The Development of the Missing-Letter Effect Revisited.

When participants read a text for comprehension while identifying a target letter, the letter is more often missed in a frequent function word than in a less frequent content word. This is the missing-letter effect. Studies have shown the importance of both frequency and word function. The role of each of these factors in development is less understood. The goal of this study was to revisit the influence of frequency and word function in the missing-letter effect in development with better-controlled stimuli. Two hundred sixteen participants took part in this study and were divided into five groups (6-7 years, 8 years, 9 years, 10-11 years, and university students). They were asked to read four experimental texts for comprehension and to circle a target letter. The results showed a basic missing-letter effect with more omissions for a frequent function word than a less frequent content word for every group. When frequency was controlled, we found a word function effect as early as 6-7 years of age, with more omissions for a function word than a content word. In contrast, when word function was controlled, an effect of frequency was only significant for adults and 8-year-olds. These results clarify discrepancies in the literature and support the importance of rigorous stimuli control.

The Role of Vocabulary Skills in a Storybook-Based Intervention to Stimulate Emotion Comprehension in Preschoolers.

Understanding emotions is an important predictor of children's mental health and school adjustment. However, interventions to improve this skill are not always accessible to all children. In 2019, Roy, Dénommée, and Quenneville developed stories with content specifically designed to 'teach' about emotions. Because it is a literacy-oriented intervention, it is possible that vocabulary may play a role in learning. This project explored the role of vocabulary in understanding emotion in preschool children and its learning. Forty-three preschoolers (19 control and 24 experimental) were evaluated on vocabulary skills and emotion comprehension. For multiple components, results showed an effect of time of measure, regardless of group. However, the addition of receptive vocabulary as a covariate made this effect non-significant. Results revealed that the stories were an effective strategy in promoting emotion comprehension for Components Belief and Reminder; two skills that are in the process of development in this age group. Furthermore, vocabulary skills did not impact the interaction for Belief for post-test gains and, for Reminder, while emotional vocabulary skills impacted the interaction at post-test, receptive vocabulary did not.

The Use of Dyadic Reading in Stimulating the Comprehension of Emotions.

According to the model proposed by Pons, Doudin, and Harris , children develop nine components of emotion comprehension between the ages of three to twelve. Studies reveal that children's comprehension of emotions can be stimulated by adults reading books designed for this purpose to preschool-aged children. The aim of this study is to explore whether dyadic reading is an effective strategy for stimulating emotion comprehension in school-aged children. Elementary school children (3rd, 4th and 5th grade) participated in the experimental or the control group. The Test of Emotion Comprehension (TEC) was administered at pretest and post-test. Participants in the experimental group read the books on emotion comprehension for five sessions, while participants in the control group read classroom books. Results revealed that reading the emotion comprehension books increased the TEC post-test scores significantly from pretest for children in the experimental group, compared to the control group. For the Components Reminder, Belief and Morality scores at post-test were significantly increased from pretest for children in the experimental group, compared to the control group. Results suggest that dyadic book readings are successful in helping children with both complex components of their emotion comprehension and simpler ones. This intervention could be of use for teaching school-aged children emotion comprehension easily, effectively, and at low-cost.

Longitudinal examination of youth readmission to mental health inpatient units.

OBJECTIVE: Significant barriers exist for youth in obtaining mental health services. These barriers are exacerbated by growing demand, attributed partially to children and adolescents who have repeat hospital admissions. The purpose of this study was to identify demographic, socioeconomic and clinical predictors of readmission to inpatient psychiatric services in New Brunswick, Canada. METHOD: Key demographic, support and clinical predictors of readmission were identified. The New Brunswick Discharge Abstract Database (DAD) was used to compile a cohort of all children and adolescents ages 3-19 years with psychiatric hospital admissions between 1 April 2003 and 31 March 2014 (N = 3825). Primary analyses consisted of Kaplan-Meier survival methods with log-rank tests to assess time-to-readmission variability, and Cox regression to identify significant predictors of readmission. RESULTS: In total, 27.8% of admitted children and adolescents experienced at least one readmission within the 10-year period, with 57.3% readmitted to hospital within 90 days following discharge. Bivariate results indicated that male, upper-middle socioeconomic status (SES) youths aged 11-15 years from nonrural communities were most likely to be readmitted. Notable predictors of increased readmission likelihood were older age, being male, higher SES, referral to care by medical practitioner, discharge to another health facility, psychosis, and previous psychiatric admission. CONCLUSION: A significant portion of the variance in readmission was accounted for by youth demographic characteristics (i.e. age, SES, geographic location) and various support structures, including referrals to inpatient care and aftercare support services. KEY PRACTITIONER MESSAGE: Readmission to inpatient psychiatric care among youth is affected by a number of multifaceted risk factors across individual, environmental and clinical domains. This study used provincial population-scale longitudinal administrative data to demonstrate the influence of various individual and demographic factors on likelihood of readmission, which is notably absent from the majority of studies that make use of smaller, short-term data samples. Ensuring that multiple factors outside of the clinical context are considered when examining readmission among youth may contribute to a more thorough understanding of youth hospitalization patterns.

Molecular basis of mood and cognitive adverse events elucidated via a combination of pharmacovigilance data mining and functional enrichment analysis.

Drug-induced Mood- and Cognition-related adverse events (MCAEs) are often only detected during the clinical trial phases of drug development, or even after marketing, thus posing a major safety concern and a challenge for both pharmaceutical companies and clinicians. To fill some gaps in the understanding and elucidate potential biological mechanisms of action frequently associated with MCAEs, we present a unique workflow linking observational population data with the available knowledge at molecular, cellular, and psychopharmacology levels. It is based on statistical analysis of pharmacovigilance reports and subsequent signaling pathway analyses, followed by evidence-based expert manual curation of the outcomes. Our analysis: (a) ranked pharmaceuticals with high occurrence of such adverse events (AEs), based on disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database, and (b) identified 120 associated genes and common pathway nodes possibly underlying MCAEs. Nearly two-thirds of the identified genes were related to immune modulation, which supports the critical involvement of immune cells and their responses in the regulation of the central nervous system function. This finding also means that pharmaceuticals with a negligible central nervous system exposure may induce MCAEs through dysregulation of the peripheral immune system. Knowledge gained through this workflow unravels putative hallmark biological targets and mediators of drug-induced mood and cognitive disorders that need to be further assessed and validated in experimental models. Thereafter, they can be used to substantially improve in silico/in vitro/in vivo tools for predicting these adversities at a preclinical stage.

Opportunities for use of one species for longer-term toxicology testing during drug development: A cross-industry evaluation.

An international expert working group representing 37 organisations (pharmaceutical/biotechnology companies, contract research organisations, academic institutions and regulatory bodies) collaborated in a data sharing exercise to evaluate the utility of two species within regulatory general toxicology studies. Anonymised data on 172 drug candidates (92 small molecules, 46 monoclonal antibodies, 15 recombinant proteins, 13 synthetic peptides and 6 antibody-drug conjugates) were submitted by 18 organisations. The use of one or two species across molecule types, the frequency for reduction to a single species within the package of general toxicology studies, and a comparison of target organ toxicities identified in each species in both short and longer-term studies were determined. Reduction to a single species for longer-term toxicity studies, as used for the development of biologicals (ICHS6(R1) guideline) was only applied for 8/133 drug candidates, but might have been possible for more, regardless of drug modality, as similar target organ toxicity profiles were identified in the short-term studies. However, definition and harmonisation around the criteria for similarity of toxicity profiles is needed to enable wider consideration of these principles. Analysis of a more robust dataset would be required to provide clear, evidence-based recommendations for expansion of these principles to small molecules or other modalities where two species toxicity testing is currently recommended.

Nanowire forest of pnictogen-chalcogenide alloys for thermoelectricity.

Pnictogen and chalcogenide compounds have been seen as high-potential materials for efficient thermoelectric conversion over the past few decades. It is also known that with nanostructuration, the physical properties of these pnictogen-chalcogenide compounds can be further enhanced towards a more efficient heat conversion. Here, we report the reduced thermal conductivity of a large ensemble of Bi2Te3 alloy nanowires (70 nm in diameter) with selenium for n-type and antimony for p-type (Bi2Te3-ySey and Bi2-xSbxTe3 respectively). The nanowire growth was carried out through electrodeposition in nanoporous aluminium oxide templates with high aspect ratios leading to a forest (109 per centimetre square) of nearly identical nanowires. The temperature dependence of thermal conductivity for the nanowire ensembles was acquired through a highly sensitive 3ω measurement technique. The change in the thermal conductivity of nanowires is largely affected by the roughness in addition to the size effect due to enhanced boundary scattering. The major factor that influences the thermal conductivity was found to be the ratio of the rms roughness to the correlation length of the nanowire. With a high Seebeck coefficient and electrical conductivity at room temperature, the overall thermoelectric figure of merit ZT allows the consideration of such forests of nanowires as efficient potential building blocks of future TE devices.

Measurement of anisotropic thermal conductivity of a dense forest of nanowires using the 3ω method.

The 3ω method is a dynamic measurement technique developed for determining the thermal conductivity of thin films or semi-infinite bulk materials. A simplified model is often applied to deduce the thermal conductivity from the slope of the real part of the ac temperature amplitude as a function of the logarithm of frequency, which in-turn brings a limitation on the kind of samples under observation. In this work, we have measured the thermal conductivity of a forest of nanowires embedded in nanoporous alumina membranes using the 3ω method. An analytical solution of 2D heat conduction is then used to model the multilayer system, considering the anisotropic thermal properties of the different layers, substrate thermal conductivity, and their thicknesses. Data treatment is performed by fitting the experimental results with the 2D model on two different sets of nanowires (silicon and BiSbTe) embedded in the matrix of nanoporous alumina templates, having thermal conductivities that differ by at least one order of magnitude. These experimental results show that this method extends the applicability of the 3ω technique to more complex systems having anisotropic thermal properties.

Highly sensitive pseudo-differential ac-nanocalorimeter for the study of the glass transition.

We present a nanocalorimeter designed for the measurement of the dynamic heat capacity of thin films. The microfabricated sensor, the thermal conditioning of the sensor, as well as the highly stable and low noise electronic chain allow measurements of the real and imaginary parts of the complex specific heat with a resolution Δ C/C of about 10(-5). The performances of this quasi-differential nanocalorimeter were tested on a model of polymeric glass-former, the polyvinyl acetate (PVAc). The high stability and low noise of the device are essential for accurate studies on non-equilibrium slow relaxing systems such as glasses.

Specific heat measurement of thin suspended SiN membrane from 8 K to 300 K using the 3ω-Völklein method.

We present a specific heat measurement technique adapted to thin or very thin suspended membranes from low temperature (8 K) to 300 K. The presented device allows the measurement of the heat capacity of a 70 ng silicon nitride membrane (50 or 100 nm thick), corresponding to a heat capacity of 1.4 × 10(-10) J/K at 8 K and 5.1 × 10(-8) J/K at 300 K. Measurements are performed using the 3ω method coupled to the Völklein geometry. This configuration allows the measurement of both specific heat and thermal conductivity within the same experiment. A transducer (heater/thermometer) is used to create an oscillation of the heat flux on the membrane; the voltage oscillation appearing at the third harmonic which contains the thermal information is measured using a Wheatstone bridge set-up. The heat capacity measurement is performed by measuring the variation of the 3ω voltage over a wide frequency range and by fitting the experimental data using a thermal model adapted to the heat transfer across the membrane. The experimental data are compared to a regular Debye model; the specific heat exhibits features commonly seen for glasses at low temperature.

Glassy behavior of denatured DNA films studied by differential scanning calorimetry.

We use differential scanning calorimetry (DSC) to study the properties of DNA films, made of oriented fibers, heated above the thermal denaturation temperature of the double helical form. The films show glassy properties that we investigate in two series of experiments, a slow cooling at different rates followed by a DSC scan upon heating and aging at a temperature below the glass transition. Introducing the fictive temperature to characterize the glass allows us to derive quantitative information on the relaxations of the DNA films, in particular to evaluate their enthalpy barrier. A comparison with similar aging studies on PVAc highlights some specificities of the DNA samples.

The translational efficacy of a nonsteroidal progesterone receptor antagonist, 4-[3-cyclopropyl-1-(mesylmethyl)-5-methyl-1H-pyrazol-4-yl]oxy,-2,6-dimethylbenzonitrile (PF-02413873), on endometrial growth in macaque and human.

There is considerable ongoing investment in the research and development of selective progesterone receptor (PR) modulators for the treatment of gynecological conditions such as endometriosis. Here, we provide the first report on the clinical evaluation of a nonsteroidal progesterone receptor antagonist 4-[3-cyclopropyl-1-(mesylmethyl)-5-methyl-1H-pyrazol-4-yl]oxy,-2,6-dimethylbenzonitrile (PF-02413873) in healthy female subjects. In in vitro assays, PF-02413873 behaved as a selective and fully competitive PR antagonist, blocking progesterone binding and PR nuclear translocation. The pharmacological mode of action of PF-02413873 seems to differ from the founding member of the class of steroidal PR antagonists, 11ß-4-dimethylaminophenyl-17ß-hydroxy-17α-propinyl-4,9-estradiene-3-one (RU-486; mifepristone). Exposure-effect data from studies in the cynomolgus macaque, however, demonstrated that PF-02413873 reduced endometrial functionalis thickness to a comparable degree to RU-486 and this effect was accompanied by a decrease in proliferation rate (as measured by bromodeoxyuridine incorporation) for both RU-486 and high-dose PF-02413873. These data were used to underwrite a clinical assessment of PF-02413873 in a randomized, double-blinded, third-party open, placebo-controlled, dose-escalation study in healthy female volunteers with dosing for 14 days. PF-02413873 blocked the follicular phase increase in endometrial thickness, the midcycle lutenizing hormone surge, and elevation in estradiol in a dose-dependent fashion compared with placebo. This is the first report of translational efficacy data with a nonsteroidal PR antagonist in cynomolgus macaque and human subjects.

Surface roughness and EDS characterization of a Y-TZP dental ceramic treated with the CoJet™ Sand.

OBJECTIVES: (1) To determine the surface roughness and material loss of a Y-TZP ceramic before and after tribochemical grit blasting and (2) to characterize the changes in elemental surface composition and the phase transformations after tribochemical treatment. METHODS: Machined bar shaped specimens (Zeno, Wieland) were subdivided into three groups. After grit blasting for 10, 20 and 30s respectively, half of the specimens of each group were ultrasonically cleaned in ethanol for 10min. The other half was rinsed with a water spray. Surface roughness was measured using an electro-mechanical profilometer. The elemental composition of the samples was obtained by energy dispersive X-ray spectroscopy (EDS). X-ray diffraction (XRD) was used for phase transformations determination. RESULTS: The median Ra increased significantly from 0.24 to 0.32-0.38µm after grit blasting. Augmentations were also noted for R(max), R(v) and R(p). The highest roughness parameters were, obtained for water sprayed specimens and samples abraded for 30s. Loss of material ranged between 1 and 3µm for 30s grit blasting. Tetragonal and cubic phases were identified in 'as machined' specimens. Grit blasting resulted in domain switching and lattice deformations. The elemental composition comprised Si and Al. The duration of grit blasting did not significantly, influence the atomic percentages of Si or Al. Significantly lower values for both Si and Al were noted, after ultrasonic cleaning. SIGNIFICANCE: Grit blasting with CoJet™ Sand resulted in an increase of surface roughness, a removal of maximum 3µm of material and coated the surface with submicron silica and alumina particles.

Microseism and infrasound generation by cyclones.

A two-dimensional cylindrical shear-flow wave theory for the generation of microseisms and infrasound by hurricanes and cyclones is developed as a linearized theory paralleling the seminal work by Longuet-Higgins which was limited to one-dimensional plane waves. Both theories are based on Bernoulli's principle. A little appreciated consequence of the Bernoulli principle is that surface gravity waves induce a time dependent pressure on the sea floor through a vertical column of water. A significant difference exists between microseisms detected at the bottom of each column and seismic signals radiated into the crust through coherence over a region of the sea floor. The dominant measured frequency of radiated microseisms is matched by this new theory for seismic data gathered at the Fordham Seismic Station both for a hurricane and a mid-latitude cyclone in 1998. Implications for Bernoulli's principle and this cylindrical stress flow theory on observations in the literature are also discussed.

Experience from a long-term carcinogenicity study with intraperitoneal injection of biosoluble synthetic mineral fibers.

The carcinogenic potential in the intraperitoneal cavity of three newly developed biosoluble insulation glass wool fibers (M, P, and V) and one newly developed biosoluble insulation stone wool fiber (O) was investigated and compared to that of a previously developed soluble glass fiber (B). The in vitro dissolution coefficient of the three glass wool fibers ranged from 450 to 1037 ng/cm(2) x h and was 523 ng/cm(2) x h for the stone wool fiber. The in vitro dissolution coefficient of the B fiber was 580 ng/cm(2) x h. Groups of female Wistar rats (strain Crl: Wi BR) were exposed by repeated injections to doses of 0.5, 2, and 5 x 10(9) WHO fibers, which corresponds to between 41 mg to 724 mg fiber injected. In addition, 2 groups of crocidolite were used as positive controls at doses of 0.1 x 10(9) and 1 x 10(9) WHO fibers (0.5 and 5 mg). The in vitro dissolution coefficient of crocidolite is estimated to be approximately 1 ng/cm(2) x h. The protocol of the study and the size distribution of the test samples conformed to the European Commission Protocol EUR 18748 EN, and the study was executed under Good Laboratory Practice conditions. Two of the new insulation wools, fibers M and 0, showed no statistically significant tumorigenic response even at the very high dose of 5 x 10(9) WHO fibers injected. Fibers P and V showed a small tumorigenic response in the ip cavity similar in magnitude to the B fiber, which has been declared in the German fiber regulations as a noncarcinogenic fiber. The response to the soluble insulation fibers was notably different from that of the known carcinogen crocidolite, which produced 53% tumors at a comparatively low dose of 0.1 x 10(9) WHO fibers. The incidence of mesothelioma was found to be highly correlated to the incidence of intra-abdominal nodules and masses at different sites. The incidence of abdominal nodules and masses was highly correlated to the number of animals with ascites. The incidence of chronic peritonitis with fibrotic nodules at different organs also correlated with the incidence of mesotheliomas. Differences in etiology were observed between the massive doses of the highly soluble insulation wools when injected directly into the ip cavity and the lower doses of the extremely insoluble fiber crocidolite. The variability in this reaction and the impairment of animal health put into question the value of these massive doses in evaluating the carcinogenic response of soluble insulation wools. All of the fibers tested fulfilled the exoneration criteria with respect to carcinogenicity according to the European Directive 97/69/EC ("an appropriate intra-peritoneal test has not expressed signs of excessive carcinogenicity"). The dose as defined in the EC-Protocol EUR 18748 EN was 1 x 10(9) WHO fibers with a defined geometric spectrum. The influence of fiber dimensions on the ip tumor response and the difficulty in assessing the influence of the difference in background levels between this and previous studies make direct application of the German TRGS 905 criteria difficult; however, by comparison to fiber B, which in the TRGS 905 is considered as a noncarcinogenic fiber, all of the synthetic mineral fiber types tested in this study also appear to meet the intended German criteria for exoneration.

Determination of Viable Bacterial Populations in Raw Milk within 20 Minutes by Using a Direct Epifluorescent Filter Technique.

The results from a shortened procedure for the direct epifluorescent filter technique (DEFT) determination of viable bacterial populations in raw milk were compared to standard plate counts. Shortening the prefiltration trypsin-Triton X-100 incubation period from 10 to 3 min enabled the completion of the analysis within 20 min. The short DEFT method results had a correlation coefficient (r) of 0.81 with plate counts. With respect to precision, the average difference between values of duplicate plate count analyses was 0.16 log units; that of the short DEFT was 0.14 log units. The slopes of the regressions equations were less than 1, indicating that a direct correlation is not achieved. Short DEFT values were 0.17 log units higher than those of plate counts on milk samples containing less than 10,000 CFU/ml. For milk samples containing counts over 10,000 CFU/ml, short DEFT values averaged only 0.05 log units above plate count readings. Daily preparation of the stain appears unnecessary since acridine orange solutions stored for up to 2 days at 4°C did not produce results significantly (P > 0.05) different from those obtained with fresh solutions. The short DEFT method has potential for the assessment of the bacteriological quality of raw milk in tanker deliveries.