Disproportional decrease in office blood pressure compared with 24-hour ambulatory blood pressure with antihypertensive treatment: dependency on pretreatment blood pressure levels

The long-term relationship between 24-hour ambulatory blood pressure (ABP) and office BP in patients on therapy is not well documented. From a registry we included all patients in whom antihypertensive therapy needed to be uptitrated. Drug treatment included the direct renin inhibitor aliskiren or an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker or drugs not blocking the renin-angiotensin system, alone or on top of an existing drug regimen. In all patients, office BP and 24-hour ABP were obtained at baseline and after 1 year with validated devices. In the study population of 2722 patients, there was a good correlation between the change in office BP and 24-hour ABP (systolic: r=0.39; P<0.001; diastolic: r=0.34; P<0.001). However, the numeric decrease in office BP did not correspond to the decrease in ABP in a 1:1 fashion, for example, a decrease of 10, 20, and 30 mm Hg corresponded to a decrease of ~7.2, 10.5, and 13.9 mm Hg in systolic ABP, respectively. The disproportionally greater decrease in systolic office BP compared with ABP was dependent on the level of the pretreatment BP, which was consistently higher for office BP than ABP. The white coat effect (difference between office BP and ABP) was on average 10/5 mm Hg lower 1 year after intensifying treatment and the magnitude of that was also dependent on pretreatment BP. There was a disproportionally greater decrease in systolic office BP than in ABP, which for both office BP and ABP seemed to depend on the pretreatment BP level

Entwicklung eines zeitlichen und räumlichen Entscheidungshilfesystems gegen den Erbsenwickler (Cydia nigricana, Fabricius)

Pea moths (Cydia nigricana) can cause severe damages in pea crops (Pisum sativum). Larvae feed on the seeds in the pods and contaminate them with feces. In the cultivation of organic green peas 0.5 % damaged seeds lead to the denial of whole pea fields (Schulz & Saucke 2005). There can be a yield loss in forage peas and a loss of quality of seeds for propagation. Within the framework of the project to improve the spatial and temporal cultivation strategy of peas to get less damage due to pea moths, is the intention. For a better spatial and temporal cultivation strategy, the DSS creates a map with areas with an infestation risk factor. The higher the risk factor, the earlier the new fields should be cultivated. Therefore, the first part of the DSS works with georeferenced data, like distances between fields of the previous year and the currently planned fields and their infestation risk. The coincidence of the flowering of peas and the flight of pea moths is very important for the infestation. Hence, the second part of the DSS predicts the phenology of the pea and the development of the pea moth for a better precision of the pest control

Erbsenwickler (Cydia nigricana) in Gemüse- und Körnererbsen: Grundlagen zur Befallsprognose und Schadensprävention

Spatio-temporal distribution, combined with aspects of insect biology and ecology can influence the infestation risk of the key pea pest Cydia nigricana in vegetable- and field peas. The proximity of pea fields of the previous cultivation period highly affects the infestation potential of the moth. The presented study aims to monitor the infestation development in three different regions in Germany (North Hesse, Saxony, Saxony-Anhalt) in four consecutive years and to relate empirical pest incidences to key factors as crop abundance, the distance to previous pea fields, the pea plant phenology and climatic conditions. In a next step, these data will form the basis for the elaboration of a computer-aided decision support system, which assists farmers in implementing preventive strategies based on risk avoidance

Challenges and Perspectives of Quantitative Functional Sodium Imaging (fNaI).

Brain function has been investigated via the blood oxygenation level dependent (BOLD) effect using magnetic resonance imaging (MRI) for the past decades. Advances in sodium imaging offer the unique chance to access signal changes directly linked to sodium ions (23Na) flux across the cell membrane, which generates action potentials, hence signal transmission in the brain. During this process 23Na transiently accumulates in the intracellular space. Here we show that quantitative functional sodium imaging (fNaI) at 3T is potentially sensitive to 23Na concentration changes during finger tapping, which can be quantified in gray and white matter regions key to motor function. For the first time, we measured a 23Na concentration change of 0.54 mmol/l in the ipsilateral cerebellum, 0.46 mmol/l in the contralateral primary motor cortex (M1), 0.27 mmol/l in the corpus callosum and -11 mmol/l in the ipsilateral M1, suggesting that fNaI is sensitive to distributed functional alterations. Open issues persist on the role of the glymphatic system in maintaining 23Na homeostasis, the role of excitation and inhibition as well as volume distributions during neuronal activity. Haemodynamic and physiological signal recordings coupled to realistic models of tissue function will be critical to understand the mechanisms of such changes and contribute to meeting the overarching challenge of measuring neuronal activity in vivo

On the hadronic contribution to sterile neutrino production

Sterile neutrinos with masses in the keV range are considered to be a viable candidate for warm dark matter. The rate of their production through active-sterile neutrino transitions peaks, however, at temperatures of the order of the QCD scale, which makes it difficult to estimate their relic abundance quantitatively, even if the mass of the sterile neutrino and its mixing angle were known. We derive here a relation, valid to all orders in the strong coupling constant, which expresses the production rate in terms of the spectral function associated with active neutrinos. The latter can in turn be expressed as a certain convolution of the spectral functions related to various mesonic current-current correlation functions, which are being actively studied in other physics contexts. In the naive weak coupling limit, the appropriate Boltzmann equations can be derived from our general formulae.Comment: 28 pages. v2: small clarifications added, published versio

Venlafaxine’s therapeutic reference range in the treatment of depression revised: a systematic review and meta-analysis

Introduction The selective serotonin and norepinephrine reuptake inhibitor venlafaxine is among the most prescribed antidepressant drugs worldwide and, according to guidelines, its dose titration should be guided by drug-level monitoring of its active moiety (AM) which consists of venlafaxine (VEN) plus active metabolite O-desmethylvenlafaxine (ODV). This indication of therapeutic drug monitoring (TDM), however, assumes a clear concentration/effect relationship for a drug, which for VEN has not been systematically explored yet. Objectives We performed a systematic review and meta-analysis to investigate the relationship between blood levels, efficacy, and adverse reactions in order to suggest an optimal target concentration range for VEN oral formulations for the treatment of depression. Methods Four databases (MEDLINE (PubMed), PsycINFO, Web of Science Core Collection, and Cochrane Library) were systematically searched in March 2022 for relevant articles according to a previously published protocol. Reviewers independently screened references and performed data extraction and critical appraisal. Results High-quality randomized controlled trials investigating concentration/efficacy relationships and studies using a placebo lead-in phase were not found. Sixty-eight articles, consisting mostly of naturalistic TDM studies or small noncontrolled studies, met the eligibility criteria. Of them, five cohort studies reported a positive correlation between blood levels and antidepressant effects after VEN treatment. Our meta-analyses showed (i) higher AM and (ii) higher ODV concentrations in patients responding to VEN treatment when compared to non-responders (n = 360, k = 5). AM concentration-dependent occurrence of tremor was reported in one study. We found a linear relationship between daily dose and AM concentration within guideline recommended doses (75–225 mg/day). The population-based concentration ranges (25–75% interquartile) among 11 studies (n = 3200) using flexible dosing were (i) 225–450 ng/ml for the AM and (ii) 144–302 ng/ml for ODV. One PET study reported an occupancy of 80% serotonin transporters for ODV serum levels above 85 ng/ml. Based on our findings, we propose a therapeutic reference range for AM of 140–600 ng/ml. Conclusion VEN TDM within a range of 140 to 600 ng/ml (AM) will increase the probability of response in nonresponders. A titration within the proposed reference range is recommended in case of non-response at lower drug concentrations as a consequence of VEN’s dual mechanism of action via combined serotonin and norepinephrine reuptake inhibition. Drug titration towards higher concentrations will, however, increase the risk for ADRs, in particular with supratherapeutic drug concentrations

Current CONtrolled Transmit And Receive Coil Elements (C2ONTAR) for Parallel Acquisition and Parallel Excitation Techniques at High-Field MRI

A novel intrinsically decoupled transmit and receive radio-frequency coil element is presented for applications in parallel imaging and parallel excitation techniques in high-field magnetic resonance imaging. Decoupling is achieved by a twofold strategy: during transmission elements are driven by current sources, while during signal reception resonant elements are switched to a high input impedance preamplifier. To avoid B0 distortions by magnetic impurities or DC currents a resonant transmission line is used to relocate electronic components from the vicinity of the imaged object. The performance of a four-element array for 3 T magnetic resonance tomograph is analyzed by means of simulation, measurements of electromagnetic fields and bench experiments. The feasibility of parallel acquisition and parallel excitation is demonstrated and compared to that of a conventional power source-driven array of equivalent geometry. Due to their intrinsic decoupling the current-controlled elements are ideal basic building blocks for multi-element transmit and receive arrays of flexible geometry

Elevated Flt3L predicts long-term survival in patients with high-grade gastroenteropancreatic neuroendocrine neoplasms

BACKGROUND: The clinical management of high-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) is challenging due to disease heterogeneity, illustrating the need for reliable biomarkers facilitating patient stratification and guiding treatment decisions. FMS-like tyrosine kinase 3 ligand (Flt3L) is emerging as a prognostic or predictive surrogate marker of host tumoral immune response and might enable the stratification of patients with otherwise comparable tumor features. METHODS: We evaluated Flt3L gene expression in tumor tissue as well as circulating Flt3L levels as potential biomarkers in a cohort of 54 patients with GEP-NEN. RESULTS: We detected a prominent induction of Flt3L gene expression in individual G2 and G3 NEN, but not in G1 neuroendocrine tumors (NET). Flt3L mRNA expression levels in tumor tissue predicted the disease-related survival of patients with highly proliferative G2 and G3 NEN more accurately than the conventional criteria of grading or NEC/NET differentiation. High level Flt3L mRNA expression was associated with the increased expression of genes related to immunogenic cell death, lymphocyte effector function and dendritic cell maturation, suggesting a less tolerogenic (more proinflammatory) phenotype of tumors with Flt3L induction. Importantly, circulating levels of Flt3L were also elevated in high grade NEN and correlated with patients' progression-free and disease-related survival, thereby reflecting the results observed in tumor tissue. CONCLUSIONS: We propose Flt3L as a prognostic biomarker for high grade GEP-NEN, harnessing its potential as a marker of an inflammatory tumor microenvironment. Flt3L measurements in serum, which can be easily be incorporated into clinical routine, should be further evaluated to guide patient stratification and treatment decisions

Cluster Lenses

Clusters of galaxies are the most recently assembled, massive, bound structures in the Universe. As predicted by General Relativity, given their masses, clusters strongly deform space-time in their vicinity. Clusters act as some of the most powerful gravitational lenses in the Universe. Light rays traversing through clusters from distant sources are hence deflected, and the resulting images of these distant objects therefore appear distorted and magnified. Lensing by clusters occurs in two regimes, each with unique observational signatures. The strong lensing regime is characterized by effects readily seen by eye, namely, the production of giant arcs, multiple-images, and arclets. The weak lensing regime is characterized by small deformations in the shapes of background galaxies only detectable statistically. Cluster lenses have been exploited successfully to address several important current questions in cosmology: (i) the study of the lens(es) - understanding cluster mass distributions and issues pertaining to cluster formation and evolution, as well as constraining the nature of dark matter; (ii) the study of the lensed objects - probing the properties of the background lensed galaxy population - which is statistically at higher redshifts and of lower intrinsic luminosity thus enabling the probing of galaxy formation at the earliest times right up to the Dark Ages; and (iii) the study of the geometry of the Universe - as the strength of lensing depends on the ratios of angular diameter distances between the lens, source and observer, lens deflections are sensitive to the value of cosmological parameters and offer a powerful geometric tool to probe Dark Energy. In this review, we present the basics of cluster lensing and provide a current status report of the field.Comment: About 120 pages - Published in Open Access at: http://www.springerlink.com/content/j183018170485723/ . arXiv admin note: text overlap with arXiv:astro-ph/0504478 and arXiv:1003.3674 by other author