investigation and inappropriate treatment.Research is supported by funding from the Wellcome Trust (210755/Z/18/Z to KC) and NIHR Cambridge Biomedical Research Centre (CM, MG, KC)