STAR: Steiner tree approximation in relationship-graphs

Large-scale graphs and networks are abundant in modern information systems: entity-relationship graphs over relational data or Web-extracted entities, biological networks, social online communities, knowledge bases, and many more. Often such data comes with expressive node and edge labels that allow an interpretation as a semantic graph, and edge weights that reflect the strengths of semantic relations between entities. Finding close relationships between a given set of two, three, or more entities is an important building block for many search, ranking, and analysis tasks. From an algorithmic point of view, this translates into computing the best Steiner trees between the given nodes, a classical NP-hard problem. In this paper, we present a new approximation algorithm, coined STAR, for relationship queries over large graphs that do not fit into memory. We prove that for n query entities, STAR yields an O(log(n))-approximation of the optimal Steiner tree, and show that in practical cases the results returned by STAR are qualitatively better than the results returned by a classical 2-approximation algorithm. We then describe an extension to our algorithm to return the top-k Steiner trees. Finally, we evaluate our algorithm over both main-memory as well as completely disk-resident graphs containing millions of nodes. Our experiments show that STAR outperforms the best state-of-the returns qualitatively better results

The genetic structure and connectivity in two sympatric rodent species with different life histories are similarly affected by land use disturbances

The negative impact of habitat fragmentation due to human activities may be different in different species that co-exist in the same area, with consequences on the development of environmental protection plans. Here we aim at understanding the effects produced by different natural and anthropic landscape features on gene flow patterns in two sympatric species with different specializations, one generalist and one specialist, sampled in the same locations. We collected and genotyped 194 wood mice (generalist species) and 199 bank voles (specialist species) from 15 woodlands in a fragmented landscape characterized by different potential barriers to dispersal. Genetic variation and structure were analyzed in the two species, respectively. Effective migration surfaces, isolation-by-resistance (IBR) analysis, and regression with randomization were used to investigate isolation-by-distance (IBD) and the relative importance of land cover elements on gene flow. We observed similar patterns of heterozygosity and IBD for both species, but the bank vole showed higher genetic differences among geographic areas. The IBR analysis suggests that (i) connectivity is reduced in both species by urban areas but more strongly in the specialist bank vole; (ii) cultivated areas act as dispersal corridors in both species; (iii) woodlands appear to be an important factor in increasing connectivity in the bank vole, and less so in the wood mouse. The difference in dispersal abilities between a generalist and specialist species was reflected in the difference in genetic structure, despite extensive habitat changes due to human activities. The negative effects of fragmentation due to the process of urbanization were, at least partially, mitigated by another human product, i.e., cultivated terrains subdivided by hedgerows, and this was true for both species

Population pharmacokinetics and pharmacodynamic target attainment of isavuconazole against aspergillus fumigatus and aspergillus flavus in adult patients with invasive fungal diseases: Should therapeutic drug monitoring for isavuconazole be considered as mandatory as for the other mold-active azoles?

Isavuconazole is a newer broad-spectrum triazole approved for the treatment of invasive fungal disease. The objective of this study was to conduct a population pharmacokinetic and pharma-codynamic analysis of isavuconazole in a retrospective cohort of hospitalized patients. A nonlinear mixed-effect approach with Monte Carlo simulations was conducted to assess the probability of target attainment (PTA) of an area under the concentration–time curve (AUC24 h )/minimum inhibitory concentration (MIC) ratio of 33.4 (defined as efficacy threshold against A. fumigatus and A. flavus) associated with a maintenance dose (MD) of 100, 200 and 300 mg daily after loading. The cumulative fraction of response (CFR) against the EUCAST MIC distributions of A. fumigatus and A. flavus was calculated as well. The proportion of trough concentrations (Ctrough ) exceeding a defined threshold of toxicity (>5.13 mg/L) was estimated. A total of 50 patients, with a median age of 61.5 years, pro-vided 199 plasma isavuconazole concentrations. Invasive pulmonary aspergillosis was the prevalent type of infection and accounted for 80% (40/50) of cases. No clinical covariates were retained by the model. With the standard MD of 200 mg daily, CFRs were always ≥90% during the first two months of treatment. The risk of Ctrough < 1.0 mg/L was around 1%, and that of Ctrough > 5.13 mg/L was 27.7 and 39.2% at 28 and 60 days, respectively, due to isavuconazole accumulation over time. Our findings suggest that TDM for isavuconazole should not be considered as mandatory as for the other mold-active azoles voriconazole and posaconazole

Rapid and persistent selection of the K103N mutation as a majority quasispecies in a HIV1-patient exposed to efavirenz for three weeks: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Selection of the K103N mutation is associated with moderately reduced in vitro fitness of HIV. Strains bearing K103N in vivo tend to persist, even in the absence of additional drug pressure, as minority quasispecies, often undetectable in genotyping resistance testing assays, performed at standard conditions. Here, we report on the rapid and long lasting selection of a K103N bearing strain as the dominant quasispecies after very short exposure to efavirenz in vivo.</p> <p>Case presentation</p> <p>A 55-year-old Caucasian man was switched to efavirenz, zidovudine and lamivudine in February 2003, while on viral suppression in his first-line highly active anti-retroviral treatment regimen. One month later, he reported inconsistent adherence and his viremia level was 5700 c/mL. He did not attend further checkups until September 2005, when his viral load was 181,000 c/mL. The patient reported interrupting his medications approximately three weeks after simplification. The genotyping resistance testing assay was performed both on HIV RNA and HIV DNA from plasma, yielding an identical pattern with the isolate presence of the K103N mutation in the prevalent strain.</p> <p>Conclusion</p> <p>Persistence of the K103N mutation as a majority quasispecies may ensue after a very short exposure to efavirenz. Our case would therefore suggest that the presence of the K103N mutation should always be ruled out by genotyping resistance testing assays, even after minimal exposures to efavirenz.</p

Mid-regional pro-adrenomedullin as a supplementary tool to clinical parameters in cases of suspicion of infection in the emergency department

Introduction: Mid-regional proadrenomedullin (MR-proADM), a novel biomarker, has recently gained interest particularly with regards to its potential in assisting clinicians\u2019 decision making in patients with suspicion of infection in the emergency department (ED). A group of international experts, with research and experience in MR-proADM applications, produced this review based on their own experience and the currently available literature. Areas covered: The review provides evidence related to MR-proADM as a triaging tool in avoiding unnecessary admissions to hospital and/or inadequate discharge, and identifying patients most at risk of deterioration. It also covers the use of MR-proADM in the context of COVID-19. Moreover, the authors provide a proposal on how to incorporate MR-proADM into patients\u2019 clinical pathways in an ED setting. Expert opinion: The data we have so far on the application of MR-proADM in the ED is promising. Incorporating it into clinical scoring systems may aid the clinician\u2019s decision making and recognizing the \u2018ill looking well\u2019 and the \u2018well looking ill\u2019 sooner. However there are still many gaps in our knowledge especially during the ongoing COVID-19 waves. There is also a need for cost-effectiveness analysis studies especially in the era of increasing cost pressures on health systems globally

Recognition in emergency department of septic patients at higher risk of death: Beware of patients without fever

Background and Objectives: Chances of surviving sepsis increase markedly upon prompt diagnosis and treatment. As most sepsis cases initially show-up in the Emergency Department (ED), early recognition of a septic patient has a pivotal role in sepsis management, despite the lack of precise guidelines. The aim of this study was to identify the most accurate predictors of in-hospital mortality outcome in septic patients admitted to the ED. Materials and Methods: We compared 651 patients admitted to ED for sepsis (cases) with 363 controls (non-septic patients). A Bayesian mean multivariate logistic regression model was performed in order to identify the most accurate predictors of in-hospital mortality outcomes in septic patients. Results: Septic shock and positive qSOFA were identified as risk factors for in-hospital mortality among septic patients admitted to the ED. Hyperthermia was a protective factor for in-hospital mortality. Conclusions: Physicians should bear in mind that fever is not a criterium for defining sepsis; according to our results, absence of fever upon presentation might be indicative of greater severity and diagnosis of sepsis should not be delayed

Headache Worsening after COVID-19 Vaccination: An Online Questionnaire-Based Study on 841 Patients with Migraine.

Vaccines have represented the breakthrough in the fight against COVID-19. Based on reported headache attacks after vaccination in randomized controlled trials, we focused on the effects of COVID-19 vaccine administration on the migraine population, using an online questionnaire published on Italian Facebook groups oriented to headache patients. We collected data about the demographics and clinical parameters of migraine severity, COVID-19 infection, vaccination, and characteristics of headaches following vaccination. Out of 841 migraine patients filling in the questionnaire, 66.47% and 60.15% patients experienced a headache attack (from 1 hour to 7 days) after the first and the second vaccine dose, respectively. The main finding concerns headaches perceived by 57.60% of patients: attacks following vaccination were referred to as more severe (50.62% of patients), long-lasting (52.80% of patients) and hardwearing (49.69% of patients) compared to the usually experienced migraine attacks. This could be related to the production of inflammatory mediators such as type Iβ interferon. Considering the high prevalence of migraine in the general population, awareness of the possibility of headaches worsening following COVID-19 vaccination in these patients may allow both patients and clinicians to face this clinical entity with conscious serenity, and to reduce the waste of resources towards inappropriate health-care