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The solar chromosphere was daily observed in the Ca ii K line at the Mount Wilson Observatory from 1915 August to 1985 July. A digitized data base was created, which includes synoptical maps of the chromosphere in Ca ii intensity from Carrington rotations 827 to 1764. We have used the data base to investigate rotation and its differential of the chromosphere and the quiet chromosphere. The chromosphere is found to rotate faster than sunspots, but the difference in their rotation rates decreases with decreasing latitude, and near the equator they rotate at nearly the same speed. The chromosphere is obviously faster than the quiet photosphere and slightly faster than the quiet chromosphere at low latitudes, but slightly slower than the quiet chromosphere at middle latitudes. The differential degree of the rotation rate at low latitudes, ranging from largest to smallest in order, is found to be: sunspots, the chromosphere, the quiet photosphere, and the quiet chromosphere. The differential of the rotation rate is found to be different in different solar cycles for the chromosphere and the quiet chromosphere. Helioseismology observations suggest that these findings are plausible.

Synoptic maps of Ca II K-normalized intensity at ±40° latitude belt from Carrington rotations 827 (1915 August 10) to 1764 (1985 July 7) are utilized to investigate the long-term variation of the quiet chromospheric differential rotation within solar activity cycles through removing some large values of Ca II-normalized intensity. The equatorial rotation rate of the quiet chromosphere is found to be smaller than that of the chromosphere, and the absolute value of the parameter B is also found to be smaller for the quiet chromosphere than for the chromosphere on the whole, especially during periods of solar cycle maxima. Therefore, we induce that the differential of rotation rate in the quiet chromosphere seems to be enhanced by large-scale magnetic fields. The north–south asymmetry in the solar rotation is also investigated, and the asymmetry coefficients of the chromosphere and the quiet chromosphere are positively correlated in solar cycles 15–17, while they are negatively correlated in solar cycles 18–21.

Lysine acetylation in histone tails is a key post-translational modification that controls transcription activation. Histone deacetylase complexes remove histone acetylation, thereby repressing transcription and regulating the transcriptional output of each gene. Although these complexes are drug targets and crucial regulators of organismal physiology, their structure and mechanisms of action are largely unclear. Here, we present the structure of a complete human SIN3B histone deacetylase holo-complex with and without a substrate mimic. Remarkably, SIN3B encircles the deacetylase and contacts its allosteric basic patch thereby stimulating catalysis. A SIN3B loop inserts into the catalytic tunnel, rearranges to accommodate the acetyl-lysine moiety, and stabilises the substrate for specific deacetylation, which is guided by a substrate receptor subunit. Our findings provide a model of specificity for a main transcriptional regulator conserved from yeast to human and a resource of protein-protein interactions for future drug designs.

Direct numerical simulation data obtained from four pairs of turbulent, lean hydrogen–air, complex-chemistry flames are analysed to explore the influence of molecular diffusion on flame surface density, displacement speed $S_d$ and the flame surface density transport equation terms. Each pair involves (i) a flame where mixture-averaged molecular diffusivities are adopted and Lewis number $Le$ is significantly less than unity and (ii) an equidiffusive flame where all molecular diffusivities are set equal to molecular heat diffusivity of the mixture and $Le=1$ , with other things being equal. Reported results show that significantly higher turbulent burning rates simulated in the former flames result mainly from an increase in the local fuel consumption rate, whereas an increase in flame surface area plays a secondary role, especially in more intense turbulence. The rate increase stems from (i) an increase in the peak local fuel consumption rate and (ii) an increase in a width of a zone where the rate is significant. The latter phenomenon is of more importance in richer flames and both phenomena are most pronounced in the vicinity of the flame leading edges, thus indicating a crucial role played by the leading edge of a premixed turbulent flame in its propagation. Moreover, mean displacement speed differs significantly from the laminar flame speed even in the equidiffusive flames, varies substantially across flame brush and may be negative at the leading edges of highly turbulent flames.

Purpose Understanding the factors that influence prosocial behaviour during the COVID-19 pandemic is essential due to the disruption to healthcare provision. Methods We conducted an in-depth, mixed-methods cross-sectional survey, from 2 May 2020 to 15 June 2020, of medical students at medical schools in the United Kingdom. Data analysis was informed by Latané and Darley’s theory of prosocial behaviour during an emergency. Results A total of 1145 medical students from 36 medical schools responded. Although 947 (82.7%) of students were willing to volunteer, only 391 (34.3%) had volunteered. Of the students, 92.7% understood they may be asked to volunteer; however, we found deciding one’s responsibility to volunteer was mitigated by a complex interaction between the interests of others and self-interest. Further, concerns revolving around professional role boundaries influenced students’ decisions over whether they had the required skills and knowledge. Conclusion We propose two additional domains to Latané and Darley’s theory that medical students consider before making their final decision to volunteer: ‘logistics’ and ‘safety’. We highlight modifiable barriers to prosocial behaviour and provide suggestions regarding how the conceptual framework can be operationalized within educational strategies to address these barriers. Optimizing the process of volunteering can aid healthcare provision and may facilitate a safer volunteering process. Key messages What is already known on this topic: There is a discrepancy between the number of students willing to volunteer during pandemics and disasters, and those who actually volunteer. Understanding the factors that influence prosocial behaviour during the current COVID-19 pandemic and future pandemics and disasters is essential. What this study adds: We expanded on Latané and Darley’s theory of prosocial behaviour in an emergency and used this to conceptualize students’ motivations to volunteer, highlighting a number of modifiable barriers to prosocial behaviour during the COVID-19 pandemic. How this study might affect research, practice, or policy: We provide suggestions regarding how the conceptual framework can be operationalized to support prosocial behaviours during emergencies for the ongoing COVID-19 pandemic and future crises.

Upon infecting a host cell, the reticulate body (RB) form of the Chlamydia bacteria simply proliferates by binary fission for an extended period. Available data show only RB units in the infected cells 20 hours post infection (hpi), spanning nearly half way through the development cycle. With data collected every 4 hpi, conversion to the elementary body (EB) form begins abruptly at a rapid rate sometime around 24 hpi. By modeling proliferation and conversion as simple birth and death processes, it has been shown that the optimal strategy for maximizing the total (mean) EB population at host cell lysis time is a bang-bang control qualitatively replicating the observed conversion activities. However, the simple birth and death model for the RB proliferation and conversion to EB deviates in a significant way from the available data on the evolution of the RB population after the onset of RB-to-EB conversion. By working with a more refined model that takes into account a small size threshold eligibility requirement for conversion noted in the available data, we succeed in removing the deficiency of the previous models on the evolution of the RB population without affecting the optimal bang-bang conversion strategy.

BACKGROUND AND PURPOSE: Chronic carotid artery occlusion remains a poorly understood risk factor for subsequent stroke, and potential revascularization is dependent on understanding the anatomy and nature of the occlusion. Luminal imaging cannot assess the nature of an occlusion, so the internal structure of the occlusion must be inferred. The present study examines the signal characteristics of symptomatic and asymptomatic carotid occlusion that may point to management differentiation. MATERIALS AND METHODS: We prospectively recruited patients who were diagnosed with chronic carotid artery occlusion defined as longer than 4 weeks and confirmed by DSA. All patients underwent high-resolution MR vessel wall imaging examinations after enrollment. Baseline characteristics, vessel wall imaging features, and DSA features were collected and evaluated. The vessel wall imaging features included segment involvement, signal intensity, contrast enhancement, and vessel wall thickness. The symptomatic and asymptomatic chronic carotid artery occlusions were compared. RESULTS: A total of 44 patients with 48 lesions were included in this study from February 2020 to December 2020. Of the 48 lesions, 35 (72.9%) were symptomatic and 13 (27.1%) were asymptomatic. There was no difference in baseline and DSA features. On vessel wall imaging, C1 and C2 were the most commonly involved segments (91.7% and 68.8%, respectively). Compared with symptomatic lesions, asymptomatic lesions were more often isointense (69.2%) in the distal segment (P = .03). Both groups had diffuse wall thickening (80% and 100%). CONCLUSIONS: Signal characteristics between those with symptomatic and asymptomatic carotid artery occlusions differ in a statistically significant fashion, indicating a different structure of the occlusion.

Electrically assisted (EA) microforming has pervasive benefits for the fabrication of high-performance microproducts. In this research, the coupled effect between the microstructural size effect and pulsed current on the flow characteristics of 304 stainless steel sheets along thickness direction was explored by using EA micro-compression tests. The results revealed that the strain hardening rate and the deformation stress of 304 stainless steel decreases during the EA deformation, especially when the current density exceeds 57.16 A/mm2. Besides, the effect of grain size on the micro-scaled compression is gradually weakened with the augment of current density and plastic strain. The electron backscatter diffraction (EBSD) results showed in the perspective of microstructure that the decrease of flow stress and strain hardening rate with the rise of pulsed current density is related to the reduction of dislocation density and texture strength due to the dynamic recrystallization during EA deformation. The pulsed current suppresses the grain refinement of fine-grained material and promotes that of coarse-grained material, and the recrystallization rate of EA deformation increases with the decrease of initial grain size. In addition, the recrystallization texture induced by the pulsed current can promote grain deflection and weakens the effect of twins in coarse-grained material. That can explain the reason for the weakening of the grain size effect. The findings in the research have important guiding significance for understanding the coupled mechanism of electroplastic and grain size effect on the flow characteristics of difficult-to-deform material, and further promoting the application of EA micro-rolling of high-strength materials.

Membrane technology is cost effective solution for CO2 removal from natural gas. However, there is challenges during its application depending on the polymer material characteristic. Understanding on the polymer fundamental and transport properties, will enable proper design of pre-treatment and operating conditions that suits its capability envelope. Diffusivity selective membrane favors high pressure and high temperature conditions and vice versa for solubility selective polymer. On top of that, the robustness and durability of the resultant membrane, need to be evaluated with multicomponent mixture to understand the effect of competitive sorption, plasticization and aging phenomena that will seriously impacting the membrane performance during its application.

Deeper and broader sequencing of circulating tumor DNA (ctDNA) has identified a wealth of cancer markers in the circulation, resulting in a paradigm shift towards data science-driven liquid biopsies in oncology. Although panel sequencing for actionable mutations in plasma is moving towards the clinic, the next generation of liquid biopsies is increasingly shifting from analyzing digital mutation signals towards analog signals, requiring a greater role for machine learning. Concomitantly, there is an increasing acceptance that these cancer signals do not have to arise from the tumor itself. In this Opinion, we discuss the opportunities and challenges arising from increasingly complex cancer liquid biopsy data.

Global navigation satellite systems (GNSS) have been proved to be an excellent technology for retrieving precipitable water vapor (PWV). In GNSS meteorology, PWV at a station is obtained from a conversion of the zenith wet delay (ZWD) of GNSS signals received at the station using a conversion factor which is a function of weighted mean temperature (Tm) along the vertical direction in the atmosphere over the site. Thus, the accuracy of Tm directly affects the quality of the GNSS-derived PWV. Currently, the Tm value at a target height level is commonly modeled using the Tm value at a specific height and a simple linear decay function, whilst the vertical nonlinear variation in Tm is neglected. This may result in large errors in the Tm result for the target height level, as the variation trend in the vertical direction of Tm may not be linear. In this research, a new global grid-based Tm empirical model with a horizontal resolution of 1∘ × 1∘ , named GGNTm, was constructed using ECMWF ERA5 monthly mean reanalysis data over the 10-year period from 2008 to 2017. A three-order polynomial function was utilized to fit the vertical nonlinear variation in Tm at the grid points, and the temporal variation in each of the four coefficients in the Tm fitting function was also modeled with the variables of the mean, annual, and semi-annual amplitudes of the 10-year time series coefficients. The performance of the new model was evaluated using its predicted Tm values in 2018 to compare with the following two references in the same year: (1) Tm from ERA5 hourly reanalysis with the horizontal resolution of 5∘ × 5∘; (2) Tm from atmospheric profiles from 428 globally distributed radiosonde stations. Compared to the first reference, the mean RMSEs of the model-predicted Tm values over all global grid points at the 950 and 500 hPa pressure levels were 3.35 and 3.94 K, respectively. Compared to the second reference, the mean bias and mean RMSE of the model-predicted Tm values over the 428 radiosonde stations at the surface level were 0.34 and 3.89 K, respectively; the mean bias and mean RMSE of the model's Tm values over all pressure levels in the height range from the surface to 10 km altitude were −0.16 and 4.20 K, respectively. The new model results were also compared with that of the GTrop and GWMT_D models in which different height correction methods were also applied. Results indicated that significant improvements made by the new model were at high-altitude pressure levels; in all five height ranges, GGNTm results were generally unbiased, and their accuracy varied little with height. The improvement in PWV brought by GGNTm was also evaluated. These results suggest that considering the vertical nonlinear variation in Tm and the temporal variation in the coefficients of the Tm model can significantly improve the accuracy of model-predicted Tm for a GNSS receiver that is located anywhere below the tropopause (assumed to be 10 km), which has significance for applications requiring real-time or near real-time PWV converted from GNSS signals.

This investigation is to concentrate on the effect of thermal radiation on free convection of a Cu-water nanofluid in a differentially heated cavity containing a solid square block placed in the middle. The upper and lower dividers of the cavity are kept as thermally protected; The coupled equations of mass, momentum, and energy are governed the mathematical model. Finite difference method is used to solve the governing equations. All internal surfaces of the cavity are deemed as a diffused emitters and reflectors for radiation. The impacts of relevant parameters, the Rayleigh number (103?Ra?106), volume fraction of nanoparticles (0.0???0.04) and thermal radiation (Rd = 0, 1, 5, and 10), are explored. For various values of the flow parameters, the values for local and average Nusselt number are calculated. It is observed that the local and averaged Nusselt numbers are increased with an increase in the Rayleigh number and volume fraction of nanoparticles. Also, the temperature distribution of the fluid increases with an increase in the radiation parameter.

The final output signal quality of TDICCD is related to the key parameters such as working mode, output mode, signal-to-noise ratio, dynamic range and so on. We can improve these parameters of TDICCD by reasonably designing the sensor clocking. Therefore, this text discussed four methods of improved TDICCD sensor clocking to solve some problem in TDICCD application based on using the principle of TDICCD. The technique of TDICCD Taps merging can reduce the number of TDICCD Taps, which helps to reduce the size of the TDICCD rear-end circuit significantly; The technique of TDICCD continuous transfer clocking can improve the charge transfer efficiency, which helps to promote the final signal-to-noise ratio; The technique of pixel binning clocking can enlarge the dynamic range of image; The technique of TDICCD area-array working mode can extend the field of TDICCD working; The principle, derivation process, clocking sequence diagram and application range of these clocking design schemes are given in this paper. At the same time, it also explains its actual effect and the matters to be noted.

Background Studies report that survival outcomes in patients with non-muscle-invasive bladder cancer (NMIBC) are worse when cystectomy is delayed. However, no systematic evidence is available. Objective The aim of this study was to systematically review the literature to compare the long-term survival outcomes of patients with high-grade NMIBC (T1G3, including carcinoma in situ) who have early cystectomy compared to deferred radical cystectomy post-diagnosis. Materials and methods A systematic review was carried out by searching MEDLINE and related databases (Google Scholar, National Health Service Evidence) for all relevant studies published from 1946 to present. Additional studies were identified through following the references of relevant papers. Studies were included if they met the following criteria: inclusion of at least 30 patients having high-grade NMIBC, 2 groups treated with either early or deferred cystectomy with a clear temporal cut-off between groups and reported data on survival rate of at least 5 years. Results Literature was systematically reviewed, and 10 studies were included, totaling 1,516 patients who underwent either primary cystectomy or deferred cystectomy. It was found that patients who underwent early cystectomy show improved 5- to 10-year cancer-specific survival (relative risk = 0.81, p = 0.029) suggesting a significant survival benefit when compared to deferred cystectomy. Conclusions This study provides systematically gathered evidence showing benefit of early cystectomy. Despite this result, radical cystectomy greatly impairs quality of life and represents overtreatment for a significant minority. This result highlights the importance of a decisive treatment plan to minimize treatment delay.

The citral compound that contributes to the strong-lemony odour of lemongrass has high volatility and low physicochemical stability. To overcome the problems, the inclusion complex of the encapsulation technique was applied with rice starch as a coating material to improve the stability and protect against any unfavourable reaction. Therefore, this study was conducted to determine the structural characterization, citral retention and thermal properties of native rice starch, gelatinised rice starch, inclusion complex of rice starch–citral compound, and inclusion complex of rice starch–lemongrass extract. Lemongrass extract and standard citral compound were homogenised into rice starch dispersion at 80oC for 15 mins and freeze-dried at −50.0±2.0oC. The formation of the inclusion complex powder was determined using different analyses including morphological structure using the scanning electron microscope, crystallinity structure was determined with X-ray diffractometer, identification and quantification of citral compound using HS-SPME-GC-FID and the thermal properties of inclusion complex analyzed using differential scanning calorimetry. The microstructure of both inclusion complex of rice starch-lemongrass extract and rice starch-citral compound exhibited a laminated multiangular shape with crumble formation together with the characteristics of V-type pattern of crystalline complexes. The low degree of crystallinity of the inclusion complex of rice starch–lemongrass extract obtained high in citral entrapment (29.34±3.13%) with the highest concentration of citral retention (7.33±0.78 ppm). Both inclusion complex of rice starch-citral compound and rice starch-lemongrass extract displayed an endothermic peak at 138oC, which is attributed to an inclusion complex occurrence with significant difference (p

In order to satisfy the requirement of the engine heat exchangers, ultra-thin tubes with higher dimensional accuracy and better performance are required. Inconel 718, as the basic material of ultra-thin tube, is one of the materials that can meet the requirements of the engine heat exchanger. In this study, ultra-thin tubes with diameters and thicknesses of 1.50mm and 0.050mm were prepared by floating plug drawing process. The results showed that the yield strength increased and the corresponding elongation decreased with the increase of drawing passes. The wall thickness of the ultra-thin tube can be controlled by floating plug drawing. And the inner surface quality was greatly improved compared with the initial tube. The inner surface roughness can be controlled below 1.7μm. The average grain size after drawing can be reduced from 4.9μm to 2.1μm.

The densification mechanism of the electric field-assisted sintering (E-FAST) for Inconel 718 alloy miniature gears was studied using the Bernard-Granger model. Under the conditions of sintering temperature of 950 °C, 1000 °C and 1050 °C and dwelling time of 240 s, 300 s and 360 s, the Inconel 718 powders were subjected to E-FAST using the Gleeble thermal simulator, and the densification rate was up to 10−3 s−1. With the increase of the sintering temperature, the peak of the densification rate of the sintered sample was enlarged, and the time for the peak to appear became shorter. The densification of Inconel 718 alloy miniature gears was mainly concentrated in the dwelling stage. When the dwelling time reached 300 s, the densification rates of the samples under different temperature conditions were similar, indicating that the gear samples were close to full density at this time. Simulation and sintering test results show that the densification stages of the gear samples can be divided into low sintering stress stage with stress index n = 0.4 and high sintering stress stage with stress index n = 3.5. The apparent activation energy of the densification changes with the variation of the sintering stress stage.

Mutational signatures accumulate in somatic cells as an admixture of endogenous and exogenous processes that occur during an individual’s lifetime. Since dividing cells release cell-free DNA (cfDNA) fragments into the circulation, we hypothesize that plasma cfDNA might reflect mutational signatures. Point mutations in plasma whole genome sequencing (WGS) are challenging to identify through conventional mutation calling due to low sequencing coverage and low mutant allele fractions. In this proof of concept study of plasma WGS at 0.3–1.5x coverage from 215 patients and 227 healthy individuals, we show that both pathological and physiological mutational signatures may be identified in plasma. By applying machine learning to mutation profiles, patients with stage I-IV cancer can be distinguished from healthy individuals with an Area Under the Curve of 0.96. Interrogating mutational processes in plasma may enable earlier cancer detection, and might enable the assessment of cancer risk and etiology.

Introduction Professional identity formation (PIF) is a priority of medical training. Covid-19 caused disruption to medical education. We ask how this disruption impacted PIF through the lens of the activities performed – or not performed – by medical students during the first wave of the covid-19 pandemic, and perceptions of conflicts between activities. Method A pragmatic survey was distributed in spring 2020. Thematic analysis was performed of qualitative responses to two open questions. A social constructivist approach linked participants’ comments to PIF theory. Results We analysed 928 responses. Three themes surrounding students’ activities during covid-19 and their impact on identity were constructed: Conflict arose at the intersections between these themes. Students noted lack of clinical exposure was detrimental, implicitly recognising that aspects of PIF require the clinical environment. Participants were keen to volunteer but struggled with balancing academic work. Participants worried about risk to their households and the wider community and wanted their skills to add value in the clinical environment. Volunteers felt frustrated when they were unable to perform tasks aligning with their identity as a future doctor. An exception was participants who worked as interim FY1s, aligned with the role of an FY1. Conclusions Medical students feel a duty to help during crises. Conflict arises when different aspects of their identity demand different actions. Care must be taken to nurture PIF during periods of disruption.

Importance Novel therapies for SARS-CoV-2 infection are urgently needed. Antineoplastic compounds that target cellular machinery used by SARS-CoV-2 for entry and replication, including angiotensin-converting enzyme 2 (ACE2), may disrupt SARS-CoV-2 activity. Objectives To determine whether patients with cancer treated with potential ACE2-lowering antineoplastic compounds exhibit lower SARS-CoV-2 infection rates. Design, setting, and participants We used the Library of Integrated Network-Based Cellular Signatures database to identify antineoplastic compounds associated with decreased ACE2 gene expression across cell lines. We then evaluated a retrospective cohort of 1701 patients who were undergoing antineoplastic therapy at Memorial Sloan Kettering Cancer Center in New York, New York, during the COVID-19 pandemic to determine if treatment with an ACE2-lowering antineoplastic was associated with a decreased odds ratio (OR) of SARS-CoV-2 infection. Patients included in the analysis underwent active treatment for cancer and received a SARS-CoV-2 test between March 10 and May 28, 2020. Main outcome and measure The association between potential ACE2-lowering antineoplastic treatment and a positive SARS-CoV-2 test. Results In the cohort of 1701 patients, SARS-CoV-2 infection rates were determined for 949 (55.8%) female and 752 (44.2%) male patients (mean [SD] age, 63.1 [13.1] years) with diverse cancers receiving antineoplastic therapy. In silico analysis of gene expression signatures after drug treatment identified 91 compounds associated with downregulation of ACE2 across cell lines. Of the total cohort, 215 (12.6%) patients were treated with 8 of these compounds, including 3 mTOR/PI3K inhibitors and 2 antimetabolites. In a multivariable analysis of patients who received an ACE2-lowering antineoplastic adjusting for confounders, 15 of 215 (7.0%) patients had a positive SARS-CoV-2 test compared with 191 of 1486 (12.9%) patients who received other antineoplastic therapies (OR, 0.53; 95% CI, 0.29-0.88). Findings were confirmed in additional sensitivity analyses including cancer type, steroid use, and a propensity-matched subcohort. Gemcitabine treatment was associated with reduced SARS-CoV-2 infection (OR, 0.42; 95% CI, 0.17-0.87). Conclusions and relevance In this cohort study, in silico analysis of drug-associated gene expression signatures identified potential ACE2-lowering antineoplastic compounds, including mTOR/PI3K inhibitors and antimetabolites. Patients who received these compounds exhibited statistically significantly lower rates of SARS-CoV-2 infection compared with patients given other antineoplastics. Further evaluation of the biological and clinical anti-SARS-CoV-2 properties of identified antineoplastic compounds is warranted.

PhenomenonProfessional identity development is recognised as a core goal of medical education alongside knowledge and skill acquisition. Identity is a complex entity that can be conceptualised as externally influenced, but individually constructed. Integration from legitimate bystander to ‘old timer’ of the medical community of practice provides a backdrop for individual negotiation of professional identity. During Covid-19, the medical community of practice and education experienced significant disruption. We sought to investigate how these disruptions impacted professional identity development by examining conflicts between students’ identities highlighted by the pressures of the pandemic.ApproachA mixed-methods survey was distributed to medical students in the UK. The survey was active from 2nd May to 15th June 2020, during the height of the first wave of the Covid-19 pandemic in the UK. Operating within the paradigm of constructivism, we conducted a reflexive thematic analysis of qualitative responses. Analysis was focused around the disruption to medical education, actions taken by medical students during this disruption, and the tension between student actions where they existed in conflict.FindingsThree themes were constructed to describe the identities that participants felt were in conflict during the first wave of the Covid-19 pandemic: Status and role as a future doctor; status and role as a student; and status and role as a member of the wider community. Students noted that lack of clinical exposure was detrimental to their education, implicitly recognising that many aspects of professional identity formation are forged in the clinical environment. Participants were keen to volunteer clinically but struggled to balance this with academic work. Participants worried about the risk to their families and the wider community, and wanted to ensure that their skills would add value to the clinical environment. Volunteers felt frustrated when they were unable to perform tasks which aligned with their identities as future doctors, with the exception of participants who worked as interim FY1s (FiY1s), which aligned well with the roles of FY1s.InsightsAs hypothesised, the participants in this study experienced disruptions to their professional identity development during the first wave of the Covid-19 pandemic in 2020. This work provides early evidence, collected at the beginning of the pandemic, that the effects of disruptions to professional identity development were wide-reaching, often negative, and represent an important topic for future exploration. Given that the pandemic has highlighted areas of identity tension, these findings have the potential to provide insight into how medical training can better nurture professional identity development during and beyond international crises.

Glioma‐derived cell‐free DNA (cfDNA) is challenging to detect using liquid biopsy because quantities in body fluids are low. We determined the glioma‐derived DNA fraction in cerebrospinal fluid (CSF), plasma, and urine samples from patients using sequencing of personalized capture panels guided by analysis of matched tumor biopsies. By sequencing cfDNA across thousands of mutations, identified individually in each patient’s tumor, we detected tumor‐derived DNA in the majority of CSF (7/8), plasma (10/12), and urine samples (10/16), with a median tumor fraction of 6.4 × 10−3, 3.1 × 10−5, and 4.7 × 10−5, respectively. We identified a shift in the size distribution of tumor‐derived cfDNA fragments in these body fluids. We further analyzed cfDNA fragment sizes using whole‐genome sequencing, in urine samples from 35 glioma patients, 27 individuals with non‐malignant brain disorders, and 26 healthy individuals. cfDNA in urine of glioma patients was significantly more fragmented compared to urine from patients with non‐malignant brain disorders (P = 1.7 × 10−2) and healthy individuals (P = 5.2 × 10−9). Machine learning models integrating fragment length could differentiate urine samples from glioma patients (AUC = 0.80–0.91) suggesting possibilities for truly non‐invasive cancer detection., Gliomas are challenging to detect using tumor derived cell‐free DNA (cfDNA) in body fluids. In this study, two novel analysis methods (tumor‐guided sequencing and sWGS) were developed to explore the potential of using plasma and urine cfDNA as a liquid biopsy for this malignancy.

A novel Inconel 718 particulate reinforced composite filler metal was used to fabricate the Ni-based superalloy ultrathin-walled structure by vacuum brazing. The brazing process was carried out at various temperatures (1423 K, 1443 K, 1463 K). Moreover, the effects of brazing temperature and the particulate content on wettability, solidification behaviour, typical microstructural evolution and the mechanical properties of the brazed ultrathin-walled structure were investigated in detail. The results indicate that increasing reinforced particulate would result in a worse wettability and higher liquidus temperature of the composite filler metal, which is attributed to the inevitable diffusion phenomenon. The microstructure in the brazed region is mainly composed of γ-Ni solid solution, Ni 5 Si 2 , Cr 3 Ni 5 Si 2 , G-phase and Ni–Si–Nb intermetallic compound. The elevated brazing temperature would cause a significant decrease in the mechanical properties of the ultrathin-walled structure. With the addition of the reinforced particulate, the mechanical properties increase obviously and the response effect of the particulate is better at higher brazing temperature. Meanwhile, the area of the Ni-based solid solution and the dispersion degree of the eutectic phase in the brazing fillet increase as the increase of the particulate content. However, the solute loss phenomenon induced by adding excessive reinforced particulate would decrease the mechanical properties. The result reveals that the tensile strength increases by 70 MPa, 103 MPa and 100 MPa, while the elongation increases by 0.8%, 5.4% and 6.8% at various brazing temperatures, comparing with the ultrathin-walled structure using the initial filler metal.

Ultrasonic vibration (UV) has been widely applied in metal forming process due to its ability to improve the material properties. However, the mechanical response of difficult-to-deform materials with the assistance of UV is unclear, especially for the ultrathin sheet metals. Meanwhile, the current constitutive models are deficient for the description of UV assisted deformation behavior of the ultrathin material. In this research, UV assisted tensile tests with different amplitudes were performed on the ultrathin superalloy sheet, and the influences on the mechanical characteristic and microstructural evolution were explored. The experimental results indicated that the UV induced softening effect is not evident for high strength material, which is attributed to the tensile deformation characteristic of ultrathin sheet and the distinct mechanical property of superalloy. Nevertheless, the ductility of the superalloy sheet is notably enhanced under the ultrasonic amplitude of 3.18 μm, featured with the increase of elongation from 20.7% to 25.5%. Moreover, the texture is enhanced with increasing ultrasonic amplitude, and the grain misorientations are significantly changed under different UV conditions. To accurately describe the constitutive behavior of superalloy under the assistance of UV, a hybrid constitutive model separately considering stress superposition and acoustic softening effect was developed based on the dislocation evolution theory. The predicted results are in good agreement with the experimental data. These findings provide a more in-depth understanding on the mechanism of UV assisted forming and promote the application of UV assisted manufacturing processes for difficult-to-deform alloys.

Patient selection for critical care admission must balance patient safety with optimal resource allocation. This study aimed to determine the relationship between critical care admission, and postoperative mortality after abdominal surgery.This prespecified secondary analysis of a multicentre, prospective, observational study included consecutive patients enrolled in the DISCOVER study from UK and Republic of Ireland undergoing major gastrointestinal and liver surgery between October and December 2014. The primary outcome was 30-day mortality. Multivariate logistic regression was used to explore associations between critical care admission (planned and unplanned) and mortality, and inter-centre variation in critical care admission after emergency laparotomy.Of 4529 patients included, 37.8% (n=1713) underwent planned critical care admissions from theatre. Some 3.1% (n=86/2816) admitted to ward-level care subsequently underwent unplanned critical care admission. Overall 30-day mortality was 2.9% (n=133/4519), and the risk-adjusted association between 30-day mortality and critical care admission was higher in unplanned [odds ratio (OR): 8.65, 95% confidence interval (CI): 3.51-19.97) than planned admissions (OR: 2.32, 95% CI: 1.43-3.85). Some 26.7% of patients (n=1210/4529) underwent emergency laparotomies. After adjustment, 49.3% (95% CI: 46.8-51.9%, P0.001) were predicted to have planned critical care admissions, with 7% (n=10/145) of centres outside the 95% CI.After risk adjustment, no 30-day survival benefit was identified for either planned or unplanned postoperative admissions to critical care within this cohort. This likely represents appropriate admission of the highest-risk patients. Planned admissions in selected, intermediate-risk patients may present a strategy to mitigate the risk of unplanned admission. Substantial inter-centre variation exists in planned critical care admissions after emergency laparotomies.

Introduction COVID-19 led to global disruption of healthcare and many students volunteered to provide clinical support. Volunteering to work was a unique medical education opportunity; however, it is unknown whether this was a positive learning experience. Methods The COVID Ready 2 study is a national cross-sectional study of all medical students at UK medical schools. We will compare opinions of those who did and did not volunteer to determine the educational benefit and issues they faced. We will use thematic analysis to identify themes in qualitative responses, in addition to quantitative analysis. Results The primary objective is to explore the effect of volunteering during the pandemic on medical education in comparison to those who did not volunteer. Our secondary objectives are to identify: whether students would be willing to assume similar roles in a non-pandemic setting; if students found the experience more or less beneficial than traditional hospital placements and reasons for this; what the perceived benefits and disadvantages of volunteering were; the difference in perceived preparedness between students who did and did not volunteer for foundation training year one and the next academic year; training received by volunteers; and to explore issues associated with volunteering, including safety issues and issues with role and competence. Conclusions We anticipate this study will help identify volunteer structures that have been beneficial for students, so that similar infrastructures can be used in the future; and help determine whether formal voluntary roles should be introduced into the non-pandemic medical curriculum.

Introduction In response to the disruption to medical education caused by COVID-19, there is a need for wide-scale robust medical education research and the generation of research capacity for the future. Trainee research collaboratives have demonstrated they can nurture the research skills of students and trainees while delivering high quality research outputs. However, we have been unable to identify a permanent medical education research collaborative for trainees and students. Methods We started the MedEd Collaborative in September 2020 to fill this gap, consisting of a trainee- and student-led medical education research collaborative supported by senior medical education experts and clinicians. Results Our vision is to increase engagement of students and trainees in high-quality medical education research that informs practice. The MedEd Collaborative will engage students and trainees in medical education research by completing at least one national multicentre study per year, the first being the COVID Ready 2 study. This is a national cross-sectional survey of the educational impact of medical student volunteering during the COVID-19 pandemic. Conclusions We anticipate the MedEd collaborative will: increase exposure to medical education research, thereby increasing the number of medical students and trainees aiming to pursue an academic medical education career; provide training in medical education research methodologies, such as qualitative analysis; improve the quality of medical education research outputs from students and trainees; encourage collaboration between medical schools and deaneries; and provide support to other trainee research collaboratives that aim to explore education research in their own specialties.

BackgroundThe coronavirus disease 2019 pandemic has led to global disruption of healthcare. Many students volunteered to provide clinical support. Volunteering to work in a clinical capacity was a unique medical education opportunity; however, it is unknown whether this was a positive learning experience or which volunteering roles were of most benefit to students.MethodsThe COVIDReady2 study is a national cross-sectional study of all medical students at medical schools in the United Kingdom. The primary outcome is to explore the experiences of medical students who volunteered during the pandemic in comparison to those who did not. We will compare responses to determine the educational benefit and issues they faced. In addition to quantitative analysis, thematic analysis will be used to identify themes in qualitative responses.DiscussionThere is a growing body of evidence to suggest that service roles have potential to enhance medical education; yet, there is a shortage of studies able to offer practical advice for how these roles may be incorporated in future medical education. We anticipate that this study will help to identify volunteer structures that have been beneficial for students, so that similar infrastructures can be used in the future, and help inform medical education in a non-pandemic setting.Trial registrationNot Applicable.

目的 探讨IDH不同突变亚型及伴发不同基因突变在非M3型急性髓系白血病（AML）患者中的预后意义。 方法 采用二代测序技术检测2016年6月至2018年12月就诊于郑州大学第一附属医院的389例AML患者的22种基因突变情况，通过Kaplan-Meier法及Cox回归模型分析影响预后的因素。 结果 389例AML患者中，IDH1及IDH2的突变率分别为6.2%、8.7%，未发现IDH1与IDH2共突变的情况。IDH2突变型患者年龄偏大、骨髓原始细胞比例高、正常核型多见、常合并RUNX1突变及SRSF2突变。单因素方差分析发现，IDH1突变型组较野生型组的中位总生存（OS）及无进展生存（PFS）时间明显缩短（P值均

Chlamydia trachomatis is an important bacterial pathogen that has an unusual developmental switch from a dividing form (reticulate body or RB) to an infectious form (elementary body or EB). RBs replicate by binary fission within an infected host cell, but there is a delay before RBs convert into EBs for spread to a new host cell. We developed stochastic optimal control models of the Chlamydia developmental cycle to examine factors that control the number of EBs produced. These factors included the probability and timing of conversion, and the duration of the developmental cycle before the host cell lyses. Our mathematical analysis shows that the observed delay in RB-to-EB conversion is important for maximizing EB production by the end of the intracellular infection.

BACKGROUND: Salmonella is one of the most important enteric pathogenic bacteria that threatened poultry health. AIMS: This study aimed to investigate the prevalence and antimicrobial resistance of Salmonella isolates in goose farms. METHODS: A total of 244 cloacal swabs were collected from goose farms to detect Salmonella in Northeast China. Antimicrobial susceptibility, and resistance gene distribution of Salmonella isolates were investigated. RESULTS: Twenty-one Salmonella isolates were identified. Overall prevalence of Salmonella in the present study was 8.6%. Among the Salmonella isolates, the highest resistance frequencies belonged to amoxicillin (AMX) (85.7%), tetracycline (TET) and trimethoprim/sulfamethoxazole (SXT) (81%), followed by chloramphenicol (CHL) (76.2%), florfenicol (FLO) (71.4%), kanamycin (KAN) (47.6%), and gentamycin (GEN) (38.1%). Meanwhile, only 4.8% of the isolates were resistant to ciprofloxacin (CIP) and cefotaxime (CTX). None of the isolates was resistant to cefoperazone (CFP) and colistin B (CLB). Twenty isolates (95%) were simultaneously resistant to at least two antimicrobials. Ten resistance genes were detected among which the bla(TEM-1), cmlA, aac(6’)-Ib-cr, sul1, sul2, sul3, and mcr-1.1 were the most prevalent, and presented in all 21 isolates followed by tetB (20/21), qnrB (19/21), and floR (15/21). CONCLUSION: Results indicated that Salmonella isolates from goose farms in Northeast China exhibited multi-drug resistance (MDR), harboring multiple antimicrobial resistance genes. Our results will be useful to design prevention and therapeutic strategies against Salmonella infection in goose farms.

Carbon steel as materials of pipe is used in the plural oil and gas industry in Malaysia, but the corrosive working environment conditions create this type of pipe prone to corrosion. In electrical industries, Aluminum-conductor steel-reinforced (ACSR) are the most commonly used in transmission line systems due to aluminum’s light weight and cost, and carbon steel’s strand is high mechanical strength. Corrosion is an absolute phenomenon that occurs in carbon steel, but the rate of corrosion can be controlled by certain techniques. One of which is the use of environmentally friendly corrosion inhibitors or so-called green corrosion inhibitors. Moringa Leaf (Moringa Oleifera) is known to have a high content of antioxidant compounds and the use of this benefit only limited to water purification and as a food ingredient. From this issue, research was carried out on the use of Moringa leaf extract as green corrosion inhibitor on carbons steel. This research uses variations Moringa leaf powder concentration in 200 ml static seawater conditions (0 rpm) give the concentration of 200, 400, and 600, 800 and 1000 ppm to get optimal work. The linear polarization method used to determine the performance of Moringa leaf powder to reduce the corrosion reaction. In the tafel test, it was found that moringa leaf powder that is added suitable to work as inhibitor. Addition of the concentration able to reduce the corrosion rate up to 0.124 mmpy with efficiency from polarization resistance of 49.69 %, while efficiency from corrosion rate and corrosion current of 70.5% in static seawater conditions. Consequently, in inhibited solutions, the corrosion rate is indicative of the number of the free corrosion sites remaining after some sites have been blocked by inhibitor adsorption. Tafel test results found that a protective passive layer is formed on the surface of the steel make contact between the metal and sea water is reduced with existing of moringa leaf powder so that corrosion can be inhibited.

Summary Background Circulating tumour DNA (ctDNA) testing might provide a current assessment of the genomic profile of advanced cancer, without the need to repeat tumour biopsy. We aimed to assess the accuracy of ctDNA testing in advanced breast cancer and the ability of ctDNA testing to select patients for mutation-directed therapy. Methods We did an open-label, multicohort, phase 2a, platform trial of ctDNA testing in 18 UK hospitals. Participants were women (aged ≥18 years) with histologically confirmed advanced breast cancer and an Eastern Cooperative Oncology Group performance status 0–2. Patients had completed at least one previous line of treatment for advanced breast cancer or relapsed within 12 months of neoadjuvant or adjuvant chemotherapy. Patients were recruited into four parallel treatment cohorts matched to mutations identified in ctDNA: cohort A comprised patients with ESR1 mutations (treated with intramuscular extended-dose fulvestrant 500 mg); cohort B comprised patients with HER2 mutations (treated with oral neratinib 240 mg, and if oestrogen receptor-positive with intramuscular standard-dose fulvestrant); cohort C comprised patients with AKT1 mutations and oestrogen receptor-positive cancer (treated with oral capivasertib 400 mg plus intramuscular standard-dose fulvestrant); and cohort D comprised patients with AKT1 mutations and oestrogen receptor-negative cancer or PTEN mutation (treated with oral capivasertib 480 mg). Each cohort had a primary endpoint of confirmed objective response rate. For cohort A, 13 or more responses among 78 evaluable patients were required to infer activity and three or more among 16 were required for cohorts B, C, and D. Recruitment to all cohorts is complete and long-term follow-up is ongoing. This trial is registered with ClinicalTrials.gov, NCT03182634; the European Clinical Trials database, EudraCT2015-003735-36; and the ISRCTN registry, ISRCTN16945804. Findings Between Dec 21, 2016, and April 26, 2019, 1051 patients registered for the study, with ctDNA results available for 1034 patients. Agreement between ctDNA digital PCR and targeted sequencing was 96–99% (n=800, kappa 0·89–0·93). Sensitivity of digital PCR ctDNA testing for mutations identified in tissue sequencing was 93% (95% CI 83–98) overall and 98% (87–100) with contemporaneous biopsies. In all cohorts, combined median follow-up was 14·4 months (IQR 7·0–23·7). Cohorts B and C met or exceeded the target number of responses, with five (25% [95% CI 9–49]) of 20 patients in cohort B and four (22% [6–48]) of 18 patients in cohort C having a response. Cohorts A and D did not reach the target number of responses, with six (8% [95% CI 3–17]) of 74 in cohort A and two (11% [1–33]) of 19 patients in cohort D having a response. The most common grade 3–4 adverse events were raised gamma-glutamyltransferase (13 [16%] of 80 patients; cohort A); diarrhoea (four [25%] of 20; cohort B); fatigue (four [22%] of 18; cohort C); and rash (five [26%] of 19; cohort D). 17 serious adverse reactions occurred in 11 patients, and there was one treatment-related death caused by grade 4 dyspnoea (in cohort C). Interpretation ctDNA testing offers accurate, rapid genotyping that enables the selection of mutation-directed therapies for patients with breast cancer, with sufficient clinical validity for adoption into routine clinical practice. Our results demonstrate clinically relevant activity of targeted therapies against rare HER2 and AKT1 mutations, confirming these mutations could be targetable for breast cancer treatment. Funding Cancer Research UK, AstraZeneca, and Puma Biotechnology.

Ancient architecture is one of the important historical and cultural heritage content, after many years trials and hardships, there will be a variety of diseases. To better protect the ancient architecture, we need to carry out a detailed investigation to detect and assess its structural safety and stability. Exploration of ancient architecture safety detection, need for an integrated comprehensive and detailed surveying and mapping means drawing detection map, using non-destructive detection techniques to check. We based on three-dimensional laser scanning, integrated utilization technology mapping, ground penetrating radar detection technology, stress wave scanning technology, visual quality and damage prospecting techniques to detect the safety situation in Beijing Bell and Drum Towers. We put forward reasonable suggestions for appropriate repair, on the basis of a variety modal analysis detected the structures, the status of Beijing Bell and Drum Towers safety were assessed. The detection process in this paper has better prospects for the future work that explores cultural heritage of ancient architecture repair detection and appropriate assessment.

Circulating tumor-derived DNA (ctDNA) can be used to monitor cancer dynamics noninvasively. Detection of ctDNA can be challenging in patients with low-volume or residual disease, where plasma contains very few tumor-derived DNA fragments. We show that sensitivity for ctDNA detection in plasma can be improved by analyzing hundreds to thousands of mutations that are first identified by tumor genotyping. We describe the INtegration of VAriant Reads (INVAR) pipeline, which combines custom error-suppression methods and signal-enrichment approaches based on biological features of ctDNA. With this approach, the detection limit in each sample can be estimated independently based on the number of informative reads sequenced across multiple patient-specific loci. We applied INVAR to custom hybrid-capture sequencing data from 176 plasma samples from 105 patients with melanoma, lung, renal, glioma, and breast cancer across both early and advanced disease. By integrating signal across a median of >105 informative reads, ctDNA was routinely quantified to 1 mutant molecule per 100,000, and in some cases with high tumor mutation burden and/or plasma input material, to parts per million. This resulted in median area under the curve (AUC) values of 0.98 in advanced cancers and 0.80 in early-stage and challenging settings for ctDNA detection. We generalized this method to whole-exome and whole-genome sequencing, showing that INVAR may be applied without requiring personalized sequencing panels so long as a tumor mutation list is available. As tumor sequencing becomes increasingly performed, such methods for personalized cancer monitoring may enhance the sensitivity of cancer liquid biopsies.