2,880 research outputs found
Challenges for funders in monitoring compliance with policies on clinical trials registration and reporting: analysis of funding and registry data in the UK
Objectives: To evaluate compliance by researchers with funder requirements on clinical trial transparency, including identifying key areas for improvement; to assess the completeness, accuracy and suitability for annual compliance monitoring of the data routinely collected by a research funding body. /
Design: Descriptive analysis of clinical trials funded between February 2011 and January 2017 against funder policy requirements. /
Setting: Public medical research funding body in the UK. /
Data sources: Relevant clinical trials were identified from grant application details, post-award grant monitoring systems and the International Standard Randomised Controlled Trial Number (ISRCTN) registry. /
Main outcome measure: The proportion of all Medical Research Council (MRC)-funded clinical trials that were (a) registered in a clinical trial registry and (b) publicly reported summary results within 2 years of completion. /
Results: There were 175 grants awarded that included a clinical trial and all trials were registered in a public trials registry. Of 62 trials completed for over 24 months, 42 (68%) had publicly reported the main findings by 24 months after trial completion; 18 of these achieved this within 12 months of completion. 11 (18%) trials took >24 months to report and 9 (15%) completed trials had not yet reported findings. Five datasets were shared with other researchers. /
Conclusions: Compliance with the funder policy requirements on trial registration was excellent. Reporting of the main findings was achieved for most trials within 24 months of completion; however, the number of unreported trials remains a concern and should be a focus for future funder policy initiatives. Identifying trials from grant management and grant monitoring systems was challenging therefore funders should ensure investigators reliably provide trial registries with information and regularly update entries with details of trial publications and protocols
Syntactic learning by mere exposure - An ERP study in adult learners
<p>Abstract</p> <p>Background</p> <p>Artificial language studies have revealed the remarkable ability of humans to extract syntactic structures from a continuous sound stream by mere exposure. However, it remains unclear whether the processes acquired in such tasks are comparable to those applied during normal language processing. The present study compares the ERPs to auditory processing of simple Italian sentences in native and non-native speakers after brief exposure to Italian sentences of a similar structure. The sentences contained a non-adjacent dependency between an auxiliary and the morphologically marked suffix of the verb. Participants were presented four alternating learning and testing phases. During learning phases only correct sentences were presented while during testing phases 50 percent of the sentences contained a grammatical violation.</p> <p>Results</p> <p>The non-native speakers successfully learned the dependency and displayed an N400-like negativity and a subsequent anteriorily distributed positivity in response to rule violations. The native Italian group showed an N400 followed by a P600 effect.</p> <p>Conclusion</p> <p>The presence of the P600 suggests that native speakers applied a grammatical rule. In contrast, non-native speakers appeared to use a lexical form-based processing strategy. Thus, the processing mechanisms acquired in the language learning task were only partly comparable to those applied by competent native speakers.</p
Readability of state-sponsored advance directive forms in the United States: a cross sectional study
Precursors to Natural Grammar Learning: Preliminary Evidence from 4-Month-Old Infants
When learning a new language, grammar—although difficult—is very important, as grammatical rules determine the relations between the words in a sentence. There is evidence that very young infants can detect rules determining the relation between neighbouring syllables in short syllable sequences. A critical feature of all natural languages, however, is that many grammatical rules concern the dependency relation between non-neighbouring words or elements in a sentence i.e. between an auxiliary and verb inflection as in is singing. Thus, the issue of when and how children begin to recognize such non-adjacent dependencies is fundamental to our understanding of language acquisition. Here, we use brain potential measures to demonstrate that the ability to recognize dependencies between non-adjacent elements in a novel natural language is observable by the age of 4 months. Brain responses indicate that 4-month-old German infants discriminate between grammatical and ungrammatical dependencies in auditorily presented Italian sentences after only brief exposure to correct sentences of the same type. As the grammatical dependencies are realized by phonologically distinct syllables the present data most likely reflect phonologically based implicit learning mechanisms which can serve as a precursor to later grammar learning
Locomotor adaptability in persons with unilateral transtibial amputation
Background
Locomotor adaptation enables walkers to modify strategies when faced with challenging walking conditions. While a variety of neurological injuries can impair locomotor adaptability, the effect of a lower extremity amputation on adaptability is poorly understood. Objective
Determine if locomotor adaptability is impaired in persons with unilateral transtibial amputation (TTA). Methods
The locomotor adaptability of 10 persons with a TTA and 8 persons without an amputation was tested while walking on a split-belt treadmill with the parallel belts running at the same (tied) or different (split) speeds. In the split condition, participants walked for 15 minutes with the respective belts moving at 0.5 m/s and 1.5 m/s. Temporal spatial symmetry measures were used to evaluate reactive accommodations to the perturbation, and the adaptive/de-adaptive response. Results
Persons with TTA and the reference group of persons without amputation both demonstrated highly symmetric walking at baseline. During the split adaptation and tied post-adaptation walking both groups responded with the expected reactive accommodations. Likewise, adaptive and de-adaptive responses were observed. The magnitude and rate of change in the adaptive and de-adaptive responses were similar for persons with TTA and those without an amputation. Furthermore, adaptability was no different based on belt assignment for the prosthetic limb during split adaptation walking. Conclusions
Reactive changes and locomotor adaptation in response to a challenging and novel walking condition were similar in persons with TTA to those without an amputation. Results suggest persons with TTA have the capacity to modify locomotor strategies to meet the demands of most walking conditions despite challenges imposed by an amputation and use of a prosthetic limb
Lowe syndrome
Lowe syndrome (the oculocerebrorenal syndrome of Lowe, OCRL) is a multisystem disorder characterised by anomalies affecting the eye, the nervous system and the kidney. It is a uncommon, panethnic, X-linked disease, with estimated prevalence in the general population of approximately 1 in 500,000. Bilateral cataract and severe hypotonia are present at birth. In the subsequent weeks or months, a proximal renal tubulopathy (Fanconi-type) becomes evident and the ocular picture may be complicated by glaucoma and cheloids. Psychomotor retardation is evident in childhood, while behavioural problems prevail and renal complications arise in adolescence. The mutation of the gene OCRL1 localized at Xq26.1, coding for the enzyme phosphatidylinositol (4,5) bisphosphate 5 phosphatase, PtdIns (4,5)P2, in the trans-Golgi network is responsible for the disease. Both enzymatic and molecular testing are available for confirmation of the diagnosis and for prenatal detection of the disease. The treatment includes: cataract extraction, glaucoma control, physical and speech therapy, use of drugs to address behavioural problems, and correction of the tubular acidosis and the bone disease with the use of bicarbonate, phosphate, potassium and water. Life span rarely exceeds 40 years
Observation of Coherent Elastic Neutrino-Nucleus Scattering
The coherent elastic scattering of neutrinos off nuclei has eluded detection
for four decades, even though its predicted cross-section is the largest by far
of all low-energy neutrino couplings. This mode of interaction provides new
opportunities to study neutrino properties, and leads to a miniaturization of
detector size, with potential technological applications. We observe this
process at a 6.7-sigma confidence level, using a low-background, 14.6-kg
CsI[Na] scintillator exposed to the neutrino emissions from the Spallation
Neutron Source (SNS) at Oak Ridge National Laboratory. Characteristic
signatures in energy and time, predicted by the Standard Model for this
process, are observed in high signal-to-background conditions. Improved
constraints on non-standard neutrino interactions with quarks are derived from
this initial dataset
Impaired in vitro Interferon-gamma production in patients with visceral leishmaniasis is improved by inhibition of PD1/PDL-1 ligation
Visceral leishmaniasis (VL) is a neglected tropical disease that causes substantial morbidity and mortality and is a growing health problem in Ethiopia, where this study took place. Most individuals infected with Leishmania donovani parasites will stay asymptomatic, but some develop VL that, if left untreated, is almost always fatal. This stage of the disease is associated with a profound immunosuppression, characterised by impaired production of Interferonγ (IFNγ), a cytokine that plays a key role in the control of Leishmania parasites, and high expression levels of an inhibitory receptor, programmed cell death 1 (PD1) on CD4+ T cells. Here, we tested the contribution of the interaction between the immune checkpoint PD1 and its ligand PDL-1 on the impaired production of IFNγ in VL patients. Our results show that in the blood of VL patients, not only CD4+, but also CD8+ T cells express high levels of PD1 at the time of VL diagnosis. Next, we identified PDL-1 expression on different monocyte subsets and neutrophils and show that PDL-1 levels were significantly increased in VL patients. PD1/PDL-1 inhibition resulted in significantly increased production of IFNγ, suggesting that therapy using immune checkpoint inhibitors might improve disease control in these patients
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