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In this talk, I review the Hubble constant measurements from the observations of the Cosmic Microwave Background, in particular from the Planck satellite.

INTRODUZIONE-SCOPO: La sifilide è un’infezione sistemica cronica causata da Treponema pallidum subsp. pallidum. Rappresenta una delle principali infezioni batteriche a trasmissione sessuale (IST) e costituisce tuttora un rilevante problema di salute pubblica a livello mondiale. Un’accurata conoscenza dello scenario epidemiologico di tale infezione permette di comprendere meglio le dinamiche di trasmissione e di mettere in atto strategie per il controllo della sua diffusione. L’obiettivo di tale lavoro è stato quello di indagare la prevalenza di sifilide e le caratteristiche associate a tale infezione in un gruppo di soggetti afferenti ad un ambulatorio dedicato alla gestione delle IST. MATERIALI E METODI: Sono stati raccolti in maniera retrospettiva i dati riguardanti i pazienti che da gennaio 2016 a dicembre 2017 si sono recati presso l’ambulatorio IST della U.O. di Dermatologia del Policlinico Sant’Orsola di Bologna e che si sono sottoposti a indagini sierologiche per sifilide. L’iter seguito nella U.O. Microbiologia si basa sull’algoritmo inverso, che prevede l’esecuzione di un test di screening treponemico (CMIA, Architect), seguito, in caso di positività, da un secondo test treponemico di conferma (TPHA, Randox), da un test non-treponemico (RPR, Randox) e, in casi selezionati, da un eventuale WB (Mikrogen), per un migliore inquadramento diagnostico. Per tutti i pazienti con sierologia positiva sono stati raccolti dati riguardanti l’età, il sesso, la nazionalità e la presenza di altre IST. RISULTATI: Nel periodo di studio hanno effettuato screening sierologico per sifilide 5609 pazienti (65.8% maschi). Di questi, 692 (12.3%), di cui 613 maschi, sono risultati positivi ai test treponemici. L’età media dei pazienti positivi era di 41.8 anni, significativamente maggiore dei soggetti negativi (32.3 anni; P

Introduzione. Le infezioni da Chlamydia trachomatis (CT) e Neisseria gonorrhoeae (GC) rappresentano le più comuni infezioni batteriche a trasmissione sessuale (IST) nel mondo. Al di là delle localizzazioni genitali, tali microorganismi possono ritrovarsi in sede faringea, in caso di rapporti orali non protetti. Tali infezioni sono spesso asintomatiche e, se non vengono correttamente diagnosticate, rappresentano un significativo serbatoio per la trasmissione. Obiettivo di tale lavoro è stato quello di indagare l’epidemiologia delle infezioni faringee da CT e GC in un gruppo di soggetti afferenti ad un ambulatorio dedicato alla gestione delle IST. Materiali e metodi. Sono stati raccolti retrospettivamente i dati dei pazienti che da gennaio 2016 ad agosto 2018 si sono recati presso l’ambulatorio di Malattie a Trasmissione Sessuale (U.O. Dermatologia) del Policlinico Sant’Orsola-Malpighi di Bologna e che hanno eseguito un tampone faringeo per la ricerca degli acidi nucleici di CT e GC. Tutti i soggetti sottoposti a tale indagine riportavano rapporti orali non protetti. I campioni sono stati testati con una real-time PCR (VERSANT® CT/GC 1.0 Assay, Siemens) attualmente utilizzata nella routine diagnostica della U.O. di Microbiologia del Policlinico. Per ogni paziente sono stati raccolti i dati riguardanti l’età e il sesso. Risultati. Nel periodo di studio sono stati testati complessivamente 842 tamponi faringei, di cui l’85.6% provenienti da uomini. Globalmente, 145 campioni (17.2%) sono risultati positivi per CT e/o GC: in particolare il 2.5% è risultato positivo solo per CT, il 13.3% solo per GC e l’1.4% presentava una positività per entrambi i patogeni contemporaneamente. L’età media dei pazienti positivi è risultata significativamente inferiore rispetto ai negativi (32.9 ± 9.7 vs 34.7 ± 10.1 anni; P=0.04). Inoltre, non è stata rilevata nessuna differenza significativa nella distribuzione delle infezioni da CT e GC in base al sesso (P > 0.05). Infine, analizzando i dati di positività, si è evidenziata una prevalenza similare e senza differenze significative negli anni di studio (21% nel 2016, 12.6 nel 2017, 17.8% nel 2018, P = 0.07). Viceversa, si è registrato un notevole aumento dei campioni inviati per il test molecolare nell’ultimo anno (180 nel 2016, 213 nel 2017 e ben 449 negli 8 mesi del 2018). Conclusioni. Le infezioni faringee da CT e GC rappresentano una condizione molto frequente e spesso sottostimata. I nostri dati suggeriscono un’implementazione delle indagini molecolari per tali infezioni nella routine diagnostica.

Schumpeterian growth theory based on creative destruction was originally designed for continuous time innovation and growth models. However its recently expanding use in DSGE modelling calls for an easily usable discrete time recast. We here show how to construct a discrete time version of creative destruction fully equivalent to its continuous time counterpart.

We describe the stage 4 cosmic microwave background ground-based experiment CMB-S4.

Osseointegration is likely the result of an immunologically driven bone reaction to materials such as titanium. Osseointegration has resulted in the clinical possibility to anchor oral implants in jaw bone tissue. However, the mechanisms behind bony anchorage are not fully understood and complications over a longer period of time have been reported. The current study aims at exploring possible differences between copper (Cu) and polyetheretherketone (PEEK) materials that do not osseointegrate, with osseointegrating cp titanium as control. The implants were placed in rabbit tibia and selected immune markers were evaluated at 10 and 28 days of follow-up. Cu and PEEK demonstrated at both time points a higher immune activation than cp titanium. Cu demonstrated distance osteogenesis due to a maintained proinflammatory environment over time, and PEEK failed to osseointegrate due to an immunologically defined preferential adipose tissue formation on its surface. The here presented results suggest the description of two different mechanisms for failed osseointegration, both of which are correlated to the immune system.

Most countries in the world are not at the technological frontier, yet their economies grow and fluctuate. In this paper we set up a model of endogenous growth with business cycle fluctuations usable to analyze the medium frequency fluctuations in non-frontier countries. The growth mechanism is a Schumpeterian creative destruction framework, which is embedded into a real business cycle dynamic stochastic general equilibrium model, with standard and non-standard features. We allow for multinational firms entering the economy and challenging existing incumbents, and study the tension between their direct positive productivity contribution and their indirect negative contribution through the expected obsolescence of domestic innovators. We calibrate the model and show, via simulations, the potential value added from our prototype model.

International audience; Lensing of the cosmic microwave background (CMB) is now a well-developed probe of the clustering of the large-scale mass distribution over a broad range of redshifts. By exploiting the non-Gaussian imprints of lensing in the polarization of the CMB, the CORE mission will allow production of a clean map of the lensing deflections over nearly the full-sky. The number of high-S/N modes in this map will exceed current CMB lensing maps by a factor of 40, and the measurement will be sample-variance limited on all scales where linear theory is valid. Here, we summarise this mission product and discuss the science that will follow from its power spectrum and the cross-correlation with other clustering data. For example, the summed mass of neutrinos will be determined to an accuracy of 17 meV combining CORE lensing and CMB two-point information with contemporaneous measurements of the baryon acoustic oscillation feature in the clustering of galaxies, three times smaller than the minimum total mass allowed by neutrino oscillation measurements. Lensing has applications across many other science goals of CORE, including the search for B-mode polarization from primordial gravitational waves. Here, lens-induced B-modes will dominate over instrument noise, limiting constraints on the power spectrum amplitude of primordial gravitational waves. With lensing reconstructed by CORE, one can "delens" the observed polarization internally, reducing the lensing B-mode power by 60 %. This can be improved to 70 % by combining lensing and measurements of the cosmic infrared background from CORE, leading to an improvement of a factor of 2.5 in the error on the amplitude of primordial gravitational waves compared to no delensing (in the null hypothesis of no primordial B-modes). Lensing measurements from CORE will allow calibration of the halo masses of the tens of thousands of galaxy clusters that it will find, with constraints dominated by the clean polarization-based estimators. The 19 frequency channels proposed for CORE will allow accurate removal of Galactic emission from CMB maps. We present initial findings that show that residual Galactic foreground contamination will not be a significant source of bias for lensing power spectrum measurements with CORE.

Bone anchored biomaterials have become an indispensable solution for the restoration of lost dental elements and for skeletal joint replacements. However, a thorough understanding is still lacking in terms of the biological mechanisms leading to osseointegration and its contrast, unwanted peri-implant bone loss. We have previously hypothesized on the participation of immune mechanisms in such processes, and later demonstrated enhanced bone immune activation up to 4 weeks around titanium implants. The current experimental study explored and compared in a rabbit tibia model after 10 days of healing time, the bone inflammation/immunological reaction at mRNA level towards titanium, polyether ether ketone (PEEK) and copper compared to a Sham control. Samples from the test and control sites were, after a healing period, processed for gene expression analysis (polymerase chain reaction, (qPCR)) and decalcified histology tissue analysis. All materials displayed immune activation and suppression of bone resorption, when compared to sham. The M1 (inflammatory)/M2 (reparative) -macrophage phenotype balance was correlated to the proximity and volume of bone growth at the implant vicinity, with titanium demonstrating a M2-phenotype at 10 days, whereas copper and PEEK were still dealing with a mixed M1- and M2-phenotype environment. Titanium was the only material showing adequate bone growth and proximity inside the implant threads. There was a consistent upregulation of (T-cell surface glycoprotein CD4) CD4 and downregulation of (T-cell transmembrane glycoprotein CD8) CD8, indicating a CD4-lymphocyte phenotype driven reaction around all materials at 10 days.

Probabilistic reasoning skills are important in various contexts. The aim of the present study was to develop a new instrument (the Probabilistic Reasoning Scale – PRS) to accurately measure low levels of probabilistic reasoning ability in order to identify people with difficulties in this domain. Item response theory was applied to construct the scale, and to investigate differential item functioning (i.e., whether the items were invariant) across genders, educational levels, and languages. Additionally, we tested the validity of the scale by investigating the relationships between the PRS and several other measures. The results revealed that the items had a low level of difficulty. Nonetheless, the discriminative measures showed that the items can discriminate between individuals with different trait levels, and the test information function showed that the scale accurately assesses low levels of probabilistic reasoning ability. Additionally, through investigating differential item functioning, the measurement equivalence of the scale at the item level was confirmed for gender, educational status, and language (i.e., Italian and English). Concerning validity, the results showed the expected correlations with numerical skills, math-related attitudes, statistics achievement, IQ, reasoning skills, and risky choices both in the Italian and British samples. In conclusion, the PRS is an ideal instrument for identifying individuals who struggle with basic probabilistic reasoning, and who could be targeted by specific interventions.

Purpose: To evaluate the controlled release effect of Clarithromycin loaded in PLGA microspheres in a rabbit calvaria defect model. Methods: Clarithromycin-loaded PLGA microspheres (MSPs) were formulated by modified O/W single emulsion/solvent evaporation method. After characterization, in vivo animal experiment was conducted. Four critical size bone defects were created in the calvaria of New Zealand White rabbits (n=21, n=7/time point). The bone defects were randomly designated to 4 groups: Group 1: No augmentation (sham), Group 2: beta-Tricalcium phosphate (β-TCP), Group 3: beta-Tricalcium phosphate (β-TCP) with 0.12 µg clarithromycin, and Group 4: beta-Tricalcium phosphate (β-TCP) with 6.12 µg PLGA microspheres (loaded with 0.12 µg clarithromycin). After 2, 4 and 12 weeks of healing, the levels of bone regeneration were evaluated using micro- computed tomography and histology.Results: The average size of the PLGA microspheres was 26.38 μm that showed 94% encapsulation efficacy with clarithromycin. Clarithromycin release from PLGA microspheres revealed sustained release for around 4 weeks with approximately 50% release of clarithromycin during the first week. In the histological analysis, new bone formation was evident at 2 and 4 weeks of healing in all groups and bone formation increased as a function of healing time in vivo. At 12 weeks, Group 4 showed significantly higher amount of newly formed bone compared to Group 1 (p=0,002). Moreover, during the micro CT exam, Group 4 expressed significantly higher bone formation compared to Group 1 at all time points tested (p=0.00, 0.014, and 0.002 in 2, 4, and 12 weeks, respectively).Conclusions: PLGA microspheres demonstrated initial burst release of clarithromycin followed by a sustained release profile. The in vivo findings showed that β-TCP with clarithromycin-loaded microspheres can enhance bone formation in bone defects.

Dissertation, Malmö University, 2016; 372 pp. (2016). = Dissertation, Malmö University, 2016, The biomedical technologies for bone application are employed in millions of patients every year to restore function and aesthetics following trauma, diseases and congenital deformities. They achieved significant advancements in the last decades and have resulted in the development of implants that function for long periods of time. However, some fundamental clinical challenges still remain and are exacerbated by the aging of the population and by the increased life expectancy of the patients. First of all, permanent implants, despite having very high success rates, still face the risk for marginal bone loss and peri-implant osteolysis in some number of cases. Strategies to fasten, to strengthen and to maintain the bone integration of these implants are desired to enhance the implant clinical performances especially in situation of compromised bone. Secondly, the fixation of fractures and the repair of bone defects are required in a large number of clinical situations, where the intrinsic ability of bone to repair itself is limited. A constantly advocated requirement for osteosynthetic devices is the biodegradability, to avoid a second surgery for implant removal or the permanence of the device in the body for long time, with possible adverse effects. However, especially for osteosynthesis devices, materials that possess adequate mechanical properties for load-bearing applications and that biodegrade upon the substitution of new healthy osseous tissue are not yet available. Magnesium (Mg) is a material that offers potential benefits in these clinical issues. Magnesium is a natural component of the human body, which is involved in numerous enzymatic reactions and metabolic processes; thus, it is tolerated at high levels. It has a prominent role in bone homeostasis and bone health in general and it is considered bioactive, osteoconductive and angiogenetic. Therefore it could be applied as a doping agent to permanent implants and bone grafts, to increase their osseointegration. In addition, magnesium is potentially unique in the field of orthopaedic and cranio-maxillofacial surgery because it provides the mechanical properties of metals, although with an elastic modulus closer to that of cortical bone, and at the same time it degrades under physiological conditions in non-toxic by-products. Based on these clinical needs and on these observations, one aim of the current thesis was to explore the effects of the local release of Mg ions directly at the peri-implant sites on the osseointegration of titanium implants in healthy bone and in bone compromised by osteoporosis. In particular, it was of interest to attempt to elucidate the molecular and biochemical pathways that were stimulated in the peri-implant tissues by the presence of Mg ions and to correlate those to biomechanical and histomorphometrical observation. The other aim of this thesis was to characterize in vivo the degradation behaviour of 3 Mg-alloys tailored for biodegradable osteosynthesis devices and their associated bone response. In Study I to IV, the effects of the local release of Mg ions on the osseointegration of titanium implants in both healthy and osteoporotic bone were investigated. Mg ions were loaded into engineered mesoporous titanium dioxide (TiO2) carriers coated onto titanium implants. Mesoporous films acted as reservoir of drugs and bioactive substances and released them directly at the implant interface in a sustained fashion. After surface characterization of the mesoporous carriers with and without Mg ions by means of scanning electron microscopy (SEM), optical light interferometry (IFM) and atomic force microscopy (AFM), the same types of implants were implanted in animal models. In Study I, Mg-loaded implants were placed in the hind limb of rabbits for 3 weeks and examined with biomechanical analysis and histology. The results suggested that the increased local availability of Mg could accelerate and strengthen the early bone fixation of titanium implants. In Study II, the activation of biological pathways of bone healing and osseointegration of Mg-releasing implants installed in the rabbit tibia model was investigated at the gene level by means of real-time polymerase chain reaction (qPCR) after 3 weeks in vivo. The results found that several osteogenic markers (OC, RUNX-2, IGF-1) were significantly up-regulated in the presence of Mg during the first weeks of healing. This finding was correlated with the histological results, since significantly more threads for the Mg-doped implants were filled with new bone compared to the TiO2 implants without Mg. In Study III, the performance of Mg-loaded implants in bone was studied at a longer healing time of 6 weeks. It was found that the effects of Mg release are prominent in the early healing phases than compared to the later healing, presumably due to the rapid mobilization of the Mg ions from the coatings. In fact, the expression of osteogenic genes in the bone around control implants were dominantly expressed approximately 3 weeks after the dominant expression in the Mg-loaded group. Within the limitation of the observed healing period, no signs of increased inflammation and activation of bone remodelling were triggered by Mg release. In Study IV, the potential benefits of the local administration of Mg ions on implant osseointegration were tested in ovariectomized rats, which mimicked osteoporotic conditions. The presence of Mg-doped implants in osteoporotic subjects induced a significantly faster new bone formation compared to Ti controls and the activation of BMP6, an important anabolic agent that is normally suppressed in osteoporosis. In addition, other osteogenic factors, such as VEGF, were up-regulated in presence of Mg. In Study V, 3 recently developed Mg-alloys intended as temporary materials for osthesynthesis applications were tested in vivo to evaluate their degradation behaviour and the response they elicited in tissues. Mg-2Ag, Mg-10Gd and Mg-4Y-3RE in the form of mini-screws were implanted in the tibia and femur of rats for 4 and 12 weeks. Their degradation rates were investigated by means of high-resolution synchrotron-based micro computed tomography (SRµCT) and by histological sectioning. The tissue reaction to the different materials was analyzed both on histology and on 3D reconstructions of the bone-implant samples. In addition, the chemical composition of the degradation layers was assessed with Electron Probe Micro Analysis (EPMA). Finally, the expression of genes in the tissues in proximity of the mini-screws was investigated by means of qPCR employing a super-array technique. The SRµCT enabled the identification of the degradation layers, the original metal and the bone, thanks to the high spatial and density resolution. The 3-months degradation rates were similar for all materials, but the behaviour of the degradation products differed. The products of Mg-2Ag underwent rapid solubilisation. The rapid loss of sample integrity for this material led to fibrous encapsulation, rather than the desired osseous encapsulation. In the other 2 alloys, the degradation layers deposited in the same shape as the original screws and were mainly stable. That allowed the growth of bone in direct contact with the surfaces of the degradation products and they were osseointegrated at the 3-month healing time. That was confirmed on the histological slides. In addition, the chemical analysis revealed that the degradation products of the alloys were not formed by Mg, but contained Ca, P, C and O in similar amount to the surrounding bone The combination of histological, tomographic and chemical images provided new insight on the nature of the bone-to-implant interface and of the degradation products, which appeared to have great similarities to the host bone. Finally, the analysis of the genes expressed in the peri-implant bone, showed up-regulation of several genes related to osteogenesis around Mg implants compared to Ti ones. In conclusion, this thesis demonstrated that Mg is a suitable doping agent to increase the bone encapsulation of endosseous implants, especially at the early stages of healing and in particular in osteoporotic subjects. That is desirable to shorten the healing period and when early implant loading is considered an option. In addition, Mg-10Gd and Mg-4Y-3RE are biodegradable alloys with a degradation rate and behaviour that is suggested to be suitable for the new bone regeneration and the bone encapsulation.