bluuebunny/crossref_metadata_2025 huggingface dataset:
Angular Stable Miniplate Fixation of Chronic Unstable Scaphoid Nonunion
Authors: Brink Peter , Poeze Martijn , Hannemann Pascal , Schormans Philip
Published: May 2017

Background Around 5 to 15% of all scaphoid fractures result in nonunion. Treatment of long-lasting scaphoid nonunion remains a challenge for the treating surgeon. Healing of scaphoid nonunion is essential for prevention of scaphoid nonunion advanced collapse and the subsequent predictable pattern of radiocarpal osteoarthritis.

Purpose The purpose of this study was to investigate the feasibility of fixation of the scaphoid nonunion with a volar angular stable miniplate and cancellous bone grafting. We hypothesized that this technique could be successful, even in patients with previous surgery for nonunion and in patients with a long duration of nonunion.

Patients and Methods A total of 21 patients enrolled in a single-center prospective cohort study. Healing of nonunion was assessed on multiplanar computed tomography scan of the wrist at a 3-month interval. Functional outcome was assessed by measuring grip strength, range of motion, and by means of the patient-rated wrist and hand evaluation (PRWHE) questionnaire.

Results During follow-up, 19 out of 21 patients (90%) showed radiological healing of the nonunion. The range of motion did not improve significantly. Postoperative PRWHE scores decreased by 34 points. Healing occurred regardless of the length of time of the nonunion (range: 6–183 months) and regardless of previous surgery (38% of patients).

Conclusion Volar angular stable miniplate fixation with autologous cancellous bone grafting is a successful technique for the treatment of chronic unstable scaphoid nonunion, even in patients with long-lasting nonunion and in patients who underwent previous surgery for a scaphoid fracture. Rotational interfragmentary stability might be an important determining factor for the successful treatment of unstable scaphoid nonunion.

Level of Evidence Level IV.
A meta-analysis of endoscopic ultrasound–fine-needle aspiration compared to endoscopic ultrasound–fine-needle biopsy: diagnostic yield and the value of onsite cytopathological assessment
Authors: Khan Muhammad , Grimm Ian , Ali Bilal , Nollan Richard , Tombazzi Claudio , Ismail Mohammad , Baron Todd
Published: May 2017

Background The diagnostic yield of endoscopic ultrasound (EUS) guided fine-needle aspiration (FNA) is variable, and partly dependent upon rapid onsite evaluation (ROSE) by a cytopathologist. Second generation fine-needle biopsy (FNB) needles are being increasingly used to obtain core histological tissue samples.

Aims Studies comparing the diagnostic yield of EUS guided FNA versus FNB have reached conflicting conclusions. We therefore conducted a systematic review and meta-analysis to compare the diagnostic yield of FNA with FNB, and specifically evaluating the diagnostic value of ROSE while comparing the two types of needles.

Methods We searched several databases from inception to 10 April 2016 to identify studies comparing diagnostic yield of second generation FNB needles with standard FNA needles. Risk ratios (RR) were calculated for categorical outcomes of interest (diagnostic adequacy, diagnostic accuracy, and optimal quality histological cores obtained). Standard mean difference (SMD) was calculated for continuous variables (number of passes required for diagnosis). These were pooled using random effects model of meta-analysis to account for heterogeneity. Meta-regression was conducted to evaluate the effect of ROSE on various outcomes of interest.

Results Fifteen studies with a total of 1024 patients were included in the analysis. We found no significant difference in diagnostic adequacy [RR 0.98 (0.91, 1.06), (I
2 = 51 %)]. Although not statistically significant (P = 0.06), by meta-regression, in the absence of ROSE, FNB showed a relatively better diagnostic adequacy. For solid pancreatic lesions only, there was no difference in diagnostic adequacy [RR 0.96 (0.86, 1.09), (I
2 = 66 %)]. By meta-regression, in the absence of ROSE, FNB was associated with better diagnostic adequacy (P = 0.02). There was no difference in diagnostic accuracy [RR 0.99 (0.95, 1.03), (I
2 = 27 %)] or optimal quality core histological sample procurement [RR 0.97 (0.89, 1.05), (I
2 = 9.6 %)]. However, FNB established diagnosis with fewer passes [SMD 0.93 (0.45, 1.42), (I
2 = 84 %)]. The absence of ROSE was associated with a higher SMD, i. e., in the presence of an onsite pathologist, FNA required relatively fewer passes to establish the diagnosis than in the absence of an onsite pathologist.

Conclusions There is no significant difference in the diagnostic yield between FNA and FNB, when FNA is accompanied by ROSE. However, in the absence of ROSE, FNB is associated with a relatively better diagnostic adequacy in solid pancreatic lesions. Also, FNB requires fewer passes to establish the diagnosis.
Aktueller Status der Wirbelsäulenchirurgie in Deutschland – Ergebnisse einer Umfrage unter Mitgliedern der Deutschen Wirbelsäulengesellschaft
Authors: Marquardt Antje , Bühn Stefanie , Pieper Dawid , Rauschmann Michael , Fleege Christoph
Published: May 2017

Hintergrund Mono- (MSS) und bisegmentale Spondylodesen (BSS) sind in deutschen Krankenhäusern häufig durchgeführte Eingriffe. Trotz des hohen Fallvolumens gibt es kaum Daten über die Behandlungsabläufe und medizinischen Versorgungskonzepte während und nach dem Krankenhausaufenthalt. Ziel der Umfrage war es, einen detaillierten Einblick in die Behandlungsprozesse sowie medizinischen Ansätze in der elektiven MSS- und BSS-Versorgung in Deutschland zu erhalten. Auf Basis der erhobenen Daten sollen zudem Möglichkeiten für eine optimierte Patientenversorgung aufgezeigt werden.

Materialien und Methoden Über einen Newsletter wurden Mitglieder der Deutschen Wirbelsäulengesellschaft (DWG) eingeladen, an der Befragung teilzunehmen. 209 leitende Ärzte wurden zu Themen wie Verweildauer, Behandlungsablauf und Ergebnismessung befragt.

Ergebnisse Für die statistische Auswertung wurden Daten aus 142 Fragebögen berücksichtigt. In einigen Aspekten gibt es ein einheitliches Vorgehen, beispielsweise bei der präoperativen Information des Patienten über den Behandlungsablauf und der Entlassung auf Basis qualitativer Kriterien. Gleichzeitig existiert eine große Spannweite in der Verweildauer und eine starke Varianz im Vorgehen bei Rehabilitation, Restriktionen, prä- und postoperativer Ergebnismessung, radiologischer Kontrolle und interdisziplinärer Abstimmung.

Schlussfolgerung Mehr als die Hälfte der befragten Ärzte gab an, einem strukturierten Behandlungsschema zu folgen. Gleichzeitig zeigen die Ergebnisse der Befragung ein sehr heterogenes Vorgehen im Rahmen der MSS- und BSS-Versorgung in Deutschland. Zudem wird deutlich, dass dies besonders ausgeprägt ist in den Teilaspekten der Behandlung, bei denen ein Mangel an Evidenz vorliegt. Die Ergebnisse geben erste wichtige Hinweise, in welchen Aspekten Behandlungsabläufe und Organisationsstrukturen standardisiert werden können, um die Patientenversorgung zu optimieren.
Modification of Al2O3/InP interfaces using sulfur and nitrogen passivations
Authors: Wang Sheng-Kai , Sun Bing , Cao Ming-Min , Chang Hu-Dong , Su Yu-Yu , Li Hai-Ou , Liu Hong-Gang
Published: May 2017

By focusing on the Al/Al2O3/InP capacitor structure, impacts on interface modification using sulfur and nitrogen passivations against traps and charge formation are systematically investigated. Improved electrical characteristics with low leakage current density, hysteresis, interface trap density, and capacitance frequency dispersion are demonstrated after sulfur or nitride interface passivations. It is clarified that sulfur interface passivation is more effective in reducing the interface traps, while nitride interface passivation shows stronger impact on suppressing the generation of bulk and border traps and the negative interface charges. A possible model based on network modification is proposed to explain the mechanism of the different trap and charge behaviors for sulfur and nitride interface passivation.
Empirical models for estimation of diffuse solar radiation based on measured data for humid-subtropical climatic region of India
Authors: Jamil Basharat , Akhtar Naiem
Published: May 2017

Solar radiation information at the site of solar energy systems is required for proper planning and execution of energy projects. In this work, global and diffuse solar radiations were measured for a period of two years (September, 2013 to August, 2015) in the Humid Subtropical Climatic Region of India in the city of Aligarh (27.89°N, 78.08°E). Secondary standard pyranometers were used to observe solar radiation at the ground level. The measured data for Aligarh were compared with the available data for the neighboring Capital city, New Delhi (28.61°N, 77.21°E). It was observed that Aligarh has a better availability of solar energy and solar energy utilization potential. Annual average global and diffuse solar radiations were observed to be 22.12 and 7.92 MJ/m2-day, respectively, for Aligarh. Using measured solar radiation data for Aligarh, six empirical models were established to assess monthly mean diffuse solar radiation (by correlating the diffuse fraction with the sky-clearness index). Models were analyzed in terms of several statistical indicators and exhibited reasonable agreement with correlation coefficients in the range of 0.7610 to 0.8188. Models were subsequently ranked based on the Global Performance Indicator. The Global Performance Indicator (GPI) of the developed models was in the range of −1.86 to 5.84, and the highest GPI was achieved for the cubic model.
Unmagnetized fireballs in the hollow cathode geometry
Authors: Levko Dmitry
Published: May 2017

Fireballs in the hollow cathode geometry are studied using the self-consistent two-dimensional Particle-in-Cell Monte Carlo collision model. The generation of two fireballs located inside and outside the cathode is obtained. These two fireballs have different parameters and are supported by different physical mechanisms. Namely, the fireball inside the cathode is supported by the hollow cathode effect, while the fireball outside the cathode is supported by the electron beam injected through the cathode orifice and accelerated in the sheath separating two fireballs. The influence of the cathode voltage on the discharge parameters is analyzed. The saturation of the discharge current at high voltages is obtained, which is attributed to the influence of the discharge voltage on the electron beam energy relaxation length.
Biogeographical relationships and new regionalisation of high-altitude grasslands and woodlands of the central Pampean Ranges (Argentina), based on vascular plants and vertebrates
Authors: Martínez Gonzalo A. , Arana Marcelo Daniel , Oggero Antonia J. , Natale Evangelina S.
Published: May 2017

Evolutionary biogeography aims to provide a hierarchical system of biotic regionalisation for areas of the Earth that correspond to natural areas related by their common evolutionary history. In this context, the central Pampean Ranges of Argentina, formed by the mountain systems of Córdoba and San Luis, are immersed in the Chacoan dominion; however, higher-altitude environments of these mountains, namely highland grasslands and tabaquillo forests, have relationships with the Andean region and other Neotropical areas that are different from the Chacoan dominion, which would indicate that the current classification would not be natural. To clarify their biogeographic relationships, a track analysis of the distribution of the biota of vertebrates and vascular plants of the highland grasslands and tabaquillo forests of central Pampean Argentinian Ranges was conducted. The obtained distributional patterns suggest that the area under study has diverse geobiotic origins, both Andean and Neotropical, indicating that, in this area, an interaction of biota with different evolutionary origins occurs; so, its status as a biogeographic province is proposed, belonging to the South American transition zone.
Corrigendum to “Local Dirichlet forms, Hodge theory, and the Navier-Stokes equations on topologically one-dimensional fractals”
Authors: Hinz Michael , Teplyaev Alexander
Published: May 2017

The authors correct statements in “Local Dirichlet forms, Hodge theory, and the Navier-Stokes equations on topologically one-dimensional fractals”, Trans. Amer. Math. Soc. 367 (2015), 1347–1380.
The Use of Single Stent-Assisted Coiling in Treatment of Bifurcation Aneurysms: A Multicenter Cohort Study With Proposal of a Scoring System to Predict Complete Occlusion
Authors: Adeeb Nimer , Griessenauer Christoph J , Patel Apar S , Foreman Paul M , Baccin Carlos E , Moore Justin M , Gupta Raghav , Alturki Abdulrahman , Harrigan Mark R , Ogilvy Christopher S , Thomas Ajith J
Published: May 2017

BACKGROUND

The development of stent-assisted coiling has allowed for the endovascular treatment of wide-necked bifurcation aneurysms. A variety of options exist, and little is known about the optimal stent configuration in this setting. We report a large multicenter experience of stent-assisted coiling of bifurcations aneurysms using a single stent, with attention to factors predisposing to aneurysm recanalization.

OBJECTIVE

To assess the safety and efficacy of single stent-assisted coiling, in addition to analyzing the factors associated with recanalization, and proposal of a predictive scoring scale.

METHODS

A multicenter retrospective analysis of bifurcation aneurysms treated with a single stent-assisted coiling technique between 2007 and 2015 was performed. Clinical and radiographic data were collected and used to develop a scoring system to predict aneurysm occlusion.

RESULTS

A total of 74 bifurcation aneurysms were treated with single stent-assisted coiling. At a median follow-up of 15.2 mo, complete occlusion or remnant neck was achieved in 90.6% of aneurysms. Aneurysm location, maximal diameter, neck size, and alpha angle were predictive of aneurysm occlusion at last follow-up. A scoring system to predict complete occlusion based on these factors was developed. An increasing score correlated with a higher rate of complete occlusion.

CONCLUSION

The treatment of bifurcation aneurysm using single stent technique for stent-assisted coiling is safe and effective. Complete occlusion or remnant neck occlusion was achieved in 90.6% of cases. Class III aneurysms can be effectively treated using a single stent, while class I may require Y-stent technique.
U.S. Women’s Movements to End Violence against Women, Domestic Abuse, and Rape
Authors: Arnold Gretchen
Published: May 2017

Movements to end violence against women in the United States have brought the issues of rape, incest, wife-beating, and sexual harassment to public attention, given birth to community support systems for survivors, laid the foundation for research, and triggered significant cultural change. However, they have not been without their critics. After tracing the history of the battered women’s and the anti-rape movements, this chapter explores three areas of controversy surrounding both movements. The first is the charge that activists have abandoned their feminist political agendas and have become part of the social service mainstream. The second criticism is that the movements have excluded minority women and, as a result, have supported policies that do more harm than good. The third debate surrounds whether these movements have been co-opted by the state and are used more to regulate and control the poor and minorities than to challenge existing structures of power.
Gendered Activism and Outcomes
Authors: Leitz Lisa , Meyer David S.
Published: May 2017

U.S. women’s peace and anti-war activism grew from their involvement in the abolition and suffrage movements of the nineteenth century, and some have continued to foster women-focused organizations in the twenty-first century. This chapter examines the relationship between the historical development of women’s peace activism and a U.S. political system that frequently excluded women from international relations. Women enlarged the U.S. peace movement’s objectives to include issues of gender, but while some also advocated for racial and class equality, minority activists often faced prejudice and discrimination within the movement. Several tensions in women’s peace activism are explored, including the ideological debate between essentialists and social constructionists about the relationship of gender to war, as well as strategic and tactical debates between proponents of institutional politics and proponents of radical protest tactics. Involvement in this movement helped enhance women’s political and organizing skills and often nourished other activism, especially feminist activism.
Personality as a Situation
Authors: Asendorpf Jens B.
Published: May 2017

This chapter focuses on three key issues of the psychology of situations in the special case where a situation is defined by the personality of a (potential) interaction partner. First, any taxonomy of personality can be considered as a taxonomy of situations. This recognition provides a special twist to lexically derived personality taxonomies as they mainly originate from perceptions of others’ personality and, thus, from perceptions of situations. Second, in this special case statistical personality × situation interactions become personality × personality interactions, which are discussed from the perspective of the Actor-Partner Interdependence Model (APIM) and the Social Relations Model (SRM). Third, dynamical personality-environment transactions become personality–personality transactions, which are discussed from a developmental perspective. Implications for the psychology of situations are highlighted and a new model for personality × situation interactions is proposed, the Actor-Situation Interdependence Model (ASIM).
Associative Accounts of Causal Cognition
Authors: Le Pelley Mike E. , Griffiths Oren , Beesley Tom
Published: May 2017

Humans are clearly sensitive to causal structures—we can describe and understand causal mechanisms and make predictions based on them. But this chapter asks: Is causal learning always causal? Or might seemingly causal behavior sometimes be based on associations that merely encode the information that two events “go together,” not that one causes the other? This associative view supposes that people often (mis)interpret associations as supporting the existence of a causal relationship between events; they make the everyday mistake of confusing correlation with causation. To assess the validity of this view, one must move away from considering specific implementations of associative models and instead focus on the general principle embodied by the associative approach—that the rules governing learning are general-purpose, and so do not differentiate between situations involving cause–effect relationships and those involving signaling relationships that are non-causal.
Reinforcement Learning and Causal Models
Authors: Gershman Samuel J.
Published: May 2017

This chapter reviews the diverse roles that causal knowledge plays in reinforcement learning. The first half of the chapter contrasts a “model-free” system that learns to repeat actions that lead to reward with a “model-based” system that learns a probabilistic causal model of the environment, which it then uses to plan action sequences. Evidence suggests that these two systems coexist in the brain, both competing and cooperating with each other. The interplay of two systems allows the brain to negotiate a balance between cognitively cheap but inaccurate model-free algorithms and accurate but expensive model-based algorithms. The second half of the chapter reviews research on hidden state inference in reinforcement learning. The problem of inferring hidden states can be construed in terms of inferring the latent causes that give rise to sensory data and rewards. Because hidden state inference affects both model-based and model-free reinforcement learning, causal knowledge impinges upon both systems.
Causation and the Probability of Causal Conditionals
Authors: Over David E.
Published: May 2017

Indicative and counterfactual conditionals are central to reasoning in general and causal reasoning in particular. Normative theorists and psychologists have held a range of views on how natural language indicative and counterfactual conditionals, and probability judgments about them, are related to causation. There is the question of whether “causal” conditionals, referring to possible causes and effects, can be used to explain causation, or whether causation can be used to explain the conditionals. There are questions about how causation, conditionals, Bayesian inferences, conditional probability, and imaging are related to each other. Psychological results are relevant to these questions, including findings on how people make conditional inferences and judgments about possibilities, conditionals, and conditional probability. Deeper understanding of the relation between causation and conditionals will come in further research on people’s reasoning from counterfactuals as premises, and to counterfactuals as conclusions.
Documentary Archaeology
Authors: Beaudry Mary C.
Published: May 2017

Documentary archaeology involves a process that is begun afresh for each archaeological site or research project: that of ‘constructing the archive’ through integrating differing lines of evidence. For historical archaeologists, the archive includes written records, oral traditions, and material culture; often elements of the archive provide overlapping, conflicting, or entirely different insights into the past, requiring resolution and integration because of differences in scale, completeness, representativeness, temporal resolution, and lack of correspondence. This chapter explores how historical archaeologists use and analyse textual sources in writing archaeological narratives and considers the intertextuality of sources by analysing contrasting examples of success and of failure in attempts to establish a dialogue between above-ground and below-ground evidence.
Historical Change and the Competitive Advantage of Firms
Authors: Wadhwani R. Daniel , Jones Geoffrey
Published: May 2017

This chapter aims to deepen the scholarly dialogue between strategy and history. It does so by examining how historical models of change can contribute to theory and research on the competitive advantage of firms during periods of rapid innovation. Focusing on the dynamic capabilities framework, it shows how three models of historical change—evolutionary, dialectical, and constitutive—can be used to extend theory and deepen research about the origins, context, and micro-foundations of dynamic capabilities. We show how each model of historical change shaped the intellectual development of the dynamic capabilities framework, point to historical research that illustrates these processes, and discuss the methodological and conceptual implications for future research. We conclude by suggesting that recognizing and building on these historical models of change can provide a common conceptual language for a deeper dialogue between historians and strategy researchers.
Law and Social Norms
Authors: Carbonara Emanuela
Published: May 2017

Legal norms are often seen as a means to regulate behaviour when neither self-interest nor social norms produce the desired behaviour in individuals. This suggests, on the one hand, that the law should regulate those areas in which social norms do not exist and provide support and extra enforcement in those areas where social norms exist. It also suggests on the other hand that there seems to be no questioning of the intrinsic efficiency and fairness of existing social norms. This article first looks at the genesis of social norms and the mechanism of their enforcement. This allows a closer inspection of the efficiency and fairness concepts. It then considers the impact that introducing legal norms has in contexts in which social norms already exist and in those that social interaction left unregulated. The main issue here is that the social norms prevailing at some historical moment may be just an equilibrium among multiple equilibriums. Given many possible equilibriums, we need to explain why and how one equilibrium is selected and others are rejected. The scholarship on social norms emphasizes that expressive acts in law can select the equilibrium. Legal norms seemingly reinforce existing social norms, bending them towards the law when discrepancy exists and favouring their creation where social norms do not exist. However, legal regulation can also destroy existing social norms (crowding out) or it can be defeated by them (legal backlash and countervailing effects).
Reliance Upon a Toxic Staple Crop
Authors: Wilson Warren , Dufour Darna L.
Published: May 2017

In Amazonia most indigenous horticulturists prefer to cultivate the more toxic forms of manioc as a staple crop, despite the increased processing required to render them safe for consumption. This phenomenon has long intrigued anthropologists. In this chapter we describe the agricultural practices of the Tukanoan Indians in the North-west Amazon and explore their reliance on toxic varieties of manioc from agronomic, ecological, organoleptic, and ethnographic perspectives. Our findings indicate that the puzzling preference for a toxic staple crop may be explained by the higher yields produced by the more toxic forms, and also that the most salient factor in variety selection by Tukanoan women is the food into which the roots will be made. This suggests a multifaceted explanation. Moreover, we propose that present-day lack of concern about yield is a recent luxury due to artificial selection of sufficiently high-yielding manioc varieties during the development of this crop.
Ethiopic
Authors: Haile Getatchew
Published: May 2017

Ethiopia’s indirect relation to the Roman Empire justifies the inclusion of an article on its literature in this handbook. The country was one of the dioceses of the Alexandrian Church, which, in turn, was part of the Roman Empire until the Arabs conquered it in 642 ce. With this in mind, the article discusses two types of literature: epigraphs in Sabaic, Greek, and Gǝ‛ǝz languages, most of which were created before Christianity was introduced into Ethiopia in the fourth century, and Christian literature created in the Gǝ‛ǝz language and written on parchment. This second type is basically a translation from Greek sources from the Coptic Church of Alexandria. Most of the locally composed texts, which are also religious in nature, are sermons by Copts who came as metropolitans of the Aksumite Church.
COMBINED PARS PLANA VITRECTOMY AND SCLERAL FIXATION OF AN INTRAOCULAR LENS USING GORE-TEX SUTURE
Authors: Khan M. Ali , Samara Wasim A. , Gerstenblith Adam T. , Chiang Allen , Mehta Sonia , Garg Sunir J. , Hsu Jason , Gupta Omesh P.
Published: May 2017

Purpose:

To report the 1-year clinical outcomes of combined pars plana vitrectomy and ab externo scleral fixation of an intraocular lens using Gore-Tex suture.

Methods:

Retrospective, interventional case series. Outcome measures were change in visual acuity and occurrence of intraoperative and postoperative complications with minimum follow-up of 1 year.

Results:

Eighty-four eyes of 83 patients were identified. The mean best available visual acuity improved from 20/782 preoperatively to 20/65 postoperatively (P < 0.001). The mean follow-up was 598 ± 183 days (median 533 days, range 365–1,323 days). There were no intraoperative complications noted. A Bausch & Lomb Akreos AO60 intraocular lens was implanted in 77 eyes and an Alcon CZ70BD in 7 eyes. Postoperative complications included transient vitreous hemorrhage in six eyes (7.1%), cystoid macular edema in four eyes (4.8%), ocular hypertension in three eyes (3.6%), hyphema in two eyes (2.4%), and transient corneal edema in two eyes (2.4%). There were no cases of postoperative endophthalmitis, suture erosion/breakage, hypotony, retinal detachment, suprachoroidal hemorrhage, choroidal detachment, uveitis–glaucoma–hyphema syndrome, or persistent postoperative inflammation during the follow-up period.

Conclusion:

Combined pars plana vitrectomy and ab externo scleral fixation of an intraocular lens with Gore-Tex suture was well tolerated at a minimum of 1-year follow-up. No suture-related complications were encountered.
Can the Pediatric Logistic Organ Dysfunction-2 Score on Day 1 Be Used in Clinical Criteria for Sepsis in Children?*
Authors: Leclerc Francis , Duhamel Alain , Deken Valérie , Grandbastien Bruno , Leteurtre Stéphane
Published: May 2017

Objective:

A recent task force has proposed the use of Sequential Organ Failure Assessment in clinical criteria for sepsis in adults. We sought to evaluate the predictive validity for PICU mortality of the Pediatric Logistic Organ Dysfunction-2 and of the “quick” Pediatric Logistic Organ Dysfunction-2 scores on day 1 in children with suspected infection.

Design:

Secondary analysis of the database used for the development and validation of the Pediatric Logistic Organ Dysfunction-2.

Settings:

Nine university-affiliated PICUs in Europe.

Patients:

Only children with hypotension—low systolic blood pressure or low mean blood pressure using age-adapted cutoffs—and lactatemia greater than 2 mmol/L were considered in shock.

Measurements and Main Results:

We developed the quick Pediatric Logistic Organ Dysfunction-2 score on day 1 including tachycardia, hypotension, and altered mentation (Glasgow < 11): one point for each variable (range, 0–3). Outcome was mortality at PICU discharge. Discrimination (Area under receiver operating characteristic curve-95% CI) and calibration (goodness of fit test) of the scores were studied. This study included 862 children with suspected infection (median age: 12.3 mo; mortality: n = 60 [7.0%]). Area under the curve of the Pediatric Logistic Organ Dysfunction-2 score on day 1 was 0.91 (0.86–0.96) in children with suspected infection, 0.88 (0.79–0.96) in those with low systolic blood pressure and hyperlactatemia, and 0.91 (0.85–0.97) in those with low mean blood pressure and hyperlactatemia; calibration p value was 0.03, 0.36, and 0.49, respectively. A Pediatric Logistic Organ Dysfunction-2 score on day 1 greater than or equal to 8 reflected an overall risk of mortality greater than or equal to 9.3% in children with suspected infection. Area under the curve of the quick Pediatric Logistic Organ Dysfunction-2 score on day 1 was 0.82 (0.76–0.87) with systolic blood pressure or mean blood pressure; calibration p value was 0.89 and 0.72, respectively. A score greater than or equal to 2 reflected a mortality risk greater than or equal to 19.8% with systolic blood pressure and greater than or equal to 15.9% with mean blood pressure.

Conclusion:

Among children admitted to PICU with suspected infection, Pediatric Logistic Organ Dysfunction-2 score on day 1 was highly predictive of PICU mortality suggesting its use to standardize definitions and diagnostic criteria of pediatric sepsis. Further studies are needed to determine the usefulness of the quick Pediatric Logistic Organ Dysfunction-2 score on day 1 outside of the PICU.
Impact of an Alcohol Withdrawal Treatment Pathway on Hospital Length of Stay: A Retrospective Observational Study Comparing Pre and Post Pathway Implementation
Authors: MUZYK ANDREW J. , ROGERS RACHEL E. , DIGHE GARY , HARTUNG JESSICA , MUSSER ROBERT C. , STILLWAGON MARY J. , RIVELLI SARAH
Published: May 2017

Objective:

To determine if the implementation of a hospital-specific alcohol withdrawal treatment pathway used in a medical-surgical patient population decreased hospital length of stay (LOS) compared with the standard of care.

Methods:

This retrospective observational study, conducted in a large academic tertiary care hospital, involved 582 subjects who met criteria for study inclusion, with 275 subjects in the 2010 cohort and 307 in the 2012 cohort. The Alcohol Withdrawal Project Team was formed with the goal of creating a standardized approach to the recognition and treatment of alcohol withdrawal at Duke University Hospital. The group created a computerized physician order entry alcohol withdrawal treatment pathway with 4 possible treatment paths chosen on the basis of current withdrawal symptoms, vital signs, and alcohol withdrawal history. The 4 treatment paths are 1 prophylaxis; 2 mild-to-moderate withdrawal; 3 moderate-to-severe withdrawal, and 4 severe withdrawal/alcohol withdrawal delirium. Each treatment path corresponds to a different lorazepam dose and dose schedule and symptom assessment. This pathway was implemented in the hospital at the end of 2011.

Results:

Using a Cox proportional hazards model and adjusting for covariates, there was a 1 day [95% confidence interval (CI), 1-2 d] reduction in median hospital LOS between the 2010 and 2012 cohorts, 5 versus 4 days, respectively. The average ratio in hospital LOS between the 2 cohorts was 1.25 (95% CI, 1.25-1.67). The CI was estimated by bootstrapping and indicated a significantly longer LOS in the 2010 cohort compared with the 2012 cohort. Nonsignificant changes were found in the proportion of subjects admitted to the intensive care unit (24% in 2010 vs. 29.3% in 2012), LOS in the intensive care unit (7.1±8 d in 2010 vs. 5.6±6.9 d in 2012), and proportion of patients discharged with a diagnosis of delirium tremens (17.8% in 2010 vs. 15.3% in 2012).

Conclusions:

This study demonstrates the successful implementation of an alcohol withdrawal treatment pathway in a medical-surgical population hospitalized in a large tertiary care facility with significant impact on hospital LOS.
The Prognostic Value of Central Venous-to-Arterial CO2 Difference/Arterial-Central Venous O2 Difference Ratio in Septic Shock Patients with Central Venous O2 Saturation ≥80%
Authors: He Huaiwu , Long Yun , Liu Dawei , Wang Xiaoting , Tang Bo
Published: May 2017

Background:

It is a great challenge for physician to assess the relationship between O2 delivery and O2 consumption in septic shock patients with high ScvO2. Recently, the venous-to-arterial CO2 difference/arterial-central venous O2 difference ratio (P(v-a)CO2/C(a-v)O2) has shown potential for reflecting anaerobic metabolism. Therefore, we evaluated the value of using the P(v-a)CO2/C(a-v)O2 ratio to predict mortality and assess anaerobic metabolism in septic shock patients with high ScvO2 (≥ 80%).

Methods:

This was a clinical investigation of septic shock patients on the P(v-a)CO2/C(a-v)O2 ratio in the intensive care unit (ICU) department. The patients’ arterial and central venous blood gas levels were measured simultaneously at enrollment (T0) and 24 h (T24) after resuscitation.

Results:

A total of 61 patients with high ScvO2 at T24 after resuscitation were selected for analysis. The ICU mortality rate in the septic shock patients was 20% (12/61). The nonsurvivors had a significantly higher P(v-a)CO2, P(v-a)CO2/C(a-v) O2 ratio, arterial lactate level and lower lactate clearance at T24 after resuscitation. The P(v-a)CO2/C(a-v)O2 ratio had the biggest the areas under the receiver operating characteristic (AUC) for predicting ICU mortality. For predicting ICU mortality, a threshold of P(v-a)CO2/C(a-v)O2 ratio ≥1.6 was associated with a sensitivity of 83% and a specificity of 63%. Multivariate analysis showed P(v-a)CO2/C(a-v)O2 ratio at both T0 (RR 5.597, P = 0.024) and T24 (RR 5.812, P = 0.031) was an independent predictor of ICU mortality. Including the ratio into the regression model showed a bigger AUC than without the ratio (0.886 vs. 0.833).

Conclusions:

The P(v-a)CO2/C(a-v)O2 ratio is an independent predictor of ICU mortality in septic shock patients with high ScvO2 after resuscitation. It is worthy of consideration to recruit microcirculation to correct the high ratio in high ScvO2 case.
Validity of Forced Eyelid Closure Test: A Novel Clinical Screening Test for Ocular Myasthenia Gravis
Authors: Apinyawasisuk Supanut , Zhou Xinkai , Tian Jack J. , Garcia Giancarlo A. , Karanjia Rustum , Sadun Alfredo A.
Published: May 2017

Background:

Forced eyelid closure test (FECT) is a clinical screening test developed from the original Cogan lid twitch (CLT) sign to assist in the diagnosis of ocular myasthenia gravis (OMG), We evaluated the sensitivity and specificity of FECT compared with CLT and benchmarked to standard diagnostic tests.

Methods:

This study was a retrospective chart review of 48 patients using electronic medical records of those that presented with ptosis and/or diplopia at Doheny Eye Institute, University of California, Los Angeles between February 2015 and April 2016. Patients without FECT testing were excluded. FECT and CLT results, and final diagnosis were recorded. To perform FECT, the patient was asked to squeeze his or her eyelids shut for 5–10 seconds then open quickly and fixate in primary position. The excessive upward overshoot of eyelids movement indicated a positive FECT. The test was performed by a neuro-ophthalmologist before establishing the diagnosis. Patients who had equivocal test results and/or inconclusive final diagnosis were excluded.

Results:

Of the 48 patients studied, 18 patients (37.5%) had positive FECT; 15 of whom had a final diagnosis of OMG (83.3%). Of the 30 patients with negative FECT, 1 had OMG (3.3%). Of the 48 patients, 35 patients also had a documented CLT result (72.9%). CLT was positive in 11 of these 35 patients (31.4%), and 9 of these 11 had OMG (81.8%). Of the 24 patients with negative CLT, 2 of them had OMG (8.3%). Sensitivity and specificity of FECT were 94% and 91% (joint 95% confidence region: sensitivity × specificity = [0.70, 1] × [0.75, 1]). The relative true-positive fraction (rTPF) between FECT and CLT was 1.15; the relative false-positive fraction was 1.31.

Conclusions:

FECT is a simple clinical screening test with good sensitivity and specificity for OMG.
Targeting xCT-mediated glutamate release normalizes tumor angiogenesis in the brain
Authors: Fan Zheng , Broggini Thomas , Yakubov Eduard , Sehm Tina , Schürmann Sebastian , Meyer Eric P. , Stankovic Nevenka Dudvarski , Schmidt Mirko HH. , Stampanoni Marco , Czabanka Marcus A. , Nitsch Robert , Buchfelder Michael , Friedrich Oliver , Eyupoglu Ilker Y. , Savaskan Nicolai E.
Published: May 2017

Brain tumors are among the most malignant primary tumors, hallmarked by angiogenesis, neuronal destruction and brain swelling. Inhibition of the glutamate-cystein antiporter xCT (system xc−/SLC7A11) alleviates seizures, neuronal cell death and tumor-associated brain edema. Here we show enhanced tumor vessel growth and increased brain edema in xCT-expressing brain tumors. Furthermore, xCT-mediated glutamate impacts directly on endothelial cells in an N-methyl-D-aspartate receptor (NMDAR) dependent manner with intracellular Ca2+release. Cerebral intravital microscopy revealed that xCT-driven tumor vessels are functional and display increased permeability. Endothelial-cell-specific NMDAR1 knockout mice (GRINiΔEC) show suppressed endothelial sprouting and vascular density compared to control littermates. In addition, implanted gliomas in GRINiΔECmice display reduced tumor vessels in contrast to gliomas in wildtype animals. Moreover, therapeutic targeting of xCT in gliomas alleviates tumor angiogenesis to normalized levels comparable to controls. Our data reveal that xCT and its substrate glutamate specifically operate on endothelial cells and promote neoangiogenesis. Thus, targeting xCT expression and glutamate secretion in gliomas provides a novel therapeutic roadmap for normalizing tumor angiogenesis.
ORGANOID AND TISSUE PATTERNING THROUGH PHASE SEPARATION: USE OF A VERTEX MODEL TO RELATE DYNAMICS OF PATTERNING TO UNDERLYING BIOPHYSICAL PARAMETERS
Authors: Waites William , Cavaliere Matteo , Cachat Élise , Danos Vincent , Davies Jamie A.
Published: May 2017

Abstract

Exactly a century ago, D’Arcy Thompson set an agenda for understanding tissue development in terms of underlying biophysical, mathematically-tractable mechanisms. One such mechanism, discovered by Steinberg in the 1960s, is adhesion-mediated sorting of cell mixtures into homotypic groups. Interest in this phase separation mechanism has recently surged, partly because of its use to create synthetic biological patterning mechanisms and partly because it has been found to drive events critical to the formation of organoids from stem cells, making the process relevant to biotechnology as well as to basic development. Here, we construct quantitative model of patterning by phase separation, informed by laboratory data, and use it to explore the relationship between degree of adhesive difference and speed, type and extent of resultant patterning. Our results can be used three ways; to predict the outcome of mix-ing cells with known properties, to estimate the properties required to make some designed organoid system, or to estimate underlying cellular properties from observed behaviour.
Diversity of biocrust-forming cyanobacteria in a semiarid gypsiferous site from Central Spain
Authors: Cano-Díaz Concha , Mateo Pilar , Ángeles Muñoz M. , Maestre Fernando T.
Published: May 2017

Cyanobacteria are an important constituent of biocrusts, communities dominated by lichens, mosses and associated microorganisms, which are prevalent in drylands worldwide and that largely determine their functioning. Despite their importance, there are large gaps in our knowledge of cyanobacteria associated to biocrusts, particularly in areas such as the Mediterranean Basin. We studied the diversity of these cyanobacteria in a gypsiferous grassland from Central Spain using both morphological identification after cultivation and genetic analyses with the 16S rRNA gene. Eight different morphotypes were observed, most of them corresponding to filamentous and one of them to unicellular cyanobacteria. We found cyanobacterial genera typical of biocrust communities, such asMicrocoleus,SchizothrixorTolypothrix, and N-fixing cyanobacteria asScytonemaorNostoc. Genetic information allowed us to identify cultures belonging to recently described genera such asRoholtiella,NodosilineaandMojavia. In this study we describe two new phylotypes ofMicrocoleusandScytonema, which are key genera contributing to ecosystem functioning in biocrust-dominated ecosystems worldwide.
The Evolution of Small-RNA-Mediated Silencing of an Invading Transposable Element
Authors: Kelleher Erin S. , Azevedo Ricardo B. R. , Zheng Yichen
Published: May 2017

Transposable elements (TEs) are genomic parasites that impose fitness costs on their hosts by producing deleterious mutations and disrupting gametogenesis. Host genomes avoid these costs by regulating TE activity, particularly in germline cells where new insertions are heritable and TEs are exceptionally active. However, the capacity of different TE-associated fitness costs to select for repression in the host, and the role of selection in the evolution of TE regulation more generally, remain controversial. In this study, we use forward, individual-based simulations to examine the evolution of small-RNA-mediated TE regulation, a conserved mechanism for TE repression that is employed by both prokaryotes and eukaryotes. To design and parameterize a biologically realistic model, we drew on an extensive survey of empirical studies of the transposition and regulation ofP-element DNA transposons inDrosophila melanogaster. We observed that even under conservative assumptions, where small-RNA-mediated regulation reduces transposition only, repression evolves rapidly and adaptively after the genome is invaded by a new TE. We further show that the spread of repressor alleles is greatly enhanced by two additional TE-imposed fitness costs: dysgenic sterility and ectopic recombination. Finally, we demonstrate that the mutation rate to repression (i.e., the size of the mutational target) is a critical parameter that influences both the evolutionary trajectory of host repression and the associated proliferation of TEs after invasion. Our findings suggest that adaptive evolution of TE regulation may be stronger and more prevalent than previously appreciated, and provide a framework for evaluating empirical data.
Imp/Syp temporal gradients govern decommissioning ofDrosophilaneural stem cells
Authors: Yang Ching-Po , Samuels Tamsin J. , Huang Yaling , Yang Lu , Ish-Horowicz David , Davis Ilan , Lee Tzumin
Published: May 2017

Timing ofDrosophilaneuroblast decommissioning is controlled in a lineage-specific manner. Following a prepupal ecdysone pulse, the ecdysone receptor and mediator complex cause neuroblasts to shrink. Shrinking is followed by nuclear accumulation of Prospero and cell cycle exit. Only mushroom body (MB) neuroblasts escape early pupal termination. Here, we demonstrate that the opposing temporal gradients of Imp and Syp RNA-binding proteins that govern temporal fate also regulate neuroblast decommissioning. The Imp gradient declines slower in MB neuroblasts so they still express Imp when it is absent from others. The presence of Imp in MB neuroblasts prevents decommissioning partly through inhibiting the mediator complex. Moreover, a timely induction of Imp can protect many non-MB neuroblasts from aging. We also show that the increasing Syp gradient permits Prospero accumulation and neuroblast termination. Together our results reveal that progeny temporal fate and progenitor decommissioning are co-regulated in protracted neuronal lineages.
Somatic uniparental disomy of Chromosome 16p in hemimegalencephaly
Authors: Griffin Nicole G. , Cronin Kenneth D. , Walley Nicole M. , Hulette Christine M. , Grant Gerald A. , Mikati Mohamad A. , LaBreche Heather G. , Rehder Catherine W. , Allen Andrew S. , Crino Peter B. , Heinzen Erin L.
Published: May 2017

Hemimegalencephaly (HME) is a heterogeneous cortical malformation characterized by enlargement of one cerebral hemisphere. Somatic variants in mammalian target of rapamycin (mTOR) regulatory genes have been implicated in some HME cases; however, ∼70% have no identified genetic etiology. Here, we screened two HME patients to identify disease-causing somatic variants. DNA from leukocytes, buccal swabs, and surgically resected brain tissue from two HME patients were screened for somatic variants using genome-wide genotyping arrays or sequencing of the protein-coding regions of the genome. Functional studies were performed to evaluate the molecular consequences of candidate disease-causing variants. Both HME patients evaluated were found to have likely disease-causing variants in DNA extracted from brain tissue but not in buccal swab or leukocyte DNA, consistent with a somatic mutational mechanism. In the first case, a previously identified disease-causing somatic single nucleotide in MTOR was identified. In the second case, we detected an overrepresentation of the alleles inherited from the mother on Chromosome 16 in brain tissue DNA only, indicative of somatic uniparental disomy (UPD) of the p-arm of Chromosome 16. Using methylation analyses, an imprinted locus on 16p spanning ZNF597 was identified, which results in increased expression of ZNF597 mRNA and protein in the brain tissue of the second case. Enhanced mTOR signaling was observed in tissue specimens from both patients. We speculate that overexpression of maternally expressed ZNF597 led to aberrant hemispheric development in the patient with somatic UPD of Chromosome 16p possibly through modulation of mTOR signaling.