Flood dynamics in urbanised landscapes: 100 years of climate and humans' interaction.

Raising interest in the interaction between humans and climate drivers to understand the past and current development of floods in urbanised landscapes is of great importance. This study presents a regional screening of land-use, rainfall regime and flood dynamics in north-eastern Italy, covering the timeframe 1900-2010. This analysis suggests that, statistically, both climate and land-use have been contributing to a significant increase of the contribution of short duration floods to the increase in the number of flooded locations. The analysis also suggests that interaction arises, determining land-use dynamics to couple with climatic changes influencing the flood aggressiveness simultaneously. Given that it is not possible to control the climatic trend, an effective disaster management clearly needs an integrated approach to land planning and supervision. This research shows that land management and planning should include the investigation of the location of the past and future social and economic drivers for development, as well as past and current climatic trends.

[Form and extent of informed consent on anesthesia risks: evaluation of a survey of all legal experts in Austria]. / Art und Umfang der Anästhesierisikoaufklärung: Auswertung einer Befragung aller Gerichtssachverständigen in Österreich.

BACKGROUND: Statistically, the chance of a patient to win a court case because of a legally insufficient informed consent is approximately 70%. In Austria the judgment whether the anesthesia-related risk of a patient was correctly addressed depends generally on the opinion of a certified expert court witness (CW). OBJECTIVES: The opinion whether well-known anesthetic risks in a commissioned court report drawn by Austrian CWs would be considered to be "typically anesthesia-related" and "needed to be addressed" when obtaining an informed consent was evaluated. MATERIALS AND METHODS: A questionnaire was sent to all Austrian CWs with 79 known anesthesia-related risks. The percentage of CWs who considered the enumerated risks as "typically anesthesia related" and "needed to be addressed" when obtaining informed consent was evaluated. RESULTS: In 32 out of 79 risks between 40% and 60% of the CWs were of the opinion that informed consent was necessary. Therefore, in a legal dispute on whether an informed consent was legally sufficient or not, the judgment of the CWs is unpredictable. In addition, due to the large number of possible complications needed to be addressed, it is not feasible to obtain a legally compliant risk disclosure. CONCLUSION: In future new methods of knowledge transfer to the patients should be developed. In addition, a standardization of the evaluation criteria for CWs in terms of improvement of legal certainty would be desirable.

Intra-operative rewarming with Hot Dog(®) resistive heating and forced-air heating: a trial of lower-body warming.

Resistive heating is an alternative to forced-air warming which is currently the most commonly used intra-operative warming system. We therefore tested the hypothesis that rewarming rates are similar with Hot Dog(®) (Augustine Biomedical) resistive and Bair Hugger(®) (Arizant) forced-air heating systems. We evaluated 28 patients having major maxillary tumour surgery. During the establishment of invasive monitoring, patients became hypothermic, dropping their core temperature to about 35 °C. They were then randomly assigned to rewarming with lower-body resistive (n = 14) or forced-air (n = 14) heating, with each system set to 'high'. Our primary outcome was the rewarming rate during active heating over a core temperature range from 35 to 37 °C. Morphometric characteristics were comparable in both groups. Temperature increased at twice the rate in patients assigned to forced-air warming, with an estimated mean (SE) slope of 0.49 (0.03) °C.h(-1) vs 0.24 (0.02) °C.h(-1) (p < 0.001). Resistive heating warmed at half the rate of forced air.

Alternans and the influence of ionic channel modifications: Cardiac three-dimensional simulations and one-dimensional numerical bifurcation analysis.

Cardiac propagation is investigated by simulations using a realistic three-dimensional (3D) geometry including muscle fiber orientation of the ventricles of a rabbit heart and the modified Beeler-Reuter ionic model. Electrical excitation is introduced by a periodic pacing of the lower septum. Depending on the pacing frequency, qualitatively different dynamics are observed, namely, normal heart beat, T-wave alternans, and 2:1 conduction block at small, intermediate, and large pacing frequencies, respectively. In a second step, we performed a numerical stability and bifurcation analysis of a pulse propagating in a one-dimensional (1D) ring of cardiac tissue. The precise onset of the alternans instability is obtained from computer-assisted linear stability analysis of the pulse and computation of the associated spectrum. The critical frequency at the onset of alternans and the profiles of the membrane potential agree well with the ones obtained in the 3D simulations. Next, we computed changes in the wave profiles and in the onset of alternans for the Beeler-Reuter model with modifications of the sodium, calcium, and potassium channels, respectively. For this purpose, we employ the method of numerical bifurcation and stability analysis. While blocking of calcium channels has a stabilizing effect, blocked sodium or potassium channels lead to the occurrence of alternans at lower pacing frequencies. The findings regarding channel blocking are verified within three-dimensional simulations. Altogether, we have found T-wave alternans and conduction block in 3D simulations of a realistic rabbit heart geometry. The onset of alternans has been analyzed by numerical bifurcation and stability analysis of 1D wave trains. By comparing the results of the two approaches, we find that alternans is not strongly influenced by ingredients such as 3D geometry and propagation anisotropy, but depends mostly on the frequency of pacing (frequency of subsequent action potentials). In addition, we have introduced numerical bifurcation and stability analysis as a tool into heart modeling and demonstrated its efficiency in scanning a large set of parameters in the case of models with reduced conductivity. Bifurcation analysis also provides an accurate test for analytical theories of alternans as is demonstrated for the case of the restitution hypothesis.

SARS CTL vaccine candidates; HLA supertype-, genome-wide scanning and biochemical validation.

An effective Severe Acute Respiratory Syndrome (SARS) vaccine is likely to include components that can induce specific cytotoxic T-lymphocyte (CTL) responses. The specificities of such responses are governed by human leukocyte antigen (HLA)-restricted presentation of SARS-derived peptide epitopes. Exact knowledge of how the immune system handles protein antigens would allow for the identification of such linear sequences directly from genomic/proteomic sequence information (Lauemoller et al., Rev Immunogenet 2001: 2: 477-91). The latter was recently established when a causative coronavirus (SARS-CoV) was isolated and full-length sequenced (Marra et al., Science 2003: 300: 1399-404). Here, we have combined advanced bioinformatics and high-throughput immunology to perform an HLA supertype-, genome-wide scan for SARS-specific CTL epitopes. The scan includes all nine human HLA supertypes in total covering >99% of all individuals of all major human populations (Sette & Sidney, Immunogenetics 1999: 50: 201-12). For each HLA supertype, we have selected the 15 top candidates for test in biochemical binding assays. At this time (approximately 6 months after the genome was established), we have tested the majority of the HLA supertypes and identified almost 100 potential vaccine candidates. These should be further validated in SARS survivors and used for vaccine formulation. We suggest that immunobioinformatics may become a fast and valuable tool in rational vaccine design.

The influence of hormones on CD44 expression in endometrial and breast carcinomas.

The expression of distinct variant isoforms of the cell surface glycoprotein CD44 (CD44v) has been found to be associated with metastatic potential of rodent adenocarcinoma cells and with an altered prognosis in several types of human cancer. In hormone-dependent gynecological cancers, different CD44v expression patterns have been observed. The influence of ovarian steroid hormones and their antagonists on CD44v expression is still unclear, since there are only retrospective correlation studies so far. Therefore, we examined the CD44 mRNA expression in a standardized stimulation experiment in a number of breast and endometrial carcinoma cell lines varying in estrogen receptor (ER) status. Higher CD44 overall expression was observed in ER positive endometrial and breast carcinoma cell lines when compared to corresponding ER negative cell lines. The number and composition of alternatively spliced isoforms showed no clear correlation to the ER expression status. Three CD44v isoforms were detected in all cell lines expressing CD44v, two of which have not been reported previously in normal endometrial cells. These isoforms may have specific functions in this type of carcinoma. In the second part of the study, the influence of (anti-) hormones on CD44 expression in endometrial carcinoma cell lines was examined. CD44 overall expression showed an increase when the cells were grown in medium containing fetal calf serum (FCS) as compared to cells maintained in medium-free of FCS. CD44 expression was transiently increased by estradiol (1 h). The CD44 splice pattern of endometrial cancer cell lines RL95-2 and Hec-1-A, after treatment with (anti-) hormones showed constant and high expression rates for distinct CD44v-isoforms such as CD44E (CD44v8-v10). Only certain weakly expressed isoforms changed their expression level during the experimental period, but no direct correlation to hormone treatment was observed. In conclusion, estradiol or FCS increase CD44 overall expression, but there seems to be no direct influence of ovarian steroid hormones on the CD44v splice machinery in endometrial carcinoma cell lines.

Treatment with epoprostenol reverts nitric oxide non-responsiveness in patients with primary pulmonary hypertension.

OBJECTIVE: To assess whether long term treatment with epoprostenol might restore primary non-responsiveness to nitric oxide (NO) in patients with primary pulmonary hypertension. METHODS: Seven patients with primary pulmonary hypertension receiving intravenous epoprostenol continuously because of failure of NO to influence pulmonary haemodynamics during initial testing were followed over a period of 13-29 months. Afterwards, acute vascular reactivity towards NO was tested again during right heart catheterisation. RESULTS: Administration of NO after continuous epoprostenol treatment for a mean period of 18 months improved arterial oxygen saturation (p < 0.01) and cardiac index (p < 0.05), and decreased mean pulmonary artery pressure (p < 0.01) and total pulmonary vascular resistance (p < 0.01) in patients previously unresponsive to NO. CONCLUSIONS: Long term treatment with epoprostenol reverts initial refractoriness to NO in patients with primary pulmonary hypertension. Thus the addition of NO to epoprostenol treatment might cause further improvement in the course of the disease.

Controlled airway pressure therapy, nitric oxide inhalation, prone position, and extracorporeal membrane oxygenation (ECMO) as components of an integrated approach to ARDS.

BACKGROUND: Recent years have seen the introduction of innovative additive therapies for acute respiratory distress syndrome. However, because there are no reliable predictors of response to a particular therapy, potential responders to a specific therapeutic intervention may be lost. Therefore, the authors evaluated the effect of a combined therapeutic approach on the survival of patients with acute respiratory distress syndrome, when treated according to a strict algorithm. METHODS: During a 2.5-yr period, 84 patients with acute respiratory distress syndrome were assigned to a standardized treatment protocol. Data analysis was performed by retrospective review of patient charts. Patients were treated using a stepwise treatment algorithm of pressure-controlled ventilation (peak airway pressure < 35 cm H2O), positive end-expiratory pressure (PEEP; 12-15 cm H2O), permissive hypercapnia, inhaled nitric oxide (5-20 ppm), and prone positioning. These interventions were termed "conventional therapy." Response to treatment was defined as a more than 20% increase in arterial oxygen tension (PaO2). Nonresponders were triaged to extracorporeal membrane oxygenation. RESULTS: The overall survival rate was 80%. All patients received conventional therapy up to 96 h; 71 responded to conventional therapy and 59 survived (83%). Thirteen patients (15%) did not respond to conventional therapy and underwent extracorporeal membrane oxygenation; 8 of these patients (62%) survived. For the group, the mean admission lung injury score was 3.3+/-0.5, the PaO2/fractional inspired oxygen tension (F(I)O2) ratio was 96+/-45, and the Acute Physiology and Chronic Health Evaluation (APACHE) II score was 18+/-6. CONCLUSIONS: The 80% overall survival rate achieved in this group of patients with severe acute respiratory distress syndrome may in part reflect the additive beneficial effects of combined treatment methods, such as airway pressure control, nitric oxide inhalation, prone position, and early triage of nonresponders to extracorporeal membrane oxygenation.

Additive effect of nitric oxide inhalation on the oxygenation benefit of the prone position in the adult respiratory distress syndrome.

BACKGROUND: The response to inhaled nitric oxide and prone positioning was investigated in 47 patients with adult respiratory distress syndrome to test the hypothesis that inhalation of nitric oxide when in the prone position would result in additive improvement in oxygenation. METHODS: The authors prospectively studied patients of both genders who were 15 to 75 yr old and had adult respiratory distress syndrome confirmed by computed tomography (lung injury score, 3.1+/-1). RESULTS: Compared with baseline values in the supine position (T1), inhalation of 10 ppm nitric oxide for 1 h (T2) decreased the mean pulmonary artery pressure from 33+/-9 mmHg to 28+/-6 mmHg (P < 0.05; T2 vs. T1) and increased the ratio of the partial pressure of oxygen in arterial blood (PaO2) to inspired oxygen concentration (FiO2) from 115 (median first quartile [Q1] 97, median third quartile [Q3] 137) to 148 (Q1 132, Q3 196) (P < 0.05; T2 vs. T1). Cessation of nitric oxide brought the values back to baseline (T3). Two hours of prone positioning (T4) significantly increased the PaO2:FiO2 ratio (T4 vs. T3). However, after an additional hour of nitric oxide inhalation in the prone position (T5), a significant decrease of the venous admixture (from 33+/-6% to 25+/-6%; P < 0.05) and an increase of the PaO2:FiO2 ratio (from 165 [Q1 129, Q3 216] to 199 [Q1 178, Q3 316] [P < 0.05; T5 vs. T4]) were observed. CONCLUSIONS: In patients with isolated severe adult respiratory distress syndrome, inhalation of nitric oxide in the prone position significantly improved oxygenation compared with nitric oxide inhalation in the supine position or in the prone position without nitric oxide. The combination of the prone position with nitric oxide inhalation in the treatment of severe adult respiratory distress syndrome should be considered.

Cytokine patterns in patients who undergo hemofiltration for treatment of multiple organ failure.

The excessive uncontrolled activation of inflammatory cells and mediators after trauma or major surgery plays a key role in the development of adult respiratory distress syndrome and multiple organ system failure (MOSF). In the past elevated cytokine levels were shown to influence the outcome of these patients adversely. There are diverging results regarding the removal of circulating cytokines by various methods of hemopurification for clinical improvement of MOSF. Seven patients after trauma or major surgery underwent continuous venovenous hemofiltration (CVVH) for the treatment of severe organ failure of the heart and lungs (Murray score 2.74) but not for renal or liver failure. The cytokine levels were measured at the beginning and 15, 60, 120, and 240 minutes after initiation of CVVH (measure points MP1-5). Clinical improvement during the treatment was monitored, and correlation with cytokine levels was evaluated. Arterially measured tumor necrosis factor alpha rose from 11.14 ng/ml to 17.86 ng/m1 (p < 0.05). Arterial interleukin-6 (IL-6) levels significantly decreased during CVVH from 1284.7 ng/m1 to 557.9 ng/m1; IL-8 levels simultaneously decreased from an initial peak of up to 154.4 ng/m1 at MP3 to 97.3 ng/m1 at MP5. The drop in serum IL-6 and IL-8 levels closely correlated with clinical improvement. After 2 hours of CVVH the hemodynamic situation improved significantly, as revealed by a decrease in catecholamine expenditure, an increase in arterial pressure, and a decrease in pulmonary artery pressure. Moreover, 2 hours after the initiation of CVVH the oxygenation index rose significantly and correlated well with the drop in shunt fraction. The Murray score significantly fell to 1.86. The removal of IL-6 and IL-8 by CVVH after initial stimulation correlates with clinical improvement, which was demonstrated by significantly improved oxygenation and hemodynamics from 2 hours after the initiation of CVVH onward. The elimination of cytokines and several mediators by CVVH may contribute to the cardiopulmonary improvement of critically ill patients. In comparison with the clinical control group (n = 7), which was comparable in terms of MOSF, no intervention led to a similar improvement in cardiorespiratory failure, and overall two of these patients died. Moreover, patients of the control group experienced a significant longer stay at in the intensive care unit.

On sex determination in the Turkish desert woodlouse Hemilepistus elongatus (Crustacea, Isopoda, Oniscidea): searching for sex chromosomes and for sex-specific differences in simple DNA repeats.

The karyotype of male and female Hemilepistus elongatus was investigated by means of C-banding. The diploid chromosome number in both sexes is 2n = 50. By scrutinizing general morphology and localization of the constitutive heterochromatin, no heteromorphic sex chromosomes were found. All chromosome pairs in males are well paired during diakinesis. Hybridization of genomic DNA with (GACA)4 and (GATA)4 oligonucleotides revealed no sex-specific patterns. Key words : karyotype, C-banding, sex determination, simple DNA-repeats, Isopoda.

Treatment of non-insulin dependent diabetic adults with a new glycoside hydrolase inhibitor (Bay g 5421).

The hypoglycemic effect of a glycoside hydrolase inhibitor (BAY g 5421) was tested in 10 non-insulin dependent, overweight diabetics by means of continuous in vivo glucograms. There was a highly significant reduction of serum glucose with a dosage of 3 x 100 mg glycoside hydrolase inhibitor, after dosage division to 6 x 50 mg there was an additional reduction of blood glucose. This difference, however, could not be determined statistically. Insulin, glucagon and lactate as well as the triglyceride concentration remained unchanged. There were no significant side-effects. Two of the 10 patients complained of meteorism, after specific questioning three more patients offered similar complaints. Discontinuation of the preparation was not necessary.