The spectrum of phenotypes associated with mutations in steroidogenic factor 1 (SF-1, NR5A1, Ad4BP) includes severe penoscrotal hypospadias in 46,XY males without adrenal insufficiency

OBJECTIVE. Hypospadias is a frequent congenital anomaly but in most cases an underlying cause is not found. Steroidogenic factor 1 (SF-1, NR5A1, Ad4BP) is a key regulator of human sex development and an increasing number of SF-1 (NR5A1) mutations are reported in 46,XY disorders of sex development (DSD). We hypothesized that NR5A1 mutations could be identified in boys with hypospadias. DESIGN AND METHODS. Mutational analysis of NR5A1 in 60 individuals with varying degrees of hypospadias from the German DSD network. RESULTS. Heterozygous NR5A1 mutations were found in three out of 60 cases. These three individuals represented the most severe end of the spectrum studied as they presented with penoscrotal hypospadias, variable androgenization of the phallus and undescended testes (three out of 20 cases (15%) with this phenotype). Testosterone was low in all three patients and inhibin B/anti-Müllerian hormone (AMH) were low in two patients. Two patients had a clear male gender assignment. Gender re-assignment to male occurred in the third case. Two patients harbored heterozygous nonsense mutations (p.Q107X/WT, p.E11X/WT). One patient had a heterozygous splice site mutation in intron 2 (c.103-3A/WT) predicted to disrupt the main DNA-binding motif. Functional studies of the nonsense mutants showed impaired transcriptional activation of an SF-1-responsive promoter (Cyp11a). To date, adrenal insufficiency has not occurred in any of the patients. CONCLUSIONS. SF-1 (NR5A1) mutations should be considered in 46,XY individuals with severe (penoscrotal) hypospadias, especially if undescended testes, low testosterone, or low inhibin B/AMH levels are present. SF-1 mutations in milder forms of idiopathic hypospadias are unlikely to be common

Development of Models and a Unified Platform for Multiphase Load Flow Analysis and Dynamic State Estimation of Large Distribution Systems with Secondary Grids

RÉSUMÉ Cette thèse porte sur la modélisation des différentes composantes des réseaux de distribution pour les études d'écoulement de puissance multiphasé et pour l'estimation d'état. Sans utiliser les modèles appropriés, il n’est pas possible d’obtenir des résultats précis dans l’analyse des réseaux de distribution ou des systèmes électriques en général. La thèse présente aussi un algorithme d’estimation d’état générique pour les réseaux de distribution. La performance de l’algorithme est étudiée en détail en considérant les particularités des réseaux de distribution par opposition aux réseaux de transports. La thèse commence par la discussion sur la modélisation des régulateurs de tension pour l'écoulement de puissance en utilisant la méthode de Newton. En tenant compte des spécifications techniques de ces appareils, une nouvelle approche de modélisation est présentée en utilisant la formulation d’analyse nodale augmentée modifiée (MANA) et la méthode de Newton. Les résultats obtenus montrent que la technique proposée donne des résultats satisfaisants lorsque les réglages et les spécifications techniques des régulateurs sont considérés. Ensuite, une nouvelle méthode pour modéliser les machines asynchrones (IMs) dans l'écoulement de puissance déséquilibré est démontrée. La nouvelle approche de modélisation est encore basée sur la formulation de MANA et utilise la méthode de Newton. La nouvelle méthode peut être utilisée pour des IMs à cage simple ou double. Il permet de modéliser l’IM avec la puissance électrique, la puissance mécanique ou le couple mécanique comme contrainte. Le glissement de l'IM devient une variable d'écoulement de puissance et il est calculée itérativement. La puissance réactive est fonction de la puissance active et du glissement ou de la puissance active et de la tension de l’IM, donc il n'y a aucun besoin de fixer la puissance réactive. La solution proposée réduit le nombre d'itérations considérablement par rapport aux méthodes de solution à point fixe. La méthode présentée n'est pas actuellement disponible dans la littérature. Finalement, une approche de modélisation systématique est établie pour représenter les éoliennes (WTGs) de Type-III et Type-IV dans l'analyse d'écoulement de puissance multiphasée et déséquilibrée. Les contraintes sont écrites en fonction des composantes symétriques des courants injectés par les WTGs.----------ABSTRACT This thesis is on the modeling of various components of distribution systems for multiphase load flow studies and state estimation. Without employing proper models, it is not feasible to obtain accurate results in the analysis of distribution networks or power systems in general. The thesis presents also a generic state estimation solver for distribution networks. The performance of the solver is investigated in detail considering the particularities of distribution networks as opposed to transmission grids. The thesis starts by discussing the modeling of step voltage regulators for load flow using Newton’s method. By taking into account the technical specifications of these devices, a new modeling approach is presented within the modified augmented nodal analysis (MANA) formulation and Newton’s method. The results obtained show that the proposed technique gives satisfactory results as far as the settings and technical specifications of the regulators are concerned. Afterwards, a new method to model Induction Machines (IMs) in unbalanced load-flow calculations is demonstrated. The new modeling approach is again based on the MANA formulation and employs Newton’s method. The new method can be used for single and double cage IMs. It allows modeling the IM with electrical power input, mechanical power or mechanical torque output. The slip of the IM becomes a load-flow variable computed iteratively. The reactive power is a function of real power constraint and slip or voltage solution of the IM, therefore there is no need to fix the reactive power input. The proposed solution reduces the number of iterations radically as compared to fixed-point solution methods. The presented formulation is not currently available in the literature. Finally, a systematic modeling approach is established to represent Type-IV and Type-III wind turbine generators (WTGs) in multiphase and unbalanced load flow analysis. The proposed approach integrates the constraints based on the sequence components of the injected currents from WTGs. The proposed model for WTGs performs well under unbalanced conditions

An Epidemiological Study of Hyperhidrosis Patients Visiting the Ajou University Hospital Hyperhidrosis Center in Korea

Hyperhidrosis is a disorder of perspiration in excess of the body's physiologic need and significantly impacts one's occupational, physical, emotional, and social life. The purpose of our study was to investigate the characteristics of primary hyperhidrosis in 255 patients at Ajou University Hospital Hyperhidrosis Center from March 2006, to February 2008. Information collected from the medical records was: sex, sites of hyperhidrosis, age at visit, age of onset, aggravating factors, hyperhidrosis disease severity scale (HDSS) rank, family history, occupation, and past treatment. A total of 255 patient records were reviewed; 57.6% were male. Patients with a family history (34.1%) showed a lower age of onset (13.21±5.80 yr vs. 16.04±9.83 yr in those without family history); 16.5% had previous treatment, most commonly oriental medicine. Palmar and plantar sites were the most commonly affected, and 87.9% of patients felt their sweating was intolerable and always interfered with their daily activities. Our study provides some original information on the Korean primary hyperhidrosis population. Patients who have a family history show signs of disease in early age than those without family history

Hippocampal and Hippocampal-Subfield Volumes From Early-Onset Major Depression and Bipolar Disorder to Cognitive Decline

Background: The hippocampus and its subfields (HippSub) are reported to be diminished in patients with Alzheimer's disease (AD), bipolar disorder (BD), and major depressive disorder (MDD). We examined these groups vs healthy controls (HC) to reveal HippSub alterations between diseases. Methods: We segmented 3T-MRI T2-weighted hippocampal images of 67 HC, 58 BD, and MDD patients from the AFFDIS study and 137 patients from the DELCODE study assessing cognitive decline, including subjective cognitive decline (SCD), amnestic mild cognitive impairment (aMCI), and AD, via Free Surfer 6.0 to compare volumes across groups. Results: Groups differed significantly in several HippSub volumes, particularly between patients with AD and mood disorders. In comparison to HC, significant lower volumes appear in aMCI and AD groups in specific subfields. Smaller volumes in the left presubiculum are detected in aMCI and AD patients, differing from the BD group. A significant linear regression is seen between left hippocampus volume and duration since the first depressive episode. Conclusions: HippSub volume alterations were observed in AD, but not in early-onset MDD and BD, reinforcing the notion of different neural mechanisms in hippocampal degeneration. Moreover, duration since the first depressive episode was a relevant factor explaining the lower left hippocampal volumes present in groups

Hippocampal and Hippocampal-Subfield Volumes From Early-Onset Major Depression and Bipolar Disorder to Cognitive Decline

Background: The hippocampus and its subfields (HippSub) are reported to be diminished in patients with Alzheimer's disease (AD), bipolar disorder (BD), and major depressive disorder (MDD). We examined these groups vs healthy controls (HC) to reveal HippSub alterations between diseases. Methods: We segmented 3T-MRI T2-weighted hippocampal images of 67 HC, 58 BD, and MDD patients from the AFFDIS study and 137 patients from the DELCODE study assessing cognitive decline, including subjective cognitive decline (SCD), amnestic mild cognitive impairment (aMCI), and AD, via Free Surfer 6.0 to compare volumes across groups. Results: Groups differed significantly in several HippSub volumes, particularly between patients with AD and mood disorders. In comparison to HC, significant lower volumes appear in aMCI and AD groups in specific subfields. Smaller volumes in the left presubiculum are detected in aMCI and AD patients, differing from the BD group. A significant linear regression is seen between left hippocampus volume and duration since the first depressive episode. Conclusions: HippSub volume alterations were observed in AD, but not in early-onset MDD and BD, reinforcing the notion of different neural mechanisms in hippocampal degeneration. Moreover, duration since the first depressive episode was a relevant factor explaining the lower left hippocampal volumes present in groups

The development and validation of a disease-specific quality of life measure in hyperhidrosis : the Hyperhidrosis Quality of Life Index (HidroQOL©)

This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original authors and the source are credited.PURPOSE: To develop and validate a new disease-specific quality of life measure in hyperhidrosis for use in both routine clinical practice and clinical research. METHODS: Interviews and focus group discussions with hyperhidrosis patients, reported elsewhere, provided the content for the measure validated in this study (n = 71). A panel of dermatologists (n = 5) and patients (n = 7) carried out content validation. Further, item reduction and the initial construct validation were carried out in a cross-sectional study (n = 595), using the unidimensional Rasch analysis and exploratory factor analysis. Subsequently, the construct validity, reliability and responsiveness of the revised measure were assessed in a longitudinal study (n = 260). Data collection for the item reduction and the final validation phases was entirely carried out online. RESULTS: The expert panels judged the HidroQoL as content valid. Rasch analysis supported the revision of response options from five to three. Following removal of misfitting items, a set of 15 items showed optimal fit to the model (chi-squared statistic = 159.64, p = 0.07). Three additional items were retained on consideration of their importance to patients, resulting in an 18-item instrument. The items were grouped into two subscales, daily life activities and psychosocial life domains, based on results of the factor analysis. In subsequent construct validation, the HidroQoL correlated with the DLQI (r s = 0.6, p < 0.01). Reliability was high (internal consistency, Cronbach's alpha: overall scale = 0.9; test-retest reliability, Intra-class correlation = 0.9). The HidroQoL scores were sensitive to change in patients' disease severity (score change from baseline to follow-up after 15-35 days, Cohen's ES = 0.47). CONCLUSION: This study has provided the initial evidence supporting measurement properties and the use of the HidroQoL instrument in both routine clinical practice and in research, for assessing quality of life impacts in hyperhidrosis.Peer reviewedFinal Published versio