Leukaemia Incidence in Children and Adults in the Regions of Russia Most Highly Contaminated after the Chernobyl Nuclear Power Plant Accident

ABSTRACT BACKGROUND Leukaemia, especially the acute types predominant in children, may be caused by ionizing radiation. After the Chernobyl Nuclear Power Plant accident on 26 April 1986, parts of Belarus, Russia and the Ukraine were contaminated with radionuclides. To date, over 270 000 people live in such contaminated regions in Russia. This study investigates whether the leukaemia incidence rates in these regions might have increased due to the radiation. MATERIALS & METHODS A prospective population-based cohort study with a control group was carried out. Cases of leukaemia previously not registered were actively sought for in medical and administrative institutions. Each case that had occurred in the study regions between 1980 and 1998 has been ascertained and verified. A descriptive analysis was then performed on the resulting data base which included 333 leukaemia cases. RESULTS There is a slight secular trend in the standardized incidence rates both in the highly contaminated and in the control regions. This increase, however, is more marked in the control regions. The incidence rates in children (0-14) in the highly contaminated regions decrease between the pre-accident (1980 to 1986) and the first post-accident period (1987-1992) and show a slight increase towards the second post-accident period (1993-1998), whereas the incidence rates in the control regions show exactly the opposite dynamic. This makes a connection between the dynamics of the incidence rates and the radiological situation highly improbable. The comparative analysis of the leukaemia incidence rates has not revealed a statistically significant difference between the population of the highly contaminated regions of the Bryansk oblast and the combined control regions of the Kaluga oblast. CONCLUSIONS There is so far no indication of an increase in leukaemia incidence rates in the general population, neither for children nor for adults. This does not contradict the current radiobiological knowledge that cancer, especially leukaemia, can be caused by ionizing radiation. The number of expected radiation-induced cases based on the risk estimates from the Japanese cohort lies within the 95% confidence limits of the spontaneous incidence rates. It would therefore, if at all present, not be statistically detectable in a population of 222 000 with a spontaneous rate of 5.4/100 000 in men and 3.3/100 000 in women in the control regions. Considering the latency periods and the age-dependent risk-curve of radiation-induced cancers, it is highly unlikely that a radiation-related increase in leukaemia or solid tumour incidence rates will become obvious in the future. The fear and apprehension caused by the overestimation of the radiation risks create a continuous stress situation and add to the present detrimental health conditions in the population. It is therefore of utmost importance to communicate not only the results but also the reliability of the study and the soundness of the data to the affected people.ZUSAMMENFASSUNG HINTERGRUND Leukämien, insbesondere die akuten Formen, die im Kindesalter vorherrschen, können durch radioaktive Strahlung induziert werden. Durch den Unfall in Tschernobyl am 26. April 1986 sind Teile von Belarus, Russland und der Ukraine radioaktiv kontaminiert worden. Bis heute leben in Russland über 270.000 Menschen in solchen kontaminierten Gebieten. Die vorliegende Studie untersucht, ob die Leukämieinzidenzen in diesen Gebieten aufgrund der radioaktiven Strahlung angestiegen sind. MATERIAL & METHODEN Zu diesem Zweck wurde eine bevölkerungsbezogene, prospektive Kohortenstudie mit einer Kontrollgruppe durchgeführt. Jeder Leukämiefall der Jahre 1980-1998 aus den Studienregionen wurde genau nacherhoben und verifiziert. Zudem wurde aktiv in Krankenhäusern und Behörden nach nicht erhobenen Fällen gesucht. Die 333 Leukämiefälle, die sich letztendlich in der Datenbank befanden, wurden deskriptiv analysiert. ERGEBNISSE Die standardisierten Inzidenzen zeigen über die Jahre einen leicht ansteigenden Trend, sowohl in den kontaminierten als auch in den Kontrollregionen. Dieser Anstieg ist ausgeprägter in den Kontrollregionen. Die Inzidenzen bei Kindern (0-14 Jahre) fallen in den kontaminierten Regionen zwischen der Periode 1980-86 und der Periode 1987-1992 ab und steigen dann in der Periode 1993-98 wieder leicht an, wohingegen die Inzidenzen in den Kontrollregionen genau die umgekehrte Dynamik zeigen. Dies macht einen Zusammenhang mit der radioaktiven Strahlung höchst unwahrscheinlich. Die vergleichende Analyse zeigt keinen statistisch signifikanten Unterschied in den Inzidenzen zwischen den kontaminierten Regionen und den Kontrollregionen. SCHLUSSFOLGERUNGEN Es gibt keinen Hinweis auf einen Anstieg der Leukämieraten in der Allgemeinbevölkerung, weder bei Kindern noch bei Erwachsenen. Dies widerspricht nicht der strahlenbiologischen Erkenntnis, dass Tumoren, insbesondere Leukämien, durch radioaktive Strahlung induziert werden können. Die mittels der Risikokoeffizienten aus den japanischen Studien errechnete Anzahl der strahleninduzierten Leukämiefälle liegt innerhalb der 95% Konfidenzintervalle der jährlichen Fluktuation der Spontanraten. Solch induzierte Fälle wären daher – falls vorhanden – bei einer exponierten Bevölkerung von ca. 222.000 und einer in den Kontroll-regionen beobachteten Spontanrate von 5,4/100.000 (Männer) bzw. 3,3/100.000 (Frauen) statistisch nicht nachweisbar. Bedenkt man die Latenzzeiten und die altersabhängige Risikostruktur strahleninduzierter Tumore, ist ein Anstieg sowohl der Leukämieraten als auch der Raten solider Tumore aufgrund des Reaktorunfalls in Tschernobyl in der Zukunft extrem unwahrscheinlich. Die Ängste und Befürchtungen, die durch die Überschätzung der Risiken durch die radioaktive Strahlung entstanden sind, haben zu einer persistierenden Stresssituation für die Betroffenen geführt. Dieser Stress wirkt sich zusätzlich zu den aktuellen ökonomischen und sozialen Faktoren negativ auf die Gesundheit der Bevölkerung aus. Es ist daher wichtig, den Betroffenen nicht nur die Ergebnisse der vorliegenden Studie, sondern insbesondere auch die Qualität der zugrunde liegenden Daten glaubwürdig zu vermitteln

Doubling your payoff: winning pain relief engages endogenous pain inhibition

When in pain, pain relief is much sought after, particularly for individuals with chronic pain. In analogy to augmentation of the hedonic experience (“liking”) of a reward by the motivation to obtain a reward (“wanting”), the seeking of pain relief in a motivated state might increase the experience of pain relief when obtained. We tested this hypothesis in a psychophysical experiment in healthy human subjects, by assessing potential pain-inhibitory effects of pain relief “won” in a wheel of fortune game compared with pain relief without winning, exploiting the fact that the mere chance of winning induces a motivated state. The results show pain-inhibitory effects of pain relief obtained by winning in behaviorally assessed pain perception and ratings of pain intensity. Further, the higher participants scored on the personality trait novelty seeking, the more pain inhibition was induced. These results provide evidence that pain relief, when obtained in a motivated state, engages endogenous pain-inhibitory systems beyond the pain reduction that underlies the relief in the first place. Consequently, such pain relief might be used to improve behavioral pain therapy, inducing a positive, perhaps self-amplifying feedback loop of reduced pain and improved functionality

Dysfunctional Neurotransmitter Systems in Fibromyalgia, Their Role in Central Stress Circuitry and Pharmacological Actions on These Systems

Fibromyalgia is considered a stress-related disorder, and hypo- as well as hyperactive stress systems (sympathetic nervous system and hypothalamic-pituitary-adrenal axis) have been found. Some observations raise doubts on the view that alterations in these stress systems are solely responsible for fibromyalgia symptoms. Cumulative evidence points at dysfunctional transmitter systems that may underlie the major symptoms of the condition. In addition, all transmitter systems found to be altered in fibromyalgia influence the body's stress systems. Since both transmitter and stress systems change during chronic stress, it is conceivable that both systems change in parallel, interact, and contribute to the phenotype of fibromyalgia. As we outline in this paper, subgroups of patients might exhibit varying degrees and types of transmitter dysfunction, explaining differences in symptomatoloy and contributing to the heterogeneity of fibromyalgia. The finding that not all fibromyalgia patients respond to the same medications, targeting dysfunctional transmitter systems, further supports this hypothesis

Measuring pain and nociception: Through the glasses of a computational scientist. Transdisciplinary overview of methods

In a healthy state, pain plays an important role in natural biofeedback loops and helps to detect and prevent potentially harmful stimuli and situations. However, pain can become chronic and as such a pathological condition, losing its informative and adaptive function. Efficient pain treatment remains a largely unmet clinical need. One promising route to improve the characterization of pain, and with that the potential for more effective pain therapies, is the integration of different data modalities through cutting edge computational methods. Using these methods, multiscale, complex, and network models of pain signaling can be created and utilized for the benefit of patients. Such models require collaborative work of experts from different research domains such as medicine, biology, physiology, psychology as well as mathematics and data science. Efficient work of collaborative teams requires developing of a common language and common level of understanding as a prerequisite. One of ways to meet this need is to provide easy to comprehend overviews of certain topics within the pain research domain. Here, we propose such an overview on the topic of pain assessment in humans for computational researchers. Quantifications related to pain are necessary for building computational models. However, as defined by the International Association of the Study of Pain (IASP), pain is a sensory and emotional experience and thus, it cannot be measured and quantified objectively. This results in a need for clear distinctions between nociception, pain and correlates of pain. Therefore, here we review methods to assess pain as a percept and nociception as a biological basis for this percept in humans, with the goal of creating a roadmap of modelling options

Reward Enhances Pain Discrimination in Humans

The notion that reward inhibits pain is a well-supported observation in both humans and animals, allowing suppression of pain reflexes to acquired rewarding stimuli. However, a blanket inhibition of pain by reward would also impair pain discrimination. In contrast, early counterconditioning experiments implied that reward might actually spare pain discrimination. To test this hypothesis, we investigated whether discriminative performance was enhanced or inhibited by reward. We found in adult human volunteers (N = 25) that pain-based discriminative ability is actually enhanced by reward, especially when reward is directly contingent on discriminative performance. Drift-diffusion modeling shows that this relates to an augmentation of the underlying sensory signal strength and is not merely an effect of decision bias. This enhancement of sensory-discriminative pain-information processing suggests that whereas reward can promote reward-acquiring behavior by inhibition of pain in some circumstances, it can also facilitate important discriminative information of the sensory input when necessary

UNCOVERING THE PRIVACY PARADOX: THE INFLUENCE OF DISTRACTION ON DATA DISCLOSURE DECISIONS

The discrepancy between individuals’ intention to disclose data and their actual disclosure behaviour is called the privacy paradox. Although a wide range of research has investigated the privacy para-dox, it remains insufficiently understood due to mental processes’ role in decision-making being most-ly neglected. This research-in-progress provides a theoretical concept that examines the cognitive processes underlying data disclosure decisions to provide a better understanding of the privacy para-dox. We apply the Elaboration Likelihood Model (ELM), which suggests that the mental shortcuts that individuals take when making their actual data disclosure decision, which differs from their self-reported data disclosure intention, cause the privacy paradox. We propose a two-step, mixed method approach comprising a survey and an online experiment to empirically explore the intended and actu-al data disclosure. The study takes theoretical and methodological issues in prior literature into ac-count and enhances our understanding of individuals’ paradoxical data disclosure behaviour from a psychological point of view

The underestimated significance of conditioning in placebo hypoalgesia and nocebo hyperalgesia

Placebo and nocebo effects are intriguing phenomena in pain perception with important implications for clinical research and practice because they can alleviate or increase pain. According to current theoretical accounts, these effects can be shaped by verbal suggestions, social observational learning, and classical conditioning and are necessarily mediated by explicit expectation. In this review, we focus on the contribution of conditioning in the induction of placebo hypoalgesia and nocebo hyperalgesia and present accumulating evidence that conditioning independent from explicit expectation can cause these effects. Especially studies using subliminal stimulus presentation and implicit conditioning (i.e., without contingency awareness) that bypass the development of explicit expectation suggest that conditioning without explicit expectation can lead to placebo and nocebo effects in pain perception. Because only few studies have investigated clinical samples, the picture seems less clear when it comes to patient populations with chronic pain. However, conditioning appears to be a promising means to optimize treatment. In order to get a better insight into the mechanisms of placebo and nocebo effects in pain and the possible benefits of conditioning compared to explicit expectation, future studies should carefully distinguish both methods of induction

Le théâtre radiophonique de René de Obaldia

Comme Heinz Schwitzke, un des plus importants théoriciens du théâtre radiophonique de l’Allemagne de l’après-guerre, l’a obser­vé, les inventions techniques ne sont jamais des découvertes accidentelles mais elles sont intimement liées aux courants intellectuels qui les précèdent : Cela paraît étrange mais […] on inclinerait presque à dire que ce qui est le plus important dans le radio-drame avait déjà été inventé avant l’invention de la radio. Quoi qu’il en soit, les principes artistiques de..

Reduziert der Zusatz von Fumarsäure die ruminale Methanproduktion durch Beeinflussung der Populationsstruktur der mikrobiellen Gemeinschaft?

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Implicit operant learning of pain sensitization and habituation in healthy participants and fibromyalgia patients

The important role of operant learning in chronic pain is widely recognized. However, the precise mechanisms mediating between nociceptive processing, operant consequences and altered pain perception remain being unclear. The general aim of the three studies contained in this thesis was to clarify the latter. For this purpose, experimental operant learning tasks were employed that were independent of subjective pain report, in order to avoid the risk of solely changing response crite-ria. Further, intrinsic reinforcement—within the nociceptive system by reductions in nociceptive input—was applied. In contrast to extrinsic reinforcement—external to the nociceptive system e.g. by monetary reinforcement—intrinsic reinforcement directly affects pain perception. In study 1, a continuous operant conditioning procedure for enhancing pain sensitivity with different magnitudes of reinforcement and different schedules of reinforcement was implemented in healthy participants. The results indicated a dose-dependency of the operant learning. Further, enhanced pain sensitivity was the result of underlying learning rather than immediate (unconditioned) effects of reinforcement (pain relief). Together with a previous study, the independence of the operant learning mechanism from the experimental procedure was demonstrated. Thus, operant learning of pain sensitivity was demonstrated to be a valid and robust mechanism. In order to demonstrate operant learning to be implicit—i.e. learning without awareness—study 2 employed a discrete-trial operant learning procedure in healthy participants similar to a previously implemented operant learning procedure. Awareness was tested with a behavioral task (prediction of reinforcement) and a standardized interview, addressing different levels of processing. The results demonstrated that operant learning of altered pain sensitivity was implicit; neither verbalization of the operant contingencies (the relationships between behavior and stimuli associated with reinforcement) nor behavioral discrimination was necessary for successful operant learning. Study 3 repeated the same paradigm as study 2 in chronic pain patients with fibromyalgia with and without comorbid irritable bowel syndrome for testing the vulnerability of these patients to operant learning of altered pain sensitivity. In contrast to a hypothesized heightened vulnerability, operant learning was impaired in these patients compared to healthy participants. Moreover, fibromyalgia patients with and without irritable bowel syndrome respond differentially to the operant conditioning: While fibromyalgia patients with irritable bowel syndrome showed no signs of operant learning, fibromyalgia patients without irritable bowel syndrome displayed enhanced perceptual sensitization, but this enhancement was paradoxically more pronounced in the habituation learning condition than in the sensitization learning condition. Thus, parameters of operant learning of altered pain sensitivity differentiated between healthy participants and chronic pain patients as well as between different groups of chronic pain patients. In addition, a dissociation of physical stimulus intensities and subjective pain reports was observed, indicating that overt reporting is not the adequate representation level of pain perception relevant for learning altered pain sensitivity. Taken together, these studies demonstrated (1) operant learning to a be powerful, pathogenetically relevant mechanism, producing gross changes in pain sensitivity without the persons’ knowledge and (2) the necessity of behavioral discrimination paradigms that do not depend on subjective measures of pain expe-rience in the first place. The proposed implicit operant learning mechanism of altered pain sensitivity with intrinsic reinforcement provides an explanation for the gradual development of hypersensitivity in pain that is becoming chronic. These results have implications for a wide range of applications ranging from diagnostic procedures to therapeutical interventions in chronic pain