Effectiveness is a key criterion in assessing the justification of antibiotic resistance interventions. Depending on an intervention’s effectiveness, burdens and costs will be more or less justified, which is especially important for large scale population-level interventions with high running costs and pronounced risks to individuals in terms of wellbeing, integrity and autonomy. In this paper, we assess the case of routine hospital screening for multi-drug-resistant Gram-negative bacteria (MDRGN) from this perspective. Utilizing a comparison to screening programs for Methicillin-Resistant (...) Staphylococcus aureus (MRSA) we argue that current screening programmes for MDRGN in low endemic settings should be reconsidered, as its effectiveness is in doubt, while general downsides to screening programs remain. To accomplish justifiable antibiotic stewardship, MDRGN screening should not be viewed as a separate measure, but rather as part of a comprehensive approach. The program should be redesigned to focus on those at risk of developing symptomatic infections with MDRGN rather than merely detecting those colonised. (shrink)

Recent research shows that a faulty or sub‐optimally operating metabolic network can often be rescued by the targeted removal of enzyme‐coding genes – the exact opposite of what traditional gene therapy would suggest. Predictions go as far as to assert that certain gene knockouts can restore the growth of otherwise nonviable gene‐deficient cells. Many questions follow from this discovery: What are the underlying mechanisms? How generalizable is this effect? What are the potential applications? Here, I approach these questions from the (...) perspective of compensatory perturbations on networks. Relations are drawn between such synthetic rescues and naturally occurring cascades of reaction inactivation, as well as their analogs in physical and other biological networks. I specially discuss how rescue interactions can lead to the rational design of antagonistic drug combinations that select against resistance and how they can illuminate medical research on cancer, antibiotics, and metabolic diseases. Editor's suggested further reading in BioEssaysThe evolutionary context of robust and redundant cell biological mechanisms AbstractReprogramming cell fates: reconciling rarity with robustness Abstract. (shrink)

Drug development regularly has to deal with complex circumstances on two levels: the local level of pharmacological intervention on specific target proteins, and the systems level of the effects of pharmacological intervention on the organism. Different development strategies in the recent history of early drug development can be understood as competing attempts at coming to grips with these multi-level complexities. Both rational drug design and high-throughput screening concentrate on the local level, while traditional empirical search strategies (...) as well as recent systems biology approaches focus on the systems level. The analysis of these strategies reveals serious obstacles to integrating the study of interventive and systems complexity in a systematic, methodical way. Due to some fairly general properties of biological networks and the available options for pharmaceutical intervention, drug development is captured in an obstinate methodological dilemma. It is argued that at least in typical cases, drug development therefore remains dependent on coincidence, serendipity or plain luck to bridge the gap between development methodology and actual therapeutic success. (shrink)

Aim Genetic research representative of the population is crucial to understanding the underlying causes of many diseases. In a prospective evaluation of informed consent we assessed the willingness of individuals of different ethnicities, gender and drug dependence history to participate in genetic studies in which their genetic sample could be shared with a repository at the National Institutes of Health. Methods Potential subjects were recruited from the general population through the use of flyers and referrals from previous participants and (...) clinicians with knowledge of our study. They could consent to 11 separate choices so that they could specify how and with whom their genetic sample could be shared. Rates of affirmative consent were then analysed by gender, ethnicity and drug dependence history. Results Of 1416 volunteers enrolled, 99.7% gave affirmative informed consent for studies of addiction conducted in our laboratory. No significant difference was found for participation in genetic studies conducted in our laboratory by gender, ethnicity or drug dependence history. Over all 11 questions, individuals with a history of drug use were more likely to agree to consent to participate in our study than were healthy volunteers. Conclusion A high percentage of each category of gender, ethnicity and drug history, gave affirmative consent at all levels. The level of detail in and the amount of time spent reviewing the informed consent, and a relationship of trust with the clinical investigator may contribute to this outcome. (shrink)

This article addresses the relationship between content, voice, and body language in persuasive communication and the contribution of these three elements of persuasive performances to its overall persuasiveness. Findings are presented from two separate laboratory experiments. In the first experiment three versions of a video displaying a speech were shown to three different groups of participants: without vocal emphasis and without gestures of the speaker, with vocal emphasis but without gestures, with vocal emphasis and gestures. Audio tracks of the (...) first two experimental conditions were later used in the second experiment to analyze the effects of vocal emphasis when no visual cues are present. Measurement included a questionnaire as well as Real Time Response-measurement. It was found that content dominates the effect of the speech; emphasis and gestures, however, improved the perception of some features of the speech, such as liveliness and power. Audio-only versions yielded similar results but were rated more favorably in general. (shrink)

Drug regulation is fraught with inductive risk. Regulators must make a prediction about whether or not an experimental pharmaceutical will be effective and relatively safe when used by typical patients, and such predictions are based on a complex, indeterminate, and incomplete evidential basis. Such inductive risk has important practical consequences. If regulators reject an experimental drug when it in fact has a favourable benefit/harm profile, then a valuable intervention is denied to the public and a company’s material interests (...) are needlessly thwarted. Conversely, if regulators approve an experimental drug when it in fact has an unfavourable benefit/harm profile, then resources are wasted, people are needlessly harmed, and other potentially more effective treatments are underutilized. Given that such regulatory decisions have these practical consequences, non-epistemic values about the relative importance of these consequences impact the way such regulatory decisions are made (similar to the analysis of laboratory studies on the toxic effects of dioxins presented in Douglas [2000]). To balance the competing demands of the pertinent non-epistemic values, regulators must perform what I call an “inductive risk calculus.” At least in the American context this inductive risk calculus is not well-managed. (shrink)

One of the effects of the current COVID-19 pandemic is that low-income countries were pushed further into extreme poverty, exacerbating social inequalities and increasing susceptibility to drug use/abuse in people of all ages. The risks of drug abuse may not be fully understood by all members of society, partly because of the taboo nature of the subject, and partly because of the considerable gap between scientific production/understanding and communication of such knowledge to the public at large. Drug (...) use is a major challenge to social development and a leading cause of school dropout rates worldwide. Some public policies adopted in several countries in recent decades failed to prevent drug use, especially because they focused on imposing combative or coercive measures, investing little or nothing in education and prevention. Here we highlight the role of neuroscience education as a valid approach in drug use education and prevention. We propose building a bridge between schools and scientists by promoting information, student engagement and honest dialogue, and show evidence that public policy regulators should be persuaded to support such science-based education programs in their efforts to effect important positive changes in society. (shrink)

The COVID-19 pandemic has plunged the housing affordability and living sanitary conditions of China's low-income groups into a crisis. Public rental housing has made a significant contribution to alleviating this crisis, yet its exit problem has become more acute due to the impact of the epidemic. In order to explore how to effectively play the role of multi-governance in public rental housing exit, this paper adopts game theory to analyze the evolution of the behavioral strategies of government departments and (...) public rental housing tenants in public rental housing exit by combining four influencing parameters: the epidemic severity, the epidemic influence coefficient, the public participation degree, and the public reporting fairness. In response to exploring the conditions for the effective functioning of the multi-governance model under the impact of the epidemic, the influences of parameter change on the stability of the system are analyzed. The results show that when the COVID-19 epidemic impact coefficient is high, government departments need to reduce their own supervision costs to achieve better multi-governance effects; when public reports are distorted, the government departments’ own supervision capabilities determine the impact of public participation on governance effects. (shrink)

This research is part of the last study Drugs and School IX developed in the Basque Country (Spain) by the Instituto Deusto de Drogodependencias (Deusto Institute of Drug Addiction) of the University of Deusto and the data gathered by means of cluster sampling in two stages. The sample is made up of N= 6.007 girls and boys ranging from 12 to 22 years of age in Secondary Education and the aim is to answer the following new research questions based (...) on those parameters: (1) describe the reality of drug consumption and some psychosocial variables in this sample, as well as analyse several relations between variables; (2) analysing the role of school well-being, self-esteem and self-concept regarding consumption; (3) taking a close look at the moderating role of age and gender on the relationship of school well-being, self-concept and self-esteem with consumption; and (4) understand the existing interaction between all these variables, studying the moderating role of self-esteem and self-concept in the influence of school well-being on consumption. Using a correlation, hierarchical regression and mediation analysis with SPSS (v. 26) and Amos (v. 26) applications, three main conclusions were reached. Firstly, that educational and academic well-being, academic self-concept and self-esteem seem to play the role of protecting factors in adolescence, while assertiveness is linked to a higher consumption level. Secondly, that academic self-concept has a mediating effect between well-being and consumption. Some of these relations are moderated by the variables of gender and age. Thirdly, that age and gender are very relevant sociodemographic variables that must be taken into account in order to understand this phenomenon. Age has shown its covariant effect, which is especially relevant in the influence of academic well-being measured as being held back years. It has also proved to be important in order to understand its experiential or experimental and transitory character. Moreover, significant differences in consumptions have been found based on gender. (shrink)

Ventricular Fibrillation is responsible for a majority of sudden cardiac death, but little is known about how ventricular tachycardia (VT) degenerates into ventricular fibrillation. Several clinical studies focused only on preventing VT with a class III antiarrhythmic drug resulted in many deaths. Our simulations investigate the interactions between an antiarrhythmic drug likely to suppress a VT and a Figure 8 reentry. A parameter AAR is introduced to increase the action potential duration and therefore simulate various Class III drugs. (...) Simulations are ran under several conditions (phases of the reentry, values of AAR, durations). They show that a VT can be suppressed whatever the phase of the reentry but it strongly depends on the duration of the effect. It confirms that a drug which can suppress a reentry can also worsen it. It also shows a great variety of activation patterns and thus the complexity of antiarrhythmic drugs effects. Simulations also demonstrate that suppressing VT is an increasing function of AAR. (shrink)

The paper introduces the problem of unawareness into multi-dimensional Principal–Agent theory. We introduce two key parameters to describe the problem, the extent and the effect of unawareness, show under what conditions it is optimal for the Principal to propose an incomplete or a complete contract, and characterize the incentive power of optimal linear contracts. If Agents differ in their unawareness, optimal incentive schemes can be distorted for both aware and unaware Agents, because, different from standard contract theory, the single-crossing (...) property fails to hold. In this case, even aware Agents can be subject to inefficiently high or low incentives. (shrink)

The placebo drug reactions from controlled trials were studied for the first time systematically for efficacy and the safety in drug data pooled from randomized, placebo-controlled, multicentre studies. Results: The efficacy of placebo on clinical symptoms and outcome varied between the therapeutic indications. However, no placebo effects on laboratory values, as e.g. blood glucose or Hb1c in diabetics, were noted. The frequency and type of placebo-induced adverse reactions also varied between indication groups. The placebo side effect profile (...) was largely similar to the side effect profile of the active treatment. The mechanisms of placebo effects are manyfold and varied (e.g. endorphin release, conditioning), much lacks explanation. Conclusion: Since the prescription of non-evidence based medicines (= pseudoplacebos) may clearly also result in serious adverse effects, such practice may not only be non-beneficial but may even be harmful. In clinical research, the judicious use of placebo remains essential to establish the efficacy and safety, safeguarding that patients receiving placebo will not be subject to harm and are fully informed. (shrink)

Stimulants have been shown to be safe and effective for reduction of the symptoms of attention deficit hyperactivity disorder. Despite much debate, however, there has been little empirical evidence as to whether stimulants affect authenticity and moral agency in children. Singh presents evidence that stimulants do not undercut children's' sense of self and increase their experience of agency. These findings are consistent with laboratory evidence that stimulant drugs in therapeutic doses improve cognitive control over thought and behavior.

To investigate the effects of two different modes of physical activity on body composition, physical fitness, cardiometabolic risk, and psychological responses in female adolescents participating in a multi-disciplinary program. The 12-week randomized intervention included 25-adolescents with overweight divided into two groups: sports practice-SPG and functional training-FTG. The SPG intervention was divided into three sports: basketball, handball, and futsal. SPG participants performed one sport 3-times/week, over the course of 1 month. The FTG performed concurrent exercises 3-times/week. This study was registered (...) in Clinical Trials Registry Platform under number: RBR-45ywtg and registered in Local Ethics Committee number: 2,505.200/2018. The intensity of physical exercises-PE was matched between groups by the rating of perceived exertion. The primary outcome was body composition, and secondary outcomes were physical fitness, cardiometabolic risk, and psychological responses. There was a significant time-effect for body mass, body mass index, and low-density lipoprotein, all being reduced. There were increases over time for musculoskeletal mass, aerobic fitness, and high-density lipoprotein. There was a group time interaction with body fat percentage being lower post-intervention in the SPG. No significant differences were observed for the other variables. Both physical activity models were effective in improving a subset of obesity-related health parameters. The findings should be extended by further investigation using more sophisticated measures of energy expenditure.Clinical Trial Registration:https://ensaiosclinicos.gov.br/, identifier: RBR-45ywtg. (shrink)

Effective and personalized treatment relies heavily on skin disease categorization. In the stratification of skin disorders, it is crucial to identify the subtypes of illnesses to provide an efficient therapy. To attain this aim, researchers have focused their attention on cluster algorithms for the stratification of skin disorders in recent decades. But, cluster algorithms have real-world drawbacks, including experimental noises, a large number of dimensions, and a poor ability to comprehend. Cluster algorithms, in particular, determine the quality of clusters using (...) a single internal evaluation operation in the majority of cases. A single internal assessment procedure is difficult to design and robust for all datasets, which is a problem. The multi-objective particle swarm obtained high sensitivity in the existing work, but it is not able to anticipate all kinds of classes. An optimized cluster distance parameter for K-means clustering is determined using a hybrid particle swarm and moth flame optimization. Multi-objective is guided by two cluster value indices, including the K-means clustering misclassification rate and neural network classification rate. Hybrid PSO will solve the multi-objective problem to identify the optimal cluster for clustering. On the dermatological dataset from the UCI repository, MATLAB R2020a will be used to evaluate the proposed method. This will be followed by an evaluation of the proposed method’s performance using the cluster evaluation indices. (shrink)

The placebo drug reactions from controlled trials were studied for the first time systematically for efficacy and the safety in drug data pooled from randomized, placebo-controlled, multicentre studies. Results: The efficacy of placebo on clinical symptoms and outcome varied between the therapeutic indications. However, no placebo effects on laboratory values, as e.g. blood glucose or Hb1c in diabetics, were noted. The frequency and type of placebo-induced adverse reactions also varied between indication groups. The placebo side effect profile (...) was largely similar to the side effect profile of the active treatment. The mechanisms of placebo effects are manyfold and varied (e.g. endorphin release, conditioning), much lacks explanation. Conclusion: Since the prescription of non-evidence based medicines (= pseudoplacebos) may clearly also result in serious adverse effects, such practice may not only be non-beneficial but may even be harmful. In clinical research, the judicious use of placebo remains essential to establish the efficacy and safety, safeguarding that patients receiving placebo will not be subject to harm and are fully informed. (shrink)

This paper is part of a larger project to determine how to build agent-based cognitive models capable of initial associative intelligence. Our method here is to take McClelland’s 1981 “Jets and Sharks” dataset and rebuild it using a nonlinear dynamic system with an eye toward determining which parameters are necessary to govern the interactivity of agents in a multi-agent cognitive system. A few number of parameters are suggested concerning diffusion and infusion values, which are basically elementary forms of information (...) entropy, and multi-dimensional overlap from properties to objects and then from objects back to the properties that define them. While no agent-based model is presented, the success of the dynamic systems that are presented here suggest strong starting points for further research in building cognitive complex adaptive systems. (shrink)

Limitations of antiarrhythmic drugs on cardiac sudden death prevention appeared since the early 80's. The "Cardiac Arrhythmia Suppression Trial"(CAST) showed more recently that mortality was significantly higher inpatients treated with some particular antiarrhythmic drugs than in non-treated patients. In this field, our group recently demonstrated that a bolus of a Class 1B antiarrhythmic drug was able to trigger a ventricular fibrillation due to transient blocks induction. The aim of the present work was to systematically study, by use of the (...) van Capelle and Durrer (VCD) model which allows to simulate ventricular activation wave propagation, the link between arrhythmogenic effects and the ability of transient blocks to possibly degenerate in severe arrhythmias. A fragment of the ventricular wall is represented by an array of 16384elements electrically coupled. Effects of induction of one or several transient blocks, as the effects of their size and duration on possible induction of reentries have been studied. Results obtained show that various combinations between these different parameters may trigger reentries, ventricular tachycardia and/or more complex patterns assimilable to ventricular fibrillation. These results clearly evidence the fact that possible induction of transient blocks may directly be related to risk factor associated to arrhythmogenic effects of antiarrhythmic drugs. (shrink)

Molecular genetic testing has increasingly been incorporated into clinical medicine, and this trend is likely to accelerate in the future. The introduction of genetic testing into medical practice is beginning to collide head on with patents that claim ownership of correlations between human genetic variants and predisposition to disease, response to therapeutic drugs, and susceptibility to pharmacologic side effects. Patent holders or licensees of genes, genetic variants, and their genotype-phenotype correlations are already using the threat of litigation to monopolize genetic (...) tests for important well-known syndromes like Duchenne Muscular Dystrophy and inherited breast and ovarian cancer, in addition to a host of less commonly discussed conditions. (shrink)

ObjectiveStress can play a role in the onset and exacerbation of psoriasis. Psychological interventions to reduce stress have been shown to improve psychological and psoriasis-related outcomes. This pilot randomised study investigated the feasibility of a brief interaction with a Paro robot to reduce stress and improve skin parameters, after a stressor, in patients with psoriasis.MethodsAround 25 patients with psoriasis participated in a laboratory stress task, before being randomised to either interact with a Paro robot or sit quietly for 30 (...) min. Raman spectroscopy and trans-epidermal water loss were measured at baseline, after the stressor and after the intervention as indexes of acute skin changes. Psychological variables, including self-reported stress and affect, were also measured at the three time-points.ResultsNo statistically significant differences between the two conditions were found for any of the outcomes measured. However, effect sizes suggest significance could be possible with a larger sample size. Changes in the psychological and Raman spectroscopy outcomes across the experimental session were found, indicating the feasibility of the procedures.ConclusionThis pilot study showed that a brief interaction with a Paro robot was a feasible intervention for patients with psoriasis, but future trials should broaden the inclusion criteria to try to increase recruitment rates. Studying people who are highly stressed, depressed or who are stress-responders may increase the power of the intervention to show effects using a longer-term intervention. (shrink)

Convolutional neural networks, which automatically learn features from raw data to approximate functions, are being increasingly applied to the end-to-end analysis of electroencephalographic signals, especially for decoding brain states in brain-computer interfaces. Nevertheless, CNNs introduce a large number of trainable parameters, may require long training times, and lack in interpretability of learned features. The aim of this study is to propose a CNN design for P300 decoding with emphasis on its lightweight design while guaranteeing high performance, on the effects of (...) different training strategies, and on the use of post-hoc techniques to explain network decisions. The proposed design, named MS-EEGNet, learned temporal features in two different timescales in an efficient and optimized way, and was validated on three P300 datasets. The CNN was trained using different strategies and was compared with several state-of-the-art algorithms. Furthermore, variants of the baseline MS-EEGNet were analyzed to evaluate the impact of different hyper-parameters on performance. Lastly, saliency maps were used to derive representations of the relevant spatio-temporal features that drove CNN decisions. MS-EEGNet was the lightest CNN compared with the tested SOA CNNs, despite its multiple timescales, and significantly outperformed the SOA algorithms. Post-hoc hyper-parameter analysis confirmed the benefits of the innovative aspects of MS-EEGNet. Furthermore, MS-EEGNet did benefit from transfer learning, especially using a low number of training examples, suggesting that the proposed approach could be used in BCIs to accurately decode the P300 event while reducing calibration times. Representations derived from the saliency maps matched the P300 spatio-temporal distribution, further validating the proposed decoding approach. This study, by specifically addressing the aspects of lightweight design, transfer learning, and interpretability, can contribute to advance the development of deep learning algorithms for P300-based BCIs. (shrink)

Cancer and its treatment pose challenges that affect not only patients but also their significant others, including intimate partners. Accumulating evidence suggests that couples’ ability to communicate effectively plays a major role in the psychological adjustment of both individuals and the quality of their relationship. Two key conceptual models have been proposed to account for how couple communication impacts psychological and relationship adjustment: the social-cognitive processing (SCP) model and the relationship intimacy (RI) model. These models posit different mechanisms and outcomes, (...) and thus have different implications for intervention. The purpose of this project is to test and compare the utility of these models using comprehensive and methodologically rigorous methods. Aims are: (1) to examine the overall fit of the SCP and RI models in explaining patient and partner psychological and relationship adjustment as they occur on a day-to-day basis and over the course of 1 year; (2) to examine the fit of the models for different subgroups (males vs. females, and patients vs. partners); and (3) to examine the utility of various methods of assessing communication by examining the degree to which baseline indices from different measurement strategies predict self-reported adjustment at 1-year follow up. The study employs a longitudinal, multi-method approach to examining communication processes including: standard self-report questionnaires assessing process and outcome variables collected quarterly over the course of 1 year; smartphone-based ecological momentary assessments to sample participant reports in real time; and laboratory-based couple conversations from which we derive observational measures of communicative behavior and affective expression, as well as vocal indices of emotional arousal. Participants are patients with stage II-IV breast, colon, rectal, or lung cancer and their spouses/partners, recruited from two NCI-designated comprehensive cancer centers. Results will be published in scientific journals, presented at scientific conferences, and conveyed to a larger audience through infographics and social media outlets. Findings will inform theory, measurement, and the design and implementation of efficacious interventions aimed at optimizing both patient and partner well-being. (shrink)

A novel data-driven model-free adaptive control approach is first proposed by combining the advantages of model-free adaptive control and data-driven optimal iterative learning control, and then its stability and convergence analysis is given to prove algorithm stability and asymptotical convergence of tracking error. Besides, the parameters of presented approach are adaptively adjusted with fuzzy logic to determine the occupied proportions of MFAC and DDOILC according to their different control performances in different control stages. Lastly, the proposed fuzzy DDMFAC approach is (...) applied to the control of particle quality in drug development phase of spray fluidized-bed granulation process, and its control effect is compared with MFAC and DDOILC and their fuzzy forms, in which the parameters of MFAC and DDOILC are adaptively adjusted with fuzzy logic. The effectiveness of the presented FDDMFAC approach is verified by a series of simulations. (shrink)

Transcranial magnetic stimulation, as a relatively new type of treatment, is a safe and non-invasive method for pain therapy. Here, we used CiteSpace software to visually analyze 440 studies concerning transcranial magnetic stimulation in pain research from 2010 to 2021, indexed by Web of Science, to clarify the research hotspots in different periods and characterize the process of discovery in this field. The United States ranked first in this field. Lefaucheur JP, Fregni F, and Andrade ACD made great contributions to (...) this field of study. The most prolific institution was University of São Paulo. The four main hot keywords were neuropathic pain, motor cortex, connectivity, and non-invasive brain stimulation. There were three main points that were generally accepted: definite analgesic effect of high-frequency rTMS of M1 contralateral to pain side in neuropathic pain; there are inconclusive recommendations regarding rTMS of the dorsolateral prefrontal cortex in fibromyalgia and neuropathic pain; there is low-quality evidence that single doses of high-frequency rTMS of the motor cortex may have short-term effects on chronic pain. This bibliometric analysis indicated that prospective, multi-center, large-sample, randomized controlled trials are still needed to further verify the effectiveness of various transcranial magnetic stimulation parameters in pain research. (shrink)

Phenomena like meat sharing in hunter-gatherers, self-sacrifice in intergroup conflicts, and voluntary contribution to public goods provision in laboratory experiments have led to the development of numerous theories on the evolution of altruistic in-group beneficial behavior in humans. Many of these theories abstract away from the effects of kinship on the incentives for public goods provision, though. Here, it is investigated analytically how genetic relatedness changes the incentive structure of that paradigmatic game which is conventionally used to model and (...) experimentally investigate collective action problems: the linear public goods game. Using recent anthropological data sets on relatedness in 61 contemporary hunter-gatherer and horticulturalist societies the relevant parameters of this model are then estimated. It turns out that the kinship patterns observed in these societies substantially reduce the negative effect of increasing group size on incentives for public goods provision. It is suggested, therefore, that renewed attention should be given to inclusive fitness theory in the context of public goods provision also in sizable groups, because its explanatory power with respect to this central problem in the evolution of human cooperativeness and altruism might have been substantially underrated. (shrink)

Infertility is a huge problem nowadays, not only from the medical but also from the social point of view. A key step to improve treatment outcomes is the possibility of effective prediction of treatment result. In a situation when a phenomenon with more than 2 states needs to be explained, e.g. pregnancy, miscarriage, non-pregnancy, the use of multinomial logistic regression is a good solution. The aim of this paper is to select those features that have a significant impact on achieving (...) clinical pregnancy as well as those that determine the occurrence of spontaneous miscarriage. Two multi-factor models were obtained, used in predicting infertility treatment outcomes. One of the models enabled to conclude that the number of follicles and the percentage of retrieved mature oocytes have a significant impact when prediction of treatment outcome is made on the basis of information about oocytes. The other model, built on the basis of information about embryos, showed the significance of the number of fertilized oocytes, the percentage of at least 7-cell embryos on day 3, the percentage of blasts on day 5, and the day of transfer. (shrink)

The lifetime prevalence of major depressive disorder in adolescents is reported to be as high as 20%; thus, MDD constitutes a significant social and public health burden. MDD is often associated with nonsuicidal self-injury behavior, but the contributing factors including cognitive function have not been investigated in detail. To this end, the present study evaluated cognitive impairment and psychosocial factors in associated with MDD with NSSI behavior. Eighteen and 21 drug-naïve patients with first-episode MDD with or without NSSI and (...) 24 healthy control subjects were enrolled in the study. The Hamilton Anxiety Scale, Hamilton Depression Scale, Adolescent Self-injury Questionnaire, Beck Scale for Suicide Ideation–Chinese Version, Shame Scale for Middle School Students, Sensation Seeking Scale and Childhood Trauma Questionnaire were used to assess depression-related behaviors, and event-related potentials were recorded as a measure of cognitive function. The latency of the N1, N2, P3a, P3b, and P50 components of ERPs at the Cz electrode point; P50 amplitude and P50 inhibition showed significant differences between the 3 groups. CTQ scores also differed across three groups, and the NSSI– and NSSI+ groups showed significant differences in scores on the Shame Scale for Middle School Students. Thus, cognitive function was impaired in adolescents with MDD with NSSI behavior, which was mainly manifested as memory decline, attention and executive function deficits, and low anti-interference ability. We also found that childhood abuse, lack of social support, and a sense of shame contributed to NSSI behavior. These findings provide insight into the risk factors for MDD with NSSI behavior, which can help mental health workers more effectively diagnose and treat these patients. (shrink)

A series of studies in experimental philosophy have revealed that people blame others for foreseen negative side effects but do not praise them for foreseen positive ones. In order to challenge this idea, also called the Knobe effect, we develop a laboratory experiment using monetary incentives. In a game-theoretic framework we formalize the two vignettes in a neutral way, which means that we abstain from the use of any specific language terms and can easily control and vary the economic (...) parameters of the situation. We confirm the Knobe effect in one situation and present situations in which the effect vanishes or even reverses. Our results are in line with a theoretical approach where the assessment of intention is not based on the action itself but on the underlying motive – as modelled in Levine. (shrink)

In late 1912, Fritz Goos at the Hamburg Physikalisches Staatslaboratorium discovered a systematic dependency of arc-spectra wavelengths on the length of the electric arc used and on its electric parameters, such as, for instance, the current employed. In early 1913, at Heinrich Kayser's better-equipped physical laboratory in Bonn, Goos was able to confirm these effects using a large concave Rowland grating. He was able to establish that variations of between 3 mm and 10 mm in the length of the (...) arc produced wavelength differences of up to 0.02 Å violet shift and -0.007 Å redshift respectively. Further inquiry also revealed a dependency of the wavelength on the region of the arc selected for spectrometric observation. All these surprising effects were soon collectively named ‘pole effect’.As is shown in this paper, the pole effect threatened the validity of the results of the entire research tradition of high-precision spectroscopy which, around 1910, had excelled in establishing several internally coherent systems of wavelength assignments. These wavelength catalogues had been established by spectroscopists such as Heinrich Kayser, Paul Eversheim and their co-workers in Bonn, by August Herman Pfund in Baltimore, and by Charles Fabry and Henri Buisson in Marseille under the aegis of the ‘International Union for Co-Operation in Solar Research’. They had all produced locally consistent, “homogeneous” systems of wavelengths with estimated errors sometimes smaller than 0.001 Å. However, long before 1913, strange non-local inconsistencies had emerged between these systems that were of much greater magnitude than the estimated error. The discovery of the pole effect opened up the possibility that variations in the arc parameters used in the measurements, which the different teams had hitherto not specified, were responsible for the systematic differences, in their respective sets of measurements, coming to up to 0.025 Å.This paper explores the interrelations between local knowledge production, the strategies for the establishment of local coherence, and the ways in which the community of physicists and spectroscopists handled a possible threat to this coherence after 1913. Around 1930, a general agreement was reached about the physical cause of the pole effect, namely Stark effects, caused in turn by intermolecular electric fields of ions in the arc. Much before 1930, however, the community had already succeeded in standardizing the instrumentation used in high-precision spectrometry and had conformed its research practice to such an extent that from 1917 on the pole effect could be routinely circumvented in high-precision spectrometry and interferometry. Thus, experimentation along with its instrumentation, indeed had ‘a life of its own’, independent of the many unsuccessful efforts to explain the pole effect theoretically. (shrink)

The process of urban landmark-based navigation has proven to be difficult to study in a rigorous fashion, primarily due to confounding variables and the problem of obtaining reliable data in real-world contexts. The development of high-resolution, immersive virtual reality technologies has opened exciting new possibilities for gathering data on human wayfinding that could not otherwise be readily obtained. We developed a research platform using a virtual environment and electroencephalography to better understand the neural processes associated with landmark usage and recognition (...) during urban navigation tasks. By adjusting the architectural parameters of different buildings in this virtual environment, we isolated and tested specific design features to determine whether or not they served as a target for landmarking. EEG theta band event-related synchronization/desynchronization over posterior scalp areas was evaluated at the time when participants observed each target building along a predetermined self-paced route. A multi-level linear model was used to investigate the effects of salient architectural features on posterior scalp areas. Our results support the conclusion that highly salient architectural features—those that contrast sharply with the surrounding environment—are more likely to attract visual attention, remain in short-term memory, and activate brain regions associated with wayfinding compared with non-salient buildings. After establishing this main aggregate effect, we evaluated specific salient architectural features and neural correlates of navigation processing. The buildings that most strongly associated extended gaze time, location recall accuracy, and changes in theta-band neural patterns with landmarking in our study were those that incorporated rotational twist designs and natural elements such as trees and gardens. Other building features, such as unusual façade patterns or building heights, were to a lesser extent also associated with landmarking. (shrink)

Active surveillance cultures and contact precautions is a strategy to control the transmission of methicillin-resistant Staphylococcus aureus (MRSA) within healthcare facilities. Whether to implement this strategy to routinely screen and isolate inpatients with MRSA in non-outbreak (endemic) settings, or to remove it and use standard infection control precautions only is scientifically and ethically controversial, in view of the potential adverse effects of contact precautions on patients. To support the use of standard precautions only, it has been argued that active surveillance (...) to identify patients who are asymptomatically colonised with MRSA to place them in contact precautions is unjust or unfair to these patients in various ways. This paper will unpack and examine four distinct arguments, which are advanced from a medical ethics or quality improvement ethical framework, for why this is so. Our analysis shows that while these arguments highlight the injustice of current practices, they do not provide strong ethical reasons for justifying the removal of active surveillance and contact precautions to control MRSA transmission and infection. An implication of our arguments is that the ethical frame for evaluating prevention and control strategies for MRSA, a multi-drug resistant bacteria, should shift from healthcare to primarily public health. From a public health ethics perspective, whether a strategy is unjust, or how ethically significant its lack of fairness is, depends on assessing the evidence for its public health effectiveness and necessity in a given setting, and the extent of the harms and burdens patients with MRSA bear when they are on contact precautions, which remain matters of scientific debate or uncertainty. As an ethical consideration in the debate, the chief normative implication of justice is to provide us further reasons to revise current active surveillance-contact precautions practices, and for the need for research and interventions to minimise their potential adverse effects on patients. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:EugenicsMary Carrington Coutts (bio) and Pat Milmoe McCarrick (bio)The word eugenics (from the Greek eugenes or well-born) was coined in 1883 by Francis Galton, an Englishman and cousin of Charles Darwin, who applied Darwinian science to develop theories about heredity and good or noble birth (I, Kevles 1985, p. x).The entry under "eugenics" in the Encyclopedia of Bioethics notes that the term has had different meanings in different eras: (...) "a science that investigates methods to ameliorate the genetic composition of the human race; a program to foster such betterment; a social movement; and in its perverted form, a pseudo-scientific retreat for bigots and racists" (V, Ludmerer 1978, p. 457). Kevles, who places a stronger emphasis than Ludmerer on the degeneration of eugenics, says that by 1935 it "had become 'hopelessly perverted' into a pseudoscientific facade for 'advocates of race and class prejudice, defenders of vested interests of church and state, Fascists, Hitlerites, and reactionaries generally'" (I, Kevles 1985, p. 164).Phrases such as "survival of the fittest" and "struggle for existence" came into use at the end of the nineteenth century when eugenics societies were created throughout the world to popularize genetic science. "Negative eugenics" utilized marriage restriction, sterilization, or custodial commitment of those thought to have unwanted characteristics. "Positive eugenics" tried to encourage the population perceived as "superior" to have more offspring (V, Ludmerer 1978, p. 459).In the United States, after World War I, new information, such as the importance of environmental influences and the more complex concept of multi-gene effects in inheritance, diminished the scientific justification for eugenics, but this knowledge did not decrease the pressure for legislation, judicial action, or immigration controls. The U.S. Immigration Restriction Act of 1924 favored immigration from northern Europe and greatly restricted the entry of persons from other areas referred to as "biologically inferior." Between 1907 and 1937, 32 [End Page 163] states required sterilization of various citizens viewed as undesirable: the mentally ill or handicapped; those convicted of sexual, drug, or alcohol crimes; and others viewed as "degenerate" (V, Larson 1991).In Germany, interest in eugenics flourished after the turn of the century when Dr. Alfred Ploetz founded the Archives of Race-Theory and Social Biology in 1904 and the German Society of Racial Hygiene in 1905. The German term Rassenhygiene or race hygiene encompassed more than the word "eugenics;" it included all attempts to improve hereditary qualities as well as measures directed at population increase (III, Weiss 1987). By the 1920s, various German textbooks incorporated ideas of heredity and racial hygiene, and German professors were participating in the international eugenics movement. The Kaiser Wilhelm Institute of Anthropology, Human Heredity, and Eugenics was founded in 1927; by 1933 a sterilization law, the Law for the Prevention of Congenitally Ill Progeny, which originally was entitled "Eugenics in the Service of Public Welfare," indicated compulsory sterilization "for the prevention of progeny with hereditary defects" in cases of "congenital mental defects, schizophrenia, manic-depressive psychosis, hereditary epilepsy... and severe alcoholism." (III, Müller-Hill 1988, p. 10).The co-mingling of science, politics, and Weltanschauung (ideological or religious world view) caused the darkest period for eugenics when Nazi Germans embarked on their "final solution" to the Jewish "problem", or the Holocaust. The Nazi racial-hygiene program began with involuntary sterilizations and ended with genocide. Beginning with the 1933 Law for the Prevention of Congenitally Ill Progeny, 350,000 schizophrenic and other mentally ill persons were involuntarily sterilized, and marriage or sexual contact between Jews and other Germans was banned. Several hundred black children and 30,000 German Gypsies were sterilized. By 1945, when the allies liberated those remaining in Nazi concentration camps, six million Jews, 750,000 Gypsies, and 70,000 German psychiatric patients had been killed by the Nazis (III, Müller-Hill 1992, p. 47). As a result of the German experience, eugenic thought dropped to its nadir, and to the present day, the term "eugenics" invokes a sense of horror in some people.Great Britain, the United States, and Germany were the countries most involved with eugenic science in the first half of this century, but interest was present in Europe and other... (shrink)

Since testing for HIV infection became possible in 1985, testing of pregnant women has been conducted primarily on a voluntary, ‘opt-in’ basis. Faden, Geller and Powers, Bayer, Wilfert, and McKenna, among others, have suggested that with the development of more reliable testing and more effective therapy to reduce maternal-fetal transmission, testing should become either routine with ‘opt-out’ provisions or mandatory. We ask, in the light of the new rapid tests for HIV, such as OraQuick, and the development of antiretroviral treatment (...) that can reduce maternal-fetal transmission rates to <2%, whether that time is now. Illustrating our argument with cases from the United States (US), Kenya, Peru, and an undocumented Mexican worker in the US, we show that when testing is accompanied by assured multi-drug therapy for the mother, the argument for opt-out or mandatory testing for HIV in pregnancy is strong, but that it is problematic where testing is accompanied by adverse events such as spousal abuse or by inadequate intrapartum or follow-up treatment. The difference is not a ‘double standard’, but reflects the presence of conflicts between the health interests of the mother and the fetus – conflicts that would be abrogated by the assurance of adequate, continuing multi-drug therapy. In light of these conflicts, where they still occur, careful processes of informed consent are appropriate, rather than opt-out or mandatory testing. (shrink)

"Cluster randomized trials," in which groups of patients are randomly assigned to different therapeutic interventions, provide a powerful way of evaluating drugs. CRTs have not been widely used, in good part because of concerns about whether patients must give informed consent to participate in them. A better understanding of how CRTs fit into clinical practice resolves the concerns.

The historical background of the discovery of adverse health effects of medicines, food additives, pesticides, and other chemicals is reviewed, and the development of national and international regulations and testing procedures to protect the public against the toxic effects of these drugs and chemicals is outlined. Ethical considerations of the safety evaluation of drugs and chemicals by human experimentation and animal toxicity studies, ethical problems associated with clinical trials, with the falsification of clinical and toxicological data, and with inadequate experimental (...) methodology, are reviewed, and the ethics of the marketing of drugs and their post-marketing surveillance, are similarly considered. These ethical problems are illustrated with many specific examples, including the drugs neoarsphenamine, chloramphenicol, thalidomide, diethyl stilboestrol and benoxaprofen. (shrink)

This article critically examines current responses to multi-drug resistant tuberculosis and argues that bioethics needs to be willing to engage in a more radical critique of the problem than is currently offered. In particular, we need to focus not simply on market-driven models of innovation and anti-microbial solutions to emergent and re-emergent infections such as TB. The global community also needs to address poverty and the structural factors that entrench inequalities—thus moving beyond the orthodox medical/public health frame of (...) reference. (shrink)

Precision medicine and molecular systems medicine (MSM) are highly utilized and successful approaches to improve understanding, diagnosis, and treatment of many diseases from bench-to-bedside. Especially in the COVID-19 pandemic, molecular techniques and biotechnological innovation have proven to be of utmost importance for rapid developments in disease diagnostics and treatment, including DNA and RNA sequencing technology, treatment with drugs and natural products and vaccine development. The COVID-19 crisis, however, has also demonstrated the need for systemic thinking and transdisciplinarity and the limits (...) of MSM: the neglect of the bio-psycho-social systemic nature of humans and their context as the object of individual therapeutic and population-oriented interventions. COVID-19 illustrates how a medical problem requires a transdisciplinary approach in epidemiology, pathology, internal medicine, public health, environmental medicine, and socio-economic modeling. Regarding the need for conceptual integration of these different kinds of knowledge we suggest the application of general system theory (GST). This approach endorses an organism-centered view on health and disease, which according to Ludwig von Bertalanffy who was the founder of GST, we call Organismal Systems Medicine (OSM). We argue that systems science offers wider applications in the field of pathology and can contribute to an integrative systems medicine by (i) integration of evidence across functional and structural differentially scaled subsystems, (ii) conceptualization of complex multilevel systems, and (iii) suggesting mechanisms and non-linear relationships underlying the observed phenomena. We underline these points with a proposal on multi-level systems pathology including neurophysiology, endocrinology, immune system, genetics, and general metabolism. An integration of these areas is necessary to understand excess mortality rates and polypharmacological treatments. In the pandemic era this multi-level systems pathology is most important to assess potential vaccines, their effectiveness, short-, and long-time adverse effects. We further argue that these conceptual frameworks are not only valid in the COVID-19 era but also important to be integrated in a medicinal curriculum. (shrink)

Wheat is the most imperative crop for man feeding and is planted in numerous countries under rainfed conditions in semiarid zones. It is necessary for decision-makers and governments to predict the yield of rainfed wheat before harvest and to determine the effect of the major factors on it. Different methods have been suggested for forecasting yield with various levels of accuracy. One of these approaches is the statistical regression model, which is simple and applicable for regions with scarce data available. (...) Since the weather is the most important factor affecting the production of wheat, particularly in rainfed cultivation, regression models using weather parameters are very common. However, the coefficients of these models are location based and should be determined locally. Therefore, in this research, backward multiple linear regression technique based on relative importance metrics was used to determine the most important effective weather parameters on rainfed wheat productions in Fars Province, south of Iran, during 2006–2013. The influence of each parameter in the final model was analyzed using the values of LMG relative importance metric. The result indicated that sunshine hours had the biggest LMG and, therefore, was the most effective parameter. Also, among the other considered parameters, rainy days, minimum relative humidity, and average relative humidity with LMG values of 21.97%, 21.69%, and 21.62%, respectively, had the most effects on rainfed wheat yield in the studied area. All parameters except for the sunshine hours positively affected rainfed wheat yield. The most important reason for the significance of these parameters can be the prevailing dry and semidry climate in the southern areas of Iran. The proposed model for determination of weather parameters effects on rainfed wheat could be a great guidance and aid for different stakeholders such as farmers, decision-makers, and governments. (shrink)

This paper proposes an agent community based information retrieval method, which uses agent communities to manage and look up information related to users. An agent works as a delegate of its user and searches for information that the user wants by communicating with other agents. The communication between agents is carried out in a peer-to-peer computing architecture. In order to retrieve information related to a user query, an agent uses two histories : a query/retrieved document history(Q/RDH) and a query/sender agent (...) history(Q/SAH). The former is a list of pairs of a query and retrieved documents, where the queries were sent by the agent itself. The latter is a list of pairs of a query and sender agents and shows ``who sent what query to the agent''. This is useful to find a new information source. Making use of the Q/SAH is expected to cause a collaborative filtering effect, which gradually creates virtual agent communities, where agents with the same interests stay together. Our hypothesis is that a virtual agent community reduces communication loads to perform a search. As an agent receives more queries, then more links to new knowledge are achieved. From this behavior, a ``give and take''(or positive feedback) effect for agents seems to emerge. We implemented this method with Multi-Agents Kodama which has been developed in our laboratory, and conducted preliminary experiments to test the hypothesis. The empirical results showed that the method was much more efficient than a naive method employing 'broadcast' techniques only to look up a target agent. (shrink)

The quest for effective medicines is very old. In modern times two important tools have been developed to evaluate efficacy of drugs: superiority and non-inferiority types of clinical trials. The former tests the null hypothesis of μ (the difference between a tested drug and comparator) ≤ 0 against μ > 0; the latter tests the null hypothesis of μ ≤ - Δ against, μ > - Δ, where Δ is the clinical difference from the comparator. In a superiority trial, (...) a new drug is tested against a placebo; in a non-inferiority trial, a new drug is tested against active treatment. In this paper, arguments are presented to show that a superiority trial against a placebo is scientifically sound but ethically unacceptable, whereas a non-inferiority trial against active treatment is ethically sound but scientifically not reliable. Switching from a superiority type of trial with placebo to a non-inferiority trial with an active-control — following the latest revision of Declaration of Helsinki — is in practice switching from the violation of the uncertainty principle to uncertainty of results. Given human and financial resources, it appears an academic question as to which is more unethical: to violate patients’ rights or to produce results without scientific value. All presented considerations lead to the conclusion that the use of a superiority trial of design with an active control instead of placebo will satisfy scientific needs, expectation of patients, and the ancient quest for effective medicines. In the era of Good (Clinical, Laboratory, Manufacture) Practice, the attention of those performing clinical trials is focused on the procedure, not always on its essence. However even the excellent performance of a trial which is not worth doing is fruitless. (shrink)

A new multi-stage deterministic model for the transmission dynamics of syphilis, which incorporates disease transmission by individuals in the early latent stage of syphilis infection and the reversions of early latent syphilis to the primary and secondary stages, is formulated and rigorously analysed. The model is used to assess the population-level impact of preventive and therapeutic measures against the spread of the disease in a community. It is shown that the disease-free equilibrium of the model is globally-asymptotically stable whenever (...) the associated control reproduction number is less than unity. A special case of the model is shown to have a unique and globally-asymptotically stable endemic equilibrium whenever the associated reproduction number exceeds unity. Uncertainty and sensitivity analysis of the model, using parameter values and ranges relevant to syphilis transmission dynamics in Nigeria, show that the top three parameters that drive the syphilis infection are the disease transmission rate, compliance in condom use and efficacy of condom. Numerical simulations of the model show that the targeted treatment of secondary syphilis cases is more effective than the targeted treatment of individuals in the primary or early latent stage of syphilis infection. (shrink)

Response to commentary. We are grateful to Crockett and Craigie for their interesting remarks on our paper. We accept Crockett’s claim that there is a need for caution in drawing inferences about patient groups from work on healthy volunteers in the laboratory. However, we believe that the evidence we cited established a strong presumption that many of the patients who are routinely taking a medication, including many people properly prescribed the medication for a medical condition, have morally significant aspects (...) of their cognition and behavior modified in a way that is unintended and may sometimes be unwelcome. Crockett notes that in some cases the effects of long-term drug use may differ, sometimes markedly, from the effects of short-term use. However, if acute use of a drug affects a neural system involved in mediating moral cognition or behavior, this nevertheless provides some evidence that chronic use of the drug may affect that same system and thus have morally significant effects. It is also plausible, in some cases, that an acute moral effect would give rise to a chronic moral effect via cognitive mechanisms. ... (shrink)

Talk of mechanisms is ubiquitous in the natural sciences. Interdisciplinary fields such as biochemistry and pharmacy frequently discuss mechanisms with the assistance of diagrams. Such diagrams usually depict entities as structures or boxes and activities or interactions as arrows. While some of these arrows may indicate causal or componential relations, others may represent temporal or operational orders. Importantly, what kind of relation an arrow represents may not only vary with context but also be underdetermined by empirical data. In this manuscript, (...) we investigate how an analysis of pharmacological mechanisms in terms of producing and underlying mechanisms—as discussed in the contemporary philosophy of science—may shed light on these issues. Specifically, we shall argue that while pharmacokinetic mechanisms usually describe causal chains of production, pharmacodynamics tends to focus on mechanisms of action underlying the in vivo effects of a drug. Considering the action of thyroid gland hormones in the human body as a case study, we further demonstrate that pharmacodynamic schemes tend to incorporate entities and interactions on multiple levels. Yet, traditional pharmacodynamic schemes are sketched “flat”, i.e., non-hierarchically. We suggest that transforming flat pharmacodynamic schemes into mechanistic multi-level representations may assist in disentangling the different kinds of mechanisms and relations depicted by arrows in flat schemes. The resulting Baumkuchen model provides a powerful and practical alternative to traditional flat schemes, as it explicates the relevant mechanisms and relations more clearly. On a more general note, our discussion demonstrates how pharmacology and related disciplines may benefit from applying concepts from the new mechanist philosophy to guide the interpretation of scientific diagrams. (shrink)

We live in an age defined in large part by various facets of neoliberalism. In particular, the market world has impinged on virtually every aspect of food and agriculture. Moreover, most nation-states and many international governance bodies incorporate aspects of neoliberal perspectives. Multi-stakeholder initiatives, with their own standards, certifications, and accreditations are evidence of both the continuing hegemony of neoliberalism as well as various responses to it. Importantly, to date even attempts to limit neoliberal hegemony through MSIs have been (...) largely within the parameters established by those same neoliberal agendas. However, neoliberalism is itself in crisis as a result of climate change, the continuing financial crisis, and rising food prices. The founding myths of neoliberalism are still widely held, having the effect of closing off alternative paths to the future. Yet, this need not be the case. Alternatives to the current MSIs that promote justice, democracy, and equality can still be constructed. (shrink)