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Summary: Lipid nanoparticle (LNP) encapsulated self-amplifying RNA (saRNA) is a novel technology formulated as a low dose vaccine against COVID-19. Methods: A phase I first-in-human dose-ranging trial of a saRNA COVID-19 vaccine candidate LNP-nCoVsaRNA, was conducted at Imperial Clinical Research Facility, and participating centres in London, UK. Participants received two intramuscular (IM) injections of LNP-nCoVsaRNA at six different dose levels, 0·1-10·0mg, given four weeks apart. An open-label dose escalation was followed by a dose evaluation. Solicited adverse events (AEs) were collected for one week from enrolment, with follow-up at regular intervals (1-8 weeks). The binding and neutralisation capacity of anti-SARS-CoV-2 antibody raised in participant sera was measured by means of an anti-Spike (S) IgG ELISA, immunoblot, SARS-CoV-2 pseudoneutralisation and wild type neutralisation assays. Findings: 192 healthy individuals with no history or serological evidence of COVID-19, aged 18-45 years were enrolled. The vaccine was well tolerated with no serious adverse events related to vaccination. Seroconversion at week six whether measured by ELISA or immunoblot was related to dose (both p

Background: The proportional hazards (PH) assumption is often not met in the IO clinical trials due to the delayed effect. The landmark analysis could be performed as sensitivity analysis to evaluate the efficacy of the treatment despite the impact of the violation of PH assumption, but analysis results can vary according to the different landmarks. The goal of the paper was to raise the awareness in both the statistical and clinical communities regarding the importance of the change point in the IO delayed effect clinical trials, in order for the improvement of the existing landmark analysis method.Methods: Pre-define the change point as an objective choice of landmark time of landmark analysis was recommended for the IO trials with delayed effect to avoid additional biases caused by the choice of landmark. We called this method change point landmark analysis (CPLA). Monte Carlo simulation was implemented to explore test power and type I error of CPLA. A simulated example was also conducted to evaluate the advantages of change point recognition on the landmark analysis.Results: CPLA showed the high power comparing to the earlier landmark choices and the later landmark choices, especially when the impact of the delayed effect was earlier than the median survival time. The type I errors of CPLA are also well controlled.Conclusions: the change point is a good objective choice of landmark in landmark analysis, which could resolve the objectively pre-defined challenge which is the critical requirement of the landmark analysis.

Background: Exacerbations are an important cause of morbidity in asthma, particularly in severe disease. Previous studies have identified variables associated with exacerbations, although little is known about risk factors in real-life populations of severe asthma. Methods: We determined the influence of demographics, disease characteristics and biomarkers of inflammation on the frequency of severe exacerbations in 872 adults with refractory asthma recruited to the British Thoracic Society Severe Asthma Registry. Results: 717 (82%) of subjects gave a history of ≥2 severe exacerbations in the last year and almost two-thirds had ≥4. Frequent exacerbations were significantly associated with younger age, higher BMI, higher ACQ score, worse asthma quality-of-life score, higher anxiety and depression score, history of GORD, increased unscheduled GP/emergency visits and hospital admissions in the last year and higher exhaled nitric oxide (FeNO). Preliminary analyses revealed independent variables associated with an increased risk of exacerbations were ACQ score, unscheduled GP/emergency visits in the last year, number of hospital admissions in the last year and FeNO in the total population and blood eosinophils in those not on maintenance oral steroids. Conclusion: Over 80% of a real-life population of adults with severe refractory asthma gave a history of frequent (≥2) severe exacerbations in the last year. Clinical outcomes and inflammatory variables were independent risk factors for severe exacerbations in this population. Further analysis will examine whether combining the independent risk factors in a scoring system can identify those at greatest risk of severe exacerbations.

A video-based surveillance system for passengers includes face detection, face tracking and face recognition. In general, the final recognition result of the video-based surveillance system is usually determined by the cumulative recognition results. Under this strategy, the correctness of face tracking plays an important role for the system recognition rate. For face tracking, the challenges of face tracking on a moving platform are that the space and time information used for conventional face tracking algorithms may be lost. Consequently, conventional face tracking algorithms can barely handle the face tracking on a moving platform. In this paper, we have verified the state-of-the-art technologies for face detection, face tracking and face recognition on a moving platform. In the mean time, we also proposed a new strategy for face tracking on a moving platform or face tracking under very low frame rate. The steps of the new strategy for face detection are: (1) classification the detected faces over a certain period instead of every frame (2) Tracking of each passenger is equivalent to reconstruct the time order of certain period for each passenger. If the cumulative recognition results are the only part needed for the surveillance system, step 2 can be skipped. In addition, if the additional information from the passengers is required, such as path tracking, lip read, gesture recognition, etc, time order reconstruction in step 2 can offer the information required.

The authority officer relies on facial mug-shots to spot suspects among crowds. Passing through a check point, the facial displays and printouts operate in low resolution fixed poses. Thus, a databases-cuing video is recommended for real-time surveillance with Aided-Target Recognition (AiTR) prompting the inspector taking a closer second look at a specific passenger. Taking advantage of commercial available Face Detection System on Chips (SOC) at 0.04sec, we develop a fast and smart algorithm to sort facial poses among passengers. We can increase the overlapping POFs (pixels on faces) in matching mug shots at arbitrary poses with sorted facial poses. Lemma: We define the long exposure as time average of facial poses and the short exposure as single facial pose in a frame of video in 30 Hz. The fiduciary triangle is defined among two eyes and nose-top. Theorem Self-Reference Matched Filtering (Szu et al. Opt Comm. 1980; JOSA, 1982) to Facial-Pose: If we replace the desirable output of Weiner filter as the long exposure, then the filter can select a short exposure as the normal view. Corollary: Given a short exposure as normal view, the fiduciary triangle can decide all poses from left-to-right and top-to-down.

AiTR is well developed field of R/D. Nonetheless. a relativel y poor under-sampled infrared video may achieve a sharper imagery by smart pre-processing, similar to super-resolution attempts; the differenc e is in the details. We took a local adaptive contrast enhancement to exploit the pixel intensity correlation, such as smoothness, contrast, and continuity, among neighborhood pixels of variable region sizes, so-called adaptive local contrast enhancement. The final success or failure rate of AiTR will depend on the choice of cost function, such as LMS, etc. In that, we found that a sparse samples do not satisfy the usual underlying Gaussian assu mption, of which the Maximum Likelihood, the Bayesian, the Fisher Rao criteria, etc. are usually depending on a priori assumption of dense sampling approaching the Gaussian statistics. Thus, in this paper, we have developed a sparse sampling classifier, called the min-Max classifier for Aided Target Recognition (AiTR), to minimize the intra-class dispersion and at the same to maximize the inter-class separation to select the optimum features vectors. As a standard test case, we choose Petland eigen-faces to benchmark our performance. We apply Szu’s lossless divide and conquer th eorem solving the NP Complete TSP solution to treat the multiple classes AiTR, in order to ach ieve min-Max classifier more efficiently than pair-wise SVM classifier.

Multi-spectral videos have been used in many different fields, however, most prevalently, in the military and medical application areas. Computer vision experts are especially interested in using satellite-grade infrared (IR) sensors for object detection, recognition and identification (DRI) tasks. There has however, been increased interest in using multi-spectral videos for tasks such as inspection/surveillance, image synthesis, N-D object modeling, collision avoidance and intelligent navigation system development. Implicit in the acquisition and processing of videos (and images) for 3D rigid-body objects are the issues of restoration and registration via the traditional affine transformation. In this paper, we present a dynamic scheme for passive-ID recognition of a 3D deformable object, a live hamster; a recognition-ID generated by the fusion of a long-infrared (LIR), 8-12 mum, and middle-infrared (MIR), 5-8 mum, video cameras. This fusion, based on the nonlinear blind demixing of pixels, was previously applied to perform early passive breast cancer detection. By combining blind pixel demixing of a pair of spectral videos (image sequences) and the adaptive neighborhood histogram modification method, we have generalized local video restoration and registration for a live animal in a concealed environment.

The UAVs (Unmanned Air Vehicles) have great potentials in different civilian applications, such as oil pipeline surveillance, precision farming, forest fire fighting (yearly), search and rescue, boarder patrol, etc. The related industries of UAVs can create billions of dollars for each year. However, the road block of adopting UAVs is that it is against FAA (Federal Aviation Administration) and ATC (Air Traffic Control) regulations. In this paper, we have reviewed the latest technologies and researches on UAV navigation and obstacle avoidance. We have purposed a system design of Jittering Mosaic Image Processing (JMIP) with stereo vision and optical flow to fulfill the functionalities of autonomous UAVs.

We have developed a real-time EOIR video counter-jittering sub-pixel image correction algorithm for a single mini- Unmanned Air Vehicle (m-UAV) for surveillance and communication (Szu et al. SPIE Proc. V 5439 5439, pp.183-197, April 12, 2004 ). In this paper, we wish to plan and execute the next challenge---- a team of m-UAVs. The minimum unit for a robust chain saw communication must have the connectivity of five second-nearest-neighbor members with a sliding, arbitrary center. The team members require an authenticity check (AC) among a unit of five, in order to carry out a jittering mosaic image processing (JMIP) on-board for every m-UAV without gimbals. The JMIP does not use any NSA security protocol ("cardinal rule: no-man, no-NSA codec"). Besides team flight dynamics ( Szu et al "Nanotech applied to aerospace and aeronautics: swarming,' AIAA 2005-6933 Sept 26-29 2005) , several new modules: AOA, AAM, DSK, AC, FPGA are designed, and the JMIP must develop their own control, command and communication system, safeguarded by the authenticity and privacy checks presented in this paper. We propose a Nonlinear Invertible (deck of card) Shuffler (NIS) algorithm , which has a Feistel structure similar to the Data Encryption Standard (DES) developed by Feistel et. al. at IBM in the 1970's; but DES is modified here by a set of chaotic dynamical shuffler Key (DSK) , as re-computable lookup tables generated by every on-board Chaotic Neural Network (CNN). The initializations of CNN are periodically provided by the private version of RSA from the ground control to team members to avoid any inadvertent failure of broken chain among m-UAVs. Efficient utilization of communication bandwidth is necessary for a constantly moving and jittering m-UAV platform, e.g. the wireless LAN protocol wastes the bandwidth due to a constant need of hand-shaking procedures (as demonstrated by NRL; though sensible for PCs and 3 rd gen. mobile phones). Thus, the chaotic DSK must be embedded in a fault-tolerant Neural Network Associative Memory for the error-resilientconcealment mosaic image chip re-sent. However, the RSA public and private keys, chaos typing and initial value are given on set or sent to each m-UAV so that each platform knows only its private key. AC among 5 team members are possible using a reverse RSA protocol. A hashed image chip is coded by the sender's private key and nobody else knows in order to send to it to neighbors and the receiver can check the content by using the senders public key and compared the decrypted result with on-board image chips. We discover a fundamental problem of digital chaos approach in a finite state machine, of which a fallacy test of a discrete version is needed for a finite number of bits, as James Yorke advocated early. Thus, our proposed chaotic NIS for bits stream protection becomes desirable to further mixing the digital CNN outputs. The fault tolerance and the parallelism of Artificial Neural Network Associative Memory are necessary attributes for the neighborhood smoothness image restoration. The associated computational cost of O(N 2 ) deems to be worthy, because the Chaotic version CNN of N-D can further provide the privacy only for the lost image chip (N=8x8) re-sent requested by its neighbors and the result is better performed than a simple 1-D logistic map. We gave a preliminary design of low end of FPGA firmware that to compute all on board seemed to be possible.

Electronic mails are adopted worldwide; most are easily hacked by hackers. In this paper, we purposed a free, fast and convenient hybrid privacy system to protect email communication. The privacy system is implemented by combining private security RSA algorithm with specific chaos neural network encryption process. The receiver can decrypt received email as long as it can reproduce the specified chaos neural network series, so called spatial-temporal keys. The chaotic typing and initial seed value of chaos neural network series, encrypted by the RSA algorithm, can reproduce spatial-temporal keys. The encrypted chaotic typing and initial seed value are hidden in watermark mixed nonlinearly with message media, wrapped with convolution error correction codes for wireless 3rd generation cellular phones. The message media can be an arbitrary image. The pattern noise has to be considered during transmission and it could affect/change the spatial-temporal keys. Since any change/modification on chaotic typing or initial seed value of chaos neural network series is not acceptable, the RSA codec system must be robust and fault-tolerant via wireless channel. The robust and fault-tolerant properties of chaos neural networks (CNN) were proved by a field theory of Associative Memory by Szu in 1997. The 1-D chaos generating nodes from the logistic map having arbitrarily negative slope a = p/q generating the N-shaped sigmoid was given first by Szu in 1992. In this paper, we simulated the robust and fault-tolerance properties of CNN under additive noise and pattern noise. We also implement a private version of RSA coding and chaos encryption process on messages.

Video compression was widely adopted for bandwidth saving reasons in Internet and in digital TV. Although advanced compression methodologies were exceedingly desirable for much higher compression ratios and much better quality of a streaming video, the standard compression methods remained nevertheless at the level of JPEG2000 for single frames of images using DCT & wavelets, and MPEG using DCT and exhaustive pixel correlations for the optical flow compression for the video. However, with the recent advent of sophisticated sensory technologies for NASA space missions, both the frame rate and the resolution of video streams become soon beyond the traditional capability of those DCT based compression methods. The goal was to find fundamental units of video that could be applied to the ultra-high frame rates of video streams. In this paper a novel implementation of video compression was based on the singularity maps in both space and time for the first time.

Modern cameras can cut passengers' faces into boxes in 0.04 s per frame in parallel without time stamps. Unfortunately, that cre- ates random storage without the tracking capability, and one can no longer meet the 5 W's challenge—"who speaks what, where and when." We de- velop a time-order reconstruction methodology which sorts the boxes as follows. i. A morphological image preprocessing to overcome the facial changes is based on the peripheral invariance of a human visual system when focusing on a maximum overlapping central region. ii. Replacing the Wiener matched filter desired output with an averaged but blurred long exposure, one can select the best matched sharp short exposures called the anchor faces β's. iii. The time-order neighborhood chaining is done by an iterative self-affirmation logic that demands a mutually agreed- upon minimum distance: whether or not the two nearest neighbors of β, namely face A and face C, also consider β to be their two nearest neigh- bors. The reconstruction procedure mathematically amounts to a product of two triple correlation functions sharing an intermediate state. We have thus demonstrated the time-order helps us associate a video submanifold with the acoustic manifold that solves the 5 W's challenge. C 2011 Society of

A seven-year follow-up in 1973 of a prospective cardiovascular study of 1820 initially, healthy, middle-aged Chinese men of 40-59 years of age identified 1745 (95.9%) known survivors, 49 (2.7%) interim deaths, and 26 (1.4) who could not be traced. Of the survivors, 1462 (83.8%) were re-examined, 292 (16.7%) had another treadmill test of maximal exercise, and 283 (16.2%) failed to return for re-examination. On the basis of interim surveillance of hospital admissions, questionnaires and re-examination, a greater incidence of noncardiovascular events (338 or 18.6%) than evidence of cardiovascular disease (220 or 12.1%) was found while the majority (1021 or 56.1%) remained healthy. Total mortality was 0.29 for men under 50 and 0.76 per 100 person-years for men of 50 or more years of age. Only nine, or 18.4% of the deaths were due to cardiovascular causes, and unexpectedly for this population sample, only three were attributed to stroke. When cardiovascular morbidity was related to presence of ST depression after maximal exercise, to hypertension at rest by WHO criteria, to both findings, or to absence of either on initial intake examination, incidence increased from 2.3% for NEITHER group, to 5.7% for ST group, to 11.9% for HT group, and to 25.0% for BOTH groups. Re-examination revealed more evidence of cardiovascular disease than did surveillance of hospital admissions. Additional to effects of aging and mild adiposity, longitudinal changes in blood pressure and ST depression, increasing in the NEITHER group, but less frequent in the other groups, showed some evidence of regression toward the mean, as well as emerging disease and the confounding effects of uncontrolled treatment of hypertension in many. The potential for prediction of subsequent cardiovascular morbidity or mortality appeared stronger for hypertension than for postexertional ST depression, although the two were additive in this population, which is more prone to hypertension and stroke but now is developing clinical manifestations of coronary heart disease more frequently.

Cardiovascular, aerobic, and ventilatory responses to a multistage treadmill test of near-maximal exercise were determined in 208 middle-aged Chinese men to provide standards in health, and to identify differences in relation to hypertension, coronary heart disease, chronic pulmonary disease and stroke. Except in patients with hypertension, exercise duration was shortened and symptom-limited oxygen uptake was reduced in all disease groups. Unexpectedly, stroke patients exhibited lower heart rate responses to exercise than did patients with coronary heart disease.

A prospective study of cardiovascular disease was started in Taiwan in 1965 with the initial emphasis on ischemic heart disease. In the first year of screening examination, 942 middle-aged Chinese men were examined. The multi-stage treadmill test and double Master two-step test were used in addition to the complete clinical history, physical examination and various laboratory tests. Seventy-five (8%) of the 942 patients given the treadmill exercise test showed S-T segment depression of 1 mm. or more after exercise; 89 showed either an S-T segment depression of 0.5 to 0.9 mm. or a respiratory variation of junctional and segmental S-T depressions. The remainder showed S-T segment changes of lesser magnitude. The procedure for the exercise test was modified in the early recovery period to diminish the occurrence of postexercise hypotension in Chinese men. As a result of this modification, the maximal frequency of appearance of postexercise abnormal S-T depression was delayed to four to six minutes after maximal exercise. The prevalence of resting and postexercise T abnormalities was significantly different when persons with abnormal S-T depressions were compared with age-matched controls. Also, the prevalence of a high amplitude R in the left precordial lead differed significantly between the groups with and without abnormal S-T segment depressions ( p

Maximal exercise testing of 241 healthy, highly selected, middle-aged American men in Taiwan and Hong Kong revealed a lower prevalence of ST-segment depression than among American men in Seattle. This difference was attributed to circumstances restricting availability of American men in Taiwan and Hong Kong with risk factors ordinarily associated with this response. ST depression, when present, was usually manifested after a delay of 4 to 5 min in the American men studied in the Orient, as previously noted, in healthy Chinese men. This delay is attributed to the circulatory effects of walking slowly for 2 min after maximal exercise which prevents venous pooling and a rapid decrease in cardiac output and coronary perfusion. Occurrence of ST depression in these selected American men in the Orient was more frequently associated with higher systolic pressure and minor ST-T abnormalities in the resting electrocardiogram than in American men in Seattle.

1. 1. A comparative study of physical characteristics and exercise performance of Chinese men of 40 to 59 years of age included 100 pedicabmen and 1,346 men from the upper socioeconomic class in Taipei, Taiwan. The daily arduous physical exertion and restricted diet imposed by meager earnings of the pedicabmen provided a group which approached the ultimate in minimizing risk factors for coronary heart disease. 2. 2. The pedicabmen were of comparable age and height, yet significantly lower mean body weight, skinfolds, circumferences of arm and waist, and serum concentrations of cholesterol and uric acid were characteristic of greater physical conditioning and prolonged dietary restrictions. Heart size was slightly larger, while greater exercise capacity, delayed acceleration of exertional heart rate, and more rapid postexertional deceleration of heart rate documented physical conditioning of the cardiovascular system. 3. 3. Whereas the usual trend for progressive increments in age-specific prevalence of S-T segment depression after maximal exertion was clearly demonstrated in men from the upper socioeconomic classes, the slight increase in a small number of older pedicabmen was not statistically significant. The protective role of dietary restrictions and/or enhanced physical activity imposed by a low socioeconomic status might be inferred from these observations.

Ninety-four or 7% of 1,346 healthy middle-aged Chinese men who underwent a graded treadmill test of maximal exercise showed post-exercise ST-segment depression. Stepwise linear discriminant function analysis showed that the major factors associated with this response were systolic blood pressures at maximal exercise, age, and certain resting ECG abnormalities, and to a lesser extent, systolic and diastolic pressure at rest, resting heart rate, and cigarette smoking. Hypertensive subjects showed at least a fourfold increase of post-exercise ST depression as compared with age-matched normotensive controls. Since coronary atherosclerosis is rare among Chinese, the study is of particular interest in demonstrating some factors related to ST depression after maximal exercise, particularly the effect of higher systemic pressure, in a group of middle-aged Chinese men.

BACKGROUND: Acute appendicitis is the most common surgical emergency in children. Differentiation of acute appendicitis from conditions that do not require operative management can be challenging in children. This study aimed to identify the optimum risk prediction model to stratify acute appendicitis risk in children. METHODS: We did a rapid review to identify acute appendicitis risk prediction models. A prospective, multicentre cohort study was then done to evaluate performance of these models. Children (aged 5-15 years) presenting with acute right iliac fossa pain in the UK and Ireland were included. For each model, score cutoff thresholds were systematically varied to identify the best achievable specificity while maintaining a failure rate (ie, proportion of patients identified as low risk who had acute appendicitis) less than 5%. The normal appendicectomy rate was the proportion of resected appendixes found to be normal on histopathological examination. FINDINGS:15 risk prediction models were identified that could be assessed. The cohort study enrolled 1827 children from 139 centres, of whom 630 (34·5%) underwent appendicectomy. The normal appendicectomy rate was 15·9% (100 of 630 patients). The Shera score was the best performing model, with an area under the curve of 0·84 (95% CI 0·82-0·86). Applying score cutoffs of 3 points or lower for children aged 5-10 years and girls aged 11-15 years, and 2 points or lower for boys aged 11-15 years, the failure rate was 3·3% (95% CI 2·0-5·2; 18 of 539 patients), specificity was 44·3% (95% CI 41·4-47·2; 521 of 1176), and positive predictive value was 41·4% (38·5-44·4; 463 of 1118). Positive predictive value for the Shera score with a cutoff of 6 points or lower (72·6%, 67·4-77·4) was similar to that of ultrasound scan (75·0%, 65·3-83·1). INTERPRETATION: The Shera score has the potential to identify a large group of children at low risk of acute appendicitis who could be considered for early discharge. Risk scoring does not identify children who should proceed directly to surgery. Medium-risk and high-risk children should undergo routine preoperative ultrasound imaging by operators trained to assess for acute appendicitis, and MRI or low-dose CT if uncertainty remains. FUNDING: None.