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The main objective of the present study is to identify the best structural model for both aeroelastic and structural analysis of unswept rectangular wings with aspect ratios between 2 to 5. The paper presents a detailed study of the similarities and differences between the classical beam and plate theories, which provides new insight into this classical problem. To perform the aeroelastic analysis, the three-dimensional Peters aerodynamic model is coupled with classical plate theory. This combination leads to a new simpler three-dimensional aeroelastic model that can reduce the computational time. The results have been evaluated using both the unpublished and highly cited experimental data. Interestingly, by performing both structural and aeroelastic analyses, a comment can be stated that, even for relatively low aspect ratios ([Formula: see text]) of thin rectangular cantilever plates, the model based on the beam theory is closer to the experimental model compared to the plate theory. This finding may be unexpected by many researchers. Also, using a novel approach, it has been shown that the most significant difference between the beam and plate theories results arises from a subtle difference in the displacement field, which has not been given attention so far.

Peer reviewed: True, OBJECTIVE: To examine the association of physician burnout with the career engagement and the quality of patient care globally. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, PsycINFO, Embase, and CINAHL were searched from database inception until May 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Observational studies assessing the association of physician burnout (including a feeling of overwhelming emotional exhaustion, feelings of cynicism and detachment from job defined as depersonalisation, and a sense of ineffectiveness and little personal accomplishment) with career engagement (job satisfaction, career choice regret, turnover intention, career development, and productivity loss) and the quality of patient care (patient safety incidents, low professionalism, and patient satisfaction). Data were double extracted by independent reviewers and checked through contacting all authors, 84 (49%) of 170 of whom confirmed their data. Random-effect models were used to calculate the pooled odds ratio, prediction intervals expressed the amount of heterogeneity, and meta-regressions assessed for potential moderators with significance set using a conservative level of P

Objective: We sought to describe short term outcomes in patients with large vessel occlusion acute ischemic stroke (LVOAIS) who were treated with intravenous tenecteplase (TNK) as compared to alteplase, focusing on reduction in the need for mechanical thrombectomy (MT). Background: In LVOAIS, TNK has shown improved reperfusion and outcomes with a similar safety profile to alteplase. Ultra-early reperfusion has been described with TNK which would prevent the need for MT. We analyze the magnitude of this effect in a “real-world” setting. Design/Methods: In this retrospective study, demographic, clinical, and imaging information from patients with LVOAIS treated with intravenous thrombolysis was collected. Data was compared between the group treated with TNK and alteplase. Results: One hundred eighty-six patients met the criteria for the study (LVOAIS and candidates for IV thrombolysis and MT). Of these, 144 patients received tPA and 42 received TNK. Nine had clinical improvement prior to groin puncture and did not require angiography. This phenomenon occurred in 2.1% who received IV tPA and 14.3% who received TNK (p=0.005). For 8.2 patients treated with TNK rather than tPA, one catheter angiography would be prevented. When combining the number of patients who had recanalization on angiography before MT, and those who had clinical improvement prior to angiography, there were a total of 23 patients. This was noted in 9.7% of patients who received tPA, and 21.4% of those who received TNK (p=0.043). For 8.5 patients treated with TNK rather than tPA, one patient will have spontaneous recanalization either angiographically or with clinical improvement, preventing the need for MT. Conclusions: Intravenous TNK in patients with LVOAIS reduces the need for catheter angiography and mechanical thrombectomy.

Multirotor analytical dynamic inflow models in the literature, such as pressure potential superposition inflow model or velocity potential superposition inflow model (VPSIM), have been shown to capture the fundamental inflow interference effects between the rotors. Some of the differences in inflow predictions seen between these analytic models and high-fidelity wake models are attributed to missing real flow effects such as wake distortion, contraction, decay, swirl, etc. As such, correction terms are needed in the analytically derived multirotor finite-state inflow models, because of the potential flow and rigid wake assumptions they are based on, in order to capture some of the missing real flow effects in them. This paper develops a systematic methodology for arriving at the needed correction terms in the VPSIM through comparisons of its inflow predictions with those of a viscous vortex particle model (VVPM). Also, a procedure is developed to assess the relative importance of individual real flow effects and the associated corrections needed for improving the overall fidelity of the VPSIM. The developed methodology is applied to the Harrington coaxial rotor using its geometric and aerodynamic data from the literature. It is shown that the addition of swirl coupling correction terms to the VPSIM significantly improves its correlations with the VVPM. Further, it is shown that the required corrections are reasonably insensitive to thrust sharing ratio conditions between the rotors.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. For advanced HCC, sorafenib was considered the standard of care for more than ten years. Recently the atezolizumab and bevacizumab combination has become standard of care for these patients without contraindications to either immune checkpoint inhibitors or antiangiogenic therapy. We now review the practical aspects of the atezolizumab and bevacizumab combination, including current evidence, indications, contraindications, management of adverse events, sequencing of this combination, areas of current knowledge gaps and future areas of active clinical research of this combination for busy clinicians in clinical practice.

The combined petrosal approach is an excellent method to access the petroclival region but has the inherent risk of injury to the temporal lobe and Vein of Labbé. Tentorial peeling has the potential to largely eliminate these risks during the classic combined transpetrosal approach.Anatomical dissection of three adult injected non-formalin fixed cadaveric heads was performed. Combined petrosal approach with tentorial peeling was completed. A tentorial incision just superior and parallel to the superior petrosal sinus was made to enable peeling of the tentorium into two layers, the posterior fossa tentorial leaf (PFTL), and the temporal tentorial leaf (TTL).Tentorial peeling clearly exposed the continuity between the temporal dura and the TTL as well as the continuity between the presigmoid dura and the PFTL. This enabled the creation of a large dural flap extending to the tentorial incisura, providing wide access to the petroclival region without any exposure of the temporal lobe and/or basal temporal veins. Techniques to create the dural flap without trochlear nerve injury were also explored.The technique of tentorial peeling into two distinct layers has the potential to reduce the morbidity associated with temporal lobe retraction and venous injury. Further cadaveric studies and surgical case series are needed to validate this important surgical nuance in transpetrosal approaches.

As part of the SARS-CoV‑2 pandemic, the district of Heinsberg developed into an infectiological epicentre for Germany in February 2020. Our hospital, which is located in the immediate vicinity, reacted very quickly in addition to adapting patient care by implementing an organizational structure for recording SARS-CoV-2-positive employees, patients and their contact persons.The infections recorded in contact tracing were analysed and, based on an exemplary outbreak, infection chains and follow-up processes were evaluated.Comprehensive data on contact types, oropharyngeal swab results for SARS-CoV‑2 and quarantine days were documented and retrospectively evaluated using a self-developed database.Of the 568 employees recorded by in-house contact tracing, 32 employees (1.2%, n = 2567) were detected as SARS-CoV‑2 positive. Of those, 50% (n = 16) tested positive due to contact tracing, 15.6% (n = 5) were recorded by routine smears and 34.4% (n = 11) were returning travellers. The variable PCR results of the control smears from these positive employees were noticeable. In 18.8% (n = 6) of the initially negative control smears, positive PCR results were found in the following control smear. The inhouse contact tracing team was able to detect infection clusters on non-COVID-19 wards at an early stage and, together with clinical hygiene and the public health department, initiated comprehensive measures to limit the spread of the virus. Infection chains could thus be interrupted.The work of the clinic's own contact tracing unit has proven to be an essential part of clinical pandemic management not least against the background of new waves of infection and is indispensable for the detection of local infection clusters.HINTERGRUND: Im Rahmen der SARS-CoV-2-Pandemie entwickelte sich der Kreis Heinsberg im Februar 2020 zu einem infektiologischen Epizentrum für Deutschland. Unser in unmittelbarer Nachbarschaft gelegenes Krankenhaus implementierte neben der Anpassung der Patientenversorgung sofort zusätzlich eine krankenhausinterne Organisationsstruktur zur Erfassung SARS-CoV-2-positiver Mitarbeiter, Patienten und deren Kontaktpersonen.Die im Contact Tracing erfassten Infektionen wurden analysiert und anhand eines beispielhaften Ausbruchs Infektionsketten und Nachverfolgungsprozesse evaluiert.Daten zu Kontakten, Abstrichergebnissen und Quarantänetagen wurden mittels einer eigenen Datenbank dokumentiert und retrospektiv ausgewertet.568 Mitarbeiter wurden vom krankenhausinternen Contact Tracing erfasst. 32 Mitarbeiter (1,2 %, n = 2567) wurden als SARS-CoV-2-positiv erfasst. 50 % (16) davon wurden im Rahmen der Kontaktpersonennachverfolgung positiv getestet, 15,6 % (5) durch Routineabstriche erfasst. 34,4 % (11) waren Reiserückkehrer. Auffällig waren variable PCR-Ergebnisse der Kontrollabstriche dieser positiven Mitarbeiter. Bei 18,8 % (6) wurden bei zunächst negativem Kontrollabstrich im folgenden Kontrollabstrich wieder positive PCR-Ergebnisse gefunden. Das eigene Contact Tracing konnte Infektionshäufungen auf Non-COVID-19-Stationen frühzeitig aufdecken und gemeinsam mit der Klinikhygiene und dem Gesundheitsamt umfassende Maßnahmen zur Begrenzung der Virusausbreitung einleiten. Infektionsketten konnten früh durchbrochen werden.Ein krankenhausinternes Contact Tracing erweist sich vor allem bei nicht auszuschließenden zukünftigen Infektionswellen als ein wesentlicher Bestandteil des klinischen Pandemiemanagements und ist essenziell zur Aufdeckung von lokalen Infektionsclustern.

Tocochromanols (vitamin E) are an essential part of the human diet. Plant products, including maize (Zea mays L.) grain, are the major dietary source of tocochromanols; therefore, breeding maize with higher vitamin content (biofortification) could improve human nutrition. Incorporating exotic germplasm in maize breeding for trait improvement including biofortification is a promising approach and an important research topic. However, information about genomic prediction of exotic-derived lines using available training data from adapted germplasm is limited. In this study, genomic prediction was systematically investigated for nine tocochromanol traits within both an adapted (Ames Diversity Panel [AP]) and an exotic-derived (Backcrossed Germplasm Enhancement of Maize [BGEM]) maize population. Although prediction accuracies up to 0.79 were achieved using genomic best linear unbiased prediction (gBLUP) when predicting within each population, genomic prediction of BGEM based on an AP training set resulted in low prediction accuracies. Optimal training population (OTP) design methods fast and unique representative subset selection (FURS), maximization of connectedness and diversity (MaxCD), and partitioning around medoids (PAM) were adapted for inbreds and, along with the methods mean coefficient of determination (CDmean) and mean prediction error variance (PEVmean), often improved prediction accuracies compared with random training sets of the same size. When applied to the combined population, OTP designs enabled successful prediction of the rest of the exotic-derived population. Our findings highlight the importance of leveraging genotype data in training set design to efficiently incorporate new exotic germplasm into a plant breeding program.

Objective: Research into firm-level exporting, has been criticised for being excessively fragmented and inconsistent. The objective of this paper is to review extant research on export performance and propose a research framework which will go beyond the currently studied relationships and variables, and therefore formulate several recommendations for future research. Research Design & Methods: In doing so, the review adopts a broader view of export performance, which accounts for the possibility of a negative development of export ventures. Findings: The paper finds that institution-based, resource-based and industry-based views have been often used to address the determinants of export performance. While there are some complex interactions between host-country institutional factors, firm-level factors, and industry-level factors, these have been studied to a lesser extent. Also, the review highlights the need for a more nuanced and fine-grained understanding of export strategy, particularly embracing modern business models and devoting more attention to foreign market partners. Implications & Recommendations: Scholars should be more sensitive to previously neglected variables which can enhance the understanding of export performance and lead to more comprehensive empirical studies. Contribution & Value Added: The paper includes a conceptual framework proposing directions for future research, whereby a broader understanding of export performance is adopted, including also the possibility of export exits.

Objectives Gene rearrangements involving NTRK1, NTRK2, NTRK3, ROS1 and ALK have been identified in many types of cancer, including non-small cell lung cancer (NSCLC). Data in malignant pleural mesothelioma (MPM), lung neuroendocrine tumors (NETs) and small-cell lung cancer (SCLC) are lacking. Given the activity of NTRK, ROS-1 and ALK inhibitors in tumors harboring gene fusions, we sought to explore such rearrangements in these less common tumors in addition to NSCLC. Methods Archival tumor tissue from patients with MPM, lung NETs, SCLC and NSCLC were used to create tissue microarrays. Immunohistochemistry (IHC) was performed using a cocktail of antibodies against TRK, ROS1 and ALK. IHC positive samples underwent RNA sequencing using the ArcherDX FusionPlex CTL diagnostic assay. Clinical data were obtained through retrospective chart review. Results We performed IHC on 1116 samples: 335 MPMs, 522 NSCLCs, 105 SCLCs and 154 lung NETs. There were 23 IHC positive cases (2.1%) including eight MPMs (2.4%), eight NETs (5.2%), five SCLC (4.8%) and two NSCLC (0.4%). The following fusions were detected: one MPM with an NTRK ex10-TPM3 ex8, another MPM with an ALK ex20-EML4ex13, one lung intermediate-grade NET (atypical carcinoid) with an ALK ex20-EML4 ex6/intron6, and two NSCLCs with an ALK ex20-EML4 ex6/intron6 rearrangement. None of the patients received targeted treatment. Conclusions To our knowledge, we report for the first time NTRK and ALK rearrangements in a small subset of MPM. An ALK rearrangement was also detected in lung intermediate-grade NET (or atypical carcinoid). Our data suggest that IHC could be a useful screening test in such patients to ensure that all therapeutic strategies including targeted therapy are utilized.

In the long term, primary and secondary supply of refined copper satisfies demand. Numerous models exist to explain and predict demand and secondary supply; however, the projection of primary supply relies mostly on detailed knowledge of potential mining projects and on existing ore reserves and resources. Much discussion has occurred historically regarding the availability of resources and reserves for the future. Chile, being the largest copper producer, also has the largest reserves in the world; therefore, it retains its potential to be a key player in future supply. This article explores some of the most relevant resource and technological challenges that may emerge with an accelerated development of brownfield and greenfield copper mining projects in Chile through 2035, without considering economic, regulatory, and environmental constraints. A “Full Scenario” was created to accommodate these conditions and restrictions. It includes estimates of future ore reserves, copper production, plant capacity, ore grades, energy and water consumption, greenhouse gas (GHG) emissions, and generation of tailings. Maximum production would exceed 10 million tons of contained copper from 2027 to 2030, with a resulting decrease of ore grades and the growth of energy and water consumption. The growth of indirect GHG emissions through 2035 is estimated at 18.4% less than copper production growth, because all new electric energy for this scenario would be based on renewable energy. Also, all new water used by 38 out of the 42 mining projects considered would be seawater, and some of the continental water used in 2019 would cease to be used in mining.

Utrophin modulation is a promising therapeutic strategy for Duchenne muscular dystrophy (DMD), which should be applicable to all patient populations. Following on from ezutromid, the first-generation utrophin modulator, we describe the development of a second generation of utrophin modulators, based on the bioisosteric replacement of the sulfone group with a phosphinate ester and substitution of the metabolically labile naphthalene with a haloaryl substituent. The improved physicochemical and absorption, distribution, metabolism, and excretion (ADME) properties, further reflected in the enhanced pharmacokinetic profile of the most advanced compounds, 30 and 27, led to significantly better in vivo exposure compared to ezutromid and alleviation of the dystrophic phenotype in mdx mice. While 30 was found to have dose-limiting hepatotoxicity, 27 and its enantiomers exhibited limited off-target effects, resulting in a safe profile and highlighting their potential utility as next-generation utrophin modulators suitable for progression toward a future DMD therapy.

Mining jurisdictions avid to attract international investments to find and exploit their mineral deposits contend for international capitals. This led to policymakers, analysts, and companies to think about the factors affecting the competitiveness of mining districts. The traditional paradigm states that the capacity of a country or jurisdiction to attract investments and develop its local industry is a function exclusively of the quantity and quality of the ore deposits within its territory. On the other hand, the alternative view suggests that the previous conception is incomplete, because companies not only look for a good geologic potential but also for a favorable investment climate (Tilton 1992). Through cross-country econometric models covering the years 1996 to 2014, this work supports the alternative paradigm of mining competitiveness and tries to contribute to a better understanding of the relationship between the geological potential and the investment climate when determining the attraction of mining investments. The study concludes that, in order to develop a local mining industry, a country should have a wealthy natural endowment, but also it must offer a good investment climate. In addition, it shows that both variables are related through a multiplicative effect, but once public policies and other contextual variables reach certain reasonable levels (the “investment climate threshold”), jurisdictions compete almost exclusively based on its natural endowment. These results have significant implications for the implementation of public policies, especially in periods when mining contribution to social welfare is under scrutiny.

In the recent decades, the accuracy and robust of finite state inflow model to provide the velocity on the disk have been greatly improved. It is adequate to compute the thrust, pitch and roll moment real time for normal flight conditions. For lifting rotor flying close to a non-penetrable surface, the wake will interact with the inflow of the lifting rotor. Additionally, for co-axial rotors the wake of the upper rotor influences the lower rotor. Therefore, it is necessary to develop a model to compute the flow field in the wake since the Peters-He model cannot give the induced velocity below the rotor disk. In this paper, the improved finite state model will be introduced to compute the axial induced velocity everywhere in the flow field including wake and downstreamregions. The adjoint theorem will be introduced, and the computational efficiency of the convolution method and numerical algorithm for computing the adjoint varibales with time delay will be compared. With the parameters of a Harrington rotor, the results in the time domain for such a rotor in hover and forward flight conditions will also be illustrated.

ObjectivesThis study aimed to determine the effectiveness of Covishield vaccine among residents of congregate residential facilities.DesignA prospective cohort study in congregate residential facilities.SettingDharamshala, Himachal Pradesh, India, from December 2020 to July 2021.ParticipantsResidents of all ages in seven facilities—three monasteries, two old age homes and two learning centres—were enrolled.ExposuresFirst and second doses of Covishield vaccine against SARS-CoV-2 infection.Main outcomes measuresPrimary outcome was development of COVID-19. Secondary outcome was unfavourable outcomes, defined as a composite of shortness of breath, hospitalisation or death. Vaccine effectiveness (%) was calculated as (1−HR)×100.ResultsThere were 1114 residents (median age 31 years) participating in the study, 82% males. Twenty-eight per cent (n=308/1114) were unvaccinated, 50% (n=554/1114) had received one dose and 23% (n=252/1114) had received two doses of Covishield. The point prevalence of COVID-19 for the facilities ranged from 11% to 57%. Incidence rates (95% CI) of COVID-19 were 76 (63 to 90)/1000 person-months in the unvaccinated, 25 (18 to 35)/1000 person-months in recipients of one dose and 9 (4 to 19)/1000 person-months in recipients of two doses. The effectiveness of first and second doses of Covishield were 71% (adjusted HR (aHR) 0.29; 95% CI 0.18 to 0.46; pConclusionCovishield was effective in preventing SARS-CoV-2 infection and reducing disease severity in highly transmissible settings during the second wave of the pandemic driven by the Delta variant.

Objective Necrotizing enterocolitis (NEC) is the most common and lethal gastrointestinal disease affecting preterm infants. NEC develops suddenly and is characterized by gut barrier destruction, an inflammatory response, intestinal necrosis and multi-system organ failure. There is currently no method for early NEC detection, and the pathogenesis of NEC remains unclear. Design To further understand the molecular mechanisms that support NEC, we used solution phase hybridization and next-generation DNA sequencing of bisulfite converted DNA to perform targeted genome-wide analysis of DNA methylation at high read depth. Results We found that ileal samples from surgical NEC infants (n = 5) exist in a broadly hypermethylated state relative to their non-NEC counterparts (n = 9). These trends were not uniform, with hypermethylation being most consistently observed outside CpG islands and promoters. We further identified several biologically interesting gene promoters that displayed differential methylation in NEC and a number of biological pathways that appear dysregulated in NEC. We also found that DNA methylation patterns identified in ileal NEC tissue were correlated with those found and published previously in stool samples from NEC-affected infants. Conclusion We confirmed that surgical NEC is associated with broad DNA hypermethylation in the ileum, and this may be detectable in stool samples of affected individuals. Thus, an epigenomic liquid biopsy of stool may have significant potential as a biomarker with respect to the diagnostic/predictive detection of NEC. Our findings, along with recent similar observations in colon, suggest that epigenomic dysregulation is a significant feature of surgical NEC. These findings motivate future studies which will involve the longitudinal screening of samples obtained prior to the onset of NEC. Our long-term goal is the development of novel screening, diagnostic and phenotyping methods for NEC.