Cadherin‐mediated cell‐cell adhesion is perturbed in protein tyrosine kinase (PTK)‐transformed cells. While cadherins themselves appear to be poor PTK substrates, their cytoplasmic binding partners, the Arm catenins, are excellent PTK substrates and therefore good candidates for mediating PTK‐induced changes in cadherin behavior. These proteins, p120ctn, β‐catenin and plakoglobin, bind to the cytoplasmic region of classical cadherins and function to modulate adhesion and/or bridge cadherins to the actin cytoskeleton. In addition, as demonstrated recently for β‐catenin, these proteins also have crucial signaling (...) roles that may or may not be related to their effects on cell‐cell adhesion. Tyrosine phosphorylation of cadherin complexes is well documented and widely believed to modulate cell adhesiveness. The data to date, however, is largely correlative and the mechanism of action remains unresolved. In this review, we discuss the current literature and suggest models whereby tyrosine phosphorylation of Arm catenins contribute to regulation or perturbation of cadherin function. (shrink)

PurposeAlthough an increasing body of literature suggests a relationship between brain irradiation and deterioration of neurocognitive function, it remains as the standard therapeutic and prophylactic modality in patients with brain tumors. This review was aimed to abstract and evaluate the prediction models for radiation-induced neurocognitive decline in patients with primary or secondary brain tumors.MethodsMEDLINE was searched on October 31, 2021 for publications containing relevant truncation and MeSH terms related to “radiotherapy,” “brain,” “prediction model,” and “neurocognitive impairments.” Risk of bias was (...) assessed using the Prediction model Risk Of Bias ASsessment Tool.ResultsOf 3,580 studies reviewed, 23 prediction models were identified. Age, tumor location, education level, baseline neurocognitive score, and radiation dose to the hippocampus were the most common predictors in the models. The Hopkins verbal learning and the trail making tests were the most frequent outcome assessment tools. All studies used regression as machine learning method. All models were judged to have a high risk of bias mainly due to issues in the analysis.ConclusionExisting models have limited quality and are at high risk of bias. Following recommendations are outlined in this review to improve future models: developing cognitive assessment instruments taking into account the peculiar traits of the different brain tumors and radiation modalities; adherence to model development and validation guidelines; careful choice of candidate predictors according to the literature and domain expert consensus; and considering radiation dose to brain substructures as they can provide important information on specific neurocognitive impairments. (shrink)

California has focused on health equity in the state’s COVID-19 reopening plan. The Blueprint for a Safer Economy assigns each of California’s 58 counties into 1 of 4 tiers based on 2 metrics: test positivity rate and adjusted case rate. To advance to the next less-restrictive tier, counties must meet that tier’s test positivity and adjusted case rate thresholds. In addition, counties must have a plan for targeted investments within disadvantaged communities, and counties with more than 106 000 residents must (...) meet an equity metric. California's explicit incorporation of health equity into its reopening plan underscores the interrelated fate of its residents during the COVID-19 pandemic and creates incentives for action. This article evaluates the benefits and challenges of this novel health equity focus, and outlines recommendations for other US states to address disparities in their reopening plans. (shrink)

Research suggests that some fathers and birth partners can experience post-traumatic stress disorder after witnessing a traumatic birth. Birth-related PTSD may impact on many aspects of fathers’ and birth partners’ life, including relationship breakdown, self-blame and reducing plans for future children. Despite the potential impact on birth partners’ lives there is currently no measure of birth-related PTSD validated for use with birth partners. The current study therefore adapted the City Birth Trauma Scale for use with birth partners. The City Birth (...) Trauma Scale is a 29-item questionnaire developed to measure birth-related PTSD according to DSM-5 criteria: stressor criteria, symptoms of re-experiencing, avoidance, negative cognitions and mood, and hyperarousal, as well as duration of symptoms, significant distress or impairment, and exclusion criteria or other causes. A sample of 301 fathers/birth partners was recruited online and completed measures of birth-related PTSD, bonding, and demographic details. Results showed the City Birth Trauma Scale had good reliability and psychometric and construct validity. The fathers/birth partners version has the same two-factor structure as the original scale: general symptoms and birth-related symptoms, which accounted for 51% of the variance. PTSD symptoms were associated with preterm birth and maternal and infant complications. Overall, the City Birth Trauma Scale provides a promising measure of PTSD following childbirth that can be used in research and clinical practice. (shrink)

Since the introduction of the computer in the early 1950's, the investigation of artificial intelligence has followed three chief avenues: the discovery of self-organizing systems; the building of working models of human behavior, incorporating specific psychological theories; and the building of "heuristic" machines, without bias in favor of humanoid characteristics. While this work has used philosophical logic and its results may illustrate philosophical problems, the artificial intelligence program is by now an intricate, organized specialty. This book, therefore, has a quite (...) specialized audience of its own although it can be very valuable to those philosophers who are interested and competent in using this pioneering material. Five scientific papers report attempts to solve five different kinds of problems. Bertram Raphael describes an attempt to build a memory structure that converts the information input into a systematic model by "understanding" the informational statements as they are made. Daniel Bobrow's machine can set up algebraic equations from informal verbal statements. M. Ross Quillan asks: "What sort of representational format can permit the 'meanings' of words to be stored?" Thomas Evans' machine, Analogy, serves as a model for "pattern-recognition" rather than the "common-property" method of semantic memory. Fischer Black has developed a logical deduction mechanism for question-answering which keeps track of where we are and avoids endless deduction. The editor and John McCarthy contribute more general chapters, providing the historical background of cybernetics, and dealing with the problem of formalizing a concept of causality. Minsky ends the volume with his view that our convictions on dualism, consciousness, free will, and the like are used in the attempt to explain the complicated interactions between parts of our model of ourselves.--M. B. M. (shrink)

Children with developmental language disorder (DLD) have significant deficits in language ability that cannot be attributed to neurological damage, hearing impairment, or intellectual disability. The symptoms displayed by children with DLD differ across languages. In English, DLD is often marked by severe difficulties acquiring verb inflection. Such difficulties are less apparent in languages with rich verb morphology like Spanish and Italian. Here we show how these differential profiles can be understood in terms of an interaction between properties of the input (...) language, and the child's ability to learn predictive relations between linguistic elements that are separated within a sentence. We apply a simple associative learning model to sequential English and Spanish stimuli and show how the model's ability to associate cues occurring earlier in time with later outcomes affects the acquisition of verb inflection in English more than in Spanish. We relate this to the high frequency of the English bare form (which acts as a default) and the English process of question formation, which means that (unlike in Spanish) bare forms frequently occur in third‐person singular contexts. Finally, we hypothesize that the pro‐drop nature of Spanish makes it easier to associate person and number cues with the verb inflection than in English. Since the factors that conspire to make English verb inflection particularly challenging for learners with weak sequential learning abilities are much reduced or absent in Spanish, this provides an explanation for why learning Spanish verb inflection is relatively unaffected in children with DLD. (shrink)

Within bioethics as well as in broader clinical practice, support for transgender and gender‐questioning adolescent access to pubertal suppression has often relied heavily on the desire to prevent risky, self‐destructive, and suicidal behavior. We argue that framing justifications for access to puberty suppression in this way can actually be harmful to both individual patients as well as to the broader trans population. This justification for access to care makes such access precarious, limits its scope, and introduces perverse incentives to the (...) patient population that is being served. We go on to offer an alternative, positive defense of access to puberty‐blocking treatment for transgender youth grounded in the child's right to an open future. We argue that decisions related to pubertal suppression are both importantly weighty and potentially irreversible, and show why this justification is preferable to so‐called “informed consent” approaches. (shrink)

ABSTRACTThe visual system has been found to prioritise emotional stimuli so robustly that their presence can temporarily “blind” people to non-emotional targets in their direct line of vision. This...

Why do we spend so much of our time passing on amusing anecdotes, making wisecracks,watching The Simpsons? In Inside Jokes, Matthew Hurley, DanielDennett, and Reginald Adams offer an evolutionary and cognitive perspective.

Some things are funny -- jokes, puns, sitcoms, Charlie Chaplin, The Far Side, Malvolio with his yellow garters crossed -- but why? Why does humor exist in the first place? Why do we spend so much of our time passing on amusing anecdotes, making wisecracks, watching _The Simpsons_? In _Inside Jokes_, Matthew Hurley, Daniel Dennett, and Reginald Adams offer an evolutionary and cognitive perspective. Humor, they propose, evolved out of a computational problem that arose when our long-ago ancestors were (...) furnished with open-ended thinking. Mother Nature -- aka natural selection -- cannot just order the brain to find and fix all our time-pressured misleaps and near-misses. She has to bribe the brain with pleasure. So we find them funny. This wired-in source of pleasure has been tickled relentlessly by humorists over the centuries, and we have become addicted to the endogenous mind candy that is humor. (shrink)

BackgroundThe demand for peer reviewers is often perceived as disproportionate to the supply and availability of reviewers. Considering characteristics associated with peer review behaviour can allow for the development of solutions to manage the growing demand for peer reviewers. The objective of this research was to compare characteristics among two groups of reviewers registered in Publons.MethodsA descriptive cross-sectional study design was used to compare characteristics between individuals completing at least 100 peer reviews from January 2018 to December 2018 as and (...) a control group of peer reviewers completing between 1 and 18 peer reviews over the same time period. Data was provided by Publons, which offers a repository of peer reviewer activities in addition to tracking peer reviewer publications and research metrics. Mann Whitney tests and chi-square tests were conducted comparing characteristics of mega peer reviewers to the control group of reviewers.ResultsA total of 1596 peer reviewers had data provided by Publons. A total of 396 M peer reviewers and a random sample of 1200 control group reviewers were included. A greater proportion of mega peer reviews were male as compared to the control reviewers. Mega peer reviewers demonstrated a significantly greater average number of total publications, citations, receipt of Publons awards, and a higher average h index as compared to the control group of reviewers.ConclusionsMega peer reviewers registered in the Publons database also had a higher number of publications and citations as compared to a control group of reviewers. Additional research that considers motivations associated with peer review behaviour should be conducted to help inform peer reviewing activity. (shrink)

Over the last few decades, neuroimaging techniques have transformed our understanding of the brain and the effect of neurological conditions on brain function. More recently, light-based modalities such as functional near-infrared spectroscopy have gained popularity as tools to study brain function at the bedside. A recent application is to assess residual awareness in patients with disorders of consciousness, as some patients retain awareness albeit lacking all behavioural response to commands. Functional near-infrared spectroscopy can play a vital role in identifying these (...) patients by assessing command-driven brain activity. The goal of this review is to summarise the studies reported on this topic, to discuss the technical and ethical challenges of working with patients with disorders of consciousness, and to outline promising future directions in this field. (shrink)

BackgroundPreprint usage is growing rapidly in the life sciences; however, questions remain on the relative quality of preprints when compared to published articles. An objective dimension of quality that is readily measurable is completeness of reporting, as transparency can improve the reader’s ability to independently interpret data and reproduce findings.MethodsIn this observational study, we initially compared independent samples of articles published in bioRxiv and in PubMed-indexed journals in 2016 using a quality of reporting questionnaire. After that, we performed paired comparisons (...) between preprints from bioRxiv to their own peer-reviewed versions in journals.ResultsPeer-reviewed articles had, on average, higher quality of reporting than preprints, although the difference was small, with absolute differences of 5.0% [95% CI 1.4, 8.6] and 4.7% [95% CI 2.4, 7.0] of reported items in the independent samples and paired sample comparison, respectively. There were larger differences favoring peer-reviewed articles in subjective ratings of how clearly titles and abstracts presented the main findings and how easy it was to locate relevant reporting information. Changes in reporting from preprints to peer-reviewed versions did not correlate with the impact factor of the publication venue or with the time lag from bioRxiv to journal publication.ConclusionsOur results suggest that, on average, publication in a peer-reviewed journal is associated with improvement in quality of reporting. They also show that quality of reporting in preprints in the life sciences is within a similar range as that of peer-reviewed articles, albeit slightly lower on average, supporting the idea that preprints should be considered valid scientific contributions. (shrink)

In this introduction to part 4 of the Common Knowledge symposium “Peace by Other Means,” the journal's editor assesses the argument made by Peace, the spokesperson of Erasmus in his Querela Pacis, that the desire to impute and avenge wrongs against oneself is insatiable and at the root of both individual and social enmities. He notes that, in a symposium about how to resolve and prevent enmity, most contributions have to date expressed caveats about how justice and truth must take (...) precedence over peace, how recovery from ill treatment may be impossible, how quietism is not a moral option, and how realism demands a national policy and a personal strategy of, at best, contingent forgiveness. He concedes that the attitudes of those opposed to quietism are healthy but suggests that there may be goods worthier than health of human devotion. This essay concludes that the main differences between what it terms “judgmental” and “irenic” regimes are disagreements over anthropology and metaphysics. The presumptions that truths are objectively knowable and that human beings are moral and rational agents characterize judgmental regimes; irenic regimes are characterized by disillusionment with those assumptions. (shrink)

This book applies Augustine's thought to current questions of teaching and learning. The essays are written in an accessible style and is not intended just for experts on Augustine or church history.

BackgroundBased on an actual case in which a psychiatrist was called in to assess a patient’s capacity to refuse treatment, the aim of this study is to discuss how to manage this ethical and clinical issue and the dilemmas faced by the medical team.Case presentation: The case involved a 45-year-old female patient diagnosed with breast cancer who refused treatment. Since the mastology team had doubts about the patient’s mental state and given that she refused to consent to surgery, a forensic (...) psychiatric consult was requested.ConclusionThe forensic psychiatry team concluded that the patient’s decision-making capacity was preserved. The team suggested some actions to help the specialists deal with the ethical conflict. A reflection is proposed about the role of psychiatrists when an ethical dilemma involving decision-making capacity emerges in clinical situations, elucidating their work not only as physicians who determine diagnoses and conducts, but also as agents of transformation in the doctor–patient re... (shrink)

We have synthesized a 582,970-base pair Mycoplasma genitalium genome. This synthetic genome, named M. genitalium JCVI-1.0, contains all the genes of wild-type M. genitalium G37 except MG408, which was disrupted by an antibiotic marker to block pathogenicity and to allow for selection. To identify the genome as synthetic, we inserted "watermarks" at intergenic sites known to tolerate transposon insertions. Overlapping "cassettes" of 5 to 7 kilobases (kb), assembled from chemically synthesized oligonucleotides, were joined by in vitro recombination to produce intermediate (...) assemblies of approximately 24 kb, 72 kb ("1/8 genome"), and 144 kb ("1/4 genome"), which were all cloned as bacterial artificial chromosomes in Escherichia coli. Most of these intermediate clones were sequenced, and clones of all four 1/4 genomes with the correct sequence were identified. The complete synthetic genome was assembled by transformation-associated recombination cloning in the yeast Saccharomyces cerevisiae, then isolated and sequenced. A clone with the correct sequence was identified. The methods described here will be generally useful for constructing large DNA molecules from chemically synthesized pieces and also from combinations of natural and synthetic DNA segments. 10.1126/science.1151721. (shrink)

BackgroundAlthough the number of reporting guidelines has grown rapidly, few have gone through an updating process. The STARD statement (Standards for Reporting Diagnostic Accuracy), published in 2003 to help improve the transparency and completeness of reporting of diagnostic accuracy studies, was recently updated in a systematic way. Here, we describe the steps taken and a justification for the changes made.ResultsA 4-member Project Team coordinated the updating process; a 14-member Steering Committee was regularly solicited by the Project Team when making critical (...) decisions. First, a review of the literature was performed to identify topics and items potentially relevant to the STARD updating process. After this, the 85 members of the STARD Group were invited to participate in two online surveys to identify items that needed to be modified, removed from, or added to the STARD checklist. Based on the results of the literature review process, 33 items were presented to the STARD Group in the online survey: 25 original items and 8 new items; 73 STARD Group members (86 %) completed the first survey, and 79 STARD Group members (93 %) completed the second survey.Then, an in-person consensus meeting was organized among the members of the Project Team and Steering Committee to develop a consensual draft version of STARD 2015. This version was piloted in three rounds among a total of 32 expert and non-expert users. Piloting mostly led to rewording of items. After this, the update was finalized. The updated STARD 2015 list now consists of 30 items. Compared to the previous version of STARD, three original items were each converted into two new items, four original items were incorporated into other items, and seven new items were added.ConclusionsAfter a systematic updating process, STARD 2015 provides an updated list of 30 essential items for reporting diagnostic accuracy studies. (shrink)

In this study, we apply MOSAIC (model of syntax acquisition in children) to the simulation of the developmental patterning of children's optional infinitive (OI) errors in 4 languages: English, Dutch, German, and Spanish. MOSAIC, which has already simulated this phenomenon in Dutch and English, now implements a learning mechanism that better reflects the theoretical assumptions underlying it, as well as a chunking mechanism that results in frequent phrases being treated as 1 unit. Using 1, identical model that learns from child‐directed (...) speech, we obtain a close quantitative fit to the data from all 4 languages despite there being considerable cross‐linguistic and developmental variation in the OI phenomenon. MOSAIC successfully simulates the difference between Spanish (a pro‐drop language in which OI errors are virtually absent) and obligatory subject languages that do display the OI phenomenon. It also highlights differences in the OI phenomenon across German and Dutch, 2 closely related languages whose grammar is virtually identical with respect to the relation between finiteness and verb placement. Taken together, these results suggest that (a) cross‐linguistic differences in the rates at which children produce OIs are graded, quantitative differences that closely reflect the statistical properties of the input they are exposed to and (b) theories of syntax acquisition need to consider more closely the role of input characteristics as determinants of quantitative differences in the cross‐linguistic patterning of phenomena in language acquisition. (shrink)

Human moral judgement may have evolved to maximize the individual's welfare given parochial culturally constructed moral systems. If so, then moral condemnation should be more severe when transgressions are recent and local, and should be sensitive to the pronouncements of authority figures (who are often arbiters of moral norms), as the fitness pay-offs of moral disapproval will primarily derive from the ramifications of condemning actions that occur within the immediate social arena. Correspondingly, moral transgressions should be viewed as less objectionable (...) if they occur in other places or times, or if local authorities deem them acceptable. These predictions contrast markedly with those derived from prevailing non-evolutionary perspectives on moral judgement. Both classes of theories predict purportedly species-typical patterns, yet to our knowledge, no study to date has investigated moral judgement across a diverse set of societies, including a range of small-scale communities that differ substantially from large highly urbanized nations. We tested these predictions in five small-scale societies and two large-scale societies, finding substantial evidence of moral parochialism and contextual contingency in adults' moral judgements. Results reveal an overarching pattern in which moral condemnation reflects a concern with immediate local considerations, a pattern consistent with a variety of evolutionary accounts of moral judgement. (shrink)

The most important argument against the B-theory of time is the paraphrase argument. The major defense against that argument is the “new” tenseless theory of time, which is built on what I will call the “indexical reply” to the paraphrase argument. The move from the “old” tenseless theory of time to the new is most centrally a change of viewpoint about the nature and determiners of ontological commitment. Ironically, though, the new tenseless theorists have generally not paid enough sustained, direct (...) attention to that notion. I will defend a general criterion of ontological commitment and apply it to generate a version of the new tenseless theory of time. I will argue that many of the extant versions of the new tenseless theory of time (specifically, all those which seek to identify tenseless truth-conditions of tensed sentences as a way out of apparent ontological commitment to tensed features of reality) are unsatisfactory because their general criterion of ontological commitment is inadequate. Those versions of the new tenseless theory which are adequate (specifically, those which identify tenseless truthmakers for tensed sentences) actually entail the criterion of ontological commitment that I defend, despite appearances to the contrary. (shrink)