It is unclear how much adolescents’ lives were disrupted throughout the COVID-19 pandemic or what risk factors predicted such disruption. To answer these questions, 1,080 adolescents in 9 nations were surveyed 5 times from March 2020 to July 2022. Rates of adolescent COVID-19 life disruption were stable and high. Adolescents who, compared to their peers, lived in nations with higher national COVID-19 death rates, lived in nations with less stringent COVID-19 mitigation strategies, had less confidence in their government’s response to COVID-19, complied at higher rates with COVID-19 control measures, experienced the death of someone they knew due to COVID-19, or experienced more internalizing, externalizing, and smoking problems reported more life disruption due to COVID-19 during part or all of the pandemic. Additionally, when, compared to their typical levels of functioning, adolescents experienced spikes in national death rates, experienced less stringent COVID-19 mitigation measures, experienced less confidence in government response to the COVID-19 pandemic, complied at higher rates with COVID-19 control measures, experienced more internalizing problems, or smoked more at various periods during the pandemic, they also experienced more COVID-19 life disruption. Collectively, these findings provide new insights that policymakers can use to prevent the disruption of adolescents’ lives in future pandemics.

We report the experimental results of the commissioning phase in the 10 PW laser beamline of the Shanghai Superintense Ultrafast Laser Facility (SULF). The peak power reaches 2.4 PW on target without the last amplifying during the experiment. The laser energy of 72 ± 9 J is directed to a focal spot of approximately 6 μm diameter (full width at half maximum) in 30 fs pulse duration, yielding a focused peak intensity around 2.0 × 1021 W/cm2. The first laser-proton acceleration experiment is performed using plain copper and plastic targets. High-energy proton beams with maximum cut-off energy up to 62.5 MeV are achieved using copper foils at the optimum target thickness of 4 μm via target normal sheath acceleration. For plastic targets of tens of nanometers thick, the proton cut-off energy is approximately 20 MeV, showing ring-like or filamented density distributions. These experimental results reflect the capabilities of the SULF-10 PW beamline, for example, both ultrahigh intensity and relatively good beam contrast. Further optimization for these key parameters is underway, where peak laser intensities of 1022–1023 W/cm2 are anticipated to support various experiments on extreme field physics.

Frequent freezing injury greatly influences winter wheat production; thus, effective prevention and a command of agricultural production are vital. The freezing injury monitoring method integrated with ‘3S’ (geographic information systems (GIS), global positioning system (GPS) and remote sensing (RS)) technology has an unparalleled advantage. Using HuanJing (HJ)-1A/1B satellite images of a winter wheat field in Shanxi Province, China plus a field survey, crop types and winter wheat planting area were identified through repeated visual interpretations of image information and spatial analyses conducted in GIS. Six vegetation indices were extracted from processed HJ-1A/1B satellite images to determine whether the winter wheat suffered from freezing injury and its degree of severity and recovery, using change vector analysis (CVA), the freeze injury representative vegetation index and the combination of the two methods, respectively. Accuracy of the freezing damage classification results was verified by determining the impact of freezing damage on yield and quantitative analysis. The CVA and the change of normalized difference vegetation index (ΔNDVI) monitoring results were different so a comprehensive analysis of the combination of CVA and ΔNDVI was performed. The area with serious freezing injury covered 0.9% of the total study area, followed by the area of no freezing injury (3.5%), moderate freezing injury (10.2%) and light freezing injury (85.4%). Of the moderate and serious freezing injury areas, 0.2% did not recover; 1.2% of the no freezing injury and light freezing injury areas showed optimal recovery, 15.6% of the light freezing injury and moderate freezing injury areas showed poor recovery, and the remaining areas exhibited general recovery.

This paper first uses a low-speed stereoscopic particle image velocimetry (SPIV) system to measure the convergent statistical quantities of the flow field and then simultaneously measure the time-resolved flow field and the wall mass transfer rate by a high-speed SPIV system and an electrochemical system, respectively. We measure the flow field and wall mass transfer rate under upstream pipe Reynolds numbers between 25 000 and 55 000 at three specific locations behind the orifice plate. Moreover, we apply proper orthogonal decomposition (POD), stochastic estimation and spectral analysis to study the properties of the flow field and the wall mass transfer rate. More importantly, we investigate the large-scale coherent structures’ effects on the wall mass transfer rate. The collapse of the wall mass transfer rates’ spectra by the corresponding time scales at the three specific positions of orifice flow suggest that the physics of low-frequency wall mass transfer rates are probably the same, although the flow fields away from the wall are quite different. Furthermore, the spectra of the velocity reconstructed by the most energetic eigenmodes agree well with the wall mass transfer rate in the low-frequency region, suggesting that the first several energetic eigenmodes capture the flow dynamics relevant to the low-frequency variation of the wall mass transfer. Stochastic estimation results of the velocity field associated with large wall mass transfer rate at all three specific locations further reveal that the most energetic coherent structures are correlated with the wall mass transfer rate.

ABSTRACT IMPACT: We are developing the 3D perfusion system for use with patient-derived bacteria to further characterize the mechanism behind bacterial-induced inflammation and cancer. OBJECTIVES/GOALS: We previously reported the adherent invasive E. coli NC101 promote colorectal cancer (CRC) in mice. FimH, a mannose-specific adhesin on type 1 fimbriae, is involved in bacterial surface adhesion. Herein, we investigated the role of FimH in E. coli NC101-induced adherence and carcinogenesis in a novel 3D perfusion culture imaging plate. METHODS/STUDY POPULATION: E. coli NC101 gene fimH was deleted byï ŲRed Recombinase System. Biofilm formation was assessed by crystal violet and congo red staining. 5 dpf (wild-type strain) zebrafish embryos were infected in 6x107 cfu/ml wild type (WT) or fimH-deleted (ï ,,fimH) E. coli NC101 for 24hr and gut dissected for bacterial culture. A 2D/3D infection culture system for IEC-6 and HT-29 cells was infected for 4 hr and imaged and then DNA damage examined by comet assay, cell cycle andÎ3H2AX accumulation. Germ-free (GF) Il10-/- (colitis) mice were orally gavaged with 108 cfu WT orï ,,fimH E. coli NC101 for 16 weeks. E. coli colonization were quantified by plate culture and qPCR. Lipocalin2 was quantified by ELISA. PCNA and β-catenin were evaluated by immunohistochemistry (IHC). RESULTS/ANTICIPATED RESULTS: Biofilm formation was reduced by more than 40% (p<0.05) in E. coli NC101ï ,,fimH compared to WT strain. Zebrafish larvae showed a 41% decrease in intestinal colonization ofï ,,fimH compared to WT (p<0.05). E. coli NC101-induced DNA damage was reduced by 67% (p<0.0001) in HT-29 cells infected withï ,,fimH compared to WT strain. Using the 3D infection system, a 46% decrease in yH2AX (p<0.05) and 42% decrease in G2 cell cycle arrest (p<0.05) was observed inï ,,fimH infected IEC-6 cells compared to WT strain. Furthermore, ï ,,fimH infected Il10-/- mice showed decreased colonization (p<0.01), decreased intestinal inflammation (p<0.05), decreased stool lipocalin2 level (p<0.01), and reduction of PCNA positive cells in the intestine (p<0.05) compared to mice infected with WT strain. DISCUSSION/SIGNIFICANCE OF FINDINGS: Adhesin protein FimH is required by E. coli NC101 to colonize and promote colitis and carcinogenesis both in a 3D perfusion culture and in mice and may serve as potential therapeutic target.

The Dayao Paleolithic site, located in Inner Mongolia on the eastern margin of China's vast northwestern drylands, was a lithic quarry-workshop utilized by Pleistocene human migrants through the region. Determining the age of this activity has previously yielded controversial results. Our magnetostratigraphic and OSL dating results suggest the two artifact-bearing paleosols are correlated with MIS 5 and 7, respectively. Correlating paleoclimatic data with marine δ18O records leads us to conclude that two sandy gravel layers containing many artifacts in the lower part of the Dayao sequence were formed during MIS 9 and 11, if not earlier. Our results reveal that the earliest human occupation at the Dayao site occurred before ca. 400 ka during a relatively warm and moist interglacial period, similar to several subsequent occupations, documenting the earliest and northernmost archaeological assemblage yet reported in China's arid northwest. We conclude that the northward and southward displacements of the East Asian summer monsoon rain belt during past interglacial-glacial cycles were responsible for the discontinuous human occupation detected at the Dayao site. The penetration of this precipitation regime into dryland ecologies via the Huanghe (Yellow River) Valley effectively created a corridor for hominin migration into China's arid northwest.

IFRS 17 Insurance Contracts is a new accounting standard currently expected to come into force on 1 January 2023. It supersedes IFRS 4 Insurance Contracts. IFRS 17 establishes key principles that entities must apply in all aspects of the accounting of insurance contracts. In doing so, the Standard aims to increase the usefulness, comparability, transparency and quality of financial statements.

A fundamental concept introduced by IFRS 17 is the contractual service margin (CSM). This represents the unearned profit that an entity expects to earn as it provides services. However, as a principles-based standard, IFRS 17 results in entities having to apply significant judgement when determining the inputs, assumptions and techniques it uses to determine the CSM at each reporting period.

In general, the Standard resolves broad categories of mismatches which arise under IFRS 4. Notable examples include mismatches between assets recorded at current market value and liabilities calculated using fixed discount rates as well as inconsistencies in the timing of profit recognition over the duration of an insurance contract. However, there are requirements of IFRS 17 that may create economic or accounting mismatches of its own. For example, new mismatches could arise between the measurement of underlying contracts and the corresponding reinsurance held. Additionally, mismatches can still arise between the measurement of liabilities and the assets that support the liabilities.

This paper explores the technical, operational and commercial issues that arise across these and other areas focusing on the CSM. As a standard that is still very much in its infancy, and for which wider consensus on topics is yet to be achieved, this paper aims to provide readers with a deeper understanding of the issues and opportunities that accompany it.

OBJECTIVES/GOALS: We seek to develop a 3D perfusion culture imaging plate for human fecal bacteria co-culture with epithelial cells in a structure that mimics the gut epithelium. We will develop this system for use with patient fecal samples to characterize patient risk of developing cancer. METHODS/STUDY POPULATION: E. coli NC101, a strain that harbors the pks gene island, produces the genotoxin colibactin which causes DNA damage that can lead to colorectal cancer development. The genotoxic ability of this bacterium is dependent upon cell-to-cell contact. Here, we present 3D printed E. coli NC101 and intestinal epithelial cells (IEC-6) in a perfusion imaging plate, enabling visualization of the cytotoxic effects of the bacteria in real time using confocal microscopy, in combination with flow cytometry analysis for cell cycle arrest (a surrogate marker of DNA damage). RESULTS/ANTICIPATED RESULTS: 40,000 IEC-6 cells were 3D printed in a cylindrical layer in our triple well imaging plate. The cells were infected at an MOI of 100 for 18 hours and time lapse images of the infection were recorded by confocal microscopy. The cells were then harvested for analysis by flow cytometry for cell cycle arrest as a measure of DNA damage. Our images and flow cytometry data show that E. coli NC101 co-localizes with IEC-6 cells and causes cell cycle arrest in phase G2 (infected %G2 = 40.1), compared to uninfected cells (%G2 = 24.7, P = 0.034). Mutant strains lacking adhesion protein FimH or the ability to produce colibactin do not cause G2 cell cycle arrest (P = 0.844 and P = 0.644, respectively). DISCUSSION/SIGNIFICANCE OF IMPACT: We are able to recapitulate the DNA damage phenotype of E. coli NC101 in our 3D culture system. We show here that host-microbe interactions leading to cancer can be modeled in our 3D perfusion system, and we will next use patient fecal samples in our culture system.

The Working Party has produced this report in order to prompt readers to engage at an early stage in InsurTech projects, through considering (i) the full range of risks associated with InsurTech developments, (ii) the lifecycle of an InsurTech venture and how any risk considerations may vary over this lifecycle and (iii) the extent to which InsurTech ventures align with risk strategy and risk appetite.

The report contains practical guidance for actuaries, risk professionals, insurance companies and their Boards on these considerations, and can be used to facilitate appropriate questioning, to help ensure that InsurTech-related business decisions are fully cognisant of the risk management issues and to help ensure the success of projects.

The Working Party developed this guidance having carried out an industry survey on a number of risk management topics relating to InsurTech, as well as having carried out interviews with a number of relevant senior stakeholders across the insurance industry, in order to better understand current sentiment and how risk management plays a part when considering opportunities in InsurTech. The Working Party views on the findings from these activities are summarised in the report.

Knowledge, attitudes and practices (KAP) of the population regarding severe fever with thrombocytopenia syndrome (SFTS) in endemic areas of Lu'an in China were assessed before and after an intervention programme. The pre-intervention phase was conducted using a sample of 425 participants from the 12 selected villages with the highest rates of endemic SFTS infection. A predesigned interview questionnaire was used to assess KAP. Subsequently, an intervention programme was designed and applied in the selected villages. KAP was re-assessed for each population in the selected villages using the same interview questionnaire. Following 2 months of the programme, 339 participants had completed the re-assessed survey. The impact of the intervention programme was evaluated using suitable statistical methods. A significant increase in the KAP and total KAP scores was noted following the intervention programme, whereas the proportion of correct knowledge, the positive attitudes and the effective practices toward SFTS of respondents increased significantly. The intervention programme was effective in improving KAP level of SFTS in populations that were resident in endemic areas.

Piglets are characteristically cold intolerant and thus susceptible to high mortality. However, browning of white adipose tissue (WAT) can induce non-shivering thermogenesis as a potential strategy to facilitate the animal’s response to cold. Whether cold exposure can induce browning of subcutaneous WAT (sWAT) in piglets in a similar manner as it can in humans remains largely unknown. In this study, piglets were exposed to acute cold (4°C, 10 h) or chronic cold exposure (8°C, 15 days), and the genes and proteins of uncoupling protein 1 (UCP1)-dependent and independent thermogenesis, mitochondrial biogenesis, lipogenic and lipolytic processes were analysed. Interestingly, acute cold exposure induced browning of porcine sWAT, smaller adipocytes and the upregulated expression of UCP1, PGC1α, PGC1β, C/EBPβ, Cidea, UCP3, CKMT1 and PM20D1. Conversely, chronic cold exposure impaired the browning process, reduced mitochondrial numbers and the expression of browning markers, including UCP1, PGC1α and PRDM16. The present study demonstrated that acute cold exposure (but not chronic cold exposure) induces porcine sWAT browning. Thus, browning of porcine sWAT could be a novel strategy to balance the body temperature of piglets, and thus could be protective against cold exposure.

This paper reports the lead concentration and flux (where accumulation rate is available) along the route of the 1990 International Trans-Antarctic Expedition. The lead concentration in Larsen Ice Shelf and Antarctic Peninsula, the western part of the route, was 7.4 ± 4.1 pg g−1. The lead concentration in East Antarctic snow (South Pole to Mirny station) was 2 3 times higher than that in West Antarctica (Larsen Ice Shelf to South Pole). Taking into account the difference in site conditions, the difference between the above value over this area in 1989 and the value of 6.3 ±3.3 pg g−1 at a site within this area in 1980 (Wolff and Peel, 1985) is not significant. Because the relative contribution of soil dust, volcanoes and the oceans to lead concentration in Antarctica is about 0.5 pg g−1 under modern climatic conditions (Boutron and Patterson, 1987), it is believed that the lead in Antarctic surface snow is dominated by pollution input. The lead-concentration increase from west to east over the trans-Antarctic route suggests that remote Antarctica has been impacted by anthropogenic activities. The lowest lead flux (0.064 ng cn-2 a−1) was on the Antarctic Plateau, mainly reflecting the background global pollution. The mean flux of 0.273 ng cnT2 a−1 in the western part of the route (Larsen Ice Shelf to the Ellsworth Mountains) may result from the pollution input from the Southern Hemisphere. In addition to the influence of global and/or hemispheric pollution, local activities (notably the use of leaded gasolene) appear to have affected the region from Pionerskaya to Mirny.

Measurements of crystal size have been made on seven firn cores drilled at sites covering a range of mean annual temperature from –12.6° to –52.5°C and a range of accumulation rate from 52 to 315 kg m−2 a−1. The sorting coefficient, which gives a measure of the dispersion of crystal sizes within a sample, shows an overall pattern when data from all cores are grouped together as a function of depth. The values are generally small near the surface, increasing to a maximum around 8 m depth, then decreasing but becoming more diffuse at greater depths. Below about 5 m depth, the crystal size increases at an essentially constant rate, which depends on temperature, but in the upper 5 or 7 m the size increases at 1.5 to 2 times this rate. The seasonal variation in temperature enhances the effective mean growth rate of crystals in the near-surface layers compared to conditions with a constant mean temperature and accounts for a part of that increase. But it is likely that vapour diffusion along strong vertical temperature gradients causes the greater part of the observed increase in growth rate. The dependence of crystal-growth rate on temperature is consistent with the Arrhenius-type relation found by other studies.

Fourteen shallow snow/firn cores were drilled with the Polar Ice Coring Office light-weight hand-coring auger in Wilkes Land, along a line approximately long. 111°E between lat. 66° and 74°S. Five of these cores, all between 20 and 30 m deep, are studied in detail in this paper: LJ, BJ, GC30, GC40 and GC46. The physical geographical conditions differ at these five stations, but the general trend is for mean annual accumulation rate and mean annual temperature to decrease farther south, with increasing elevation. At the southernmost station, GC46, the mean annual temperature is –52.5°C, and accumulation rate is 52 kg m−2 a−1.

The density measurements of the snow/firn were made in a cold-room at temperatures from –14− to –18−C, by taking consecutive samples from the core and measuring the mass of each sample of known volume. The characteristics of the initial densification (to a density of 550 kg m−3) – variation in snow/firn density with depth, the densification rate of snow/firn, and the compactive viscosity coefficient of snow/firn – are studied, and the factors affecting this initial densification process are discussed.

The following observations were made and conclusions reached:

1. 1. Plots of all the measurements, from each core, of density against depth showed three different patterns. The first type, typical of the coastal areas, shows a very great variability of density at shallow depth, reducing with an increase in depth. The second, typical of the high inland stations, shows a smaller scatter of densities at shallow depth, again reducing with an increase in depth. The third type is a pattern intermediate between these two. So, the range of density fluctuation with a depth range in any core is greater at the top of the core than at the bottom, and at the same depth in different cores the variation in density is greater where the mean annual temperature is higher.

2. 2. The snow/firn density increases with an increase in depth at all stations, and the densification rate is higher at stations with higher mean annual temperature.

3. 3. The mean density of snow/firn in the top 1 m decreases farther inland, and this decrease appears to be closely related to the decrease in temperature.

4. 4. The mean densification rate is compared with the mean annual temperature and the mean annual accumulation rate over the past 40 years in the most southerly cores. The mean annual temperature is found to be the more important factor affecting the densification rate in the surface snow/firn on the cold ice sheet.

5. 5. At each station, for ρ = 550 kg m−3, a linear relationship is found between log compactive-viscosity coefficient of snow/firn and mean annual temperature for a constant density. If only stations with a mean annual temperature below –25°C (i.e. no melt features are present in the stratigraphy) are considered, then these results from Wilkes Land are very similar to the results obtained by Nishimura and others (1983) from Mizuho Plateau, East Antarctica.

Through-Silicon-Via (TSV) is considered to be the most potential solution for 3D electronic packaging, and the mechanical properties of TSV-Cu are critical for TSV reliability improving. In this paper, to make deeply understand the creep behavior of TSV-Cu, nanoindentation creep tests were conducted to obtain its creep parameters. At first, the TSV specimens were fabricated by means of a typical TSV manufacturing process. Then a combination programmable procedure of the constant indentation strain rate method and the constant load method was employed to study the creep behavior of TSV-Cu. To understand the influence of the previous loading schemes, including the different values of the indentation strain and the maximum depths, the nanoindentation creep tests under different loading conditions were conducted. The values of creep strain rate sensitivity m were derived from the corresponding displacement-holding time curves, and the mean value of m finally determined was 0.0149. The value of m is considered no obvious correlation with the different indentation strain rates and the maximum depths by this method. Furthermore, the mechanism for the room temperature creep was also discussed, and the grain boundaries might play an significant role in this creep behavior.

A symmetric Mach 12·76 hypersonic flow in a 90° corner, formed by 30° swept back intersecting 8° wedges, was investigated in detail through numerical simulation using locally conical Navier-Stokes equations. Three different numerical schemes for spatial discretisation, MacCormack central differencing, van Leer’s flux vector splitting and Osher’s flux difference splitting, were studied to compare their capabilities to capture both strong shock waves and thin shear layers. Comparison with experimental data was made to validate the simulation. The numerical simulation provided further insight into the flowfield and a pair of counter-rotating vortices were discovered near the junction of the corner.

At the end of 2013, China reported a countrywide outbreak of measles. From January to May 2014, we investigated the clinical and immunological features of the cases of the outbreak admitted to our hospital. In this study, all 112 inpatients with clinically diagnosed measles were recruited from the 302 Military Hospital of China. The virus was isolated from throat swabs from these patients, and cytokine profiles were examined. By detecting the measles virus of 30 of the 112 patients, we found that this measles outbreak was of the H1 genotype, which is the major strain in China. The rates of complications, specifically pneumonia and liver injury, differed significantly in patients aged <8 months, 8 months to 18 years, and >18 years: pneumonia was more common in children, while liver injury was more common in adults. Pneumonia was a significant independent risk factor affecting measles duration. Compared to healthy subjects, measles patients had fewer CD4+IL-17+, CD4+IFN-γ+, and CD8+IFN-γ+ cells in both the acute and recovery phases. In contrast, measles patients in the acute phase had more CD8+IL-22+ cells than those in recovery or healthy subjects. We recommend that future studies focus on the age-related distribution of pneumonia and liver injury as measles-related complications as well as the association between immunological markers and measles prognosis.