SUFFICIENT OPTIMALITY CONDITIONS FOR THE MOREAU-YOSIDA TYPE REGULARIZATION CONCEPT APPLIED TO SEMILINEAR ELLIPTIC OPTIMAL CONTROL PROBLEMS WITH POINTWISE STATE CONSTRAINTS

We develop sufficient optimality conditions for a Moreau-Yosidaregularized optimal control problem governed by a semilinear ellipticPDE with pointwise constraints on the state and the control. We makeuse of the equivalence of a setting of Moreau-Yosida regularization to a special setting of the virtual control concept,for which standard second order sufficient conditions have been shown. Moreover, we present a numerical example,solving a Moreau-Yosida regularized model problem with an SQP method

Regularization error estimates for semilinear elliptic optimal control problems with pointwise state and control constraints

In this paper a class of semilinear elliptic optimal control problem with pointwise state and control constraints is studied. A sufficient second order optimality condition and uniqueness of the dual variables are assumed for that problem. Sufficient second order optimality conditions are shown for regularized problems with small regularization parameter. Moreover, error estimates with respect to the regularization parameter are derived

Primäre Kopfschmerzen bei Patienten mit juveniler myoklonischer Epilepsie

In der vorliegenden klinischen Arbeit wurden die Prävalenzen sowie Risikofaktoren für die primären Kopfschmerzen Migräne und Spannungskopfschmerz bei 75 Patienten mit juveniler myoklonischer Epilepsie (JME) untersucht. Die Klassifizierung der Kopfschmerzen erfolgte anhand eines validierten Fragebogens. Die Kopfschmerzprävalenzen wurden mit den Prävalenzen in der Normalbevölkerung aus der Literatur verglichen. Bei 47 der 75 Patienten mit JME fanden sich interiktal rezidivierende Kopfschmerzen. 31 Patienten hatten Migräne. Das relative Risiko (RR) im Vergleich zur Normalbevölkerung betrug 4.4. Zwanzig Patienten hatten Migräne ohne Aura (RR 3.6) und 11 Migräne mit Aura (RR 7.3). Bei 14 Patienten mit Migräne fanden sich zusätzlich auch Spannungskopfschmerzen. 16 Patienten litten ausschließlich unter Spannungskopfschmerzen. Das relative Risiko für Spannungskopfschmerzen betrug 3.4. Risikofaktor für Migräne im Allgemeinen und Migräne ohne Aura war weibliches Geschlecht; für Migräne mit Aura eine Migräne bei Verwandten ersten Grades. Für Migräne und Migräne mit Aura fand sich eine Assoziation mit mehr als einem generalisierten tonisch-klonischen Anfall pro Monat. Migräne ohne Aura hingegen war mit häufigen Absencen assoziiert. Die Auswertung der EEGs ergab keine signifikanten Unterschiede zwischen JME-Patienten mit Kopfschmerzen und den Patienten ohne Kopfschmerzen. Limitierender Faktor bei der Interpretationen der vorliegenden Ergebnisse stellt die geringe Patientenzahl von 75 JME-Patienten bei einer Rücklaufquote von 61% dar. Wesentliches Ergebnis unserer Studie ist die signifikant erhöhte Kopfschmerzprävalenz bei Patienten mit JME. V. a. die Prävalenz der Migräne ist im Vergleich zur Normalbevölkerung deutlich erhöht. Die Ergebnisse lassen einen gemeinsamen – bisher nicht näher bekannten – pathophysiologischen und genetischen Mechanismus der JME und Migräne vermuten

Appraisals of emotion-eliciting events: Testing a theory of discrete emotions.

A recent theory Why 1 Two individuals will feel the same emotion to the extent that their appraisals of a situation are the same. Two individuals with different appraisals, or the same individual with different appraisals at different times, will feel different emotions. Thus, by identifying emotion-causing patterns of appraisal, such theories may be able to explain how an infinite variety of situations can elicit the same emotion and may also be able to explain the apparent variability across people and over time in emotional responses to the same event. The challenge for appraisal theorists is to specify the patterns of appraisal that can produce particular emotions. In the present generation of appraisal theories, Roseman (1979) proposed that five appraisals influence emotions: (a) motivational state: whether an individual's motive in a given situation is aversive (a punishment that he or she seeks to avoid) or appetitive (a reward that he or she seeks to attain), (b) situational state: whether the motivational state (the punishment or reward) is present or absent in the situation to which the individual is reacting, (c) probability: whether the occurrence of an outcome is uncertain or certain, (d) legitimacy: whether a negative outcome is deserved or a positive outcome is deserved in the situation, and (e) agency: whether an outcome is caused by impersonal circumstances, some other person, or the self. In testing this theory, Roseman (1983) found that each of the five appraisals had a significant effect on emotion ratings and that the overall pattern of relationships between particular combinations of appraisals and particular emotions corresponded significantly to theoretical predictions. Post hoc analyses suggested that the effects of the motivational state and situational state appraisals (interacting to determine whether an outcome was appraised as negative vs. positive), and of probability, con-

Headache in juvenile myoclonic epilepsy

The objective of this study was to assess the prevalence of and risk factors for primary headaches in juvenile myoclonic epilepsy (JME). Headache was classified in 75 patients with JME using a questionnaire, and its prevalence was correlated with the literature on the general population and clinical data. Headache was present in 47 patients. Thirty-one had migraine [20 migraine without aura (MO), 11 migraine with aura (MA)]. Fourteen patients with migraine had tension-type headache (TTH) in addition. Sixteen had only TTH. Comparison with the general population revealed a significantly higher prevalence of migraine (RR 4.4), MO (3.6), MA (7.3) and TTH (3.4) in JME. Risk factors for migraine and MO were female gender and for MA family history of migraine in first-degree relatives. Migraine and MA were associated with fairly controlled generalized tonic clonic seizures, MO with absences. Together with its strong genetic background, JME appears to be an attractive homogenous subtype of epilepsy for genetic research on migraine

There is inadequate evidence to support the division of the genus Borrelia

There are surely scientific, genetic or ecological 60 arguments which show that differences exist between the relapsing fever (RF) spirochaetes and the Lyme borreliosis (LB) group of spirochaetes, both of which belong to the genus Borrelia. In a recent publication, Adeolu and Gupta (Adeolu & 63 Gupta, 2014) proposed dividing the genus Borrelia into two genera on the basis of genetic differences revealed by comparative genomics. The new genus name for the LB group of spirochaetes, Borreliella, has subsequently been entered in GenBank for some species of the group and in a validation list (List of new names and new combinations previously effectively, but not validly, published) (Oren & Garrity, 2015). However, rapidly expanding scientific knowledge and considerable conflicting evidence combined with the adverse consequences of splitting the genus Borrelia make such a drastic step somewhat premature. In our opinion, the basis of this division rests on preliminary evidence and should be rescinded

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Review of Intrinsic Motivation in Simulation-based Game Testing

This paper presents a review of intrinsic motivation in player modeling, with a focus on simulation-based game testing. Modern AI agents can learn to win many games; from a game testing perspective, a remaining research problem is how to model the aspects of human player behavior not explained by purely rational and goal-driven decision making. A major piece of this puzzle is constituted by intrinsic motivations, i.e., psychological needs that drive behavior without extrinsic reinforcement such as game score. We first review the common intrinsic motivations discussed in player psychology research and artificial intelligence, and then proceed to systematically review how the various motivations have been implemented in simulated player agents. Our work reveals that although motivations such as competence and curiosity have been studied in AI, work on utilizing them in simulation-based game testing is sparse, and other motivations such as social relatedness, immersion, and domination appear particularly underexplored