Predictive feedback control and Fitts' law

Fitts’ law is a well established empirical formula, known for encapsulating the “speed-accuracy trade-off”. For discrete, manual movements from a starting location to a target, Fitts’ law relates movement duration to the distance moved and target size. The widespread empirical success of the formula is suggestive of underlying principles of human movement control. There have been previous attempts to relate Fitts’ law to engineering-type control hypotheses and it has been shown that the law is exactly consistent with the closed-loop step-response of a time-delayed, first-order system. Assuming only the operation of closed-loop feedback, either continuous or intermittent, this paper asks whether such feedback should be predictive or not predictive to be consistent with Fitts law. Since Fitts’ law is equivalent to a time delay separated from a first-order system, known control theory implies that the controller must be predictive. A predictive controller moves the time-delay outside the feedback loop such that the closed-loop response can be separated into a time delay and rational function whereas a non- predictive controller retains a state delay within feedback loop which is not consistent with Fitts’ law. Using sufficient parameters, a high-order non-predictive controller could approximately reproduce Fitts’ law. However, such high-order, “non-parametric” controllers are essentially empirical in nature, without physical meaning, and therefore are conceptually inferior to the predictive controller. It is a new insight that using closed-loop feedback, prediction is required to physically explain Fitts’ law. The implication is that prediction is an inherent part of the “speed-accuracy trade-off”

Pelvic mass associated with raised CA 125 for benign condition: a case report

<p>Abstract</p> <p>Background</p> <p>Raised CA 125 with associated pelvic mass is highly suggestive of ovarian malignancy, but there are various other benign conditions that can be associated with pelvic mass and a raised CA 125.</p> <p>Case presentation</p> <p>We present a case of 19 year old, Caucasian British woman who presented initially with sudden onset right sided iliac fossa pain and on imaging was found to have 9.8 × 4.5 cm complex cystic mass in right adnexa with a raised CA 125 of 657, which was initially thought to be highly suspicious of cancer but was subsequently found to be due to pelvic inflammatory disease on histology.</p> <p>Conclusion</p> <p>This case highlights the fact that though a pelvic mass with raised CA 125 is highly suggestive of malignancy, pelvic inflammatory disease should always be considered as a differential diagnosis especially in a young patient and a thorough sexual history and screening for pelvic infection should always be carried out in these patients.</p

Parks and Tourism

To protect biodiversity, parks agencies need political and financial support. Recreational visitors can bring both, but commercial tourism carries risks

Toward optimal implementation of cancer prevention and control programs in public health: A study protocol on mis-implementation

Abstract Background Much of the cancer burden in the USA is preventable, through application of existing knowledge. State-level funders and public health practitioners are in ideal positions to affect programs and policies related to cancer control. Mis-implementation refers to ending effective programs and policies prematurely or continuing ineffective ones. Greater attention to mis-implementation should lead to use of effective interventions and more efficient expenditure of resources, which in the long term, will lead to more positive cancer outcomes. Methods This is a three-phase study that takes a comprehensive approach, leading to the elucidation of tactics for addressing mis-implementation. Phase 1: We assess the extent to which mis-implementation is occurring among state cancer control programs in public health. This initial phase will involve a survey of 800 practitioners representing all states. The programs represented will span the full continuum of cancer control, from primary prevention to survivorship. Phase 2: Using data from phase 1 to identify organizations in which mis-implementation is particularly high or low, the team will conduct eight comparative case studies to get a richer understanding of mis-implementation and to understand contextual differences. These case studies will highlight lessons learned about mis-implementation and identify hypothesized drivers. Phase 3: Agent-based modeling will be used to identify dynamic interactions between individual capacity, organizational capacity, use of evidence, funding, and external factors driving mis-implementation. The team will then translate and disseminate findings from phases 1 to 3 to practitioners and practice-related stakeholders to support the reduction of mis-implementation. Discussion This study is innovative and significant because it will (1) be the first to refine and further develop reliable and valid measures of mis-implementation of public health programs; (2) bring together a strong, transdisciplinary team with significant expertise in practice-based research; (3) use agent-based modeling to address cancer control implementation; and (4) use a participatory, evidence-based, stakeholder-driven approach that will identify key leverage points for addressing mis-implementation among state public health programs. This research is expected to provide replicable computational simulation models that can identify leverage points and public health system dynamics to reduce mis-implementation in cancer control and may be of interest to other health areas

Strain-controlled criticality governs the nonlinear mechanics of fibre networks

Disordered fibrous networks are ubiquitous in nature as major structural components of living cells and tissues. The mechanical stability of networks generally depends on the degree of connectivity: only when the average number of connections between nodes exceeds the isostatic threshold are networks stable (Maxwell, J. C., Philosophical Magazine 27, 294 (1864)). Upon increasing the connectivity through this point, such networks undergo a mechanical phase transition from a floppy to a rigid phase. However, even sub-isostatic networks become rigid when subjected to sufficiently large deformations. To study this strain-controlled transition, we perform a combination of computational modeling of fibre networks and experiments on networks of type I collagen fibers, which are crucial for the integrity of biological tissues. We show theoretically that the development of rigidity is characterized by a strain-controlled continuous phase transition with signatures of criticality. Our experiments demonstrate mechanical properties consistent with our model, including the predicted critical exponents. We show that the nonlinear mechanics of collagen networks can be quantitatively captured by the predictions of scaling theory for the strain-controlled critical behavior over a wide range of network concentrations and strains up to failure of the material

Validity of a novel computerized cognitive battery for mild cognitive impairment

BACKGROUND: The NeuroTrax Mindstreams computerized cognitive assessment system was designed for widespread clinical and research use in detecting mild cognitive impairment (MCI). However, the capability of Mindstreams tests to discriminate elderly with MCI from those who are cognitively healthy has yet to be evaluated. Moreover, the comparability between these tests and traditional neuropsychological tests in detecting MCI has not been examined. METHODS: A 2-center study was designed to assess discriminant validity of tests in the Mindstreams Mild Impairment Battery. Participants were 30 individuals diagnosed with MCI, 29 with mild Alzheimer's disease (AD), and 39 healthy elderly. Testing was with the Mindstreams battery and traditional neuropsychological tests. Receiver operating characteristic (ROC) analysis was used to examine the ability of Mindstreams and traditional measures to discriminate those with MCI from cognitively healthy elderly. Between-group comparisons were made (Mann-Whitney U test) between MCI and healthy elderly and between MCI and mild AD groups. RESULTS: Mindstreams outcome parameters across multiple cognitive domains significantly discriminated among MCI and healthy elderly with considerable effect sizes (p < 0.05). Measures of memory, executive function, visual spatial skills, and verbal fluency discriminated best, and discriminability was at least comparable to that of traditional neuropsychological tests in these domains. CONCLUSIONS: Mindstreams tests are effective in detecting MCI, providing a comprehensive profile of cognitive function. Further, the enhanced precision and ease of use of these computerized tests make the NeuroTrax system a valuable clinical tool in the identification of elderly at high risk for dementia

Extracellular vesicles released following heat stress induce bystander effects in unstressed populations

Cells naïve to stress can display the effects of stress, such as DNA damage and apoptosis when they are exposed to signals from stressed cells; this phenomenon is known as the bystander effect. We previously showed that bystander effects induced by ionising radiation are mediated by extracellular vesicles (EVs). Bystander effect can also be induced by other types of stress, including heat shock, but it is unclear whether EVs are involved. Here we show that EVs released from heat shocked cells are also able to induce bystander damage in un-stressed populations. Naïve cells treated with media conditioned by heat shocked cells showed higher levels of DNA damage and apoptosis than cells treated with media from control cells. Treating naïve cells with EVs derived from media conditioned by heat shocked cells also induced a bystander effect when compared to control, with DNA damage and apoptosis increasing whilst the level of cell viability was reduced. We demonstrate that treatment of naïve cells with heat shocked cell-derived EVs leads to greater invasiveness in a trans-well matrigel assay. Finally, we show that naïve cells treated with EVs from heat-shocked cells are more likely to survive a subsequent heat shock, suggesting that these EVs mediate an adaptive response. We propose that EVs released following stress mediate an intercellular response that leads to apparent stress in neighbouring cells but also greater robustness in the face of a subsequent insult

Persistence of contrasting traditions in cultural evolution: Unpredictable payoffs generate slower rates of cultural change

We report an experimental test of the hypothesis that contrasting traditions will persist for longer, maintaining cultural differences between otherwise similar groups, under conditions of uncertainty about payoffs from individual learning. We studied the persistence of two alternative, experimentally-introduced, task solutions in chains of human participants. In some chains, participants were led to believe that final payoffs would be difficult to predict for an innovative solution, and in others, participants were aware that their final payoff would be directly linked to their immediate solution. Although the difference between the conditions was illusory (only participants' impressions were manipulated, not actual payoffs) clear differences were found between the conditions. Consistent with predictions, in the chains that were less certain about final payoffs, the distinctive variants endured over several replacement "generations" of participants. In contrast, in the other chains, the influence of the experimentally-introduced solutions was rapidly diluted by participants' exploration of alternative approaches. The finding provides support for the notion that rates of cultural change are likely to be slower for behaviors for which the relationship between performance and payoff may be hard to predict

Voxel-wise comparisons of cellular microstructure and diffusion-MRI in mouse hippocampus using 3D Bridging of Optically-clear histology with Neuroimaging Data (3D-BOND)

A key challenge in medical imaging is determining a precise correspondence between image properties and tissue microstructure. This comparison is hindered by disparate scales and resolutions between medical imaging and histology. We present a new technique, 3D Bridging of Optically-clear histology with Neuroimaging Data (3D-BOND), for registering medical images with 3D histology to overcome these limitations. Ex vivo 120 × 120 × 200 μm resolution diffusion-MRI (dMRI) data was acquired at 7 T from adult C57Bl/6 mouse hippocampus. Tissue was then optically cleared using CLARITY and stained with cellular markers and confocal microscopy used to produce high-resolution images of the 3D-tissue microstructure. For each sample, a dense array of hippocampal landmarks was used to drive registration between upsampled dMRI data and the corresponding confocal images. The cell population in each MRI voxel was determined within hippocampal subregions and compared to MRI-derived metrics. 3D-BOND provided robust voxel-wise, cellular correlates of dMRI data. CA1 pyramidal and dentate gyrus granular layers had significantly different mean diffusivity (p > 0.001), which was related to microstructural features. Overall, mean and radial diffusivity correlated with cell and axon density and fractional anisotropy with astrocyte density, while apparent fibre density correlated negatively with axon density. Astrocytes, axons and blood vessels correlated to tensor orientation

Revealing the molecular signatures of host-pathogen interactions.

Advances in sequencing technology and genome-wide association studies are now revealing the complex interactions between hosts and pathogen through genomic variation signatures, which arise from evolutionary co-existence