The present work analyses the behaviour of aqueous solutions of N,N-dimethylethylenediamine as chemical solvent for carbon dioxide separation by gas-liquid absorption. The interest of this molecule is centred on the presence of different types of amino centres that confer the capability to act as typical solvent based on mixtures of amines taking into account the suitable behaviour of some mixtures. For this reason a comparison between diamine and amine blend solvents has been carried out in order to understand the differences between these solvents using absorption and NMR studies. This experimental work analyses the influence of amine type, concentration and ratio between different amines. Also, the effect of gas flow rate used in the bubble column reactor upon the absorption kinetics has been analysed.

Medical Algorithm: Early Introduction of Food Allergens in High Risk PopulationsHelen R Fisher,1,2 Gideon Lack,1,2,3 Graham Roberts,4,5,6 Henry T Bahnson,7 George Du Toit.1,2,31Paediatric Allergy Group, Department of Women and Children’s Heath, School of Life Course Sciences, King’s College London, London, United Kingdom2Paediatric Allergy Group, Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College London, London, United Kingdom.3Children’s Allergy Service, Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom.4The David Hide Asthma and Allergy Research Centre, St Mary’s Hospital, Newport, UK.5NIHR Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.6Faculty of Medicine, Clinical and Experimental Sciences, Human Development in Health Academic Units, University of Southampton, Southampton, UK.7Immune Tolerance Network, Benaroya Research Institute, Seattle, WashingtonCorresponding Authour:Professor George Du ToitPaediatric AllergyBlock B, South WingSt Thomas’ HospitalLondonSE1 7EHTel: 0207 188 9784Email: [email protected] Count: 602Tables: 0Figures: 1Oral Tolerance Induction (OTI) is the only RCT-proven effective intervention for preventing childhood food allergy.(1) OTI to peanut is effective in a general population, with the greatest effect, 81% RRR, noted in the high-risk population.(2) OTI also reduced egg allergy in the general population.(1) Many governmental and allergy societies now recommend introducing peanut in infancy and some suggest other foods, such as well-cooked egg, are also introduced. Choosing which infants should undergo OTI, at what age, to which foods, and under which circumstances is critical for successful OTI prevention in populations where food allergy is a public health concern.Infants with eczema are at increased risk of food allergy but infants from the general population are also at risk and contribute most cases at a population level. Risk of food sensitisation or food allergy increase with age; OTI is most likely to be successful when started in early infancy. Oral tolerance induction from 4 months of age, when completed using standard foods, is safe for nutrition, growth and general child health outcomes (3). Commencing multiple food OTI at 4 months of age, has no detrimental effect on established breastfeeding.(4) All children should adopt a diverse weaning diet, including allergenic foods such as well-cooked egg and peanut, as soon as weaning commences. High risk children should not delay weaning but start weaning and actively include peanut and well-cooked egg, as soon as developmentally ready; usually at about 4 months of age (Fig 1).A 2g/week dosing regime of peanut and well-cooked egg in early infancy is more effective in inducing oral tolerance than later introduction.(5) A lower dosing regime has not been shown to be effective in preventing allergy but, importantly, does not increase allergy risk above that of children who introduce allergenic foods in later infancy.(4) There are limited data regarding the efficacy of OTI to other allergenic foods, or the dose required.(1) All infants should aim to consume about 2g of peanut protein and well-cooked egg per week; parents of high-risk infants should give these amounts more diligently. Given the benefit observed for peanut and egg, it is reasonable for all weaning infants to additionally incorporate 2g of other common and nutritious food allergens; cow’s milk (e.g. as yoghurt), wheat, fish and sesame.Whether children should undergo allergy testing and/or have their first feed of peanut under medical supervision is contested. This cautious approach, potentially requiring large numbers of children to access specialist allergy care, must be balanced against the risks of severe allergic reaction, particularly as most allergic reactions occur on first oral exposure. RCTs of OTI using whole foods had no cases of anaphylaxis on first exposure (4, 6) although anaphylaxis has occurred to OTI using pasteurised whole egg powder.(7) Children with no personal food allergy risk factors do not require testing prior to, or medical supervision during, their first consumption of peanut or well-cooked egg. Children with moderate to severe eczema, or with an existing food allergy should undergo allergy testing +/- OFC at a specialist allergy centre(8), if doing so would not cause undue delay to OTI. It is likely that rapid access to allergy services will be further compromised as a consequence of the COVID-19 pandemic. It may however be that access to SpIgE is available through GP or paediatrician which, if ≥0.35KiU/L, will require referral for OFC. If negative (<0.35KiU/L) the food may be introduced at home following precautionary measures for the first feed: child is well; parent is aware of the signs of IgE mediated reaction has, access to medical support if required and age-appropriate form of the food is given incrementally (Figure 1).

Adolescent and young adult (AYA) patients need additional support while they experience the challenges associated with their age. They need specific training to learn the knowledge and skills required to confidently self-manage their allergies and/or asthma. Transitional care is a complex process which should address the psychological, medical, educational and vocational needs of AYA in the developmentally appropriate way. The European Academy of Allergy and Clinical Immunology has developed a clinical practice guideline to provide evidence-based recommendations for healthcare professionals to support the transitional care of AYA with allergy and/or asthma. This guideline was developed by a multi-disciplinary working panel of experts and patient representatives based on two recent systematic reviews. It sets out a series of general recommendations on operating a clinical service for AYA, which include: (i) starting transition early (11-13 years), (ii) using a structured, multidisciplinary approach, (iii) ensuring AYA fully understand their condition and have resources they can access, (iv) active monitoring of adherence and (v) discussing any implications for further education and work. Specific allergy and asthma transition recommendations include (i) simplifying medication regimes and using reminders; (ii) focusing on areas where AYA are not confident and involving peers in training AYA patients; (iii) identifying and managing psychological and socioeconomic issues impacting disease control and quality of life; (iv) enrolling the family in assisting AYA to undertake self-management and (v) encouraging AYA to let their friends know about their allergies and asthma. These recommendations may need to be adapted to fit into national healthcare systems.

Background: Multiplex tests allow for measurement of allergen-specific IgE responses to multiple allergen extracts and components and have several advantages for large cohort studies. Due to significant methodological differences, test systems are difficult to integrate in meta-analyses/systematic reviews since there is a lack of datasets with direct comparison. We aimed to create models for statistical integration of allergen-specific IgE to peanut/tree nut allergens from three IgE-test platforms. Methods: Plasma from Canadian and Austrian children with peanut/tree nut sensitization and a cohort of sensitized, high-risk, pre-school asthmatics (total n=166) were measured with three R&D multiplex IgE test platforms: Allergy Explorer, ALEX (Macro Array Dx), MeDALL-chip (Mechanisms of Development of Allergy) (Thermo Fisher), and EUROLINE (EUROIMMUN). Skin prick test (n=51) and ImmunoCAP (n=62) results for extracts were available in a subset. Regression models (Multivariate Adaptive Regression Splines, local polynomial regression) were applied if >30% of samples were positive to the allergen. Intra-test correlations between PR-10 and nsLTP allergens were assessed. Results: Using two regression methods, we demonstrated the ability to model allergen-specific relationships with acceptable measures of fit (r2=94-56%) for peanut and tree nut sIgE testing at the extract and component-level, in order from highest to lowest: Ara h 2, Ara h 6, Jug r 1, Ana o 3, Ara h 1, Jug r 2, Cor a 9. Conclusion: Our models support the notion that conversion is reasonably possible between sIgE multiplex platforms for allergen extracts and components and may provide options to aggregate data for future meta-analysis.

Background: Arteriovenous access (AV) thrombosis is important and preventable problem among chronic hemodialysis (HD) patients. On the other hand, systolic blood pressure (SBP) alteration relates with higher cardiovascular mortality among these patients. In this study, we investigated the relation between SBP changes and arteriovenous access (AV) thrombosis. Methods: 50 HD patients with thrombosis and 50 HD patients without thrombosis were included in the study. Odds ratios and 95% confidence intervals were estimated with multivariate adjusted logistic regression models to determine the association between potential thrombosis-related risk factors and thrombosis risk. Results: Elder adults, women, and patients with arteriovenous grafts, lower intradialytic SBP and higher SBP variations during dialysis sessions had higher incidence of AV access thrombosis. Chronic inflammation and mineral metabolism related parameters were also found to be abnormal at the time of AV access thrombosis. Conclusions: Close monitoring and management of intra-dialytic hypotension, SBP variation in every dialysis session and correction of biochemical parameters are critical for earlier identification and prevention of AV access thrombosis in HD patients.

A document by Mohamad Syafeeq Faeez Md Noh. Click on the document to view its contents.

Aims: Accumulating evidence links COVID-19 incidence and outcomes with vitamin D status. We investigated if an interaction existed between vitamin D levels and social deprivation in those with and without COVID-19 infection. Methods: Upper- or lower-respiratory tract samples from 104 patients were tested for SARS-CoV-2 RNA in accordance with Public Health England criteria (January–May 2020) using RT-PCR. The latest serum total 25-hydroxyvitamin D(25-OHD) levels, quantified by LC-MS/MS, was obtained for each patient (September 2019–April 2020). Index of Multiple Deprivation (IMD) was generated for each patient. Univariate and logistic regression analyses examined associations between age, gender, 25-OHD, IMD score and SARS-CoV-2 result in the total cohort and subgroups. Results: In the total cohort, a positive SARS-CoV-2 test was significantly associated with lower 25-OHD levels and higher IMD. A positive test was associated with higher IMD in the male subgroup and with lower 25-OHD levels in those aged >72 years. Low 25-OHD and IMD quintile 5 were separately associated with positive COVID-19 outcome in the cohort. Patients in IMD quintile 5 with vitamin D levels ≤34.4 nmol/L were most likely to have a positive COVID-19 outcome, even more so if aged >72 years (OR: 19.07, 95%CI: 1.71–212.25; p=0.016). Conclusions: In this cohort, combined low vitamin D levels and higher social deprivation were most associated with COVID-19 infection. In older age, this combination was even more significant. Our data supports the recommendations for normalising vitamin D levels in those with deficient / insufficient levels and in groups at high-risk for deficiency.

A document by Leonell Freytes. Click on the document to view its contents.

Mitotane is the only drug approved for treating adrenocortical carcinoma (ACC) by the FDA since 1959, despite the controversy regarding its efficacy in prolonging patient survival. This drug has cytotoxic effects on tumor tissue by inducing cell death and antisecretory effects on adrenal cells by inhibiting the synthesis of adrenocortical steroids involved in the pathogenesis of ACC. To reach the therapeutic plasma concentration, high doses of mitotane are usually necessary, which may result in several adverse effects. This suggests that important pharmacological features are involved in the mechanisms of action of this drug, such as first pass metabolism, tissue accumulation, and extensive time needed for drug elimination. However, few studies have reported the pharmacological aspects of mitotane, and they did not provide sufficient evidence regarding monitoring mitotane’s therapeutic effects. Therefore, this review summarized the chemistry, pharmacokinetics and pharmacodynamics, therapeutic effects, toxic effects, and new perspectives of mitotane treatment that are currently under investigation. Understanding the pharmacological profile of mitotane can improve the monitoring and efficacy of this drug in ACC treatment and can further provide useful information for the development of new drugs with specific action against ACC with fewer adverse effects.

Outcomes in partial sternotomy for aortic root surgery: the new routine procedure?Running Head: Partial sternotomy for aortic root repair

Primary bone composite sarcoma is a very rare entity that primarily affects adolescent and young adult patients. It usually combines areas of liposarcoma and osteosarcoma and up to 60% of cases have metastatic disease at diagnosis. It is a highly aggressive pathology with intrinsic resistance to conventional treatment schemes for bone sarcomas. The prognosis is poor, with long term survival rates that do not exceed 30%. We present the case of an adolescent female diagnosed with a primary agressive bone composite sarcoma with rhabdomyosarcoma foci and loco-regional lymph node involvement.

Our purpose is to assess epidemiological agent-based models– or ABMs - of the SARS-CoV-2 pandemic methodologically. The rapid spread of the outbreak requires fast-paced decision-making regarding mitigation measures. However, the evidence for the efficacy of non-pharmaceutical interventions such as imposed social distancing and school or workplace closures is scarce: few observational studies use quasi-experimental research designs, and conducting randomized controlled trials seems infeasible. Additionally, evidence from the previous coronavirus outbreaks of SARS and MERS lacks external validity, given the significant differences in contagiousness of those pathogens relative to SARS-CoV-2. To address the pressing policy questions that have emerged as a result of COVID-19, epidemiologists have produced numerous models that range from simple compartmental models to highly advanced agent-based models. These models have been criticized for involving simplifications and lacking empirical support for their assumptions. In order to address these voices and methodologically appraise epidemiological ABMs, we consider AceMod (the model of the COVID-19 epidemic in Australia) as an example of the modeling practice. Our case study shows that, although epidemiological ABMs involve simplifications of various sorts, the key characteristics of social interactions and the spread of SARS-CoV-2 are represented sufficiently accurately. This is the case because these modelers treat empirical results as inputs for constructing modeling assumptions and rules that the agents follow; and they use calibration to assert the adequacy to benchmark variables. Given this, we claim that the best epidemiological ABMs are models of actual mechanisms and deliver both mechanistic and difference-making evidence. Furthermore, the efficacy claims are not only internally valid but also adequately describe the effects of interventions in the targets of the models. We also discuss the limitations of ABMs and put forward policy recommendations.

Cor triatriatum is a rare congenital heart disease. A 57-years-old woman had cor triatriatum with severe mitral valve regurgitation (MR) and atrial fibrillation (AF). We perfomed mitral valve repair, left atrial appendage resection, and maze procedure by resection of the anomalous septum in the left atrium. At result, MR was controllable and AF disappeared after the operation. Although there is no established maze procedure with cor triatriatum, removing the septum was effective to complete it.

Cardiac pseudoaneurysm is a contained rupture of the cardiac wall. Rarely symptomatic, the risk of death by stroke or rupture is high and suggests surgical treatment. Surgical strategy depends on its anatomical considerations. We reported the case of a submitral pseudoaneurysm. We excluded it by a conservative transmitral approach, without any short- and long-term complication.

Metabolic pathways have emerged as cornerstones in carcinogenic deregulation providing new therapeutic strategies for cancer management. This is illustrated by the recent discovery of a cholesterol metabolic branch involving the biochemical transformation of 5,6-epoxycholesterol (5,6-ECs). 5,6-ECs have been shown to be differentially metabolized in breast cancers (BC) compared to normal breast tissue. 5,6-ECs are metabolized into the tumour promoter oncosterone in BC, while they are transformed into the tumour suppressor metabolite dendrogenin A (DDA) in normal breast tissue. Blocking oncosterone’s mitogenic and invasive potential will represent new opportunities for BC treatment. The reactivation of DDA biosynthesis, or its use as a drug, represents promising therapeutic approaches such as DDA-deficiency complementation, activation of BC cell re-differentiation and BC chemoprevention. This review presents current knowledge as to the 5,6-EC metabolic pathway in BC focusing on the 5,6-EC metabolic enzymes ChEH and HSD11B2, and on 5,6-EC metabolite targets LXRβ and GR.

Complete vibrational assignments have been performed for free base, cationic and hydrochloride species derived from antiviral adamantadine by combination of hybrid B3LYP with the 6-31G* and 6-311++G** basis sets and the SQMFF methodology. Normal internal coordinates and scaling factors were used to obtain the harmonic force fields and scaled force constants of three species in gas phase and in aqueous solution. Bond lengths and angles of cationic and hydrochloride species show very good concordances with the experimental of amantadinium azide. The cationic species reveals higher solvation energy value, as compared with antiviral agents, however, brincidofovir, the antiviral used to ebola disease presents a higher reactivity against to adamantadine. Positive value of Mulliken charge on N1 of hydrochloride species in solution could justify the ionic character of H29•••Cl30 bond, as evidenced by bond order and AIM calculations. The hydrochloride species is the most reactive in both media while the cationic species the less reactive. High electrophilicity and nucleophilicity indexes of cationic species in both media justify its higher hydration. Good concordances were observed between experimental and predicted 1H and 13C NMR and electronic spectra. In solution, the three species are present as revealed by the experimental UV spectrum of hydrochloride amantadine

This work proposes a novel population-balance based model for a bubbling fluidized bed reactor. This model considers two continuum phases: bubble and emulsion. The evolution of the bubble size distribution was modeled using a population balance, considering both axial and radial motion. This sub-model involves a new mathematical form for the aggregation frequency, which predicts the migration of bubbles from the reactor wall towards the reactor center. Additionally, the reacting particles were considered as a lagrangian phase, which exchanges mass with the emulsion phases. For each particle, the variation of the pore size distribution was also considered. The model presented here accurately predicted the experimental data for biochar gasification in a lab-scale bubbling fluidized bed reactor. Finally, the aggregation frequency is shown to serve as a scaling parameter.

Giant congenital melanocytic nevi are brown-black lesions larger than 20 cm caused by benign proliferation of melanocytes. They either regress or progress in time in matters of thickness and size and may transform to malignancies. Here we report a twelve year old patient with giant melanocytic nevus of the scalp.