Utilizing cost-effective portable equipment to enhance COVID-19 variant tracking both on-site and at a large scale.

Despite optimistic predictions on the eventual end of COVID-19 (Coronavirus Disease 2019), caution is necessary regarding the emergence of new variants to sustain a positive outlook and effectively address any potential future outbreaks. However, ongoing efforts to track COVID-19 variants are concentrated in developed countries and unique social practices and remote habitats of indigenous peoples present additional challenges. By combining small-sized equipment that is easily accessible and inexpensive, we performed SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) whole genome sequencing and measured the sample-to-answer time and accuracy of this portable variant tracking tool. Our portable design determined the variant of SARS-CoV-2 in an infected individual within 9 hours and 15 minutes without external power or internet connection, surpassing the speed of previous portable tools. It took only 16 minutes to complete sequencing run, whole genome assembly, and lineage determination using a single standalone laptop. We then demonstrated the capability to produce 289 SARS-CoV-2 whole genome sequences in a single portable sequencing run, representing a significant improvement over an existing throughput of 96 sequences per run. We verified the accuracy of portable sequencing by comparison with two other independent sequencing methods. We showed that our high-throughput data consistently represented the circulating variants in Los Angeles, United States, when compared with publicly available sequences. Our scheme is designed to be flexible, rapid, and accurate, making it a valuable tool for large-scale surveillance operations in low- and middle-income countries as well as targeted surveys for vulnerable populations in remote locations.IMPORTANCEThere have been significant efforts to track COVID-19 (Coronavirus Disease 2019) variants, accumulating over 15 million SARS-CoV-2 sequences as of 2023. However, the distribution of global survey data is highly skewed, with nearly half of all countries having inadequate or low levels of genomic surveillance. In addition, indigenous peoples face more severe threats from COVID-19, due to their generally remote residence and unique social practices. Cost-effective portable sequencing tools have been used to investigate Ebola and Zika outbreaks. However, these tools have a sample-to-answer time of around 24 hours and require an internet connection for data transfer to an off-site cloud server. In our study, we rapidly determined COVID-19 variants using only small and inexpensive equipment, with a completion time of 9 hours and 15 minutes. Furthermore, we produced 289 near-full-length SARS-CoV-2 genome sequences from a single portable Nanopore sequencing run, representing a threefold increase in throughput compared with existing Nanopore sequencing methods.

Detecting outliers beyond tolerance limits derived from statistical process control in patient-specific quality assurance.

BACKGROUND: Tolerance limit is defined on pre-treatment patient specific quality assurance results to identify "out of the norm" dose discrepancy in plan. An out-of-tolerance plan during measurement can often cause treatment delays especially if replanning is required. In this study, we aim to develop an outlier detection model to identify out-of-tolerance plan early during treatment planning phase to mitigate the above-mentioned risks. METHODS: Patient-specific quality assurance results with portal dosimetry for stereotactic body radiotherapy measured between January 2020 and December 2021 were used in this study. Data were divided into thorax and pelvis sites and gamma passing rates were recorded using 2%/2 mm, 2%/1 mm, and 1%/1 mm gamma criteria. Statistical process control method was used to determine six different site and criterion-specific tolerance and action limits. Using only the inliers identified with our determined tolerance limits, we trained three different outlier detection models using the plan complexity metrics extracted from each treatment field-robust covariance, isolation forest, and one class support vector machine. The hyperparameters were optimized using the F1-score calculated from both the inliers and validation outliers' data. RESULTS: 308 pelvis and 200 thorax fields were used in this study. The tolerance (action) limits for 2%/2 mm, 2%/1 mm, and 1%/1 mm gamma criteria in the pelvis site are 99.1% (98.1%), 95.8% (91.1%), and 91.7% (86.1%), respectively. The tolerance (action) limits in the thorax site are 99.0% (98.7%), 97.0% (96.2%), and 91.5% (87.2%). One class support vector machine performs the best among all the algorithms. The best performing model in the thorax (pelvis) site achieves a precision of 0.56 (0.54), recall of 1.0 (1.0), and F1-score of 0.72 (0.70) when using the 2%/2 mm (2%/1 mm) criterion. CONCLUSION: The model will help the planner to identify an out-of-tolerance plan early so that they can refine the plan further during the planning stage without risking late discovery during measurement.

Repurposing DailyQA3 for an efficient and spot position sensitive daily quality assurance tool for proton therapy.

INTRODUCTION: Daily quality assurance is an integral part of a radiotherapy workflow to ensure the dose is delivered safely and accurately to the patient. It is performed before the first treatment of the day and needs to be time and cost efficient for a multiple gantries proton center. In this study, we introduced an efficient method to perform QA for output constancy, range verification, spot positioning accuracy and imaging and proton beam isocenter coincidence with DailyQA3. METHODS: A stepped acrylic block of specific dimensions is fabricated and placed on top of the DailyQA3 device. Treatment plans comprising of two different spread-out Bragg peaks and five individual spots of 1.0 MU each are designed to be delivered to the device. A mathematical framework to measure the 2D distance between the detectors and individual spot is introduced and play an important role in realizing the spot positioning and centering QA. Lastly, a 5 months trends of the QA for two gantries are presented. RESULTS: The outputs are monitored by two ion chambers in the DailyQA3 and a tolerance of ± 3 % $ \pm 3\% $ are used. The range of the SOBPs are monitored by the ratio of ion chamber signals and a tolerance of ± 1 mm $ \pm 1\ {\mathrm{mm}}$ is used. Four diodes at ± 10 cm $ \pm 10\ {\mathrm{cm}}$ from the central ion chambers are used for spot positioning QA, while the central ion chamber is used for imaging and proton beam isocenter coincidence QA. Using the framework, we determined the absolute signal threshold corresponding to the offset tolerance between the individual proton spot and the detector. A 1.5 mm $1.5\ {\mathrm{mm}}$ tolerances are used for both the positioning and centering QA. No violation of the tolerances is observed in the 5 months trends for both gantries. CONCLUSION: With the proposed approach, we can perform four QA items in the TG224 within 10 min.

An arrayed optofluidic system for three-dimensional (3D) focal control via electrowetting.

A new lens capability for three-dimensional (3D) focal control is presented using an optofluidic system consisting of n × n arrayed liquid prisms. Each prism module contains two immiscible liquids in a rectangular cuvette. Using the electrowetting effect, the shape of the fluidic interface can be rapidly adjusted to create its straight profile with the prism's apex angle. Consequently, an incoming ray is steered at the tilted interface due to the refractive index difference between two liquids. To achieve 3D focal control, individual prisms in the arrayed system are simultaneously modulated, allowing incoming light rays to be spatially manipulated and converged on a focal point located at Pfocal (fx, fy, fz) in 3D space. Analytical studies were conducted to precisely predict the prism operation required for 3D focal control. Using three liquid prisms positioned on the x-, y-, and 45°-diagonal axes, we experimentally demonstrated 3D focal tunability of the arrayed optofluidic system, achieving focal tuning along lateral, longitudinal, and axial directions as wide as 0 ≤ fx ≤ 30 mm, 0 ≤ fy ≤ 30 mm, and 500 mm ≤ fz ≤ ∞. This focal tunability of the arrayed system allows for 3D control of the lens's focusing power, which could not be attained by solid-type optics without the use of bulky and complex mechanical moving components. This innovative lens capability for 3D focal control has potential applications in eye-movement tracking for smart displays, autofocusing of smartphone cameras, or solar tracking for smart photovoltaic systems.

Effective dose of remimazolam co-administered with remifentanil to facilitate I-gel insertion without neuromuscular blocking agents: an up-and-down sequential allocation trial.

BACKGROUND: Remimazolam is a new anesthetic drug developed and is an ultra-short-acting agent with rapid onset and offset. The pharmacology of this drug seems to be ideal for short surgeries eligible for I-gel insertion. Therefore, this study aimed to determine the optimal bolus dose of remimazolam for I-gel insertion when co-administered with remifentanil without neuromuscular blocking agents (NMBAs). METHODS: Patients aged 19-65 years with American Society of Anesthesiologists physical status I or II scheduled for general anesthesia were enrolled. The first dose of remimazolam was 0.15 mg/kg and remifentanil was co-administered at an effect-site concentration (Ce) of 3.0 ng/mL. The dose of remimazolam for the following patient was decreased or increased by 0.05 mg/kg depending on the success or failure of I-gel insertion in the previous patient. RESULTS: The remimazolam bolus dose required for successful I-gel insertion in 50% of adult patients using modified Dixon's up-and-down method with remifentanil Ce 3.0 ng/mL and no NMBAs was 0.280 ± 0.048 mg/kg. Isotonic regression analysis showed that the 50% and 95% effective doses were 0.244 (83% confidence interval [CI] 0.213-0.313) mg/kg and 0.444 (95% CI 0.436-0.448) mg/kg, respectively. The mean time to loss of consciousness (Modified Observer's Assessment of Alertness/Sedation score < 2) was 52.2 s. Three patients (12.0%) showed a reduction in systolic blood pressure of more than 30% from baseline. CONCLUSIONS: Selecting the appropriate dose of remimazolam/remifentanil without NMBAs makes it feasible to insert the I-gel. TRIAL REGISTRATION: This study protocol was registered at http://cris.nih.go.kr (KCT0007801, 12th, October, 2022).

A transit portal dosimetry method for respiratory gating quality assurance with a dynamic 3D printed tumor phantom.

BACKGROUNDS: Respiratory gating is one of the motion management techniques that is used to deliver radiation dose to a tumor at a specific position under free breathing. However, due to the dynamic feedback process of this approach, regular equipment quality assurance (QA) and patient-specific QA checks need to be performed. This work proposes a new QA methodology using electronic portal imaging detector (EPID) to determine the target localization accuracy of phase gating. METHODS: QA tools comprising 3D printed spherical tumor phantoms, programmable stages, and an EPID detector are characterized and assembled. Algorithms for predicting portal dose (PD) through moving phantoms are developed and verified using gamma analysis for two spherical tumor phantoms (2 cm and 4 cm), two different 6 MV volumetric modulated arc therapy plans, and two different gating windows (30%-70% and 40%-60%). Comparison between the two gating windows is then performed using the Wilcoxon signed-rank test. An optimizer routine, which is used to determine the optimal window, based on maximal gamma passing rate (GPR), was applied to an actual breathing curve and breathing plan. This was done to ascertain if our method yielded a similar result with the actual gating window. RESULTS: High GPRs of more than 97% and 91% were observed when comparing the predicted PD with the measured PD in moving phantom at 2 mm/2% and 1 mm/1% levels, respectively. Analysis of gamma heatmaps shows an excellent agreement with the tumor phantom. The GPR of 40%-60% PD was significantly lower than that of the 30%-70% PD at the 1 mm/1% level (p = 0.0064). At the 2 mm/2% level, no significant differences were observed. The optimizer routine could accurately predict the center of the gating window to within a 10% range. CONCLUSION: We have successfully performed and verified a new method for QA with the use of a moving phantom with EPID for phase gating with real-time position management.

Temperature Compensation of Fiber Bragg Grating Sensors in Smart Strand.

Compared to other types of sensors, fiber optic sensors have improved accuracy and durability. Recently, the Smart Strand was developed to maximize the advantages of fiber optic sensors for measuring the cable forces in prestressed concrete structures or cable-supported bridges. The Smart Strand has fiber Bragg gratings (FBGs) embedded in a core wire of the seven-wire strand. Similar to other sensors, the strain measured at an FBG is affected by temperature; therefore, the temperature effect that is not related to the mechanical strain should be compensated for or corrected in the long-term measurement subjected to temperature variation. However, a temperature compensation procedure for the FBG has yet to be established, and relevant studies have used different formulas for the compensation. Moreover, when the FBG sensors are packaged with a certain material-such as fiber reinforced polymer-for protection, it is important to consider the interaction between the FBG, packaging material, and host material during thermal behavior. Therefore, this study proposed a reasonable procedure for temperature compensation for the FBG sensors embedded in packaging material and host material. In particular, the thermal sensitivity of the Smart Strand was intensively investigated. The proposed theoretical formulas were validated through comparison with data obtained from various specimens in a temperature-controlled chamber. Finally, the procedure was applied to correct the data measured using the Smart Strands in a 20-m-long full-scale specimen for about a year, thus resulting in a realistic trend of the long-term prestressing force.

Cultural dimensions of individualism and collectivism and risk of opioid misuse: A test of Social Cognitive Theory.

BACKGROUND: Despite the critical role social and cultural contexts play in pain experience, limited theoretical and empirical attention has been devoted to the interplay between social, cognitive, cultural, and psychological factors in chronic pain management and the risk of opioid misuse. METHODS: Using structural equation modeling, the present study tested the Social Cognitive Theory (SCT) of chronic pain management and risk of opioid misuse in the context of intraindividual cultural dimensions of individualism and collectivism among 316 ethnically diverse adults with chronic pain in the United States. RESULTS: Social cognitive predictors account for a significant amount of variance in pain dysfunction and risk of opioid misuse in adults with chronic pain. Satisfaction with pain support was positively associated with both greater pain acceptance and greater pain self-efficacy. Individualism was found to be positively associated with satisfaction with pain support, pain self-efficacy, and pain acceptance but negatively associated with the risk of opioid misuse. Collectivism was positively associated with the risk of opioid misuse. CONCLUSIONS: The study findings not only empirically support using SCT for adults with chronic pain, but also provide a more thorough conceptual framework that highlights the intracultural diversity and interplay among social, cognitive, and psychological factors that affect pain experience and the risk of opioid misuse among adults with chronic pain.

Different outcomes of multiple sialadenitis involving the submandibular and zygomatic salivary glands in a Welsh Corgi dog.

A ten-year-old indoor, castrated male Cardigan Welsh Corgi (Canis familiaris) presented with the chief complaints of chronic vomiting, retching, hypersalivation, and bilateral submandibular masses for two months. The systemic examinations, including serum chemistry, radiography, ultrasonography, and fluoroscopy, were unremarkable. A fine-needle aspiration revealed bilateral submandibular sialadenitis. Broad-spectrum antibiotics with phenobarbital were prescribed to alleviate the ptyalism. Thereafter, the left submandibular glands were normalised, and the right submandibular glands decreased to half their size. Three weeks later, the animal had an emergency visit because of a sudden left exophthalmos. Computed tomography and magnetic resonance imaging revealed enlarged left zygomatic and right mandibular salivary glands. The affected glands were surgically removed; the histopathologic examination confirmed non-septic sialadenitis, and the patient was finally diagnosed with idiopathic sialadenitis. Vomiting continued after the gland removal and the dog required a gradual increase in the phenobarbital dosage and an additional antiepileptic drug (potassium bromide) to manage the symptoms. The patient died eight months later from an unknown cause. This case report of bilateral submandibular sialadenitis concurrent with unilateral zygomatic sialadenitis in a Welsh Corgi dog suggests that when multiple salivary glands are involved, the response to anti-epileptic drugs and the prognosis is poor compared to that involving a single salivary gland.

Microdrop Human Immunodeficiency Virus Sequencing for Incidence and Drug Resistance Surveillance.

BACKGROUND: Precise and cost-efficient human immunodeficiency virus (HIV) incidence and drug resistance surveillances are in high demand for the advancement of the 90-90-90 "treatment for all" target. METHODS: We developed microdrop HIV sequencing for the HIV incidence and drug resistance assay (HIDA), a single-blood-draw surveillance tool for incidence and drug resistance mutation (DRM) detection. We amplified full-length HIV envelope and pol gene sequences within microdroplets, and this compartmental amplification with long-read high-throughput sequencing enabled us to recover multiple unique sequences. RESULTS: We achieved greater precision in determining the stage of infection than current incidence assays, with a 1.2% false recency rate (proportion of misclassified chronic infections) and a 262-day mean duration of recent infection (average time span of recent infection classification) from 83 recently infected and 81 chronically infected individuals. Microdrop HIV sequencing demonstrated an increased capacity to detect minority variants and linked DRMs. By screening all 93 World Health Organization surveillance DRMs, we detected 6 pretreatment drug resistance mutations with 2.6%-13.2% prevalence and cross-linked mutations. CONCLUSIONS: HIDA with microdrop HIV sequencing may promote global HIV real-time surveillance by serving as a precise and high-throughput cross-sectional survey tool that can be generalized for surveillance of other pathogens.

Gut microbiome in people living with HIV is associated with impaired thiamine and folate syntheses.

People living with HIV have a high incidence of cardiovascular and neurological diseases as comorbid disorders that are commonly linked to inflammation. While microbial translocation can augment inflammation during HIV infection, functional microbiome shifts that may increase pro-inflammatory responses have not been fully characterized. In addition, defining HIV-induced microbiome changes has been complicated by high variability among individuals. Here we conducted functional annotation of previously-published 16S ribosomal RNA gene sequences of 305 HIV positive and 249 negative individuals, with adjustment for geographic region, sex, sexual behavior, and age. Metagenome profiles were inferred from these individuals' 16S data. HIV infection was associated with impaired microbial vitamin B synthesis; around half of the gene families in thiamine and folate biosynthesis pathways were significantly less abundant in the HIV positive group than the negative control. These results are consistent with the high prevalence of thiamine and folate deficiencies in HIV infections. These HIV-induced microbiota shifts have the potential to influence cardiovascular and neurocognitive diseases, given the documented associations between B-vitamin deficiencies, inflammation, and these diseases. We also observed that most essential amino acid biosynthesis pathways were downregulated in the microbiome of HIV-infected individuals. Microbial vitamin B and amino acid synthesis pathways were not significantly recovered by antiretroviral treatment when we compared 262 ART positive and 184 ART negative individuals. Our meta-analysis provides a new outlook for understanding vitamin B and amino acid deficiencies in HIV patients, suggesting that interventions for reversing HIV-induced microbiome shifts may aid in lessening the burdens of HIV comorbidities.

Correlations among metamorphopsia test scores, optical coherence tomography findings and multifocal electroretinogram responses in epiretinal membrane patients.

PURPOSE: To quantify metamorphopsia with a novel objective method in patients with epiretinal membrane (ERM) and to compare the relationships among metamorphopsia scores, spectral-domain optical coherence tomography (OCT) findings, and multifocal electroretinogram (mfERG) results. METHODS: This study included 52 eyes of 52 patients with idiopathic ERM who underwent comprehensive ophthalmologic examinations, including measurement of best-corrected visual acuity (BCVA), OCT, and mfERG. The degree of metamorphopsia was quantified using MonPack One® (Metrovision, Perenchies, France). On the topographic map of the early treatment diabetic retinopathy (ETDRS) grid, retinal thickness in the central, superior, inferior, nasal, and temporal subfields were measured, and metamorphopsia scores for each corresponding subfield were also obtained. The amplitudes and implicit times of mERG were elicited from each subfield. Then, the correlations among metamorphopsia scores, OCT findings, and mfERG responses were analyzed. RESULTS: The mean age of the patients was 65.3 ± 18.5 y, and the average metamorphopsia score of the individual subfields was 2.03 ± 1.18. Initial BCVA was 0.50 ± 0.12 logMAR, but there was no significant correlation between metamorphopsia scores and BCVA. The metamorphopsia scores from the central subfields showed significant correlations with central retinal thickness (CRT) (p = 0.001). The mean metamorphopsia scores in the central subfield showed a significant relationship with the mean N1 and P1 amplitudes (p = 0.001, p = 0.048, respectively), while no relationship was observed between metamorphopsia scores and mfERG amplitudes in other subfields. CONCLUSIONS: The degree of metamorphopsia in patients with ERM could be objectively quantified in each subfield using a novel metamorphopsia test. The metamorphopsia scores were significantly correlated with retinal thickness, especially at the central subfields, and the scores in the central subfields were significantly correlated with the N1 and P1 amplitudes of mfERG. Thus, the metamorphopsia test can be a useful method to evaluate metamorphopsia symptoms for patients with ERM.

Duration-dependent margins for prostate radiotherapy-a practical motion mitigation strategy.

BACKGROUND AND OBJECTIVE: The magnitude of intra-fractional prostate displacement (change from initial position over time) is associated with the duration of the patient lying on the radiotherapy treatment couch. This study reports a minute-by-minute association and calculates the impact of this displacement on duration-dependent margins using real-time intra-fractional position data monitored by four-dimensional transperineal ultrasound (4D TPUS). MATERIALS AND METHODS: A total of 55 patients were recruited prospectively. Intra-fractional position of the prostate was monitored in real-time using a 4D TPUS Clarity® system. A total of 1745 monitoring sessions were analysed. Van Herk's margin recipe (2.5∑ + 1.64((σ2 + σp2)1/2 - σp)) was used to estimate the duration-dependant margins for every minute, up to the 15th minute. Linear regression analysis was then performed on the overall margins against time and direction. RESULTS: The mean intra-fractional position was 0.76 mm Inferior (Inf), 0 mm Lateral (Lat) and 0.94 mm Posterior (Post) at the 15th minute. A minimum margin expansion of 2.42 mm (Superior/Inf), 1.02 mm (Left/Right) and 2.65 mm (Anterior/Post) was required for an 8­minute treatment compared to 4.29 mm (Sup/Inf), 1.84 mm (Lt/Rt) and 4.63 mm (Ant/Post) for a 15-minute treatment. The required margin expansion increased linearly (R2 = 0.99) in all directions (p < 0.01). However, while there was no statistically significant difference (p = 0.10) in the required margin expansion in the Sup/Inf and Ant/Post directions respective of the time duration, the margins were much bigger compared to those in the Lt/Rt direction (p < 0.01). CONCLUSION: We report our experience in deriving the minimum duration-dependant margin to generate the required planning target volume for prostate radiotherapy. The required margin increases linearly in all directions within the 15-min duration; thus, the margin will depend on the duration of the technique chosen (IMRT/VMAT/3DCRT/proton).

HIITE: HIV-1 incidence and infection time estimator.

Motivation: Around 2.1 million new HIV-1 infections were reported in 2015, alerting that the HIV-1 epidemic remains a significant global health challenge. Precise incidence assessment strengthens epidemic monitoring efforts and guides strategy optimization for prevention programs. Estimating the onset time of HIV-1 infection can facilitate optimal clinical management and identify key populations largely responsible for epidemic spread and thereby infer HIV-1 transmission chains. Our goal is to develop a genomic assay estimating the incidence and infection time in a single cross-sectional survey setting. Results: We created a web-based platform, HIV-1 incidence and infection time estimator (HIITE), which processes envelope gene sequences using hierarchical clustering algorithms and informs the stage of infection, along with time since infection for incident cases. HIITE's performance was evaluated using 585 incident and 305 chronic specimens' envelope gene sequences collected from global cohorts including HIV-1 vaccine trial participants. HIITE precisely identified chronically infected individuals as being chronic with an error less than 1% and correctly classified 94% of recently infected individuals as being incident. Using a mixed-effect model, an incident specimen's time since infection was estimated from its single lineage diversity, showing 14% prediction error for time since infection. HIITE is the first algorithm to inform two key metrics from a single time point sequence sample. HIITE has the capacity for assessing not only population-level epidemic spread but also individual-level transmission events from a single survey, advancing HIV prevention and intervention programs. Availability and implementation: Web-based HIITE and source code of HIITE are available at http://www.hayounlee.org/software.html. Supplementary information: Supplementary data are available at Bioinformatics online.

CCMP: Software-as-a-service approach for fully-automated microbiome profiling.

Microbiome profiling holds great promise for the development of novel disease biomarkers and therapeutics. Next-generation sequencing is currently the preferred method for microbiome data collection and multiple standardized tools, packages, and pipelines have been developed for the purpose of raw data processing and microbial annotation. However, these currently available pipelines come with entry-level barriers such as high-performance hardware, software installation, and sequential command-line scripting that often deter end-users. We thus created Cloud Computing for Microbiome Profiling (CCMP, https://ccmp.usc.edu), a public cloud-based web tool which combines the analytical power of current microbiome analysis platforms with a user-friendly interface. CCMP is a free-of-charge software-as-a-service (SaaS) that simplifies user experience by enabling users to complete their analysis in a single step, uploading raw sequencing data files. Once users upload 16S ribosomal RNA gene sequence data, our pipeline performs taxonomic annotation, abundance profiling, and statistical tests to report microbiota signatures altered by diseases or experimental conditions. CCMP took a 125 gigabyte (GB) input of 16S ribosomal RNA gene sequence data from 1052 specimens in FASTQ format and reported figures and tables of taxonomic annotations, statistical tests, α and ß diversity calculations, and principal coordinate analyses within 21 h. CCMP is the first fully-automated web interface that integrates three key solutions for large-scale data analysis: cloud computing, fast file transfer technology, and microbiome analysis tools. As a reliable platform that supplies consistent microbiome analysis, CCMP will advance microbiome research by making effortful bioinformatics easily accessible to public.

Conditions for laryngeal mask airway placement in terms of oropharyngeal leak pressure: a comparison between blind insertion and laryngoscope-guided insertion.

BACKGROUND: Insertion under laryngoscopic guidance has been used to achieve ideal positioning of the laryngeal mask airway (LMA). However, to date, the efficacy of this technique has been evaluated only using fiberoptic evaluation, and the results have been conflicting. Other reliable tests to evaluate the efficacy of this technique have not been established. Recently, it has been suggested that the accuracy of LMA placement can be determined by clinical signs such as oropharyngeal leak pressure (OPLP). The aim of this study was to assess the efficacy of LMA insertion under laryngoscopic guidance using OPLP as an indicator. METHODS: After approved by the institutional ethics committee, a prospective comparison of 100 patients divided into 2 groups (50 with blind technique and 50 with the laryngoscope technique) were evaluated. An LMA (LarySeal™, Flexicare medical Ltd., UK) was inserted using the blind approach in the blind insertion group and using laryngoscopy in the laryngoscope-guided insertion group. The OPLP, fiberoptic position score, whether the first attempt at LMA insertion was successful, time taken for insertion, ease of LMA insertion, and adverse airway events were recorded. RESULTS: Data were presented as mean ± standard deviation. The OPLP was higher in the laryngoscope-guided insertion group than in the blind insertion group (21.4 ± 8.6 cmH2O vs. 18.1 ± 6.1 cmH2O, p = 0.031). The fiberoptic position score, rate of success in the first attempt, ease of insertion, and pharyngolaryngeal adverse events were similar between both groups. The time taken for insertion of the LMA was significantly longer in the laryngoscope-guided insertion group, compared to blind insertion group (35.9 ± 9.5 s vs. 28.7 ± 9.5 s, p < 0.0001). CONCLUSION: Laryngoscope-guided insertion of LMA improves the airway seal pressure compared to blind insertion. Our result suggests that it may be a useful technique for LMA insertion. TRIAL REGISTRATION: cris.nih.go.kr , identifier: KCT0001945 (2016-06-17).

Development of Optical Fiber Based Measurement System for the Verification of Entrance Dose Map in Pencil Beam Scanning Proton Beam.

This study describes the development of a beam monitoring system for the verification of entrance dose map in pencil beam scanning (PBS) proton therapy based on fiber optic radiation sensors (FORS) and the validation of this system through a feasibility study. The beam monitoring system consisted of 128 optical fibers optically coupled to photo-multiplier tubes. The performance of the beam monitoring system based on FORS was verified by comparing 2D dose maps of square-shaped fields of various sizes, which were obtained using conventional dosimeters such as MatriXX and EBT3 film, with those measured using FORS. The resulting full-width at half maximum and penumbra were compared for PBS proton beams, with a ≤2% difference between each value, indicating that measurements using the conventional dosimetric tool corresponded to measurements based on FORS. For irregularly-shaped fields, a comparison based on the gamma index between 2D dose maps obtained using MatriXX and EBT3 film and the 2D dose map measured by the FORS showed passing rates of 96.9 ± 1.3% and 96.2 ± 1.9%, respectively, confirming that FORS-based measurements for PBS proton therapy agreed well with those measured using the conventional dosimetric tools. These results demonstrate that the developed beam monitoring system based on FORS is good candidate for monitoring the entrance dose map in PBS proton therapy.

SPMM: estimating infection duration of multivariant HIV-1 infections.

MOTIVATION: Illustrating how HIV-1 is transmitted and how it evolves in the following weeks is an important step for developing effective vaccination and prevention strategies. It is currently possible through DNA sequencing to account for the diverse array of viral strains within an infected individual. This provides an unprecedented opportunity to pinpoint when each patient was infected and which viruses were transmitted. RESULTS: Here we develop a mathematical tool for early HIV-1 evolution within a subject whose infection originates either from a single or multiple viral variants. The shifted Poisson mixture model (SPMM) provides a quantitative guideline for segregating viral lineages, which in turn enables us to assess when a subject was infected. The infection duration estimated by SPMM showed a statistically significant linear relationship with that by Fiebig laboratory staging (P = 0.00059) among 37 acutely infected subjects. Our tool provides a functional approach to understanding early genetic diversity, one of the most important parameters for deciphering HIV-1 transmission and predicting the rate of disease progression. AVAILABILITY AND IMPLEMENTATION: SPMM, webserver, is available at http://www.hayounlee.org/web-tools.html. CONTACT: hayoun@usc.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Exfoliation of black phosphorus in ionic liquids.

We report the characterization and formation of sonication-assisted liquid phase exfoliation of bulk black phosphorus (BP) crystals with the incorporation of two representative ionic liquids (ILs) ([Emim][Tf2N] and [Bmim][Tf2N]) as green dispersing media was attempted, which resulted in stable dispersion of multi-layer BP flakes with unsuspected high oxidation resistance and chemical/structural integrity due to the presence of IL layer on top of BP flakes. There are two unveiled issues for the generation of BP dispersion in ILs. First, thin films of BP flakes can be simply prepared through our approach. Because self-oxidation of BP in ambient condition can be significantly minimized in ILs, vacuum filtration step can be adopted to produce BP thin films in ambient condition. Second, the binding of IL molecules on BP flakes has been firstly demonstrated by the time-of-flight secondary ion mass spectrometry characterization. In addition to the exploitation of ILs as the green solvents with less environmental harmfulness, IL-based exfoliation of BP might be easily scalable because harsh control of atmospheric oxygen and moisture is unnecessary in this approach.

Molecular clock of HIV-1 envelope genes under early immune selection.

BACKGROUND: The molecular clock hypothesis that genes or proteins evolve at a constant rate is a key tool to reveal phylogenetic relationships among species. Using the molecular clock, we can trace an infection back to transmission using HIV-1 sequences from a single time point. Whether or not a strict molecular clock applies to HIV-1's early evolution in the presence of immune selection has not yet been fully examined. RESULTS: We identified molecular clock signatures from 1587 previously published HIV-1 full envelope gene sequences obtained since acute infection in 15 subjects. Each subject's sequence diversity linearly increased during the first 150 days post infection, with rates ranging from [Formula: see text] to [Formula: see text] with a mean of [Formula: see text] per base per day. The rate of diversification for 12 out of the 15 subjects was comparable to the neutral evolution rate. While temporal diversification was consistent with evolution patterns in the absence of selection, mutations from the founder virus were highly clustered on statistically identified selection sites, which diversified more than 65 times faster than non-selection sites. By mathematically quantifying deviations from the molecular clock under various selection scenarios, we demonstrate that the deviation from a constant clock becomes negligible as multiple escape lineages emerge. The most recent common ancestor of a virus pair from distinct escape lineages is most likely the transmitted founder virus, indicating that HIV-1 molecular dating is feasible even after the founder viruses are no longer detectable. CONCLUSIONS: The ability of HIV-1 to escape from immune surveillance in many different directions is the driving force of molecular clock persistence. This finding advances our understanding of the robustness of HIV-1's molecular clock under immune selection, implying the potential for molecular dating.