原著

出生直後の普通および無菌モルモット,ならびに分娩前後のモルモットに異種蛋白を経口強制投与し,その腸管透過性,感作状態,母乳中への異種蛋白の移行および免疫原性に関して免疫学的諸反応で検討,また乳児突然死の発生機序を幼若モルモット気管感作(牛乳)法と気管内誘発注入により起こる臨床症状,アナフィラキシーショック後の血中抗牛乳抗体の変動,および呼吸器官の病理組織学的検討などを行なった。1. 出生直後の普通および無菌モルモットで異種抗毒素が経口投与後30分で血中に移行,また出生直後のウマ血清または牛乳の投与で0.5ヵ月後感作が成立していた。2. 分娩前後モルモットに異種抗毒素を経口投与し血中,母乳中に抗毒素蛋白の移行排出を認め,母乳中に移行した抗毒素ウマ血清あるいは牛乳で子モルモットが感作される。親モルモット,子モルモットでのウマ血清および牛乳の組合せ投与実験で,子モルモットは両抗原に感作される。3. 幼若モルモットの気管内微量牛乳注入後1.5ヵ月に感作成立を認め,誘発注入により臨床上アナフィラキシーショックが出現,その際抗牛乳抗体価は1/2〜1/4に減少した。肺の変化は機能的の無気肺像が特異所見であり,死因は内部窒息によるものと推定した。以上の結果から,乳児突然死は牛乳アレルギー状態における牛乳誤嚥誘発の上に成立するものを含むものと推定した。Immunogenicity of foreign protein was studied by forced oral administration in ordinary and germ-free newborn guinea pigs and to mother animals before and after delivery, examining its intestinal permeability, sensitization of babies, and transition into mother\u27s milk. The heterogeneous tetanus antitoxin passed into blood stream of newborns within 30 minutes after its oral administration, and sensitized the babies half a month after administration of horse serum or cow milk immediately after birth. Antitoxin protein transited to mother\u27s milk after its oral administration before or after delivery and sensitized the babies receiving the milk. Combined administration of two different proteins to mothers and newborns resulted in sensitization of baby animals with both antigens. Mechanisms of sudden death in infancy were examined by intratracheal administration of a very small amount of whole cow milk to baby guinea pigs which were easily sensitized and their antibody titers lowered to 1/2 to 1/4, causing severe anaphylactic shock in most cases. After this challenge, atelectasis of the lungs was found and this may lead to internal asphyxia causing death. Therefore, the sudden death in infancy may be due to miss-swallowing of cow milk into the trachea in milk-allergic condition

A decade of GOSAT Proxy satellite CH4_{4} observations

This work presents the latest release (v9.0) of the University of Leicester GOSAT Proxy XCH4 dataset. Since the launch of the GOSAT satellite in 2009, these data have been produced by the UK National Centre for Earth Observation (NCEO) as part of the ESA Greenhouse Gas Climate Change Initiative (GHG-CCI) and Copernicus Climate Change Services (C3S) projects. With now over a decade of observations, we outline the many scientific studies achieved using past versions of these data in order to highlight how this latest version may be used in the future. We describe in detail how the data are generated, providing information and statistics for the entire processing chain from the L1B spectral data through to the final quality-filtered column-averaged dry-air mole fraction (XCH4) data. We show that out of the 19.5 million observations made between April 2009 and December 2019, we determine that 7.3 million of these are sufficiently cloud-free (37.6 %) to process further and ultimately obtain 4.6 million (23.5 %) high-quality XCH4 observations. We separate these totals by observation mode (land and ocean sun glint) and by month, to provide data users with the expected data coverage, including highlighting periods with reduced observations due to instrumental issues. We perform extensive validation of the data against the Total Carbon Column Observing Network (TCCON), comparing to ground-based observations at 22 locations worldwide. We find excellent agreement with TCCON, with an overall correlation coefficient of 0.92 for the 88 345 co-located measurements. The single-measurement precision is found to be 13.72 ppb, and an overall global bias of 9.06 ppb is determined and removed from the Proxy XCH4 data. Additionally, we validate the separate components of the Proxy (namely the modelled XCO2 and the XCH4/XCO2 ratio) and find these to be in excellent agreement with TCCON. In order to show the utility of the data for future studies, we compare against simulated XCH4 from the TM5 model. We find a high degree of consistency between the model and observations throughout both space and time. When focusing on specific regions, we find average differences ranging from just 3.9 to 15.4 ppb. We find the phase and magnitude of the seasonal cycle to be in excellent agreement, with an average correlation coefficient of 0.93 and a mean seasonal cycle amplitude difference across all regions of -0.84 ppb

Ensemble-based satellite-derived carbon dioxide and methane column-averaged dry-air mole fraction data sets (2003-2018) for carbon and climate applications

Satellite retrievals of column-averaged dry-air mole fractions of carbon dioxide (CO₂) and methane (CH₄), denoted XCO₂ and XCH₄, respectively, have been used in recent years to obtain information on natural and anthropogenic sources and sinks and for other applications such as comparisons with climate models. Here we present new data sets based on merging several individual satellite data products in order to generate consistent long-term climate data records (CDRs) of these two Essential Climate Variables (ECVs). These ECV CDRs, which cover the time period 2003–2018, have been generated using an ensemble of data products from the satellite sensors SCIAMACHY/ENVISAT and TANSO-FTS/GOSAT and (for XCO₂) for the first time also including data from the Orbiting Carbon Observatory 2 (OCO-2) satellite. Two types of products have been generated: (i) Level 2 (L2) products generated with the latest version of the ensemble median algorithm (EMMA) and (ii) Level 3 (L3) products obtained by gridding the corresponding L2 EMMA products to obtain a monthly 5∘×5∘ data product in Obs4MIPs (Observations for Model Intercomparisons Project) format. The L2 products consist of daily NetCDF (Network Common Data Form) files, which contain in addition to the main parameters, i.e., XCO₂ or XCH₄, corresponding uncertainty estimates for random and potential systematic uncertainties and the averaging kernel for each single (quality-filtered) satellite observation. We describe the algorithms used to generate these data products and present quality assessment results based on comparisons with Total Carbon Column Observing Network (TCCON) ground-based retrievals. We found that the XCO₂ Level 2 data set at the TCCON validation sites can be characterized by the following figures of merit (the corresponding values for the Level 3 product are listed in brackets) – single-observation random error (1σ): 1.29 ppm (monthly: 1.18 ppm); global bias: 0.20 ppm (0.18 ppm); and spatiotemporal bias or relative accuracy (1σ): 0.66 ppm (0.70 ppm). The corresponding values for the XCH₄ products are single-observation random error (1σ): 17.4 ppb (monthly: 8.7 ppb); global bias: −2.0 ppb (−2.9 ppb); and spatiotemporal bias (1σ): 5.0 ppb (4.9 ppb). It has also been found that the data products exhibit very good long-term stability as no significant long-term bias trend has been identified. The new data sets have also been used to derive annual XCO₂ and XCH₄ growth rates, which are in reasonable to good agreement with growth rates from the National Oceanic and Atmospheric Administration (NOAA) based on marine surface observations. The presented ECV data sets are available (from early 2020 onwards) via the Climate Data Store (CDS, https://cds.climate.copernicus.eu/, last access: 10 January 2020) of the Copernicus Climate Change Service (C3S, https://climate.copernicus.eu/, last access: 10 January 2020)

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Explosive pleuritis

The objective of the present paper is to describe the clinical and computed tomography features of 'explosive pleuritis', an entity first named by Braman and Donat in 1986, and to propose a case definition. A case report of a previously healthy, 45-year-old man admitted to hospital with acute onset pleuritic chest pain is presented. The patient arrived at the emergency room at 15:00 in mild respiratory distress; the initial chest x-ray revealed a small right lower lobe effusion. The subsequent clinical course in hospital was dramatic. Within 18 h of admission, he developed severe respiratory distress with oxygen desaturation to 83% on room air and dullness of the right lung field. A repeat chest x-ray, taken the morning after admission, revealed complete opacification of the right hemithorax. A computed tomography scan of the thorax demonstrated a massive pleural effusion with compression of pulmonary tissue and mediastinal shift. Pleural fluid biochemical analysis revealed the following concentrations: glucose 3.5 mmol/L, lactate dehydrogenase 1550 U/L, protein 56.98 g/L, amylase 68 U/L and white blood cell count 600 cells/mL. The pleural fluid cultures demonstrated light growth of coagulase-negative staphylococcus and viridans streptococcus, and very light growth of Candida albicans. Cytology was negative for malignant cells. Thoracotomy was performed, which demonstrated a loculated parapneumonic effusion that required decortication. The patient responded favourably to the empirical administration of intravenous levofloxacin and ceftriaxone, and conservative surgical methods in the management of the empyema. This report also discusses the patient's rapidly progressing pleural effusion and offers a potential case definition for explosive pleuritis. Explosive pleuritis is a medical emergency defined by the rapid development of a pleural effusion involving more than 90% of the hemithorax over 24 h, which causes compression of pulmonary tissue and mediastinal shift to the contralateral side