An investigation into an outbreak of Salmonella Newport infections in Canada was initiated in July 2020. Cases were identified across several provinces through whole-genome sequencing (WGS). Exposure data were gathered through case interviews. Traceback investigations were conducted using receipts, invoices, import documentation, and menus. A total of 515 cases were identified in seven provinces, related by 0–6 whole-genome multi-locus sequence typing (wgMLST) allele differences. The median age of cases was 40 (range 1–100), 54% were female, 19% were hospitalized, and three deaths were reported. Forty-eight location-specific case sub-clusters were identified in restaurants, grocery stores, and congregate living facilities. Of the 414 cases with exposure information available, 71% (295) had reported eating onions the week prior to becoming ill, and 80% of those cases who reported eating onions, reported red onion specifically. The traceback investigation identified red onions from Grower A in California, USA, as the likely source of the outbreak, and the first of many food recall warnings was issued on 30 July 2020. Salmonella was not detected in any tested food or environmental samples. This paper summarizes the collaborative efforts undertaken to investigate and control the largest Salmonella outbreak in Canada in over 20 years.

In 2018, an Ionplus 200 kV MIni-CArbon DAting System (MICADAS) accelerator mass spectrometer (AMS) was installed at the Laboratory of AMS Dating and the Environment, Nanjing University (NJU-AMS Laboratory), China. The NJU-AMS Laboratory is largely devoted to research on radiocarbon dating and 14C analysis in fields of earth, environmental and archaeological sciences. The laboratory has successfully employed various pretreatment methods, including routine pretreatment of tree rings, buried wood and subfossil wood, seeds, charcoal, pollen concentrates, organic matter, and shells. In this study, operational status of the NJU-AMS is presented, and results of radiocarbon measurements made on different sample types are reported. Measurements on international standards, references of known age, and blank samples demonstrate that the NJU-AMS runs stably and has good reproducibility on measurement of single samples. The facility is capable of measuring 14C in samples with the precision and accuracy that meet the requirements for investigating annual 14C changes, history-prehistory age dating, and Late Quaternary stratigraphic chronology research.

Background: Many hospitals have implemented admission SARS-CoV-2 testing to evaluate for the need for transmission-based precautions. However, a positive test in an asymptomatic patient may represent (1) active infection, signifying infectiousness; (2) false positivity; or (3) past infection with prolonged viral shedding. We used a strand-specific SARS-CoV-2 reverse real-time polymerase chain reaction (rRT-PCR) assay to assess infectivity among asymptomatic patients with a positive SARS-CoV-2 PCR admission test. Methods: We used a 2-step rRT-PCR specific to the minus strand of the SARS-CoV-2 envelope gene. We reviewed records of patients with a positive SARS-CoV-2 PCR who were also tested for the strand-specific SARS-CoV-2 PCR within 2 days of admission at Stanford Health Care during July 2020–April 2022. We restricted our analysis to each patient’s first test. We calculated the percentage of detectable minus strand-specific tests among asymptomatic patients over time and gathered descriptive statistics for age, sex, and immunocompromised state. Results: In total, 848 admitted patients had strand-specific SARS-CoV-2 assays performed. Of 532 patients with a strand-specific assay done within 2 days of admission, 242 (45%) were asymptomatic. Among asymptomatic patients, the mean age was 56 years (range, 19–99), 133 (55%) were male, 50 (21%) had immunocompromising conditions, and 30 (12%) were admitted for a surgical procedure. In total, 21 (9%; range, 4%–25% per quarter) had detectable minus strand-specific assays (Fig. 1). Conclusions: Most asymptomatic patients tested for SARS-CoV-2 on admission were not infectious. Hospitals using SARS-CoV-2 PCR admission testing may need to re-evaluate the continued use of this practice.

Fig. 1. Minus strand-specific SARS-CoV-2 assay percentage positivity per quarter among asymptomatic patients tested within 2 days of admission. The peak positivity in November 2021–January 2022 quarter coincided with the SARS-CoV-2 omicron variant surge in our county.

Disclosure: None

Background: SARS-CoV-2 viral load decreases over time after illness onset. However, immunocompromised patients may take longer for viral load decrease or have a more erratic viral-load trajectory. We used strand-specific assay data from admitted patients to evaluate viral-load trajectories after illness onset. Methods: We reviewed records of hospitalized patients with a positive SARS-CoV-2 PCR and tested using the strand-specific SARS-CoV-2 PCR during July 2020–April 2022. At Stanford Healthcare, we use a 2-step reverse real-time polymerase chain reaction (rRT-PCR) assay specific to the minus strand of the SARS-CoV-2 envelope gene to assess infectivity. Restricting our analysis to each patient’s first strand-specific assay, we used logistic regression models to compare patients with single versus multiple assays. Among patients with multiple tests, we compared those who had an upward trajectory in cycle threshold (Ct) values (a surrogate of decreasing viral load) versus those who did not. We analyzed presence of symptoms, immunocompromised state, immunosuppression reason, and severe COVID-19 leading to ICU care in univariate and multivariate models that further adjust for additional covariates. Significant differences were assessed using logistic regression odds ratios and an α level of 0.05. Results: In total, 848 inpatients were included. Among them, 703 were tested only once and 145 were tested 2–6 times. The longest duration of minus-strand detection was 163 days. In univariate analyses, patients with a single minus-strand assay had lower odds of being symptomatic (OR, 0.55), of being immunocompromised (OR, 0.58), and of being admitted to the ICU with severe COVID-19 (OR, 0.49). In the multivariate analysis, being admitted to the ICU with severe COVID-19 was the only significant variable associated with having >1 test (OR, 2.44). Among patients who had multiple strand-specific SARS-CoV-2 assays, 119 had upward minus-strand trends of Ct values (as expected) and 26 did not. Being immunocompromised was associated with nonrising minus-strand CT values (OR, 33.3) when holding all other covariates in the model constant. Conclusions: Immunocompromised patients with COVID-19 tend to actively replicate for longer and have unexpected viral trajectories compared to immunocompetent patients. Among immunocompromised patients, suspension of transmission-based precautions may require a case-by-case evaluation.

Disclosures: None

We used a strand-specific RT-qPCR to evaluate viral replication as a surrogate for infectiousness among 242 asymptomatic inpatients with a positive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) admission test. Only 21 patients (9%) had detectable SARS-CoV-2 minus-strand RNA. Because most patients were found to be noninfectious, our findings support the suspension of asymptomatic admission testing.

As a major approach for controlling electromagnetic (EM) waves, metamaterials have experienced an abundant and rapid development in the 21st century. They have provided flexible and powerful techniques for controlling EM waves and brought many unique applications that are difficult to realise with natural materials. With increasing demands on dynamic controls of the EM waves, many innovations have been conducted in both three-dimensional metamaterials and two-dimensional metasurfaces, in which the meta-atom has been gradually evolved from passive to active. In 2014, coding and digital mechanisms were initially introduced to the metamaterials, further advancing the appearance of digitally programmable metamaterials. The programmable metamaterials have shown great potentials in not only real-time manipulations of the EM waves, but also direct information processing on the EM wave level. In this article, we present an in-depth review of the programmable EM metamaterials and metasurfaces, focusing on the programmable features including theoretical concepts, implementing methods and applications in EM controls. We first give a short retrospect of traditional metamaterials and metasurfaces, followed by the concepts and detailed discussions of digital coding and field-programmable metamaterials. Then, we introduce space-domain, time-domain and space–time-domain programmable metamaterials and metasurfaces, mainly focusing on their theories, functionalities, experimental implementations, and system-level applications. Finally, we conclude the current advances of the programmable metamaterials and metasurfaces, and give a prospect for the future developments.

Studies on humans that exploit contemporary data-intensive, high-throughput ‘omic’ assay technologies, such as genomics, transcriptomics, proteomics and metabolomics, have unequivocally revealed that humans differ greatly at the molecular level. These differences, which are compounded by each individual’s distinct behavioral and environmental exposures, impact individual responses to health interventions such as diet and drugs. Questions about the best way to tailor health interventions to individuals based on their nuanced genomic, physiologic, behavioral, etc. profiles have motivated the current emphasis on ‘precision’ medicine. This review’s purpose is to describe how the design and execution of N-of-1 (or personalized) multivariate clinical trials can advance the field. Such trials focus on individual responses to health interventions from a whole-person perspective, leverage emerging health monitoring technologies, and can be used to address the most relevant questions in the precision medicine era. This includes how to validate biomarkers that may indicate appropriate activity of an intervention as well as how to identify likely beneficial interventions for an individual. We also argue that multivariate N-of-1 and aggregated N-of-1 trials are ideal vehicles for advancing biomedical and translational science in the precision medicine era since the insights gained from them can not only shed light on how to treat or prevent diseases generally, but also provide insight into how to provide real-time care to the very individuals who are seeking attention for their health concerns in the first place.

In view of the cooperative guidance problem with time delay, this paper proposes a two-stage time-delay prescribed-time cooperative guidance law in the three-dimensional (3D) space. In the first stage, by introducing a time scaling function and time-delay consensus, the proposed cooperative guidance law can overcome the negative influence of time delay to guaranteed the desired convergence performance. Derived from the Lyapunov convergence analysis, the time-delay stability of the first stage can be ensured and the convergence time can be described as the relationship between delayed time and mission-assigned convergence time. Then, taking the prescribed-time-related convergence time as the switching point, the second stage begins with suitable initial conditions and all interceptors are governed by proportional navigation guidance. Finally, comparative simulations are performed to demonstrate the effectiveness and superiority of the proposed time-delay guidance law.

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.

OBJECTIVES/GOALS: In a familial case where 10 of 17 members inherited EA/LVNC in an autosomal dominant pattern, we discovered a novel, damaging missense variant in the gene KLHL26 that segregates with disease and comprises an altered electrostatic surface profile, likely decoupling the CUL3-interactome. We hypothesize that this KLHL26 variant is etiologic of EA/LVNC. METHODS/STUDY POPULATION: We differentiated a family trio (a heart-healthy daughter and EA/LVNC-affected mother and daughter) of induced pluripotent stem cells into cardiomyocytes (iPSC-CMs) in a blinded manner on three iPSC clones per subject. Using flow cytometry, immunofluorescence, and biomechanical, electrophysiological, and automated contraction methods, we investigated iPSC-CM differentiation efficiency between D10-20, contractility analysis and cell cycle regulation at D20, and sarcomere organization at D60. We further conducted differential analyses following label-free protein and RNA-Seq quantification at D20. Via CRISPR-Cas9 gene editing, we plan to characterize KLHL26 variant-specific iPSC-CM alterations and connect findings to discoveries from patient-specific studies. RESULTS/ANTICIPATED RESULTS: All iPSC lines differentiated into CMs with an increased percentage of cTnT+ cells in the affected daughter line. In comparison to the unaffected, affected iPSC-CMs had fewer contractions per minute and altered calcium transients, mainly a higher amount of total calcium release, faster rate of rise and faster rate of fall. The affected daughter line further had shorter shortening and relaxation times, higher proliferation, lower apoptosis, and a smaller cell surface area per cardiac nucleus. The affected mother line trended in a similar direction to the affected daughter line. There were no gross differences in sarcomere organization between the lines. We also discovered differential expression of candidate proteins such as kinase VRK1 and collagen COL5A1 from proteomic profiling. DISCUSSION/SIGNIFICANCE: These discoveries suggest that EA/LVNC characteristics or pathogenesis may result from decreased contractile ability, altered calcium transients, and cell cycle dysregulation. Through the KLHL26 variant correction and introduction in the daughter lines, we will build upon this understanding to inform exploration of critical clinical targets.

A 2-year fertilization experiment was conducted to study the effect of different ratios of organic (pig) manure on wheat yield and nitrogen use efficiency (NUE). The four treatments were no nitrogen (N) (CK); 100% chemical fertilizer N (urea; T1); 70% chemical fertilizer N + 30% organic manure N (T2) and 50% chemical fertilizer N + 50% organic manure N (T3), with the same amount of applied nitrogen (120 kg/ha). The results showed the maximum grain yield (3049 kg/ha), crop nitrogen uptake (216 kg/ha), NUE (65.4%) and accumulated nitrate nitrogen (NO3−-N in 0–200 cm, 142 kg/ha) were observed in the T1 among all treatments in the first year. However, the largest grain yield (5074 kg/ha), crop nitrogen uptake (244 kg/ha) and NUE (82.5%) were under T2 treatment in the second year. Furthermore, T2 had the maximum NO3−-N content in 0–100 cm layer (116 kg/ha), especially 0–40 cm layer, and the lowest NO3−-N content in 100–200 cm (58.8 kg/ha). However, 50% organic manure N in T3 increased apparent nitrogen loss by 39.0% compared to that in T2. Therefore, 30% organic manure N application was more conducive for enhancing wheat yield and NUE and promoting environmental safety after 1-year fertilization time.

Guangxi, a province in southwestern China, has the second highest reported number of HIV/AIDS cases in China. This study aimed to develop an accurate and effective model to describe the tendency of HIV and to predict its incidence in Guangxi. HIV incidence data of Guangxi from 2005 to 2016 were obtained from the database of the Chinese Center for Disease Control and Prevention. Long short-term memory (LSTM) neural network models, autoregressive integrated moving average (ARIMA) models, generalised regression neural network (GRNN) models and exponential smoothing (ES) were used to fit the incidence data. Data from 2015 and 2016 were used to validate the most suitable models. The model performances were evaluated by evaluating metrics, including mean square error (MSE), root mean square error, mean absolute error and mean absolute percentage error. The LSTM model had the lowest MSE when the N value (time step) was 12. The most appropriate ARIMA models for incidence in 2015 and 2016 were ARIMA (1, 1, 2) (0, 1, 2)12 and ARIMA (2, 1, 0) (1, 1, 2)12, respectively. The accuracy of GRNN and ES models in forecasting HIV incidence in Guangxi was relatively poor. Four performance metrics of the LSTM model were all lower than the ARIMA, GRNN and ES models. The LSTM model was more effective than other time-series models and is important for the monitoring and control of local HIV epidemics.

Giardia duodenalis is the most common intestinal parasite of humans in the USA, but the risk factors for sporadic (non-outbreak) giardiasis are not well described. The Centers for Disease Control and Prevention and the Colorado and Minnesota public health departments conducted a case-control study to assess risk factors for sporadic giardiasis in the USA. Cases (N = 199) were patients with non-outbreak-associated laboratory-confirmed Giardia infection in Colorado and Minnesota, and controls (N = 381) were matched by age and site. Identified risk factors included international travel (aOR = 13.9; 95% CI 4.9–39.8), drinking water from a river, lake, stream, or spring (aOR = 6.5; 95% CI 2.0–20.6), swimming in a natural body of water (aOR = 3.3; 95% CI 1.5–7.0), male–male sexual behaviour (aOR = 45.7; 95% CI 5.8–362.0), having contact with children in diapers (aOR = 1.6; 95% CI 1.01–2.6), taking antibiotics (aOR = 2.5; 95% CI 1.2–5.0) and having a chronic gastrointestinal condition (aOR = 1.8; 95% CI 1.1–3.0). Eating raw produce was inversely associated with infection (aOR = 0.2; 95% CI 0.1–0.7). Our results highlight the diversity of risk factors for sporadic giardiasis and the importance of non-international-travel-associated risk factors, particularly those involving person-to-person transmission. Prevention measures should focus on reducing risks associated with diaper handling, sexual contact, swimming in untreated water, and drinking untreated water.

The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.

The current experiment was conducted to evaluate the effects of different dietary protein levels and rumen-protected folic acid (RPFA) supplementation on ruminal fermentation, microbial enzyme activity, bacterial populations and urinary excretion of purine derivatives (PD) in growing beef steers. Low-protein (LP) or high-protein (HP) diets were fed to eight ruminally cannulated first-generation cross-bred (Blonde d'Aquitaine × Simmental) beef steers with or without RPFA supplementation. Steers were fed a total mixed ration, and dietary concentrate to maize silage ratio was 50 : 50 (dry matter (DM) basis). No interaction between dietary crude protein (CP) levels and RPFA supplementation was observed during the experiment. Ruminal pH was unaffected by RPFA supplementation, but decreased with increasing dietary CP levels. Ruminal total volatile fatty acid concentration increased with increasing dietary CP levels or RPFA supplementation. Molar proportion of acetate increased with RPFA supplementation, but tended to decrease with increasing dietary CP levels. The proportion of propionate decreased with RPFA supplementation, but was unaffected by dietary CP levels. As a result, the acetate to propionate ratio increased with RPFA supplementation, but tended to be lower for the HP diets than the LP diets. Ammonia-nitrogen content decreased with RPFA supplementation, but increased with increasing dietary CP levels. In situ ruminal degradability of maize straw and concentrate increased with increasing dietary CP levels or RPFA supplementation. Microbial enzyme (carboxymethyl-cellulase, cellobiase, xylanase, pectinase, α-amylase and protease) activity, bacterial populations (Ruminococcus albus, Ruminococcus flavefaciens, Butyrivibrio fibrisolvens, Prevotella ruminicola, Fibrobacter succinogenes and Ruminobacter amylophilus) and urinary PD excretion increased with increasing dietary CP levels or RPFA supplementation. The current study showed that increasing dietary CP levels from 109·1 to 130·7 g/kg DM or supplementing 75 mg RPFA improved ruminal fermentation and microbial protein synthesis by increasing bacterial population and microbial enzyme activity.

Radio-glaciological parameters from the Moore’s Bay region of the Ross Ice Shelf, Antarctica, have been measured. The thickness of the ice shelf in Moore’s Bay was measured from reflection times of radio-frequency pulses propagating vertically through the shelf and reflecting from the ocean, and is found to be 576 ± 8 m. Introducing a baseline of 543 ± 7m between radio transmitter and receiver allowed the computation of the basal reflection coefficient, R, separately from englacial loss. The depth-averaged attenuation length of the ice column, 〈L〉 is shown to depend linearly on frequency. The best fit (95% confidence level) is 〈L(ν)〉= (460±20) − (180±40)ν m (20 dB km−1), for the frequencies ν = [0.100–0.850] GHz, assuming no reflection loss. The mean electric-field reflection coefficient is (1.7 dB reflection loss) across [0.100–0.850] GHz, and is used to correct the attenuation length. Finally, the reflected power rotated into the orthogonal antenna polarization is <5% below 0.400 GHz, compatible with air propagation. The results imply that Moore’s Bay serves as an appropriate medium for the ARIANNA high-energy neutrino detector.