The BC Radon Data Repository (BCRDR) and BC Radon Map: Integrating disparate data sources for improved public health communication.

SETTING: The potential for exposure to indoor radon varies dramatically across British Columbia (BC) due to varied geology. Individuals may struggle to understand their exposure risk and agencies may struggle to understand the value of population-level programs and policies to mitigate risk. INTERVENTION: The BC Centre for Disease Control (BCCDC) established the BC Radon Data Repository (BCRDR) to facilitate radon research, public awareness, and action in the province. The BCRDR aggregates indoor radon measurements collected by government agencies, industry professionals and organizations, and research and advocacy groups. Participation was formalized with a data sharing agreement, which outlines how the BCCDC anonymizes and manages the shared data integrated into the BCRDR. OUTCOMES: The BCRDR currently holds 38,733 measurements from 18 data contributors. The repository continues to grow with new measurements from existing contributors and the addition of new contributors. A prominent use of the BCRDR was to create the online, interactive BC Radon Map, which includes regional concentration summaries, risk interpretation messaging, and health promotion information. Anonymized BCRDR data are also available for external release upon request. IMPLICATIONS: The BCCDC leverages existing radon measurement programs to create a large and integrated database with wide geographic coverage. The development and application of the BCRDR informs public health research and action beyond the BCCDC, and the repository can serve as a model for other regional or national initiatives.

RéSUMé: LIEU: Le potentiel d'exposition au radon à l'intérieur des bâtiments varie beaucoup d'une région à l'autre de la Colombie-Britannique en raison de la géologie variée. Les particuliers peuvent avoir du mal à comprendre leur risque d'exposition, et les organismes, à comprendre l'utilité des programmes et des politiques populationnels pour atténuer le risque. INTERVENTION: Le BC Centre for Disease Control (« le Centre ¼) a créé un organe d'archivage, le BC Radon Data Repository (BCRDR), pour faciliter la recherche, l'information, la sensibilisation du public et l'action liées au radon dans la province. Le BCRDR totalise les relevés du radon à l'intérieur des bâtiments pris par les organismes gouvernementaux, les professionnels et les organismes de l'industrie, ainsi que les groupes de recherche et de revendication. La participation est officialisée par un accord de partage de données qui décrit comment le Centre anonymise et gère les données communes du BCRDR. RéSULTATS: Le BCRDR contient actuellement 38 733 relevés de 18 contributeurs de données. Il continue de croître, avec de nouveaux relevés venant de contributeurs existants et l'ajout de nouveaux contributeurs. Il a servi, entre autres, à créer une carte du radon interactive en ligne pour la Colombie-Britannique, avec des résumés des concentrations régionales, des messages d'interprétation du risque et des informations de promotion de la santé. Sur demande, les données anonymisées du BCRDR sont également disponibles pour diffusion externe. CONSéQUENCES: Le Centre a exploité les programmes de prise de relevés du radon existants pour créer une grande base de données intégrée ayant une vaste couverture géographique. Le développement et les applications du BCRDR éclairent la recherche et l'action en santé publique au-delà du Centre, et l'organe d'archivage peut servir de modèle pour d'autres initiatives régionales ou nationales.

Voltage-sensitive dye imaging reveals dynamic spatiotemporal properties of cortical activity after spontaneous muscle twitches in the newborn rat.

Spontaneous activity in the developing brain contributes to its maturation, but how this activity is coordinated between distinct cortical regions and whether it might reflect developing sensory circuits is not well understood. Here, we address this question by imaging the spread and synchronization of cortical activity using voltage-sensitive dyes (VSDs) in the developing rat in vivo. In postnatal day 4-6 rats (n = 10), we collected spontaneous changes in VSD signal that reflect underlying membrane potential changes over a large craniotomy (50 mm2) that encompassed both the sensory and motor cortices of both hemispheres. Bursts of depolarization that occurred approximately once every 12 s were preceded by spontaneous twitches of the hindlimbs and/or tail. The close association with peripheral movements suggests that these bursts may represent a slow component of spindle bursts, a prominent form of activity in the developing somatosensory cortex. Twitch-associated cortical activity was synchronized between subregions of somatosensory cortex, which reflected the synchronized twitching of the limbs and tail. This activity also spread asymmetrically, toward the midline of the brain. We found that the spatial and temporal structure of such spontaneous cortical bursts closely matched that of sensory-evoked activity elicited via direct stimulation of the periphery. These data suggest that spontaneous cortical activity provides a recurring template of functional cortical circuits within the developing cortex and could contribute to the maturation of integrative connections between sensory and motor cortices.

Hot weather and death related to acute cocaine, opioid and amphetamine toxicity in British Columbia, Canada: a time-stratified case-crossover study.

BACKGROUND: Previous research has shown that cocaine-associated deaths occur more frequently in hot weather, which has not been described for other illicit drugs or combinations of drugs. The study objective was to evaluate the relation between temperature and risk of death related to cocaine, opioids and amphetamines in British Columbia, Canada. METHODS: We extracted data on all deaths with cocaine, opioid or amphetamine toxicity recorded as an underlying or contributing cause from BC vital statistics for 1998-2017. We used a time-stratified case-crossover design to estimate the effect of temperature on the risk of death associated with acute drug toxicity during the warmer months (May through September). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for each 10°C increase in the 2-day average maximum temperature at the residential location. RESULTS: We included 4913 deaths in the analyses. A 10°C increase in the 2-day average maximum temperature was associated with an OR of 1.43 (95% CI 1.11-1.86) for deaths with only cocaine toxicity recorded (n = 561), an OR of 1.15 (95% CI 0.99-1.33) for deaths with opioids only (n = 1682) and an OR of 1.11 (95% CI 0.60-2.04) for deaths with amphetamines only (n = 133). There were also elevated effects when toxicity from multiple drugs was recorded. Sensitivity analyses showed differences in the ORs by sex, by climatic region, and when the location of death was used instead of the location of residence. INTERPRETATION: Increasing temperatures were associated with higher odds of death due to drug toxicity, especially for cocaine alone and combined with other drugs. Targeted interventions are necessary to prevent death associated with toxic drug use during hot weather.

Mirrored bilateral slow-wave cortical activity within local circuits revealed by fast bihemispheric voltage-sensitive dye imaging in anesthetized and awake mice.

Spontaneous slow-wave oscillations of neuronal membrane potential occur about once every second in the rodent cortex and may serve to shape the efficacy of evoked neuronal responses and consolidate memory during sleep. However, whether these oscillations reflect the entrainment of all cortical regions via propagating waves or whether they exhibit regional and temporal heterogeneity that reflects processing in local cortical circuits is unknown. Using voltage-sensitive dye (VSD) imaging within an adult C57BL/6J mouse cross-midline large craniotomy preparation, we recorded this depolarizing activity across most of both cortical hemispheres simultaneously in both anesthetized and quiet awake animals. Spontaneous oscillations in the VSD signal were highly synchronized between hemispheres, and acallosal I/LnJ mice indicated that synchrony depended on the corpus callosum. In both anesthetized and awake mice (recovered from anesthesia), the oscillations were not necessarily global changes in activity state but were made up of complex local patterns characterized by multiple discrete peaks that were unevenly distributed across cortex. Although the local patterns of depolarizing activity were complex and changed over tens of milliseconds, they were faithfully mirrored in both hemispheres in mice with an intact corpus callosum, to perhaps ensure parallel modification of related circuits in both hemispheres. We conclude that within global rhythms of spontaneous activity are complex events that reflect orchestrated processing within local cortical circuits.

A descriptive analysis of blood mercury test results in British Columbia to identify excessive exposures.

OBJECTIVE: The objective of this study was to describe who in British Columbia (BC) is tested for blood mercury, the distribution of their results, and the adequacy of follow-up testing. METHODS: The BC Centre for Disease Control (BCCDC) obtained records of clinician-ordered analyses of blood mercury conducted by BC laboratories during 2009 and 2010. We conducted a descriptive analysis with statistical testing of who was tested, the distribution of their blood mercury concentrations, whose results exceeded Health Canada's proposed guidance values (8 µg/L (40 nmol/L) for children/adolescents ≤ 18 years and women 19-49 years, and 20 µg/L (100 nmol/L) for other adults), and patterns of repeat testing. RESULTS: Mercury test results for 6487 individuals were reviewed. Adults ≥ 50 years had the highest testing rates. The median blood mercury concentration for all tested persons was 1.8 µg/L. Nine percent of women aged 19-49 years had results exceeding Health Canada's provisional guidance value of 8 µg/L. Data from one of BC's two biomarker laboratories indicated that some residents of Vancouver and nearby suburbs have higher exposure to mercury than other BC residents. Of 127 individuals who had results in 2009 exceeding provisional guidance values, only 45% were tested again within 12 months. CONCLUSION: Collating and analyzing all clinical biomarker testing such as blood mercury at a provincial population level allows for assessment of the adequacy and appropriateness of follow-up testing and suggests which regional and demographic strata are at higher levels of exposure.

RéSUMé: OBJECTIF: Décrire qui, en Colombie-Britannique (C.-B.), fait l'objet de dosages du mercure sanguin, quelle est la distribution des résultats, et si les dosages de suivi sont adéquats. MéTHODE: Le BC Centre for Disease Control (BCCDC) a obtenu les dossiers de dosages du mercure sanguin demandés par les cliniciens et effectués par les laboratoires de la province en 2009 et 2010. Nous avons effectué une analyse descriptive avec des contrôles statistiques des personnes testées, de la distribution de leurs concentrations de mercure sanguin, des sujets dont les résultats dépassaient les valeurs provisoires indiquées par Santé Canada (8 µg/L [40 nmol/L] pour les enfants/adolescents de ≤ 18 ans et les femmes de 19-49 ans et 20 µg/L [100 nmol/L] pour les autres adultes) et des tendances des dosages ultérieurs. RéSULTATS: Les résultats des dosages du mercure de 6 487 personnes ont été examinés. Les taux de dosage les plus élevés ont été observés chez les adultes de ≥ 50 ans. La concentration médiane de mercure sanguin chez toutes les personnes testées était de 1,8 µg/L. Neuf p. cent des femmes de 19 à 49 ans présentaient des résultats supérieurs à la valeur provisoire de 8 µg/L indiquée par Santé Canada. Selon les données de l'un des deux laboratoires de biomarqueurs de la C.-B., l'exposition au mercure de certains résidents de Vancouver et des banlieues proches était supérieure à celle des autres résidents de la province. Sur les 127 personnes dont les résultats en 2009 dépassaient les valeurs provisoires indiquées, 45 % seulement ont fait l'objet d'un nouveau dosage dans un délai de 12 mois. CONCLUSION: La collecte et l'analyse de tous les essais cliniques sur les biomarqueurs comme le mercure sanguin à l'échelle d'une population provinciale permettent de déterminer l'adéquation et la pertinence des dosages de suivi et indiquent dans quelles strates régionales et démographiques les niveaux d'exposition sont les plus élevés.

Assessing Multiplex Tiling PCR Sequencing Approaches for Detecting Genomic Variants of SARS-CoV-2 in Municipal Wastewater.

Wastewater-based genomic surveillance of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus shows promise to complement genomic epidemiology efforts. Multiplex tiling PCR is a desirable approach for targeted genome sequencing of SARS-CoV-2 in wastewater due to its low cost and rapid turnaround time. However, it is not clear how different multiplex tiling PCR primer schemes or wastewater sample matrices impact the resulting SARS-CoV-2 genome coverage. The objective of this work was to assess the performance of three different multiplex primer schemes, consisting of 150-bp, 400-bp, and 1,200-bp amplicons, as well as two wastewater sample matrices, influent wastewater and primary sludge, for targeted genome sequencing of SARS-CoV-2. Wastewater samples were collected weekly from five municipal wastewater treatment plants (WWTPs) in the Metro Vancouver region of British Columbia, Canada during a period of increased coronavirus disease 19 (COVID-19) case counts from February to April 2021. RNA extracted from clarified influent wastewater provided significantly higher genome coverage (breadth and median depth) than primary sludge samples across all primer schemes. Shorter amplicons appeared to be more resilient to sample RNA degradation but were hindered by greater primer pool complexity in the 150-bp scheme. The identified optimal primer scheme (400 bp) and sample matrix (influent) were capable of detecting the emergence of mutations associated with genomic variants of concern, for which the daily wastewater load significantly correlated with clinical case counts. Taken together, these results provide guidance on best practices for implementing wastewater-based genomic surveillance and demonstrate its ability to inform epidemiology efforts by detecting genomic variants of concern circulating within a geographic region. IMPORTANCE Monitoring the genomic characteristics of the SARS-CoV-2 virus circulating in a population can shed important insights into epidemiological aspects of the COVID-19 outbreak. Sequencing every clinical patient sample in a highly populous area is a difficult feat, and thus sequencing SARS-CoV-2 RNA in municipal wastewater offers great promise to augment genomic surveillance by characterizing a pooled population sample matrix, particularly during an escalating outbreak. Here, we assess different approaches and sample matrices for rapid targeted genome sequencing of SARS-CoV-2 in municipal wastewater. We demonstrate that the optimal approach is capable of detecting the emergence of SARS-CoV-2 genomic variants of concern, with strong correlations to clinical case data in the province of British Columbia. These results provide guidance on best practices on, as well as further support for, the application of wastewater genomic surveillance as a tool to augment current genomic epidemiology efforts.

Long-lasting working memories of obstacles established by foreleg stepping in walking cats require area 5 of the posterior parietal cortex.

Walking animals rely on working memory to avoid obstacles. One example is the stepping of the hindlegs of quadrupeds over an obstacle. In this case, the obstacle is not visible at the time of hindleg stepping, because of its position between the fore and hindlegs, and working memory must be used to avoid it. We have previously shown that this memory is very precise and surprisingly long-lasting and that it depends on the stepping of the forelegs over the obstacle for its initiation. In this study, we test the hypothesis that area 5 in the posterior parietal cortex of cats is necessary for the maintenance of this long-lasting working memory. We report that small bilateral lesions to area 5 do not affect the amplitude of normal stepping of the hindlegs over obstacles, but they profoundly reduce the long-lasting working memory of obstacles. We propose that inputs to area 5 associated with foreleg stepping initiate long-lasting activity that maintains the memory of obstacle height in another brain region to guide the hindlegs over obstacles.

Object avoidance during locomotion.

Many animals rely on vision for navigating through complex environments and for avoiding specific obstacles during locomotion. Navigation and obstacle avoidance are tasks that depend on gathering information about the environment by vision and using this information at later times to guide limb and body movements. Here we review studies demonstrating the use of short-term visual memory during walking in humans and cats. Our own investigations have demonstrated that cats have the ability to retain a memory of an obstacle they have stepped over with the forelegs for many minutes and to use this memory to guide stepping of the hindlegs to avoid the remembered obstacle. A brain region that may be critically involved in the retention of memories of the location of obstacles is the posterior parietal cortex. Recordings from neurons in area 5 in the posterior parietal cortex in freely walking cats have revealed the existence of neurons whose activity is strongly correlated with the location of an obstacle relative to the body. How these neurons might be used to regulate motor commands remains to be established. We believe that studies on obstacle avoidance in walking cats have the potential to significantly advance our understanding of visuo-motor transformations. Current knowledge about the brain regions and pathways underlying visuo-motor transformations during walking are reviewed.

Exposure to Rats and Rat-Associated Leptospira and Bartonella Species Among People Who Use Drugs in an Impoverished, Inner-City Neighborhood of Vancouver, Canada.

Rat infestations are common, particularly in impoverished, inner-city neighborhoods. However, there has been little research into the nature and consequences of rat exposure in these neighborhoods, particularly in Canada. In this study, we sought to characterize exposure to rats and rat-associated Leptospira interrogans and Bartonella tribocorum, as well as risk factors associated with exposure, in residents (n = 202) of the Downtown Eastside (DTES) neighborhood of Vancouver, Canada. There was no evidence of exposure to rat-associated L. interrogans but 6/202 (3.0%) of participants were exposed to B. tribocorum, which is known to be circulating among DTES rats. We also found that frequent and close rat exposure was common among DTES residents, and that this exposure was particularly associated with injection drug use and outdoor income-generating activities (e.g., drug dealing). These risk factors may be good targets for interventions geared toward effectively reducing rat exposure.

Large Scale Cortical Functional Networks Associated with Slow-Wave and Spindle-Burst-Related Spontaneous Activity.

Cortical sensory systems are active with rich patterns of activity during sleep and under light anesthesia. Remarkably, this activity shares many characteristics with those present when the awake brain responds to sensory stimuli. We review two specific forms of such activity: slow-wave activity (SWA) in the adult brain and spindle bursts in developing brain. SWA is composed of 0.5-4 Hz resting potential fluctuations. Although these fluctuations synchronize wide regions of cortex, recent large-scale imaging has shown spatial details of their distribution that reflect underlying cortical structural projections and networks. These networks are regulated, as prior awake experiences alter both the spatial and temporal features of SWA in subsequent sleep. Activity patterns of the immature brain, however, are very different from those of the adult. SWA is absent, and the dominant pattern is spindle bursts, intermittent high frequency oscillations superimposed on slower depolarizations within sensory cortices. These bursts are driven by intrinsic brain activity, which act to generate peripheral inputs, for example via limb twitches. They are present within developing sensory cortex before they are mature enough to exhibit directed movements and respond to external stimuli. Like in the adult, these patterns resemble those evoked by sensory stimulation when awake. It is suggested that spindle-burst activity is generated purposefully by the developing nervous system as a proxy for true external stimuli. While the sleep-related functions of both slow-wave and spindle-burst activity may not be entirely clear, they reflect robust regulated phenomena which can engage select wide-spread cortical circuits. These circuits are similar to those activated during sensory processing and volitional events. We highlight these two patterns of brain activity because both are prominent and well-studied forms of spontaneous activity that will yield valuable insights into brain function in the coming years.

Long-term effectiveness of initiating non-nucleoside reverse transcriptase inhibitor- versus ritonavir-boosted protease inhibitor-based antiretroviral therapy: implications for first-line therapy choice in resource-limited settings.

INTRODUCTION: In many resource-limited settings, combination antiretroviral therapy (cART) failure is diagnosed clinically or immunologically. As such, there is a high likelihood that patients may stay on a virologically failing regimen for a substantial period of time. Here, we compared the long-term impact of initiating non-nucleoside reverse transcriptase inhibitor (NNRTI)- versus boosted protease inhibitor (bPI)-based cART in British Columbia (BC), Canada. METHODS: We followed prospectively 3925 ART-naïve patients who started NNRTIs (N=1963, 50%) or bPIs (N=1962; 50%) from 1 January 2000 until 30 June 2013 in BC. At six months, we assessed whether patients virologically failed therapy (a plasma viral load (pVL) >50 copies/mL), and we stratified them based on the pVL at the time of failure ≤500 versus >500 copies/mL. We then followed these patients for another six months and calculated their probability of achieving subsequent viral suppression (pVL <50 copies/mL twice consecutively) and of developing drug resistance. These probabilities were adjusted for fixed and time-varying factors, including cART adherence. RESULTS: At six months, virologic failure rates were 9.5 and 14.3 cases per 100 person-months for NNRTI and bPI initiators, respectively. NNRTI initiators who failed with a pVL ≤500 copies/mL had a 16% higher probability of achieving subsequent suppression at 12 months than bPI initiators (0.81 (25th-75th percentile 0.75-0.83) vs. 0.72 (0.61-0.75)). However, if failing NNRTI initiators had a pVL >500 copies/mL, they had a 20% lower probability of suppressing at 12 months than pVL-matched bPI initiators (0.37 (0.29-0.45) vs. 0.46 (0.38-0.54)). In terms of evolving HIV drug resistance, those who failed on NNRTI performed worse than bPI in all scenarios, especially if they failed with a viral load >500 copies/mL. CONCLUSIONS: Our results show that patients who virologically failed at six months on NNRTI and continued on the same regimen had a lower probability of subsequently achieving viral suppression and a higher chance of evolving HIV drug resistance. These results suggest that improving access to regular virologic monitoring is critically important, especially if NNRTI-based cART is to remain a preferred choice for first-line therapy in resource-limited settings.

Spontaneous cortical activity alternates between motifs defined by regional axonal projections.

Using millisecond-timescale voltage-sensitive dye imaging in lightly anesthetized or awake adult mice, we show that a palette of sensory-evoked and hemisphere-wide activity motifs are represented in spontaneous activity. These motifs can reflect multiple modes of sensory processing, including vision, audition and touch. We found similar cortical networks with direct cortical activation using channelrhodopsin-2. Regional analysis of activity spread indicated modality-specific sources, such as primary sensory areas, a common posterior-medial cortical sink where sensory activity was extinguished within the parietal association area and a secondary anterior medial sink within the cingulate and secondary motor cortices for visual stimuli. Correlation analysis between functional circuits and intracortical axonal projections indicated a common framework corresponding to long-range monosynaptic connections between cortical regions. Maps of intracortical monosynaptic structural connections predicted hemisphere-wide patterns of spontaneous and sensory-evoked depolarization. We suggest that an intracortical monosynaptic connectome shapes the ebb and flow of spontaneous cortical activity.