[Barriers to guideline adherence : Identification of barriers to guideline adherence using a survey on the AWMF S3 guideline epidemiology, diagnosis, treatment, and management of uncomplicated bacterial, community-acquired urinary tract infections in adult patients]. / Barrieren der Leitlinienadhärenz : Identifizierung von Barrieren der Leitlinienadhärenz am Beispiel einer Umfrage zur AWMF-S3-Leitlinie Epidemiologie, Diagnostik, Therapie und Management unkomplizierter bakterieller ambulant erworbener Harnwegsinfektionen bei erwachsenen Patienten.

BACKGROUND: Several studies have shown that nonadherence to guidelines is pretty common in the treatment of urinary tract infections (UTI). However, no urological study has raised the question, what are barriers or reasons for this nonadherence, yet. OBJECTIVES: Consequently, we performed a survey among German urologists with the primary endpoint identification of barriers for nonadherence to German guidelines on UTI. MATERIALS AND METHODS: A 19-item questionnaire was developed and transferred to the online portal "Survey Monkey®" (Private Equity, San Mateo, CA, USA) and tested for usability by our study group. The link for the survey was sent twice to the members of the German Society of Urology (DGU). RESULTS: Overall, 307 questionnaires were completed. The mean age of the study population was 46.7 years (standard deviation 11.5). The majority (34.9%) followed guidelines in 80% of the cases. Main reasons for nonadherence on the physicians' side were 23.4% personal experience and lacking practicality of UTI guidelines on the individual complex patient. On the open questions urologists mostly stated (11.7%) that the main reason on the physician side for nonadherence is ignorance. Therefore they, in open questions, suggest to promote guidelines more in meetings and more designed practically with shortcuts and simple layout. Patient-associated factors mentioned were mostly in 26.7%. Furthermore, German urologists stated that guidelines should also have a patient section, where the main recommendations are explained in plain language. CONCLUSION: We performed the first survey on identifying barriers for nonadherence to guidelines in urology. Despite some limitations, our results are very important for the further design of guidelines. This has the potential to improve guideline adherence.

Anomalous percolation features in molecular evolution.

Self-replication underlies every species of living beings and simple physical intuition dictates that some sort of autocatalysis invariably constitutes a necessary ingredient for the emergence of molecular life. This led Worst et al. [E. G. Worst, P. Zimmer, E. Wollrab, K. Kruse, and A. Ott, New J. Phys. 18, 103003 (2016)NJOPFM1367-263010.1088/1367-2630/18/10/103003] to study a model of molecular evolution of self-replicating molecules where spontaneous ligation and simple autocatalysis are in competition for their building blocks. We revisit this model, where irreversible aggregation leads to a transition from a regime of small molecules to macromolecules, and find an array of anomalous percolation features, some of them predicted for very specific percolation processes [R. M. D'Souza and J. Nagler, Nat. Phys. 11, 531 (2015)1745-247310.1038/nphys3378].

Critical Behaviors in Contagion Dynamics.

We study the critical behavior of a general contagion model where nodes are either active (e.g., with opinion A, or functioning) or inactive (e.g., with opinion B, or damaged). The transitions between these two states are determined by (i) spontaneous transitions independent of the neighborhood, (ii) transitions induced by neighboring nodes, and (iii) spontaneous reverse transitions. The resulting dynamics is extremely rich including limit cycles and random phase switching. We derive a unifying mean-field theory. Specifically, we analytically show that the critical behavior of systems whose dynamics is governed by processes (i)-(iii) can only exhibit three distinct regimes: (a) uncorrelated spontaneous transition dynamics, (b) contact process dynamics, and (c) cusp catastrophes. This ends a long-standing debate on the universality classes of complex contagion dynamics in mean field and substantially deepens its mathematical understanding.

Failure and recovery in dynamical networks.

Failure, damage spread and recovery crucially underlie many spatially embedded networked systems ranging from transportation structures to the human body. Here we study the interplay between spontaneous damage, induced failure and recovery in both embedded and non-embedded networks. In our model the network's components follow three realistic processes that capture these features: (i) spontaneous failure of a component independent of the neighborhood (internal failure), (ii) failure induced by failed neighboring nodes (external failure) and (iii) spontaneous recovery of a component. We identify a metastable domain in the global network phase diagram spanned by the model's control parameters where dramatic hysteresis effects and random switching between two coexisting states are observed. This dynamics depends on the characteristic link length of the embedded system. For the Euclidean lattice in particular, hysteresis and switching only occur in an extremely narrow region of the parameter space compared to random networks. We develop a unifying theory which links the dynamics of our model to contact processes. Our unifying framework may help to better understand controllability in spatially embedded and random networks where spontaneous recovery of components can mitigate spontaneous failure and damage spread in dynamical networks.

Genuine non-self-averaging and ultraslow convergence in gelation.

In irreversible aggregation processes droplets or polymers of microscopic size successively coalesce until a large cluster of macroscopic scale forms. This gelation transition is widely believed to be self-averaging, meaning that the order parameter (the relative size of the largest connected cluster) attains well-defined values upon ensemble averaging with no sample-to-sample fluctuations in the thermodynamic limit. Here, we report on anomalous gelation transition types. Depending on the growth rate of the largest clusters, the gelation transition can show very diverse patterns as a function of the control parameter, which includes multiple stochastic discontinuous transitions, genuine non-self-averaging and ultraslow convergence of the transition point. Our framework may be helpful in understanding and controlling gelation.

Universality in boundary domain growth by sudden bridging.

We report on universality in boundary domain growth in cluster aggregation in the limit of maximum concentration. Maximal concentration means that the diffusivity of the clusters is effectively zero and, instead, clusters merge successively in a percolation process, which leads to a sudden growth of the boundary domains. For two-dimensional square lattices of linear dimension L, independent of the models studied here, we find that the maximum of the boundary interface width, the susceptibility χ, exhibits the scaling χ ~ L(γ) with the universal exponent γ = 1. The rapid growth of the boundary domain at the percolation threshold, which is guaranteed to occur for almost any cluster percolation process, underlies the the universal scaling of χ.

Emergence of core-peripheries in networks.

A number of important transport networks, such as the airline and trade networks of the world, exhibit a characteristic core-periphery structure, wherein a few nodes are highly interconnected and the rest of the network frays into a tree. Mechanisms underlying the emergence of core-peripheries, however, remain elusive. Here, we demonstrate that a simple pruning process based on removal of underutilized links and redistribution of loads can lead to the emergence of core-peripheries. Links are assumed beneficial if they either carry a sufficiently large load or are essential for global connectivity. This incentivized redistribution process is controlled by a single parameter, which balances connectivity and profit. The obtained networks exhibit a highly resilient and connected core with a frayed periphery. The balanced network shows a higher resilience than the world airline network or the world trade network, revealing a pathway towards robust structural features through pruning.

Stressor timing, not cortisol, is an important embryo viability determinant in female rainbow trout Oncorhynchus mykiss.

The objective of this study was to determine whether the timing of elevated cortisol levels in adult female rainbow trout Oncorhynchus mykiss, achieved by silastic implants within the body cavity, had an effect on embryo viability. Cortisol-implanted fish experienced a significant increase in circulating levels of plasma cortisol compared with sham-implanted fish, and plasma cortisol remained elevated relative to sham-implanted fish for 4 months in each of the three treatment groups (0-4, 4-8 and 8-12 months). There were no significant differences in embryo viability, egg diameters or plasma 17ß-oestradiol levels between the cortisol and sham-implanted treatments in any of the groups. There was a significant difference in the number of subfertile females (<80% embryo viability) when the three treatments were compared. The majority of the females (75%) implanted immediately postspawn (0-4 months) produced subfertile eggs, which was significantly higher than those treated 4-8 (33%) or 8-12 (17%) months postspawn. These results imply that silastic implantation can affect oocyte development, independent of plasma cortisol levels, leading to a reduction in embryo viability.

Discriminating the effects of spatial extent and population size in cyclic competition among species.

We introduce a population model for species under cyclic competition. This model allows individuals to coexist and interact on single cells while migration takes place between adjacent cells. In contrast to the model introduced by Reichenbach, Mobilia, and Frey [Reichenbach, Mobilia, and Frey, Nature (London) 448, 1046 (2007)], we find that the emergence of spirals results in an ambiguous behavior regarding the stability of coexistence. The typical time until extinction exhibits, however, a qualitatively opposite dependence on the newly introduced nonunit carrying capacity in the spiraling and the nonspiraling regimes. This allows us to determine a critical mobility that marks the onset of this spiraling state sharply. In contrast, we demonstrate that the conventional finite size stability analysis with respect to spatial size is of limited use for identifying the onset of the spiraling regime.

Burden of antimicrobial resistance in European hospitals: excess mortality and length of hospital stay associated with bloodstream infections due to Escherichia coli resistant to third-generation cephalosporins.

OBJECTIVES: This study determined excess mortality and length of hospital stay (LOS) attributable to bloodstream infection (BSI) caused by third-generation-cephalosporin-resistant Escherichia coli in Europe. METHODS: A prospective parallel matched cohort design was used. Cohort I consisted of patients with third-generation-cephalosporin-resistant E. coli BSI (REC) and cohort II consisted of patients with third-generation-cephalosporin-susceptible E. coli BSI (SEC). Patients in both cohorts were matched for LOS before infection with patients free of the respective BSI. Thirteen European tertiary care centres participated between July 2007 and June 2008. RESULTS: Cohort I consisted of 111 REC patients and 204 controls and cohort II consisted of 1110 SEC patients and 2084 controls. REC patients had a higher mortality at 30 days (adjusted odds ratio = 4.6) and a higher hospital mortality (adjusted hazard ratio = 5.7) than their controls. LOS was increased by 8 days. For SEC patients, these figures were adjusted odds ratio = 1.9, adjusted hazard ratio = 2.0 and excess LOS = 3 days. A 2.5 times [95% confidence interval (95% CI) 0.9-6.8] increase in all-cause mortality at 30 days and a 2.9 times (95% CI 1.2-6.9) increase in mortality during entire hospital stay as well as an excess LOS of 5 days (95% CI 0.4-10.2) could be attributed to resistance to third-generation cephalosporins in E. coli BSI. CONCLUSIONS: Morbidity and mortality attributable to third-generation-cephalosporin-resistant E. coli BSI is significant. If prevailing resistance trends continue, high societal and economic costs can be expected. Better management of infections caused by resistant E. coli is becoming essential.

[Placement of stimulus electrodes and heart rate during electroconvulsive therapy]. / Die Position der Stimulationselektroden und die Herzfrequenz bei Elektrokrampftherapie.

OBJECTIVE: Bifrontal stimulation in electroconvulsive therapy (ECT) has been increasingly administered and evaluated over the past years. However, no attention has been paid to cardiac side effects of this novel form of treatment during the application of the electrical stimuli. METHOD: Cardiac responses to different electrode positions were compared intraindividually, using synchronised electrocardiograms and waveforms of pulse oximetry. RESULTS: Unilateral ECT gave rise to a marked cardiac response during stimulation. Intervals between two consecutive heartbeats increased from 0.6 ± 0.0 sec to 4.1 ± 3.4 sec (mean ± standard deviation). In contrast, stable heart actions were documented in the same patients during bifrontal stimulation. CONCLUSION: The placement of the stimulus electrodes for ECT determines the incidence of asystole events during stimulation. Bifrontal electrode positioning results in less activation of the vagus nerve than unilateral treatment. The longer distance from the electrode site to the nerve in bifrontal treatment could account for these findings.

Identification of novel genes associated with molecular sex differentiation in the embryonic gonads of rainbow trout (Oncorhynchus mykiss).

The molecular pathways in embryonic vertebrates leading to gonad formation in each sex are incompletely understood. The purpose of this study was to identify novel genes that could be associated with sex-specific gonadal differentiation in a fish, the rainbow trout (Oncorhynchus mykiss). This study was facilitated by a custom microarray based on 7,671 genes derived from embryonic rainbow trout gonad cDNA libraries and public databases. Gonad samples for total RNA isolation were obtained from pvasa-green fluorescent protein (pvasa-GFP) transgenic rainbow between 300 and 700 degree-days of development post-fertilization. The transgenic fish permitted the collection of gonads from embryonic rainbow trout during the period of molecular sex differentiation in advance of any morphologically distinguishable characteristics of sex. A bioinformatic method was used with the microarray data that looked for strong associations in gene expression patterns between known sex differentiation genes (the target genes) and novel genes (the target-associated genes) previously not allied with sex differentiation in fishes. The expression patterns of representative target genes from both sexes and their target-associated genes were independently confirmed by real-time reverse transcription polymerase chain reaction to support the validity of the bioinformatic method employed. Numerous novel genes were identified in the gonads of embryonic female and male rainbow trout that could be involved in sex-specific differentiation pathways in this fish.

Early onset of embryonic mortality in sub-fertile families of rainbow trout (Oncorhynchus mykiss).

Survival during early embryonic development is highly variable in oviparous fishes and appears to be related to events associated with the female at the time of ovulation and spawning. The goal of this study was to identify critical periods of mortality associated with early embryonic development in egg batches from female rainbow trout (Oncorhynchus mykiss) that were checked for ovulation every 5-7 days. The experiment was designed to specifically remove post-ovulatory ageing and reduce paternal variability. Embryo viability in 269 single-pair-mated families was systematically tracked at the following five stages: second cleavage (0.5 days post fertilisation (dpf)), elevated blastula (2.5 dpf), embryonic shield (6 dpf), embryonic keel (9 dpf), and retinal pigmentation (19 dpf). At each of the five stages families with embryo viability assessments of <80% were classed as sub-fertile, whereas those with >80% embryo viability were classed as fertile. Embryo viability in sub-fertile families was distinctly reduced at 0.5 dpf, in contrast to fertile families, but remained constant from that point through to 19 dpf. These results suggest that the critical period of early embryonic mortality in sub-fertile families of rainbow trout parallels events that occur at or shortly after fertilisation and is independent of post-ovulatory aging.

Adenosine triphosphate levels in steelhead (Oncorhynchus mykiss) eggs: an examination of turnover, localization and role.

The dynamics of energy production and utilization in fish eggs before and shortly after fertilization may be critical for embryo survival. Therefore, the current study examined the turnover of adenosine triphosphate (ATP) as well as examined the possible role and localization of ATP in unfertilized steelhead (Oncorhynchus mykiss) eggs and early embryos. The mean ATP level in unfertilized steelhead eggs was 1.92+/-0.10 (mean+/-S.E.M., n=17) nmol ATP per egg. Exposure of the unfertilized egg to 10 degrees C water (water activation) and fertilization resulted in comparable and substantial decreases (approx. 20-50%) in egg ATP levels within 3 min. This suggests that the energy expended at fertilization is used in response to water activation rather than fertilization per se. Unfertilized eggs maintained in ovarian fluid for 9 days at 10 degrees C under air showed a progressive decline of fertility that reached zero after 6 days. In contrast, no significant changes were seen in ATP levels throughout this 9 days period. Thus, fertility does not positively correlate with egg ATP levels in stored eggs. In the unfertilized egg, the ATP stored in the yolk accounted for approximately 1.5% of the total egg ATP. After fertilization, the concentration of ATP in the yolk increased approximately seven-fold, with the yolk and blastoderm each now accounting for approximately 20% of the total remaining ATP. Finally, to estimate the changes in oxidative metabolism following fertilization, the cyanide (KCN)-sensitive decline in total ATP was determined for unfertilized eggs and 1 day embryos. In the presence of KCN, ATP levels declined to approximately 50% within 24 h in both unfertilized eggs as well as embryos; the rates of ATP decline were not different. Therefore, there was not a discernible increase in ATP generation by oxidative phosphorylation at the time of fertilization.

Phagocytic response of macrophages from the pronephros of American plaice (Hipoglossoides platessoides) exposed to contaminated sediments from Baie des Anglais, Quebec.

Sediments of Baie des Anglais on the St. Lawrence estuary have a history of environmental contamination, but little information exists regarding their toxicity. The purpose of the present study was to determine the effects of contaminated Baie des Anglais sediments on American plaice (Hippoglossoides platessoides) immune function. Three sites in Baie des Anglais were selected which vary in proximity to local industries and in their sediment contaminant load. Sites 1 and 2 (within the bay) are the closest to shore and most heavily contaminated while sediments at Site 3, which is outside the bay, are the least contaminated. In the first experiment, American plaice were placed in cages at each site for three weeks and immune function was assessed by measuring the phagocytic activity of pronephric macrophages. At the time of sampling, plaice displayed pronephros cell immune response disturbances indicating that Site 1 and 2 were most toxic and Site 3 the least toxic. The results obtained for phagocytosis revealed that contaminants present in the sediments are bioavailable to fish, which came in contact with them and significantly affected their immune system. In the second experiment, sediments from the most toxic site, Site 1, were collected for a laboratory controlled experiment in which plaice were exposed for up to 3 months to these contaminated marine sediments, while the control group was exposed to relatively uncontaminated beach sand. At the end of the exposure period, plaice were transferred from contaminated sediment to beach sand and sampled one month later in order to determine if immune function had returned to control levels. The total number of macrophages decreased following three months of exposure, while the active macrophages had already decreased after the first month of exposure. Following the rehabilitation period a significant trend toward normal response was noted. Sediments from Baie des Anglais contain primarily less highly chlorinated PCBs and lower concentrations of the intermediate and highly chlorinated PCBs. The total concentration of PCBs (sum of 20 congeners) in the contaminated sediments was 1500 ng/g while in the beach sand, the levels were 13.6 ng/g dry weight. Only the low chlorinated PCB congeners were efficiently transferred from the sediments to the plaice liver. Together, these results suggest that the effect of chemical exposure on the phagocytosis of plaice macrophages may be reversible if the fish are returned to a non-contaminated habitat.

Estrogen receptor-alpha protein localization in the testis of the rainbow trout (Oncorhynchus mykiss) during different stages of the reproductive cycle.

Estrogen receptor-alpha (ER-alpha) is important for male reproduction in mammals; however, no information is available on ER-alpha protein distribution in the testes of fishes. The cellular localization of the rainbow trout (Oncorhynchus mykiss) ER-alpha (rtER-alpha) protein, throughout the annual reproductive cycle was determined in this study. An antibody was designed based on a 15-amino acid sequence from the D-domain of the rtER-alpha, and its specificity was confirmed using Western blot analysis. Immunohistochemical analysis revealed rtER-alpha protein to be present only in the testicular interstitium, at every stage of the annual reproductive cycle. The localization of rtER-alpha protein in the interstitial fibroblasts, the Leydig cell precursor in the rainbow trout, suggests a role for estrogens in the differentiation of these precursor cells into mature Leydig cells. This is the first study to report the cellular localization of an estrogen receptor protein in the testis of any fish species.

Testis transplantation in male rainbow trout (Oncorhynchus mykiss).

The objective of the present study was to establish a procedure for the transplantation of an intact testis from one male rainbow trout (Oncorhynchus mykiss) to another individual and evaluate the reproductive function of the transplanted testis at sexual maturity. Isogenic (cloned) male rainbow trout were produced by crossing a completely homozygous male (YY) with a homozygous female (XX) to eliminate any problem of tissue rejection. Transplantation was performed on four pairs of sexually immature animals (n = 8); each served both as a donor and recipient. The left testis was removed by making a ventral midline incision to expose the body cavity and gonads. The left testis was disconnected at the anterior and posterior points of attachment and transferred to the recipient fish where it was placed in position adjacent to the pyloric cecae. The right testis was left intact. After 4 wk, the fish were injected (i.p.) twice weekly for 8 or 9 wk with salmon pituitary extract (1.5 mg/kg) to induce precocious sexual maturation. A similar number of untreated fish were maintained as controls. Following this treatment, all the fish were killed, and the right (intact) and left (transplanted) testes were removed, weighed, and sampled for sperm. Although the mean weights of the left, transplanted testes were significantly (P: < 0.05) smaller than the intact testes (transplants = 1.2 g; intact = 3.9 g), transplanted testes were present in all animals, had increased in mass, and were sexually mature containing sperm. The mean fertility, as measured by the proportion of eggs completing first cleavage, of sperm derived from transplanted testes (92%) was no different from the sperm obtained from intact testes (84%). Similarly, there was no difference in the number of embryos attaining the eyed stage of development, after 18 days of incubation, that were derived from transplanted (84%) or intact testes (85%).