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Background:. Breast reduction, also defined as reduction mammaplasty, is one of the most common procedures performed in aesthetic surgery. Multiple techniques have been proposed throughout the years and several classification systems have been adopted according to: type of incision, pedicle blood supply (cutaneous, glandular, dermoglandular), extent of undermining, excision area, simultaneous or separate tissue excision (fat/gland, skin, or both), and combination of the aforementioned. In the present article, we share our 10 years’ experience with reduction mammaplasty and we describe our personal technique, a modified superior pedicle breast reduction. Methods:. We performed a retrospective analysis on 823 consecutive patients undergoing either aesthetic or functional reduction mammaplasty at Humanitas Research Hospital between 2009 and 2018. For each patient, we evaluated the mean resection volume and complication rate. We also assessed patients’ satisfaction (VAS scale) and aesthetic outcome (assessed by independent surgeons, scale from 1 to 5). Results:. The average patient age was 48, ranging from 17 to 77 years. The average operative time was 77 minutes, ranging from 62 to 123 minutes. After a thorough follow-up of these patients, we can conclude that our technique has a low complication rate, patients’ satisfaction is excellent, and the result is stable over time in terms of shape and symmetry (the mean VAS score was 8.1). Postoperative surgeon’s photographs evaluation scores were 4.5 ± 0.5. Average resected volume was 860gr. Conclusion:. The proposed technique is safe, fast, and simple with a relatively short learning curve, making it didactic and intuitive for young surgeons.

A atuação do Estado brasileiro na busca por um desenvolvimento econômico atrelado ao mercado globalizado vem gerando transformações no espaço ambiental e cultural dos territórios ocupados por comunidades tradicionais. Isso ocorre através da implementação de políticas públicas que incentivam o deslocamento de grandes conglomerados industriais da zona urbana para áreas de uso tradicional, remodelando a dinâmica das populações afetadas. Este artigo tem como objetivo discutir como a intervenção do Estado, através de efetivação de políticas públicas desenvolvimentistas, em territórios ocupados por populações tradicionais, pode gerar conflitos entre os propósitos da política e os interesses dessas comunidades. Para tanto, utilizou-se como estudo de caso a Resex da Prainha do Canto Verde/CE, devido à existência de parque eólico próximo ao seu território. Metodologicamente, as informações são provenientes de pesquisa bibliográfica, documental e através de dados coletados por meio de entrevistas, tendo sido utilizado a análise de conteúdo para tratamento desse material. Seu propósito, portanto, conduz a uma reflexão acerca da participação do Estado brasileiro no processo de geração de conflitos nas comunidades tradicionais, motivados por aspectos econômicos e que alteram o significado dos valores e do patrimônio coletivo das comunidades tradicionais.

Engineering T cells to express chimeric antigen receptors (CARs) specific for antigens on hematological cancers has yielded remarkable clinical responses, but with solid tumors, benefit has been more limited. This may reflect lack of suitable target antigens, immune evasion mechanisms in malignant cells, and/or lack of T cell infiltration into tumors. An alternative approach, to circumvent these problems, is targeting the tumor vasculature rather than the malignant cells directly. CLEC14A is a glycoprotein selectively overexpressed on the vasculature of many solid human cancers and is, therefore, of considerable interest as a target antigen. Here, we generated CARs from 2 CLEC14A-specific antibodies and expressed them in T cells. In vitro studies demonstrated that, when exposed to their target antigen, these engineered T cells proliferate, release IFN-γ, and mediate cytotoxicity. Infusing CAR engineered T cells into healthy mice showed no signs of toxicity, yet these T cells targeted tumor tissue and significantly inhibited tumor growth in 3 mouse models of cancer (Rip-Tag2, mPDAC, and Lewis lung carcinoma). Reduced tumor burden also correlated with significant loss of CLEC14A expression and reduced vascular density within malignant tissues. These data suggest the tumor vasculature can be safely and effectively targeted with CLEC14A-specific CAR T cells, offering a potent and widely applicable therapy for cancer.

This protocol illustrates the modelling of a protein-peptide complex using the synergic combination of in silico analysis and experimental results. To this end, we use the integrative modelling software HADDOCK, which possesses the powerful ability to incorporate experimental data, such as NMR Chemical Shift Perturbations and biochemical protein-peptide interaction data, as restraints to guide the docking process. Based on the modelling results, a rational mutagenesis approach is used to validate the generated models. The experimental results allow to select a final structural model best representing the bona fide protein-peptide complex. The described protocol can also be applied to model protein-protein complexes. There is no size limit for the macromolecular complexes that can be characterized by HADDOCK as long as the 3D structures of the individual components are available.

Neisseria meningitidis serogroup B (MenB) is the leading cause of meningococcal meningitis and sepsis in industrialized countries, with the highest incidence in infants and adolescents. Two recombinant protein vaccines that protect against MenB are now available (i.e. 4CMenB and MenB-fHbp). Both vaccines contain the Factor H Binding Protein (fHbp) antigen, which can bind the Human Factor H (fH), the main negative regulator of the alternative complement pathway, thus enabling bacterial survival in the blood. fHbp is present in meningococcal strains as three main variants which are immunologically distinct. Here we sought to obtain detailed information about the epitopes targeted by anti-fHbp antibodies induced by immunization with the 4CMenB multicomponent vaccine. Thirteen anti-fHbp human monoclonal antibodies (mAbs) were identified in a library of over 100 antibody fragments (Fabs) obtained from three healthy adult volunteers immunized with 4CMenB. Herein, the key cross-reactive mAbs were further characterized for antigen binding affinity, complement-mediated serum bactericidal activity (SBA) and the ability to inhibit binding of fH to live bacteria. For the first time, we identified a subset of anti-fHbp mAbs able to elicit human SBA against strains with all three variants and able to compete with human fH for fHbp binding. We present the crystal structure of fHbp v1.1 complexed with human antibody 4B3. The structure, combined with mutagenesis and binding studies, revealed the critical cross-reactive epitope. The structure also provided the molecular basis of competition for fH binding. These data suggest that the fH binding site on fHbp v1.1 can be accessible to the human immune system upon immunization, enabling elicitation of human mAbs broadly protective against MenB. The novel structural, biochemical and functional data are of great significance because the human vaccine-elicited mAbs are the first reported to inhibit the binding of fH to fHbp, and are bactericidal with human complement. Our studies provide molecular insights into the human immune response to the 4CMenB meningococcal vaccine and fuel the rationale for combined structural, immunological and functional studies when seeking deeper understanding of the mechanisms of action of human vaccines.

Arrhythmogenic Cardiomyopathy (ACM) is a rare inherited heart muscle disease characterised by progressive fibro-fatty replacement of the ventricular myocardium leading to life-threatening arrhythmias. We generated human induced pluripotent stem cells (hiPSCs) from a patient affected by ACM and carrying the heterozygous c.2013delC (p.K672Rfs) PKP2 mutation and then corrected the mutation using CRISPR/Cas9 technology. Both hiPSC lines expressed pluripotency markers, maintained a normal karyotype, and differentiated into derivatives of the three germ layers. This isogenic hiPSC pair represents a genetically controlled system to study the role of the c.2013delC PKP2 mutation in vitro.

Background:. The coronavirus disease 2019 (COVID-19) pandemic presented a dramatic challenge to healthcare systems. Humanitas Clinical and Research Hospital (Rozzano, MI, Italy) was declared a regional hub for the treatment of COVID-19 patients. Our plastic surgery team, in consultation with our breast surgery colleagues, decided to perform immediate implant-based breast reconstruction for patients undergoing mastectomy for cancer. In this report, we present our experience performing breast reconstruction with a new protocol in the first month following the COVID-19 pandemic in the most affected region in Italy. Methods:. We adopted a new protocol to treat patients with breast cancer during the COVID-19 pandemic. The main goals of our protocol were to reduce the risk of COVID-19 spread for both patients and clinicians, postpone nononcologic and more advanced surgery, develop rapid recovery for early patient discharge (within 24 hours from surgery) through pain management, and finally reduce postoperative consultations. Results:. The protocol was applied to 51 patients between early March and early April 2020. After 1 month, we decided to retrospectively review our experience. We found no significant differences in terms of postoperative pain and complication rate compared with our data in the pre-COVID period. Conclusion:. Our new protocol is safe and effective, enabling tumor resection and immediate implant-based breast reconstruction, without increasing risks to the patient or staff.

Background Brasilonema is a cyanobacterial genus found on the surface of mineral substrates and plants such as bromeliads, orchids and eucalyptus. B. octagenarum stands out among cyanobacteria due to causing damage to the leaves of its host in an interaction not yet observed in other cyanobacteria. Previous studies revealed that B. octagenaum UFV-E1 is capable of leading eucalyptus leaves to suffer internal tissue damage and necrosis by unknown mechanisms. This work aimed to investigate the effects of B. octagenarum UFV-E1 inoculation on Eucalyptus urograndis and to uncover molecular mechanisms potentially involved in leaf damage by these cyanobacteria using a comparative genomics approach. Results Leaves from E. urograndis saplings were exposed for 30 days to B. octagenarum UFV-E1, which was followed by the characterization of its genome and its comparison with the genomes of four other Brasilonema strains isolated from phyllosphere and the surface of mineral substrates. While UFV-E1 inoculation caused an increase in root and stem dry mass of the host plants, the sites colonized by cyanobacteria on leaves presented a significant decrease in pigmentation, showing that the cyanobacterial mats have an effect on leaf cell structure. Genomic analyses revealed that all evaluated Brasilonema genomes harbored genes encoding molecules possibly involved in plant-pathogen interactions, such as hydrolases targeting plant cell walls and proteins similar to known virulence factors from plant pathogens. However, sequences related to the type III secretory system and effectors were not detected, suggesting that, even if any virulence factors could be expressed in contact with their hosts, they would not have the structural means to actively reach plant cytoplasm. Conclusions Leaf damage by this species is likely related to the blockage of access to sunlight by the efficient growth of cyanobacterial mats on the phyllosphere, which may hinder the photosynthetic machinery and prevent access to some essential molecules. These results reveal that the presence of cyanobacteria on leaf surfaces is not as universally beneficial as previously thought, since they may not merely provide the products of nitrogen fixation to their hosts in exchange for physical support, but in some cases also hinder regular leaf physiology leading to tissue damage.

Arrhythmogenic cardiomyopathy (ACM) is an inherited heart disorder, predisposing to malignant ventricular arrhythmias leading to sudden cardiac death, particularly in young and athletic patients. Pathological features include a progressive loss of myocardium with fibrous or fibro-fatty substitution. During the last few decades, different clinical aspects of ACM have been well investigated but still little is known about the molecular mechanisms that underlie ACM pathogenesis, leading to these phenotypes. In about 50% of ACM patients, a genetic mutation, predominantly in genes that encode for desmosomal proteins, has been identified. However, the mutation-associated mechanisms, causing the observed cardiac phenotype are not always clear. Until now, the attention has been principally focused on the study of molecular mechanisms that lead to a prominent myocardium adipose substitution, an uncommon marker for a cardiac disease, thus often recognized as hallmark of ACM. Nonetheless, based on Task Force Criteria for the diagnosis of ACM, cardiomyocytes death associated with fibrous replacement of the ventricular free wall must be considered the main tissue feature in ACM patients. For this reason, it urges to investigate ACM cardiac fibrosis. In this review, we give an overview on the cellular effectors, possible triggers, and molecular mechanisms that could be responsible for the ventricular fibrotic remodeling in ACM patients.

Traumatic brain injury (TBI) represents an important public health problem and is followed by neuroinflammation and neurological dysfunctions. It has been suggested that brain trauma is often associated to deep behavioral alterations and chronic pain-like syndrome. Despite inducing minimal brain damage, mild TBI (mTBI) leads to persistent behavioral changes, including anxiety, depression, social interaction impairment, and aggressiveness. The clinical management of these symptoms is still unsatisfactory and new pharmacological treatments are needed, especially for the aggressiveness and depression. In a mouse model of mTBI, we investigated the effect of 2-Pentadecyl-2-Oxazoline (PEA-OXA), a natural compound, that is a secondary metabolite, found in green and roasted coffee beans, on both the pain perception, and neuropsychiatric dysfunctions. We found that the compound acts as a α2 adrenergic antagonist and this mechanism is here described for the first time. Mild TBI mice, starting from 14-d post-trauma, developed anxious and aggressive behavior, whilst depressive-like behavior and impaired social interactions were observed from the 60th d onward. PEA-OXA normalized all the behavioral changes investigated. We also investigated the memory impairments through Morris Water Maze (MWM) test. Both sham and mTBI mice treated with PEA-OXA showed amelioration in the reversal task of the MWM. Nevertheless, the main symptom of the long-term mTBI is represented by the depressive-like behavior, which was completely reversed by PEA-OXA repeated administration. In humans, mTBI-induced depression precedes the appearance of dementias and is characterized by a massive deficit of GABAergic transmission in the cortices. We found that PEA-OXA normalized the GABA changes in the prefrontal cortex. In order to prove the α2-mediated effect of the PEA-OXA we have performed open field test in naïve animals by microinjecting into the medial prefrontal cortex the dexomedetomidine, a selective α2 agonist with or without PEA-OXA co-injection. We found that PEA-OXA antagonized the α2 agonist effect on the locomotor activity. Moreover, PEA-OXA microinjection into the medial prefrontal cortex induced an enhancement of dopamine release. Collectively, these data suggest that this natural compound, through its multi-target activity is able to: i) ameliorate behavioral alterations (i.e. depression), ii) selectively normalize cortical GABA levels, iii) rescue the impaired neuronal activity in the prefrontal cortex.

Formyl peptide receptor type 2 (FPR2/ALX) belongs to the formyl peptide receptors (FPRs) family clustered on chromosome 19 and encodes a family of three Class A of G protein-coupled receptors (GPCRs). A short N-terminal region, an NPXXY motif in transmembrane (TM) region 7 and an E/DRY motif that bridges TM3 and TM6 stabilizing inactive receptor conformations characterize this class of receptors. In recognizing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), FPRs play a crucial role in innate immune responses. FPR2/ALX is highly expressed in myeloid cells, as well as in chondrocytes, fibroblasts, endothelial, epithelial and smooth muscle cells. FPR2/ALX mRNA expression was recently reported in the rat brainstem, spinal cord, thalamus/hypothalamus, cerebral neocortex, hippocampus, cerebellum and striatum. The central nervous system (CNS) distribution of FPR2/ALX suggests important functions in nociception. Thus, the present study was carried out to investigate the possible role of FPR2/ALX in nociception in mice. Intrathecal administration of the formyl peptide receptor type 1 (FPR1) agonist fMLF and the FPR2/ALX agonist BML-111 relieved nociception and these effects were reduced by contemporary administration of the FPR2/ALX antagonist WRW4. Furthermore, measurement of cytokines and brain-derived neurotrophic factor (BDNF) in the spinal cord of neuropathic mice demonstrated that the antinociceptive effects of BML-111 might depend on the reduction in cytokine release and BDNF in the spinal cord. These results suggest a possible role of FPR2/ALX for pain control in the spinal cord.

Temporins are one of the largest families of antimicrobial peptides with both anti-inflammatory and antimicrobial activity. Herein, for a panel of cyclic temporin L isoform analogues, the antifungal and antibiofilm activities were determined against representative Candida strains, including C. albicans, C. glabrata, C. auris, C. parapsilosis and C. tropicalis. The outcomes indicated a significant anti-candida activity against planktonic and biofilm growth for four peptides (3, 7, 15 and 16). The absence of toxicity up to high concentrations and survival after infection were assessed in vivo by using Galleria mellonella larvae, and the correlation between conformation and cytotoxicity was investigated by fluorescence assays and circular dichroism (CD). By combining fluorescence spectroscopy, CD, dynamic light scattering, confocal and atomic force microscopy, the mode of action of four analogues was hypothesized. The results pinpointed that peptide 3 emerged as a non-toxic compound showing a potent antibiofilm activity and represents a promising compound for biomedical applications.

Tanshinone IIA (TIIA) and cryptotanshinone (CRY) from Salvia miltiorrhiza Bunge were investigated for their inhibitory activity against the cyclooxygenase-2 (COX-2)/microsomal prostaglandin E synthase-1 (mPGES-1)/endothelial prostaglandin 3 (EP3) pathway using in silico, in vitro, in vivo, and ex vivo assays. From the analysis of the docking poses, both diterpenoids were able to interact significantly with COX-2, 5-lipoxygenase (5-LO), platelet-activating factor receptor (PAFR), and mPGES-1. This evidence was further corroborated by data obtained from a cell-free assay, where CRY displayed a significant inhibitory potency against mPGES-1 (IC50 = 1.9 ± 0.4 µM) and 5-LO (IC50 = 7.1 µM), while TIIA showed no relevant inhibition of these targets. This was consistent with their activity to increase mice bleeding time (CRY: 2.44 ± 0.13 min, p ≤ 0.001; TIIA: 2.07 ± 0.17 min p ≤ 0.01) and with the capability to modulate mouse clot retraction (CRY: 0.048 ± 0.011 g, p ≤ 0.01; TIIA: 0.068 ± 0.009 g, p ≤ 0.05). For the first time, our results show that TIIA and, in particular, CRY are able to interact significantly with the key proteins involved not only in the onset of inflammation but also in platelet activity (and hyper-reactivity). Future preclinical and clinical investigations, together with this evidence, could provide the scientific basis to consider these compounds as an alternative therapeutic approach for thrombotic- and thromboembolic-based diseases.

Rectal neuroendocrine tumors (NETs) are rare, with an incidence of 0.17%, but they represent 12% to 27% of all NETs and 20% of gastrointestinal NETs. Although rectal NETs are uncommon tumors, their incidence has increased over the past few years, and this is probably due to the improvement in detection rates made by advanced endoscopic procedures. The biological behavior of rectal NETs may be different: factors predicting the risk of metastases have been identified, such as size and grade of differentiation. The tendency for metastatic diffusion generally depends on the tumor size, muscular and lymphovascular infiltration, and histopathological differentiation. According to the current European Neuroendocrine Tumor Society (ENETS) guidelines, tumors that are smaller than 10 mm and well differentiated are thought to have a low risk of lymphovascular invasion, and they should be completely removed endoscopically. Rectal NETs larger than 20 mm have a higher risk of involvement of muscularis propria and high metastatic risk and are candidates for surgical resection. There is controversy over rectal NETs of intermediate size, 10–19 mm, where the metastatic risk is considered to be 10–15%: assessment of tumors endoscopically and by endoanal ultrasound should guide treatment in these cases towards endoscopic, transanal, or surgical resection.

Lianne Jeffs,1–3 Trevor Jamieson,4,5 Marianne Saragosa,5 Geetha Mukerji,3,5,6 Arsh K Jain,7 Rachel Man,7 Laura Desveaux,3,5 James Shaw,3,5 Payal Agarwal,5,8 Jennifer M Hensel,5,9 Maria Maione,10 Megan Nguyen,5 Nike Onabajo,5 R Sacha Bhatia3,5,11 1Sinai Health System, Toronto, ON M5G 1X5, Canada; 2Li Ka Shing Knowledge Institute, St Michael’s Hospital, Toronto, ON M5G 1WB, Canada; 3Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON M5S 1B2, Canada; 4Department of Medicine, University of Toronto, Division of General Internal Medicine, St Michael’s Hospital, Women’s College Hospital, Toronto, ON M5G 1WB, Canada; 5Institute for Health System Solutions and Virtual Care (WIHV), Women’s College Hospital, Toronto, ON M5S 1B2, Canada; 6Women’s College Hospital, Toronto, ON M5S 1B2, Canada; 7London Health Sciences Centre, London, ON N6A 5W9, Canada; 8Department of Family and Community Medicine, Women’s College Hospital, University of Toronto, Toronto, ON M5S 1B2, Canada; 9Department of Psychiatry, University of Toronto, Women’s College Hospital, Women’s College Research Institute, Women’s College Hospital, Toronto, ON M5S 1B2, Canada; 10St Michael’s Hospital, Toronto, ON M5G 1WB, Canada; 11University Health Network, Toronto, ON M5S 1B2, Canada Background: Although there is a growing body of literature on the outcomes and impacts of remote home management with peritoneal dialysis (PD) patients, less is understood how this virtual care solution impacts the quality and efficiency of the healthcare system care. In this context, a study was undertaken to understand the perceptions of patients and their caregivers, healthcare providers, health system decision makers, and vendors associated with a remote monitoring and tracking solution aimed at enhancing the outcomes and experiences of chronic kidney disease (CKD) patients receiving PD at home. Methods: A qualitative design using semi-structured interviews with 25 stakeholders was used in this study. Narrative data were analyzed by a thematic analysis approach. Results: The following two themes emerged from the data: (1) leveraging data to monitor and intervene to keep patients safe and (2) increasing efficiencies and having control over supplies. Discussion: Our study findings elucidated the ability of patients (and in some cases, caregivers) to monitor and trend their data and order and track directly on-line their dialysis supplies were key to their active participation in managing their CKD and keeping them safe at home. Their active participation and functionality of the virtual care solution also led to enhanced efficiencies (eg, process faster, easier, convenient, time savings) for both patients and healthcare providers. Conclusion: The virtual care solution showed promising signs of a patient-centric approach and may serve as a blueprint for other virtual care solutions for chronic disease management. Keywords: peritoneal dialysis, chronic kidney disease, virtual care, qualitative research, patient centric care

The paper aims at highlighting the relationship among democracy, public administration and ethics. Starting from the analysis of the corruption problem, the Author illustrates how ethics can direct the action of the public administration, in order to pursue the common good. In this process aimed at corroborating democracy, faith is allied with reason, confirming the centrality of dignity, freedom and equality in the Italian legal system.

In this paper a macro-block model accounting for frictional resistances is presented to assess the lateral strength of a multi-storey masonry block wall. The kinematic approach of limit analysis is used to define the load factor causing the onset of rocking-sliding mechanism under in-plane horizontal loading. A dry frictional contact condition is assumed at the rigid block interfaces, according to the Coulomb's law with non-associated flow rule. The key aspect of the proposed approach is the introduction of a criterion to evaluate the contribution of the actual frictional resistances depending on the inclination angle of the crack line. An accurate assessment of the frictional resistances is also obtained by distinguishing two different contributions (the wall own weight and additional vertical loads) and their application points. Hence, a sensitivity analysis is performed with respect to the overloading condition, the friction coefficient, and geometrical parameters such as the shape ratios of the wall and of the unit block and the number of rows. The analytical results of the proposed model are also validated against results from other existing macro and micro-block modelling approaches in terms of load factor. The comparison confirms the reliability of the proposed model that allows, with similar results, great simplification of the computational effort with respect to micro-block models.

The evaluation of the seismic safety of ancient masonry buildings usually requires compounding the need of preservation of the historical values with the need of achieving a proper level of knowledge of the parameters influencing their structural behaviour. To this aim, non-destructive techniques of instrumental investigation have lately attracted increasing attention, although the provided data are frequently not exhaustive and require to be integrated with different sources of information, such as historical documents and hypotheses of critical interpretation. Therefore, the management of this multi-source information is a crucial aspect in defining a methodological approach to the structural evaluation of the cultural heritage. This paper describes an integrated approach developed in the framework of the Project on the seismic evaluation of the Museum of Capodimonte in Naples (Italy) with reference to the typological identification of the horizontal structures upon the first level of the building. The management of the data derived from the application of the infrared thermography, integrated with the information from the visual inspections, the architectural survey and the historic analysis, has allowed obtaining a complete characterization of the structures under study.

We present the organization, instrumentation, datasets, data interpretation, modeling, and accomplishments of the multinational global atmospheric measurement program AGAGE (Advanced Global Atmospheric Gases Experiment). AGAGE is distinguished by its capability to measure globally, at high frequency, and at multiple sites all the important species in the Montreal Protocol and all the important non-carbon-dioxide (non-CO2) gases assessed by the Intergovernmental Panel on Climate Change (CO2 is also measured at several sites). The scientific objectives of AGAGE are important in furthering our understanding of global chemical and climatic phenomena. They are the following: (1) to accurately measure the temporal and spatial distributions of anthropogenic gases that contribute the majority of reactive halogen to the stratosphere and/or are strong infrared absorbers (chlorocarbons, chlorofluorocarbons – CFCs, bromocarbons, hydrochlorofluorocarbons – HCFCs, hydrofluorocarbons – HFCs and polyfluorinated compounds (perfluorocarbons – PFCs), nitrogen trifluoride – NF3, sulfuryl fluoride – SO2F2, and sulfur hexafluoride – SF6) and use these measurements to determine the global rates of their emission and/or destruction (i.e., lifetimes); (2) to accurately measure the global distributions and temporal behaviors and determine the sources and sinks of non-CO2 biogenic–anthropogenic gases important to climate change and/or ozone depletion (methane – CH4, nitrous oxide – N2O, carbon monoxide – CO, molecular hydrogen – H2, methyl chloride – CH3Cl, and methyl bromide – CH3Br); (3) to identify new long-lived greenhouse and ozone-depleting gases (e.g., SO2F2, NF3, heavy PFCs (C4F10, C5F12, C6F14, C7F16, and C8F18) and hydrofluoroolefins (HFOs; e.g., CH2 = CFCF3) have been identified in AGAGE), initiate the real-time monitoring of these new gases, and reconstruct their past histories from AGAGE, air archive, and firn air measurements; (4) to determine the average concentrations and trends of tropospheric hydroxyl radicals (OH) from the rates of destruction of atmospheric trichloroethane (CH3CCl3), HFCs, and HCFCs and estimates of their emissions; (5) to determine from atmospheric observations and estimates of their destruction rates the magnitudes and distributions by region of surface sources and sinks of all measured gases; (6) to provide accurate data on the global accumulation of many of these trace gases that are used to test the synoptic-, regional-, and global-scale circulations predicted by three-dimensional models; and (7) to provide global and regional measurements of methane, carbon monoxide, and molecular hydrogen and estimates of hydroxyl levels to test primary atmospheric oxidation pathways at midlatitudes and the tropics. Network Information and Data Repository: http://agage.mit.edu/data or http://cdiac.ess-dive.lbl.gov/ndps/alegage.html (https://doi.org/10.3334/CDIAC/atg.db1001).

A wide range of anthropogenic halocarbons is released to the atmosphere, contributing to stratospheric ozone depletion and global warming. Using measurements of atmospheric abundances for the estimation of halocarbon emissions on the global and regional scale has become an important top-down tool for emission validation in the recent past, but many populated and developing areas of the world are only poorly covered by the existing atmospheric halocarbon measurement network. Here we present 6 months of continuous halocarbon observations from Finokalia on the island of Crete in the Eastern Mediterranean. The gases measured are the hydrofluorocarbons (HFCs), HFC-134a (CH2FCF3), HFC-125 (CHF2CF3), HFC-152a (CH3CHF2) and HFC-143a (CH3CF3) and the hydrochlorofluorocarbons (HCFCs), HCFC-22 (CHClF2) and HCFC-142b (CH3CClF2). The Eastern Mediterranean is home to 250 million inhabitants, consisting of a number of developed and developing countries, for which different emission regulations exist under the Kyoto and Montreal protocols. Regional emissions of halocarbons were estimated with Lagrangian atmospheric transport simulations and a Bayesian inverse modeling system, using measurements at Finokalia in conjunction with those from Advanced Global Atmospheric Gases Experiment (AGAGE) sites at Mace Head (Ireland), Jungfraujoch (Switzerland) and Monte Cimone (Italy). Measured peak mole fractions at Finokalia showed generally smaller amplitudes for HFCs than at the European AGAGE sites except for periodic peaks of HFC-152a, indicating strong upwind sources. Higher peak mole fractions were observed for HCFCs, suggesting continued emissions from nearby developing regions such as Egypt and the Middle East. For 2013, the Eastern Mediterranean inverse emission estimates for the four analyzed HFCs and the two HCFCs were 13.9 (11.3–19.3) and 9.5 (6.8–15.1) Tg CO2eq yr−1, respectively. These emissions contributed 16.8 % (13.6–23.3 %) and 53.2 % (38.1–84.2 %) to the total inversion domain, which covers the Eastern Mediterranean as well as central and western Europe. Greek bottom-up HFC emissions reported to the UNFCCC were higher than our top-down estimates, whereas for Turkey our estimates agreed with UNFCCC-reported values for HFC-125 and HFC-143a, but were much and slightly smaller for HFC-134a and HFC-152a, respectively. Sensitivity estimates suggest an improvement of the a posteriori emission estimates, i.e., a reduction of the uncertainties by 40–80 % in the entire inversion domain, compared to an inversion using only the existing central European AGAGE observations.

Abstract 4CMenB is the first broad coverage vaccine for the prevention of invasive meningococcal disease caused by serogroup B strains. To gain a comprehensive picture of the antibody response induced upon 4CMenB vaccination and to obtain relevant translational information directly from human studies, we have isolated a panel of human monoclonal antibodies from adult vaccinees. Based on the Ig-gene sequence of the variable region, 37 antigen-specific monoclonal antibodies were identified and produced as recombinant Fab fragments, and a subset also produced as full length recombinant IgG1 and functionally characterized. We found that the monoclonal antibodies were cross-reactive against different antigen variants and recognized multiple epitopes on each of the antigens. Interestingly, synergy between antibodies targeting different epitopes enhanced the potency of the bactericidal response. This work represents the first extensive characterization of monoclonal antibodies generated in humans upon 4CMenB immunization and contributes to further unraveling the immunological and functional properties of the vaccine antigens. Moreover, understanding the mechanistic nature of protection induced by vaccination paves the way to more rational vaccine design and implementation.

Based on observations of the chlorofluorocarbons CFC-13 (chlorotrifluoromethane), ΣCFC-114 (combined measurement of both isomers of dichlorotetrafluoroethane), and CFC-115 (chloropentafluoroethane) in atmospheric and firn samples, we reconstruct records of their tropospheric histories spanning nearly 8 decades. These compounds were measured in polar firn air samples, in ambient air archived in canisters, and in situ at the AGAGE (Advanced Global Atmospheric Gases Experiment) network and affiliated sites. Global emissions to the atmosphere are derived from these observations using an inversion based on a 12-box atmospheric transport model. For CFC-13, we provide the first comprehensive global analysis. This compound increased monotonically from its first appearance in the atmosphere in the late 1950s to a mean global abundance of 3.18 ppt (dry-air mole fraction in parts per trillion, pmol mol−1) in 2016. Its growth rate has decreased since the mid-1980s but has remained at a surprisingly high mean level of 0.02 ppt yr−1 since 2000, resulting in a continuing growth of CFC-13 in the atmosphere. ΣCFC-114 increased from its appearance in the 1950s to a maximum of 16.6 ppt in the early 2000s and has since slightly declined to 16.3 ppt in 2016. CFC-115 increased monotonically from its first appearance in the 1960s and reached a global mean mole fraction of 8.49 ppt in 2016. Growth rates of all three compounds over the past years are significantly larger than would be expected from zero emissions. Under the assumption of unchanging lifetimes and atmospheric transport patterns, we derive global emissions from our measurements, which have remained unexpectedly high in recent years: mean yearly emissions for the last decade (2007–2016) of CFC-13 are at 0.48 ± 0.15 kt yr−1 (> 15 % of past peak emissions), of ΣCFC-114 at 1.90 ± 0.84 kt yr−1 (∼ 10 % of peak emissions), and of CFC-115 at 0.80 ± 0.50 kt yr−1 (> 5 % of peak emissions). Mean yearly emissions of CFC-115 for 2015–2016 are 1.14 ± 0.50 kt yr−1 and have doubled compared to the 2007–2010 minimum. We find CFC-13 emissions from aluminum smelters but if extrapolated to global emissions, they cannot account for the lingering global emissions determined from the atmospheric observations. We find impurities of CFC-115 in the refrigerant HFC-125 (CHF2CF3) but if extrapolated to global emissions, they can neither account for the lingering global CFC-115 emissions determined from the atmospheric observations nor for their recent increases. We also conduct regional inversions for the years 2012–2016 for the northeastern Asian area using observations from the Korean AGAGE site at Gosan and find significant emissions for ΣCFC-114 and CFC-115, suggesting that a large fraction of their global emissions currently occur in northeastern Asia and more specifically on the Chinese mainland.

Air quality transcends all scales with in the atmosphere from the local to the global with handovers and feedbacks at each scale interaction. Air quality has manifold effects on health, ecosystems, heritage and climate. In this review the state of scientific understanding in relation to global and regional air quality is outlined. The review discusses air quality, in terms of emissions, processing and transport of trace gases and aerosols. New insights into the characterization of both natural and anthropogenic emissions are reviewed looking at both natural (e.g. dust and lightning) as well as plant emissions. Trends in anthropogenic emissions both by region and globally are discussed as well as biomass burning emissions. In terms of chemical processing the major air quality elements of ozone, non-methane hydrocarbons, nitrogen oxides and aerosols are covered. A number of topics are presented as a way of integrating the process view into the atmospheric context; these include the atmospheric oxidation efficiency, halogen and HOx chemistry, nighttime chemistry, tropical chemistry, heat waves, megacities, biomass burning and the regional hot spot of the Mediterranean. New findings with respect to the transport of pollutants across the scales are discussed, in particular the move to quantify the impact of long-range transport on regional air quality. Gaps and research questions that remain intractable are identified. The review concludes with a focus of research and policy questions for the coming decade. In particular, the policy challenges for concerted air quality and climate change policy (co-benefit) are discussed. © 2009 Elsevier Ltd.