Specific Migratory Dendritic Cells Rapidly Transport Antigen from the Airways to the Thoracic Lymph Nodes

Antigen transport from the airway mucosa to the thoracic lymph nodes (TLNs) was studied in vivo by intratracheal instillation of fluorescein isothiocyanate (FITC)-conjugated macromolecules. After instillation, FITC+ cells with stellate morphology were found deep in the TLN T cell area. Using flow cytometry, an FITC signal was exclusively detected in CD11cmed-hi/major histocompatibility complex class II (MHCII)hi cells, representing migratory airway-derived lymph node dendritic cells (AW-LNDCs). No FITC signal accumulated in lymphocytes and in a CD11chiMHCIImed DC group containing a CD8αhi subset (non–airway-derived [NAW]-LNDCs). Sorted AW-LNDCs showed long MHCIIbright cytoplasmic processes and intracytoplasmatic FITC+ granules. The fraction of FITC+ AW-LNDCs peaked after 24 h and had reached baseline by day 7. AW-LNDCs were depleted by 7 d of ganciclovir treatment in thymidine kinase transgenic mice, resulting in a strong reduction of FITC-macromolecule transport into the TLNs. Compared with intrapulmonary DCs, AW-LNDCs had a mature phenotype and upregulated levels of MHCII, B7-2, CD40, and intracellular adhesion molecule (ICAM)-1. In addition, sorted AW-LNDCs from FITC-ovalbumin (OVA)–instilled animals strongly presented OVA to OVA-TCR transgenic T cells. These results validate the unique sentinel role of airway DCs, picking up antigen in the airways and delivering it in an immunogenic form to the T cells in the TLNs

Prognostic implications of cellular senescence in resected non-small cell lung cancer

Background: Cure and long-term survival for non-small cell lung cancer (NSCLC) remains hard to achieve. Cellular senescence, an emerging hallmark of cancer, is considered as an endogenous tumor suppressor mechanism. However, senescent cancer cells can paradoxically affect the surrounding tumor microenvironment (TME), ultimately leading to cancer relapse and metastasis. As such, the role of cellular senescence in cancer is highly controversial. Methods: In 155 formalin-fixed paraffin-embedded (FFPE) samples from surgically resected NSCLC patients with pathological tumor-node-metastasis (pTNM) stages I-IV (8th edition), cellular senescence was assessed using a combination of four immunohistochemical senescence markers, i.e., lipofuscin, p16INK4a, p21WAF1/Cip1 and Ki67, and correlated to clinicopathological parameters and outcomes, including overall survival (OS) and disease-free survival (DFS). Results: A tumoral senescence signature (SS) was present in 48 out of 155 NSCLC patients, but did not correlate to any clinicopathological parameter, except for p53 mutation status. In a histologically homogenous patient cohort of 100 patients who fulfilled the following criteria: (I) one type of histology, i.e., adenocarcinoma, (II) without known epidermal growth factor receptor (EGFR) mutation, (III) curative (R0) resection and (IV) no neoadjuvant systemic therapy or radiotherapy, the median OS and DFS for patients with a tumoral SS (n=30, 30.0%) compared to patients without a tumoral SS (n=70, 70.0%) was 53 versus 141 months (P=0.005) and 45 versus 55 months (P=0.25), respectively. In multiple Cox proportional hazards (Cox PH) model analysis correcting for age, pTNM stage I-III and adjuvant therapy, a tumoral SS remained a significant prognostic factor for OS (HR =2.03; P=0.014). Conclusions: The presence of a tumoral SS particularly based on high p16INK4a expression significantly affects OS in NSCLC adenocarcinoma. In this light, adjuvant senolytic therapy could be an interesting strategy for NSCLC patients harboring a tumoral SS, ultimately to improve survival of these patients

A review of spatial downscaling of satellite remotely sensed soil moisture

Satellite remote sensing technology has been widely used to estimate surface soil moisture. Numerous efforts have been devoted to develop global soil moisture products. However, these global soil moisture products, normally retrieved from microwave remote sensing data, are typically not suitable for regional hydrological and agricultural applications such as irrigation management and flood predictions, due to their coarse spatial resolution. Therefore, various downscaling methods have been proposed to improve the coarse resolution soil moisture products. The purpose of this paper is to review existing methods for downscaling satellite remotely sensed soil moisture. These methods are assessed and compared in terms of their advantages and limitations. This review also provides the accuracy level of these methods based on published validation studies. In the final part, problems and future trends associated with these methods are analyzed

Antibiotic Prescribing Patterns in Ghana, Uganda, Zambia and Tanzania Hospitals: Results from the Global Point Prevalence Survey (G-PPS) on Antimicrobial Use and Stewardship Interventions Implemented

Antimicrobial resistance (AMR) remains an important global public health issue with antimicrobial misuse and overuse being one of the main drivers. The Global Point Prevalence Survey (G-PPS) of Antimicrobial Consumption and Resistance assesses the prevalence and the quality of antimicrobial prescriptions across hospitals globally. G-PPS was carried out at 17 hospitals across Ghana, Uganda, Zambia and Tanzania. The overall prevalence of antimicrobial use was 50% (30–57%), with most antibiotics prescribed belonging to the WHO ‘Access’ and ‘Watch’ categories. No ‘Reserve’ category of antibiotics was prescribed across the study sites while antimicrobials belonging to the ‘Not Recommended’ group were prescribed infrequently. Antimicrobials were most often prescribed for prophylaxis for obstetric or gynaecological surgery, making up between 12 and 18% of total prescriptions across all countries. The most prescribed therapeutic subgroup of antimicrobials was ‘Antibacterials for systemic use’. As a result of the programme, PPS data are now readily available for the first time in the hospitals, strengthening the global commitment to improved antimicrobial surveillance. Antimicrobial stewardship interventions developed included the formation of AMS committees, the provision of training and the preparation of new AMS guidelines. Other common interventions included the presentation of findings to clinicians for increased awareness, and the promotion of a multi-disciplinary approach to successful AMS programmes. Repeat PPS would be necessary to continually monitor the impact of interventions implemented. Broader participation is also encouraged to strengthen the evidence base

Calibration of a water and energy balance model: Recursive parameter estimation versus particle swarm optimization

It is well known that one of the major problems in the application of land surface models is the determination of the various model parameters. In most cases, only one or a limited number of variables are used to estimate these parameters. This study evaluates the use of two fundamentally different global optimization methods, multistart weight-adaptive recursive parameter estimation (MWARPE) and particle swarm optimization (PSO), for the estimation of hydrologic model parameters on the basis of data for multiple variables. MWARPE iteratively uses the linear recursive filter equations in a Monte Carlo setting and therefore does not rely on the explicit minimization of an objective function. However, a major drawback of the MWARPE method is the high dimensionality, determined by the number of observations, of the matrix to be inverted. On the other hand, PSO is a stochastic optimization method based on the collective strength of a population of individuals with flocking or herding behavior, as observed in a wide number of biological systems. In situ observations of net radiation; latent, sensible, and ground heat fluxes; and the soil moisture profile are used to determine the parameters of a simplified water and energy balance model. Both optimization methods are analyzed in terms of model performance and computational efficiency. Comparable results, expressed in terms of the root mean square error values, were obtained for both methods. However, it was found that MWARPE tends to slightly overfit the data

Assessing the impact of the Global Point Prevalence Survey of Antimicrobial Consumption and Resistance (Global-PPS) on hospital antimicrobial stewardship programmes : results of a worldwide survey

Abstract Background The Global Point Prevalence Survey of Antimicrobial Consumption and Resistance (Global-PPS) provides a methodology to support hospitals worldwide in collecting antimicrobial use data. We aim to evaluate the impact of the Global-PPS on local antimicrobial stewardship (AMS) programmes and assess health care professionals’ educational needs and barriers for implementing AMS. Methods A cross-sectional survey was disseminated within the Global-PPS network. The target audience consisted of hospital healthcare workers, involved in local surveillance of antimicrobial consumption and resistance. This included contacts from hospitals that already participated in the Global-PPS or were planning to do so. The survey contained 24 questions that addressed the hospital’s AMS activities, experiences conducting the PPS, as well as the learning needs and barriers for implementing AMS. Results A total of 248 hospitals from 74 countries participated in the survey, of which 192 had already conducted the PPS at least once. The survey response rate was estimated at 25%. In 96.9% of these 192 hospitals, Global-PPS participation had led to the identification of problems related to antimicrobial prescribing. In 69.3% at least one of the hospital’s AMS components was initiated as a result of Global-PPS findings. The level of AMS implementation varied across regions. Up to 43.1% of all hospitals had a formal antimicrobial stewardship strategy, ranging from 10.8% in Africa to 60.9% in Northern America. Learning needs of hospitals in high-income countries and in low-and middle-income countries were largely similar and included general topics (e.g. ‘optimising antibiotic treatment’), but also PPS-related topics (e.g. ‘translating PPS results into meaningful interventions’). The main barriers to implementing AMS programmes were a lack of time (52.7%), knowledge on good prescribing practices (42.0%), and dedicated funding (39.9%). Hospitals in LMIC more often reported unavailability of prescribing guidelines, insufficient laboratory capacity and suboptimal use of the available laboratory services. Conclusions Although we observed substantial variation in the level of AMS implementation across regions, the Global-PPS has been very useful in informing stewardship activities in many participating hospitals. More is still to be gained in guiding hospitals to integrate the PPS throughout AMS activities, building on existing structures and processes

Allergen-induced changes in bone-marrow progenitor and airway dendritic cells in sensitized rats

Eosinophilic airway inflammation is orchestrated by T-helper (Th)-2 lymphocytes. We have previously demonstrated that dendritic cells (DC) are essential for the presentation of antigen to these Th2 cells leading to airway inflammation. Here, we have examined the presence of DC in the lungs, the kinetics of appearance, and the possible involvement of the bone-marrow progenitor for DC in a rat model of ovalbumin (OVA)-induced airway inflammation. Sensitized rats were exposed to 0, 1, 3, or 7 consecutive daily OVA aerosols. Control rats were sham sensitized and/or exposed to phosphate-buffered saline (PBS), and bronchoalveolar lavage (BAL) was performed 24 h after the last challenge. DC were identified in BAL fluid as low-density, low-autofluorescence, CD3 � , CD45RA � , OX62 � , OX6 � cells that had long surface extensions and strong costimulatory activity. Low but detectable amounts of BAL DC were seen in sensitized, unexposed animals. After three OVA exposures, the inflammatory infiltrate consisted of CD4 �-activated T cells, eosinophils, and monocytes. The number of BAL DC was significantly increased in OVA-sensitized/OVA-exposed animals compared with sham-sensitized or PBS-exposed animals. The kinetics of DC increase closely parallelled those in other inflammatory cells. Bone-marrow cells taken from the OVAsensitized and-exposed group were grown in the DC growth factor granulocyte macrophage colony-stimulating factor for 6 d and the yield of OX62 � OX6 � DC was 60 % higher compared with PBS-exposed o