Investigating The Physics Case of Running a B-Factory at the Y(5S) Resonance

We discuss the physics case of a high luminosity B-Factory running at the Y(5S) resonance. We show that the coherence of the B meson pairs is preserved at this resonance, and that Bs can be well distinguished from Bd and charged B mesons. These facts allow to cover the physics program of a traditional B-Factory and, at the same time, to perform complementary measurements which are not accessible at the Y(4S). In particular we show how, despite the experimental limitations in performing time-dependent measurements of Bs decays, the same experimental information can be extracted, in several cases, from the determination of time-integrated observables. In addition, a few examples of the potentiality in measuring rare Bs decays are given. Finally, we discuss how the study of Bs meson will improve the constraints on New Physics parameters in the Bs sector, in the context of the generalized Unitarity Triangle analysis.Comment: 47 pages, 22 figure

The spermidine analogue GC7 (N1-guanyl-1,7-diamineoheptane) induces autophagy through a mechanism not involving the hypusination of eIF5A

The exogenous administration of spermidine promotes longevity in many model organisms. It has been proposed that this anti-age activity of spermidine is related to this polyamine's ability to promote autophagy. Since spermidine is the substrate for the eIF5A post-translational modification by hypusination, we asked ourselves whether mature eIF5A may represent the link between spermidine and autophagy induction. To test this hypothesis, we inhibited the conversion of native eIF5A by a pharmacological approach, using the N1-guanyl-1,7-diamineoheptane (GC7), a spermidine analogue which competitively and reversibly inhibits deoxyhypusine synthase (DHS). In addition, we also employed genetic approaches by ablating both the eIF5A protein itself and DHS, the rate limiting enzyme catalyzing the conversion of lysine to hypusine. Collectively the data presented in this study demonstrate that the mature eIF5A (hypusinated form) is not involved in the autophagic pathway and that the inhibitor of DHS, GC7, produces off-target effect(s) resulting in marked induction of basal autophagy. These data are relevant in light of the fact that GC7 is considered a potent and selective inhibitor of DHS and is a potential candidate drug for cancer, diabetes and HIV therapy

Single-hit resolution measurement with MEG II drift chamber prototypes

Drift chambers operated with helium-based gas mixtures represent a common solution for tracking charged particles keeping the material budget in the sensitive volume to a minimum. The drawback of this solution is the worsening of the spatial resolution due to primary ionisation fluctuations, which is a limiting factor for high granularity drift chambers like the MEG II tracker. We report on the measurements performed on three different prototypes of the MEG II drift chamber aimed at determining the achievable single-hit resolution. The prototypes were operated with helium/isobutane gas mixtures and exposed to cosmic rays, electron beams and radioactive sources. Direct measurements of the single hit resolution performed with an external tracker returned a value of 110 $\mu$m, consistent with the values obtained with indirect measurements performed with the other prototypes.Comment: 18 pages, 18 figure

Continuity of Care During End of Life: An Evolutionary Concept Analysis

PURPOSE: The purpose of this study was to clarify the concept of continuity of care during the end of life with a focus on the patient’s perspective. METHODS: Rodgers’ method of evolutionary concept analysis was used. The analysis was based on literature published in English in the databases Cumulative Index for Nursing and Allied Health Literature, Medline, and PsycINFO. FINDINGS: Analysis revealed that the continuity at life’s end is a dynamic process that depends on the interaction among patients, families, and providers, and is strictly interwoven with the patient’s time perception. CONCLUSION: This analysis showed the complexities surrounding the patient’s experience of continuity at life’s end. IMPLICATION FOR NURSING: Nurses can benefit from a deeper understanding of the patient’s experience, both theoretically and in practice

Pressure injury progression and factors associated with different end-points in a home palliative care setting : a retrospective chart review study

CONTEXT: Patients with advanced illnesses show the highest prevalence for pressure injuries. In the palliative care setting, the ultimate goal is injury healing, but equally important is wound maintenance, wound palliation (wound-related pain and symptom management), and primary and secondary wound prevention. OBJECTIVES: To describe the course of healing for pressure injuries in a home palliative care setting according to different end-points, and to explore patient and caregiver characteristics and specific care activities associated with their achievement. METHODS: Four-year retrospective chart review of 669 patients cared for in a home palliative care service, of those 124 patients (18.5%) had at least one pressure injury with a survival rate less than or equal to six months. RESULTS: The proportion of healed pressure injuries was 24.4%. Of the injuries not healed, 34.0% were in a maintenance phase, whereas 63.6% were in a process of deterioration. Body mass index (P = 0.0014), artificial nutrition (P = 0.002), and age <70 years (P = 0.022) emerged as predictive factors of pressure injury complete healing. Artificial nutrition, age, male caregiver (P = 0.034), and spouse (P = 0.036) were factors significantly associated with a more rapid pressure injury healing. Continuous deep sedation was a predictive factor for pressure injury deterioration and significantly associated with a more rapid worsening. CONCLUSION: Pressure injury healing is a realistic aim in home palliative care, particularly for injuries not exceeding Stage II occurring at least two weeks before death. When assessing pressure injuries, our results highlight the need to also pay attention to artificial nutrition, continuous deep sedation, and the caregiver's role and gender

Fenretinide induces autophagic cell death in caspase-defective breast cancer cells

The elimination of tumor cells by apoptosis is the main mechanism of action of chemotherapeutic drugs. More recently, autophagic cell death has been shown to trigger a nonapoptotic cell death program in cancer cells displaying functional defects of caspases. Fenretinide (FenR), a synthetic derivative of retinoic acid, promotes growth inhibition and induces apoptosis in a wide range of tumor cell types. The present study was designed to evaluate the ability of fenretinide to induce caspase-independent cell death and to this aim we used the human mammary carcinoma cell line MCF-7, lacking functional caspase-3 activity. We demonstrated that in these cells fenretinide is able to trigger an autophagic cell death pathway. In particular we found that fenretinide treatment resulted in the increase in Beclin 1 expression, the conversion of the soluble form of LC3 to the autophagic vesicle-associated form LC3-II and its shift from diffuse to punctate staining and finally the increase in lysosomes/autophagosomes. By contrast, caspase-3 reconstituted MCF-7 cell line showed apoptotic cell death features in response to fenretinide treatment. These data strongly suggest that fenretinide does not invariably elicit an apoptotic response but it is able to induce autophagy when apoptotic pathway is deregulated. The understanding of the molecular mechanisms involved in fenretinide action is important for the future design of therapies employing this retinoid in breast cancer treatment

Inhibition of cell proliferation, migration and invasion of B16-F10 melanoma cells by α-mangostin

In this study, we have evaluated the potential antineoplastic effects of α-mangostin (α-M), the most representative xanthone in Garcinia mangostana pericarp, on melanoma cell lines. This xanthone markedly inhibits the proliferation of high-metastatic B16-F10 melanoma cells. Furthermore, by deeply analyzing which steps in the metastatic process are influenced by xanthone it was observed that α-M strongly interferes with homotypic aggregation, adhesion, plasticity and invasion ability of B16-F10 cells, probably by the observed reduction of metalloproteinase-9 activity. The antiproliferative and antimetastatic properties of α-M have been established in human SK-MEL-28 and A375 melanoma cells. In order to identify pathways potentially involved in the antineoplastic properties of α-M, a comparative mass spectrometry proteomic approach was employed. These findings may improve our understanding of the molecular mechanisms underlying the anti-cancer effects of α-M on melanoma

Emergence of Anaplasma Species Related to A. phagocytophilum and A. platys in Senegal

The genus Anaplasma (Anaplasmataceae, Rickettsiales) includes tick-transmitted bacterial species of importance to both veterinary and human medicine. Apart from the traditionally recognized six Anaplasma species (A. phagocytophilum, A. platys, A. bovis, A. ovis, A. centrale, A. marginale), novel strains and candidate species, also of relevance to veterinary and human medicine, are emerging worldwide. Although species related to the zoonotic A. platys and A. phagocytophilum have been reported in several African and European Mediterranean countries, data on the presence of these species in sub-Saharan countries are still lacking. This manuscript reports the investigation of Anaplasma strains related to zoonotic species in ruminants in Senegal by combining different molecular tests and phylogenetic approaches. The results demonstrated a recent introduction of Candidatus (Ca) Anaplasma turritanum, a species related to the pathogenic A. platys, possibly originating by founder effect. Further, novel undetected strains related to Candidatus (Ca) Anaplasma cinensis were detected in cattle. Based on groEL and gltA molecular comparisons, we propose including these latter strains into the Candidatus (Ca) Anaplasma africanum species. Finally, we also report the emergence of Candidatus (Ca) A. boleense in Senegal. Collectively, results confirm that Anaplasma species diversity is greater than expected and should be further investigated, and that Anaplasma routine diagnostic procedures and epidemiological surveillance should take into account specificity issues raised by the presence of these novel strains, suggesting the use of a One Health approach for the management of Anaplasmataceae in sub-Saharan Africa

Revisiting the T₂ spectrum imaging inverse problem: Bayesian regularized non-negative least squares.

Multi-echo T <sub>2</sub> magnetic resonance images contain information about the distribution of T <sub>2</sub> relaxation times of compartmentalized water, from which we can estimate relevant brain tissue properties such as the myelin water fraction (MWF). Regularized non-negative least squares (NNLS) is the tool of choice for estimating non-parametric T <sub>2</sub> spectra. However, the estimation is ill-conditioned, sensitive to noise, and highly affected by the employed regularization weight. The purpose of this study is threefold: first, we want to underline that the apparently innocuous use of two alternative parameterizations for solving the inverse problem, which we called the standard and alternative regularization forms, leads to different solutions; second, to assess the performance of both parameterizations; and third, to propose a new Bayesian regularized NNLS method (BayesReg). The performance of BayesReg was compared with that of two conventional approaches (L-curve and Chi-square (X <sup>2</sup> ) fitting) using both regularization forms. We generated a large dataset of synthetic data, acquired in vivo human brain data in healthy participants for conducting a scan-rescan analysis, and correlated the myelin content derived from histology with the MWF estimated from ex vivo data. Results from synthetic data indicate that BayesReg provides accurate MWF estimates, comparable to those from L-curve and X <sup>2</sup> , and with better overall stability across a wider signal-to-noise range. Notably, we obtained superior results by using the alternative regularization form. The correlations reported in this study are higher than those reported in previous studies employing the same ex vivo and histological data. In human brain data, the estimated maps from L-curve and BayesReg were more reproducible. However, the T <sub>2</sub> spectra produced by BayesReg were less affected by over-smoothing than those from L-curve. These findings suggest that BayesReg is a good alternative for estimating T <sub>2</sub> distributions and MWF maps