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Background Randomized controlled trials found that twice-yearly mass azithromycin administration (MDA) reduces childhood mortality, presumably by reducing infection burden. World Health Organization (WHO) issued conditional guidelines for mass azithromycin administration in high-mortality settings in sub-Saharan Africa given concerns for antibiotic resistance. While prolonged twice-yearly MDA has been shown to increase antibiotic resistance in small randomized controlled trials, the objective of this study was to determine if macrolide and non-macrolide resistance in the gut increases with the duration of azithromycin MDA in a larger setting. Methods and findings The Macrolide Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) study was conducted in Niger from December 2014 to June 2020. It was a cluster-randomized trial of azithromycin (A) versus placebo (P) aimed at evaluating childhood mortality. This is a sub-study in the MORDOR trial to track changes in antibiotic resistance after prolonged azithromycin MDA. A total of 594 communities were eligible. Children 1 to 59 months in 163 randomly chosen communities were eligible to receive treatment and included in resistance monitoring. Participants, staff, and investigators were masked to treatment allocation. At the conclusion of MORDOR Phase I, by design, all communities received an additional year of twice-yearly azithromycin treatments (Phase II). Thus, at the conclusion of Phase II, the treatment history (1 letter per 6-month period) for the participating communities was either (PP-PP-AA) or (AA-AA-AA). In Phase III, participating communities were then re-randomized to receive either another 3 rounds of azithromycin or placebo, thus resulting in 4 treatment histories: Group 1 (AA-AA-AA-AA-A, N = 51), Group 2 (PP-PP-AA-AA-A, N = 40), Group 3 (AA-AA-AA-PP-P, N = 27), and Group 4 (PP-PP-AA-PP-P, N = 32). Rectal swabs from each child (N = 5,340) were obtained 6 months after the last treatment. Each child contributed 1 rectal swab and these were pooled at the community level, processed for DNA-seq, and analyzed for genetic resistance determinants. The primary prespecified outcome was macrolide resistance determinants in the gut. Secondary outcomes were resistance to beta-lactams and other antibiotic classes. Communities recently randomized to azithromycin (groups 1 and 2) had significantly more macrolide resistance determinants than those recently randomized to placebo (groups 3 and 4) (fold change 2.18, 95% CI 1.5 to 3.51, P.sub.unadj < 0.001). However, there was no significant increase in macrolide resistance in communities treated 4.5 years (group 1) compared to just the most recent 2.5 years (group 2) (fold change 0.80, 95% CI 0.50 to 1.00, P.sub.adj = 0.010), or between communities that had been treated for 3 years in the past (group 3) versus just 1 year in the past (group 4) (fold change 1.00, 95% CI 0.78 to 2.35, P.sub.adj = 0.52). We also found no significant differences for beta-lactams or other antibiotic classes. The main limitations of our study were the absence of phenotypic characterization of resistance, no complete placebo arm, and no monitoring outside of Niger limiting generalizability. Conclusions In this study, we observed that mass azithromycin distribution for childhood mortality among preschool children in Niger increased macrolide resistance determinants in the gut but that resistance may plateau after 2 to 3 years of treatment. Co-selection to other classes needs to be monitored. Trial registration NCT02047981 https://classic.clinicaltrials.gov/ct2/show/NCT02047981., Author(s): Ahmed M. Arzika 1, Amza Abdou 1, Ramatou Maliki 1, Nassirou Beido 1, Boubacar Kadri 1, Abdoul N. Harouna 1, Abdoul N. Galo 1, Mankara K. Alio 1, Elodie [...]

A new method is proposed to measure the linear coefficient of thermal expansion (CTE) of solid metals and ceramics of micron‐sized dimensions. This approach uses a focused ion beam (FIB) to extract and transfer a slab of the sample, typically (15–20) ×10 × (3–5) µm onto a Micro‐Electro‐Mechanical Systems (MEMS) in situ heating holder inside a scanning electron microscope (SEM). CTE is thereafter calculated by image correlating the change of length (ΔL) between the fiducial marks on the slab as a function of temperature, taking advantage of the temperature calibration of the MEMS heating holder and nanometre resolution of the scanning electron microscope. The CTE results are validated to be consistent with standard copper and silicon. We further demonstrate the method on a graphene platelet reinforced copper composite and a graphite filler phase isolated from a bulk sample, these represent materials that cannot be practically synthesised or isolated at the macro‐scale. Errors associated with the measurement are discussed. LAY DESCRIPTION: Coefficient of thermal expansion (CTE) is the relative length change of a material due to temperature change. When dissimilar materials are joined and subjected to temperature change, a mismatch of their CTEs could undermine the mechanical integrity of the joint. Measurement of the CTE of materials that cannot be synthesised at the macro‐scale or practically isolated is challenging with routine techniques. A new method is proposed to measure the linear coefficient of thermal expansion (CTE) of solid metals and ceramics of micron sized dimensions. This approach uses a focused ion beam (FIB) to extract and transfer a slab of the sample, typically (15–20) ×10 × (3–5) µm, onto an in situ heating holder inside a scanning electron microscope (SEM). The relative length change of the sample is then measured as a function of temperature which is enabled by the micro heating stage. We have verified the capability of the technique by successfully measuring the CTE of standard copper and silicon samples. We further demonstrate the method on an electro‐deposited graphene platelet reinforced copper composite and an isolated graphite filler phase which could not be practically measured by conventional methods. [ABSTRACT FROM AUTHOR]

Background: Conflicting results have been reported regarding the association between psoriasis and risk of chronic kidney diseases (CKD). Furthermore, the causal nature of the possible association remains unexplored. Methods: We conducted a population‐based cross‐sectional study using data from National Health and Nutrition Examination Survey (NHANES). Logistic regression analyses were conducted to estimate potential association between psoriasis and CKD risk. Further, we evaluated causality by performing a Mendelian randomization analysis using large‐scale genome‐wide association studies of psoriasis and CKD. Inverse variance‐weighted (IVW) analysis was used as the primary method. Results: In the observational study, 16 750 participants were included. Overall, 39 of 429 patients with psoriasis had CKD (9.1%) compared with 1481 of 16 321 without psoriasis (9.1%). In the fully adjusted model, psoriasis was not associated with CKD (OR: 0.77, 95%CI: 0.53–1.10). In the MR analysis, 36 single‐nucleotide polymorphisms (SNPs) were selected as instrumental variables. The IVW analysis reported that genetically predicted psoriasis was associated with a higher risk of CKD (OR: 1.025, 95%CI: 1.001–1.049). After removing 2 SNPs associated with heterogeneity, the association remained (OR: 1.028, 95%CI: 1.006–1.050). Conclusion: Genetically predicted psoriasis was associated with a higher risk of CKD. This association may be important for clinicians to monitor kidney function and prescribe potentially nephrotoxic drugs during psoriasis management. [ABSTRACT FROM AUTHOR]

Background Mass administration of azithromycin is an established strategy for decreasing the prevalence of trachoma in endemic areas. However, nearby untreated communities could serve as a reservoir that may increase the chances of chlamydia reinfection in treated communities. Methods As part of a cluster-randomized trial in Ethiopia, 60 communities were randomized to receive mass azithromycin distributions and 12 communities were randomized to no treatments until after the first year. Ocular chlamydia was assessed from a random sample of children per community at baseline and month 12. Distances between treated and untreated communities were assessed from global positioning system coordinates collected for the study. Results The pretreatment prevalence of ocular chlamydia among 0 to 9 year olds was 43% (95% confidence interval [CI], 39%-47%), which decreased to 11% (95% CI, 9%-14%) at the 12-month visit. The posttreatment prevalence of chlamydia was significantly higher in communities that were closer to an untreated community after adjusting for baseline prevalence and the number of mass treatments during the year (odds ratio, 1.12 [95% CI, 1.03-1.22] for each 1 km closer to an untreated community). Conclusions Mass azithromycin distributions to wide, contiguous geographic areas may reduce the likelihood of continued ocular chlamydia infection in the setting of mass antibiotic treatments. [ABSTRACT FROM AUTHOR]

A study was conducted to evaluate the efficacy of mass distribution of azithromycin for trachoma control among Ethiopian children on mortality in communities. Results indicated that mass distribution of the drug was quite effective in reducing mortality.

The rate at which chlamydial infection returns to a population after mass treatment is determined and the treatment frequency required for elimination of ocular chlamydia form a community is estimated. The result indicates that elimination of infection in a hyperendynamic area is feasible with biannual mass antibiotic administrations and attainable coverage levels.

Background: The chlamydial major outer membrane protein, encoded by the ompA gene, is a primary target for chlamydial vaccine research. However, human studies of ompA-specific immunity are limited, and prior studies have been limited in differentiating re-infection from persistent infection. The purpose of this study was to assess whether children living in trachoma-endemic communities with re-infections of ocular chlamydia were more likely to be infected with a different or similar genovar. Methodology and findings: The study included 21 communities from a trachoma-hyperendemic area of Ethiopia that had been treated with a mass azithromycin distribution for trachoma. Conjunctival swabbing was offered to all children younger than 5 years of age at baseline (i.e., pre-treatment), and then at follow-up visits 2 and 6 months later. Swabs were subjected to polymerase chain reaction (PCR) to detect C. trachomatis. A random sample of 359 PCR-positive swabs, stratified by study visit and study community, was chosen for ompA sequencing. In addition, ompA sequencing was performed on all swabs of 24 children who experienced chlamydial re-infection (i.e., positive chlamydial test before treatment, negative test 2 months following mass distribution of azithromycin, and again a positive test 6 months post-treatment). ompA sequencing was successful for 351 of 359 swabs of the random sample and 44 of 48 swabs of the re-infection sample. In the random sample, ompA types clustered within households more than would be expected by chance. Among the 21 re-infected children with complete ompA data, 14 had the same ompA type before and after treatment. Conclusion: The high frequency of ompA concordance suggests incomplete genovar-specific protective immunity and the need for multiple antigens as vaccine targets. Author summary: Trachoma is the world's leading infectious cause of blindness. Periodic mass azithromycin distributions have not resulted in elimination. Re-infection is thought to be an important barrier to elimination, but studies of serovar- or genovar-specific immunity and re-infection with ocular Chlamydia trachomatis have been limited. The present study investigated chlamydial genotypes in children who were infected with ocular chlamydia before azithromycin treatment and were confirmed to have cleared the infection 2 months later, but then were again infected at 6 months. The majority of re-infections were caused by the same ompA strain that was carried pre-treatment, which suggests poor protective immunity to chlamydia. The ompA types clustered by household, suggesting members of the same household as a source of re-infection. These findings could inform future mass treatment strategies and vaccine development. [ABSTRACT FROM AUTHOR]

Self-propagating exothermic reactions (SPERs) provide intense localized heat sufficient for bonding metals or alloys with minimal heat excursion to the components, which shows great potential for the die-attach in power electronics packaging. However, the reliability of such formed joints is yet to be fully understood owing to a wide range of defects involved in the instantaneous propagating reaction and heating/cooling. In this work, the finite element analysis is performed to understand the thermal transfer and mechanical responses of materials to the SPER bonding for the die-attach of Si device onto direct bonded copper (DBC) substrate with Sn-3.0Ag-0.5Cu (SAC) solder. The simulation has been validated using the temperature distribution in SPER bonding, which shows a good agreement with the actual measured results. Moreover, a systematic investigation on the mechanical responses due to thermal mismatch reveals their effects on the thermal stress of interfaces and bonding reliability. [ABSTRACT FROM AUTHOR]