7,227 research outputs found
The Morpho-Semantics of Spanish Indefinites
I analyze the Spanish indefinites algĂșn and algunos as a paucal and a greater paucal determiner, respectively, contrary to the common assumption that views the former as singular and the latter as plural. I use Harbour's (2014) feature [±additive], and the possibility of repeating that feature, in order to do so. I propose a transparent word-internal compositional analysis of the two determiners, where alg- contributes [âadditive] to both of them. I discuss consequences for the semantics of morphological plurality in nouns and for the analysis of ignorance implicatures
An exploration of SSVEPs across development and autism spectrum conditions
This thesis contains an experimental investigation of networks dynamics across development and autism spectrum disorders (ASD). The interplay between functional segregation and integration within functional cortical networks was investigated based on the hypothesis that it plays a key role in development and ASD. Functional segregation refers to the synchronization between adjacent brain areas and functional integration indicates the synchronization between distributed brain regions. Steady-state visual evoked potentials (SSVEPs) to high contrast (90%) luminance and isoluminant chromatic (red-green) vertical gratings with two spatial frequencies (2.8 and 6 cpd) at 7.5 Hz (luminance) and 3.3 Hz (chromatic) were recorded in individuals with and without ASD. SSVEPs were analysed in the frequency and time domains to carrying out a detailed analysis of the dynamic functional connectivity elicited by perception of simple and complex visual stimuli.
The first research study explored aged-related changes in networks dynamics. Participants were 30 children aged 7 to 17 and 11 adults from the typical population. Our results suggest functional reorganization from local to distributed networks across development, and that networks underpinning medium spatial frequency change would be a useful biomarker of typical brain function. The second research study explored potential changes in networks dynamics between children with and without ASD. Participants were 20 children aged 7 to 17 (10 with ASD and 10 age-matched typically developing). The result of this study is a potential EEG biomarker to characterize atypical brain function in autism. Our results suggest a direct relationship between functional segregation and functional integration during visual perception; atypical functional connectivity in lower processing mechanisms might contribute to the disruption in long-range functional integration reported in ASD, because both abnormalities occur in concert in the autistic brain.
Overall this exploratory research shows that SSVEPs can elicit different functional networks involving local and distributed cortical brain systems, and can also show segregated and overlapping functional networks underlying neural mechanisms at early stages of visual processing during development and ASD. Therefore, SSVEPs would be a potentially useful technique to identify differences in the brains of people with and without autism
Wide scope indefinites in Russian
This paper contributes to the cross-linguistic study of indefinites by reporting on two experimental studies on the scopal and functional properties of the two Russian indefinites koe- and -to. We show that koe- allows not only wide scope readings out of syntactic islands, but also functional readings, much like English a certain. -to, on the other hand, allows all possible scopal readings and both functional and non-functional readings. We then discuss this state of affairs from the perspective of a number of prominent theories of indefinite scope
A case of pregnancy with Rhesus antibody and bicornuate uterus - a favourable outcome: a case report
Introduction:
In 1% of Rhesus negative women sensitisation occurs without any overt sensitising event during pregnancy. This accounts for late immunisation during a first pregnancy and is responsible for 18-27% of cases of alloimmunisation. The incidence of congenital uterine anomalies in a fertile population is 3.2% of which 5% are bicornuate uterus. Bicornuate uterus can lead to early miscarriages, preterm labor, fetal growth retardation and congenital malformations.
Case presentation:
A 23-year-old lady in her first pregnancy developed Anti-D antibodies at 28 weeks of gestation without any known sensitising event. In view of increasing anti-D titres, at 36 weeks she was delivered. Incidentally during caesarean section she was found to have bicornuate uterus. The neonate was treated with phototherapy and blood transfusion following delivery.
Conclusion:
Rhesus antibodies when managed by close monitoring and timely delivery can lead to favourable outcome. Bicornuate uterus does not always lead to complications like miscarriage, growth retardation or preterm labour and does not need any special intervention
Genetic origins of social networks in rhesus macaques
This is the final version of the article. Available from the publisher via the DOI in this record.Sociality is believed to have evolved as a strategy for animals to cope with their environments. Yet the genetic basis of sociality remains unclear. Here we provide evidence that social network tendencies are heritable in a gregarious primate. The tendency for rhesus macaques, Macaca mulatta, to be tied affiliatively to others via connections mediated by their social partners - analogous to friends of friends in people - demonstrated additive genetic variance. Affiliative tendencies were predicted by genetic variation at two loci involved in serotonergic signalling, although this result did not withstand correction for multiple tests. Aggressive tendencies were also heritable and were related to reproductive output, a fitness proxy. Our findings suggest that, like humans, the skills and temperaments that shape the formation of multi-agent relationships have a genetic basis in nonhuman primates, and, as such, begin to fill the gaps in our understanding of the genetic basis of sociality.We thank Bonn Aure, Jacqueline Buhl, Monica Carlson, Matthew McConnell, Elizabeth Maldonado, David Paulsen, Cecilia Penedo & the Caribbean Primate Research Center (CPRC) for assistance, and Roger Mundry for the use of PSAM software. The authors were supported by NIMH grant R01-MH089484, an Incubator Award from the Duke Institute for Brain Sciences, and a Duke Center for Interdisciplinary Decision Sciences Fellowship to LJNB. The CPRC is supported by grant 8-P40 OD012217-25 from the National Center for Research Resources (NCRR) and the Office of Research Infrastructure Programs (ORIP) of the National Institutes of Health
Differential activation of anti-erythrocyte and anti-DNA autoreactive B lymphocytes by the Yaa mutation
An as-yet-unidentified mutation, Y-linked autoimmune acceleration (Yaa), is responsible for the accelerated development of lupus-like autoimmune syndrome in mice. In view of a possible role for Yaa as a positive regulator of BCR signaling, we have explored whether the expression of the Yaa mutation affects the development and activation of transgenic autoreactive B cells expressing either 4C8 IgM anti-RBC or Sp6 IgM anti-DNA. In this study, we show that the expression of the Yaa mutation induced a lethal form of autoimmune hemolytic anemia in 4C8 transgenic C57BL/6 mice, likely as a result of activation of 4C8 anti-RBC autoreactive B cells early in life. This was further supported, although indirectly, by increased T cell-independent IgM production in spleens of nontransgenic C57BL/6 mice bearing the Yaa mutation. In contrast, Yaa failed to induce activation of Sp6 anti-DNA autoreactive B cells, consistent with a lack of increased IgM anti-DNA production in nontransgenic C57BL/6 Yaa mice. Our results suggest that Yaa can activate autoreactive B cells in a BCR-dependent manner, related to differences in the form and nature of autoantigens
Efficacy and safety of once-daily fluticasone furoate/vilanterol (100/25 mcg) versus twice-daily fluticasone propionate/salmeterol (250/50 mcg) in COPD patients
SummaryBackgroundFluticasone furoate/vilanterol (FF/VI) is an inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA), recently approved as once-daily maintenance therapy for COPD. We compared the lung function effects of FF/VI with those of twice-daily fluticasone propionate/salmeterol (FP/SAL).MethodsThree 12 week studies comparing FF/VI and FP/SAL were conducted. Patients aged â„40 years with moderate-to-very severe COPD were randomized to receive double-blind, double-dummy FF/VI 100/25Â mcg once-daily, or FP/SAL 250/50Â mcg twice-daily for 12 weeks following a 2 week placebo run-in period. The primary endpoint of each study was change from baseline trough in 0â24Â h weighted mean FEV1 (wmFEV1) on Day 84. Safety was also assessed.ResultsIn Study 1 (HZC113109) (intent-to-treat n: FF/VIÂ =Â 260; FP/SALÂ =Â 259), the increase from baseline in 0â24Â h wmFEV1 was significantly greater with FF/VI than FP/SAL (Î80Â mL, PÂ <Â 0.001). In Study 2 (HZC112352) (intent-to-treat n: FF/VIÂ =Â 259; FP/SALÂ =Â 252) and Study 3 (RLV116974) (intent-to-treat n: FF/VIÂ =Â 412; FP/SALÂ =Â 416), the increase from baseline in 0â24Â h wmFEV1 was not significantly greater with FF/VI than FP/SAL (Î29Â mL, PÂ =Â 0.267; Î25Â mL, PÂ =Â 0.137). The treatment difference was statistically but not clinically significant in a pooled analysis (Î41Â mL, PÂ <Â 0.001). Pooled adverse events (FF/VI 27%; FP/SAL 28%) and serious adverse events (FF/VI 2%; FP/SAL 3%) were similar between treatments.ConclusionsOur data suggest that once-daily FF/VI 100/25Â mcg provides FEV1 improvement in COPD that is at least comparable with that conferred by twice-daily FP/SAL 250/50Â mcg, although interpretation is limited by differences in individual study outcomes. The safety profiles of FF/VI 100/25Â mcg and FP/SAL 250/50Â mcg are similar.Clinical trial registrationclinicaltrials.gov: NCT01323634; NCT01323621; NCT01706328. GlaxoSmithKline study codes: HZC113109; HZC112352; RLV116974
Safety and tolerability of subcutaneous trastuzumab at home administration, results of the phase IIIb open-label BELIS study in HER2-positive early breast cancer
Purpose The subcutaneous (SC) administration of trastuzumab is highly preferred by patients. At home, administration of trastuzumab SC might further improve patient benefit. The aims of the BELIS study are to evaluate the safety and tolerability of trastuzumab SC when administered at home by a healthcare professional (HCP) and to evaluate patient-reported outcomes for treatment experience of at home cancer therapy. Methods This open-label phase IIIb study enrolled HER2-positive early breast cancer patients in Belgium and Israel who completed the first six cycles of trastuzumab IV (neo)adjuvant therapy. The study consisted of three consecutive treatment periods: three cycles of trastuzumab IV and SC each at the hospital and six cycles of trastuzumab SC at home. Results Between November 2013 and December 2014, 23 centres enrolled 102 patients in the intent-to-treat population of which 101 patients entered the safety population. No new safety signals were detected with as expected, more mild administration site events with trastuzumab SC when compared to IV treatment. All patients agreed that they had benefit from at home administration to a large (18/81; 22%) or very large (63/81; 78%) extent. All HCPs (21/21) agreed that SC is the quickest method from start of preparation to finish of administration and that less resource use is needed. Conclusion The results of the BELIS study support that trastuzumab SC can be safely administered at home by a HCP and all patients considered this setting as beneficial. HCPs consider the SC formulation as the quickest method to administer trastuzumab
Single-nucleus RNA-seq2 reveals functional crosstalk between liver zonation and ploidy.
Funder: Cancer Research UKSingle-cell RNA-seq reveals the role of pathogenic cell populations in development and progression of chronic diseases. In order to expand our knowledge on cellular heterogeneity, we have developed a single-nucleus RNA-seq2 method tailored for the comprehensive analysis of the nuclear transcriptome from frozen tissues, allowing the dissection of all cell types present in the liver, regardless of cell size or cellular fragility. We use this approach to characterize the transcriptional profile of individual hepatocytes with different levels of ploidy, and have discovered that ploidy states are associated with different metabolic potential, and gene expression in tetraploid mononucleated hepatocytes is conditioned by their position within the hepatic lobule. Our work reveals a remarkable crosstalk between gene dosage and spatial distribution of hepatocytes
âTrial and errorâŠâ, ââŠhappy patientsâ and ââŠan old toy in the cupboardâ: a qualitative investigation of factors that influence practitioners in their prescription of foot orthoses
Background: Foot orthoses are used to manage of a plethora of lower limb conditions. However, whilst the theoretical
foundations might be relatively consistent, actual practices and therefore the experience of patients is likely to be less so.
The factors that affect the prescription decisions that practitioners make about individual patients is unknown and hence
the way in which clinical experience interacts with knowledge from training is not understood. Further, other influences
on orthotic practice may include the adoption (or not) of technology. Hence the aim of this study was to explore, for
the first time, the influences on orthotic practice.
Methods: A qualitative approach was adopted utilising two focus groups (16 consenting participants in total; 15
podiatrists and 1 orthotist) in order to collect the data. An opening question âWhat factors influence your orthotic
practice?â was followed with trigger questions, which were used to maintain focus. The dialogue was recorded
digitally, transcribed verbatim and a thematic framework was used to analyse the data.
Results: There were five themes: (i) influences on current practice, (ii) components of current practice, (iii) barriers
to technology being used in clinical practice, (iv) how technology could enhance foot orthoses prescription and
measurement of outcomes, and (v) how technology could provide information for practitioners and patients. A final
global theme was agreed by the researchers and the participants: âCurrent orthotic practice is variable and does not
embrace technology as it is perceived as being not fit for purpose in the clinical environment. However, practitioners
do have a desire for technology that is usable and enhances patient focussed assessment, the interventions, the clinical
outcomes and the patientâs engagement throughout these processesâ.
Conclusions: In relation to prescribing foot orthoses, practice varies considerably due to multiple influences.
Measurement of outcomes from orthotic practice is a priority but there are no current norms for achieving this.
There have been attempts by practitioners to integrate technology into their practice, but with largely negative
experiences. The process of technology development needs to improve and have a more practice, rather than
technology focus
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