"Where am I?" A snapshot of the developmental topographical disorientation among young Italian adults

In the last decade, several cases affected by Developmental Topographical Disorientation (DTD) have been described. DTD consists of a neurodevelopmental disorder affecting the ability to orient in the environment despite well-preserved cognitive functions, and in the absence of a brain lesion or other neurological or psychiatric conditions. Described cases showed different impairments in navigational skills ranging from topographic memory deficits to landmark agnosia. All cases lacked a mental representation of the environment that would allow them to use high-order spatial orientation strategies. In addition to the single case studies, a group study performed in Canada showed that the disorder is more widespread than imagined. The present work intends to investigate the occurrence of the disorder in 1,698 young Italian participants. The sample is deliberately composed of individuals aged between 18 and 35 years to exclude people who could manifest the loss of the ability to navigate as a result of an onset of cognitive decline. The sample was collected between 2016 and 2019 using the Qualtrics platform, by which the Familiarity and Spatial Cognitive Style Scale and anamnestic interview were administered. The data showed that the disorder is present in 3% of the sample and that the sense of direction is closely related to town knowledge, navigational strategies adopted, and gender. In general, males use more complex navigational strategies than females, although DTD is more prevalent in males than in females, in line with the already described cases. Finally, the paper discusses which protective factors can reduce DTD onset and which intervention measures should be implemented to prevent the spread of navigational disorders, which severely impact individuals' autonomy and social relationships

Optimal Constraints on Local Primordial Non-Gaussianity from the Two-Point Statistics of Large-Scale Structure

One of the main signatures of primordial non-Gaussianity of the local type is a scale-dependent correction to the bias of large-scale structure tracers such as galaxies or clusters, whose amplitude depends on the bias of the tracers itself. The dominant source of noise in the power spectrum of the tracers is caused by sampling variance on large scales (where the non-Gaussian signal is strongest) and shot noise arising from their discrete nature. Recent work has argued that one can avoid sampling variance by comparing multiple tracers of different bias, and suppress shot noise by optimally weighting halos of different mass. Here we combine these ideas and investigate how well the signatures of non-Gaussian fluctuations in the primordial potential can be extracted from the two-point correlations of halos and dark matter. On the basis of large $N$-body simulations with local non-Gaussian initial conditions and their halo catalogs we perform a Fisher matrix analysis of the two-point statistics. Compared to the standard analysis, optimal weighting- and multiple-tracer techniques applied to halos can yield up to one order of magnitude improvements in \fnl-constraints, even if the underlying dark matter density field is not known. We compare our numerical results to the halo model and find satisfactory agreement. Forecasting the optimal \fnl-constraints that can be achieved with our methods when applied to existing and future survey data, we find that a survey of $50h^{-1}\mathrm{Gpc}^3$ volume resolving all halos down to 10^{11}\hMsun at $z=1$ will be able to obtain \sigma_{\fnl}\sim1 (68% cl), a factor of $\sim20$ improvement over the current limits. Decreasing the minimum mass of resolved halos, increasing the survey volume or obtaining the dark matter maps can further improve these limits, potentially reaching the level of \sigma_{\fnl}\sim0.1. (abridged)Comment: V1: 23 pages, 12 figures, submitted to PRD. V2: 24 pages, added appendix and citations, matched to PRD published versio

An effective theory of accelerated expansion

We work out an effective theory of accelerated expansion to describe general phenomena of inflation and acceleration (dark energy) in the Universe. Our aim is to determine from theoretical grounds, in a physically-motivated and model independent way, which and how many (free) parameters are needed to broadly capture the physics of a theory describing cosmic acceleration. Our goal is to make as much as possible transparent the physical interpretation of the parameters describing the expansion. We show that, at leading order, there are five independent parameters, of which one can be constrained via general relativity tests. The other four parameters need to be determined by observing and measuring the cosmic expansion rate only, H(z). Therefore we suggest that future cosmology surveys focus on obtaining an accurate as possible measurement of $H(z)$ to constrain the nature of accelerated expansion (dark energy and/or inflation).Comment: In press; minor changes, results unchange

Neoadjuvant eribulin mesylate following anthracycline and taxane in triple negative breast cancer: Results from the HOPE study

Background Eribulin mesylate (E) is indicated for metastatic breast cancer patients previously treated with anthracycline and taxane. We argued that E could also benefit patients eligible for neoadjuvant chemotherapy. Methods Patients with primary triple negative breast cancer 2 cm received doxorubicin 60 mg/m2 and paclitaxel 200 mg/m2 x 4 cycles (AT) followed by E 1.4 mg/m2 x 4 cycles. Primary endpoint was pathological complete response (pCR) rate; secondary and explorative endpoints included clinical/metabolic response rates and safety, and biomarker analysis, respectively. Using a two-stage Simon design, 43 patients were to be included provided that 4 of 13 patients had achieved pCR in the first stage of the study. Results In stage I of the study 13 women were enrolled, median age 43 years, tumor size 2–5 cm in 9/13 (69%), positive nodal status in 8/13 (61%). Main grade 3 adverse event was neutropenia (related to AT and E in 4 and 2 cases, respectively). AT followed by E induced clinical complete + partial responses in 11/13 patients (85%), pCR in 3/13 (23%). Median measurements of maximum standardized uptake value (SUVmax) resulted 13, 3, and 1.9 at baseline, after AT and E, respectively. Complete metabolic response (CMR) occurred after AT and after E in 2 and 3 cases, respectively. Notably, 2 of the 5 (40%) patients with CMR achieved pCR at surgery. Immunostaining of paired pre-/post-treatment tumor specimens showed a reduction of β-catenin, CyclinD1, Zeb-1, and c-myc expression, in the absence of N-cadherin modulation. The study was interrupted at stage I due to the lack of the required patients with pCR. Conclusions Despite the early study closure, preoperative E following AT showed clinical and biological activity in triple negative breast cancer patients. Furthermore, the modulation of β-catenin pathway core proteins, supposedly outside the domain of epithelial–mesenchymal transition, claims for further investigation. Trial registration EU Clinical Trial Register, EudraCT number 2012-004956-12

Anti-angiogenic and anti-proliferative graphene oxide nanosheets for tumor cell therapy

Graphene oxide (GO) is a bidimensional novel material that exhibits high biocompatibility and angiogenic properties, mostly related to the intracellular formation of reactive oxygen species (ROS). In this work, we set up an experimental methodology for the fabrication of GO@peptide hybrids by the immobilization, via irreversible physical adsorption, of the Ac-(GHHPH)4-NH2 peptide sequence, known to mimic the anti-angiogenic domain of the histidine-proline-rich glycoprotein (HPRG). The anti-proliferative capability of the graphene-peptide hybrids were tested in vitro by viability assays on prostate cancer cells (PC-3 line), human neuroblastoma (SH-SY5Y), and human retinal endothelial cells (primary HREC). The anti-angiogenic response of the two cellular models of angiogenesis, namely endothelial and prostate cancer cells, was scrutinized by prostaglandin E2 (PGE2) release and wound scratch assays, to correlate the activation of inflammatory response upon the cell treatments with the GO@peptide nanocomposites to the cell migration processes. Results showed that the GO@peptide nanoassemblies not only effectively induced toxicity in the prostate cancer cells, but also strongly blocked the cell migration and inhibited the prostaglandin-mediated inflammatory process both in PC-3 and in HRECs. Moreover, the cytotoxic mechanism and the internalization efficiency of the theranostic nanoplatforms, investigated by mitochondrial ROS production analyses and confocal microscopy imaging, unraveled a dose-dependent manifold mechanism of action performed by the hybrid nanoassemblies against the PC-3 cells, with the detection of the GO-characteristic cell wrapping and mitochondrial perturbation. The obtained results pointed out to the very promising potential of the synthetized graphene-based hybrids for cancer therapy

Prospects in Constraining the Dark Energy Potential

We generalize to non-flat geometries the formalism of Simon et al. (2005) to reconstruct the dark energy potential. This formalism makes use of quantities similar to the Horizon-flow parameters in inflation, can, in principle, be made non-parametric and is general enough to be applied outside the simple, single scalar field quintessence. Since presently available and forthcoming data do not allow a non-parametric and exact reconstruction of the potential, we consider a general parametric description in term of Chebyshev polynomials. We then consider present and future measurements of H(z), Baryon Acoustic Oscillations surveys and Supernovae type 1A surveys, and investigate their constraints on the dark energy potential. We find that, relaxing the flatness assumption increases the errors on the reconstructed dark energy evolution but does not open up significant degeneracies, provided that a modest prior on geometry is imposed. Direct measurements of H(z), such as those provided by BAO surveys, are crucially important to constrain the evolution of the dark energy potential and the dark energy equation of state, especially for non-trivial deviations from the standard LambdaCDM model.Comment: 22 pages, 7 figures. 2 references correcte

Neuroendocrine Tumors: A Comprehensive Review on Nutritional Approaches

Simple Summary Neuroendocrine neoplasms and their main subtype neuroendocrine tumors have an increasing incidence worldwide, associated with a high survival and prevalence rate. Both the tumor itself and systemic therapy can have an impact on patients' nutrition. Conversely, preliminary data suggest that malnutrition has a negative impact on the development and prognosis of neuroendocrine tumors, as does obesity. The aim of this review is to condense the latest evidence on the role of the most widely used dietary patterns, the Mediterranean diet, the ketogenic diet and intermittent fasting, in the context of neuroendocrine tumors. Nutritional plans are an integral part of the multidisciplinary treatment team of patients with neuroendocrine tumors because they improve the patient's quality of life. The nutritional approach must be tailored, based on nutritional needs and nutritionally manageable signs and/or symptoms related to drug treatment. Neuroendocrine neoplasms are a heterogeneous group of neoplasms with increasing incidence, high prevalence, and survival worldwide. About 90% of cases are well differentiated forms, the so-called neuroendocrine tumors (NETs), with slow proliferation rates and prolonged survival but frequent development of liver metastases and endocrine syndromes. Both the tumor itself and systemic therapy may have an impact on patient nutrition. Malnutrition has a negative impact on outcome in patients with NETs, as well as obesity. In addition, obesity and metabolic syndrome have been shown to be risk factors for both the development and prognosis of NET. Therefore, dietary assessment based on body composition and lifestyle modifications should be an integral part of the treatment of NET patients. Nutrition plans, properly formulated by a dietician, are an integral part of the multidisciplinary treatment team for patients with NETs because they allow an improvement in quality of life, providing a tailored approach based on nutritional needs and nutritional manageable signs and/or symptoms related to pharmacological treatment. The aim of this review is to condense the latest evidence on the role of the most used dietary models, the Mediterranean diet, the ketogenic diet, and intermittent fasting, in the context of NETs, while considering the clinical and molecular mechanisms by which these dietary models act