The geographic distribution of un-immunized children in Ontario,Canada: Hotspot detection using Bayesian spatial analysis

BackgroundIn Ontario, Canada, little is currently known about the extent to which un-immunized children may cluster geographically. Our objectives were to: describe the geographic distribution of fully un-immunized children; identify geographic clusters (hotspots) of un-immunized children; and to characterize the contribution of spatial effects and covariates on hotspots, where found.MethodsOur analytic cohort consisted of Ontario students aged 7–17 years in the 2016–2017 school year. We defined students as un-immunized if they had zero doses of any vaccine and a non-medical exemption recorded in Ontario’s registry. We calculated unadjusted proportions of un-immunized students by Census Subdivision (CSD) and then used a sequential approach to identify hotspots starting first with hotspot identification at the CSD level and then probed identified hotspots further by Dissemination Area (DA) and including covariates. Hotspots were identified using the Besag-York-Mollie Bayesian spatial model and were defined as areas with >95% probability of having two times the proportion of un-immunized students, relative to the province overall.ResultsWe identified 15,208 (0.94%) un-immunized children within our cohort consisting of more than 1.61 million students. Unadjusted proportions of un-immunized students varied greatly by geography, ranging from 0% to 21.5% by CSD. We identified 16 hotspot CSDs which clustered in five distinct areas, all of which were located in southern Ontario. The contribution of covariates and spatial effects on the risk of having un-immunized students varied greatly across hotspot areas.ConclusionsAlthough the provincial proportion (0.94%) of un-immunized students is small, geographical clustering of such students is evident in Ontario and in some areas presents an important risk for future outbreaks. Further qualitative work within these hotspot areas would be a helpful next step to better characterize the factors associated with vaccine refusal in these communities.     

Minority mating advantage of certain eye color mutants ofDrosophila melanogaster. III. Female discrimination and genetic background

A repetition of certain experiments done 2 years previously with two eye color mutants,brown andscarlet, inDrosophila melanogaster was undertaken to reconfirm results; however, initial tests revealed that strains or conditions had changed so that females were less discriminating. Testing was undertaken with changes in genetic background and certain laboratory conditions, with single females courted by equal numbers of two eye color types of males (3 red,R: 3 orange,O). These eye colors were produced as (1) mutants off the shelf, (2) recombinants from an outcross to a wild-type strain (CS), (3) mutants as in Experiment 1 but with male types stored either together or separately, and (4) recombinants from a double outcross of flies from Experiment 2 to hybrids from two additional wild strains,LS andOR. Experiment 4 producedR andO males that courted nearly equally (as in previous experiments), in contrast with about 70% courtship byR males in the other experiments. Females discriminated in favor of those second to court in G₀, G₁, and a repeat of G₀; however, with two generations of inbreeding, discrimination by this criterion lessened to become nonsignificant. In Experiments 1 and 2,O females favored second-courting males, butR females in hose experiments and all females in Experiment 3 mated more randomly. Effects of storing males either together or separately were not significant. About 20–30% of the females (low threshold) were highly receptive immediately after first courtship. Those trials plus any in which only a single type of male courted were omitted from estimations of female discrimination; a possible bias incurred by such omission against females that might have initial preferences was found to be nonsignificant. Discriminating ability was discussed as a fitness property inDrosophila populations.This research was supported in part by National Science Foundation Grant DEB 79-03259.     

高压氧对幼龄小鼠自发活动及分辨学习的影响

目的 :探讨不同压力的高压氧处理后 ,幼龄小鼠对新异环境的探究行为和自发活动的变化以及分辨学习的影响。方法 :用开场行为模型和Y 迷宫分辨学习模型观察小鼠的各项行为指标。结果 :与对照相比 ,吸 10 1 3kPa高压氧的幼龄小鼠学习记忆能力明显提高 ;吸 2 5 3 3kPa高压氧的幼龄小鼠学习记忆能力无明显变化 ,但其在新异环境中的自发行为明显减少。结论 :实验结果提示 :慢性吸入 10 1 3kPa高压氧有益于幼龄小鼠脑的生长发育 ,增强脑功能活动 ,但其作用机制还有待于进一步研究     

多通道人工耳蜗在语前聋儿童及青少年中的应用

目的　通过对植入人工耳蜗的语前聋儿童和青少年的听力和语言能力的评估 ,探讨我国儿童在使用人工耳蜗后的听力和言语能力发展规律及影响因素。方法　 2 5例行人工耳蜗植入的语前聋儿童及青少年患者参与本组测试。选用《聋儿听觉言语康复评估方法》作为测试材料 ,分别进行声音、言语声和环境声的辨别 ,数词、单字词、双字词、3字词、韵母、声母、声调、封闭项列短句的识别 ,开放项列字词和开放项列短句识别 ,语言清晰度 ,模仿句长 ,听话识图和看图说话等方面测试。结果　受试者术后均能感知到声音 ,辨别不同类别的声音。封闭项列测试结果全部大于机会水平 ,正确识别率随人工耳蜗使用时间而不断增加 ,随植入时年龄的增长而呈下降趋势。术后约半年显现开放项列识别能力 ,使用人工耳蜗后对患儿的言语发育具有较大帮助。结论　尽早对语前聋患儿植入人工耳蜗及进行术后康复 ,以达改善听力 ,提高语言能力 ,促进身心全面发展的目的。     

Molecular evolution of SARS-CoV-2 from December 2019 to August 2022

Severe acute respiratorysyndrome coronavirus-2 (SARS-CoV-2) pandemic spread rapidly and this scenario is concerning worldwide, presenting more than 590 million coronavirus disease 2019 cases and 6.4 million deaths. The emergence of novel lineages carrying several mutations in the spike protein has raised additional public health concerns worldwide during the pandemic. The present study review and summarizes the temporal spreading and molecular evolution of SARS-CoV-2 clades and variants worldwide. The evaluation of these data is important for understanding the evolutionary histories of SARSCoV-2 lineages, allowing us to identify the origins of each lineage of this virus responsible for one of the biggest pandemics in history. A total of 2897 SARS-CoV-2 whole-genome sequences with available information from the country and sampling date (December 2019 to August 2022), were obtained and were evaluated by Bayesian approach. The results demonstrated that the SARS-CoV-2 the time to the most recent common ancestor (tMRCA) in Asia was 2019-12-26 (highest posterior density 95% [HPD95%]: 2019-12-18; 2019-12-29), in Oceania 2020-01-24 (HPD95%: 2020-01-15; 2020-01-30), in Africa 2020-02-27 (HPD95%: 2020-02-21; 2020-03-04), in Europe 2020-02-27 (HPD95%: 2020-02-20; 2020-03-06), in North America 2020-03-12 (HPD95%: 2020-03-05; 2020-03-18), and in South America 2020-03-15 (HPD95%: 2020-03-09; 2020-03-28). Between December 2019 and June 2020, 11 clades were detected (20I [Alpha] and 19A, 19B, 20B, 20C, 20A, 20D, 20E [EU1], 20F, 20H [Beta]). From July to December 2020, 4 clades were identified (20J [Gamma, V3], 21 C [Epsilon], 21D [Eta], and 21G [Lambda]). Between January and June 2021, 3 clades of the Delta variant were detected (21A, 21I, and 21J). Between July and December 2021, two variants were detected, Delta (21A, 21I, and 21J) and Omicron (21K, 21L, 22B, and 22C). Between January and June 2022, the Delta (21I and 21J) and Omicron (21K, 21L, and 22A) variants were detected. Finally, between July and August 2022, 3 clades of Omicron were detected (22B, 22C, and 22D). Clade 19A was first detected in the SARS-CoV-2 pandemic (Wuhan strain) with origin in 2019-12-16 (HPD95%: 2019-12-15; 2019-12-25); 20I (Alpha) in 2020-11-24 (HPD95%: 2020-11-15; 2021-12-02); 20H (Beta) in 2020-11-25 (HPD95%: 2020-11-13; 2020-11-29); 20J (Gamma) was 2020-12-21 (HPD95%: 2020-11-05; 2021-01-15); 21A (Delta) in 2020-09-20 (HPD95%: 2020-05-17; 2021-02-03); 21J (Delta) in 2021-02-26 (2020-11-02; 2021-04-24); 21M (Omicron) in 2021-01-25 (HPD95%: 2020-09-16; 2021-08-08); 21K (Omicron) in 2021-07-30 (HPD95%: 2021-05-30; 2021-10-19); 21L (Omicron) in 2021-10-03 (HPD95%: 2021-04-16; 2021-12-23); 22B (Omicron) in 2022-01-25 (HPD95%: 2022-01-10; 2022-02-05); 21L in 2021-12-20 (HPD95%: 2021-05-16; 2021-12-31). Currently, the Omicron variant predominates worldwide, with the 21L clade branching into 3 (22A, 22B, and 22C). Phylogeographic data showed that Alpha variant originated in the United Kingdom, Beta in South Africa, Gamma in Brazil, Delta in India, Omicron in South Africa, Mu in Colombia, Epsilon in the United States of America, and Lambda in Peru. The COVID-19 pandemic has had a significant impact on global health worldwide and the present study provides an overview of the molecular evolution of SARS-CoV-2 lineage clades (from the Wuhan strain to the currently circulating lineages of the Omicron).     

Effects of diazepam and hydromorphone in triazolam-trained humans under a novel-response drug discrimination procedure

Seven healthy normal male and female volunteers (21–31 years) were trained to discriminate between the benzodiazepine triazolam (0.32 mg/70 kg, PO; e.g., drug A) and placebo (e.g., drug B) under a three-choice, instructed novel response drug discrimination procedure. Once the criterion for discrimination was met (i.e., >85% correct responding on four consecutive sessions), dose-effect curves were determined for triazolam (0.1–0.56 mg/70 kg), the benzodiazepine diazepam (10–32 mg/70 kg) and the opioid agonist hydromorphone (1–6 mg/70 kg). Subjects met the criterion for discrimination within four to six sessions. Triazolam and diazepam produced dose-related increases in triazolam-appropriate responding and no novel-appropriate responding at any dose tested. In contrast, hydromorphone generally increased novel-appropriate responding in a dose-related manner, with placebo-appropriate responding and some triazolam-appropriate responding at intermediate doses occurring also. Triazolam and diazepam produced qualitatively similar increases on several measures of sedative drug effects; hydromorphone increased ratings of like novel and sedative-like effects in subjects who discriminated hydromorphone as novel relative to those who did not. These results indicate that the novel response drug discrimination procedure enhances the specificity of the triazolam-placebo discrimination.This work was supported by USPH grants DA-06205, T32-DA-07242 and Research Scientist Development Award DA-00109 (J.R.H.) from the National Institute on Drug Abuse.     

Wielding the implement of law: Distilling new rights and responsibilities in the age of the ‘new genetics’

The law has, to date, been slow to respond to advances in genetics, but in many ways this may be propitious. History teaches us that there is an ever-present risk that the law will be used merely to embody knee-jerk reactions to new developments in medicine and science, frequently to the detriment of all interested parties. Adequate and appropriate legal responses to genetic research can only come once a full debate on the problems to be addressed has taken place, and when society as a whole is appraised of the options at hand. This article offers an overview of the problems which are thrown up for the law by 'new genetics', including the problem of reconciling competing claims to genetic information from family members, insurers and employers, as well as the dilemma of determining how to regulate the potential range of uses of new genetic knowledge. The article offers some views on how we might use the law to proceed sensibly and productively in the future.     

Borna disease virus-induced hippocampal dentate gyrus damage is associated with spatial learning and memory deficits

In neonatally inoculated rats, Borna disease virus (BDV) leads to a persistent infection of the brain in the absence of an inflammatory response and is associated with neuroanatomic, developmental, physiologic, and behavioral abnormalities. One of the most dramatic sites of BDV-associated damage in the neonatal rat brain is the dentate gyrus, a neuroanatomic region believed to play a major role in spatial learning and memory. The absence of a generalized inflammatory response to neonatal BDV infection permits direct effects of viral damage to the dentate gyrus to be examined. In this report, neonatally BDV-infected rats at various stages of dentate gyrus degeneration were evaluated in the Morris water maze, a swimming test that assesses the rats' capacity to navigate by visual cues. Our data demonstrate progressive spatial learning and memory deficits in BDV-infected rats that coincided with a gradual decline in the estimated hippocampal dentate gyrus neuron density.     

识别人类白血病白细胞的生物传感器研究

本文介绍一种以平面热解石墨电极为工作电极,用于识别人类白血病白细胞的半微分伏安型生物传感器。综合使用作者提出的四个电化学识别指标（氧化峰电位Ｅｐ,不同扫描电位下氧化峰电位的差值ΔＥｐ,膜上单位细胞数的氧化峰电流Ｉｐ／ｃｅｌｓ以及氧化扫描与还原扫描相应的出峰情况）,实现了对人类正常与异常白细胞、各种临床分型白血病白细胞的识别。     

The discriminative stimulus properties of LY233708, a selective serotonin reuptake inhibitor, in the pigeon

Rationale: Understanding the contribution of the various serotonin (5-HT) receptor subtypes to the behavioral effects of selective serotonin reuptake inhibitors (SSRIs) may contribute to the discovery of increasingly effective drugs for the treatment of conditions such as depression, panic and obsessive-compulsive disorders. Objectives: A drug discrimination procedure was used to determine whether the administration of an SSRI was associated with a specific interoceptive stimulus cue and to what extent that cue was related to activation of the 5-HT_1A receptor. Method: Pigeons were trained to discriminate 20 mg/kg of the short acting, SSRI, LY233708 dihydrochloride dihydrate [(–)-cis-1-(6-chloro-1,2,3,4- tetrahydro-1-methyl-2-naphthalenyl)piperazine] from saline. Results: LY233708 induced a specific, dose-related stimulus cue. The SSRIs, fluoxetine and citalopram, induced dose-related responding on the LY233708-associated key. In contrast, nisoxetine, a selective norepinephrine uptake inhibitor, induced responding on the saline-associated key. The prototypical 5-HT_1A agonist, 8-OH-DPAT [8-hydroxy-(2-di-n-propylamino)tetralin] substituted for LY233708. This generalization was blocked by the selective 5-HT_1A antagonist, WAY-100635 [N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-N-(2-pyridinyl) cyclohexanecarboxamide]. Conclusion: These data demonstrate that an SSRI can induce a specific, stable discriminative stimulus that appears to involve activation of the 5-HT_1A receptor in the pigeon. Received: 11 January 1999 / Final version: 7 May 1999