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Although the effectiveness of vaccination at preventing hospitalization and severe coronavirus disease (COVID-19) has been reported in numerous studies, the detailed mechanism of innate immunity occurring in host cells by breakthrough infection is unclear. One hundred forty-six patients were included in this study. To determine the effects of vaccination and past infection on innate immunity following SARS-CoV-2 infection, we analyzed the relationship between anti–SARS-CoV-2 S Abs and biomarkers associated with the deterioration of COVID-19 (IFN-λ3, C-reactive protein, lactate dehydrogenase, ferritin, procalcitonin, and D-dimer). Anti-S Abs were classified into two groups according to titer: high titer (≥250 U/ml) and low titer (

Background Acute exacerbation (AE) of interstitial lung disease (ILD) is a life-threatening condition that can cause idiopathic pulmonary fibrosis (IPF) and non-IPF. One of the causes of the poor prognostic outcomes of AE-ILD is believed to be the coagulation cascade due to tissue damage. We investigated whether coagulopathy in patients with AE-ILD occurred locally in the lungs using laboratory data. Methods A total of 81 patients with chronic and acute ILD were enrolled in this study. A retrospective analysis was performed in two groups: a chronic ILD group comprising 63 outpatients and an acute ILD group comprising 18 inpatients diagnosed with AE-ILD. Results ROC analysis of SP-D, TAT, D-dimer, and PIC levels indicated that these four markers might be good diagnostic markers of AE-ILD. Spearman’s correlation coefficient analysis revealed a positive correlation between SP-D and TAT (r=0.711, p=0.004), D-dimer (r=0.626, p=0.011), and PIC (r=0.741, p=0.002). Multiple regression analysis performed for TAT values with age, male sex, baseline use of anticoagulant drugs, acute ILD, IL-6 value, and SP-D value showed that the model could explain 57.6% of TAT values (R2 = 0.609, adjusted R2 = 0.576). In addition, the baseline use of anticoagulant drugs (β=-6.8092, pConclusion SP-D, TAT, D-dimer, and PIC may be useful markers for diagnosing AE-ILD. Based on these four serum markers, the present study suggests that coagulopathy caused by AE-ILD may occur locally in the lungs.

Information on marine CO2 system variability has been limited along the northeast Pacific Inside Passage despite the region's rich biodiversity, abundant fisheries, and developing aquaculture industry. Beginning in 2017, the Alaska Marine Highway System M/V Columbia has served as a platform for surface underway data collection while conducting twice weekly ∼1600 km transits between Bellingham, Washington, and Skagway, Alaska. Marine CO2 system patterns were evaluated using measurements made over a 2-year period, which revealed the seasonal cycle as the dominant mode of temporal variability. The amplitude of this signal varied spatially and was modulated by the relative influences of tidal mixing, net community production, and the magnitude and character of freshwater input. Surface water pHT (total hydrogen ion scale) and aragonite saturation state (Ωarag) were determined using carbon dioxide partial pressure (pCO2) data with alkalinity derived from a regional salinity-based relationship, which was evaluated using intervals of discrete seawater samples and underway pH measurements. High-pCO2, low-pHT, and corrosive Ωarag conditions (Ωarag

Variation in environmental conditions across a species’ range can alter their responses to environmental change through local adaptation and acclimation. Evolutionary responses, however, may be challenged in ecosystems with tightly coupled environmental conditions, where changes in the covariance of environmental factors may make it more difficult for species to adapt to global change. Here, we conduct a 3-month-long mesocosm experiment and find evidence for local adaptation/acclimation in populations of red sea urchins, Mesocentrotus franciscanus , to multiple environmental drivers. Moreover, populations differ in their response to projected concurrent changes in pH, temperature, and dissolved oxygen. Our results highlight the potential for local adaptation/acclimation to multivariate environmental regimes but suggest that thresholds in responses to a single environmental variable, such as temperature, may be more important than changes to environmental covariance. Therefore, identifying physiological thresholds in key environmental drivers may be particularly useful for preserving biodiversity and ecosystem functioning.

Although previous studies have revealed that elevated D-dimer in the early stage of coronavirus 2019 (COVID-19) indicates pulmonary intravascular coagulation, the state of coagulation/fibrinolysis disorder with normal D-dimer is unknown. The study aimed to investigate how coagulation/fibrinolysis markers affect severe respiratory failure in the early stage of COVID-19. Among 1043 patients with COVID-19, 797 patients were included in our single-center retrospective study. These 797 patients were divided into two groups, the normal D-dimer and elevated D-dimer groups and analyzed for each group. A logistic regression model was fitted for age, sex, body mass index (BMI) ≥ 30 kg/m2, fibrinogen ≥ 617 mg/dL, thrombin-antithrombin complex (TAT) ≥ 4.0 ng/mL, and plasmin-alpha2-plasmin inhibitor-complex (PIC) > 0.8 µg/mL. A multivariate analysis of the normal D-dimer group demonstrated that being male and TAT ≥ 4.0 ng/mL significantly affected severe respiratory failure. In a multivariate analysis of the elevated D-dimer group, BMI ≥ 30 kg/m2 and fibrinogen ≥ 617 mg/dL significantly affected severe respiratory failure. The elevated PIC did not affect severe respiratory failure in any group. Our study demonstrated that hypercoagulation due to SARS-CoV-2 infection may occur even during a normal D-dimer level, causing severe respiratory failure in COVID-19.

We introduce three new Empirical Seawater Property Estimation Routines (ESPERs) capable of predicting seawater phosphate, nitrate, silicate, oxygen, total titration seawater alkalinity, total hydrogen scale pH (pHT), and total dissolved inorganic carbon (DIC) from up to 16 combinations of seawater property measurements. The routines generate estimates from neural networks (ESPER_NN), locally interpolated regressions (ESPER_LIR), or both (ESPER_Mixed). They require a salinity value and coordinate information, and benefit from additional seawater measurements if available. These routines are intended for seawater property measurement quality control and quality assessment, generating estimates for calculations that require approximate values, original science, and producing biogeochemical property context from a data set. Relative to earlier LIR routines, the updates expand their functionality, including new estimated properties and combinations of predictors, a larger training data product including new cruises from the 2020 Global Data Analysis Project data product release, and the implementation of a first-principles approach for quantifying the impacts of anthropogenic carbon on DIC and pHT. We show that the new routines perform at least as well as existing routines, and, in some cases, outperform existing approaches, even when limited to the same training data. Given that additional training data has been incorporated into these updated routines, these updates should be considered an improvement over earlier versions. The routines are intended for all ocean depths for the interval from 1980 to ~2030 c.e., and we caution against using the routines to directly quantify surface ocean seasonality or make more distant predictions of DIC or pHT., 1,823

To evaluate the efficacy and safety of nafamostat combined with favipiravir for coronavirus disease 2019.We conducted a multicenter, randomized, single-blind, placebo-controlled parallel assignment study in hospitalized patients with mild-to-moderate coronavirus disease 2019 pneumonia. Patients were randomly assigned to receive favipiravir alone (n=24) or nafamostat with favipiravir (n=21). Outcomes included changes in the WHO Clinical Progression Scale score, time to improvement in body temperature, and improvement in oxygen saturation (SpOThere was no significant difference in changes in the Clinical Progression Scale between nafamostat with favipiravir and favipiravir alone groups (median, -0·444 vs. -0·150, respectively; least-squares mean difference, -0·294; p=0·364). Time to improvement in body temperature was significantly shorter in the combination group (5·0 days; 95% CI, 4·0-7·0) than in the favipiravir group (9·0 days; 95% CI, 7·0-18·0; p=0·009). Changes in SpOAlthough our study showed no differences in clinical progression, earlier defervescence and recovery of SpOThis study was registered in the Japan Registry of Clinical Trials (identifier: jRCTs031200026) and WHO's International Clinical Trial Registry Platform (identifier: JPRN-jRCTs031200026).

Background: Early intramuscular administration of SARS-CoV-2-neutralising monoclonal antibody combination, tixagevimab–cilgavimab, to non-hospitalised adults with mild to moderate COVID-19 has potential to prevent disease progression. We aimed to evaluate the safety and efficacy of tixagevimab–cilgavimab in preventing progression to severe COVID-19 or death. Methods: TACKLE is an ongoing, phase 3, randomised, double-blind, placebo-controlled study conducted at 95 sites in the USA, Latin America, Europe, and Japan. Eligible participants were non-hospitalised adults aged 18 years or older with a laboratory-confirmed SARS-CoV-2 infection (determined by RT-PCR or an antigen test) from any respiratory tract specimen collected 3 days or less before enrolment and who had not received a COVID-19 vaccination. A WHO Clinical Progression Scale score from more than 1 to less than 4 was required for inclusion and participants had to receive the study drug 7 days or less from self-reported onset of mild to moderate COVID-19 symptoms or measured fever. Participants were randomly assigned (1:1) to receive either a single tixagevimab–cilgavimab 600 mg dose (two consecutive 3 mL intramuscular injections, one each of 300 mg tixagevimab and 300 mg cilgavimab) or placebo. Randomisation was stratified (using central blocked randomisation with randomly varying block sizes) by time from symptom onset, and high-risk versus low-risk of progression to severe COVID-19. Participants, investigators, and sponsor staff involved in the treatment or clinical evaluation and monitoring of the participants were masked to treatment-group assignments. The primary endpoints were severe COVID-19 or death from any cause through to day 29, and safety. This study is registered with ClinicalTrials.gov, NCT04723394. Findings: Between Jan 28, 2021, and July 22, 2021, 1014 participants were enrolled, of whom 910 were randomly assigned to a treatment group (456 to receive tixagevimab–cilgavimab and 454 to receive placebo). The mean age of participants was 46·1 years (SD 15·2). Severe COVID-19 or death occurred in 18 (4%) of 407 participants in the tixagevimab–cilgavimab group versus 37 (9%) of 415 participants in the placebo group (relative risk reduction 50·5% [95% CI 14·6–71·3]; p=0·0096). The absolute risk reduction was 4·5% (95% CI 1·1–8·0; p Interpretation: A single intramuscular tixagevimab–cilgavimab dose provided statistically and clinically significant protection against progression to severe COVID-19 or death versus placebo in unvaccinated individuals and safety was favourable. Treating mild to moderate COVID-19 earlier in the disease course with tixagevimab–cilgavimab might lead to more favourable outcomes.

Acidification-induced changes in neurological function have been documented in several tropical marine fishes. Here, we investigate whether similar patterns of neurological impacts are observed in a temperate Pacific fish that naturally experiences regular and often large shifts in environmental pH/pCO

Global‐scale ocean acidification has spurred interest in the capacity of seagrass ecosystems to increase seawater pH within crucial shoreline habitats through photosynthetic activity. However, the dynamic variability of the coastal carbonate system has impeded generalization into whether seagrass aerobic metabolism ameliorates low pH on physiologically and ecologically relevant timescales. Here we present results of the most extensive study to date of pH modulation by seagrasses, spanning seven meadows (Zostera marina) and 1000 km of U.S. west coast over 6 years. Amelioration by seagrass ecosystems compared to non‐vegetated areas occurred 65% of the time (mean increase 0.07 ± 0.008 SE). Events of continuous elevation in pH within seagrass ecosystems, indicating amelioration of low pH, were longer and of greater magnitude than opposing cases of reduced pH or exacerbation. Sustained elevations in pH of >0.1, comparable to a 30% decrease in [H+], were not restricted only to daylight hours but instead persisted for up to 21 days. Maximal pH elevations occurred in spring and summer during the seagrass growth season, with a tendency for stronger effects in higher latitude meadows. These results indicate that seagrass meadows can locally alleviate low pH conditions for extended periods of time with important implications for the conservation and management of coastal ecosystems., The most extensive study to date of pH modulation by seagrasses, spanning seven meadows (Zostera marina) and 1000 km of U.S. west coast over 6 years. Amelioration of low pH by seagrass ecosystems occurred most of the time, where events of continuous elevation in pH were longer and of greater magnitude than opposing cases of reduced pH or exacerbation. Sustained elevations in pH were not restricted only to daylight hours. Maximal pH elevations occurred in spring and summer during the seagrass growth season, with a tendency for stronger effects in higher latitude meadows.

The California Current System is thought to be particularly vulnerable to ocean acidification, yet pH remains chronically undersampled along this coast, limiting our ability to assess the impacts of ocean acidification. To address this observational gap, we integrated the Deep-Sea-DuraFET, a solid-state pH sensor, onto a Spray underwater glider. Over the course of a year starting in April 2019, we conducted seven missions in central California that spanned 161 glider days and >1600 dives to a maximum depth of 1000 m. The sensor accuracy was estimated to be ± 0.01 based on comparisons to discrete samples taken alongside the glider (n = 105), and the precision was ±0.0016. CO2 partial pressure, dissolved inorganic carbon, and aragonite saturation state could be estimated from the pH data with uncertainty better than ± 2.5%, ± 8 μmol kg−1, and ± 2%, respectively. The sensor was stable to ±0.01 for the first 9 months but exhibited a drift of 0.015 during the last mission. The drift was correctable using a piecewise linear regression based on a reference pH field at 450 m estimated from published global empirical algorithms. These algorithms require accurate O2 as inputs; thus, protocols for a simple predeployment air calibration that achieved accuracy of better than 1% were implemented. The glider observations revealed upwelling of undersaturated waters with respect to aragonite to within 5 m below the surface near Monterey Bay. These observations highlight the importance of persistent observations through autonomous platforms in highly dynamic coastal environments.

Ion-sensitive field effect transistor-based pH sensors have been shown to perform well in high frequency and long-term ocean sampling regimes. The Honeywell Durafet is widely used due to its stability, fast response, and characterization over a large range of oceanic conditions. However, potentiometric pH monitoring is inherently complicated by the fact that the sensors require careful calibration. Offsets in calibration coefficients have been observed when comparing laboratory to field-based calibrations and prior work has led to the recommendation that an in situ calibration be performed based on comparison to discrete samples. Here, we describe our work toward a self-calibration apparatus integrated into a SeapHOx pH, dissolved oxygen, and CTD sensor package. This Self-Calibrating SeapHOx is capable of autonomously recording calibration values from a high quality, traceable, primary reference standard: equimolar tris buffer. The Self-Calibrating SeapHOx's functionality was demonstrated in a 6-d test in a seawater tank at Scripps Institution of Oceanography (La Jolla, California, U.S.A.) and was successfully deployed for 2 weeks on a shallow, coral reef flat (Lizard Island, Australia). During the latter deployment, the tris-based self-calibration using 15 on-board samples exhibited superior reproducibility to the standard spectrophotometric pH-based calibration using > 100 discrete samples. Standard deviations of calibration pH using tris ranged from 0.002 to 0.005 whereas they ranged from 0.006 to 0.009 for the standard spectrophotometric pH-based method; the two independent calibration methods resulted in a mean pH difference of 0.008. We anticipate that the Self-Calibrating SeapHOx will be capable of autonomously providing climate quality pH data, directly linked to a primary seawater pH standard, and with improvements over standard calibration techniques.

A substantial body of research now exists demonstrating sensitivities of marine organisms to ocean acidification (OA) in laboratory settings. However, corresponding in situ observations of marine species or ecosystem changes that can be unequivocally attributed to anthropogenic OA are limited. Challenges remain in detecting and attributing OA effects in nature, in part because multiple environmental changes are co-occurring with OA, all of which have the potential to influence marine ecosystem responses. Furthermore, the change in ocean pH since the industrial revolution is small relative to the natural variability within many systems, making it difficult to detect, and in some cases, has yet to cross physiological thresholds. The small number of studies that clearly document OA impacts in nature cannot be interpreted as a lack of larger-scale attributable impacts at the present time or in the future but highlights the need for innovative research approaches and analyses. We summarize the general findings in four relatively well-studied marine groups (seagrasses, pteropods, oysters, and coral reefs) and integrate overarching themes to highlight the challenges involved in detecting and attributing the effects of OA in natural environments. We then discuss four potential strategies to better evaluate and attribute OA impacts on species and ecosystems. First, we highlight the need for work quantifying the anthropogenic input of CO2 in coastal and open-ocean waters to understand how this increase in CO2 interacts with other physical and chemical factors to drive organismal conditions. Second, understanding OA-induced changes in population-level demography, potentially increased sensitivities in certain life stages, and how these effects scale to ecosystem-level processes (e.g. community metabolism) will improve our ability to attribute impacts to OA among co-varying parameters. Third, there is a great need to understand the potential modulation of OA impacts through the interplay of ecology and evolution (eco–evo dynamics). Lastly, further research efforts designed to detect, quantify, and project the effects of OA on marine organisms and ecosystems utilizing a comparative approach with long-term data sets will also provide critical information for informing the management of marine ecosystems.

Biogeochemical-Argo (BGC-Argo) is a network of profiling floats carrying sensors that enable observation of as many as six essential biogeochemical and bio-optical variables: oxygen, nitrate, pH, chlorophyll a, suspended particles, and downwelling irradiance. This sensor network represents today's most promising strategy for collecting temporally and vertically resolved observations of biogeochemical properties throughout the ocean. All data are freely available within 24 hours of transmission. These data fill large gaps in ocean-observing systems and support three ambitions: gaining a better understanding of biogeochemical processes (e.g., the biological carbon pump and air–sea CO2 exchanges) and evaluating ongoing changes resulting from increasing anthropogenic pressure (e.g., acidification and deoxygenation); managing the ocean (e.g., improving the global carbon budget and developing sustainable fisheries); and carrying out exploration for potential discoveries. The BGC-Argo network has already delivered extensive high-quality global data sets that have resulted in unique scientific outcomes from regional to global scales. With the proposed expansion of BGC-Argo in the near future, this network has the potential to become a pivotal observation system that links satellite and ship-based observations in a transformative manner.

To investigate changes in ocean structure during the spring transition and responses of biological activity, two BGC-Argo floats equipped with oxygen, fluorescence (to estimate chlorophyll a concentration – Chl a), backscatter (to estimate particulate organic carbon concentration – [POC]), and nitrate sensors conducted daily vertical profiles of the water column from a depth of 2000 m to the sea surface in the western North Pacific from January to April of 2018. Data for calibrating each sensor were obtained via shipboard sampling that occurred when the floats were deployed and recovered. During the float-deployment periods, repeated meteorological disturbances passed over the study area and caused the mixed layer to deepen. After deep-mixing events, the upper layer restratified and nitrate concentrations decreased while Chl a and POC concentrations increased, suggesting that spring mixing events promote primary productivity through the temporary alleviation of nutrient and light limitation. At the end of March, POC accumulation rates and nitrate decrease rates within the euphotic zone (0–70 m) were the largest of the four events observed, ranging from +84 to +210 mmol C m−2 d−1 and –28 to –49 mmol N m−2 d−1, respectively. The subsurface consumption rate of oxygen (i.e., the degradation rate of organic matter) after the fourth event (the end of March) was estimated to be –0.62 micromol O2 kg−1 d−1. At depths of 300–400 m (below the mixed layer), the POC concentrations increased slightly throughout the observation period. The POC flux at a depth of 300 m was estimated to be 1.1 mmol C m−2 d−1. Our float observation has made it possible to observed biogeochemical parameters, which previously could only be estimated by shipboard observation and experiments, in the field and in real time.

Information on marine CO2 system variability has been limited along the Inside Passage of the Pacific Northwest coast of North America despite the region’s rich biodiversity, abundant fisheries, and developing aquaculture industry. Beginning in 2017, the Alaska Marine Highway System M/V Columbia has served as a platform for surface underway data collection while conducting twice weekly ~1600-km transits between Bellingham, Washington and Skagway, Alaska. This dataset allowed for the assessment of marine CO2 system patterns along the Inside Passage, including quantification of the relative importance of key drivers in shaping pCO2 variability. Surface water pH and aragonite saturation state (Ωarag) were determined using the pCO2 data with alkalinity from a regional salinity-based relationship, which was evaluated with discrete seawater samples and underway pH measurements. Low pH and corrosive (Ωarag < 1) Ωarag conditions were seen during winter and in persistent tidal mixing zones, and corrosive Ωarag values were also seen in areas that receive significant glacial melt in summer. The time-of-detection was computed and revealed that tidal mixing zones may be sentinel observing sites with relatively short time spans of observation needed to capture secular trends in seawater pCO2 equivalent to the contemporary atmospheric CO2 increase. Finally, anthropogenic CO2 was estimated and showed notable time and space variability. We theoretically considered the change in hydrogen ion concentration ([H+]), pH, and Ωarag over the industrial era and to an atmospheric pCO2 level consistent with a 1.5 °C warmer climate and revealed greater changes in [H+] and pH in winter as opposed to larger Ωarag change in summer. In addition, the contemporary acidification signal everywhere along the Inside Passage exceeded the global average, with Johnstone Strait and the Salish Sea standing out as potential bellwethers for biological OA impacts. In theory, roughly half the acidification signal experienced thus far over the industrial era may be expected over the coming 15 years with an atmospheric CO2 trajectory that continues to be shaped by fossil-fuel development.

Acidification-induced changes in cognitive function and behavior have recently been documented in tropical marine fishes, raising concerns about related shifts in species interactions. Here, we investigate whether similar patterns of broad neurological impacts are observed in a temperate Pacific fish that experiences regular and often large shifts in environmental pH due to upwelling events and other natural phenomena. In two manipulative laboratory experiments, we tested the effect of acidification, as well as pH variability, on gene expression in the brain tissue of a common temperate kelp forest/estuarine fish, Embiotoca jacksoni. We found that patterns of global gene expression in brain tissue differed significantly across pH level treatments. Additionally, differential gene expression analysis and gene set enrichment analysis identified significant differential expression of specific genes and gene sets both in comparisons of static pH level treatments as well as in static vs. variable pH treatment comparisons where mean pH was consistent. Enriched gene sets included those related to ion transport, signaling pathways, mRNA processing and splicing, and epigenetic regulation of gene expression, among others. Importantly, we found that pH variability decreased the number of differentially expressed genes detected between high and low pH treatments, and that the inter-individual variability in gene expression was significantly greater in variable pH treatments than static treatments of the same mean pH. By demonstrating a broad shift in brain gene expression, these results provide important confirmation of neurological impacts of acidification in a temperate fish species, which are likely to translate to shifts in behavior. This study also provides critical insight into the potential of natural environmental variability to mediate the impacts of ocean acidification.

BackgroundAlthough several studies have reported an association between atherosclerosis-related diseases and COVID-19, the relationship between COVID-19 severity and atherosclerosis progression remains unclear. The aim of this study is to determine the coronary artery calcium score (CACS) prognostic value in patients with COVID-19 using indices such as deterioration in oxygenation and CT images of the chest.MethodsThis was a single-centre retrospective study of 53 consecutive patients with COVID-19 in Narita who were admitted to our hospital between March 2020 and August 2020. CACS was calculated based on non-gated CT scans of the chest performed on admission day. The patients were divided into the following two groups based on CACS: group 1 (CACS ≥180, n=11) and group 2 (CACS ResultsMultivariable logistic regression analysis of age, sex, smoking history, diabetes, hypertension, dyslipidaemia, number of days from symptom onset to hospitalisation and CACS of ≥180 was performed. It revealed that unlike CACS of ConclusionCACS may be a prognosis marker of COVID-19 severity. Although coronary artery calcification is not typically assessed in pneumonia cases, it may provide a valuable clinical indicator for predicting severe COVID-19 outcomes.

Background Although high-flow nasal cannula (HFNC) oxygen treatment has been frequently used in coronavirus disease 2019 (COVID-19) patients with acute respiratory failure after the 3rd wave of the pandemic in Japan, the usefulness of the indicators of ventilator avoidance, including respiratory rate-oxygenation (ROX) index and other parameters, namely oxygen saturation/fraction of inspired oxygen ratio and respiratory rate (RR), remain unclear. Methods Between January and May 2021, our institution treated 189 COVID-19 patients with respiratory failure requiring oxygen, among which 39 patients requiring HFNC treatment were retrospectively analyzed. The group that switched from HFNC treatment to conventional oxygen therapy (COT) was defined as the HFNC success group, and the group that switched from HFNC treatment to a ventilator was defined as the HFNC failure group. We followed the patients' oxygenation parameters for a maximum of 30 days. Results HFNC treatment success occurred in 24 of 39 patients (62%) treated with HFNC therapy. Compared with the HFNC failure group, the HFNC success group had a significantly higher degree of RR improvement in the univariate analysis. Logistic regression analysis of HFNC treatment success adjusting for age, respiratory improvement, and a ROX index ≥5.55 demonstrated that an improved RR was associated with HFNC treatment success. The total COT duration was significantly shorter in the HFNC success group than in the HFNC failure group. Conclusions HFNC treatment can be useful for ventilator avoidance and allow the quick withdrawal of oxygen administration. RR improvement may be a convenient, useful, and simple indicator of HFNC treatment success.

The role of immune checkpoint inhibitors in metastatic lung cancer has been established in recent years and the pretherapeutic profiles of the tumor microenvironment in responders have been increasingly reported. The role of salvage surgery and the immune profiles of the posttherapeutic specimens in patients achieving an objective response have rarely been studied. We report a case of metastatic lung cancer treated by anti‐programmed death‐1 Ab followed by surgical resection. The immune status of the tumor was assessed, showing germinal center formation, memory B cell infiltration, and a high frequency of interferon gamma ‐secreting T cells., The role of salvage surgery and the immune profiles of posttherapeutic specimens in patients achieving an objective response with immune checkpoint inhibitors have rarely been studied. We report a case of metastatic lung cancer treated by anti‐programmed death‐1 Ab followed by surgical resection. The immune status of the tumor microenvironment was assessed, showing germinal center formation, memory B cell infiltration, and a high frequency of T cells with a T helper 1 phenotype.

Purpose of Review We summarize recent progress on autonomous observations of ocean carbonate chemistry and the development of a network of sensors capable of observing carbonate processes at multiple temporal and spatial scales. Recent Findings The development of versatile pH sensors suitable for both deployment on autonomous vehicles and in compact, fixed ecosystem observatories has been a major development in the field. The initial large-scale deployment of profiling floats equipped with these new pH sensors in the Southern Ocean has demonstrated the feasibility of a global autonomous open-ocean carbonate observing system. Summary Our developing network of autonomous carbonate observations is currently targeted at surface ocean CO2 fluxes and compact ecosystem observatories. New integration of developed sensors on gliders and surface vehicles will increase our coastal and regional observational capability. Most autonomous platforms observe a single carbonate parameter, which leaves us reliant on the use of empirical relationships to constrain the rest of the carbonate system. Sensors now in development promise the ability to observe multiple carbonate system parameters from a range of vehicles in the near future.

During 2015–2016, an El Nino and associated warm water event caused widespread coral bleaching across the equatorial Pacific. Here, we combine 8 yr of benthic monitoring data from permanent photoquadrats with remotely sensed and in situ temperature measurements to assess the impact of the warming event on benthic communities at Palmyra Atoll. We quantified bleaching prevalence across two distinct reef habitats using the best available data. On the fore reef (~ 10 m depth), we quantified bleaching severity within 100–200 m2 large-area plots using the custom visualization and analysis software, Viscore. On the reef terrace (~ 5 m depth), we used 95 focal colonies across three species that have been monitored annually since 2014. The 2015–2016 warm water event was the most extreme such event recorded on Palmyra in the past several decades with a maximum cumulative heat stress (degree heating weeks) of 11.9 °C-weeks. On the fore reef, 90% of live coral cover exhibited some degree of bleaching (32% severe bleaching). On the shallow reef terrace, bleaching was observed in 93% of the focal colonies across all species. Overall, coral cover declined 9% on the fore reef from 2014 to 2017, whereas coral cover did not change on the terrace. These contrasting results may be associated with typical daily temperature ranges on the terrace that are three times greater than on the fore reef. Permanent photoquadrats showed that turf algae initially colonized skeletons of recently dead corals but transitioned to crustose coralline algae within a year. Collectively, our study emphasizes that comprehensive monitoring of benthic communities over time combined with in situ temperature data can provide taxonomically precise trajectories of community change during and following thermal stress.

Two Argo floats equipped with oxygen, chlorophyll (Chl), backscatter, and nitrate sensors conducted daily vertical profiles of the water column from a depth of 2000 m to the sea surface in the western North Pacific from January to April of 2018. Data for calibrating each sensor were obtained via shipboard sampling that occurred when the floats were deployed and recovered. Float backscatter observations were converted to particulate organic carbon (POC) concentrations using an empirical relationship derived from contemporaneous float profiles of backscatter and shipboard observations of suspended organic carbon particles. During the float deployment periods, repeated meteorological disturbances (storms) passed over the study area and caused the mixed layer to deepen. During these events, nitrate was entrained from deeper layers into the surface mixed layer, while Chl and POC in the surface mixed layer were redistributed into deeper layers. After the storms, the upper layer gradually restratified, nitrate concentrations in the surface layer decreased, and Chl and POC concentrations increased. When the floats observed the same water mass, the net community production within the euphotic layer (0–70 m), determined from the increases in POC, was 126–664 mg C m−2 d−1 (10.5–55.3 mmol C m−2 d−1) close to the values reported from a nearby area. The C/N ratio of the increase in POC and the decrease in nitrate was closed to the Redfield ratio, which indicates that the sensors were able to observe the net biochemical processes in this area despite the relatively low concentrations of nitrate and POC. To determine the fate of particles transported from the surface ocean to the twilight layer, the ratio of oxygen consumption and nitrate regeneration rates were compared. This O2/N ratio approached the Redfield ratio when the floats followed the same water mass continuously, but the consumption rate of POC was significantly lower than what would be expected based on the oxygen consumption and nitrate release rates. This suggests that dissolved organic carbon was the main substrate for the respiration in the twilight layer.

Equimolal tris (2-amino-2-hydroxymethyl-propane-1,3-diol) buffer in artificial seawater is a well characterized and commonly used standard for oceanographic pH measurements. We evaluated the stability of tris pH when stored in purportedly gas-impermeable bags across a variety of experimental conditions, including bag type and storage in air vs. seawater over 300 d. Bench-top spectrophotometric pH analysis revealed that the pH of tris stored in bags decreased at a rate of 0.0058±0.0011 yr−1 (mean slope ±95 % confidence interval of slope). The upper and lower bounds of expected pH change at t=365 d, calculated using the averages and confidence intervals of slope and intercept of measured pH change vs. time data, were −0.0042 and −0.0076 from initial pH. Analyses of total dissolved inorganic carbon confirmed that a combination of CO2 infiltration and/or microbial respiration led to the observed decrease in pH. Eliminating the change in pH of bagged tris remains a goal, yet the rate of pH change is lower than many processes of interest and demonstrates the potential of bagged tris for sensor calibration and validation of autonomous in situ pH measurements.

The differential diagnosis of reactive mesothelial hyperplasia and mesothelioma is difficult. We present a rare case of diffuse pleural thickening with thoracic contraction that was indistinguishable from mesothelioma. A 66-year-old woman with no history of asbestos exposure visited our hospital with a complaint of dyspnea. The clinical findings included circumferential pleural thickening on chest computed tomography image and a high concentration of hyaluronic acid in the pleural fluid. Pleural biopsies obtained by thoracoscopy under local anesthesia were pathologically consistent with mesothelioma, but the patient refused to take any kind of mesothelioma treatments. Four months later, she consented to a surgical pleural biopsy under general anesthesia to obtain larger tissue samples, which included typical proliferating polygonal cells positive for CAM5.2, calretinin, WT-1, D2-40, CK5/6, epithelial membrane antigen, and glucose transporter-1 and negative for carcinoembryonic antigen, BerEP4, and MOC31. The analysis was consistent with diagnosis of epithelioid mesothelioma. Fluorescence in situ hybridization, however, showed the presence of p16 gene, and the expression of BRCA1-associated protein-1 was detected by immunohistochemistry. Our final diagnosis was diffuse pleural thickening unrelated to asbestos exposure. Differential diagnosis of diffuse pleural thickening and malignant mesothelioma is thus difficult and routine immunohistochemical examinations are often insufficient for accurate diagnosis. Multiple diagnostic methods are required for correct diagnosis in a clinically marginal case.

Coral reefs are facing intensifying stressors, largely due to global increases in seawater temperature and decreases in pH. However, there is extensive environmental variability within coral reef ecosystems, which can impact how organisms respond to global trends. We deployed spatial arrays of autonomous sensors across distinct shallow coral reef habitats to determine patterns of spatiotemporal variability in seawater physicochemical parameters. Temperature and pH were positively correlated over the course of a day due to solar heating and light‐driven metabolism. The mean temporal and spatial ranges of temperature and pH were positively correlated across all sites, with different regimes of variability observed in different reef types. Ultimately, depth was a reliable predictor of the average diel ranges in both seawater temperature and pH. These results demonstrate that there is widespread environmental variability on diel timescales within coral reefs related to water column depth, which needs to be included in assessments of how global change will locally affect reef ecosystems.