A population of intermediate-mass black holes in dwarf starburst galaxies up to redshift=1.5

We study a sample of $\sim$50,000 dwarf starburst and late-type galaxies drawn from the COSMOS survey with the aim of investigating the presence of nuclear accreting black holes (BHs) as those seed BHs from which supermassive BHs could grow in the early Universe. We divide the sample into five complete redshift bins up to $z=1.5$ and perform an X-ray stacking analysis using the \textit{Chandra} COSMOS-Legacy survey data. After removing the contribution from X-ray binaries and hot gas to the stacked X-ray emission, we still find an X-ray excess in the five redshift bins that can be explained by nuclear accreting BHs. This X-ray excess is more significant for $z<0.5$. At higher redshifts, these active galactic nuclei could suffer mild obscuration, as indicated by the analysis of their hardness ratios. The average nuclear X-ray luminosities in the soft band are in the range 10$^{39}-10^{40}$ erg s$^{-1}$. Assuming that the sources accrete at $\geq$ 1\% the Eddington rate, their BH masses would be $\leq$ 10$^{5}$ M$_{\odot}$, thus in the intermediate-mass BH regime, but their mass would be smaller than the one predicted by the BH-stellar mass relation. If instead the sources follow the correlation between BH mass and stellar mass, they would have sub-Eddington accreting rates of $\sim$ 10$^{-3}$ and BH masses 1-9 $\times$ 10$^{5}$ M$_{\odot}$. We thus conclude that a population of intermediate-mass BHs exists in dwarf starburst galaxies, at least up to $z$=1.5, though their detection beyond the local Universe is challenging due to their low luminosity and mild obscuration unless deep surveys are employed.Comment: 10 pages, 7 figures, ApJ in pres

Intermediate-mass black holes in dwarf galaxies out to redshift ∼\sim 2.4 in the Chandra COSMOS Legacy Survey

We present a sample of 40 AGN in dwarf galaxies at redshifts $z \lesssim$ 2.4. The galaxies are drawn from the \textit{Chandra} COSMOS-Legacy survey as having stellar masses $10^{7}\leq M_{*}\leq3 \times 10^{9}$ M$_{\odot}$. Most of the dwarf galaxies are star-forming. After removing the contribution from star formation to the X-ray emission, the AGN luminosities of the 40 dwarf galaxies are in the range $L_\mathrm{0.5-10 keV} \sim10^{39} - 10^{44}$ erg s$^{-1}$. With 12 sources at $z > 0.5$, our sample constitutes the highest-redshift discovery of AGN in dwarf galaxies. The record-holder is cid\_1192, at $z = 2.39$ and with $L_\mathrm{0.5-10 keV} \sim 10^{44}$ erg s$^{-1}$. One of the dwarf galaxies has $M_\mathrm{*} = 6.6 \times 10^{7}$ M$_{\odot}$ and is the least massive galaxy found so far to host an AGN. All the AGN are of type 2 and consistent with hosting intermediate-mass black holes (BHs) with masses $\sim 10^{4} - 10^{5}$ M$_{\odot}$ and typical Eddington ratios $> 1\%$. We also study the evolution, corrected for completeness, of AGN fraction with stellar mass, X-ray luminosity, and redshift in dwarf galaxies out to $z$ = 0.7. We find that the AGN fraction for $10^{9}< M_{*}\leq3 \times 10^{9}$ M$_{\odot}$ and $L_\mathrm{X} \sim 10^{41}-10^{42}$ erg s$^{-1}$ is $\sim$0.4\% for $z \leq$ 0.3 and that it decreases with X-ray luminosity and decreasing stellar mass. Unlike massive galaxies, the AGN fraction seems to decrease with redshift, suggesting that AGN in dwarf galaxies evolve differently than those in high-mass galaxies. Mindful of potential caveats, the results seem to favor a direct collapse formation mechanism for the seed BHs in the early Universe.Comment: 16 pages, 10 figures, accepted for publication in MNRA

Compton-thick AGN in the NuSTAR era II: A deep NuSTAR and XMM-Newton view of the candidate Compton thick AGN in NGC 1358

We present the combined NuSTATR and XMM-Newton 0.6-79 keV spectral analysis of a Seyfert 2 galaxy, NGC 1358, which we selected as a candidate Compton thick (CT-) active galactic nucleus (AGN) on the basis of previous Swift/BAT and Chandra studies. According to our analysis, NGC 1358 is confirmed to be a CT-AGN using physical motivated models, at >3 $\sigma$ confidence level. Our best-fit shows that the column density along the 'line-of-sight' of the obscuring material surrounding the accreting super-massive black hole is N$\rm _H$ = [1.96--2.80] $\times$ 10$^{24}$ cm$^{-2}$. The high-quality data from NuSTAR gives the best constraints on the spectral shape above $\sim$10 keV to date on NGC 1358. Moreover, by combining NuSTAR and XMM-Newton data, we find that the obscuring torus has a low covering factor ($f_c$ <0.17), and the obscuring material is distributed in clumps, rather than uniformly. We also derive an estimate of NGC 1358's Eddington ratio, finding it to be $\lambda_{\rm Edd}$ $\sim$$4.7_{-0.3}^{+0.3}$ $\times$ 10$^{-2}$, which is in acceptable agreement with previous measurements. Finally, we find no evidence of short-term variability, over a $\sim$100 ks time-span, in terms of both 'line-of-sight' column density and flux.Comment: 12 pages, 6 figure

PRM102 Budget Impact Analysis of Delayed-Release Dimethylfumarate In The Treatment of Relapsing-Remitting Multiple Sclerosis In Italy

INTRODUCTION: Multiple Sclerosis (MS) is a condition with a significant economic and social burden that affects young adults, in their active working phase. The most recent evaluations show an annual average social cost of € 38-39 thousand per patient. Today the approval of the new oral therapies allows physicians to select further options that can meet patients’ clinical unmet needs. OBJECTIVES: To evaluate the economic impact of a recently approved therapy, delayed-release dimethyl-fumarate (DMF; also known as gastro-resistant DMF), on the overall management costs of relapsing-remitting multiple sclerosis (RRMS) in Italy. METHODS: A budget impact model, adopting the perspective of the Italian National Healthcare Service (NHS), was used to compare healthcare costs of two different treatment scenarios: a) base-case, where DMF is not available for RRMS patients (Scenario A), vs. b) alternative-case, where DMF is available for RRMS patients (Scenario B). Healthcare costs sustained by the Italian NHS to manage the RRMS population (drug treatment, administration, therapy and disease monitoring, relapse management, treatment-related adverse events) have been calculated over 3 years and compared for the two scenarios. Impact of relapses for the disease modifying therapies (DMTs) included in the analysis was estimated using an elaboration of the results from published mixed treatment comparison. RRMS population treated with DMTs was estimated using Italian prevalence and incidence data. According to these estimates, the number of treated patients amounted to 36,078 at Year 1, 38,832 at Year 2, and 40,673 at Year 3. RESULTS: According to the current price and to the assumptions reported in the methodology section, it was estimated that the introduction of DMF (Scenario B) determines a decrease of the budget impact, if compared with the base case (Scenario A) in the perspective of Italian NHS. Over three years, the budget impact would be € 1,376 mln in the Scenario A and € 1,354 mln in the Scenario B (-22.18 mln €; -1.61% relative budget variation). The main drivers for cost-saving were pharmacological treatment costs and reduced burden of relapses (corresponding to more than 1,800 avoided relapses). CONCLUSIONS: At the current cost conditions applied in Italy and according to the described assumptions, the use of DMF is economically sustainable for the Italian NHS. Plausibly, the introduction and usage of this new therapy in RRMS patients will ensure clinical benefits for patients without resulting in additional costs for the Italian NHS. [In Italian

Pathogenetic, Clinical, and Prognostic Features of Adult t(4;11)(q21;q23)/MLL-AF4 Positive B-Cell Acute Lymphoblastic Leukemia

Translocation t(4;11)(q21;q23) leading to formation of MLL-AF4 fusion gene is found in about 10% of newly diagnosed B-cell acute lymphoblastic leukemia (ALL) in adult patients. Patients expressing this chromosomal aberration present typical biological, immunophenotypic, and clinical features. This form of leukemia is universally recognized as high-risk leukemia and treatment intensification with allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission (CR) could be a valid option to improve prognosis, but data obtained from the literature are controversial. In this review, we briefly describe pathogenetic, clinical, and prognostic characteristics of adult t(4;11)(q21;q23)/MLL-AF4 positive ALL and provide a review of the clinical outcome reported by the most important cooperative groups worldwide

IMPROVING ANIMAL WELFARE, ANIMAL PRODUCTION QUALITY AND FOOD SAFETY WITH ADVANCED SENSOR SYSTEMS

The livestock production main purpose is to satisfy the customer requirements at a price that enables the producer to make a profit. This trend moved the farm concept to the new control and monitoring technology system to support its operations. This new idea of the farm takes the name of \u201cPrecision farming technology\u201d (PFT). The objective of the researches described in this thesis is to study and evaluate different type of technologies used in the PFT. To achieve this objective, six different trials were done; in the first trial, it was evaluated the use of an electronic system for automatic calving detection; in the second trial, it was designed, developed and tested a GPS/GSM birth alarm for cattle-grazing; in the third trial, it was evaluated the oestrus detection in a dairy cattle farm with the Herd Navigator\u2122; in the fourth trial, it was analysed the reproduction and economical performances in a dairy cattle farm with the Herd Navigator\u2122; in the fifth trial, it was designed and tested a low cost GPS/GPRS collar to combat cattle rustling; in the sixth trial, it was studied a GPS collar to trace the epidemiological issues in a flock. In the first study, the technical performance of the C6 birth control system\uae was analysed. The C6 birth control system\uae is an electronic device that detects the time of the expulsion phase during the calving. A number of 53 Holstein was fitted on the day 280\ub15 of gestation with the C6 birth control system\uae, which was left in place until confirmation of calving. Sensitivity and positive predictive value of the system were calculated as 100% and 95%, respectively. The partum events occurring at the group fitted with the system were compared with the analogous occurred at 59 animals without device. When alarmed by the system the farm staffs were in the calving barn during the expulsion phase in the 100% of the cases. On the contrary the cows without the device were assisted only in 17% of the cases (P<0.001). The aim of the second trial was the development of a GPS/GSM birth alarm for cattle-grazing (GPS-CAL). At the expulsion phase, during the calving, the system sent a Short message Service (SMS) to the farmer\u2019s phone. In the SMS there were indicated the GPS coordinates where the cow was calving. Three tests were done: a) laboratory test to evaluate the battery life and the GPS\u2019s accuracy; b) field test in a commercial dairy farm with small pasture; c) field test in a commercial cattle farm in the Apennines. The laboratory tests showed a battery life of one month. The GPS accuracy was 1,237 m. In field \u201cb\u201d were tested 18 calving. In field \u201cc\u201d were tested 8 calving. In the total of 26 calving the GPS-CAL sent the SMS with the correct cow calving position. The third study was related to the Herd Navigator\u2122 monitoring of cows reproduction performances. The Herd Navigator\u2122 is a system that automatically programs the analysis of milk progesterone samples from selected specific cows of the herd. In a commercial dairy farm, the same 156 cows were monitored with both a Herd Navigator\u2122 and a DeLaval\uae activity system. Sensitivity and positive predictive value of the systems were calculated as 100% and 96% for Herd Navigator\u2122, and as 49% and 70% for activity meter. The test definitely, demonstrates a significant difference (P<0.001) between the two-oestrus detection systems both for sensitivity and positive predictive value, with higher performances for the Herd Navigator\u2122 system. The aim of the fourth trial was verify the Herd Navigator\u2122 benefits on the reproduction management in a commercial dairy farm - with automatic milking system - located in mountain areas. Reproductive and economical data were recorded before and one year after the Herd Navigator\u2122 installation. The number of days open (DO) was reduced from 166 to 103 days. The same reduction has been identified in the number of days between the first and the second insemination that was passed from 45 days before the Herd Navigator\u2122 introduction, to 28 days.. Another important value was the 80% reduction in the number of days required to identify an abortion (from 31 to 6 days). The preliminary results obtained confirm the usefulness of the system for the reproduction management. A model was developed using literature and commercial data to evaluate the potential economic benefits of the introduction of this technology. The model considers the benefits deriving from the decrease of reproduction problems and the reduction of days open. Considering the effects related to the above aspects, in a case study involving 70 dairy cows a 5 year time of investment return has been calculated. In the fifth trial, it was developed a low-cost GPS/GSM collar, using commercial hardware and implementing specific software, to track animals\u2019 movements within a grazing area and get alert from animals\u2019 trespassing of virtual fences. A Phase I study was conducted from September 2008 to June 2009 to build the GPS/GSM collar, while a Phase II study was conducted in July 2009 to test the GPS collar under real operating conditions. The GPS/GSM collar production costs did not exceed \u20ac 1.000, including software and labour required for its construction. Field tests highlighted the potentiality of the GPS/GSM collar as anti-theft system. Battery life was the most limiting factor of the system due to the high power consumption of the GPS receiver and the high frequency GPS sampling (30-s intervals) required by anti-theft monitoring. The aims of the last trial were study and evaluate a new system for the epidemiological monitoring in a flock. The OVItrace collar was a GPS / GPRS device connected to the management software. The system tracks and traces the path of the flock in real time. An OVItrace collar was placed onto a donkey in a flock. During the test stability and functionality of the system were verified. In particular, a number of 1563 location data has been recorded, with the exact definition of the location and the flock identification. Position requests were sent either via software (web-app) or via smartphone. In both cases the collar has promptly sent the position, ensuring a quick test for the field epidemiological analysis. However the OVItrace gives a number of further information in real time of the flock\u2019s path. The OVItrace collar use can be considered a good system for the epidemiological monitoring

DTPA-Functionalized silica-based monoliths for the removal of transition and lanthanide ions from aqueous phase

Transition and rare-earth metals are essential raw materials used in a wide range of technological applications; moreover, their consumption is often associated with high production of wastes­. Therefore, their recycling and recovery from end-of-life products or metal-contaminated aqueous environments is of considerable importance from a circular economy perspective. In our study, synthetic mesoporous silica monoliths, obtained by sol-gel synthesis[1] and functionalized with chelating groups are used for the recovery of metal ions from aqueous matrices (MONO-DTPA). The monoliths were characterized using a multi-technique approach and were tested in the recovery of paramagnetic Gd3+, Cu2+ and Co2+ ions from aqueous solutions, using 1H-NMR relaxometry to evaluate their uptake performance in real time and in simple conditions[2]. Detailed information on the kinetics of the capture process was also extrapolated. Finally, the possibility to regenerate the solid sorbents was evaluated. The modified silica monoliths were able to recover an appreciable amount of both di- and trivalent metal ions. The best results were obtained in the case of Cu2+ after 24 hours of contact, with a recovered amount of 0.29 mmol/g corresponding to 18.48 mg/g (Fig. 1, A). The capture performance of MONO-DTPA has been shown to be superior to that of natural or synthetic materials commonly used for metal ion removal (Fig 1, B). [1] V. Miglio, C. Zaccone, C. Vittoni, I. Braschi, E. Buscaroli, G. Golemme, L. Marchese and C. Bisio, Molecules 2021, 26, 1316 [2] S. Marchesi, S. Nascimbene, M. Guidotti, C. Bisio and F. Carniato, Dalton Trans. 2022, 51, 4502–4509

The Xmm-Newton Spectrum of a Candidate Recoiling Supermassive Black Hole: An Elusive Inverted P-Cygni Profile

We present a detailed spectral analysis of new XMM-Newton data of the source CXOC J100043.1+020637, also known as CID-42, detected in the COSMOS survey at z = 0.359. Previous works suggested that CID-42 is a candidate recoiling supermassive black hole (SMBH) showing also an inverted P-Cygni profile in the X-ray spectra at ~6 keV (rest) with an iron emission line plus a redshifted absorption line (detected at 3σ in previous XMM-Newton and Chandra observations). Detailed analysis of the absorption line suggested the presence of ionized material flowing into the black hole at high velocity. In the new long XMM-Newton observation, while the overall spectral shape remains constant, the continuum 2-10 keV flux decrease of ~20% with respect to previous observation and the absorption line is undetected. The upper limit on the intensity of the absorption line is EW \u3c 162 eV. Extensive Monte Carlo simulations show that the nondetection of the line is solely due to variation in the properties of the inflowing material, in agreement with the transient nature of these features, and that the intensity of the line is lower than the previously measured with a probability of 98.8%. In the scenario of CID-42 as a recoiling SMBH, the absorption line can be interpreted as being due to an inflow of gas with variable density that is located in the proximity of the SMBH and recoiling with it. New monitoring observations will be requested to further characterize this line

Moving beyond DNA: towards functional analysis of the vaginal microbiome by non-sequencing-based methods

Over the last two decades, sequencing-based methods have revolutionised our understanding of niche-specific microbial complexity. In the lower female reproductive tract, these approaches have enabled identification of bacterial compositional structures associated with health and disease. Application of metagenomics and metatranscriptomics strategies have provided insight into the putative function of these communities but it is increasingly clear that direct measures of microbial and host cell function are required to understand the contribution of microbe–host interactions to pathophysiology. Here we explore and discuss current methods and approaches, many of which rely upon mass-spectrometry, being used to capture functional insight into the vaginal mucosal interface. In addition to improving mechanistic understanding, these methods offer innovative solutions for the development of diagnostic and therapeutic strategies designed to improve women’s health