What Aimed Movement Models Fit Distal Pointing With Varying Depth?

OBJECTIVE: With the rapid improvements in drone technology, there is an increasing interest in distal pointing to diffuse drones. This study investigated the effect of depth on distal pointing when the hand does not traverse the entire distance from start to target so that the most suitable mathematical model can be assessed. BACKGROUND: Starting from the Fitts paradigm, researchers have proposed different models to predict movement time when the distance to the target is variable. They do consider distance, but they are based on statistical modeling rather than the underlying control mechanisms. METHODS: Twenty-four participants volunteered for an experiment in a full-factorial Fitts' paradigm task (3 levels of movement amplitude *7 levels of target width *3 levels of distance from participant to screen). Movement time and the number of errors were the dependent variables. RESULTS: Depth has a significant effect when the target width is small, but depth has no effect when the target width is large. The angular version of the two-part model is superior to the one-part Fitts' model at larger distances. Besides, Index of difficulty for distal pointing, IDDP with adjustable k achieves the best fit even though the model is very sensitive to the value of k and the complexity of the model could be resulting in an overfitting. The result implies that the effects of movement amplitude and target width are not comparable and grouping them to form a dependent index of difficulty can be misleading especially when distance is an added variable. CONCLUSION: The angular version of the two-part model is a viable and meaningful description for distal pointing. Even though the IDDP with adjustable k is the best predictor for movement time when depth is an added variable, there is no physical interpretation for it. APPLICATION: A reasonable predictive model for performance assessments and predictions in distal pointing.

Efficient recall of SARS-CoV-2 variant-reactive B cells and T responses in the elderly upon heterologous mRNA vaccines as boosters.

Waning antibody levels against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the emergence of variants of concern highlight the need for booster vaccinations. This is particularly important for the elderly population, who are at a higher risk of developing severe coronavirus disease 2019 (COVID-19) disease. While studies have shown increased antibody responses following booster vaccination, understanding the changes in T and B cell compartments induced by a third vaccine dose remains limited. We analyzed the humoral and cellular responses in subjects who received either a homologous messenger RNA(mRNA) booster vaccine (BNT162b2 + BNT162b2 + BNT162b2; ''BBB") or a heterologous mRNA booster vaccine (BNT162b2 + BNT162b2 + mRNA-1273; ''BBM") at Day 0 (prebooster), Day 7, and Day 28 (postbooster). Compared with BBB, elderly individuals (≥60 years old) who received the BBM vaccination regimen display higher levels of neutralizing antibodies against the Wuhan and Delta strains along with a higher boost in immunoglobulin G memory B cells, particularly against the Omicron variant. Circulating T helper type 1(Th1), Th2, Th17, and T follicular helper responses were also increased in elderly individuals given the BBM regimen. While mRNA vaccines increase antibody, T cell, and B cell responses against SARS-CoV-2 1 month after receiving the third dose booster, the efficacy of the booster vaccine strategies may vary depending on age group and regimen combination.

A meta-analytic framework to adjust for bias in external control studies.

While randomized controlled trials (RCTs) are the gold standard for estimating treatment effects in medical research, there is increasing use of and interest in using real-world data for drug development. One such use case is the construction of external control arms for evaluation of efficacy in single-arm trials, particularly in cases where randomization is either infeasible or unethical. However, it is well known that treated patients in non-randomized studies may not be comparable to control patients-on either measured or unmeasured variables-and that the underlying population differences between the two groups may result in biased treatment effect estimates as well as increased variability in estimation. To address these challenges for analyses of time-to-event outcomes, we developed a meta-analytic framework that uses historical reference studies to adjust a log hazard ratio estimate in a new external control study for its additional bias and variability. The set of historical studies is formed by constructing external control arms for historical RCTs, and a meta-analysis compares the trial controls to the external control arms. Importantly, a prospective external control study can be performed independently of the meta-analysis using standard causal inference techniques for observational data. We illustrate our approach with a simulation study and an empirical example based on reference studies for advanced non-small cell lung cancer. In our empirical analysis, external control patients had lower survival than trial controls (hazard ratio: 0.907), but our methodology is able to correct for this bias. An implementation of our approach is available in the R package ecmeta.

A frequentist approach to dynamic borrowing.

There has been growing interest in leveraging external control data to augment a randomized control group data in clinical trials and enable more informative decision making. In recent years, the quality and availability of real-world data have improved steadily as external controls. However, information borrowing by directly pooling such external controls with randomized controls may lead to biased estimates of the treatment effect. Dynamic borrowing methods under the Bayesian framework have been proposed to better control the false positive error. However, the numerical computation and, especially, parameter tuning, of those Bayesian dynamic borrowing methods remain a challenge in practice. In this paper, we present a frequentist interpretation of a Bayesian commensurate prior borrowing approach and describe intrinsic challenges associated with this method from the perspective of optimization. Motivated by this observation, we propose a new dynamic borrowing approach using adaptive lasso. The treatment effect estimate derived from this method follows a known asymptotic distribution, which can be used to construct confidence intervals and conduct hypothesis tests. The finite sample performance of the method is evaluated through extensive Monte Carlo simulations under different settings. We observed highly competitive performance of adaptive lasso compared to Bayesian approaches. Methods for selecting tuning parameters are also thoroughly discussed based on results from numerical studies and an illustration example.

Accuracy of a Rapid Multiplex Polymerase Chain Reaction Plus a Chromogenic Phenotypic Test Algorithm for Detection of Extended-Spectrum ß-Lactamase and Carbapenemase-Producing Gram-Negative Bacilli in Positive Blood Culture Bottles.

We studied the performance of an algorithm combining multiplex polymerase chain reaction with phenotypic detection of extended-spectrum ß-lactamases and carbapenemases directly from positive blood culture bottles in patients with gram-negative bacteremia and found good concordance with routine cultures. Such an algorithm may be a tool to improve time to optimal therapy in patients with gram-negative bacteremia.

Antibody Response of Heterologous vs Homologous Messenger RNA Vaccine Boosters Against the Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant: Interim Results from the PRIBIVAC Study, a Randomized Clinical Trial.

BACKGROUND: Waning antibody levels post-vaccination and the emergence of variants of concern (VOCs) capable of evading protective immunity have raised the need for booster vaccinations. However, which combination of coronavirus disease 2019 (COVID-19) vaccines offers the strongest immune response against the Omicron variant is unknown. METHODS: This randomized, participant-blinded, controlled trial assessed the reactogenicity and immunogenicity of different COVID-19 vaccine booster combinations. A total of 100 BNT162b2-vaccinated individuals were enrolled and randomized 1:1 to either homologous (BNT162b2 + BNT162b2 + BNT162b2; "BBB") or heterologous messenger RNA (mRNA) (BNT162b2 + BNT162b2 + mRNA-1273; "BBM") booster vaccine. The primary end point was the level of neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type and VOCs at day 28. RESULTS: A total of 51 participants were allocated to BBB and 49 to BBM; 50 and 48, respectively, were analyzed for safety and immunogenicity outcomes. At day 28 post-boost, mean SARS-CoV-2 spike antibody titers were lower with BBB (22 382 IU/mL; 95% confidence interval [CI], 18 210 to 27 517) vs BBM (29 751 IU/mL; 95% CI, 25 281 to 35 011; P = .034) as was the median level of neutralizing antibodies: BBB 99.0% (interquartile range [IQR], 97.9% to 99.3%) vs BBM 99.3% (IQR, 98.8% to 99.5%; P = .021). On subgroup analysis, significant higher mean spike antibody titer, median surrogate neutralizing antibody level against all VOCs, and live Omicron neutralization titer were observed only in older adults receiving BBM. Both vaccines were well tolerated. CONCLUSIONS: Heterologous mRNA-1273 booster vaccination compared with homologous BNT123b2 induced a stronger neutralizing response against the Omicron variant in older individuals. CLINICAL TRIALS REGISTRATION: NCT05142319.

Very Low-Efficiency Droop in 293 nm AlGaN-Based Light-Emitting Diodes Featuring a Subtly Designed p-Type Layer.

This paper reports an AlGaN-based ultraviolet-B light-emitting diode (UVB-LED) with a peak wavelength at 293 nm that was almost free of efficiency droop in the temperature range from 298 to 358 K. Its maximum external quantum efficiencies (EQEs), which were measured at a current density of 88.6 A cm-2, when operated at 298, 318, and 338 K were 2.93, 2.84, and 2.76%, respectively; notably, however, the current droop (J-droop) in each of these cases was less than 1%. When the temperature was 358 K, the maximum EQE of 2.61% occurred at a current density of 63.3 A cm-2, and the J-droop was 1.52%. We believe that the main mechanism responsible for overcoming the J-droop was the uniform distribution of the concentrations of injected electrons and holes within the multiple quantum wells. Through the subtle design of the p-type AlGaN layer, with the optimization of the composition and doping level, the hole injection efficiency was enhanced, and the Auger recombination mechanism was inhibited in an experimental setting.

Tri-modal management of primary small cell carcinoma of the pancreas (SCCP): a rare neuroendocrine carcinoma (NEC).

BACKGROUND: Primary small cell carcinoma of the pancreas (SCCP) is a rare malignant neuroendocrine carcinoma (NEC). Typically, it presents with lymphovascular invasion as well as metastasis at the time of diagnosis which portends a dismal prognosis. Treatment is typically based on therapy used for other aggressive NECs such as small cell lung cancer. Although multimodal surgery, radiation and chemotherapy may improve prognosis, the outcome generally remains poor. CASE PRESENTATION: Here we present a primary SCCP managed with neoadjuvant multi-agent chemotherapy combined with radiotherapy and surgery CONCLUSIONS: Multi-disciplinary therapy resulted in an ongoing 28 + month radiographic complete response and overall survival.

Testing for SARS-CoV-2: Can We Stop at 2?

The COVID-19 epidemic requires accurate identification and isolation of confirmed cases for effective control. This report describes the effectiveness of our testing strategy and highlights the importance of repeat testing in suspected cases in our cohort.

Study of Metal-Semiconductor-Metal CH3NH3PbBr3 Perovskite Photodetectors Prepared by Inverse Temperature Crystallization Method.

Numerous studies have addressed the use of perovskite materials for fabricating a wide range of optoelectronic devices. This study employs the deposition of an electron transport layer of C60 and an Ag electrode on CH3NH3PbBr3 perovskite crystals to complete a photodetector structure, which exhibits a metal-semiconductor-metal (MSM) type structure. First, CH3NH3PbBr3 perovskite crystals were grown by inverse temperature crystallization (ITC) in a pre-heated circulator oven. This oven was able to supply uniform heat for facilitating the growth of high-quality and large-area crystals. Second, the different growth temperatures for CH3NH3PbBr3 perovskite crystals were investigated. The electrical, optical, and morphological characteristics of the perovskite crystals were analyzed by X-ray diffraction (XRD), scanning electron microscopy (SEM), ultraviolet-visible spectroscopy, and photoluminescence (PL). Finally, the CH3NH3PbBr3 perovskite crystals were observed to form a contact with the Ag/C60 as the photodetector, which revealed a responsivity of 24.5 A/W.

An alternative tool for triaging patients with possible acute coronary symptoms before admission to a chest pain unit.

OBJECTIVE: This study aimed to develop a triage tool to more effectively triage possible ACS patients presenting to the emergency department (ED) before admission to a protocol-driven chest pain unit (CPU). METHODS: Seven hundred ninety-three clinical cases, randomly selected from 7962 possible ACS cases, were used to develop and test an ACS triage model using cluster analysis and stepwise logistic regression. RESULTS: The ACS triage model, logit (suspected ACS patient)=-5.283+1.894×chest pain+1.612×age+1.222×male+0.958×proximal radiation pain+0.962×shock+0.519×acute heart failure, with a threshold value set at 2.5, was developed to triage patients. Compared to four existing methods, the chest-pain strategy, the Zarich's strategy, the flowchart, and the heart broken index (HBI), the ACS triage model had better performance. CONCLUSION: This study developed an ACS triage model for triaging possible ACS patients. The model could be used as a rapid tool in EDs to reduce the workloads of ED nurses and physicians in relation to admissions to the CPU.

Syphilis Masquerading As Mass Lesions: The Utility of Modern-Day Imaging and Molecular Sequencing in Clinical Diagnosis.

Syphilis has been known to present in a myriad of symptoms throughout the ages, and until this day, the diagnosis remains elusive to the modern physician. We present 2 unusual cases of syphilis that posed diagnostic challenges even in the current era of new and advancing diagnostic tests.

Graphical message transmission using the monotonic vibration function of a smart phone.

This study aimed at evaluating four vibrotactile capabilities for perceiving graphical information presented on a smart phone. Thirty-two blindfolded college students participated in four experiments to test their capabilities of two-point discrimination, relative and absolute judgments of line thickness, and recognition of basic shapes. All the information was received through the default vibration function of the phone, sensed by their scanning fingers. The results showed a good two-point discrimination accuracy rate, reaching 98.8% when the distance between two points was set at 3.2 mm; the relative judgment of line thickness reached the level of 78.3% accuracy when the two-line width difference ratio was set at 3%; the absolute judgment reached the level of 78.8% when the participants recognised line thickness from one of two. Overall, especially for the shapes judgment, the information transmitted by the various codes may be quite low. These findings should inspire advanced investigations and provide design guidelines. PRACTITIONER SUMMARY: This study tested four vibrotactile capabilities for perception of graphical information when solely using the monotonic vibration function of a smart phone. The results show low information transmission. These findings encourage advanced investigations of new coding systems so that relevant mobile applications could be developed to help the visually impaired.

Measuring individual corrective reaction time using the intermittent illumination model.

The corrective reaction time (tcr) is an essential motor property when modelling hand control movements. Many studies designed experiments to estimate tcr, but reported only group means with inconsistent definitions. This study proposes an alternative methodology using Drury's (1994) intermittent illumination model. A total of 24 participants performed circular tracking movements under five levels of visual information delay using a modified monitor in a darkened room. Measured movement speeds and the manipulated delays were used with the model to estimate tcr of individuals and test effects of gender and path width. The results showed excellent model fits and demonstrated individual differences of tcr, which was 273 ms on average and ranged from 87 to 441 ms. The wide range of tcr values was due to significant effects of gender and path width. Male participants required shorter tcr compared to female participants, especially for narrow path widths. PRACTITIONER SUMMARY: This study reports the corrective reaction time (tcr) of individuals using a novel methodology. The estimated tcr ranged from 87 to 441 ms, helping model hand control movements, such as aiming and tracking. The methodology can be continuously applied to study tcr under conditions with various performers and movements.

First SARS-CoV-2 Omicron infection as an effective immune booster among mRNA vaccinated individuals: final results from the first phase of the PRIBIVAC randomised clinical trial.

BACKGROUND: Understanding how SARS-CoV-2 breakthrough infections impacts the breadth of immune responses against existing and pre-emergent SARS-CoV-2 strains is needed to develop an evidence-based long-term immunisation strategy. METHODS: We performed a randomised, controlled trial to assess the immunogenicity of homologous (BNT162b2) versus heterologous (mRNA-1273) booster vaccination in 100 BNT162b2-vaccinated infection-naïve individuals enrolled from October 2021. Post hoc analysis was performed to assess the impact of SARS-CoV-2 infection on humoral and cellular immune responses against wild-type SARS-CoV-2 and/or Omicron subvariants. FINDINGS: 93 participants completed the study at day 360. 71% (66/93) of participants reported first SARS-CoV-2 Omicron infection by the end of the study with similar proportions of infections between homologous and heterologous booster groups (72.3% [34/47] vs 69.6% [32/46]; p = 0.82). Mean wildtype SARS-CoV-2 anti-S-RBD antibody level was significantly higher in heterologous booster group compared with homologous group at day 180 (14,588 IU/mL; 95% CI, 10,186-20,893 vs 7447 IU/mL; 4646-11,912; p = 0.025). Participants who experienced breakthrough infections during the Omicron BA.1/2 wave had significantly higher anti-S-RBD antibody levels against wildtype SARS-CoV-2 and antibody neutralisation against BA.1 and pre-emergent BA.5 compared with infection-naïve participants. Regardless of hybrid immunity status, wildtype SARS-CoV-2 anti-S-RBD antibody level declined significantly after six months post-booster or post-SARS-CoV-2 infection. INTERPRETATION: Booster vaccination with mRNA-1273 was associated with significantly higher antibody levels compared with BNT162b2. Antibody responses are narrower and decline faster among uninfected, vaccinated individuals. Boosters may be more effective if administered shortly before infection outbreaks and at least six months after last infection or booster. FUNDING: Singapore NMRC, USFDA, MRC.

Immunogenicity of mRNA vs. BBV152 vaccine boosters against Omicron subvariants: Final results from Phase B of the PRIBIVAC study, a randomized clinical trial.

BACKGROUND: BBV152 (Covaxin™) is a whole-virion inactivated SARS-CoV-2 vaccine mixed with an immune adjuvant. We aimed to compare immune responses after booster vaccination with heterologous BBV152 versus homologous mRNA vaccine. METHODS: We conducted a randomized, participant-blinded, controlled trial. Fifty mRNA-vaccinated participants were enrolled and randomized to receive an mRNA booster (n = 26) or BBV152 (n = 24). Blood samples were collected pre-vaccination, and at Day 7, 28, 180 and 360 post-booster for analysis of humoral and cellular immune responses. Primary end point was the SARS-CoV-2 anti-spike antibody titer at day 28. RESULTS: Recruitment began in January 2022 and was terminated early due to the BBV152 group meeting pre-specified criteria for futility. At Day 28 post-boost, mean SARS-CoV-2 spike antibody titers were lower with BBV152 (2004 IU/mL; 95 % confidence interval [CI], 1132-3548) vs mRNA (26,669 IU/mL; 95 % CI, 21,330-33,266; p < 0.0001), but comparable levels of spike-specific CD4 and cytotoxic T-cells were observed. Anti-spike antibody titers remained significantly different at Day 180: BBV152 4467 IU/mL (95 % CI, 1959-10,186) vs mRNA 20,749 IU/mL (95 % CI, 12,303-35,075; p = 0.0017). Levels of surrogate virus neutralizing antibodies against ancestral and Omicron subvariants BA.1 and BA.2 were significantly higher among mRNA recipients at Day 180, including after adjusting for intercurrent infection. By Day 360, anti-spike antibody titers and neutralizing antibody levels against Omicron subvariants became similar between vaccine groups. By the end of the study, 16 in each arm (mRNA 64 % and BBV152 69.6 %) had breakthrough infections and time to COVID-19 infection between vaccine groups were similar (p = 0.63). CONCLUSIONS: Wild-type SARS-CoV-2 anti-spike antibody titer and surrogate virus neutralizing test levels against wild-type SARS-CoV-2 and Omicron subvariants BA.1/BA.2/BA.5 were significantly higher at Day 28 and 180 in individuals who received booster vaccination with an mRNA vaccine compared with BBV152. CLINICAL TRIAL REGISTRATION NUMBER: NCT05142319.

Suppressed quantum-confined Stark effect in InGaN-based LEDs with nano-sized patterned sapphire substrates.

This paper demonstrates that quantum-confined Stark effect (QCSE) within the multiple quantum wells (MQWs) can be suppressed by the growths of InGaN-based light-emitting diodes (LEDs) on the nano-sized patterned c-plane sapphire substrates (PCSSs) with reducing the space. The efficiency droop is also determined by QCSE. As verified by the experimentally measured data and the ray-tracing simulation results, the suppressed efficiency droop for the InGaN-based LED having the nano-sized PCSS with a smaller space of 200 nm can be acquired due to the weaker function of the QCSE within the MQWs as a result of the smaller polarization fields coming from the lower compressive strain in the corresponding epitaxial layers.

Verification of models for ballistic movement time and endpoint variability.

A hand control movement is composed of several ballistic movements. The time required in performing a ballistic movement and its endpoint variability are two important properties in developing movement models. The purpose of this study was to test potential models for predicting these two properties. Twelve participants conducted ballistic movements of specific amplitudes using a drawing tablet. The measured data of movement time and endpoint variability were then used to verify the models. This study was successful with Hoffmann and Gan's movement time model (Hoffmann, 1981; Gan and Hoffmann 1988) predicting more than 90.7% data variance for 84 individual measurements. A new theoretically developed ballistic movement variability model, proved to be better than Howarth, Beggs, and Bowden's (1971) model, predicting on average 84.8% of stopping-variable error and 88.3% of aiming-variable errors. These two validated models will help build solid theoretical movement models and evaluate input devices. PRACTITIONER SUMMARY: This article provides better models for predicting end accuracy and movement time of ballistic movements that are desirable in rapid aiming tasks, such as keying in numbers on a smart phone. The models allow better design of aiming tasks, for example button sizes on mobile phones for different user populations.

Identification of Healthy Tissue from Malignant Tissue in Surgical Margin Using Raman Spectroscopy in Oral Cancer Surgeries.

Accurate identification of tissue types in surgical margins is essential for ensuring the complete removal of cancerous cells and minimizing the risk of recurrence. The objective of this study was to explore the clinical utility of Raman spectroscopy for the detection of oral squamous cell carcinoma (OSCC) in both tumor and healthy tissues obtained from surgical resection specimens during surgery. This study enrolled a total of 64 patients diagnosed with OSCC. Among the participants, approximately 50% of the cases were classified as the most advanced stage, referred to as T4. Raman experiments were conducted on cryopreserved tissue samples collected from patients diagnosed with OSCC. Prominent spectral regions containing key oral biomarkers were analyzed using the partial least squares-support vector machine (PLS-SVM) method, which is a powerful multivariate analysis technique for discriminant analysis. This approach effectively differentiated OSCC tissue from non-OSCC tissue, achieving a sensitivity of 95.7% and a specificity of 93.3% with 94.7% accuracy. In the current study, Raman analysis of fresh tissue samples showed that OSCC tissues contained significantly higher levels of nucleic acids, proteins, and several amino acids compared to the adjacent healthy tissues. In addition to differentiating between OSCC and non-OSCC tissues, we have also explored the potential of Raman spectroscopy in classifying different stages of OSCC. Specifically, we have investigated the classification of T1, T2, T3, and T4 stages based on their Raman spectra. These findings emphasize the importance of considering both stage and subsite factors in the application of Raman spectroscopy for OSCC analysis. Future work will focus on expanding our tissue sample collection to better comprehend how different subsites influence the Raman spectra of OSCC at various stages, aiming to improve diagnostic accuracy and aid in identifying tumor-free margins during surgical interventions.