Modelling: Understanding pandemics and how to control them.

New disease challenges, societal demands and better or novel types of data, drive innovations in the structure, formulation and analysis of epidemic models. Innovations in modelling can lead to new insights into epidemic processes and better use of available data, yielding improved disease control and stimulating collection of better data and new data types. Here we identify key challenges for the structure, formulation, analysis and use of mathematical models of pathogen transmission relevant to current and future pandemics.

Modelling varicella vaccination - What does a lack of surge in herpes zoster incidence tell us about exogenous boosting?

Background: For decades, assessments of the impact of universal varicella vaccination on the epidemiology of varicella and herpes zoster (HZ) have been made using mathematical modelling. Decreased virus circulation and the resulting diminished exogenous boosting have been predicted to lead to a surge in HZ incidence. Lately, the exogenous boosting hypothesis has been challenged due to a lack of an extensive surge in HZ incidence in countries with, by now long-standing universal varicella vaccination.

Key questions for modelling COVID-19 exit strategies.

Combinations of intense non-pharmaceutical interventions (lockdowns) were introduced worldwide to reduce SARS-CoV-2 transmission. Many governments have begun to implement exit strategies that relax restrictions while attempting to control the risk of a surge in cases. Mathematical modelling has played a central role in guiding interventions, but the challenge of designing optimal exit strategies in the face of ongoing transmission is unprecedented.

"How do online and offline sampling compare in a multinational study of drug use and nightlife behaviour?".

Background: Online sampling is widely used to recruit hard to reach samples such as drug users at nightlife events. We conducted the first study comparing differences in demographics, drug use and nightlife behaviour between an online sample of young adults engaging with the European nightlife scene, and an offline sample recruited at nightclubs and festivals in Europe.

Methods: Online participants who attended at least six nightlife events in the past 12 months were recruited using social media advertising (May-November 2017).

Updated Indicators to Evaluate Harmful Drug Use, in Particular, Poly-Drug Use.

Background: Drug use indicators that are capable of measuring the individual levels of harm following drug use, and in particular, poly-drug use, have previously been proposed, based on individual drug and frequency of use data and expert rankings of harms related to various substances. These indicators allow the estimation of risk profiles for selected groups of individuals and comparisons, both over time and between populations. Recent advances regarding the ranking of drug use harms allow a refinement of these indicators, separating the effects on self and others.

Determination of the conformational states of strychnine in solution using NMR residual dipolar couplings in a tensor-free approach.

Small molecules with rotatable bonds can occupy different conformational states in solution as a consequence of their thermal fluctuations. The accurate determination of the structures of such states, as well as of their statistical weights, has been challenging because of the technical difficulties in extracting information from experimental measurements, which are normally averaged over the conformational space available. Here, to achieve this objective, we present an approach based on a recently proposed tensor-free method for incorporating NMR residual dipolar couplings as structural restraints in replica-averaged molecular dynamics simulations.

Influenza in workplaces: transmission, workers' adherence to sick leave advice and European sick leave recommendations.

Background: Knowledge about influenza transmission in the workplace and whether staying home from work when experiencing influenza-like illness can reduce the spread of influenza is crucial for the design of efficient public health initiatives.

Aim: This review synthesizes current literature on sickness presenteeism and influenza transmission in the workplace and provides an overview of sick leave recommendations in Europe for influenza.

Methods: A search was performed on Medline, Embase, PsychINFO, Cinahl, Web of Science, Scopus and SweMed to identify studies related to workplace contacts, -transmission, -interventions and compliance with recommendations to take sick leave.

Four key challenges in infectious disease modelling using data from multiple sources.

Public health-related decision-making on policies aimed at controlling epidemics is increasingly evidence-based, exploiting multiple sources of data. Policy makers rely on complex models that are required to be robust, realistically approximating epidemics and consistent with all relevant data. Meeting these requirements in a statistically rigorous and defendable manner poses a number of challenging problems.

Methods for estimating incidence of drug use: a review.

Several methods for estimating drug use incidence, that have been used in the literature or that could be used, having been used in a different framework, are described and commented. The applicability of the different methods depends on available data and knowledge about relevant parameters. The many similarities between drug use incidence estimation and estimation of disease incidence are highlighted, but also the distinguishing aspects that make drug use incidence estimation a challenge to standard statistical methods.

Estimates of cocaine use in Milan.

A comparative analysis of three different estimation methods of cocaine use in Milan, Italy, is carried out, including an analysis of the size and trends of the underlying reference population. The three cocaine use estimates are derived from wastewater analysis, a "street" survey and one-source capture-recapture analysis of administrative sanctions for drug possession. All three data sources span several years during the decade 2000-2010.

Alternative splicing tends to avoid partial removals of protein-protein interaction sites.

Background: Anecdotal evidence of the involvement of alternative splicing (AS) in the regulation of protein-protein interactions has been reported by several studies. AS events have been shown to significantly occur in regions where a protein interaction domain or a short linear motif is present. Several AS variants show partial or complete loss of interface residues, suggesting that AS can play a major role in the interaction regulation by selectively targeting the protein binding sites.

ADP ribosylation adapts an ER chaperone response to short-term fluctuations in unfolded protein load.

Gene expression programs that regulate the abundance of the chaperone BiP adapt the endoplasmic reticulum (ER) to unfolded protein load. However, such programs are slow compared with physiological fluctuations in secreted protein synthesis. While searching for mechanisms that fill this temporal gap in coping with ER stress, we found elevated levels of adenosine diphosphate (ADP)-ribosylated BiP in the inactive pancreas of fasted mice and a rapid decline in this modification in the active fed state.

Effect of vaccines and antivirals during the major 2009 A(H1N1) pandemic wave in Norway--and the influence of vaccination timing.

To evaluate the impact of mass vaccination with adjuvanted vaccines (eventually 40% population coverage) and antivirals during the 2009 influenza pandemic in Norway, we fitted an age-structured SEIR model using data on vaccinations and sales of antivirals in 2009/10 in Norway to Norwegian ILI surveillance data from 5 October 2009 to 4 January 2010. We estimate a clinical attack rate of approximately 30% (28.7-29.

Adsorption and reduction of glutathione disulfide on α-Al2O3 nanoparticles: experiments and modeling.

Glutathione disulfide (GSSG; γ-GluCysGly disulfide) was used as a physiologically relevant model molecule to investigate the fundamental adsorption mechanisms of polypeptides onto α-alumina nanoparticles. Its adsorption/desorption behavior was studied by enzymatic quantification of the bound GSSG combined with zeta potential measurements of the particles. The adsorption of GSSG to alumina nanoparticles was rapid, was prevented by alkaline pH, was reversed by increasing ionic strength, and followed a nearly ideal Langmuir isotherm with a standard Gibbs adsorption energy of -34.

Supramolecular self-assembly driven by electrostatic repulsion: The 1D aggregation of rubrene pentagons on Au111.

At present, organic molecules are among the best candidate "building blocks" for the construction of self-assembling nanoscale devices based on metal substrates. Control of the formation of specific patterns in the submonolayer regime is usually achieved by appropriate choice and/or functionalization of the adsorbates. The effect of this intervention, though, is limited by the typically short-range character of the bonding.

Drosophila lethal giant larvae neoplastic mutant as a genetic tool for cancer modeling.

Drosophila lethal giant larvae (lgl) is a tumour suppressor gene whose function in establishing apical-basal cell polarity as well as in exerting proliferation control in epithelial tissues is conserved between flies and mammals. Individuals bearing lgl null mutations show a gradual loss of tissue architecture and an extended larval life in which cell proliferation never ceases and no differentiation occurs, resulting in prepupal lethality. When tissues from those individuals are transplanted into adult normal recipients, a subset of cells, possibly the cancer stem units, are again able to proliferate and give rise to metastases which migrate to distant sites killing the host.

Social contacts and mixing patterns relevant to the spread of infectious diseases.

Background: Mathematical modelling of infectious diseases transmitted by the respiratory or close-contact route (e.g., pandemic influenza) is increasingly being used to determine the impact of possible interventions.

Scenarios of diffusion and control of an influenza pandemic in Italy.

To predict the spread of a pandemic strain of influenza virus in Italy and the impact of control measures, we developed a susceptible-exposed, but not yet infectious-infectious-recovered, and no longer susceptible (SEIR) deterministic model with a stochastic simulation component. We modelled the impact of control measures such as vaccination, antiviral prophylaxis and social distancing measures. In the absence of control measures, the epidemic peak would be reached about 4 months after the importation of the first cases in Italy, and the epidemic would last about 7 months.

Structure and energetics of diphenylalanine self-assembling on Cu(110).

We investigate the dynamical features of the adsorption of diphenylalanine molecules on the Cu(110) surface and of their assembling into supramolecular structures by a combination of quantum and classical atomistic modeling with dynamic scanning tunneling microscopy and spectroscopic experiments. Our results reveal a self-assembling mechanism in which isolated adsorbed molecules change their conformation and adsorption mode as a consequence of their mutual interactions. In particular, the formation of zwitterions after proton transfer between initially neutral molecules is found to be the key event of the assembling process, which stabilizes the supramolecular structures.

Epidemiology and costs of herpes zoster: background data to estimate the impact of vaccination.

In 2004, we conducted a study in Piemonte (Italy), in order to describe incidence, treatment, hospitalizations and costs of herpes zoster (HZ), in population over 14 years of age. Twenty-four regional general practitioners, with 26,394 patients >14 years in charge (0.71% of the regional population), reported prospectively all diagnosed HZ cases.

Changes in the expression of hypothalamic lipid sensing genes in rat model of intrauterine growth retardation (IUGR).

Intrauterine growth retardation (IUGR) has been linked to the development of type 2 diabetes in later life. The mechanisms underlying this phenomenon are unknown. Recent data suggest that some of the molecular defects underlying type 2 diabetes reside in the CNS.

[Assessment of the potential impact in Italy of extensive varicella vaccination programs based on a mathematical model].

A mathematical model has been developed in order to assess the effect of extended programs of varicella vaccination on the epidemiology of the disease in Italy. The effect of different vaccination options have been estimated by the change in incidence of the disease and age distribution of cases over a short and long period of time. The developed mathematical model reproduces chickenpox transmission and immunisation; five strategies different for target age of vaccination and/or proportion of vaccinated subjects have been considered.

[Hypothyroidism and megacolon].

A 71 years old woman, affected by ischemic heart disease from the age of 50 and by chronic constipation was admitted to the emergency department for drowsiness, intense dyspnea and acute abdominal distension. Laparotomy evidenced a megacolon. Because of the age and sex of the patient the congenital form of the megacolon was ruled out.