On First-Passage Times and Sojourn Times in Finite QBD Processes and Their Applications in Epidemics

In this paper, we revisit level-dependent quasi-birth-death processes with finitely many possible values of the level and phase variables by complementing the work of Gaver, Jacobs, and Latouche (Adv. Appl. Probab. 1984), where the emphasis is upon obtaining numerical methods for evaluating stationary probabilities and moments of first-passage times to higher and lower levels. We provide a matrix-analytic scheme for numerically computing hitting probabilities, the number of upcrossings, sojourn time analysis, and the random area under the level trajectory. Our algorithmic solution is inspired from Gaussian elimination, which is applicable in all our descriptors since the underlying rate matrices have a block-structured form. Using the results obtained, numerical examples are given in the context of varicella-zoster virus infections

An Analysis of STIS HST UV Spectra of M33 early B Supergiants

We present terminal velocities of M33 B-supergiants, obtained from STIS HST spectra as part of our programme to investigate the Wind Momentum -- Luminosity Relationship (WLR) in the Local Group. Terminal velocities are derived from their NV, CIV, and SiIV resonance lines in UV spectra. Comparing with IUE spectra of Galactic B-supergiants we found evidence of low metallicity in three of our objects. %%The terminal velocities are found to be consistent with the %%values found for Galactic stars, except for B-133. For this The terminal velocities are consistent with the corresponding values of Galactic stars, except for B-133. For this star we find a very large vterm and a red SiIV component deeper than the blue one, that might be an indication of binarity. The average ratio between terminal and turbulent wind velocities is 0.25, well above the value found for Galactic stars.Comment: 9 pages, 6 figure

Blue luminous stars in nearby galaxies - UIT005: a possible link to the luminous blue variable stage

(abridged) A detailed study of the blue supergiant UIT005 (B2-2.5Ia+) in M33 is presented. The results of our quantitative spectral analysis indicate that the star is a very luminous, log(L/Lsun)~5.9 dex, and massive, M~50 Msun, object, showing a very high nitrogen-to-oxygen ratio in its surface (N/O~8, by mass). Based on the derived Mg and Si abundances, we argue that this high N/O ratio cannot be the result of an initial low O content due to its location on the disk of M33, known to present a steep metallicity gradient. In combination with the He abundance, the most plausible interpretation is that UIT005 is in an advanced stage of evolution, showing in its surface N enrichment and O depletion resulting from mixing with CNO processed material from the stellar interior. A comparison with the predictions of current stellar evolutionary models indicates that there are significant discrepancies, in particular with regard to the degree of chemical processing, with the models predicting a much lower degree of O depletion than observed. At the same time, the mass-loss rate derived in our analysis is an order of magnitude lower than the values considered in the evolutionary calculations. Based on a study of the surrounding stellar population and the nearby cluster NGC588, using WFPC2 photometry, we suggest that UIT005 could be in fact a runaway star from this cluster.Comment: Accepted for publication by ApJ, 11 figures, 45 page

The Young Stellar Population of IC1613. I. A New Catalogue of OB Associations

Context: Determining the parameters of massive stars is crucial to understand many processes in galaxies and the Universe, since these objects are important sources of ionization, chemical enrichment and momentum. 10m class telescopes enable us to perform detailed quantitative spectroscopic analyses of massive stars in other galaxies, sampling areas of different metallicity. Relating the stars to their environment is crucial to understand the physical processes ruling their formation and evolution. Aims: In preparation for the GTC, our goal is to build a catalogue of massive star candidates in the metal-poor irregular galaxy IC1613 with high astrometric accuracy, apt for the current generation of multi-object spectrographs. A census of OB associations in this galaxy is also needed, to provide important additional information about age and environment of the candidate OB stars. Methods: From INT-WFC observations, we have built an astrometric and photometric catalogue of stars in IC1613. Candidate blue massive stars are preselected from their colors. A friends-of-friends algorithm is developed to find their clustering in the galaxy. While a common physical origin for all the members of the associations cannot be ensured, this is a necessary first step to place candidate OB stars in a population context. Results: We have produced a deep catalogue of targets in IC1613 that covers a large field of view. To achieve high astrometric accuracy a new astrometric procedure is developed for the INT-WFC data. We have also built a catalogue of OB associations in IC1613. We have found that they concentrate in the central regions, specially in the HII bubbles. The study of extinction confirms that it is patchy, with local values of color-excess above the foreground value.Comment: Accepted for publication in Astronomy and Astrophysics. 16 pages + appendix (14 pages); 20 figure

On the nature of candidate luminous blue variables in M33

Luminous blue variables (LBVs) are expected to play an important role in massive stellar evolution as well as being the progenitors of some of the most luminous supernovae known. In this paper we provide a multiwavelength study of the population of (candidate) LBVs identified within M33. New spectra provide an observational baseline of >4yr with respect to published data, which is well suited to identifying LBV outbursts. Multi-epoch optical and mid-IR surveys of M33 further constrain the variability of the sample and permit a search for dusty circumstellar ejecta. Spectroscopic and photometric variability appears common amongst the sample, although in many cases further observations will be required to determine its physical origin. Nevertheless, we report a new outburst of M33 Var C, while the transition of the WNLh star B517 to a cooler B supergiant phase between 1993-2010 confirms an LBV classification. Proof-of-concept quantitative analysis is provided for Romano's star; the results being consistent with the finding that its bolometric luminosity varies during its LBV excursions. The combination of the temperature and luminosity of two stars, the B hypergiant [HS80] 110A and the cool hypergiant B324, appears to be in violation of the empirical Humphreys-Davidson limit. Mid-IR observations demonstrate that a number of candidates appear associated with hot circumstellar dust, although no objects as extreme as Eta Carinae are identified. The combined multiwavelength dataset suggests that the population of LBVs studied is contaminated by stars demonstrating the B[e] phenomenon. Of these, a subset of optically faint, low luminosity stars associated with hot dust are of particular interest since they appear similar to the likely progenitors of SN 2008S and the 2008 NGC300 transient, albeit suffering less intrinsic extinction. [ABRIDGED]Comment: 23 pages, 14 figures, accepted for publication in Astronomy and Astrophysic

The MIXR sample: AGN activity versus star formation across the cross-correlation of WISE, 3XMM, and FIRST/NVSS

We cross-correlate the largest available mid-infrared (Wide-field Infrared Survey Explorer - WISE), X-ray (3XMM) and radio (Faint Images of the Radio Sky at Twenty centimetres+NRAO VLA Sky Survey) catalogues to define the MIXR sample of AGN and star-forming galaxies. We pre-classify the sources based on their positions on the WISE colour/colour plot, showing that the MIXR triple selection is extremely effective to diagnose the star formation and AGN activity of individual populations, even on a flux/magnitude basis, extending the diagnostics to objects with luminosities and redshifts from SDSS DR12. We recover the radio/mid-IR star formation correlation with great accuracy, and use it to classify our sources, based on their activity, as radio-loud and radio-quiet active galactic nuclei (AGN), low excitation radio galaxies/low ionization nuclear emission line regions, and non-AGN galaxies. These diagnostics can prove extremely useful for large AGN and galaxy samples, and help develop ways to efficiently triage sources when data from the next generation of instruments becomes available. We study bias in detail, and show that while the widely used WISE colour selections for AGN are very successful at cleanly selecting samples of luminous AGN, they miss or misclassify a substantial fraction of AGN at lower luminosities and/or higher redshifts. MIXR also allows us to test the relation between radiative and kinetic (jet) power in radio-loud AGN, for which a tight correlation is expected due to a mutual dependence on accretion. Our results highlight that long-term AGN variability, jet regulation, and other factors affecting the Q/Lbol relation, are introducing a vast amount of scatter in this relation, with dramatic potential consequences on our current understanding of AGN feedback and its effect on star formation

Effects of IL-8 up-regulation on cell survival and osteoclastogenesis in multiple myeloma

[EN]IL-8 promotes cancer cell growth, survival, angiogenesis, and metastasis in several tumors. Herein, we investigated the sources of IL-8 production in multiple myeloma (MM) and its potential roles in MM pathogenesis. We found that bone marrow cells from patients with MM secreted higher amounts of IL-8 than healthy donors. IL-8 production was detected in cultures of CD138+ plasma cells and CD138(-) cells isolated from bone marrows of MM patients, and in three of seven human myeloma cell lines (HMCLs) analyzed. Interactions between MM and stromal cells increased IL-8 secretion by stromal cells through cell-cell adhesion and soluble factors. Interestingly, 1L8 expression also increased in HMCLs, stromal cells, and osteoclasts after treatment with the antimyeloma drugs melphalan and bortezomib. In fact, the effect of bortezomib on IL-8 production was higher than that exerted by stromal-MM cell interactions. Addition of exogenous IL-8 did not affect growth of HMCLs, although it protected cells from death induced by serum starvation through a caspase-independent mechanism. Furthermore, IL-8 induced by stromal-MM cell interactions strongly contributed to osteoclast formation in vitro, because osteoclastogenesis was markedly reduced by IL-8 specific neutralizing antibodies. In conclusion, our results implicate IL-8 in myeloma bone disease and point to the potential utility of an anti IL-8 therapy to prevent unwanted effects of IL-8 up-regulation on survival, angiogenesis, and osteolysis in MM.Spanish RTICC, Spanish Association against Cancer (AECC), the INNOCAMPUS Program , Spanish ISCIII-FIS (PI12/02591) and FEDER, Regional Council from Castilla y León (Consejería de Educación) and the Network of Centers for Regenerative Medicine and Cellular Therapy from Castilla y León

Mortality and pulmonary complications in patients undergoing surgery with perioperative sars-cov-2 infection: An international cohort study

Background The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (740%) had emergency surgery and 280 (248%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (261%) patients. 30-day mortality was 238% (268 of 1128). Pulmonary complications occurred in 577 (512%) of 1128 patients; 30-day mortality in these patients was 380% (219 of 577), accounting for 817% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 175 [95% CI 128-240], p<00001), age 70 years or older versus younger than 70 years (230 [165-322], p<00001), American Society of Anesthesiologists grades 3-5 versus grades 1-2 (235 [157-353], p<00001), malignant versus benign or obstetric diagnosis (155 [101-239], p=0046), emergency versus elective surgery (167 [106-263], p=0026), and major versus minor surgery (152 [101-231], p=0047). Interpretation Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

The Beaker phenomenon and the genomic transformation of northwest Europe

From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain’s gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries