Signed and written languages are intimately related in proficient signing readers. Here, we tested whether deaf native signing beginning readers are able to make rapid use of ongoing sign language to facilitate recognition of written words. Deaf native signing children received prime target pairs with sign word onsets as primes and written words as targets. In a control group of hearing children, spoken word onsets were instead used as primes. Targets either were completions of the German signs or of the (...) spoken word onsets. Task of the participants was to decide whether the target word was a possible German word. Sign onsets facilitated processing of written targets in deaf children similarly to spoken word onsets facilitating processing of written targets in hearing children. In both groups, priming elicited similar effects in the simultaneously recorded event related potentials, starting as early as 200 ms after the onset of the written target. These results suggest that beginning readers can use ongoing lexical processing in their native language – be it signed or spoken – to facilitate written word recognition. We conclude that intimate interactions between sign and written language might in turn facilitate reading acquisition in deaf beginning readers. (shrink)

Early-Onset Schizophrenia (EOS) and Attention Deficit-Hyperactivity Disorder (ADHD) are early- onset neurodevelopmental disorders associated with cognitive deficits. The current study represents the first attempt to compare these groups on a comprehensive cognitive test battery in a longitudinal design over 25 years in order to enhance our knowledge of particular patterns resulting from the interaction between normal maturational processes and different illness processes of these disorders. In the baseline study, 19 adolescents with schizophrenia were compared to 20 (...) adolescents with ADHD and 30 healthy controls (HC), all between 12 and 18 years of age. After 13 years (T2) and after 25 years (T3) they were re-evaluated with the cognitive test battery. A cognitive Composite Score was used in a linear mixed model. The EOS group had a significant cognitive stagnation or deterioration from T1 to T2 compared to HC. However, the EOS group had the most positive change from T2 to T3, supporting a stable level of cognitive performance over the 25 year span. The ADHD group improved or had similar development as the HC group from T1 to T2. They continued to improve significantly compared to the HC group from T2 to T3. Individuals in the EOS group performed more impaired on the cognitive composite score compared to the HC group and the ADHD group at all three time points. Results might indicate a neurodevelopmental pathway of EOS with subnormal cognitive development specific in adolescence. In comparison, the ADHD group had a more consistent cognitive maturation supporting a maturational delay hypothesis of ADHD. (shrink)

Autism and early-onset schizophrenia share common dimensions of social communication deficits. The possible role of common genetic factors has to be seriously considered, such as the serotonin transporter gene that influences the severity of social communication impairments (negative symptoms) and hallucinations (positive symptoms). Autism and the negative syndrome of schizophrenia might be at one extreme of a continuum, and paranoid schizophrenia (positive symptoms) at the other extreme.

The aim of this article is to explore how metaphor is mobilized to frame and describe the lived experience of dementia in a corpus of illness narratives compiled from 10 blogs initiated and maintained by individuals diagnosed with early-onset dementia. The article is set against the background of contemporary healthcare practices and discourse around chronic illness and focuses on the metaphors that patients use to communicate about their dementia experience in relation to three basic psychological needs: autonomy, competence (...) and relatedness, which are essential for human well-being and are heavily challenged in complex medical situations. Results are discussed in terms of the framing metaphors provide of the emotional, psychological impact of dementia and their implications for patient-centered care. This study expands prior work by researching metaphors used for a condition that has been scarcely explored from this point of view and by focusing on the patient’s perspective exclusively. (shrink)

Is it right to use pre-implantation genetic diagnosis to select an embryo free of the gene for early-onset Alzheimer’s disease?A 30 year old woman with the gene for early-onset Alzheimer’s disease, who seems certain to develop the disease by the time she is 40, has used IVF and preimplantation genetic diagnosis to select an embryo that is free of the mutant gene. The woman, a geneticist, has given birth to a mutation-free child. This marks the first (...) time that preimplantation genetic diagnosis has been used to “weed out” an embryo with the defect.1–3Early-onset Alzheimer’s is an inherited, incurable disease striking people …. (shrink)

I note with interest the Controversy regarding a baby born free of an inherited predisposition to early onset Alzheimer’s disease through the use of preimplantation genetic diagnosis .1,2 As the medical geneticist for the PGD programme for single gene disorders in Melbourne, Australia, I have seen many couples who have considered PGD for a wide range of genetic conditions. My observation is that many couples look to PGD for “milder” conditions and adult onset conditions for which they (...) are not comfortable to have traditional prenatal diagnosis and termination of pregnancy.An example of this is that in the last 11 years our unit has undertaken 13 prenatal diagnoses for Huntington’s disease from nine couples, whereas in the two years that we have been offering it we have had six requests for PGD for Huntington’s disease and three couples …. (shrink)

The meaningful consideration of cultural practices, values and beliefs is a necessary component in the effective translation of advancements in neuroscience to clinical practice and public discourse. Society’s immense investment in biomedical science and technology, in conjunction with an increasingly diverse socio-cultural landscape, necessitates the study of how potential discoveries in neurodegenerative diseases such as Alzheimer disease are perceived and utilized across cultures. Building on the work of neuroscientists, ethicists and philosophers, we argue that the growing field of neuroethics provides (...) a pragmatic and constructive pathway to guide advancements in neuroscience in a manner that is culturally nuanced and relevant. Here we review a case study of one issue in culturally oriented neuroscience research where it is evident that traditional research ethics must be broadened and the values and needs of diverse populations considered for meaningful and relevant research practices. A global approach to neuroethics has the potential to furnish critical engagement with cultural considerations of advancements in neuroscience. (shrink)

Abstract2020 saw the rapid onset of a global pandemic caused by the SARS‐CoV‐2 virus. For healthcare systems worldwide, the pandemic called upon quick organization ensuring treatment and containment measures for the new virus disease. Nurses were seen as constituting a vital instrumental professional component in this study. Due to the pandemic's unpredictable and potentially dangerous nature, nurses have faced unprecedented risks and challenges. Based on interviews and free text comment from a survey, this study explores how ethical challenges related (...) to “being a nurse” during the COVID‐19 pandemic was experienced and understood by Danish hospital‐based nurses. Departing from anthropologist Jarett Zigon's notion of moral breakdown, the study demonstrates how the rapid onset of the pandemic constitutes a moral breakdown raising ethical demands for nurses. Analytically we identify three different ethical demands experienced by the nurses. These ethical demands are Nursing and societal ethical demands, Nursing and personal ethical demands, and Nursing and conflicting ethical demands. These demands represent not only very different understandings of ethical demands but also different understandings of ethical acts that are seen as necessary to respond to these demands. (shrink)

On 24 July 2017, the long-running, deeply tragic and emotionally fraught case of Charlie Gard reached its sad conclusion. Following further medical assessment of the infant, Charlie’s parents and doctors finally reached agreement that continuing medical treatment was not in Charlie’s best interests. Life support was subsequently withdrawn and Charlie died on 28 July 2017.Box 1 ### Case summary and timeline21–23 Charlie Gard was born at full term, apparently healthy, in August 2016. At a few weeks of age his parents (...) noticed early signs of muscle weakness. At 2 months of age, he was admitted to Great Ormond Street Hospital with poor feeding, failure to thrive and respiratory failure. He was admitted to intensive care, where investigations led to the diagnosis of a rare severe mitochondrial disorder – infantile onset encephalomyopathic mitochondrial DNA depletion syndrome. The specific genetic form of MDDS in Charlie Gard had previously been reported in approximately 15 infants, with typical clinical features including early onset, rapid progression and death in infancy.24 By that point, Charlie was paralysed and unable to breathe without respiratory support. He was found to have congenital deafness, and his heart, liver and kidneys were affected by the disorder. Doctors felt that Charlie’s prognosis was extremely poor. In early 2017, Charlie’s parents identified an experimental treatment, previously used in a different form of MDDS, which they hoped might benefit Charlie. In mouse models of a myopathic form of MDDS, early supplementation with deoxypryrimidine nucleosides apparently bypasses the genetic defect and leads to a reduction in the biochemical defect and in the severity of the clinical phenotype.25 26 Doctors at GOSH initially planned to use nucleoside treatment in Charlie, but in January he developed evidence of electrical seizures, and clinicians became convinced that treatment, both continued intensive care and the requested …. (shrink)

Single-sided deafness (SSD) or profound unilateral hearing loss obligates the only serviceable ear to capture all acoustic information. This loss of binaural function taxes cognitive resources for accurate listening performance, especially under adverse environments or challenging tasks. We hypothesized that adults with SSD would manifest both functional and structural brain plasticity compared to controls with normal binaural hearing. We evaluated functional alterations using magnetoencephalographic imaging (MEGI) of brain activation during performance of a moderately difficult auditory syllable sequence reproduction task (...) and assessed structural integrity using diffusion tensor magnetic resonance imaging (DTI). MEGI showed the SSD cohort to have increased induced oscillations in the theta band over the left superior temporal cortex and decreased induced gamma band oscillations over the frontal and parietal cortices between 175-475 ms following stimulus onset. DTI showed the SSD cohort to have extensive fractional anisotropy reduction in both auditory and non-auditory tracts and regions. Overlaying functional and structural changes revealed by the two imaging techniques demonstrated close registration of cortical areas and white matter tracts that expressed brain plasticity. Hence, complete loss of input from one ear in adulthood triggers both functional and structural alterations to dorsal temporal and frontal-parietal areas. (shrink)

The processing of a language involves a neural language network including temporal, parietal, and frontal cortical regions. This applies to spoken as well as signed languages. Previous research suggests that spoken language proficiency is associated with resting-state functional connectivity between language regions and other regions of the brain. Given the similarities in neural activation for spoken and signed languages, rsFC-behavior associations should also exist for sign language tasks. In this study, we explored the associations between rsFC and two types of (...) linguistic skills in sign language: phonological processing skill and accuracy in elicited sentence production. Fifteen adult, deaf early signers were enrolled in a resting-state functional magnetic resonance imaging study. In addition to fMRI data, behavioral tests of sign language phonological processing and sentence reproduction were administered. Using seed-to-voxel connectivity analysis, we investigated associations between behavioral proficiency and rsFC from language-relevant nodes: bilateral inferior frontal gyrus and posterior superior temporal gyrus. Results showed that worse sentence processing skill was associated with stronger positive rsFC between the left IFG and left sensorimotor regions. Further, sign language phonological processing skill was associated with positive rsFC from right IFG to middle frontal gyrus/frontal pole although this association could possibly be explained by domain-general cognitive functions. Our findings suggest a possible connection between rsFC and developmental language outcomes in deaf individuals. (shrink)

New-born screening programs for congenital disorders and chronic disease are expanding worldwide and children “at risk” are identified by nationwide tracking systems at the earliest possible stage. These practices are never neutral and raise important social and ethical questions. An emergent concern is that a reflexive professionalism should interrogate the ever earlier interference in children’s lives. The Flemish community of Belgium was among the first to generalize the screening for hearing loss in young children and is an interesting case to (...) study the public justification of early interventions for families with deaf children. This article uses a critical lens to study the archive of the government child healthcare organization in Flanders in order to uncover underlying constructions of childhood, deafness, and preventive health. We focus on two interrelated themes. The first is the notion of exclusion of the human factor through the mediation of technology. The second is the idea of deafness as endangering a healthy development, an impairment that can nevertheless be treated if detected early enough. It is argued that, since deafness cannot be viewed as a life-threatening condition, the public interest which is implicitly defended is not the rescue of deaf children rather the exclusion of otherness. (shrink)

Background: The aim of this study was to investigate associations between demographic and clinical variables and duration of untreated psychosis (DUP) in a sample of cases of psychosis across an adult early intervention in psychosis service and a child and adolescent community team. Method: Cross-sectional baseline data for cases of psychosis across the two teams on the caseload at a given time point were collected, including age of onset, gender, ethnicity, referral route, and DUP. Results: The median DUP (...) across the entire sample was 91 days, while those patients with initial treatment for psychosis from the child and adolescent team had a median DUP of 69 days. Using multiple linear regression, there were two variables that showed a significant association with DUP: referral route (p < .001), and age of onset, with earlier age of onset associated with shorter DUP (p = .015). Conclusion: These findings are discussed in relation to possible explanatory factors, with particular focus on service-level variables and pathways to care. It is suggested that the involvement of child and adolescent teams is vital to the work of early intervention in psychosis services. (shrink)

New-born screening programs for congenital disorders and chronic disease are expanding worldwide and children “at risk” are identified by nationwide tracking systems at the earliest possible stage. These practices are never neutral and raise important social and ethical questions. An emergent concern is that a reflexive professionalism should interrogate the ever earlier interference in children’s lives. The Flemish community of Belgium was among the first to generalize the screening for hearing loss in young children and is an interesting case to (...) study the public justification of early interventions for families with deaf children. This article uses a critical lens to study the archive of the government child healthcare organization in Flanders in order to uncover underlying constructions of childhood, deafness, and preventive health. We focus on two interrelated themes. The first is the notion of exclusion of the human factor through the mediation of technology. The second is the idea of deafness as endangering a healthy development, an impairment that can nevertheless be treated if detected early enough. It is argued that, since deafness cannot be viewed as a life-threatening condition, the public interest which is implicitly defended is not the rescue of deaf children rather the exclusion of otherness. (shrink)

What do spelling errors look like in children with sign language knowledge but with variation in hearing background, and what strategies do these children rely on when they learn how to spell in written language? Earlier research suggests that the spelling of children with hearing loss is different, because of their lack of hearing, which requires them to rely on other strategies. In this study, we examine whether, and how, different variables such as hearing degree, sign language knowledge and bilingualism (...) may affect the spelling strategies of children with Swedish sign language, Svenskt teckenspråk, (STS) knowledge, and whether these variables can be mirrored in these children’s spelling. The spelling process of nineteen children with STS knowledge (mean age: 10.9) with different hearing degrees, born into deaf families, is described and compared with a group of fourteen hearing children without STS knowledge (mean age: 10.9). Keystroke logging was used to investigate the participants’ writing process. The spelling behavior of the children was further analyzed and categorized into different spelling error categories. The results indicate that many children showed exceptionally few spelling errors compared to earlier studies, and they demonstrated good typing skills. Also, deaf children showed a tendency to rely on a visual strategy during spelling, which may result in incorrect, but visually similar, words, i.e. a type of spelling errors not found in texts by hearing children with STS knowledge. The deaf children also showed direct transfer from STS in their spelling. A sounding strategy was found in the hard-of-hearing children with STS knowledge, together with hearing children of deaf adults (CODAs), rather than a visual strategy. Nevertheless, the children with STS knowledge demonstrated fewer spelling errors in general, that may also derive from their early exposure of STS, also enabling them to use the fingerspelling strategy. Overall, this study suggests that the ability to hear and to use sign language, together and respectively, play a significant role for the spelling patterns and spelling strategies used by the children with and without hearing loss. (shrink)

Early onset puberty is increasingly prevalent among girls globally according to many scientists and clinicians. In the medical and scientific literature early sexual development is described as a problem for girls and as a frightening prospect for parents. News media and popular environmentalist accounts amplify these figurations, raising powerful concerns about the sexual predation of early developing girls by men and boys and the loss of childhood innocence. In this article the author frames one feminist approach (...) to early puberty, arguing that feminist theorists should both take scientific work around population changes in sexual development seriously and use their critical skills to unpick and challenge the discourses constituting early development as a matter of concern. The author suggests that contemporary academic and policy debates on the ‘sexualization’ of girls have important resonance for critical explorations of early puberty. These debates currently pay little attention to the physiological aspects of sexual development and could be enriched by so doing. As in the case of ‘sexualization’, issues of class, racialization and agency are central to understanding and challenging normative concerns about girls’ early sexual development. (shrink)

In this paper we investigate whether timing in monolingual acquisition interacts with age of onset and input effects in child bilingualism. Six different morpho-syntactic and semantic phenomena acquired early, late or very late are considered, with their timing in L1 acquisition varying between age 3 (subject-verb agreement) and after age 6 (case marking). Data from simultaneous bilingual children (2L1) whose mean age of onset to German was three months are compared with data from early second language (...) learners of German (eL2) whose mean age of onset to German was 35 months as well as with data from monolingual children. To explore change over time, children were tested twice at the ages of 4;4 years and 5;8 years. The main findings were that 2L1 children had an advantage over their eL2 peers in early acquired phenomena, which disappeared with time, whereas in late acquired phenomena 2L1 and eL2 children did not differ. Moreover, 2L1 children performed like monolingual children in early acquired phenomena but had a disadvantage in the late acquired phenomena with the amount of delay decreasing with time. We conclude that age of onset effects are modulated by effects of timing in monolingual acquisition. Contrary to expectation, input in terms of language dominance, measured as the dominant language used at home, did not affect simultaneous bilingual children’s performance in any of the phenomena. We discuss the implications of our findings for the hypothesis that acquisition of late phenomena is determined by input alone and suggest an alternative concept: the learner’s internal need for time to master a phenomenon, which is determined by its complexity and cross-linguistic robustness. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:ADOLESCENCE, INDIFFERENTIATION, AND THE ONSET OF PSYCHOSIS Henri Grivois Hôtel-Dieu, Paris The onset of psychosis happens, by definition, only once. The first psychotic episode is unforeseeable and risks being overlooked. Left to itself its future is uncertain, and the prognosis is potentially unfavorable. The variety of its manifestations as well as its thymic and cognitive instability explains why so little is written on this subject. The psychiatric (...) literature, by its almost exclusive reference to evolved psychoses, has not distinguished the qualities peculiar to the onset of psychosis (nascent psychosis). Yet recent research reflects an interest in early diagnosis of psychosis to secure qualitative improvements and the chance ofa favorable outcome for patients. A special approach must be used for patients during the stage of nascent psychosis. Something must be done, but early treatment is not enough. Psychotropic medication has no more than a sedative effect and there are few specifics at this stage (Swain 175). Further, one risks obliterating the patient's lived experience. The entire battery of interventions, above all the first consultations, must follow from a rigorously organized and intensive strategy to directly engage with this subjective experience. For many years at l'Hôtel-Dieu, a general hospital situated in the center of Paris, we have harnessed ourselves to this task. First I shall describe the existence of centrality. It constitutes the most characteristic and permanent trait of the onset of psychosis. From the concept of concernment, I propose a phenomenological morphogenesis of the initial sequence of psychosis. Next I turn to the state of indifferentiation that overcomes the subject, and then to the vulnerability peculiar to adolescents. I shall end with some fundamental epidemiological data. Henri Grivois1 05 Centrality To be mad is not only the feeling of being uniquely in contact with all humanity, whether as alienated from it or as uniting all of it in oneself conceived as the only member of the species. It is this certainly but also more than this. It is to infer that one occupies a unique place in the human world. It is the feeling of being encircled by everyone. Without being responsible, the patient is placed in the forefront of some grandiose project. His centrality, whatever the mode ofexpression, orients him towards a form of mental disorder. As a general rule, at the beginning, centrality is never explicit and passes unnoticed. The physical and verbal behavior of the patient suffice to accuse him, without any further investigation, of unintelligibility and incoherence. Centrality is above all an emotion about which we should admit that we know almost nothing. People with nascent psychosis are the prey of intuitions impossible to comprehend. Like Rimbaud's drunken boat, they flee, drifting or hiding themselves, coming back and taking offagain. They are therefore incapable, wherever they go, of living an instant of unconcern. Incapable of expressing their singular rapport with the world, they keep silent. Very soon nevertheless centrality engenders a torrent of questions. Silently, voicelessly, patients apprehend in an almost automatic manner the responses to these questions in the verbal and gestural behavior of others. Since Esquirol (Gauchet and Swain 464) identified hallucinatory phenomena as the cause of psychosis, they have occupied a disproportionate place in mental science for 200 years. This construction of the concept of hallucination in psychiatry, key to the orthodox vision of psychosis, assures a watchful vigilance to rule out every non-symptomatic treatment ofpatients. Hours or perhaps days later, no longer capable of abstaining from interpretation, patients begin to sketch out an explanation ofthe prodigious situation which they have experienced. They interrogate their relation to others and the intentions and the degree of unanimity of people towards them. Invoking demons and monsters often gives their explanations a first coherence which is in harmony with the scale of their experience. On their side the psychiatrists, to facilitate verbalizing the experience, suggest paraphrases of a general order: influence, mental automatism, exterior action, xenopathia, etc. To mask centrality, to get away from it, or in response to the gravity of the event, the patients, in search of some responsibility, envisage more elaborate scenarios: mission, conspiracy, trial, condemnation. A political vocabulary, more plausible but less universal than a... (shrink)

Previous studies have suggested that musical training in childhood is beneficial for sociability. However, it remains unclear how age of onset of group music lessons is associated with the late sociability of children from a long-term perspective. This study investigated associations between group music lessons conducted at a music school and children’s levels of sociability by focusing on the age of onset of the lessons. We conducted a survey of 276 children aged 4–5 years (M = 58.5 months) (...) and 6–7 years (M = 82.7 months) who commenced music lessons at ages 1, 2, 4, and 6 years. We found that (1) the empathy scores of children aged 6–7 years who began lessons when 1-year-old were greater than those who began lessons when 4-years-old, (2) the communication scores of children aged 4–5 years who began lessons when 1-year-old were greater than those who began lessons when older than 1 year, and (3) the empathy and extraversion scores were high in those aged 6–7 years who began lessons in that age range. The results suggest that early onset of music lessons could positively influence children’s sociability; in contrast, after about age 7 years, children who already had high sociability may be more inclined to select group music lessons. By focusing on the impact of regular group music lessons from a very young age on later levels of sociability, these results further elucidate the effects of musical lessons. In sum, participation in group music lessons 2–4 times per month can be effective social training for very young children and foster their later sociability. (shrink)

The article deals with surdotiflopedagogika, a doctrine of special education for deaf–blind–mute children as it was developed in the USSR in the 1920s and 1930s. In the spirit of social constructivism of the early Stalinist society, surdotiflopedagogika presents itself as a technology for the manufacture of socially useful human beings out of handicapped children with sight and hearing impairments, “half-animals, half-plants”. Surdotiflopedagogika’s institutionalization and rationale as these were evolving under the special patronage of Maxim Gorkij are analysed. Its experimental (...) aspect is also discussed. Exploring and implementing the most advanced ideas in the technology of communication, surdotiflopedagogika sought to compensate for the loss of speech, hearing, and sight by supplying the child with mechanical and human prostheses, including other people (assistants), technical devices, techniques of the body, and multiple communication codes to be translated from one into another. In the case of Soviet deaf-blind education, the Soviet subject appears as a technologically enhanced, collectively shared, and extended body in a permanent process of translation, internal as well as external. Technologies of language and acculturation that are of particular interest. Surdotiflopedagogika’s method as it appears in the theoretical writing of Ivan Afanasjevič Sokoljanskij (1889–1960), the teacher of the legendary deaf-blind author and educator Ol’ga Ivanovna Skorokhodova (1914?–1982) are given particular attention. (shrink)

Background Preserving persons’ dignity is integral to nursing. More research is needed to explore how a diversity of patients, particularly those that experience illness from a young age, experience dignity. Aim Describe the characteristics of dignity for persons living with serious illness. Research design Using a secondary data set of twenty audio-recorded interviews, a thematic content analysis was conducted to identify characteristics of dignity. The research team employed van Gennip et al.’s, 2013 “Model of Dignity in Illness” (1) to create (...) a codebook, which the authors utilized to independently code twenty narrative interview transcripts. Participants and research context Twenty persons living with serious illness of heart failure and/or dialysis-dependent renal failure who were admitted in an acute care hospital. Ethical considerations This study was approved on August 26, 2019, by the Colorado Multiple Institutional Review Board (COMIRB) IRB Protocol #19-1874. Findings Early-onset participants expressed markedly different dignity concerns than late-onset participants. In the individual domain, early-onset participants felt that their illness was “normal”; they did not experience the “healthy person to patient” transition described by older onset participants. In the relational domain, early-onset participants expressed that their relationships had already integrated their illness while late-onset participants felt that their illness harmed many of their relationships. In the societal domain, early-onset participants described dignity concerns related to how society impacted their ability to financially support themselves during their illness. Discussion Differences in the dignity experience of early-onset and late-onset participants are informed by Erikson’s “Model of Development” and by Aranda and Jones feminist critique of dignity in healthcare. Conclusions Persons with early-onset illness experience dignity differently. Awareness of the importance of work and financial independence to the experience of dignity for seriously ill patients may enhance persons’ dignity experience. (shrink)

Background: The vascular depression hypothesis emphasizes the significance of vascular lesions in late-life depression. At present, no meta-analytic model has investigated whether a difference in hyperintensity burden compared to controls between late-life and late-onset depression is evident. By including a substantial number of studies, focusing on a meaningful outcome measure, and considering several moderating and control variables, the present meta-analysis investigates the severity of hyperintensity burden in major depressive disorder (MDD) and bipolar disorder (BD). A major focus of the (...) present meta-analysis refers to the role of age at illness onset. It is analyzed whether late-onset rather than late-life depression characterizes vascular depression. Method: In total, 68 studies were included in the meta-analysis and a multilevel random effects model was calculated using Hedges’ g as the effect size measure. Results: The severity of hyperintensity burden was significantly greater in the patient group compared to the control group. This effect was evident regarding the whole patient group (g = 0.229) as well as both depression subgroups, with a significantly greater effect in BD (g = 0.374) compared to MDD (g = 0.189). Hyperintensity burden was more pronounced in late-onset depression than in early-onset depression or late-life depression. A considerable heterogeneity between the included studies was observed, which is reflected by the large variability in effects sizes. Conclusion: In conclusion, the present meta-analysis underscores the association of hyperintensities with MDD and BD. Especially late-onset depression is associated with an increased hyperintensity burden, which is in line with the vascular depression hypothesis. The results suggest that it might be more feasible to confine the concept of vascular depression specifically to late-onset depression as opposed to late-life depression. Further research is needed to understand the causal mechanisms that might underlie the relation between hyperintensity burden and depression. (shrink)

To define the determinants of impaired facial emotion recognition (FER) in patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS), we examined 76 patients with unilateral MTLE-HS, 36 prior to antero-mesial temporal lobectomy (AMTL) and 40 after AMTL, and 28 healthy control subjects with a FER test consisting of 60 items (20 each for anger, fear, and happiness). Mean percentages of the accurate responses were calculated for different subgroups: right vs. left MTLE-HS, early (age at onset (...) <6 years) vs. late-onset, and before vs. after AMTL. After controlling for years of education, duration of epilepsy and number of antiepileptic drugs (AEDs) taken, on multivariate analysis, fear recognition was profoundly impaired in early-onset right MTLE-HS patients compared to other MTLE patients and control subjects. Happiness recognition was significantly better in post-AMTL MTLE-HS patients compared to pre-AMTL patients while anger and fear recognition did not differ. We conclude that patients with right MTLE-HS with age at seizure onset <6 years are maximally predisposed to impaired fear recognition. In them, right AMTL does not further worsen FER abilities. Longitudinal studies comparing FER in the same patients before and after AMTL will be required to refine and confirm our cross-sectional observations. (shrink)

In this article, we report the results of a survey of North American adults conducted between March 24 and 30, 2020 at the onset of the COVID-19 pandemic. Respondents completed the COVID-TIS and the 21-item Depression, Anxiety, and Stress Scale, indicated their level of COVID-infection concern for themselves and close others, and provided demographic information. The results indicated: during its early stage, the pandemic produced only moderate levels of material and psychological change; the pandemic produced mild to moderate (...) levels of psychological distress; respondents who lost their jobs as a result of the pandemic experienced more change and more psychological distress than those who did not, and younger respondents and less well-educated ones experienced more psychological distress than older respondents. Unexpectedly, respondents indicated that they were more concerned that friends and family members would become infected with COVID-19 than that they would be. We conclude by speculating that these results are driven less by the immediate changes brought about by the pandemic and more by uncertainty concerning its long-term economic and social impact. (shrink)

The identification and avoidance of disease susceptibility in embryos is the most common goal of preimplantation genetic diagnosis (PGD). Most jurisdictions that accept but regulate the availability of PGD restrict it to what are characterized as ‘serious’ conditions. Line-drawing around seriousness is not determined solely by the identification of a genetic mutation. Other factors seen to be relevant include: impact on health or severity of symptoms; degree of penetrance (probability of genotype being expressed as a genetic disorder); potential for therapy; (...) rate of progression; heritability; and age of onset. In the original applications of PGD, most, if not all of these factors were seen as necessary but none was seen as sufficient for determining whether a genetic condition was labelled ‘serious’. This, however, is changing as impact on health or severity of symptoms is coming to eclipse the other considerations. This paper investigates how age of onset (primarily in the context of the United Kingdom (UK)) has become considerably less significant as a criterion for determining ethically acceptable applications of PGD. Having moved off the threshold of permitting PGD testing for only fatal (or seriously debilitating), early-onset diseases, I will investigate reasons for why age of onset will not do any work to discriminate between which adult-onset diseases should be considered serious or not. First I will explain the rationale underpinning age of onset as a factor to be weighed in making determinations of seriousness. Next I will challenge the view that later-onset conditions are less serious for being later than earlier-onset conditions. The final section of the paper will discuss some of the broader disability concerns at stake in limiting access to PGD based upon determinations of the ‘seriousness’ of genetic conditions. Instead of advocating a return to limiting PGD to only early-onset conditions, I conclude that the whole enterprise of trying to draw lines of what is to count as a ‘serious’ condition is itself problematic and in certain ways morally misleading. (shrink)

Precise and timely diagnosis of Parkinson’s disease is important to control its progression among subjects. Currently, a neuroimaging technique called dopaminergic imaging that uses single photon emission computed tomography (SPECT) with 123I-Ioflupane is popular among clinicians for detecting Parkinson’s disease in early stages. Unlike other studies, which consider only low-level features like gray matter, white matter, or cerebrospinal fluid, this study explores the non-linear relation between different biomarkers (SPECT + biological) using deep learning and multivariate logistic regression. Striatal binding (...) ratios are obtained using 123I-Ioflupane SPECT scans from four brain regions which are further integrated with five biological biomarkers to increase the diagnostic accuracy. Experimental results indicate that this investigated approach can differentiate subjects with 100% accuracy. The obtained results outperform the ones reported in the literature. Furthermore, logistic regression model has been developed for estimating the Parkinson’s disease onset probability. Such models may aid clinicians in diagnosing this disease. (shrink)

In the 20th century, the boundaries of psychosis emerged as an area in which psychiatric judgement faced numerous and profound uncertainties. Between obvious neuroses and personality and reactive disorders on the one hand, and unquestionable psychoses on the other, psychiatrists faced a world of suspected cases of schizophrenia, doubtful personality disorder diagnoses or probable cases of psychosis constituting a garden of equivocal clinical presentations in which both individual psychiatrists and the discipline as a whole were confronted with the limits of (...) their knowledge. This article examines how psychiatrists from two German university clinics managed the multiple uncertainties involved in diagnosing cases of early psychosis between 1950 and 1980. Based on the analysis of a sample of records, we propose a pragmatic interpretation of the ways in which these uncertainties were recorded by psychiatrists. How were uncertainties and doubts expressed in the records and managed by clinicians? What means were used to dispel doubt? What were the consequences for patients of these diagnostic uncertainties? The article defines an uncertainty diagnosis as a diagnosis expressed with reservations by its author and recorded as such in a medical file. Depending on the nature of the uncertainty, the types of evidence used by the professionals and how this evidence was dealt with, we have identified three types of uncertainty diagnoses: suspicion, plausibility and probability diagnoses. The article then reflects on the role of the patients themselves in shaping these uncertain situations. (shrink)

This study provides new longitudinal evidence on two major types of gesture–speech combination that play different roles in children’s early language. We analysed the spontaneous production of 10 Italian children observed monthly from 10–12 to 23–25 months of age. We evaluated the extent to which the developmental trends observed in children’s early gesture–word and word–word productions can predict subsequent verbal abilities. The results indicate that “complementary” and “supplementary” gesture–speech combinations predict subsequent language development in a different manner: While (...) the onset of “supplementary” combinations predicts the onset of two-word combinations, the use of “complementary” combinations at 12 and 18 months predicts the vocabulary and the ability to produce more words utterances at 2 years of age. Moreover, the results suggest that both “complementary” and “supplementary” crossmodal combinations are good predictive indexes of early verbal skills during the second year of age. (shrink)

This study provides new longitudinal evidence on two major types of gesture–speech combination that play different roles in children’s early language. We analysed the spontaneous production of 10 Italian children observed monthly from 10–12 to 23–25 months of age. We evaluated the extent to which the developmental trends observed in children’s early gesture–word and word–word productions can predict subsequent verbal abilities. The results indicate that “complementary” and “supplementary” gesture–speech combinations predict subsequent language development in a different manner: While (...) the onset of “supplementary” combinations predicts the onset of two-word combinations, the use of “complementary” combinations at 12 and 18 months predicts the vocabulary and the ability to produce more words utterances at 2 years of age. Moreover, the results suggest that both “complementary” and “supplementary” crossmodal combinations are good predictive indexes of early verbal skills during the second year of age. (shrink)

In order to study whether there exist a period of activity in the human early visual cortex that contributes exclusively to visual awareness, we applied transcranial magnetic stimulation over the early visual cortex and measured subjective visual awareness during visual forced-choice symbol or orientation discrimination tasks. TMS produced one dip in awareness 60–120 ms after stimulus onset, while forced-choice orientation discrimination was suppressed between 60 and 90 ms and symbol discrimination between 60 and 120 ms. Thus, a (...) time window specific to visual awareness was found only in the orientation condition at 120 ms. The results imply that both conscious and unconscious perception depend on activity in early visual areas. On the basis of previous estimates of neural processing speed, we suggest that the late part of the activity period most likely involve local extrastriate–striate interactions which provide the contents for visual awareness but are not themselves sufficient for awareness to arise. (shrink)

Cellular processes are highly dependent on a dynamic proteome that undergoes structural and functional rearrangements to allow swift conversion between different cellular states. By inducing proteasomal degradation of inhibitory or stimulating factors, ubiquitylation is particularly well suited to trigger such transitions. One prominent example is the remodelling of the centrosome upon cell cycle exit, which is required for the formation of primary cilia – antenna‐like structures on the surface of most cells that act as integrative hubs for various extracellular signals. (...) Over the last decade, many reports on ubiquitin‐related events involved in the regulation of ciliogenesis have emerged. Very often, these processes are considered to be initiated ad hoc, that is, directly before its effect on cilia biogenesis becomes evident. While such a temporal restriction may hold true for the majority of events, there is evidence that some of them are initiated earlier during the cell cycle. Here, we provide an overview of ubiquitin‐dependent processes in ciliogenesis and discuss available data that indicate such an early onset of proteolytic regulation within preceding cell cycle stages. (shrink)

Background Scientific and technological advancements in mapping and understanding the interrelated pathways through which biological and environmental exposures affect disease development create new possibilities for detecting disease risk factors. Early detection of such risk factors may help prevent disease onset or moderate the disease course, thereby decreasing associated disease burden, morbidity, and mortality. However, the ethical implications of screening for disease risk factors are unclear and the current literature provides a fragmented and case-by-case picture. Methods To identify key (...) ethical considerations arising from the early detection of disease risk factors, we performed a systematic scoping review. The Scopus, Embase, and Philosopher’s Index databases were searched for peer-reviewed, academic records, which were included if they were written in English or Dutch and concerned the ethics of (1) early detection of (2) disease risk factors for (3) disease caused by environmental factors or gene-environment interactions. All records were reviewed independently by at least two researchers. Results After screening 2034 titles and abstracts, and 112 full papers, 55 articles were included in the thematic synthesis of the results. We identified eight common ethical themes: (1) Reliability and uncertainty in early detection, (2) autonomy, (3) privacy, (4) beneficence and non-maleficence, (5) downstream burdens on others, (6) responsibility, (7) justice, and (8) medicalization and conceptual disruption. We identified several gaps in the literature, including a relative scarcity of research on ethical considerations associated with environmental preventive health interventions, a dearth of practical suggestions on how to address expressed concerns about overestimating health capacities, and a lack of insights into preventing undue attribution of health responsibility to individuals. Conclusions The ethical concerns arising with the early detection of risk factors are often interrelated and complex. Comprehensive ethical analyses are needed that are better embedded in normative frameworks and also assess and weigh the expected benefits of early risk factor detection. Such research is necessary for developing and implementing responsible and fair preventive health policies. (shrink)

In many animals, early development of the embryo is characterized by synchronous, biphasic cell divisions. These cell divisions are controlled by maternally inherited proteins and RNAs. A critical question in developmental biology is how the embryo transitions to a later pattern of asynchronous cell divisions and transfers the prior maternal control of development to the zygotic genome. The most‐common model regarding how this transition from maternal to zygotic control is regulated posits that this is a consequence of the limitation (...) of maternal gene products, due to their titration during early cell divisions. Here we discuss a recent article by Crest et al.1 that instead proposes that the balance of Cyclin‐dependent Kinase 1 and Cyclin B (Cdk1‐CycB) activity relative to that of the Drosophila checkpoint kinase Chk1 determines when asynchronous divisions begin. BioEssays 29:949–952, 2007. © 2007 Wiley Periodicals, Inc. (shrink)