7D BIM FOR SUSTAINABILITY ASSESSMENT IN DESIGN PROCESSES: A CASE STUDY OF DESIGN OF ALTERNATIVES IN SEVERE CLIMATE AND HEAVY USE CONDITIONS

Introduction: The emerging of energy and environmental thread has fostered a new cultural design approach to Sustainable Architecture that aims to conceive and implement buildings with a low environmental impact. In this context the role of Building Information Modelling (BIM), as a support tool for sustainable integrated design, acquires great relevance. The purpose of this study is to investigate BIM potential in both addressing preliminary design choices and supporting complex analysis during the advanced design phase, within the whole sustainable design process. A technological rail building is assumed as a case study: the Operation Control Centre for the new Oman Railway, whose preliminary project was elaborated by the Italian engineering society Italferr s.p.a. Methods: The BIM approach is used to identify possible problems and deficiencies in the preliminary project, which may represent a good basis for a next design improvements proposal. The next phase consists in investigating and experimenting BIM tools potential in supporting the Conceptual Design, by using Autodesk® Revit® and IES VE® software suites, for the modelling and the energy analysis of different conceptual design solutions. Once the optimal building shape is established, the study focuses on the evaluation of sustainability effects brought by the structural building component, in particular for what concerns its materials environmental impact. Results and discussion: The analysis of the preliminary project shows the potential of BIM in the control of many performance parameters of a building in the design phase, revealing all the design problems associated to the lack of an integral multi-disciplinary approach during the initial phases of the process. The possibility of looking into a series of solutions in a quick and in-depth manner permits an accurate assessment of the most adequate form for a building based on the place in which it is set, thus joining current technological design methods to traditional bio-climatic methods, reinstating the strong and inevitable link between site and building

Correction of beta-thalassemia major by gene transfer in haematopoietic progenitors of pediatric patients

Beta-thalassemia is a common monogenic disorder due to mutations in the beta-globin gene and gene therapy, based on autologous transplantation of genetically corrected haematopoietic stem cells (HSCs), holds the promise to treat patients lacking a compatible bone marrow (BM) donor. We recently showed correction of murine beta-thalassemia by gene transfer in HSCs with the GLOBE lentiviral vector (LV), expressing a transcriptionally regulated human beta-globin gene. Here, we report successful correction of thalassemia major in human cells, by studying a large cohort of pediatric patients of diverse ethnic origin, carriers of different mutations and all candidates to BM transplantation. Extensive characterization of BM-derived CD34(+) cells before and following gene transfer shows the achievement of high frequency of transduction, restoration of haemoglobin A synthesis, rescue from apoptosis and correction of ineffective erythropoiesis. The procedure does not significantly affect the differentiating potential and the relative proportion of haematopoietic progenitors. Analysis of vector integrations shows preferential targeting of transcriptionally active regions, without bias for cancer-related genes. Overall, these results provide a solid rationale for a future clinical translation

Differential Inhibitor Sensitivity between Human Kinases VRK1 and VRK2

Human vaccinia-related kinases (VRK1 and VRK2) are atypical active Ser-Thr kinases implicated in control of cell cycle entry, apoptosis and autophagy, and affect signalling by mitogen activated protein kinases (MAPK). The specific structural differences in VRK catalytic sites make them suitable candidates for development of specific inhibitors. In this work we have determined the sensitivity of VRK1 and VRK2 to kinase inhibitors, currently used in biological assays or in preclinical studies, in order to discriminate between the two proteins as well as with respect to the vaccinia virus B1R kinase. Both VRK proteins and vaccinia B1R are poorly inhibited by inhibitors of different types targeting Src, MEK1, B-Raf, JNK, p38, CK1, ATM, CHK1/2 and DNA-PK, and most of them have no effect even at 100 µM. Despite their low sensitivity, some of these inhibitors in the low micromolar range are able to discriminate between VRK1, VRK2 and B1R. VRK1 is more sensitive to staurosporine, RO-31-8220 and TDZD8. VRK2 is more sensitive to roscovitine, RO 31–8220, Cdk1 inhibitor, AZD7762, and IC261. Vaccinia virus B1R is more sensitive to staurosporine, KU55933, and RO 31–8220, but not to IC261. Thus, the three kinases present a different pattern of sensitivity to kinase inhibitors. This differential response to known inhibitors can provide a structural framework for VRK1 or VRK2 specific inhibitors with low or no cross-inhibition. The development of highly specific VRK1 inhibitors might be of potential clinical use in those cancers where these kinases identify a clinical subtype with a poorer prognosis, as is the case of VRK1 in breast cancer

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

A Comparison of Hand-wrist Bone and Cervical Vertebral Analyses in Measuring Skeletal Maturation

Objective: To compare skeletal maturation as measured by hand-wrist bone analysis and by cervical vertebral analysis. Materials and Methods: A radiographic hand-wrist bone analysis and cephalometric cervical vertebral analysis of 30 patients (14 males and 16 females; 7–18 years of age) were examined. The hand-wrist bone analysis was evaluated by the Bjork index, whereas the cervical vertebral analysis was assessed by the cervical vertebral maturation stage (CVMS) method. To define vertebral stages, the analysis consisted of both cephalometric (13 points) and morphologic evaluation of three cervical vertebrae (concavity of second, third, and fourth vertebrae and shape of third and fourth vertebrae). These measurements were then compared with the hand-wrist bone analysis, and the results were statistically analyzed by the Cohen . concordance index. The same procedure was repeated after 6 months and showed identical results. Results: The Cohen . index obtained (mean . SD) was 0.783 . 0.098, which is in the significant range. The results show a concordance of 83.3%, considering that the estimated percentage for each case is 23.3%. The results also show a correlation of CVMS I with Bjork stages 1–3 (interval A), CVMS II with Bjork stage 4 (interval B), CVMS III with Bjork stage 5 (interval C), CVMS IV with Bjork stages 6 and 7 (interval D), and CVMS V with Bjork stages 8 and 9 (interval E). Conclusions: Vertebral analysis on a lateral cephalogram is as valid as the hand-wrist bone analysis with the advantage of reducing the radiation exposure of growing subjects

Characterization of the rescued �Voghera� sweet pepper landrace grown in northern Italy

A traditional Italian sweet pepper landrace, �Peperone di Voghera�, which faced the risk of extinction, was analyzed for its genetic, phenological, morphological, agronomic and biochemical traits. An extant population was compared with cultivars �Quadrato d�Asti�, �Cuneo�, and �Giallo d�Asti�, cultivated in the same area, in order to evaluate the chance of the landrace recovery. Amplified fragment length polymorphism (AFLP) analysis demonstrated that Voghera landrace is distinct with respect to reference cultivars, thus excluding extensive genetic contamination and providing a molecular basis of both phenological and biochemical differences. Leaf chlorophyll content is lower, fruits start ripening earlier than controls, and yield (1100-1300 g plant-1) does not significantly differ. Sensitivity to root pathogens, the main factor that led to the decline in the past, does not seem to compromise the future chance of recovery. Vitamin C concentration is high (200-240 mg/100 g) and preserved by cold storage; more than 25% of vitamin C is also kept in pickled fruits. �Voghera� landrace has nutritional and gastronomic properties that can be appreciated by consumers. The high internal genetic variability shown by AFLP analysis indicates that future selection work is necessary to fully maintain the original traits of the landrace and to improve it