pinecone/core-2020-05-10-deduplication huggingface dataset:
Cooperativity and allostery in haemoglobin function.

Tetrameric haemoglobins display a cooperative ligand binding behaviour, which has been attributed to the functional interrelationship between multiple ligand binding sites. The quantitative description of this feature was initially carried out with a phenomenological approach, which was limited to the functional effect of the occupancy by a ligand molecule of a binding site on further binding steps. However, subsequent development of structural-functional models for the description of the cooperativity in haemoglobin brought about a much deeper information on the interrelationships between ligand binding at the heme and structural variations occurring in the surrounding free subunits. This approach opened the way to the evolution of the concept of allostery, which is intended as the structural-functional effect exerted by the presence of a ligand in a binding site on other binding sites present in the same molecule. This concept can be applied to either sites for the same ligand (homotropic allostery) and for sites of different ligands (heterotropic allostery). Several models trying to take into account the continuous building up of structural and functional information on the physicochemical properties of haemoglobin have been developed along this line. (c) 2008 IUBMB
The impact of parental gender, catastrophizing, and situational threat upon parental behaviour to child pain: a vignette study

Background: This study examined which parents report to be solicitous or discouraging in response to their child's pain, and when they do so. Methods: Using a vignette methodology, mothers (n = 472) and fathers (n = 271) imagined their child in pain situations varying in duration (1 day or several weeks) and cause of pain (known or unknown biomedical cause). Results: In general, fathers demonstrated similar tendencies toward solicitousness than mothers, but reported to engage more in discouraging behaviours. In line with expectations, parents who catastrophized about their child's pain reported a higher inclination to engage in solicitous behaviours. Only for fathers, high catastrophizing was also related to a higher report of discouraging behaviours. However, the effects of catastrophizing differed across situations varying in duration and cause of pain. Specifically, the effect of parental catastrophizing upon self-reported solicitous behaviours was particularly strong when imagining their child in pain with unknown biomedical cause. Further, high catastrophizing in fathers only translated in a higher inclination for discouraging responses when imagining their child in pain of short duration. Conclusions: The findings of the current study highlight the importance of parental catastrophizing in explaining parental behavioural tendencies in response to their child in pain. Further, reported behaviours were found to vary across pain situations, attesting to the importance of studying parental behaviour 'in context'
Acceptance as a Process Variable in Relation to Catastrophizing in Multidisciplinary Pain Treatment

Background The underlying processes of change that contribute to the effectiveness of multidisciplinary pain treatment require clarification. Previous research has found support for pain acceptance as a process variable in acceptance-based treatment. Preliminary findings indicate that pain acceptance may also be a process variable in traditional cognitive behavioural therapy (CBT). The aim of this study was to investigate the role of pain acceptance as a process variable in CBT relative to two empirically supported process variables, namely catastrophizing and pain intensity. Methods Patients with chronic pain (n?=?186) attended a 3-week, multidisciplinary pain programme, which was CBT based. Patients completed a measure of pain intensity; the Chronic Pain Acceptance Questionnaire; the catastrophizing subscale of the Pain Response Self-Statements Scale; the Roland Morris Disability Questionnaire; the Depression Anxiety and Stress Scale; and two measures of physical functioning at pretreatment, post-treatment and 3-month follow-up. Results Both acceptance and catastrophizing showed statistically significant and clinically relevant changes from pre- to post-treatment. Changes in both acceptance and catastrophizing showed a significant correlation with changes in almost all of the outcome variables. Regression analyses demonstrated that change in acceptance was a significant predictor of changes in depression, disability, timed walk and sit-to-stand performance, after controlling for changes in catastrophizing and pain intensity. Conclusions Although not specifically targeted in CBT treatment, acceptance of pain was an important process variable that contributed to CBT treatment outcomes after controlling for changes in pain intensity and catastrophizing. Implications for future research and clinical practice are discussed
Keeping pain out of your mind: the role of attentional set in pain

Background : The involuntary capture of attention by pain may, to some extent, be controlled by psychological variables. In this paper, we investigated the effect of attentional set (i.e., the collection of task-related features that a person is monitoring in order to successfully pursue a goal) on pain.
Methods : Two experiments are reported in which the task relevance of the modality and spatial location of a target stimulus was manipulated. In both experiments, somatosensory and auditory stimuli were presented on each trial. In experiment 1, 29 participants were cued on each trial to localize either a somatosensory or an auditory target. In experiment 2, 37 participants were cued on each trial to identify either a somatosensory or an auditory target at a particular location.
Results : In experiment 1, self-reported pain intensity and unpleasantness were reduced when participants had to localize the auditory target. The location of the painful stimulus relative to the location of the auditory target did not affect pain. In experiment 2, again, pain intensity and unpleasantness ratings were reduced when participants identified the auditory target. Now, the location of the painful stimulus relative to the location of the auditory target moderated the effect. Pain intensity was less when the painful stimulus was at a different location than the auditory target.
Conclusions : Results are discussed in terms of the attentional set hypothesis, and we argue that the effectiveness of distraction tasks depends on the degree to which the task-relevant features of the distraction task are distinct from pain-related features
On the moderating role of age in the relationship between pain and cognition

Contains fulltext :
                  116594.pdf (publisher's version ) (Open Access)Background A relationship between pain perception and cognitive function is evident. However, the directionality of this association is unclear and may be influenced by age. That is, inverse associations between pain and cognition have been reported in young and middle-aged chronic pain patients, whereas higher clinical pain ratings have been associated with better cognitive performance in older chronic pain patients. Therefore, this study examined the possible moderating role of age in the pain-cognition relationship. Method Twenty-two younger and 24 older chronic pain participants completed neuropsychological tests of psychomotor speed, memory and executive function. They also completed the McGill Pain Questionnaire to evaluate clinical pain. Results Interaction analyses revealed that age indeed moderates the relationship between clinical pain ratings and cognitive functions. In the younger age group, pain ratings were inversely related to memory and executive function. In the older age group, a positive relationship was found between pain ratings and executive function, whereas the inverse association of clinical pain with memory was no longer present. Conclusions This study was the first to confirm the hypothesis that age is an important moderator of the relationship between pain and cognition. An important finding is that in older adults, most inverse effects of pain on cognition are either no longer present or may even be reversed. The positive relationship between pain and executive function may indicate age-related reduced integrity of a shared underlying neural substrate
Fear-learning deficits in subjects with fibromyalgia syndrome?

BACKGROUND: Fibromyalgia syndrome (FMS) is frequently associated with psychiatric conditions, particularly anxiety. Deficits in contingency learning during fear conditioning have been hypothesized to increase anxiety and, consequently, pain sensation in susceptible individuals. The goal of this study was to examine the relationship between contingency learning and pain experience in subjects with FMS and rheumatoid arthritis (RA). METHODS: Fourteen female FMS subjects, 14 age-matched female RA subjects and 14 age-matched female healthy controls (HCs) were included in a fear-conditioning experiment. The conditioned stimulus (CS) consisted of visual signs, the unconditioned stimulus (US) of thermal stimuli. CS- predicted low-temperature exposure (US), while CS+ was followed by low or high temperature. RESULTS: In the FMS group, only 50% of the subjects were aware of the US-CS contingency, whereas 86% of the RA subjects and all of the HCs were aware of the contingency. CS+ induced more anxiety than CS- in RA subjects and HCs. As expected, low-temperature exposure was experienced as less painful after CS- than after CS+ in these subjects. FMS subjects did not show such adaptive conditioning. The effects of the type of CS on heart rate changes were significant in the HCs and the aware FMS subjects, but not in the unaware FMS subjects. CONCLUSIONS: Contingency learning deficits represent a potentially promising and specific, but largely unstudied, psychopathological factor in FMS. Deficits in contingency learning may increase anxiety and, consequently, pain sensation. These findings have the potential to contribute to the development of novel therapeutic approaches for FMS
Ecological Momentary Assessment for chronic pain in fibromyalgia using a smartphone: A randomized crossover study

Background: Daily diaries are a useful way of measuring fluctuations in pain-related
symptoms. Although this approach entails a repeated assessment, traditional diaries do
not assure the gathering of data in real-time, and therefore do not solve the problem of
retrospective assessment. Ecological momentary assessment (EMA) and, more
concretely, real-time data capture (RTDC) by means of electronic diaries can help to
improve repeated assessment in chronic pain.
Method: The present work contributes to this line of research by comparing the
accuracy and acceptability of an RTDC method running on a smartphone using a
crossover design for a sample with a low level of education and low familiarity with
technology. Forty-seven women diagnosed with fibromyalgia were randomly assigned
to one of two conditions: 1) paper diary – smartphone diary, and 2) smartphone diary –
paper diary, using each assessment method for one week.
Results: The findings of this study showed that the smartphone diary made it possible
to gather more accurate and complete ratings of relevant variables. Besides, this method
was well accepted by a sample of fibromyalgia patients referred by a public hospital
with a large proportion of participants with low level of education and low familiarity
with technology.
Conclusion: The findings of this study support the use of smartphones for ecological
momentary assessment in the field of chronic pain. These methods could help clinicians
and researchers to gather more accurate ratings of relevant pain-related variables even in
populations with low educational levels and low familiarity with technology
Modulation of pain threshold by virtual body ownership

Appropriate sensorimotor correlations can result in the illusion of ownership of exogenous body parts. Nevertheless, whether and how the illusion of owning a new body part affects human perception, and in particular pain detection, is still poorly investigated. Recent findings have shown that seeing one's own body is analgesic, but it is not known whether this effect is transferable to newly embodied, but exogenous, body parts. In recent years, results from our laboratory have demonstrated that a virtual body can be felt as one's own, provided realistic multisensory correlations
Effects of mindfulness and distraction on pain depend on individual differences in pain catastrophizing: an experimental study

BackgroundThe aim of this study was to investigate whether the perception of experimental pain was different during a mindfulness manipulation than during a distraction manipulation. Furthermore, it was examined if effects were moderated by dispositional pain catastrophizing.
MethodsUndergraduate students (n=51) completed self-report measures of pain catastrophizing and mindfulness. Subsequently, they were administered a series of mildly painful heat stimuli, which they had to rate. During pain induction, participants listened to either a pre-recorded mindfulness instruction (mindfulness group) or a pre-recorded story (distraction group).
ResultsAfter controlling for baseline experimental pain ratings, we found no overall group effect, indicating that there was no difference in experienced pain between the mindfulness group and the distraction group. However, a significant moderation effect was found. When dispositional pain catastrophizing was high, pain was less pronounced in the mindfulness group than in the distraction group, whereas the opposite effect was found when the level of pain catastrophizing was low.
ConclusionsThe findings suggest that in persons with a high level of catastrophic thinking about pain, mindfulness-based coping may be a better approach than distraction
Pharmacokinetics of Ceftriaxone in Liver‐Transplant Recipients

The disposition of ceftriaxone was studied after a single 2 g intravenous dose in seven patients 3 to 5 days after liver transplantation. Ceftriaxone concentrations in plasma, urine, and bile were measured by HPLC, and plasma protein binding was determined by equilibrium dialysis. Plasma protein binding was nonlinear, and the unbound fraction varied between 0.05 and 0.56. Both capacity and affinity were markedly different from reported values for normal subjects. The pharmacokinetic parameters obtained were: total body clearance (TBC), 11.2 ± 7.8 mL/hr/kg total and 44.8 ± 29.1 mL/hr/kg unbound; volume of distribution (Varea), 224 ± 76 mh/kg total and 767 ± 432 mL/kg unbound; steady‐state volume of distribution (Vss), 212 ± 68 mh/kg total and 651 ± 368 mL/kg unbound; terminal disposition half‐life (t1/2), 21.6 ± 14.3 hour total and 16.3 ±11.1 hour unbound. TBC for both total and free drug was considerably lower than literature values for normal subjects. Vareafor total drug was greater than normal whereas the corresponding value for free drug was smaller than normal. The plasma ceftriaxone concentrations at 12 and 24 hours were above the reported minimum inhibitory concentration (MIC). The fraction of the administered dose excreted in urine over 24 hours was 38 ± 29% and did not differ markedly from that reported for normal subjects. Less than 2% of the administered dose was excreted in 24‐hour bile; however, biliary concentrations were always above MIC. Ceftriaxone can be administered once or twice daily at a dose of 2 g/day for prophylaxis in liver transplant recipients. 1991 American College of Clinical Pharmacolog
An intelligent and cost-effective computer dosing system for individualizing FK506 therapy in transplantation and autoimmune disorders

The accuracy and precision of an intelligent dosing system (IDS) for FK506 in predicting doses to achieve target drug levels has been prospectively evaluated in transplant and autoimmune patients. For dose individualization, the knowledge base is updated with patient-specific feedback including the current dose, drug level, and the new target level. The study population of 147 patients consisted of 97 transplant patients (liver and kidney) and 50 patients with autoimmune disorders. Patients in the transplant study group were entered sequentially and followed as a cohort. Patients in the autoimmune study group were randomly assigned to one of three predefined FK506 concentration windows (low, 0.1-.3; medium, 0.4-.7; and high, 0.8-1.3 ng/mL) as part of a concentration controlled clinical trial. Predictions of steady-state plasma drug levels were made throughout the clinical course of autoimmune patients and during the first 6 weeks post-transplant in liver and kidney recipients. FK506 concentration in plasma was measured by a monoclonal antibody based ELISA assay. Accuracy was computed as the mean prediction error (mpe). Precision was computed as the root mean squared prediction error (rmspe). The accuracy of the IDS in each study group was as follows: 0.016 ng/mL (liver), -0.034 ng/mL (kidney), and -0.022 ng/mL (autoimmune). Because the 95% confidence interval included zero in each case, the IDS showed no bias. The precision of the IDS in each study group was as follows: 0.133 ng mL (liver), 0.1903 ng/mL (kidney), and 0.1188 ng/mL (autoimmune). These results indicate that the FK506 IDS is both accurate and very precise (reproducible) in transplant and autoimmune patients. The performance of the FK506 compares favorably with previously reported pharmacokinetic dosing methods such as population nomograms and adaptive control feedback methods (least-squares and Bayesian). Based on our findings, this IDS should have a number of important uses relevant to the drug development process, the prescribing physician and the individual patient. It provides an efficient method for implementing concentration controlled clinical trials. It should accelerate the physician's learning curve while at the same time help to maximize therapeutic drug efficacy and minimize toxicity with drugs exhibiting nonlinear kinetics and narrow therapeutic indices. Preliminary studies suggest that these assets result in a significant cost-benefit advantage by reducing the duration of hospitalization. Current studies are in progress to validate this and carefully measure its pharmacoeconomic impact
Pharmacokinetics of FK506 in liver transplant recipients after continuous intravenous infusion

The first-dose pharmacokinetics of FK506 was studied in nine orthotopic liver transplant patients receiving continuous intravenous infusion of 0.15 mg/kg/day. Multiple blood samples were obtained during the infusion and plasma FK506 concentrations were measured by enzyme-linked immunosorbent assay. The plasma clearance ranged from 0.47 to 5.8 L/minute, and the half- life ranged from 4.5 hours to 33.1 hours. These results indicate the pharmacokinetics of FK506 to be highly variable between patients. FK506 is extensively distributed outside the plasma compartment. FK506 is extensively metabolized in the body, with less than 1% of the administered dose being excreted in the urine as unchanged FK506. The large variability in FK506 kinetics during the immediate postoperative period is attributed to the variability in the functional status of the liver in the transplant patients. Because of the long half-life of FK506, it takes more than 45 hours to reach steady-state concentrations after continuous infusion. Based on the estimated kinetic parameters, it appears that a combination of a bolus or a rapid infusion of .02 mg/kg with a continuous infusion of 0.05 mg/kg/day will provide and maintain a concentration of more than 2 ng/mL from the beginning of the drug treatment
The Politics of Welfare State Reform

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                  178395.pdf (publisher's version ) (Open Access)This article presents and discusses the state of the art in political science research on welfare state reform. While scholars first aimed at explaining the emergence and growth of the welfare state, national variation in its development, and crises of welfare state regimes, more recently the focus has shifted to the persistence and reform of the major welfare state institutions. Research in this direction has typically adopted an institutionalist perspective, stressing how institutional settings affect the feasibility and direction of reforms. These studies have shed light on important aspects of the question, in particular by demonstrating the role of path dependency and veto players in reform processes, but suffer from two main problems, namely the difficulty of defining the dependent variable in an appropriate way, and the neglect of the importance of power resources
Individual and Contextual Determinants of Electoral Participation

Individual-level explanations of electoral participation typically argue that non-voting is determined by a combination of facilitative and motivational factors. We advance the argument that, beyond individual characteristics, there are pivotal contextual features which enable or impede individual action through specific incentive structures. Thus, contextual factors influence the individual propensity to vote or to abstain. For the first time the data of Selects 2003 allows for the testing of contextual effects, at least on the cantonal level. Several multilevel analyses show that high party competition, compulsory voting, and strong Catholicism foster individual participation. The findings clearly indicate that an individual's propensity to vote is influenced by personal characteristics as well as by cantonal attributes
The Hobbesian case for multilateralism

In this paper an analysis of Hobbes' argument in favor of the Leviathan is combined with a reassessment in a new security environment. The analysis shows that Hobbes' premises are complex and lead to conclusions that differ from the realist as well as from the world-state position, both attributed to Hobbesian logic in IR theory. A strict application of the Hobbesian argument in today's security context leads to a rationale of multilateral institution-building among states. In the first part of the paper the internationalist analogy in the concept of war of all against all is uncovered and analyzed in relation to the security dilemma, domestic analogy, and methodological individualism. The second part reassesses the Hobbesian security rationale in a security environment which is assumed to be shaped by transnational terrorism and nuclear WMD
Empirical modeling of policy diffusion in federal states: the dyadic approach

Policy diffusion is a common phenomenon in federal states: indeed, one of the normative justifications of decentralized policy making is that it permits the development and spread of best practices. Following Berry and Berry (1990), event-history analysis has been the method of choice for the quantitative investigation of policy diffusion, but Volden (2006) has recently introduced a dyadic variant of this method in which units of analysis are not states but, instead, pairs of states. This article discusses the dyadic approach with a particular focus on the diffusion of policies in Switzerland. The goal is not to introduce a new method, but rather to provide a practical overview for researchers interested in using it. The article shows how the method has migrated from the international relations literature to the policy-diffusion literature, describes the typical structure of a dyadic dataset in a diffusion context, and discusses several modeling issues. The usefulness of the dyadic approach is illustrated empirically with the example of health-insurance subsidy policies in Swiss cantons