Contemporaneous fluctuations in T cell responses to persistent herpes virus infections

The classical paradigm for T cell dynamics suggests that the resolution of a primary acute virus infection is followed by the generation of a long-lived pool of memory T cells that is thought to be highly stable. Very limited alteration in this repertoire is expected until the immune system is re-challenged by reactivation of latent viruses or by cross-reactive pathogens. Contradicting this view, we show here that the T cell repertoire specific for two different latent herpes viruses in the peripheral blood displayed significant contemporaneous co-fluctuations of virus-specific CD8(+) T cells. The coordinated responses to two different viruses suggest that the fluctuations within the T cell repertoire may be driven by sub-clinical viral reactivation or a more generalized 'bystander' effect. The later contention was supported by the observation that, while absolute number of CD3(+) T cells and their subsets and also the cell surface phenotype of antigen-specific T cells remained relatively constant, a loss of CD62L expression in the total CD8(+) T cell population was coincident with the expansion of tetramer-positive virus-specific T cells. This study demonstrates that the dynamic process of T cell expansion and contractions in persistent viral infections is not limited to the acute phase of infection, but also continues during the latent phase of infection.

Was an increase in cocaine use among injecting drug users in New South Wales, Australia, accompanied by an increase in violent crime?

Background: A sharp reduction in heroin supply in Australia in 2001 was followed by a large but transient increase in cocaine use among injecting drug users (IDU) in Sydney. This paper assesses whether the increase in cocaine use among IDU was accompanied by increased rates of violent crime as occurred in the United States in the 1980s. Specifically, the paper aims to examine the impact of increased cocaine use among Sydney IDU upon police incidents of robbery with a weapon, assault and homicide. Methods: Data on cocaine use among IDU was obtained from the Illicit Drug Reporting System (IDRS). Monthly NSW Police incident data on arrests for cocaine possession/ use, robbery offences, homicides, and assaults, were obtained from the Bureau of Crime Statistics and Research. Time series analysis was conducted on the police data series where possible. Semi-structured interviews were conducted with representatives from law enforcement and health agencies about the impacts of cocaine use on crime and policing. Results: There was a significant increase in cocaine use and cocaine possession offences in the months immediately following the reduction in heroin supply. There was also a significant increase in incidents of robbery where weapons were involved. There were no increases in offences involving firearms, homicides or reported assaults. Conclusion: The increased use of cocaine among injecting drug users following the heroin shortage led to increases in violent crime. Other States and territories that also experienced a heroin shortage but did not show any increases in cocaine use did not report any increase in violent crimes. The violent crimes committed did not involve guns, most likely because of its stringent gun laws, in contrast to the experience of American cities that have experienced high rates of cocaine use and violent crime.

Higher-order CpG-DNA stimulation reveals distinct activation requirements for marginal zone and follicular B cells in lupus mice

Mouse follicular B cells express TLR9 and respond vigorously to stimulation with single-stranded CpG-oligodeoxynucleotides (ODN). Surprisingly, follicular B cells do not respond to direct stimulation with other TLR9 ligands, such as bacterial DNA or class A(D) CpG-ODN capable of forming higher-order structures, unless other cell types are present. Here, we show that priming with interferons or with B cell-activating factor, or simultaneous co-engagement of the B cell receptor for antigen (BCR), can overcome this unresponsiveness. The effect of interferons occurs at the transcriptional level and is mediated through an autocrine/paracrine loop, which is dependent on IRF-1, IL-6 and IL-12 p40. We hypothesize that the lack of bystander activation of follicular B cells with more complex CpG ligands may be an important safety mechanism for avoiding autoimmunity. This will prevent resting B cells from responding to foreign or self-derived hypomethylated double-stranded CpG ligands unless these ligands are either delivered through the B cell receptor or under conditions where B cells are simultaneously co-engaged by activated plasmacytoid dendritic cells or TH1 cells. A corollary is that the heightened responsiveness of lupus B cells to TLR9-induced stimulation cannot be ascribed to unprimed follicular B cells, but is rather mediated by hypersensitive marginal zone B cells.

Memory conformity: Actors and bystanders

This dissertation explored memory conformity effects on people who interacted with a confederate and of bystanders to that interaction. Two studies were carried out. Study 1 was conducted in the field. A male confederate approached a group of people at the beach and had a brief interaction. About a minute later a research assistant approached the group and administered a target-absent lineup to each person in the group. Analyses revealed that memory conformity occurred during the lineup task. Bystanders were twice as likely to conform as those who interacted with the confederate. Study 2 was carried out in a laboratory under controlled conditions. Participants were exposed to two events during their time in the laboratory. In one event, participants were shown a brief video with no determinate roles assigned. In the other event participants were randomly assigned to interact with a confederate (actor condition) or to witness that interaction (bystander condition). Participants were given memory tests on both events to understand the effects of participant role (actor vs. bystander) on memory conformity. Participants answered second to all questions, following a confederate acting as a participant, who disseminated misinformation on critical questions. Analyses revealed no significant differences in memory conformity between actors and bystanders during the movie memory task. However, differences were found for the interaction memory task such that bystanders conformed more than actors on two of four critical questions. Bystanders also conformed more than actors during a lineup identification task. The results of these studies suggest that the role a person plays in an interaction affects how susceptible they are to information from a co-witness. Theoretical and applied implications are discussed. First, the results are explained through the use of two models of memory. Second, recommendations are made for forensic investigators.

SURVEILLANCE OF, AND THE IMPACT OF COMMUNITY POLICING ON ARREST-RELATED DEATHS (ARDS): Exploring the surveillance of ARDs and the opportunities to prevent them in the United States

Thesis (Master's)--University of Washington, 2016-08

Time Delays on the Identification of the Need for CPR for Limited English Proficient 9-1-1 Callers

Thesis (Master's)--University of Washington, 2016-08

Serial killer: il database mondiale

Lo studio dei serial killer, quanto mai complesso e poliedrico, è reso difficoltoso, in parte, anche dall’attuale progresso, che ha portato questi soggetti devianti ad evolversi notevolmente sia in termini di astuzia (staging) che di mobilità. Tutto ciò dimostra che negli omicidi seriali, nonostante l'importante lavoro da parte di alcuni studiosi che sono riusciti a proporre contributi teorici di notevole importanza, è particolarmente frequente la c.d. “cecità di collegamento” fra omicidi perpetrati dalla medesima persona, ma in parti diverse nel mondo. È, quindi, indispensabile la costruzione di una banca dati mondiale che consenta a tutte le forze di polizia di avere sempre a disposizione informazioni raccolte sulla scena del crimine relativamente ad omicidi particolarmente aberranti e privi di un particolare movente. Sarà quindi compito del profiler, con strumenti di supporto creati ad hoc e tecnologicamente avanzati, reperire sulla scena del crimine queste informazioni attraverso una metodologia chiara e condivisa, che saranno, grazie alla banca dati, messe a disposizione di tutte le forze di polizia. The complex and multisided study of serial killers is partly made difficult by the current level of progress that has led these deviant people to evolve in relation to the aspects of shrewdness (concerning the staging) and mobility. Despite the important work of some scholars who proposed important theories, all this shows that, concerning serial murders, it is still particularly frequent not to pay attention to links among homicides committed by the same person but in different parts of the world. It is therefore crucial to develop a worldwide database that allows all police forces to access information collected on crime scenes of murders which are particularly absurd and committed without any apparent reason. It will then be up to the profiler, through ad hoc and technologically advanced tools, to collect this information on the crime scene that would be made available to all police forces thanks to the worldwide database.

Social dominance modulates eavesdropping in zebrafish

Group living animals may eavesdrop on signalling interactions between conspecifics and integrate it with their own past social experience in order to optimize the use of relevant information from others. However, little is known about this interplay between public (eavesdropped) and private social information. To investigate it, we first manipulated the dominance status of bystander zebrafish. Next, we either allowed or prevented bystanders from observing a fight. Finally, we assessed their behaviour towards the winners and losers of the interaction, using a custom-made video-tracking system and directional analysis. We found that only dominant bystanders who had seen the fight revealed a significant increase in directional focus (a measure of attention) towards the losers of the fights. Furthermore, our results indicate that information about the fighters' acquired status was collected from the signalling interaction itself and not from post-interaction status cues, which implies the existence of individual recognition in zebrafish. Thus, we show for the first time that zebrafish, a highly social model organism, eavesdrop on conspecific agonistic interactions and that this process is modulated by the eavesdroppers' dominance status. We suggest that this type of integration of public and private information may be ubiquitous in social learning processes.

Soixante ans de règlements de compte au Québec

Objectifs. Les objectifs de ce mémoire sont au nombre de deux. Le premier objectif est scindé en deux : l’objectif 1A est d’évaluer l’apport et la validité/fiabilité de l’analyse descriptive des règlements de compte amorcée par Cordeau dans sa thèse de doctorat de 1991 puis d’étendre la portée de cette analyse descriptive de part et d’autre des années 1970-1986. Ceci sera fait afin de voir si les règlements de compte de la période de Cordeau diffèrent de notre ensemble; l’objectif 1B est d’évaluer différents taux afin de voir lesquels nous permettent de mieux comprendre les grandes tendances des règlements de compte et leurs vagues. Enfin, le deuxième objectif est d’utiliser l’analyse de réseau afin de confirmer certains points ressortant de l’analyse descriptive des règlements de comptes et d’analyser la structure sociale du règlement de compte au Québec entre 1953 et 2013. Méthodologie. En faisant appel à Allô Police et plusieurs autres sources médiatiques, nous avons constitué une base de données des règlements de comptes québécois entre de 1953 à 2013. Nos analyses font appel à une approche holistique qui intègre à la fois l’analyse statistique descriptive, les tableaux croisés, l’analyse temporelle et l’analyse de réseau afin de bien cerner la question des règlements de compte. Résultats. Nos principaux résultats sont au nombre de quatre: 1) les grandes tendances qu’avait trouvées Cordeau entre 1970-1986 s’appliquent pour l’ensemble des règlements de compte de 1953 à 2013. Ainsi, peu de variations importantes ont été observées entre nos règlements de compte et ceux de Cordeau ; 2) les taux alternatifs se basant sur la population carcérale ou criminelle ne permettent pas de mieux comprendre les règlements de compte par rapport à un taux basé sur la population générale. Par contre, les proportions proposées par Morselli et al (2008) amènent une meilleure conception des périodes d’effervescences du milieu; 3) les groupes criminels qui sont plus exposés à la violence sont aussi ceux qui ont le plus recours à la violence et; 4) les indépendants occupent une place importante parmi les victimes de règlements de compte et ont donc une place importante dans le milieu criminel. Conclusion. Nos résultats font état du besoin d’intégrer différentes approches théoriques et méthodologiques afin de bien cerner la question complexe qu’est le règlement de compte. Avec les avenues de recherches identifiées à la fin de ce mémoire, nous espérons que la relève sera en mesure de mettre à profit les apprentissages de ce mémoire.

Soixante ans de règlements de compte au Québec

Objectifs. Les objectifs de ce mémoire sont au nombre de deux. Le premier objectif est scindé en deux : l’objectif 1A est d’évaluer l’apport et la validité/fiabilité de l’analyse descriptive des règlements de compte amorcée par Cordeau dans sa thèse de doctorat de 1991 puis d’étendre la portée de cette analyse descriptive de part et d’autre des années 1970-1986. Ceci sera fait afin de voir si les règlements de compte de la période de Cordeau diffèrent de notre ensemble; l’objectif 1B est d’évaluer différents taux afin de voir lesquels nous permettent de mieux comprendre les grandes tendances des règlements de compte et leurs vagues. Enfin, le deuxième objectif est d’utiliser l’analyse de réseau afin de confirmer certains points ressortant de l’analyse descriptive des règlements de comptes et d’analyser la structure sociale du règlement de compte au Québec entre 1953 et 2013. Méthodologie. En faisant appel à Allô Police et plusieurs autres sources médiatiques, nous avons constitué une base de données des règlements de comptes québécois entre de 1953 à 2013. Nos analyses font appel à une approche holistique qui intègre à la fois l’analyse statistique descriptive, les tableaux croisés, l’analyse temporelle et l’analyse de réseau afin de bien cerner la question des règlements de compte. Résultats. Nos principaux résultats sont au nombre de quatre: 1) les grandes tendances qu’avait trouvées Cordeau entre 1970-1986 s’appliquent pour l’ensemble des règlements de compte de 1953 à 2013. Ainsi, peu de variations importantes ont été observées entre nos règlements de compte et ceux de Cordeau ; 2) les taux alternatifs se basant sur la population carcérale ou criminelle ne permettent pas de mieux comprendre les règlements de compte par rapport à un taux basé sur la population générale. Par contre, les proportions proposées par Morselli et al (2008) amènent une meilleure conception des périodes d’effervescences du milieu; 3) les groupes criminels qui sont plus exposés à la violence sont aussi ceux qui ont le plus recours à la violence et; 4) les indépendants occupent une place importante parmi les victimes de règlements de compte et ont donc une place importante dans le milieu criminel. Conclusion. Nos résultats font état du besoin d’intégrer différentes approches théoriques et méthodologiques afin de bien cerner la question complexe qu’est le règlement de compte. Avec les avenues de recherches identifiées à la fin de ce mémoire, nous espérons que la relève sera en mesure de mettre à profit les apprentissages de ce mémoire.

Some problems and errors in cytogenetic biodosimetry

Human radiosensitivity is a quantitative trait that is generally subject to binomial distribution. Individual radiosensitivity, however, may deviate significantly from the mean (by 2-3 standard deviations). Thus, the same dose of radiation may result in different levels of genotoxic damage (commonly measured as chromosome aberration rates) in different individuals. There is significant genetic component in individual radiosensitivity. It is related to carriership of variant alleles of various single-nucleotide polymorphisms (most of these in genes coding for proteins functioning in DNA damage identification and repair); carriership of different number of alleles producing cumulative effects; amplification of gene copies coding for proteins responsible for radioresistance, mobile genetic elements, and others. Among the other factors influencing individual radioresistance are: radioadaptive response; bystander effect; levels of endogenous substances with radioprotective and antimutagenic properties and environmental factors such as lifestyle and diet, physical activity, psychoemotional state, hormonal state, certain drugs, infections and others. These factors may have radioprotective or sensibilising effects. Apparently, there are too many factors that may significantly modulate the biological effects of ionising radiation. Thus, conventional methodologies for biodosimetry (specifically, cytogenetic methods) may produce significant errors if personal traits that may affect radioresistance are not accounted for.

Microglia as therapeutic targets in retinal degeneration: role of translocator protein (18 κDa) (TSPO) and minocycline.

Microglia are the resident immune cells of the central nervous system (CNS) and play an important role in innate immune defense as well as tissue homeostasis. Chronic microglial reactivity, microgliosis, is a general hallmark of inflammatory and degenerative diseases that affect the CNS, including the retina. There is increasing evidence that chronic microgliosis is more than just a bystander effect, but rather actively contributes to progression of degeneration through processes such as toxic nitric oxide (NO) production and even phagocytosis of stressed but viable photoreceptors. Therefore immunmodulation of microglia presents a possible therapeutic strategy for retinal degenerations. Notably, the expression of the mitochondrial translocator protein 18 (κDa) (TSPO) is highly elevated in reactive microglia as seen in several neuroinflammatory diseases such as Alzheimer’s disease, Parkinson’s disease and multiple sclerosis. Therefore it is used as a gliosis biomarker in the brain. Moreover TSPO ligands show potent effects in resolving neuroinflammatory brain disorders. However, TSPO expression in the eye had not been investigated before. Further, it was unknown whether TSPO ligands’ potent immunomodulatory effects could be used to treat retinal degenerations. To fill this gap, the study aimed to analyze whether TSPO is also a potential biomarker for degenerative processes in the retina. Moreover the thesis attempted to determine whether a specific TSPO ligand, XBD173, might modulate microglial reactivity and is a potent therapeutic, to treat retinal degenerative diseases. The findings revealed that TSPO is strongly upregulated in microglial cells of retinoschisin-deficient (RS1-/y) mice, a model of inherited retinal degeneration and in a murine light damage model. A co-localization of TSPO and microglia was furthermore detectable in human retinal sections, indicating a potential role for TSPO as a biomarker for retinal degenerations. In vitro assays showed that the TSPO ligand XBD173 effectively inhibited features of microglial activation such as morphological transformation into reactive phagocytes and enhanced expression of pro-inflammatory cytokines. XBD173 also reduced microglial migration and proliferation and reduced their neurotoxic potential on photoreceptor cells. In two independent mouse models of light-induced retinal degeneration, the treatment with XBD173 reduced accumulation of amoeboid, reactive microglia in the outer retina and attenuated degenerative processes, indicated by a nearly preserved photoreceptor layer. A further question addressed in this thesis was whether minocycline, an antibiotic with additional anti-inflammatory properties is able to reduce microglial neurotoxicity and to protect the retina from degeneration. Minocycline administration dampened microglial pro-inflammatory gene expression, NO production and neurotoxicity on photoreceptors. Interestingly, in addition to its immunomodulatory effect, minocycline also increased the viability of photoreceptors in a direct manner. In the light damage model, minocycline administration counter-acted microglial activation and blocked retinal degeneration. Taken together these results identified TSPO as a biomarker for microglial reactivity and as therapeutic target in the retina. Targeting TSPO with XBD173 was able to reverse microglial reactivity and could prevent degenerative processes in the retina. In addition, the study showed that the antibiotic minocycline effectively counter-regulates microgliosis and light-induced retinal degeneration. Considering that microgliosis is a major contributing factor for retinal degenerative disorders, this thesis supports the concept of a microglia-directed therapy to treat retinal degeneration.

The Burden of Injury in Iowa, December 2008

Injuries are a major public health concern that affects the lives of all Iowans, regardless of age, race, gender, or size of county. Unintentional injuries are the leading cause of death for Iowans between the ages of 1 and 34, while suicides and/or homicides also rank among the top 5 leading causes of death for Iowans between the ages of 1 and 54. Unintentional injury is the 5th leading cause of death for all Iowans, with over 1,500 injury deaths occurring on average each year (from 2002‐ 2006) in Iowa. Injuries also lead to more than 17,000 hospitalizations in Iowa each year and more than 250,000 emergency department (ED) visits. Further, untold numbers of Iowans do not seek medical care for many of the injuries they may incur. Because injuries are preventable, they lead to unnecessary medical costs, economic losses, reduced productivity, and immense physical and emotional strain.

Morigerando las costumbres. Canalizando las disputas. A propósito de los conflictos en los pueblos heredianos. 1885-1915.

Resumen Explica porqué se produjo un bajo número de homicidios en los pueblos de la provincia de Heredia ente 1885 y 1915, a pesar de que los conflictos intercomunales eran frecuentes. Abstract Explains why fewer homicides took place in villages in the province Heredia, between 1885 y 1915, although there were frequently intercomunal conflicts.

La violenza di genere: analisi della casistica autoptica di femminicidio e degli ammonimenti del Questore per stalking e per violenza domestica della citta metropolitana di Bologna

Il presente lavoro tratta il tema della violenza di genere, in particolare femminicidio, stalking e violenza domestica per la connessione tra questi intercorrente nell’escalation violenta. Spesso, i femminicidi sono preceduti da stalking o ripetuti episodi di violenza fisica prettamente consumata in ambito domestico e relazioni affettive pregresse/attuali. La prima parte del lavoro descrive ambito scientifico e giuridico, internazionale e nazionale, della violenza di genere, dimensione del fenomeno ed evoluzione normativa a tutela delle vittime, come richiesto dalla Convenzione di Istanbul. La seconda parte affronta aspetti medico-legali della violenza di genere (attività di patologia forense, genetica forense e tossicologia forense nei femminicidi, assistenza medico-legale alla vittima di maltrattamenti e violenza sessuale, valutazione medico-legale del danno alla persona per stalking). La terza parte presenta lo studio su casistica autoptica di femminicidi del 1950-2019 e provvedimenti di ammonimento del Questore per stalking e per violenza domestica del 2009-2020 nella provincia bolognese. Secondo i risultati il femminicidio è un fenomeno di “vecchia data”, in un quadro normativo-culturale che “tollerava” violenza a danno di vittime femminili. L’andamento del fenomeno è costante fino a oggi con modifiche di cause e mezzi del decesso. L’aumentata età media delle vittime richiama il crescente fenomeno dell’elder abuse. Negli ammonimenti per stalking e per violenza domestica analizzati prevalgono vittime di genere femminile e autori di genere maschile, in vicende affettive e familiari. Lo studio approfondito delle caratteristiche di autori e vittime di femminicidio, stalking e violenza domestica permette di individuare indicatori di rischio per implementare strategie di prevenzione mirate. Il punto di vista privilegiato medico-legale può assumere un ruolo centrale insieme alle altre figure coinvolte in prevenzione, repressione e contrasto alla violenza di genere. Solo un rigoroso approccio metodologico multidisciplinare può aiutare nella prevenzione. La ricerca in tale ambito è il punto di forza della gestione multidisciplinare della vittima.