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The number of subduction zones that facilitated the northward translation of the Anatolide‐Tauride continental terrane derived from Gondwana to the southern margin of Eurasia at the longitude of western Turkey is debated. We hypothesized that if two north dipping subduction zones facilitated incipient collision in western Turkey, a late Cretaceous arc would have formed within the Neotethys and along the southern margin of Eurasia. To determine if an island arc formed within the Neotethys we investigated the sedimentary record of the Central Sakarya basin, which was deposited along the southern margin of Eurasia from 85 to 45 million years ago. Detrital zircon deposited within the lower levels of the Central Sakarya basin (the Değirmenözü Formation) are associated with south to north‐directed paleocurrents and exhibit a unimodal late Cretaceous age peak sourced from isotopically juvenile mantle melts. Zircon maximum depositional ages from the Değirmenözü Formation cluster between 95 and 90 Ma and are 5–10 Myr older than biostratigraphic depositional ages. Between 95 and 80 Ma, a 12‐unit shift from mantle to crustal derived εHf values occurs in the overlying Yenipazar Formation. We explain the absence of Paleozoic, Eurasian‐sourced detrital zircon, the rapid shift from mantle to crustal derived εHf values, and lag time in terms of passive margin subduction within an isolated intra‐oceanic subduction zone, whose island arc was reworked from south to north into the Central Sakarya basin during incipient collision. Thus, widely outcropping late Cretaceous plutonic rocks within Eurasia must have belonged to an additional convergent margin. Key Points: We leveraged the isotopic signature of subducted passive margin to test incipient collision models in northwest TurkeyPassive margin subduction resulted in the development of an isolated intra‐oceanic basinTwo north dipping subduction zones facilitated incipient collision in the region [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID‐19) interferes with the vascular endothelium. It is not known whether COVID‐19 additionally affects arterial stiffness. Methods: This case–control study compared brachial‐ankle pulse wave (baPWV) and carotid‐femoral pulse wave velocities (cfPWV) of acutely ill patients with and without COVID‐19. Results: Twenty‐two COVID‐19 patients (50% females, 77 [67–84] years) were compared with 22 age‐ and sex‐matched controls. In COVID‐19 patients, baPWV (19.9 [18.4–21.0] vs. 16.0 [14.2–20.4], P = 0.02) and cfPWV (14.3 [13.4–16.0] vs. 11.0 [9.5–14.6], P = 0.01) were higher than in the controls. In multiple regression analysis, COVID‐19 was independently associated with higher cfPWV (β = 3.164, P = 0.004) and baPWV (β = 3.532, P = 0.003). PWV values were higher in nonsurvivors. In survivors, PWV correlated with length of hospital stay. Conclusion: COVID‐19 appears to be related to an enhanced PWV reflecting an increase in arterial stiffness. Higher PWV might be related to an increased length of hospital stay and mortality. [ABSTRACT FROM AUTHOR]

Background and purpose: Limited data are available in the literature for upper limb impairment in multiple sclerosis (MS). This study aimed to report the distribution of values of hand grip strength (HGS), of the box and block test (BBT) and of the nine‐hole peg test (9HPT) correlated with demographic and clinical data in subjects with MS. Methods: This study involved five Italian neurological centres. The inclusion criteria were age ≥ 18, MS diagnosis, stable disease phase, right‐hand dominance. All subjects underwent HGS, BBT and 9‐HPT evaluation. Results: In all, 202 subjects with MS were enrolled: 137 females; mean age 48.4 years; mean Expanded Disability Status Scale (EDSS) 4.17; mean disease duration 14.12 years; disease course 129 relapsing–remitting, 21 primary progressive and 52 secondary progressive MS subjects; mean right HGS 25.3 kg, left 23.2 kg; mean right BBT 45.7 blocks, left 44.9 blocks; mean right 9‐HPT 30.7 s, left 33.4 s. All results were statistically significantly different compared to healthy controls. HGS, BBT and 9‐HPT were associated with age, EDSS and disease duration, whilst disease course correlated with BBT and 9‐HPT. The BBT and 9‐HPT scores significantly differed according to level of disability (EDSS ≤3.0, 3.5–5.5, ≥6.0). Conclusion: Hand grip strength and BBT value distribution in a large MS population is reported. Correlations between HGS, BBT and 9‐HPT were generally low. [ABSTRACT FROM AUTHOR]

Background and purpose: The literature provides contrasting results on the efficacy of levetiracetam (LEV) in multiple sclerosis (MS) patients with cerebellar signs. It was sought to evaluate the efficacy of LEV on upper limb movement in MS patients. Methods: In this multicenter double‐blind placebo‐controlled crossover study, MS patients with prevalently cerebellar signs were randomly allocated into two groups: LEV followed by placebo (group 1) or placebo followed by LEV (group 2). Clinical assessments were performed by a blinded physician at T0 (day 1), T1 (day 22), T2 (2‐week wash‐out period, day 35) and T3 (day 56). The primary outcome was dexterity in the arm with greater deficit, assessed by the nine‐hole peg test (9HPT). Secondary clinical outcomes included responders on the 9HPT (∆9HPT >20%), tremor activity of the daily living questionnaire and self‐defined upper limb impairment, through a numeric rating scale. Kinematic evaluation was performed using a digitizing tablet, providing data on normalized jerk, aiming error and centripetal acceleration. Results: Forty‐eight subjects (45.2 ± 10.4 years) were randomly allocated into two groups (n = 24 each). 9HPT significantly improved in the LEV phase in both groups (P < 0.001). The LEV treatment phase led to a significant improvement (P < 0.01) of all clinical outcomes in group 1 and in dexterity in group 2. No significant changes were reported during both placebo phases in the two groups. Considering the kinematic analysis, only normalized jerk significantly improved after treatment with LEV (T0–T1) in group 1. Conclusions: Levetiracetam treatment seems to be effective in improving upper limb dexterity in MS patients with cerebellar signs. [ABSTRACT FROM AUTHOR]

Debate persists concerning the timing and geodynamics of intercontinental collision, style of syncollisional deformation, and development of topography and fold‐and‐thrust belts along the >1,700‐km‐long İzmir‐Ankara‐Erzincan suture zone (İAESZ) in Turkey. Resolving this debate is a necessary precursor to evaluating the integrity of convergent margin models and kinematic, topographic, and biogeographic reconstructions of the Mediterranean domain. Geodynamic models argue either for a synchronous or diachronous collision during either the Late Cretaceous and/or Eocene, followed by Eocene slab breakoff and postcollisional magmatism. We investigate the collision chronology in western Anatolia as recorded in the sedimentary archives of the 90‐km‐long Sarıcakaya Basin perched at shallow structural levels along the İAESZ. Based on new zircon U‐Pb geochronology and depositional environment and sedimentary provenance results, we demonstrate that the Sarıcakaya Basin is an Eocene sedimentary basin with sediment sourced from both the İAESZ and Söğüt Thrust fault to the south and north, respectively, and formed primarily by flexural loading from north‐south shortening along the syncollisional Söğüt Thrust. Our results refine the timing of collision between the Anatolides and Pontide terranes in western Anatolia to Maastrichtian‐Middle Paleocene and Early Eocene crustal shortening and basin formation. Furthermore, we demonstrate contemporaneous collision, deformation, and magmatism across the İAESZ, supporting synchronous collision models. We show that regional postcollisional magmatism can be explained by renewed underthrusting instead of slab breakoff. This new İAESZ chronology provides additional constraints for kinematic, geodynamic, and biogeographic reconstructions of the Mediterranean domain. Plain Language Summary: The timeline of continent‐continent collisions and the creation of topography, volcanic activity, and thrust faults in Anatolia (Turkey) are highly debated. Continent‐continent collision occurs when oceanic crust between two continental plates has been entirely consumed back into the Earth's interior along a subduction zone. Previous work in western Anatolia suggests that 66–60 million years ago continent‐continent collision was followed by catastrophic rupturing of the sinking oceanic crust, a process known as slab breakoff. Numerical models and field observations demonstrate that slab breakoff is followed by rebound and surface uplift of the overriding plate producing local extension and interrupting sedimentation. By studying a syncollisional sedimentary basin, we determined the sedimentary infill is 52–48 million years old and sourced from both continents, indicating collision must have occurred prior to 52 million years ago. This timing validates previous predictions of synchronous collision across western and central Turkey. Furthermore, the timing of basin infill directly overlaps with the timing of proposed slab breakoff. Our observations and data contradict predictions of the slab breakoff model making breakoff an unlikely candidate. Instead, we propose continued shortening and collision as the cause for the co‐occurrence of sedimentary basin formation, deformation, and volcanism observed throughout western Turkey. Key Points: The Sarıcakaya Basin is an Eocene sedimentary basin formed by flexural loading from the syncollisional Sogut Thrust faultSarıcakaya Basin magmatism and deformation chronology are similar to central Anatolia, supporting synchronous collision across AnatoliaEocene thrust loading, sedimentation, and convergence in the Sarıcakaya Basin contradict previous interpretations of Eocene slab breakoff [ABSTRACT FROM AUTHOR]

Abstract: The common forage grass Lolium perenne has evolved with the systemic fungal endophyte Epichloë festucae var. lolii. The endophyte provides herbivore resistance to the grass due to defensive alkaloids, some of which are toxic to grazing livestock. In this field study, we determine whether distribution of the endophyte‐grass association changes along a land‐use intensity gradient on 87 managed grasslands in three German regions. Endophyte infections were detected in 66% of the studied sites and infection rates within infected sites ranged from 1% to 95%. Alkaloid concentrations of lolitrem B (vertebrate toxin) exceeded the toxicity thresholds in 50 (14%) of 351 infected plants and of peramine (invertebrate deterrent/toxin) in 12 (3%) of 351 plants. Infection rates and alkaloid concentrations were not significantly affected by land‐use intensity and region, but alkaloid concentrations were higher in summer compared to spring. We conclude that risks for livestock intoxication are currently low, as (i) average alkaloid concentrations per grassland were always below toxicity thresholds and as (ii) none of the grasslands was dominated by L. perenne. We suggest avoidance of grass monocultures in Europe to keep intoxication risks for livestock low; we also recommend regular examination of seeds and grasslands, as seed producers might accidentally distribute infected seeds, and as climate warming might further enhance the distribution of Epichloë endophytes in European grasslands. [ABSTRACT FROM AUTHOR]

Background: Subclinical chronic inflammation could be the driving force behind the recently revealed association between abnormal nailfold capillaries as well as autoantibodies and long-term mortality in patients with incipient Raynaud's phenomenon. Whether laboratory markers that reflect a chronic inflammatory process are directly related to mortality in Raynaud's phenomenon is not known.Methods: In total, 2958 patients with incipient Raynaud's phenomenon without previously known connective tissue disease (CTD) were enrolled. At their initial presentation, laboratory tests for C-reactive protein (CRP), leucocytes, fibrinogen and the haemoglobin concentration were obtained. In addition, nailfold capillaries and antinuclear antibodies (ANA) were assessed. Patients' mortality was recorded through a median follow-up period of 9.3 years.Results: Baseline CRP, fibrinogen and haemoglobin concentration were associated with long-term mortality in an individual analysis of patients with incipient Raynaud's phenomenon. In a multivariable model including patients' age, nailfold capillaries and ANA, a low haemoglobin concentration remained independently related to future mortality. Amongst potential predictors for mortality in patients with Raynaud's phenomenon, a low haemoglobin concentration was most strongly related to patients' mortality risk.Conclusion: In Raynaud's phenomenon, laboratory markers that can be attributed to a chronic inflammatory state independently yield prognostic information in addition to the presence of abnormal nailfold capillaries and ANA. Amongst all prognostic markers, the haemoglobin concentration is most strongly related to patients' mortality in Raynaud's phenomenon. [ABSTRACT FROM AUTHOR]

The last decades saw numerous prospective clinical trials using different haemoglobin levels as transfusion triggers for packed red blood cell transfusion. In most studies, a restrictive strategy with a lower haemoglobin value as transfusion trigger and a lower haemoglobin target range was compared to a more liberal strategy with higher patient haemoglobin values already triggering transfusion. While such studies answered some important clinical questions in well‐defined study patient populations, many more questions in this field are still open. Studies in patients suffering from acute or chronic neurological disorders, whether traumatic or not, trials in haematological or gynaecological patients are still very scarce or were performed in extremely small cohorts. In addition, the haemoglobin measurement in daily clinical routine suffers from methodological, technical and operational shortcomings. This might impair clinical decisions regarding transfusion triggers. Preoperative anaemia poses a risk for the perioperative outcome of the patient. Thus, it is worthwhile to explore a potential causal relationship between the extent of preoperative anaemia and perioperative mortality. From the existing retrospective trial data comparing preoperative anaemia and perioperative outcome, no such decision can be taken. The best transfusion strategy and the optimal dosing for packed red blood cells are still missing in most indications. Sufficiently powered, prospective, randomized, controlled clinical transfusion trials for packed red blood cells in most clinical settings are urgently needed to reduce ill‐founded clinical decisions and to base transfusion strategies on clinical evidence and scientific study results. [ABSTRACT FROM AUTHOR]

Abstract: Hydropower‐related damage to fish remains a great challenge, making objective monitoring of turbine‐related fish injury a necessity. The catch of fish at turbine outlets is currently realised by net fishing, but potential catch‐related injuries are largely unknown. Catch efficiency and fish‐friendliness in relation to fish handling, exposure time, floating debris and fish biomass of four fish recovery installations were assessed using seven species. Highly species‐specific lethal and sublethal effects were observed. Exposure time had the strongest effects on catch‐related damage, being up to 150‐fold increase after 12 hr compared to 1 hr. Up to 84% mortality occurred in the most sensitive species Thymallus thymallus L. Besides exposure time, higher current speed and biomass within the net resulted in greater fish damage. To minimise catch‐related effects, keeping emptying periods <1–2 hr and considering the effects of current speed, fish and debris biomass are crucial to increase data comparability among studies. [ABSTRACT FROM AUTHOR]

Abstract: In the fields of mechanical engineering, friction is ubiquitous. It is a fundamental cause of energy loss and wear. Another concern is the occurrence of comfort‐relevant friction induced vibrations. Prominent examples of this are NVH phenomena such as brake squeal, which is being investigated at great expense by the German automotive industry and academia, to determine its causes and potential influencing factors. For this purpose, numerous specialized measurements are performed, and models of varying complexity are used. All of these measurements and models have the common trait that the coefficient of friction (COF), defined as the ratio of the tangential force and normal force, has a decisive influence on the systems' stability. To parameterize the friction coefficient in macroscopic models, measurements must be performed. In this case, often an average value over time and over various loading procedures is used. As the measurements reveal, the coefficient of friction is in reality not constant, but is subject to a high degree of dynamics on various time scales, caused by complex processes in the boundary layer. A treatment of the coefficient of friction as a steady‐state parameter, or even as a constant, is thus a major reduction. The large variability of the coefficient of friction causes a corresponding variance in the stability limits of the models considered. This phenomenon is observed in the real world, where squealing seems to have a non‐deterministic behavior. This suggests uncertainties in the modeling of the friction coefficient. Due to the various types of uncertainty (variability, incompleteness and inaccuracy), the entire problem is a matter of polymorphic uncertainty. This paper focuses on the modeling of the friction coefficient, taking into account the various causes of uncertainty. Selections of raw data obtained at the authors institute throughout many years of research on friction phenomena in brake systems will be evaluated and classified with respect to its uncertainty properties. (© 2017 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

Background: To ensure safe general anesthesia, manually controlled anesthesia requires constant monitoring and numerous manual adjustments of the gas dosage, especially for low- and minimal-flow anesthesia. Oxygen flow-rate and administration of volatile anesthetics can also be controlled automatically by anesthesia machines using the end-tidal control technique, which ensures constant end-tidal concentrations of oxygen and anesthetic gas via feedback and continuous adjustment mechanisms. We investigated the hypothesis that end-tidal control is superior to manually controlled minimal-flow anesthesia (0.5 l/min).Methods: In this prospective trial, we included 64 patients undergoing elective surgery under general anesthesia. We analyzed the precision of maintenance of the sevoflurane concentration (1.2-1.4%) and expiratory oxygen (35-40%) and the number of necessary adjustments.Results: Target-concentrations of sevoflurane and oxygen were maintained at more stable levels with the use of end-tidal control (during the first 15 min 28% vs. 51% and from 15 to 60 min 1% vs. 19% deviation from sevoflurane target, P < 0.0001; 45% vs. 86% and 5% vs. 15% deviation from O2 target, P < 0.01, respectively), while manual controlled minimal-flow anesthesia required more interventions to maintain the defined target ranges of sevoflurane (8, IQR 6-12) and end-tidal oxygen (5, IQR 3-6). The target-concentrations were reached earlier with the use of end-tidal compared with manual controlled minimal-flow anesthesia but required slightly greater use of anesthetic agents (6.9 vs. 6.0 ml/h).Conclusions: End-tidal control is a superior technique for setting and maintaining oxygen and anesthetic gas concentrations in a stable and rapid manner compared with manual control. Consequently, end-tidal control can effectively support the anesthetist. [ABSTRACT FROM AUTHOR]

In the present article, experimental and theoretical investigations regarding field-effect transistors based on two-dimensional (2D) materials are presented. First, the properties of contacts between a metal and 2D material are discussed. To this end, metal-to-graphene contacts as well to transition metal dichalcogenides (TMD) are studied. Whereas metal-graphene contacts can be tuned with an appropriate back-gate, metal-TMD contacts exhibit strong Fermi level pinning showing substantially limited maximum possible drive current. Next, tungsten diselenide (WSe2) field-effect transistors are presented. Employing buried-triple-gate substrates allows tuning source, channel and drain by applying appropriate gate voltages so that the device can be reconfigured to work as n-type, p-type and as so-called band-to-band tunnel field-effect transistor on the same WSe2 flake. [ABSTRACT FROM AUTHOR]

This study compares the effectiveness and representativeness of electrofishing, snorkelling, seining, baited lift netting, multi-mesh gillnetting, baited fish traps, fyke netting, angling and longline fishing, considering three typical lentic flood-plain habitats at different times of day. Electrofishing was by far the most effective method yielding highest species richness, species trait representation and catch per unit of effort ( CPUE), followed by seining. For single species like dace Leuciscus leuciscus, European ruffe Gymnocephalus cernua, common bream Abramis brama and silver bream Blicca bjoerkna, seining was more effective than electrofishing. With both methods, some species were more consistently caught during night, dusk or dawn than during daylight. All other methods tested cannot be generally recommended for fish community assessments in shallow backwaters due to their low representativeness of species inventory and generally low CPUE. Based on these results, electrofishing of 30 m transect replicates at different times of day for monitoring the fish community in shallow backwaters, can be recommended, enabling the maximum possible comparability to adjacent river habitats. Seining should be considered as an alternative if accessibility of habitats is restricted or electrofishing is prohibited. The 25 species detected in the backwaters also suggest that these habitats contribute a large proportion of fish diversity and should be included in standard assessments of river ecological status. [ABSTRACT FROM AUTHOR]

Knowledge on the extent and mechanisms of fish damage caused by hydropower facilities is important for their ecological improvement. Herein, a novel field-based fish injury assessment protocol is proposed that includes vitality and four general health criteria, as well as nine lethal and sub-lethal injury types across 18 body parts. The protocol was validated using 3,087 specimens from four species of hatchery-reared fish, as well as 2,262 specimens from 32 species of wild fish. The protocol allowed a detailed and systematic evaluation of different fish injury types in the field. Injuries related to handling and to contact with different parts of the hydropower structure could be distinguished applying multivariate statistics. This approach allows quantification and comparison of fish injuries across sites, and can help to identify the technologies and operational procedures that minimise damage to fish. It may also be useful to assess fish health in other contexts including aquaculture. [ABSTRACT FROM AUTHOR]

Heavily modified water bodies (HMWB) are characterized by monotonous and straightened channel morphologies with high degrees of bank enforcement. They often lack shallow bank habitats, which are considered important for critical life stages of fishes. In this study, three principle options to engineer shallow stream zones were assessed concerning the value of the created habitats for larval, juvenile and adult stages of fishes in 30 sites from three HMWB. The construction scheme of the juvenile habitats comprised different degrees of embankment ranging from rip-rap structures with steep bank angles to almost nature-like construction schemes with very flat river-banks and sparing usage of structural enrichment such as boulders and dead wood. In general, the differences between the three habitat types were more pronounced in density of different life stages than in the presence or absence of species or certain life stages. A steep bank angle and a high degree of engineering such as placement of rip-rap embankment, boulders or dead wood structure in the habitats were hardly accepted by early larval and juvenile stages of rheophilic fishes. In contrast, the construction scheme of a nature-like habitat with a flat bank angle (<10%), low water depth (mean = 24 cm) and a sparing usage of coarse woody debris (CWD) and boulders had the highest success. Other investigated habitat types did not provide additional benefit, neither in terms of supporting additional species and life stages, nor in high individual numbers and should thus only be implemented when land for restoration is scarce and nature-like habitats cannot be realized. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background Efficacy testing of immunotherapy in field studies is often hampered by variation of airborne allergens. Standardized allergen exposure in challenge chamber settings might be an alternative. Therefore, we developed a universal technique to create an atmosphere loaded with allergen particles of adjustable size from aqueous solutions of licensed allergen extracts. Objective The aim of this study was to apply this technique and test the safety and efficacy of challenges with house dust mite ( HDM) allergen in the Fraunhofer allergen challenge chamber. Methods Aerosol particles carrying HDM allergen were produced by spray-drying of an aqueous solution containing HDM allergen and lactose. In a monocenter, placebo-controlled, single-blind, dose-escalation pilot study, 18 subjects with perennial allergic rhinitis and sensitization to HDM were exposed to HDM allergen for 4 h at either 250, 500, 1000 SQE/m3 or lactose alone (0 SQE/m3) 7 days apart. The dose of 500 SQE/m³ was repeated to investigate reproducibility. Total nasal symptom score ( TNSS) was the primary endpoint. Results Exposure to HDM increased TNSS (mean ± SD) to 3.4 ± 1.8, 3.3 ± 2.1, and 3.6 ± 2.0 at 250, 500 and 1000 SQE/m3, respectively, while lactose alone did not change TNSS (0.7 ± 0.6). The results were reproducible at 500 SQE/m3. Pulmonary function and adverse event frequency did not change with escalation of allergen dose. Conclusion This HDM allergen particle generation is safe, specific and reproducible and can therefore be used for efficacy testing of immunotherapy and for basic clinical research. [ABSTRACT FROM AUTHOR]

Background Small bowel obstruction ( SBO) is a potentially life-threatening condition which may be caused by a variety of pathologies such as postoperative adhesions or malignant diseases. Little is known on alterations in gut physiology during SBO, although its comprehension is essential to improve treatment which may help to prevent subsequent organ failure prior to surgical resolution. We aimed to investigate afferent nerve sensitivity and intestinal inflammatory response during SBO to identify possible targets of treatment. Methods C57Bl6 mice were anesthetized, and a midline laparotomy was performed. A small bowel loop was ligated 5 cm proximal to ileo-cecal valve to induce SBO. Control animals received a sham midline laparotomy. SBO animals and controls were sacrificed after 3, 9, or 24 h (each n = 6). A dilated segment of small intestine located 1.5 cm oral to the ligature was prepared for multi-unit mesenteric afferent nerve recordings in vitro. Histological assessment of leukocyte infiltration was performed by myeloperoxidase ( MPO). Pro-inflammatory cytokine expression was quantified by RT- PCR. Data are mean ± SEM. Key Results Afferent firing to serosal 5- HT (500 μM) peaked at 3.9 ± 0.2 impulse/s 24 h after induction of SBO compared to 2.4 ± 0.1 impulse/s in sham controls ( p < 0.05). Serosal bradykinin (0.5 μM) led to an increase in peak afferent firing of 5.3 ± 0.5 impulse/s in 24 h SBO animals compared to 3.5 ± 0.2 impulse/s in sham controls ( p < 0.05). No differences in 5- HT and BK sensitivity were observed in 3 and 9 h SBO animals compared to controls. Continuous mechanical ramp distension of the intestinal loop was followed by a pressure-dependent rise in afferent nerve discharge that was reduced in 3 h SBO animals compared to sham controls ( p < 0.05). MPO stains showed a rise in leukocyte infiltration of the intestine in SBO animals at 9 and 24 h ( p < 0.05). Il-6 but not TNF-a gene expression was increased at 9 and 24 h in SBO animals compared to sham controls ( p < 0.05). Conclusions & Inferences Afferent nerve sensitivity is increased 24 h after induction of SBO. SBO led to a delayed onset intestinal inflammatory response. Inflammatory mediators released during this inflammatory response may be responsible for a later increase in afferent sensitivity. Agents with anti-inflammatory action may, therefore, have a beneficial effect during SBO and may subsequently help to prevent possible organ dysfunction. [ABSTRACT FROM AUTHOR]

Objectives: To address the diagnostic value of circulating microRNAs (miRNAs) in patients presenting with acute chest pain.Design: In a prospective, international, multicentre study, six miRNAs (miR-133a, miR-208b, miR-223, miR-320a, miR-451 and miR-499) were simultaneously measured in a blinded fashion in 1155 unselected patients presenting with acute chest pain to the emergency department. The final diagnosis was adjudicated by two independent cardiologists. The clinical follow-up period was 2 years.Results: Acute myocardial infarction (AMI) was the adjudicated final diagnosis in 224 patients (19%). Levels of miR-208b, miR-499 and miR-320a were significantly higher in patients with AMI compared to those with other final diagnoses. MiR-208b provided the highest diagnostic accuracy for AMI (area under the receiver operating characteristic curve 0.76, 95% confidence interval 0.72-0.80). This diagnostic value was lower than that of the fourth-generation cardiac troponin T (cTnT; 0.84) or the high-sensitivity cTnT (hs-cTnT; 0.94; both P < 0.001 for comparison). None of the six miRNAs provided added diagnostic value when combined with cTnT or hs-cTnT (ns for the comparison of combinations vs. cTnT or hs-cTnT alone). During follow-up, 102 (9%) patients died. Levels of MiR-208b were higher in patients who died within 30 days, but the prognostic accuracy was low to moderate. None of the miRNAs predicted long-term mortality.Conclusion: The miRNAs investigated in this study do not seem to provide incremental diagnostic or prognostic value in patients presenting with suspected AMI. [ABSTRACT FROM AUTHOR]

Objectives To address the diagnostic value of circulating micro RNAs (mi RNAs) in patients presenting with acute chest pain. Design In a prospective, international, multicentre study, six mi RNAs (miR-133a, miR-208b, miR-223, miR-320a, miR-451 and miR-499) were simultaneously measured in a blinded fashion in 1155 unselected patients presenting with acute chest pain to the emergency department. The final diagnosis was adjudicated by two independent cardiologists. The clinical follow-up period was 2 years. Results Acute myocardial infarction ( AMI) was the adjudicated final diagnosis in 224 patients (19%). Levels of miR-208b, miR-499 and miR-320a were significantly higher in patients with AMI compared to those with other final diagnoses. MiR-208b provided the highest diagnostic accuracy for AMI (area under the receiver operating characteristic curve 0.76, 95% confidence interval 0.72-0.80). This diagnostic value was lower than that of the fourth-generation cardiac troponin T ( cTnT; 0.84) or the high-sensitivity cTnT (hs- cTnT; 0.94; both P < 0.001 for comparison). None of the six miRNAs provided added diagnostic value when combined with cTnT or hs- cTnT (ns for the comparison of combinations vs. cTnT or hs- cTnT alone). During follow-up, 102 (9%) patients died. Levels of MiR-208b were higher in patients who died within 30 days, but the prognostic accuracy was low to moderate. None of the mi RNAs predicted long-term mortality. Conclusion The mi RNAs investigated in this study do not seem to provide incremental diagnostic or prognostic value in patients presenting with suspected AMI. [ABSTRACT FROM AUTHOR]

Stream substratum plays a key role for many riverine species and has become a focus topic in the context of structural habitat improvements. There is a lack of studies that compare the effectiveness of different substratum restoration measures. Herein, we compare four restoration techniques (two different gravel introductions, substratum raking and sickle-formed constrictor) that were carried out in six replicate rivers. Each measure was monitored for changes in physicochemical substratum quality and the effects of the construction work on downstream sites. Generally, the effects on physicochemical substratum quality were highly variable between restoration types and rivers and strongly decreased within 1 year. Most pronounced changes of substratum quality were detected for the gravel introductions. Substratum raking and the sickle-formed constrictor had the smallest effects, which were dependent on the original substratum composition of the restored sites. At the same time, substratum raking caused an average fine sediment deposition of 17 kg m−2 on downstream sites, being sixfold higher than for the other measures. Consequently, all of the investigated substratum restoration techniques are confined to short-term improvement of substratum quality. This finding, together with the observed damage on downstream sites, suggests that a rethinking of the currently applied restoration techniques is required, better considering catchment and natural substratum dynamics in river restoration. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective To evaluate the reasons that complete remission is not achieved or maintained with original treatment in some patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) treated with rituximab (RTX) or with cyclophosphamide/azathioprine (CYC/AZA). Methods The Rituximab in AAV trial was a randomized, double-blind, placebo-controlled trial comparing the rate of remission induction among patients treated with RTX (n = 99) and patients treated with CYC followed by AZA (n = 98). Glucocorticoids were tapered over a period of 5 months. The primary outcome measure was lack of disease activity without glucocorticoid treatment at 6 months. To determine the most important reason for failure to achieve the primary outcome, 7 hierarchical categories of reasons were defined retrospectively (uncontrolled disease, adverse event leading to therapy discontinuation, severe flare, limited flare, Birmingham Vasculitis Activity Score for Wegener's Granulomatosis >0, prednisone treatment at any dosage, and other). Results Although remission (lack of disease activity) was achieved in 170 of the 197 patients (86%) in the first 6 months, the primary outcome measure was not achieved in 42%. There were 3 deaths. Twenty-four percent of the patients failed to achieve the primary end point due to active disease: 10 (5%) experienced uncontrolled disease in the first month and 37 (19%) experienced flares after initial improvement. In the majority of such patients, treatment with blinded crossover or according to best medical judgment led to disease control. Ninety-one percent of patients who had uncontrolled disease or experienced a severe flare had proteinase 3 (PR3)-ANCA. When patients with uncontrolled disease were excluded from analysis, those who were PR3-ANCA positive were found to experience fewer flares when treated with RTX compared to CYC/AZA (8 of 59 [14%] versus 20 of 62 [32%]; P = 0.02). Neither ANCA titers nor B cell counts predicted disease flare. Conclusion Current treatment regimens are largely successful in controlling AAV, but in approximately one-fourth of patients, active disease persists or recurs in the first 6 months despite treatment. PR3- ANCA positivity is a risk factor for recurrence or persistence of severe disease. ANCA titers and B cell detectability are poor predictors of both disease relapse and disease quiescence in the first 6 months. [ABSTRACT FROM AUTHOR]

In this study, a comparison of point abundance sampling ( PAS) electrofishing, angling with two different hook sizes and trap-based fishing was performed in a non-wadeable river to analyse their effects on catch per unit effort ( CPUE) and population characteristics of invasive round goby Neogobius melanostomus. PAS electrofishing was identified as the most effective (mean ± s.e. CPUE = 57 ± 4 N. melanostomus min−1) and least selective method in terms of size, feeding status and species composition. Angling had the second highest CPUE, but was more size selective and resulted in a higher proportion of males compared to electrofishing [overall sex ratio angling (female:male) = 1:0·92, electrofishing 1:0·65]. Owing to low CPUE (0·012 ± 0·004) and low frequency of occurrence, minnow traps were least suitable for N. melanostomus population assessment. The results of this study suggest that a higher degree of standardization and inter-calibration is useful to achieve better comparability of population data of invasive N. melanostomus and other benthic fish species. [ABSTRACT FROM AUTHOR]

ABSTRACT The introduction of weirs into stream ecosystems resulted in modifications of serial continuity and in the decline of riverine fish species. Successful river restoration requires information on the ecological functionality of fish bypass channels that are considered an ecological improvement according to the European Water Framework Directive. In this study, we compared the functionality of three nature-oriented fish passes as compensatory habitats and migration corridors for fishes. Fish passes differed significantly from upstream and downstream reaches of the weirs, revealing higher current speed, lower water depth, smaller channel width and greater habitat variability. Following these structural differences, they provided key habitats for juvenile, small and rheophilic fishes that are typically underrepresented in highly modified water bodies. All fish passes were used as migration corridors, with increased fish movements during high discharge and at spawning periods. Because river stretches with high variability of current speed and water depth are scarce in highly modified water bodies, fish passes can play an important role as compensatory habitats and should thus be considered more intensively in habitat assessments and river restoration. Ideally, fish bypasses should mirror the natural discharge dynamics and consider all occurring fish species and sizes. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background and Objectives G-CSF-mobilized peripheral blood stem cells have long replaced marrow as the major source for allogeneic transplants. Conclusive evidence questioning the long-term safety of G-CSF for donors has not been provided, but the cumulative number of followed donors remains insufficient to rule out rare adverse events. A long-term active follow-up study of G-CSF-mobilized healthy volunteer donors was therefore performed. Patients and Methods Two hundred and three successive donors were evaluated pre-apheresis, subjected to G-CSF-mobilization/apheresis, and actively followed for 5 years by the same physicians and laboratories. Follow-up laboratory work included standard biochemical/haematological tests and T-cell phenotyping. Results Donor epidemiology was typical for reported stem cell donor cohorts. Acute adverse effects of G-CSF and apheresis were mild and transient, consistent with the previous reports. Mean circulating CD34+ cells after nine doses of G-CSF were 124 per μl. Other biochemical/haematological parameters were also altered, consistent with G-CSF treatment. Spleen enlargement was modest. At first follow-up, all clinical and laboratory parameters had normalized. Leucocyte/lymphocyte counts and CD4/CD8 ratios were the same as during premobilization work-up and remained unchanged throughout. A single severe but likely unrelated adverse event, a case of papillary thyroid carcinoma, was reported. Conclusion The studies add an observation time of almost 500 donor years to the growing body of evidence of the long-term safety of G-CSF for allogeneic donor stem cell mobilization. [ABSTRACT FROM AUTHOR]

Background: The residual risk for bacterial contamination in blood components especially in platelets is one to two orders of magnitude higher than for transfusion relevant viral infections. The majority of all bacterial transmitted fatalities occurred at the end of platelet shelf life. Therefore, the maximum shelf life of platelet concentrates (PC) was reduced to 4 days after blood donation in Germany in 2008. Methods: A new continuous non-invasive bacterial detection method was developed by O2 measurements in the platelet fluids and tested with 10 transfusion relevant bacteria species. Results: The bacterial concentration at the time point of a positive signal of PreSense O2 ranged between 102 and 105 CFU mL−1. Harmful transfusion-transmitted bacterial infection would have probably been prevented by this novel technology. Only strict anaerobic bacteria strains like Clostridium perfringens were not detected within the study period of 72 h. Conclusions: The described non-invasive bacterial detection method represents a new approach to prevent transmission of bacterial infection in platelets. The method is characterised by the advantage that all investigations can be performed until right up to the time of transfusion, and therefore, reduce the risk for sample errors to a minimum. [ABSTRACT FROM AUTHOR]

Demographic changes in developed countries as their populations age lead to a steady increase in the consumption of standard blood components. Complex therapeutic procedures like haematopoietic stem cell transplantation, cardiovascular surgery and solid organ transplantation are options for an increasing proportion of older patients nowadays. This trend is likely to continue in coming years. On the other hand, novel aspects in transplant regimens, therapies for malignant diseases, surgical procedures and perioperative patient management have led to a moderate decrease in blood product consumption per individual procedure. The ageing of populations in developed countries, intra-society changes in the attitude towards blood donation as an important altruistic behaviour and the overall alterations in our societies will lead to a decline in regular blood donations over the next decades in many developed countries. Artificial blood substitutes or in vitro stem cell-derived blood components might also become alternatives in the future. However, such substitutes are still in early stages of development and will therefore probably not alleviate this problem within the next few years. Taken together, a declining donation rate and an increase in the consumption of blood components require novel approaches on both sides of the blood supply chain. Different blood donor groups require specific approaches and, for example, inactive or deferred donors must be re-activated. Optimal use of blood components requires even more attention. [ABSTRACT FROM AUTHOR]

Bailine S, Fink M, Knapp R, Petrides G, Husain MM, Rasmussen K, Sampson S, Mueller M, McClintock SM, Tobias KG, Kellner CH. Electroconvulsive therapy is equally effective in unipolar and bipolar depression. Objective: To determine the relative efficacy of electroconvulsive therapy (ECT) in the treatment of bipolar (BP) and unipolar (UP) depressive illness and clarify its role in BP depression. Method: Patients referred for ECT with both UP and BP depressions. [classified by Structured Clinical Interview for DSM (SCID-I) criteria for history of mania] were included in a multi-site collaborative, double-masked, randomized controlled trial of three electrode placements – right unilateral, bifrontal or bitemporal – in a permutated block randomization scheme. Results: Of 220 patients, 170 patients (77.3%) were classified as UP and 50 (22.7%) as BP depression in the intent-to-treat sample. The remission and response rates and numbers of ECT for both groups were equivalent. Conclusion: Both UP and BP depressions remit with ECT. Polarity is not a factor in the response rate. In this sample ECT did not precipitate mania in depressed patients. Treatment algorithms for UP and BP depression warrant re-evaluation. [ABSTRACT FROM AUTHOR]

Background Evidence is accumulating that the pollen exsudate contains an array of non-allergenic, pro-inflammatory and immunomodulatory substances acting on the innate and adaptive immune system. In this context, pollen-associated E1-phytoprostanes (PPE1) were shown to licence human monocyte-derived dendritic cells for T-helper type 2 (Th2) polarization of naïve T cells. Objective This study aims at analysing the impact of pollen-associated lipid mediators on cytokine secretion and maturation of 6-sulfo LacNAc+ dendritic cells (slanDCs), the most abundant native dendritic cell (DC) in human peripheral blood, and further dissecting the biologically active substance(s) within aqueous pollen extracts. Results Aqueous birch pollen extracts dose-dependently inhibited the lipopolysaccharide (LPS)-induced IL-12 p70 production, while the levels of IL-6 remained unaffected. PPE1 inhibited secretion of both IL-12 p70 and IL-6. Aqueous pollen extracts, but not PPE1 or F1-phytoprostanes significantly reduced the LPS-induced surface expression of the maturation markers CD80, CD83, CD40 and CCR-7, an effect that was independent of proteins and that was still present in a 3 kDa cut-off fraction of the pollen extract. These effects were observed irrespective of the atopy status of the donors. Finally, slanDCs exposed to aqueous pollen extracts were impaired in eliciting an IFN-γ response in naïve CD4+ T cells. Conclusion Our data show that slanDCs, a subset of human blood DCs with constitutively high potency to induce Th1 responses, are susceptible to the Th2 polarizing effect of low molecular weight, non-protein factors derived from pollen. Cite this as: S. Gilles, D. Jacoby, C. Blume, M. J. Mueller, T. Jakob, H. Behrendt, K. Schaekel and C. Traidl-Hoffmann, Clinical & Experimental Allergy, 2010 (40) 269–278. [ABSTRACT FROM AUTHOR]

Postinfectious irritable bowel syndrome may develop subsequent to acute bacterial enteritis. We therefore hypothesized that intestinal afferents may develop hypersensitivity upon exposure to luminal lipopolysaccharide (LPS) from pathogens but not from commensal bacteria and that this may be prostaglandin mediated. Extracellular recordings of jejunal afferents were obtained in vivo from male Wistar rats ( n = 5 per group; 300–400 g). Lipopolysaccharide from Escherichia coli (E-LPS), Salmonella typhimurium (S-LPS) or vehicle were infused into the intestinal lumen at 5 mg mL−1. The selective 5-HT3-receptor agonist 2-methyl-5-HT (2m5-HT, 15 μgkg−1, i.v.) was administered at 15-min intervals before and up to 2 h after S-LPS administration. Intraluminal E-LPS had no effect on mesenteric afferent nerve discharge at baseline. By contrast, afferent discharge increased from 21.7 ± 0.3 impsec−1 to 28.8 ± 3.4 impsec−1 40 min after S-LPS administration (mean ± SEM; P < 0.05) and reached 38.8 ± 4.1 impsec−1 after 2 h ( P < 0.05). The afferent response to 2m5-HT was enhanced 30 min following S-LPS by 30.9 ± 3.9% ( P < 0.05) and remained elevated thereafter. The increase in baseline discharge and sensitivity to 2m5-HT following S-LPS was prevented by pretreatment with naproxen (COX inhibitor, 10 mgkg−1 i.v.) or AH-6809 (EP1/EP2 receptor antagonist, 1 mg kg−1). Intestinal afferents do not alter their discharge rate to LPS from E. coli but to LPS from the pathogenic bacterium S. typhimurium. The latter response entails afferent sensitisation to 2m5-HT that depends on prostanoid release. This acute sensitisation may prime the intestinal afferent innervation for a later development of persistent hypersensitivity. [ABSTRACT FROM AUTHOR]

Objective The primary aim of this study was to determine the desires and wishes of pregnant patients vis-à-vis their external genital anatomy after female genital mutilation (FGM) in the context of antenatal care and delivery in a teaching hospital setting in Switzerland. Our secondary aim was to determine whether women with FGM and non-mutilated women have different fetal and maternal outcomes. Design A retrospective case–control study. Setting A teaching hospital. Population One hundred and twenty-two patients after FGM who gave consent to participate in this study and who delivered in the Department of Obstetrics and Gynaecology in the University Hospital of Berne and 110 controls. Methods Data for patients’ wishes concerning their FGM management, their satisfaction with the postpartum outcome and intrapartum and postpartum maternal and fetal data. As a control group, we used a group of pregnant women without FGM who delivered at the same time and who were matched for maternal age. Main outcome measures Patients’ satisfaction after delivery and defibulation after FGM, maternal and fetal delivery data and postpartum outcome measures. Results Six percent of patients wished to have their FGM defibulated antenatally, 43% requested a defibulation during labour, 34% desired a defibulation during labour only if considered necessary by the medical staff and 17% were unable to express their expectations. There were no differences for FGM patients and controls regarding fetal outcome, maternal blood loss or duration of delivery. FGM patients had significantly more often an emergency Caesarean section and third-degree vaginal tears, and significantly less first-degree and second-degree tears. Conclusion An interdisciplinary approach may support optimal antenatal and intrapartum management and also the prevention of FGM in newborn daughters. [ABSTRACT FROM AUTHOR]

Herbal preparations are evolving as promising agents for the treatment of functional gastrointestinal disorders which are considered to be secondary to visceral hypersensitivity. We aimed to determine whether a new combination of six herbal extracts reduces the sensitivity of intestinal afferents in rat. Male Wistar rats (250–350 g, n = 6 per group) were gavaged with either vehicle or 2.5, 5 or 10 mL kg−1 of STW 5-II, a herbal preparation which contains six extracts. Two hours later, animals were anaesthetized and extracellular multi-unit mesenteric afferent nerve recordings were obtained in the proximal jejunum in vivo. Afferent discharge to 5-hydroxy-tryptamine (5-HT) (5, 10, 20 and 40 μg kg−1, i.v.), luminal distension (0–60 mmHg) and bradykinin (BK) (15, 30 and 60 μg kg−1, i.v.) was recorded. At baseline, spontaneous afferent discharge was not different following pretreatment with the various doses of STW 5-II compared with vehicle. The pressure-dependent increase in afferent discharge to intraluminal ramp distension and the dose-dependent increase in afferent firing following 5-HT were also uninfluenced by STW 5-II pretreatment. In contrast, the afferent nerve responses to 15, 30 and 60 μg kg−1 of BK were reduced following 10 mL kg−1 STW 5-II with peaks at 106 ± 19, 153 ± 22 and 156 ± 25 imp s−1 compared with 160 ± 15, 228 ± 14 and 220 ± 16 imp s−1 following vehicle pretreatment (mean ± SEM, P < 0.05). Intestinal afferent sensitivity to BK which plays a prime role in nociception was reduced following STW 5-II. Thus, STW 5-II may be of therapeutic use for conditions that involve neuronal hypersensitivity and the release of BK in the intestine. [ABSTRACT FROM AUTHOR]

Background Angiotensin converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB) exhibit beneficial antidiabetic effects in patients with type 2 diabetes independent of their blood pressure-lowering effects. Some antidiabetic properties of ARB and ACE-I might by exerted by activation of peroxisome proliferator-activated receptor gamma (PPARγ). However, it is not clear whether this action is drug specific. Materials and methods The binding affinity of telmisartan, valsartan, lisinopril, rosiglitazone and angiotensin II to PPARγ was assessed in a cell-free assay system. PPARγ signalling was studied in isolated skeletal muscle cells using Western blot analysis of phosphorylated protein kinase B (pAKT) and phosphorylated insulin like growth factor-1 receptor (pILGF-1R). Further, the ability of the drugs under study to stimulate the release of the adipocytokine visfatin was investigated in isolated human adipocytes, skeletal muscle cells, and umbilical vein endothelial cells (HUVEC). Results The binding affinity to PPARγ was highest for telmisartan with a half-maximal effective concentration of 463 nM, followed by lisinopril (2·9 µM) and valsartan (6·2 µM). In skeletal muscle cells phosphorylation of ILGF-1R was 2-fold increased after incubation with telmisartan or valsartan and 1·7-fold with lisinopril. pAKT expression was enhanced after incubation with telmisartan, valsartan and with lisinopril. The release of visfatin from adipocytes was 1·6-fold increased after treatment with lisinopril and about 2·0-fold increased with telmisartan and valsartan. Similar results were obtained in skeletal muscle cells and HUVEC. Conclusions Our data confirm agonism of telmisartan, valsartan and lisinopril on PPARγ. Pharmacokinetic differences may explain different potencies of PPARγ stimulation by drugs acting on the renin-angiotensin system in clinical settings. [ABSTRACT FROM AUTHOR]

1. Blood-derived monocytes/macrophages within the intima of the arterial wall are the main source of inflammatory cytokines and factors contributing to lesion growth, plaque instability and thrombotic events. In the present study, we assessed the hypothesis that mRNA expression levels of candidate genes of atherosclerosis in circulating CD14+ blood monocytes are associated with coronary heart disease (CHD). 2. We investigated mRNA expression levels using reverse transcription–polymerase chain reaction of genes involved in cholesterol uptake (macrophage scavenger receptor ( MSR1), scavenger receptor class B member 1 ( SRB1), lectin-like oxidized low-density lipoprotein (LDL) receptor 1 ( LOX1), CD36, LDL receptor ( LDLR)), reverse cholesterol transport (apolipoprotein E ( ApoE), ATP-binding cassette sub-family A member 1 ( ABCA1)) and inflammation (tumour necrosis factor-α ( TNF-α), macrophage inflammatory protein-1α ( MIP-1α), interleukin-6 ( IL-6), tissue factor) in CD14+ monocytes from 119 consecutively recruited patients and found that median CD36 mRNA expression levels were significantly increased in patients with CHD compared with controls (111 × 103 vs 96 × 103 copies/106 copies β-actin, respectively; n = 79 and 40, respectively; P < 0.05), despite a high interindividual variability in gene expression. 3. A common T → C polymorphism (rs2151916) located only 14 bp upstream of the upstream transcriptional start site did not influence CD36 expression. 4. Expression levels of the other candidate genes investigated in the present study did not show any statistically significant differences between patients with CHD and controls. 5. We conclude that CD36 mRNA expression is significantly increased in patients with CHD and may serve as an indicator of CHD burden. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the effects of extracorporeal radial shock wave therapy on the hindlimb function of dogs suffering from hip osteoarthritis. Twenty-four client-owned dogs with hip osteoarthritis were investigated; 18 of them received radial shockwave therapy and six were left untreated as controls. Force plate analysis on a treadmill was used to assess the dogs' hindlimb function before treatment and four weeks after the last treatment, and the treated dogs were re-evaluated three and six months after the treatment The parameters chosen for evaluation were peak vertical force and vertical impulse, and the calculated symmetry indices. In the treated dogs, differences between the ground reaction forces exerted by the right and left hindlegs disappeared four weeks after the treatment, whereas in the control dogs only the peak vertical force distribution changed significantly. The significant improvement in the treated dogs was confirmed by changes in the symmetry indices. Significant improvements in vertical impulse and peak vertical force were observed three months after the treatment [ABSTRACT FROM AUTHOR]

We describe a method for high-pressure freezing and rapid freeze-substitution of cells in tissue culture which provides excellent preservation of membrane detail with negligible ice segregation artefacts. Cells grown on sapphire discs were placed ‘face to face’ without removal of tissue culture medium and frozen without the protection of aluminium planchettes. This reduction in thermal load of the sample/holder combination resulted in freezing of cells without visible ice-crystal artefact. Freeze-substitution at −90°C for 60 min in acetone containing 2% uranyl acetate, followed by warming to −50°C and embedding in Lowicryl HM20 gave consistent and clear membrane detail even when imaged without section contrasting. Preliminary data indicates that the high intrinsic contrast of samples prepared in this way will be valuable for tomographic studies. Immunolabelling sensitivity of sections of samples prepared by this rapid substitution technique was poor; however, reducing the uranyl acetate concentration in the substitution medium to 0.2% resulted in improved labelling. Samples substituted in this lower concentration of uranyl acetate also gave good membrane detail when imaged after section contrasting. [ABSTRACT FROM AUTHOR]

Jasmonic acid and its methyl ester are signalling molecules involved in regulating development and stress responses in plants. 12-Oxo-phytodienoic acid, a precursor in jasmonic acid biosynthesis, is also biologically active. Both oxylipins accumulate after pathogen infection. To understand the function of 12-oxo-phytodienoic acid vs. jasmonic acid in plant pathogen interactions, the susceptibility of the dde2 mutant, defective in 12-oxo-phytodienoic acid and jasmonic acid biosynthesis and the opr3 mutant, which synthesizes 12-oxo-phytodienoic acid but not jasmonic acid was investigated. dde2 and opr3 were more resistant to Pseudomonas syringae. The effect was stronger in the dde2 mutant as in opr3 indicating that both oxylipins regulate pathogen resistance to P. syringae. dde2 was more susceptible to Botrytis cinerea suggesting that 12-oxo-phytodienoic acid is important in mediating the defence against B. cinerea. Expression of Pr1 and Pr2 was increased in both mutants after mock infiltration but not or only slightly enhanced after P. syringae infection. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Renal involvement in systemic lupus erythematosus (SLE) is associated with poor prognosis. Currently available renal biomarkers are relatively insensitive and nonspecific for diagnosing SLE nephritis. Previous research suggests that neutrophil gelatinase-associated lipocalin (NGAL) is a high-quality renal biomarker of acute kidney injury, while its usefulness in SLE is unclear. We undertook this study to determine the relationship between urinary NGAL excretion and SLE disease activity or damage, with a focus on nephritis. METHODS: A cohort of 35 patients diagnosed as having SLE prior to age 16 years (childhood-onset SLE) was assessed for disease activity (using the Systemic Lupus Erythematosus Disease Activity Index 2000 update) and damage (using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology SLE Damage Index) in a double-blind, cross-sectional study. Information on current markers of renal function and disease was obtained and compared with NGAL levels (ng/mg of urinary creatinine) measured by enzyme-linked immunosorbent assay. Eight children with juvenile idiopathic arthritis (JIA) served as controls. RESULTS: NGAL levels did not differ with the age, weight, height, sex, or race of the patients. Patients with childhood-onset SLE had significantly higher NGAL levels than did those with JIA (P < 0.0001). NGAL levels were strongly to moderately correlated with renal disease activity and renal damage (Spearman's r >/= 0.47, P < 0.0001 for both comparisons), but not with extrarenal disease activity or extrarenal damage. NGAL levels of >0.6 ng/mg urinary creatinine were 90% sensitive and 100% specific for identifying childhood-onset SLE patients with biopsy-proven nephritis. CONCLUSION: Urinary NGAL is a promising potential biomarker of childhood-onset SLE nephritis. The results of the current study require validation in a larger cohort to more accurately delineate urinary NGAL excretion in relation to the diverse SLE phenotypes. [ABSTRACT FROM AUTHOR]

This study was conducted to establish a new approach forin vivoculture ofin vitroproduced embryos in the bovine oviduct by transvaginal endoscopy. Embryos werein vitromatured, fertilized and cultured for 1–4 days and assigned to groups consisting of 10–30 embryos. Embryos were transferred unilaterally into oviducts of 24 heifers by the means of transvaginal endoscopy. After 3–6 days ofin vivoincubation embryos were re-collected. Experiment I aimed to evaluate the capability of embryos to migrate to the uterus. The uterine horns of four animals were flushed first, followed by a combined flushing of both oviducts and uterine horns resulting in collection rates of 31 and 34%, respectively. In experiment II, the transfer of embryos into the oviduct close to ovulation (day 1–2– experiment IIA) or at a more advanced cyclic stage (day 3– experiment IIB) succeeded in the collection of 46 and 34% of the transferred complexes, of which 13 and 37% showed the blastocyst stage. This is the first report of successful recovery of transferable blastocysts by transvaginal endoscopy after tubalin vivoculture in the homologous species of originallyin vitroproduced embryos. [ABSTRACT FROM AUTHOR]

The availability of recombinant allergens and recent advances in biochip technology led to the development of a novel test system for the detection of allergen-specific IgE. To test the performance of this allergen microarray in a serological analytical study. Standard allergens contained in grass pollen (Phl p 1, Phl p 2, Phl p 5 and Phl p 6) and tree pollen (Bet v 1 and Bet v 2) were used as a model system. The detection of allergen-specific serum IgE using microarrays was compared with standard test systems: CAP/RAST and an in-house ELISA. In order to test the analytical sensitivity of the assays, geometric dilutions of a serum pool containing high levels of pollen-specific IgE from allergic individuals were tested in each system. To assess the analytical specificity, the sera of 51 patients with presumptive allergic symptoms were collected before diagnosis. Thereafter, the results for grass/tree-pollen-specific IgE were compared. The microarray has a good dynamic range similar to the CAP/RAST system. Microarray and ELISA showed comparable analytical sensitivity exceeding the CAP/RAST system. With respect to the analytical specificity, no significant cross-reactivity of the allergens was observed. For two of the allergens tested, weak positive signals were detected in the microarray test system, whereas they were not detectable by CAP/RAST. A good correlation of presently used methods to detect serum IgE and the novel microarray test system was observed. As a next step, a careful validation of this method for a multitude of allergens and a thorough clinical evaluation has to be provided. Microarray testing of allergen-specific IgE can be presumed to be the method of choice for a prospective component-resolved diagnosis of Type I allergy, and the basis for the design and monitoring of a patient-tailored specific immunotherapy in the future. [ABSTRACT FROM AUTHOR]

Summary We suggest that the coapplication of recombinant allergens and microarray technology can lead to the development of new forms of multi-allergen tests which allow the determining and monitoring of complex sensitization profiles of allergic patients in single assays. The allergen extracts which have so far been used for diagnosis only allowed the determining of whether an allergic patient is sensitized against a particular allergen source, but the disease-eliciting allergens could not be identified. Through the application of recombinant DNA technology a rapidly growing panel of recombinant allergen molecules has become available which meanwhile comprises the epitope spectrum of most of the important allergen sources. We demonstrate that microarray technology can be used to establish multi-allergen tests consisting of microarrayed recombinant allergen molecules. Microarrayed recombinant allergens can be used to determine and monitor the profile of disease-eliciting allergens using single tests that require minute amounts of serum from allergic patients. The wealth of diagnostic information gained through microarray-based allergy testing will likely improve diagnosis, prevention and treatment of allergy. [ABSTRACT FROM AUTHOR]

This paper considers an area of clinical research that has been delegated by physician-researchers to nurses and others in the United States, that of clinical trials co-ordination. It uses interviews with nurse trial co-ordinators to explore the occupational processes by which the boundaries of work enactment and the definition of work have been established by nurses and others. It then discusses the occupational processes that have been established to formalize a role for nurses in clinical research. It raises the question of (and offers speculation on) whether specialization alone will distinguish nursing from other occupational groups engaged in clinical research work. [ABSTRACT FROM AUTHOR]

Objective The purpose of this study was to investigate whether the prenatal diagnosis of a ‘lean’ umbilical cord in otherwise normal fetuses identifies fetuses at risk of being small for gestational age (SGA) at birth and of having distress in labor. The umbilical cord was defined as lean when its cross-sectional area on ultrasound examination was below the 10th centile for gestational age. Method Pregnant women undergoing routine sonographic examination were included in the study. Inclusion criteria were gestational age greater than 20 weeks, intact membranes, and singleton gestation. The sonographic cross-sectional area of the umbilical cord was measured in a plane adjacent to the insertion into the fetal abdomen. Umbilical artery Doppler waveforms were recorded during fetal apnea and fetal anthropometric parameters were measured. Results During the study period, 860 patients met the inclusion criteria, of whom 3.6% delivered a SGA infant. The proportion of SGA infants was higher among fetuses who had a lean umbilical cord on ultrasound examination than among those with a normal umbilical cord (11.5% vs. 2.6%, p < 0.05). Fetuses with a lean cord had a risk 4.4-fold higher of being SGA at birth than those with a normal umbilical cord. After 25 weeks of gestation, this risk was 12.4 times higher when the umbilical cord was lean than when it was of normal size. The proportion of fetuses with meconium-stained amniotic fluid at delivery was higher among fetuses with a lean cord than among those with a normal umbilical cord (14.6% vs. 3.1%, p < 0.001). The proportion of infants who had a 5-min Apgar score < 7 was higher among those who had a lean cord than among those with normal umbilical cord (5.2% vs. 1.3%, p < 0.05). Considering only patients admitted in labor with intact membranes and who delivered an appropriate-for-gestational-age infant, the proportion of fetuses who had oligohydramnios at the time of delivery was higher among those who h... [ABSTRACT FROM AUTHOR]