High-Precision Orientation of Three-Component Magnetic Downhole Logs

The possible benefits of measuring the magnetic flux density in three components continuously along a borehole have been recognized a long time ago by researchers who developed models and interpretation schemes for 3-component magnetic borehole data (Parker and Daniell,1979; Gallet and Courtillot, 1989).Common borehole methods provide data not allowing for an orientation with respect to a global reference, since this requires a highly accurate orienta tion system independent of the magnetic measurements. A first attempt to obtain the orientation of the sonde was made by Bosum et al. (1988) using a mechanical gyro and accelerometers. However, at that time the data quality of the gyro did not allow for a continuous 3-component measurement. Steveling et al. (2003) provide an example from the Hawaii Scientific Drilling Project (HSDP) drill hole, where directional information of magnetization was used to separate massive lavas from hyaloclastites. However, their directional analysis was limited to the inclination because information on the tool rotation around the vertical axis was not available.Here, we describe the successful development of an orientation procedure with very high resolution independent of magnetic data. Test data were acquired in the 2.5-km-deep ICDP Outokumpu Research Hole in eastern Finland (Kukkonen, 2007) with the so-called Göttinger Borehole Magnetometer (GBM). The sonde uses three fiber optic gyros (FOGs) exhibiting a small drift of 1.5°h-1 and a high resolution of 9x10-5 degrees. In combination with a built-in Förster magnetometer triplet, the GBM can record the magnetic field in three components as well as the tool orientation continuously. In the Outokumpu drill hole, errors (root mean square) were 0.14° for the inclination and 1.4° for the declination of the magnetic flux density

Nutrition in Pancreatic Cancer: A Review

Background: Pancreatic cancer is the fourth leading cause of cancer-related mortality in both genders. More than 80% of patients suffer from significant weight loss at diagnosis and over time develop severe cachexia. Early nutritional support is therefore essential. Summary: This review evaluates the different nutritional therapies, such as enteral nutrition, parenteral nutrition and special nutritional supplements, on nutritional status, quality of life and survival. Key Message: Due to the high prevalence of malnutrition and the rapid development of anorexia-cachexia-syndrome, early nutritional intervention is crucial and supported by clinical data. Practical Implications: Enteral nutrition should be preferred over parenteral nutrition. Omega-3 fatty acids and L-carnitine are promising substances for the prevention of severe cachexia, but further randomized controlled trials are needed to establish generally accepted guidelines on nutrition in pancreatic cancer

Protocol for a randomised, double-blind, placebo-controlled study of grass allergen immunotherapy tablet for seasonal allergic rhinitis: time course of nasal, cutaneous and immunological outcomes

BACKGROUND: Seasonal Allergic Rhinitis is characterised by inflammation of the nasal mucosa upon exposure to common aeroallergens, affecting up to 20-25 % of the population. For those patients whose symptoms are not controlled by standard medical treatment, allergen specific immunotherapy is a therapeutic alternative. Although several studies have shown changes in immunologic responses as well as long term tolerance following treatment with a sublingual allergy immunotherapy tablet, a detailed time course of the early mechanistic changes of local and systemic T and B cell responses and the effects on B cell repertoire in the nasal mucosa have not been fully examined. METHODS/DESIGN: This is a randomized, double-blind, single-centre, placebo controlled, two arm time course study based in the United Kingdom comparing sublingual allergy immunotherapy tablet (GRAZAX(®), ALK-Abello Horsholm, Denmark) plus standard treatment with placebo plus standard treatment. Up to 50 moderate to severe grass pollen allergic participants will be enrolled to ensure randomisation of at least 44. Further, we shall enrol 20 non-atopic volunteers. Screening will be completed before eligible atopic participants are randomised to one of the two treatment arms in a 1 to 1 ratio. The primary endpoint will be the total nasal symptom score assessed over 60 min following grass pollen nasal allergen challenge after 12 months of treatment. Clinical assessments and/or mechanistic analyses on blood, nasal fluid, brushing and biopsies will be performed at baseline at 1, 2, 3, 4 (coinciding with the peak pollen season), 6 and 12 months of treatment. After 12 months of treatment, unblinding will take place. Those atopic participants receiving active treatment will continue therapy for another 12 months followed by a post treatment phase of 12 months. Assessments and collection of biologic samples from these participants will take place again at 24 and at 36 months from the start of treatment. The 20 healthy, non-atopic controls will undergo screening and one visit only coinciding with the 12 month visit for the atopic participants. DISCUSSION: The trial will end in April 2017. The trial is registered with ClinicalTrials.gov and the trial identifying number is NCT02005627. TRIAL REGISTRATION: Primary Registry: ClinicalTrials.gov, Trial Identifying number: NCT02005627, Secondary identifying numbers: EudraCT number: 2013-003732-72 REC: 13/EM/0351, Imperial College London (Sponsor): 13IC0847, Protocol Version 6.0, Date: 16.05.2014

Korruption: ein ungerechtfertigter Eingriff in internationale Menschenrechte? Chancen und Grenzen einer opferbezogenen Korruptionsperspektive

<p><b>Daily carbohydrate (A) and sugar (B) intake by groups and subgroups.</b> Carbohydrate (A) and sugar intake (B) as illustrated in percent. The boxes cover the first quartile on the bottom and the third quartile on the top. Whiskers reach from the minimum to the maximum value excluding outliers (illustrated by dots). Shift-working group and shift-working nursing-staff subgroup cover identical cohorts. NG, non-shift-working group; SG, shift-working group; SN, shift-working nursing-staff subgroup; NO, non-shift-working office-staff subgroup; NN, non-shift-working nursing-staff subgroup *p<0.05.</p

Allergen-specific IgG+ memory B cells are temporally linked to IgE memory responses

BACKGROUND: Immunoglobulin E (IgE) are least abundant, tightly regulated and IgE producing B cells are rare. The cellular origin and evolution of IgE responses are poorly understood. OBJECTIVE: To investigate the cellular and clonal origin of IgE memory responses following mucosal allergen exposure by sublingual immunotherapy (SLIT). METHODS: In a randomized double-blind, placebo-controlled, time-course SLIT study, peripheral blood mononuclear cells (PBMCs) and nasal biopsies were collected from forty adults with seasonal allergic rhinitis at baseline, 4, 8, 16, 28 and 52 weeks. RNA was extracted from PBMCs, sorted B cells and nasal biopsies for VH repertoire sequencing. Moreover, monoclonal antibodies were derived from single B cell transcriptomes. RESULTS: Combining VH repertoire sequencing and single cell transcriptomics yielded direct evidence of a parallel boost of two clonally and functionally related B cell subsets of short-lived IgE+ plasmablasts and IgG+ memory B cells (termed IgGE). Mucosal grass pollen allergen exposure by SLIT resulted in highly diverse IgE and IgGE repertoires. These were extensively mutated and appeared relative stable as per heavy chain isotype, somatic hypermutations and clonal composition. Single IgGE + memory B cell and IgE+ pre-plasmablast transcriptomes encoded antibodies that were specific for major grass pollen allergens and were able to elicit basophil activation at very low allergen concentrations. CONCLUSION: For the first time, we have shown that upon mucosal allergen exposure, human IgE memory resides in allergen-specific IgG+ memory B cells. These rapidly switch isotype and expand into short-lived IgE+ plasmablasts and serve as a potential target for therapeutic intervention

Sex-Specific associations of brain-derived neurotrophic factor and cardiorespiratory fitness in the general population

The brain-derived neurotrophic factor (BDNF) was initially considered to be neuron-specific. Meanwhile, this neurotrophin is peripherally also secreted by skeletal muscle cells and increases due to exercise. Whether BDNF is related to cardiorespiratory fitness (CRF) is currently unclear. We analyzed the association of serum BDNF levels with CRF in the general population (Study of Health in Pomerania (SHIP-TREND) from Northeast Germany; n = 1607, 51% female; median age 48 years). Sex-stratified linear regression models adjusted for age, height, smoking, body fat, lean mass, physical activity, and depression analyzed the association between BDNF and maximal oxygen consumption (VO2peak), maximal oxygen consumption normalized for body weight (VO2peak/kg), and oxygen consumption at the anaerobic threshold (VO2@AT). In women, 1mL/min higher VO2peak, VO2peak/kg, and VO2@AT were associated with a 2.43 pg/mL (95% confidence interval [CI]: 1.16 to 3.69 pg/mL; p = 0.0002), 150.66 pg/mL (95% CI: 63.42 to 237.90 pg/mL; p = 0.0007), and 2.68 pg/mL (95% CI: 0.5 to 4.8 pg/mL; p = 0.01) higher BDNF serum concentration, respectively. No significant associations were found in men. Further research is needed to understand the sex-specific association between CRF and BDNF. © 2019 by the authors. Licensee MDPI, Basel, Switzerland

Sex-Specific Associations of Brain-Derived Neurotrophic Factor and Cardiorespiratory Fitness in the General Population

The brain-derived neurotrophic factor (BDNF) was initially considered to be neuron-specific. Meanwhile, this neurotrophin is peripherally also secreted by skeletal muscle cells and increases due to exercise. Whether BDNF is related to cardiorespiratory fitness (CRF) is currently unclear. We analyzed the association of serum BDNF levels with CRF in the general population (Study of Health in Pomerania (SHIP-TREND) from Northeast Germany; n = 1607, 51% female; median age 48 years). Sex-stratified linear regression models adjusted for age, height, smoking, body fat, lean mass, physical activity, and depression analyzed the association between BDNF and maximal oxygen consumption (VO2peak), maximal oxygen consumption normalized for body weight (VO2peak/kg), and oxygen consumption at the anaerobic threshold (VO2@AT). In women, 1mL/min higher VO2peak, VO2peak/kg, and VO2@AT were associated with a 2.43 pg/mL (95% confidence interval [CI]: 1.16 to 3.69 pg/mL; p = 0.0002), 150.66 pg/mL (95% CI: 63.42 to 237.90 pg/mL; p = 0.0007), and 2.68 pg/mL (95% CI: 0.5 to 4.8 pg/mL; p = 0.01) higher BDNF serum concentration, respectively. No significant associations were found in men. Further research is needed to understand the sex-specific association between CRF and BDNF. © 2019 by the authors. Licensee MDPI, Basel, Switzerland

40Ar/39Ar ages for deep (~3.3 km) samples from the Hawaii Scientific Drilling Project, Mauna Kea volcano, Hawaii

The Hawaii Scientific Drilling Project recovered core from a 3.5 km deep hole from the flank of MaunaKea volcano, providing a long, essentially continuous record of the volcano’s physical and petrologicdevelopment that has been used to infer the chemical and physical characteristics of the Hawaiian mantle plume. Determining a precise accumulation rate via 40Ar/39Ar dating of the shield-stage tholeiites, which constitute 95–98% of the volcano’s volume is challenging. We applied 40Ar/39Ar dating using laser- and furnace-heating in two laboratories (Berkeley and Curtin) to samples of two lava flows from deep in the core (~3.3 km). All determinations yield concordant isochron ages, ranging from 612 +/- 159 to 871 +/- 302 ka (2delta; with P = 0.90). The combined data yield an age of 681 +/- 120 ka (P = 0.77) for pillow lavas near the bottom of the core. This new age, when regressed with 40Ar/39Ar isochron ages previously obtained for tholeiites higher in the core, defines a constant accumulation rate of 8.4 +/- 2.6 m/ka that can be used to interpolate the ages of the tholeiites in the HSDP core with a mean uncertainty of about 83 ka. For example at ~3300 mbsl, the age of 664 +/- 83 ka estimated from the regression diverges at the 95% confidence level from the age of 550 ka obtained from the numerical model of DePaolo and Stolper (1996). The new data have implications for the timescale of the growth of Hawaiian volcanoes, the paleomagnetic record in the core, and the dynamics of the Hawaiian mantle plume

AllergoOncology: Danger signals in Allergology and Oncology. A European Academy of Allergy and Clinical Immunology (EAACI) Position Paper

The immune system interacts with many nominal ‘danger’ signals, endogenous danger-associated (DAMP), exogenous pathogen (PAMP) and allergen (AAMP)-associated molecular patterns. The immune context under which these are received can promote or prevent immune activating or inflammatory mechanisms and may orchestrate diverse immune responses in allergy and cancer. Each can act either by favouring a respective pathology or by supporting the immune response to confer protective effects, depending on acuity or chronicity. In this Position Paper under the collective term danger signals or DAMPs, PAMPs and AAMPs, we consider their diverse roles in allergy and cancer and the connection between these in AllergoOncology. We focus on their interactions with different immune cells of the innate and adaptive immune system and how these promote immune responses with juxtaposing clinical outcomes in allergy and cancer. While danger signals present potential targets to overcome inflammatory responses in allergy, these may be reconsidered in relation to a history of allergy, chronic inflammation and autoimmunity linked to the risk of developing cancer, and with regard to clinical responses to anti-cancer immune and targeted therapies. Cross-disciplinary insights in AllergoOncology derived from dissecting clinical phenotypes of common danger signal pathways may improve allergy and cancer clinical outcomes