Science is perception: what can our sense of smell tell us about ourselves and the world around us?

Human sensory processes are well understood: hearing, seeing, perhaps even tasting and touch—but we do not understand smell—the elusive sense. That is, for the others we know what stimuli causes what response, and why and how. These fundamental questions are not answered within the sphere of smell science; we do not know what it is about a molecule that … smells. I report, here, the status quo theories for olfaction, highlighting what we do not know, and explaining why dismissing the perception of the input as ‘too subjective’ acts as a roadblock not conducive to scientific inquiry. I outline the current and new theory that conjectures a mechanism for signal transduction based on quantum mechanical phenomena, dubbed the ‘swipe card’, which is perhaps controversial but feasible. I show that such lines of thinking may answer some questions, or at least pose the right questions. Most importantly, I draw links and comparisons as to how better understanding of how small (10’s of atoms) molecules can interact so specially with large (10 000’s of atoms) proteins in a way that is so integral to healthy living. Repercussions of this work are not just important in understanding a basic scientific tool used by us all, but often taken for granted, it is also a step closer to understanding generic mechanisms between drug and receptor, for example

Conformal prediction for frequency-severity modeling

We present a nonparametric model-agnostic framework for building prediction intervals of insurance claims, with finite sample statistical guarantees, extending the technique of split conformal prediction to the domain of two-stage frequency-severity modeling. The effectiveness of the framework is showcased with simulated and real datasets. When the underlying severity model is a random forest, we extend the two-stage split conformal prediction procedure, showing how the out-of-bag mechanism can be leveraged to eliminate the need for a calibration set and to enable the production of prediction intervals with adaptive width

Management of the Sickle Cell Trait: An Opinion by Expert Panel Members.

The number of individuals with the sickle cell trait exceeds 300 million worldwide, making sickle cell disease one of the most common monogenetic diseases globally. Because of the high frequency of sickle cell disease, reproductive counseling is of crucial importance. In addition, unlike other carrier states, Sickle Cell Trait (SCT) seems to be a risk factor for several clinical complications, such as extreme exertional injury, chronic kidney disease, and complications during pregnancy and surgery. This expert panel believes that increasing knowledge about these clinical manifestations and their prevention and management can be a useful tool for all healthcare providers involved in this issue

Plasmablastic lymphoma of the stomach : a case report

We report the case of a 53 year-old woman with a gastric tumor showing morphological, phenotypical and molecular features of a plasmablastic lymphoma, a recently recognized subtype of diffuse large B-cell lymphoma. The tumor was composed of plasmablast-like cells, lacked CD45 and B-cell associated antigens, expressed the plasma cellassociated antigen CD38, and showed clonally rearranged IgH genes in the absence of bcl-2 and bcl-6 genes rearrangement

Selecting b-thalassemia patients for gene therapy: a decision-making algorithm

The Societ\ue0 Italiana Talassemie ed Emoglobinopatie (Italian Society of Thalassemias and Hemoglobinopathies, SITE) has developed this document based on multidisciplinary discussions of a panel of experts to provide guidance on the identification and selection of patients with transfusion-dependent beta-thalassemia (\u3b2-TDT) who could benefit from gene therapy. Currently, allogeneic transplantation of hematopoietic stem cells is the only curative and most widely used therapy treatment for \u3b2-TDT. However, recent trials of gene therapy have reported very promising results in terms of overall survival and thalassemia-free survival and are opening a new landscape of treatment. This algorithm for the selection of patients suitable for gene therapy and the supporting notes were formulated by consensus review after an evaluation of currently available scientific evidence using validated criteria. The evidence was interpreted with caution because clinical trial experience of gene therapy is currently limited, a conventional treatment is available for patients with \u3b2-TDT and the availability of gene therapy will, at least initially, be quite limited. Clinical experience of allogeneic transplantation in \u3b2-TDT, which began in 1981, immediately showed the importance of patient risk stratification in order to achieve the best results (see the Pesaro experience and their classification of patients according to risk). Published data in the literature and the recent analysis of clinical evidence by the European Registry of Hemoglobinopathies of a large number of patients (2011 and 2018 analyses) confirm that young patient age (<14 years) and the availability of a human leukocyte antigen (HLA)-identical family donor are factors that offer the best outcome from allogeneic transplantation. Current knowledge of, and experience with, non-conventional treatments, such as allogeneic transplantation and gene therapy, are discussed in order to identify the best available treatment and indication for these patients according to their characteristics. At this point in time, when we can see the emergence of \u2018the age of gene therapy\u2019, it is essential to establish the optimal patient setting in which gene therapy can be applied, or better, to define the setting that represents the most suitable indication for gene therapy, identify the patients who should have clinical priority for access to the procedure, and set out requirements and recommendations for the identification of qualified treatment centers for gene therapy. When considering changes to the treatment of patients with \u3b2-TDT, including gene therapy, it is essential that a detailed consultation is held with the patient and their caregiver/family to discuss all possible risks and potential benefits from the treatment. Discussion of this aspect of care is outside of the scope of this document but remains an important element of patient care

Morbidity and mortality of sickle cell disease patients is unaffected by splenectomy: evidence from three decades of follow-up in a high-income setting

Sickle cell disease (SCD) is a globally widespread hereditary red cell disorder characterized by the production of pathological hemoglobin S (HbS).1 Patients with SCD include homozygous subjects for HbS (SS) and compound heterozygotes with HbS/HbC (SC) or HbS/β+/0-thalassemia (Sβ0/β+). In Italy, SCD is endemic with HbS/β+/0-thalassemia being prevalent in areas of southern Italy. In the last two decades, the number of SCD patients across Italy has increased due to migration from sub-Saharan Africa and th