This paper combines experimental, theoretical and quantitative approaches to syntactic microvariation. The empirical goal is to clarify the situation with respect to wh-doubling (also: wh-copying... Show moreThis paper combines experimental, theoretical and quantitative approaches to syntactic microvariation. The empirical goal is to clarify the situation with respect to wh-doubling (also: wh-copying) in varieties of German and Dutch. With a large-scale survey in the German and Dutch language areas we sought to establish which speakers allow wh-doubling, which speakers allow right-complexity, i.e., configurations in which the lower copy of the wh-dependency is more complex that the higher one, and which speakers allow left-complexity, i.e., the reverse, with a more complex higher copy. We also wanted to know whether there are associations between these properties, to identify groups of speakers and dialects. We found three types of grammars: (i) a grammar that allows both wh-doubling and right- and left-complexity; (ii) a grammar that allows wh-doubling and has a strong preference for right-complexity over left-complexity; and (iii) a grammar that does not allow any wh-doubling configuration. This shows that there is a clear limit to variation in this domain. Grammars with a preference for left-complexity do not exist. We then point out the consequences of these findings for the copy theory of movement, and for analyses that enrich this theory with the option of partial deletion. Show less
The relation between religiosity and well-being is one of the most researched topics in the psychology of religion, yet the directionality and robustness of the effect remains debated. Here, we... Show moreThe relation between religiosity and well-being is one of the most researched topics in the psychology of religion, yet the directionality and robustness of the effect remains debated. Here, we adopted a many-analysts approach to assess the robustness of this relation based on a new cross-cultural dataset (N = 10, 535 participants from 24 countries). We recruited 120 analysis teams to investigate (1) whether religious people self-report higher well-being, and (2) whether the relation between religiosity and self-reported well-being depends on perceived cultural norms of religion (i.e., whether it is considered normal and desirable to be religious in a given country). In a two-stage procedure, the teams first created an analysis plan and then executed their planned analysis on the data. For the first research question, all but 3 teams reported positive effect sizes with credible/confidence intervals excluding zero (median reported b = 0.120). For the second research question, this was the case for 65% of the teams (median reported b = 0.039). While most teams applied (multilevel) linear regression models, there was considerable variability in the choice of items used to construct the independent variables, the dependent variable, and the included covariates. Show less
The advent of pneumococcal conjugate vaccines led to the near disappearance of most of the included serotypes in high-income settings but also the rise of nonvaccine-type colonization and disease.... Show moreThe advent of pneumococcal conjugate vaccines led to the near disappearance of most of the included serotypes in high-income settings but also the rise of nonvaccine-type colonization and disease. Alternative strategies, using genetically conserved proteins as antigens, have been evaluated preclinically and clinically for years, so far unsuccessfully. One possible explanation for the failure of these efforts is that the choice of antigens may not have been sufficiently guided by an understanding of the gene expression pattern in the context of infection. Here, we present a targeted transcriptomic analysis of 160 pneumococcal genes encoding bacterial surface-exposed proteins in mouse models, human colonization, and human meningitis. We present the overlap of these different transcriptomic profiles. We identify two bacterial genes that are highly expressed in the context of mouse and human infection: SP_0282, an IID component of a mannose phosphotransferase system (PTS), and SP_1739, encoding RNase Y. We show that these two proteins can confer protection against pneumococcal nasopharyngeal colonization and intraperitoneal challenge in a murine model and generate opsonophagocytic antibodies. This study emphasizes and confirms the importance of studies of pneumococcal gene expression of bacterial surface proteins during human infection and colonization and may pave the way for the selection of a protein-based vaccine candidate. Show less
Strinzel, M.; Brown, J.; Kaltenbrunner, W.; Rijcke, S. de; Hill, M. 2021
Background: Smoking is more prevalent and persistent among lower socio-economic status (SES) compared with higher-SES groups, and contributes greatly to SES-based health inequities. Few... Show moreBackground: Smoking is more prevalent and persistent among lower socio-economic status (SES) compared with higher-SES groups, and contributes greatly to SES-based health inequities. Few interventions exist that effectively help lower-SES smokers quit. This study evaluated "De StopCoach", a mobile phone delivered eHealth intervention targeted at lower-SES smokers based on the evidence-based StopAdvisor, in a real-world setting (five municipalities) in The Netherlands in 2019-2020.Method: We conducted individual semi-structured interviews with project leaders, healthcare professionals, and participating smokers (N = 22), and examined log data from the app (N = 235). For practical reasons, SES of app users was not measured. Qualitative data were analysed using the Framework Approach, with the Consolidated Framework for Implementation Research (CFIR) and Unified Theory of Acceptance and Use of Technology (UTAUT) as theoretical models.Results: Qualitative data showed that factors from the Intervention and Setting domains were most important for the implementation. StopCoach seemed suitable for lower-SES smokers in terms of performance and effort expectancy, especially when integrated with regular smoking cessation counseling (SCC). Key barriers to implementation of the app were limited integration of the app in SCC programs in practice, difficulty experienced by project leaders and healthcare professionals to engage the local community, and barriers to SCC more generally (e.g., perceived resistance to quitting in patients) that prevented healthcare professionals from offering the app to smokers. Quantitative data showed that 48% of app users continued using the app after the preparation phase and pre-quit day, and that 33% of app users had attempted to quit. Both app adherence and quit attempts were more likely if smokers also received SCC from a professional coach. Posthoc analyses suggest that adherence is related to higher likelihood of a quit attempt among participants with and without a professional coach.Conclusions: Smokers, healthcare professionals and project leaders indicated in the interviews that the StopCoach app would work best when combined with SCC. It also appears from app log that app adherence and quit attempts by app users can be facilitated by combining the app with face-to-face SCC. As such, blended care appears promising for helping individual smokers quit, as it combines the best of regular SCC and eHealth. Further research on blended care for lower-SES smokers is needed. Show less
BackgroundDeletions removing 100s-1000s kb of DNA, and variable numbers of poorly characterised genes, are often found in patients with a wide range of developmental abnormalities. In such cases,... Show moreBackgroundDeletions removing 100s-1000s kb of DNA, and variable numbers of poorly characterised genes, are often found in patients with a wide range of developmental abnormalities. In such cases, understanding the contribution of the deletion to an individual's clinical phenotype is challenging.MethodsHere, as an example of this common phenomenon, we analysed 41 patients with simple deletions of similar to 177 to similar to 2000 kb affecting one allele of the well-characterised, gene dense, distal region of chromosome 16 (16p13.3), referred to as ATR-16 syndrome. We characterised deletion extents and screened for genetic background effects, telomere position effect and compensatory upregulation of hemizygous genes.ResultsWe find the risk of developmental and neurological abnormalities arises from much smaller distal chromosome 16 deletions (similar to 400 kb) than previously reported. Beyond this, the severity of ATR-16 syndrome increases with deletion size, but there is no evidence that critical regions determine the developmental abnormalities associated with this disorder. Surprisingly, we find no evidence of telomere position effect or compensatory upregulation of hemizygous genes; however, genetic background effects substantially modify phenotypic abnormalities.ConclusionsUsing ATR-16 as a general model of disorders caused by CNVs, we show the degree to which individuals with contiguous gene syndromes are affected is not simply related to the number of genes deleted but depends on their genetic background. We also show there is no critical region defining the degree of phenotypic abnormalities in ATR-16 syndrome and this has important implications for genetic counselling. Show less
Ghoussaini, M.; Edwards, S.L.; Michailidou, K.; Nord, S.; Lari, R.C.S.; Desai, K.; ... ; Australian Ovarian Canc Management 2018
We present a large, comprehensive survey of rovibrational CO line emission at 4.7 {$μ$}m from 69 protoplanetary disks, obtained with CRIRES on the ESO Very Large Telescope at the highest available... Show moreWe present a large, comprehensive survey of rovibrational CO line emission at 4.7 {$μ$}m from 69 protoplanetary disks, obtained with CRIRES on the ESO Very Large Telescope at the highest available spectral resolving power (R = 95,000, {$Delta$}v = 3.2 km s$^{-1}$). The CO fundamental band ({$Delta$}v = 1) is a well-known tracer of warm gas in the inner, planet-forming regions of gas-rich disks around young stars, with the lines formed in the super-heated surfaces of the disks at radii of 0.1-10 AU. Consistent with earlier studies, the presence of 100-1000 K CO is found to be ubiquitous around young stars which still retain disks. Our high spectral resolution data provide new insight into the kinematics of the inner disk gas. The observed line profiles are complex and reveal several different components. Pure double-peaked Keplerian profiles are surprisingly uncommon in our sample, beyond the frequency expected based on disk inclination. The majority of the profiles are consistent with emission from a disk plus a slow (few km s$^{-1}$) molecular disk wind. This is evidenced by analysis of different classes as well as an overall tendency for line profiles to have excess emission on their blue side. The data support the notion that thermal molecular winds are common for young disks. Thanks to the high spectral resolution, narrow absorption lines and weak emission lines from isotopologues and from vibrationally excited levels are readily detected. In general, $^{13}$CO lines trace cooler gas than the bulk $^{12}$CO emission and may arise from further out in the disk, as indicated by narrower line profiles. A high fraction of the sources show vibrationally excited emission (~{}50%) which is correlated with accretion luminosity, consistent with ultraviolet fluorescent excitation. Disks around early-type Herbig AeBe stars have narrower line profiles, on average, than their lower-mass late-type counterparts, due to their increased luminosity. Evolutionary changes in CO are also seen. Removal of the protostellar envelope between class I and II results in the disappearance of the strong absorption lines and CO ice feature characteristic of class I spectra. However, CO emission from class I and II objects are similar in detection frequency, excitation, and line shape, indicating that inner disk characteristics are established early. Show less
In this work, we introduce the use of H I Pfund {$β$} (Pf{$β$} 4.6538 {$μ$}m) as a tracer of mass accretion from protoplanetary disks onto young stars. Pf{$β$} was serendipitously observed in... Show moreIn this work, we introduce the use of H I Pfund {$β$} (Pf{$β$} 4.6538 {$μ$}m) as a tracer of mass accretion from protoplanetary disks onto young stars. Pf{$β$} was serendipitously observed in NIRSPEC and CRIRES surveys of CO fundamental emission, amounting to a sample size of 120 young stars with detected Pf{$β$} emission. Using a subsample of disks with previously measured accretion luminosities, we show that Pf{$β$} line luminosity is well correlated with accretion luminosity over a range of at least three orders of magnitude. We use this correlation to derive accretion luminosities for all 120 targets, 65 of which are previously unreported in the literature. The conversion from accretion luminosity to accretion rate is limited by the availability of stellar mass and radius measurements; nevertheless, we also report accretion rates for 67 targets, 16 previously unmeasured. Our large sample size and our ability to probe high extinction values allow for relatively unbiased comparisons between different types of disks. We find that the transitional disks in our sample have lower than average Pf{$β$} line luminosities, and thus accretion luminosities, at a marginally significant level. We also show that high Pf{$β$} equivalent width is a signature of transitional disks with high inner disk gas/dust ratios. In contrast, we find that disks with signatures of slow disk winds have Pf{$β$} luminosities comparable to those of other disks in our sample. Finally, we investigate accretion rates for stage I disks, including significantly embedded targets. We find that stage I and stage II disks have statistically indistinguishable Pf{$β$} line luminosities, implying similar accretion rates, and that the accretion rates of stage I disks are too low to be consistent with quiescent accretion. Our results are instead consistent with both observational and theoretical evidence that stage I objects experience episodic, rather than quiescent, accretion. Show less
Mellstrom, D.; Brown, J.; Bone, H.; Chapurlat, R.; Franchimont, N.; Brandi, M.; ... ; Papapoulos, S. 2012
