Greater Margin Of Safety Research Articles

Improving Pedestrian Safety with Head-Up Display Warning in a Connected Environment

In this paper, the potential of using a head-up display (HUD) in the connected environment to improve a vehicle’s running comfort and pedestrian safety is tested, by providing warning information to drivers in advance. To achieve this objective, driving simulation technology is used to construct the connected environment and develop the HUD, and the effectiveness of the system is then tested. Specifically, thirty-four participants were recruited to conduct driving simulation experiments in six scenarios: three warning display types (Baseline/Head-down display/Head-up display) combined with two weather conditions (clear weather/foggy weather). The effects of the three different warning display types on braking risk-avoidance strategy were studied by comparing the drivers’ performance during the perception and decision stage (position of accelerator-pedal release, position of first braking), the risk-avoidance manipulation stage (maximum deceleration, braking distance) and the risk-avoidance result stage (minimum collision distance, position of minimum speed). The influences of weather conditions and driver attributes were also considered. When the HUD warnings were activated, drivers started to decelerate further away from pedestrians, with a more stable and moderate deceleration process and a greater safety margin between the vehicle and the pedestrians. Using HUD warnings in foggy conditions improved drivers’ perception and decision abilities, this study confirmed the great benefits that HUD warnings in the connected environment can bring to traffic safety, especially under risky situations and inclement weathers. The research results provide a reference for the more humanized and rationalized optimization design of these warning systems.

Fuel performance evaluation of two high burnup PWR core designs during normal operation, control rod withdrawal, and control rod ejection scenarios

There is interest among utilities to extend the current, 18-month operating cycle to 24 months. Economically, this extension would require greater than 5 % enrichment and peak rod average discharge burnup levels above 62 GWd/MTU. A notable challenge of increasing enrichment is the resulting additional excess reactivity encountered during the early stages of fuel life. To accommodate, burnable absorbers beyond soluble boron are introduced into the fuel system. In high burnup fuels, the possibilities of cladding lift-off and fuel melting increase due, in part, to increased rod internal pressures and limited fuel thermal conductivity, respectively. This work collaboratively employs PARCS, RELAP5-3D, and BISON to compare the fuel performance of two high burnup fuel candidates with higher than 5 % enrichment. The fuel performance parameters were compared to current NRC guidance. The results demonstrate an annular fuel design with homogenously blended gadolinium as a burnable absorber operates with greater safety margins during normal operation, allowing for additional operational flexibility. During normal operation, the core design utilizing Integral Fuel Burnable Absorber pins contained fuel pins which reached plenum pressures above 15.5 MPa by the end of the first fuel cycle and fuel pins experienced cladding hoop strains above 1 %. In the Gd core design, only two observed pins experienced plenum pressures above 15.5 MPa and no pins exceeded 1 % cladding hoop strain. During the control rod withdrawal scenario, plenum pressures for pins in both designs marginally exceeded system pressure, however neither experienced excessive hoop strain. The Gd core design experienced a maximum fuel temperature of 2418 K, which is significantly higher than the Integral Fuel Burnable Absorber design at 2157 K, but still within regulatory guidance. We predicted that the fuel in both could return to service after the CRW event. We also predicted that cladding would not fail during the Control Rod Ejection in either core design. Generally, the Integral Fuel Burnable Absorber core design performed with greater safety margin with regards to temperature during normal operation and the transient events. However, the Gd core design performed with greater safety margin regarding plenum pressure and hoop strain limits during normal operation and both transient events.

Task difficulty, risk feeling, and safety margin in the determination of driver behavior to prepare for traffic conflicts

Unpredictable pedestrian and cyclist behavior associated with their appearance on the road in blind spots contributes to traffic near-misses or crashes. When experienced drivers are confronted with uncertainty, they take defensive measures called hazard-anticipatory driving, such as decreasing the vehicle velocity and/or increasing the lateral distance. Our research sought to understand the motivational determinants and perceptual processes that determine driver behavior in preparation for traffic conflicts with covert hazards.This study aimed to investigate the influence of driving experience on drivers’ perceptions and behaviors to prepare for traffic conflicts. Two experiments were designed with 8 experienced and 13 inexperienced participants. In Experiment 1, participants were asked to provide their subjective impressions of task difficulty, feeling of risk, and statistical risk pertaining to assess their perceptions of the separation between task demand and capability after viewing animation clips of road scenes with blind intersections under different forced speeds. In Experiment 2, participants drove using a driving simulator in scenes with blind intersections, similar to those in Experiment 1. We sought to explore the motivational determinants of behavior regarding the relationship between subjective feelings and objective safety margins.The results showed that the driver’s perception of task difficulty correlated with their driving speed, and inexperienced participants tended to underestimate task difficulty compared to experienced participants. The task difficulty and the feeling of risk were strongly correlated regardless of experience, and estimation of statistical risk differed depending on experience. The subjective task difficulty (and/or risk feeling) and objective safety margin were strongly correlated for experienced participants. Experienced participants who perceived a higher degree of difficulty in the forced-paced driving task tended to have greater safety margins in the self-paced driving task. These findings suggest that experienced participants with individually tolerable safety margins adjust their driving velocity and/or lateral distance in the control of task difficulty (and/or risk feeling) to prepare for traffic conflicts. Therefore, the underestimation of task difficulty should be considered when designing effective measures, such as driver assistance systems, to guide inexperienced drivers toward normative behaviors.

Systemic Ropivacaine Concentrations Following Local Infiltration Analgesia and Femoral Nerve Block in Older Patients Undergoing Total Knee Arthroplasty.

The study examined the pharmacokinetic profile of fixed formulation mixtures comprising 225 mg of ropivacaine for local infiltration analgesia with or without epinephrine, and femoral nerve block in older patients presenting for orthopedic surgery and explored potential influences of block type, age, and body weight on this profile. Twenty four patients scheduled for total knee arthroplasty were randomly assigned to three groups: femoral nerve block, local infiltration analgesia with epinephrine and local infiltration analgesia without epinephrine. Blood samples were collected at 10, 30, 60, and 120 min following the block and total plasma concentrations of ropivacaine were quantified by high performance liquid chromatography. The mean individual peak total plasma concentrations of ropivacaine in local infiltration analgesia with and without epinephrine, and femoral nerve block group were 0.334, 0.490 and 0.545 μg mL-1 (p = 0.16). Local infiltration with epinephrine group had significantly lower plasma ropivacaine concentrations at 30, 60 and 120 minutes. The plasma ropivacaine concentrations exceeded 2.2 μg mL-1 in one patient. Age, but not body weight, had a moderate correlation with peak plasma ropivacaine concentration (r = 0.37, p = 0.08). Administration of a fixed 225 mg dose of ropivacaine for local infiltration analgesia with epinephrine and femoral nerve block results in plasma ropivacaine concentrations below the toxicity threshold, indicating their safety. The use of local infiltration analgesia with epinephrine provides a greater safety margin, as local infiltration analgesia without epinephrine may lead to ropivacaine concentrations associated with symptoms of local anesthetic toxicity.

Effect of the level of alveolar atrophy on implant placement accuracy in guided surgery for full-arch restorations supported by four implants: an in vitro study

BackgroundA fixed screw-retained full-arch restoration supported by four implants is a popular treatment option for edentulous arches. Optimal alignment of implants is quite challenging in extremely atrophied edentulous cases, and a small amount of deviation is expected during guided surgery. This study aimed to compare implant accuracy among edentulous jaws with various levels of atrophy.MethodsFive separate copies of each Cawood and Howell model (III–V) were produced for the maxilla and mandible. A total of 120 implants (30 models). The implant accuracy was assessed based on angular deviations at the base (angle, 3D offset, distal, vestibular, and apical) and tip (3D offset, distal, vestibular, and apical).ResultsThe atrophy level of the jaws had a statistically significant effect on deviation; implants showed greater deviation from the planned location as the atrophy level increased.ConclusionGiven that implant deviation increased with the degree of atrophy, a greater safety margin from important anatomical structures is recommended when planning implant location for guided surgery in Cawood and Howell V cases.

Abstract 1137: Identification of a high selective SMARCA2 degrader which effectively suppresses the SMARCA4-deficient tumors in vitro and in vivo

Abstract The SWI/SNF chromatin-remodeling complex plays essential roles in a variety of cellular processes including differentiation, proliferation and DNA repair. Mammalian SWI/SNF complexes always contain one of two mutually exclusive and structurally highly related ATPases: SMARCA2/BRM or SMARCA4/BRG1, as its catalytic subunit, which hydrolyze ATP to drive nucleosome movement. It is reported that absence of SMARCA4 are present in several cancers and these SMARCA4 deficient cells highly depend on its paralog SMARCA2 for survival. Furthermore, concurrent inhibition of SMARCA2 and SMARCA4 is fatal to normal cells. Therefore, it holds great therapeutic promise to treat SMARCA4 deficient cancers with selective SMARCA2 degraders while leaving SMARCA4 wild type cells unaffected. Here, we report that SCR-9140 is a high selective SMARCA2 degrader which demonstrates superior anti-tumor activity and low cytotoxicity against non-malignant cells. SCR-9140 strongly degrades SMARCA2 with DC50 of <1 nM and achieves the complete protein degradation (Dmax of >95%) and also shows 100-fold degradation selectivity over SMARCA4 with DC50 of around 100 nM and Dmax of <60% in HiBiT knock-in SW1573 cells. Across a panel of SMARCA4 deficient tumor cell lines, SCR-9140 potently inhibits proliferation with IC50 values ranging from 1 to 50 nM. Due to the high selectivity over SMARCA4, SCR-9140 neither inhibits proliferation of SW1573 (SMARCA2-WT SMARCA4-WT) cells nor NCI-H1581 (SMARCA2-DEL SMARCA4-DEL) cells with IC50s of over 2000 nM. The degraders with poor selectivity of SMARCA2/4 (DC50 ratio: < 10 folds, Dmax of SMARCA4 > 80%) strongly inhibit the SW1573 cells proliferation with IC50s < 100nM, while there are no significant effects on the NCI-H1581 cells ascribing to the absence of targets. Furthermore, SCR-9140 demonstrates weak cytotoxicity on non-malignant cells, such as WI-38 (human lung fibroblast cells), THLE-2 (human liver cells), and human PBMC, rendering it the greater therapeutic window. In a CDX model of NSCLC, SCR-9140 effectively inhibits tumor growth and TGI correlates well with SMARCA2 degradation in tumors. In conclusion, our potent and selective SMARCA2 degrader, SCR-9140 induces strong synthetic lethality in SMARCA4 deficient cells in vitro and in vivo and shows great safety margin in normal cells. Citation Format: Feng Zhou, Zhiyong Yu, Ruonan Chen, Feng Tang, Peng Gu, Wenqing Yang, Liting Xue, Ping Chen, Renhong Tang. Identification of a high selective SMARCA2 degrader which effectively suppresses the SMARCA4-deficient tumors in vitro and in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1137.

Methodical control of the difficult pediatric airway: two case reports

BackgroundManagement of children who present with a history of impossible mask ventilation or difficult tracheal intubation is fraught with challenges. Despite this, the “airway stress test” of an inhalational induction is frequently employed risking airway obstruction, breath holding, apnea, and laryngospasm.Case presentationsWe present two cases of children with anticipated difficult airway management. The first child (14-year-old African American boy) had severe mucopolysaccharidosis with a history of failed anesthetic induction and failed airway management. The second child (3-year-old African American girl) had progressive lymphatic infiltration of the tongue, resulting in severe macroglossia. We describe a technique that forgoes inhalational induction, incorporates recent pediatric airway guidelines, and provides a greater margin of safety. The technique encompasses the use of drugs that facilitate sedation for intravenous access, without respiratory depression or airway obstruction, titrated use of medications to achieve anesthetic depth while preserving ventilatory drive and airway tone, and the continuous provision of directed oxygen flow during airway manipulation. Propofol and volatile gases were avoided to preserve airway tone and respiratory drive.ConclusionsWe emphasize that an intravenous induction technique utilizing medications that preserve airway tone and ventilatory drive, and the use of continuous oxygen flow throughout airway manipulation, allows for successful management of children with a difficult airway. The common practice of volatile inhalational induction should be avoided in anticipated difficult pediatric airways.

Analysis of progressive collapse of building using ETABS

Increasing seismicity and a proportionate rise in the construction of tall buildings have increased the relevance of progressive collapse analysis for building structures. This paper aims to compare the Demand Capacity Ratio (DCR) values of two buildings, which were modelled according to the guidelines of IS 1893 (part 1) - 2016 and Probabilistic Seismic Hazard Assessment (PSHA), using linear static analysis. The analysis was conducted using ETABS software, following the guidelines of IS:456–2000 and IS:1893 (part 1) - 2016, with DCR serving as an indicative parameter. The failure of the corner column and the peripheral column were examined. The DCR values of adjacent columns and beams were calculated to check their failure and analyse the collapse. Among the two models analysed, it was observed that the model designed according to the guidelines of IS 1893 (part 1) - 2016 exhibited a lower DCR value, suggesting a higher level of resistance to progressive collapse and a greater margin of safety. The insights gained from this study can contribute to the development of more resilient and robust design practices, ultimately ensuring the safety and structural integrity of buildings during extreme events.

A COMPARATIVE STUDY BETWEEN CAUDAL ROPIVACAINE AND ROPIVACAINE PLUS DEXAMETHASONE FOR INFRAUMBILICAL SURGERY IN PEDIATRIC PATIENTS

Background: Caudal block is one of the most popular regional block in children with high success rate for infra-umbilical surgeries. Among local anaesthetics ropivacaine provides a greater margin of safety, less motor blockade, less neurological and cardiac toxicity and similar duration of analgesia compared to bupivacaine. Addition of dexamethasone as an additive to local anesthesia decreases the postoperative rescue analgesia consumption.This study was designed to compare the effectiveness of intra-operative and postoperative analgesia on adding dexamethasone to 0.15% ropivacaine with 0.15%ropvacaine given alone. A prospective double blinded Materials: randomised controlled study was conducted consisting of 60 patients undergoing infra-umbilical surgeries under general anesthesia with Caudal block. Patients were randomised into two groups. Group A received 0.15% Inj.ropivacaine 1.5ml/kg with 1ml normal saline and Group B received 0.15% Inj.Ropivacaine 1.5ml/kg with 0.1mg/kg Inj.dexamethasone in caudal block Results: Mean FLACC pain score was comparable and statistically not signicant (P=0.083) in both groups upto 30min postoperatively. At 60min mean pain score in group A was 0.30 ± 0.54 and in group B was 0 (P=0.005) which was statistically signicant. In group A 40%(12) patients required rescue analgesia whereas in group B only 10%(3) patients required analgesia(P= 0.007) Patients remained hemodynamically stable throughout the procedure. After 60min Conclusion: postoperatively FLACC score was signicantly higher in group A as compared to group B. It concludes that addition of dexamethasone signicantly reduced postoperative pain and need for rescue analgesia without any side effects.

A deductive design method to simplify ASCE 41-17 nonlinear static procedure preserving the adjusted collapse margin ratio of steel moment frames

The present study offers a deductive design procedure based on designs that have been optimally screened in accordance with ASCE 41-17's nonlinear static procedure (NSP). The subsequent phase inferred a linear static methodology from the design philosophy underlying the NSP of ASCE 41-17. The deduced design procedure is applied to provide a set of optimal 6-story SMRF designs under two load patterns: the code-based and the first-mode shape patterns. The optimal designs by the proposed deduced linear procedure are compared with those optimized under ASCE 41-17's NSP using FEMA p695 metrics. Consequently, the adjusted collapse margin ratio is evaluated for both design approaches using incremental dynamic analyses. A linearization algorithm is suggested for idealizing pushover curves. The evaluation results demonstrate that the deduced linear static design produces designs that are comparable to those of the ASCE 41-17's NSP without necessitating a sophisticated inelastic analysis. Using the code-based lateral load pattern, the linear static design resulted in a greater margin of safety against collapse and heavier designs with respect to applying the first-mode shape load pattern. The deduced design procedure yields an idea that supports a seismic design philosophy to prevent conflict between design and retrofit standards.

Calculation and investigation of the stress-strain state of a nitrided gear wheel

The article presents an analysis of the stress-strain state of the nitrided gear design using the SolidWorks Simulation and APM WinMachine (FEM) programs. Models, methods and examples of calculations are given. As a result of nitriding, the surface hardness of the product increases, the safety factor increases. The experiment proved that the optimal temperature for the formation of a nitrided layer with a hardness of 11,740– 12,003 MPa for corrosion-resistant heat-resistant steel grade 12Kh18N9T was 570–590°C with a nitriding time of 48 hours. It is shown that after nitriding, the steel under study has a homogeneous structure with clearly defined transition layers, the average thickness of the nitrided layer is 60–90 microns. The stress-strain state of the product before and after nitriding, which determines the internal stresses and deformation of the wheel tooth, shows that the static characteristics are approximately equal. However, a wheel hardened by nitriding has a higher hardness, a greater safety margin and it is less prone to deformation under high loads

A Comparison of Central Venous Access to the Internal Jugular Vein and Two Standard Approaches to the Subclavian Vein: A Study of Cross-Sectional Areas Using Computed Tomography Scans.

IntroductionThe supraclavicular approach to the subclavian vein has been cited as having many advantages to the infraclavicular approach, including a larger short-axis cross-sectional area, a greater margin of safety, and fewer complications.MethodsTo examine whether a larger short-axis cross-sectional area of the subclavian vein at the supraclavicular fossa is a potential explanation for the reduction in attempts with the supraclavicular approach seen in a previous study, we examined computed tomography scans from 50 patients (24 M, 26 F). The short-axis cross-sectional areas of the subclavian vein at the mid-clavicular line, the subclavian vein in the supraclavicular fossa, and the internal jugular vein at the level of the thyroid cartilage were calculated.ResultsThe internal jugular vein short-axis cross-sectional area was significantly larger than the subclavian vein short-axis cross-sections measured at each location. We found no difference between the short-axis cross-sectional areas of the subclavian vein or when comparing measurements as a factor of gender, age, or race. Weight had a significant relationship to the short-axis cross-sectional area of the internal jugular vein and subclavian vein at the mid-clavicular vein.ConclusionsOn supine computed tomographic imaging, the subclavian vein short-axis cross-section was not larger in the supraclavicular fossa than the mid-clavicular line. The short-axis cross-sectional area of the subclavian vein at the supraclavicular fossa does not appear to contribute to the decrease in attempts to access it. Weight, but not necessarily height, appears to be correlated with central vein size.

Oral adenocarcinoma observed in Boa constrictor maintained in captivity

Information on neoplasms in animals has increased over time, and these studies have helped in the management of reptiles that present tumors. There are similar incidences of neoplasms between homeothermic and ectothermic animals. Furthermore, there are usually more than one type of tumor present. The treatment of wild animals afflicted with cancer usually happens late, contributing to their low life expectancy. Thus, the present work aimed to describe an infrequent case of oral tumor in Boa constrictor. The tumor was observed in an adult female animal, raised in an exhibition area of the Zoo and Botanical Park of the Emílio Goeldi Museum, located in Belém, State of Pará, Brazil. Macroscopically, the mass presented morphologically with an irregular, multilobulated surface, color that varied from white to grey, hemorrhagic areas and its extension was 3.9 x 2.3 cm. The neoplasm was surgically removed, and the histopathological evaluation revealed an adenocarcinoma, with a papillary-like development pattern and a moderate degree of differentiation. The animal died three months after diagnosis due to starvation. The necropsy showed that there was tumor recrudescence and no metastases. Given the impossibility of surgical removal with a greater margin of safety, and adjuvant therapies, this condition favoured the resurgence of the neoplasm. This compromised the animal’s ability to feed and consequently lead to death. Malignant neoplasms in reptiles may have an unfavourable clinical evolution for the maintenance of life, requiring specific therapeutic care such as chemotherapy. Scientific contributions on tumors in these animals are essential for the medical treatment of wild animals, and the conservation of wild species.

Comparison between Ropivacaine 0.5% And Levobupivacaine 0.5% in Axillary Brachial Plexus Block for Upperlimb Surgeries in a Tertiary Health Care Centre of Tripura- A Observational Study

Introduction Axillary brachial plexus block is an anesthetic option used for surgeries of arm, forearm and elbow. The use of USG has significantly improved the quality of nerve blocks by direct visualization of nerves and related anatomical structures, needle trajectory and spread of local anesthesia during injection and significantly increases the success rate. Various drugs like Ropivacaine, bupivacine and Levobupivacaine are preferred due to greater margin of safety. However the efficacy of Levobupivacaine in Axillary Brachial Plexus Block has not been studied much. Therefore ,we designed this study to compare the clinical effect of Ropivacaine with Levobupivacaine for ABPB using USG technique. Methodology It’s a hospital- based Comparative study done in Department of Anesthesiology, AGMC & GBPH from July 2016 to June 2018 (2 years) where 60 patients aged between 18-55 years with ASA grade 1 & 2 who are posted for upper limb surgery were randomly allocated into two groups of 30 each. Patients belonging to ASA grade (3& 4) and age <18years,>55years, Patient with h/o bleeding diathesis, neuromuscular disorder, morbid obesity, prolonged drug therapy & local site infection were excluded from the study. USG guided axillary nerve block performed under aseptic condition. Sensory and motor blocks were assessed in each nerve territory at 2, 5, 10, 15, 20, 25, and 30 mins, 6 hr, 12 hr , 18hr, and 24 hrs after LA injection after LA injection. Onset of block, duration block and quality of analgesia has been compared. For the duration of the study, the presence of hypotension, bradycardia, hypoxia or nausea and vomiting was recorded and treated according to standard clinical practice. Result Among 60 study subjects Mean age was 34.7±12.6 years and majority of the study subjects were males (73.3%) and 26.7% were females. The pre-operative parameters e.g. age, sex, body weight etc. were compared between two groups but there was no statistically significant difference between the two groups (p>0.05). The onset of motor blockade among patients of Ropivacaine group was also shorter than patients received Levobupivacaine which was significant. Duration of sensory blockade was shorter in Ropivacaine group & duration of motor blockade was also shorter in Ropivacaine group than Levobupivacaine group and these difference were found to be statistically significant (p<0.05). There was no significant change in vital parameters after administration of both the drugs when observed at specific time intervals. VAS Scores were comparable in both the groups. Conclusion The following conclusion can be made from the present study • Ropivacaine has faster onset of sensory and motor blockade when compared with Levobupivacaine. • But duration of both sensory and motor blockade was lesser than Levobupivacaine • Ropivacaine provides stable haemodynamic profile similar to Levobupivacaine. • It provides satisfactory intra-operative &post-operative analgesia comparable to Levo

Psychotropics for Treatment of Substance Use Disorders in Adolescents: A Brief Review

Substance use disorders (SUD) remain a long-standing problem for adolescents. Medication assisted treatment (MAT) is now standard treatment for adult SUD but less common in adolescents. This article provides a brief summary of the available psychotropics used to treat SUD in adolescent patients; psychotropics should be considered as one part of a multi-disciplinary approach to treatment of SUD. Due to the growing impact of the opioid public health crisis in the adolescent population, pediatricians have an expanding role in identifying and treatment of opioid use disorders, in addition to other substance use disorders. Pediatricians and adolescent medicine physicians are critically important in the solution to the addiction problem. There is expanding evidence that treatment of SUDs must be integrated into multiple parts of the delivery care system, including primary care settings. Medications Used to Treat Opioid Use Disorders (OUD): Methadone and buprenorphine are the two primary methods of MAT available to treat OUD. Methadone is highly regulated and only available to patients over age 18 in the United States. Buprenorphine/naloxone is FDA-approved for patients age ≥16, with the American Academy of Pediatrics Committee on Substance Use and Prevention (2016) recommending improved pediatrician access to buprenorphine training and MAT consideration for adolescents. Buprenorphine/Naloxone (Suboxone) and Buprenorphine (Subutex): Buprenorphine is a schedule III drug, requiring additional prescriber trainings and requirements. Buprenorphine is a mu-opioid partial agonist with greater safety margins than full agonists and less withdrawal. It is often combined 4:1 with naloxone, an antagonist; Alho, et al. found that this combination reduced “street value”, likely decreasing abuse potential.

Time-Dependent Reliability Analysis of Buried Water Distribution Network: Combined Finite-Element and Probabilistic Approach

Corrosion deterioration is the predominant factor for a large number of cast iron (CI) water main breaks. The reliability of CI pipelines decreases overtime as corrosion growth on pipe walls significantly reduces the strength of pipeline materials. To predict the reliability of water pipelines accurately, this study used a finite-element analysis (FEA) approach to determine the maximum pipeline stress at various stages of the pipeline’s life. A series of FEAs was performed to consider uncertainties in parameters associated with stress analysis. The circumferential stress was found to be the most critical stress for pipelines. Time-variant circumferential stress was obtained by accounting for the time-dependent corrosion pit growth on the pipeline wall. The time-variant failure probability of pipelines was determined by comparing the circumferential stress and the tensile failure strength of the pipeline at the burst limit state. The FEA model developed in this study was validated with the results obtained from previous studies. Monte Carlo simulation was performed to generate the fragility curves in a probabilistic manner. This study also compared the fragility curves obtained utilizing FEA and conventional equations (elastic ring theory and the Spangler formula). The results showed that analytical equations are too conservative and provide a higher failure probability of pipeline. A sensitivity analysis was performed to identify the relative importance of parameters contributing to the pipeline’s performance. Additionally, the reliability of the water distribution network (WDN) was calculated based on the minimum cut set (MCS) and graph decomposition methods. The results showed that the two methods provide similar outcomes, however, MCS provides a greater safety margin. The proposed approach was illustrated for an example WDN.

Evolution of postoperative pituitary adenoma resection cavities assessed by magnetic resonance imaging and implications regarding radiotherapy timing and modality

PurposeThis study evaluates the temporal evolution of the spatial relationship between the pituitary adenoma transsphenoidal surgical cavity and the adjacent optic chiasm and discusses implications on timing and choice of radiotherapy modality. MethodsThis retrospective observational review analyzed factors that might influence the postoperative relationship between the surgical cavity and the optic chiasm, including tumor type, craniocaudal tumor and resection cavity dimensions, the preoperative distance between tumor and the optic chiasm, the presence of cavernous sinus invasion, and the choice of intraoperative packing material. Changes observed on magnetic resonance imaging in the preoperative, immediate (within 72 h), and delayed (≥3 months) postoperative periods were compared. ResultsSixty-five patient histories were analyzed. Preoperatively, the pituitary adenoma was apposed to the optic chiasm in 43 patients (66%). Postoperatively, 34 patients (52%) in the immediate postoperative period and 54 patients (83%) in the delayed postoperative period had a distance ≥2 mm between the resection cavity and the optic chiasm. This distance provides a greater margin of safety with adjuvant radiosurgery. Preoperative tumor size showed a strong association with postoperative descent of the optic chiasm. ConclusionsPreoperative tumor size and degree of mass effect on the optic chiasm predict postoperative changes. In this study, the distance between the resection cavity and the optic chiasm was greater at ≥3 months postoperatively than in the immediate postoperative period, regardless of preoperative mass effect, indicating radiotherapy planning should be deferred to ≥3 months postoperatively when not precluded by aggressive histological characteristics that necessitate more immediate treatment. PrecisTo investigate the temporal relationship between the postoperative sellar surgical cavity and the adjacent optic apparatus after transsphenoidal resection of pituitary adenomas and the implications for radiotherapy.

Repeated extreme heatwaves result in higher leaf thermal tolerances and greater safety margins.

The frequency and severity of heatwave events are increasing, exposing species to conditions beyond their physiological limits. Species respond to heatwaves in different ways, however it remains unclear if plants have the adaptive capacity to successfully respond to hotter and more frequent heatwaves. We exposed eight tree populations from two climate regions grown under cool and warm temperatures to repeated heatwave events of moderate (40°C) and extreme (46°C) severity to assess adaptive capacity to heatwaves. Leaf damage and maximum quantum efficiency of photosystem II (Fv /Fm ) were significantly impacted by heatwave severity and growth temperatures, respectively; populations from a warm-origin avoided damage under moderate heatwaves compared to those from a cool-origin, indicating a degree of local adaptation. We found that plasticity to heatwave severity and repeated heatwaves contributed to enhanced thermal tolerance and lower leaf temperatures, leading to greater thermal safety margins (thermal tolerance minus leaf temperature) in a second heatwave. Notably, while we show that adaptation and physiological plasticity are important factors affecting plant adaptive capacity to thermal stress, plasticity of thermal tolerances and thermal safety margins provides the opportunity for trees to persist among fluctuating heatwave exposures.

Survival benefit of endocrine dysfunction following immune checkpoint inhibitors for nonthyroidal cancers.

Our goal is to review pertinent data evaluating the association between immune checkpoint inhibitor (ICI)-induced endocrine dysfunction and survival in cancer patients as well as to understand the potential molecular links between these. ICIs have revolutionized cancer therapy but have also led to multiple immune-related adverse events (irAEs). Studies have demonstrated a link between the development of irAEs and improved survival, suggesting that ICI-induced antitumor immunity and autoimmunity are coupled. Thyroid irAEs are most frequently and strongly associated with improved survival, particularly in the context of overt thyroid dysfunction. Other endocrine irAEs, such as hypophysitis and diabetes are quite rare wherein the treatment approach or the disease process itself may mitigate improvement in survival. Preclinical and translational data indicate a role for CD4+ T cells, regulatory T cells and/or cytokines mediating irAEs, including thyroiditis. The development of irAEs is associated with improved tumor responses and survival in cancer patients. Thyroid irAEs, alone or in combination with other irAEs, are most strongly associated with improved outcomes. Biomarkers of response to ICIs are lacking, despite well-characterized pathologic and genomic susceptibilities predicting ICI efficacy. Early detection of thyroid irAEs may identify patients most likely to have durable antitumor response to ICIs. Although irAEs and antitumor immunity appear 'coupled', translational studies indicate the potential for their 'uncoupling', which could enable antitumor efficacy with greater safety margins.

Comparison of clinical efficacy of ropivacaine and lignocaine with adrenaline for implant surgery anesthesia: a split-mouth randomized controlled clinical trial.

BackgroundThe primary indication for using long-acting anesthetics in dentistry is extensive dental procedures that require pulpal anesthesia beyond 90 min and management of postoperative pain. Ropivacaine is an amide local anesthetic that is available at various concentrations with inherent vasoconstrictive properties at low concentrations. Ropivacaine has a 75% greater margin of safety than bupivacaine. Ropivacaine can be a good alternative to bupivacaine as a local anesthetic in dental implant surgery as it provides a longer duration of both pulpal and soft tissue anesthesia after mandibular nerve block and lowers CNS and cardiovascular toxicity. This study aimed to evaluate and compare the clinical efficacy of ropivacaine and lignocaine for implant surgery anesthesia.MethodsFifteen patients with bilateral edentulous sites indicated for implant placement were recruited for this study. Patients aged 20–60 years of both sexes were randomly recruited. Thirty implant placements were performed in the test and control groups using ropivacaine and lignocaine with adrenaline as local anesthetics, respectively.ResultsThe results were analyzed statistically. The duration of anesthesia was significantly higher in the test group than in the control group. Ropivacaine was found to be superior to lignocaine in terms of the quality of anesthesia. The comparison of mean visual analog scale scores showed ropivacaine to have better anesthetic and analgesic effects than the control group.ConclusionRopivacaine 0.75% provides a significantly longer duration of anesthesia than lignocaine 2% with adrenaline. Ropivacaine 0.75% decreased intraoperative and postoperative analgesia compared to lignocaine 2% with adrenaline. Hence, ropivacaine 0.75% can be used as an alternative to lignocaine in implant surgeries and other intraoral surgical procedures that require a longer duration of anesthesia and analgesia.