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.

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.

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.

[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].

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.

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.

Quantification of rainbow trout (Oncorhynchus mykiss) estrogen receptor-alpha messenger RNA and its expression in the ovary during the reproductive cycle.

This study developed a quantitative reverse transcription-polymerase chain reaction (RT-PCR) method to measure estrogen receptor-alpha (ERalpha) mRNA in the rainbow trout (Oncorhynchus mykiss). Using RT-PCR, and primers based on the known ERalpha DNA sequence in this species, cDNA sequences representing most of the protein coding region were obtained from ovary poly A(+) RNA. Using these DNA sequences as probes in Northern blot hybridizations confirmed that a single transcript of 4.2 kilobases in poly A(+) RNA could be detected in liver and ovary RNA. For the quantitative RT-PCR assay an internal standard RNA molecule was produced to control for inherent inter-tube differences in amplification efficiency and permit accurate quantification of ERalpha mRNAs. The quantitative RT-PCR assay proved to be highly specific for ERalpha mRNA with a detection limit of 6.9 fg, which corresponds to 273 fg ERalpha mRNA/microg total RNA. The quantitative RT-PCR assay was used to measure the levels of ERalpha mRNA in ovaries of rainbow trout at different stages of reproductive development. Ovarian ERalpha mRNA expression was found during two distinct periods of reproductive development, in pre-vitellogenic ovaries of fish with ovarian follicle diameters (OFDs) 1000 microm. ERalpha mRNA could not be detected in the ovaries of fish with OFDs >100 microm but 2000 microm.

High incidence of a male-specific genetic marker in phenotypic female chinook salmon from the Columbia River.

Numerous populations of anadromous salmonids in the northwestern United States have been declining for many years, resulting in Endangered Species Act listings and in some cases extinction. The degradation of river ecosystems has been proposed as one of the major reasons for the inability of salmon to maintain their populations. However, the specific factors interfering with the reproduction and survival of salmon during the freshwater phase of their life cycle have not been fully described. This study was initiated to determine the incidence of phenotypic sex reversal in wild, fall chinook salmon (Oncorhynchus tshawytcha) that returned to spawn in the Columbia River. Fish were sampled at different locations within this watershed to determine whether they were faithfully expressing their genotype. We report a high incidence (84%) of a genetic marker for the Y chromosome in phenotypic females sampled from the wild, which was not observed in female fish raised in hatcheries. It appears likely that female salmon with a male genotype have been sex reversed, creating the potential for an abnormal YY genotype in the wild that would produce all-male offspring and alter sex ratios significantly.

Stimulation of in vitro ovarian estradiol-17 beta synthesis in the rainbow trout by the carbohydrate-poor protein fraction from sockeye salmon pituitary glands.

The role of carbohydrate-poor (Con A I) and carbohydrate-rich (Con A II) pituitary protein fractions, isolated from sockeye salmon (Oncorhynchus nerka), were investigated pertaining to in vitro estradiol-17 beta (E2) production by rainbow trout (Oncorhynchus mykiss) ovarian follicles. During the early vitellogenic phase of the reproductive cycle, using defolliculated ovarian follicle preparations (outer epithelium-thecal layer absent), it was demonstrated that the Con A I fraction was capable of increasing E2 production, in the presence of exogenous testosterone (T) as the substrate. Under similar conditions the Con A II fraction (containing the maturational gonadotropin) was inactive. However the Con A II fraction or T, separately, increased E2 production by intact ovarian follicles, whereas the Con A I fraction did not. A mechanism proposed to explain the regulation of ovarian E2 synthesis involves the Con A I fraction enhancing aromatase activity in granulosa cells permitting an increased conversion of T to E2.

Steroids involved with final oocyte maturation in the winter flounder.

A number of androgens and progestogens including 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (17,20-P) were examined in female winter flounder as possible maturation inducing steroids (MIS). During final oocyte maturation serum levels of testosterone (T) and 17 beta-hydroxy-5 beta-androsten-3-one (5 beta-T) peaking at over 200 ng/ml and pregnenolone (PE) at 40 ng/ml were the predominant steroids found from each major group. High levels of T and 5 beta-T were correlated with oocyte stages characterized by germinal vesicle migration. Of the PEs measured, maximum serum levels of PE, 3 beta,17 alpha-hydroxy-5-pregnen-20-one (17-PE) and 3 beta,17 alpha, 20 beta-dihydroxy-5-pregnene (17,20-PE) were found during later oocytes stages associated with germinal vesicle breakdown. Levels of 17,20-P, an established MIS in most fish, were almost non-detectable (less than 0.1 ng/ml serum) in females throughout all stages of final oocyte maturation. Incubations of ovarian follicles in vitro with physiological concentrations of T and 5 beta-T indicated that these steroids could induce all stages of final oocyte maturation. Similar in vitro incubations showed that 17-PE and 17,20-PE were only effective on germinal vesicle breakdown. The principal conclusions are that T, 5 beta-T and the PEs can be considered as MISs in winter flounder and the PE pathway predominates during the final stages of oocyte maturation in winter flounder in contrast to progesterones which predominate in other fish species, mostly salmonids, studies to date.

Guanidino compound levels in brain regions of non-dialyzed uremic patients.

Guanidino compounds have been suggested to contribute to the complex neurological complications associated with uremia. Several of them have previously been reported to accumulate in physiological fluids of renal insufficient subjects. We report on guanidino compound levels in 28 brain regions in control and uremic brains. In all brain regions studied, in controls as well as in uremic patients, concentrations of alpha-keto-delta-guanidinovaleric acid, alpha-N-acetylarginine and beta-guanidinopropionic acid remained below detection limits. Creatine, guanidinoacetic acid, argininic acid, gamma-guanidinobutyric acid, arginine and homoarginine were not increased in uremic patients. Argininic acid and homoarginine were detectable in some brain regions only. Creatine concentrations varied from 2500 +/- 2100 nmol/g tissue in hypophysis to 10500 +/- 1200 nmol/g tissue in cerebellar cortex. Even more pronounced regional differences were found for gamma-guanidinobutyric acid with the lowest concentration in the caudate nucleus (0.6 +/- 0.3 nmol/g tissue) and highest in substantia nigra, pallidum and cerebellar dentate nucleus (8.3 +/- 2.8 nmol/g tissue). The guanidinosuccinic acid levels were below detection limit in controls in the majority of brain regions. Taking into account the detection limit of guanidinosuccinic acid for a certain amount of tissue applied to the analytical system, important increases (approx. up to > 100 fold) were observed in all brain regions of uremic patients. Accumulation of guanidinosuccinic acid increased with increasing degree of renal failure with levels up to 65 nmol/g tissue in the hypophysis. Creatinine concentrations were also found to be increased in uremic brain regions but increases seemed to be less strictly related to serum urea levels. Guanidine and methylguanidine were found only occasionally in brain regions of controls while respectively 100- and 30-fold increases were found in brain regions of uremic subjects. Levels of guanidinosuccinic acid and creatinine in uremic brain were comparable to those previously observed in brain of experimental animals displaying convulsions following intraperitoneal injection of the respective compounds. Our findings further establish guanidino compounds as probable uremic toxins contributing to the neurological complications in uremia.

Necrotizing fasciitis precipitating diabetic ketoacidotic coma.

Necrotizing fasciitis is a rapidly spreading infection of the subcutaneous tissue and fascia; diabetes mellitus appears to be the most frequent underlying disease. Early diagnosis and immediate aggressive surgical therapy are paramount to curtail morbidity and mortality, but diagnosis is often difficult and unnecessarily delayed. We describe a case of necrotizing fasciitis precipitating diabetic ketoacidotic coma where correct diagnosis was not made until the 14th hospital day. We stress the fact that physicians caring for critically ill patients should be keenly aware of the possibility of necrotizing fasciitis when tending diabetic patients with unexplained fever; failure to recognize the disease can have devastating results. Finally, we believe this to be the first reported case of diabetic ketoacidotic coma precipitated by necrotizing fasciitis.

Erythropoietin response is blunted in critically ill patients.

OBJECTIVES: Critically ill patients often develop anaemia which can be related to a number of factors. However, the exact causes of anaemia in many patients remain unexplained. We hypothesized that the relationship between erythropoietin (EPO) and haematocrit may be altered in critically ill patients. DESIGN: Serum concentrations of EPO were serially determined by the ELISA method in 36 critically ill, non-hypoxaemic patients who stayed more than 7 days in the Intensive Care Unit, including 22 patients with sepsis and 14 without. Eighteen ambulatory patients with iron-deficiency anaemia served as a control group. SETTING: Two University Hospital Intensive Care Departments. RESULTS: A significant inverse correlation between serum EPO and haematocrit levels was found in the control patients (r = -0.81, p < 0.001), but not in the critically ill patients (r = -0.09, NS), except in a subgroup of non-septic patients without renal failure (r = -0.61, p < 0.01). CONCLUSIONS: EPO levels can be inappropriately low in critically ill patients, so that EPO deficiency may contribute to the development of anaemia in these patients. This phenomenon is observed not only in the presence of acute renal failure, but also in the presence of sepsis.

The pedagogic characteristics of a clinical conference for senior residents and faculty.

OBJECTIVE: To determine the pedagogic characteristics of a clinical conference for senior pediatric residents and selected faculty. PARTICIPANTS AND SETTING: Nineteen senior pediatric residents and 14 selected faculty members participated in a daily clinical conference at Children's Hospital, Boston, Mass. DESIGN: Qualitative research design using videotapes of nine consecutive hour-long sessions to generate pedagogic topics to be investigated using a questionnaire administered to participating residents and faculty. Narrative responses were analyzed to find pedagogic themes. RESULTS: Analysis of videotapes generated the following three topics: What facilitated learning? What was learned? What makes the process of teaching and learning effective? In the questionnaire residents indicated that learning was facilitated by resident-faculty interactions (19/19), faculty participation (19/19), and information resources (12/19). Content learned included information (16/19), approach to diagnosis (11/19), management strategies (14/19), and different perspective (14/19). An effective process of teaching and learning was attributed to case-based resident initiated discussion (19/19), facilitation by the chief resident (16/19), and non-competitive discussions in which expert faculty played a nondominant role (19/19). Faculty identified identical factors relating to all three themes. The mean rating of the conference was 4.5/5 (SD, +/- 0.50) and 4.7/5 (SD, +/- 0.45) by residents and faculty, respectively (Likert scale, 1 to 5). CONCLUSIONS: The pedagogic effectiveness of this conference was attributed to a resident-centered, case-based learning format and a discussion process characterized by noncompetitive interactions among faculty and residents, strong group facilitation by the chief resident, and participation of faculty experts in a nondominant role.

6-keto-PGF1 alpha levels and prostacyclin therapy in 2 adult patients with hemolytic-uremic syndrome.

Evidence supports the hypothesis that plasma prostacyclin activity is deficient in hemolytic-uremic syndrome (HUS). We studied 2 adult patients with HUS. Plasma levels of 6-keto-PGF1 alpha, the stable metabolite of prostacyclin, were measured by radioimmunoassay. Both patients were found to have elevated 6-keto-PGF1 alpha levels. These findings are in contradiction with the prostacyclin deficiency hypothesis and with earlier reports of low or undetectable plasma levels of this metabolite. The patients were treated with IV prostacyclin after a single plasma exchange. The first patient, admitted with advanced renal failure, obtained a rapid remission but renal function did not recover; the second patient, admitted with a less pronounced degree of renal failure, reacted slowly to therapy but renal function partially recovered. We believe that, if any benefit is to be expected from prostacyclin therapy in HUS, it should be started early in the course of the disease.