Infants and children under 6 years old spend most of daily time in Child Care Centers (CCCs), especially in the tropical regions like Singapore. Environmental exposure and associated risk during this ...early critical developmental stage is of great public concern. In this study, seven representative volatile organic compounds (VOCs) and five typical phthalates were analyzed in the indoor and outdoor air samples collected from 32 Singapore CCCs. The median of total VOC and phthalate concentration in indoor air was 19.03 and 5.41 μg m−3; respectively. For both indoors and outdoors environment, benzene, toluene and xylene were the dominant VOC contributors (more than 68%). For indoor air phthalates, di(2-ethylhexyl) phthalate and di-butyl phthalate (DBP) accounts for 60–76%. The level of both VOCs and phthalates in indoor environment was significantly higher than that in outdoor, with an average indoor/outdoor ratio of 1.24 and 1.45; respectively. A strong correlation (r > 0.50, p < 0.05) was observed between indoor and outdoor air compounds. VOC and phthalate levels have no significant difference between CCCs with split-unit and centrally ventilated air conditioners. Monte Carlo simulation was used to estimate exposure uncertainty and variability for the risk assessment. Overall, the concentrations of VOC were below the healthy reference values from either EPA Integrated Risk Information System (IRIS) or Singapore guideline. However, similar to other countries’ report, benzene, DBP, ethylbenzene and naphthalene were at levels that could exceed the stringent standards such as Office of Environmental Health Hazard Assessment (OEHHA) cancer and reproductive health-based benchmarks.
Display omitted
•VOCs and Phthalates were widely detected in the Child Care Centers air samples.•VOCs and Phthalates in the indoor air was significantly higher than that in outdoor.•Monte Carlo simulation applied to estimate uncertainty of exposure risk assessment.
ABSTRACT
Unlike for serotype II feline coronaviruses (FCoV II), the cellular receptor for serotype I FCoV (FCoV I), the most prevalent FCoV serotype, is unknown. To provide a platform for assessing ...the pattern by which FCoV I attaches to its host receptor(s), HEK293 cell lines that stably express the ectodomains of the spike (S) proteins derived from a FCoV I feline enteric coronavirus strain UU7 (FECV UU7) and a feline infectious peritonitis virus strain UU4 (FIPV UU4) were established. Using the recombinant S proteins as probes to perform S protein affinity histochemistry in paraffin‐embedded tissues, although no tissue or enteric binding of FECV UU7 S protein was detected, it was found that by immunohistochemistry that the tissue distribution of FIPV UU4 S protein‐bound cells correlated with that of FIPV antigen‐positive cells and lesions associated with FIP and that the affinity binding of FIPV UU4 S protein on macrophages was not affected by enzymatic removal of host cell‐surface sialic acid with neuraminidase. These findings suggest that a factor(s) other than sialic acid contribute(s) to the macrophage tropism of FIPV strain UU4. This approach allowed obtaining more information about both virus–host cell interactions and the biological characteristics of the unidentified cellular receptor for FCoV I.
We develop a Petrov–Galerkin stabilization method for multiscale convection–diffusion transport systems. Existing stabilization techniques add a limited number of degrees of freedom in the form of ...bubble functions or a modified diffusion, which may not be sufficient to stabilize multiscale systems. We seek a local reduced-order model for this kind of multiscale transport problems and thus, develop a systematic approach for finding reduced-order approximations of the solution. We start from a Petrov–Galerkin framework using optimal weighting functions. We introduce an auxiliary variable to a mixed formulation of the problem. The auxiliary variable stands for the optimal weighting function. The problem reduces to finding a test space (a dimensionally reduced space for this auxiliary variable), which guarantees that the error in the primal variable (representing the solution) is close to the projection error of the full solution on the dimensionally reduced space that approximates the solution. To find the test space, we reformulate some recent mixed Generalized Multiscale Finite Element Methods. We introduce snapshots and local spectral problems that appropriately define local weight and trial spaces. In particular, we use energy minimizing snapshots and local spectral decompositions in the natural norm associated with the auxiliary variable. The resulting spectral decomposition adaptively identifies and builds the optimal multiscale space to stabilize the system. We discuss the stability and its relation to the approximation property of the test space. We design online basis functions, which accelerate convergence in the test space, and consequently, improve stability. We present several numerical examples and show that one needs a few test functions to achieve an error similar to the projection error in the primal variable irrespective of the Peclet number.
Purpose: This study aims to develop a liquid biopsy assay to identify HCC and differentially diagnose hepatocellular carcinoma (HCC) from colorectal carcinoma (CRC) liver metastasis. Methods: ...Thirty-two microRNAs (“HallMark-32” panel) were designed to target the ten cancer hallmarks in HCC. Quantitative PCR and supervised machine learning models were applied to develop an HCC-specific diagnostic model. One hundred thirty-three plasma samples from intermediate-stage HCC patients, colorectal cancer (CRC) patients with liver metastasis, and healthy individuals were examined. Results: Six differentially expressed microRNAs (“Signature-Six” panel) were identified after comparing HCC and healthy individuals. The microRNA miR-221-3p, miR-223-3p, miR-26a-5p, and miR-30c-5p were significantly down-regulated in the plasma of HCC samples, while miR-365a-3p and miR-423-3p were significantly up-regulated. Machine learning models combined with HallMark-32 and Signature-Six panels demonstrated promising performance with an AUC of 0.85-0.96 (p ≤ 0.018) and 0.84-0.93 (p ≤ 0.021), respectively. Further modeling improvement by adjusting sample quality variation in the HallMark-32 panel boosted the accuracy to 95% ± 0.01 and AUC to 0.991 (95% CI 0.96-1, p = 0.001), respectively. Even in alpha fetoprotein (AFP)-negative (< 20ng/mL) HCC samples, HallMark-32 still achieved 100% sensitivity in identifying HCC. The Cancer Genome Atlas (TCGA, n=372) analysis demonstrated a significant association between HallMark-32 and HCC patient survival. Conclusion: To the best of our knowledge, this is the first report to utilize circulating miRNAs and machine learning to differentiate HCC from CRC liver metastasis. In this setting, HallMark-32 and Signature-Six are promising non-invasive tests for HCC differential diagnosis and distinguishing HCC from healthy individuals.
The authors review trend and cohort surveys and administrative data comparing prevalence of mental disorders during, versus, and before the COVID-19 pandemic and changes in mental health disparities. ...Best evidence suggests clinically significant anxiety-depression point prevalence increased by relative-risk (RR) = 1.3 to 1.5 during the pandemic compared with before. This level of increase is much less than the implausibly high RR = 5.0 to 8.0 estimates reported in trend studies early in the pandemic based on less-appropriate comparisons. Changes in prevalence also occurred during the pandemic, but relative prevalence appears not to have changed substantially over this time.
Previous global analyses, with known underdiagnosis and single cause per death attribution systems, provide only a small insight into the suspected high population health effect of sickle cell ...disease. Completed as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, this study delivers a comprehensive global assessment of prevalence of sickle cell disease and mortality burden by age and sex for 204 countries and territories from 2000 to 2021.
We estimated cause-specific sickle cell disease mortality using standardised GBD approaches, in which each death is assigned to a single underlying cause, to estimate mortality rates from the International Classification of Diseases (ICD)-coded vital registration, surveillance, and verbal autopsy data. In parallel, our goal was to estimate a more accurate account of sickle cell disease health burden using four types of epidemiological data on sickle cell disease: birth incidence, age-specific prevalence, with-condition mortality (total deaths), and excess mortality (excess deaths). Systematic reviews, supplemented with ICD-coded hospital discharge and insurance claims data, informed this modelling approach. We employed DisMod-MR 2.1 to triangulate between these measures—borrowing strength from predictive covariates and across age, time, and geography—and generated internally consistent estimates of incidence, prevalence, and mortality for three distinct genotypes of sickle cell disease: homozygous sickle cell disease and severe sickle cell β-thalassaemia, sickle-haemoglobin C disease, and mild sickle cell β-thalassaemia. Summing the three models yielded final estimates of incidence at birth, prevalence by age and sex, and total sickle cell disease mortality, the latter of which was compared directly against cause-specific mortality estimates to evaluate differences in mortality burden assessment and implications for the Sustainable Development Goals (SDGs).
Between 2000 and 2021, national incidence rates of sickle cell disease were relatively stable, but total births of babies with sickle cell disease increased globally by 13·7% (95% uncertainty interval 11·1–16·5), to 515 000 (425 000–614 000), primarily due to population growth in the Caribbean and western and central sub-Saharan Africa. The number of people living with sickle cell disease globally increased by 41·4% (38·3–44·9), from 5·46 million (4·62–6·45) in 2000 to 7·74 million (6·51–9·2) in 2021. We estimated 34 400 (25 000–45 200) cause-specific all-age deaths globally in 2021, but total sickle cell disease mortality burden was nearly 11-times higher at 376 000 (303 000–467 000). In children younger than 5 years, there were 81 100 (58 800–108 000) deaths, ranking total sickle cell disease mortality as 12th (compared to 40th for cause-specific sickle cell disease mortality) across all causes estimated by the GBD in 2021.
Our findings show a strikingly high contribution of sickle cell disease to all-cause mortality that is not apparent when each death is assigned to only a single cause. Sickle cell disease mortality burden is highest in children, especially in countries with the greatest under-5 mortality rates. Without comprehensive strategies to address morbidity and mortality associated with sickle cell disease, attainment of SDG 3.1, 3.2, and 3.4 is uncertain. Widespread data gaps and correspondingly high uncertainty in the estimates highlight the urgent need for routine and sustained surveillance efforts, further research to assess the contribution of conditions associated with sickle cell disease, and widespread deployment of evidence-based prevention and treatment for those with sickle cell disease.
Bill & Melinda Gates Foundation.
As countries with endemic canine rabies progress towards elimination by 2030, it will become necessary to employ techniques to help plan, monitor, and confirm canine rabies elimination. Sequencing ...can provide critical information to inform control and vaccination strategies by identifying genetically distinct virus variants that may have different host reservoir species or geographic distributions. However, many rabies testing laboratories lack the resources or expertise for sequencing, especially in remote or rural areas where human rabies deaths are highest. We developed a low-cost, high throughput rabies virus sequencing method using the Oxford Nanopore MinION portable sequencer. A total of 259 sequences were generated from diverse rabies virus isolates in public health laboratories lacking rabies virus sequencing capacity in Guatemala, India, Kenya, and Vietnam. Phylogenetic analysis provided valuable insight into rabies virus diversity and distribution in these countries and identified a new rabies virus lineage in Kenya, the first published canine rabies virus sequence from Guatemala, evidence of rabies spread across an international border in Vietnam, and importation of a rabid dog into a state working to become rabies-free in India. Taken together, our evaluation highlights the MinION's potential for low-cost, high volume sequencing of pathogens in locations with limited resources.
In the United States, review of digital whole slide images (WSIs) using specific systems is approved for primary diagnosis but has not been implemented for intraoperative consultation.
To evaluate ...the safety of review of WSIs and compare the efficiency of review of WSIs and glass slides (GSs) for intraoperative consultation.
Ninety-one cases previously submitted for frozen section evaluation were randomly selected from 8 different anatomic pathology subspecialties. GSs from these cases were scanned on a Leica Aperio AT2 scanner at ×20 magnification (0.25 μm/pixel). The slides were deidentified, and a short relevant clinical history was provided for each slide. Nine board-certified general pathologists who do not routinely establish primary diagnoses using WSIs reviewed the WSIs using Leica Aperio ImageScope viewing software. After a washout period of 2-3 weeks, the pathologists reviewed the corresponding GSs using a light microscope (Olympus BX43). The pathologists recorded the diagnosis and time to reach the diagnosis. Intraobserver concordance, time to diagnosis, and specificity and sensitivity compared to the original diagnosis were evaluated.
The rate of intraobserver concordance between GS results and WSI results was 93.7%. Mean time to diagnosis was 1.25 minutes for GSs and 1.76 minutes for WSIs (P < .001). Specificity was 91% for GSs and 90% for WSIs; sensitivity was 92% for GSs and 92% for WSIs.
Time to diagnosis was longer with WSIs than with GSs, and scanning GSs and uploading the data to whole slide imaging systems takes time. However, review of WSIs appears to be a safe alternative to review of GSs. Use of WSIs allows reporting from a remote site during a public health emergency such as the COVID-19 pandemic and facilitates subspecialty histopathology services.
Abstract
Background
Uncertainty about risk of illness and the value of influenza vaccines negatively affects vaccine uptake among persons targeted for influenza vaccination.
Methods
During 2016–2019, ...we followed a cohort of healthcare personnel (HCP) targeted for free‐of‐charge influenza vaccination in five Lima hospitals to quantify risk of influenza, workplace presenteeism (coming to work despite illness), and absenteeism (taking time off from work because of illness). The HCP who developed acute respiratory illnesses (ARI) (≥1 of acute cough, runny nose, body aches, or feverishness) were tested for influenza using reverse‐transcription polymerase chain reaction (rt‐PCR).
Findings
The cohort (2968 HCP) contributed 950,888 person‐days. Only 36 (6%) of 605 HCP who participated every year were vaccinated. The HCP had 5750 ARI and 147 rt‐PCR‐confirmed influenza illnesses. The weighted incidence of laboratory‐confirmed influenza was 10.0/100 person‐years; 37% used antibiotics, and 0.7% used antivirals to treat these illnesses. The HCP with laboratory‐confirmed influenza were present at work while ill for a cumulative 1187 hours.
Interpretation
HCP were frequently ill and often worked rather than stayed at home while ill. Our findings suggest the need for continuing medical education about the risk of influenza and benefits of vaccination and stay‐at‐home‐while‐ill policies.
Smart grid network facilitates reliable and efficient power generation and transmission. The power system can adjust the amount of electricity generated based on power usage information submitted by ...end users. Sender authentication and user privacy preservation are two important security issues on this information flow. In this paper, we propose a scheme such that even the control center (power operator) does not know which user makes the requests of using more power or agreements of using less power until the power is actually used. At the end of each billing period (i.e., after electricity usage), the end user can prove to the power operator that it has really requested to use more power or agreed to use less power earlier. To reduce the total traffic volume in the communications network, our scheme allows gateway smart meters to help aggregate power usage information, and the power generators to determine the total amount of power that needs to be generated at different times. To reduce the impact of attacking traffic, our scheme allows gateway smart meters to help filter messages before they reach the control center. Through analysis and experiments, we show that our scheme is both effective and efficient.
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