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One typical use of negation is to refer to exceptions. In a visual display showing several similar items (majority) and one exception, referring to the exception by negating the majority should therefore be pragmatically felicitous. We investigated whether comprehenders are sensitive to these pragmatic aspects when processing negative sentences and having to identify the according items in the visual display. In Experiment 1, participants read affirmative and negative sentences referring to either the exception or the majority object in strongly biased displays. Additionally, unbiased displays were implemented, showing equal numbers of objects of each type. Identification times of the correct referent were shorter with the biased display independent of sentence polarity. Also, picking the exceptional item in the biased display was faster than picking a majority item, independent of sentence polarity. Thus, participants did not specifically profit from pragmatically felicitous conditions when processing negation. Critically, in the biased displays, the exceptional object was highly salient, which might have initially drawn the participant’s attention to this object, resulting in a general speed-up. Therefore, in Experiment 2, we used a biased display with reduced saliency of the exceptional object. Again negation did not result in a specific speed-up due to pragmatically correct negation use. Thus, negation does not seem to facilitate the identification of an exceptional object.
Frontotemporal dementia (FTD) is a devastating neurodegenerative condition for which there is currently no effective treatment. Although it is much less common than Alzheimer’s disease, the impact of FTD is increased by its relatively early onset and high heritability. Clinical heterogeneity and overlap with other neurodegenerative and psychiatric syndromes complicate diagnosis. However, recent advances in our understanding of the molecular basis of FTD provide a foundation for the development of much-needed biomarkers and targeted therapies. This review provides a summary of the recently revised clinical criteria for FTD, highlights diagnostic challenges, briefly summarizes recent molecular discoveries and then focuses on promising developments in biomarkers and clinical trials.
A 69-year old, left-handed man presented at initial consultation with a history of difficulty with short-term recall for 18 months. There were neither obvious behavioral changes nor changes in long-term memory. He also denied any difficulty with lexical retrieval. There was no difficulty in comprehension and no topographic disorientation. He would occasionally feel down, but it seemed to be appropriate to the situation with no sustained depression. On collateral history from his wife, she noted that the cognitive symptoms began about 3 years prior. This was described as gradually progressive memory loss initially having difficulty in recalling recent events, and then subsequently needing written cues or reminders for appointments. An example of this was he could not recall who they had dinner with from several nights prior. Another would be he would tend to forget that they had just eaten recently and could not recall what they ate.
A 62-year-old right-handed lady presented at initial consultation with an 18 months history of slowly progressive short-term memory problems and personality change. She denied having any problems herself, suggesting some lack of insight. However, the collateral history obtained from her daughter made it clear that she had problems with progressive worsening of her short-term memory in the past 18 months, severe enough to be of concern in the last year. She reported that she had a poor episodic memory for conversations and recent events. As an example, her daughter gave examples that the patient was frequently unable to remember previous conversations. Also, she mentioned that she was prone to forget the discussed topic in the middle of conversations.
Choice of suicide method can strongly influence the outcome of suicidal behaviour, and is an important aspect of the process and planning involved in a suicide attempt. Yet, the reasons why individuals consider, choose or discard particular methods are not well understood.
This is the first study to explore method choices among people with a history of suicidal behaviour and individuals who have experienced, but not enacted, suicidal thoughts.
Via an online survey, we gathered open-ended data about choice of methods in relation to suicidal thoughts and behaviours, including reasons for and against specific means of harm.
A total of 712 respondents had attempted suicide, and a further 686 experienced suicidal thoughts (but not acted on them). Self-poisoning was the most commonly contemplated and used method of suicide, but most respondents had considered multiple methods. Method choices when contemplating suicide included a broader range of means than those used in actual attempts, and more unusual methods, particularly if perceived to be lethal, ‘easy’, quick, accessible and/or painless. Methods used in suicide attempts were, above all, described as having been accessible at the time, and were more commonly said to have been chosen impulsively. Key deterrents against the use of specific methods were the presence of and impact on other people, especially loved ones, and fears of injury and survival.
Exploration of method choices can offer novel insights into the transition from suicidal ideation to behaviour. Results underscore the need for preventative measures to restrict access to means and delay impulsive behaviour.
The processes and planning involved in choosing and attempting to die by a particular method of suicide are not well understood. Accounts from those who have thought about or attempted suicide using a specific method might allow us to better understand the ways in which people come to think about, plan and enact a suicide attempt.
To understand from first-person accounts the processes and planning involved in a suicide attempt on the railway.
Thematic analysis was conducted of qualitative interviews (N = 34) undertaken with individuals who had contemplated or attempted suicide by train.
Participants explained how they decided upon a particular method, time and place for a suicide attempt. Plans were described as being contingent on a number of elements (including the likelihood of being seen or interrupted), rather than being fixed in advance. Participants mentally rehearsed and evaluated a particular method, which would sometimes involve imagining in detail what would happen before, during and after an attempt. The extent to which this involved others (train drivers, partners, friends) was striking.
By giving people free reign to describe in their own words the processes they went through in planning and undertaking a suicide attempt, and by not interpreting such accounts through a lens of deficit and pathology, we can arrive at important insights into how people come to think and feel about, plan and enact a suicide attempt. The findings have implications in terms of understanding suicide risk and prevention more broadly.
The Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) cohort study of the Canadian Consortium on Neurodegeneration in Aging (CCNA) is a national initiative to catalyze research on dementia, set up to support the research agendas of CCNA teams. This cross-country longitudinal cohort of 2310 deeply phenotyped subjects with various forms of dementia and mild memory loss or concerns, along with cognitively intact elderly subjects, will test hypotheses generated by these teams.
The COMPASS-ND protocol, initial grant proposal for funding, fifth semi-annual CCNA Progress Report submitted to the Canadian Institutes of Health Research December 2017, and other documents supplemented by modifications made and lessons learned after implementation were used by the authors to create the description of the study provided here.
The CCNA COMPASS-ND cohort includes participants from across Canada with various cognitive conditions associated with or at risk of neurodegenerative diseases. They will undergo a wide range of experimental, clinical, imaging, and genetic investigation to specifically address the causes, diagnosis, treatment, and prevention of these conditions in the aging population. Data derived from clinical and cognitive assessments, biospecimens, brain imaging, genetics, and brain donations will be used to test hypotheses generated by CCNA research teams and other Canadian researchers. The study is the most comprehensive and ambitious Canadian study of dementia. Initial data posting occurred in 2018, with the full cohort to be accrued by 2020.
Availability of data from the COMPASS-ND study will provide a major stimulus for dementia research in Canada in the coming years.
There is a suicide on the British railways every 36 hours. However, the reasons why people choose to die by train are not well understood.
To explore factors influencing and discouraging the decision to attempt suicide on the railway networks.
We conducted an online survey and qualitative interviews with individuals who had contemplated or attempted suicide by train.
A total of 353 survey responders had considered and 23 had attempted suicide at rail locations (including railways and metro/underground); a third of these cases were impulsive. The most frequently reported motivations for contemplating or attempting suicide were perceptions of quick and certain lethality (54 and 37%, respectively) and easy access to rail settings (33 and 38%, respectively). The main factor discouraging people from rail suicide was its wider impact, especially on train drivers (19%). In qualitative interviews (N = 34) the desire to avoid intervention from others was also a common motivating factor for attempting suicide on the railway networks.
People attempt suicide by train because railway settings are easy to access and because of an inaccurate perception of certain and quick lethality. Tackling exaggerated perceptions of lethality may help reduce suicides by train.
There are suggestions that large evening meals are associated with greater BMI. This study reviewed systematically the association between evening energy intake and weight in adults and aimed to determine whether reducing evening intake achieves weight loss. Databases searched were MEDLINE, PubMed, Cinahl, Web of Science, Cochrane Library of Clinical Trials, EMBASE and SCOPUS. Eligible observational studies investigated the relationship between BMI and evening energy intake. Eligible intervention trials compared weight change between groups where the proportion of evening intake was manipulated. Evening intake was defined as energy consumed during a certain time – for example 18.00–21.00 hours – or self-defined meal slots – that is ‘dinner’. The search yielded 121 full texts that were reviewed for eligibility by two independent reviewers. In all, ten observational studies and eight clinical trials were included in the systematic review with four and five included in the meta-analyses, respectively. Four observational studies showed a positive association between large evening intake and BMI, five showed no association and one showed an inverse relationship. The meta-analysis of observational studies showed a non-significant trend between BMI and evening intake (P=0·06). The meta-analysis of intervention trials showed no difference in weight change between small and large dinner groups (−0·89 kg; 95 % CI −2·52, 0·75, P=0·29). This analysis was limited by significant heterogeneity, and many trials had an unknown or high risk of bias. Recommendations to reduce evening intake for weight loss cannot be substantiated by clinical evidence, and more well-controlled intervention trials are needed.
Feature Inheritance (Richards 2007) entails that uninterpretable features originate on the phase head C or v* and are then transferred to the associated Agree head, T or V. In the present article, it is argued that the French que–qui alternation is the locus of a Case contrast, implying that nominative Case originates on the complementiser and only becomes associated with T as a consequence of feature transfer. Que–qui thus provides new, Case-based empirical support for the theory of Feature Inheritance. The article also suggests that the que–qui alternation has an important implication for Chomsky's recent application of dynamic antisymmetry, reinterpreted in terms of labelling, to the issue of subject extraction failure. Specifically, the alternation appears to indicate that Case-matching is required, in addition to phi-feature agreement, in order for extraction to be blocked by labelling.
Human rabies encephalitis is rare in Canada, with only five cases reported in the past 30 years. The first and only patient who contracted rabies encephalitis in British Columbia died in 2003. Here we provide the first detailed clinical and pathological description of that case, which had several unusual features, including preexisting immunosuppression, paralytic presentation, prolonged survival, focal lesions on neuroimaging and severe neuropathology with focal necrosis, intense inflammation, and abundant viral inclusion bodies.
Mutations in the progranulin gene (GRN) are a common cause of familial frontotemporal dementia. We used a comprehensive neuropsychological battery to investigate whether early cognitive changes could be detected in GRN mutation carriers before dementia onset. Twenty-four at-risk members from six families with known GRN mutations underwent detailed neuropsychological testing. Group differences were investigated by domains of attention, language, visuospatial function, verbal memory, non-verbal memory, working memory and executive function. There was a trend for mutation carriers (n=8) to perform more poorly than non-carriers (n=16) across neuropsychological domains, with significant between group differences for visuospatial function (p<.04; d=0.92) and working memory function (p<.02; d=1.10). Measurable cognitive differences exist before the development of frontotemporal dementia in subjects with GRN mutations. The neuropsychological profile of mutation carriers suggests early asymmetric, right hemisphere brain dysfunction that is consistent with recent functional imaging data from our research group and the broader literature. (JINS, 2014, 20, 1–10)
Patient registries represent an important method of organizing “real world” patient information for clinical and research purposes. Registries can facilitate clinical trial planning and recruitment and are particularly useful in this regard for uncommon and rare diseases. Neuromuscular diseases (NMDs) are individually rare but in aggregate have a significant prevalence. In Canada, information on NMDs is lacking. Barriers to performing Canadian multicentre NMD research exist which can be overcome by a comprehensive and collaborative NMD registry.
We describe the objectives, design, feasibility and initial recruitment results for the Canadian Neuromuscular Disease Registry (CNDR).
The CNDR is a clinic-based registry which launched nationally in June 2011, incorporates paediatric and adult neuromuscular clinics in British Columbia, Alberta, Ontario, Quebec, New Brunswick and Nova Scotia and, as of December 2012, has recruited 1161 patients from 12 provinces and territories. Complete medical datasets have been captured on 460 “index disease” patients. Another 618 “non-index” patients have been recruited with capture of physician-confirmed diagnosis and contact information. We have demonstrated the feasibility of blended clinic and central office-based recruitment. “Index disease” patients recruited at the time of writing include 253 with Duchenne and Becker muscular dystrophy, 161 with myotonic dystrophy, and 71 with ALS.
The CNDR is a new nationwide registry of patients with NMDs that represents an important advance in Canadian neuromuscular disease research capacity. It provides an innovative platform for organizing patient information to facilitate clinical research and to expedite translation of recent laboratory findings into human studies.
Iodine deficiency affects an estimated 241 million school-aged children in the world. Little is known about iodine deficiency in relation to auditory function, except for the fact that deaf–mutism is one of the features of cretinism. In the present review, we documented the scientific knowledge on the role of iodine and hypothyroidism in the auditory system. We found that ear development and hearing function depend on thyroid hormones. Multiple pathways are involved in this, including both inner ear morphology as well as neurological processes. Conductive as well as sensorineural hearing loss is found in studies with animals that were rendered hypothyroidic. In humans, auditory impairment is reported frequently in relation to hypothyroidism, ranging from mild disturbances to severe handicap. Auditory impairment has been related more explicitly to congenital hypothyroidism than to acquired hypothyroidism. The critical period for thyroid function-related hearing maturation is the first and second trimesters of pregnancy. Although only a limited number of studies have directly investigated the relationship between iodine deficiency and auditory function, most studies point toward an association. However, evidence from good randomised controlled trials is lacking. Inclusion of auditory outcomes in iodine supplementation studies is therefore to be recommended, especially for trials in pregnancy. Hearing deficit is an invisible abnormality, but has major consequences for educational and social skills if not detected. In view of this, auditory impairment should be mapped in iodine-deficient areas in order to realistically estimate the magnitude of the problem.
Population modelling is an invaluable tool for identifying effective management strategies for threatened species whose populations are too small for experimental manipulation. Recently developed Bayesian approaches allow us to combine deterministic models with probability distributions to create stochastic models that account for uncertainty. We illustrate this approach in the case of the takahe Porphyrio hochstetteri, an Endangered flightless rail, which is supported by one of New Zealand's costliest recovery programmes. Using mark–recapture and logistic regression models implemented in a Bayesian framework we calculated demographic parameters for a fully stochastic population model based on 25 years of data collected from the last wild population of takahe in the Murchison Mountains, Fiordland. Our model results show that stoat trapping, captive rearing and cross-fostering of eggs/chicks in wild pairs all have a positive effect on takahe demography. If it were not for these management actions the Fiordland population would probably be declining (λ = 0.985; confidence interval, CI = 0.39–1.08), with a non-negligible risk of quasi-extinction (P = 16%) within 20 years. The captive rearing of eggs and chicks has been the main factor responsible for the positive growth observed during the last decade but in the future expanding stoat trapping to cover the entire Murchison Mountains would be the single most beneficial management action for the takahe population (λ = 1.038; CI = 0.86–1.10), followed by captive rearing (λ = 1.027; CI = 0.85–1.09).