Vibrio cholerae is a prototypical noninvasive mucosal pathogen, yet infection generates long-lasting protection against subsequent disease. Vibriocidal antibody responses are an imperfect but ...established correlate of protection against cholera following both infection and vaccination. However, vibriocidal antibody responses are likely a surrogate marker for longer-lasting functional immune responses that target the O-polysaccharide antigen at the mucosal surface. While the current bivalent inactivated oral whole cell vaccine is being increasingly used to prevent cholera in areas where the disease is a threat, the most significant limitation of this vaccine is it offers relatively limited direct protection in young children. Future strategies for cholera vaccination include the development of cholera conjugate vaccines and the further development of live attenuated vaccines. Ultimately, the goal of a multivalent vaccine for cholera and other childhood enteric infections that can be incorporated into a standard immunization schedule should be realized.
We present the first ever global, spatially resolved reconstruction of the star formation history (SFH) of the Large Magellanic Cloud (LMC), based on the application of our StarFISH analysis software ...to the multiband photometry of 20 million of its stars from the Magellanic Clouds Photometric Survey. The general outlines of our results are consistent with previously published results: following an initial burst of star formation, there was a quiescent epoch from approximately 12 to 5 Gyr ago. Star formation then resumed and has proceeded until the current time at an average rate of roughly 0.2 M yr-1, with temporal variations at the factor of 2 level. The re-ignition of star formation about 5 Gyr ago, in both the LMC and Small Magellanic Cloud (SMC), is suggestive of a dramatic event at that time in the Magellanic system. Among the global variations in the recent star formation rate are peaks at roughly 2 Gyr, 500 Myr, 100 Myr, and 12 Myr. The peaks at 500 Myr and 2 Gyr are nearly coincident with similar peaks in the SFH of the SMC, suggesting a joint history for these galaxies extending back at least several Gyr. The chemical enrichment history recovered from our StarFISH analysis is in broad agreement with that inferred from the LMC's star cluster population, although our constraints on the ancient chemical enrichment history are weak. We conclude from the concordance between the star formation and chemical enrichment histories of the field and cluster populations that the field and cluster star formation modes are tightly coupled.
Although cholera has been present in Latin America since 1991, it had not been epidemic in Haiti for at least 100 years. Recently, however, there has been a severe outbreak of cholera in Haiti.
We ...used third-generation single-molecule real-time DNA sequencing to determine the genome sequences of 2 clinical Vibrio cholerae isolates from the current outbreak in Haiti, 1 strain that caused cholera in Latin America in 1991, and 2 strains isolated in South Asia in 2002 and 2008. Using primary sequence data, we compared the genomes of these 5 strains and a set of previously obtained partial genomic sequences of 23 diverse strains of V. cholerae to assess the likely origin of the cholera outbreak in Haiti.
Both single-nucleotide variations and the presence and structure of hypervariable chromosomal elements indicate that there is a close relationship between the Haitian isolates and variant V. cholerae El Tor O1 strains isolated in Bangladesh in 2002 and 2008. In contrast, analysis of genomic variation of the Haitian isolates reveals a more distant relationship with circulating South American isolates.
The Haitian epidemic is probably the result of the introduction, through human activity, of a V. cholerae strain from a distant geographic source. (Funded by the National Institute of Allergy and Infectious Diseases and the Howard Hughes Medical Institute.).
Fundamental understanding of the interaction between glass and ceramic phases with a running crack and the mechanisms by which propagation is hindered or altered as compared to the precursor parent ...glasses remains elusive for the lithium disilicate glass‐ceramics. We herein conduct extensive molecular dynamics simulations to reveal some atomic details that are otherwise extremely challenging to be probed by experiments. The results show that the crack propagation pathway in glass‐ceramics is dramatically different as compared to the precursor parent glass. In glassy sample, clean crack branching seems to be triggered by multiple cavitation events ahead of crack tip. In glass‐ceramic samples, however, branching is characterized by microcracks at multiple glass‐nanocrystal interface sites, clean nanocrystal cleavage along certain crystalline plane, and even secondary cracks due to the percolation of multiple microcracks. Additionally, the nanocrystal distribution, total volume fraction, and aspect ratio also have pronounced effects on the propagation of a primary crack and can lead to very diverse crack patterns.
The close‐up of crack front for the glass and glass‐ceramics sample. Multiple cavities are primarily populated in the glass sample, while microcrack originated at the glass‐nanocrystal interface, secondary crack induced by the percolation of microcracks, and cleavage inside the nanocrystal at certain crystalline plane are observed in the glass‐ceramics sample.
•Deformation of alkali aluminosilicate glass during scratch process is investigated.•Friction coefficient reduces with increasing the elasticity of glass substrates.•Role of each element in response ...to applied stress during scratching is identified.•Response of alkali elements to applied stress changes dramatically by ion exchange.
Flaws on glass surfaces significantly reduce mechanical strength by concentrating applied stresses on their tips. Since these surface defects are formed by surface contact loading, such as scratching, it is crucial to enhance scratch resistance for high mechanical strength. In this regard, we investigate contributions of individual elements of alkali aluminosilicate glass (15Na2O∙5MgO∙11Al2O3∙69SiO2) to surface deformations during scratching by utilizing molecular dynamics simulations. It is found that the friction coefficient is inversely proportional to the amount of elastic deformation. Analyses of local atomic structure demonstrate that Mg and Al mainly contribute to the elastic response, whereas Na tends to heavily participate in plastic deformation. Chemical strengthening of glass further enhances the elastic behavior of Mg and Al and alters the characteristic of alkali elements from plastic to elastic participation. Atomic-level understanding of individual roles of glass elements is expected to contribute to developing advanced glasses with high surface damage resistance.
Correlates of Protection for Cholera Iyer, Anita S; Harris, Jason B
The Journal of infectious diseases,
12/2021, Volume:
224, Issue:
Supplement_7
Journal Article
Peer reviewed
Open access
Abstract
A correlate of protection (CoP) is a measured adaptive immune response to vaccination or infection that is associated with protection against disease. However, the degree to which a CoP can ...serve as a surrogate end point for vaccine efficacy should depend on the robustness of this association. While cholera toxin is a dominant target of the human antibody response to Vibrio cholerae infection, antitoxin responses are not associated with long-term immunity, and are not effective CoPs for cholera. Instead, protection appears to be mediated by functional antibodies that target the O-polysaccharide coated V. cholerae outer membrane. Vibriocidal antibodies, which are complement-dependent bactericidal antibodies, remain the most accepted CoP for cholera and are used as surrogate end points in some vaccine studies. However, the association between vibriocidal antibody titers and immunity is not absolute, and they are unlikely to reflect a mechanistic correlate of protection against cholera.
Antimicrobial resistance (AMR) in bacteria poses a major risk to global public health, with many factors contributing to the observed increase in AMR. International travel is one recognized ...contributor. The purpose of this review is to summarize current knowledge regarding the acquisition, carriage and spread of AMR bacteria by international travelers.
Recent studies have highlighted that travel is an important risk factor for the acquisition of AMR bacteria, with approximately 30% of studied travelers returning with an acquired AMR bacterium. Epidemiological studies have shown there are three major risk factors for acquisition: travel destination, antimicrobial usage and travelers' diarrhea (TD). Analyses have begun to illustrate the AMR genes that are acquired and spread by travelers, risk factors for acquisition and carriage of AMR bacteria, and local transmission of imported AMR organisms.
International travel is a contributor to the acquisition and dissemination of AMR organisms globally. Efforts to reduce the burden of AMR organisms should include a focus on international travelers. Routine genomic surveillance would further elucidate the role of international travel in the global spread of AMR bacteria.
Zimbabwe offers the most recent example of the tragedy that befalls a country and its people when cholera strikes. The 2008-2009 outbreak rapidly spread across every province and brought rates of ...mortality similar to those witnessed as a consequence of cholera infections a hundred years ago. In this Review we highlight the advances that will help to unravel how interactions between the host, the bacterial pathogen and the lytic bacteriophage might propel and quench cholera outbreaks in endemic settings and in emergent epidemic regions such as Zimbabwe.
Healthcare facilities around the world routinely use radioactive sources to diagnose and treat illness. To effectively manage the security of radioactive sources, these facilities need to understand ...the risk, which is comprised of threat, vulnerability, and consequences. The threat component of risk requires knowledge of potential adversaries and understanding their capabilities and intentions. To help articulate the multiple layers of threat and support better informed decisions, the research developed a risk-based methodology to evaluate radiological security at the facility level. The methodology is applied to a radiological dispersal device (RDD) incident from three radionuclides of concern: 137Cs, 60Co, and 192Ir. The results of the research have led to the creation of a potential facility risk index (PFRI). The PFRI is mathematically represented as the exponential product of the maximum expected utility among the threat groups, the sum of geographic vulnerability and cultural vulnerability, and net consequences. The PFRI is a novel risk index that quantifies the facility risk on a scale of 1 to 10, 1 being "very low risk" and 10 being "very high risk." A MATLAB-based graphical user interface (GUI) tool was also developed to enable the radiological facility (i.e., healthcare facility) staff to conduct self-assessments and manage their most valuable assets. The PFRI methodology is a useful starting point for any healthcare facility risk assessment and is a valuable input for decision makers considering potential investments in security upgrades.
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