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We have developed two independent methods for measuring the one-dimensional power spectrum of the transmitted flux in the Lyman-α forest. The first method is based on a Fourier transform and the second on a maximum-likelihood estimator. The two methods are independent and have different systematic uncertainties. Determination of the noise level in the data spectra was subject to a new treatment, because of its significant impact on the derived power spectrum. We applied the two methods to 13 821 quasar spectra from SDSS-III/BOSS DR9 selected from a larger sample of over 60 000 spectra on the basis of their high quality, high signal-to-noise ratio (S/N), and good spectral resolution. The power spectra measured using either approach are in good agreement over all twelve redshift bins from 〈z〉 = 2.2 to 〈z〉 = 4.4, and scales from 0.001 km s-1 to 0.02 km s-1. We determined the methodological andinstrumental systematic uncertainties of our measurements. We provide a preliminary cosmological interpretation of our measurements using available hydrodynamical simulations. The improvement in precision over previously published results from SDSS is a factor 2-3 for constraints on relevant cosmological parameters. For a ΛCDM model and using a constraint on H0 that encompasses measurements based on the local distance ladder and on CMB anisotropies, we infer σ8 = 0.83 ± 0.03 and ns = 0.97 ± 0.02 based on Hi absorption in the range 2.1 < z < 3.7. © ESO, 2013.

Despite an abundance of information available for dealing with patients with BRCA-1 and BRCA-2 mutations, little guidance is available to assist the surgeon in dealing with the genetically high-risk patient recently diagnosed with breast cancer. A retrospective review was undertaken of 170 patients who underwent genetic counseling and testing over a 3-year period from March 2000 to March 2003. Forty-three of the 170 patients tested were diagnosed with breast cancer prior to genetic testing. Nine patients (20.9%) tested positive for a deleterious mutation. Fifty-eight percent underwent genetic counseling prior to definitive cancer surgery. Five of the 25 patients who underwent lumpectomy tested positive for a deleterious mutation. Testing results became available during systemic therapy or radiation was delayed until results were known. After counseling, all five patients testing positive went on to bilateral prophylactic mastectomy and reconstruction. None had radiation therapy. Because of a strong family history, eight patients elected to undergo prophylactic mastectomy and reconstruction prior to obtaining genetic test results; and despite compelling histories, all eight tested negative for a mutation. Treatment algorithms are developed to manage patients that are first discovered to be at high risk for a BRCA-1 or BRCA-2 mutation at the time they are diagnosed with breast cancer. Patients diagnosed with breast cancer who are discovered to be at high risk for a genetic mutation should undergo counseling prior to definitive surgery. This maximizes the time that patients have to consider options for prophylaxis and monitoring should their test be positive. It also prevents women who would otherwise be candidates for breast preservation from undergoing unnecessary radiation therapy should they chose prophylactic mastectomy in the face of a positive test. [ABSTRACT FROM AUTHOR]

Introduction: Pre-erythrocytic malaria vaccines hold the promise of inducing sterile protection thereby preventing the morbidity and mortality associated with Plasmodium infection. The main surface antigen of P. falciparum sporozoites, i.e., the circumsporozoite protein (CSP), has been extensively explored as a target of such vaccines with significant success in recent years. Systematic adjuvant selection, refinements of the immunization regimen, and physical properties of the antigen may all contribute to the potential of increasing the efficacy of CSP-based vaccines. Protection appears to be dependent in large part on CSP antibodies. However due to a knowledge gap related to the exact correlates of immunity, there is a critical need to improve our ability to down select candidates preclinically before entering clinical trials including with controlled human malaria infections (CHMI)., Methods: We developed a novel multiplex competition assay based on well-characterized monoclonal antibodies (mAbs) that target crucial epitopes across the CSP molecule. This new tool assesses both, quality and epitope-specific concentrations of vaccine-induced antibodies by measuring their equivalency with a panel of well-characterized, CSP-epitope-specific mAbs., Results: Applying this method to RTS,S-immune sera from a CHMI trial demonstrated a quantitative epitope-specificity profile of antibody responses that can differentiate between protected vs. nonprotected individuals. Aligning vaccine efficacy with quantitation of the epitope fine specificity results of this equivalency assay reveals the importance of epitope specificity., Discussion: The newly developed serological equivalence assay will inform future vaccine design and possibly even adjuvant selection. This methodology can be adapted to other antigens and disease models, when a panel of relevant mAbs exists, and could offer a unique tool for comparing and down-selecting vaccine formulations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Bolton, MacGill, Locke, Regules and Bergmann-Leitner.)

This study demonstrates the impact of adjuvant on the development of T follicular helper (Tfh) and B cells, and their influence on antibody responses in mice vaccinated with SARS-CoV-2-spike-ferritin-nanoparticle (SpFN) adjuvanted with either Army Liposome Formulation containing QS-21 (SpFN + ALFQ) or Alhydrogel ® (SpFN + AH). SpFN + ALFQ increased the size and frequency of germinal center (GC) B cells in the vaccine-draining lymph nodes and increased the frequency of antigen-specific naive B cells. A single vaccination with SpFN + ALFQ resulted in a higher frequency of IL-21-producing-spike-specific Tfh and GC B cells in the draining lymph nodes and spleen, S-2P protein-specific IgM and IgG antibodies, and elicitation of robust cross-neutralizing antibodies against SARS-CoV-2 variants as early as day 7, which was enhanced by a second vaccination. This was associated with the generation of high titer, high avidity binding antibodies. The third vaccination with SpFN + ALFQ elicited high levels of neutralizing antibodies against the Omicron variant. No cross-neutralizing antibodies against Omicron were induced with SpFN + AH. These findings highlight the importance of ALFQ in orchestrating early induction of antigen-specific Tfh and GC B cell responses and long-lived plasma cells in the bone marrow. The early engagement of S-2P specific naive B cells and high titer IgM antibodies shape the development of long-term neutralization breadth., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Recent work has suggested that an additional ≲6.9  eV per baryon of heating in the intergalactic medium is needed to reconcile hydrodynamical simulations with Lyman-α forest absorption line widths at redshift z≃0.1. Resonant conversion of dark photon dark matter into low frequency photons is a viable source of such heating. We perform the first hydrodynamical simulations including dark photon heating and show that dark photons with mass m&#95;{A^{'}}∼8×10^{-14}  eV c^{-2} and kinetic mixing ε∼5×10^{-15} can alleviate the heating excess. A prediction of this model is a nonstandard thermal history for underdense gas at z≳3.

Human immunodeficiency virus (HIV) and malaria infection rates overlap across sub-Saharan Africa, but factors influencing their co-occurrence are unclear. In a case-control study, we investigated whether malaria exposure increases risk of type 1 (HIV-1) acquisition. Prior to seroconverting, HIV-positive cases had significantly higher malaria-associated antibodies compared to HIV-negative controls, linking malaria exposure to HIV-1 acquisition., Competing Interests: Potential conflicts of interest . The authors: No potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background & Aims: Pancreatic ductal adenocarcinoma (PDAC) incidence is rising worldwide, and most patients present with an unresectable disease at initial diagnosis. Measurement of carbohydrate antigen 19-9 (CA19-9) levels lacks adequate sensitivity and specificity for early detection; hence, there is an unmet need to develop alternate molecular diagnostic biomarkers for PDAC. Emerging evidence suggests that tumor-derived exosomal cargo, particularly micro RNAs (miRNAs), offer an attractive platform for the development of cancer-specific biomarkers. Herein, genomewide profiling in blood specimens was performed to develop an exosome-based transcriptomic signature for noninvasive and early detection of PDAC., Methods: Small RNA sequencing was undertaken in a cohort of 44 patients with an early-stage PDAC and 57 nondisease controls. Using machine-learning algorithms, a panel of cell-free (cf) and exosomal (exo) miRNAs were prioritized that discriminated patients with PDAC from control subjects. Subsequently, the performance of the biomarkers was trained and validated in independent cohorts (n = 191) using quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays., Results: The sequencing analysis initially identified a panel of 30 overexpressed miRNAs in PDAC. Subsequently using qRT-PCR assays, the panel was reduced to 13 markers (5 cf- and 8 exo-miRNAs), which successfully identified patients with all stages of PDAC (area under the curve [AUC] = 0.98 training cohort; AUC = 0.93 validation cohort); but more importantly, was equally robust for the identification of early-stage PDAC (stages I and II; AUC = 0.93). Furthermore, this transcriptomic signature successfully identified CA19-9 negative cases (<37 U/mL; AUC = 0.96), when analyzed in combination with CA19-9 levels, significantly improved the overall diagnostic accuracy (AUC = 0.99 vs AUC = 0.86 for CA19-9 alone)., Conclusions: In this study, an exosome-based liquid biopsy signature for the noninvasive and robust detection of patients with PDAC was developed., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal outcomes with coronavirus disease 2019 (COVID-19) is that the immune response to the SARS-CoV-2 spike protein is enriched for antibodies directed against epitopes shared with endemic beta-coronaviruses and has a lower proportion of antibodies targeting the more protective variable regions of the spike. The magnitude of antibody responses to the SARS-CoV-2 full-length spike protein, its domains and subunits, and the SARS-CoV-2 nucleocapsid also correlated strongly with responses to the endemic beta-coronavirus spike proteins in individuals admitted to an intensive care unit (ICU) with fatal COVID-19 outcomes, but not in individuals with nonfatal outcomes. This correlation was found to be due to the antibody response directed at the S2 subunit of the SARS-CoV-2 spike protein, which has the highest degree of conservation between the beta-coronavirus spike proteins. Intriguingly, antibody responses to the less cross-reactive SARS-CoV-2 nucleocapsid were not significantly different in individuals who were admitted to an ICU with fatal and nonfatal outcomes, suggesting an antibody profile in individuals with fatal outcomes consistent with an "original antigenic sin" type response.

In this work, an iterative method based on the four-microphone transfer matrix approach was developed for evaluating the sound speed and attenuation constant of air within a standing wave tube. When the air inside the standing wave tube is treated as the material under test, i.e., as if it were a sample of porous material, the transfer matrix approach can be used to identify the air's acoustic properties. The wavenumber within the tube is complex owing to the formation of a visco-thermal boundary layer on the inner circumference of the tube. Starting from an assumed knowledge of the air properties, an iterative method can be applied in the post-processing stage to estimate the complex wavenumber. Experimental results presented here show that although the results are sensitive to ambient temperature, a semi-empirical formula previously proposed by Temkin [(1981). Elements of Acoustics (John Wiley & Sons)] matches closely with the measured sound speed and attenuation constant, as does a theoretical formulation proposed by Lahiri et al. [(2014). J. Sound Vib. 333(15), 3440-3458]. Further, it is shown that the Temkin [(1981). Elements of Acoustics (John Wiley & Sons)] and Lahiri et al. [(2014). J. Sound Vib. 333(15), 3440-3458] predictions accurately represent the variation of sound speed with frequency, in contrast to the formula recommended in the ASTM E1050 standard [(2019). American Society for Testing and Materials], in which the sound speed is assumed to be independent of frequency.

Reliably assessing exposure to mosquitoes carrying malaria parasites continues to be a challenge due to the lack of reliable, highly sensitive diagnostics with high-throughput potential. Here, we describe an approach that meets these requirements by simultaneously measuring immune responses to both disease vector and pathogen, using an electro-chemiluminescence-based multiplex assay platform. While using the same logistical steps as a classic ELISA, this platform allows for the multiplexing of up to ten antigens in a single well. This simple, reproducible, quantitative readout reports the magnitude, incidence, and prevalence of malaria infections in residents of malaria-endemic areas. By reporting exposure to both insect vectors and pathogen, the approach also provides insights into the efficacy of drugs and/or other countermeasures deployed against insect vectors aimed at reducing or eliminating arthropod-borne diseases. The high throughput of the assay enables the quick and efficient screening of sera from individuals for exposure to Plasmodium even if they are taking drug prophylaxis. We applied this assay to samples collected from controlled malaria infection studies, as well as those collected in field studies in malaria-endemic regions in Uganda and Kenya. The assay was sensitive to vector exposure, malaria infection, and endemicity, demonstrating its potential for use in malaria serosurveillance.

Explosive devices, either conventional or improvised, are common sources of injuries during combat, civil unrest, and terror attacks, resulting in trauma from exposure to blast. A blast wave (BW), a near-instantaneous rise in pressure followed by a negative pressure, propagates through the body in milliseconds and can affect physiology for days/months after exposure. Epidemiological data show that blast-related casualties result in significantly higher susceptibility to wound infections, suggesting long-lasting immune modulatory effects from blast exposure. The mechanisms involved in BW-induced immune changes are poorly understood. We evaluated the effects of BW on the immune system using an established murine model. Animals were exposed to BWs (using an Advanced Blast Simulator), followed by longitudinally sampling for 14 days. Blood, bone marrow, and spleen were analyzed for changes in the 1) complete blood count (CBC), and 2) composition of bone marrow cells (BMC) and splenocytes, and 3) concentrations of systemic cytokines/chemokines. Our data demonstrate that BW results in transient bone marrow failure and long-term changes in the frequency and profile of progenitor cell populations. Viability progressively decreased in hematopoietic stem cells and pluripotent progenitor cells. Significant decrease of CD4 + T cells in the spleen indicates reduced functionality of adaptive immune system. Dynamic changes in the concentrations of several cytokines and chemokines such as IL-1α and IL-17 occurred potentially contributing to dysregulation of immune response after trauma. This work lays the foundation for identifying the potential mechanisms behind BW's immunosuppressive effects to inform the recognition of this compromised status is crucial for the development of therapeutic interventions for infections to reduce recovery time of wounded patients injured by explosive devices., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bergmann-Leitner, Bobrov, Bolton, Rouse, Heyburn, Pavlovic, Garry, Alamneh, Long, Swierczewski, Tyner, Getnet, Sajja and Antonic.)

Near-field acoustical holography (NAH) is a useful tool for sound field reconstruction and sound source identification. In NAH, a basis model is first selected to represent the physical sound field, and then a near-field measurement is made with a microphone array. Next, the parameters in the selected model can be estimated based on the measurements by using an inverse approach, resulting in the sound field near the source being reconstructed so that the sound source location can be identified. But, in addition to being able to reconstruct the near-field of a source, the far-field can also be predicted with the identified sound source model. A significant amount of work has been performed to study the near-field reconstruction capability of different NAH algorithms, but there has been a limited number of publications in which the far-field prediction accuracy, based on the near-field measurement constructed model, has been considered. In the present experimental work, two multi-transducer loudspeakers were placed side-by-side to create a multi-component sound source, and two sets of measurements were conducted: an intensity probe scanned the sound field generated by the loudspeakers in both the near-field (0.05 m) and far-field (0.48 m) such that the true near- and far-field intensity spatial distributions and total sound power could be identified. Then, based on the near-field pressure measurements, four acoustical holography algorithms, statistically optimized near-field acoustical holography, wideband acoustical holography, l 1 -norm minimization, and a hybrid compressive sampling method were used to predict the near- and far-field sound intensity distributions. The near- and far-field prediction results were compared with the direct measurement, and the sound field reconstruction accuracy was studied. It was found that all of the algorithms were able to reconstruct the near-field well when the near-field measurements were used to construct the model. It was found that with the abovementioned models, far-field reconstructions could correctly predict the spatial sound field distribution, but in all of the cases, the total sound power was underestimated.

The acoustical behavior of air-saturated aerogel powders in the audible frequency range is not well understood. It is not clear, for example, which physical processes control the acoustic absorption and/or attenuation in a very light, loose granular mix in which the grain diameter is on the order of a micron. The originality of this work is the use of a Biot-type poro-elastic model to fit accurately the measured absorption coefficients of two aerogel powders with particle diameters in the range 1-40 μm. It is shown that these materials behave like a viscoelastic layer and their absorption coefficient depends strongly on the root mean square sound pressure in the incident wave. Furthermore, it was found that the loss factor controlling the energy dissipation due to the vibration of the elastic frame is a key model parameter. The value of this parameter decreased progressively with the frequency and sound pressure. In contrast, other fitted parameters in the Biot-type poro-elastic model, e.g., the stiffness of the elastic frame and pore size, were found to be relatively independent of the frequency and amplitude of the incident wave. It is shown that these materials absorb acoustic waves very efficiently around the frequencies of the frame resonance.

Immune correlates of protection remain elusive for most vaccines. An identified immune correlate would accelerate the down-selection of vaccine formulations by reducing the need for human pathogen challenge studies that are currently required to determine vaccine efficacy. Immunization via mosquito-delivered, radiation-attenuated P. falciparum sporozoites (IMRAS) is a well-established model for efficacious malaria vaccines, inducing greater than 90% sterile immunity. The current immunoprofiling study utilized samples from a clinical trial in which vaccine dosing was adjusted to achieve only 50% protection, thus enabling a comparison between protective and non-protective immune signatures. In-depth immunoprofiling was conducted by assessing a wide range of antigen-specific serological and cellular parameters and applying our newly developed computational tools, including machine learning. The computational component of the study pinpointed previously un-identified cellular T cell subsets (namely, TNFα-secreting CD8 + CXCR3 - CCR6 - T cells, IFNγ-secreting CD8 + CCR6 + T cells and TNFα/FNγ-secreting CD4 + CXCR3 - CCR6 - T cells) and B cell subsets (i.e., CD19 + CD24 hi CD38 hi CD69 + transitional B cells) as important factors predictive of protection (92% accuracy). Our study emphasizes the need for in-depth immunoprofiling and subsequent data integration with computational tools to identify immune correlates of protection. The described process of computational data analysis is applicable to other disease and vaccine models.

The emergence of variants of concern, some with reduced susceptibility to COVID-19 vaccines underscores consideration for the understanding of vaccine design that optimizes induction of effective cellular and humoral immune responses. We assessed a SARS-CoV-2 spike-ferritin nanoparticle (SpFN) immunogen paired with two distinct adjuvants, Alhydrogel ® or Army Liposome Formulation containing QS-21 (ALFQ) for unique vaccine evoked immune signatures. Recruitment of highly activated multifaceted antigen-presenting cells to the lymph nodes of SpFN+ALFQ vaccinated mice was associated with an increased frequency of polyfunctional spike-specific memory CD4 + T cells and K b spike-(539-546)-specific long-lived memory CD8 + T cells with effective cytolytic function and distribution to the lungs. The presence of this epitope in SARS-CoV, suggests that generation of cross-reactive T cells may be induced against other coronavirus strains. Our study reveals that a nanoparticle vaccine, combined with a potent adjuvant that effectively engages innate immune cells, enhances SARS-CoV-2-specific durable adaptive immune T cell responses., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Organisms harbour myriad microbes which can be parasitic or protective against harm. The costs and benefits resulting from these symbiotic relationships can be context-dependent, but the evolutionary consequences to hosts of these transitions remain unclear. Here, we mapped the Leucobacter genus across 13,715 microbiome samples (163 studies) to reveal a global distribution as a free-living microbe or a symbiont of animals and plants. We showed that across geographically distant locations (South Africa, France, Cape Verde), Leucobacter isolates vary substantially in their virulence to an associated animal host, Caenorhabditis nematodes. We further found that multiple Leucobacter sequence variants co-occur in wild Caenorhabditis spp. which combined with natural variation in virulence provides real-world potential for Leucobacter community composition to influence host fitness. We examined this by competing C. elegans genotypes that differed in susceptibility to different Leucobacter species in an evolution experiment. One Leucobacter species was found to be host-protective against another, virulent parasitic species. We tested the impact of host genetic background and Leucobacter community composition on patterns of host-based defence evolution. We found host genotypes conferring defence against the parasitic species were maintained during infection. However, when hosts were protected during coinfection, host-based defences were nearly lost from the population. Overall, our results provide insight into the role of community context in shaping host evolution during symbioses., (© 2021 The Authors. Molecular Ecology published by John Wiley & Sons Ltd.)

Rubisco assimilates CO2 to form the sugars that fuel life on earth. Correlations between rubisco kinetic traits across species have led to the proposition that rubisco adaptation is highly constrained by catalytic trade-offs. However, these analyses did not consider the phylogenetic context of the enzymes that were analyzed. Thus, it is possible that the correlations observed were an artefact of the presence of phylogenetic signal in rubisco kinetics and the phylogenetic relationship between the species that were sampled. Here, we conducted a phylogenetically resolved analysis of rubisco kinetics and show that there is a significant phylogenetic signal in rubisco kinetic traits. We re-evaluated the extent of catalytic trade-offs accounting for this phylogenetic signal and found that all were attenuated. Following phylogenetic correction, the largest catalytic trade-offs were observed between the Michaelis constant for CO2 and carboxylase turnover (∼21-37%), and between the Michaelis constants for CO2 and O2 (∼9-19%), respectively. All other catalytic trade-offs were substantially attenuated such that they were marginal (<9%) or non-significant. This phylogenetically resolved analysis of rubisco kinetic evolution also identified kinetic changes that occur concomitant with the evolution of C4 photosynthesis. Finally, we show that phylogenetic constraints have played a larger role than catalytic trade-offs in limiting the evolution of rubisco kinetics. Thus, although there is strong evidence for some catalytic trade-offs, rubisco adaptation has been more limited by phylogenetic constraint than by the combined action of all catalytic trade-offs., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

The antigenic drift theory states that influenza evolves via the gradual accumulation of mutations, decreasing a host's immune protection against previous strains. Influenza vaccines are designed accordingly, under the premise of antigenic drift. However, a paradox exists at the centre of influenza research. If influenza evolved primarily through mutation in multiple epitopes, multiple influenza strains should co-circulate. Such a multitude of strains would render influenza vaccines quickly inefficacious. Instead, a single or limited number of strains dominate circulation each influenza season. Unless additional constraints are placed on the evolution of influenza, antigenic drift does not adequately explain these observations. Here, we explore the constraints placed on antigenic drift and a competing theory of influenza evolution - antigenic thrift. In contrast to antigenic drift, antigenic thrift states that immune selection targets epitopes of limited variability, which constrain the variability of the virus. We explain the implications of antigenic drift and antigenic thrift and explore their current and potential uses in the context of influenza vaccine design.

Serological assessment of SARS-CoV-2 specific responses are an essential tool for determining the prevalence of past SARS-CoV-2 infections in the population especially when testing occurs after symptoms have developed and limited contact tracing is in place. The goal of our study was to test a new 10-plex electro-chemiluminescence-based assay to measure IgM and IgG responses to the spike proteins from multiple human coronaviruses including SARS-CoV-2, assess the epitope specificity of the SARS-CoV-2 antibody response against full-length spike protein, receptor-binding domain and N-terminal domain of the spike protein, and the nucleocapsid protein. We carried out the assay on samples collected from three sample groups: subjects diagnosed with COVID-19 from the U.S. Army hospital at Camp Humphreys in Pyeongtaek, South Korea; healthcare administrators from the same hospital but with no reported diagnosis of COVID-19; and pre-pandemic samples. We found that the new CoV-specific multiplex assay was highly sensitive allowing plasma samples to be diluted 1:30,000 with a robust signal. The reactivity of IgG responses to SARS-CoV-2 nucleocapsid protein and IgM responses to SARS-CoV-2 spike protein could distinguish COVID-19 samples from non-COVID-19 and pre-pandemic samples. The data from the three sample groups also revealed a unique pattern of cross-reactivity between SARS-CoV-2 and SARS-CoV-1, MERS-CoV, and seasonal coronaviruses HKU1 and OC43. Our findings show that the CoV-2 IgM response is highly specific while the CoV-2 IgG response is more cross-reactive across a range of human CoVs and also showed that IgM and IgG responses show distinct patterns of epitope specificity. In summary, this multiplex assay was able to distinguish samples by COVID-19 status and characterize distinct trends in terms of cross-reactivity and fine-specificity in antibody responses, underscoring its potential value in diagnostic or serosurveillance efforts., Competing Interests: The authors have declared that no competing interests exist.

Background: Optimal curative therapy for locally advanced esophageal and esophagogastric junction (EGJ) cancer might not be offered to elderly patients due to patient and treating physician perception of the high risk of therapy. To understand the risk of multimodality curative therapy, including surgical resection in the elderly population, we studied our experience with curative therapy in this patient population and compared the risks and outcomes with those in a younger population., Study Design: Between January 1, 2004 and December 31, 2019, four hundred and five consecutive patients with esophageal or EGJ cancer underwent primary treatment at our institution, including esophagectomy. Data collected included demographic information, tumor stage, preoperative Charlson Comorbidity Index scores, treatment variables, and short- and long-term outcomes. Patients who were 70 years or older were classified as the "older" group and patients younger than 70 years were "younger.", Results: One hundred and eighty-eight younger (mean age 59 years) and 94 older (mean age 74 years) patients received neoadjuvant chemoradiotherapy and surgical resection for stage II and higher cancer. Preoperative American Society of Anesthesiologist and Charlson Comorbidity Index scores were significantly worse in the older group. Postoperative atrial fibrillation and urinary retention developed more often in the older group. Despite this, the rate of postoperative Clavien-Dindo complication severity scores of 3 or higher, perioperative mortality rates, and lengths of stay were similar. Long-term age-adjusted survival rate was 44.8% at 5 years for the group 70 years or older and 39% for the group younger than 70 years (NS)., Conclusions: Patients 70 years and older with locally advanced esophageal or EGJ cancer should be evaluated for optimal curative therapy including neoadjuvant chemoradiotherapy and surgical resection. Although preoperative risk scoring and postoperative atrial arrythmias are higher in the older group, short- and long-term outcomes are not inferior in these patients., (Copyright © 2020 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

The circumsporozoite protein (CSP) is the main surface antigen of malaria sporozoites, a prime vaccine target, and is known to have polymorphisms in the C-terminal region. Vaccines using a single allele may have lower efficacy against genotypic variants. Recent studies have found evidence suggesting the efficacy of the CSP-based RTS,S malaria vaccine may be limited against P. falciparum CSP alleles that diverge from the 3D7 vaccine allele, particularly in this polymorphic C-terminal region. In order to assess the breadth of the RTS,S-induced antibody responses against CSP C-terminal antigenic variants, we used a novel multiplex assay to measure reactivity of serum samples from a recent RTS,S study against C-terminal peptides from 3D7 and seven additional CSP alleles that broadly represent the genetic diversity found in circulating P. falciparum field isolates. We found that responses to the variants showed, on average, a ~ 30-fold reduction in reactivity relative to the vaccine-matched 3D7 allele. The extent of this reduction, ranging from 21 to 69-fold, correlated with the number of polymorphisms between the variants and 3D7. We calculated antibody breadth of each sample as the median relative reactivity to the seven CSP variants compared to 3D7. Surprisingly, protection from 3D7 challenge in the RTS,S study was associated with higher C-terminal antibody breadth. These findings suggest CSP C-terminal-specific avidity or fine-specificity may play a role in RTS,S-mediated protection and that breadth of C-terminal CSP-specific antibody responses may be a marker of protection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Acoustic radiation modes (ARMs) have been widely used in noise control engineering. For an arbitrarily shaped radiator, ARMs are usually obtained by using the boundary element method (BEM). For high frequencies and large structures, the BEM calculation is usually time consuming. An alternative method was recently developed in which the ARMs are obtained by using generalized singular value decomposition and spherical harmonic functions. In this paper, spheroidal harmonic functions are used instead of spherical harmonic functions. The proposed method is potentially more efficient for ARM calculations for structures with one dimension significantly larger than the other two.

BackgroundThe progression and geographical distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United Kingdom (UK) and elsewhere is unknown because typically only symptomatic individuals are diagnosed. We performed a serological study of blood donors in Scotland in the spring of 2020 to detect neutralising antibodies to SARS-CoV-2 as a marker of past infection and epidemic progression.AimOur objective was to determine if sera from blood bank donors can be used to track the emergence and progression of the SARS-CoV-2 epidemic.MethodsA pseudotyped SARS-CoV-2 virus microneutralisation assay was used to detect neutralising antibodies to SARS-CoV-2. The study comprised samples from 3,500 blood donors collected in Scotland between 17 March and 18 May 2020. Controls were collected from 100 donors in Scotland during 2019.ResultsAll samples collected on 17 March 2020 (n = 500) were negative in the pseudotyped SARS-CoV-2 virus microneutralisation assay. Neutralising antibodies were detected in six of 500 donors from 23 to 26 March. The number of samples containing neutralising antibodies did not significantly rise after 5-6 April until the end of the study on 18 May. We found that infections were concentrated in certain postcodes, indicating that outbreaks of infection were extremely localised. In contrast, other areas remained comparatively untouched by the epidemic.ConclusionAlthough blood donors are not representative of the overall population, we demonstrated that serosurveys of blood banks can serve as a useful tool for tracking the emergence and progression of an epidemic such as the SARS-CoV-2 outbreak.

Only a small fraction of the antigens expressed by malaria parasites have been evaluated as vaccine candidates. A successful malaria subunit vaccine will likely require multiple antigenic targets to achieve broad protection with high protective efficacy. Here we describe protective efficacy of a novel antigen, Plasmodium yoelii (Py) E140 (PyE140), evaluated against P. yoelii challenge of mice. Vaccines targeting PyE140 reproducibly induced up to 100% sterile protection in both inbred and outbred murine challenge models. Although PyE140 immunization induced high frequency and multifunctional CD8+ T cell responses, as well as CD4+ T cell responses, protection was mediated by PyE140 antibodies acting against blood stage parasites. Protection in mice was long-lasting with up to 100% sterile protection at twelve weeks post-immunization and durable high titer anti-PyE140 antibodies. The E140 antigen is expressed in all Plasmodium species, is highly conserved in both P. falciparum lab-adapted strains and endemic circulating parasites, and is thus a promising lead vaccine candidate for future evaluation against human malaria parasite species., Competing Interests: The authors have read the journal’s policy and have the following conflicts: ECS, KJL, and JCA are named inventors on a patent application US PCT/US18/25510 covering methods and compositions for vaccinating against malaria. JCA is a named inventor on US patent number 10, 195, 260, US Patent Application No. 16/230,512, and related foreign applications covering the PfE140 antigen. NR, KO, JW, and JCA are/were employed by CAMRIS International, which is a commercial company that owns the rights to the PfE140 antigen under patent number 10, 195, 260. This does not alter our adherence to PLOS ONE policies on sharing data and materials. ERPi Inc., Meso Scale Diagnostics, Sanaria, and General Dynamics Information Technology Inc. are current affiliations for some authors who previously contributed to the study. Neither ERPi Inc., Meso Scale Diagnostics, Sanaria, nor General Dynamics Information Technology Inc. made any contribution to the study.

Background: Profiling immune responses induced by either infection or vaccination can provide insight into identification of correlates of protection. Furthermore, profiling of serological responses can be used to identify biomarkers indicative of exposure to pathogens. Conducting such immune surveillance requires readout methods that are high-throughput, robust, and require small sample volumes. While the enzyme-linked immunosorbent assay (ELISA) is the classical readout method for assessing serological responses, the advent of multiplex assays has significantly increased the throughput and capacity for immunoprofiling. This report describes the development and assay performance (sensitivity, linearity of detection, requirement for multiple dilutions for each sample, intra- and inter-assay variability) of an electro-chemiluminescence (ECLIA)-based multiplex assay., Methods: The current study describes the development of a multiplex ECLIA-based assay and characterizes the sensitivity, linear range, and inter- and intra-assay variability of the ECLIA platform and its agreement with the traditional ELISA. Special emphasis was placed on potential antigenic competition when testing closely related antigens in the multiplex format., Results: Multiplexing of antigens in ECLIA provides significant practical benefits in terms of reducing sample volume requirements and experimental time. Beyond the practical advantages of multiplexing, the ECLIA provides superior assay performance when compared to the ELISA. Not only does ECLIA show good agreement with the ELISA assay, but the linear range of ECLIA is also sufficiently wide to permit single-dilution measurements of concentration without the need to do serial dilutions. The lack of antigenic competition allows the simultaneous testing of closely related antigens, such as plate antigens representing different alleles of the same protein, which can inform about cross-reactivities-or lack thereof-of serological responses., Conclusion: The advantages of the newly developed tool for assessing the antigen profiles of serological responses may ultimately lead to the identification of biomarkers associated with various disease stages and or protection against disease.

Acoustic radiation modes (ARMs) have been widely used in noise control engineering owing to their convenient sound-power characteristics. However, the evaluation of ARMs for non-regular structures can be computationally intensive: it usually involves solving the boundary integral equation (BIE) by using the boundary element method in order to obtain the sound power radiation resistance matrix, followed by a singular value decomposition to obtain the radiation modes. The proposed procedure involves projecting spherical harmonics onto an enclosing surface, followed by the application of generalized singular value decomposition, with the result that the need to solve the BIE is eliminated, which potentially reduces the computational effort significantly.

Near-field Acoustical Holography is a powerful tool for sound source identification and sound field reconstruction. Generally, many microphone measurements are required to construct a source model that can span the whole sound source region while simultaneously avoiding measurement errors and ensuring a high spatial sampling rate. That type of measurement is economically costly and hard to perform in industrial environments. Motivated by the desire to be able to use a relatively small number of microphone measurements to reconstruct a sound field and to accurately identify sound source locations, an Equivalent Source Method (ESM) is considered here. In particular, the focus is on the combination of a monopole-distribution ESM and a relatively small number of microphone measurements, thus creating an under-determined system. Wideband Acoustical Holography and l 1 -norm Convex Optimization are introduced to solve this under-determined inverse problem. Based on the attributes of these two methods, a hybrid method combining the best features of each is proposed to identify sound source locations.

Background: Neoadjuvant therapy (NT) for borderline resectable pancreatic cancer (BRPC) has evolved to include multi-agent regimens and chemoradiation. We report our experience and compare outcomes of initially resectable pancreatic cancer (IRPC) vs BRPC receiving NT across two eras of chemotherapy regimens., Methods: Data were collected retrospectively on pancreaticoduodenectomy patients between January 2008 and October 2015. Outcomes and survival were compared based on patient, laboratory and treatment factors., Results: 195 patients were included and 133 had IRPC and 62 BRPC. IRPC operations were shorter (449 min vs 520 min, p = 0.003), had less blood loss (663 ml vs 954 ml, p = 0.002) and involved fewer vascular resections (29% vs 76%, p = 0.002). The rate of R0 resection was identical (82%, p = 1) and the IRPC group had higher node-positive ratio (19.3% vs 7.2% p < 0.0001). 15 patients received a single agent regimen while 47 received multi-agent regimens with 90% receiving radiation.Survival was similar between BRPC and IRPC (log-rank p = 0.7). Histopathologic response (CAP grade 0 or 1) was not associated with survival (p = 0.13), but completion of ≥4 cycles of multi-agent pre-operative chemotherapy (p = 0.001) and complete response to NT (p = 0.04) were significant predictors of survival., Conclusions: BRPC patients treated with NT have similar morbidity and survival to their IRPC counterparts. Pathologic response and modern NT are associated with improved survival., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

The equivalent source methods (ESM) that have been developed to this point can generally be classified into two categories: one in which a relatively large number of lower order sources are fixed at various locations, and one in which a series of higher order sources are fixed at one location. The present work started with a model in the latter category, but the individual sources were then allowed to move separately to locations which were determined by using a nonlinear optimization procedure based on the measured sound field data. To test this approach, experiments were conducted using a small loudspeaker cabinet; measurements were made using an array of microphones on all sides of the loudspeaker. It was found that by allowing the source components to move, the sound field representation in both the near and far fields was improved, particularly at high frequencies, compared to the model with fixed source locations. By comparison with results obtained from boundary element calculations based on laser vibrometer measurements of the loudspeaker's diaphragm and tweeter velocities, it was found that the proposed ESM can also be used to accurately predict the sound pressure distribution on the source surface.

Based on the idea that a layer of properly designed and manufactured fibrous material can serve as both a sound absorber and a structural damper, an approach is introduced in this article to design the microstructure of a fibrous layer for it to provide optimal damping performance. To begin with, previous work related to structural damping by fibrous layers was reviewed. Then the most appropriate models from the literature were adapted for use in the current study. A system comprising an aluminum panel and a limp fibrous layer was driven by a line force, and both the spatial velocity response of the panel and the power distribution within the system were calculated to quantify the degree of damping provided by the fibrous layer, which helped identify the airflow resistivity that provides optimal damping for any frequency and panel of interest. Given the optimal airflow resistivity, a model relating fiber microstructure to airflow resistivity was used to infer the optimal microstructure required to achieve the optimal damping performance. One finding of the current work, for example, was that as the target frequency was reduced, the fiber size required to achieve the optimal damping performance increased.

We present constraints on the masses of extremely light bosons dubbed fuzzy dark matter (FDM) from Lyman-α forest data. Extremely light bosons with a de Broglie wavelength of ∼1  kpc have been suggested as dark matter candidates that may resolve some of the current small scale problems of the cold dark matter model. For the first time, we use hydrodynamical simulations to model the Lyman-α flux power spectrum in these models and compare it to the observed flux power spectrum from two different data sets: the XQ-100 and HIRES/MIKE quasar spectra samples. After marginalization over nuisance and physical parameters and with conservative assumptions for the thermal history of the intergalactic medium (IGM) that allow for jumps in the temperature of up to 5000 K, XQ-100 provides a lower limit of 7.1×10^{-22}  eV, HIRES/MIKE returns a stronger limit of 14.3×10^{-22}  eV, while the combination of both data sets results in a limit of 20×10^{-22}  eV (2σ C.L.). The limits for the analysis of the combined data sets increases to 37.5×10^{-22}  eV (2σ C.L.) when a smoother thermal history is assumed where the temperature of the IGM evolves as a power law in redshift. Light boson masses in the range 1-10×10^{-22}  eV are ruled out at high significance by our analysis, casting strong doubts that FDM helps solve the "small scale crisis" of the cold dark matter models.

Though the ultrasonic excitation of surface waves in solids is generally realized through the use of a contact transducer, remote excitation would enable standoff testing in applications such as the nondestructive evaluation of structures. With respect to the optimal incident wave profile, bounded inhomogeneous waves, which include an exponentially decaying term, have been shown to improve the surface wave excitation efficiency as compared to Gaussian and square waves. The purpose of this work is to investigate the effect of varying the incident wave spatial decay rate, as applied to both lossless fluid-solid interfaces and to solids with viscoelastic losses included. The Fourier method is used to decompose the incident profile and subsequently compute the reflected wave profile. It is shown that inhomogeneous plane wave theory predicts, to a close approximation, the location of the minimum in the local reflection coefficient with respect to the decay rate for bounded incident waves. Moreover, plane wave theory gives a reasonable indication of the decay rate that maximizes the surface wave excitation efficiency.

The metamaterial under investigation here consists of a periodic arrangement of unit plates in a grid-like frame such that there is a contrast in the local areal mass between cell interior and cell wall. In the low frequency range and under normal incidence this metamaterial panel exhibits a sound transmission loss significantly larger than the transmission loss of an unstructured panel with the same homogeneous mass per unit area. However, when the incident sound field is diffuse, the relative advantage of the metamaterial barrier is reduced or eliminated. A sequence of experiments is documented to demonstrate that the relative advantage of the metamaterial barrier can be realized even in a diffuse sound field by creating a hybrid barrier system which embeds the metamaterial layer between a normalizing waveguide layer on the incident side and an absorbing layer on the transmitted side. The sound normalizing waveguide layer is a lattice structure, and the absorbing layer is high performance glass fiber mat. By using measurements of the transmission loss of a 1.2 m square panel system the role of each of these components is demonstrated.