Intellectual outcome, motor skills and BMI of children with congenital hypothyroidism: a population-based study

AIM: To evaluate intellectual outcome, motor skills and anthropometric data of children with congenital hypothyroidism (CH). METHODS: Children with permanent CH who were born in 1999 in Bavaria were eligible for this prospective, population-based study. Cognitive performance was evaluated by the Kaufman Assessment Battery for Children and motor skills were assessed by the motor test, Motoriktest für vier-bis sechsjahrige Kinder (MOT) 4-6. RESULTS: Eighteen of 21 eligible children participated (86%). Median age of the children was 5.5 years (range 4.9-5.8). Treatment with levothyroxine was started after a median of 7.2 days (range 4-15) with a median dose of 12.0 microg/kg (range 7.2-17.0). Mean intelligence quotient (IQ) of the children was 100.4 (standard deviation [SD] 10.1): no children had IQ values below the normal range. Reactivity and speed of movement were significantly reduced in children with CH. Children with an initial thyroid-stimulating hormone (TSH) value of >200 mU/L performed significantly worse than children with TSH value of

Variability in pain response to a non-pharmacological intervention across repeated routine pain exposure in preterm infants: a feasibility study

AIM: To explore the variability in pain response in preterm infants across time who received sucrose during routine heel stick. METHOD: Single group, exploratory repeated measures design. SETTING: Two tertiary level neonatal intensive care units (NICU) in Switzerland. SUBJECTS: Nine preterm infants born between 28 2/7 and 31 4/7 weeks of gestation during their first 14 days of life. MEASUREMENTS: Pain was assessed by the Bernese Pain Scale for Neonates (BPSN), the Premature Infant Pain Profile (PIPP) and the Visual Analogue Scale (VAS). Salivary cortisol was analysed. RESULTS: 72-94% of the variability was within-subject variability, indicating inconsistency of pain responses across the 5 heel sticks. Interrater agreement was highest during heel sticks 1-3 and decreased during heel stick 4 and 5, indicating a possible alteration of pain patterns. No significant differences in the amount of cortisol could be detected before and after the heel sticks (p = 0.55), indicating no stress-induced peak after the painful intervention. However, a general gradual decrease of cortisol levels across time could be detected. CONCLUSION: A high variability in pain response among preterm neonates across time could be described. Consistency of cortisol levels before and after the heel sticks could indicate the effectiveness of sucrose across time.

Glomerular filtration rate estimates decrease during high altitude expedition but increase with Lake Louise acute mountain sickness scores

AIM: Acute mountain sickness (AMS) can result in pulmonary and cerebral oedema with overperfusion of microvascular beds, elevated hydrostatic capillary pressure, capillary leakage and consequent oedema as pathogenetic mechanisms. Data on changes in glomerular filtration rate (GFR) at altitudes above 5000 m are very limited. METHODS: Thirty-four healthy mountaineers, who were randomized to two acclimatization protocols, undertook an expedition on Muztagh Ata Mountain (7549 m) in China. Tests were performed at five altitudes: Zurich pre-expedition (PE, 450 m), base camp (BC, 4497 m), Camp 1 (C1, 5533 m), Camp 2 (C2, 6265 m) and Camp 3 (C3, 6865 m). Cystatin C- and creatinine-based (Mayo Clinic quadratic equation) GFR estimates (eGFR) were assessed together with Lake Louise AMS score and other tests. RESULTS: eGFR significantly decreased from PE to BC (P < 0.01). However, when analysing at changes between BC and C3, only cystatin C-based estimates indicated a significant decrease in GFR (P = 0.02). There was a linear decrease in eGFR from PE to C3, with a decrease of approx. 3.1 mL min(-1) 1.73 m(-2) per 1000 m increase in altitude. No differences between eGFR of the two groups with different acclimatization protocols could be observed. There was a significant association between eGFR and haematocrit (P = 0.01), whereas no significant association between eGFR and aldosterone, renin and brain natriuretic peptide could be observed. Finally, higher AMS scores were significantly associated with higher eGFR (P = 0.01). CONCLUSIONS: Renal function declines when ascending from low to high altitude. Cystatin C-based eGFR decreases during ascent in high altitude expedition but increases with AMS scores. For individuals with eGFR <40 mL min(-1) 1.73 m(-2), caution may be necessary when planning trips to high altitude above 4500 m above sea level.

Human basophils and eosinophils are the direct target leukocytes of the novel IL-1 family member IL-33

In mice, interleukin-18 (IL-18) regulates Th1- or Th2-type immune responses depending on the cytokine environment and effector cells involved, and the ST2-ligand, IL-33, primarily promotes an allergic phenotype. Human basophils, major players in allergic inflammation, constitutively express IL-18 receptors, while ST2 surface expression is inducible by IL-3. Unexpectedly, freshly isolated basophils are strongly activated by IL-33, but, in contrast to mouse basophils, do not respond to IL-18. IL-33 promotes IL-4, IL-13 and IL-8 secretion in synergy with IL-3 and/or FcepsilonRI-activation, and enhances FcepsilonRI-induced mediator release. These effects are similar to that of IL-3, but the signaling pathways engaged are distinct because IL-33 strongly activates NF-kappaB and shows a preference for p38 MAP-kinase, while IL-3 acts through Jak/Stat and preferentially activates ERK. Eosinophils are the only other leukocyte-type directly activated by IL-33, as evidenced by screening of p38-activation in peripheral blood cells. Only upon CD3/CD28-ligation, IL-33 weakly enhances Th2 cytokine expression by in vivo polarized Th2 cells. This study on primary human cells demonstrates that basophils and eosinophils are the only direct target leukocytes for IL-33, suggesting that IL-33 promotes allergic inflammation and Th2 polarization mainly by the selective activation of these specialized cells of the innate immune system.

Proliferation and apoptosis in mammary epithelium during the rat oestrous cycle

AIM: During each oestrous cycle, the mammary gland is subject to changes in ovarian hormone levels. It responds with limited proliferation, differentiation and regression. To understand the processes resulting in these changes, particularly the regulation of cell death, we examined protein levels in mammary epithelium during the oestrous cycle of the Sprague-Dawley rat. METHODS: Studies of serum hormone levels, vaginal smears, uterine weight and morphology, mammary gland morphology, proliferation and apoptotic indices, and protein levels during the stages of the Sprague-Dawley rat oestrous cycle were used to examine the response of mammary epithelium to the oestrous cycle. RESULTS: Proliferation of mammary epithelium was greater in diestrus and proestrus, while apoptosis was increased in metestrus and diestrus. Growth factor-, hormone- and anchorage-mediated cell survival signalling, indicated by activation of Stat5A, FAK and Akt 1 and expression of anti-apoptotic Bcl-2 family members, was greater in proestrus and reduced in metestrus. In contrast, the levels of pro-apoptotic Bcl-2 family members and proteins associated with apoptosis in mammary epithelium (TGFbeta3, pStat3) were increased during metestrus and diestrus. CONCLUSION: Decreases in growth factor, hormone and cell attachment survival signals corresponded with increased apoptosis during the second half of the oestrous cycle. The protein levels detected during oestrus suggest parallels to apoptosis in mammary involution.

Non-infectious causes of uveitis in 70 Swiss children

Many diseases are linked with uveitis, but few studies have specifically looked at the noninfectious triggers of childhood uveitis in Central Europe. The charts of 70 paediatric patients with non-infectious uveitis admitted to the Department of Pediatrics, University of Bern, Switzerland, between 1983 and 1998 were therefore reviewed. In the patients the age at presentation with uveitis ranged between 0.3 and 16 y, median 8.5 y. Based on the localization, uveitis anterior was diagnosed in most cases (n = 40; 57%), followed by panuveitis (n = 20; 29%) and uveitis posterior (n = 10; 14%). Uveitis was chronic in 54 (77%) and acute in 16 (23%), bilateral in 38 (54%) and unilateral in 32 (46%) cases. An associated condition was noted in 32 (46%) cases: juvenile idiopathic arthritis in 24 cases, sarcoidosis and juvenile spondyloarthropathy in 3 cases, and Sjögren's syndrome and Behçet's disease in 1 case each. In the remaining 38 (54%) patients, no associated condition was diagnosed. It is concluded that in Swiss children, uveitis can be due to a wide spectrum of non-infectious diseases, juvenile idiopathic arthritis being the leading cause. In the majority of the children, no associated condition was recognized.

C-C chemokine receptor 6-regulated entry of TH-17 cells into the CNS through the choroid plexus is required for the initiation of EAE

Interleukin 17-producing T helper cells (T(H)-17 cells) are important in experimental autoimmune encephalomyelitis, but their route of entry into the central nervous system (CNS) and their contribution relative to that of other effector T cells remain to be determined. Here we found that mice lacking CCR6, a chemokine receptor characteristic of T(H)-17 cells, developed T(H)-17 responses but were highly resistant to the induction of experimental autoimmune encephalomyelitis. Disease susceptibility was reconstituted by transfer of wild-type T cells that entered into the CNS before disease onset and triggered massive CCR6-independent recruitment of effector T cells across activated parenchymal vessels. The CCR6 ligand CCL20 was constitutively expressed in epithelial cells of choroid plexus in mice and humans. Our results identify distinct molecular requirements and ports of lymphocyte entry into uninflamed versus inflamed CNS and suggest that the CCR6-CCL20 axis in the choroid plexus controls immune surveillance of the CNS.

Bildanalyse und technologischer Standard - ein kritischer Rückblick auf Multimedia

In dem Beitrag geht es um einen Rückblick auf die Anfänge des manipulierbaren, digitalen Bildes im Kontext der Kunst. An einem Fallbeispiel, dem Johannesaltar des Rogier van der Weyden, erfolgt eine praktische Auseinandersetzung mit den technologisch bedingten Grenzen der Bildanalyse. Dies mündet in eine kritische Bilanz vorfabrizierter Wissensvermittlung und Sichtbarkeitserfahrung nicht nur im Bereich der Kunstgeschichte. Die These lautet von daher ganz allgemein gefasst: Tradierte Bildlichkeit fristet ihr Dasein nicht mehr allein im musealen Raum, sondern ist bereits in einen technologisch bedingten transferiert.

Puzik_Inkrementelle_Umformung

Der Artikel beschreibt neue Ansätze in der inkrementellen Einzelpunkt-Umformung plattenförmiger Kunststoff-Werkstoffe. Die inkrementelle Umformung ist ein innovatives und verglichen mit konventionellen Umformverfahren kostengünstiges Fertigungsverfahren. Insbesondere für Prototypen und Kleinserienfertigungen gibt es Kosteneinsparungen, da auf große und teure Umformwerkzeuge verzichtet werden kann. Das Abfahren eines Umformstempels auf kreisförmigen Bahnen ermöglicht die Formgebung komplexer dreidimensionaler Produkte. Im Gegensatz zum Tiefziehen kann aufgrund der geringen Umformkräfte und Steifigkeitsminderung des Kunststoffmaterials durch Erwärmung auf einen Industrieroboter zurückgegriffen werden. Im Weiteren soll die Idee und Prozess-Entwicklung des Ansatzes zur inkrementellen Kunststoffumformung (IKU) beschrieben werden. Das Potential und die Vorteile dieses Verfahrens gegenüber bestehenden Verfahren werden gezeigt, bevor die nötigen Schritte für die Herstellung eines Kunststoffformteils dargestellt werden. Die Realisierung der Prozessidee mit Hilfe eines prototypischen Roboterwerkzeugs wird anhand erster Umformergebnisse verschiedener Kunststoffbauteile vorgestellt. Weitere ermittelte Optimierungsschritte und Verbesserungen dieses Fertigungsprozesses werden abschließend dargestellt, um ein zukünftiges und industriell einsetzbares, roboterbasiertes, inkrementelles Umformverfahren weiter zu entwickeln.

Early Versus Late Effort in Dynamic Agencies with Unverifiable Information

In this paper we analyze a dynamic agency problem where contracting parties do not know the agent's future productivity at the beginning of the relationship. We consider a two-period model where both the agent and the principal observe the agent's second-period productivity at the end of the first period. This observation is assumed to be non-verifiable information. We compare long-term contracts with short-term contracts with respect to their suitability to motivate effort in both periods. On the one hand, short-term contracts allow for a better fine-tuning of second-period incentives as they can be aligned with the agent's second-period productivity. On the other hand, in short-term contracts first-period effort incentives might be distorted as contracts have to be sequentially optimal. Hence, the difference between long-term and short-term contracts is characterized by a trade-off between inducing effort in the first and in the second period. We analyze the determinants of this trade-off and demonstrate its implications for performance measurement and information system design.

Biovolatilisation: a poorly studied pathway of the arsenic biogeochemical cycle

It has been known for over a hundred years that microorganisms can produce volatile arsenic (As) species, termed “arsines”. However, this topic has received relatively little attention compared to As behaviour in soils and biotransformation through the trophic level in the marine and terrestrial environment. We believe this is due to long-standing misconceptions regarding volatile As stability and transport as well as an absence, until recently, of appropriate sampling methods. First and foremost, an attempt is made to unify arsines' designations, notations and formulas, taking into account all the different terms used in the literature. Then, the stability of As volatile species is discussed and new analytical developments are explored. Further, the special cases of diffuse low-level emissions (e.g. soil and sediment biovolatilisation), and point sources with high-level emissions (geothermal environments, landfills, and natural gas) are comprehensively reviewed. In each case, future possible areas of research and unknown mechanisms are identified and their importance towards the global As biogeochemical cycle is explored. This review gathers new information regarding mechanisms, stability, transport and sampling of the very elusive arsines and shows that more research should be conducted on this important process.