Emerging micro-scale medical devices are showing promise, whether in delivering drugs or extracting diagnostic biomarkers from skin. In progressing these devices through animal models towards ...clinical products, understanding the mechanical properties and skin tissue structure with which they interact will be important. Here, through measurement and analytical modelling, we advanced knowledge of these properties for commonly used laboratory animals and humans (~30 g to ~150 kg). We hypothesised that skin's stiffness is a function of the thickness of its layers through allometric scaling, which could be estimated from knowing a species' body mass. Results suggest that skin layer thicknesses are proportional to body mass with similar composition ratios, inter- and intra-species. Experimental trends showed elastic moduli increased with body mass, except for human skin. To interpret the relationship between species, we developed a simple analytical model for the bulk elastic moduli of skin, which correlated well with experimental data. Our model suggest that layer thicknesses may be a key driver of structural stiffness, as the skin layer constituents are physically and therefore mechanically similar between species. Our findings help advance the knowledge of mammalian skin mechanical properties, providing a route towards streamlined micro-device research and development onto clinical use.
Albedo (or solar reflectivity) plays an important role in the thermal behavior of pavements and other ground surfaces, and their resultant impacts on humans and the environment. This study developed ...a new albedo measurement system with a dual-pyranometer and automatic data acquisition system, and used it to conduct field measurements of albedo on different pavement materials and for long-term monitoring of albedo. The albedo values were obtained for commonly used land cover materials including asphalt, concrete and interlocking concrete paver surfacing materials with different designs and some other materials. These new data can help reduce the uncertainty in understanding, evaluating and modeling the thermal behavior and environmental impacts of ground surfaces with different albedos.
The seasonal effects of albedo on pavement thermal performance were examined through experimental measurements. An empirical relationship between the cooling effect of increased albedo on a pavement's high temperature and solar radiation was developed. The cooling effect has a positive correlation with the peak solar radiation intensity. This simple correlation can be used to roughly estimate the cooling or heating effect of changing albedo on pavement for various climates and seasons with different solar radiation intensities.
► A new and convenient albedo measurement method and system was developed. ► New data on differences in land cover albedo were documented. ► Factors affecting field measurement of albedo were investigated. ► Seasonal effects of albedo on pavement temperature were examined. ► A correlation for quantifying cooling effect of increased albedo was developed.
Objectives/Hypothesis
Quantitative measures of swallowing function may improve the reliability and accuracy of modified barium swallow (MBS) study interpretation. Quantitative study analysis has not ...been widely instituted, however, secondary to concerns about the time required to make measures and a lack of research demonstrating impact on MBS interpretation. This study compares the accuracy of the penetration/aspiration (PEN/ASP) scale (an observational visual‐perceptual assessment tool) to quantitative measures of airway closure timing relative to the arrival of the bolus at the upper esophageal sphincter in identifying a failure of airway protection during deglutition.
Study Design
Retrospective review of clinical swallowing data from a university‐based outpatient clinic.
Methods
Swallowing data from 426 patients were reviewed. Patients with normal PEN/ASP scores were identified, and the results of quantitative airway closure timing measures for three liquid bolus sizes were evaluated. The incidence of significant airway closure delay with and without a normal PEN/ASP score was determined. Inter‐rater reliability for the quantitative measures was calculated.
Results
In patients with a normal PEN/ASP score, 33% demonstrated a delay in airway closure on at least one swallow during the MBS study. There was no correlation between PEN/ASP score and airway closure delay. Inter‐rater reliability for the quantitative measure of airway closure timing was nearly perfect (intraclass correlation coefficient = 0.973).
Conclusions
The use of quantitative measures of swallowing function, in conjunction with traditional visual perceptual methods of MBS study interpretation, improves the identification of airway closure delay, and hence, potential aspiration risk, even when no penetration or aspiration is apparent on the MBS study.
Level of Evidence
4. Laryngoscope, 127:2314–2318, 2017
The amount of time adolescents spend communicating via digital technologies such as smartphones has led to concerns that computer-mediated communication (CMC) is displacing face-to-face (FtF) ...interactions and disrupting social development. Although many studies have examined CMC in adolescents' relationships with friends, few studies have examined the role of CMC in adolescents' renegotiation of closeness and autonomy with parents. To examine this issue, we administered an online daily diary with 169 U.S. adolescents to estimate the time they spend in CMC and FtF interactions and the number of texts they exchange with friends and parents. On the last day of the survey, we asked adolescents about their emotional closeness to friends and parents and their balance of closeness and volition with parents. Overall, we found more evidence for social stimulation than displacement effects of CMC. Texts and CMC time with friends predicted friend closeness after accounting for FtF time with friends; texts with parents predicted parent closeness after accounting for FtF time with parents. We also found support for our hypothesis that CMC would be associated with greater adolescent volition. CMC time with parents predicted greater volitional dependence (volition plus closeness) whereas texts with friends predicted greater independent decision-making (volition plus distance). We discuss how communication technologies are integrated into U.S. adolescents' relationships with friends and parents and how CMC can facilitate, rather than stifle, adolescents' adjustment of autonomy-relatedness with parents and their construction of emotional closeness with friends.
Louis Pasteur is traditionally considered as the progenitor of modern immunology because of his studies in the late nineteenth century that popularized the germ theory of disease, and that introduced ...the hope that all infectious diseases could be prevented by prophylactic vaccination, as well as also treated by therapeutic vaccination, if applied soon enough after infection. However, Pasteur was working at the dawn of the appreciation of the microbial world, at a time when the notion of such a thing as an immune system did not exist, certainly not as we know it today, more than 130 years later. Accordingly, why was Pasteur such a genius as to discern how the immune system functions to protect us against invasion by the microbial world when no one had even made the distinction between fungi, bacteria, or viruses, and no one had formulated any theories of immunity. A careful reading of Pasteur's presentations to the Academy of Sciences reveals that Pasteur was entirely mistaken as to how immunity occurs, in that he reasoned, as a good microbiologist would, that appropriately attenuated microbes would deplete the host of vital trace nutrients absolutely required for their viability and growth, and not an active response on the part of the host. Even so, he focused attention on immunity, preparing the ground for others who followed. This review chronicles Pasteur's remarkable metamorphosis from organic chemist to microbiologist to immunologist, and from basic science to medicine.
SARS-CoV-2 messenger RNA vaccination in healthy individuals generates immune protection against COVID-19. However, little is known about SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed ...patients. We investigated induction of antigen-specific antibody, B cell and T cell responses longitudinally in patients with multiple sclerosis (MS) on anti-CD20 antibody monotherapy (n = 20) compared with healthy controls (n = 10) after BNT162b2 or mRNA-1273 mRNA vaccination. Treatment with anti-CD20 monoclonal antibody (aCD20) significantly reduced spike-specific and receptor-binding domain (RBD)-specific antibody and memory B cell responses in most patients, an effect ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. By contrast, all patients with MS treated with aCD20 generated antigen-specific CD4 and CD8 T cell responses after vaccination. Treatment with aCD20 skewed responses, compromising circulating follicular helper T (T
) cell responses and augmenting CD8 T cell induction, while preserving type 1 helper T (T
1) cell priming. Patients with MS treated with aCD20 lacking anti-RBD IgG had the most severe defect in circulating T
responses and more robust CD8 T cell responses. These data define the nature of the SARS-CoV-2 vaccine-induced immune landscape in aCD20-treated patients and provide insights into coordinated mRNA vaccine-induced immune responses in humans. Our findings have implications for clinical decision-making and public health policy for immunosuppressed patients including those treated with aCD20.
The deployment of effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to eradicate the coronavirus disease 2019 (COVID-19) pandemic. Many licensed ...vaccines confer protection by inducing long-lived plasma cells (LLPCs) and memory B cells (MBCs), cell types canonically generated during germinal center (GC) reactions. Here, we directly compared two vaccine platforms—mRNA vaccines and a recombinant protein formulated with an MF59-like adjuvant—looking for their abilities to quantitatively and qualitatively shape SARS-CoV-2-specific primary GC responses over time. We demonstrated that a single immunization with SARS-CoV-2 mRNA, but not with the recombinant protein vaccine, elicited potent SARS-CoV-2-specific GC B and T follicular helper (Tfh) cell responses as well as LLPCs and MBCs. Importantly, GC responses strongly correlated with neutralizing antibody production. mRNA vaccines more efficiently induced key regulators of the Tfh cell program and influenced the functional properties of Tfh cells. Overall, this study identifies SARS-CoV-2 mRNA vaccines as strong candidates for promoting robust GC-derived immune responses.
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•SARS-CoV-2 mRNA vaccines elicit potent GC B cell responses•GC responses are associated with a robust development of neutralizing antibodies•SARS-CoV-2 mRNA vaccines promote antigen-specific Tfh cells•Key elements of the Tfh cell program are modulated by SARS-CoV-2 mRNA vaccines
Herein, Lederer et al. show a nucleic-acid-based vaccine platform for SARS-CoV-2 that potently induces germinal center (GC) responses. GCs are microanatomical sites harboring the formation of high-quality, protective antibody responses. Such vaccine platforms can be promising candidates to mitigate the COVID-19 pandemic.
SARS-CoV-2 mRNA vaccines have shown remarkable clinical efficacy, but questions remain about the nature and kinetics of T cell priming. We performed longitudinal antigen-specific T cell analyses on ...healthy SARS-CoV-2-naive and recovered individuals prior to and following mRNA prime and boost vaccination. Vaccination induced rapid antigen-specific CD4+ T cell responses in naive subjects after the first dose, whereas CD8+ T cell responses developed gradually and were variable in magnitude. Vaccine-induced Th1 and Tfh cell responses following the first dose correlated with post-boost CD8+ T cells and neutralizing antibodies, respectively. Integrated analysis revealed coordinated immune responses with distinct trajectories in SARS-CoV-2-naive and recovered individuals. Last, whereas booster vaccination improved T cell responses in SARS-CoV-2-naive subjects, the second dose had little effect in SARS-CoV-2-recovered individuals. These findings highlight the role of rapidly primed CD4+ T cells in coordinating responses to the second vaccine dose in SARS-CoV-2-naive individuals.
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•mRNA vaccines generate antigen-specific T cells in a coordinated immune response•Vaccine-induced T cells resemble the durable memory cells primed by infection•Th1 and cTfh cell responses to the first dose correlate with second-dose responses•SARS-CoV-2-recovered individuals benefit from the first but not the second dose
SARS-CoV-2 mRNA vaccines have demonstrated remarkable efficacy, but T cell responses to vaccination have not been well studied. In a longitudinal cohort, Painter et al. show that mRNA vaccines activate SARS-CoV-2-specific T cells that could contribute to durable immunity. The findings highlight the central role of T cells in the two-dose vaccine regimen for individuals not previously infected with SARS-CoV-2.
This research employs pepsin-containing membranes to digest proteins online after a capillary electrophoresis (CE) separation and prior to tandem mass spectrometry. Proteolysis after the separation ...allows the peptides from a given protein to enter the mass spectrometer in a single plug. Thus, migration time can serve as an additional criterion for confirming the identification of a peptide. The membrane resides in a sheath-flow electrospray ionization (ESI) source to enable digestion immediately before spray into the mass spectrometer, thus limiting separation of the digested peptides. Using the same membrane, digestion occurred reproducibly during 20 consecutive CE analyses performed over a 10 h period. Additionally, after separating a mixture of six unreduced proteins with CE, online digestion facilitated protein identification with at least 2 identifiable peptides for all the proteins. Sequence coverages were >75% for myoglobin and carbonic anhydrase II but much lower for proteins containing disulfide bonds. Development of methods for efficient separation of reduced proteins or identification of cross-linked peptides should enhance sequence coverages for proteins with disulfide bonds. Migration times for the peptides identified from a specific protein differed by <∼30 s, which allows for rejection of some spurious peptide identifications.
This research employs pepsin-containing membranes to digest proteins online after a capillary electrophoresis separation and prior to tandem mass spectrometry, allowing the peptides from a protein to enter the mass spectrometer in a single plug.
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