Performance evaluation of the Sysmex XN-1000V in side-by-side comparison with the Siemens ADVIA 120 and manual methods for healthy CD Sprague-Dawley rats and CD-1 mice.

BACKGROUND: The Sysmex XN-1000V automated hematology analyzer with multispecies software was released in June 2017 for use in research laboratories. Laser light, impedance, fluorescent staining, and fluorescent flow cytometry are used to analyze whole blood for CBC, reticulocyte counts, and WBC counts, including a 5-part differential leukocyte analysis. OBJECTIVES: A side-by-side comparison of the Sysmex XN-1000V with the Siemens ADVIA 120 in analyzing blood from healthy mice and rats will provide insight into the performance of the new analyzer and its capabilities for use in drug development studies. Method correlation analyses on normal mouse and rat hematology data collected with both analyzers and manual reference methods will help determine the reliability of the data produced using the Sysmex XN-1000V analyzer. METHODS: Whole blood samples collected in K2 EDTA from healthy CD-1 mice and CD Sprague-Dawley rats were analyzed in parallel with the XN-1000V and ADVIA 120 analyzers. Male and female mice, approximately 6-9 weeks old, and male and female rats, approximately 7-9 weeks old, were included in this study. Manual reference methods for WBC differential leukocyte analysis and packed cell volume (PCV) measurements were also performed. EP Evaluator version 11.2 (Data Innovations LLC, South Burlington, VT, USA) was used for method comparison statistical analysis. RESULTS: Most hematologic parameters for naïve mice and rats achieved correlation in the fair to excellent range, with the majority showing very good to excellent correlation with low biases (<11.0%) for cohorts analyzed separately and when cohort data were combined. CONCLUSIONS: The Sysmex XN-1000V Hematology Analyzer provided comparable results to those obtained from the Siemens ADVIA 120. We found the Sysmex XN-1000V Hematology Analyzer to be acceptable for use in drug development studies for rats and mice.

Perinatal bacterial colonization and neonatal early-onset sepsis: A case-control study.

BACKGROUND: The utility of determining maternal-neonatal surface colonization as detected by standard microbiological cultures around the time of birth is unclear. The aim of this study is to evaluate the association between maternal and neonatal surface colonization at birth and neonatal early onset sepsis (EOS). OBJECTIVE: To investigate the association of white matter hyperintensities (WMHs) present in the brain with AD CSF biomarker levels. METHODS: We conducted a case-control study of newborns admitted to the neonatal department of a referral women's and children's hospital from 2009 to 2017. Cases were infants with blood-culture-confirmed EOS (<3 days of life), and controls were infants without EOS randomly chosen based on the cases' date of birth. Maternal genitourinary and neonatal ear swab cultures were used to determine bacterial surface colonization status. RESULTS: Fifty-one infants were diagnosed with EOS during the study period, where Escherichia coli (45%), and Group B Streptococcus (23%) accounted for 68% of infecting organisms. Compared to infants without EOS, those infected were more likely to have surface colonization of the mothers (60% vs 40%, p = 0.048) and infants (90% vs 11%, p < 0.001). In univariate analysis, chorioamnionitis [7.1 (95% CI 2.9, 16.8)], small-for-gestational-age [OR 0.08 (95% CI 0.02, 0.4)], exposure to antibiotics around time of birth [2.3 (95% CI 1.0, 5.1)], maternal surface colonization [2.2 (95% CI 1.0, 4.9)] and neonatal surface colonization [23.5 (95% CI 7.3, 76.1)] were significantly associated with EOS. Adjusting for potential confounders, neonatal colonization remained significantly associated with neonatal EOS [AOR 15.0 (95% CI 3.5, 64.2), p < 0.001]. CONCLUSION: In our setting with predominant Gram-negative EOS, neonatal colonization but not maternal colonization was significantly associated with EOS in the newborn.

Study of the naturally occurring radionuclide Beryllium-7 (Be-7) in Hong Kong.

Beryllium-7 (Be-7) is one of the naturally occurring radionuclides being monitored under the Global Atmosphere Watch Programme of the World Meteorological Organization. Be-7 mainly originates from cosmic rays. It can be used as a tracer to facilitate understanding of the atmospheric vertical transport by observing its spatial and temporal distribution characteristics. The Hong Kong Observatory has been operating an environmental radiation monitoring programme for decades, and long record of Be-7 activity concentration data in airborne particulate samples are available to characterize the behaviour of Be-7 in the lower atmosphere in Hong Kong. In this study, Be-7 activity concentration data of airborne particulates collected at three locations in Hong Kong from 1993 to 2020 are examined. Temporal variations are analyzed. In particular, the long-term monthly average Be-7 activity concentrations are found to be most sensitive to precipitation. The relevant data analysis, as well as key factors affecting the Be-7 activity concentrations in the lower atmosphere in Hong Kong, will be described.

Survival Benefit Associated With Resection of Locally Advanced Pancreatic Cancer After Upfront FOLFIRINOX Versus FOLFIRINOX Only: Multicenter Propensity Score-matched Analysis.

OBJECTIVE: This study compared median OS after resection of LAPC after upfront FOLFIRINOX versus a propensity-score matched cohort of LAPC patients treated with FOLFIRINOX-only (ie, without resection). BACKGROUND: Because the introduction of FOLFIRINOX chemotherapy, increased resection rates in LAPC patients have been reported, with improved OS. Some studies have also reported promising OS with FOLFIRINOX-only treatment in LAPC. Multicenter studies assessing the survival benefit associated with resection of LAPC versus patients treated with FOLFIRINOX-only are lacking. METHODS: Patients with non-progressive LAPC after 4 cycles of FOLFIRINOX treatment, both with and without resection, were included from a prospective multicenter cohort in 16 centers (April 2015-December 2019). Cox regression analysis identified predictors for OS. One-to-one propensity score matching (PSM) was used to obtain a matched cohort of patients with and without resection. These patients were compared for OS. RESULTS: Overall, 293 patients with LAPC were included, of whom 89 underwent a resection. Resection was associated with improved OS (24 vs 15 months, P < 0.01), as compared to patients without resection. Before PSM, resection, Charlson Comorbidity Index, and Response Evaluation Criteria in Solid Tumors (RECIST) response were predictors for OS. After PSM, resection remained associated with improved OS [Hazard Ratio (HR) 0.344, 95% confidence interval (0.222-0.534), P < 0.01], with an OS of 24 versus 15 months, as compared to patients without resection. Resection of LAPC was associated with improved 3-year OS (31% vs 11%, P < 0.01). CONCLUSIONS: Resection of LAPC after FOLFIRINOX was associated with increased OS and 3-year survival, as compared to propensity-score matched patients treated with FOLFIRINOX-only.

Room temperature laser power standard using a microfabricated, electrical substitution bolometer.

The design and performance of a room temperature electrical substitution radiometer for use as an absolute standard for measuring continuous-wave laser power over a wide range of wavelengths, beam diameters, and powers are described. The standard achieves an accuracy of 0.46% (k = 2) for powers from 10 mW to 100 mW and 0.83% (k = 2) for powers from 1 mW to 10 mW and can accommodate laser beam diameters (1/e2) up to 11 mm and wavelengths from 300 nm to 2 µm. At low power levels, the uncertainty is dominated by sensitivity to fluctuations in the thermal environment. The core of the instrument is a planar, silicon microfabricated bolometer with vertically aligned carbon nanotube absorbers, commercial surface mount thermistors, and an integrated heater. Where possible, commercial electronics and components were used. The performance was validated by comparing it to a National Institute of Standards and Technology primary standard through a transfer standard silicon trap detector and by comparing it to the legacy "C-series" standards in operation at the U.S. Air Force Metrology and Calibration Division (AFMETCAL).

Development of the Asia Pacific Consortium on Osteoporosis (APCO) Framework: clinical standards of care for the screening, diagnosis, and management of osteoporosis in the Asia-Pacific region.

Guidelines for doctors managing osteoporosis in the Asia-Pacific region vary widely. We compared 18 guidelines for similarities and differences in five key areas. We then used a structured consensus process to develop clinical standards of care for the diagnosis and management of osteoporosis and for improving the quality of care. PURPOSE: Minimum clinical standards for assessment and management of osteoporosis are needed in the Asia-Pacific (AP) region to inform clinical practice guidelines (CPGs) and to improve osteoporosis care. We present the framework of these clinical standards and describe its development. METHODS: We conducted a structured comparative analysis of existing CPGs in the AP region using a "5IQ" model (identification, investigation, information, intervention, integration, and quality). One-hundred data elements were extracted from each guideline. We then employed a four-round Delphi consensus process to structure the framework, identify key components of guidance, and develop clinical care standards. RESULTS: Eighteen guidelines were included. The 5IQ analysis demonstrated marked heterogeneity, notably in guidance on risk factors, the use of biochemical markers, self-care information for patients, indications for osteoporosis treatment, use of fracture risk assessment tools, and protocols for monitoring treatment. There was minimal guidance on long-term management plans or on strategies and systems for clinical quality improvement. Twenty-nine APCO members participated in the Delphi process, resulting in consensus on 16 clinical standards, with levels of attainment defined for those on identification and investigation of fragility fractures, vertebral fracture assessment, and inclusion of quality metrics in guidelines. CONCLUSION: The 5IQ analysis confirmed previous anecdotal observations of marked heterogeneity of osteoporosis clinical guidelines in the AP region. The Framework provides practical, clear, and feasible recommendations for osteoporosis care and can be adapted for use in other such vastly diverse regions. Implementation of the standards is expected to significantly lessen the global burden of osteoporosis.

SARS-CoV-2 viral RNA load dynamics in the nasopharynx of infected children.

It is important to understand the temporal trend of the paediatric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load to estimate the transmission potential of children in schools and communities. We determined the differences in SARS-CoV-2 viral load dynamics between nasopharyngeal samples of infected asymptomatic and symptomatic children. Serial cycle threshold values of SARS-CoV-2 from the nasopharynx of a cohort of infected children were collected for analysis. Among 17 infected children, 10 (58.8%) were symptomatic. Symptomatic children, when compared to asymptomatic children, had higher viral loads (mean cycle threshold on day 7 of illness 28.6 vs. 36.7, P = 0.02). Peak SARS-CoV-2 viral loads occurred around day 2 of illness in infected children. Although we were unable to directly demonstrate infectivity, the detection of significant amount of virus in the upper airway of asymptomatic children suggest that they have the potential to shed and transmit SARS-CoV-2. Our study highlights the importance of contact tracing and screening for SARS-CoV-2 in children with epidemiological risk factors regardless of their symptom status, in order to improve containment of the virus in the community, including educational settings.

Comparing Eyesi Virtual Reality Simulator and Traditional Teaching Methods for Direct Ophthalmoscopy: Students' Perspectives at Indiana University School of Medicine.

Background The fundus examination is an essential part of any ophthalmologic evaluation. However, medical students and primary care physicians often lack confidence with direct ophthalmoscopy. Virtual reality simulators are being employed in medical education to teach this technically challenging examination. Objective To compare medical student ratings of the Eyesi Direct Ophthalmoscope Simulator and traditional small group teaching methods for learning direct ophthalmoscopy skills. Methods All medical students at Indiana University School of Medicine traditionally learn direct ophthalmoscopy in their first 2 years during a small group session led by a physician instructor. Students who later enrolled in ophthalmology clinical electives during 2019 and 2020 were invited to additionally complete the Eyesi Direct Ophthalmoscope Simulator virtual reality curriculum. A voluntary, anonymous survey was sent between June and August 2020 to students who had completed both the traditional and Eyesi simulator sessions. Students were asked to rate their confidence in performing direct ophthalmoscopy following each session, and to indicate which teaching method was superior and why. Chi-square analysis was used to compare categorical variables. Results Students' confidence ratings for performing direct ophthalmoscopy were significantly higher following completion of the Eyesi simulator session compared with the traditional small group session ( p < 0.001). Four-fifths of respondents felt that the Eyesi simulator was superior to the traditional small group for learning the skills of direct ophthalmoscopy, while one-fifth felt that the two sessions were equally effective ( p < 0.001). None of the students responded that the small group session was the superior teaching method. Conclusion The Eyesi Direct Ophthalmoscope Simulator was rated highly among medical students and offers distinct learning advantages that could not be replicated in a traditional small group environment, such as providing numerous examples of pathological findings and allowing unlimited examination time without concern for patient's inconvenience or light exposure. The Eyesi simulator is a promising tool for teaching direct ophthalmoscopy to medical students. Ultimately, familiarity with the fundus examination will enable future physicians across specialties to better evaluate and appropriately refer patients with ocular fundus pathology.

Analyzing the shear-induced sensitization of mechanosensitive ion channel Piezo-1 in human aortic endothelial cells.

Mechanosensitive ion channels mediate endothelial responses to blood flow and orchestrate their physiological function in response to hemodynamic forces. In this study, we utilized microfluidic technologies to study the shear-induced sensitization of endothelial Piezo-1 to its selective agonist, Yoda-1. We demonstrated that shear stress-induced sensitization is brief and can be impaired when exposing aortic endothelial cells to low and proatherogenic levels of shear stress. Our results suggest that shear stress-induced sensitization of Piezo-1 to Yoda-1 is independent of cell-cell adhesion and is mediated by the PI3K-AKT signaling pathway. We also found that shear stress increases the membrane density of Piezo-1 channels in endothelial cells. To further confirm our findings, we performed experiments using a carotid artery ligation mouse model and demonstrated that transient changes in blood-flow pattern, resulting from a high-degree ligation of the mouse carotid artery alters the distribution of Piezo-1 channels across the endothelial layer. These results suggest that shear stress influences the function of Piezo-1 channels via changes in membrane density, providing a new model of shear-stress sensitivity for Piezo-1 ion channel.

Time to Rt < 1 for COVID-19 public health lockdown measures.

The epidemiological target of lockdowns is to drive down the effective reproduction number (Rt) to less than 1. A key unknown is the duration that lockdowns need to be in place to achieve this and which lockdown measures are effective. Daily number of laboratory confirmed community coronavirus 2019 cases were extracted from regular reports from the Ministry of Health Singapore from 20 March 2020 to 4 May 2020. We generated daily Rt to estimate the time needed for these public health lockdown measures to control the spread of severe acute respiratory syndrome coronavirus 2 as demonstrated by Rt < 1. It took about 14 days of nationwide lockdown for the Rt trend to change and start falling. The upper limit of the 95% confidence interval for time to Rt < 1 was day 15 of lockdown. We have shown that it is possible to start 'bending the Rt curve' about 2 weeks after implementation of specific lockdown measures with strict compliance.

Mechanical breathing in organic electrochromics.

The repetitive size change of the electrode over cycles, termed as mechanical breathing, is a crucial issue limiting the quality and lifetime of organic electrochromic devices. The mechanical deformation originates from the electron transport and ion intercalation in the redox active material. The dynamics of the state of charge induces drastic changes of the microstructure and properties of the host, and ultimately leads to structural disintegration at the interfaces. We quantify the breathing strain and the evolution of the mechanical properties of poly(3,4-propylenedioxythiophene) thin films in-situ using customized environmental nanoindentation. Upon oxidation, the film expands nearly 30% in volume, and the elastic modulus and hardness decrease by a factor of two. We perform theoretical modeling to understand thin film delamination from an indium tin oxide (ITO) current collector under cyclic load. We show that toughening the interface with roughened or silica-nanoparticle coated ITO surface significantly improves the cyclic performance.

A Novel GaN Metal-Insulator-Semiconductor High Electron Mobility Transistor Featuring Vertical Gate Structure.

A novel structure scheme by transposing the gate channel orientation from a long horizontal one to a short vertical one is proposed and verified by technology computer-aided design (TCAD) simulations to achieve GaN-based normally-off high electron mobility transistors (HEMTs) with reduced on-resistance and improved threshold voltage. The proposed devices exhibit high threshold voltage of 3.1 V, high peak transconductance of 213 mS, and much lower on-resistance of 0.53 mΩ·cm2 while displaying better off-state characteristics owing to more uniform electric field distribution around the recessed gate edge in comparison to the conventional lateral HEMTs. The proposed scheme provides a new technical approach to realize high-performance normally-off HEMTs.

Invasive paediatric Elizabethkingia meningoseptica infections are best treated with a combination of piperacillin/tazobactam and trimethoprim/sulfamethoxazole or fluoroquinolone.

OBJECTIVES: Elizabethkingia meningoseptica is a multi-drug-resistant organism that is associated with high mortality and morbidity in newborn and immunocompromised patients. This study aimed to identify the best antimicrobial therapy for treating this infection. METHODS: A retrospective descriptive study was conducted from 2010 to 2017 in a tertiary paediatric hospital in Singapore. Paediatric patients aged 0 to 18 years old with a positive culture for E. meningoseptica from any sterile site were identified from the hospital laboratory database. The data collected included clinical characteristics, antimicrobial susceptibility and treatment, and clinical outcomes. RESULTS: Thirteen cases were identified in this study. Combination therapy with piperacillin/tazobactam and trimethoprim/sulfamethoxazole or a fluoroquinolone resulted in a cure rate of 81.8  %. The mortality rate was 15.4  % and neurological morbidity in patients with bacteraemia and meningitis remained high (75 %). CONCLUSIONS: Treatment with combination therapy of piperacillin/tazobactam and trimethoprim/sulfamethoxazole or a fluroquinolone was effective in this study, with low mortality rates being observed.

Structural characteristics of a mitochondrial control region from M yotis bat (Vespertilionidae) mitogenomes based on sequence datasets.

The datasets included sequences of a control region from Myotis bat mitogenomes. The control region (1706-2005 bp) of the Myotis mitogenomes was divided into three domains similar to that of other mammals, which included the common conserved blocks (ETAS domain, Central domain, and CSB domain). Several long tandem repeat sequences were present between the upstream of control regions and ETAS1. The size, base composition, and copy number of the long tandem repeat sequences differed between the Myotis species. Short tandem repeat sequences were also found between CSB1 and CSB2 in the CSB domain.

Complete Genome Sequence Analysis and Characterization of Selected Iron Regulation Genes of Pasteurella Multocida Serotype A Strain PMTB2.1.

Although more than 100 genome sequences of Pasteurella multocida are available, comprehensive and complete genome sequence analysis is limited. This study describes the analysis of complete genome sequence and pathogenomics of P. multocida strain PMTB2.1. The genome of PMTB2.1 has 2176 genes with more than 40 coding sequences associated with iron regulation and 140 virulence genes including the complete tad locus. The tad locus includes several previously uncharacterized genes such as flp2, rcpC and tadV genes. A transposable phage resembling to Mu phages was identified in P. multocida that has not been identified in any other serotype yet. The multi-locus sequence typing analysis assigned the PMTB2.1 genome sequence as type ST101, while the comparative genome analysis showed that PMTB2.1 is closely related to other P. multocida strains with the genomic distance of less than 0.13. The expression profiling of iron regulating-genes of PMTB2.1 was characterized under iron-limited environment. Results showed significant changes in the expression profiles of iron-regulating genes (p < 0.05) whereas the highest expression of fecE gene (281 fold) at 30 min suggests utilization of the outer-membrane proteins system in iron acquisition at an early stage of growth. This study showed the phylogenomic relatedness of P. multocida and improved annotation of important genes and functional characterization of iron-regulating genes of importance to the bacterial growth.

Electrohydrodynamic printing process monitoring by microscopic image identification.

Electrohydrodynamic printing (EHDP) is able to precisely manipulate the position, size, and morphology of micro-/nano-fibers and fabricate high-resolution scaffolds using viscous biopolymer solutions. However, less attention has been paid to the influence of EHDP jet characteristics and key process parameters on deposited fiber patterns. To ensure the printing quality, it is very necessary to establish the relationship between the cone shapes and the stability of scaffold fabrication process. In this work, we used a digital microscopic imaging technique to monitor EHDP cones during printing, with subsequent image processing algorithms to extract related features, and a recognition algorithm to determine the suitability of Taylor cones for EHDP scaffold fabrication. Based on the experimental data, it has been concluded that the images of EHDP cone modes and the extracted features (centroid, jet diameter) are affected by their process parameters such as nozzle-substrate distance, the applied voltage, and stage moving speed. A convolutional neural network is then developed to classify these EHDP cone modes with the consideration of training time consumption and testing accuracy. A control algorithm will be developed to regulate the process parameters at the next stage for effective scaffold fabrication.

Molecular characteristics of infection and colonization isolates of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA).

Staphylococcus aureus is a gram-positive coccus that colonizes the skin and mucous membranes, particularly the anterior nares. Recently, community-acquired MRSA (CA-MRSA) has emerged as a cause of skin and soft-tissue infections in healthy individuals. These strains are sensitive to antimicrobials, carry genes for Panton-Valentine leukocidin (PVL) toxin, and feature the staphylococcal cassette chromosome mec (SCCmec) type IV or V. The suspected mode of transmission involves close contact with carriers, leading to skin or nasal colonization that results in subsequent active infection. This study was undertaken to determine the molecular characteristics of CA-MRSA isolates in children presenting with wound infections at Likas Hospital, Sabah, Malaysia, and the possible mode of transmission. The results showed that the majority of CA-MRSA infection isolates were from scalp abscesses (49%) in 1-5-year-old children (70%) in the Filipino (54%) community. The presence of the mec gene was detected in all isolates and the PVL virulence factor was found in 92% of the isolates. SCCmec typing revealed that 57% of the isolates were untypable, 35% harbored the SCCmecIVa element, and one each had SCCmecIVc, SCCmecV, or SCCmecII. Sixteen S. aureus strains were isolated from nasal swabs in 19 family members of index patients. Fourteen of these cultures were positive for catalase, coagulase, and DNAase. All of the colonization isolates carried the mecA gene and only a third were positive for the PVL toxin. SCCmec typing showed that 79% of the isolates were untypable and two had SCCmecIVa element and one had SCCmecV element. When five pairs of infection and colonizing isolates were compared by spa typing, only two pairs showed identical spa type with possible transmission between the patient and family contact. Further studies are necessary to establish CA-MRSA transmission by performing multiple-site cultures multiple times instead of one-time naresonly sample collection.

Periodontal treatment in private dental practice: a case-based survey.

BACKGROUND: This study aimed to assess the management and referral patterns of Victorian general dental practitioners based on periodontal diagnosis. METHODS: Following ethics approval, Victorian general dental practitioners were invited to complete five randomized text-based periodontitis scenario questionnaires. Based on their diagnosis, respondents were asked for their management options and asked to specify who would perform these treatments. Respondents were also asked about referral procedures. RESULTS: One hundred and thirty-five dentists attempted the survey. Most were in group practice and based in Melbourne. Of the total respondents, 22.5% worked in a practice employing a hygienist. The management of periodontal disease was appropriate, and treatment options increased with severity. As severity increased, patients were more likely to be referred to a periodontist. Periodontal services referred by general dentists to dental hygienists increased with the number of days the hygienists worked within a practice. Over- and underdiagnosis did not markedly affect management. The recommendation of antibiotics, mouthwashes and periodontal surgery varied depending on year and school of graduation. CONCLUSIONS: The general dentists that completed the survey are managing periodontal conditions appropriately and according to current guidelines.

Estimating true hospital morbidity of complications associated with mumps outbreak, England, 2004/05.

Mumps outbreaks in highly vaccinated populations continue to be reported globally. Therefore, quantifying the burden of mumps morbidity accurately will be necessary to better assess the impact of mumps vaccination programmes. We aim to estimate the true morbidity resulting from mumps complications in terms of hospitalised orchitis, meningitis, oophoritis and pancreatitis in England during the outbreak in 2004/05. This outbreak in England led to a clear increase in hospitalisations coded to mumps for complications of orchitis in those born in the 1970s and 1980s and possibly for meningitis in those born in the 1980s. A simple statistical model, based on analysing time trends for diagnosed complications in hospital databases with routine laboratory surveillance data, found that the actual morbidity was much higher. There were 2.5 times (166 cases) more mumps orchitis cases in the 1970s cohort and 2.0 times (708 cases) more mumps orchitis cases in the 1980s cohort than complications coded to mumps in hospital databases. Our study demonstrated that the mumps outbreak in England 2004/05 resulted in a substantial increase in hospitalised mumps complications, and the model we used can improve the ascertainment of morbidity from a mumps outbreak.