Optimising the Treatment of Invasive Candidiasis – A Case for Combination Therapy

Invasive candidiasis is a rising global health threat with increasing incidence, persistently high mortality and diminishing treatment options. Antifungal resistance has rapidly emerged and spread, with multidrug resistant species deemed an urgent and serious threat (US CDC). While acknowledging the key role of antifungal stewardship and infection control in curbing spread, we examine the role of antifungal monotherapy in driving resistance and the potential for combination therapy to prevent stress adaptation and emergence of drug resistance. In addition to its role in mitigating resistance, combination treatment may improve drug penetration, expedite fungal clearance, and allow lower, less toxic doses of individual drugs to be used. A growing body of laboratory-based evidence suggests that antifungal combinations can yield synergistic activity against Candida spp, including against frequently multidrug resistant Candida auris. It is imperative to test these combinations in clinical trials, incorporating resistance endpoints as a marker of success

Alternative scenarios: harnessing mid-level providers and evidence-based practice in primary dental care in England through operational research

Background: In primary care dentistry, strategies to reconfigure the traditional boundaries of various dental professional groups by task sharing and role substitution have been encouraged in order to meet changing oral health needs. Aim: The aim of this research was to investigate the potential for skill mix use in primary dental care in England based on the undergraduate training experience in a primary care team training centre for dentists and mid-level dental providers. Methods: An operational research model and four alternative scenarios to test the potential for skill mix use in primary care in England were developed, informed by the model of care at a primary dental care training centre in the south of England, professional policy including scope of practice and contemporary evidence-based preventative practice. The model was developed in Excel and drew on published national timings and salary costs. The scenarios included the following: “No Skill Mix”, “Minimal Direct Access”, “More Prevention” and “Maximum Delegation”. The scenario outputs comprised clinical time, workforce numbers and salary costs required for state-funded primary dental care in England. Results: The operational research model suggested that 73% of clinical time in England’s state-funded primary dental care in 2011/12 was spent on tasks that may be delegated to dental care professionals (DCPs), and 45- to 54-year-old patients received the most clinical time overall. Using estimated National Health Service (NHS) clinical working patterns, the model suggested alternative NHS workforce numbers and salary costs to meet the dental demand based on each developed scenario. For scenario 1:“No Skill Mix”, the dentist-only scenario, 81% of the dentists currently registered in England would be required to participate. In scenario 2: “Minimal Direct Access”, where 70% of examinations were delegated and the primary care training centre delegation patterns for other treatments were practised, 40% of registered dentists and eight times the number of dental therapists currently registered would be required; this would save 38% of current salary costs cf. “No Skill Mix”. Scenario 3: “More Prevention”, that is, the current model with no direct access and increasing fluoride varnish from 13.1% to 50% and maintaining the same model of delegation as scenario 2 for other care, would require 57% of registered dentists and 4.7 times the number of dental therapists. It would achieve a 1% salary cost saving cf. “No Skill Mix”. Scenario 4 “Maximum Delegation” where all care within dental therapists’ jurisdiction is delegated at 100%, together with 50% of restorations and radiographs, suggested that only 30% of registered dentists would be required and 10 times the number of dental therapists registered; this scenario would achieve a 52% salary cost saving cf. “No Skill Mix”. Conclusion: Alternative scenarios based on wider expressed treatment need in national primary dental care in England, changing regulations on the scope of practice and increased evidence-based preventive practice suggest that the majority of care in primary dental practice may be delegated to dental therapists, and there is potential time and salary cost saving if the majority of diagnostic tasks and prevention are delegated. However, this would require an increase in trained DCPs, including role enhancement, as part of rebalancing the dental workforce

Convergent and parallel evolution in life habit of the scallops (Bivalvia: Pectinidae)

<p>Abstract</p> <p>Background</p> <p>We employed a phylogenetic framework to identify patterns of life habit evolution in the marine bivalve family Pectinidae. Specifically, we examined the number of independent origins of each life habit and distinguished between convergent and parallel trajectories of life habit evolution using ancestral state estimation. We also investigated whether ancestral character states influence the frequency or type of evolutionary trajectories.</p> <p>Results</p> <p>We determined that temporary attachment to substrata by byssal threads is the most likely ancestral condition for the Pectinidae, with subsequent transitions to the five remaining habit types. Nearly all transitions between life habit classes were repeated in our phylogeny and the majority of these transitions were the result of parallel evolution from byssate ancestors. Convergent evolution also occurred within the Pectinidae and produced two additional gliding clades and two recessing lineages. Furthermore, our analysis indicates that byssal attaching gave rise to significantly more of the transitions than any other life habit and that the cementing and nestling classes are only represented as evolutionary outcomes in our phylogeny, never as progenitor states.</p> <p>Conclusions</p> <p>Collectively, our results illustrate that both convergence and parallelism generated repeated life habit states in the scallops. Bias in the types of habit transitions observed may indicate constraints due to physical or ontogenetic limitations of particular phenotypes.</p

Body mass index and dental caries in children and adolescents : a systematic review of literature published 2004 to 2011

The objectiveThe authors undertook an updated systematic review of the relationship between body mass index and dental caries in children and adolescents.MethodThe authors searched Medline, ISI, Cochrane, Scopus, Global Health and CINAHL databases and conducted lateral searches from reference lists for papers published from 2004 to 2011, inclusive. All empirical papers that tested associations between body mass index and dental caries in child and adolescent populations (aged 0 to 18 years) were included.ResultsDental caries is associated with both high and low body mass index.ConclusionA non-linear association between body mass index and dental caries may account for inconsistent findings in previous research. We recommend future research investigate the nature of the association between body mass index and dental caries in samples that include a full range of body mass index scores, and explore how factors such as socioeconomic status mediate the association between body mass index and dental caries.<br /

Translational toxicology in setting occupational exposure limits for dusts and hazard classification – a critical evaluation of a recent approach to translate dust overload findings from rats to humans

Background We analyze the scientific basis and methodology used by the German MAK Commission in their recommendations for exposure limits and carcinogen classification of “granular biopersistent particles without known specific toxicity” (GBS). These recommendations are under review at the European Union level. We examine the scientific assumptions in an attempt to reproduce the results. MAK’s human equivalent concentrations (HECs) are based on a particle mass and on a volumetric model in which results from rat inhalation studies are translated to derive occupational exposure limits (OELs) and a carcinogen classification. Methods We followed the methods as proposed by the MAK Commission and Pauluhn 2011. We also examined key assumptions in the metrics, such as surface area of the human lung, deposition fractions of inhaled dusts, human clearance rates; and risk of lung cancer among workers, presumed to have some potential for lung overload, the physiological condition in rats associated with an increase in lung cancer risk. Results The MAK recommendations on exposure limits for GBS have numerous incorrect assumptions that adversely affect the final results. The procedures to derive the respirable occupational exposure limit (OEL) could not be reproduced, a finding raising considerable scientific uncertainty about the reliability of the recommendations. Moreover, the scientific basis of using the rat model is confounded by the fact that rats and humans show different cellular responses to inhaled particles as demonstrated by bronchoalveolar lavage (BAL) studies in both species. Conclusion Classifying all GBS as carcinogenic to humans based on rat inhalation studies in which lung overload leads to chronic inflammation and cancer is inappropriate. Studies of workers, who have been exposed to relevant levels of dust, have not indicated an increase in lung cancer risk. Using the methods proposed by the MAK, we were unable to reproduce the OEL for GBS recommended by the Commission, but identified substantial errors in the models. Considerable shortcomings in the use of lung surface area, clearance rates, deposition fractions; as well as using the mass and volumetric metrics as opposed to the particle surface area metric limit the scientific reliability of the proposed GBS OEL and carcinogen classification.International Carbon Black Associatio

Shedding Light on the Galaxy Luminosity Function

From as early as the 1930s, astronomers have tried to quantify the statistical nature of the evolution and large-scale structure of galaxies by studying their luminosity distribution as a function of redshift - known as the galaxy luminosity function (LF). Accurately constructing the LF remains a popular and yet tricky pursuit in modern observational cosmology where the presence of observational selection effects due to e.g. detection thresholds in apparent magnitude, colour, surface brightness or some combination thereof can render any given galaxy survey incomplete and thus introduce bias into the LF. Over the last seventy years there have been numerous sophisticated statistical approaches devised to tackle these issues; all have advantages -- but not one is perfect. This review takes a broad historical look at the key statistical tools that have been developed over this period, discussing their relative merits and highlighting any significant extensions and modifications. In addition, the more generalised methods that have emerged within the last few years are examined. These methods propose a more rigorous statistical framework within which to determine the LF compared to some of the more traditional methods. I also look at how photometric redshift estimations are being incorporated into the LF methodology as well as considering the construction of bivariate LFs. Finally, I review the ongoing development of completeness estimators which test some of the fundamental assumptions going into LF estimators and can be powerful probes of any residual systematic effects inherent magnitude-redshift data.Comment: 95 pages, 23 figures, 3 tables. Now published in The Astronomy & Astrophysics Review. This version: bring in line with A&AR format requirements, also minor typo corrections made, additional citations and higher rez images adde

Sloan Digital Sky Survey IV: Mapping the Milky Way, Nearby Galaxies, and the Distant Universe

We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median $z\sim 0.03$). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between $z\sim 0.6$ and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July

Morphologically Conservative but Physiologically Diverse: The Mode of Stasis in Anostraca (Crustacea: Branchiopoda)

The essay discusses whether biotic and abiotic environments differ in their ability to speed up or slow down morphological change and the generation of new lineages. Examples from the class Branchiopoda show that morphological conservatism is associated with enemy free space in species-poor habitats dominated by abiotic factors, while Red Queen mechanisms are predominant in larger systems with complex biotic interactions. Splitting of Branchiopod main lineages is associated with increased fish predation during the Devonian. The order Cladocera adapted and remained in larger aquatic systems, and subsequently generated a variety of new families, genera and species. The order Anostraca, on the other hand, maintained its ancestral morphology and survived only as “living fossils” in isolated ponds of harsh habitats. Despite their archaic morphology, however, they possess highly sophisticated adaptations to local physicochemical properties of their extreme environment. Hence, although morphologically conservative and possessing traits typical for “living fossils”, anostracan physiological abilities are closely adapted to the challenging and variable physicochemical conditions of ponds and ephemeral pools