Evaluation of cardiac ischaemia in cardiac asymptomatic newly diagnosed untreated patients with primary hypothyroidism

BACKGROUND: Hypothyroidism is regarded as a risk factor for coronary artery disease. Possible factors involved in this association are hyperlipidaemia and hypertension, both occurring with increased frequency in hypothyroid patients. The aim of our study was to evaluate signs/symptoms of cardiac ischaemia in untreated hypothyroid patients without angina pectoris, since this has never been performed before. METHODS: 51 consecutive cardiac asymptomatic patients (mean age 47, range 22 to 86 years) were studied by dobutamine stress echocardiography and bicycle ergometry. RESULTS: Mean values of body mass index, resting heart rate and blood pressure were 28.5 kg/m2, 68 beats/min and 129/81 mmHg, respectively. Median TSH was 51.9 mU/l, mean FT4 7.3 +/- 2.9 pmol/l (mean +/- SD), TT3 1.6 +/- 0.6 nmol/l and total cholesterol was 5.8 +/- 1.6 mmol/l. None of the patients had symptoms of angina pectoris during dobutamine stress echocardiography or bicycle ergometry and no evidence of myocardial ischaemia was demonstrated. Exercise tolerance, assessed by dividing the maximum achieved workload by the target performance (depending on body height, sex and age), was diminished in 38% of patients, and significantly related to the degree of hypothyroidism. CONCLUSION: No angina pectoris or cardiac ischaemia at exercise or stress was found in cardiac asymptomatic hypothyroid patients. The precise role of hypothyroidism as a risk factor for coronary artery disease should be further elucidated

Postpartum thyroiditis and autoimmune thyroiditis in women of childbearing age: recent insights and consequences for antenatal and postnatal care

Postpartum thyroiditis is a syndrome of transient or permanent thyroid dysfunction occurring in the first year after delivery and based on an autoimmune inflammation of the thyroid. The prevalence ranges from 5-7%. We discuss the role of antibodies (especially thyroid peroxidase antibodies), complement, activated T cells, and apoptosis in the outbreak of postpartum thyroiditis. Postpartum thyroiditis is conceptualized as an acute phase of autoimmune thyroid destruction in the context of an existing and ongoing process of thyroid autosensitization. From pregnancy an enhanced state of immune tolerance ensues. A rebound reaction to this pregnancy-associated immune suppression after delivery explains the aggravation of autoimmune syndromes in the puerperal period, e.g., the occurrence of clinically overt postpartum thyroiditis. Low thyroid reserve due to autoimmune thyroiditis is increasingly recognized as a serious health problem. 1) Thyroid autoimmunity increases the probability of spontaneous fetal loss. 2) Thyroid failure due to autoimmune thyroiditis-often mild and subclinical-can lead to permanent and significant impairment in neuropsychological performance of the offspring. 3) Evidence is emerging that as women age subclinical hypothyroidism-as a sequel of postpartum thyroiditis-predisposes them to cardiovascular disease. Hence, postpartum thyroiditis is no longer considered a mild and transient disorder. Screening is considered

"Песня караульного у тюрмы" Тараса Шевченка та її прототексти

This paper briefly illustrates a method to represent national energy systems and the geographical details of CCS infrastructures in the same technical-economic model. In the MARKAL-TIMES modeling framework a model of Morocco, Portugal and Spain with both spatial and temporal details has been implemented. As a function of assumptions on the development to 2050 of mitigation levels, economic growth and CO2 capture-transport storage characteristics, dozens of scenarios were prepared with the TIMES-COMET model. A few results on optimal levels of CCS contribution to mitigation compared to other energy system options are presented. The results also indicate the least cost lay out of the main capture, transport and storage infrastructures. It is concluded that the availability of CCS after 2020 will reduce the cost of mitigation in the Iberian Peninsula as soon as the EU GHG emissions reduction targets become more stringent than decided so far

Controlling secondary flow in Taylor-Couette turbulence through spanwise-varying roughness

Highly turbulent Taylor-Couette flow with spanwise-varying roughness is investigated experimentally and numerically (direct numerical simulations (DNS) with an immersed boundary method (IBM)) to determine the effects of the spacing and axial width $s$ of the spanwise varying roughness on the total drag and {on} the flow structures. We apply sandgrain roughness, in the form of alternating {rough and smooth} bands to the inner cylinder. Numerically, the Taylor number is $\mathcal{O}(10^9)$ and the roughness width is varied between $0.47\leq \tilde{s}=s/d \leq 1.23$, where $d$ is the gap width. Experimentally, we explore $\text{Ta}=\mathcal{O}(10^{12})$ and $0.61\leq \tilde s \leq 3.74$. For both approaches the radius ratio is fixed at $\eta=r_i/r_o = 0.716$, with $r_i$ and $r_o$ the radius of the inner and outer cylinder respectively. We present how the global transport properties and the local flow structures depend on the boundary conditions set by the roughness spacing $\tilde{s}$. Both numerically and experimentally, we find a maximum in the angular momentum transport as function of $\tilde s$. This can be atributed to the re-arrangement of the large-scale structures triggered by the presence of the rough stripes, leading to correspondingly large-scale turbulent vortices.Comment: 20 pages, 7 figures, draft for JF

Cardiac and metabolic effects in patients who present with a multinodular goitre

Twenty-six consecutive patients who presented with clinically euthyroid multinodular goitre were studied for an overnight fasting serum lipid profile and 24 h Holter monitoring. Mean serum TSH was 0.6 +/- 0.4 vs 2.4 +/- 1.3 mU/l (p < 0.0001) and mean TT3 2.4 +/- 0.4 vs 2.0 +/- 0.5 nmol/l (p = 0.009) in patients vs controls (n = 15) while mean FT4 was not different from controls. Total serum HDL, LDL cholesterol and triglycerides were lower in patients but creatinine, ferritin and SHBG levels did not differ between patients and controls. The 24-hour ambulatory continuous ECG recordings did not demonstrate significant differences in mean, minimal and maximal heart rate between the study and the control group. Nocturnal heart rate, measured between 23.00 and 06.00 hours, also showed no differences between the two groups. Atrial fibrillation was absent in both the study and the control group. Premature atrial and ventricular complexes occurred equally frequently in both groups. Comparison of patients with a serum TSH below 0.4 mU/l (n = 11) and patients with a TSH above 0.4 mU/l revealed no differences. In conclusion, in consecutive patients who present with multinodular goitre, effects were found on the lipid profile, but not on the heart. It is argued that in this type of patients, cardiac effects depend on the degree of subclinical hyperthyroidism

Single subject transcriptome analysis to identify functionally signed gene set or pathway activity

Analysis of single-subject transcriptome response data is an unmet need of precision medicine, made challenging by the high dimension, dynamic nature and difficulty in extracting meaningful signals from biological or stochastic noise. We have proposed a method for single subject analysis that uses a mixture model for transcript fold-change clustering from isogenically paired samples, followed by integration of these distributions with Gene Ontology Biological Processes (GO-BP) to reduce dimension and identify functional attributes. We then extended these methods to develop functional signing metrics for gene set process regulation by incorporating biological repressor relationships encoded in GO-BP as negatively regulates edges. Results revealed reproducible and biologically meaningful signals from analysis of a single subject's response, opening the door to future transcriptomic studies where subject and resource availability are currently limiting. We used inbred mouse strains fed different diets to provide isogenic biological replicates, permitting rigorous validation of our method. We compared significant genotype-specific GO-BP term results for overlap and rank order across three replicate pairs per genotype, and cross-methods to reference standards (limma+FET, SAM+FET, and GSEA). All single-subject analytics findings were robust and highly reproducible (median area under the ROC curve=0.96, n=24 genotypes x 3 replicates), providing confidence and validation of this approach for analyses in single subjects. R code is available online at http://www.lussiergroup.org/publications/PathwayActivityUniversity of Arizona Health Sciences CB2, the BIO5 Institute; NIH [U01AI122275, HL132532, CA023074, 1UG3OD023171, 1R01AG053589-01A1, 1S10RR029030]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Developing a 'personalome' for precision medicine: emerging methods that compute interpretable effect sizes from single-subject transcriptomes

The development of computational methods capable of analyzing -omics data at the individual level is critical for the success of precision medicine. Although unprecedented opportunities now exist to gather data on an individual's -omics profile (personalome'), interpreting and extracting meaningful information from single-subject -omics remain underdeveloped, particularly for quantitative non-sequence measurements, including complete transcriptome or proteome expression and metabolite abundance. Conventional bioinformatics approaches have largely been designed for making population-level inferences about average' disease processes; thus, they may not adequately capture and describe individual variability. Novel approaches intended to exploit a variety of -omics data are required for identifying individualized signals for meaningful interpretation. In this review-intended for biomedical researchers, computational biologists and bioinformaticians-we survey emerging computational and translational informatics methods capable of constructing a single subject's personalome' for predicting clinical outcomes or therapeutic responses, with an emphasis on methods that provide interpretable readouts. Key points: (i) the single-subject analytics of the transcriptome shows the greatest development to date and, (ii) the methods were all validated in simulations, cross-validations or independent retrospective data sets. This survey uncovers a growing field that offers numerous opportunities for the development of novel validation methods and opens the door for future studies focusing on the interpretation of comprehensive personalomes' through the integration of multiple -omics, providing valuable insights into individual patient outcomes and treatments.National Institute of Health (NIH)/Office of the Director Precision Medicine Initiative [1UG3OD023171-01]; Precision Medicine Initiative of the Center for Biomedical Informatics and Biostatistics of the University of Arizona Health Sciences; NIH/National Heart, Lung, and Blood Institute [HL126609-01, HL132523, U01 HL125208]; NIH/National Cancer Institute [P30CA023074, 1R01CA190696-01]; NIH/National Institute of Allergy and Infectious Diseases [U01AI122275-01]Open access articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Decrease of free thyroxine levels after controlled ovarian hyperstimulation

Controlled ovarian hyperstimulation could lead to opposing effects on thyroid function. Therefore, in a prospective study of 65 women undergoing controlled ovarian hyperstimulation, thyroid hormones, T4-binding globulin, TPO antibodies, gonadotropins, estradiol, and PRL were measured before and after controlled ovarian hyperstimulation. After ovarian stimulation (mean +/- SE of mean): free T4 decreased, 14.4 +/- 0.2 vs. 12.9 +/- 0.2 pmol/L (P < 0.0001); thyroid-stimulating hormone increased, 2.3 +/- 0.3 vs. 3.0 +/- 0.4 mU/L (P < 0.0001); T4-binding globulin increased, 25.2 +/- 0.7 vs. 33.9 +/- 0.9 mg/L (P < 0.0001); total T4 increased, 98.1 +/- 2.3 vs. 114.6 +/- 2.5 nmol/L (P < 0.0001); total T3 increased, 2.0 +/- 0.04 vs. 2.3 +/- 0.07 nmol/L (P < 0.0001); TPO antibodies decreased, 370 +/- 233 U/mL vs. 355 +/- 224 U/mL (P < 0.0001); LH decreased, 8.1 +/- 1.1 vs. 0.4 +/-0.1 U/L (P < 0.0001); FSH did not change, 6.5 +/- 0.6 vs. 7.9 +/- 0.9 U/L (P = 0.08); human CG increased, <2 +/- 0.0 vs. 195 +/- 16 U/L (P < 0.0001); estradiol increased, 359.3 +/- 25.9 pmol/L vs. 3491.8 +/-298.3 pmol/L (P < 0.0001); and PRL increased, 0.23 +/- 0.02 vs. 0.95 +/- 0.06 U/L (P < 0.0001). Because low maternal free T4 and elevated maternal thyroid-stimulating hormone levels during early gestation have been reported to be associated with impaired psychomotor development in the offspring, our findings indicate the need for additional studies in the children of women who where exposed to high levels of estrogens around the time of conception

Ischaemic heart disease in Turkish migrants with type 2 diabetes mellitus in The Netherlands: wait for the next generation?

OBJECTIVE: To study the prevalence of ischaemic heart disease in Turkish and Surinam-Asian migrants with type 2 diabetes mellitus in the Netherlands as compared with Europeans. METHODS: In a consecutive case-control study, 59 Turkish and 62 Surinam-Asian patients were compared with 185 Europeans referred to a diabetes clinic for treatment of type 2 diabetes in the period 1992 to 1998. Main outcome measures were ischaemic heart disease and its associated risk factors. RESULTS: The prevalence of ischaemic heart disease was lower (9%) in the Turks (p < 0.02), but higher (29%) in the Surinam-Asians compared with the Europeans (23%). The Turks (52 +/- 10 years) and Surinam-Asians (46 +/- 12 years) were younger than the Europeans (64 +/- 11 years, p < 0.001). Body mass index was 32 +/- 5 (p < 0.001) in the Turks, 27 +/- 5 in the Surinam-Asians (p < 0.05) and 29 +/- 5 in the Europeans. Turkish patients smoked less (23%, p < 0.05) and used less alcohol (4%, p < 0.05) than the Europeans. Proteinuria was found in 24% of the Turks (p < 0.05), 37% of the Surinam-Asians (NS) and 46% of the Europeans. In univariate analysis ischaemic heart disease was related to Turkish origin, OR 0.34 (0.14-0.83) p < 0.02, to Surinam-Asian origin, OR 1.84 (1.00-3.38) p = 0.05, and smoking, OR 1.78 (1.18-2.68) p < 0.01. Other variables were not related to ischaemic heart disease. Multivariate analysis in a model with ethnicity and smoking showed significant relations between ischaemic heart disease and Turkish ethnicity, OR 0.19 (0.06-0.65) p = 0.007, Surinam-Asian origin, OR 2.77 (1.45-5.28) p = 0.002, and smoking, OR 1.79 (1.20-2.66) p = 0.004. CONCLUSION: Type 2 diabetes mellitus in different ethnic groups results in a significant difference in incidence of ischaemic heart disease. The most remarkable finding is a low incidence of ischaemic heart disease in the Turkish patients with type 2 diabetes, independent of smoking. The high prevalence of ischaemic heart disease in young migrant Asians with diabetes is confirmed

Business process modelling and visualisation to support e-government decision making: Business/IS alignment

© 2017 Springer-Verlag. The final publication is available at Springer via https://doi.org/10.1007/978-3-319-57487-5_4.Alignment between business and information systems plays a vital role in the formation of dependent relationships between different departments in a government organization and the process of alignment can be improved by developing an information system (IS) according to the stakeholders’ expectations. However, establishing strong alignment in the context of the eGovernment environment can be difficult. It is widely accepted that business processes in the government environment plays a pivotal role in capturing the details of IS requirements. This paper presents a method of business process modelling through UML which can help to visualise and capture the IS requirements for the system development. A series of UML models have been developed and discussed. A case study on patient visits to a healthcare clinic in the context of eGovernment has been used to validate the models