四川省核技术利用辐射安全监管对策研究

本文概述了四川省核技术利用及辐射安全监管的基本情况和特点,对全省辐射安全监管中存在的能力不足、手段单一及辐射安全主体责任落实不够等主要问题进行了分析,并提出了针对性的对策建议,为进一步提升全省辐射安全监管能力提供参考。     

A phase 1/2 randomised placebo-controlled study of the COVID-19 vaccine mRNA-1273 in healthy Japanese adults: An interim report

IntroductionThe mRNA vaccine, mRNA-1273/TAK-919, encodes the prefusion-stabilised spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report interim results of the first study evaluating safety and immunogenicity of mRNA-1273 in healthy Japanese participants.MethodsThis phase 1/2, randomised, observer-blind, placebo-controlled trial, conducted in Japan (two sites), enrolled healthy adults aged ≥ 20 years with no prior exposure to investigational coronavirus vaccines/treatments, and no known history/risk of SARS-CoV-2 infection. Participants were stratified by age (< 65/≥ 65 years) and randomised to receive two doses of 100 μg mRNA-1273 or placebo administered as intramuscular injections 28 days apart. Primary outcomes were safety and immunogenicity assessed by anti-SARS-CoV-2-spike protein-binding antibody level (bAb). A secondary outcome was SARS-CoV-2 neutralising antibody (nAb) response.ResultsParticipants were enrolled between 21 January and 3 February 2021, and 200 were randomised: mRNA-1273, n = 150 (< 65 years, n = 100; ≥ 65 years, n = 50); placebo, n = 50 (< 65 years, n = 40; ≥ 65 years, n = 10). Solicited adverse events (AEs) through 7 days after each vaccination occurred in 144/150 (96%) and 19/50 (38%) participants in the mRNA-1273 and placebo arms, respectively. In the mRNA-1273 arm, injection-site pain, myalgia and fatigue were the most frequently reported solicited AEs after each vaccination, irrespective of age. Robust immune responses occurred with mRNA-1273 (n = 147) with a bAb geometric mean fold rise (95% confidence interval [CI]) from baseline of 1009 (865, 1177) and a nAb of 21.7 (19.8, 23.8) at day 57. Seroconversion rates (95% CI) for bAb and nAb were both 100% (97.5, 100) at day 57. No such response occurred with placebo (n = 49).ConclusionTwo doses of 100 μg mRNA-1273 given 28 days apart demonstrated an acceptable safety profile and induced significant anti-SARS-CoV-2 immune responses in a Japanese population aged ≥ 20 years. Funding: Takeda Pharmaceutical Company Limited and Japan Agency for Medical Research and Development (AMED). ClinicalTrials.gov: NCT04677660.     

Acute unsolicited adverse events following BNT162b2 vaccine in Saudi Arabia,a real-world data

BackgroundAcute adverse events and anaphylaxis were reported after the administration of coronavirus disease (COVID-19) mRNA vaccines. We aim to explore the nature and outcome of adverse events following BNT162B2 vaccine in a community vaccination center, Riyadh, Saudi Arabia.MethodWithin 30 min post vaccination, all acute adverse events (AAEs) that occurred before March 31st, 2021, and in people older than 16 years were reviewed (AAE group). We used the case definition of Brighton collaboration on vaccine safety to define anaphylaxis. Patients’ demographics, comorbidities, allergy history, and outcome at disposition were collected. Observation duration after vaccination was short (<15 min) or extended (<3 h). Statistical analysis was performed to study AAEs association with the study variables and outcomes.ResultsOut of 71,221 vaccine recipients, 144 (0.002%) had developed 345 AAEs, at a rate of 48.4 events per 10,000 dose administered. The majority of cases in AAE group were first dose recipients (93.8%) and previously healthy (59%), while the minority had a previous history of allergy (6.3%) or a laboratory-confirmed COVID-19 (4.2%). We found a significant association between female gender and the occurrence of any AAE (p-value = 0.002). Per every 10,000 doses administered, non-anaphylactic AAEs were dizziness (17.8), headache (9.7), nausea (7.1), or syncope (3.2). Only one in every ten AAEs was considered serious and resulted in an extended observation (4.8 per 10,000 doses), but only 1/144 required hospitalization for non-anaphylaxis reasons (0.1 per 10,000 doses). According to the Brighton collaboration definition of anaphylaxis, no single case of high certainty anaphylaxis was recorded. No death was documented in this cohort.ConclusionAcute adverse events due to BNT162b2 vaccine were rare and mostly non-serious with a tendency to occur more in women. Further prospective studies on larger vaccine recipients to evaluate the incidence of anaphylaxis in the Saudi population are warranted.     

Serum-free purified Vero rabies vaccine is safe and immunogenic in children: Results of a randomized phase II pre-exposure prophylaxis regimen study

BackgroundA serum-free, highly purified Vero rabies vaccine (PVRV-NG) has been developed with no animal or human components and low residual DNA content. A phase II randomized clinical study aimed to demonstrate the non-inferiority of the immune response and assess the safety profile of PVRV-NG versus a licensed human diploid cell culture rabies vaccine (HDCV) in a pre-exposure regimen in healthy children and adolescents in the Philippines.MethodologyChildren aged 2–11 years and adolescents aged 12–17 years were randomized (2:1) to receive three injections of either PVRV-NG or HDCV (on day [D] 0, D7 and D28). Rabies virus-neutralizing antibodies (RVNA) were measured at D0, D42 and 6 months after the first injection (month [M] 6). Safety was assessed during the vaccination period and up to 28 days after the last vaccination. Serious adverse events were followed until 6 months after last vaccination.Principal findings342 healthy participants (171 children and 171 adolescents) were randomized and followed for 6 months after the last dose. All participants in both groups had an RVNA titer ≥ 0.5 IU/ml at D42, demonstrating non-inferiority in seroconversion rate for PVRV-NG versus HDCV. Over 90% of participants had RVNA titer ≥ 0.5 IU/ml at M6. PVRV-NG was well tolerated after each vaccination and up to 6 months following the last dose. There were no major safety concerns during the study, and the type and severity of solicited adverse events was similar for both treatment groups.ConclusionsThis study demonstrated the non-inferior immune profile of PVRV-NG compared with HDCV in a pre-exposure setting within a pediatric population. PVRV-NG was well tolerated with no safety concerns. This study is registered at ClinicalTrials.gov (NCT01930357) and EU Clinical Trials Register (2015–003203-30).     

Immune non-interference and safety study of Vi-DT typhoid conjugate vaccine with a measles,mumps and rubella containing vaccine in 9–15 months old Nepalese infants

BackgroundTyphoid fever is a common disease in developing countries especially in the Indian subcontinent and Africa. The available typhoid conjugate vaccines (TCV) have been found to be highly immunogenic in infants and children less than 2 years of age. Many countries are planning to adopt TCV in their routine EPI programs around 9 months of age when measles containing vaccines are given. Therefore, Vi-DT TCV was tested in 9–15 months aged healthy infants in Nepal to demonstrate non-interference with a measles containing vaccine.MethodsThis was a randomized, open label, phase III study to assess the immune non-interference, safety, and reactogenicity of Vi-DT typhoid conjugate vaccine when given concomitantly with measles, mumps and rubella (MMR) vaccine. A total of 360 participants aged 9–15 months were enrolled and randomized equally into Vi-DT + MMR (180 participants) or MMR alone (180 participants) group and were evaluated for immunogenicity and safety 28 days post vaccination.ResultsUsing the immunogenicity set, difference between proportions (95% CI) of the Vi-DT + MMR group vs MMR alone group were ?2.73% (-8.85, 3.38), ?3.19% (-11.25, 4.88) and 2.91% (-3.36, 9.18) for sero-positivity rate of anti-measles, anti-mumps and anti- rubella, respectively. Only the lower bound of the range in difference of the proportions for sero-positivity rate of anti-mumps did not satisfy the non-inferiority criteria as it was above the ?10% limit, which may not be of clinical significance. These results were confirmed in the per protocol set. There were no safety concerns reported from the study and both Vi-DT + MMR and MMR alone groups were comparable in terms of solicited and unsolicited adverse events .ConclusionsResults indicated that there is non-interference of MMR vaccine with Vi-DT and Vi-DT conjugate vaccine could be considered as an addition to the EPI schedule among children at risk of contracting typhoid.     

转基因食品与健康

转基因技术已被许多国家广泛用于生产转基因动物和农作物。转基因食品在其生产过程和内在品质方面都占有明显优势。但人们对其食用安全性却心存疑虑,近年来国际食品贸易也因此受到很大影响。世界各国及有关组织已经重视对转基因食品的安全性和营养价值进行评价,现正讨论制定转基因食品的国际安全,有的国家目前对这类食品实施食品标签的特殊标示管理。     

Prospective randomized clinical study in general surgery comparing a new low molecular weight heparin with unfractionated heparin in the prevention of thrombosis

A prospective, randomized, controlled clinical trial was performed comparing the antithrombotic efficacy of the low molecular weight heparin LMWH 21–23, (Braun) with an unfractionated heparin in elective general surgical patients over an observation period of 7 postoperative days. A total of 230 patients were admitted: 103 (group I) received low molecular weight heparin and 100 (group II) low-dose unfractionated heparin treatment given subcutaneously. In group I 41 patients (46%) were operated on for malignant disease and in group II 54 patients (54%). Due to the large amount of great abdominal procedures the intra- and perioperative application of hydroxyethyl starch was allowed for volume substitution. None of the patients died due to fatal pulmonary embolism. In group I four patients revealed positive ¹²⁵I-labeled fibrinogen uptake (3.9%); two patients belonged to the hydroxyethyl starch subgroup. In group II five patients displayed a positive fibrinogen uptake (5%); two belonged to the hydroxyethyl starch subgroup. The results of the hemostaseological investigations (e.g., prothrombin time, activated partial thromboplastin time, thrombin clotting time, fibrinogen, antithrombin III, protein C, plasminogen, ₂-antiplasmin , tissue-type plasminogen activator, plasminogen activator inhibitor) revealed no statistically significant differences between groups I and II or their subgroups, although a tendency to prolonged clotting times was observed. The antifactor Xa activity values, however, displayed a statistically significant difference between the two groups (P < 0.05). The antifactor Xa activity measured up to 0.16 U/ml for the low molecular weight heparin (group I) and 0.05 U/ml for the unfractionated heparin (group II) in the postoperative period. Major bleeding complications were not encountered in this study. Fundamental for the low incidence of thrombosis, the additive administration of hydroxyethyl starch appeared in almost one-third of the patients in both study groups.Abbreviations APTT activated partial thromboplastin time - aXa anti-factor Xa - DVT deep venous thrombosis - FUT ¹²⁵I-labeled fibrinogen uptake test - HES hydroxyethyl starch - LMWH low molecular weight heparin - PE pulmonary embolism - UFH unfractioned heparin     

Transient decrease in sound tolerance levels following hearing deprivation in normal-hearing subjects

ObjectiveTo determine the circadian influence on sound sensitivity produced by temporal hearing deprivation in healthy normal human subjects.DesignParticipants underwent bilateral earplugging before completion of anthropometry, the author's developed questionnaire, the Hamilton Anxiety and Depression Inventory, pure tone audiometry (PTA), stapedial reflex thresholds (SRT), distortion products otoacoustic emissions input/output (DPOAE-I/O), and uncomfortable loudness levels (ULLs). Afterward, the participants were randomly divided into group A, starting at 8:00 a.m. and finishing at 8:00 p.m., and group B, starting at 4:00 p.m. and ending at 4:00 a.m. Serum cortisol levels and audiological test results were obtained at the beginning and end of the session and 24-h free urinary cortisol levels were measured.Study sampleThirty healthy volunteers.ResultsPTA was 2.68 and 3.33 dB HL in groups A and B, respectively, with no statistical difference between them. ULLs were significantly lower in group A compared to group B, with an average of 8.1 dB SPL in group A and 3.3 dB SPL in group B (p < 0.0001). A SRT shift was observed in group A, with no difference in group B, and a night shift in DPOAE-I/O in group B.ConclusionsReduced loudness tolerance is demonstrated during daytime hearing deprivation in contrast to nighttime; this may be due to increased central gain in the awake cortex.     

Experimental analysis of the human perception threshold of a DC electric field

To study the biological effects of extremely low frequency (ELF) electric fields, a fundamental study is conducted of the human perception threshold of an electric field. The perception threshold is measured with human subjects, and the results are analysed. It is clear that field perception is based on the movement of hair and not on other sensations. Variance in the perception threshold and its causes are investigated. The perception threshold decreases by almost 30% as the relative humidity increases from 50 to 90%. The perception threshold is also dependent on the physical condition (length and density) of the hair and the psychological condition (degree of awareness) of the subject. The dependence on these is much smaller than that on relative humidity. The cause of the gender difference in the threshold is ascribed to the difference in the physical condition of the hair. Through this study, some factors to be taken into account for the safety standard are made clear.     

The influence of personal protection, environmental hygiene and exposure to pesticides on the health of immigrant farm workers in a desert country

Farm workers in developing countries tend not to use protective measures while handling pesticides. This study investigates the use of personal protection equipment and the practice of safety and hygiene procedures in the handling of pesticides in agriculture. Methods: Through a multi-stage sampling technique, one-fifth of the farms in a region were selected and all the farm workers at these farms were included in the study. A comparison population matching in age, socio-economic status and stay in the region was selected. A specifically designed questionnaire was used to collect information on the use of protective measures and the practice of safety and hygiene during work and on the disposal of empty pesticide containers. Blood pressure and erythrocyte acetylcholinesterase (AChE) activity were measured in the exposed and the unexposed populations. Results: Protective equipment was worn by a minority of farm workers – gloves, by 35%; work coveralls, by 36%; a scarf to cover the nose and mouth, by 39%; and shoes at work, by 79%. With regard to personal hygiene measures, 83% of the workers changed clothes after work and the same proportion took a shower after work; 63% and 46% drank and ate while at work respectively; and 11% used articles of domestic use in the preparation of pesticides on the farm. Most of the farm workers (96%) were asked to prepare pesticides for spraying by the foreman and 61% were asked to spray the pesticides on the crops. AChE activity was highly significantly depleted in the exposed population as compared with the unexposed population. Conclusions: AChE depletion was found to be negatively associated with the use of gloves, of work coveralls, and of a scarf to cover the nose and mouth and with the implementation of safety and hygiene procedures on the farm. AChE depletion was positively associated with the frequency of pesticide spraying. Received: 30 January 1998 / Accepted: 19 August 1998