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To document changes in evaluation protocols for acute invasive fungal sinusitis during the coronavirus disease 2019 pandemic, and to analyse concordance between clinical and histopathological diagnoses based on new practice guidelines.
Methods
Protocols for the evaluation of patients with suspected acute invasive fungal sinusitis both prior and during the coronavirus disease 2019 period are described. A retrospective analysis of patients presenting with suspected acute invasive fungal sinusitis from 1 May to 30 June 2021 was conducted, with assessment of the concordance between clinical and final diagnoses.
Results
Among 171 patients with high clinical suspicion, 160 (93.6 per cent) had a final histopathological diagnosis of invasive fungal sinusitis, concordant with the clinical diagnosis, with sensitivity of 100 per cent, positive predictive value of 93.6 per cent and negative predictive value of 100 per cent.
Conclusion
The study highlights a valuable screening tool with good accuracy, involving emphasis on ‘red flag’ signs in high-risk populations. This could be valuable in situations demanding the avoidance of aerosol-generating procedures and in resource-limited settings facilitating early referral to higher level care centres.
South Africa has embarked on major health policy reform to deliver universal health coverage through the establishment of National Health Insurance (NHI). The aim is to improve access, remove financial barriers to care, and enhance care quality. Health technology assessment (HTA) is explicitly identified in the proposed NHI legislation and will have a prominent role in informing decisions about adoption and access to health interventions and technologies. The specific arrangements and approach to HTA in support of this legislation are yet to be determined. Although there is currently no formal national HTA institution in South Africa, there are several processes in both the public and private healthcare sectors that use elements of HTA to varying extents to inform access and resource allocation decisions. Institutions performing HTAs or related activities in South Africa include the National and Provincial Departments of Health, National Treasury, National Health Laboratory Service, Council for Medical Schemes, medical scheme administrators, managed care organizations, academic or research institutions, clinical societies and associations, pharmaceutical and devices companies, private consultancies, and private sector hospital groups. Existing fragmented HTA processes should coordinate and conform to a standardized, fit-for-purpose process and structure that can usefully inform priority setting under NHI and for other decision makers. This transformation will require comprehensive and inclusive planning with dedicated funding and regulation, and provision of strong oversight mechanisms and leadership.
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
Aims
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
Method
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
Results
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Conclusions
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
The Quaternary Isotope Laboratory (QIL) at the University of Washington was launched in 1969 and directed by Minze Stuiver until his retirement in 1998. Here we review some of the scientific work undertaken in the QIL and the memories of some of Minze’s former students and colleagues.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
Evaluation of a mandatory immunization program to increase and sustain high immunization coverage for healthcare personnel (HCP).
Design:
Descriptive study with before-and-after analysis.
Setting:
Tertiary-care academic medical center.
Participants:
Medical center HCP.
Methods:
A comprehensive mandatory immunization initiative was implemented in 2 phases, starting in July 2014. Key facets of the initiative included a formalized exemption review process, incorporation into institutional quality goals, data feedback, and accountability to support compliance.
Results:
Both immunization and overall compliance rates with targeted immunizations increased significantly in the years after the implementation period. The influenza immunization rate increased from 80% the year prior to the initiative to >97% for the 3 subsequent influenza seasons (P < .0001). Mumps, measles and varicella vaccination compliance increased from 94% in January 2014 to >99% by January 2017, rubella vaccination compliance increased from 93% to 99.5%, and hepatitis B vaccination compliance from 95% to 99% (P < .0001 for all comparisons). An associated positive effect on TB testing compliance, which was not included in the mandatory program, was also noted; it increased from 76% to 92% over the same period (P < .0001).
Conclusions:
Thoughtful, step-wise implementation of a mandatory immunization program linked to professional accountability can be successful in increasing immunization rates as well as overall compliance with policy requirements to cover all recommended HCP immunizations.
This is the first report on the association between trauma exposure and depression from the Advancing Understanding of RecOvery afteR traumA(AURORA) multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience.
Methods
We focus on participants presenting at EDs after a motor vehicle collision (MVC), which characterizes most AURORA participants, and examine associations of participant socio-demographics and MVC characteristics with 8-week depression as mediated through peritraumatic symptoms and 2-week depression.
Results
Eight-week depression prevalence was relatively high (27.8%) and associated with several MVC characteristics (being passenger v. driver; injuries to other people). Peritraumatic distress was associated with 2-week but not 8-week depression. Most of these associations held when controlling for peritraumatic symptoms and, to a lesser degree, depressive symptoms at 2-weeks post-trauma.
Conclusions
These observations, coupled with substantial variation in the relative strength of the mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated in more in-depth analyses of the rich and evolving AURORA database to find new targets for intervention and new tools for risk-based stratification following trauma exposure.
The Murchison Widefield Array (MWA) has observed the entire southern sky (Declination,
$\delta< 30^{\circ}$
) at low radio frequencies, over the range 72–231MHz. These observations constitute the GaLactic and Extragalactic All-sky MWA (GLEAM) Survey, and we use the extragalactic catalogue (EGC) (Galactic latitude,
$|b| >10^{\circ}$
) to define the GLEAM 4-Jy (G4Jy) Sample. This is a complete sample of the ‘brightest’ radio sources (
$S_{\textrm{151\,MHz}}>4\,\text{Jy}$
), the majority of which are active galactic nuclei with powerful radio jets. Crucially, low-frequency observations allow the selection of such sources in an orientation-independent way (i.e. minimising the bias caused by Doppler boosting, inherent in high-frequency surveys). We then use higher-resolution radio images, and information at other wavelengths, to morphologically classify the brightest components in GLEAM. We also conduct cross-checks against the literature and perform internal matching, in order to improve sample completeness (which is estimated to be
$>95.5$
%). This results in a catalogue of 1863 sources, making the G4Jy Sample over 10 times larger than that of the revised Third Cambridge Catalogue of Radio Sources (3CRR;
$S_{\textrm{178\,MHz}}>10.9\,\text{Jy}$
). Of these G4Jy sources, 78 are resolved by the MWA (Phase-I) synthesised beam (
$\sim2$
arcmin at 200MHz), and we label 67% of the sample as ‘single’, 26% as ‘double’, 4% as ‘triple’, and 3% as having ‘complex’ morphology at
$\sim1\,\text{GHz}$
(45 arcsec resolution). We characterise the spectral behaviour of these objects in the radio and find that the median spectral index is
$\alpha=-0.740 \pm 0.012$
between 151 and 843MHz, and
$\alpha=-0.786 \pm 0.006$
between 151MHz and 1400MHz (assuming a power-law description,
$S_{\nu} \propto \nu^{\alpha}$
), compared to
$\alpha=-0.829 \pm 0.006$
within the GLEAM band. Alongside this, our value-added catalogue provides mid-infrared source associations (subject to 6” resolution at 3.4
$\mu$
m) for the radio emission, as identified through visual inspection and thorough checks against the literature. As such, the G4Jy Sample can be used as a reliable training set for cross-identification via machine-learning algorithms. We also estimate the angular size of the sources, based on their associated components at
$\sim1\,\text{GHz}$
, and perform a flux density comparison for 67 G4Jy sources that overlap with 3CRR. Analysis of multi-wavelength data, and spectral curvature between 72MHz and 20GHz, will be presented in subsequent papers, and details for accessing all G4Jy overlays are provided at https://github.com/svw26/G4Jy.
The entire southern sky (Declination,
$\delta< 30^{\circ}$
) has been observed using the Murchison Widefield Array (MWA), which provides radio imaging of
$\sim$
2 arcmin resolution at low frequencies (72–231 MHz). This is the GaLactic and Extragalactic All-sky MWA (GLEAM) Survey, and we have previously used a combination of visual inspection, cross-checks against the literature, and internal matching to identify the ‘brightest’ radio-sources (
$S_{\mathrm{151\,MHz}}>4$
Jy) in the extragalactic catalogue (Galactic latitude,
$|b| >10^{\circ}$
). We refer to these 1 863 sources as the GLEAM 4-Jy (G4Jy) Sample, and use radio images (of
${\leq}45$
arcsec resolution), and multi-wavelength information, to assess their morphology and identify the galaxy that is hosting the radio emission (where appropriate). Details of how to access all of the overlays used for this work are available at https://github.com/svw26/G4Jy. Alongside this we conduct further checks against the literature, which we document here for individual sources. Whilst the vast majority of the G4Jy Sample are active galactic nuclei with powerful radio-jets, we highlight that it also contains a nebula, two nearby, star-forming galaxies, a cluster relic, and a cluster halo. There are also three extended sources for which we are unable to infer the mechanism that gives rise to the low-frequency emission. In the G4Jy catalogue we provide mid-infrared identifications for 86% of the sources, and flag the remainder as: having an uncertain identification (129 sources), having a faint/uncharacterised mid-infrared host (126 sources), or it being inappropriate to specify a host (2 sources). For the subset of 129 sources, there is ambiguity concerning candidate host-galaxies, and this includes four sources (B0424–728, B0703–451, 3C 198, and 3C 403.1) where we question the existing identification.
To develop and validate the Discrepancy-based Evidence for Loss of Thinking Abilities (DELTA) score. The DELTA score characterizes the strength of evidence for cognitive decline on a continuous spectrum using well-established psychometric principles for improving detection of cognitive changes.
Methods:
DELTA score development used neuropsychological test scores from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort (two tests each from Memory, Executive Function, and Language domains). We derived regression-based normative reference scores using age, gender, years of education, and word-reading ability from robust cognitively normal ADNI participants. Discrepancies between predicted and observed scores were used for calculating the DELTA score (range 0–15). We validated DELTA scores primarily against longitudinal Clinical Dementia Rating-Sum of Boxes (CDR-SOB) and Functional Activities Questionnaire (FAQ) scores (baseline assessment through Year 3) using linear mixed models and secondarily against cross-sectional Alzheimer’s biomarkers.
Results:
There were 1359 ADNI participants with calculable baseline DELTA scores (age 73.7 ± 7.1 years, 55.4% female, 100% white/Caucasian). Higher baseline DELTA scores (stronger evidence of cognitive decline) predicted higher baseline CDR-SOB (ΔR2 = .318) and faster rates of CDR-SOB increase over time (ΔR2 = .209). Longitudinal changes in DELTA scores tracked closely and in the same direction as CDR-SOB scores (fixed and random effects of mean + mean-centered DELTA, ΔR2 > .7). Results were similar for FAQ scores. High DELTA scores predicted higher PET-Aβ SUVr (ρ = 324), higher CSF-pTau/CSF-Aβ ratio (ρ = .460), and demonstrated PPV > .9 for positive Alzheimer’s disease biomarker classification.
Conclusions:
Data support initial development and validation of the DELTA score through its associations with longitudinal functional changes and Alzheimer’s biomarkers. We provide several considerations for future research and include an automated scoring program for clinical use.
BirdLife International´s Important Bird and Biodiversity Areas (IBA) Programme has identified, documented and mapped over 13,000 sites of international importance for birds. IBAs have been influential with governments, multilateral agreements, businesses and others in: (1) informing governments’ efforts to expand protected area networks (in particular to meet their commitments through the Convention on Biological Diversity); (2) supporting the identification of Ecologically or Biologically Significant Areas (EBSAs) in the marine realm, (3) identifying Wetlands of International Importance under the Ramsar Convention; (4) identifying sites of importance for species under the Convention on Migratory Species and its sister agreements; (5) identifying Special Protected Areas under the EU Birds Directive; (6) applying the environmental safeguards of international finance institutions such as the International Finance Corporation; (7) supporting the private sector to manage environmental risk in its operations; and (8) helping donor organisations like the Critical Ecosystems Partnership Fund (CEPF) to prioritise investment in site-based conservation. The identification of IBAs (and IBAs in Danger: the most threatened of these) has also triggered conservation and management actions at site level, most notably by civil society organisations and local conservation groups. IBA data have therefore been widely used by stakeholders at different levels to help conserve a network of sites essential to maintaining the populations and habitats of birds as well as other biodiversity. The experience of IBA identification and conservation is shaping the design and implementation of the recently launched Key Biodiversity Areas (KBA) Partnership and programme, as IBAs form a core part of the KBA network.
Rising sea levels due to climate change can have severe consequences for coastal populations and ecosystems all around the world. Understanding and projecting sea-level rise is especially important for low-lying countries such as the Netherlands. It is of specific interest for vulnerable ecological and morphodynamic regions, such as the Wadden Sea UNESCO World Heritage region.
Here we provide an overview of sea-level projections for the 21st century for the Wadden Sea region and a condensed review of the scientific data, understanding and uncertainties underpinning the projections. The sea-level projections are formulated in the framework of the geological history of the Wadden Sea region and are based on the regional sea-level projections published in the Fifth Assessment Report of the Intergovernmental Panel on Climate Change (IPCC AR5). These IPCC AR5 projections are compared against updates derived from more recent literature and evaluated for the Wadden Sea region. The projections are further put into perspective by including interannual variability based on long-term tide-gauge records from observing stations at Den Helder and Delfzijl.
We consider three climate scenarios, following the Representative Concentration Pathways (RCPs), as defined in IPCC AR5: the RCP2.6 scenario assumes that greenhouse gas (GHG) emissions decline after 2020; the RCP4.5 scenario assumes that GHG emissions peak at 2040 and decline thereafter; and the RCP8.5 scenario represents a continued rise of GHG emissions throughout the 21st century. For RCP8.5, we also evaluate several scenarios from recent literature where the mass loss in Antarctica accelerates at rates exceeding those presented in IPCC AR5.
For the Dutch Wadden Sea, the IPCC AR5-based projected sea-level rise is 0.07±0.06m for the RCP4.5 scenario for the period 2018–30 (uncertainties representing 5–95%), with the RCP2.6 and RCP8.5 scenarios projecting 0.01m less and more, respectively. The projected rates of sea-level change in 2030 range between 2.6mma−1 for the 5th percentile of the RCP2.6 scenario to 9.1mma−1 for the 95th percentile of the RCP8.5 scenario. For the period 2018–50, the differences between the scenarios increase, with projected changes of 0.16±0.12m for RCP2.6, 0.19±0.11m for RCP4.5 and 0.23±0.12m for RCP8.5. The accompanying rates of change range between 2.3 and 12.4mma−1 in 2050. The differences between the scenarios amplify for the 2018–2100 period, with projected total changes of 0.41±0.25m for RCP2.6, 0.52±0.27m for RCP4.5 and 0.76±0.36m for RCP8.5. The projections for the RCP8.5 scenario are larger than the high-end projections presented in the 2008 Delta Commission Report (0.74m for 1990–2100) when the differences in time period are considered. The sea-level change rates range from 2.2 to 18.3mma−1 for the year 2100.
We also assess the effect of accelerated ice mass loss on the sea-level projections under the RCP8.5 scenario, as recent literature suggests that there may be a larger contribution from Antarctica than presented in IPCC AR5 (potentially exceeding 1m in 2100). Changes in episodic extreme events, such as storm surges, and periodic (tidal) contributions on (sub-)daily timescales, have not been included in these sea-level projections. However, the potential impacts of these processes on sea-level change rates have been assessed in the report.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
Aims
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Method
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
Results
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
Conclusions
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Layered transition metal dichalcogenides (TMDs) represent a diverse, emerging source of two-dimensional (2D) nanostructures with broad application in optoelectronics and energy. Chemical functionalization has evolved into a powerful tool to tailor properties of these 2D TMDs; however, functionalization strategies have been largely limited to the metallic 1T-polytype. The work herein illustrates that 2H-semiconducting liquid-exfoliated tungsten disulfide (WS2) undergoes a spontaneous redox reaction with gold (III) chloride (AuCl3). Au nanoparticles (NPs) predominantly nucleate at nanosheet edges with tuneable NP size and density. AuCl3 is preferentially reduced on multi-layer WS2 and resulting large Au aggregates are easily separated from the colloidal dispersion by simple centrifugation. This process may be exploited to enrich the dispersions in laterally large, monolayer nanosheets. It is proposed that thiol groups at edges and defects sides reduce the AuCl3 to Au0 and are in turn oxidized to disulfides. Optical emission, i.e. photoluminescence, of the monolayers remained pristine, while the electrocatalytic activity towards the hydrogen evolution reaction is significantly improved. Taken together, these improvements in functionalization, fabrication, and catalytic activity represent an important advance in the study of these emerging 2D nanostructures.