Learning the rules of collective cell migration using deep attention networks.

Collective, coordinated cellular motions underpin key processes in all multicellular organisms, yet it has been difficult to simultaneously express the 'rules' behind these motions in clear, interpretable forms that effectively capture high-dimensional cell-cell interaction dynamics in a manner that is intuitive to the researcher. Here we apply deep attention networks to analyze several canonical living tissues systems and present the underlying collective migration rules for each tissue type using only cell migration trajectory data. We use these networks to learn the behaviors of key tissue types with distinct collective behaviors-epithelial, endothelial, and metastatic breast cancer cells-and show how the results complement traditional biophysical approaches. In particular, we present attention maps indicating the relative influence of neighboring cells to the learned turning decisions of a 'focal cell'-the primary cell of interest in a collective setting. Colloquially, we refer to this learned relative influence as 'attention', as it serves as a proxy for the physical parameters modifying the focal cell's future motion as a function of each neighbor cell. These attention networks reveal distinct patterns of influence and attention unique to each model tissue. Endothelial cells exhibit tightly focused attention on their immediate forward-most neighbors, while cells in more expansile epithelial tissues are more broadly influenced by neighbors in a relatively large forward sector. Attention maps of ensembles of more mesenchymal, metastatic cells reveal completely symmetric attention patterns, indicating the lack of any particular coordination or direction of interest. Moreover, we show how attention networks are capable of detecting and learning how these rules change based on biophysical context, such as location within the tissue and cellular crowding. That these results require only cellular trajectories and no modeling assumptions highlights the potential of attention networks for providing further biological insights into complex cellular systems.

[Outpatient Psychotherapy for Children and Adolescents with Intellectual Disability]. / Ambulante Psychotherapie für Kinder und Jugendliche mit geistiger Behinderung.

Outpatient Psychotherapy for Children and Adolescents with Intellectual Disability The psychiatric morbidity risk for people with intellectual disability is considerably increased. Psychotherapy is considered as one possible treatment. Among experts the caresituation is described as substantial insufficient. This study investigated the perspective of psychotherapists for children and adolescents in the German state North Rhine-Westphalia regarding the care situation of outpatient psychotherapy for children and adolescents with intellectual disability. The participants received a questionnaire (a) about the care situation, (b) how they consider their training to treat these patients and (c) the possibility for free answers. In this cross-section study 185 licensed psychotherapists for children and adolescents filled out a semi-standardized online-questionnaire. The data were analyzed descriptively; free answers were categorized according to Mayring. Additionally, group differences were tested. (a) The psychotherapeutic supply situation for children and adolescents with intellectual disability was rated as insufficient. Clients with learning disability or minor intellectual disability are mainly treated. This group of people benefits from psychotherapy. (b) The training for treating these clients was rated as inadequate. (c) Qualitative analysis refers that request for psychotherapy is seen as difficult; cognitive orientated treatments need modification. The psychotherapeutic care situation for children and adolescents with intellectual disability appears insufficient. This topic should be part of the training curriculum for psychotherapists.

Locked Out.

Brain-computer interfaces (BCIs) can enable communication for persons in severe paralysis including locked-in syndrome (LIS); that is, being unable to move or speak while aware. In cases of complete loss of muscle control, termed "complete locked-in syndrome," a BCI may be the only viable solution to restore communication. However, a widespread ignorance regarding quality of life in LIS, current BCIs, and their potential as an assistive technology for persons in LIS, needlessly causes a harmful situation for this cohort. In addition to their medical condition, these persons also face social barriers often perceived as more impairing than their physical condition. Through social exclusion, stigmatization, and frequently being underestimated in their abilities, these persons are being locked out in addition to being locked-in. In this article, we (1) show how persons in LIS are being locked out, including how key issues addressed in the existing literature on ethics, LIS, and BCIs for communication, such as autonomy, quality of life, and advance directives, may reinforce these confinements; (2) show how these practices violate the United Nations Convention on the Rights of Persons with Disabilities, and suggest that we have a moral responsibility to prevent and stop this exclusion; and (3) discuss the role of BCIs for communication as one means to this end and suggest that a novel approach to BCI research is necessary to acknowledge the moral responsibility toward the end users and avoid violating the human rights of persons in LIS.

On balance: weighing harms and benefits in fundamental neurological research using nonhuman primates.

One of the most controversial areas of animal research is the use of nonhuman primates for fundamental research. At the centre of the controversy is the question of whether the benefits of research outweigh the harms. We argue that the evaluation of harms and benefits is highly problematic. We describe some common procedures in neurological research using nonhuman primates and the difficulties in evaluating the harm involved. Even if the harm could be quantified, it is unlikely that it could be meaningfully aggregated over different procedures, let alone different animals. A similar problem arises for evaluating benefits. It is not clear how benefits could be quantified, and even if they could be, values for different aspects of expected benefits cannot be simply added up. Sorting harms and benefits in three or four categories cannot avoid the charge of arbitrariness and runs the risk of imposing its structure on the moral decision. The metaphor of weighing or balancing harms and benefits is inappropriate for the moral decision about whether to use nonhuman primates for research. Arguing that the harms and benefits in this context are incommensurable, we suggest describing the moral consideration of harms and benefits as a coherent trade-off. Such a decision does not require commensurability. It must be well-informed about the suffering involved and the potential benefits, it must be consistent with the legal, regulatory and institutional framework within which it is made, and it must cohere with other judgments in relevant areas.

Multiple re-encounter approach to radical pair reactions and the role of nonlinear master equations.

We formulate a multiple-encounter model of the radical pair mechanism that is based on a random coupling of the radical pair to a minimal model environment. These occasional pulse-like couplings correspond to the radical encounters and give rise to both dephasing and recombination. While this is in agreement with the original model of Haberkorn and its extensions that assume additional dephasing, we show how a nonlinear master equation may be constructed to describe the conditional evolution of the radical pairs prior to the detection of their recombination. We propose a nonlinear master equation for the evolution of an ensemble of independently evolving radical pairs whose nonlinearity depends on the record of the fluorescence signal. We also reformulate Haberkorn's original argument on the physicality of reaction operators using the terminology of quantum optics/open quantum systems. Our model allows one to describe multiple encounters within the exponential model and connects this with the master equation approach. We include hitherto neglected effects of the encounters, such as a separate dephasing in the triplet subspace, and predict potential new effects, such as Grover reflections of radical spins, that may be observed if the strength and time of the encounters can be experimentally controlled.

The Asilomar Survey: Stakeholders' Opinions on Ethical Issues Related to Brain-Computer Interfacing.

Brain-Computer Interface (BCI) research and (future) applications raise important ethical issues that need to be addressed to promote societal acceptance and adequate policies. Here we report on a survey we conducted among 145 BCI researchers at the 4th International BCI conference, which took place in May-June 2010 in Asilomar, California. We assessed respondents' opinions about a number of topics. First, we investigated preferences for terminology and definitions relating to BCIs. Second, we assessed respondents' expectations on the marketability of different BCI applications (BCIs for healthy people, BCIs for assistive technology, BCIs-controlled neuroprostheses and BCIs as therapy tools). Third, we investigated opinions about ethical issues related to BCI research for the development of assistive technology: informed consent process with locked-in patients, risk-benefit analyses, team responsibility, consequences of BCI on patients' and families' lives, liability and personal identity and interaction with the media. Finally, we asked respondents which issues are urgent in BCI research.

Conceptual and ethical issues with brain-hardware interfaces.

PURPOSE OF REVIEW: Progress in neurosciences, increasing computational power, and ongoing miniaturization of micro-technological components enable both a better understanding of human brain functions and development of new diagnostic and therapeutic tools. Research and development as well as clinical application of devices designed for recording neural signals from the brain or stimulating brain areas respectively raise conceptual and ethical questions. RECENT FINDINGS: Ethical issues of stimulating devices are mainly discussed in the field of deep brain stimulation. The debate with respect to its use for Parkinson's disease focuses on patients' benefit and unintended consequences - sometimes framed as questions of identity and change of personality. As deep brain stimulation is currently tested for a broad variety of different diseases, including psychiatric disorders, minimal conscious state and Alzheimer's disease, recently increasing ethical attention is paid to issues of clinical research and clinical innovation. However, with respect to recording devices, specific implications for patients' autonomy and responsibility are at the core of the discussion. SUMMARY: Brain-hardware interfaces need continuing ethical discussion to realize their full beneficial potential and avoid the pitfalls of hasty application.

Ethical brain stimulation - neuroethics of deep brain stimulation in research and clinical practice.

Deep brain stimulation (DBS) is a clinically established procedure for treating severe motor symptoms in patients suffering from end-stage Parkinson's disease, dystonia and essential tremor. Currently, it is tested for further indications including psychiatric disorders like major depression and a variety of other diseases. However, ethical issues of DBS demand continuing discussion. Analysing neuroethical and clinical literature, five major topics concerning the ethics of DBS in clinical practice were identified: thorough examination and weighing of risks and benefits; selecting patients fairly; protecting the health of children in paediatric DBS; special issues concerning patients' autonomy; and the normative impact of quality of life measurements. In exploring DBS for further applications, additionally, issues of research ethics have to be considered. Of special importance in this context are questions such as what additional value is generated by the research, how to realise scientific validity, which patients should be included, and how to achieve an acceptable risk-benefit ratio. Patients' benefit is central for ethical evaluation. This criterion can outweigh very serious side-effects, and can make DBS appropriate even in paediatrics. Because standard test procedures evade central aspects of patients' benefits, measuring quality of life should be supplemented by open in-depth interviews to provide a more adequate picture of patients' post-surgical situation. To examine its entire therapeutic potential, further research in DBS is needed. Studies should be based on solid scientific hypotheses and proceed cautiously to benefit severely suffering patients without putting them to undue risks.

Bath-optimized minimal-energy protection of quantum operations from decoherence.

We put forward a general strategy for dynamic control that ensures bath-optimized fidelity of a desired multidimensional quantum operation in the presence of non-Markovian baths and noises with stationary autocorrelations. It benefits from the vast freedom of arbitrary, not just pulsed, time-dependent control. This allows the dramatic reduction of the invested energy and the corresponding error compared to pulsed control.

Stem cells, nuclear transfer and respect for embryos.

Harvesting human embryonic stem (hES) cells is a highly controversial field of research because it rests on the destruction of human embryos. Altering the procedure of nuclear transfer (NT) is suggested to generate hES cell lines without ethical obstacles by claiming that no embryo would be involved. While discussing the nature of an embryo and related central questions concerning their moral status and the respect they deserve, this paper argues that the entity created by somatic cell nuclear transfer (SCNT) or altered nuclear transfer (ANT) is an embryo and has the same moral status as a natural embryo. Respect for the embryo is expressed by the ethical principles of proportionality, probability and subsidiarity. This paper argues that the human embryo should only be taken for research with high ranking goals, which are proven in animal experimentation and for which there are no alternatives. This makes ANT obsolete and shows that SCNT to produce hES cells is premature at the present time.

Positive remodeling of the coronary arteries detected by magnetic resonance imaging in an asymptomatic population: MESA (Multi-Ethnic Study of Atherosclerosis).

OBJECTIVES: The purpose of this study was to assess coronary arterial remodeling as a marker of subclinical atherosclerosis using coronary wall magnetic resonance imaging (MRI) in an asymptomatic population-based cohort. BACKGROUND: In early atherosclerosis, compensatory enlargement of both the outer wall of the vessel as well as the lumen, termed compensatory enlargement or positive remodeling, occurs before luminal narrowing. METHODS: One hundred seventy-nine participants in the MESA (Multi-Ethnic Study of Atherosclerosis) trial were evaluated using black-blood coronary wall MRI. Coronary cross-sectional area (vessel size), lumen area, and mean wall thickness of the proximal coronary arteries were measured. RESULTS: Men had a greater vessel size, lumen area, and mean wall thickness than women (38.3 +/- 11.3 mm2 vs. 32.6 +/- 9.4 mm2, 6.7 +/- 3.2 mm2 vs. 5.3 +/- 2.4 mm2, and 2.0 +/- 0.3 mm vs. 1.9 +/- 0.3 mm, respectively, p < 0.05). No significant coronary artery narrowing was present by magnetic resonance angiography. Overall, coronary vessel size increased 25.9 mm2 per millimeter increase in coronary wall thickness, whereas lumen area increased only slightly at 3.1 mm2 for every millimeter increase in wall thickness (difference in slopes, p < 0.0001). Adjusting for age and sex, participants with an Agatston score >0 were more likely to have wall thickness >2.0 mm (odds ratio: 2.0, 95% confidence interval: 1.01 to 3.84). CONCLUSIONS: Coronary wall MRI detected positive arterial remodeling in asymptomatic men and women with subclinical atherosclerosis.

Moving minds: ethical aspects of neural motor prostheses.

Modern brain technology is a highly dynamic and innovative field of research with great potential for medical applications. Recent advances in recording neural signals from the brain by brain-machine interfacing presage new therapeutic options for paralyzed people by means of neural motor prostheses. This paper examines foreseeable ethical questions related to the research on brainmachine interfaces and their possible future applications. It identifies four major topics that need to be considered: first, the questions of personality and its possible alterations; second, responsibility and its possible constraints; third, therapeutic applications and their possible exceedance; and fourth, questions of research ethics that arise when progressing from animal experimentation to application to human subjects. This paper, in identifying and addressing the ethical questions raised by brain-machine interfaces, presents concerns that need to be considered if possible prosthetics based on modern brain technology are to be used cautiously and responsibly.