Network visualization for outbreak response: Mapping the Ebola Virus Disease (EVD) chains of transmission in N'Zérékoré, Guinea.

BACKGROUND: During the 2014-2015 Ebola Virus Disease (EVD) outbreak in N'Zérékoré, Forested Guinea, modes of transmission remained unexamined for a number of new cases. We used network visualization to investigate EVD transmission chains (TC) in seven sub-prefectures of N'Zérékoré in order to adapt outbreak response. METHODS: Between August 2014 and February 2015, the EVD outbreak response team including the World Health Organization (WHO) and local health authorities routinely collected information among new cases regarding hospital visits, cases within a household, participation in burials, as well as dates of symptom onset, serial intervals (SI) and exposure to EVD. SI's were defined as the interval between symptom onset in an index case and symptom onset in a secondary case infected by that index case. Cases who reported hospital visits, contact with a case in the household or participating in burials were attributed to these exposures. RESULTS: We identified seven TC (two urban and five rural) gathering characteristics of 109 probable/confirmed cases. Overall, 61% (66 cases, SI range: 7-20 days) were household related, 32% (35 cases, SI range 8-30 days) were household or burial related and 7% (8 cases, SI range: 4-20 days) were hospital-related. In the urban chains (18 cases, SI range: 7-20 days), 12 cases were household related and 6 cases were hospital related, none where household or burial related. In the rural chains (84 cases, SI range: 7-30 days), 60% (50 cases) were household related, 1% (1 case) was hospital related and 39% (34 cases) were household or burial related. No cases reported multiple exposures. CONCLUSIONS: Network visualization during field response is crucial in enhancing local control strategies, refining outbreak response and aiding rapid response teams in insuring psychosocial and socio-economic recovery. Urban settings need to focus on reducing hospital EVD transmission whereas rural settings should focus on raising awareness of transmission within a household and safeguarding EVD burials.

A fluorescent probe assay (Heparin Red) for direct detection of heparins in human plasma.

Heparins are widely used anticoagulant drugs. The current monitoring practice for heparin in plasma, such as the chromogenic anti-factor Xa assay, relies on heparin-triggered activation of antithrombin, an inhibitor of coagulation proteases. Such assays are not applicable to the detection of non-anticoagulant heparins, an emerging class of drug candidates for therapeutic applications unrelated to anticlotting activity. This study describes the application of a commercially available fluorescent probe assay (Heparin Red) for the direct and sensitive detection of the "chemical" heparin in plasma, independent of any anticoagulant activity. The quantification range is about 0-5 µg/mL for both unfractionated heparin (corresponding to 0-1 IU/mL) and the low molecular weight heparin enoxaparin. The Heparin Red assay is of particular value for the quantification of non-anticoagulant heparins, as exemplified by the low molecular weight heparin derivative tafoxiparin and a N-desulfated-N-reacetylated heparin. Heparin octa- and decasaccharides are also detected. Graphical abstract Heparin quantification in plasma by mixing the sample with the Heparin Red reagent and fluorescence readout.

[Stress parameters and behaviour of horses in walkers with and without the use of electricity]. / Stressbelastung und Verhalten von Pferden in stromführenden gegenüber nicht stromführenden Führanlagen.

In order to investigate stress responses of horses in walkers with and without electricity, 12 horses were trained during 3 weeks in a horse walker with and without the use of electricity (3.7 kV). To evaluate the stress response, cortisol levels in the blood were measured, the heart rate was monitored using the Polar® system and the behaviour was evaluated. Neither the cortisol levels nor the heart rates showed any relevant statistically significant difference between horses moved in the horse walker with or without the use of electricity. The highest cortisol levels and heart rates were recorded during the first week (habituation period). A significant difference could be observed regarding spontaneous compartment changes: while this happened mainly during the first week and before the first use of electricity, no horses changed compartments in the periods when electricity was used and thereafter. The results of this study indicate that the use of electricity in the horse walker does not seem to cause significant detectable stress in the horses.

Pour comparer le stress ressenti par les chevaux dans les marcheurs, on a placé 12 chevaux durant 3 semaines dans un marcheur avec ou sans courant électrique (3.7 kV) dans les séparations. On a mesuré le taux de cortisol sanguin et la fréquence cardiaque au moyen d'un appareil Polar® et noté le comportement des chevaux. Ni les taux de cortisol ni les fréquences cardiaques ne présentaient de différences significatives entre les chevaux placés dans un marcheur avec ou sans courant électrique dans les séparations. Les taux de cortisol et les fréquences cardiaques les plus élevés ont été observés dans la première semaine (phase d'accoutumance). Des différences significatives de comportement ont par contre été constatées quant aux paramètres «changement spontané de compartiment¼ et «contact avec la séparation¼: alors que ces faits se produisaient particulièrement durant la première semaine et avant le premier usage du courant électrique, les chevaux ne changeaient plus de compartiment pendant et après l'emploi de l'électricité. Les résultats de cette étude indiquent que l'emploi de l'électricité dans les séparations des marcheurs ne cause pas de stress mesurable significatif pour les chevaux.

Formation and relaxation of RbHe exciplexes on He nanodroplets studied by femtosecond pump and picosecond probe spectroscopy.

Vibrationally resolved photoionization spectra of RbHe exciplexes forming on He nanodroplets are recorded using femtosecond pump-probe spectroscopy with amplitude-shaped probe pulses. The time-evolution of the spectra reveals an exciplex formation time ~10 ps followed by vibrational relaxation extending up to ≳ 1 ns. This points to an indirect, time-delayed desorption process of RbHe off the He surface.

Coherent population trapping with controlled interparticle interactions.

We investigate coherent population trapping in a strongly interacting ultracold Rydberg gas. Despite the strong van der Waals interactions and interparticle correlations, we observe the persistence of a resonance with subnatural linewidth at the single-particle resonance frequency as we tune the interaction strength. This narrow resonance cannot be understood within a mean-field description of the strong Rydberg-Rydberg interactions. Instead, a many-body density matrix approach, accounting for the dynamics of interparticle correlations, is shown to reproduce the observed spectral features.

Dynamics of low-energy helium vapor pulses.

We report results of experiments in which pulses of helium vapor are produced by a current pulse in a chromium film covered with superfluid helium at around 0.3 K. The pulses were detected by a titanium bolometer operating at 0.47 K. The shape of the detected signal is a strong function of the power of the initiating current pulse. For low powers the signal from a single current pulse also contains a single peak, but for higher powers, a single current pulse produces two and then at the highest powers, three peak signals. To analyze the origin of these phenomena we report results of hybrid gas-dynamics and hydrodynamics simulations, which demonstrate that the signals arise from shock waves formed in the vapor. The shock waves form due to the presence of a gradient in the small ambient background of helium vapor in the chamber and are extremely sensitive to the pulse power.

Effects of a heparin-binding protein on blood coagulation and platelet function.

The objective of this study was to characterize the heparin-binding properties of a protein secreted by mouse myeloma cells. The characterization was performed using clinical assays, such as heparin activity assays and heparin-induced thrombocytopenia (HIT) platelet activation assays. The tests were performed in the presence of heparin, low-molecular-weight heparins (LMWH), or heparinoids and either heparin-binding protein (HBP) or saline to determine whether the HBP affects the activity of heparins. The characterization of the HBP using heparin activity assays showed that the HBP shortened the prolonged clotting times of the activated partial thromboplastin time (aPTT) and thrombin clotting time induced by high concentrations of unfractionated heparin. The chromogenic assays for antithrombin (AT), thrombin inhibition, and factor Xa inhibition demonstrated that this effect is related to heparin concentrations below 0.5 IU/ml. The Heptest assay did not detect these differences. The HBP did not modify the anticoagulant effect of any LMWH or low- or high-sulfated glycosaminoglycans in the aPTT assay. Activation of donor platelets in the presence of unfractionated heparin, platelet factor 4 (PF4), and HIT-serum was not counteracted by the HBP in any of the assays. The characterization of the HBP using a PF4-enzyme-linked immunosorbent assay (ELISA) confirmed the lack of structural identity with PF4. However, the optical density data indicated that the protein structure may be similar to PF4 by binding to a PF4 antibody. These data suggest that the HBP isolated from mouse myeloma cells has a low affinity to heparin and interacts with the secondary binding site to AT and also perhaps to PF4.

Sub-miniature ExB sector-field mass spectrometer.

A novel sub-miniature double-focusing sector-field mass spectrometer has been fabricated at the University of Minnesota using a combination of conventional machining methods and thin film patterning techniques typically used in the sensor technology industry. Its design is based on the mass separation capabilities of a 90 degrees cylindrical crossed electric and magnetic sector-field analyzer with a 2-cm radius, which under proper conditions is able to effectively cancel the angular and chromatic dispersion of the ion beam, thus improving the resolving power of the instrument. Simulations using finite element analysis and computer modeling were employed to verify and optimize the performance of the proposed instrument before and during its fabrication. The prototype was able to attain a resolving power of 106 full-width at half-maximum (FWHM), a detection limit close to 10 parts per million, a dynamic range of 5 orders of magnitude and a mass range up to 103 Da. Its overall size, including the magnet assembly, is 3.5 cm wide, 6 cm long and 7.5 cm tall, it weighs 0.8 kg, and its power consumption was measured to be 2.5 W. The performance of the instrument was found to be comparable to that of commercial residual gas analyzers, at a fraction of the cost. All these characteristics make this miniature mass spectrometer suitable for portable and low-cost analytical instrumentation.

Determination of serotonin release from platelets by enzyme immunoassay in the diagnosis of heparin-induced thrombocytopenia.

[14C]-Serotonin release assay (14C-SRA) from platelets is considered to be the most sensitive test for laboratory confirmation of heparin-induced thrombocytopenia (HIT). This study compared 14C-SRA with an enzyme immunoassay (EIA) to determine the release of serotonin from platelets in the presence of heparin and serum from HIT patients. The normal range (median, 2.5 and 97.5 percentiles) of serotonin release from platelets in healthy subjects (n = 149) is 38 ng/ml (19 and 62) measured by EIA-SRA. Serum from HIT patients (n = 42) released 2548 ng/ml (244 and 7987) serotonin in the presence of 0.1 IU/ml heparin and 29 ng/ml (13 and 76) in the presence of 100 IU/ml heparin. One hundred per cent and 15% of HIT samples exhibited an elevated serotonin release from platelets in the presence of 0.1 IU/ml low molecular weight (LMW) heparin, 2100 ng/ml (869 and 5968), or danaparoid, 272 ng/ml (143 and 403), respectively. The sensitivity and specificity of the EIA-SRA was 100% and 97.4% and of the 14C-SRA 100% and 92.9% in HIT patients. No false-positive results were found in patients receiving heparin (n = 28), in patients with elevated levels of bilirubin (n = 5), in patients with antiphospholipid antibody syndrome (n = 10) or in non-HIT patients (n = 78) with both assays. The EIA technique to quantify serotonin release from platelets provides a reliable non-radioactive method to diagnose heparin-induced thrombocytopenia and to assess in vitro crossreactivity of low molecular weight heparins and heparinoid.

Long-term anticoagulation of outpatients with adverse events to oral anticoagulants using low-molecular-weight heparin.

Bleeding complications are one of the major risks during oral anticoagulation. If further anticoagulation is indicated, low-molecular-weight heparin (LMWH) may offer an alternative treatment in those patients. In a prospective, nonrandomized study, 120 patients have been switched from oral anticoagulants to LMWH because of bleeding complications or other severe side effects during treatment with vitamin K antagonists. Indication for further anticoagulation was prophylaxis of recurrent thromboembolism, artificial heart valve replacement, atrial fibrillation with embolism and cardiomyopathy. The treatment period ranged from 2 months to 10.8 years. No fatal embolism occurred. One major but not severe episode of gastrointestinal bleeding occurred in a patient with an as yet unknown colon carcinoma. The cumulative treatment period amounts to 250 years. No drop in platelet count occurred in any patient. No other side effects were observed. LMWH was injected subcutaneously at doses ranging from 2500 to 15,000 anti-factor Xa units per day by the patient himself. The dose was adjusted on the basis of body weight, bleeding risk and thromboembolic risk. The results indicate that LMWH may be effectively and safely used as alternative anticoagulant regimen in patients with side effects or other complications on oral anticoagulants.

Resistance and vulnerability of crustaceans to cytolytic sea anemone toxins.

Crustaceans (Mithraculus, Neopetrolisthes, Periclimenes, Stenorhynchus sp.) living in association with sea anemones, shore crabs (Metopograpsus oceanicus) and brine shrimps (Artemia salina) were found to be resistent to the exposure of cytolytic sea anemone toxins (up to 100 micrograms/ml) and to other membrane-active compounds such as gramicidin A and saponin. The gill filaments of the crustaceans were not affected, indicating that the chitin layer protects the epithelium from the action of the cytolytic toxins. However, crustaceans are highly susceptible to sea anemone toxins when injected parenterally.

[The Heidelberg trichina dispute. A parasitologic episode from the year 1840]. / Der Heidelberger Trichinenstreit. Eine parasitologische Episode aus dem Jahr 1840.

Since the initial zoological description of "Trichina spiralis" (later renamed "Trichinella spiralis") by Owen in 1835 several other scientists had observed trichinas in human muscles, when an inglorious dispute about priorities arose between the anatomists Kobelt and Bischoff at the Heidelberg University in 1840 because of one of those findings. The genesis of trichinosis was only to be explained in 1860 by Zenker, while Bischoff, who was among the leading 19th century embryologists, then still believed in a "generatio spontanea" as it has been described in the context of the chronological outline of the "trichina dispute".

[The effect of prophylactically administered n-acetylcysteine on clinical indicators for tissue oxygenation during hyperoxic ventilation in cardiac risk patients]. / Einfluss der prophylaktischen Gabe von N-Azetylzystein auf klinische Indikatoren der Gewebeoxygenierung unter Hyperoxie bei kardialen Risikopatienten.

UNLABELLED: Hyperoxic ventilation, used to prevent hypoxia during potential periods of hypoventilation, has been reported to paradoxically decrease whole-body oxygen consumption (VO2). Reduction in nutritive blood flow due to oxygen radical production is one possible mechanism. We investigated whether pretreatment with the sulfhydryl group donor and O2 radical scavenger N-acetylcysteine (NAC) would preserve VO2 and other clinical indicators of tissue oxygenation in cardiac risk patients. METHODS: Thirty patients, requiring hemodynamic monitoring (radial and pulmonary artery catheters) because of cardiac risk factors, were included in this randomized investigation. All patients exhibited stable clinical conditions (hemodynamics, body temperature, hemoglobin, F1O2 < 0.5). Cardiac output was determined by thermodilution and VO2 by cardiovascular Fick. After baseline measurements, patients randomly received either 150 mg kg-1 NAC (n = 15) or placebo (n = 15) in 250 ml 5% dextrose i.v. over a period of 30 min. Measurements were repeated 30 min after starting NAC or placebo infusion, 30 min after starting hyperoxia (F1O2 = 1.0), and 30 min after resetting the original F1O2. RESULTS: There were no significant differences between groups in any of the measurements before treatment and after the return to baseline F1O2 at the end of the study, respectively. NAC, but not placebo infusion, caused a slight but not significant increase in cardiac index (CI), left ventricular stroke work index (LVSWI) and a decrease in systemic vascular resistance. Significant differences between groups during hyperoxia were: VO2 (NAC: 108 +/- 38 ml min-1m-2 vs placebo: 79 +/- 22 ml min-1m-2; P < or = 0.05), CI (NAC: 4.6 +/- 1.0 vs placebo: 3.7 +/- 1.11 min-1m-2; P < or = 0.05) and LVSWI (NAC: 47 +/- 12 vs placebo: 38 +/- 9; P < or = 0.05). The mean decrease of VO2 was 22% in the NAC group vs 47% in the placebo group (P < or = 0.05) and the mean difference between groups in venoarterial carbon dioxide gradient (PvaCO2) was 14% (P < or = 0.05). ST segment depression ( > 0.2 mV) was significantly less marked in the NAC group (NAC: -0.02 +/- 0.17 vs placebo: -0.23 +/- 0.15; P < or = 0.05). CONCLUSIONS: NAC helped preserve VO2, oxygen delivery, CI, LVSWI and PvaCO2 during brief hyperoxia in cardiac risk patients. Clinical signs of myocardial ischemia did not occur such as ST-depression if patients were prophylactically treated with NAC. This suggests that pretreatment with NAC could be considered to attenuate impaired tissue oxygenation and to preserve myocardial performance better in cardiac risk patients during hyperoxia.

["...that subsequently homeopathy will become nowhere as common as in veterinary medicine"--the history of veterinary homeopathy in Germany]. / "...dass in der Folge die Homöopathie nirgends allgemeiner werden wird, als wie in der Thierarznei"--Zur Geschichte der Veterinärhomöopathie in Deutschland.

The subject of this article is the historical development of veterinary homoeopathy in Germany until 1945. Turning away from drastic healing methods around 1800, Samuel Hahnemann started to develop his homoeopathic system which since the 1820ies was also applied in the treatment of animals, especially by laymen. The number of homoeopathically-oriented veterinarians remained small. This is also true for veterinary-homoeopathic articles claiming to be scientific while there was a considerable number of popular articles to be found. The professors of the veterinary teaching institutions rejected homoeopathy. At the end of the 19th century hardly anything was heard about veterinary homoeopathy, at least among the professionals. Scientific success in human and veterinary medicine pushed Hahnemann's teachings and those of his successors into the background. In the 1920ies homoeopathy was revived and the position of the renowned surgeon August Bier played an important part in that. Members of the "Studiengemeinschaft für tierärztliche Homöopathie" (Study Group for Veterinary Homoeopathy) which was founded in 1936 started to investigate the effects of homoeopathic drugs systematically. The war put an end to this project. The present situation of veterinary homoeopathy in Germany can be described as follows: Neither have allopathy and homoeopathy been united, as it had been predicted, nor has classical medicine accepted homoeopathy as a scientific discipline. Hahnemann's demand to make his teachings a part of the veterinary studies remains unfulfilled until today.

[History of veterinary medicine as a branch of learning--lessons and possibilities]. / Geschichte der Veterinärmedizin als Lehrfach--Aufgaben und Möglichkeiten.

History of veterinary medicine--which has always been under-rated in the curricula--is the only discipline within the professional training of a veterinary surgeon which encompasses all subjects. It therefore has a uniting, virtually encyclopaedic, mediating function. The intention of a lecture must be to impart a historic view, to inspire the students to consider the responsibility which man has for animals, and to make them sensitive in their professional life for a critical reflection of the basic intellectual concepts of our time and our society beyond the limits of their knowledge of veterinary medicine. It is the veterinary surgeon's "professional culture"--and an essential part of it is the history of veterinary medicine and domestic animals--which demands that this permanent reflection be the basis for the meaningful work of a veterinary surgeon.

["With effort and much pain and an unspeakable, truly stupid patience." Theodor Ludwig Wilhelm von Bischoff (1807-1882) as an embryologist]. / "Mit Aufwand und vieler Mühe und einer unsäglichen, wahrhaft stupiden Geduld" Theodor Ludwig Wilhelm von Bischoff (1807-1882) als Embryologe.

Theodor L. W. von Bischoff (1807-1882), who worked as an anatomist and physiologist in Heidelberg, Giessen and Munich, is among the most excellent embryologists of the 19th century. His work on the history of development of mammals and of man (1842), his finding proof of spontaneous periodic ovulation in mammals (1844), but above all his directive monographies on rabbits, dogs, guinea pigs and deer (1842-1854) provided the most comprehensive research into the history of the development of mammals which had been done so far. He was less successful, however, with his physiological research including a project on urea as a measure for metabolic activity (1853) which had been initiated by Justus Liebig. The same is true for his studies of the weight of the human brain and his comparative anatomical research into the anatomy of the skull and brain of primates, which had been his main interest since 1860. Bischoff, who had been raised to nobility for his merits, did not confine his activities to science, but engaged in questions of medical education and in the politics of his profession as a member of influential committees, fiercely opposing the admission of women to medical studies (1872).