The real issues with in-ground SUDS in Scotland

The aim of this research was to produce enhanced detailing and improved operation of in-ground SUDS. Data from on-site monitoring at three filter drain and three infiltration trench systems were analysed and the results were combined with information gathered from 40 assessments of in-situ systems in Eastern Scotland. Current findings showed that almost 50% of all systems were found to be unsatisfactory and more than half of these were rated as having failed. 36% provided fair and 16%, good performance. Only one system was considered to be performing excellently. Several reasons were identified for the poor performance. The principal cause of problems was runoff from unstabilised areas or construction runoff, which was found to be affecting the systems’ longevity. Almost 30% of all sites were affected by construction runoff. Another major problem was related to system maintenance since maintenance programs were generally not in place. This study has shown that regular maintenance is vital for the longevity of in-ground SUDS

Increased serum levels of macrophage migration inhibitory factor in patients with primary Sjögren's syndrome

The objective of this study was to analyse levels of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) in patients with primary Sjögren's syndrome (pSS) and to examine associations of MIF with clinical, serological and immunological variables. MIF was determined by ELISA in the sera of 76 patients with pSS. Further relevant cytokines (IL-1, IL-6, IL-10, IFN-γ and TNF-α) secreted by peripheral blood mononuclear cells (PBMC) were determined by ELISPOT assay. Lymphocytes and monocytes were examined flow-cytometrically for the expression of activation markers. Results were correlated with clinical and laboratory findings as well as with the HLA-DR genotype. Healthy age- and sex-matched volunteers served as controls. We found that MIF was increased in patients with pSS compared with healthy controls (p < 0.01). In particular, increased levels of MIF were associated with hypergammaglobulinemia. Further, we found a negative correlation of MIF levels with the number of IL-10-secreting PBMC in pSS patients (r = -0.389, p < 0.01). Our data indicate that MIF might participate in the pathogenesis of primary Sjögren's syndrome. MIF may contribute to B-cell hyperactivity indicated by hypergammaglobulinemia. The inverse relationship of IL-10 and MIF suggests that IL-10 works as an antagonist of MIF in pSS

Transforming Growth Factor β1 Oppositely Regulates the Hypertrophic and Contractile Response to β-Adrenergic Stimulation in the Heart

BACKGROUND: Neuroendocrine activation and local mediators such as transforming growth factor-β₁ (TGF-β₁) contribute to the pathobiology of cardiac hypertrophy and failure, but the underlying mechanisms are incompletely understood. We aimed to characterize the functional network involving TGF-β₁, the renin-angiotensin system, and the β-adrenergic system in the heart. METHODS: Transgenic mice overexpressing TGF-β₁ (TGF-β₁-Tg) were treated with a β-blocker, an AT₁-receptor antagonist, or a TGF-β-antagonist (sTGFβR-Fc), were morphologically characterized. Contractile function was assessed by dobutamine stress echocardiography in vivo and isolated myocytes in vitro. Functional alterations were related to regulators of cardiac energy metabolism. RESULTS: Compared to wild-type controls, TGF-β₁-Tg mice displayed an increased heart-to-body-weight ratio involving both fibrosis and myocyte hypertrophy. TGF-β₁ overexpression increased the hypertrophic responsiveness to β-adrenergic stimulation. In contrast, the inotropic response to β-adrenergic stimulation was diminished in TGF-β₁-Tg mice, albeit unchanged basal contractility. Treatment with sTGF-βR-Fc completely prevented the cardiac phenotype in transgenic mice. Chronic β-blocker treatment also prevented hypertrophy and ANF induction by isoprenaline, and restored the inotropic response to β-adrenergic stimulation without affecting TGF-β₁ levels, whereas AT₁-receptor blockade had no effect. The impaired contractile reserve in TGF-β₁-Tg mice was accompanied by an upregulation of mitochondrial uncoupling proteins (UCPs) which was reversed by β-adrenoceptor blockade. UCP-inhibition restored the contractile response to β-adrenoceptor stimulation in vitro and in vivo. Finally, cardiac TGF-β₁ and UCP expression were elevated in heart failure in humans, and UCP--but not TGF-β₁--was downregulated by β-blocker treatment. CONCLUSIONS: Our data support the concept that TGF-β₁ acts downstream of angiotensin II in cardiomyocytes, and furthermore, highlight the critical role of the β-adrenergic system in TGF-β₁-induced cardiac phenotype. Our data indicate for the first time, that TGF-β₁ directly influences mitochondrial energy metabolism by regulating UCP3 expression. β-blockers may act beneficially by normalizing regulatory mechanisms of cellular hypertrophy and energy metabolism

Toxoplasma gondii Actively Inhibits Neuronal Function in Chronically Infected Mice

Upon infection with the obligate intracellular parasite Toxoplasma gondii, fast replicating tachyzoites infect a broad spectrum of host cells including neurons. Under the pressure of the immune response, tachyzoites convert into slow-replicating bradyzoites, which persist as cysts in neurons. Currently, it is unclear whether T. gondii alters the functional activity of neurons, which may contribute to altered behaviour of T. gondii–infected mice and men. In the present study we demonstrate that upon oral infection with T. gondii cysts, chronically infected BALB/c mice lost over time their natural fear against cat urine which was paralleled by the persistence of the parasite in brain regions affecting behaviour and odor perception. Detailed immunohistochemistry showed that in infected neurons not only parasitic cysts but also the host cell cytoplasm and some axons stained positive for Toxoplasma antigen suggesting that parasitic proteins might directly interfere with neuronal function. In fact, in vitro live cell calcium (Ca2+) imaging studies revealed that tachyzoites actively manipulated Ca2+ signalling upon glutamate stimulation leading either to hyper- or hypo-responsive neurons. Experiments with the endoplasmatic reticulum Ca2+ uptake inhibitor thapsigargin indicate that tachyzoites deplete Ca2+ stores in the endoplasmatic reticulum. Furthermore in vivo studies revealed that the activity-dependent uptake of the potassium analogue thallium was reduced in cyst harbouring neurons indicating their functional impairment. The percentage of non-functional neurons increased over time In conclusion, both bradyzoites and tachyzoites functionally silence infected neurons, which may significantly contribute to the altered behaviour of the host

Writing in Britain and Ireland, c. 400 to c. 800

No abstract available

Biografieforschung: theoretische Perspektiven und methodologische Konzepte für eine re-konstruktive Geschlechterforschung

Die Biografieforschung bezeichnet einen komplexen Forschungsansatz, der auf eine lange Geschichte des wissenschaftlichen Interesses an "persönlichen Dokumenten" verweisen kann. Sie ist eine voraussetzungsvolle Forschungsperspektive, die sich in zentralen Aspekten ihres Vorgehens auf Biografien als theoretisches Konzept, als historisch-empirischen Gegenstand und als komplexe methodologische Strategie bezieht. Andere Begriffe, welche oftmals synonym gebraucht, in der Biografieforschung aber systematisch unterschieden werden, sind "Lebensgeschichte" und "Lebenslauf". Die Autorin skizziert die Perspektiven einer rekonstruktiven Geschlechterforschung innerhalb der Biografieforschung, wozu sie auf die Differenzierungen empirischer Forschung, die methodologischen Prinzipien sowie auf Datenerhebung und Datenanalyse eingeht. Sie hebt insbesondere drei Kontextrelationen bei der Interpretation eines biografischen Textes hervor: Biografie, Interaktion, kulturelle Muster und soziale Regeln. Das skizzierte Konzept von Biografieforschung begreift sie als ein offenes Programm, das vielfältige Anknüpfungspunkte zu aktuellen theoretischen Diskussionen in der Geschlechterforschung aufweist. (ICI2

GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment

Afterworld Spaces in Medieval Visionary Texts of Irish Provenance

Benz M, Weitbrecht J. Afterworld Spaces in Medieval Visionary Texts of Irish Provenance. In: Keller WR, Schlüter D, eds. A Fantastic and Abstruse Latinity? Hiberno-Continental Cultural and Literary Interactions in the Middle Ages. Studien und Texte zur Keltologie. Vol 12. Münster: Nodus Publikationen; 2017: 117-140

Assessment of Environmental Flows from Complexity to Parsimony—Lessons from Lesotho

Over the last decade, Environmental Flow Assessment (EFA) has focused scientific attention around heavily-modified hydrosystems, such as flow regulated releases downstream of dams. In this light, numerous approaches of varying complexity have been developed, the most holistic of which incorporate hydrological, hydraulic, biological and water quality inputs, as well as socioeconomic issues. Finding the optimal flow releases, informing policy and determining an operational framework are often the main focus. This work exhibits a simplification of the DRIFT framework, and is regarded as the first holistic EFA approach, consisting of three modules, namely hydrological, hydraulic and fish quality. A novel conceptual classification for fish quality is proposed, associating fish fauna requirements with hydraulic characteristics, exported by fish survey analyses. The new methodology was applied and validated successfully at three stream sites in Lesotho, where DRIFT was formerly employed

Mycophenolate sodium treatment in patients with primary Sjögren syndrome: a pilot trial

The aim of this study was to evaluate the efficacy and safety of mycophenolate sodium (MPS) in patients with primary Sjögren syndrome (pSS) refractory to other immunosuppressive agents. Eleven patients with pSS were treated with MPS up to 1,440 mg daily for an observation period of 6 months in this single-center, open-label pilot trial. At baseline, after 3 months, and after 6 months, we examined the clinical status, including glandular function tests, as well as different laboratory parameters associated with pSS. In addition, subjective parameters were determined on the basis of different questionnaires. Treatment with MPS was well tolerated in 8 of 11 patients. Due to vertigo or gastrointestinal discomfort, two patients did not complete the trial. One patient developed pneumonia 2 weeks after treatment and was withdrawn. In the remaining patients, MPS treatment resulted in subjective improvement of ocular dryness on a visual analogue scale and a reduced demand for artificial tear supplementations. However, no significant alterations of objective parameters for dryness of eyes and mouth were observed, although a substantial improvement of glandular functions occurred in two patients with short disease duration. In addition, treatment with MPS resulted in significant reduction of hypergammaglobulinemia and rheumatoid factors as well as an increase of complement levels and white blood cells. MPS promises to be an additional therapeutic option for patients with pSS, at least in those with shorter disease duration. Further investigations about the efficacy and safety of MPS in pSS have to be performed in larger numbers of patients