Risk reduction in pesticide application - A conceptual framework

Pesticides are heavily criticised by environmental groups and others who argue that their inefficient application pollutes our environment. They are, however, still essential to support food production and human well being. The complex process of transferring a pesticide from a container to the biological target requires a holistic approach to look at all sources of pesticide losses to reduce risks in application. As the majority of pesticides are applied as sprays, a conceptual framework of the spray application process from spray planning (e.g. dose selection, timing, treatment plan), mixing, filling and cleaning, spray atomisation, transport and deposition, weathering and run off is considered. This is an attempt to help identify those areas of the spray application process of most importance for the protection of the environment and human health

Transport, magnetic, and structural properties of La0.7_{0.7}Ce0.3_{0.3}MnO3_3 thin films. Evidence for hole-doping

Cerium-doped manganite thin films were grown epitaxially by pulsed laser deposition at $720 ^\circ$C and oxygen pressure $p_{O_2}=1-25$Pa and were subjected to different annealing steps. According to x-ray diffraction (XRD) data, the formation of CeO$_2$ as a secondary phase could be avoided for $p_{O_2}\ge 8$Pa. However, transmission electron microscopy shows the presence of CeO$_2$ nanoclusters, even in those films which appear to be single phase in XRD. With O$_2$ annealing, the metal-to-insulator transition temperature increases, while the saturation magnetization decreases and stays well below the theoretical value for electron-doped La$_{0.7}$Ce$_{0.3}$MnO$_3$ with mixed Mn$^{3+}$/Mn$^{2+}$ valences. The same trend is observed with decreasing film thickness from 100 to 20 nm, indicating a higher oxygen content for thinner films. Hall measurements on a film which shows a metal-to-insulator transition clearly reveal holes as dominating charge carriers. Combining data from x-ray photoemission spectroscopy, for determination of the oxygen content, and x-ray absorption spectroscopy (XAS), for determination of the hole concentration and cation valences, we find that with increasing oxygen content the hole concentration increases and Mn valences are shifted from 2+ to 4+. The dominating Mn valences in the films are Mn$^{3+}$ and Mn$^{4+}$, and only a small amount of Mn$^{2+}$ ions can be observed by XAS. Mn$^{2+}$ and Ce$^{4+}$ XAS signals obtained in surface-sensitive total electron yield mode are strongly reduced in the bulk-sensitive fluorescence mode, which indicates hole-doping in the bulk for those films which do show a metal-to-insulator transition.Comment: 8 pages, 10 figure

Triple-Modal Imaging of Magnetically-Targeted Nanocapsules in Solid Tumours In Vivo

Triple-modal imaging magnetic nanocapsules, encapsulating hydrophobic superparamagnetic iron oxide nanoparticles, are formulated and used to magnetically target solid tumours after intravenous administration in tumour-bearing mice. The engineered magnetic polymeric nanocapsules m-NCs are ~200 nm in size with negative Zeta potential and shown to be spherical in shape. The loading efficiency of superparamagnetic iron oxide nanoparticles in the m-NC was ~100%. Up to ~3- and ~2.2-fold increase in tumour uptake at 1 and 24 h was achieved, when a static magnetic field was applied to the tumour for 1 hour. m-NCs, with multiple imaging probes (e.g. indocyanine green, superparamagnetic iron oxide nanoparticles and indium-111), were capable of triple-modal imaging (fluorescence/magnetic resonance/nuclear imaging) in vivo. Using triple-modal imaging is to overcome the intrinsic limitations of single modality imaging and provides complementary information on the spatial distribution of the nanocarrier within the tumour. The significant findings of this study could open up new research perspectives in using novel magnetically-responsive nanomaterials in magnetic-drug targeting combined with multi-modal imaging

A time-resolved fluorescence immunoassay for the measurement of testosterone in saliva: Monitoring of testosterone replacement therapy with testosterone buciclate

Monitoring of testosterone replacement therapy requires a reliable method for testosterone measurement. Determination of salivary testosterone, which reflects the hormone's biologically active plasma fraction, is a superior technique for this purpose. The aim of the present study was to establish a new sensitive time-resolved fluorescence immunoassay for the accurate measurement of testosterone levels in saliva and to validate it by monitoring testosterone replacement therapy in eight hypogonadal men. A clinical phase I- study with the new ester testosterone buciclate was performed to search for new testosterone preparations to produce constant serum levels in the therapy of male hypogonadism. After two control examinations eight male patients with primary hypogonadism were randomly assigned to two treatment groups (n = 2x4) and given single doses of either 200 mg (group I) or 600 mg (group II) testosterone buciclate intramuscularly. Saliva and blood samples were obtained 1, 2, 3, 5 and 7 days post injection and then weekly for three months. The time-resolved fluorescence immunoassay for salivary testosterone shows a detection limit of 16 pmol/l, an intra-assay CV of 8.9% (at a testosterone concentration of 302 pmol/l), an inter-assay CV of 8.7% (at a testosterone concentration of 305 pmol/l) and a good correlation with an established radioimmunsassay of r = 0.89. The sample volume required by this method is only 180 mu l for extraction and duplicate determination. The assay procedure requires no more than three hours. In group I (200 mg) testosterone did not increase to normal levels either in saliva or in serum. However, in group II, androgen levels increased significantly and were maintained in the normal range for up to 12 weeks with maximal salivary testosterone levels of 303 +/- 18 pmol/l (mean+/-SE) and maximal testosterone levels of 13.1 +/- 0.9 nmol/l (mean+/-SE) in serum in study week 6 and 7. The time-resolved fluorescence immunoassay for salivary testosterone provides a useful tool for monitoring androgen status in men and women and is well suited for the follow-up of testosterone replacement therapy on an outpatient basis. The long-acting ester testosterone buciclate is a promising agent for substitution therapy of male hypogonadism and in combination with testosterone monitoring in saliva offers an interesting new perspective for male contraception

Isolation of human β-defensin-4 in lung tissue and its increase in lower respiratory tract infection

BACKGROUND: Human β-defensin-4 (hBD-4), a new member of the β-defensin family, was discovered by an analysis of the genomic sequence. The objective of this study was to clarify hBD-4 expression in human lung tissue, along with the inducible expression in response to infectious stimuli, localization, and antimicrobial activities of hBD-4 peptides. We also investigated the participation of hBD-4 in chronic lower respiratory tract infections (LRTI) by measuring the concentrations of hBD-4 peptides in human bronchial epithelial lining fluid (ELF). METHODS: The antimicrobial activity of synthetic hBD-4 peptides against E. coli and P. aeruginosa was measured by radial diffusion and colony count assays. We identified hBD-4 in homogenated human lung tissue by reverse-phase high-performance liquid chromatography coupled with a radioimmunoassay (RIA). Localization of hBD-4 was studied through immunohistochemical analysis (IHC). We investigated the effects of lipopolysaccharide (LPS) on hBD-4 expression and its release from small airway epithelial cells (SAEC). We collected ELF from patients with chronic LRTI using bronchoscopic microsampling to measure hBD-4 concentrations by RIA. RESULTS: hBD-4 exhibited salt-sensitive antimicrobial activity against P. aeruginosa. We detected the presence of hBD-4 peptides in human lung tissue. IHC demonstrated the localization of hBD-4-producing cells in bronchial and bronchiolar epithelium. The levels of hBD-4 peptides released from LPS-treated SAECs were higher than those of untreated control cells. ELF hBD-4 was detectable in 4 of 6 patients with chronic LRTI, while the amounts in controls were all below the detectable level. CONCLUSION: This study suggested that hBD-4 plays a significant role in the innate immunity of the lower respiratory tract

The ASTRA Toolbox: A platform for advanced algorithm development in electron tomography

We present the ASTRA Toolbox as an open platform for 3D image reconstruction in tomography. Most of the software tools that are currently used in electron tomography offer limited flexibility with respect to the geometrical parameters of the acquisition model and the algorithms used for reconstruction. The ASTRA Toolbox provides an extensive set of fast and flexible building blocks that can be used to develop advanced reconstruction algorithms, effectively removing these limitations. We demonstrate this flexibility, the resulting reconstruction quality, and the computational efficiency of this toolbox by a series of experiments, based on experimental dual-axis tilt series

The impact of COPD on polyneuropathy : results from the German COPD cohort COSYCONET

Background: Peripheral neuropathy is a common comorbidity in COPD. We aimed to investigate associations between alterations commonly found in COPD and peripheral neuropathy, with particular emphasize on the distinction between direct and indirect effects. Methods: We used visit 4 data of the COPD cohort COSYCONET, which included indicators of polyneuropathy (repeated tuning fork and monofilament testing), excluding patients with diabetes a/o increased HbA1c. These indicators were analysed for the association with COPD characteristics, including lung function, blood gases, 6-min walk distance (6-MWD), timed-up-and-go-test (TUG), exacerbation risk according to GOLD, C-reactive protein (CRP), and ankle-brachial index (ABI). Based on the results of conventional regression analyses adjusted for age, BMI, packyears and gender, we utilized structural equation modelling (SEM) to quantify the network of direct and indirect relationships between parameters. Results: 606 patients were eligible for analysis. The indices of polyneuropathy were highly correlated with each other and related to base excess (BE), ABI and TUG. ABI was linked to neuropathy and 6-MWD, exacerbations depended on FEV1, 6-MWD and CRP. The associations could be summarized into a SEM comprising polyneuropathy as a latent variable (PNP) with three measured indicator variables. Importantly, PNP was directly dependent on ABI and particularly on BE. When also including patients with diabetes and/or elevated values of HbA1c (n = 742) the SEM remained virtually the same. Conclusion: We identified BE and ABI as major determinants of peripheral neuropathy in patients with COPD. All other associations, particularly those with lung function and physical capacity, were indirect. These findings underline the importance of alterations of the micromilieu in COPD, in particular the degree of metabolic compensation and vascular status

High probability of comorbidities in bronchial asthma in Germany

Clinical experience has shown that allergic and non-allergic respiratory, metabolic, mental, and cardiovascular disorders sometimes coexist with bronchial asthma. However, no study has been carried out that calculates the chance of manifestation of these disorders with bronchial asthma in Saarland and Rhineland-Palatinate, Germany. Using ICD10 diagnoses from health care institutions, the present study systematically analyzed the co-prevalence and odds ratios of comorbidities in the asthma population in Germany. The odds ratios were adjusted for age and sex for all comorbidities for patients with asthma vs. without asthma. Bronchial asthma was strongly associated with allergic and with a lesser extent to non-allergic comorbidities: OR 7.02 (95% CI:6.83–7.22) for allergic rhinitis; OR 4.98 (95%CI:4.67–5.32) allergic conjunctivitis; OR 2.41 (95%CI:2.33–2.52) atopic dermatitis; OR 2.47 (95%CI:2.16–2.82) food allergy, and OR 1.69 (95%CI:1.61–1.78) drug allergy. Interestingly, increased ORs were found for respiratory diseases: 2.06 (95%CI:1.64–2.58) vocal dysfunction; 1.83 (95%CI:1.74–1.92) pneumonia; 1.78 (95%CI:1.73–1.84) sinusitis; 1.71 (95%CI:1.65–1.78) rhinopharyngitis; 2.55 (95%CI:2.03–3.19) obstructive sleep apnea; 1.42 (95%CI:1.25–1.61) pulmonary embolism, and 3.75 (95%CI:1.64–8.53) bronchopulmonary aspergillosis. Asthmatics also suffer from psychiatric, metabolic, cardiac or other comorbidities. Myocardial infarction (OR 0.86, 95%CI:0.79–0.94) did not coexist with asthma. Based on the calculated chances of manifestation for these comorbidities, especially allergic and respiratory, to a lesser extent also metabolic, cardiovascular, and mental disorders should be taken into consideration in the diagnostic and treatment strategy of bronchial asthma