56 research outputs found
Advances in the Imaging of Pituitary Tumors
© 2020 Elsevier Inc. In most patients with pituitary adenomas magnetic resonance imaging (MRI) is essential to guide effective decision-making. T1- and T2-weighted sequences allow the majority of adenomas to be readily identified. Supplementary MR sequences (e.g. FLAIR; MR angiography) may also help inform surgery. However, in some patients MRI findings are ‘negative’ or equivocal (e.g. with failure to reliably identify a microadenoma or to distinguish postoperative change from residual/recurrent disease). Molecular imaging [e.g. 11C-methionine PET/CT coregistered with volumetric MRI (Met-PET/MRCR)] may allow accurate localisation of the site of de novo or persistent disease to guide definitive treatment (e.g. surgery or radiosurgery)
Localisation of an occult thyrotropinoma with C-methionine PET-CT before and after somatostatin analogue therapy
A 75-year-old woman presented to her local endocrine service with tiredness, palpitations, and enlargement of a longstanding goitre. Unexpectedly, her thyrotropin (thyroid-stimulating hormone [TSH]) concentration was not suppressed (6·3 mU/L; reference range 0·35–5·5) despite raised concentrations of thyroid hormones (free thyroxine [T] 89·1 pmol/L [reference range 10–19·8]; free triiodothyronine [T] 11·7 pmol/L [3·0–6·5]). After exclusion of laboratory assay interference, a thyrotropin-releasing hormone test showed an attenuated response (TSH at 0 min was 6·1 mU/L, at 20 min was 6·8 mU/L, and at 60 min was 8·5 mU/L), raising suspicion of a thyrotropinoma (also known as TSHoma). However, pituitary MRI was normal. The patient was referred to our centre for further assessment. On repeat MRI, the pituitary gland showed mild asymmetry (right larger than left; figure A). Functional imaging with 11C-methionine (C-Met) PET-CT revealed intense tracer uptake (denoting active peptide synthesis) on the right side of the sella (red hot spot in figure A). Treatment with a depot somatostatin analogue (SSA) led to resolution of symptoms and normalisation of thyroid function (TSH 0·6 mU/L, free T 12·5 pmol/L, and free T 3·8 pmol/L). Repeat C-Met PET-CT showed absence of the right-sided focal hot spot (figure B). 14 months into treatment, the patient had several hypoglycaemic episodes, which resolved after discontinuation of SSA. However, thyrotoxicosis recurred (TSH 4·3 mU/L, free T 38·1 pmol/L, free T 11·6 pmol/L), and repeat C-Met PET-CT revealed the reappearance of the right-sided hot spot (figure C). During pituitary surgery, a microthyrotropinoma was resected from the right side of the gland (figure D). The patient remains in clinical and biochemical remission more than 12 months after surgery and has normal pituitary function
The Ethnic 'Other' in Ukrainian History Textbooks: The Case of Russia and the Russians
This paper examines portrayals of Russia and the Russians in two generations of Ukrainian history textbooks. It observes that the textbooks are highly condemning of Ukraine's main ethnic other in the guise of foreign ruler: the tsarist authorities and the Soviet regime are always attributed dubious and malicious intentions even if there is appreciation for some of their policies. By contrast, the books, certainly those of the second generation, refrain from presenting highly biased accounts of the ethnic other as a national group (i.e. Russians). Instances where negative judgements do fall onto Russians are counterbalanced by excerpts criticizing ethnic Ukrainians or highlighting conflicting interests within the Ukrainian ethnic group. The negative appraisal of the ethnic other as foreign ruler is clearly instrumental for the nation-building project as it sustains a discourse legitimating the existence of Ukraine as independent state. However, recent trends in history education, the paper concludes, suggest that the importance of nurturing patriotism as a national policy objective is diminishing
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A Novel TRH Receptor Mutation
CONTEXT: Isolated central congenital hypothyroidism (CCH) is rare and evades diagnosis on TSH-based congenital hypothyroidism (CH) screening programs in the United Kingdom. Accordingly, genetic ascertainment facilitates diagnosis and treatment of familial cases. Recognized causes include TSH β subunit (TSHB) and Ig superfamily member 1 (IGSF1) mutations, with only two previous reports of biallelic, highly disruptive mutations in the TRH receptor (TRHR) gene. CASE DESCRIPTION: A female infant presenting with prolonged neonatal jaundice was found to have isolated CCH, with TSH of 2.2 mU/L (Reference range, 0.4-3.5) and free T4 of 7.9 pmol/L (0.61 ng/dL) (Reference range, 10.7-21.8 pmol/L). Because TSHB or IGSF1 mutations are usually associated with profound or X-linked CCH, TRHR was sequenced, and a homozygous mutation (p.P81R) was identified, substituting arginine for a highly conserved proline residue in transmembrane helix 2. Functional studies demonstrated normal cell membrane expression and localization of the mutant TRHR; however, its ability to bind radio-labelled TRH and signal via Gqα was markedly impaired, likely due to structural distortion of transmembrane helix 2. CONCLUSIONS: Two previously reported biallelic, highly disruptive (nonsense; R17*, in-frame deletion and single amino acid substitution; p.[S115-T117del; A118T]) TRHR mutations have been associated with CCH; however, we describe the first deleterious, missense TRHR defect associated with this phenotype. Importantly, the location of the mutated amino acid (proline 81) highlights the functional importance of the second transmembrane helix in mediating hormone binding and receptor activation. Future identification of other naturally occurring TRHR mutations will likely offer important insights into the molecular basis of ligand binding and activation of TRHR, which are still poorly understood.Our research is supported by funding from the Wellcome Trust (100585/Z/12/Z to NS, 095564/Z/11/Z to KC, ISF), the National Institute for Health Research Cambridge Biomedical Research Centre (OK, ISF, KC, MG, NS), the Evelyn Trust (OK), the European Research Council (ISF), and the Bernard Wolfe Health Neuroscience Endowment (ISF).This is the final version of the article. It first appeared from the Endocrine Society via http://dx.doi.org/10.1210/jc.2015-391
Toward Predicting Success and Failure in CS2: A Mixed-Method Analysis
Factors driving success and failure in CS1 are the subject of much study but
less so for CS2. This paper investigates the transition from CS1 to CS2 in
search of leading indicators of success in CS2. Both CS1 and CS2 at the
University of North Carolina Wilmington (UNCW) are taught in Python with annual
enrollments of 300 and 150 respectively. In this paper, we report on the
following research questions: 1) Are CS1 grades indicators of CS2 grades? 2)
Does a quantitative relationship exist between CS2 course grade and a modified
version of the SCS1 concept inventory? 3) What are the most challenging aspects
of CS2, and how well does CS1 prepare students for CS2 from the student's
perspective? We provide a quantitative analysis of 2300 CS1 and CS2 course
grades from 2013--2019. In Spring 2019, we administered a modified version of
the SCS1 concept inventory to 44 students in the first week of CS2. Further, 69
students completed an exit questionnaire at the conclusion of CS2 to gain
qualitative student feedback on their challenges in CS2 and on how well CS1
prepared them for CS2. We find that 56% of students' grades were lower in CS2
than CS1, 18% improved their grades, and 26% earned the same grade. Of the
changes, 62% were within one grade point. We find a statistically significant
correlation between the modified SCS1 score and CS2 grade points. Students
identify linked lists and class/object concepts among the most challenging.
Student feedback on CS2 challenges and the adequacy of their CS1 preparations
identify possible avenues for improving the CS1-CS2 transition.Comment: The definitive Version of Record was published in 2020 ACM Southeast
Conference (ACMSE 2020), April 2-4, 2020, Tampa, FL, USA. 8 page
A novel IGSF1 mutation in a large Irish kindred highlights the need for familial screening in the IGSF1 deficiency syndrome
Objective: Loss-of-function mutations in IGSF1 result in X-linked central congenital hypothyroidism (CeCH), occurring in isolation or associated with additional pituitary hormone deficits. Intrafamilial penetrance is highly variable and a minority of heterozygous females are also affected. We identified and characterized a novel IGSF1 mutation and investigated its associated phenotypes in a large Irish kindred. Design, Patients and Measurements: A novel hemizygous IGSF1 mutation was identified by direct sequencing in two brothers with CeCH, and its functional consequences were characterized in vitro. Genotype-phenotype correlations were investigated in the wider kindred. Results: The mutant IGSF1 protein (c.2318T > C, p.L773P) exhibited decreased plasma membrane expression in vitro due to impaired trafficking from the endoplasmic reticulum. Ten hemizygous males and 11 heterozygous females exhibited characteristic endocrine deficits. Ireland operates a TSH-based CH screening programme, which does not detect CeCH; therefore, genetic ascertainment preceded biochemical diagnosis of moderate CH in five of seven boys as well as their 75-year-old grandfather. Clinical features potentially attributable to hypothyroidism were variable; normal free T3 (FT3) and low/low normal reverse T3 (rT3) concentrations suggested that preferential deiodination of FT4 to FT3 may help maintain tissue euthyroidism in some individuals. However, neonatal jaundice, delayed speech or growth, and obesity were observed in seven subjects in whom diagnosis was delayed. Conclusions: As observed with other IGSF1 mutations, p.L773P results in variably penetrant IGSF1 deficiency syndrome. Our observations emphasize the need for multi-generation genetic ascertainment in affected families, especially where TSH-based CH screening programmes may fail to detect CeCH at birth
Polycystic ovary syndrome
The document attached has been archived with permission from the editor of the Medical Journal of Australia. An external link to the publisher’s copy is included.Polycystic ovary syndrome (PCOS) affects 5-20% of women of reproductive age worldwide. The condition is characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology (PCOM) - with excessive androgen production by the ovaries being a key feature of PCOS. Metabolic dysfunction characterized by insulin resistance and compensatory hyperinsulinaemia is evident in the vast majority of affected individuals. PCOS increases the risk for type 2 diabetes mellitus, gestational diabetes and other pregnancy-related complications, venous thromboembolism, cerebrovascular and cardiovascular events and endometrial cancer. PCOS is a diagnosis of exclusion, based primarily on the presence of hyperandrogenism, ovulatory dysfunction and PCOM. Treatment should be tailored to the complaints and needs of the patient and involves targeting metabolic abnormalities through lifestyle changes, medication and potentially surgery for the prevention and management of excess weight, androgen suppression and/or blockade, endometrial protection, reproductive therapy and the detection and treatment of psychological features. This Primer summarizes the current state of knowledge regarding the epidemiology, mechanisms and pathophysiology, diagnosis, screening and prevention, management and future investigational directions of the disorder.Robert J Norman, Ruijin Wu and Marcin T Stankiewic
L’intelligence artificielle et le dermatologue [Artificial intelligence and the skin specialist]
Artificial intelligence's progress is spread on front pages of both lay and scientific journals. After Chess, after Go, before Dota2 and Starcraft, super-trained softwares have equaled or out-performed dermatologists. But what is the future of these computer programs and how will they change clinical practice for both the general practitioner and the skin specialist? It is time to ask these questions, even though the promises of these new technologies are not yet available
Minimum wage legislation, work conditions and employment
SIGLEAvailable from British Library Document Supply Centre-DSC:3597.9512(CEPR-DP--1524) / BLDSC - British Library Document Supply CentreGBUnited Kingdo
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