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Background. Online, algorithmically driven prognostic tools are increasingly important in medical decision making. Institutions developing such tools need to be able to communicate the precision and accuracy of the information in a trustworthy manner, and so many attempt to communicate uncertainties but also use institutional logos to underscore their trustworthiness. Bringing together theories on trust, uncertainty, and psychological distance in a novel way, we tested whether and how the communication of uncertainty and the presence of institutional logos together affected trust in medical information, the prognostic tool itself, and treatment decisions. Methods. A pilot and 2 online experiments in which UK (experiment 1) and worldwide (experiment 2) participants (N total  = 4,724) were randomized to 1 of 12 arms in a 3 (uncertainty cue) × 4 (institutional cue) between-subjects design. The stimulus was based on an existing medical prognostic tool. Results. Institutional trust was consistently associated with trust in the prognostic tool itself, while uncertainty information had no consistent effect. Institutional trust predicted the amount of weight participants reported placing on institutional endorsements in their decision making and the likelihood of switching from passive to active treatment in a hypothetical scenario. There was also a significant effect of psychological distance to (perceived hypotheticality of) the scenario. Conclusions/Implications. These results underline the importance of institutions demonstrating trustworthiness and building trust with their users. They also suggest that users tend to be insensitive to communications of uncertainty and that communicators may need to be highly explicit when attempting to warn of low precision or quality of evidence. The effect of the perceived hypotheticality of the scenario underscores the importance of realistic decision-making scenarios for studies and the role of familiarity with the decision dilemma generally., Highlights: In a world where information for medical decision making is increasingly going to be provided through digital, online tools, institutions providing such tools need guidance on how best to communicate about their trustworthiness and precision.We find that people are fairly insensitive to cues designed to communicate uncertainty around the outputs of such tools. Even putting "ATTENTION" in bold font or explicitly pointing out the weaknesses in the data did not appear to affect people's decision making using the tool's outputs. Institutions should take note, and further work is required to determine how best to communicate uncertainty in a way that elicits appropriate caution in lay users.People were much more sensitive to institutional logos associated with the outputs. Generalized institutional trust (rather than trust in the specific institution whose logo was shown) was associated with how trustworthy, accurate, and reliable the tool, its algorithm, and the numbers it produced were perceived to be. This underscores the role of societal trust in institutions at large.Finally, as a note to researchers, we found a significant effect of how hypothetical or believable participants felt the experimental scenario was. This is a variable that seems rarely controlled for in studies and yet played as much of a role as some of our variables of interest, so we suggest that it is measured in future experiments., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The Winton Centre for Risk & Evidence Communication is funded by a donation from the David & Claudia Harding Foundation. This project first arose thanks to the M2D project. This study was reviewed by the Psychological Research Ethics Committee at the University of Cambridge (PRE.2018.083). Online consent was obtained from all participants. Karin S. Moser https://orcid.org/0000-0003-0120-9327 Alexandra L.J. Freeman https://orcid.org/0000-0002-4115-161X Data and code can be found on the Open Science Framework: https://osf.io/b7gju/., (© The Author(s) 2024.)

Risk matrices communicate the likelihood and potential impact of risks and are often used to inform decision-making around risk mitigations. The merits and demerits of risk matrices in general have been discussed extensively, yet little attention has been paid to the potential influence of color in risk matrices on their users. We draw from fuzzy-trace theory and hypothesize that when color is present, individuals are likely to place greater value on reducing risks that cross color boundaries (i.e., the boundary-crossing effect), leading to sub-optimal decision making. In two randomized controlled studies, employing forced-choice and willingness-to-pay measures to investigate the boundary-crossing effect in two different color formats for risk matrices, we find preliminary evidence to support our hypotheses that color can influence decision making. The evidence also suggests that the boundary-crossing effect is only present in, or is stronger for, higher numeracy individuals. We therefore recommend that designers should consider avoiding color in risk matrices, particularly in situations where these are likely to be used by highly numerate individuals, if the communication goal is to inform in an unbiased way., (© 2023 The Authors. Risk Analysis published by Wiley Periodicals LLC on behalf of Society for Risk Analysis.)

Background: Clinicians are often advised to use pictographs to communicate risk, but whether they offer benefits when communicating risk imprecision (e.g., 65%-79%) is unknown., Purpose: To test whether any of three approaches to visualizing imprecision would more effectively communicate breast and ovarian cancer risk for BRCA1 pathogenic variant carriers., Methods: 1,300 UK residents were presented with a genetic report with information about BRCA1 -related risks, with random assignment to one of four formats: no visualization (text alone), or a pictograph using shaded icons, a gradient, or arrows marking range endpoints. We also tested pictographs in two layouts. Analysis of variance (ANOVA) and regression was employed., Results: There was no effect of format. Participants shown pictographs vs. text alone had better uptake of breast cancer risk messages ( p < .05, η 2 = 0.003). Pictographs facilitated memory for the specific amount of risk ( p < 0.001, η 2 = 0.019), as did the tabular layout. Individuals not having completed upper secondary education may benefit most., Conclusions: We found weak evidence in favor of using simple pictographs with ranges to communicate BRCA risk (versus text alone), and of the tabular layout., Innovation: Testing different ways of communicating imprecision within pictographs is a novel and promising line of research., Competing Interests: The Authors declare that there is no conflict of interest., (© 2021 The Author(s).)

Purpose: Our objective was to apply a user-centered design process to identify phrases, graphics, and ways of communicating numerical risks that could be used to help patients understand their cancer risk and next steps on receiving BRCA1 genetic test results (positive, negative, and variants of uncertain significance)., Methods: The first phase of the study, a user-centered design process, consisted of 4 rounds of interviews (N = 42, including 13 health care professionals and 16 patients having undergone BRCA testing). The second was a randomized, between-participants experimental study of 456 United Kingdom residents that compared the resulting reports to reports used in a United Kingdom national genomic laboratory hub. Outcomes were subjective and objective comprehension, communication efficacy, actionability, and perceived risk., Results: Subjective comprehension, communication efficacy, and actionability were all higher for the user-centered reports, with no difference in perceived risk. Comprehension of participants viewing user-centered reports was significantly better on 2 items, directionally (but not significantly) better on 6 items, and directionally (but not significantly) worse on 2 items., Conclusion: Our results imply that user-centered design is a promising approach for developing materials about complex genetic risks. We suggest wordings that are likely to lead to improved comprehension when communicating BRCA-associated risks., Competing Interests: Conflict of Interest The authors declare no conflict of interest. G.R., A.C.E.L., and A.L.J.F. are employed by the Winton Centre for Risk and Evidence Communication at the University of Cambridge, which is supported by the David & Claudia Harding Foundation. L.C. was supported by Health Education England and is employed by East and North Hertfordshire NHS Trust. Additional funding was provided by Cancer Research UK. These bodies have no financial interest in the research and had no role in the design of the study, collection/analysis of data, or decision to publish., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Risk matrices are a common way to communicate the likelihood and potential impacts of a variety of risks. Until now, there has been little empirical work on their effectiveness in supporting understanding and decision making, and on how different design choices affect these. In this pair of online experiments (total n = 2699), we show that risk matrices are not always superior to text for the presentation of risk information, and that a nonlinear/geometric labeling scheme helps matrix comprehension (when the likelihood/impact scales are nonlinear). To a lesser degree, results suggested that changing the shape of the matrix so that cells increase in size nonlinearly facilitates comprehension as compared to text alone, and that comprehension might be enhanced by integrating further details about the likelihood and impact onto the axes of the matrix rather than putting them in a separate key. These changes did not affect participants' preference for reducing impact over reducing likelihood when making decisions about risk mitigation. We recommend that designers of risk matrices consider these changes to facilitate better understanding of relationships among risks., (© 2021 The Authors. Risk Analysis published by Wiley Periodicals LLC on behalf of Society for Risk Analysis.)

Digital health represents an important step in the management of chronic diseases also in light of the reform of proximity care that is intended to be implemented as part of the Recovery Plan (PNRR). For this purpose, the inclusion of digital health tools in the care pathways is strategic. A specific Working Group of the MaCroScopio Project defined a taxonomic, methodological and cultural framework within which the development of digital health can be promoted. This would ensure that the introduction of this type of technological innovation addresses not only the need for a more efficient health system but also the real patients' healthcare requirements. At the same time it fosters the reduction of healthcare access inequalities, instead of their exacerbation.

Background: Predict Prostate is a freely available online personalised risk communication tool for men with nonmetastatic prostate cancer. Its accuracy has been assessed in multiple validation studies, but its clinical impact among patients has not hitherto been assessed., Objective: To assess the impact of the tool on patient decision-making and disease perception., Design, Setting, and Participants: A multicentre randomised controlled trial was performed across eight UK centres among newly diagnosed men considering either active surveillance or radical treatment. A total of 145 patients were included between 2018 and 2020, with median age 67 yr (interquartile range [IQR] 61-72) and prostate-specific antigen 6.8 ng/ml (IQR 5.1-8.8)., Intervention: Participants were randomised to either standard of care (SOC) information or SOC and a structured presentation of the Predict Prostate tool., Outcome Measurements and Statistical Analysis: Validated questionnaires were completed by assessing the impact of the tool on decisional conflict, uncertainty, anxiety, and perception of survival., Results and Limitations: Mean Decisional Conflict Scale scores were 26% lower in the Predict Prostate group (mean = 16.1) than in the SOC group (mean = 21.7; p = 0.027). Scores on the "support", "uncertainty", and "value clarity" subscales all favoured Predict Prostate (all p < 0.05). There was no significant difference in anxiety scores or final treatment selection between the two groups. Patient perception of 15-yr prostate cancer-specific mortality (PCSM) and overall survival benefit from radical treatment were considerably lower and more accurate among men in the Predict Prostate group (p < 0.001). In total, 57% of men reported that the Predict Prostate estimates for PCSM were lower than expected, and 36% reported being less likely to select radical treatment. Over 90% of patients in the intervention group found it useful and 94% would recommend it to others., Conclusions: Predict Prostate reduces decisional conflict and uncertainty, and shifts patient perception around prognosis to be more realistic. This randomised trial demonstrates that Predict Prostate can directly inform the complex decision-making process in prostate cancer and is felt to be useful by patients. Future larger trials are warranted to test its impact upon final treatment decisions., Patient Summary: In this national study, we assessed the impact of an individualised risk communication tool, called Predict Prostate, on patient decision-making after a diagnosis of localised prostate cancer. Men were randomly assigned to two groups, which received either standard counselling and information, or this in addition to a structured presentation of the Predict Prostate tool. Men who saw the tool were less conflicted and uncertain in their decision-making, and recommended the tool highly. Those who saw the tool had more realistic perception about their long-term survival and the potential impact of treatment upon this., Take Home Message: The use of an individualised risk communication tool, such as Predict Prostate, reduces patient decisional conflict and uncertainty when deciding about treatment for nonmetastatic prostate cancer. The tool leads to more realistic perceptions about survival outcomes and prognosis., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: Describe demographical, social and psychological correlates of willingness to receive a COVID-19 vaccine., Setting: Series of online surveys undertaken between March and October 2020., Participants: A total of 25 separate national samples (matched to country population by age and sex) in 12 different countries were recruited through online panel providers (n=25 334)., Primary Outcome Measures: Reported willingness to receive a COVID-19 vaccination., Results: Reported willingness to receive a vaccine varied widely across samples, ranging from 63% to 88%. Multivariate logistic regression analyses reveal sex (female OR=0.59, 95% CI 0.55 to 0.64), trust in medical and scientific experts (OR=1.28, 95% CI 1.22 to 1.34) and worry about the COVID-19 virus (OR=1.47, 95% CI 1.41 to 1.53) as the strongest correlates of stated vaccine acceptance considering pooled data and the most consistent correlates across countries. In a subset of UK samples, we show that these effects are robust after controlling for attitudes towards vaccination in general., Conclusions: Our results indicate that the burden of trust largely rests on the shoulders of the scientific and medical community, with implications for how future COVID-19 vaccination information should be communicated to maximise uptake., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To assess the effects of different official information on public interpretation of a personal COVID-19 PCR test result., Design: A 5×2 factorial, randomised, between-subjects experiment, comparing four wordings of information about the test result and a control arm of no additional information; for both positive and negative test results., Setting: Online experiment using recruitment platform Respondi., Participants: UK participants (n=1744, after a pilot of n=1657) quota-sampled to be proportional to the UK national population on age and sex., Interventions: Participants were given a hypothetical COVID-19 PCR test result for 'John' who was presented as having a 50% chance of having COVID-19 based on symptoms alone. Participants were randomised to receive either a positive or negative result for 'John', then randomised again to receive either no more information, or text information on the interpretation of COVID-19 test results copied in September 2020 from the public websites of the UK's National Health Service, the USA's Centers for Disease Control, New Zealand's Ministry of Health or a modified version of the UK's wording. Information identifying the source of the wording was removed., Main Outcome Measures: Participants were asked 'What is your best guess as to the percent chance that John actually had COVID-19 at the time of his test, given his result?'; questions about their feelings of trustworthiness in the result, their perceptions of the quality of the underlying evidence and what action they felt 'John' should take in the light of his result., Results: Of those presented with a positive COVID-19 test result for 'John', the mean estimate of the probability that he had the virus was 73% (71.5%-74.5%); for those presented with a negative result, 38% (36.7%-40.0%). There was no main effect of information (wording) on these means. However, those participants given the official information from the UK website, which did not mention the possibility of false negatives or false positives, were more likely to give a categorical (100% or 0%) answer (UK: 68/343, 19.8% (15.9%-24.4%); control group: 42/356, 11.8% (8.8%-15.6%)); the reverse was true for those viewing the New Zealand (NZ) wording, which highlighted the uncertainties most explicitly (20/345: 5.8% (3.7%-8.8%)). Aggregated across test result (positive/negative), there was a main effect of wording (p<0.001) on beliefs about how 'John' should behave, with those seeing the NZ wording marginally more likely to agree that 'John' should continue to self-isolate than those viewing the control or the UK wording. The proportion of participants who felt that a symptomatic individual who tests negative definitely should not self-isolate was highest among those viewing the UK wording (31/178, 17.4% (12.5%-23.7%)), and lowest among those viewing the NZ wording (6/159, 3.8% (1.6%-8.2%)). Although the NZ wording was rated harder to understand, participants reacted to the uncertainties given in the text in the expected direction: there was a small main effect of wording on trust in the result (p=0.048), with people perceiving the test result as marginally less trustworthy after having read the NZ wording compared with the UK wording. Positive results were generally viewed as more trustworthy and as having higher quality of evidence than negative results (both p<0.001)., Conclusions: The public's default assessment of the face value of both the positive and negative test results (control group) indicate an awareness that test results are not perfectly accurate. Compared with other messaging tested, participants shown the UK's 2020 wording about the interpretation of the test results appeared to interpret the results as more definitive than is warranted. Wording that acknowledges uncertainty can help people to have a more nuanced and realistic understanding of what a COVID-19 test result means, which supports decision making and behavioural response., Preregistration and Data Repository: Preregistration of pilot at osf.io/8n62f, preregistration of main experiment at osf.io/7rcj4, data and code available online (osf.io/pvhba)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Throughout the COVID-19 pandemic, social and traditional media have disseminated predictions from experts and nonexperts about its expected magnitude. How accurate were the predictions of 'experts'-individuals holding occupations or roles in subject-relevant fields, such as epidemiologists and statisticians-compared with those of the public? We conducted a survey in April 2020 of 140 UK experts and 2,086 UK laypersons; all were asked to make four quantitative predictions about the impact of COVID-19 by 31 Dec 2020. In addition to soliciting point estimates, we asked participants for lower and higher bounds of a range that they felt had a 75% chance of containing the true answer. Experts exhibited greater accuracy and calibration than laypersons, even when restricting the comparison to a subset of laypersons who scored in the top quartile on a numeracy test. Even so, experts substantially underestimated the ultimate extent of the pandemic, and the mean number of predictions for which the expert intervals contained the actual outcome was only 1.8 (out of 4), suggesting that experts should consider broadening the range of scenarios they consider plausible. Predictions of the public were even more inaccurate and poorly calibrated, suggesting that an important role remains for expert predictions as long as experts acknowledge their uncertainty., Competing Interests: The authors have declared that no competing interests exist.

As increasing amounts of data accumulate on the effects of the novel coronavirus SARS-CoV-2 and the risk factors that lead to poor outcomes, it is possible to produce personalized estimates of the risks faced by groups of people with different characteristics. The challenge of how to communicate these then becomes apparent. Based on empirical work (total n = 5520, UK) supported by in-person interviews with the public and physicians, we make recommendations on the presentation of such information. These include: using predominantly percentages when communicating the absolute risk, but also providing, for balance, a format which conveys a contrasting (higher) perception of risk (expected frequency out of 10 000); using a visual linear scale cut at an appropriate point to illustrate the maximum risk, explained through an illustrative 'persona' who might face that highest level of risk; and providing context to the absolute risk through presenting a range of other 'personas' illustrating people who would face risks of a wide range of different levels. These 'personas' should have their major risk factors (age, existing health conditions) described. By contrast, giving people absolute likelihoods of other risks they face in an attempt to add context was considered less helpful. We note that observed effect sizes generally were small. However, even small effects are meaningful and relevant when scaled up to population levels., (© 2021 The Authors.)

Competing Interests: Competing interests: None declared.

Misinformation about COVID-19 is a major threat to public health. Using five national samples from the UK ( n = 1050 and n = 1150), Ireland ( n = 700), the USA ( n = 700), Spain ( n = 700) and Mexico ( n = 700), we examine predictors of belief in the most common statements about the virus that contain misinformation. We also investigate the prevalence of belief in COVID-19 misinformation across different countries and the role of belief in such misinformation in predicting relevant health behaviours. We find that while public belief in misinformation about COVID-19 is not particularly common, a substantial proportion views this type of misinformation as highly reliable in each country surveyed. In addition, a small group of participants find common factual information about the virus highly unreliable. We also find that increased susceptibility to misinformation negatively affects people's self-reported compliance with public health guidance about COVID-19, as well as people's willingness to get vaccinated against the virus and to recommend the vaccine to vulnerable friends and family. Across all countries surveyed, we find that higher trust in scientists and having higher numeracy skills were associated with lower susceptibility to coronavirus-related misinformation. Taken together, these results demonstrate a clear link between susceptibility to misinformation and both vaccine hesitancy and a reduced likelihood to comply with health guidance measures, and suggest that interventions which aim to improve critical thinking and trust in science may be a promising avenue for future research., Competing Interests: We declare we have no competing interests., (© 2020 The Authors.)

Rationale: Complex immune dysregulation in interferon (IFN) and T cell response has been observed in human immunodeficiency virus (HIV-1)-infected patients as well as in coronavirus disease-2019 (COVID-19) patients. However, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)/HIV-1 coinfection has been described in only few cases worldwide and no data are available on immunological outcomes in HIV-1-patients infected with SARS-CoV-2. Hence, this study aims to compare type I IFN response and T cell activation levels between a SARS-CoV-2/HIV-1-coinfected female patient and age-matched HIV-1-positive or uninfected women., Patient Concerns: A 52-year-old woman diagnosed with SARS-CoV-2/HIV-1 coinfection, ten HIV-1-positive women and five age-matched-healthy individuals were enrolled in this study., Diagnoses: SARS-CoV-2 infection caused severe pneumonia in the second week of illness in HIV-1-positive patient under protease inhibitors. Chest high-resolution computed tomography images of the SARS-CoV-2/HIV-1-coinfected patient showed bilateral ground-glass opacities., Interventions: SARS-CoV-2/HIV-1-coinfected female patient under darunavir/cobicistat regimen received a 7-days hydroxychloroquine therapy. Analysis of IFNα/β mRNA levels and CD4 and CD8 T cell (CD38, human leukocyte antigen-DR [HLA-DR], CD38 HLA-DR) frequencies were performed by RT/real-time PCR assays and flow cytometry, respectively. Median relative difference (MRD) was calculated for each immunological variable. For values greater than reference, MRD should be a positive number and for values that are smaller, MRD should be negative., Outcomes: The severe pneumonia observed in SARS-CoV-2/HIV-1-positive patient under protease inhibitors was reversed by a 7-days hydroxychloroquine therapy. At the end of treatment, on day 7, patient reported resolution of fever, normalization of respiratory rate (14 breaths/min), and improved oxygen arterial pressure with a FiO2 of 30%. MRD values for IFNα/β and CD4 and CD8 T cells expressing CD38 and/or HLA-DR found in SARS-CoV-2-/HIV-1-coinfected woman were approximatively equal to 0 when refereed respectively to HIV-1-positive female patients [MRDs IFNα/β: median -0.2545 (range: -0.5/0.1); T cells: median -0.11 (range: -0.8/1.3)] and ≥ 6 when referred to healthy individuals [MRDs IFNα/β: median 28.45 (range: 15/41.9); T cells: median 10 (range 6/22)]., Lessons: These results indicate that SARS-CoV-2 infection in HIV-1-positive female patient was associated with increased levels of IFNα/β-mRNAs and T cell activation compared to healthy individuals.

Purpose: Guidelines recommend that genetic reports should be clear to nonspecialists, including patients. We investigated the feasibility of creating reports for cystic fibrosis carrier testing through a rapid user-centered design process that built on a previously developed generic template. We evaluated the new reports' communication efficacy and effects on comprehension against comparable reports used in current clinical practice., Methods: Thirty participants took part in three rounds of interviews. Usability problems were identified and rectified in each round. One hundred ninety-three participants took part in an evaluation of the resulting reports measuring subjective comprehension, risk probability comprehension, perceived communication efficacy, and other factors, as compared with standard reports., Results: Participants viewing the user-centered reports rated them as clearer, easier to understand, and more effective at communicating key information than standard reports. Both groups ended up with equivalent knowledge of risk probabilities, although we observed differences in how those probabilities were perceived., Conclusion: Our findings demonstrate that by starting with a patient-friendly generic report template and modifying it for specific scenarios with a rapid user-centered design process, reports can be produced that are more effective at communicating key information. The resulting reports are now being implemented into clinical care.

This article uses computational and statistical methods for analyzing the concept of liberty 1600-1800. Based on a bespoke set of tools for parsing conceptual structures it contributes to the literature on the concept of liberty and engages with the thesis concerning negative liberty first put forward by Isaiah Berlin and subsequently modified by Quentin Skinner.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Behaviorally and pathologically relevant cortico-thalamo-cortical oscillations are driven by diverse interacting cell-intrinsic and synaptic processes. However, the mechanism that gives rise to the paroxysmal oscillations of absence seizures (ASs) remains unknown. Here we report that, during ASs in behaving animals, cortico-thalamic excitation drives thalamic firing by preferentially eliciting tonic rather than T-type Ca 2+ channel (T-channel)-dependent burst firing in thalamocortical (TC) neurons and by temporally framing thalamic output via feedforward reticular thalamic (NRT)-to-TC neuron inhibition. In TC neurons, overall ictal firing was markedly reduced and bursts rarely occurred. Moreover, blockade of T-channels in cortical and NRT neurons suppressed ASs, but such blockade in TC neurons had no effect on seizures or on ictal thalamic output synchrony. These results demonstrate ictal bidirectional cortico-thalamic communications and provide the first mechanistic understanding of cortico-thalamo-cortical network firing dynamics during ASs in behaving animals.

The paper describes a highly space-resolved characterization of the surface mechanical properties of the posterior human corneal layer (Descemet's membrane). This has been accomplished with Atomic Force Microscopy (AFM) nano-indentation by using a probe with a sharp tip geometry. Results indicate that the contact with this biological tissue in liquid occurs with no (or very low) adhesion. More importantly, under the same operating conditions, a broad distribution of penetration depth can be measured on different x-y positions of the tissue surface, indicating a high inhomogeneity of surface stiffness, not yet clearly reported in the literature. An important contribution to such inhomogeneity should be ascribed to the discontinuous nature of the collagen/proteoglycans fibers matrix tissue, as can be imaged by AFM when the tissue is semi-dry. Using classical contact mechanics calculations adapted to the specific geometry of the tetrahedral tip it has been found that the elastic modulus E of the material in the very proximity of the surface ranges from 0.23 to 2.6 kPa., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: To investigate the adhesive and stiffness properties of prestripped Descemet membrane endothelial keratoplasty (DMEK) lenticules in different preservation conditions (with and without dextran)., Methods: The study included 3 conditions: (C1) tissues collected from tissue culture media (TCM), stripped and preserved in TCM; (C2) tissues collected from transport media (TM) (TCM supplemented with 6% dextran T-500), stripped and preserved in TM; and (C3) tissues collected from TCM, stripped and preserved in TM. Using a hinge, 9.5-mm stripped DMEK lenticules were restored back on the stroma and preserved for 4 days at room temperature (RT) in different conditions as above. Nine tissues, 3 from each condition, were used to check the adhesive (fibronectin, laminin, and vitronectin) and elastic properties (fibrillin, elastin, and collagen VI) using different antibodies. Six tissues, 2 from each condition, were used to check the stiffness properties after preservation using atomic force microscopy (AFM) nanoindentation method., Results: On the Descemet membrane, fibronectin was strongly expressed in C2 and C3, whereas laminin was intense in C2 postpreservation. Vitronectin was expressed in all the conditions. Elastic proteins were not expressed in either of the conditions apart from collagen VI, which was expressed on the posterior stroma. Atomic force microscopy showed higher stiffness in C3 and an insignificant but lower rigidity in C2 as compared to C1., Conclusions: The tissues from C2 showed expression of adherent proteins and lower stiffness. Dextran may be suitable in preservation of DMEK grafts before and after preparation. Less stiff tissues may help reduce manipulations required in the recipient eye during DMEK surgery.

Background: Clinical trials play a key role in advancing medical knowledge, improving patient care and promoting economic growth in Europe. We have assessed the clinical trial activity in any respiratory diseases in Europe, with a specific focus on Italy., Methods: Information from public sources (EFPIA, clinicaltrials.gov, clinicaltrialsregister. eu, AIFA) was used to describe clinical trial activity of in respiratory diseases in Europe and by country., Results: In 2015, 3908 clinical trials were reported in Europe, 386 in respiratory diseases (9.9%). Germany was the first country both as absolute number (76 trials) and as percentage within country trials (14%), followed by Poland. Spain, Italy and France were the countries with the lowest number and percentage of trials in respiratory diseases. In 2013, the Italian Drug Agency reported 9 trials with respiratory compounds in Italy (2.1% of overall trials, 12ˆ position in the therapeutic area rank), 33% in phase 2 and 66% in phase 3. No phase 1 or phase 4 trials were reported for respiratory trials. Prevalence of respiratory trials by non-profit sponsors (28.3%) was below the average for the country (38.3%)., Conclusions: Europe has a greater potential for clinical research on drugs for respiratory diseases, particularly in countries with less activity, such as Spain, France and Italy, that should identify and implement actions to increase attractiveness for clinical trials of drugs., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In this paper, we deal with anisotropy in an idealized granular material made of a collection of frictional, elastic, contacting particles. We present a theoretical analysis for an aggregate of particles isotropically compressed and then sheared, in which two possible contacts laws between particles are considered: a linear contact law, where the contact stiffness is constant; and a nonlinear contact law, where the contact stiffness depends on the overlapping between particles. In the former case the anisotropy observed in the aggregate is associated with particle arrangement. In fact, although the aggregate is initially characterized by an isotropic network of contacts, during the loading, an anisotropic texture develops, which is measured by a fabric tensor. With a nonlinear contact law it is possible to develop anisotropy because contacting stiffnesses are different, depending on the orientation of the contact vectors with respect to the axis of the applied deformation. We find that before the peak load is reached, an aggregate made of particles with a linear contact law develops a much smaller anisotropy compared with that of an aggregate with a nonlinear law.

We compared the ability of three different contextual models of lexical semantic memory (BEAGLE, Latent Semantic Analysis, and the Topic model) and of a simple associative model (POC) to predict the properties of semantic networks derived from word association norms. None of the semantic models were able to accurately predict all of the network properties. All three contextual models over-predicted clustering in the norms, whereas the associative model under-predicted clustering. Only a hybrid model that assumed that some of the responses were based on a contextual model and others on an associative network (POC) successfully predicted all of the network properties and predicted a word's top five associates as well as or better than the better of the two constituent models. The results suggest that participants switch between a contextual representation and an associative network when generating free associations. We discuss the role that each of these representations may play in lexical semantic memory. Concordant with recent multicomponent theories of semantic memory, the associative network may encode coordinate relations between concepts (e.g., the relation between pea and bean, or between sparrow and robin), and contextual representations may be used to process information about more abstract concepts., (Copyright © 2015 Cognitive Science Society, Inc.)

This corrects the article DOI: 10.1103/PhysRevE.92.062404.

We investigate the loading and unloading behavior of soft solids in adhesive contact with randomly rough profiles. The roughness is assumed to be described by a self-affine fractal on a limited range of wave vectors. A spectral method is exploited to generate such randomly rough surfaces. The results are statistically averaged, and the calculated contact area and applied load are shown as a function of the penetration, for loading and unloading conditions. We found that the combination of adhesion forces and roughness leads to a hysteresis loading-unloading loop. This shows that energy can be lost simply as a consequence of roughness and van der Waals forces, as in this case a large number of local energy minima exist and the system may be trapped in metastable states. We numerically quantify the hysteretic loss and assess the influence of the surface statistical properties and the energy of adhesion on the hysteresis process.

Human ratings of valence, arousal, and dominance are frequently used to study the cognitive mechanisms of emotional attention, word recognition, and numerous other phenomena in which emotions are hypothesized to play an important role. Collecting such norms from human raters is expensive and time consuming. As a result, affective norms are available for only a small number of English words, are not available for proper nouns in English, and are sparse in other languages. This paper investigated whether affective ratings can be predicted from length, contextual diversity, co-occurrences with words of known valence, and orthographic similarity to words of known valence, providing an algorithm for estimating affective ratings for larger and different datasets. Our bootstrapped ratings achieved correlations with human ratings on valence, arousal, and dominance that are on par with previously reported correlations across gender, age, education and language boundaries. We release these bootstrapped norms for 23,495 English words.

Circular convolution and random permutation have each been proposed as neurally plausible binding operators capable of encoding sequential information in semantic memory. We perform several controlled comparisons of circular convolution and random permutation as means of encoding paired associates as well as encoding sequential information. Random permutations outperformed convolution with respect to the number of paired associates that can be reliably stored in a single memory trace. Performance was equal on semantic tasks when using a small corpus, but random permutations were ultimately capable of achieving superior performance due to their higher scalability to large corpora. Finally, "noisy" permutations in which units are mapped to other units arbitrarily (no one-to-one mapping) perform nearly as well as true permutations. These findings increase the neurological plausibility of random permutations and highlight their utility in vector space models of semantics.

In the last decade regulators, payers and health care providers tried to react to three major problems in drug development and drug use in clinical practice: the pharmaceutical R&D productivity crisis, the immaturity of benefit-risk profile for several newly approved drugs and the overall impact on economic sustainability of reimbursing new high cost drugs in their systems. The potentiality of create a continuum between the evidence requirements relevant for registration, for reimbursement and for post authorization research is clear. All different parties involved, like regulators, HTA agencies, scientific communities and manufacturers, are working to improve the knowledge profile of new drugs in order to anticipate the patient access to innovation, limiting or preventing the clinical and economical risks deriving from an incomplete safety and effectiveness profile. The Italian example of "New Drugs AIFA Registries", with or without the application of risk sharing schemes (cost sharing, pay for performance, etc.), introduced a new process and increased the sensitivity on this topic. However this might probably represents only a partial answer to the problem of how to set up the governance of coverage with evidence, drug utilization monitoring, comparative effectiveness research, outcome research programs and may be how to link them to access, pricing and reimbursement. The step change in post authorization research could be to "integrate" different sources and stakeholders in a wider and continuous approach, in a well designed and inclusive "second generation" HTA approach, where all resources (competencies, data, funding) will concur to increase the evidence profile and reduce the risks, and where any "evidence generation approach" is really compliant with the standard and rules of best research practices.

We contrasted the predictive power of three measures of semantic richness-number of features (NFs), contextual dispersion (CD), and a novel measure of number of semantic neighbors (NSN)-for a large set of concrete and abstract concepts on lexical decision and naming tasks. NSN (but not NF) facilitated processing for abstract concepts, while NF (but not NSN) facilitated processing for the most concrete concepts, consistent with claims that linguistic information is more relevant for abstract concepts in early processing. Additionally, converging evidence from two datasets suggests that when NSN and CD are controlled for, the features that most facilitate processing are those associated with a concept's physical characteristics and real-world contexts. These results suggest that rich linguistic contexts (many semantic neighbors) facilitate early activation of abstract concepts, whereas concrete concepts benefit more from rich physical contexts (many associated objects and locations).

Recent research has challenged the notion that word frequency is the organizing principle underlying lexical access, pointing instead to the number of contexts that a word occurs in (Adelman, Brown, & Quesada, 2006). Counting contexts gives a better quantitative fit to human lexical decision and naming data than counting raw occurrences of words. However, this approach ignores the information redundancy of the contexts in which the word occurs, a factor we refer to as semantic diversity. Using both a corpus-based study and a controlled artificial language experiment, we demonstrate the importance of contextual redundancy in lexical access, suggesting that contextual repetitions in language only increase a word's memory strength if the repetitions are accompanied by a modulation in semantic context. We introduce a cognitive process mechanism to explain the pattern of behaviour by encoding the word's context relative to the information redundancy between the current context and the word's current memory representation. The model gives a better account of identification latency data than models based on either raw frequency or document count, and also produces a better-organized space to simulate semantic similarity.

How do people understand the everyday, yet intricate, behaviors that unfold around them? In the present research, we explored this by presenting viewers with self-paced slideshows of everyday activities and recording looking times, subjective segmentation (breakpoints) into action units, and slide-to-slide physical change. A detailed comparison of the joint time courses of these variables showed that looking time and physical change were locally maximal at breakpoints and greater for higher level action units than for lower level units. Even when slideshows were scrambled, breakpoints were regarded longer and were more physically different from ordinary moments, showing that breakpoints are distinct even out of context. Breakpoints are bridges: from one action to another, from one level to another, and from perception to conception.

Phenomena in a variety of verbal tasks--for example, masked priming, lexical decision, and word naming--are typically explained in terms of similarity between word-forms. Despite the apparent commonalities between these sets of phenomena, the representations and similarity measures used to account for them are not often related. To show how this gap might be bridged, we build on the work of Hannagan, Dupoux, and Christophe, Cognitive Science 35:79-118, (2011) to explore several methods of representing visual word-forms using holographic reduced representations and to evaluate them on their ability to account for a wide range of effects in masked form priming, as well as data from lexical decision and word naming. A representation that assumes that word-internal letter groups are encoded relative to word-terminal letter groups is found to predict qualitative patterns in masked priming, as well as lexical decision and naming latencies. We then show how this representation can be integrated with the BEAGLE model of lexical semantics (Jones & Mewhort, Psychological Review 114:1-37, 2007) to enable the model to encompass a wider range of verbal tasks.

Big craniofacial resections for highly invasive malignant neoplasm, including skull base and maxillary bones, always represent a difficult chance for the reconstructive surgeon. In these cases it is not easy to restore anatomy and function simultaneously even adopting complex microsurgical techniques. In maxillofacial and oral surgery, simple bone homotransplantation for small bone segments reconstruction has been developing as popular technique and tissue banks offer not only bone segments but also many different tissues including complex body parts. In this paper we present, a case report of a homotransplantation of a complete temporomandibular joint (TMJ) together with a portion of the medial skull base and mandibular ramus folded with an ante-brachial fascio-periosteal free flap as secondary reconstruction after nearly 5 years from the removal of a sarcoma of the TMJ involving the skull base and a follow up of more than 30 months.

Computational models of lexical semantics, such as latent semantic analysis, can automatically generate semantic similarity measures between words from statistical redundancies in text. These measures are useful for experimental stimulus selection and for evaluating a model's cognitive plausibility as a mechanism that people might use to organize meaning in memory. Although humans are exposed to enormous quantities of speech, practical constraints limit the amount of data that many current computational models can learn from. We follow up on previous work evaluating a simple metric of pointwise mutual information. Controlling for confounds in previous work, we demonstrate that this metric benefits from training on extremely large amounts of data and correlates more closely with human semantic similarity ratings than do publicly available implementations of several more complex models. We also present a simple tool for building simple and scalable models from large corpora quickly and efficiently.

The class 1 integron In28, found in the multidrug resistance transposon Tn1403, was found to be located in the res site of the backbone transposon and is flanked by a 5-bp direct duplication, indicating that it reached this position by transposition. In28 has a backbone structure related to that of In4, but has lost internal sequences, including the sul1 gene, due to an IS6100-mediated deletion. In28 also lacks the partial copy of IS6100 found in In4 and contains different gene cassettes, blaP1, cmlA1, and aadA1. In1, the class 1 integron found in the multidrug resistance plasmid R46, is also located in a putative res site and belongs to the In4 group. In1 has a shorter internal deletion than In28 and has also lost one end. Additional integrons with structures related to In4 were also found in databases, and most of them had also lost either one end or internal regions or both. Tn610 belongs to this group.

The class 1 integron integrase, IntI1, recognizes two distinct types of recombination sites, attI sites, found in integrons, and members of the 59-be family, found in gene cassettes. The efficiencies of the integrative version of the three possible reactions, i.e., between two 59-be, between attI1 and a 59-be, or between two attI1 sites, were compared. Recombination events involving two attI1 sites were significantly less efficient than the reactions in which a 59-be participated, and the attI1 x 59-be reaction was generally preferred over the 59-be x 59-be reaction. Recombination of attI1 with secondary sites was less efficient than the 59-be x secondary site reaction.

Integrons are genetic elements known for their role in the acquisition and expression of genes conferring antibiotic resistance. Such acquisition is mediated by an integron-encoded integrase, which captures genes that are part of gene cassettes. To test whether integrons occur in environments with no known history of antibiotic exposure, PCR primers were designed to conserved regions of the integrase gene and the gene cassette recombination site. Amplicons generated from four environmental DNA samples contained features typical of the integrons found in antibiotic-resistant and pathogenic bacteria. The sequence diversity of the integrase genes in these clones was sufficient to classify them within three new classes of integron. Since they are derived from environments not associated with antibiotic use, integrons appear to be more prevalent in bacteria than previously observed.

In this work, we present evidence that indicates that RuvABC proteins resolve Holliday junctions in a way that prevents dimer formation in vivo. First, although arrested replication forks are rescued by recombinational repair in cells deficient for the Rep helicase, rep mutants do not require the XerCD proteins or the dif site for viability. This shows that the recombination events at arrested replication forks are generally not accompanied by the formation of chromosome dimers. Secondly, resolution of dimers into monomers is essential in the rep ruv strain because of an increased frequency of RecFOR recombination events in the chromosome of this mutant. This suggests that, in the absence of the Ruv proteins, chromosomal recombination leads to frequent dimerization. Thirdly, dif or xerC mutations increase the UV sensitivity of ruv-deficient cells 100-fold, whereas they do not confer UV sensitivity to ruv+ cells. This shows that recombinational repair of UV lesions is not accompanied by dimer formation provided that the RuvABC proteins are active. The requirement for dimer resolution in ruv strains is suppressed by the expression of the RusA Holliday junction resolvase; therefore, RusA also prevents dimer formation. We conclude that the inviability arising from a high frequency of dimer formation in rep or UV-irradiated cells is only observed in the absence of known enzymes that resolve Holliday junctions.

Integrons and the site-specific recombination systems encoded by them provide a simple mechanism for the addition of new genes to bacterial chromosomes. Although there is substantial divergence among the four known integron-encoded integrases, they all recognize the recombination sites, known as 59-base elements, that are associated with genes that are packaged in gene cassettes. In contrast, the integron-associated recombination sites, attl sites, are preferentially recognized by the cognate integrase.

Objective: Despite the fact that gastrointestinal disorders represent one of the most common reasons for medical consultations, formal assessment of patients' health-related quality of life (HRQOL) has been carried out only in a few studies, and in most cases generic questionnaires have been adopted. Because the specific issue of living with dyspeptic problems has been addressed in very few cases and no questionnaire has been shown to be appropriate for the Italian setting, a prospective project was launched to develop a specific HRQOL questionnaire for dyspepsia sufferers tailored to Italian patients but also appropriate in other cultural settings., Methods: The project consisted in a 3-yr, three-phase survey, in which different versions of the quality of life in peptic disease questionnaire (QPD) were developed through expert and patient focus groups and empiric field studies and then administered to patients recruited in five multicenter studies. Standard psychometric techniques were used to evaluate the validity, reliability, responsiveness, and patient acceptability of the QPD., Results: Three different versions of the QPD questionnaire were self-administered to more than 4000 patients. The final 30-item version, measuring three health concepts related to dyspeptic disease (anxiety induced by pain, social restriction, symptom perception), fulfilled the recommended psychometric criteria in terms of reliability and validity, correlated with health concepts measured with a well-known independent generic HRQOL instrument (the SF-36 Health Survey questionnaire) and was relatively invariant to diagnosis and sociodemographic variables; it also correlated with a measure of gastric pain frequency and was able to detect meaningful differences over time., Conclusions: Although further validation studies in different cultural and linguistic settings are mandatory before any firm conclusions can be drawn regarding the cross-cultural validity of the QPD, the data obtained provide evidence of the psychometric validity and robustness of the questionnaire when used in a fairly large, well-characterized population of Italian dyspeptic patients.