Business Cases for Major Public Infrastructure Projects in Canada

When governments announce that they are going to spend vast sums of taxpayers’ money on a new public infrastructure project, you can be certain they will praise all the terrific new benefits that the project will bring to citizens, making everyone’s life easier, safer, greener and better. But this does not tell us whether we are better off as a society, after accounting for the cost of these projects borne by taxpayers today and well into the future. In reality, there is a meaningful risk that a project undertaken without a proper business case could end up making citizens’ lives worse. That new commuter train might look sleek and shiny and seem convenient for some, but a close business case analysis of recent transit projects in Canada’s three largest cities suggests that in as many as four cases out of 21 projects, the burden of paying for the projects does not justify the public investment. In a review of thirteen recent public transit projects in the Greater Toronto and Hamilton Area (GTHA), at least three projects had benefits that fell short of the costs. Yet, all three projects went ahead (or have been funded). Only one project showed large net benefits for citizens once all considerations were accounted for. Three projects showed small net benefits – of a size that can be easily offset by a modest cost over-run. The six remaining projects did not have any publicly available business cases. In the Greater Montreal area, a review of three recent major transit projects turned up no evidence of a publicly available business case for any of them. As a result, Montrealers are in the dark as to how much benefit or value destruction the three projects are responsible for. Things are far more encouraging in Vancouver, however, where three out of the five major transit projects undertaken or funded in recent years were backed by business cases showing a net benefit. Only one project did not show a net benefit and one project did not have a business case. Of course, business cases only make projections about net benefits. Rarely, if ever, do governments undertake an ex post review to determine whether their estimates were correct and if the project has delivered — or destroyed — the value expected. Given that these projects can run into the billions of dollars, tie up immense amounts of government resources, and can cause any number of disruptions to business and families, it is remarkable how little cost-benefit scrutiny is brought to bear on them. Without these ex post business cases, there can be no lessons learned from past projects. There can be no assurance that we can make better investment decisions going forward

Fish Skin Graft: Narrative Review and First Application for Abdominal Wall Dehiscence in Children

Summary: Acellular fish skin grafts (FSGs) are tissue-based products created by minimally processing the skin of the Atlantic cod (Gadus morhua). The FSG is rich in omega-3 and facilitates tissue regeneration by supporting revascularization and ingrowth in the proliferation and remodeling phases of wound healing. FSG is structurally more similar to human skin than antiviral-processed skin substitutes such as amniotic membrane, and there are no known prion, bacterial, or viral diseases that can be transmitted from North-Atlantic cod to humans. The FSG is processed using a proprietary method that preserves the structure and lipid composition of the skin. FSG is CE marked, and US Food and Drug Administration cleared for multiple clinical applications in partial and full-thickness wounds. FSG is currently the only acellular dermal matrix product that does not originate from mammalian tissues. For this narrative review, Medline and UpToDate were used to include a total of 21 articles published from 2015 to 2022 about fish skin graft use. We also reported a case of a 7-year-old boy who underwent treatment with FSG for abdominal wall dehiscence at our department of pediatric surgery, IRCCS Sant’Orsola- Malpighi, Alma Mater Studiorum, University of Bologna, University Hospital of Bologna. FSG provides a valuable and sustainable treatment that improves wound healing in both adult and pediatric populations. We described the first application of an FSG for wound dehiscence of the abdominal wall in a pediatric patient, reporting how FSG was completely reabsorbed and improved the skin’s repai

Standard model anomalies: Lepton flavour non-universality and lepton g-2

We critically analyze the body of results that hints to the existence of New Physics from possible violations of lepton universality observed by the LHCb experiment in the $\mu/e$ ratios $R_{K}$ and $R_{K^*}$ to the $g-2$ lepton anomalies. The analysis begins with a theoretical, in depth, study of the $\mu/e$ ratios $R_{K}$ and $R_{K^*}$ as well as the process $B_s \rightarrow \mu^+ \mu^-$. Here we consider the impact of complex Wilson coefficients and derive constraints on their imaginary and real parts. We then move to a comprehensive comparison with experimental results. We show that, by fitting a single Wilson coefficient, the deviations from the Standard Model are at the $4.7\sigma$ level when including only the hadronic insensitive observables while it increases to $6.1\sigma$ when including also the hadronic sensitive ones. When switching on all relevant Wilson coefficients and combining both hadronic sensitive and insensitive data into the fit, the deviation from the Standard Model peaks at 7.2$\sigma$ and decreases at the $4.9\sigma$ level if we assume that the central values of $R_K$ and $R_K^{\ast}$ are taken to be unity. We further estimate the non-perturbative long distance hadronic contributions and show that their inclusion still requires New Physics to fit the data. We then introduce the $g-2$ lepton anomalies results. Different theoretical models are considered that can explain the discrepancies from the Standard Model. In the final part of our work we estimate the impact of the forthcoming data from LHCb (coming from LHC Run3) and Belle II, when it will have accumulated about $5~ab^{-1}$

A mouse embryonic stem cell bank for inducible overexpression of human chromosome 21 genes

BACKGROUND: Dosage imbalance is responsible for several genetic diseases, among which Down syndrome is caused by the trisomy of human chromosome 21. RESULTS: To elucidate the extent to which the dosage imbalance of specific human chromosome 21 genes perturb distinct molecular pathways, we developed the first mouse embryonic stem (ES) cell bank of human chromosome 21 genes. The human chromosome 21-mouse ES cell bank includes, in triplicate clones, 32 human chromosome 21 genes, which can be overexpressed in an inducible manner. Each clone was transcriptionally profiled in inducing versus non-inducing conditions. Analysis of the transcriptional response yielded results that were consistent with the perturbed gene's known function. Comparison between mouse ES cells containing the whole human chromosome 21 (trisomic mouse ES cells) and mouse ES cells overexpressing single human chromosome 21 genes allowed us to evaluate the contribution of single genes to the trisomic mouse ES cell transcriptome. In addition, for the clones overexpressing the Runx1 gene, we compared the transcriptome changes with the corresponding protein changes by mass spectroscopy analysis. CONCLUSIONS: We determined that only a subset of genes produces a strong transcriptional response when overexpressed in mouse ES cells and that this effect can be predicted taking into account the basal gene expression level and the protein secondary structure. We showed that the human chromosome 21-mouse ES cell bank is an important resource, which may be instrumental towards a better understanding of Down syndrome and other human aneuploidy disorders

Standard model anomalies: lepton flavour non-universality, g − 2 and W-mass

International audienceWe critically analyze the body of results that hints to the existence of New Physics from possible violations of lepton universality observed by the LHCb experiment in the μ/e ratios R$_{K}$ and ${R}_{K^{\ast }}$ to the g − 2 lepton anomalies. The analysis begins with a theoretical, in depth, study of the μ/e ratios R$_{K}$ and ${R}_{K^{\ast }}$ as well as the process B$_{s}$→ μ$^{+}$μ$^{−}$. Here we consider the impact of complex Wilson coefficients and derive constraints on their imaginary and real parts. We then move to a comprehensive comparison with experimental results. We show that, by fitting a single Wilson coefficient, the deviations from the Standard Model are at the 4.7σ level when including only the hadronic insensitive observables while it increases to 6.1σ when including also the hadronic sensitive ones. When switching on all relevant Wilson coefficients and combining both hadronic sensitive and insensitive data into the fit, the deviation from the Standard Model peaks at 7.2σ and decreases at the 4.9σ level if we assume that the central values of R$_{K}$ and ${R}_K^{\ast }$ are taken to be unity. We further estimate other unaccounted for SM contributions and show that their inclusion still requires New Physics to fit the data. We then introduce the g − 2 lepton anomalies as well as the most recent W-mass results. Different theoretical models are considered that can explain the discrepancies from the Standard Model. In the final part of our work we estimate the impact of the forthcoming data from LHCb (coming from LHC Run3) and Belle II, when it will have accumulated about 5 ab$^{−1}$

Quality control for biomarker determination in oncology: the experience of the Italian Network for Quality Assessment of Tumor Biomarkers (INQAT)

Biomarker analysis and evaluation in oncology is the product of a number of processes (including managerial, technical and interpretation steps) which need to be monitored and controlled to prevent and correct errors and guarantee a satisfactory level of quality. Several biomarkers have recently moved to clinical validation studies and successively to clinical practice without any definition of standard procedures and/or quality control (QC) schemes necessary to guarantee the reproducibility of the laboratory information. In Italy several national scientific societies and single researchers have activated - often on a pilot level - specific external quality assessment protocols, thereby potentially jeopardizing the clinical reality even further. In view of the seriousness of the problem, in 1998 the Italian Ministry of Health sponsored a National Survey Project to coordinate and standardize the procedures and to develop QC programs for the analysis of cancer biomarkers of potential clinical relevance. Twelve QC programs focused on biomarkers and concerning morphological, immunohistochemical, biochemical, molecular, and immunoenzymatic assays were coordinated and implemented. Specifically, external QC programs for the analytical phase of immunohistochemical p53, Bcl-2, c-erb-2/neu/HER2, and microvessel density determination, of morphological evaluation of tumor differentiation grade, and of molecular p53 analysis were activated for the first time within the project. Several hundreds of Italian laboratories took part in these QC programs, the results of which are available on the web site of the Network (www.cqlaboncologico.it). Financial support from the Italian Government and the National Research Council (CNR) will guarantee the pursuit of activities that will be extended to new biomarkers, to preanalytical phases of the assays, and to revision of the criteria of clinical usefulness for evaluating the cost/benefit ratio