bluuebunny/crossref_metadata_2025 huggingface dataset:
Using amniotic membrane for anal sphincter repair in animal model
Authors: Izadpanah Ahmad , Rezazadehkermani Mohammad , Ghaderi Mohammadali , Rahimikazerooni Salar , Safarpour Alireza , Homayouni Kaynoosh , Mokhtari Maral , Bananzadeh Alimohammad
Published: February 2016

Purpose Sphincter repair is the primary management for fecal incontinence especially in traumatic causes. Regardless of progression in the method and material of sphincter repair, the results are still disappointing. This study evaluates the efficacy of using amniotic membrane during sphincteroplasty regarding its effects in healing of various tissues.

Methods Rabbits undergone sphincterotomy and after three weeks end to end sphincteroplasty was done. Animals divided to three groups: classic sphincteroplasty, sphincteroplasty with fresh amniotic membrane and sphincteroplasty with decellularized amniotic membrane. Three weeks after sphincteroplasty animals were sacrificed and sphincter complex was sent for histopathologic evaluation. Sphincter muscle diameter and composition of sphincter was evaluated. Before sphincterotomy, before and after sphincteroplasty electromyography of sphincter at the site of repair were recorded.

Results No statistical significant difference was seen between groups even in histopathology or electromyography.

Conclusion Although amniotic showed promising effects in the healing of different tissue in animal and human studies it was not effective in healing of injured sphincter.
Telling Reflections: Teaching Sustainably in a Complex Learning Environment
Authors: Prescott Debbie
Published: February 2016

This article examines learning design in a postgraduate preservice teacher setting. The overarching aim was to embed environmentally responsive approaches throughout two companion units for diverse student cohorts. This article reports on a teacher educator self-study in a regional university with extensive online delivery for large units (300–800 students) in a 1-year course. The author examines how assessment tasks in literacy- and numeracy-oriented units are designed to meaningfully integrate environmental sustainability using contextual cues, collaborative learning, complex tasks, and reflexivity. The author argues for the use of these four key guidelines of environmentally responsive pedagogies alongside environmental education programs to emphasise messages of sustainability even in units that are not traditionally environmentally oriented. Challenges include problematising the nature of effective teaching and dealing with the complexities of purposeful learning. Innovative unit learning design alone, however, is inadequate if the surrounding systems are fragmented and seen as separate to learning about sustainability.
Why Law Matters by Alon Harel*
Authors: Weinrib Jacob
Published: February 2016

Alon Harel’sWhy Law Mattersarticulates a powerful and neglected approach for justifying legal institutions.  Pushing back against the instrumentalist approach that dominates contemporary legal theory, he argues that legal institutions are not simply tools for realizing extrinsic values, but are themselves constitutive features of a just society.  On this view, law is not an instrument for bringing about something that matters; rather, law itself matters and Harel elaborates a series of rich and insightful arguments to explain why.  In this brief review, I will sketch the connection between Harel’s non-instrumental methodology and his account of (1) the nature of rights, (2) the distinctiveness of state authority, and (3) the justificatory basis of constitutional governance.  I close with some critical comments about the non-instrumental justifications that Harel develops.
Staying Busy While Doing Nothing? Dworkin’s Complicated Relationship with Pragmatism
Authors: Nye Hillary
Published: February 2016

Ronald Dworkin was an outspoken critic of pragmatism, and engaged in extensive and at times virulent disagreements with Richard Posner and Richard Rorty. Yet, I argue here, that Dworkin himself had a number of deeply pragmatist commitments. I examine how we can square these two aspects of Dworkin’s thought. I suggest that part of the answer lies in seeing that there are different strands of pragmatism, and that Dworkin falls on the more objective, Peircean side of the divide, while Rorty and Posner belong more in the skeptical, Jamesian camp. But even with this distinction in mind, we should note the substantial overlap between the views of Dworkin and his pragmatist interlocutors—in particular, their anti-archimedeanism and their rejection of metaphysics. Attentiveness to this shared perspective is helpful in illuminating Dworkin’s disagreements with legal positivists. The more foundational divide, I argue, is between analytic legal philosophers who aim to provide an account of the metaphysics of law, and those, like Dworkin and the pragmatists, who reject such a project. I conclude by discussing the implications of Dworkin’s pragmatism for legal philosophy. I argue that it may lead to what some have recently called ‘eliminativism’, and engage with some new and prominent work on this current topic in legal philosophy.
Corporate Criminals and Punishment Theory
Authors: Rich Sylvia
Published: February 2016

Corporations are subject to criminal law and sentencing provisions in most legal jurisdictions in the world. This article considers how leading punishment theories apply to corporations. Corporations are, this article argues, group agents with the capacity to make moral judgments. It follows from this that retributivism, the dominant theory of punishment for moral agents, ought to be understood as a component justification of corporate punishment. However, a more fundamental problem arises in the attempt to apply punishment theory to corporations: punishment involves suffering, and corporations cannot suffer in the relevant sense. This means that corporations cannot be punished, though they can be harmed. I explore the possibilities of simply abandoning the word ‘punishment’ and creating sentences that are not at the same time punishments. This has the drawback of limiting what the criminal law can accomplish when it comes to addressing corporate malfeasance. I find that at least one practical consequence for corporate sentencing follows from this theoretical distinction: sentencers have more legitimate authority to raise upper limits for sentences for corporations than they do for individuals, though there are still principles that dictate the need for upper limits. Despite the impossibility of true punishment, the theories of retributivism, deterrence and rehabilitation are still relevant when sentencing corporations.
Federal-State Jural Relations: A Neo-Hohfeldian Approach to the Study of Federalism
Authors: Sagar Arun
Published: February 2016

The division of powers between Federal and State governments and its interpretation by constitutional courts are fundamental elements of a federal system and of Federal-State power relations. The exclusivity or concurrence of powers, supremacy, and the problem of implied powers are some of the issues that appear in the constitutional law of most federations, and indeed stem from the very logic of a federal structure. However, the theoretical literature on federalism has not produced any satisfactory explanation of this logic. This article shows how W.N. Hohfeld’s fundamental legal conceptions may be used to analyse Federal-State relations, and how they are directly applicable in the context of ‘intergovernmental immunities’. The article then elaborates a theory of ‘tertiary’ legal relations, i.e., those arising when the two levels of government act in their regulatory capacity; these relations flow from the triangular nature of the relationship between the two governments and those subject to legislation. The correlations identified between Federal and State powers provide a conceptual framework within which different constitutional questions may be analysed. Adopting Hohfeld’s method of highlighting legal concepts in extracts from judicial decisions, the article uses examples from the case-law of several different federal countries.
Inner–outer interactions of large-scale structures in turbulent channel flow
Authors: Hwang Jinyul , Lee Jin , Sung Hyung Jin , Zaki Tamer A.
Published: February 2016

Direct numerical simulation data of turbulent channel flow ($Re_{{\it\tau}}=930$) are used to investigate the statistics of long motions of streamwise velocity fluctuations ($u$), and the interaction of these structures with the near-wall disturbances, which is facilitated by their associated large-scale circulations. In the log layer, the negative-$u$ structures are organized into longer streamwise extent (${>}3{\it\delta}$) in comparison to the positive-$u$ counterparts. Near the wall, the footprint of negative-$u$ structures is relatively narrow in comparison to the footprint of positive-$u$ structures. This difference is due to the opposite spanwise motions in the vicinity of the footprints, which are either congregative or dispersive depending on the circulation of the outer roll cells. Conditional sampling of the footprints shows that the spanwise velocity fluctuations ($w$) are significantly enhanced by the dispersive motions of high-speed structures. On the other hand, the near-wall congregative motions of negative-$u$ structures generate relatively weak $w$ but intense negative-$u$ regions due, in part, to the spanwise collective migration of near-wall streaks. The concentrated near-wall regions of negative-$u$ upwell during the merging of the outer long scales – an effect that is demonstrated using statistical analysis of the merging process. This leads to a reduction of the convection speed of downstream negative-$u$ structures and thus promotes the merging with upstream ones. These top-down and bottom-up interactions enhance the spatial coherence of long negative-$u$ structures in the log region.
Analysis of Agreement between Expired-Air Carbon Monoxide Monitors
Authors: Karelitz Joshua L. , Michael Valerie C. , Perkins Kenneth A.
Published: February 2016

Introduction: The current study examined the level of agreement in expired-air carbon monoxide (CO) values, focusing especially on those confirming abstinence, between the two most commonly used CO monitors, the Vitalograph BreathCO and the Bedfont piCO+ Smokerlyzer.

Methods: Expired-air samples were collected via both monitors from adult dependent smokers (44 M, 34 F) participating in studies using CO values to confirm abstinence durations of: 24 hours, 12 hours, or no abstinence. All met DSM-IV nicotine dependence criteria and had a mean (SD) Fagerström Test of Cigarette Dependence score of 5.1 (1.8). Paired data collected across multiple visits were analyzed by regression-based Bland–Altman method of Limits of Agreement (LoA).

Findings: Analysis indicated a lack of agreement in CO measurement between monitors. Overall, the Bedfont monitor gave mean (±SEM) readings 3.83 (±0.23) ppm higher than the Vitalograph monitor. Mean differences between monitors were larger for those ad lib smoking (5.65 ± 0.38 ppm) than those abstaining 12–24 hours (1.71 ± 0.13 ppm). Yet, there also was not consistent agreement in classification of 24-hour abstinence between monitors.

Conclusions: Systematic differences in CO readings demonstrate these two very common monitors may not result in interchangeable values, and reported outcomes in smoking research based on CO values may depend on the monitor used.
The Global Laboratory of Tobacco Control: Research to Advance Tobacco Cessation in LMICs
Authors: Parascandola Mark , Bloch Michele
Published: February 2016

For over half a century, the U.S. National Cancer Institute (NCI) has supported research on tobacco and health, which has contributed to reductions in tobacco-caused morbidity and mortality in the U.S. But while tobacco use has been slowly declining in most high-income nations, including the US, it has continued to increase in other parts of the globe. Of the 800 million adult men who currently smoke cigarettes, over 80% are in low- and middle-income countries (LMICs), and these countries will bear an increasing share of the health and economic burden of tobacco use. At the same time, there are additional challenges to implementing tobacco control programs in LMICs, including a diversity of tobacco products, limited capacity and resources for tobacco control, and competing health priorities. While a large body of evidence has been generated around tobacco dependence treatment and other measures in high-income countries, this work is only partly applicable to many LMICs. In this paper we focus on research needs and opportunities around tobacco cessation interventions for LMICs, highlighting four areas: understanding diverse tobacco products, development of low-cost cessation interventions, integrating tobacco cessation into health systems, and understanding tobacco use behaviors across different contexts. Expanding tobacco control research and research capacity in LMICs is crucial to reducing tobacco use and cancer rates worldwide. Furthermore, research conducted in countries around the world can yield important insights for understanding tobacco use behaviors and the effectiveness of tobacco control interventions in the US.
Prevalence of Haemoproteus sp. in Galápagos blue-footed boobies: effects on health and reproduction
Authors: LEE-CRUZ LARISA , CUNNINGHAM ANDREW A. , MARTÍNEZ PAMELA , CRUZ MARILYN , GOODMAN SIMON J. , HAMER KEITH C.
Published: February 2016

Populations of blue-footed boobies in the Galápagos Islands have declined by at least 50% compared with numbers recorded during the 1960s. Recently, concern has been expressed about potential adverse effects of introduced blood parasites; in particular, malarial parasites (i.e.Plasmodiumsp.), which are frequently pathogenic and can cause mortality and morbidity in birds, and blood parasites of the genusHaemoproteus, which can reduce fitness. We screened blue-footed boobies at six breeding colonies within Galápagos for both genera of parasite. At two sites, we also investigated whether there was any relationship between infection status and physiological condition or breeding success. We found a high prevalence ofHaemoproteusspp. in adults and chicks using PCR, although none was found on blood smears. We found no evidence ofPlasmodium.Effects of parasitism on the condition of birds were limited. Also, there was no evidence that infection withHaemoproteusadversely affected breeding success or chick growth. Our results suggest that poor success of breeding birds was not strongly associated withHaemoproteusinfection. However, regular colony monitoring and examination of dead birds are necessary to assess whether acuteHaemoproteusinfection might be responsible for some mortality, particularly of chicks.
Multiculturalisme et laïcité en France : les trois républicanismes du rapport Stasi
Authors: LEYVA KAREL
Published: February 2016

Dès les dernières décennies du XXesiècle, le républicanisme a été l’objet d’un intérêt renouvelé au sein de la théorie politique contemporaine. En France, c’est surtout à partir de 1989 que ce renouveau se constate. Certains défis posés par la diversité culturelle et religieuse occupent dès lors le devant de la scène philosophique, et il est possible de distinguer une pluralité de perspectives, chacune se réclamant d’interprétations spécifiques du républicanisme et, par conséquent, se positionnant différemment pour répondre à ces défis. Sur cet horizon, l’article situe le rapport de la Commission de réflexion sur l’application du principe de laïcité dans la République.
Raymond Klibansky (1905-2005) : un philosophe engagé
Authors: GROFFIER ETHEL
Published: February 2016

Présentation:

L’année 2015 marque le dixième anniversaire de la mort de Raymond Klibansky, philosophe et historien des idées canadien. La revueDialoguelui rend hommage en publiant le texte qui suit de Mme Ethel Groffier, veuve de Raymond Klibansky et chercheure émérite au Centre de recherche Paul-André Crépeau en droit privé et comparé de l’Université McGill. Dans cette intervention, Mme Groffier rappelle l’importance de l’engagement dans la vie et l’œuvre de ce remarquable philosophe.

Né en France au mois d’octobre 1905 dans une famille allemande, éduqué en Allemagne à partir de la Première guerre, exilé en Angleterre en 1933, Raymond Klibansky s’installa à Montréal dès 1946, à l’invitation de l’Université McGill. Sa carrière académique au Canada et à l’étranger fut admirable et reconnue par de nombreux hommages. Il laisse derrière lui une œuvre imposante, tant en philosophie qu’en histoire des idées modernes; parmi ces idées, il s’attacha particulièrement à la tolérance et à la liberté, qui inspirèrent toute sa vie.

Luc Langlois
Evidence for prey preference partitioning in the middle Eocene high-diversity crocodylian assemblage of the Geiseltal-Fossillagerstätte, Germany utilizing skull shape analysis
Authors: HASTINGS ALEXANDER K. , HELLMUND MEINOLF
Published: February 2016

The Geiseltal fossil collection from southern Sachsen-Anhalt Germany contains remarkably well-preserved fossils of middle Eocene age. These include several crocodylian skulls, representing at least four different genera with a fifth genus represented by two mandibular rami. As sites with this many crocodylian genera are unknown in modern ecosystems, it has been hypothesized that these crocodylians may have differences in habit as compared to living crocodylians. In order to test similarities between the Geiseltal crocodylians and extant species, an analysis was conducted using geometric morphometrics to quantify shape in crocodylian skulls of all living species (n= 218) and all well-preserved crocodylian skulls of the Geiseltal fauna (n= 28). A relative warps analysis was used to quantify and compare skull shape, revealingAllognathosuchusandBoverisuchusto be very distinct from each other as well as fromAsiatosuchusandDiplocynodon. Overlap in shape alone exists between someDiplocynodonand someAsiatosuchus, but there was significant difference in adult size. When compared with extant crocodylians, three Geiseltal genera occupied distinctly non-modern morphospace in the first two relative warps axes. Comparison of the diets of living crocodylians with similarly shaped skulls was used to reconstruct the prey preferences of the Geiseltal crocodylians, revealing differences in specialization. During the middle Eocene high global temperatures, partitioning of prey preference may have allowed this group to attain its higher than usual diversity, reducing the amount of direct competition.
The vomeronasal organ – incidence in a Bulgarian population
Authors: Stoyanov G , Moneva K , Sapundzhiev N , Tonchev A B
Published: February 2016

Background:

The vomeronasal organ is an accessory olfactory organ found in vertebrates that specialises in the chemoreception of pheromones. This study aimed to explore the existence and occurrence of the vomeronasal organ in adult humans.

Methods:

A total of 966 consecutive video recordings of out-patient nasopharyngolaryngoscopies performed at the St Marina University Hospital, Varna, Bulgaria, were retrospectively reviewed.

Results:

Data analysis showed that from the evaluable cases, the organ was evident on the left side of the nasal septum in 14.93 per cent, on the right side in 21.15 per cent and bilaterally in 2.35 per cent of cases. The vomeronasal organ was present in a total of 26.83 per cent of the investigated subjects.

Conclusion:

More research should be focused on revealing the incidence and functionality of the organ, and on its preservation in surgical manipulations that affect the nasal septum and other nearby structures.
Last of the green: identifying priority sites to prevent plant extinctions in Brazil
Authors: Diniz Milena F. , Gonçalves Tatiel V. , Brito Daniel
Published: February 2016

The identification and protection of Alliance for Zero Extinction sites at the national level is of great importance to safeguard biodiversity and achieve the targets of the Convention on Biological Diversity for 2020. Here we identify priority species and sites for the Brazilian flora. We evaluated the protection status of each site, taking into account whether or not it was located within a protected area, and the anthropogenic pressure on the site, using human density and gross domestic product as surrogates. We identified a total of 234 trigger species at 140 sites. Most of the sites are located in the Atlantic Forest and the Cerrado; only 21 are within protected areas. There was no relationship of human density and annual gross domestic product per capita with the level of site protection. The low proportion of Alliance for Zero Extinction sites protected shows that Brazil is lagging behind in global conservation efforts to protect such sites.
PHILOSOPHY AND MEDICINE IN JEWISH PROVENCE,ANNO1199: SAMUEL IBN TIBBON AND DOEG THE EDOMITE TRANSLATING GALEN'STEGNI
Authors: Freudenthal Gad , Fontaine Resianne
Published: February 2016

Galen'sTechnê iatrikê(Tegni, for short) was translated into Hebrew three times. The first two translations were executed in the Midi, around the year 1199: once from Constantine the African's Latin version, by an anonymous physician who used the pseudonym “Doeg the Edomite”; and a second time from Arabic, by Samuel Ibn Tibbon in Béziers, using as hisVorlageḤunayn Ibn Isḥāq's Arabic version (al-Ṣināʿa al-saġīra), accompanied by ʿAlī Ibn Riḍwān's commentary. (Samuel Ibn Tibbon's authorship of this translation has been called into doubt, but is reestablished in a paper by Gad Freudenthal in this issue ofASP.) A third translation, again from Latin and including Ibn Riḍwān's commentary, was done by Hillel ben Samuel in Rome, in the late thirteenth century, but is not considered in this paper.

We present theTegniand discuss its history. We then ask why this work was translated into Hebrew twice, at precisely the same time and area. We show that both translators responded to the need of Jewish physicians who read only Hebrew. Doeg's translation was part of his vast project of making the greater part of the Salernitan corpus available in Hebrew. Samuel Ibn Tibbon translated theTegniwith Ibn Riḍwān's commentary both because he was responding to a social need and because he was in the process of switching his profession from physician to translator of philosophic works. Galen's medico-philosophic text was a perfect fit for his intellectual evolution from a philosophically minded physician to a philosopher-scientist.
DIALECTICIANS AND DIALECTICS IN AVERROES’LONG COMMENTARYON GAMMA 2 OF ARISTOTLE'SMETAPHYSICS
Authors: Halper Yehuda
Published: February 2016

While Averroes’ work is often considered to represent the culmination of the method of Aristotelian demonstration in Arabic philosophy, a short passage of hisLong Commentaryon Aristotle'sMetaphysicsΓ.2 emphasizes the prominence of dialectic and calls for a re-examination of dialectic and demonstration in Averroes’ philosophical works. In this passage Averroes describes dialectic as an acceptable form of philosophy and the dialectician as a kind of scientist. In putting dialectic and demonstration on an equal, or nearly equal footing, Averroes seems to go against his own account of the dialectical and demonstrative classes of people in theDecisive Treatise. Moreover, this interpretation ofMetaphysicsΓ.2 also contradicts Averroes’ explanation of the same passage in theMiddle Commentaryon theMetaphysicsas well as Aristotle's own description of dialectic throughout theMetaphysics. That is, in theLong Commentaryon theMetaphysics, Averroes departs from his earlier views, and describes dialectic as a necessary part of metaphysics, even though the centrality of dialectic argumentation could call into question the entire project of metaphysics and consequently of the sciences whose demonstrations rely on metaphysical ground,i.e., all sciences. Averroes does not emphasize this view, but its presence is nevertheless unambiguous.
Inapproximability of the Partition Function for the Antiferromagnetic Ising and Hard-Core Models
Authors: GALANIS ANDREAS , ŠTEFANKOVIČ DANIEL , VIGODA ERIC
Published: February 2016

Recent inapproximability results of Sly (2010), together with an approximation algorithm presented by Weitz (2006), establish a beautiful picture of the computational complexity of approximating the partition function of the hard-core model. Let λc($\mathbb{T}_{\Delta}$) denote the critical activity for the hard-model on the infinite Δ-regular tree. Weitz presented anFPTASfor the partition function when λ < λc($\mathbb{T}_{\Delta}$) for graphs with constant maximum degree Δ. In contrast, Sly showed that for all Δ ⩾ 3, there exists εΔ> 0 such that (unless RP = NP) there is noFPRASfor approximating the partition function on graphs of maximum degree Δ for activities λ satisfying λc($\mathbb{T}_{\Delta}$) < λ < λc($\mathbb{T}_{\Delta}$) + εΔ.

We prove that a similar phenomenon holds for the antiferromagnetic Ising model. Sinclair, Srivastava and Thurley (2014) extended Weitz's approach to the antiferromagnetic Ising model, yielding anFPTASfor the partition function for all graphs of constant maximum degree Δ when the parameters of the model lie in the uniqueness region of the infinite Δ-regular tree. We prove the complementary result for the antiferromagnetic Ising model without external field, namely, that unless RP = NP, for all Δ ⩾ 3, there is noFPRASfor approximating the partition function on graphs of maximum degree Δ when the inverse temperature lies in the non-uniqueness region of the infinite tree$\mathbb{T}_{\Delta}$. Our proof works by relating certain second moment calculations for random Δ-regular bipartite graphs to the tree recursions used to establish the critical points on the infinite tree.
The “No-Patient” Run: 2,698 Patients Evaluated but Not Transported by Paramedics
Authors: Selden Brad S. , Schnitzer Patricia G. , Nolan Francis X. , Veronesi James F.
Published: February 2016

Patients evaluated by paramedics but not transported by ambulance to the hospital (“no-patient” runs or NPR) form a large part of the volume of ambulance runs in many emergency medical service (EMS) systems and account for 50–90 % of litigation brought against paramedics. Since there are no published studies of this important population, this paper provides a demographic description of the encounters and the prehospital patient disposition in one EMS system. Of all EMS runs for 1987 in the system studied, 2,698 (26.1 %) met NPR criteria. Mean run time for the NPR was 18.5±10.5 min versus 43.1 min for patients transported. The proportion of NPR was unrelated to sex or EMS response type, but was increased in those over age 40 years (p<.001) (Chi square), but was less for those over age 50 years (p<.001) compared to all ages. The proportion of NPR was associated with hour of the day (p<.01), with the highest proportion seen between 0000–0559 hours when overall run volume was lowest. The most frequent prehospital assessments in NPR were minor trauma (25.3 % of NPR), blunt head trauma (18.5%), and no illness or injury (15.9%). Most NPR patients were evaluated by medics and released (46.5%), while 22.7% sought medical care by private vehicle. Treatment or monitoring was performed in 17.6% and refused in 23.8% of NPR cases. Patient disposition was: released to friends/relatives (39.1%); presumed alone (35.5%); to police (18.2%); or other medical care (7.3 %). Medical control physician contact was not required, but was used in 2.1% of NPR cases.

This is the first study of NPR in an EMS system. It describes patient demographics, disposition, and differences from transported patients. Emergency Medical Services providers specifically should examine this population in their systems to maintain patient care standards and decrease medicolegal risks.
Observed Benefits to On-site Medical Services during an Annual 5-day Electronic Dance Music Event with Harm Reduction Services
Authors: Munn Matthew Brendan , Lund Adam , Golby Riley , Turris Sheila A.
Published: February 2016

Background

With increasing attendance and media attention, large-scale electronic dance music events (EDMEs) are a subset of mass gatherings that have a unique risk profile for attendees and promoters. Shambhala Music Festival (Canada) is a multi-day event in a rural setting with a recognized history of providing harm reduction (HR) services alongside medical care.

Study/Objective

This manuscript describes the medical response at a multi-day electronic music festival where on-site HR interventions and dedicated medical care are delivered as parallel public health measures.

Methods

This study was a descriptive case report. Medical encounters and event-related data were documented prospectively using an established event registry database.

Results

In 2014, Shambhala Music Festival had 67,120 cumulative attendees over a 7-day period, with a peak daily attendance of 15,380 people. There were 1,393 patient encounters and the patient presentation rate (PPR) was 20.8 per one thousand. The majority of these (90.9%) were for non-urgent complaints. The ambulance transfer rate (ATR) was 0.194 per one thousand and 0.93% of patient encounters were transferred by ambulance. No patients required intubation and there were no fatalities.

Harm reduction services included mobile outreach teams, distribution of educational materials, pill checking facilities, a dedicated women’s space, and a “Sanctuary” area that provided non-medical peer support for overwhelmed guests. More than 10,000 encounters were recorded by mobile and booth-based preventive and educational services, and 2,786 pills were checked on-site with a seven percent discard rate.

Conclusion

Dedicated medical and HR services represent two complementary public health strategies to minimize risk at a multi-day electronic music festival. The specific extent to which HR strategies reduce the need for medical care is not well understood. Incorporation of HR practices when planning on-site medical care has the potential to inform patient management, reduce presentation rates and acuity, and decrease utilization and cost for local, community-based health services.

MunnMB, LundA, GolbyR, TurrisSA. Observed benefits to on-site medical services during an annual 5-day electronic dance music event with harm reduction services. Prehosp Disaster Med. 2016;31(2):228–234.
Maternal high-fat feeding in pregnancy programs atherosclerotic lesion size in the ApoE*3 Leiden mouse
Authors: Tarling E. J. , Ryan K. J. P. , Austin R. , Kugler S. J. , Salter A. M. , Langley-Evans S. C.
Published: February 2016

Periods of rapid growth seen during the early stages of fetal development, including cell proliferation and differentiation, are greatly influenced by the maternal environment. We demonstrate here that over-nutrition, specifically exposure to a high-fat dietin utero, programed the extent of atherosclerosis in the offspring of ApoE*3 Leiden transgenic mice. Pregnant ApoE*3 Leiden mice were fed either a control chow diet (2.8% fat,n=12) or a high-fat, moderate-cholesterol diet (MHF, 19.4% fat,n=12). Dams were fed the chow diet during the suckling period. At 28 days postnatal age wild type and ApoE*3 Leiden offspring from chow or MHF-fed mothers were fed either a control chow diet (n=37) or a diet rich in cocoa butter (15%) and cholesterol (0.25%), for 14 weeks to induce atherosclerosis (n=36). Offspring from MHF-fed mothers had 1.9-fold larger atherosclerotic lesions (P<0.001). There was no direct effect of prenatal diet on plasma triglycerides or cholesterol; however, transgenic ApoE*3 Leiden offspring displayed raised cholesterol when on an atherogenic diet compared with wild-type controls (P=0.031). Lesion size was correlated with plasma lipid parameters after adjustment for genotype, maternal diet and postnatal diet (R2=0.563,P<0.001). ApoE*3 Leiden mothers fed a MHF diet developed hypercholesterolemia (plasma cholesterol two-fold higher than in chow-fed mothers,P=0.011). The data strongly suggest that maternal hypercholesterolemia programs later susceptibility to atherosclerosis. This is consistent with previous observations in humans and animal models.
Why Do Adolescents Self-Harm?
Authors: Rasmussen Susan , Hawton Keith , Philpott-Morgan Sion , O'Connor Rory C.
Published: February 2016

Abstract. Background: Given the high rates of self-harm among adolescents, recent research has focused on a better understanding of the motives for the behavior. Aims: The present study had three aims: to investigate (a) which motives are most frequently endorsed by adolescents who report self-harm; (b) whether motives reported at baseline predict repetition of self-harm over a 6-month period; and (c) whether self-harm motives differ between boys and girls. Method: In all, 987 school pupils aged 14–16 years completed a lifestyle and coping questionnaire at two time points 6 months apart that recorded self-harm and the associated motives. Results: The motive "to get relief from a terrible state of mind" was the most commonly endorsed reason for self-harm (in boys and girls). Interpersonal reasons (e.g., "to frighten someone") were least commonly endorsed. Regression analyses showed that adolescents who endorsed wanting to get relief from a terrible state of mind at baseline were significantly more likely to repeat self-harm at follow-up than those adolescents who did not cite this motive. Conclusion: The results highlight the complex nature of self-harm. They have implications for mental health provision in educational settings, especially in relation to encouraging regulation of emotions and help-seeking.
Two macrophage migration inhibitory factors regulate starfish larval immune cell chemotaxis
Authors: Furukawa Ryohei , Tamaki Kana , Kaneko Hiroyuki
Published: February 2016

Immune cell recruitment is critical step in the inflammatory response and associated diseases. However, the underlying regulatory mechanisms are poorly understood in invertebrates. Mesenchyme cells of the starfish larvae, which allowed Metchnikoff to complete his landmark experiments, are important model for analysis of immune cell migration. The present study investigated the role of macrophage migration inhibitory factor (MIF)—an evolutionarily conserved cytokine that is functionally similar to chemokines—in the larvae of the starfish Patiria (Asterina) pectinifera, which were found to possess two orthologs, ApMIF1 and ApMIF2. ApMIF1 and ApMIF2 clustered with mammalian MIF and its homolog d‐dopachrome tautomerase (DDT), respectively, in the phylogenetic analysis. In contrast to the functional similarity between mammalian MIF and DDT, ApMIF1 knockdown resulted in the excessive recruitment of mesenchyme cells in vivo, whereas ApMIF2 deficiency inhibited the recruitment of these cells to foreign bodies. Mesenchyme cells migrated along a gradient of recombinant ApMIF2 in vitro, whereas recombinant ApMIF1 completely blocked ApMIF2‐induced directed migration. Moreover, the expression patterns of ApMIF1 and ApMIF2 messenger RNA in bacteria‐challenged mesenchyme cells were consistent with in vivo observations of cell behaviors. These results indicate that ApMIF1 and ApMIF2 act as chemotactic inhibitory and stimulatory factors, respectively, and coordinately regulate mesenchyme cell recruitment during the immune response in starfish larvae. This is the first report describing opposing functions for MIF‐ and DDT‐like molecules. Our findings provide novel insight into the mechanisms underlying immune regulation in invertebrates.
Genome-wide screening identifies a KCNIP1 copy number variant as a genetic predictor for atrial fibrillation
Authors: Tsai Chia-Ti , Hsieh Chia-Shan , Chang Sheng-Nan , Chuang Eric Y. , Ueng Kwo-Chang , Tsai Chin-Feng , Lin Tsung-Hsien , Wu Cho-Kai , Lee Jen-Kuang , Lin Lian-Yu , Wang Yi-Chih , Yu Chih-Chieh , Lai Ling-Ping , Tseng Chuen-Den , Hwang Juey-Jen , Chiang Fu-Tien , Lin Jiunn-Lee
Published: February 2016

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Previous genome-wide association studies had identified single-nucleotide polymorphisms in several genomic regions to be associated with AF. In human genome, copy number variations (CNVs) are known to contribute to disease susceptibility. Using a genome-wide multistage approach to identify AF susceptibility CNVs, we here show a common 4,470-bp diallelic CNV in the first intron of potassium interacting channel 1 gene (KCNIP1) is strongly associated with AF in Taiwanese populations (odds ratio=2.27 for insertion allele; P=6.23 × 10−24). KCNIP1 insertion is associated with higher KCNIP1 mRNA expression. KCNIP1-encoded protein potassium interacting channel 1 (KCHIP1) is physically associated with potassium Kv channels and modulates atrial transient outward current in cardiac myocytes. Overexpression of KCNIP1 results in inducible AF in zebrafish. In conclusions, a common CNV in KCNIP1 gene is a genetic predictor of AF risk possibly pointing to a functional pathway.
Endomucin prevents leukocyte–endothelial cell adhesion and has a critical role under resting and inflammatory conditions
Authors: Zahr Alisar , Alcaide Pilar , Yang Jinling , Jones Alexander , Gregory Meredith , dela Paz Nathaniel G. , Patel-Hett Sunita , Nevers Tania , Koirala Adarsha , Luscinskas Francis W. , Saint-Geniez Magali , Ksander Bruce , D’Amore Patricia A. , Argüeso Pablo
Published: February 2016

Endomucin is a membrane-bound glycoprotein expressed luminally by endothelial cells that line postcapillary venules, a primary site of leukocyte recruitment during inflammation. Here we show that endomucin abrogation on quiescent endothelial cells enables neutrophils to adhere firmly, via LFA-1-mediated binding to ICAM-1 constitutively expressed by endothelial cells. Moreover, TNF-α stimulation downregulates cell surface expression of endomucin concurrent with increased expression of adhesion molecules. Adenovirus-mediated expression of endomucin under inflammatory conditions prevents neutrophil adhesion in vitro and reduces the infiltration of CD45+ and NIMP-R14+ cells in vivo. These results indicate that endomucin prevents leukocyte contact with adhesion molecules in non-inflamed tissues and that downregulation of endomucin is critical to facilitate adhesion of leukocytes into inflamed tissues.
Transcriptional silencing of long noncoding RNA GNG12-AS1 uncouples its transcriptional and product-related functions
Authors: Stojic Lovorka , Niemczyk Malwina , Orjalo Arturo , Ito Yoko , Ruijter Anna Elisabeth Maria , Uribe-Lewis Santiago , Joseph Nimesh , Weston Stephen , Menon Suraj , Odom Duncan T. , Rinn John , Gergely Fanni , Murrell Adele
Published: February 2016

Long noncoding RNAs (lncRNAs) regulate gene expression via their RNA product or through transcriptional interference, yet a strategy to differentiate these two processes is lacking. To address this, we used multiple small interfering RNAs (siRNAs) to silence GNG12-AS1, a nuclear lncRNA transcribed in an antisense orientation to the tumour-suppressor DIRAS3. Here we show that while most siRNAs silence GNG12-AS1 post-transcriptionally, siRNA complementary to exon 1 of GNG12-AS1 suppresses its transcription by recruiting Argonaute 2 and inhibiting RNA polymerase II binding. Transcriptional, but not post-transcriptional, silencing of GNG12-AS1 causes concomitant upregulation of DIRAS3, indicating a function in transcriptional interference. This change in DIRAS3 expression is sufficient to impair cell cycle progression. In addition, the reduction in GNG12-AS1 transcripts alters MET signalling and cell migration, but these are independent of DIRAS3. Thus, differential siRNA targeting of a lncRNA allows dissection of the functions related to the process and products of its transcription.
Using synthetic bacterial enhancers to reveal a looping-based mechanism for quenching-like repression
Authors: Brunwasser-Meirom Michal , Pollak Yaroslav , Goldberg Sarah , Levy Lior , Atar Orna , Amit Roee
Published: February 2016

We explore a model for ‘quenching-like’ repression by studying synthetic bacterial enhancers, each characterized by a different binding site architecture. To do so, we take a three-pronged approach: first, we compute the probability that a protein-bound dsDNA molecule will loop. Second, we use hundreds of synthetic enhancers to test the model’s predictions in bacteria. Finally, we verify the mechanism bioinformatically in native genomes. Here we show that excluded volume effects generated by DNA-bound proteins can generate substantial quenching. Moreover, the type and extent of the regulatory effect depend strongly on the relative arrangement of the binding sites. The implications of these results are that enhancers should be insensitive to 10–11 bp insertions or deletions (INDELs) and sensitive to 5–6 bp INDELs. We test this prediction on 61 σ54-regulated qrr genes from the Vibrio genus and confirm the tolerance of these enhancers’ sequences to the DNA’s helical repeat.
Stabilization of p21 by mTORC1/4E-BP1 predicts clinical outcome of head and neck cancers
Authors: Llanos Susana , García-Pedrero Juana M. , Morgado-Palacin Lucia , Rodrigo Juan P. , Serrano Manuel
Published: February 2016

The levels, regulation and prognostic value of p21 in head and neck squamous cell carcinomas (HNSCC) has been puzzling for years. Here, we report a new mechanism of regulation of p21 by the mTORC1/4E-BP1 pathway. We find that non-phosphorylated 4E-BP1 interacts with p21 and induces its degradation. Accordingly, hyper-activation of mTORC1 results in phosphorylation of 4E-BP1 and stabilization of p21. In HNSCC, p21 levels strongly correlate with mTORC1 activity but not with p53 status. Finally, clinical data indicate that HNSCC patients with p21 and phospho-S6-double-positive tumours present a better disease-specific survival. We conclude that over-activation of the mTORC1/4E-BP1/p21 pathway is a frequent and clinically relevant alteration in HNSCC.
RAG2 and XLF/Cernunnos interplay reveals a novel role for the RAG complex in DNA repair
Authors: Lescale Chloé , Abramowski Vincent , Bedora-Faure Marie , Murigneux Valentine , Vera Gabriella , Roth David B. , Revy Patrick , de Villartay Jean-Pierre , Deriano Ludovic
Published: February 2016

XRCC4-like factor (XLF) functions in classical non-homologous end-joining (cNHEJ) but is dispensable for the repair of DNA double-strand breaks (DSBs) generated during V(D)J recombination. A long-standing hypothesis proposes that, in addition to its canonical nuclease activity, the RAG1/2 proteins participate in the DNA repair phase of V(D)J recombination. Here we show that in the context of RAG2 lacking the C-terminus domain (Rag2c/c mice), XLF deficiency leads to a profound lymphopenia associated with a severe defect in V(D)J recombination and, in the absence of p53, increased genomic instability at V(D)J sites. In addition, Rag2c/cXLF−/−p53−/− mice develop aggressive pro-B cell lymphomas bearing complex chromosomal translocations and gene amplifications involving Igh and c-myc/pvt1 loci. Our results reveal an unanticipated functional interplay between the RAG complex and XLF in repairing RAG-induced DSBs and maintaining genome integrity during antigen receptor gene assembly.
Mito-priming as a method to engineer Bcl-2 addiction
Authors: Lopez Jonathan , Bessou Margaux , Riley Joel S. , Giampazolias Evangelos , Todt Franziska , Rochegüe Tony , Oberst Andrew , Green Douglas R. , Edlich Frank , Ichim Gabriel , Tait Stephen W. G.
Published: February 2016

Most apoptotic stimuli require mitochondrial outer membrane permeabilization (MOMP) in order to execute cell death. As such, MOMP is subject to tight control by Bcl-2 family proteins. We have developed a powerful new technique to investigate Bcl-2-mediated regulation of MOMP. This method, called mito-priming, uses co-expression of pro- and anti-apoptotic Bcl-2 proteins to engineer Bcl-2 addiction. On addition of Bcl-2 targeting BH3 mimetics, mito-primed cells undergo apoptosis in a rapid and synchronous manner. Using this method we have comprehensively surveyed the efficacy of BH3 mimetic compounds, identifying potent and specific MCL-1 inhibitors. Furthermore, by combining different pro- and anti-apoptotic Bcl-2 pairings together with CRISPR/Cas9-based genome editing, we find that tBID and PUMA can preferentially kill in a BAK-dependent manner. In summary, mito-priming represents a facile and robust means to trigger mitochondrial apoptosis.
Lack of association between IL-10 and IL-18 gene promoter polymorphisms and Parkinson’s disease with cognitive impairment in a Chinese population
Authors: Liu Zhenhua , Guo Jifeng , Wang Yaqin , Li Kai , Kang Jifeng , Wei Yang , Sun Qiying , Xu Qian , Xu Changshui , Yan Xinxiang , Tang Beisha
Published: February 2016

Inflammatory processes have been implicated in the pathogenesis of Parkinson’s disease (PD), including the development of PD-associated cognitive impairment. Whether genetic variants of inflammatory cytokine genes influence the risk of cognitive impairment in PD is unknown. In this study, we investigated single nucleotide polymorphisms (SNPs) in the IL-10 promoter (rs1800871 and rs1800872) and in the IL-18 promoter (rs1946518 and rs187238) in a Han Chinese cohort (N = 933). PD patients (N = 460) and controls (N = 473) were genotyped. Additionally, 268 PD patients were divided into three subgroups [cognitively normal (PD-NC), mild cognitive impairment (PD-MCI) and with dementia (PD-D)] on the basis of their performance on a battery of neuropsychological tests. No associations were found between the aforementioned polymorphisms and cognitive impairment in PD; thus no confirmatory evidence for the hypothesis of IL-10 and IL-18 alleles modulating the risk of cognitive impairment in Chinese PD patients was obtained.
Under the hood of statistical learning: A statistical MMN reflects the magnitude of transitional probabilities in auditory sequences
Authors: Koelsch Stefan , Busch Tobias , Jentschke Sebastian , Rohrmeier Martin
Published: February 2016

Within the framework of statistical learning, many behavioural studies investigated the processing of unpredicted events. However, surprisingly few neurophysiological studies are available on this topic and no statistical learning experiment has investigated electroencephalographic (EEG) correlates of processing events with different transition probabilities. We carried out an EEG study with a novel variant of the established statistical learning paradigm. Timbres were presented in isochronous sequences of triplets. The first two sounds of all triplets were equiprobable, while the third sound occurred with either low (10%), intermediate (30%), or high (60%) probability. Thus, the occurrence probability of the third item of each triplet (given the first two items) was varied. Compared to high-probability triplet endings, endings with low and intermediate probability elicited an early anterior negativity that had an onset around 100 ms and was maximal at around 180 ms. This effect was larger for events with low than for events with intermediate probability. Our results reveal that, when predictions are based on statistical learning, events that do not match a prediction evoke an early anterior negativity, with the amplitude of this mismatch response being inversely related to the probability of such events. Thus, we report a statistical mismatch negativity (sMMN) that reflects statistical learning of transitional probability distributions that go beyond auditory sensory memory capabilities.