bluuebunny/crossref_metadata_2025_split huggingface dataset:
Probability of success for phase III after exploratory biomarker analysis in phase II
Authors: Götte Heiko , Kirchner Marietta , Sailer Martin Oliver 
Published: February 2017

The probability of success or average power describes the potential of a future trial by weighting the power with a probability distribution of the treatment effect. The treatment effect estimate from a previous trial can be used to define such a distribution.During the development of targeted therapies, it is common practice to look for predictive biomarkers. The consequence is that the trial population for phase III is often selected on the basis of the most extreme result from phase II biomarker subgroup analyses. In such a case, there is a tendency to overestimate the treatment effect. We investigate whether the overestimation of the treatment effect estimate from phase II is transformed into a positive bias for the probability of success for phase III. We simulate a phase II/III development program for targeted therapies. This simulation allows to investigate selection probabilities and allows to compare the estimated with the true probability of success.We consider the estimated probability of success with and without subgroup selection. Depending on the true treatment effects, there is a negative bias without selection because of the weighting by the phase II distribution. In comparison, selection increases the estimated probability of success. Thus, selection does not lead to a bias in probability of success if underestimation due to the phase II distribution and overestimation due to selection cancel each other out.We recommend to perform similar simulations in practice to get the necessary information about the risk and chances associated with such subgroup selection designs.
Quantitative analysis of malondialdehyde‐guanine adducts in genomic DNA samples by liquid chromatography/tandem mass spectrometry
Authors: Yates Sally A. , Dempster Nicola M. , Murphy Mark F. , Moore Sharon A. 
Published: February 2017

RationaleThe lipid peroxidation product malondialdehyde forms M1dG adducts with guanine bases in genomic DNA. The analysis of these adducts is important as a biomarker of lipid peroxidation, oxidative stress and inflammation which may be linked to disease risk or exposure to a range of chemicals.MethodsGenomic DNA samples were subjected to acid hydrolysis to release the adducts in the base form (M1G) alongside the other purines. A liquid chromatography/mass spectrometry method was optimised for the quantitation of the M1G adducts in genomic DNA samples using product ion and multiple reaction monitoring (MRM) scans.ResultsProduct ion scans revealed four product ions from the precursor ion; m/z 188 → 160, 133, 106 and 79. The two smallest ions have not been observed previously and optimisation of the method revealed that these gave better sensitivity (LOQ m/z 79: 162 adducts per 107 nucleotides; m/z 106: 147 adducts per 107 nucleotides) than the other two ions. An MRM method gave similar sensitivity but the two smallest product ions gave better accuracy (94–95%). Genomic DNA treated with malondialdehyde showed a linear dose‐response relationship.ConclusionsA fast reliable sample preparation method was used to release adducts in the base form rather than the nucleoside. The methods were optimised to selectively analyse the adducts in the presence of other DNA bases without the need for further sample clean‐up. Analysis of genomic DNA gave results consistent with previous work and was applied to new samples. Thus, the method is suitable for the analysis of M1(d)G adducts in biological samples. Copyright © 2017 John Wiley & Sons, Ltd.
Sexual Disorders Caused by Antidepressants: Considerations in the Context of Brain Hemisphere Functions
Authors: Rotenberg Vadim S. 
Published: February 2017

Abstract
All phases of normal sexual activity are under the control of the right hemisphere coupled with limbic structures, and depression is characterized by the functional insufficiency of this system. At the same time, those modern antidepressants that cause sexual disorders are activating the left hemisphere and determine its domination on the expense of the right one and disturb free and spontaneous emotional interrelationships, sexual behavior and pleasure. Those antidepressants that do not cause sexual dysfunction are not activating predominantly the left hemisphere structures and activate the limbic brain zones responsible for reward, reinforcement and emotional excitement.
Meta-analysis of Plasma Interleukine-6 Levels in Patients with Depressive Disorder
Authors: Bizik Gustav 
Published: February 2017

AbstractGrowing body of evidence suggests that inflammatory processes play an important role in the pathophysiology and the clinical course of depressive disorder, as well as several others major psychiatric and somatic conditions. Interleukin (IL-6), one of the proinflammatory cytokines, has been extensively examined in a number of studies among depressed patients. To assess quantitatively the relationship between depression and IL-6, a systematic review of relevant literature published to October 2009 was performed and relevant data were meta-analysed using random-effects model. A positive association was found (standardized difference in means=1.055, p>0,001), although a significant heterogeneity among studies (Q(15)=141, p<0,001) points to relevance of further subgroup analyses.
Two Black Boxes: a Fable
Authors: Dennett Daniel 
Published: February 2017

Abstract
Once upon a time, there were two large black boxes, A and B, connected by a long insulated copper wire. On box A there were two buttons, marked *a* and *b*, and on box B there were three lights, red, green, and amber. Scientists studying the behavior of the boxes had observed that whenever you pushed the *a* button on box A, the red light flashed briefly on box B, and whenever you pushed the *b* button on box A, the green light flashed briefly. The amber light never seemed to flash. They performed a few billion trials, under a very wide variety of conditions, and found no exceptions. There seemed to them to be a causal regularity.
Event-related Potentials and Their Applications
Authors: Landa Leos , Krpoun Zdenek , Kolarova Martina , Kasparek Tomas 
Published: February 2017

AbstractEvent-related potentials (ERPs) are characterised as brain voltage fluctuations associated in time with some physical or mental occurrence and represent a non-invasive technique reflecting activity of complex neuronal networks responsible for new stimuli detection and discriminative behaviour of individuals. ERPs are measured using electroencephalography and their applications became widespread since 1960s of the last century. This review brings introduction into the ERPs technique and characteristics of the individual ERPs components (particularly wave P300, Contingent Negative Variation, Mismatch Negativity and Bereitschaftspotential). In addition, it summarizes changes of ERPs associated with neurologic and psychiatric diseases and finally, it mentions possible use of this approach for purposes of experimental psychology.
Quantum Theory of Iconic Memory
Authors: Bass Ludvik 
Published: February 2017

Abstract
The undifferentiated event in the consciousness of an observer, introduced by von Neumann in his quantum theory of measurement, is elaborated to interpret experiments by which Sperling demonstrated iconic memory. The numerous quadruplets of letters known to Sperling’s subjects implicitly but not consciously are interpreted as quantum states in a superposition reducible to any of its components by von Neumann’s event in consciousness. The potential loss by decoherence of all information implicit in the superposition, and its possible retention by a secondary observer within the same organism, may be aspects of the biological evolution as of a precursor of the quantum computer.
Consciousness and Anesthesia: Towards a New Integrated Paradigm
Authors: Rzyman Robert 
Published: February 2017

Abstract
According to reported studies there is increasing evidence that an actual level of anesthesia may exist on a continuum between usual awareness and states of unconsciousness. Recent findings also indicate that levels of anesthesia may be related to specific disturbances in neural correlate of consciousness that is mainly based on large scale synchronization in the brain. Further research studies have also shown that these specific changes during loss of consciousness may be reflected in decreased large scale synchronization in the brain that is caused by decreased cooperation among simultaneously active neural assemblies. In this context, concept of cognitive unbinding has been proposed that is mainly caused by decreased synchronizaton and cooperation among neural assemblies, which leads to decreased level of consciousness and in the extreme case to global anesthesia. Several recent studies suggest that these findings could be very useful for detecting intraoperative awareness which may lead to serious adverse effects and symptoms of posttraumatic stress disorder (PTDS). According to these data episodes of intraoperative awareness could be detected by various techniques focused on detecting binding processes reflecting a level of dependence in neural activation.
Sociodemographic and Clinical Characteristics of Victimized Versus Non-Victimized Patients with Schizophrenia: An Egyptian Study
Authors: El Missiry Ahmed , El Meguid Marwa Abd , Soltan Marwa , Missiry Marwa El 
Published: February 2017

Abstract
Persons with mental disorders living in the community are liable for victimization and are considered as a high-risk group. Objective of this study was to explore the sociodemographic variables and clinical characteristics related to victimization of patients with schizophrenia in comparison to their nonvictimized counterparts. One hundred patients were recruited from the inpatient wards and outpatient clinics of the Institute of Psychiatry, Ain Shams University. They were subjected to Structured Clinical Interview for DSM-IV Axis I diagnosis (Clinical Version); Positive and Negative Syndrome Scale (PANSS); Global Assessment of Functioning (GAF); Clinical Global Impression (CGI); designed extensive questionnaire to elicit demographic data; inquiry about drug compliance and Victimization Questionnaire. Results show that 70 patients of the studied sample were non-victimized and 30 patients were victimized. Victimized patients were significantly younger, living mainly in urban areas, had less frequent history of bullying at school. There were exposed significantly to higher frequency of family domestic violence and childhood abuse. They scored higher for all subscales and in total PANSS scores and they were less compliant on medication than did their non-victimized counterparts. Until now studies of victimization of mentally ill did not draw the attention of researchers and clinicians in Arab world. This study proves that victimization is not uncommon among patients with schizophrenia; Clinicians should include assessment for victimization of their patients as a routine work. The current study provides preliminary data for clinicians and policy makers to consider strategies to protect patients with various mental illnesses from being victimized.
“Split Mind” and EEG Gamma Activity in Schizophrenia
Authors: Simek Jakub 
Published: February 2017

Abstract
Synchronous high frequency (Gamma band) activity has been proposed as a candidate mechanism for the integration or ‘binding’ of distributed brain activities that are closely related to integrative cognitive processing and conscious awareness which is significantly affected in schizophrenia. According to recent evidence schizophrenia is related to temporal disintegration of brain networks which is closely linked to cognitive dysmetria to abnormal integration of sensory input with stored information. These findings indicate that disconnection and disturbed gamma synchrony and neural binding may represent a specific correlate of mental disintegration in schizophrenia. From historical perspectives these findings are in agreement with basic thinking about schizophrenia that was proposed by Bleuler when he introduced the term schizophrenia as “split mind”. These data have important implications for understanding of basic mechanism related to schizophrenia and also its therapy that in the future perspectives might be much focused on specific influences on cognitive functions using psychotherapeutic approaches in close correspondence with pharmacological treatment strategies.
A Compositional Modelling and Verification Framework for Stochastic Hybrid Systems
Authors: Wang Shuling , Zhan Naijun , Zhang Lijun 
Published: February 2017

Abstract
In this paper, we propose a general compositional approach for modelling and verification of stochastic hybrid systems (SHSs). We extend Hybrid CSP (HCSP), a very expressive process algebra-like formal modeling language for hybrid systems, by introducing probability and stochasticity to model SHSs, which we call stochastic HCSP (SHCSP). Especially, non-deterministic choice is replaced by probabilistic choice, ordinary differential equations are replaced by stochastic differential equations (SDEs), and communication interrupts are generalized by communication interrupts with weights. We extend Hybrid Hoare Logic to specify and reason about SHCSP processes: On the one hand, we introduce the probabilistic formulas for describing probabilistic states, and on the other hand, we propose the notions of local stochastic differential invariants for characterizing SDEs and global loop invariants for repetition. Throughout the paper, we demonstrate our approach by an aircraft running example.
Derivation and Validation of a Novel Physiological Emergency Surgery Acuity Score (PESAS)
Authors: Sangji Naveen F. , Bohnen Jordan D. , Ramly Elie P. , Velmahos George C. , Chang David C. , Kaafarani Haytham M. A. 
Published: February 2017

AbstractBackgroundWe present a novel and abbreviated Physiological Emergency Surgery Acuity Score (PESAS) that assesses the severity of disease at presentation in patients undergoing Emergency Surgery (ES).MethodsUsing the 2011 ACS‐NSQIP database, we identified all patients who underwent “emergent” surgery. The following methodology was designed: (1) identification of independent predictors of 30‐day mortality that are markers of acuity; (2) derivation of PESAS based on the relative impact (i.e., odds ratio) of each predictor; and (3) measurement of the c‐statistic. The PESAS was validated using the 2012 ACS‐NSQIP database.ResultsFrom 24,702 ES cases, a 15‐point score was derived. This included 10 components with a range of 0 and 15 points. Its c‐statistic was 0.80. Mortality gradually increased from 1.7 to 40.6 to 100% at scores of 0, 8, and 15, respectively. In the validation phase, PESAS c‐statistic remained stable.ConclusionPESAS is a novel score that assesses the acuity of disease at presentation in ES patients and strongly correlates with postoperative mortality risk. PESAS could prove useful for preoperative counseling and for risk‐adjusted benchmarking.
Periodic solutions with prescribed energy for some Keplerian N-body problems
Authors: Ambrosetti Antonio , Tanaka Kazunaga , Vitillaro Enzo 
Published: February 2017

We prove the existence of periodic solutions with prescribed energy for a class of

N

-body type problems with Keplerian like interaction.

Résumé

Nous prouvons l’existence de solutions périodiques d’énergie prescrite pour une classe de problèmes à

N

corps avec interaction de type képlérien.
Further remarks on the lower semicontinuity of polyconvex integrals
Authors: Celada Pietro , Dal Maso Gianni 
Published: February 2017

We study some lower semicontinuity properties of polyconvex integrals of the form

\int _{\mathrm{\Omega }}f\left(M\left(\nabla u\right)\right)dx

, where

Ω ⊂ ℝ^n

,

u: Ω → ℝ^m

, and

M(∇u)

denotes the family of the determinants of all minors of the gradient matrix

∇u

. In particular, we study the lower semicontinuity along sequences converging strongly in

L^1(Ω,ℝ^m)

when the integrand depends only on the minors of

∇u

up to a given order, and the lower semicontinuity along sequences converging strongly in

L

1(Ω, ℝ^n)

and bounded in

W^{1,n−1}(Ω, ℝ^n)

in the special case

m = n$.

Résumé

Nous étudions la semicontinuité inférieure d’intégrales polyconvexes de la forme

\int _{\mathrm{\Omega }}f\left(M\left(\nabla u\right)\right)dx

, où

Ω ⊂ ℝ^n

,

u: Ω → ℝ^m

, et

M(∇u)

désigne le vecteur des déterminants de tous les mmeurs de la matrice gradient

∇u

. En particulier, nous étudions la semicontinuité inférieure sur les suites convergentes fortement en

L^1(Ω,ℝ^m)

lorsque l’integrande dépend seulement des mineurs de

∇u

jusqu’à un certain ordre et la semicontinuité inférieure sur les suites convergentes fortement en

L^1(Ω,ℝ^m)

et bornées en

W^{1,n−1}(Ω, ℝ^n)

dans le cas spécial

m = n

.
A general mountain pass principle for locating and classifying critical points
Authors: Ghoussoub N. , Preiss D. 
Published: February 2017

A general “Mountain Pass” principle that extends the theorem of Ambrosetti-Rabinowitz and which gives more information about the location of critical points, is established. This theorem also covers the problem of the “limiting case”, i.e. when “the separating mountain range has zero altitude”. It is also shown how this principle yields localized versions of recent results of Hofer and Pucci–Serrin concerning the structure of the critical set.

Résumé
On démontre une extension du théorème de col d’Ambrosetti-Rabinowitz dans laquelle une information auxiliaire sur la position du point critique est établie. On en déduit, d’une part, des résultats nouveaux, notamment le cas « limite » et d’autre part des démonstrations simples de résultats récents de Hofer et Pucci–Serrin sur la structure de l’ensemble critique.
Heat flow and boundary value problem for harmonic maps
Authors: Kung-Ching Chang 
Published: February 2017

We prove an existence result for the heat flow, and apply minimax principles to deduce existence and multiplicity results for harmonic mар.

Résumé
On démontre un théorème d’existence pour l’équation de la chaleur, et on déduit des résultats d’existence et de multiplicité pour divers problèmes aux limites associés aux applications harmoniques.
Elevated carbon dioxide and temperature alters aggregate specific methane consumption in a tropical vertisol
Authors: KOLLAH B. , AHIRWAR U. , MOHANTY S. R. 
Published: February 2017

SUMMARYExperiments were carried out to determine methane (CH4) consumption in different soil (vertisol) aggregates under elevated carbon dioxide (eCO2) and temperature. Soil aggregates of <0·25 mm diameter (microaggregates), 0·25–1 mm diameter (mesoaggregates) and 1–2 mm diameter (macroaggregates) were incubated under different CO2(400, 800 and 1200 µm/mor ppm CO2) and temperature (25, 35 and 45 °C) conditions. Methane consumption was high in mesoaggregates and low in microaggregates under ambient CO2and temperature (25 °C). However, eCO2and temperature significantly inhibited CH4consumption and decreased culturable microbial numbers. Methane consumption in mesoaggregates was inhibited by 21–66% at 800–1200 ppm of CO2. Principal component analysis designated soil aggregate size as the most important component of variation, followed by temperature and CO2. Ordination biplot indicated eCO2and temperature impacted negatively on CH4consumption and culturable methanotrophs. Results highlighted that mesoaggregates of 0·25–1·00 mm are hotspots for CH4consumption and that rising atmospheric CO2and temperature may inhibit CH4consumption significantly in a tropical vertisol.
Indigenous Land Rights and Caribbean Reparations Discourse
Authors: STRECKER AMY 
Published: February 2017

AbstractIn March 2014, a meeting of CARICOM states approved a ten-point plan of the Caribbean Reparations Commission to achieve reparatory justice for the victims of slavery, genocide and racial apartheid in the Caribbean. With assistance from the London-based law firm Leigh Day, the aim is to reach a negotiated settlement with the governments of Britain, France and the Netherlands. What makes this case different from previous discussions on Caribbean reparations is that the claim includes an indigenous component, with ‘native genocide’ included in the title and an ‘indigenous peoples’ development program’ included within the ten-point plan for reparations. Yet reparations are problematic in the Caribbean context due to the ongoing violation of indigenous rights internally. This article analyzes the various dimensions of the Caribbean reparations discourse with regard to contemporary indigenous communities in the region. It highlights the problems at regional level with regard to state responsibility and indigenous rights, particularly in relation to land, and argues that this presents a problematic element in the claim due to the fact that violations are being perpetrated against indigenous peoples by the same states who are representing them in the Caribbean Reparations Commission. Finally, it discusses the onus on European governments to acknowledge past wrongs and the potential of ‘cultural reparations’ to contribute to the Caribbean reparatory justice programme more generally.
Psychiatric diagnoses in older people with intellectual disability in comparison with the general population: a register study
Authors: Axmon A. , Björne P. , Nylander L. , Ahlström G. 
Published: February 2017

Aims.To describe the occurrence of psychiatric diagnoses in a specialist care setting in older people with intellectual disability (ID) in relation to those found in the same age group in the general population.Method.A cohort of people with ID (n= 7936), aged 55 years or more in 2012, was identified, as was an age and sex-matched cohort from the general population (n= 7936). Information regarding psychiatric diagnoses during 2002–2012 was collected from the National Patient Register, which contains records from all inpatient care episodes and outpatient specialist visits in Sweden. The mean age at the start of data collection (i.e. January 1st, 2002) was 53 years (range 44–85 years).Results.Seventeen per cent (n= 1382) of the people in the ID cohort had at least one psychiatric diagnosis recorded during the study period. The corresponding number in the general population cohort was 10% (n= 817), which translates to an odds ratio (OR) of 1.84. The diagnoses recorded for the largest number of people in the ID cohort were ‘other’ (i.e. not included in any of the diagnostic groups) psychiatric diagnoses (10% of the cohort had at least one such diagnosis recorded) and affective disorders (7%). In the general population cohort, the most common diagnoses were affective disorders (4%) and alcohol/substance-abuse-related disorders (4%). An increased odds of having at least one diagnosis was found for all investigated diagnoses except for alcohol/substance-abuse-related disorders (OR = 0.56). The highest odds for the ID cohort was found for diagnosis of psychotic disorder (OR = 10.4) followed by attention deficit/hyperactive disorder (OR = 3.81), dementia (OR = 2.71), personality disorder (OR = 2.67), affective disorder (OR = 1.74) and anxiety disorder (OR = 1.36). People with ID also had an increased odds of psychiatric diagnoses not included in any of these groups (OR = 8.02). The percentage of people with ID who had at least one diagnosis recorded during the study period decreased from more than 30% among those aged 55–59 years in 2012 (i.e. born 1953–1957) to approximately 20% among those aged 75+ years in 2012 (i.e. born in or before 1937).Conclusions.Older people with ID seem to be more likely to have psychiatric diagnoses in inpatient or outpatient specialist care than their peers in the general population. If this is an effect of different disorder prevalence, diagnostic difficulties or differences in health care availability remains unknown. More research is needed to understand the diagnostic and treatment challenges of psychiatric disorders in this vulnerable group.