Social nudges for vaccination: How communicating herd behaviour influences vaccination intentions.

OBJECTIVES: This Registered Report attempted to conceptually replicate the finding that communicating herd immunity increases vaccination intentions (Betsch, et al., 2017, Nat. Hum. Behav., 0056). An additional objective was to explore the roles of descriptive social norms (vaccination behaviour of others) and the herd-immunity threshold (coverage needed to stop disease transmission). DESIGN: An online experiment with a 2 (herd-immunity explanation: present vs. absent) × 3 (descriptive norm: high vs. low vs. absent) × 2 (herd-immunity threshold: present vs. absent) between-subjects fractional design. METHODS: Sample consisted of 543 people (aged 18-64) residing in the United Kingdom. Participants first received an explanation of herd immunity emphasising social benefits (protecting others) in both textual and animated-infographic form. Next, they were faced with fictitious information about the disease, the vaccine, their country's vaccination coverage (80% or 20%), and the herd-immunity threshold (90%). Vaccination intention was self-rated. RESULTS: Compared to the control, communicating social benefits of herd immunity was effective in increasing vaccination intentions (F(1,541) = 6.97, p = .009, Partial Eta-Squared = 0.013). Communicating the descriptive norm or the herd-immunity threshold alongside the herd-immunity explanation demonstrated no observable effect. CONCLUSION: Communicating social benefits of herd immunity increased self-reported vaccination intentions against a fictitious disease, replicating previous findings. Although this result is positive, the practical relevance may be limited. Further research into the effect of social nudges to motivate vaccination is required, particularly with respect to the recent pandemic context and varying levels of vaccine hesitancy.

Differential drug susceptibility patterns of Mycobacterium chimaera and other members of the Mycobacterium avium-intracellulare complex.

OBJECTIVES: To determine MIC distributions for Mycobacterium chimaera, Mycobacterium intracellulare, Mycobacterium colombiense and Mycobacterium avium, and to derive tentative epidemiological cut-off (ECOFF) values. METHODS: A total of 683 bacterial isolates (M. chimaera, n = 203; M. intracellulare, n = 77; M. colombiense, n = 68; M. avium, n = 335) from 627 patients were tested by broth microdilution according to CLSI protocol M24-A2 on Sensititre RAPMYCOI plates. MICs were interpreted based on CLSI breakpoints for clarithromycin, and tentative breakpoints for amikacin, moxifloxacin and linezolid. Tentative ECOFFs were determined by visual approximation and the ECOFFinder algorithm. RESULTS: Modal MIC, MIC50 and MIC90 values were within ± one dilution step from the respective aggregated data set for 47/48 (97.9%), 48/48 (100%) and 48/48 (100%) species-drug combinations. Clarithromycin wild-type populations were mostly classified as susceptible (MIC90 4-8 mg/L; S ≤8 mg/L). Rifabutin MICs were lower than those of rifampicin. Tentative moxifloxacin, linezolid and amikacin breakpoints split wild-type populations. No ECOFFs could be set for rifampicin, ethambutol, ciprofloxacin, isoniazid, trimethoprim/sulfamethoxazole and doxycycline because of truncation of MIC distributions. Agreement between the visually determined and the modelled 97.5% ECOFFs was 90.9%. All 99.0% ECOFFs were one titre step higher than by visual approximation. CONCLUSIONS: Drug susceptibility patterns of M. chimaera are comparable to those of closely related species. Except for clarithromycin, breakpoints for Mycobacterium avium-intracellulare complex should be re-evaluated. Statistical determination of the 99.0% ECOFF may be superior to visual approximation.

Changes in the physical state of sucrose during dark chocolate processing.

Dark chocolate tablets were manufactured using 100% crystalline sucrose, 50% crystalline and 50% amorphous sucrose, and 100% amorphous sucrose. The physical state of sucrose was determined by differential scanning calorimetry (DSC) and X-ray diffraction. DSC scans of dark chocolate samples containing amorphous sucrose were characterized by a glass transition at 63 degrees C, a sucrose crystallization peak at 105 degrees C, and a melting endotherm at 188 degrees C. Independent of the amount of amorphous or crystalline sucrose used for the preparation of dark chocolate, all final chocolate products provided a single melting endotherm at 188 degrees C and a crystalline X-ray diffraction pattern. These results indicated that sucrose crystallized during production of dark chocolate and that no amorphous sucrose was present in the final chocolate products.

Semisynthetic des-(B27-B30)-insulins with modified B26-tyrosine.

Semisynthetic des-(B27-B30)-insulins containing modified B26-tyrosine residues were prepared to refine the understanding of the importance of position B26 with regard to biological and structural properties of the hormone. The following shortened insulin analogues were synthesized by trypsin-catalysed peptide-bond formation between the C-terminal amino acid ArgB22 of des-(B23-B30)-insulin and synthetic tetrapeptides as amino components: des-(B27-B30)-insulin, des-(B27-B30)-insulin-B26-methyl ester, -B26-carboxamide with varying C-terminal hydrophobicity of the B-chain, and [Tyr(NH2)B26]-, [Tyr(NO2)B26]-, [Tyr(I2)B26]-, [D-TyrB26]des-(B27-B30)-insulin-B26-carboxamide containing non-proteinogenic amino acids in position B26. Starting from insulin and an excess of synthetic Gly-Phe-Phe-Tyr-OMe as nucleophile, des-(B27-B30)-insulin-B26-methyl ester--the formal transpeptidation product at ArgB22--was formed in one step. Biological in vitro properties (binding to cultured human IM-9 lymphocytes, relative lipogenic potency in isolated rat adipocytes) of all semisynthetic analogues are reported, ranging from slightly decreased to two-fold receptor affinity and nearly three-fold biopotency relative to insulin. If the C-terminal tetrapeptide B27-B30 is removed, full relative insulin activity is still preserved, while the shortening results in the loss of ability to associate in solution. Only after carboxamidation or methyl esterification of TyrB26 the self-association typical of native insulin can be observed, and the CD-spectral effects in the near UV spectrum related to association and hexamerization of the native hormone are qualitatively reestablished. The results of this investigation underline the importance of position B26 to the modulation of hormonal properties and solution structure of the shortened insulins.

Enzyme-assisted semisynthesis of shortened B26-modified insulins.

The role of the invariant residue B26-tyrosine in determining the structural and biological properties of insulin has been extensively investigated by the use of semisynthetic des-(B27-B30)-insulins with modifications of position B26. Apart from the conventional trypsin-catalyzed peptide bond formation between the C-terminal amino acid ArgB22 of des-(B23-B30)-insulin and synthetic tetrapeptides we elaborated a new approach using des-(B26-B30)-insulin as substrate in alpha-chymotrypsin-mediated syntheses. Results obtained from bioassays and CD-spectroscopy underline the importance of position B26 to the association of the native molecule and to the modulation of structural and hormonal properties of shortened insulins.