Meta-analysis identifies seven susceptibility loci involved in the atopic march.

Eczema often precedes the development of asthma in a disease course called the 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P=2.1 × 10(-8)) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P=5.3 × 10(-9)). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema.

Inflammatory markers in pediatric stroke: An attempt to better understanding the pathophysiology

BACKGROUND The mechanisms of childhood and perinatal arterial ischemic stroke (AIS) are poorly understood. Multiple risk factors include cerebral arteriopathy, congenital cardiac disease, infection, sickle cell disease, and maternal-fetal conditions in neonates. For infections and parainfectious conditions being the most important a possible inflammatory pathophysiology has long been suspected. This pilot study aims to detect, whether there are any abnormalities of inflammatory markers associated with childhood and neonatal stroke. METHODS The concentration of 23 different metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs), endothelial factors, vascular cell adhesion proteins, and cytokines in plasma were measured in 12 children with AIS, 7 healthy age matched controls and 6 full term neonates with perinatal AIS. RESULTS At the time of the acute event children with AIS had significantly elevated levels of MMP-9, TIMP4, IL-6, IL-8 and CRP compared to controls (p < 0.05). Except for lower IL-6 and CRP levels the pattern of children with a history of varizella-zoster virus (VZV) and other viral infections did not differ to the non-infectious group. Median levels of MMP-1, MMP-2, TIMP-1, TIMP-2, sE-selectin, sICAM-1, sVCAM-1, IL-8, IL-10, TNF-alpha, VEGF, Fetuin A were found to be higher in the neonatal group when compared with older children. CONCLUSION This pilot study supports the assumption of an inflammatory process and up-regulation of metalloproteinases and their inhibitors, and altered pattern of circulating pro-inflammatory cytokines, CRP and vWF levels in pediatric and neonatal AIS. It highlights the feasibility but also difficulties for similar larger future studies that should aim to clarify childhood stroke etiopathogenesis and consecutive further therapeutic options.

Paleolimnological evidence for increased landslide activity due to forest clearing and land-use since 3600 cal BP in the western Swiss Alps

Schwarzsee is located in the western Swiss Alps, in a region that has been affected by numerous landslides during the Holocene, as evidenced by geological surveys. Lacustrine sediments were cored to a depth of 13 m. The vegetation history of the lake's catchment was reconstructed and investigated to identify possible impacts on slope stability. The pollen analyses record development of forest cover during the middle and late Holocene, and provide strong evidence for regional anthropogenic influence such as forest clearing and agricultural activity. Vegetation change is characterized by continuous landscape denudation that begins at ca. 4300 cal. yrs BP, with five distinct pulses of increased deforestation, at 3650, 2700, 1500, 900, and 450 cal. yrs BP. Each pulse can be attributed to increased human impact, recorded by the appearance or increase of specific anthropogenic indicator plant taxa. These periods of intensified deforestation also appear to be correlated with increased landslide activity in the lake's catchment and increased turbidite frequency in the sediment record. Therefore, this study gives new evidence for a strong influence of vegetation changes on slope stability during the middle and late Holocene in the western Swiss Alps, and may be used as a case study for anthropogenically induced landslide activity.

Dopaminergic denervation severity depends on COMT Val158Met polymorphism in Parkinson's disease.

BACKGROUND Catecholamine-O-methyl-tranferase (COMT) initiates dopamine degradation. Its activity is mainly determined by a single nucleotide polymorphism in the COMT gene (Val158Met, rs4680) separating high (Val/Val, COMT(HH)), intermediate (Val/Met, COMT(HL)) and low metabolizers (Met/Met, COMT(LL)). We investigated dopaminergic denervation in the striatum in PD patients according to COMT rs4680 genotype. METHODS Patients with idiopathic PD were assessed for motor severity (UPDRS-III rating scale in OFF-state), dopaminergic denervation using [123I]-FP-CIT SPECT imaging, and genotyped for the COMT rs4680 enzyme. [123I]-FP-CIT binding potential (BP) for each voxel was defined by the ratio of tracer-binding in the region of interest (striatum, caudate nucleus and putamen) to that in a region of non-specific activity. Genotyping was performed using TaqMan(®) SNP genotyping assay. We used a regression model to evaluate the effect of COMT genotype on the BP in the striatum and its sub-regions. RESULTS Genotype distribution was: 11 (27.5%) COMT(HH), 26 (65%) COMT(HL) and 3 (7.5%) COMT(LL). There were no significant differences in disease severity, treatments, or motor scores between genotypes. When adjusted to clinical severity, gender and age, low and intermediate metabolizers showed significantly higher rates of striatal denervation (COMT(HL+LL) BP = 1.32 ± 0.04) than high metabolizers (COMT(HH), BP = 1.6 ± 0.08; F(1.34) = 9.0, p = 0.005). Striatal sub-regions showed similar results. BP and UPDRS-III motor scores (r = 0.44, p = 0.04) (p < 0.001) were highly correlated. There was a gender effect, but no gender-genotype interaction. CONCLUSIONS Striatal denervation differs according to COMT-Val158Met polymorphism. COMT activity may play a role as a compensatory mechanism in PD motor symptoms.

Na 1 Nachlass Max Horkheimer, 42 - Korrespondenzen u.a. mit Kurt Pinthus (p. I 21, 1-130)

1 Brief von Max Horkheimer an Pierre van Paassen, 31.01.1944; 1 Brief von Max Horkheimer an Frederick M. Padelford, 25.03.1941; 1 Exposé und Beilage von Karl O. Paetel sowie sowie Briefwechsel mit Karl A. Wittfogel; 2 Briefe zwischen Karl A. Wittfogel und Margot von Mendelssohn, 01.06.1941, 04.06.1941; 2 Briefe von Max Horkheimer an D. D. Paige, August 1944; 2 Briefe zwischen Maria Pape und Max Horkheimer, 23.07.1949, 29.07.1949; 1 Brief von Fritz Pappenheim an Max Horkheimer, 11.03.1939; 2 Briefe zwischen Claire Patek-Hohenadl und Max Horkheimer, 18.02.1945, 02.03.1945; 4 Briefe zwischen Wilhelm Pauck und Max Horkheimer, 1938; 2 Briefe von Max Horkheimer an Thomas Peardon, September 1941; 2 Briefe zwischen Christine Peck und Max Horkheimer, 01.02.1944, 16.02.1944; 2 Briefe zwischen Alexander H. Pekelis und Max Horkheimer, 20.10.1941, 29.10.1941; 4 Briefe zwischen Pendle Hill Wallingford und Max Horkheimer, 21.05.1940, 1940; 1 Einladung von The People Lobby an Max Horkheimer, April 1937; 1 Brief von Franz L. Neumann an Selig Perlman, 08.10.1941; 2 Briefe zwischen Florence Pfleger und Max Horkheimer, 30.10.1944, 06.11.1944; 2 Briefe zwischen The Philharmonic-Symphony Society of New York und Max Horkheimer, 11.06.1936, 22.06.1936; 2 Briefe zwischen Philosophical Library New York und Max Horkheimer, 09.09.1941; 2 Briefe von Max Horkheimer an Donald A. Piatt, Oktober 1940; 1 Brief von Max Horkheimer an Alfred Pinkus, 27.08.1942; 20 Briefe und Beilage zwischen Kurt Pinthus und Max Horkheimer, 1940-1942; 1 Brief von Friedrich Pollock an das American Consul General Berlin, 20.05.1941; 1 Brief von Friedrich Pollock an den National Refugee Service New York, 30.04.1941; 4 Briefe zwischen The Emergency Committee in Aid of Displaced Foreign Scholars, New York und Friedrich Pollock, 27.09.1940-1941; 1 Brief von Max Horkheimer an John Simon Guggeheim von der Memorial Foundation, 08.11.1940; 3 Brief zwischen Robert Plank und Max Horkheimer, 12.07.1944, 1944; 4 Briefe und 1 Beilage zwischen Richard S. Plant und Max Horkheimer, Januar 1939; 2 Briefe zwischen Caroline S. Platt und Max Horkheimer, 06.05.1942, 08.05.1942; 1 Brief und 2 Beilagen vom Pledge for Peace Committee New York an Max Horkheimer, 10.04.1944; 1 Brief vom Popular Publications, Inc. New York an Mein, 23.10.1939; 2 Briefe von Else Heim an die Popular Publikations, Inc. New York, 1939; 1 Brief und 1 Beilage von Frederick Pollock an Leonard Powers, 03.06.1941; 2 Briefe zwischen S. Pressburger udn Max Horkheimer, 18.06.1939, 05.07.1939; 2 Briefe zwsichen dem Preston Hotel, Swampscott und Max Horkheimer, 28.04.1937, 08.05.1937; 1 Brief von Lucio José F. Weil an das Preston Hotel, Swampscott, 25.06.1936; 5 Briefe zwischen F. V. Preve und Max Horkheimer, 1937; 4 Briefe zwischen Rena Proulx und Max Horkheimer, 1934, 1937; 2 Briefe zwischen dem Psychatry Journal of the Biology and the Pathology of Interpersonal Relations Washington und Max Horkheimer, 21.08.1939, 11.09.1939;

Efficiency from pharmacy inventory technology: A means to improving quality in non-profit hospitals

Hospitals, like all organizations, have both a mission and a finite supply of resources with which to accomplish that mission. Because the inventory of therapeutic drugs is among the more expensive resources needed by a hospital to achieve its mission, a conceptual model of structure plus process equals outcome posits that adequate emphasis should be placed on optimization of the organization's investment in this important structural resource to provide highest quality outcomes. Therefore emphasis should be placed on the optimization of pharmacy inventory because lowering the financial investment in drug inventory and associated costs increases productive efficiency, a key element of quality. ^ In this study, a post-intervention analysis of a hospital pharmacy inventory management technology implementation at The University of Texas M.D. Anderson Cancer Center was conducted to determine if an intervention which reduced a hospital's financial investment in pharmaceutical inventory provided an opportunity to incrementally optimize the organization's mix of structural resources thereby improving quality of care. The results suggest that hospital pharmacies currently lacking technology to support automated purchasing logistics and perpetual, real-time inventory management for drugs may achieve measurable benefits from the careful implementation of such technology, enabling the hospital to lower its investment in on-hand inventory and, potentially, to reduce overall purchasing expenditures. ^ The importance of these savings to the hospital and potentially to the patient should not be underestimated for their ability to generate funding for previously unfunded public health programs or in their ability to provide financial relief to patients in the form of lower drug costs given the current climate of escalating healthcare costs and tightening reimbursements.^

Diatoms, total organic carbon, and total nitrogen of sediment core Dethlingen, Germany

To provide insights into the long-term evolution of aquatic ecosystems without human interference, we here evaluate a decadal- to centennial-scale-resolution diatom record spanning about 12 ka of the Holsteinian interglacial (Marine Isotope Stage 11c). Using a partially varved sediment core from the Dethlingen palaeolake (northern Germany), which has previously been studied for palynological and microfacies signals, we document the co-evolution of the aquatic and surrounding terrestrial environment. The diatom record is dominated by the genera Stephanodiscus, Aulacoseira, Ulnaria and Fragilaria. Based on the diatom assemblages and physical sediment properties, the evolution of the Dethlingen palaeolake can be subdivided into three major phases. During the oldest phase (lasting ~1900 varve years), the lake was ~10-15 m deep and characterized by anoxic bottom-water conditions and a high nutrient content. The following ~5600 years exhibited water depths >20 m, maximum diatom and Pediastrum productivity, and a peak in allochtonous nutrient input. During this phase, water-column mixing became more vigorous, resulting in a breakdown of anoxia. The youngest lake phase (~4000-5000 years) was characterized by decreasing water depth, turbulent water conditions and decreased nutrient loading. Based on our palaeolimnological data, we conclude that the evolution of the Dethlingen palaeolake during the Holsteinian interglacial responded closely to (i) changes within the catchment area (as documented by vegetation and sedimentation) related to the transition from closed forests growing on nutrient-rich soils (mesocratic forest phase) to open forests developing on poor soils (oligocratic forest phase), and (ii) short-term climate variability as reflected in centennial-scale climate perturbations.

(Table 1) Geochemistry of feldspars at DSDP Holes 62-464 and 62-465A

Labradorite is the principal feldspar in tholeiitic basalt from Deep Sea Drilling Project Site 464, on northern Hess Rise. Andesine and oligoclase constitute most primary feldspar in the reportedly trachytic rocks from southern Hess Rise at Site 465. Secondary sanidine(?) has replaced the primary phases at Site 465. The secondary potassium feldspar probably resulted from reaction of trachyte with potassium-bearing hydrothermal fluids or sea water.

Reefs shift from net accretion to net erosion along a natural environmental gradient

Coral reefs persist in an accretion-erosion balance and ocean acidification resulting from anthropogenic CO2 emissions threatens to shift this balance in favor of net reef erosion. Corals and calcifying algae, largely responsible for reef accretion, are vulnerable to environmental changes associated with ocean acidification, but the direct effects of lower pH on reef erosion has received less attention, particularly in the context of known drivers of bioerosion and natural variability. This study examines the balance between reef accretion and erosion along a well-characterized natural environmental gradient in Kane'ohe Bay, Hawai'i using experimental blocks of coral skeleton. Comparing before and after micro-computed tomography (µCT) scans to quantify net accretion and erosion, we show that, at the small spatial scale of this study (tens of meters), pH was a better predictor of the accretion-erosion balance than environmental drivers suggested by prior studies, including resource availability, temperature, distance from shore, or depth. In addition, this study highlights the fine-scale variation of pH in coastal systems and the importance of microhabitat variation for reef accretion and erosion processes. We demonstrate significant changes in both the mean and variance of pH on the order of meters, providing a local perspective on global increases in pCO2. Our findings suggest that increases in reef erosion, combined with expected decreases in calcification, will accelerate the shift of coral reefs to an erosion-dominated system in a high-CO2 world. This shift will make reefs increasingly susceptible to storm damage and sea-level rise, threatening the maintenance of the ecosystem services that coral reefs provide.