In Search of Patient Zero: Visual Analytics of Pathogen Transmission Pathways in Hospitals.

Pathogen outbreaks (i.e., outbreaks of bacteria and viruses) in hospitals can cause high mortality rates and increase costs for hospitals significantly. An outbreak is generally noticed when the number of infected patients rises above an endemic level or the usual prevalence of a pathogen in a defined population. Reconstructing transmission pathways back to the source of an outbreak - the patient zero or index patient - requires the analysis of microbiological data and patient contacts. This is often manually completed by infection control experts. We present a novel visual analytics approach to support the analysis of transmission pathways, patient contacts, the progression of the outbreak, and patient timelines during hospitalization. Infection control experts applied our solution to a real outbreak of Klebsiella pneumoniae in a large German hospital. Using our system, our experts were able to scale the analysis of transmission pathways to longer time intervals (i.e., several years of data instead of days) and across a larger number of wards. Also, the system is able to reduce the analysis time from days to hours. In our final study, feedback from twenty-five experts from seven German hospitals provides evidence that our solution brings significant benefits for analyzing outbreaks.

[Improvement of emergency physician education through simulator training. Consideration on the basis of the model project "NASimSaar25"]. / Verbesserung der Notarztausbildung durch Simulatortraining. Betrachtung anhand des Modellprojekts "NASimSaar25"

BACKGROUND: Prehospital emergency medicine is a challenge for trainee emergency physicians. Rare injuries and diseases as well as patients in extreme age groups can unexpectedly face emergency physicians. In the regulations on medical education the German Medical Association requires participation in 50 emergency missions under the supervision of an experienced emergency physician. This needs to be improved because on-the-job training does not generally represent the whole spectrum of emergency medicine and a good and structured training under on call conditions is nearly impossible. AIM: The subject of the model project described was whether practical training for emergency physicians can be achieved by participation in simulation training instead of real emergency situations. MATERIAL AND METHODS: After modification of the Saarland regulations on medical education it was possible to replace up to 25 participations in emergency missions by simulation training. The concept of the course NASimSaar25 requires participants to complete 25 simulator cases in 3 days in small training groups. Emergency situations from all medical disciplines need to be treated. A special focus is on the treatment of life-threatening and rare diseases and injuries. Modern simulators and actors are used. The debriefings are conducted by experienced tutors based on approved principles. Medical contents, learning targets from the field of crew resource management (CRM) and soft skills are discussed in these debriefings. RESULTS: Education in the field of emergency medicine can be improved by simulator-based learning and training. However, practical work under a tutor in real and clinical experience cannot be completely replaced by simulation. Simulator training can only be successful if theoretical knowledge has already been acquired. CONCLUSION: A simulator-based course concept can result in an improvement of emergency medical education. The model project NASimSaar25 was well received by the target audience and mostly very well evaluated in terms of learning and reality. If this project becomes established the demand on simulation-based training will increase. The training should achieve a consistent standard of quality.

New phenotypes of the drought-tolerant cbp20 Arabidopsis thaliana mutant have changed epidermal morphology.

This paper provides a detailed phenotypic analysis of the abscisic acid (ABA) hypersensitive Cap Binding Protein 20 (cbp20) mutant. Some hitherto undescribed changes were found in the tissue structure and epidermal morphology of this mutant. These include more and smaller cells in the epidermis, a thicker cuticle and more frequent occurrence of trichomes on leaf surfaces. Some of these traits may contribute to the physiological processes responsible for the water-saving behaviour of the mutant. Abnormal spatial patterns between stomatal pore complexes were also found on various organs of the mutant. All these observations indicate profoundly disturbed development of epidermal tissue in the cbp20 mutant, which has not previously been reported for this class of mutants. A potential connection between the new phenotypes and disturbed miRNA metabolism and mRNA splicing of the mutant is discussed.

Acetylsalicylic acid effervescent 1000 mg (Aspirin) in acute migraine attacks; a multicentre, randomized, double-blind, single-dose, placebo-controlled parallel group study.

In this multicentre, randomized, double-blind, single-dose study a total of 374 patients generally suffering from migraine attacks suitable for treatment with non-prescription drugs, received either oral acetylsalicylic acid effervescent 1000 mg (ASAE) or effervescent placebo for the treatment of an acute migraine attack. Of the 343 patients fulfilling the criteria for efficacy analysis 169 patients took acetylsalicylic acid and 174 placebo. Response rates (reduction of headache severity from severe or moderate to mild or no pain at 2 h after administration) were 55.0% for acetylsalicylic acid and 36.8% for placebo (P < 0.001). Twenty-nine percent of patients in the active treatment group were pain-free after 2 h compared with 16.7% in the placebo group (P = 0.007). No headache recurred within 24 h post-dose in 84.6% of patients in the active group and in 85.1% of patients in the placebo group. Effervescent placebo reduced nausea and vomiting to the same degree as the active drug. Adverse events of acetylsalicylic acid (8.3%) were generally mild or moderate and comparable to those of placebo (2.9%). This study shows that oral ASAE is safe and effective for the treatment of acute migraine attacks.

Single-cell analysis of T-cell receptor-gamma rearrangements in large-cell anaplastic lymphoma.

Large-cell anaplastic lymphomas (LCAL) are characterized by their distinctive morphology together with expression of the CD30 antigen. In addition, a chromosomal translocation, t(2;5) (p23; q35), can be detected in most cases. A significant proportion of LCALs carry rearrangements of the T-cell receptor-gamma (TCR-gamma) locus and display a T-cell phenotype. In about a third of the cases, another type of non-Hodgkin-lymphoma precedes LCAL. Early transformations of non-Hodgkin's lymphoma into LCAL might escape clinical detection in a significant number of cases. The existence of clonally related lymphoid cells within the lymph node infiltrates must be claimed in these cases. Recently, a small-cell-predominant variant of LCAL was described in which only few large tumor cells expressing the CD30 antigen are found together with numerous small lymphocytes, which are frequently CD30-. This observation in particular prompted us to investigate the clonal relationship of the tumor cell compartment and admixed small lymphocytes in one case of common LCAL with T-cell genotype. For this purpose, we chose to amplify rearranged TCR-gamma sequences from single cells isolated from immunostained frozen sections by using a micromanipulator. A total of 119 cells were investigated. Amplification products were obtained in 17 of 79 CD3+ cells, 12 of 30 CD30+ cells, and three of 10 CD20+ cells. The nucleotide sequences were determined in 28 cells by nonradioactive sequencing. In 11 CD30+ cells, the predominant rearrangement of TCR-gamma was identified. No clonal diversity was observed. The small CD3+ lymphocytes were unrelated to the anaplastic CD30+ tumor cells. This report describes a method to analyze rearrangements of the TCR-gamma in single cells isolated from immunostained frozen sections. Application of this technique revealed an absence of clonal diversity in a case of LCAL and documented the polyclonal nature of admixed small CD3+ lymphocytes.

Detection of T-cell clonality in paraffin-embedded tissues.

In lymph node diagnosis, difficulties are frequently encountered with the differential diagnosis of reactive and neoplastic T-cell proliferations. Immunohistochemistry is of limited use, and fresh frozen material for DNA studies is not available in many cases. We have established a polymerase chain reaction (PCR) technique to amplify rearranged T-cell receptor (TCR)-gamma sequences from paraffin-embedded material. Our method differs from other techniques previously described in that it uses four sets of family-specific variable (V)gamma primers. Clonality of the investigated T cells is reflected not only by the varying lengths of amplified products but also by differences in the relative amount of rearranged V gamma families. Preliminary studies indicate that this approach can provide information about the presence of predominant T-cell clones within the sample and thus help to classify the lymph node lesion. With this technique we were able to confirm clonality in seven of 12 T-cell lymphomas in paraffin-embedded tissues.

Angioimmunoblastic lymphadenopathy type of T-cell lymphoma and angioimmunoblastic lymphadenopathy: a clinicopathological and molecular biological study of 13 Chinese patients using polymerase chain reaction and paraffin-embedded tissues.

The morphological classification of angioimmunoblastic lymphadenopathy (AILD) or T-cell lymphoma of AILD-type (AILD-TCL) is still a subject of considerable difficulty and controversy. The aim of the current study was to examine the value of clinical, morphological, immunohistochemical variables in paraffin-embedded tissues in predicting the clonality of the respective lesion. Fifteen lymph node biopsies derived from 13 patients from Chengdu, China, were diagnosed as AILD or AILD-TCL and included in this study. The specimens were examined using a panel of monoclonal antibodies and a scoring system of morphological features. Clonality of the paraffin-embedded material was investigated using a novel polymerase chain reaction-technique to amplify rearranged T-cell receptor (TCR)-gamma sequences. Additional experiments were carried out to investigate the presence of clonal rearrangements of the immunoglobulin heavy chain (IgH) locus. We found clonal rearrangements of the TCR-gamma locus in 9 out of 15 lymph node biopsies. In 3 patients, the predominant cell clones carried clonal IgH and TCR-gamma rearrangements whereas 1 patient with polyclonal TCR-gamma pattern displayed IgH-monoclonality. The statistical evaluation of morphological and immunohistochemical data indicated that no single variable was able significantly to predict the clonality of the lesion. Furthermore, demonstrable clonality for the TCR-gamma or the IgH loci of a lesion did not correlate with a bad clinical course. Our data correlate with findings of other studies investigating AILD-TCL in Caucasian populations.

[Does an information booklet on gastrointestinal endoscopy reduce anxiety for these examinations? Results of a randomized study with 379 patients]. / Reduziert ein Informationsheft über die Magen- bzw. Dickdarmspiegelung die Angst vor diesen Untersuchungen? Ergebnisse einer randomisierten Studie mit 379 Patienten.

A randomized controlled trial was performed between June and December 1989 in 379 outpatients to evaluate whether a patient information booklet is able to reduce anxiety levels before gastroscopy or colonoscopy. Anxiety levels were measured by a Visual Analogue Scale (VAS) in all patients entering the office. Half of the patients received the information booklet about the endoscopic investigations and half did not. VAS was measured again directly before endoscopy in each patient. All patient groups were comparable. The median anxiety level of gastroscopy patients before and after reading the information booklet was 5.3 (2.5-10) and 4.9 (0.8-10), and for colonoscopy patients 6.0 (2.5-10) vs 5.0 (0.7-10). So not much difference concerning the anxiety level before and after reading the patient information booklet was found. Thus better than an information booklet, for every patient an individualized technique of the endoscopist may reduce patient anxiety before gastroscopy or colonoscopy.

The anti-motion sickness mechanism of ginger. A comparative study with placebo and dimenhydrinate.

A controlled, double-blind study was carried out to determine whether nystagmus response to optokinetic or vestibular stimuli might be altered by some agent contained in powdered ginger root (Zingiber officinale). For comparative purposes, the test subjects were examined after medication with ginger root, placebo and with dimenhydrinate. Eye movements were recorded using standard ENG equipment and evaluation was performed by automatic nystagmus analysis. It could be demonstrated that the effect of ginger root did not differ from that found at baseline, or with placebo, i.e. it had no influence on the experimentally induced nystagmus. Dimenhydrinate, on the other hand, was found to cause a reduction in the nystagmus response to caloric, rotatory and optokinetic stimuli. From the present study it can be concluded that neither the vestibular nor the oculomotor system, both of which are of decisive importance in the occurrence of motion sickness, are influenced by ginger. A CNS mechanism, which is characteristic of the conventional anti-motion sickness drugs, can thus be excluded as regards ginger root. It is more likely that any reduction of motion-sickness symptoms derives from the influence of the ginger root agents on the gastric system.

LC/MS determination of bromazepam, clopenthixol, and reserpine in serum of a non-fatal case of intoxication.

Combined liquid chromatography and mass spectrometry (LC/MS) with a moving belt interface can be used as a rapid method for the determination of bromazepam, clopenthixol, and reserpine in serum samples obtained from cases of acute overdoses with combinations of these drugs. Low resolution detection limits are about 100 pg for the three drugs, while in high resolution mode the detection limit for bromazepam is shown to be at least 35 pg. Accurate masses were obtained in a serum sample within 5 ppm using high voltage scanning over a narrow mass range for about 10 ng of bromazepam and clopenthixol, respectively. Chemical deactivation of the belt was shown to effectively reduce memory effects and to improve the desorption characteristics of the belt leading to higher yields of evaporated intact molecules.

Bohr effect, electron spin resonance spectroscopy and subunit dissociation of the hemoglobin components from the turtle Phrynops hilarii.

Isoelectric points of the two haemoglobin components from the fresh-water turtle, Phrynops hilarii, were estimated by isoelectric focusing electrophoresis (IEF) to be 7.6 and 6.3, respectively for component I (CI) and component II (CII). For further studies, CI and CII were isolated by ion exchange chromatography. At pH 7.1, the estimated intraerythrocytic pH, at 25 degrees C, the values of P50, for the stripped haemoglobins, are: 19 torr for CI; 40 torr for CII and 28 torr for the whole haemolysate (pht). Oxygen binding with the stripped isolated components (CI and CII) and with the whole haemolysate (pht) show that delta log P50/delta pH, in the pH interval from 6.8 to 8.5, to be: CI = -0.35; CII = -0.80 and pht = -0.47. The Bohr curves for CI and CII intercept at pH 7.8. eta 50 for CI was 3 and invariant with pH. CII, at the more acid pH range showed biphasic Hill plots. pht shows a eta 50 that varies with pH. CI is affected by ATP, ADP, GTP and slightly by CO2, whereas CII is totally insensitive to CO2 and ATP. Additionally both components are not affected by inositol phosphates. Electron spin resonance (ESR) spectra of both components at pH 8.4 and 6.4 show that CI fails to undergo a R----T transition, while CII, with the higher Bohr effect, undergoes the R----T transition driven by pH. Molecular sieving studies of the liquid nitrogen stored CI, CII and pht show them to be disulphide polymers, CI with an apparent mol. wt of 150 X 10(3) and CII and pht of 100 X 10(3).(ABSTRACT TRUNCATED AT 250 WORDS)

Radiation-induced free radicals in solid 5-halouracil derivatives: single crystals of 5-iododeoxyuridine.

X-irradiation of single crystals of 5-iododeoxyuridine (IUdR) in the temperature range 8-300 K produces mainly four different radicals which have been studied by electron spin resonance (e.s.r.) and electron nuclear double resonance (ENDOR)-spectroscopy. At low temperatures, a pi-anion is formed which shows predominantly an interaction of the unpaired electron with a proton at carbon C6 of the base (-11.8 G, -23.9 G, -4.6 G). Above 10-20 K, the anion protonates at C6 to yield a RC-I(CH2)-R' radical comprising alpha-iodo and beta-methylene proton hyperfine interactions. The primary oxidation product is an O5'-situated alkoxy radical RCH2O which shows inequivalent beta-proton couplings of about 100 G and 35 G together with a highly anisotropic g-tensor. Upon warming to 265 K, a C2'-located radical on the deoxyribose is formed which is stable at room temperature. A detailed account of its spectral features as obtained by ENDOR exhibits three different alpha-type couplings, two small beta-protons and a dipolar interaction. Other radicals, not reproducibly observed, involve a C5'-hydroxyalkyl radical and a species related to the base cation at low temperatures.

1H electron-nuclear double resonance of cobalt hemoglobin.

Proton 1H electron-nuclear double resonance spectra were obtained from cobalt-substituted hemoglobin A. For oxy cobalt-substituted hemoglobin (CoHb), two major couplings were found. One is exchangeable by deuterium and has a coupling of approximately 5.6 MHz which is assigned to the N epsilon 2-proton of the distal histidine (E7), interacting with the ligand. The other splitting (approximately 2.4-3.2 MHz) is attributed to a methyl-proton on Val (E11). No coupling of protons on the proximal side is resolved. Deoxy CoHb exhibits only one prominent interaction (approximately 1.3 MHz) which is assigned to one of the protons on the proximal histidine (F8). The influence of the distal amino acids His (E7) and Val (E11) on the ligand affinity in oxy CoHb is discussed.

Diadenosine tetraphosphate hydrolase from mouse liver. Purification to homogeneity and partial characterization.

An enzyme hydrolyzing diadenosine 5',5"'P1, P4-tetraphosphate (Ap4A) to AMP and ATP has been purified to apparent homogeneity from mouse liver cell extracts. The isolation procedure comprised ammonium sulfate precipitation, chromatography on Sephadex G-75. DEAE-cellulose, blue Sepharose and AMP-Sepharose. The enzyme is a single polypeptide chain with a native Mr = 64,000 with a Km of 1.66 microM and Vmax of 1.25 mumol/min. AMP, ADP, Ap4, GTP, Gp4, Ap3A, Ap5A, Gp3G, and Gp5G are noncompetitive inhibitors of the Ap4A hydrolase activity, whereas Gp4G inhibits Ap4A hydrolysis competitively with a Ki of 6 microM. Theophylline, caffeine, and isobutylmethylxanthine do not or only slightly inhibit Ap4A hydrolysis. Mitogenic factors have no effect on the enzymatic activity of Ap4A hydrolase, excluding that a direct influence of internalized mitogens on Ap4A degradation could be responsible for mitogen-dependent fluctuation of intracellular Ap4A pool sizes.