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Funder: British Lung Foundation (BLF); doi: https://doi.org/10.13039/501100000351, Funder: Royal Society through a University Research Fellowship and the Engineering and Physical Sciences Research Council (EPRSC), Funder: China Scholarship Council (CSC); doi: https://doi.org/10.13039/501100004543, Mesothelioma is an aggressive cancer that is associated with exposure to asbestos. Although asbestos is banned in several countries, including the UK, an epidemic of mesothelioma is predicted to affect middle-income countries during this century owing to their heavy consumption of asbestos. The prognosis for patients with mesothelioma is poor, reflecting a failure of conventional chemotherapy that has ultimately resulted from an inadequate understanding of its biology. However, recent work has revolutionised the study of mesothelioma, identifying genetic and pathophysiological vulnerabilities, including the loss of tumour suppressors, epigenetic dysregulation and susceptibility to nutrient stress. We discuss how this knowledge, combined with advances in immunotherapy, is enabling the development of novel targeted therapies.

T1 Figure 1ConclusionsOverall, this largest paediatric single cell COVID-19 study to date showed significant differences in response to SARS-CoV-2 between children and adults, reflecting the changes of the immune landscape over developmental time, which in children are dominated by naive and innate responses.

While a substantial proportion of adults infected with SARS-CoV-2 progress to develop severe disease, children rarely manifest respiratory complications. Therefore, understanding differences in the local and systemic response to SARS-CoV-2 infection between children and adults may provide important clues about the pathogenesis of SARS-CoV-2 infection. To address this, we first generated a healthy reference multi-omics single cell data set from children (n=30) in whom we have profiled triple matched samples: nasal and tracheal brushings and PBMCs, where we track the developmental changes for 42 airway and 31 blood cell populations from infancy, through childhood to adolescence. This has revealed the presence of naive B and T lymphocytes in neonates and infants with a unique gene expression signature bearing hallmarks of innate immunity. We then contrast the healthy reference with equivalent data from severe paediatric and adult COVID-19 patients (total n=27), from the same three types of samples: upper and lower airways and blood. We found striking differences: children with COVID-19 as opposed to adults had a higher proportion of innate lymphoid and non-clonally expanded naive T cells in peripheral blood, and a limited interferon-response signature. In the airway epithelium, we found the highest viral load in goblet and ciliated cells and describe a novel inflammatory epithelial cell population. These cells represent a transitional regenerative state between secretory and ciliated cells; they were found in healthy children and were enriched in paediatric and adult COVID-19 patients. Epithelial cells display an antiviral and neutrophil-recruiting gene signature that is weaker in severe paediatricversusadult COVID-19. Our matched blood and airway samples allowed us to study the spatial dynamics of infection. Lastly, we provide a user-friendly interface for this data1as a highly granular reference for the study of immune responses in airways and blood in children.

This paper presents the results of growth rate and condition index analysis of Mytilus galloprovincialis in integrated system and monoculture. The aim of this study was to show if there are differences in growth and condition index of mussels between integrated multi-trophic aquaculture (IMTA) and monoculture farming. The growth rate and condition index were monitored during a 13-month study at three different sites: 1) close to fish cages (NBL), 2) 100 m removed from fish cages (NUD), 3) at a monoculture mussel farm (SVN) around 8 km far away from cages. The most intense growth of mussels was recorded in spring, and the least intense in summer. After 13 months, monitored individuals at all three locations achieved commercial size. The growth rate was very similar at all sites. The condition index showed spatial and temporal differences. Condition index values on site NUD were mostly higher compared to SVN and NBL, which were very similar, exept for the period from October to December when CI was similar on NBL and NUD site and higher in comparation with SVN. CI values on NBL an NUD site during cold period indicate on fact that mussels probably feed on the nutrients from fish farm origins.The highest mortality rate was recorded at the NBL site, probably due to the effects of fouling organisms., Cilj ovog istraživanja bio je pokazati postojanja mogućih razlika u rastu i kondicijskom indeksu dagnji (Mytilus galloprovincialis) u integralnom multi-trofičkom uzgoju i uzgoju u monokulturi. Rast i kondicijski indeks praćeni su tijekom razdoblja od 13 mjeseci na tri postaje: 1) u blizini uzgajališta ribe (NBL), 2) 100 m od uzgajališta ribe (NUD), 3) u monokulturi (SVN) na uzgajalištu koje je oko 8 km udaljeno od kaveza sa ribom. Najintenzivniji rast zabilježen je tijekom proljetnog razdoblja, a najmanje intenzivan tijekom ljetnog. Nakon 13 mjeseci, praćene jedinke su na sve tri pozicije dostigle komercijalnu dužinu. Stopa rasta je bila slična na sve tri pozicije, dok je kondicijski indeks pokazao prostorne i vremenske razlike. Vrijednosti kondicionog indeksa na postaji NUD bile su više od vrijendosti na postajama SVN i NBL, koje su međusobno bile prilično slične, osim u razdoblju od listopada do prosinca kada su vrijednosti kondicijskog indeksa bile slične na postajama NBL i NUD, a veće u usporedbi sa vrijednostima na postaji SVN poziciji. Vrijednosti kondicionog indeksa na postajama NBL i NUD tijekom hladnog perioda godine ukazuju na to da se dagnje vjerovatno hrane nutrijentima porijeklom sa uzgajališta riba. Visoki mortalitet zabilježen je na postaji NBL, najvjerojatnije zbog obraštajnih organizama.

Background and aim of the study The animal models of congenital diaphragmatic hernia (CDH) have contributed to identify several signaling pathways potentially associated to the pathogenesis of lung hypoplasia. However, due to their in vivo nature, these models can only demonstrate the consequence of the malformation and thus are not adequate to evaluate different factors which may have influence on pulmonary hypoplasia separately. In particular, it is still unclear at what extent physical constraint produced by herniated abdominal viscera affects the lung development. We aim at developing a novel ex vivo model harnessing an innovative three-dimensional (3D) printing technique to recapitulate the lung development impaired by physical constraint in CDH. Methods Lungs harvested from E12.5 mouse embryos were embedded in Matrigel solution and maintained in air-liquid interphase (ALI) culture conditions. On the following day (equivalent to E13.5), a 3D structure surrounding the outer surface of the left lobe was built by polymerization of a chemically modified Polyethylene-glycol (PEG) solution, which was added to Matrigel and selectively cross-linked through a two-photon laser. Main results The 3D structure mimics the physical constraint observed in CDH. Live imaging demonstrates decreased growth and delayed branching impeded by 3D structure. After 4 days of culture, the size of the lobe and the number of epithelial branching of the lung surrounded by 3D structure were significantly decreased compared to the control lungs cultured without physical constraint. Conclusions We envision our model as an innovative way to investigate the pathogenesis of pulmonary hypoplasia of CDH. This model has a potential to be applied to human embryo, paving the way for a deeper understanding of the molecular pathways implicated in the mechanism of pulmonary hypoplasia.

The European Respiratory Society (ERS) International Congress is the largest respiratory congress and brings together leading experts in all fields of respiratory medicine and research. ERS Assembly 3 shapes the basic and translational science aspects of this congress, aiming to combine cutting-edge novel developments in basic research with novel clinical findings. In this article, we summarise a selection of the scientific highlights from the perspective of the three groups within Assembly 3. In particular, we discuss new insights into the pathophysiology of the human alveolus, novel tools in organoid development and (epi)genome editing, as well as insights from the presented abstracts on novel therapeutic targets being identified for idiopathic pulmonary fibrosis., The amount of basic and translational science presented at #ERSCongress is steadily increasing, showing novel cutting-edge technologies and models. http://bit.ly/2GgXIJi

The article deals with the problem of energy saving by optimizing heat loss and measures for energy recovery in the existing preschools. The paper presents a theoretical basis, simulation and computations - calculations of heating energy needs for established models, by using appropriate software packages. The program and development of models for improving energy qualities of the envelope, with the tendency of switching to renewable energy sources, are defined. The methods used in this paper include the method of modelling based on the digital simulation of the representative facility, as well as local visits and interviews with relevant researchers, policy makers and preschool educators. The survey is conducted through a case study on the territory of the City of Nis.

At the time of changing economic circumstances, adaptation and conversion of historic structures is an increasingly popular approach. Some historical buildings are very suitable for the revitalization into the modern hotels. The paper analyzes the relationship of the hotel, the city and its architectural heritage, as well as some of the factors that led to the eruption of alternative models of hotels, shown through a series of successful solutions. Many challenges of hotel design in historic buildings are listed and corresponding solutions are offered. Some methodological directions are indicated, and certain guidelines and principles for further activities in this field are formulated. In conclusion their applicability in practice is discussed, and certain disadvantages and limitations are listed. Key words : historic building, hotel, adaptation, revitalization, architecture, design

Ulaganja u izgradnju novih vrtića su na nezavidnoj razini u Srbiji. S druge strane, postojeći objekti su zastarjeli, devastirani i ne ispunjavaju važeće propise, posebice u pogledu energetske učinkovitosti. Boravak djece u takvim objektima predstavlja značajan društveni problem te je stoga neophodna obnova ovih objekata. U radu su prikazane mjere energetske oporabe i metode za njihovu provedbu u okviru sveobuhvatne revitalizacije postojećih dječjih vrtića. Kroz studiju slučaja, provedena je analiza energetske i troškovne učinkovitosti za tri paketa mjera, a rezultati su prezentirani i diskutirani. Navedene su prednosti primijenjene metode, kao i potencijalna područja provedbi rezultata. Osim toga, dane su neke preporuke za buduća istraživanja, i naglašena su ograničenja u primjeni dobivenih rezultata., Investments in the construction of new kindergartens are at a low level in Serbia. On the other hand, the existing facilities are outdated, devastated and do not meet current regulations, especially in terms of energy efficiency. The attendance of children in such facilities represents a significant social issue and therefore, the refurbishment of these structures is necessary. This paper presents measures for energy recovery and methods of their implementation within the framework of a comprehensive revitalization of the existing kindergartens. Through a case study, an analysis of energy efficiency and cost effectiveness for three sets of measures has been conducted, the findings of which are presented and discussed. The advantages of the applied methods are listed, as well as the potential areas for the implementation of the results. In addition, some recommendations for the future research are given and the limitations in the application of the obtained results are emphasized.

The majority of art museums all over the world have found their accommodation in buildings whose primary function and service, at the time of construction, was completely different. Conversion was more a rule than an exception during (not so long) museum history, and it is unambiguous that typological structure of renaissance and baroque palaces have had dominant influence on museum organization and structure. The further important step forward, considering museum accommodation in historical buildings, happened after the Second World War, with reevaluation and representation of old artistic works by means of new architectonic tools. During the late seventies, reaction of artists to contemporary prevailing trends in museum architecture resulted in creation of numerous unconventional museums, placed in abandoned industrial facilities, warehouses, powerplants, on the margins of official culture, as a contrast to the overdesigned museums as sites of luxury and entertainment. Not long afterwards, the network of museum institutions has accepted the vital elements of this "parallel cultural system" concept and reaffirmed conversion as an equally worthy solution for collection accommodation and temporary exhibition space. In this paper, we have presented the history of conversion as a part of museum architectural typology evolution, advantages and disadvantages of conversion, as well as the contribution of conversion to the sustainable urban development.

Based on case history and clinical and electrophysiological examinations, the authors report on a case of an 8-year-old girl who was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy. The disease was complicated by deafness and kidney fibrosis. During treatment with methylprednisolone and intravenous immunoglobulin, followed by mycophenolate mofetil, prompt improvement of neurological findings occurred. The improvement of hearing was poor. Because the pathogenesis of chronic inflammatory demyelinating polyradiculoneuropathy has still not been clear, and on the grounds of several cases of chronic inflammatory demyelinating polyradiculoneuropathy conjoined with the kidney disease described in literature (glomerulopathy, interstitial nephritis), every patient with chronic inflammatory demyelinating polyradiculoneuropathy needs to undergo the urinalyses.

Background/Aim. Hemodynamic stress is the leading cause of acute renal failure (ARF) in premature neonates. Incidence of ARF in this population is between 8 and 24%. The aim of this study was to determine the frequency of presence of ARF in premature neonates, as well as its impact on their survival. Methods. A retrospective study of 114 premature neonates [(gestational age, GA less than 37 gestation weeks (gw)] admitted to the Intensive Care Unit (ICU) at the Pediatric Clinic, Institute of Child and Youth Healthcare of Vojvodina in 2007 was conducted. Serum creatinine, urea and bilirubine were determined on the 3rd day of life in 65 newborns who met inclusion criteria. ARF was diagnosed in 16 newborns (n=16/65; 25%). Results. The premature neonates with ARF had significantly lower GA [

Primary spontaneous pneumothorax (PSP) occurs in apparently healthy young people with an incidence of 12.5 cases per 100 000 per year [1]. Attempts to develop standardised care guidelines for this condition have been severely hampered by a lack of high-quality clinical research into this condition. The American College of Chest Physicians (CHEST) concluded in 2001 that “insufficient data exist…to develop an evidence-based document” and so produced a consensus statement based on expert opinion [2]. Similarly, the British Thoracic Society (BTS) 2010 guidelines are based predominantly on nonanalytical studies and expert opinion [3]. In both documents, the size of the presenting PSP is used to determine initial treatment. A “small” PSP without respiratory compromise is thought not to require intervention, while a “large” PSP has typically been treated either by aspiration or intrapleural drainage. Implicit in these definitions is the belief that large pneumothoraces will not respond well to conservative management. Remarkably, no consensus regarding the definition of PSP severity exists, with CHEST and the BTS each using different arbitrary measurements of the presentation chest radiograph. When these measurements were compared directly to one another, they showed poor correlation [4]. This lack of a clinically useful radiological biomarker for pneumothoraces requiring intervention hinders the development of evidence-based care of this condition. We wished to determine whether the BTS definition of large pneumothorax (>2 cm at the hilum) or CHEST definition (>3 cm from apex to cupola) better predicts the requirement for intercostal chest drain (ICD) insertion., Hilar rather than apical interpleural distance more accurately predicts need for intercostal chest drain insertion http://ow.ly/JvKFY

Dermoid cysts are the most common type of ovarian tumour and should be removed due to possible complications. We report a case of a woman who suffered severe granulomatous peritonitis following laparoscopic removal of a dermoid cyst. This required laparotomy, with subsequent enterocutaneous fistula formation. This case demonstrates the importance of adequate irrigation and the use of an endobag in removing dermoid cysts laparoscopically.

We report the case of a 77 year-old Caucasian woman with a past medical history of breast cancer who presented to our institution with a five-week history of progressive shortness of breath associated with abdominal distension, anorexia, change in bowel habit and cough. She had an ejection systolic murmur and a pansystolic murmur radiating to the axilla, a raised jugular venous pressure, abdominal distension with shifting dullness and hepatomegaly 16 cm below the costal margin. Blood results revealed a normocytic anemia with deranged liver function tests, renal impairment and a raised C-reactive protein. Chest radiograph demonstrated a raised right hemidiaphragm (Fig. 1A). Transtho

65-year-old woman presented with slowly progressing dysphagia of two to three years’ duration. The patient’s dysphagia was intermittent and was associated with solid food during the initial phase, but progressed to difficulty with swallowing liquids. During the few months before presentation, she also experienced heartburn, nausea and vomiting. She denied significant weight loss or anorexia. Her medical history was notable for cholecystectomy 11 years previously, and she was taking ranitidine. Physical examination and routine laboratory investigations including complete blood count, renal and liver function tests were within the normal range. She underwent gastroscopy followed by a barium swallow, which demonstrated an epiphrenic diverticulum and a midesophageal diverticulum (Figure 1). Following barium swallow, she underwent esophageal manometry (Figure 2). This demonstrated simultaneous contraction in the esophageal body of normal amplitude and duration (Figure 2). The resting lower esophageal sphincter pressure was elevated (49 mmHg), but the relaxation was complete (Figure 2), confirming an atypical variant achalasia. Gastroscopy also demonstrated epiphrenic diverticulum and a ‘tight’ gastroesophageal junction without a mucosal abnormality. The endoscope was passed through the gastroesophageal junction with a slight resistance.

Common variable immunodeficiency is a primary immunodeficiency disease characterized by reduced serum immunoglobulins and heterogeneous clinical features. Recurrent pyogenic infections of upper and lower respiratory tracts are the main clinical manifestations of common variable immunodeficiency. Hemolytic uremic syndrome is a multisystemic disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia, and organ ischemia due to platelet aggregation in the arterial microvasculature. This is one of the rare cases of patients diagnosed with common variable immunodeficiency, which was complicated by hemolytic uremic syndrome.

Introduction and Objectives Attempts to develop standardised guidelines in the management of primary spontaneous pneumothorax (PSP) have been severely hampered by a lack of high quality clinical research. The American College of Chest Physicians (ACCP) and BTS guidelines are based on non-analytical studies and expert opinion. Remarkably, no consensus regarding the definition of PSP severity exists, with the ACCP and BTS each using different arbitrary measurements: hilar size > 2cm (BTS) versus apical size >3cm (ACCP). The objective of this study is to define the critical size of PSP. Methods A multi-centre prospective comparison of 168 consecutive patients presenting with PSP was performed in 13 NHS hospitals in the East of England over a period of 15 months. We compared the ability of the BTS and ACCP definitions to predict the eventual need for intercostal chest drain (ICD) insertion. Since current BTS guidelines state that pleural aspiration should be attempted prior to drainage in non-compromised PSP patients, we reasoned that ICD insertion was a valid endpoint. Using a logistic regression model that included hospital, age, hilar size, apical size and the hilar-apical interaction, we generated receiver operating characteristic (ROC) curves reflecting the probability of either measure correctly predicting the eventual need for ICD. Results One hundred and sixteen of 168 patients for whom data were collected had been treated according to BTS guidelines. Of these, 39 eventually required ICD insertion. The correlation between hilar and apical distances was high (0.7). The logistic regression showed that hilar distance was statistically significant (p Conclusion Guidelines based on hilar distance, such as the BTS’s, are likely to be more informative in predicting the eventual need for ICD. However, the two distances are highly correlated. This study, for the first time, provides an evidence-based clinically relevant definition of PSP requiring ICD that will guide treatment and serve as the foundation for subsequent trials.

Objective The progression of liver cirrhosis eventually increases cardiac output, while blood pressure and systemic vascular resistance are reduced. A complex behavior of portal hemodynamic to hepatic artery and system circulation has not yet been presented. There is a lack in knowledge about the correlation of local and systemic circulation parameters to the degree of liver failure, with respect to presence of ascites and esophageal varices. Patients and Methods The study sample was 76 patients hospitalized for established alcoholic liver cirrhosis. Patients were divided into groups according to Child-Pugh clinical score; grade A (n = 24), B (n = 18) and C (n = 18). Ascites was found in 28 patients and esophageal varices in 46. Portal vein flow velocity (PVFV), hepatic artery resistance index (HARI), heart and great vessels within mediastinal cavity were assessed with ultrasound devices equipped with spectral Doppler. Results Significant differences in mean blood pressure, systemic vascular resistance index (SVRI) minute volume, cardiac index and PVFV were found in the group of patients with the most severe stage (C). In regard to presence of ascites statistically significant difference was observed in elevated mean blood pressure and SVRI. Correlation was found between conjugated HARI to blood pressure and to SVRI. Conclusions In patients with liver cirrhosis there is an inversely reciprocal relationship of conjugated HARI with PVFV, correlating to disease grade. PVFV in cirrhosis decreases and HARI values were over 0.7. Study demonstrated that combining echocardiography with abdominal Doppler ultrasound served as valuable non-invasive diagnostic insight in liver and systemic circulation among different grade of cirrhosis.

A great number of preschool buildings in Serbia, mainly in south-eastern part of Central Serbia, have been examined as a part of scientific project carried at Faculty of Civil Engineering and Architecture in Nis. Even though this is an on-going project with data still being collected, there has been sufficient material to make an overview of field situation and draft framework for proposed reconstruction strategy as a main goal of this study. This analysis presents the basis for examining and valorizing local preschool facilities. In addition to treating structural, environmental and aesthetic (internal and external) properties of the buildings, we carried out analysis of energy status of preschool buildings. Investigation of foreign experience with the process of revitalization of this group of buildings has served as the framework for the final part of the chapter, which offers suggestions for improving quality of preschool facilities in Serbia.

Introduction Operations on the common bile duct may lead to potentially serious complications such as biliary peritonitis. T-tube insertion is performed to reduce the risk of this occurring postoperatively. Biliary leakage at the point of insertion into the common bile duct, or along the fistula, can sometimes occur after T-tube removal and this has been reported extensively in the literature. We report a case where the site at which the T-tube fistula leaked proved to be the point of contact between the fistula and the anterior abdominal wall, a previously unreported complication. Case presentation A 36-year-old sub-Saharan African woman presented with gallstone-induced pancreatitis and, once her symptoms settled, laparoscopic cholecystectomy was performed, common bile duct stones were removed and a T-tube was inserted. Three weeks later, T-tube removal led to biliary peritonitis due to the disconnection of the T-tube fistula which was recannulated laparoscopically using a Latex drain. Conclusion This case highlights a previously unreported mechanism for bile leak following T-tube removal caused by detachment of a fistula tract at its contact point with the anterior abdominal wall. Hepatobiliary surgeons should be aware of this mechanism of biliary leakage and the use of laparoscopy to recannulate the fistula.