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The bone tissue can regenerate itself completely and continuously; however, large-scale bone defects may overpower this self-regenerative process. Furthermore, the aging population, the increment in obesity incidence, and the sedentary lifestyles are serious risk factors for bone diseases' development which are associated with the self-regenerative process's failure, high morbidity, and mortality rates. Thus, there is an ever-growing need for strategic approaches targeting bone replacement, its remodelling, and its regeneration. Bone scaffolds have successfully been used as synthetic bone grafts for many years, yet recent bone tissue engineering strategies attempt to explore their multifunctionality by investigating them as drug delivery systems. Bone diseases' treatments can be substantially difficult due to the avascular nature of the surrounding cartilage; thus, targeted drug delivery to the bone can be advantageous: it provides local high drug concentrations and minimizes adverse effects while securing a space for new, healthy tissue growth. Despite the promising scientific progress, studies underlining bone scaffolds' use as local drug delivery systems are not abundant. Hence, this work reviews bone scaffolds' therapeutic interest for local drug delivery in five distinct bone disorders-osteomyelitis, osteoporosis, osteoarthritis, osteosarcoma, and cancer bone metastasis. Additionally, it presents the challenges of this possible therapeutic approach and its future perspectives. Albeit bone scaffolds present therapeutic benefits by acting as drug delivery systems, further pre-clinical and clinical assessments are needed to strengthen their understanding and enable research evidence translation into clinical practice. The mismatch between scientific evolution and regulatory frameworks remains one of the major future challenges.

EOS is an open-source software for a variety of computational tasks in flavor physics. Its use cases include theory predictions within and beyond the Standard Model of particle physics, Bayesian inference of theory parameters from experimental and theoretical likelihoods, and simulation of pseudo events for a number of signal processes. EOS ensures high-performance computations through a C++ back-end and ease of usability through a Python front-end. To achieve this flexibility, EOS enables the user to select from a variety of implementations of the relevant decay processes and hadronic matrix elements at run time. In this article, we describe the general structure of the software framework and provide basic examples. Further details and in-depth interactive examples are provided as part of the EOS online documentation., Comment: 32 pages, 8 figures, 4 ancillary Jupyter example notebooks

Grandparents play an important role in their family’s lives. However, little is known about the demography of grandparenthood. Given dramatic recent changes in fertility, we explore the role of number of children and age at first birth in the timing of the transition into grandparenthood focusing on Italy, a country with well-known North-South fertility differentials. We used data from the 2009 Italian Survey ‘Family and Social Relations’ (N = 10,186) to estimate median ages of grandparenthood across three birth cohorts of parents (1920–29; 1930–39; 1940–49). Findings show an overall postponement of age of grandparenthood of 5 years, shifting for women from early to mid- or late-50s (in the South and North, respectively). Such postponement is largely driven by family compositional changes: although the age of grandparenthood among mothers of three or more children has not changed much over cohorts, the percentage of mothers with such characteristic decreased significantly. The heterogeneity in experiencing the transition to grandparenthood has implications for intergenerational transfers and other roles in later life.

We discuss the possibility of performing precise tests of $\mu/e$ universality in $B \to\pi \ell^+\ell^-$ decays. We show that in wide regions of the dilepton invariant mass spectrum the ratio between muonic and electronic decay widths can be predicted with high accuracy, both within and beyond the Standard Model. We present numerical expressions which can be used to extract precise information on short-distance dynamics if a deviation from universality is observed in the data., Comment: 9 pages, 3 figures

Perforator flaps surgery barely damages underlying muscle function, but only clinical qualitative evidences exist about muscle preservation after surgical dissection. We have employed for the first time electromyography and nerve conduction studies in evaluating the latissimus dorsi electrical muscle function after thoraco-dorsal artery perforator flap dissection in a retrospective cohort study. We included ten consecutive patients requiring axillary reconstruction with thoraco-dorsal artery perforator flap, from June 2017 to June 2018. All patients were suffering from hidradenitis suppurativa. Electromyography (EMG) and nerve conduction study (NCS) were conducted on each patient, both before and after the operation. Differences between pre- and postoperative amplitude and latency values were calculated. Postoperative signal amplitude and latency means did not differ significantly from the preoperative one. Operative time and area of excision did not correlate with changes of electrical function. This is the first quantitative analysis performed for the evaluation of muscle electrical activity after perforator flap surgery. Perforator pedicle intra-muscular dissection does not cause any injury to the muscle fibers. TDAP flap confirms to be a safe procedure for latissimus dorsi muscle function. Level of evidence: Level III, therapeutic study.

We provide updated predictions for the hadronic decays $$\bar{B}_s^0\rightarrow D_s^{(*)+} \pi ^-$$ B ¯ s 0 → D s ( ∗ ) + π - and $$\bar{B}^0\rightarrow D^{(*)+} K^-$$ B ¯ 0 → D ( ∗ ) + K - . They are based on $${\mathcal {O}}(\alpha _s^2)$$ O ( α s 2 ) results for the QCD factorization amplitudes at leading power and on recent results for the $$\bar{B}_{(s)} \rightarrow D_{(s)}^{(*)}$$ B ¯ ( s ) → D ( s ) ( ∗ ) form factors up to order $$\mathcal{O}(\Lambda _\mathrm{QCD}^2/m_c^2)$$ O ( Λ QCD 2 / m c 2 ) in the heavy-quark expansion. We give quantitative estimates of the matrix elements entering the hadronic decay amplitudes at order $$\mathcal{O}(\Lambda _\mathrm{QCD}/m_b)$$ O ( Λ QCD / m b ) for the first time. Our results are very precise, and uncover a substantial discrepancy between the theory predictions and the experimental measurements. We explore two possibilities for this discrepancy: non-factorizable contributions larger than predicted by the QCD factorization power counting, and contributions beyond the Standard Model. We determine the $$f_s/f_d$$ f s / f d fragmentation fraction for the CDF, D0 and LHCb experiments for both scenarios.

We carry out a comprehensive analysis of the full set of $\bar{B}_q \to D_q^{(*)}$ form factors for spectator quarks $q=u,d,s$ within the framework of the Heavy-Quark Expansion (HQE) to order $\mathcal{O}(\alpha_s, 1/m_b, 1/m_c^2)$. In addition to the available lattice QCD calculations we make use of two new sets of theoretical constraints: we produce for the first time numerical predictions for the full set of $\bar{B}_s \to D_s^{(*)}$ form factors using Light-Cone Sum Rules with $B_s$-meson distribution amplitudes. Furthermore, we reassess the QCD three-point sum rule results for the Isgur-Wise functions entering all our form factors for both $q=u,d$ and $q=s$ spectator quarks. These additional constraints allow us to go beyond the commonly used assumption of $SU(3)_F$ symmetry for the $\bar B_s\to D_s^{(*)}$ form factors, especially in the unitarity constraints which we impose throughout our analysis. We find the coefficients of the IW functions emerging at $\mathcal{O}(1/m_c^2)$ to be consistent with the naive $\mathcal{O}(1)$ expectation, indicating a good convergence of the HQE. While we do not find significant $SU(3)$ breaking, the explicit treatment of $q=s$ as compared to a simple symmetry assumption renders the unitarity constraints more effective. We find that the (pseudo)scalar bounds are saturated to a large degree, which affects our theory predictions. We analyze the phenomenological consequences of our improved form factors by extracting $|V_{cb}|$ from $\bar B\to D^{(*)}\ell\nu$ decays and producing theoretical predictions for the lepton-flavour universality ratios $R(D)$, $R(D^*)$, $R(D_s)$ and $R(D_s^*)$, as well as the $\tau$- and $D_q^*$ polarization fractions for the $\bar B_q\to D_q^{(*)}\tau\nu$ modes., Comment: 16 pages, 3 figures, 7 tables, includes ancillary files; v2: minor changes to the text, conclusions unchanged, 2 missing files added, as accepted for publication in EPJC

Background NGS from plasma samples in non-squamous cell lung carcinoma (NSCC) can aid in the detection of actionable genomic alterations. However, the absolute clinical value of NGS in liquid biopsy (LB) made at baseline is currently uncertain. We assessed the impact of plasma-based NGS using an in-house test and an outsourced test in comparison to a routine molecular pathology workflow. Methods Twenty-four advanced/metastatic treatment-naïve NSCC patients were prospectively included. NGS analyses were conducted both in-house using the Oncomine cfTNA Panel and in an external testing center using the Foundation Liquid assay. NGS analysis and/or specific molecular based assays were conducted in parallel on tissue or cytological samples. Results Both LB tests were well correlated. Tissue NGS results were obtained in 67% of patients and demonstrated good correlation with LB assays. Activating EGFR mutations were detected using LB tests in three patients. PD-L1 expression assessed in tissue sections enabled the initiation of pembrolizumab treatment in five patients. Conclusion NGS from LB is feasible in routine clinical practice using an in-house or an outsourced test at baseline. However, the impact on therapy selection was limited in this small series of patients and LB was not able to replace tissue-based testing in our hands.

We carry out an analysis of the full set of ten $$\bar{B}\rightarrow D^{(*)}$$B¯→D(∗) form factors within the framework of the Heavy-Quark Expansion (HQE) to order $$\mathcal {O}\left( \alpha _s,\,1/m_b,\,1/m_c^2\right) $$Oαs,1/mb,1/mc2, both with and without the use of experimental data. This becomes possible due to a recent calculation of these form factors at and beyond the maximal physical recoil using QCD light-cone sum rules, in combination with constraints from lattice QCD, QCD three-point sum rules and unitarity. We find good agreement amongst the various theoretical results, as well as between the theoretical results and the kinematical distributions in $$\bar{B}\rightarrow D^{(*)}\lbrace e^-,\mu ^-\rbrace \bar{\nu }$$B¯→D(∗){e-,μ-}ν¯ measurements. The coefficients entering at the $$1/m_c^2$$1/mc2 level are found to be of $$\mathcal {O}(1)$$O(1), indicating convergence of the HQE. The phenomenological implications of our study include an updated exclusive determination of $$|V_{cb}|$$|Vcb| in the HQE, which is compatible with both the exclusive determination using the BGL parametrization and with the inclusive determination. We also revisit predictions for the lepton-flavour universality ratios $$R_{D^{(*)}}$$RD(∗), the $$\tau $$τ polarization observables $$P_\tau ^{D^{(*)}}$$PτD(∗), and the longitudinal polarization fraction $$F_L$$FL. Posterior samples for the HQE parameters are provided as ancillary files, allowing for their use in subsequent studies.

A dataset of XBT (eXpendable BathyThermograph) temperature profiles collected by ships of opportunity along the Genova–Palermo route, since September 1999, is analyzed, together with altimetric observations and model results, with the purpose of identifying and characterizing robust circulation features along the track and investigating their variability. An anticyclone is found in the Ligurian Sea, just north of the Corsica Channel, not present in previous descriptions of the Mediterranean Sea circulation. It appears to be a recurrent feature, better defined and stronger in summer and in the beginning of autumn. In the northern part of the Tyrrhenian Sea, the well-known Bonifacio dipole shows a similar seasonality, in agreement with previous observations. However, the Bonifacio anticyclone also displays a strong interannual variability, not previously recorded, with significant variations in position and shape. In fact, the data suggest the existence of two distinct summer circulation regimes related to the position and shape of the Ligurian anticyclone. When the latter is wider, filling the entire region north of the Corsica Channel, the circulation in the northern Tyrrhenian Sea is isolated from that in the Ligurian Sea, in agreement with the common picture. However, the altimeter maps show that there are several cases in the last two decades in which the Ligurian anticyclone is small and displaced to the west, allowing an inflow through the Corsica Channel into the Tyrrhenian Sea. The two regimes appear to result from a delicate balance between the forcings acting in the two sub-basins and the topographic constraints.

Intergenerational support is important throughout the individual life course and a major mechanism of cultural continuity. In this study, we analyse support between older parents and their adult children among international migrant and non-migrant populations in North, Centre and Southern Europe. Data from the Survey of Health, Ageing and Retirement in Europe are used to compare upward and downward practical support, grandparenting, and frequency of contact among 62,213 parent–child dyads. Findings indicate limited differences in support between migrants and non-migrants as well as between migrants of various origins. However, persistent differences in intergenerational support across Europe along a north–south gradient are found irrespective of migrant status.

The three-site Pati-Salam gauge model provides a consistent description for the hints of lepton-flavor non-universality observed in $B$ decays, connecting the present pattern of "anomalies" to the origin of the Standard Model Yukawa couplings. We present here a detailed analysis of the model predictions for a series of low-energy observables, mainly in $B$ and $\tau$ physics. The model is in good agreement with present data and predicts a well-defined pattern of non-standard effects in low-energy observables that could allow us to test it in the near future. Particularly interesting are the predictions of large $\tau\to\mu$ Lepton Flavor Violating processes, such as $\tau \to \mu\gamma$, $\tau \to 3\mu$, $B\to K \tau \mu$, and $B_s\to\tau\mu$. Also $\mu \to 3 e$, $\mu \to e\gamma$, and $K_L \to \mu e$ decays could be not far from the present exclusion bounds, although this conclusion is more model dependent., Comment: 47 pages, 18 figures. v2: typos corrected and references added. Extended discussion on the model parameters. Matching the journal version

We calculate the fully-differential rate of the decays $$B\rightarrow P\tau (\rightarrow \mu \bar{\nu }\nu )\bar{\nu }$$ where $$P = D,\pi $$ , background to the semimuonic decays $$B\rightarrow P\mu \bar{\nu }$$ . The decays with a $$3\nu $$ final state can have a sizable impact on the experimental analyses of the ratios $$R_D$$ and $$R_\pi $$ , depending on the event selection in the analysis. We outline a strategy which permits the extraction of $$R_P \mathcal {B}(\tau \rightarrow \mu \bar{\nu }\nu )$$ from the neutrino-inclusive rate. Our analytic results can also be used to test both existing and upcoming experimental analyses. We further provide Monte Carlo samples of the 5D rate of the neutrino-inclusive decays $$B\rightarrow P\mu X_{\bar{\nu }}$$ .

The term thyroid tumours of uncertain malignant potential (TT-UMP) has been proposed for a subgroup of follicular-patterned thyroid tumours for which benignancy or malignancy cannot be assessed with certainty. The frequency, diagnostic reproducibility, immunohistochemistry and molecular genetic profiling of such tumours have been poorly explored. We, therefore, investigated (1) the frequency of TT-UMP diagnosed in a single institution (Nice, France: 2004-2008), (2) the observer variation among four pathologists, (3) whether immunohistochemical and molecular genetic profiling of TT-UMP provide additional information concerning such lesions. A series of 31 diagnosed TT-UMP (2.9%) out of 1,078 consecutive thyroidectomies were analysed. It comprised 15 follicular thyroid tumours of UMP (FT-UMP) and 16 well-differentiated tumours of UMP (WDT-UMP). Observer concordance was 70% for all TT-UMP. More than 50% of FT-UMP expressed galectin-3 and CK19, whereas more than 50% of WDT-UMP expressed HBME-1. Five cases of TT-UMP showed N-RAS mutations, while one showed H-RAS mutation and another PAX8/PPARgamma rearrangement. In conclusion, the frequency of TT-UMP is low in our institution. Diagnostic reproducibility is within the same range as other published data on follicular-patterned thyroid tumours. The ancillary methods have a low impact on aiding diagnosis of such lesions.

The own-children method (OCM) applied to the Italian Labour Force Survey (ILFS) is an alternative way to give information on fertility for the years before the survey. By deriving children information and the population at risk on the basis of parents’ characteristics, a large-scale dataset for fertility analysis in Italy becomes available, also to reconstruct event histories. The quality assessment provided by comparing the total fertility rate (TFR) calculated on ILFS with the official regional and national TFRs by ISTAT gives us usable outcomes.

We address the problem of the entanglement generation in an electron-scattering by a 1D double-barrier resonant tunnelling device. In particular we analyze the role played by transport resonances in the appearance of quantum correlations between the energy states of the electrons. The entanglement is not sensitive to the presence of Breit-Wigner resonances, while it may be controlled by manipulating Fano resonances. Such a behavior is ascribed to the different mechanisms characterizing the two types of processes.

In recent years the dynamics of entanglement formation between two distinguishable charged particles has been investigated for scattering events in bulk semiconductors. The aim of this work is to overcome the hypothesis of distinguishable carriers. Here we present a quantitative evaluation of the entanglement dynamics for electron-electron collisions in a 2D system applying a method, suitable for indistinguishable particles, based on the Slater rank and the von Neumann entropy of the reduced density matrix. The quantum entanglement of both spatial and spin degrees of freedom is computed for various initial conditions of the system.