Mapping the feel of the arm with the sight of the object: on the embodied origins of infant reaching

For decades, the emergence and progression of infant reaching was assumed to be largely under the control of vision. More recently, however, the guiding role of vision in the emergence of reaching has been downplayed. Studies found that young infants can reach in the dark without seeing their hand and that corrections in infants\u27 initial hand trajectories are not the result of visual guidance of the hand, but rather the product of poor movement speed calibration to the goal. As a result, it has been proposed that learning to reach is an embodied process requiring infants to explore proprioceptively different movement solutions, before they can accurately map their actions onto the intended goal. Such an account, however, could still assume a preponderant (or prospective) role of vision, where the movement is being monitored with the scope of approximating a future goal-location defined visually. At reach onset, it is unknown if infants map their action onto their vision, vision onto their action, or both. To examine how infants learn to map the feel of their hand with the sight of the object, we tracked the object-directed looking behavior (via eye-tracking) of three infants followed weekly over an 11-week period throughout the transition to reaching. We also examined where they contacted the object. We find that with some objects, infants do not learn to align their reach to where they look, but rather learn to align their look to where they reach. We propose that the emergence of reaching is the product of a deeply embodied process, in which infants first learn how to direct their movement in space using proprioceptive and haptic feedback from self-produced movement contingencies with the environment. As they do so, they learn to map visual attention onto these bodily centered experiences, not the reverse. We suggest that this early visuo-motor mapping is critical for the formation of visually-elicited, prospective movement control

Incidentally Discovered Endocarditis Leading to the Diagnosis of an Epidermal Growth Factor Receptor Mutant Metastatic Pulmonary Malignancy of Occult Primary Tumor

Introduction: Non-bacterial thrombotic endocarditis is well documented in the literature to occur in patients with known malignancies. It is, however, much less common for patients to be diagnosed with marantic endocarditis as the presenting sign of an unknown primary malignancy. Case Presentation: We discuss a case in which a patient was undergoing routine surveillance for his known heart failure with a transthoracic echocardiogram when an aortic valve vegetation was discovered. After further investigation, he was found to have metastatic adenocarcinoma of the lung. Next-generation sequencing was utilized to identify an EGFR mutation, which led to the patient being treated with osimertinib. Conclusion: Adequate treatment of his primary malignancy, along with anticoagulation, led to overall clinical improvement of the patient

Patient and Physician Factors Associated with First Diagnosis of Non-affective Psychotic Disorder in Primary Care

Primary care physicians play a central role in pathways to care for first-episode psychosis, and their increased involvement in early detection could improve service-related outcomes. The aim of this study was to estimate the proportion of psychosis first diagnosed in primary care, and identify associated patient and physician factors. We used linked health administrative data to construct a retrospective cohort of people aged 14-35 years with a first diagnosis of non-affective psychosis in Ontario, Canada between 2005-2015. We restricted the sample to patients with help-seeking contacts for mental health reasons in primary care in the six months prior to first diagnosis of psychotic disorder. We used modified Poisson regression models to examine patient and physician factors associated with a first diagnosis of psychosis in primary care. Among people with early psychosis (n = 39,449), 63% had help-seeking contacts in primary care within six months prior to first diagnosis. Of those patients, 47% were diagnosed in primary care and 53% in secondary/tertiary care. Patients factors associated with lower likelihood of diagnosis in primary care included male sex, younger age, immigrant status, and comorbid psychosocial conditions. Physician factors associated with lower likelihood of diagnosis in primary care included solo practice model, urban practice setting, international medical education, and longer time since graduation. Our findings indicate that primary care is an important contact for help-seeking and diagnosis for a large proportion of people with early psychosis. For physicians less likely to diagnose psychosis in primary care, targeted resources and interventions could be provided to support them in caring for patients with early psychosis

Phenotypic covariance of longevity, immunity and stress resistance in the Caenorhabditis nematodes

Background \ud Ageing, immunity and stresstolerance are inherent characteristics of all organisms. In animals, these traits are regulated, at least in part, by forkhead transcription factors in response to upstream signals from the Insulin/Insulin– like growth factor signalling (IIS) pathway. In the nematode Caenorhabditis elegans, these phenotypes are molecularly linked such that activation of the forkhead transcription factor DAF-16 both extends lifespan and simultaneously increases immunity and stress resistance. It is known that lifespan varies significantly among the Caenorhabditis species but, although DAF-16 signalling is highly conserved, it is unclear whether this phenotypic linkage occurs in other species. Here we investigate this phenotypic covariance by comparing longevity, stress resistance and immunity in four \ud Caenorhabditis species. \ud \ud Methodology/Principal Findings \ud We show using phenotypic analysis of DAF-16 influenced phenotypes that among four closely related Caenorhabditis nematodes, the gonochoristic species (Caenorhabditis remanei and Caenorhabditis brenneri) have diverged \ud significantly with a longer lifespan, improved stress resistance and higher immunity than the hermaphroditic species (C. elegans and Caenorhabditis briggsae). Interestingly, we also observe significant differences in expression levels between the daf-16 homologues in these species using Real-Time PCR, which positively correlate with the observed phenotypes. Finally, we provide additional evidence in support of a role for DAF-16 in regulating phenotypic coupling by using a combination of wildtype isolates, constitutively active daf-16 mutants and bioinformatic analysis. \ud \ud Conclusions \ud The gonochoristic species display a significantly longer lifespan (p < 0.0001)and more robust immune and stress response (p<0.0001, thermal stress; p<0.01, heavy metal stress; p<0.0001, pathogenic stress) than the hermaphroditic species. Our data suggests that divergence in DAF-16 mediated phenotypes may underlie many of the differences observed between these four species of Caenorhabditis nematodes. These findings are further supported by the correlative higher daf-16 expression levels among the gonochoristic species and significantly higher lifespan, immunity and stress tolerance in the constitutively active daf-16 hermaphroditic mutants

Phenotypic covariance of Longevity, Immunity and Stress Resistance in the Caenorhabditis Nematodes

Background: Ageing, immunity and stresstolerance are inherent characteristics of all organisms. In animals, these traits are regulated, at least in part, by forkhead transcription factors in response to upstream signals from the Insulin/Insulin–like growth factor signalling (IIS) pathway. In the nematode Caenorhabditis elegans, these phenotypes are molecularly linked such that activation of the forkhead transcription factor DAF-16 both extends lifespan and simultaneously increases immunity and stress resistance. It is known that lifespan varies significantly among the Caenorhabditis species but, although DAF-16 signalling is highly conserved, it is unclear whether this phenotypic linkage occurs in other species. Here we investigate this phenotypic covariance by comparing longevity, stress resistance and immunity in four Caenorhabditis species. \ud \ud Methodology/Principal Findings: We show using phenotypic analysis of DAF-16 influenced phenotypes that among four closely related Caenorhabditis nematodes, the gonochoristic species (Caenorhabditis remanei and Caenorhabditis brenneri) have diverged significantly with a longer lifespan, improved stress resistance and higher immunity than the hermaphroditic species (C. elegans and Caenorhabditis briggsae). Interestingly, we also observe significant differences in expression levels between the daf-16 homologues in these species using Real-Time PCR, which positively correlate with the observed phenotypes. Finally, we provide additional evidence in support of a role for DAF-16 in regulating phenotypic coupling by using a combination of wildtype isolates, constitutively active daf-16 mutants and bioinformatic analysis. \ud \ud Conclusions: The gonochoristic species display a significantly longer lifespan (p<0.0001) and more robust immune and stress response (p<0.0001, thermal stress; p<0.01, heavy metal stress; p<0.0001, pathogenic stress) than the hermaphroditic species. Our data suggests that divergence in DAF-16 mediated phenotypes may underlie many of the differences observed between these four species of Caenorhabditis nematodes. These findings are further supported by the correlative higher daf-16 expression levels among the gonochoristic species and significantly higher lifespan, immunity and stress tolerance in the constitutively active daf-16 hermaphroditic mutants

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Source Credibility: On the Independent Effects of Trust and Expertise

ABSTRACT - Marketing researchers and practitioners have tended to assume that a more trustworthy source is more credible than a less trustworthy source. However, previous studies have either confounded trustworthiness with expertise and/or attractiveness, or found that trustworthiness did not influence persuasion. In the 2 x 3 between subjects factorial experiment three levels of source expertise were crossed by two levels of trustworthiness. Careful pretesting assured that the manipulations did not influence ratings of source attractiveness. The results supported the hypotheses developed from attribution theory that sources perceived to have external reasons for making a persuasive argument will be discounted. In addition, the results revealed that expert sources influenced perceptions of the product&apos;s qualities