Prevention and Attenuation of Covid-19 with the BNT162b2 and mRNA-1273 Vaccines.

BACKGROUND: Information is limited regarding the effectiveness of the two-dose messenger RNA (mRNA) vaccines BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) in preventing infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and in attenuating coronavirus disease 2019 (Covid-19) when administered in real-world conditions. METHODS: We conducted a prospective cohort study involving 3975 health care personnel, first responders, and other essential and frontline workers. From December 14, 2020, to April 10, 2021, the participants completed weekly SARS-CoV-2 testing by providing mid-turbinate nasal swabs for qualitative and quantitative reverse-transcriptase-polymerase-chain-reaction (RT-PCR) analysis. The formula for calculating vaccine effectiveness was 100% × (1 - hazard ratio for SARS-CoV-2 infection in vaccinated vs. unvaccinated participants), with adjustments for the propensity to be vaccinated, study site, occupation, and local viral circulation. RESULTS: SARS-CoV-2 was detected in 204 participants (5%), of whom 5 were fully vaccinated (≥14 days after dose 2), 11 partially vaccinated (≥14 days after dose 1 and <14 days after dose 2), and 156 unvaccinated; the 32 participants with indeterminate vaccination status (<14 days after dose 1) were excluded. Adjusted vaccine effectiveness was 91% (95% confidence interval [CI], 76 to 97) with full vaccination and 81% (95% CI, 64 to 90) with partial vaccination. Among participants with SARS-CoV-2 infection, the mean viral RNA load was 40% lower (95% CI, 16 to 57) in partially or fully vaccinated participants than in unvaccinated participants. In addition, the risk of febrile symptoms was 58% lower (relative risk, 0.42; 95% CI, 0.18 to 0.98) and the duration of illness was shorter, with 2.3 fewer days spent sick in bed (95% CI, 0.8 to 3.7). CONCLUSIONS: Authorized mRNA vaccines were highly effective among working-age adults in preventing SARS-CoV-2 infection when administered in real-world conditions, and the vaccines attenuated the viral RNA load, risk of febrile symptoms, and duration of illness among those who had breakthrough infection despite vaccination. (Funded by the National Center for Immunization and Respiratory Diseases and the Centers for Disease Control and Prevention.).

Corrigendum: Greater post-Neolithic wealth disparities in Eurasia than in North America and Mesoamerica.

This corrects the article DOI: 10.1038/nature24646.

The persistence of ancient settlements and urban sustainability.

We propose a dedicated research effort on the determinants of settlement persistence in the ancient world, with the potential to significantly advance the scientific understanding of urban sustainability today. Settlements (cities, towns, villages) are locations with two key attributes: They frame human interactions and activities in space, and they are where people dwell or live. Sustainability, in this case, focuses on the capacity of structures and functions of a settlement system (geography, demography, institutions) to provide for continuity of safe habitation. The 7,000-y-old experience of urbanism, as revealed by archaeology and history, includes many instances of settlements and settlement systems enduring, adapting to, or generating environmental, institutional, and technological changes. The field of urban sustainability lacks a firm scientific foundation for understanding the long durée, relying instead on narratives of collapse informed by limited case studies. We argue for the development of a new interdisciplinary research effort to establish scientific understanding of settlement and settlement system persistence. Such an effort would build upon the many fields that study human settlements to develop new theories and databases from the extensive documentation of ancient and premodern urban systems. A scientific foundation will generate novel insights to advance the field of urban sustainability.

Greater post-Neolithic wealth disparities in Eurasia than in North America and Mesoamerica.

How wealth is distributed among households provides insight into the fundamental characters of societies and the opportunities they afford for social mobility. However, economic inequality has been hard to study in ancient societies for which we do not have written records, which adds to the challenge of placing current wealth disparities into a long-term perspective. Although various archaeological proxies for wealth, such as burial goods or exotic or expensive-to-manufacture goods in household assemblages, have been proposed, the first is not clearly connected with households, and the second is confounded by abandonment mode and other factors. As a result, numerous questions remain concerning the growth of wealth disparities, including their connection to the development of domesticated plants and animals and to increases in sociopolitical scale. Here we show that wealth disparities generally increased with the domestication of plants and animals and with increased sociopolitical scale, using Gini coefficients computed over the single consistent proxy of house-size distributions. However, unexpected differences in the responses of societies to these factors in North America and Mesoamerica, and in Eurasia, became evident after the end of the Neolithic period. We argue that the generally higher wealth disparities identified in post-Neolithic Eurasia were initially due to the greater availability of large mammals that could be domesticated, because they allowed more profitable agricultural extensification, and also eventually led to the development of a mounted warrior elite able to expand polities (political units that cohere via identity, ability to mobilize resources, or governance) to sizes that were not possible in North America and Mesoamerica before the arrival of Europeans. We anticipate that this analysis will stimulate other work to enlarge this sample to include societies in South America, Africa, South Asia and Oceania that were under-sampled or not included in this study.

The relationship between body size and stridulatory sound production in loricariid catfishesa).

Sound production capabilities and characteristics in Loricariidae, the largest catfish family, have not been well examined. Sounds produced by three loricariid catfish species, Otocinclus affinis, Pterygoplichthys gibbiceps, and Pterygoplichthys pardalis, were recorded. Each of these species produces pulses via pectoral-fin spine stridulation by rubbing the ridged condyle of the dorsal process of the pectoral-fin spine base against a matching groove-like socket in the pectoral girdle. Light and scanning electron microscopy were used to examine the dorsal process of the pectoral-fin spines of these species. Mean distances between dorsal process ridges of O. affinis, P. gibbiceps, and P. pardalis were 53, 161, and 329 µm, respectively. Stridulation sounds occurred during either abduction (type A) or adduction (type B). O. affinis produced sounds through adduction only and P. pardalis through abduction only, whereas P. gibbiceps often produced pulse trains alternating between abduction and adduction. In these species, dominant frequency was an inverse function of sound duration, fish total length, and inter-ridge distance on the dorsal process of the pectoral-fin spine and sound duration increased with fish total length. While stridulation sounds are used in many behavioral contexts in catfishes, the functional significance of sound production in Loricariidae is currently unknown.

Physical effects of sound exposure from underwater explosions on Pacific mackerel (Scomber japonicus): Effects on the inner ear.

Studies of the effects of sounds from underwater explosions on fishes have not included examination of potential effects on the ear. Caged Pacific mackerel (Scomber japonicus) located at seven distances (between approximately 35 and 800 m) from a single detonation of 4.5 kg of C4 explosives were exposed. After fish were recovered from the cages, the sensory epithelia of the saccular region of the inner ears were prepared and then examined microscopically. The number of hair cell (HC) ciliary bundles was counted at ten preselected 2500 µm2 regions. HCs were significantly reduced in fish exposed to the explosion as compared to the controls. The extent of these differences varied by saccular region, with damage greater in the rostral and caudal ends and minimal in the central region. The extent of effect also varied in animals at different distances from the explosion, with damage occurring in fish as far away as 400 m. While extrapolation to other species and other conditions (e.g., depth, explosive size, and distance) must be performed with extreme caution, the effects of explosive sounds should be considered when environmental impacts are estimated for marine projects.

Messenger RNA Vaccine Effectiveness Against Coronavirus Disease 2019 Among Symptomatic Outpatients Aged ≥16 Years in the United States, February-May 2021.

Evaluations of vaccine effectiveness (VE) are important to monitor as coronavirus disease 2019 (COVID-19) vaccines are introduced in the general population. Research staff enrolled symptomatic participants seeking outpatient medical care for COVID-19-like illness or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing from a multisite network. VE was evaluated using the test-negative design. Among 236 SARS-CoV-2 nucleic acid amplification test-positive and 576 test-negative participants aged ≥16 years, the VE of messenger RNA vaccines against COVID-19 was 91% (95% confidence interval, 83%-95%) for full vaccination and 75% (55%-87%) for partial vaccination. Vaccination was associated with prevention of most COVID-19 cases among people seeking outpatient medical care.

A Visual Hydrogen Sensor Prototype for Monitoring Magnesium Implant Biodegradation.

Alternative metals such as magnesium (Mg) and its alloys have been recently developed for clinical applications such as temporary implants for bone and tissue repair due to their desirable mechanical properties and ability to biodegrade harmlessly in vivo by releasing Mg2+, OH-, and H2 as biodegradation products. The current methods for monitoring in vivo Mg-alloy biodegradation are either invasive and/or costly, complex, or require large equipment and specially trained personnel, thus making real-time and point-of-care monitoring of Mg-alloy implants problematic. Therefore, innovative methods are critically needed. The objective of this research was to develop a novel, thin, and wearable visual H2 sensor prototype for noninvasive monitoring of in vivo Mg-implant biodegradation in medical research and clinical settings with a fast response time. In this work, we successfully demonstrate such a prototype composed of resazurin and catalytic bimetallic gold-palladium nanoparticles (Au-Pd NPs) incorporated into a thin agarose/alginate hydrogel matrix that rapidly changes color from blue to pink upon exposure to various levels of H2 at a constant flow rate. The irreversible redox reactions occurring in the sensor involve H2, in the presence of Au-Pd NPs, converting resazurin to resorufin. To quantify the sensor color changes, ImageJ software was used to analyze photographs of the sensor taken with a smartphone during H2 exposure. The sensor concentration range was from pure H2 down to limits of detection of 6 and 8 µM H2 (defined via two methods). This range is adequate for the intended application of noninvasively monitoring in vivo Mg-alloy implant biodegradation in animals for medical research and patients in clinical settings.

Interim Estimates of Vaccine Effectiveness of BNT162b2 and mRNA-1273 COVID-19 Vaccines in Preventing SARS-CoV-2 Infection Among Health Care Personnel, First Responders, and Other Essential and Frontline Workers - Eight U.S. Locations, December 2020-March 2021.

Messenger RNA (mRNA) BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccines have been shown to be effective in preventing symptomatic COVID-19 in randomized placebo-controlled Phase III trials (1,2); however, the benefits of these vaccines for preventing asymptomatic and symptomatic SARS-CoV-2 (the virus that causes COVID-19) infection, particularly when administered in real-world conditions, is less well understood. Using prospective cohorts of health care personnel, first responders, and other essential and frontline workers* in eight U.S. locations during December 14, 2020-March 13, 2021, CDC routinely tested for SARS-CoV-2 infections every week regardless of symptom status and at the onset of symptoms consistent with COVID-19-associated illness. Among 3,950 participants with no previous laboratory documentation of SARS-CoV-2 infection, 2,479 (62.8%) received both recommended mRNA doses and 477 (12.1%) received only one dose of mRNA vaccine.† Among unvaccinated participants, 1.38 SARS-CoV-2 infections were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) per 1,000 person-days.§ In contrast, among fully immunized (≥14 days after second dose) persons, 0.04 infections per 1,000 person-days were reported, and among partially immunized (≥14 days after first dose and before second dose) persons, 0.19 infections per 1,000 person-days were reported. Estimated mRNA vaccine effectiveness for prevention of infection, adjusted for study site, was 90% for full immunization and 80% for partial immunization. These findings indicate that authorized mRNA COVID-19 vaccines are effective for preventing SARS-CoV-2 infection, regardless of symptom status, among working-age adults in real-world conditions. COVID-19 vaccination is recommended for all eligible persons.

Indicator Dyes and Catalytic Nanoparticles for Irreversible Visual Hydrogen Sensing.

Using ultraviolet-visible (UV-vis) absorption spectroscopy, we have tested the reactivity of various indicator molecules combined with catalytic bimetallic gold-palladium nanoparticles (Au-Pd NPs) in solution for an irreversible and visual response to H2. Our aim was to identify the most suitable indicator/Au-Pd NP system for the future development of a thin, wearable, and visual H2 sensor for noninvasive monitoring of in vivo Mg-implant biodegradation in research and clinical settings with fast response time. The indicators studied were bromothymol blue, methyl red, and resazurin, and the reactions of each system with H2 in the presence of Au-Pd NPs caused visual and irreversible color changes that were concluded to proceed via redox processes. The resazurin/Au-Pd NP system was deemed best-suited for our research objectives because (1) this system had the fastest color change response to H2 at levels relevant to in vivo Mg-implant biodegradation compared to the other indicator/Au-Pd NP systems tested, (2) the observed redox chemistry with H2 followed well-understood reaction pathways reported in the literature, and (3) the redox products were nontoxic and appropriate for medical applications. Studying the effects of the concentrations of H2, Au-Pd NPs, and resazurin on the color change response time within the resazurin/Au-Pd NP system revealed that the H2-sensing elements can be optimized to achieve a faster or slower color change with H2 by varying the relative amounts of resazurin and Au-Pd NPs in solution. The results from this study are significant for future optical H2 sensor design.

The role of hyoid muscles in biotremor production in Chamaeleo calyptratus.

The production of biotremors has been described in veiled chameleons (Chamaeleo calyptratus), but the mechanism by which they are produced is unknown. We gathered muscle activation data via electromyography (EMG), with simultaneous recordings of biotremors using an accelerometer, to test for the role of hyoid muscles in biotremor production. We recorded a mean biotremor frequency of 150.87 Hz for females and 136.01 Hz for males. The durations of activity and the latencies to onset and offset for the M. sternohyoideus profundus (SP), M. sternohyoideus superficialis (SS), Mm. mandibulohyoideus (MH) and M. levator scapulae (LS) were all significantly correlated with biotremor durations and biotremor onset and offset, respectively. Linear mixed-effect regression model comparisons of biotremor duration indicated that models containing either the MH and/or the SP and LS account for the most variation in biotremor duration. Twitch times for the SP (100 ms) and the SS (132 ms) at field active body temperature, however, were individually too slow to produce the biotremors at the observed frequency without alteration after production by other anatomical structures. These results implicate the SP, SS, MH and LS in the production of biotremors, but the exact mechanism of production requires further study.

Anti-Cancer and Ototoxicity Characteristics of the Curcuminoids, CLEFMA and EF24, in Combination with Cisplatin.

In this study, we investigated whether the curcuminoids, CLEFMA and EF24, improved cisplatin efficacy and reduced cisplatin ototoxicity. We used the lung cancer cell line, A549, to determine the effects of the curcuminoids and cisplatin on cell viability and several apoptotic signaling mechanisms. Cellular viability was measured using the MTT assay. A scratch assay was used to measure cell migration and fluorescent spectrophotometry to measure reactive oxygen species (ROS) production. Western blots and luminescence assays were used to measure the expression and activity of apoptosis-inducing factor (AIF), caspases-3/7, -8, -9, and -12, c-Jun N-terminal kinases (JNK), mitogen-activated protein kinase (MAPK), and proto-oncogene tyrosine-protein kinase (Src). A zebrafish model was used to evaluate auditory effects. Cisplatin, the curcuminoids, and their combinations had similar effects on cell viability (IC50 values: 2-16 µM) and AIF, caspase-12, JNK, MAPK, and Src expression, while caspase-3/7, -8, and -9 activity was unchanged or decreased. Cisplatin increased ROS yield (1.2-fold), and curcuminoid and combination treatments reduced ROS (0.75-0.85-fold). Combination treatments reduced A549 migration (0.51-0.53-fold). Both curcuminoids reduced auditory threshold shifts induced by cisplatin. In summary, cisplatin and the curcuminoids might cause cell death through AIF and caspase-12. The curcuminoids may potentiate cisplatin's effect against A549 migration, but may counteract cisplatin's effect to increase ROS production. The curcuminoids might also prevent cisplatin ototoxicity.

Determination of trichloroethylene by using self-referenced SERS and gold-core/silver-shell nanoparticles.

A surface-enhanced Raman scattering (SERS) method has been developed to determine the concentration of trichloroethylene (TCE) in environmental water. Au-core/Ag-shell nanoparticles containing 4-mercaptophenylboronic acid (4-MPBA) between the core and shell are used as the SERS substrate. 4-MPBA serves as an internal reference with a Raman shift at 534 cm-1. TCE reacts with 4-mercaptopyridine (4-MPy) in a so-called Fujiwara reaction. With the presence of TCE in water, the consumption of 4-MPy results in a change in the intensity of its Raman signal at 1220 cm-1. The ratio of the Raman shift at 1220 cm-1 and 534 cm-1 decreases linearly in the 0.2 to 1.0 µM TCE concentration range, and the detection limit of TCE is as low as 8 ppb (60 nM). The method has been successfully applied to the determination of TCE in spiked lake water. Graphical abstract Gold-core/silver-shell nanoparticles with internal reference embedded have been fabracated to improve the quantitative measurement of SERS. These nanoparticles as SERS substrates, are used to indirectly quantify the concentration of trichloroethylene (a typical halogenated organic compound) by the consumption of 4-mercaptopyridine through the Fujiwara reaction.

Relationship Between Hair Cell Loss and Hearing Loss in Fishes.

Exposure to intense sound or ototoxic chemicals can damage the auditory hair cells of vertebrates, resulting in hearing loss. Although the relationship between such hair cell damage and auditory function is fairly established for terrestrial vertebrates, there are limited data available to understand this relationship in fishes. Although investigators have measured either the morphological damage of the inner ear or the functional deficits in the hearing of fishes, very few have directly measured both in an attempt to find a relationship between the two. Those studies that have examined both auditory hair cell damage in the inner ear and the resulting hearing loss in fishes are reviewed here. In general, there is a significant linear relationship between the number of hair cells lost and the severity of hearing threshold shifts, although this varies between species and different hair cell-damaging stimuli. After trauma to the fish ear, auditory hair cells are able to regenerate to control level densities. With this regeneration also comes a restoration of hearing. Thus there is also a significant relationship between hair cell recovery and hearing recovery in fishes.

Causes and Consequences of Sensory Hair Cell Damage and Recovery in Fishes.

Sensory hair cells are the mechanotransductive receptors that detect gravity, sound, and vibration in all vertebrates. Damage to these sensitive receptors often results in deficits in vestibular function and hearing. There are currently two main reasons for studying the process of hair cell loss in fishes. First, fishes, like other non-mammalian vertebrates, have the ability to regenerate hair cells that have been damaged or lost via exposure to ototoxic chemicals or acoustic overstimulation. Thus, they are used as a biomedical model to understand the process of hair cell death and regeneration and find therapeutics that treat or prevent human hearing loss. Secondly, scientists and governmental natural resource managers are concerned about the potential effects of intense anthropogenic sounds on aquatic organisms, including fishes. Dr. Arthur N. Popper and his students, postdocs and research associates have performed pioneering experiments in both of these lines of fish hearing research. This review will discuss the current knowledge regarding the causes and consequences of both lateral line and inner ear hair cell damage in teleost fishes.

Archaeology as a social science.

Because of advances in methods and theory, archaeology now addresses issues central to debates in the social sciences in a far more sophisticated manner than ever before. Coupled with methodological innovations, multiscalar archaeological studies around the world have produced a wealth of new data that provide a unique perspective on long-term changes in human societies, as they document variation in human behavior and institutions before the modern era. We illustrate these points with three examples: changes in human settlements, the roles of markets and states in deep history, and changes in standards of living. Alternative pathways toward complexity suggest how common processes may operate under contrasting ecologies, populations, and economic integration.

Effects of exposure to pile driving sounds on fish inner ear tissues.

Impulsive pile driving sound can cause injury to fishes, but no studies to date have examined whether such injuries include damage to sensory hair cells in the ear. Possible effects on hair cells were tested using a specially designed wave tube to expose two species, hybrid striped bass (white bass Morone chrysops × striped bass Morone saxatilis) and Mozambique tilapia (Oreochromis mossambicus), to pile driving sounds. Fish were exposed to 960 pile driving strikes at one of three treatment levels: 216, 213, or 210dB re 1 µPa(2)·s cumulative Sound Exposure Level. Both hybrid striped bass and tilapia exhibited barotraumas such as swim bladder ruptures, herniations, and hematomas to several organs. Hybrid striped bass exposed to the highest sound level had significant numbers of damaged hair cells, while no damage was found when fish were exposed at lower sound levels. Considerable hair cell damage was found in only one out of 11 tilapia specimens exposed at the highest sound level. Results suggest that impulsive sounds such as from pile driving may have a more significant effect on the swim bladders and surrounding organs than on the inner ears of fishes, at least at the sound exposure levels used in this study.

Communication via Biotremors in the Veiled Chameleon (Chamaeleo calyptratus): Part II-Social Contexts.

This study extends recent research demonstrating that the veiled chameleon (Chamaeleo calyptratus) can produce and detect biotremors. Chameleons were paired in various social contexts: dominance (male-male; female-female C. calyptratus); courtship (male-female C. calyptratus); heterospecific (C. calyptratus + C. gracilis); and inter-size class dominance (adult + juvenile C. calyptratus). Simultaneous video and accelerometer recordings were used to monitor their behavior and record a total of 398 biotremors. Chamaeleo calyptratus produced biotremors primarily in conspecific dominance and courtship contexts, accounting for 84.7% of the total biotremors recorded, with biotremor production varying greatly between individuals. Biotremors were elicited by visual contact with another conspecific or heterospecific, and trials in which chameleons exhibited visual displays and aggressive behaviors were more likely to record biotremors. Three classes of biotremor were identified-hoots, mini-hoots, and rumbles, which differed significantly in fundamental frequency, duration, and relative intensity. Biotremor frequency decreased with increasing signal duration, and frequency modulation was evident, especially in hoots. Overall, the data show that C. calyptratus utilizes substrate-borne vibrational communication during conspecific and possibly heterospecific interactions.

Communication via Biotremors in the Veiled Chameleon (Chamaeleo calyptratus): Part I- Biotremor Production and Response to Substrate-Borne Vibrations.

Biotremors are vibrations, usually surface waves along the boundary of a medium, produced by an organism. While substrate-borne vibrations are utilized by different reptile species, true conspecific communication via biotremors has not yet been demonstrated in lizards. Recent research revealed that the veiled chameleon (Chamaeleo calyptratus) produces biotremors. The prerequisites for any communication system are the ability of an organism to produce and detect a signal. We tested C. calyptratus behavioral responses to vibrations by placing them on a dowel attached to a shaker, emitting vibrations of 25, 50, 150, 300, and 600 Hz and compared their locomotory velocity before and after the stimulus. Adult chameleons exhibited a freeze response to 50 and 150 Hz, while juveniles exhibited a similar response to frequencies between 50 and 300 Hz. In a second experiment, chameleons were induced to produce biotremors via experimenter contact. These biotremors ranged in mean fundamental frequency from 106.4 to 170.3 Hz and in duration from 0.06 to 0.29 s. Overall, two classes of biotremors were identified, "hoots" and "mini-hoots," which differed significantly in mean relative signal intensity (-7.5 and -32.5 dB, respectively). Juvenile chameleons 2 months of age were able to produce biotremors, suggesting this behavior may serve a wide range of ecological functions throughout ontogeny. Overall, the data demonstrate that C. calyptratus can both produce and detect biotremors that could be used for intraspecific communication.