An analysis of physiological responses as indicators of driver takeover readiness in conditionally automated driving.

By the year 2045, it is projected that Autonomous Vehicles (AVs) will make up half of the new vehicle market. Successful adoption of AVs can reduce drivers' stress and fatigue, curb traffic congestion, and improve safety, mobility, and economic efficiency. Due to the limited intelligence in relevant technologies, human-in-the-loop modalities are still necessary to ensure the safety of AVs at current or near future stages, because the vehicles may not be able to handle all emergencies. Therefore, it is important to know the takeover readiness of the drivers to ensure the takeover quality and avoid any potential accidents. To achieve this, a comprehensive understanding of the drivers' physiological states is crucial. However, there is a lack of systematic analysis of the correlation between different human physiological responses and takeover behaviors which could serve as important references for future studies to determine the types of data to use. This paper provides a comprehensive analysis of the effects of takeover behaviors on the common physiological indicators. A program for conditional automation was developed based on a game engine and applied to a driving simulator. The experiment incorporated three types of secondary tasks, three takeover events, and two traffic densities. Brain signals, Skin Conductance Level (SCL), and Heart Rate (HR) of the participants were collected while they were performing the driving simulations. The Frontal Asymmetry Index (FAI) (as an indicator of engagement) and Mental Workload (MWL) were calculated from the brain signals to indicate the mental states of the participants. The results revealed that the FAI of the drivers would slightly decrease after the takeover alerts were issued when they were doing secondary tasks prior to the takeover activities, and the higher difficulty of the secondary tasks could lead to lower overall FAI during the takeover periods. In contrast, The MWL and SCL increased during the takeover periods. The HR also increased rapidly at the beginning of the takeover period but dropped back to a normal level quickly. It was found that a fake takeover alert would lead to lower overall HR, slower increase, and lower peak of SCL during the takeover periods. Moreover, the higher traffic density scenarios were associated with higher MWL, and a more difficult secondary task would lead to higher MWL and HR during the takeover activities. A preliminary discussion of the correlation between the physiological data, takeover scenario, and vehicle data (that relevant to takeover readiness) was then conducted, revealing that although takeover event, SCL, and HR had slightly higher correlations with the maximum acceleration and reaction time, none of them dominated the takeover readiness. In addition, the analysis of the data across different participants was conducted, which emphasized the importance of considering standardization or normalization of the data when they were further used as input features for estimating takeover readiness. Overall, the results presented in this paper offer profound insights into the patterns of physiological data changes during takeover periods. These findings can be used as benchmarks for utilizing these variables as indicators of takeover preparedness and performance in future research endeavors.

Predictive Value of CT Biomarkers in Lung Transplantation Survival: Preliminary Investigation in a Diverse, Underserved, Urban Population.

INTRODUCTION: Survival following lung transplant is low. With limited donor lung availability, predicting post-transplant survival is key. We investigated the predictive value of pre-transplant CT biomarkers on survival. METHODS: In this single-center retrospective cohort study of adults in a diverse, underserved, urban lung transplant program (11/8/2017-5/20/2022), chest CTs were analyzed using TeraRecon to assess musculature, fat, and bone. Erector spinae and pectoralis muscle area and attenuation were analyzed. Sarcopenia thresholds were 34.3 (women) and 38.5 (men) Hounsfield Units (HU). Visceral and subcutaneous fat area and HU, and vertebral body HU were measured. Demographics and pre-transplant metrics were recorded. Survival analyses included Kaplan-Meier and Cox proportional hazard. RESULTS: The study cohort comprised 131 patients, 50 women, mean age 60.82 (SD 10.15) years, and mean follow-up 1.78 (SD 1.23) years. Twenty-nine percent were White. Mortality was 32.1%. Kaplan-Meier curves did not follow the proportional hazard assumption for sex, so analysis was stratified. Pre-transplant EMR metrics did not predict survival. Women without sarcopenia at erector spinae or pectoralis had 100% survival (p = 0.007). Sarcopenia did not predict survival in men and muscle area did not predict survival in either sex. Men with higher visceral fat area and HU had decreased survival (p = 0.02). Higher vertebral body density predicted improved survival in men (p = 0.026) and women (p = 0.045). CONCLUSION: Pre-transplantation CT biomarkers had predictive value in lung transplant survival and varied by sex. The absence of sarcopenia in women, lower visceral fat attenuation and area in men, and higher vertebral body density in both sexes predicted survival in our diverse, urban population.

Comparative evaluation of pericervical dentin preservation and fracture resistance of root canal-treated teeth with rotary endodontic file systems of different types of taper - An in vitro study.

Aims: The aim of this study was to evaluate and compare the pericervical dentin preservation and fracture resistance of root canal-treated teeth with rotary endodontic file systems of different types of taper. Subjects and Methods: Thirty-two single-rooted human-extracted premolars were used. They were mounted in wax, and preoperative cone-beam computed tomography (CBCT) scans were taken with 11 × 8 Field of view (FOV). The evaluation of the pericervical dentin thickness was done at the cementoenamel junction level. After pre-CBCT, the 32 samples were divided into four groups (n = 8) - Group A: fixed tapered hand files, Group B: variable regressive tapered TruNatomy, Group C: progressive tapered ProTaper Gold, and Group D: fixed tapered HyFlex EDM. Following instrumentation, postoperative CBCT scans were taken to evaluate pericervical dentin thickness. Obturation was done and access cavity was restored with composite. Fracture strength was checked for all the samples using "universal testing machine" until fracture, and calculated in newtons (N). Statistical Analysis Used: Student's t-test and ANOVA test, along with Tukey's post hoc analysis, were used for comparing mean values between the groups, and P < 0.05 was considered statistically significant. Results: The results of this study showed that there is no statistically significant difference in preserving pericervical dentin with file system of different types of taper and fracture resistance between the groups. Conclusions: Within the limitations of the study, it was concluded that different types of file taper systems used for root canal preparation have no significant effect on the preservation of pericervical dentin and fracture resistance of teeth.

Veering to a Continuous Platform of Fused Deposition Modeling Based 3D Printing for Pharmaceutical Dosage Forms: Understanding the Effect of Layer Orientation on Formulation Performance.

Three-dimensional (3D) printing of pharmaceuticals has been centered around the idea of personalized patient-based 'on-demand' medication. Fused deposition modeling (FDM)-based 3D printing processes provide the capability to create complex geometrical dosage forms. However, the current FDM-based processes are associated with printing lag time and manual interventions. The current study tried to resolve this issue by utilizing the dynamic z-axis to continuously print drug-loaded printlets. Fenofibrate (FNB) was formulated with hydroxypropyl methylcellulose (HPMC AS LG) into an amorphous solid dispersion using the hot-melt extrusion (HME) process. Thermal and solid-state analyses were used to confirm the amorphous state of the drug in both polymeric filaments and printlets. Printlets with a 25, 50, and 75% infill density were printed using the two printing systems, i.e., continuous, and conventional batch FDM printing methods. Differences between the two methods were observed in the breaking force required to break the printlets, and these differences reduced as the infill density went up. The effect on in vitro release was significant at lower infill densities but reduced at higher infill densities. The results obtained from this study can be used to understand the formulation and process control strategies when switching from conventional FDM to the continuous printing of 3D-printed dosage forms.

Shared autonomy in assistive mobile robots: a review.

PURPOSE: Shared autonomy has played a major role in assistive mobile robotics as it has the potential to effectively balance user satisfaction and smooth functioning of systems by adapting itself to each user's needs and preferences. Many shared control paradigms have been developed over the years. However, despite these advancements, shared control paradigms have not been widely adopted as there are several integral aspects that have not fully matured. The purpose of this paper is to discuss and review various aspects of shared control and the technologies leading up to the current advancements in shared control for assistive mobile robots. METHODS: A comprehensive review of the literature was conducted following a dichotomy of studies from the pre-2000 and the post-2000 periods to focus on both the early developments and the current state of the art in this domain. RESULTS: A systematic review of 135 research papers and 7 review papers selected from the literature was conducted. To facilitate the organization of the reviewed work, a 6-level ladder categorization was developed based on the extent of autonomy shared between the human and the robot in the use of assistive mobile robots. This taxonomy highlights the chronological improvements in this domain. CONCLUSION: It was found that most prior studies have focussed on basic functionalities, thus paving the way for research to now focus on the higher levels of the ladder taxonomy. It was concluded that further research in the domain must focus on ensuring safety in mobility and adaptability to varying environments.Implications for rehabilitationShared autonomy in assistive mobile robots plays a vital role in effectively adapting to ensure safety while also considering the user comfort.User's immediate desires should be considered in decision making to ensure that the users are in control of the assistive robots.The current focus of research should be towards successful adaptation of the assistive mobile robots to varying environments to assure safety of the user.

Oral Delivery of Niclosamide as an Amorphous Solid Dispersion That Generates Amorphous Nanoparticles during Dissolution.

Niclosamide is an FDA-approved anthelmintic that is being studied in clinical trials as a chemotherapeutic and broad-spectrum antiviral. Additionally, several other applications are currently in the preclinical stage. Unfortunately, niclosamide is a poorly water soluble molecule, with reduced oral bioavailability, which hinders its use for new indications. Moreover, niclosamide is a poor glass former; in other words, the molecule has a high tendency to recrystallize, and it is virtually impossible to generate a stable amorphous solid employing the neat molecule. Previously, our group reported the development of an amorphous solid dispersion (ASD) of niclosamide (niclosamide ASD) that generates nanoparticles during its dissolution, not only increasing niclosamide's apparent solubility from 6.6 ± 0.4 to 481.7 ± 22.2 µg/mL in fasted state simulated intestinal fluid (FaSSIF) but also its oral bioavailability 2.6-fold in Sprague-Dawley rats after being administered as a suspension. Nevertheless, niclosamide ASD undergoes recrystallization in acidic media, and an enteric oral dosage form is needed for its translation into the clinic. In this work, we further characterized the nanoparticles that generated during the dissolution of the niclosamide ASD. Cryogenic transmission electron microscopy (Cryo-TEM) and wide-angle X-ray scattering (WAXS) revealed that the nanoparticles were amorphous and had a particle size of ~150 nm. The oral dosage forms of niclosamide ASD were formulated using commercial enteric capsules (Capsuline® and EudracapTM) and as enteric-coated tablets. The enteric dosage forms were tested using pH-shift dissolution and acid-uptake tests, using the USP type II dissolution apparatus and the disintegration apparatus, respectively. The capsules exhibited a higher percentage of weight gain, and visual rupture of the Capsuline capsules was observed. Eudracap capsules protected the formulation from the acidic media, but polymer gelling and the formation of a nondispersible plug were noted during dissolution testing. In contrast, enteric-coated tablets protected the formulation from acid ingress and maintained the performance of niclosamide ASD granules during dissolution in FaSSIF media. These enteric-coated tablets were administered to beagle dogs at a niclosamide dose of 75 mg/kg, resulting in plasma concentrations of niclosamide higher than those reported in the literature using solubilized niclosamide at a higher dose (i.e., 100 mg/kg). In summary, an enteric oral dosage form of niclosamide ASD was formulated without hindering the generation of nanoparticles while maintaining the increase in the niclosamide's apparent solubility. The enteric-coated tablets successfully increased the niclosamide plasma levels in dogs when compared to a niclosamide solution prepared using organic solvents.

Using Routine Chest Computed Tomography to Diagnose Pulmonary Embolism.

OBJECTIVE: This study investigated the use of routine contrast-enhanced chest computed tomography (CT) to diagnose unsuspected pulmonary embolism (PE). METHODS: All adult routine contrast-enhanced chest CTs performed at Montefiore in 2018 were included. Pulmonary artery enhancement was measured by placing regions of interest in the pulmonary vasculature. Adequate enhancement was defined as 200 Hounsfield units (HU) or greater. Presence or absence of PE was noted. Descriptive statistics and logistic regression analysis were performed. RESULTS: A total of 3164 CTs were evaluated (55.8% women; mean age, 63.2 years). Main pulmonary enhancement was highly correlated with peripheral enhancement. Of all cases, 28.7% (907 of 3164) reached the 200 HU threshold. Greater enhancement was associated with female sex, older age, outpatients, and contrast amount administered. Pulmonary embolism-positive cases comprised 1.8% (58 of 3164) of total cases. Furthermore, 39.7% (23 of 58) of PE-positive cases reached the 200 HU threshold. CONCLUSIONS: Over one quarter of routine contrast-enhanced chest CT scans met the 200 HU threshold indicative of adequate pulmonary artery enhancement, including nearly half of the 2% of examinations positive for PE.

Sensor Acquisition and Allocation for Real-Time Monitoring of Articulated Construction Equipment in Digital Twins.

The visibility available to an equipment operator on a dynamic construction site can often be blocked by various obstacles such as materials, temporary or permanent facilities, other equipment, and workers. Equipment monitoring in real-time digital twins can thus play a crucial role in accident prevention. This paper develops a scalable technical approach and presents a prototype application framework for transmitting real world sensor data to update 3D equipment models inside a graphical digital twin for concurrent visualization of a monitored construction operation. The developed framework and workflow can be extended to visualize any construction operation, as it occurs, inside a dynamic 3D world simply by outfitting the real equipment with appropriate sensors and connecting them to their virtual counterparts. The implemented proof-of-concept interface is described in the context of a real-time 3D digital twin for assisting excavator operators prevent unintended strikes with underground utilities. Experiments to validate the proposed technical approach by simulating the real-time motion of a backhoe loader's articulated arm using orientation sensors installed on its boom, stick, and bucket are described. The experimental results characterize the scope and potential reasons for spatio-temporal discrepancies that can occur between a monitored real operation and its replicated digital twin. The effect of an operator warning mechanism based on preset safety thresholds is also investigated and described.

Novel 3D Printed Modular Tablets Containing Multiple Anti-Viral Drugs: a Case of High Precision Drop-on-Demand Drug Deposition.

3D printed drug delivery systems have gained tremendous attention in pharmaceutical research due to their inherent benefits over conventional systems, such as provisions for customized design and personalized dosing. The present study demonstrates a novel approach of drop-on-demand (DoD) droplet deposition to dispense drug solutions precisely on binder jetting-based 3D printed multi-compartment tablets containing 3 model anti-viral drugs (hydroxychloroquine sulfate - HCS, ritonavir and favipiravir). The printing pressure affected the printing quality whereas the printing speed and infill density significantly impacted the volume dispersed on the tablets. Additionally, the DoD parameters such as nozzle valve open time and cycle time affected both dispersing volume and the uniformity of the tablets. The solid-state characterization, including DSC, XRD, and PLM, revealed that all drugs remained in their crystalline forms. Advanced surface analysis conducted by microCT imaging as well as Artificial Intelligence (AI)/Deep Learning (DL) model validation showed a homogenous drug distribution in the printed tablets even at ultra-low doses. For a four-hour in vitro drug release study, the drug loaded in the outer layer was released over 90%, and the drug incorporated in the middle layer was released over 70%. In contrast, drug encapsulated in the core was only released about 40%, indicating that outer and middle layers were suitable for immediate release while the core could be applied for delayed release. Overall, this study demonstrates a great potential for tailoring drug release rates from a customized modular dosage form and developing personalized drug delivery systems coupling different 3D printing techniques.

Three-Dimensional Printing of a Container Tablet: A New Paradigm for Multi-Drug-Containing Bioactive Self-Nanoemulsifying Drug-Delivery Systems (Bio-SNEDDSs).

This research demonstrates the use of fused deposition modeling (FDM) 3D printing to control the delivery of multiple drugs containing bioactive self-nano emulsifying drug-delivery systems (SNEDDSs). Around two-thirds of the new chemical entities being introduced in the market are associated with some inherent issues, such as poor solubility and high lipophilicity. SNEDDSs provide for an innovative and easy way to develop a delivery platform for such drugs. Combining this platform with FDM 3D printing would further aid in developing new strategies for delivering poorly soluble drugs and personalized drug-delivery systems with added therapeutic benefits. This study evaluates the performance of a 3D-printed container system containing curcumin (CUR)- and lansoprazole (LNS)-loaded SNEDDS. The SNEDDS showed 50% antioxidant activity (IC50) at concentrations of around 330.1 µg/mL and 393.3 µg/mL in the DPPH and ABTS radical scavenging assay, respectively. These SNEDDSs were loaded with no degradation and leakage from the 3D-printed container. We were able to delay the release of the SNEDDS from the hollow prints while controlling the print wall thickness to achieve lag phases of 30 min and 60 min before the release from the 0.4 mm and 1 mm wall thicknesses, respectively. Combining these two innovative drug-delivery strategies demonstrates a novel option for tackling the problems associated with multi-drug delivery and delivery of drugs susceptible to degradation in, i.e., gastric pH for targeting disease conditions throughout the gastrointestinal tract (GIT). It is also envisaged that such delivery systems reported herein can be an ideal solution to deliver many challenging molecules, such as biologics, orally or near the target site in the future, thus opening a new paradigm for multi-drug-delivery systems.

Investigation of the Fused Deposition Modeling Additive Manufacturing I: Influence of Process Temperature on the Quality and Crystallinity of the Dosage Forms.

With the advancements in cutting-edge technologies and rapid development of medical sciences, patient-focused drug development (PFDD) through additive manufacturing (AM) processes is gathering more interest in the pharmaceutical area than ever. Hence, there is an urgent need for researchers to comprehensively understand the influence of three-dimensional design on the development of novel drug delivery systems (DDSs). For this research, fused deposition modeling (FDM) 3D printing was investigated, and phenytoin (PHT) was selected as the model drug. The primary purpose of the current investigation was to understand the influence of AM process on the pharmaceutical products' quality. A series of comparative studies, including morphology, solid-state analysis, and in vitro drug release studies between additive manufactured filaments (printlets) and extruded filaments, were conducted. The FDM-based AM showed adequate reproducibility by manufacturing printlets with consistent qualities; however, the model slicing orientation significantly affected the print qualities. The texture analysis studies showed that the mechanical properties (breaking behavior) of additive manufactured printlets were varied from the extruded filaments. Additionally, the higher printing temperature also influenced the solid state of the drug where the process assisted in PHT's amorphization in the printed products, which further affected their mechanical properties and in vitro drug release performances. The current investigation illustrated that the AM process would change the printed objects' macrostructure over the conventional products, and the printing temperature and slicing will significantly affect the printing process and product qualities.

Canal transportation and centering ability of root canals prepared using rotary and reciprocating systems with and without PathFiles in cone-beam computed tomography-based three-dimensional molar prototypes.

BACKGROUND: It is important to use instruments that cause minimal changes in the canal path for root canal preparation. There is inadequate literature comparing rotary and reciprocating systems and hand files. No study used three-dimensional printed models to compare rotary, reciprocating, and hand files. AIMS: We aimed to assess the canal transportation and centering ability of WaveOne Gold, ProTaper Gold, and NiTi Flex K-file systems with and without glide path preparation. MATERIAL AND METHODS: Forty-nine resin models were randomly divided into Group I A - WaveOne Gold with WaveOne Gold Glider and Group I B - WaveOne Gold without glide path; Group II A - ProTaper Gold with ProGlider and Group II B - ProTaper Gold without glide path; and Group III A - NiTi Flex K-files with no. 10 stainless steel K-file and Group III B - NiTi Flex K-files without glide path. Pre- and postinstrumentation cross-sectional images at levels 3, 5, 7, 9, and 11 mm were compared. RESULTS: WaveOne Gold caused the least canal transportation and improved centering ability (P < 0.05). NiTi Flex K-files transported the canal more than others in the apical levels (3, 5 mm). Glide path creation reduced canal transportation and improved canal-centering ability. CONCLUSIONS: WaveOne Gold system has better centering ability and lesser canal transportation than ProTaper Gold and NiTi Flex K-file. Glide path creation reduced canal transportation and improved canal-centering ability.

Non-traumatic hemoperitoneum in the ED setting: causes, characteristics, prevalence and sex differences.

PURPOSE: Prevalence and sex differences of non-traumatic hemoperitoneum in the Emergency Department has not been studied in the literature. METHODS: Following IRB approval, multiple keyword searches were used to identify all cases of hemoperitoneum over a 55-month period. Cases were reviewed to confirm and quantify the hemoperitoneum. Maximum attenuation was used to grade blood density. Medical records were reviewed to determine cause, interventions and outcomes in each patient. RESULTS: Of the 171 verified cases of non-traumatic hemoperitoneum, 76% of cases were in women. CT exams in women were positive for hemoperitoneum 0.25% of the time, while 0.13% were positive in men. Regarding size, 25.7% were large, 24.5% were moderate and 49.7% were small. Contrast-enhanced studies had HU values of 103 ± 19 (range 47-146) which were significantly higher than for non-enhanced studies with values of 82 ± 19 (range 43-121, p < 0.001). The most common cause of non-traumatic hemoperitoneum was ruptured ovarian cyst which was found in 58% of women (76 cases). Of these, 69 patients received observation, 6 patients underwent surgery and 1 patient received Vitamin K. For the 95 non-ovarian cyst cases, 65% patients were admitted and then discharged, 22% were discharged from the ED, 12% expired and 1% were transferred to a different hospital. Post-procedure hemorrhage was the second to most common cause in women (24/130 = 18%) and the most common etiology in men (14/41 = 34%). CONCLUSIONS: In women, ovarian cyst rupture was the most common etiology of hemoperitoneum. Post-procedure hemorrhage was second in women and the most common etiology in men. Although unusual causes of hemoperitoneum will be encountered, understanding the most common causes of hemoperitoneum can provide a reasonable starting point when attempting to determine the most likely etiology of hemoperitoneum in any individual patient.

Comparison of Optical Low-Coherence Reflectometry and Swept-Source OCT-Based Biometry Devices in Dense Cataracts.

PURPOSE: To investigate agreement between biometric measurements obtained from the Lenstar LS 900 (Haag-Streit AG) based on optical low-coherence reflectometry (OLCR) and the Tomey OA-2000 (Tomey Corporation) based on swept-source optical coherence tomography (SS-OCT) in dense cataracts. METHODS: In this prospective observational study, axial length, keratometry, anterior chamber depth (ACD), lens thickness, and central corneal thickness (CCT) were measured in 124 eyes of 76 patients. Intraocular lens prediction errors and absolute prediction errors were assessed based on postoperative manifest refraction. Analyses used were paired t test, Pearson correlation coefficient (r), and Bland-Altman plots. RESULTS: Failure in axial length measurements was noted in 28 eyes (22.58%) with OCLR compared to 2 eyes (1.6%) with SS-OCT. Although not statistically significant, axial length measurements were clinically higher with SS-OCT (23.78 ± 1.76 mm) compared to OCLR (23.72 ± 1.58 mm) (P = .81) (r = 0.23; P = .01). There was a significant trend toward myopic intraocular lens prediction with SS-OCT (-0.09 ± 0.48) compared to OLCR (0.09 ± 0.41, P < .01) (r = 0.25, P = .01). There was good agreement for keratometric and ACD values between the two devices. SS-OCT gave significantly higher values of lens thickness compared to OCLR (4.44 ± 0.44 vs 4.18 ± 0.48 mm, P < .01) (r = 0.39, P < .01). CCT measured with OCLR was significantly higher than SS-OCT (525.64 ± 27.0 vs 513.21 ± 29.24 µm; P < .01) (r = 0.98, P < .01). CONCLUSIONS: One-fifth of the patients with dense cataracts failed axial length measurement on OCLR. SS-OCT gives clinically higher axial length measurements leading to more myopic intraocular lens prediction errors postoperatively. OCLR provides higher pachymetry and lower lens thickness values compared to the SS-OCT device. [J Refract Surg. 2020;36(8):557-564.].

A comparative evaluation of cyclic fatigue resistance of FlexiCON (Edge Endo) files in rotary versus reciprocating motion at various curvatures - An in vitro study.

AIM: The aim of the study to compare the cyclic fatigue resistance of FlexiCON (Edge Endo) files in rotary versus reciprocating motion in coronal, middle, and apical curvature of the simulated artificial canal. MATERIALS AND METHODS: A total number of 36 new files, 25 mm length of ISO size 25 at the tip and a taper of 0.06, were used for the study and divided into two groups of 18 files each. Group I: FlexiCON X3, was used in a rotary motion and Group II: FlexiCON X1 was used in a reciprocating motion. Cyclic fatigue testing was conducted in a custom-made device that allowed for a reproducible simulation of a curved canal. The canal system, which comprised two adjustable stainless steel blocks, had a 60° angle of curvature and 3 mm width. The groups were further divided into three subgroups with six files in each, representing apical curvature (Group Ia/IIa), middle curvature (Group Ib/IIb), and Coronal curvature (Group Ic/IIc). Using X-Smart plus motor, files were used in rotary and reciprocating mode and the number of cycles to failure was recorded. STATISTICAL ANALYSIS: Data were analyzed using ANOVA and Post hoc followed by Dunnett's test and unpaired t-test using Statistical Package for the Social Sciences 16 version. RESULTS: FlexiCON X1 reciprocating files showed the maximum cyclic fatigue resistance at coronal curvature (1936.50 ± 1.09) followed by middle (1514.50 ± 1.07) and apical curvature (1487.50 ± 6.75), while FlexiCON X3 rotary files showed the maximum cyclic fatigue at the middle curvature (1106.00 ± 4.21), followed by coronal (920.00 ± 1.16) and apical curvature (757.00 ± 5.34). The statistical analysis revealed a statistically significant difference (P = 0.001) between the two groups. CONCLUSION: FlexiCON X1 reciprocating files showed better cyclic fatigue resistance at coronal, middle, and apical curvature compared to FlexiCON X3 rotary files.

Ventricular Myocardial Fat: An Unexpected Biomarker for Long-term Survival?

PURPOSE: To examine the association between myocardial fat, a poorly understood finding frequently observed on non-contrast CT, and all-cause mortality in patients with and without a history of prior MI. MATERIALS AND METHODS: A retrospective cohort from a diverse urban academic center was derived from chronic myocardial infarction (MI) patients (n = 265) and three age-matched patients without MI (n = 690) who underwent non-contrast chest CT between 1 January 2005-31 December 2008. CT images were reviewed for left and right ventricular fat. Electronic records identified clinical variables. Kaplan-Meier and Cox proportional hazard analyses assessed the association between myocardial fat and all-cause mortality. The net reclassification improvement assessed the utility of adding myocardial fat to traditional risk prediction models. RESULTS: Mortality was 40.1% for the no MI and 71.7% for the MI groups (median follow-up, 6.8 years; mean age, 73.7 ± 10.6 years). In the no MI group, 25.7% had LV and 49.9% RV fat. In the MI group, 32.8% had LV and 42.3% RV fat. LV and RV fat was highly associated (OR 5.3, p < 0.001). Ventricular fat was not associated with cardiovascular risk factors. Myocardial fat was associated with a reduction in the adjusted hazard of death for both the no MI (25%, p = 0.04) and the MI group (31%, p = 0.018). Myocardial fat resulted in the correct reclassification of 22% for the no MI group versus the Charlson score or calcium score (p = 0.004) and 47% for the MI group versus the Charlson score (p = 0.0006). CONCLUSIONS: Patients with myocardial fat have better survival, regardless of MI status, suggesting that myocardial fat is a beneficial biomarker and may improve risk stratification. KEY POINTS: • Myocardial fat is commonly found on chest CT, yet is poorly understood • Myocardial fat is associated with better survival in patients with and without prior MI and is not associated with traditional cardiovascular risk factors • This finding may provide clinically meaningful prognostic value in the risk stratification of patients.

Patent foramen ovale in patients with pulmonary embolism: A prognostic factor on CT pulmonary angiography?

BACKGROUND: Patent foramen ovale (PFO) in patients with acute pulmonary embolism (PE) represents a risk factor for mortality, but this has not been evaluated for CT pulmonary angiography (CTPA). The purpose of the present study was to assess the relationship between PFO and mortality in patients with acute PE diagnosed on CTPA. MATERIALS AND METHODS: This retrospective study included 268 adults [173 women, mean age 61 (range 22-98) years] diagnosed with acute PE on non-ECG-gated 64-slice CTPA in 2012 at our medical center. The images were reviewed for PFO by a panel of cardiothoracic radiologists with an average of 11 years of experience (range 1-25 years). CT signs of right heart strain and PE level were noted. Transthoracic echocardiograms (TTE), when available (n = 207), were reviewed for PFO by a cardiologist with subspecialty training in advanced imaging and with 3 years of experience. The main outcome was 30-day mortality. Fischer's exact test was utilized to compare mortality. RESULTS: PFO prevalence on CTPA was 22% (58/268) and 4% (9/207) on TTE. Overall 30-day mortality was 6% (16/268), 9% (5/58) for patients with PFO and 5% (11/210) for those without (p = 0.35). CT signs of right heart strain trended with higher mortality, but statistically significant only for hepatic vein contrast reflux [14% (6/44) vs 4% (10/224), p = 0.03]; right ventricular (RV) to left ventricular (LV) diameter ratio >1 [8% (13/156) vs RV:LV ≤ 1 3% (3/112), p = 0.07], septal bowing [10% (4/42) vs without 5% (12/226), p = 0.30]. CONCLUSION: PFO was demonstrated on CTPA in a proportion similar to the known population prevalence, while routine TTE was less sensitive. Mortality was non-significantly higher in patients with acute PE and PFO in this moderate-sized study. A larger study to answer this clinically important question is worthwhile.

Economic impacts of avian influenza outbreaks in Kerala, India.

This study assessed the short-run impact to poultry farmers, duck hatcheries, control costs, compensation paid to stakeholders (transfer payments) and market reactions on own and substitute product prices and backwater tourism (boat operators) due to avian influenza (AI) outbreaks in Kuttanad region of Kerala, India, during 2014. The primary data from 91 poultry farms (duck farms, broiler chicken and backyard poultry), four hatcheries and 90 backwater boat owners were collected through pre-tested schedules. The secondary data on transfer payments and expenditure incurred to control AI were collected from developmental departments and were analysed. The estimated loss (culling live birds, eggs and feed destruction) per duck farm was USD 9,181, USD 3,889 and USD 156 in case of commercial farms reared for meat, dual-purpose and backyard farms, respectively. The loss incurred by small-scale broiler and backyard poultry farms was USD 453 and USD 40, respectively. The loss incurred by large and small duck hatcheries was USD 11,963 and USD 5,790, respectively, due to culling of hatchlings, young birds and destroying eggs. The government invested USD 744,890 to contain the disease spread through massive culling, surveillance and monitoring of poultry and humans due to zoonotic nature of the disease. A sharp market reaction on own and substitute product prices and eight weeks' time lag in price recovery was observed. The consequential impact on tourism especially for the backwater boat operators amounted to a loss of USD 2,280/boat due to fall in tourist inflow. Since, control measures are post-incidence, it is necessary to adopt appropriate preventive bio-security measures at the farm level besides periodical screening of domestic birds in migratory birds' flyway locations like Kuttanad to reduce the AI burden on various stakeholders including government.

Can the generic antiretroviral industry support access to a universal antiretroviral regimen?

PURPOSE OF REVIEW: The generic antiretroviral (ARV) industry played a critical role in the massive scale-up of HIV treatment in low-income and middle-income countries since 2000. As the global community looks ahead to a universal antiretroviral regimen, this article considers the industry's role in supporting universal access to affordable, simpler, more durable, and tolerable HIV treatment regimens. RECENT FINDINGS: Generic manufacturers made treatment scale-up in low-income and middle-income countries possible through reducing prices, combining molecules from different originator companies to develop optimal fixed-dose combinations, and investing in production capacity to meet escalating demand. Achieving scale-up of a universal regimen will require continued partnership in these areas. Collaboration on the demand and supply sides of the ARV marketplace will be required to foster a healthy and sustainable marketplace for new regimens. This includes clear priority setting from the global treatment community on priority products; predictable demand; regulatory prioritization of optimal products; effective tendering and procurement practices that enable multiple suppliers to participate in the market; coordinated product introduction efforts between Ministries of Health, partners, and civil society; and transparency from both buyers and suppliers to promote and monitor supply security. SUMMARY: New regimens will benefit people living with HIV, as well as buyers and generic suppliers, by maximizing existing production capacity and treatment budgets to reach the 90-90-90 goals.

A cost-savings analysis of a candidate universal antiretroviral regimen.

PURPOSE OF REVIEW: Despite significant strides in tackling HIV/AIDS in low-income and middle-income countries (LMICs), many treatment shortcomings remain, with limited drug selection to patients emerging as a critical challenge. The potential cost-savings benefits of adopting newer drugs as near-universal first-line antiretroviral (ARV) regimens that also provide improved clinical outcomes are discussed. RECENT FINDINGS: In the near term, a fixed-dose combination of dolutegravir (DTG or D) with tenofovir disoproxil fumarate (TDF), and either lamivudine or emtricitabine (XTC), that is, tenofovir disoproxil fumarate/XTC/DTG (TXD) (X = XTC), could represent a near-universal first-line antiretroviral regimen offering significant clinical benefit, commodity savings, and overall health system savings. In the longer term, tenofovir alafenamide fumarate (TAF) could further reduce the cost of the first-line treatment backbone, with possible clinical benefits. Relative to the current generic standard of care in first-line, currently priced at ∼USD 90 per patient per year (pppy), high-volume production of TXD could lead to price reductions of ∼USD 20 pppy, whereas high-volume production of tenofovir alafenamide fumarate/XTC/DTG (TAFXD) could offer a reduction of ∼USD 40 pppy. SUMMARY: With TXD in the near term, and TAFXD in the longer term, patients can benefit from better tolerated and more durable treatment, and programs will benefit by simplifying patient care and reducing cost to cover more patients.