Reassessing reverse triage in future conflict.

Future warfare will likely involve near-peer or peer-peer conflict in which there is a great risk of mass casualty scenarios. Because of anti-access and area denial, air superiority will not be guaranteed, which will hamper rapid evacuation of casualties as well as resupply. Under such circumstances, military medical personnel may be forced, due to the constraints of the battlefield and tactical necessity to return servicemembers to duty, to implement reverse triage in which servicemembers with less severe injuries are treated first. However, reverse triage is potentially incongruent with international humanitarian law. Furthermore, should reverse triage need to be implemented, from the extant military doctrine it is not certain when this would be appropriate or the steps that might be followed, which highlight the gaps that exist before reverse triage should be considered as military doctrine on the battlefield. Lastly, we question the psychological impact that reverse triage could portend on military medical personnel, unit morale and unit cohesion. While there have been recent recommendations that reverse triage might need to be implemented in a near-term future conflict, these issues linger. It is time for Western militaries to assess the merits of reverse triage and the potential drawbacks.

Neuroendocrine Lesions Arising From Mediastinal Teratoma-A Case Report and Literature Review.

Background. Neuroendocrine lesions arising from mediastinal teratomas are rare tumors with only small number of patients reported in literature. The behavior of these lesions appears to be different from traditional neuroendocrine neoplasms. A comprehensive review will be valuable for histologic assessment and treatment planning for similar cases. Case presentation. We present an example of a 57-year-old man who presented with cough. Subsequent work-up revealed an anterior mediastinal mass of 2.1 cm on computed tomography. The patient underwent robot-assisted thoracoscopic thymectomy. Histological examination revealed a mature cystic teratoma with a neuroendocrine component consisting of clusters of tumor cells with round to oval nuclei and a "salt-and-pepper" chromatin pattern. The tumor cells were immunoreactive to cytokeratin, synaptophysin, chromogranin, and INSM1, with a Ki-67 proliferative index of 4%. A histological diagnosis was mature teratoma with well-differentiated low-grade neuroendocrine tumor (carcinoid) was made. The patient was well and without disease after complete surgical excision at 10 months. Literature review. Literature reviewed yielded 13 examples of neuroendocrine lesions arising from mediastinal teratomas. No disease-related mortality was reported, even in lesions with high-grade neuroendocrine, carcinomatous, or immature teratomatous components. Conclusions. Surgical removal is the mainstay of treatment of these lesions, and the presence of a neuroendocrine component does not appear to negatively affect prognosis.

Abundant hydrocarbons in the disk around a very-low-mass star.

Very-low-mass stars (those less than 0.3 solar masses) host orbiting terrestrial planets more frequently than other types of stars. The compositions of those planets are largely unknown but are expected to relate to the protoplanetary disk in which they form. We used James Webb Space Telescope mid-infrared spectroscopy to investigate the chemical composition of the planet-forming disk around ISO-ChaI 147, a 0.11-solar-mass star. The inner disk has a carbon-rich chemistry; we identified emission from 13 carbon-bearing molecules, including ethane and benzene. The high column densities of hydrocarbons indicate that the observations probe deep into the disk. The high carbon-to-oxygen ratio indicates radial transport of material within the disk, which we predict would affect the bulk composition of any planets forming in the disk.

The impact of kit, environment, and sampling contamination on the observed microbiome of bovine milk.

In low-microbial biomass samples such as bovine milk, contaminants can outnumber endogenous bacteria. Because of this, milk microbiome research suffers from a critical knowledge gap, namely, does non-mastitis bovine milk contain a native microbiome? In this study, we sampled external and internal mammary epithelia and stripped and cisternal milk and used numerous negative controls, including air and sampling controls and extraction and library preparation blanks, to identify the potential sources of contamination. Two algorithms were used to mathematically remove contaminants and track the potential movement of microbes among samples. Results suggest that the majority (i.e., >75%) of sequence data generated from bovine milk and mammary epithelium samples represents contaminating DNA. Contaminants in milk samples were primarily sourced from DNA extraction kits and the internal and external skin of the teat, while teat canal and apex samples were mainly contaminated during the sampling process. After decontamination, the milk microbiome displayed a more dispersed, less diverse, and compositionally distinct bacterial profile compared with epithelial samples. Similar microbial compositions were observed between cisternal and stripped milk samples, as well as between teat apex and canal samples. Staphylococcus and Acinetobacter were the predominant genera detected in milk sample sequences, and bacterial culture showed growth of Staphylococcus and Corynebacterium spp. in 50% (7/14) of stripped milk samples and growth of Staphylococcus spp. in 7% (1/14) of cisternal milk samples. Our study suggests that microbiome data generated from milk samples obtained from clinically healthy bovine udders may be heavily biased by contaminants that enter the sample during sample collection and processing workflows.IMPORTANCEObtaining a non-contaminated sample of bovine milk is challenging due to the nature of the sampling environment and the route by which milk is typically extracted from the mammary gland. Furthermore, the very low bacterial biomass of bovine milk exacerbates the impacts of contaminant sequences in downstream analyses, which can lead to severe biases. Our finding showed that bovine milk contains very low bacterial biomass and each contamination event (including sampling procedure and DNA extraction process) introduces bacteria and/or DNA fragments that easily outnumber the native bacterial cells. This finding has important implications for our ability to draw robust conclusions from milk microbiome data, especially if the data have not been subjected to rigorous decontamination procedures. Based on these findings, we strongly urge researchers to include numerous negative controls into their sampling and sample processing workflows and to utilize several complementary methods for identifying potential contaminants within the resulting sequence data. These measures will improve the accuracy, reliability, reproducibility, and interpretability of milk microbiome data and research.

Exploring associations between the teat apex metagenome and Staphylococcus aureus intramammary infections in primiparous cows under organic directives.

The primary objective of this study was to identify associations between the prepartum teat apex microbiome and the presence of Staphylococcus aureus intramammary infections (IMI) in primiparous cows during the first 5 weeks after calving. We performed a case-control study using shotgun metagenomics of the teat apex and culture-based milk data collected longitudinally from 710 primiparous cows on five organic dairy farms. Cases had higher odds of having S. aureus metagenomic DNA on the teat apex prior to parturition compared to controls (OR = 38.9, 95% CI: 14.84-102.21). Differential abundance analysis confirmed this association, with cases having a 23.8 higher log fold change (LFC) in the abundance of S. aureus in their samples compared to controls. Of the most prevalent microorganisms in controls, those associated with a lower risk of post-calving S. aureus IMI included Microbacterium phage Min 1 (OR = 0.37, 95% CI: 0.25-0.53), Corynebacterium efficiens (OR = 0.53, 95% CI: 0.30-0.94), Kocuria polaris (OR = 0.54, 95% CI: 0.35-0.82), Micrococcus terreus (OR = 0.64, 95% CI: 0.44-0.93), and Dietzia alimentaria (OR = 0.45, 95% CI: 0.26-0.75). Genes encoding for Microcin B17 AMPs were the most prevalent on the teat apex of cases and controls (99.7% in both groups). The predicted abundance of genes encoding for Microcin B17 was also higher in cases compared to controls (LFC 0.26). IMPORTANCE: Intramammary infections (IMI) caused by Staphylococcus aureus remain an important problem for the dairy industry. The microbiome on the external skin of the teat apex may play a role in mitigating S. aureus IMI risk, in particular the production of antimicrobial peptides (AMPs) by commensal microbes. However, current studies of the teat apex microbiome utilize a 16S approach, which precludes the detection of genomic features such as genes that encode for AMPs. Therefore, further research using a shotgun metagenomic approach is needed to understand what role prepartum teat apex microbiome dynamics play in IMI risk.

Emission lines due to ionizing radiation from a compact object in the remnant of Supernova 1987A.

The nearby Supernova 1987A was accompanied by a burst of neutrino emission, which indicates that a compact object (a neutron star or black hole) was formed in the explosion. There has been no direct observation of this compact object. In this work, we observe the supernova remnant with JWST spectroscopy, finding narrow infrared emission lines of argon and sulfur. The line emission is spatially unresolved and blueshifted in velocity relative to the supernova rest frame. We interpret the lines as gas illuminated by a source of ionizing photons located close to the center of the expanding ejecta. Photoionization models show that the line ratios are consistent with ionization by a cooling neutron star or a pulsar wind nebula. The velocity shift could be evidence for a neutron star natal kick.

Identification of a broad sarbecovirus neutralizing antibody targeting a conserved epitope on the receptor-binding domain.

Omicron, as the emerging variant with enhanced vaccine tolerance, has sharply disrupted most therapeutic antibodies. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the subgenus Sarbecovirus, members of which share high sequence similarity. Herein, we report one sarbecovirus antibody, 5817, which has broad-spectrum neutralization capacity against SARS-CoV-2 variants of concern (VOCs) and SARS-CoV, as well as related bat and pangolin viruses. 5817 can hardly compete with six classes of receptor-binding-domain-targeted antibodies grouped by structural classifications. No obvious impairment in the potency is detected against SARS-CoV-2 Omicron and subvariants. The cryoelectron microscopy (cryo-EM) structure of neutralizing antibody 5817 in complex with Omicron spike reveals a highly conserved epitope, only existing at the receptor-binding domain (RBD) open state. Prophylactic and therapeutic administration of 5817 potently protects mice from SARS-CoV-2 Beta, Delta, Omicron, and SARS-CoV infection. This study reveals a highly conserved cryptic epitope targeted by a broad sarbecovirus neutralizing antibody, which would be beneficial to meet the potential threat of pre-emergent SARS-CoV-2 VOCs.

Utility of nucleic acid amplification test in the detection of tuberculosis in biological fluids from suspected TB patients in a cardiovascular center in the Philippines.

BACKGROUND: TB NAAT is highly sensitive and can therefore be a helpful tool used in confirming M. tuberculosis. In a prospective study, we evaluated the utility of TB NAAT in the detection of tuberculosis in biological fluids from suspected TB patients. METHODS: We compared tuberculosis nucleic acid amplification test and acid-fast bacilli smears with Lowenstein-Jensen culture, from patients with a clinical suspicion of tuberculosis disease. We calculated the sensitivity, specificity, PPV and NPV. RESULTS: Using the Lowenstein-Jensen culture as the gold standard for detection of Mycobacterium tuberculosis, the TB-NAAT showed sensitivity of 66.67 %, specificity of 93.67 %, and gave a positive predictive value of 44.44 %. CONCLUSION: We conclude that the TB-NAAT is a quick and consistent diagnostic test for TB detection. However, due to a comparably lower sensitivity than other previous studies, the utility of TB-NAAT alone may not be sufficient in the screening of TB patients. Likewise, the TB-NAAT cannot detect non-tuberculous mycobacteria, for which additional analysis may be needed.

Amino acid substitution L232F in non-structural protein 6 identified as a possible human-adaptive mutation in clade B MERS coronaviruses.

IMPORTANCE: Viral host adaptation plays an important role in inter-species transmission of coronaviruses and influenza viruses. Multiple human-adaptive mutations have been identified in influenza viruses but not so far in MERS-CoV that circulates widely in dromedary camels in the Arabian Peninsula leading to zoonotic transmission. Here, we analyzed clade B MERS-CoV sequences and identified an amino acid substitution L232F in nsp6 that repeatedly occurs in human MERS-CoV. Using a loss-of-function reverse genetics approach, we found the nsp6 L232F conferred increased viral replication competence in vitro, in cultures of the upper human respiratory tract ex vivo, and in lungs of mice infected in vivo. Our results showed that nsp6 L232F may be an adaptive mutation associated with zoonotic transmission of MERS-CoV. This study highlighted the capacity of MERS-CoV to adapt to transmission to humans and also the need for continued surveillance of MERS-CoV in camels.

Lab-on-a-chip optical biosensor platform: a micro-ring resonator integrated with a near-infrared Fourier transform spectrometer.

In this paper, we demonstrated the design and experimental results of the near-infrared lab-on-a-chip optical biosensor platform that monolithically integrates the MRR and the on-chip spectrometer on the silicon-on-insulator (SOI) wafer, which can eliminate the external optical spectrum analyzer for scanning the wavelength spectrum. The symmetric add-drop MRR biosensor is designed to have a free spectral range (FSR) of ∼19 nm and a bulk sensitivity of ∼73 nm/RIU; then the drop-port output resonance peaks are reconstructed from the integrated spatial-heterodyne Fourier transform spectrometer (SHFTS) with the spectral resolution of ∼3.1 nm and the bandwidth of ∼50 nm, which results in the limit of detection of 0.042 RIU.

Outflows from the youngest stars are mostly molecular.

The formation of stars and planets is accompanied not only by the build-up of matter, namely accretion, but also by its expulsion in the form of highly supersonic jets that can stretch for several parsecs1,2. As accretion and jet activity are correlated and because young stars acquire most of their mass rapidly early on, the most powerful jets are associated with the youngest protostars3. This period, however, coincides with the time when the protostar and its surroundings are hidden behind many magnitudes of visual extinction. Millimetre interferometers can probe this stage but only for the coolest components3. No information is provided on the hottest (greater than 1,000 K) constituents of the jet, that is, the atomic, ionized and high-temperature molecular gases that are thought to make up the jet's backbone. Detecting such a spine relies on observing in the infrared that can penetrate through the shroud of dust. Here we report near-infrared observations of Herbig-Haro 211 from the James Webb Space Telescope, an outflow from an analogue of our Sun when it was, at most, a few times 104 years old. These observations reveal copious emission from hot molecules, explaining the origin of the 'green fuzzies'4-7 discovered nearly two decades ago by the Spitzer Space Telescope8. This outflow is found to be propagating slowly in comparison to its more evolved counterparts and, surprisingly, almost no trace of atomic or ionized emission is seen, suggesting its spine is almost purely molecular.

Water in the terrestrial planet-forming zone of the PDS 70 disk.

Terrestrial and sub-Neptune planets are expected to form in the inner (less than 10 AU) regions of protoplanetary disks1. Water plays a key role in their formation2-4, although it is yet unclear whether water molecules are formed in situ or transported from the outer disk5,6. So far Spitzer Space Telescope observations have only provided water luminosity upper limits for dust-depleted inner disks7, similar to PDS 70, the first system with direct confirmation of protoplanet presence8,9. Here we report JWST observations of PDS 70, a benchmark target to search for water in a disk hosting a large (approximately 54 AU) planet-carved gap separating an inner and outer disk10,11. Our findings show water in the inner disk of PDS 70. This implies that potential terrestrial planets forming therein have access to a water reservoir. The column densities of water vapour suggest in-situ formation via a reaction sequence involving O, H2 and/or OH, and survival through water self-shielding5. This is also supported by the presence of CO2 emission, another molecule sensitive to ultraviolet photodissociation. Dust shielding, and replenishment of both gas and small dust from the outer disk, may also play a role in sustaining the water reservoir12. Our observations also reveal a strong variability of the mid-infrared spectral energy distribution, pointing to a change of inner disk geometry.

Maternal n-3 PUFA Intake During Pregnancy and Perinatal Mental Health Problems: A Systematic Review of Recent Evidence.

PURPOSE OF REVIEW: Pregnant women are vulnerable to mental health problems. Increasing evidence shows that omega-3 polyunsaturated fatty acid (n-3 PUFA) intake during pregnancy is beneficial to maternal perinatal mental health. A systematic review is needed to examine the associations reported in recent studies. The objective of this review was to provide an updated review on the association of antenatal n-3 PUFA intake via different sources (seafood, fish, overall diet, and supplementation) with perinatal mental health problems including depression, anxiety, and psychological distress. RECENT FINDINGS: Searches were performed in Web of Science, Embase, PubMed, and APA PsycInfo databases on 21 June 2021. A total of 2133 records were screened. Data including the name of the first author, publication year, study design, sample characteristics, dietary assessment time and tools, mental health outcome measures, and other relevant information were extracted. In total, 13 articles were included in this review and assessed qualitatively. The results demonstrated that dietary intake of n-3 PUFA during pregnancy was associated with perinatal mental health, but the effect of n-3 PUFA supplementation was influenced by pre-existing medical conditions, socio-demographic characteristics, and dietary and lifestyle patterns during pregnancy. Our review found that sources of n-3 PUFA may have differential effects on woman's mental health during and after pregnancy. Further research using large-size cohort or well-controlled trial protocol is needed to determine the effect of n-3 PUFA supplementation during pregnancy on perinatal mental health.

A point-of-care biosensor for rapid detection and differentiation of COVID-19 virus (SARS-CoV-2) and influenza virus using subwavelength grating micro-ring resonator.

In the context of continued spread of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 and the emergence of new variants, the demand for rapid, accurate, and frequent detection is increasing. Moreover, the new predominant strain, Omicron variant, manifests more similar clinical features to those of other common respiratory infections. The concurrent detection of multiple potential pathogens helps distinguish SARS-CoV-2 infection from other diseases with overlapping symptoms, which is significant for providing tailored treatment to patients and containing the outbreak. Here, we report a lab-on-a-chip biosensing platform for SARS-CoV-2 detection based on the subwavelength grating micro-ring resonator. The sensing surface is functionalized by specific antibody against SARS-CoV-2 spike protein, which could produce redshifts of resonant peaks by antigen-antibody combination, thus achieving quantitative detection. Additionally, the sensor chip is integrated with a microfluidic chip featuring an anti-backflow Y-shaped structure that enables the concurrent detection of two analytes. In this study, we realized the detection and differentiation of COVID-19 and influenza A H1N1. Experimental results indicate that the limit of detection of our device reaches 100 fg/ml (1.31 fM) within 15 min detecting time, and cross-reactivity tests manifest the specificity of the optical diagnostic assay. Furthermore, the integrated packaging and streamlined workflow facilitate its use for clinical applications. Thus, the biosensing platform presents a promising approach for attaining highly sensitive, selective, multiplexed, and quantitative point-of-care diagnosis and distinction between COVID-19 and influenza.

Corrigendum: XAV-19, a swine glyco-humanized polyclonal antibody against SARS-CoV-2 spike receptor-binding domain, targets multiple epitopes and broadly neutralizes variants.

[This corrects the article DOI: 10.3389/fimmu.2021.761250.].

Comparing the incubation period, serial interval, and infectiousness profile between SARS-CoV-2 Omicron and Delta variants.

In January 2022, the SARS-CoV-2 Omicron variants initiated major outbreaks and dominated the transmissions in Hong Kong, displacing an earlier outbreak seeded by the Delta variants. To provide insight into the transmission potential of the emerging variants, we aimed to compare the epidemiological characteristics of the Omicron and Delta variants. We analyzed the line-list clinical and contact tracing data of the SARS-CoV-2 confirmed cases in Hong Kong. Transmission pairs were constructed based on the individual contact history. We fitted bias-controlled models to the data to estimate the serial interval, incubation period and infectiousness profile of the two variants. Viral load data were extracted and fitted to the random effect models to investigate the potential risk modifiers for the clinical viral shedding course. Totally 14 401 confirmed cases were reported between January 1 and February 15, 2022. The estimated mean serial interval (4.4 days vs. 5.8 days) and incubation period (3.4 days vs. 3.8 days) were shorter for the Omicron than the Delta variants. A larger proportion of presymptomatic transmission was observed for the Omicron (62%) compared to the Delta variants (48%). The Omicron cases had higher mean viral load over an infection course than the Delta cases, with the elder cases appearing more infectious than the younger cases for both variants. The epidemiological features of Omicron variants were likely an obstacle to contact tracing measures, imposed as a major intervention in settings like Hong Kong. Continuously monitoring the epidemiological feature for any emerging SARS-CoV-2 variants in the future is needed to assist officials in planning measures for COVID-19 control.

Genetic diversity and molecular epidemiology of Middle East Respiratory Syndrome Coronavirus in dromedaries in Ethiopia, 2017-2020.

Middle East respiratory syndrome coronavirus (MERS-CoV) is enzootic in dromedary camels and causes zoonotic infection and disease in humans. Although over 80% of the global population of infected dromedary camels are found in Africa, zoonotic disease had only been reported in the Arabia Peninsula and travel-associated disease has been reported elsewhere. In this study, genetic diversity and molecular epidemiology of MERS-CoV in dromedary camels in Ethiopia were investigated during 2017-2020. Of 1766 nasal swab samples collected, 61 (3.5%) were detected positive for MERS-CoV RNA. Of 484 turbinate swab samples collected, 10 (2.1%) were detected positive for MERS-CoV RNA. Twenty-five whole genome sequences were obtained from these MERS-CoV positive samples. Phylogenetically, these Ethiopian camel-originated MERS-CoV belonged to clade C2, clustering with other East African camel strains. Virus sequences from camel herds clustered geographically while in an abattoir, two distinct phylogenetic clusters of MERS-CoVs were observed in two sequential sampling collections, which indicates the greater genetic diversity of MERS-CoV in abattoirs. In contrast to clade A and B viruses from the Arabian Peninsula, clade C camel-originated MERS-CoV from Ethiopia had various nucleotide insertions and deletions in non-structural gene nsp3, accessory genes ORF3 and ORF5 and structural gene N. This study demonstrates the genetic instability of MERS-CoV in dromedaries in East Africa, which indicates that the virus is still actively adapting to its camel host. The impact of the observed nucleotide insertions and deletions on virus evolution, viral fitness, and zoonotic potential deserves further study.

Randomized Trial of Tenofovir With or Without Peginterferon Alfa Followed by Protocolized Treatment Withdrawal in Adults With Chronic Hepatitis B.

INTRODUCTION: Hepatitis B surface antigen (HBsAg) loss is associated with improved long-term outcomes of patients with chronic hepatitis B but is infrequently achieved with current monotherapies. We assessed whether combination strategies that included treatment withdrawal enhanced HBsAg loss. METHODS: A randomized (1:1) trial of tenofovir disoproxil fumarate (TDF) for 192 weeks with or without peginterferon (PegIFN) alfa-2a for the first 24 weeks, followed by withdrawal of TDF at week 192 with 48 weeks of off-treatment follow-up to week 240. The primary end point was HBsAg loss at week 240. RESULTS: Of 201 participants (52% HBeAg positive, 12%/6% genotype A/A2, 7% cirrhosis) randomized to TDF + PegIFN (n = 102) or TDF alone (n = 99), 6 participants had lost HBsAg at the end of the treatment phase (week 192), 5 (5.3%) in the combination group, and 1 (1.0%) in the TDF alone group ( P = 0.09). By week 240, 9 participants had cleared HBsAg, 5.3% in combination, and 4.1% in monotherapy arms ( P = 0.73). HBsAg decline and loss occurred earlier with TDF + PegIFN than TDF, with a ≥1-logIU/mL qHBsAg decline by week 24 in 28% in TDF + PegIFN compared with 6% in TDF ( P = 0.04). HBsAg loss occurred in 7 of 12 (58%) with hepatitis B virus subgenotype A2 (all HBeAg positive) compared with only 2 of 189 (1%) with other hepatitis B virus genotypes and in 8 of 93 (8.6%) HBeAg positive vs 1 of 87 (1.1%) HBeAg negative. DISCUSSION: PegIFN combined TDF followed by protocolized TDF withdrawal led to earlier but not higher percentages of HBsAg clearance. Pretreatment HBeAg positivity and subgenotype A2 were strongly associated with HBsAg clearance.

Asymmetric comb waveguide for strong interactions between atoms and light.

Coupling quantum emitters and nanostructures, in particular cold atoms and optical waveguides, has recently raised a large interest due to unprecedented possibilities of engineering light-matter interactions. In this work, we propose a new type of periodic dielectric waveguide that provides strong interactions between atoms and guided photons with an unusual dispersion. We design an asymmetric comb waveguide that supports a slow mode with a quartic (instead of quadratic) dispersion and an electric field that extends far into the air cladding for an optimal interaction with atoms. We compute the optical trapping potential formed with two guided modes at frequencies detuned from the atomic transition. We show that cold Rubidium atoms can be trapped as close as 100 nm from the structure in a 1.3-mK-deep potential well. For atoms trapped at this position, the emission into guided photons is largely favored, with a beta factor as high as 0.88 and a radiative decay rate into the slow mode 10 times larger than the free-space decay rate. These figures of merit are obtained at a moderately low group velocity of c/50.