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COVID-19 related deaths underestimate the pandemic burden on mortality because they suffer from completeness and accuracy issues. Excess mortality is a popular alternative, as it compares observed with expected deaths based on the assumption that the pandemic did not occur. Expected deaths had the pandemic not occurred depend on population trends, temperature, and spatio-temporal patterns. In addition to this, high geographical resolution is required to examine within country trends and the effectiveness of the different public health policies. In this tutorial, we propose a framework using R to estimate and visualise excess mortality at high geographical resolution. We show a case study estimating excess deaths during 2020 in Italy. The proposed framework is fast to implement and allows combining different models and presenting the results in any age, sex, spatial and temporal aggregation desired. This makes it particularly powerful and appealing for online monitoring of the pandemic burden and timely policy making.

Supplemental material, sj-docx-1-mdm-10.1177_0272989X221132257 for Use of Advanced Flexible Modeling Approaches for Survival Extrapolation from Early Follow-up Data in two Nivolumab Trials in Advanced NSCLC with Extended Follow-up by M. A. Chaudhary, M. Edmondson-Jones, G. Baio, E. Mackay, J. R. Penrod, D. J. Sharpe, G. Yates, S. Rafiq, K. Johannesen, M. K. Siddiqui, J. Vanderpuye-Orgle and A. Briggs in Medical Decision Making

Small angle neutron scattering experiments performed on a powder of gamma-Fe2O3 nanoparticles reveal the existence of a temperature-dependent magnetic signal, increasing with decreasing temperature. The extra scattering appearing below 275 K is fitted to the sum of a Lorentzian and a Lorentzian squared. The first contribution is attributed to the spin correlations in the particle core, with a correlation length of 2.6 nm at T = 4 K. The second contribution indicates the presence of frozen clusters of coupled particles, with a correlation length that increases with decreasing temperature, up to 60 nm.

Eight children with previously untreated ANLL received an induction regimen consisting of daunomycin and ara-C. All patients achieved complete remission. Post-remission chemotherapy was ara-C 3 g/m2 given i.v. over 3 h, at 12-h intervals, for four doses, and L-asparaginase 6000 IU/m2 i.m. 3 h after the fourth infusion of ara-C; four cycles were given over a period of five to eight months. Two patients received additional treatment. All eight patients relapsed 2–14 months after the treatment was stopped. No benefit was demonstrated by consolidation treatment given with these modalities.

This study focuses on the introduction of different types of insulation materials into existing building systems in Europe, where the chosen scenarios differ by climate zone and according to the Köppen climate classification. The insulation materials used are specifically: natural fibre materials, mineral fibre materials and artificial materials. The analysis in question was based on the assessment of the risk of interstitial condensation between the existing masonry and the insulation and the WCI [Kg/m2] (Water Content in the Insulation), through various simulations in dynamic mode, over a reference period of 10 years prior to the energy upgrading intervention. The case study buildings were taken from TABULA and divided by climatic zone, for the years of construction from 1945 to 1969 related to the building typology of single-family houses, wherein each building system the insulation was placed towards the warm side with a fixed thickness of 5 cm. The simulations concerned: a) the application scenario, b) the type of stratigraphy chosen, (c) exposure of the existing building system. The outputs generated by the simulations provided the data to determine in which type of building, depending on the insulating materials, interstitial condensation is formed or not. It was shown that only for the climate zones of the cities of Oslo and Brussels, associated with their own building typologies, for the insulating materials: mineral and natural, there is the formation of interstitial condensation.

Introduction: Bisphosphonates are the first-choice treatment for osteoporosis. They effectively increase bone mineral density, reduce markers of bone resorption, and lower the incidence of new fractures in patients with osteoporosis-related fracture. However, the efficacy observed in clinical trials may not be realized in a real-life setting, partly due to poor adherence to therapy, with a significant worsening of clinical outcomes. Several issues contribute to poor adherence to osteoporosis medication, including inconvenient dosing regimens and concerns about possible adverse events. Although strategies to improve adherence have been investigated, new approaches are required. Areas covered: We review available data and propose a new approach to improve adherence to osteoporosis therapy in clinical practice. We present the current evidence and personal experience from a group of Italian osteoporosis experts. Expert opinion: To improve adherence, we propose a multifaceted approach, which includes the Triad Model suggested by the World Health Organization, direct observed therapy and the use of drugs with longer administration intervals, e.g., zoledronic acid. The integration of these strategies may provide the basis for a marked increase in adherence to osteoporosis therapy, and improved clinical outcomes in a real-life scenario. © 2011 Informa UK, Ltd.

Purpose: In vivo evaluation of good manufacturing practice-grade targeted liposomal doxorubicin (TVT-DOX), bound to a CD13 isoform expressed on the vasculature of solid tumors, in human tumor xenografts of neuroblastoma, ovarian cancer, and lung cancer. Experimental Design: Mice were implanted with lung, ovarian, or neuroblastoma tumor cells via the pulmonary, peritoneal, or orthotopic (adrenal gland) routes, respectively, and treated, at different days post inoculation, with multiple doses of doxorubicin, administered either free or encapsulated in untargeted liposomes (Caelyx) or in TVT-DOX. The effect of TVT-DOX treatment on tumor cell proliferation, viability, apoptosis, and angiogenesis was studied by immunohistochemical analyses of neoplastic tissues and using the chick embryo chorioallantoic membrane assay. Results: Compared with the three control groups (no doxorubicin, free doxorubicin, or Caelyx), statistically significant improvements in survival was seen in all three animal models following treatment with 5 mg/kg (maximum tolerated dose) of TVT-DOX, with long-term survivors occurring in the neuroblastoma group; increased survival was also seen at a dose of 1.7 mg/kg in mice bearing neuroblastoma or ovarian cancer. Minimal residual disease after surgical removal of neuroblastoma primary mass, and the enhanced response to TVT-DOX, was visualized and quantified by bioluminescence imaging and with magnetic resonance imaging. When treated with TVT-DOX, compared with Caelyx, all three tumor models, as assayed by immunohistochemistry and chorioallantoic membrane, showed statistically significant reductions in cell proliferation, blood vessel density, and microvessel area, showing increased cell apoptosis. Conclusion: TVT-DOX should be evaluated as a novel angiostatic strategy for adjuvant therapy of solid tumors.

Stress of many kinds (psychological, physical, metabolic) is able to induce endocrine modifications in humans, such as growth hormone (GH), prolactin (PRL), luteinizing hormone (LH), glucagon and cortisol release. Argon laser photocoagulation of the retina (RP), the treatment of choice for diabetic retinopathy, is a painful and stressful maneuvre and represents a direct injury onto a nervous tissue. Therefore it was decided to evaluate the possible endocrine modifications induced by RP in diabetic patients affected by retinopathy. In 19 insulin-dependent diabetic patients (12 men and 7 women), RP induced cortisol release in all cases, GH and PRL release in men, but not in women, and no modification of LH and glucagon plasma levels; in 12 similar patients receiving saline infusions without RP, no endocrine modifications were observed. It is concluded that RP elicits GH, PRL and cortisol release in diabetic patients.

We address in this article the problem of performing a statistical survey of a group of individuals present in a certain population when information about the complete list of the members is missing or partially unknown. This problem is particularly relevant in immigration analysis, where many of the individuals are possibly illegal migrants and therefore not formally registered or accounted for in official statistics. We propose a sample method that integrates information provided by specific surveys and subjective knowledge available to the researcher about the geo-social reality of interest.