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In this work, we develop the quantum theory of gravity in the gravitational compressed space. The equivalence of spatial compression to the Lorentz contraction of special relativity, supported by the relative gravitational red-shift using the black hole clock, leads to the brane potential and gives the minimum length at which the extra dimensions become dominant, comparable to that of the Schwarzschild radius. For Planck mass the minimum length is almost Planck’s length. When doing the quantization of the theory, we find that those responsible for the evolution of time for luminous matter, graviton and for dark matter, the axion, have the property that in compressed gravitational space, naked and dressed propagators are equal and coincide with the corresponding naked propagators.

Background Older patients, generally defined as individuals age >75 years, are less likely to receive percutaneous coronary intervention (PCI) for treatment of acute myocardial infarction (AMI) compared to younger patients. This is due to the paucity of evidence derived from randomized trials, concerns about possible PCI–related side effects, and multimorbidity. We investigated the prognostic impact of PCI in a large population of patients hospitalized with AMI in the period 2003–2018, by using the administrative Lombardy Health Database. Methods We analyzed data of all patients >75 years hospitalized with AMI (both STEMI and NSTEMI) from 2003 to 2018 in Lombardy. Patients were grouped according to whether they were treated or not with PCI during index hospitalization. The primary outcome was in–hospital mortality. One–year mortality and 1–year re–hospitalization for acute heart failure (AHF) or AMI were considered as secondary endpoints. Results During the study period, 116,063 patients (mean age 83±6; 48% males; 46% STEMI) were hospitalized with a primary diagnosis of AMI. Thirty–seven percent of them (n=42,912) were treated with PCI. The in–hospital mortality rate in the entire cohort was 12%. It was significantly lower in patients treated with PCI than in those not treated with PCI (6% vs. 15%; P Conclusions Our real–world data showed that in patients with AMI >75 years of age, PCI use is associated with a significantly lower in–hospital mortality and up to 1 year. This work was partly financed by the Italian Ministry of Health and the Lombardia Region (Grant NET–2016–02364191; EASY–NET)

Renal cell carcinoma (RCC) has traditionally been considered radioresistant with a limited role for conventional fractionation as a local approach. Nevertheless, since the appearance of stereotactic body radiation therapy (SBRT), radiotherapy (RT) has been increasingly employed in the management of metastatic RCC (mRCC). The aim of this study was to evaluate the role of SBRT for synchronous and metachronous oligo metastatic RCC patients in terms of local control, delay of systemic treatment, overall survival and toxicity. A Monocentric single institution retrospective data collection was performed. Inclusion criteria were: (1) oligo-recurrent or oligo-progressive disease (less than 5 metastases) in mRCC patients after radical/partial nephrectomy or during systemic therapy, (2) metastasectomy or other metastasis-directed, rather than SBRT not feasible, (3) any contraindication to receive systemic therapy (such as comorbidities), (4) all the histologies were included, (5) available signed informed consent form for treatment. Tumor response and toxicity were evaluated using the response evaluation criteria in solid tumors and the Common Terminology Criteria for Adverse Events version 4.03, respectively. Progression-free survival in-field and out-field (in-field and out-field PFS) and overall survival (OS) were calculated via the Kaplan–Meier method. The drug treatment-free interval was calculated from the start of SBRT to the beginning of any systemic therapy. From 2010 to December 2018, 61 patients with extracranial and intracranial metastatic RCC underwent SBRT on 83 lesions. Intracranial and extracranial lesions were included. Forty-five (74%) patients were treated for a solitary metastatic lesion. Median RT dose was 25 Gy (range 10–52) in 5–10 fractions. With a median follow-up of 2.3 years (range 0–7.15), 1-year in-field PFS was 70%, 2-year in-field PFS was 55%. One year out-field PFS was 39% and 1-year OS was 78%. Concomitant systemic therapy was employed for only 11 (18%) patients, for the others 50 (82%) the drug treatment-free rate was 70% and 50% at 1 and 2 years, respectively. No > G1 acute and late toxicities were reported. The pattern of failure was pre-dominantly out-of-field, even if the population was negatively selected and the used RT dose could be considered palliative. Therefore, SBRT appears to be a well-tolerated, feasible and safe approach in oligo metastatic RCC patients with an excellent in-field PFS. SBRT might play a role in the management of selected RCC patients allowing for a delay systemic therapy begin (one out of two patients were free from new systemic therapy at 2 years after SBRT). Further research on SBRT dose escalation is warranted.

This study examines the relationship between the board of directors and cash holdings before and during the global financial crisis. We focus on the main demographic characteristics of the board: CEO duality, independent directors, and board size. Employing a sample of listed Italian industrial firms over the period 2003–2013, our empirical findings show the different behaviors of the members of the board of directors in determining cash holdings in normal conditions and during a crisis. In normal periods, in line with agency theory, a vigilant board—characterized by a high proportion of independent directors—reduces cash holdings. Diversely, the presence of CEO duality and larger boards increase cash holdings. In times of crisis, members of the board of directors abandon their monitoring duties or opportunistic behavior and become more participative to help the firm to survive. The results suggest that the effects of the board of directors’ characteristics are contingent on a firm’s external environment.

Undercarboxylated-Osteocalcin (ucOCN), acting on its putative receptor GPRC6A, was shown to stimulate testosterone (T) production by Leydig cells in rodents, in parallel with the hypothalamus-pituitary-gonadal axis (HPG) mediated by luteinizing hormone (LH). The aim of this cross-sectional study was to evaluate the association among serum ucOCN, rs2247911 polymorphism of GPRC6A gene and the endocrine/semen pattern in a cohort of infertile males, possibly identifying an involvement of the ucOCN-GPRC6A axis on testis function.190 males, including 74 oligozoospermic subjects, 58 azoosperminc patients and 58 normozoospermic controls, were prospectively recruited at the Orient Hospital for Infertility, Assisted Reproduction and Genetics in Syria (Study N. 18FP), from July 2018 to June 2020. Outpatient evaluation included the clinical history, anthropometrics and a fasting blood sampling for hormonals, serum OCN (both carboxylated and undercarboxylated), glycemic and lipid profile and screening for rs2247911 GPRC6A gene polymorphism.Higher serum ucOCN associated with higher T and HDL-cholesterol (respectively: r = 0.309, P 0.001 and r = 0.248, P = 0.001), and with lower FSH (r = - 0.327, P 0.001) and LDL-cholesterol (r = - 0.171; P = 0.018). Patients bearing the GG genotype of rs2247911 had higher sperm count compared to GA genotype (P = 0.043) and, compared to both AG and AA genotypes, had higher serum T (P = 0.004, P = 0.001) and lower triglycerides levels (P = 0.002, P 0.001). Upon normalization for LH levels and body mass index, rs2274911 and ucOCN were significantly associated with higher serum T at linear stepwise regression analysis (P = 0.013, P = 0.007).Our data suggest the involvement of ucOCN-GPRC6A axis in the regulation of T production by the testis, subsidiary to HPG.

SUMMARYThe horizontal to vertical spectral ratio (HVSR) of seismic noise is often used to investigate site effects, and it is usually assumed to be a stable feature of the site considered. Here we show that such an assumption is not always justified, and may lead to incorrect conclusions. The HVSR analysis was performed on ambient seismic noise recordings lasting from weeks to months at many sites in Calabria, Italy. Results show a variety of site effects, from the resonance of a shallow sedimentary layer to the polarized amplification of horizontal ground motion associated with topographic effects. We describe the results of seven sites whose HVSR is characterized by dual content: one that is persistent, and another appearing only occasionally. Two sites very near the coast of the Tyrrhenian sea and five sites in the Calabrian Arc mountains show the most remarkable results. The shape of the HVSR changes significantly at these sites when the amplitude of background noise increases in a broad frequency band during periods of bad weather. The occasional contribution to the HVSR consists of one or more peaks, depending on the site, that appear only when the amplitude of ambient noise is higher than usual. The seven sites where we observe the HVSR variability are all located in complex geological environments, on mountains, ridges or foothills. A variation of the HVSR correlated with the day–night cycle is also observed at some of these sites.

Background: Suboptimal meta-analyses with misleading conclusions are frequently published in the health areas, and they can compromise decision making in clinical practice. Aim of the review: This systematic review aimed to map the characteristics of published meta-analyses of pharmacy services and their association with the study conclusions. Method: We searched electronic databases (PubMed, Scopus, and Web of Science) to identify published meta-analyses of pharmacy services up to January 2019. Components of meta-analyses were extracted (i.e. studies’ metadata; methods used in the systematic review; description of the statistical model used for the meta-analysis; main results; conflict of interest and funding source). The methodological quality was evaluated using the R-AMSTAR tool. Results: A total of 85 meta-analyses were included, with 2016 as the median publication year. Overall, the methodological quality of meta-analyses of pharmacy services was considered suboptimal. Only one-third of authors registered a protocol; complete search strategy and raw data were provided by 55.3% and 9.4% of studies, respectively. Evidence strength (GRADE) was evaluated in only 19.2% of studies. PRISMA and Cochrane recommendations were stated to be followed in 60% and 27.4% of articles, respectively. Around half of studies performed sensitivity analysis, however, the prediction interval was presented by only one meta-analysis. Studies that favoured the pharmacists’ interventions poorly discussed the methodological quality and heterogeneity of primary trials. Conclusion: Poor conduction and reporting were observed in meta-analyses of pharmacy services, especially in those that favoured the pharmacist’s interventions. Reproducibility and transparency should be rigorously ensured by journal editors and peer-reviewers.

Background:Second generation direct acting-antivirals are safe and effective treatments for chronic hepatitis C patients.Objective:We aimed to conduct a systematic review of case reports and case series to evaluate the safety of the drugs, highlighting a compilation of AE not previously reported in other reviews.Methods:The search was performed in four electronic databases and included only case reports and case series that evaluated interferon-free therapies and provided safety outcomes.Results:Initially 1,235 records were retrieved, and after screening 30 studies were included in the analysis (23 case reports and 7 case series). A total of 39 patients were included, receiving eight different interferon-free treatments. Nineteen patients discontinued treatment (only 8 of these achieved treatment response). Other 19 patients achieved SVR without discontinuation. Rare adverse events were observed, including breast hypertrophy, retinopathy and drug-induced infection. Some patients were in an advanced stage of the disease, and were therefore unable to withstand treatment due to the appearance of complications.Conclusion:In this sense, it is important to monitor the use of these drugs that can favor the appearance of serious AE. (PROSPERO registration number CRD42016051680).

Quantum Field Theory (QFT) is a difficult subject, plagued by puzzling infinities. Its most formidable challenge is the existence of many non-renormalizable QFT theories, for which the number of infinities is itself infinite. We will here appeal to a rather non-conventional QFT approach developed in [J. of Phys. Comm. 2 115029 (2018)] that uses Schwartz’ distribution theory (SDT). This technique avoids the need for counterterms. In the SDT approach to QFT, infinities arise due to the presence of products of distributions with coincident point singularities. In the present study, we will carefully discuss a simple QFT-model devised by Bollini and Giambiagi. Because of its simplicity, it makes easy to appreciate just how it is possible to successfully deal with the issue of non-renormalizability via SDT., Facultad de Ciencias Exactas, Instituto de Física La Plata

Burkitt lymphoma/leukemia (BL/L) is an aggressive oncohematological disease. This study evaluated the population-based prognosis and survival on BL/L as well as if BL/L behaved as a risk factor for the development of second primary cancers (SPCs) and if other first tumors behaved as risk factors for the occurrence of BL/L as an SPC. A retrospective cohort using the Surveillance, Epidemiology and End Results (SEER) Program (2008–2016) was performed. Kaplan–Meier, time-dependent covariate Cox regression and Poisson regression models were conducted. Overall, 3094 patients were included (median, 45 years, IQR, 22–62). The estimated overall survival was 65.4 months (95% CI, 63.6–67.3). Significantly more deaths occurred for older patients, black race, disease at an advanced stage, patients without chemotherapy/surgery and patients who underwent radiotherapy. Hodgkin lymphomas (nodal) (RR, 7.6 (3.9–15.0, p &lt, 0.001)), Kaposi sarcomas (34.0 (16.8–68.9, 0.001)), liver tumors (3.4 (1.2–9.3, p = 0.020)) and trachea, mediastinum and other respiratory cancers (15.8 (2.2–113.9, p = 0.006)) behaved as risk factors for the occurrence of BL/L as an SPC. BL/L was a risk factor for the occurrence of SPCs as acute myeloid leukemias (4.6 (2.1–10.4, 0.001)), Hodgkin lymphomas (extranodal) (74.3 (10.0–549.8, 0.001)) and Kaposi sarcomas (35.1 (12.1–101.4, 0.001)). These results may assist the development of diagnostic and clinical recommendations for BL/L.

Background Burkitt lymphoma (BL) is an aggressive hematologic cancer. This study synthetized the evidence about the efficacy and safety of chemotherapy treatments used in patients with BL using the World Health Organization classification. Materials and Methods A systematic review of interventional studies was performed. A search was carried out in PubMed, Scopus, and Web of Science, with additional manual and gray literature searches. The methodological quality of articles was assessed with the Newcastle-Ottawa scale. Results We identified 1358 studies; 9 nonrandomized studies satisfied the eligibility criteria (n = 544 patients). The BL epidemiologic variants were sporadic BL (44.5%), endemic BL (47.2%), and immunodeficiency-associated BL (8.3%). Regarding chemotherapy protocols, 4 groups were identified: based on CODOX-M/IVAC (n = 4), EPOCH (n = 1), BFM (n = 1), and simplified treatment schemes used in African countries (n = 3). Most studies had moderate quality. Empirically and qualitatively, the best options for adults with sporadic BL were ‘DA-EPOCH-R’ (7-year overall survival [OS], 100%; 95% confidence interval [CI], 82-100), ‘HDR + LD into CODOX-M/IVAC’ (2-year OS, 84%), and ‘RD-CODOX-M/IVAC’ (4-year progression-free survival, 92%; 95% CI, 77-100); in pediatric patients, the ‘BFM-NHL-90-like’ showed promising results (3-year OS, 90%). For immunodeficiency-associated BL, the ‘SC-EPOCH-RR’ demonstrated a good therapeutic profile (6-year OS, 90%; 95% CI, 60-98). The ‘Malawi 2012-2014′ (1-year OS, 73%; 95% CI, 61-85) could be the treatment choice in endemic BL (African countries). The main adverse events were hematologic. Conclusion Selecting chemotherapy protocols for BL should be grounded in its epidemiologic variants. Further studies with greater methodological quality are needed to strengthen the evidence.

Renal cell carcinoma (RCC) has traditionally been considered radioresistant with a limited role for conventional fractionation as a local approach. Nevertheless, since the appearance of stereotactic body radiation therapy (SBRT), radiotherapy (RT) has been increasingly employed in the management of metastatic RCC (mRCC). The aim of this study was to evaluate the role of SBRT for synchronous and metachronous oligo metastatic RCC patients in terms of local control, delay of systemic treatment, overall survival and toxicity.A Monocentric single institution retrospective data collection was performed. Inclusion criteria were: (1) oligo-recurrent or oligo-progressive disease (less than 5 metastases) in mRCC patients after radical/partial nephrectomy or during systemic therapy, (2) metastasectomy or other metastasis-directed, rather than SBRT not feasible, (3) any contraindication to receive systemic therapy (such as comorbidities), (4) all the histologies were included, (5) available signed informed consent form for treatment. Tumor response and toxicity were evaluated using the response evaluation criteria in solid tumors and the Common Terminology Criteria for Adverse Events version 4.03, respectively. Progression-free survival in-field and out-field (in-field and out-field PFS) and overall survival (OS) were calculated via the Kaplan-Meier method. The drug treatment-free interval was calculated from the start of SBRT to the beginning of any systemic therapy.From 2010 to December 2018, 61 patients with extracranial and intracranial metastatic RCC underwent SBRT on 83 lesions. Intracranial and extracranial lesions were included. Forty-five (74%) patients were treated for a solitary metastatic lesion. Median RT dose was 25 Gy (range 10-52) in 5-10 fractions. With a median follow-up of 2.3 years (range 0-7.15), 1-year in-field PFS was 70%, 2-year in-field PFS was 55%. One year out-field PFS was 39% and 1-year OS was 78%. Concomitant systemic therapy was employed for only 11 (18%) patients, for the others 50 (82%) the drug treatment-free rate was 70% and 50% at 1 and 2 years, respectively. No G1 acute and late toxicities were reported.The pattern of failure was pre-dominantly out-of-field, even if the population was negatively selected and the used RT dose could be considered palliative. Therefore, SBRT appears to be a well-tolerated, feasible and safe approach in oligo metastatic RCC patients with an excellent in-field PFS. SBRT might play a role in the management of selected RCC patients allowing for a delay systemic therapy begin (one out of two patients were free from new systemic therapy at 2 years after SBRT). Further research on SBRT dose escalation is warranted.

Gravity is so different from other fundamental forces that it is now essentially treated as a non-fundamental force of entropic origin. A number of good studies have been carried out in this direction. Quantum gravity has also significantly improved our understanding by combining gravity well with quantum physics. However, there are still many impediments to our understanding especially in the limits of extreme. The effects of quantum gravity start appearing on the scene at Planck length which is the smallest length in nature idealized so far. While as this study incorporates a model which is valid for potential energy corrections at small distances but we have also given a bold try to use it confidently for the corrections at very large distances as well. The model uses two techniques namely Boltzmann and Tsallis statistical approaches to explore the thermodynamics within the ambit of brane world model giving its further modified version. We have computed partition function by using both Boltzmann and Tsallis statistical approaches and then used it to study thermodynamics of the brane world model. We have analyzed both analytically and graphically, the thermodynamic quantities like Helmholtz free energy and specific heat. The thermodynamic stability of the model is also discussed depending on the number of galaxies., Comment: 34 pages, 9 Figures