Developmental stability in a cystic fibrosis mouse model

The aim of this study was to investigate the influence of cystic fibrosis (CF) and chronic experimental lung  infection with Pseudomonas aeruginosa on developmental instability and behaviour in the transgenic  Cftrtm1Unc -TgN(FABPCFTR) mouse compared to different heterozygote (CFTR+/-) and wildtype (CFTR+/+)  controls. Developmental instability measured as fluctuating asymmetry (FA), body weight and open-field  behaviour were assessed in CFTR-/-, CFTR+/- and CFTR+/+ mice. FA and different behavioural tests were  investigated in relation to tracheotomy and lung infection with P. aeruginosa. Body weight was in general  decreased in the CFTR-/- mice and increased in the CFTR+/- mice. CFTR-/- mice had a significantly higher  degree of FA (4%-5.5%) than all other groups (1%-3%) (P<0.001), while having cystic fibrosis did not  seem to influence the behaviour of these mice indicating that the clinical impact from the model is rather  low, which is positive from a welfare point of view. FA and motor performance was influenced by neither  the lung infection nor the tracheotomy. Tracheotomy increased the level of fear in the light-dark box  (P<0.05), and the lung infection decreased activity in the open field (P<0.05). From this we may conclude  that well-being expressed as changed behaviour is a result of the lung infection more than a consequence  of the mutation.

Sputtering and Characterization ofMAX-Phase Forming Cr Al C and Ti Al C Coatings and Their Application on γ-Based Titanium Aluminides

MAX-phases are of increasing interest as coating material for high temperatureapplications due to their unique metallic as well as ceramic properties. Herein,the deposition of Cr2AlC and Ti3AlC2or Ti2AlC MAX-phase forming coatings bymagnetron sputtering is demonstrated. Using pure elemental targets, themanufacturing with a coating thickness of above 7 m is established. TheMAX-phase forming coatings are characterized by high-temperature X-ray dif-fraction (HT-XRD) measurements and provide a good oxidation behavior due tothe development of protective thermally grown oxide layers. The performance ofthe MAX-phases is strongly depended on the substrate material and theaccompanying interdiffusion processes. Therefore, the Ti–Al–C coating is favoredfor TiAl alloys due to the thermodynamic stability of the Ti2AlC MAX phase inparticular in the presence of the γ-TiAl phase. An excellent oxidation behavior isconrmed up to 300 h at 850C due to the development of an alumina layerabove a homogenous Ti2AlC phase coating. The Cr2AlC MAX-phase coatingdegrades after 100 h at 800C due to interdiffusion processes between coatingand substrate and the accompanying development of carbides and nitridephases. Nevertheless, the oxidation resistance of the Cr–Al– C-coated TiAl alloy isgiven by the formation of the Ti2AlC MAX-phase

Participant Reactions to Two-Way Immersion (TWI) Programs

The purpose of this study was to elicit participant reactions to two-way immersion (TWI) programs in the United States of America. A large number of recent studies have focused on instructor views and perspectives of two-way immersion programs, so this study aimed to gain insight from students who are, or who have, participated in TWI programs throughout North America. One hundred fifty-one TWI schools throughout the United States were contacted and asked to participate in this study. Two similar surveys were developed, one for current TWI students, and another for former TWI students. Students from these two groups were asked to fill out a confidential online survey that addressed specific linguistic skills, abilities, and preferences, as well as connection to the cultures of the target language. Forty-eight percent of the survey respondents were native speakers of English, and the remaining 52% were non-native speakers of English. The number of respondents to the former student survey was so low that the data were inconclusive, and, therefore, will not be included in this study. Since the survey was conducted online, the data were stored in a comma-delimited format for further evaluation. The data were then tallied and analyzed for common themes

Overestimation of Postpartum Depression Prevalence Based on a 5-item Version of the EPDS:Systematic Review and Individual Participant Data Meta-analysis

Objective:The Maternal Mental Health in Canada, 2018/2019, survey reported that 18% of 7,085 mothers who recently gave birth reported "feelings consistent with postpartum depression" based on scores >= 7 on a 5-item version of the Edinburgh Postpartum Depression Scale (EPDS-5). The EPDS-5 was designed as a screening questionnaire, not to classify disorders or estimate prevalence; the extent to which EPDS-5 results reflect depression prevalence is unknown. We investigated EPDS-5 >= 7 performance relative to major depression prevalence based on a validated diagnostic interview, the Structured Clinical Interview for DSM (SCID).Methods:We searched Medline, Medline In-Process & Other Non-Indexed Citations, PsycINFO, and the Web of Science Core Collection through June 2016 for studies with data sets with item response data to calculate EPDS-5 scores and that used the SCID to ascertain depression status. We conducted an individual participant data meta-analysis to estimate pooled percentage of EPDS-5 >= 7, pooled SCID major depression prevalence, and the pooled difference in prevalence.Results:A total of 3,958 participants from 19 primary studies were included. Pooled prevalence of SCID major depression was 9.2% (95% confidence interval [CI] 6.0% to 13.7%), pooled percentage of participants with EPDS-5 >= 7 was 16.2% (95% CI 10.7% to 23.8%), and pooled difference was 8.0% (95% CI 2.9% to 13.2%). In the 19 included studies, mean and median ratios of EPDS-5 to SCID prevalence were 2.1 and 1.4 times.Conclusions:Prevalence estimated based on EPDS-5 >= 7 appears to be substantially higher than the prevalence of major depression. Validated diagnostic interviews should be used to establish prevalence

Overestimation of Postpartum Depression Prevalence Based on a 5-item Version of the EPDS: Systematic Review and Individual Participant Data Meta-analysis

Objective:The Maternal Mental Health in Canada, 2018/2019, survey reported that 18% of 7,085 mothers who recently gave birth reported "feelings consistent with postpartum depression" based on scores >= 7 on a 5-item version of the Edinburgh Postpartum Depression Scale (EPDS-5). The EPDS-5 was designed as a screening questionnaire, not to classify disorders or estimate prevalence; the extent to which EPDS-5 results reflect depression prevalence is unknown. We investigated EPDS-5 >= 7 performance relative to major depression prevalence based on a validated diagnostic interview, the Structured Clinical Interview for DSM (SCID).Methods:We searched Medline, Medline In-Process & Other Non-Indexed Citations, PsycINFO, and the Web of Science Core Collection through June 2016 for studies with data sets with item response data to calculate EPDS-5 scores and that used the SCID to ascertain depression status. We conducted an individual participant data meta-analysis to estimate pooled percentage of EPDS-5 >= 7, pooled SCID major depression prevalence, and the pooled difference in prevalence.Results:A total of 3,958 participants from 19 primary studies were included. Pooled prevalence of SCID major depression was 9.2% (95% confidence interval [CI] 6.0% to 13.7%), pooled percentage of participants with EPDS-5 >= 7 was 16.2% (95% CI 10.7% to 23.8%), and pooled difference was 8.0% (95% CI 2.9% to 13.2%). In the 19 included studies, mean and median ratios of EPDS-5 to SCID prevalence were 2.1 and 1.4 times.Conclusions:Prevalence estimated based on EPDS-5 >= 7 appears to be substantially higher than the prevalence of major depression. Validated diagnostic interviews should be used to establish prevalence

Comparison of major depression diagnostic classification probability using the SCID, CIDI, and MINI diagnostic interviews among women in pregnancy or postpartum: An individual participant data meta‐analysis

OBJECTIVES: A previous individual participant data meta-analysis (IPDMA) identified differences in major depression classification rates between different diagnostic interviews, controlling for depressive symptoms on the basis of the Patient Health Questionnaire-9. We aimed to determine whether similar results would be seen in a different population, using studies that administered the Edinburgh Postnatal Depression Scale (EPDS) in pregnancy or postpartum. METHODS: Data accrued for an EPDS diagnostic accuracy IPDMA were analysed. Binomial generalised linear mixed models were fit to compare depression classification odds for the Mini International Neuropsychiatric Interview (MINI), Composite International Diagnostic Interview (CIDI), and Structured Clinical Interview for DSM (SCID), controlling for EPDS scores and participant characteristics. RESULTS: Among fully structured interviews, the MINI (15 studies, 2,532 participants, 342 major depression cases) classified depression more often than the CIDI (3 studies, 2,948 participants, 194 major depression cases; adjusted odds ratio [aOR] = 3.72, 95% confidence interval [CI] [1.21, 11.43]). Compared with the semistructured SCID (28 studies, 7,403 participants, 1,027 major depression cases), odds with the CIDI (interaction aOR = 0.88, 95% CI [0.85, 0.92]) and MINI (interaction aOR = 0.95, 95% CI [0.92, 0.99]) increased less as EPDS scores increased. CONCLUSION: Different interviews may not classify major depression equivalently

Deposition of Ti2AlC MAX-phase based coating on γ-TiAl to improve the oxidation resistance

Currently, the application of intermetallic γ-TiAl alloys is limited by their deterioration in strength and creep resistance at elevated temperatures as well as by reduced oxidation resistance above 800 °C. The deposition of protective coatings is a promising opportunity to enhance the oxidation resistance by several orders of magnitude. Moreover, additive manufacturing processes have enabled the production of components with more complex geometries. Thus, a design of turbine blades with internal cooling made of γ-TiAl is feasible in the near future. In this context, the deposition of thermal barrier coatings and, therefore, protective coatings become important. MAX-phases are of increasing interest as coating material for high temperature applications due to their unique combination of metallic and ceramic properties. Especially the alumina forming MAX phases of Cr2AlC, Ti2AlC or Ti2AlN are promising as oxidation resistant coatings. Unfortunately, degradation of MAX phases is observed when applied on various Ti- or Ni-based alloys by interdiffusion processes between coating and alloy and the associated Al-depletion. This degradation is not present when MAX-phases are applied on the Al-rich γ-TiAl based alloys, which leads to an inward diffusion of Al from the substrate alloy into the coating and finally to a stabilization of the thermally grown alumina layer. Moreover, MAX-phases are known as a ductile material and could therefore prevent the deterioration of the mechanical properties especially the fatigue behavior of such coated components in contrast to the common intermetallic, protective but brittle coatings on γ-TiAl alloys. In the present work a Ti2AlC MAX-phase based coating were deposited by DC magnetron sputtering. Using three, pure elemental target materials of Ti, Al and C and a two-fold rotation a homogenous all-around coating was applied on the γ-TiAl alloy TiAl48-2-2 with a coating thickness of 10 µm. After the deposition process the stochiometric Ti2AlC coating was x-ray amorphous, therefore a post-heat treatment at 800°C for 1 h was performed to achieve the desired hexagonal MAX-Phase. Finally, the MAX-phase coated TiAl48-2-2 alloy was subjected to the cyclic oxidation test at 850°C in laboratory air up to 100 1h-cycles. The Ti2AlC MAX-phase coated TiAl48-2-2 alloy exhibits an excellent oxidation behavior at 850°C, due to the formation of a thermally grown alumina top layer. The phase formations during the heat treatment were analysed by HT-XRD measurements showing a homogenous coating microstructure of the hexagonal Ti2AlC phase below α-Al2O3 oxide layer. The interface reaction zones between the coating and the TGO, as well as between the coating and the TiAl48-2-2 substrate alloy were analyzed by SEM with EDS and especially by high-resolution STEM

Enabling Cr2AlC MAX Phase as Sustainable Bond Coat for Ni-Superalloys

Al2O3-forming MAX phases, such as Cr2AlC, are a promising alternative to state-of-the-art MCrAlY bond coats (BC) for Ni-superalloys. Not only do they offer great corrosion resistance, desirable mechanical properties and a crack self-healing effect, but they are also more affordable and sustainable by avoiding elements such as Ni and Co. However, depletion of Al from the MAX phases due interdiffusion with the substrate is a major issue. Diffusion barriers (DB) are therefore required for enabling the full potential of MAX phases as BCs for Ni-superalloys . In this work, CrN is investigated as a potential DB material. Specimens with a CrN DB (ca. 1 µm thick) between IN718 substrates and Cr-Al-C coatings were compared to specimens without a DB. A surplus amount of Al was deliberately added, resulting in a hybrid Cr2AlC-Cr5Al8 coating (ca. 10 µm thick), where Cr5Al8 serves as Al reservoir phase. The CrN coatings were deposited using reactive magnetron sputtering, whereas Cr2AlC was synthesised using conventional DC magnetron sputtering. Both coating systems were tested in isothermal and cyclic oxidation experiments at 800°C for up 100 h and 100 cycles (60 min heating, 10 min cooling) in air, respectively. Subsequently, the oxidation and interdiffusion behaviour of the specimens was characterised by means of XRD, SEM, EDX, WDX, and TGA. The CrN DB successfully suppresses interdiffusion under the investigated circumstances. Not only was the loss of Al completely prevented (Fig. 1), but no elements from the substrate alloy were detected in the BC either, indicating optimal conditions for growing a protective Al2O3 top layer. While the microstructure of the coating systems with DB was almost unaffected, a pronounced interdiffusion zone (IDZ), with no remaining Cr2AlC phase, formed in specimens without DB for oxidation times equal to or longer than 25 h or 25 cycles, respectively. Furthermore, porous Cr-carbides and other mechanically disadvantageous phases, such as brittle beta-NiAl, formed in the IDZ due to Al diffusion into the IN718 substrates in specimens without DB. In conclusion, it is evident that CrN is an effective DB under the investigated conditions, increasing the life time substantially and thus enabling Cr2AlC as a sustainable and affordable BC material

Azithromycin Blocks Quorum Sensing and Alginate Polymer Formation and Increases the Sensitivity to Serum and Stationary-Growth-Phase Killing of Pseudomonas aeruginosa and Attenuates Chronic P. aeruginosa Lung Infection in Cftr−/− Mice▿

The consequences of O-acetylated alginate-producing Pseudomonas aeruginosa biofilms in the lungs of chronically infected cystic fibrosis (CF) patients are tolerance to both antibiotic treatments and effects on the innate and the adaptive defense mechanisms. In clinical trials, azithromycin (AZM) has been shown to improve the lung function of CF patients. The present study was conducted in accordance with previous in vitro studies suggesting that the effect of AZM may be the inhibition of alginate production, blockage of quorum sensing (QS), and increased sensitivity to hydrogen peroxide and the complement system. Moreover, we show that AZM may affect the polymerization of P. aeruginosa alginate by the incomplete precipitation of polymerized alginate and high levels of readily dialyzable uronic acids. In addition, we find that mucoid bacteria in the stationary growth phase became sensitive to AZM, whereas cells in the exponential phase did not. Interestingly, AZM-treated P. aeruginosa lasI mutants appeared to be particularly resistant to serum, whereas bacteria with a functional QS system did not. We show in a CF mouse model of chronic P. aeruginosa lung infection that AZM treatment results in the suppression of QS-regulated virulence factors, significantly improves the clearance of P. aeruginosa alginate biofilms, and reduces the severity of the lung pathology compared to that in control mice. We conclude that AZM attenuates the virulence of P. aeruginosa, impairs its ability to form fully polymerized alginate biofilms, and increases its sensitivity to complement and stationary-phase killing, which may explain the clinical efficacy of AZM