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In recent years, the discovery of massive quasars at
has provided a striking challenge to our understanding of the origin and growth of supermassive black holes in the early Universe. Mounting observational and theoretical evidence indicates the viability of massive seeds, formed by the collapse of supermassive stars, as a progenitor model for such early, massive accreting black holes. Although considerable progress has been made in our theoretical understanding, many questions remain regarding how (and how often) such objects may form, how they live and die, and how next generation observatories may yield new insight into the origin of these primordial titans. This review focusses on our present understanding of this remarkable formation scenario, based on the discussions held at the Monash Prato Centre from November 20 to 24, 2017, during the workshop ‘Titans of the Early Universe: The Origin of the First Supermassive Black Holes’.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
To sustainably improve cleaning of high-touch surfaces (HTSs) in acute-care hospitals using a multimodal approach to education, reduction of barriers to cleaning, and culture change for environmental services workers.
The study was conducted in 2 academic acute-care hospitals, 2 community hospitals, and an academic pediatric and women’s hospital.
Frontline environmental services workers.
A 5-module educational program, using principles of adult learning theory, was developed and presented to environmental services workers. Audience response system (ARS), videos, demonstrations, role playing, and graphics were used to illustrate concepts of and the rationale for infection prevention strategies. Topics included hand hygiene, isolation precautions, personal protective equipment (PPE), cleaning protocols, and strategies to overcome barriers. Program evaluation included ARS questions, written evaluations, and objective assessments of occupied patient room cleaning. Changes in hospital-onset C. difficile infection (CDI) and methicillin-resistant S. aureus (MRSA) bacteremia were evaluated.
On average, 357 environmental service workers participated in each module. Most (93%) rated the presentations as ‘excellent’ or ‘very good’ and agreed that they were useful (95%), reported that they were more comfortable donning/doffing PPE (91%) and performing hand hygiene (96%) and better understood the importance of disinfecting HTSs (96%) after the program. The frequency of cleaning individual HTSs in occupied rooms increased from 26% to 62% (P < .001) following the intervention. Improvement was sustained 1-year post intervention (P < .001). A significant decrease in CDI was associated with the program.
A novel program that addressed environmental services workers’ knowledge gaps, challenges, and barriers was well received and appeared to result in learning, behavior change, and sustained improvements in cleaning.
Cascading effects of high trophic levels onto lower trophic levels have been documented in many ecosystems. Some studies also show evidence of extended trophic cascades, in which guilds dependent on lower trophic levels, but uninvolved in the trophic cascade themselves, are affected by the trophic cascade due to their dependence on lower trophic levels. Top-down effects of large mammals on plants could lead to a variety of extended trophic cascades on the many guilds dependent on plants, such as pollinators. In this study, floral-visitor and floral abundances and assemblages were quantified within a series of 1-ha manipulations of large-mammalian herbivore density in an African savanna. Top-down effects of large mammals on the composition of flowers available for floral visitors are first shown, using regressions of herbivore activity on metrics of floral and floral-visitor assemblages. An extended trophic cascade is also shown: the floral assemblage further altered the assemblage of floral visitors, according to a variety of approaches, including a structural equation modelling approach (model with an extended trophic cascade was supported over a model without, AICc weight = 0.984). Our study provides support for extended trophic cascades affecting floral visitors, suggesting that trophic cascades can have impacts throughout entire communities.
With the emergence of modern techniques of environmental analysis and widespread availability of accessible tools and quantitative data, the question of environmental determinism is once again on the agenda. This paper is theoretical in character, attempting, for the benefit of drawing up research designs, to understand and evaluate the character of environmental determinism. We reach three main conclusions: (1) in a typical pattern of research design, studies seek to detect simultaneous shifts in the environmental and archaeological records, variously positing the former to have influenced, triggered or caused the latter; (2) the question of determinism involves uncertainty about the justification for the above research design in particular in what comes to biologism and the concept of environmental thresholds on the one hand and the externality of the drivers of transformation in human groups and societies on the other; (3) adapting the concepts of the social production of vulnerability and the social basis of hazards from anthropology may help to clarify the available research design choices at hand.
There is no suitable vaccine against human visceral leishmaniasis (VL) and available drugs are toxic and/or present high cost. In this context, diagnostic tools should be improved for clinical management and epidemiological evaluation of disease. However, the variable sensitivity and/or specificity of the used antigens are limitations, showing the necessity to identify new molecules to be tested in a more sensitive and specific serology. In the present study, an immunoproteomics approach was performed in Leishmania infantum promastigotes and amastigotes employing sera samples from VL patients. Aiming to avoid undesired cross-reactivity in the serological assays, sera from Chagas disease patients and healthy subjects living in the endemic region of disease were also used in immunoblottings. The most reactive spots for VL samples were selected, and 29 and 21 proteins were identified in the promastigote and amastigote extracts, respectively. Two of them, endonuclease III and GTP-binding protein, were cloned, expressed, purified and tested in ELISA experiments against a large serological panel, and results showed high sensitivity and specificity values for the diagnosis of disease. In conclusion, the identified proteins could be considered in future studies as candidate antigens for the serodiagnosis of human VL.
The mammal family Tenrecidae (Afrotheria: Afrosoricida) is endemic to Madagascar. Here we present the conservation priorities for the 31 species of tenrec that were assessed or reassessed in 2015–2016 for the IUCN Red List of Threatened Species. Six species (19.4%) were found to be threatened (4 Vulnerable, 2 Endangered) and one species was categorized as Data Deficient. The primary threat to tenrecs is habitat loss, mostly as a result of slash-and-burn agriculture, but some species are also threatened by hunting and incidental capture in fishing traps. In the longer term, climate change is expected to alter tenrec habitats and ranges. However, the lack of data for most tenrecs on population size, ecology and distribution, together with frequent changes in taxonomy (with many cryptic species being discovered based on genetic analyses) and the poorly understood impact of bushmeat hunting on spiny species (Tenrecinae), hinders conservation planning. Priority conservation actions are presented for Madagascar's tenrecs for the first time since 1990 and focus on conserving forest habitat (especially through improved management of protected areas) and filling essential knowledge gaps. Tenrec research, monitoring and conservation should be integrated into broader sustainable development objectives and programmes targeting higher profile species, such as lemurs, if we are to see an improvement in the conservation status of tenrecs in the near future.
Before an intervention is publicly funded within the United Kingdom, the cost-effectiveness is assessed by the National Institute of Health and Care Excellence (NICE). The efficacy of an intervention across the patients’ lifetime is often influential of the cost-effectiveness analyses, but is associated with large uncertainties. We reviewed committee documents containing company submissions and evidence review group (ERG) reports to establish the methods used when extrapolating survival data, whether these adhered to NICE Technical Support Document (TSD) 14, and how uncertainty was addressed.
A systematic search was completed on the NHS Evidence Search webpage limited to single technology appraisals of cancer interventions published in 2017, with information obtained from the NICE Web site.
Twenty-eight appraisals were identified, covering twenty-two interventions across eighteen diseases. Every economic model used parametric curves to model survival. All submissions used goodness-of-fit statistics and plausibility of extrapolations when selecting a parametric curve. Twenty-five submissions considered alternate parametric curves in scenario analyses. Six submissions reported including the parameters of the survival curves in the probabilistic sensitivity analysis. ERGs agreed with the company's choice of parametric curve in nine appraisals, and agreed with all major survival-related assumptions in two appraisals.
TSD 14 on survival extrapolation was followed in all appraisals. Despite this, the choice of parametric curve remains subjective. Recent developments in Bayesian approaches to extrapolation are not implemented. More precise guidance on the selection of curves and modelling of uncertainty may reduce subjectivity, accelerating the appraisal process.
(1) To characterise changes in dead space fraction during the first 120 post-operative hours in neonates undergoing stage 1 palliation for hypoplastic left heart syndrome, including hybrid procedure; (2) to document whether dead space fraction varied by shunt type (Blalock–Taussig shunt and Sano) and hybrid procedure; and (3) to determine the association between dead space fraction and outcomes.
Retrospective chart review in neonates undergoing stage 1 palliation for hypoplastic left heart syndrome in a cardiac intensive care unit over a consecutive 30-month period. A linear mixed model was used to determine the differences in dead space over time. Multivariable linear regression and a multivariable linear mixed model were used to assess the association between dead space and outcomes at different time points and over time, respectively.
Thirty-four neonates received either a Blalock–Taussig shunt (20.5%), Sano shunt (59%), or hybrid procedure (20.5%). Hospital mortality was 8.8%. Dead space fractions in patients undergoing the hybrid procedure were significantly lower on day 1 (p = 0.01) and day 2 (p = 0.02) and increased over time. A dead space fraction >0.6 on post-operative days 3–5 was significantly associated with decreased duration of mechanical ventilation in all surgical groups (p < 0.001).
Dead space fraction >0.6 on post-operative days 3–5 was associated with lower duration of mechanical ventilation in all surgical groups. A more comprehensive, prospective assessment of dead space in this delicate patient population would likely be beneficial in improving outcomes.
We prove the following 30 year-old conjecture of Győri and Tuza: the edges of every n-vertex graph G can be decomposed into complete graphs C1,. . .,Cℓ of orders two and three such that |C1|+···+|Cℓ| ≤ (1/2+o(1))n2. This result implies the asymptotic version of the old result of Erdős, Goodman and Pósa that asserts the existence of such a decomposition with ℓ ≤ n2/4.
Background: Intensive care unit-acquired weakness (ICU-AW) is associated with poorer outcome of critically ill patients. Microcirculatory changes and altered vascular permeability of skeletal muscles might contribute to the pathogenesis of ICU-AW. Muscular ultrasound (MUS) displays increased muscle echogenicity, although its pathogenesis is uncertain. Objective: We investigated the combined measurement of serum and ultrasound markers to assess ICU-AW and clinical patient outcome. Methods: Fifteen patients and five healthy controls were longitudinally assessed for signs of ICU-AW at study days 3 and 10 using a muscle strength sum score. The definition of ICU-AW was based on decreased muscle strength assessed by the muscular research council-sum score. Ultrasound echogenicity of extremity muscles was assessed using a standardized protocol. Serum markers of inflammation and endothelial damage were measured. The 3-month outcome was assessed on the modified Rankin scale. Results: ICU-AW was present in eight patients, and seven patients and the control subjects did not develop ICU-AW. The global muscle echogenicity score (GME) differed significantly between controls and patients (mean GME, 1.1 ± 0.06 vs. 2.3 ± 0.41; p = 0.001). Mean GME values significantly decreased in patients without ICU-AW from assessment 1 (2.30 ± 0.48) to assessment 2 (2.06 ± 0.45; p = 0.027), which was not observed in patients with ICU-AW. Serum levels of syndecan-1 at day 3 significantly correlated with higher GME values at day 10 (r = 0.63, p = 0.012). Furthermore, the patients’ GME significantly correlated with mRS at day 100 (r = 0.67, p = 0.013). Conclusion: The combined use of muscular ultrasound and inflammatory biomarkers might be helpful to diagnose ICU-AW and to predict long-term outcome in critical illness.
Resting state functional magnetic resonance imaging studies have identified functional connectivity patterns associated with acute undernutrition in anorexia nervosa (AN), but few have investigated recovered patients. Thus, a trait connectivity profile characteristic of the disorder remains elusive. Using state-of-the-art graph–theoretic methods in acute AN, the authors previously found abnormal global brain network architecture, possibly driven by local network alterations. To disentangle trait from starvation effects, the present study examines network organization in recovered patients.
Graph–theoretic metrics were used to assess resting-state network properties in a large sample of female patients recovered from AN (recAN, n = 55) compared with pairwise age-matched healthy controls (HC, n = 55).
Indicative of an altered global network structure, recAN showed increased assortativity and reduced global clustering as well as small-worldness compared with HC, while no group differences at an intermediate or local network level were evident. However, using support-vector classifier on local metrics, recAN and HC could be separated with an accuracy of 70.4%.
This pattern of results suggests that long-term recovered patients have an aberrant global brain network configuration, similar to acutely underweight patients. While the finding of increased assortativity may represent a trait marker of AN, the remaining findings could be seen as a scar following prolonged undernutrition.
We evaluated the effects of cattle manure and inoculation with arbuscular mycorrhizal fungi (AMF) in maize plants growing in a semiarid area of Brazilian north-east in 2012 and 2013. Three isolates of AMF (Acaulospora longula URM-FMA 07 and URM-FMA 03, Claroideoglomus etunicatum UNIVASF 06A) were used, with or without the application of cattle manure, during two growing cycles. In the first year, significant effects of inoculation were detected for straw yield only when the manure was applied. In the second year, there was an interaction between fertilisation and inoculation for plant height and grain yield, with the highest values in the fertilised treatments. Inoculation with A. longula demonstrated that mycorrhizal inoculation in field-grown plants could be an alternative management for improving plant growth and grain yield, reducing the use of cattle manure. The AMF sporulation and mycorrhizal colonisation were improved after inoculation, and A. longula URM-FMA 07 increased sporulation by more than 15 times while inoculation with C. etunicatum increased sporulation by more than 3 times. The mycorrhizal inoculation is a management practice that can be useful for recovering or maintaining AMF infective propagules in soil, showing potential to be used in large-scale field conditions in Brazilian semiarid. Although mycorrhisation presents high agricultural relevance due to benefits promoted to the soil and plants, the knowledge about the factors influencing the interactions among microorganisms, soil and plants need to be broadened aiming to achieve successful crop management in semiarid regions.